A single dynamic observer-based module for design of simultaneous fault detection, isolation and tracking control scheme

NASA Astrophysics Data System (ADS)

Davoodi, M.; Meskin, N.; Khorasani, K.

2018-03-01

The problem of simultaneous fault detection, isolation and tracking (SFDIT) control design for linear systems subject to both bounded energy and bounded peak disturbances is considered in this work. A dynamic observer is proposed and implemented by using the H∞/H-/L1 formulation of the SFDIT problem. A single dynamic observer module is designed that generates the residuals as well as the control signals. The objective of the SFDIT module is to ensure that simultaneously the effects of disturbances and control signals on the residual signals are minimised (in order to accomplish the fault detection goal) subject to the constraint that the transfer matrix from the faults to the residuals is equal to a pre-assigned diagonal transfer matrix (in order to accomplish the fault isolation goal), while the effects of disturbances, reference inputs and faults on the specified control outputs are minimised (in order to accomplish the fault-tolerant and tracking control goals). A set of linear matrix inequality (LMI) feasibility conditions are derived to ensure solvability of the problem. In order to illustrate and demonstrate the effectiveness of our proposed design methodology, the developed and proposed schemes are applied to an autonomous unmanned underwater vehicle (AUV).

Note: Effect of the parasitic forced vibration in an atom gravimeter

NASA Astrophysics Data System (ADS)

Chen, Le-Le; Luo, Qin; Zhang, Heng; Duan, Xiao-Chun; Zhou, Min-Kang; Hu, Zhong-Kun

2018-06-01

The vibration isolator usually plays an important role in atom interferometry gravimeters to improve their sensitivity. We show that the parasitic forced vibration of the Raman mirror, which is induced by external forces acting on the vibration isolator, can cause a bias in atom gravimeters. The mechanism of how this effect induces an additional phase shift in our interferometer is analyzed. Moreover, modulation experiments are performed to measure the dominant part of this effect, which is caused by the magnetic force between the passive vibration isolator and the coil of the magneto-optic trap. In our current apparatus, this forced vibration contributes a systematic error of -2.3(2) × 10-7 m/s2 when the vibration isolator works in the passive isolation mode. Even suppressed with an active vibration isolator, this effect can still contribute -6(1) × 10-8 m/s2; thus, it should be carefully considered in precision atom gravimeters.

Isolation of exosomes from whole blood by integrating acoustics and microfluidics.

PubMed

Wu, Mengxi; Ouyang, Yingshi; Wang, Zeyu; Zhang, Rui; Huang, Po-Hsun; Chen, Chuyi; Li, Hui; Li, Peng; Quinn, David; Dao, Ming; Suresh, Subra; Sadovsky, Yoel; Huang, Tony Jun

2017-10-03

Exosomes are nanoscale extracellular vesicles that play an important role in many biological processes, including intercellular communications, antigen presentation, and the transport of proteins, RNA, and other molecules. Recently there has been significant interest in exosome-related fundamental research, seeking new exosome-based biomarkers for health monitoring and disease diagnoses. Here, we report a separation method based on acoustofluidics (i.e., the integration of acoustics and microfluidics) to isolate exosomes directly from whole blood in a label-free and contact-free manner. This acoustofluidic platform consists of two modules: a microscale cell-removal module that first removes larger blood components, followed by extracellular vesicle subgroup separation in the exosome-isolation module. In the cell-removal module, we demonstrate the isolation of 110-nm particles from a mixture of micro- and nanosized particles with a yield greater than 99%. In the exosome-isolation module, we isolate exosomes from an extracellular vesicle mixture with a purity of 98.4%. Integrating the two acoustofluidic modules onto a single chip, we isolated exosomes from whole blood with a blood cell removal rate of over 99.999%. With its ability to perform rapid, biocompatible, label-free, contact-free, and continuous-flow exosome isolation, the integrated acoustofluidic device offers a unique approach to investigate the role of exosomes in the onset and progression of human diseases with potential applications in health monitoring, medical diagnosis, targeted drug delivery, and personalized medicine.

Isolation of exosomes from whole blood by integrating acoustics and microfluidics

PubMed Central

Wu, Mengxi; Ouyang, Yingshi; Wang, Zeyu; Zhang, Rui; Huang, Po-Hsun; Chen, Chuyi; Li, Hui; Li, Peng; Quinn, David; Dao, Ming; Suresh, Subra

2017-01-01

Exosomes are nanoscale extracellular vesicles that play an important role in many biological processes, including intercellular communications, antigen presentation, and the transport of proteins, RNA, and other molecules. Recently there has been significant interest in exosome-related fundamental research, seeking new exosome-based biomarkers for health monitoring and disease diagnoses. Here, we report a separation method based on acoustofluidics (i.e., the integration of acoustics and microfluidics) to isolate exosomes directly from whole blood in a label-free and contact-free manner. This acoustofluidic platform consists of two modules: a microscale cell-removal module that first removes larger blood components, followed by extracellular vesicle subgroup separation in the exosome-isolation module. In the cell-removal module, we demonstrate the isolation of 110-nm particles from a mixture of micro- and nanosized particles with a yield greater than 99%. In the exosome-isolation module, we isolate exosomes from an extracellular vesicle mixture with a purity of 98.4%. Integrating the two acoustofluidic modules onto a single chip, we isolated exosomes from whole blood with a blood cell removal rate of over 99.999%. With its ability to perform rapid, biocompatible, label-free, contact-free, and continuous-flow exosome isolation, the integrated acoustofluidic device offers a unique approach to investigate the role of exosomes in the onset and progression of human diseases with potential applications in health monitoring, medical diagnosis, targeted drug delivery, and personalized medicine. PMID:28923936

Ion transport regulation by prostaglandins in mouse macrophages.

PubMed

Braquet, P; Diez, J; Garay, R

1985-01-01

Although the prostaglandins PGE1, PGE2 and PGF2 alpha had no effect on ion transport in isolated human erythrocytes, they modulated ion transport in isolated mouse macrophages, apparently through the mediation of cAMP, by inhibiting the NA+, K+ cotransport system, stimulating the Na+, K+ pump, and stimulating the Na+: Ca++ exchange mechanism.

Studies on the factors modulating indole-3-acetic acid production in endophytic bacterial isolates from Piper nigrum and molecular analysis of ipdc gene.

PubMed

Jasim, B; Jimtha John, C; Shimil, V; Jyothis, M; Radhakrishnan, E K

2014-09-01

The study mainly aimed quantitative analysis of IAA produced by endophytic bacteria under various conditions including the presence of extract from Piper nigrum. Analysis of genetic basis of IAA production was also conducted by studying the presence and diversity of the ipdc gene among the selected isolates. Five endophytic bacteria isolated previously from P. nigrum were used for the study. The effect of temperature, pH, agitation, tryptophan concentration and plant extract on modulating IAA production of selected isolates was analysed by colorimetric method. Comparative and quantitative analysis of IAA production by colorimetric isolates under optimal culture condition was analysed by HPTLC method. Presence of ipdc gene and thereby biosynthetic basis of IAA production among the selected isolates were studied by PCR-based amplification and subsequent insilico analysis of sequence obtained. Among the selected bacterial isolates from P. nigrum, isolate PnB 8 (Klebsiella pneumoniae) was found to have the maximum yield of IAA under various conditions optimized and was confirmed by colorimetric, HPLC and HPTLC analysis. Very interestingly, the study showed stimulating effect of phytochemicals from P. nigrum on IAA production by endophytic bacteria isolated from same plant. This study is unique because of the selection of endophytes from same source for comparative and quantitative analysis of IAA production under various conditions. Study on stimulatory effect of phytochemicals on bacterial IAA production as explained in the study is a novel approach. Studies on molecular basis of IAA production which was confirmed by sequence analysis of ipdc gene make the study scientifically attractive. Even though microbial production of IAA is well known, current report on detailed optimization, effect of plant extract and molecular confirmation of IAA biosynthesis is comparatively novel in its approach. © 2014 The Society for Applied Microbiology.

On the sensitivity of 4 different CPV module technologies to relevant ambient and operation conditions

NASA Astrophysics Data System (ADS)

Domínguez, César; Besson, Pierre

2014-09-01

The sensitivity of four different CPV module technologies to most operating conditions relevant to CPV systems has been studied, namely DNI, spectrum, cell and lens temperature and clearness of the sky. In order to isolate the influence of a single operation parameter, the analysis of long-term outdoor monitoring data is required. The effect of lens temperature on cell current has been found to vary greatly between modules due to the different optical architectures studied. Maximum sensitivity is found for silicone-on-glass primary lenses. The VOC thermal coefficient was found to vary between module technologies, probably due to differences in maximum local effective concentration.

Module isolation devices

DOEpatents

Carolan, Michael Francis; Cooke, John Albert; Buzinski, Michael David

2010-04-27

A gas flow isolation device includes a gas flow isolation valve movable from an opened condition to a closed condition. The module isolation valve in one embodiment includes a rupture disk in flow communication with a flow of gas when the module isolation valve is in an opened condition. The rupture disk ruptures when a predetermined pressure differential occurs across it causing the isolation valve to close. In one embodiment the valve is mechanically linked to the rupture disk to maintain the valve in an opened condition when the rupture disk is intact, and which permits the valve to move into a closed condition when the rupture disk ruptures. In another embodiment a crushable member maintains the valve in an open condition, and the flow of gas passed the valve upon rupturing of the rupture disk compresses the crushable member to close the isolation valve.

Housing conditions modulate the reinforcing properties of cocaine in adolescent mice that binge on fat.

PubMed

Blanco-Gandía, M Carmen; Montagud-Romero, Sandra; Aguilar, María A; Miñarro, José; Rodríguez-Arias, Marta

2018-01-01

Binge eating is a specific form of overeating characterized by intermittent, excessive eating. To date, several studies have addressed the effects that bingeing on fat has on the rewarding effects of drugs of abuse, but they have found contradictory and highly variable results. Housing conditions could modulate these results, as most studies employ isolated animals to measure the exact amount of food that is ingested. The aim of this study was to evaluate the effects of housing conditions on the response of mice to cocaine, modulated by bingeing on a high-fat diet during adolescence. After 40days of binge-eating for 2h, three days a week (PND 29-69), the reinforcing effects of a non-effective dose of cocaine (1mg/kg) was evaluated using the conditioned place preference (CPP) paradigm. The anxiolytic profile using the Elevated Plus Maze and circulating leptin and corticosterone levels were also assessed. Our results show a significant escalation in the consumption of a high-fat diet between the first and the last week in both types of housed mice. Among the grouped mice, only those exposed to high-fat binge (HFB) developed CPP. Conversely, isolated mice fed with standard diet were more sensitive to the rewarding effects of a subthreshold dose of cocaine than those fed with HFB. Plasma leptin levels were elevated in both groups that developed CPP. Although isolated animals presented higher corticosterone levels with respect to the grouped ones, anxiety levels did not differ. Therefore, our results highlight the importance of housing conditions on the effects that a high-fat diet exerts on cocaine reward. Copyright © 2017 Elsevier Inc. All rights reserved.

Unstart coupling mechanism analysis of multiple-modules hypersonic inlet.

PubMed

Hu, Jichao; Chang, Juntao; Wang, Lei; Cao, Shibin; Bao, Wen

2013-01-01

The combination of multiplemodules in parallel manner is an important way to achieve the much higher thrust of scramjet engine. For the multiple-modules scramjet engine, when inlet unstarted oscillatory flow appears in a single-module engine due to high backpressure, how to interact with each module by massflow spillage, and whether inlet unstart occurs in other modules are important issues. The unstarted flowfield and coupling characteristic for a three-module hypersonic inlet caused by center module II and side module III were, conducted respectively. The results indicate that the other two hypersonic inlets are forced into unstarted flow when unstarted phenomenon appears on a single-module hypersonic inlet due to high backpressure, and the reversed flow in the isolator dominates the formation, expansion, shrinkage, and disappearance of the vortexes, and thus, it is the major factor of unstart coupling of multiple-modules hypersonic inlet. The coupling effect among multiple modules makes hypersonic inlet be more likely unstarted.

[Pathogenic activity modulation of Escherichia coli TL+ toxin with an isolated protein of Giardia intestinalis and a synthetic peptide].

PubMed

Jiménez-Cardoso, E; Eligio-García, L; Jiménez-Cardoso, J M; Angeles-Anguiano, E; Tobilla-Mercado, J M; Castañeda, G

2001-01-01

It is know that a protein from Giardia intestinalis works as a substrate for V. cholerae and Escherichia coli. The toxic activity of both activates protein G form intestinal mucosa with a pathogenic activity results. In the present study, the pathogenic activity of subunit A of Vibrio cholerae toxin (ADP-ribosyltranferase) using isolated fragments from: Giardia intestinalis and a synthetic peptide were used as modulators in vivo. Adult Neo Zealand males rabbits with ileal loop were prepared and different mixtures of heat labile enterotoxin obtained from Escherichia coli H10407 and ARF protein isolated by electrofocusing from Giardia intestinalis Portland I were inoculated in the loops. The toxin activity was evaluated by luminal liquid secretion and cyclic AMP concentration in tissues (each loop). ADP ribosyltranferase activity was modulated, due to a decreased of luminal secretion and cAMP in tissues. Such results were seen when synthetic peptide and subunit A from Vibrio cholerae were used. The ADP ribosyltranferase activity of heat labile Escherichia coli and Vibrio cholerae toxins were modified by in vitro and in vivo interaction with ARF protein, which modified pathogenic effect over rabbits intestinal epithelium.

Modulation of the proteome of peripheral blood mononuclear cells from HIV-1 infected patients by drugs of abuse

PubMed Central

Reynolds, Jessica L.; Mahajan, Supriya D.; Aalinkeel, Ravikunar; Nair, Bindukumar; Sykes, Donald E.; Agosto-Mujica, Arnadri; Hsiao, Chiu Bin; Schwartz, Stanley A.

2010-01-01

We used proteomic analyses to assess how drug abuse modulates immunologic responses to infections with the human immunodeficiency virus type 1 (HIV-1). Two dimensional (2D) difference gel electrophoresis was utilized to determine changes in the proteome of peripheral blood mononuclear cells (PBMC) isolated from HIV-1 positive donors that occurred after treatment with cocaine or methamphetamine. Both drugs differentially regulated the expression of several functional classes of proteins. We further isolated specific subpopulations of PBMC to determine which subpopulations were selectively affected by treatment with drugs of abuse. Monocytes, B cells and T cells were positively or negatively selected from PBMC isolated from HIV-1 positive donors. Our results demonstrate that cocaine and methamphetamine modulate gene expression primarily in monocytes and T cells, the primary targets of HIV-1 infection. Proteomic data were validated with quantitative, real-time PCR. These studies elucidate the molecular mechanisms underlying the effects of drugs of abuse on HIV-1 infections. Several functionally relevant classes of proteins were identified as potential mediators of HIV-1 pathogenesis and disease progression associated with drug abuse. PMID:19543960

Development of data acquisition and over-current protection systems for a suppressor-grid current with a neutral-beam ion source

NASA Astrophysics Data System (ADS)

Wei, LIU; Chundong, HU; Sheng, LIU; Shihua, SONG; Jinxin, WANG; Yan, WANG; Yuanzhe, ZHAO; Lizhen, LIANG

2017-12-01

Neutral beam injection is one of the effective auxiliary heating methods in magnetic-confinement-fusion experiments. In order to acquire the suppressor-grid current signal and avoid the grid being damaged by overheating, a data acquisition and over-current protection system based on the PXI (PCI eXtensions for Instrumentation) platform has been developed. The system consists of a current sensor, data acquisition module and over-current protection module. In the data acquisition module, the acquired data of one shot will be transferred in isolation and saved in a data-storage server in a txt file. It can also be recalled using NBWave for future analysis. The over-current protection module contains two modes: remote and local. This gives it the function of setting a threshold voltage remotely and locally, and the forbidden time of over-current protection also can be set by a host PC in remote mode. Experimental results demonstrate that the data acquisition and over-current protection system has the advantages of setting forbidden time and isolation transmission.

Iron from haemoglobin and haemin modulates nucleotide hydrolysis in Trichomonas vaginalis.

PubMed

Vieira, Patrícia de Brum; Silva, Nícolas Luiz Feijó; Kist, Luiza Wilges; Oliveira, Giovanna Medeiros Tavares de; Bogo, Maurício Reis; Carli, Geraldo Atillio de; Macedo, Alexandre José; Tasca, Tiana

2015-04-01

Extracellular ATP may act as a danger signalling molecule, inducing inflammation and immune responses in infection sites. The ectonucleotidases NTPDase and ecto-5'-nucleotidase are enzymes that modulate extracellular nucleotide levels; these enzymes have been previously characterised in Trichomonas vaginalis. Iron plays an important role in the complex trichomonal pathogenesis. Herein, the effects of iron on growth, nucleotide hydrolysis and NTPDase gene expression in T. vaginalis isolates from female and male patients were evaluated. Iron from different sources sustained T. vaginalis growth. Importantly, iron from haemoglobin (HB) and haemin (HM) enhanced NTPDase activity in isolates from female patients and conversely reduced the enzyme activity in isolates from male patients. Iron treatments could not alter the NTPDase transcript levels in T. vaginalis. Furthermore, our results reveal a distinct ATP, ADP and AMP hydrolysis profile between isolates from female and male patients influenced by iron from HB and HM. Our data indicate the participation of NTPDase and ecto-5'-nucleotidase in the establishment of trichomonas infection through ATP degradation and adenosine production influenced by iron.

Two structurally distinct chalcone dimers from Helichrysum zivojinii and their activities in cancer cell lines.

PubMed

Aljančić, Ivana S; Vučković, Ivan; Jadranin, Milka; Pešić, Milica; Dorđević, Iris; Podolski-Renić, Ana; Stojković, Sonja; Menković, Nebojša; Vajs, Vlatka E; Milosavljević, Slobodan M

2014-02-01

Dimers tomoroside A (1) and tomoroside B (2) of the co-occuring known chalcone monomer (3), along with the seven known flavonoid glucosides (4-10), were isolated from the aerial parts of Helichrysum zivojinii Černjavski & Soška. The structures of the isolated compounds were elucidated by spectroscopic techniques. Compound 1 inhibited topo IIα and hif-1α expression and stimulated doxorubicin anticancer effect, while 2 increased the expression of hif-1α, probably acting as antioxidant and redox status modulator. Notably, 2 synergized with Tipifarnib showing potential to improve the action of this new chemotherapeutic involved in the modulation of mitogene activated protein (MAP) kinase signaling pathway. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ground Isolation Circuit for Isolating a Transmission Line from Ground Interference

NASA Technical Reports Server (NTRS)

Davidson, Craig A. (Inventor)

1996-01-01

This invention relates generally to a system for isolating ground interference from a transmission line, e.g., a ground isolation circuit for isolating a wideband transmission signal (such as a video signal) from ground by modulating the base signal on a carrier signal to permit the transmission signal to be isolated. In one embodiment, the circuit includes a pair of matched mixer circuits, each of which receives a carrier signal from the same oscillator circuit. The first mixer circuit also receives the baseband signal input, after appropriate conditioning, and modulates the baseband signal onto the carrier signal. In a preferred embodiment the carrier signal has a predetermined frequency which is at least two times the frequency of the baseband signal. The modulated signal (which can comprise an rf signal) is transmitted via an rf transmission line to the second mixer, which demodulates the rf signal to recover the baseband signal. Each port of the mixer connects to an isolation transformer to ensure isolation from ground interference. The circuit is considered to be of commercial value in that it can provide isolation between transmitting and receiving circuits, e.g., ground isolation for television circuits or high frequency transmitters, without the need for video transformers or optical isolators, thereby reducing the complexity, power consumption, and weight of the system.

Lab-on-a-chip for the isolation and characterization of circulating tumor cells.

PubMed

Stakenborg, Tim; Liu, Chengxu; Henry, Olivier; O'Sullivan, Ciara K; Fermer, Christian; Roeser, Tina; Ritzi-Lehnert, Marion; Hauch, Sigfried; Borgen, Elin; Laddach, Nadja; Lagae, Liesbet

2010-01-01

A smart miniaturized system is being proposed for the isolation and characterization of circulating tumor cells (CTCs) directly from blood. Different microfluidic modules have been designed for cell enrichment and -counting, multiplex mRNA amplification as well as DNA detection. With the different modules at hand, future effort will focus on the integration of the modules in a fully automated, single platform.

Unstart Coupling Mechanism Analysis of Multiple-Modules Hypersonic Inlet

PubMed Central

Wang, Lei; Cao, Shibin

2013-01-01

The combination of multiplemodules in parallel manner is an important way to achieve the much higher thrust of scramjet engine. For the multiple-modules scramjet engine, when inlet unstarted oscillatory flow appears in a single-module engine due to high backpressure, how to interact with each module by massflow spillage, and whether inlet unstart occurs in other modules are important issues. The unstarted flowfield and coupling characteristic for a three-module hypersonic inlet caused by center module II and side module III were, conducted respectively. The results indicate that the other two hypersonic inlets are forced into unstarted flow when unstarted phenomenon appears on a single-module hypersonic inlet due to high backpressure, and the reversed flow in the isolator dominates the formation, expansion, shrinkage, and disappearance of the vortexes, and thus, it is the major factor of unstart coupling of multiple-modules hypersonic inlet. The coupling effect among multiple modules makes hypersonic inlet be more likely unstarted. PMID:24348146

Surround Inhibition in the Primary Motor Cortex is Task-specifically Modulated in Non-professional Musicians but not in Healthy Controls During Real Piano Playing.

PubMed

Márquez, Gonzalo; Keller, Martin; Lundbye-Jensen, Jesper; Taube, Wolfgang

2018-03-01

Research has indicated that at the onset of a finger movement, unwanted contractions of adjacent muscles are prevented by inhibiting the cortical areas representing these muscles. This so-called surround inhibition (SI) seems relevant for the performance of selective finger movements but may not be necessary for tasks involving functional coupling between different finger muscles. Therefore, the present study compared SI between isolated finger movement and complex selective finger movements while playing a three-finger sequence on the piano in nine non-professional musicians and 10 untrained control participants. Transcranial magnetic stimulation (TMS) was applied to the contralateral motor cortex to assess SI in the first dorsal interosseous (FDI), abductor pollicis brevis (APB) and abductor digiti minimi (ADM) during the movement preparation and the late phasic phases. The results reveal stronger SI during the preparation phase than during the phasic phase (30.6% vs. 10.7%; P < 0.05) in the isolated-finger condition in both musicians and controls. Results also show higher SI in musicians during the preparation phase of the isolated finger condition compared to the preparation phase of the three-finger sequence (40% vs. 15%; P < 0.05). However, the control group did not show this task-specific modulation of SI (isolated: 25% vs. sequence: 25%; P > 0.05). Thus, musicians were able to modulate SI between conditions whereas control participants revealed constant levels of SI. Therefore, it may be assumed that long-term training as observed in skilled musicians is accompanied by task-specific effects on SI modulation potentially relating to the ability to perform selective and complex finger movements. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Modulation of Hepatic and Renal Metabolism and Toxicity of Trichloroethylene and Perchloroethylene by Alterations in Status of Cytochrome P450 and Glutathione

PubMed Central

Lash, Lawrence H.; Putt, David A.; Huang, Paul; Hueni, Sarah E.; Parker, Jean C.

2007-01-01

The relative importance of metabolism of trichloroethylene (Tri) and perchloroethylene (Perc) by the cytochrome P450 (P450) and glutathione (GSH) conjugation pathways in their acute renal and hepatic toxicity was studied in isolated cells and microsomes from rat kidney and liver after various treatments to modulate P450 activity/expression or GSH status. Inhibitors of P450 stimulated GSH conjugation of Tri and, to a lesser extent, Perc, in both kidney cells and hepatocytes. Perc was a more potent, acute cytotoxic agent in isolated kidney cells than Tri but Perc-induced toxicity was less responsive than Tri-induced toxicity to modulation of P450 status. These observations are consistent with P450-dependent bioactivation being more important for Tri than for Perc. Incubation of isolated rat hepatocytes with Tri produced no acute cytotoxicity in isolated hepatocytes while Perc produced comparable cytotoxicity as in kidney cells. Modulation of P450 status in hepatocytes produced larger changes in Tri- and Perc-induced cytotoxicity than in kidney cells, with non-selective P450 inhibitors increasing toxicity. Induction of CYP2E1 with pyridine also markedly increased sensitivity of hepatocytes to Tri but had little effect on Perc-induced cytotoxicity. Increases in cellular GSH concentrations increased Tri- and Perc-induced cytotoxicity in kidney cells but not in hepatocytes, consistent with the role of GSH conjugation in Tri- and Perc-induced nephrotoxicity. In contrast, depletion of cellular GSH concentrations moderately decreased Tri- and Perc-induced cytotoxicity in kidney cells but increased cytotoxicity in hepatocytes, again pointing to the importance of different bioactivation pathways and modes of action in kidney and liver. PMID:17433522

Hypercapnic acidosis modulates inflammation, lung mechanics, and edema in the isolated perfused lung.

PubMed

De Smet, Hilde R; Bersten, Andrew D; Barr, Heather A; Doyle, Ian R

2007-12-01

Low tidal volume (V(T)) ventilation strategies may be associated with permissive hypercapnia, which has been shown by ex vivo and in vivo studies to have protective effects. We hypothesized that hypercapnic acidosis may be synergistic with low V(T) ventilation; therefore, we studied the effects of hypercapnia and V(T) on unstimulated and lipopolysaccharide-stimulated isolated perfused lungs. Isolated perfused rat lungs were ventilated for 2 hours with low (7 mL/kg) or moderately high (20 mL/kg) V(T) and 5% or 20% CO(2), with lipopolysaccharide or saline added to the perfusate. Hypercapnia resulted in reduced pulmonary edema, lung stiffness, tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in the lavage and perfusate. The moderately high V(T) did not cause lung injury but increased lavage IL-6 and perfusate IL-6 as well as TNF-alpha. Pulmonary edema and respiratory mechanics improved, possibly as a result of a stretch-induced increase in surfactant turnover. Lipopolysaccharide did not induce significant lung injury. We conclude that hypercapnia exerts a protective effect by modulating inflammation, lung mechanics, and edema. The moderately high V(T) used in this study stimulated inflammation but paradoxically improved edema and lung mechanics with an associated increase in surfactant release.

Does Temperature and UV Exposure History Modulate the Effects of Temperature and UV Stress on Symbiodinium Growth Rates?

EPA Science Inventory

Temperature and ultraviolet radiation (UV) alone or in combination are known to inhibit the growth of Symbiodinium isolates. This conclusion was drawn from a number of studies having widely different exposure scenarios. Here we have examined the effects of pre-exposure acclimat...

Isolation and chemical characterization of agelaiatoxin8 (AvTx8) from Agelaia vicina wasp venom and its biological effects on GABA neurotransmission.

PubMed

Pizzo, Andrea B; Beleboni, Renê O; Gomes Carolino, Ruither O; de Oliveira, Luciana; Miranda, Antonio; Coutinho-Netto, Joaquim; Fontana, Andréia C K; Dos Santos, Wagner Ferreira

2017-10-01

Arthropod venoms are sources of molecules that may be useful tools to investigate molecular mechanisms of putative new medicines and laboratory drugs. Here we show the effects of the compound agelaiatoxin-8 (AVTx8), isolated from Agelaia vicina venom, on γ-aminobutyric acid (GABA) neurotransmission in rat brain synaptosomes. Analysis reveals that AvTx8 is composed by 14 amino acid residues with a molecular weight (MW) of 1567 Da. AvTx8 increased GABA release and inhibited GABA uptake in synaptosomes from rat cerebral cortex. AvTx8 inhibited GABA uptake and increased GABA release in the presence of Ca + , Na + , and K + channel blockers, suggesting that it acts directly on GABA transporters. In addition, AvTx8 significantly decreases GABA binding in synaptic membranes from rat brain cortex, suggesting that it also modulates the activity of GABA receptors. Moreover, AvTx8 decreased GAT-1- and GAT-3-mediated GABA uptake in transfected COS-7 cells. Accordingly, we suggest that AvTx8 modulates GABA neurotransmission and might provide a novel entry point for identifying a new class of GABA-modulating neuroprotective drugs. © 2017 Wiley Periodicals, Inc.

ISS Expedition 18 Sandra Magnus on the Treadmill Vibration Isolation and Stabilization (TVIS) in Service Module (SM)

NASA Image and Video Library

2009-02-12

ISS018-E-030101 (12 Feb. 2009) --- Astronaut Sandra Magnus, Expedition 18 flight engineer, equipped with a bungee harness, exercises on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

ISS Expedition 18 Sandra Magnus on the Treadmill Vibration Isolation and Stabilization (TVIS) in Service Module (SM)

NASA Image and Video Library

2009-02-12

ISS018-E-030096 (12 Feb. 2009) --- Astronaut Sandra Magnus, Expedition 18 flight engineer, equipped with a bungee harness, exercises on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

Determinants of bird species richness, endemism, and island network roles in Wallacea and the West Indies: is geography sufficient or does current and historical climate matter?

PubMed Central

Dalsgaard, Bo; Carstensen, Daniel W; Fjeldså, Jon; Maruyama, Pietro K; Rahbek, Carsten; Sandel, Brody; Sonne, Jesper; Svenning, Jens-Christian; Wang, Zhiheng; Sutherland, William J

2014-01-01

Island biogeography has greatly contributed to our understanding of the processes determining species' distributions. Previous research has focused on the effects of island geography (i.e., island area, elevation, and isolation) and current climate as drivers of island species richness and endemism. Here, we evaluate the potential additional effects of historical climate on breeding land bird richness and endemism in Wallacea and the West Indies. Furthermore, on the basis of species distributions, we identify island biogeographical network roles and examine their association with geography, current and historical climate, and bird richness/endemism. We found that island geography, especially island area but also isolation and elevation, largely explained the variation in island species richness and endemism. Current and historical climate only added marginally to our understanding of the distribution of species on islands, and this was idiosyncratic to each archipelago. In the West Indies, endemic richness was slightly reduced on islands with historically unstable climates; weak support for the opposite was found in Wallacea. In both archipelagos, large islands with many endemics and situated far from other large islands had high importance for the linkage within modules, indicating that these islands potentially act as speciation pumps and source islands for surrounding smaller islands within the module and, thus, define the biogeographical modules. Large islands situated far from the mainland and/or with a high number of nonendemics acted as links between modules. Additionally, in Wallacea, but not in the West Indies, climatically unstable islands tended to interlink biogeographical modules. The weak and idiosyncratic effect of historical climate on island richness, endemism, and network roles indicates that historical climate had little effects on extinction-immigration dynamics. This is in contrast to the strong effect of historical climate observed on the mainland, possibly because surrounding oceans buffer against strong climate oscillations and because geography is a strong determinant of island richness, endemism and network roles. PMID:25505528

Theoretical analysis of a method for extracting the phase of a phase-amplitude modulated signal generated by a direct-modulated optical injection-locked semiconductor laser

NASA Astrophysics Data System (ADS)

Lee, Hwan; Cho, Jun-Hyung; Sung, Hyuk-Kee

2017-05-01

The phase modulation (PM) and amplitude modulation (AM) of optical signals can be achieved using a direct-modulated (DM) optical injection-locked (OIL) semiconductor laser. We propose and theoretically analyze a simple method to extract the phase component of a PM signal produced by a DM-OIL semiconductor laser. The pure AM component of the combined PM-AM signal can be isolated by square-law detection in a photodetector and can then be used to compensate for the PM-AM signal based on an optical homodyne method. Using the AM compensation technique, we successfully developed a simple and cost-effective phase extraction method applicable to the PM-AM optical signal of a DM-OIL semiconductor laser.

Draft Genome Sequences from a Novel Clade of Bacillus cereus Sensu Lato Strains, Isolated from the International Space Station.

PubMed

Venkateswaran, Kasthuri; Checinska Sielaff, Aleksandra; Ratnayake, Shashikala; Pope, Robert K; Blank, Thomas E; Stepanov, Victor G; Fox, George E; van Tongeren, Sandra P; Torres, Clinton; Allen, Jonathan; Jaing, Crystal; Pierson, Duane; Perry, Jay; Koren, Sergey; Phillippy, Adam; Klubnik, Joy; Treangen, Todd J; Rosovitz, M J; Bergman, Nicholas H

2017-08-10

The draft genome sequences of six Bacillus strains, isolated from the International Space Station and belonging to the Bacillus anthracis - B. cereus - B. thuringiensis group, are presented here. These strains were isolated from the Japanese Experiment Module (one strain), U.S. Harmony Node 2 (three strains), and Russian Segment Zvezda Module (two strains). Copyright © 2017 Venkateswaran et al.

Photodynamic injury of isolated crayfish neuron and surrounding glial cells: the role of p53

NASA Astrophysics Data System (ADS)

Sharifulina, S. A.; Uzdensky, A. B.

2015-03-01

The pro-apoptotic transcription factor p53 is involved in cell responses to injurious impacts. Using its inhibitor pifithrin- α and activators tenovin-1, RITA and WR-1065, we studied its potential participation in inactivation and death of isolated crayfish mechanoreceptor neuron and satellite glial cells induced by photodynamic treatment, a strong inducer of oxidative stress. In dark, p53 activation by tenovin-1 or WR-1065 shortened activity of isolated neurons. Tenovin-1 and WR-1065 induced apoptosis of glial cells, whereas pifithrin-α was anti-apoptotic. Therefore, p53 mediated glial apoptosis and suppression of neuronal activity after axotomy. Tenovin-1 but not other p53 modulators induced necrosis of axotomized neurons and surrounding glia, possibly, through p53-independent pathway. Under photodynamic treatment, p53 activators tenovin-1 and RITA enhanced glial apoptosis indicating the pro-apoptotic activity of p53. Photoinduced necrosis of neurons and glia was suppressed by tenovin-1 and, paradoxically, by pifithrin-α. Modulation of photoinduced changes in the neuronal activity and necrosis of neurons and glia was possibly p53-independent. The different effects of p53 modulators on neuronal and glial responses to axotomy and photodynamic impact were apparently associated with different signaling pathways in neurons and glial cells.

Discharging a DC bus capacitor of an electrical converter system

DOEpatents

Kajouke, Lateef A; Perisic, Milun; Ransom, Ray M

2014-10-14

A system and method of discharging a bus capacitor of a bidirectional matrix converter of a vehicle are presented here. The method begins by electrically shorting the AC interface of the converter after an AC energy source is disconnected from the AC interface. The method continues by arranging a plurality of switching elements of a second energy conversion module into a discharge configuration to establish an electrical current path from a first terminal of an isolation module, through an inductive element, and to a second terminal of the isolation module. The method also modulates a plurality of switching elements of a first energy conversion module, while maintaining the discharge configuration of the second energy conversion module, to at least partially discharge a DC bus capacitor.

Passive Isolators for use on the International Space Station

NASA Technical Reports Server (NTRS)

Houston, Janice; Gattis, Christy

2003-01-01

The value of the International Space Station (ISS) as a premier microgravity environment is currently at risk due to structure-borne vibration. The vibration sources are varied and include crew activities such as exercising or simply moving from module to module, and electro- mechanical equipment such as fans and pumps. Given such potential degradation of usable microgravity, anything that can be done to dampen vibration on-orbit will significantly benefit microgravity users. Most vibration isolation schemes, both active and passive, have proven to be expensive - both operationally and from the cost of integrating isolation systems into primary/secondary structural interfaces (e.g., the ISS module/rack interface). Recently, passively absorptive materials have been tested at the bolt interfaces between the operating equipment and support structure (secondary/tertiary structural interfaces). The results indicate that these materials may prove cost-effective in mitigating the vibrational problems of the ISS. We report herein tests of passive absorbers placed at the interface of a vibration-inducing component: the Development Distillation Assembly, a subassembly of the Urine Processing Assembly, which is a rotating centrifuge and cylinder assembly attached to a mounting plate. Passive isolators were installed between this mounting plate and its support shelf. Three materials were tested: BISCO HT-800, Sorbothane 30 and Sorbothane 50, plus a control test with a hard shim. In addition, four distinct combinations of the HT-800 and Sorbothane 50 were tested. Results show a significant (three orders of magnitude) reduction of transmitted energy, as measured in power spectral density (PSD), using the isolation materials. It is noted, however, that passive materials cannot prevent the transmission of very strong forces or absorb the total energy induced from structural resonances.

Negative Emotion Does Not Modulate Rapid Feature Integration Effects

PubMed Central

Trübutschek, Darinka; Egner, Tobias

2012-01-01

Emotional arousal at encoding is known to facilitate later memory recall. In the present study, we asked whether this emotion-modulation of episodic memory is also evident at very short time scales, as measured by “feature integration effects,” the moment-by-moment binding of relevant stimulus and response features in episodic memory. This question was motivated by recent findings that negative emotion appears to potentiate first-order trial sequence effects in classic conflict tasks, which has been attributed to emotion-modulation of conflict-driven cognitive control processes. However, these effects could equally well have been carried by emotion-modulation of mnemonic feature binding processes, which were perfectly confounded with putative control processes in these studies. In the present experiments, we tried to shed light on this question by testing explicitly whether feature integration processes, assessed in isolation of conflict–control, are in fact susceptible to negative emotion-modulation. For this purpose, we adopted a standard protocol for assessing the rapid binding of stimulus and response features in episodic memory (Experiment 1) and paired it with the presentation of either neutral or fearful background face stimuli, shown either at encoding only (Experiment 2), or at both encoding and retrieval (Experiment 3). Whereas reliable feature integration effects were observed in all three experiments, no evidence for emotion-modulation of these effects was detected, in spite of significant effects of emotion on response times. These findings suggest that rapid feature integration of foreground stimulus and response features is not subject to modulation by negative emotional background stimuli and further suggest that previous reports of emotion-modulated trial–transition effects are likely attributable to the effects of emotion on cognitive control processes. PMID:22509172

Effect of social isolation on 24-h pattern of stress hormones and leptin in rats.

PubMed

Perelló, Mario; Chacon, Fernando; Cardinali, Daniel P; Esquifino, Ana I; Spinedi, Eduardo

2006-03-13

This work analyzes the effect of social isolation of growing male rats on 24-h changes of plasma prolactin, growth hormone, ACTH and leptin, and on plasma and adrenal corticosterone concentrations. At 35 days of life, rats were either individually caged or kept in groups (6-8 animals per cage) under a 12:12 h light/dark schedule (lights on at 08:00 h). A significant arrest of body weight gain regardless of unchanged daily food intake was found in isolated rats after 2 weeks of isolation. On the 4th week, rats were killed at 6 time intervals during a 24-h cycle, beginning at 09:00 h. In isolated rats the 24-h pattern of all parameters tested became distorted, as assessed by Cosinor analysis. When analyzed as a main factor in a factorial analysis of variance, isolation decreased plasma prolactin and growth hormone, increased plasma leptin and corticosterone while decreased adrenal corticosterone. Plasma corticosterone levels correlated significantly with plasma ACTH and with adrenal corticosterone levels in group-caged rats only. These changes can be attributed to an effect of mild stress on the endogenous clock that modulates the circadian hormone release.

Effects of low-doses of Bacillus spp. from permafrost on differentiation of bone marrow cells.

PubMed

Kalyonova, L F; Novikova, M A; Kostolomova, E G

2015-01-01

The effects of a new microorganism species (Bacillus spp., strain M3) isolated from permafrost specimens from Central Yakutia (Mamontova Mountain) on the bone marrow hemopoiesis were studied on laboratory mice. Analysis of the count and immunophenotype of bone marrow cells indicated that even in low doses (1000-5000 microbial cells) these microorganisms modulated hemopoiesis and lymphopoiesis activity. The percentage of early hemopoietic precursors (CD117(+)CD34(-)) increased, intensity of lymphocyte precursor proliferation and differentiation (CD25(+)CD44(-)) decreased, and the percentage of lymphocytes released from the bone marrow (CD25(+)CD44(+)) increased on day 21 after injection of the bacteria. These changes in activity of hemopoiesis were associated with changes in the level of regulatory T lymphocytes (reduced expression of TCRαβ) and were most likely compensatory. The possibility of modulating hemopoiesis activity in the bone marrow by low doses of one microorganism strain isolated from the permafrost could be useful for evaluating the effects of other low dose bacteria on the bone marrow hemopoiesis.

Effects of climate oscillations on wildland fire potential in the continental United States

Treesearch

Shelby A. Mason; Peter E. Hamlington; Benjamin D. Hamlington; W. Matt Jolly; Chad M. Hoffman

2017-01-01

The effects of climate oscillations on spatial and temporal variations in wildland fire potential in the continental U.S. are examined from 1979 to 2015 using cyclostationary empirical orthogonal functions (CSEOFs). The CSEOF analysis isolates effects associated with the modulated annual cycle and the El Niño–Southern Oscillation (ENSO). The results show that, in early...

Microchip Module for Blood Sample Preparation and Nucleic Acid Amplification Reactions

PubMed Central

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

2001-01-01

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

The central responsiveness of the acute cerveau isolé rat.

PubMed

User, P; Gottesmann, C

1982-01-01

The electrophysiological patterns of the frontal cortex and dorsal hippocampus were studied in the acute cerveau isolé rat. Central and peripheral stimulations were performed in order to modulate these patterns. The results showed that the permanent alternation of high amplitude spindle bursts and low voltage activity in the anterior neocortex of the acute cerveau isolé was influenced neither by olfactory nor by posterior hypothalamic stimulation. In contrast, these two kinds of stimulation easily modulated the continuous low frequency theta rhythm, recorded in the dorsal hippocampus, in terms of amplitude and in overall frequency. This modulation of the theta rhythm in the acute cerveau isolé rat mimics the changes observed when the normal rat comes from the intermediate stage of sleep (as characterized in the the acute intercollicular transected rat by high amplitude spindle bursts at frontal cortex level and low frequency theta activity in the dorsal hippocampus) to rapid sleep. These results further suggest that, during the intermediate stage (as in the cerveau isolé preparation), the hippocampus montonous theta activity appears through a brainstem disinhibitory process releasing the forebrain limbic pacemaker(s). During the following rapid sleep phase, the theta rhythm would be modulated by pontine activity influences acting on the theta generators.

Conduct of Operations. MAS-121. Waste Isolation Division (WID). Management and Supervisor Training (MAST) Program.

ERIC Educational Resources Information Center

Westinghouse Electric Corp., Carlsbad, NM.

This learning module, which is part of a management and supervisor training program for managers and supervisors employed at the Department of Energy's Waste Isolation Division, is designed to teach trainees to apply conduct of operations principles to their area(s) of responsibility. The following topics are covered in the module's individual…

Industrial Safety. MAS-123. Waste Isolation Division (WID). Management and Supervisor Training (MAST) Program.

ERIC Educational Resources Information Center

Westinghouse Electric Corp., Carlsbad, NM.

This learning module, which is part of a management and supervisor training program for managers and supervisors employed at the Department of Energy's Waste Isolation Division, is designed to prepare trainees to promote and monitor the industrial safety program at their plant. The following topics are covered in the module's individual sections:…

Module failure isolation circuit for paralleled inverters. [preventing system failure during power conditioning for spacecraft applications

NASA Technical Reports Server (NTRS)

Nagano, S. (Inventor)

1979-01-01

A module failure isolation circuit is described which senses and averages the collector current of each paralled inverter power transistor and compares the collector current of each power transistor the average collector current of all power transistors to determine when the sensed collector current of a power transistor in any one inverter falls below a predetermined ratio of the average collector current. The module associated with any transistor that fails to maintain a current level above the predetermined radio of the average collector current is then shut off. A separate circuit detects when there is no load, or a light load, to inhibit operation of the isolation circuit during no load or light load conditions.

Task set persistence modulates word reading following resolution of picture-word interference.

PubMed

Masson, Michael E J; Bub, Daniel N; Ishigami, Yoko

2007-12-01

We extend the finding that word reading slows following successful responses to a color-word Stroop interference task (Masson, Bub, Woodward, & Chan, 2003). Word reading was assessed in a picture-word interference task in which subjects alternated between naming a picture (with either a word or a row of Xs superimposed on it) and reading a word. For the word-reading task, words were presented either in isolation or superimposed on a picture. Word reading was slower after subjects responded to a bivalent stimulus that required resolution of conflict (naming a picture with a word superimposed on it) than after they responded to a stimulus that involved no conflict (naming a picture with Xs superimposed on it), indicating modulation of dominant task performance. This effect was found when word-reading targets were superimposed on pictures but not when those targets were presented in isolation. Modulation of word reading, therefore, appears to be the result of interference from a persistent picture-naming task set, cued by a stimulus configuration that invites execution of both competing tasks.

Curcumin mediates anticancer effects by modulating multiple cell signaling pathways.

PubMed

Kunnumakkara, Ajaikumar B; Bordoloi, Devivasha; Harsha, Choudhary; Banik, Kishore; Gupta, Subash C; Aggarwal, Bharat B

2017-08-01

Curcumin, a component of a spice native to India, was first isolated in 1815 by Vogel and Pelletier from the rhizomes of Curcuma longa (turmeric) and, subsequently, the chemical structure of curcumin as diferuloylmethane was reported by Milobedzka et al. [(1910) 43., 2163-2170]. Since then, this polyphenol has been shown to exhibit antioxidant, anti-inflammatory, anticancer, antiviral, antibacterial, and antifungal activities. The current review primarily focuses on the anticancer potential of curcumin through the modulation of multiple cell signaling pathways. Curcumin modulates diverse transcription factors, inflammatory cytokines, enzymes, kinases, growth factors, receptors, and various other proteins with an affinity ranging from the pM to the mM range. Furthermore, curcumin effectively regulates tumor cell growth via modulation of numerous cell signaling pathways and potentiates the effect of chemotherapeutic agents and radiation against cancer. Curcumin can interact with most of the targets that are modulated by FDA-approved drugs for cancer therapy. The focus of this review is to discuss the molecular basis for the anticancer activities of curcumin based on preclinical and clinical findings. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

The influence of plan modulation on the interplay effect in VMAT liver SBRT treatments.

PubMed

Hubley, Emily; Pierce, Greg

2017-08-01

Volumetric modulated arc therapy (VMAT) uses multileaf collimator (MLC) leaves, gantry speed, and dose rate to modulate beam fluence, producing the highly conformal doses required for liver radiotherapy. When targets that move with respiration are treated with a dynamic fluence, there exists the possibility for interplay between the target and leaf motions. This study employs a novel motion simulation technique to determine if VMAT liver SBRT plans with an increase in MLC leaf modulation are more susceptible to dosimetric differences in the GTV due to interplay effects. For ten liver SBRT patients, two VMAT plans with different amounts of MLC leaf modulation were created. Motion was simulated using a random starting point in the respiratory cycle for each fraction. To isolate the interplay effect, motion was also simulated using four specific starting points in the respiratory cycle. The dosimetric differences caused by different starting points were examined by subtracting resultant dose distributions from each other. When motion was simulated using random starting points for each fraction, or with specific starting points, there were significantly more dose differences in the GTV (maximum 100cGy) for more highly modulated plans, but the overall plan quality was not adversely affected. Plans with more MLC leaf modulation are more susceptible to interplay effects, but dose differences in the GTV are clinically negligible in magnitude. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Plant and Industry Experience. MAS-122. Waste Isolation Division (WID). Management and Supervisor Training (MAST) Program.

ERIC Educational Resources Information Center

Westinghouse Electric Corp., Carlsbad, NM.

This learning module, which is part of a management and supervisor training program for managers and supervisors employed at the Department of Energy's Waste Isolation Division, is designed to prepare trainees to use plant and industry experience to improve plant safety and reliability. The following topics are covered in the module's individual…

Introduction to the MAST Program. MAS-100. Waste Isolation Division (WID). Management and Supervisor Training (MAST) Program.

ERIC Educational Resources Information Center

Westinghouse Electric Corp., Carlsbad, NM.

This module is part of a set of management and supervisor training (MAST) materials developed by the Department of Energy for the Waste Isolation Division. Its stated purpose is to provide participants with knowledge and skills necessary to take full advantage of the MAST learning experience. The module contains program guidelines, sample…

Antibacterial, anti-inflammatory and probiotic potential of Enterococcus hirae isolated from the rumen of Bos primigenius.

PubMed

Arokiyaraj, Selvaraj; Hairul Islam, Villianur Ibrahim; Bharanidharan, R; Raveendar, Sebastian; Lee, Jinwook; Kim, Do Hyung; Oh, Young Kyoon; Kim, Eun-Kyung; Kim, Kyoung Hoon

2014-07-01

In the present study bacterial strains were isolated from the rumen fluids of Bos primigenius and investigated their in vitro probiotic properties with potent antibacterial activity and anti-inflammatory effects. 9 g positive bacterial isolates were obtained and three isolates could able to tolerate gastric conditions, high bile salt concentrations and exhibited significant bactericidal effect against the enteric pathogens Vibrio cholera, Enterococcus faecalis, Enterobacter aerogens, Pseudomonas aeruginosa, Escherichia coli and Salmonella typhi. Moreover it showed above 70% cell surface hydrophobicity, significant low-invasion ability and potential adherence capacity in Caco-2 cells when compared with the control. The proinflammatory cytokines (TNF-α) was greatly reduced in rumen bacteria treatment and ARBS-1 modulate the immune response by activating the IL-4 secretion in parallel to TNF-α suppression. The 16s rRNA gene sequence of the active isolates were identified as Enterococcus hirae (ARBS-1), Pediococcus acidilactici (ARBS-4) and Bacillus licheniformis (ARBS-7). This study revealed the probiotic bactericidal properties of E. hirae obtained from the rumen of B. primigenius with potential antibacterial and anti-inflammatory effects. Future studies with the strains may yield some novel probiotic product for livestock's.

Studies on Modulation of Gut Microbiota by Wine Polyphenols: From Isolated Cultures to Omic Approaches

PubMed Central

Dueñas, Montserrat; Cueva, Carolina; Muñoz-González, Irene; Jiménez-Girón, Ana; Sánchez-Patán, Fernando; Santos-Buelga, Celestino; Moreno-Arribas, M. Victoria; Bartolomé, Begoña

2015-01-01

Moderate consumption of wine seems to produce positive health effects derived from the occurrence of bioactive polyphenols. The gut microbiota is involved in the metabolism of phenolic compounds, and these compounds and/or their metabolites may modulate gut microbiota through the stimulation of the growth of beneficial bacteria and the inhibition of pathogenic bacteria. The characterization of bacterial metabolites derived from polyphenols is essential in order to understand their effects, including microbial modulation, and therefore to associate dietary intake with particular health effects. This review aims to summarize the current information about the two-way “wine polyphenols–gut microbiota” interaction, from a perspective based on the experimental and analytical designs used. The availability of advanced methods for monitoring bacterial communities, along with the combination of in vitro and in vivo models, could help to assess the metabolism of polyphenols in the human body and to monitor total bacterial communities, and, therefore, to elucidate the implications of diet on the modulation of microbiota for delivering health benefits. PMID:26785335

Bactericidal activity of culture fluid components of Lactobacillus fermentum strain 90 TS-4 (21) clone 3, and their capacity to modulate adhesion of Candida albicans yeast-like fungi to vaginal epithelial cells.

PubMed

Anokhina, I V; Kravtsov, E G; Protsenko, A V; Yashina, N V; Yermolaev, A V; Chesnokova, V L; Dalin, M V

2007-03-01

Antagonistic activities of L. fermentum strain 90 TS-4 (21), L. casei ATCC 27216, and L. acidophilus ATCC 4356 and bactericidal activity of lactobacillus culture fluid towards E. coli strain K12, S. aureus, and S. epidermidis test cultures were studied. The bactericidal effect of L. fermentum strain 90 TS-4 (21) clone 3 culture fluid preparation (pH 6.0) on the test cultures was dose-dependent. Adhesion of C. albicans yeast-like fungi to vaginal epitheliocytes was more pronounced for strains isolated from women with asymptomatic infection than for strains isolated from women with manifest forms. L. fermentum strain 90 TS-4 (21) clone 3 culture fluid preparation modulated adhesion of yeast-like fungi only if the fungal strain was initially highly adherent.

Isolating spectral cues in amplitude and quasi-frequency modulation discrimination by reducing stimulus duration.

PubMed

Borucki, Ewa; Berg, Bruce G

2017-05-01

This study investigated the psychophysical effects of distortion products in a listening task traditionally used to estimate the bandwidth of phase sensitivity. For a 2000 Hz carrier, estimates of modulation depth necessary to discriminate amplitude modulated (AM) tones and quasi-frequency modulated (QFM) were measured in a two interval forced choice task as a function modulation frequency. Temporal modulation transfer functions were often non-monotonic at modulation frequencies above 300 Hz. This was likely to be due to a spectral cue arising from the interaction of auditory distortion products and the lower sideband of the stimulus complex. When the stimulus duration was decreased from 200 ms to 20 ms, thresholds for low-frequency modulators rose to near-chance levels, whereas thresholds in the region of non-monotonicities were less affected. The decrease in stimulus duration appears to hinder the listener's ability to use temporal cues in order to discriminate between AM and QFM, whereas spectral information derived from distortion product cues appears more resilient. Copyright © 2017. Published by Elsevier B.V.

Local and systemic immune mechanisms underlying the anti-colitis effects of the dairy bacterium Lactobacillus delbrueckii.

PubMed

Santos Rocha, Clarissa; Gomes-Santos, Ana Cristina; Garcias Moreira, Thais; de Azevedo, Marcela; Diniz Luerce, Tessalia; Mariadassou, Mahendra; Longaray Delamare, Ana Paula; Langella, Philippe; Maguin, Emmanuelle; Azevedo, Vasco; Caetano de Faria, Ana Maria; Miyoshi, Anderson; van de Guchte, Maarten

2014-01-01

Several probiotic bacteria have been proposed for treatment or prevention of inflammatory bowel diseases (IBD), showing a protective effect in animal models of experimental colitis and for some of them also in human clinical trials. While most of these probiotic bacteria are isolated from the digestive tract, we recently reported that a Lactobacillus strain isolated from cheese, L. delbrueckii subsp. lactis CNRZ327 (Lb CNRZ327), also possesses anti-inflammatory effects in vitro and in vivo, demonstrating that common dairy bacteria may be useful in the treatment or prevention of IBD. Here, we studied the mechanisms underlying the protective effects of Lb CNRZ327 in vivo, in a mouse dextran sodium sulfate (DSS) colitis model. During colitis, Lb CNRZ327 modulated the production of TGF-β, IL-6, and IL-12 in colonic tissue and of TGF-β and IL-6 in the spleen, and caused an expansion of CD4+Foxp3+ regulatory T cells in the cecal lymph nodes. Moreover, a strong tendency to CD4+Foxp3+ expansion was also observed in the spleen. The results of this study for the first time show that orally administered dairy lactobacilli can not only modulate mucosal but also systemic immune responses and constitute an effective treatment of IBD.

2.3-MW Medium-Voltage, Three-Level Wind Energy Inverter Applying a Unique Bus Structure and 4.5-kV Si/SiC Hybrid Isolated Power Modules: Preprint

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

Erdman, W.; Keller, J.; Grider, D.

A high-efficiency, 2.3-MW, medium-voltage, three-level inverter utilizing 4.5-kV Si/SiC (silicon carbide) hybrid modules for wind energy applications is discussed. The inverter addresses recent trends in siting the inverter within the base of multimegawatt turbine towers. A simplified split, three-layer laminated bus structure that maintains low parasitic inductances is introduced along with a low-voltage, high-current test method for determining these inductances. Feed-thru bushings, edge fill methods, and other design features of the laminated bus structure provide voltage isolation that is consistent with the 10.4-kV module isolation levels. Inverter efficiency improvement is a result of the (essential) elimination of the reverse recoverymore » charge present in 4.5-kV Si PIN diodes, which can produce a significant reduction in diode turn-off losses as well as insulated-gate bipolar transistor (IGBT) turn-on losses. The hybrid modules are supplied in industry-standard 140 mm x 130 mm and 190 mm x 130 mm packages to demonstrate direct module substitution into existing inverter designs. A focus on laminated bus/capacitor-bank/module subassembly level switching performance is presented.« less

Velutin reduces lipopolysaccharide-induced proinflammatory cytokine TNFa and IL-6 production by inhibiting NF-Kappa B activation

USDA-ARS?s Scientific Manuscript database

Recent studies have shown that some flavonoids are modulators of proinflammatory cytokine expression. Velutin, an uncommon flavone isolated from acai (Euterpe oleraceas) berry, was tested for the effects in reducing LPS-induced TNFa and IL-6 production in RAW 264.7 peripheral macrophages and periton...

Investigating PID shunting in polycrystalline silicon modules via multiscale, multitechnique characterization

DOE PAGES

Harvey, Steven P.; Moseley, John; Norman, Andrew; ...

2018-02-27

We investigated the potential-induced degradation (PID) shunting mechanism in multicrystalline-silicon photovoltaic modules by using a multiscale, multitechnique characterization approach. Both field-stressed modules and laboratory-stressed mini modules were studied. We used photoluminescence, electroluminescence, and dark lock-in thermography imaging to identify degraded areas at the module scale. Small samples were then removed from degraded areas, laser marked, and imaged by scanning electron microscopy. We used simultaneous electron-beam induced current imaging and focused ion beam milling to mark around PID shunts for chemical analysis by time-of-flight secondary-ion mass spectrometry or to isolate individual shunt defects for transmission electron microscopy and atom-probe tomography analysis.more » By spanning a range of 10 orders of magnitude in size, this approach enabled us to investigate the root-cause mechanisms for PID shunting. We observed a direct correlation between recombination active shunts and sodium content. The sodium content in shunted areas peaks at the SiNX/Si interface and is consistently observed at a concentration of 0.1% to 2% in shunted areas. Analysis of samples subjected to PID recovery, either activated by electron beam or thermal effects only, reveals that recovery of isolated shunts correlates with diffusion of sodium out of the structural defects to the silicon surface. We observed the role of oxygen and chlorine in PID shunting and found that those species - although sometimes present in structural defects where PID shunting was observed - do not play a consistent role in PID shunting.« less

Fuel Cell/Electrochemical Cell Voltage Monitor

NASA Technical Reports Server (NTRS)

Vasquez, Arturo

2012-01-01

A concept has been developed for a new fuel cell individual-cell-voltage monitor that can be directly connected to a multi-cell fuel cell stack for direct substack power provisioning. It can also provide voltage isolation for applications in high-voltage fuel cell stacks. The technology consists of basic modules, each with an 8- to 16-cell input electrical measurement connection port. For each basic module, a power input connection would be provided for direct connection to a sub-stack of fuel cells in series within the larger stack. This power connection would allow for module power to be available in the range of 9-15 volts DC. The relatively low voltage differences that the module would encounter from the input electrical measurement connection port, coupled with the fact that the module's operating power is supplied by the same substack voltage input (and so will be at similar voltage), provides for elimination of high-commonmode voltage issues within each module. Within each module, there would be options for analog-to-digital conversion and data transfer schemes. Each module would also include a data-output/communication port. Each of these ports would be required to be either non-electrical (e.g., optically isolated) or electrically isolated. This is necessary to account for the fact that the plurality of modules attached to the stack will normally be at a range of voltages approaching the full range of the fuel cell stack operating voltages. A communications/ data bus could interface with the several basic modules. Options have been identified for command inputs from the spacecraft vehicle controller, and for output-status/data feeds to the vehicle.

Microwave influence on the isolated heart function. 2: Combined effect of radiation and some drugs

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

Pakhomov, A.G.; Dubovick, B.V.; Degtyariov, I.G.

1995-09-01

The combined effects of microwave radiation and some drugs were studied in an isolated frog auricle preparation. The experiments established that exposure to pulse-modulated 915 Mhz microwaves for up to 40 min had no effect on either the rate or the amplitude of spontaneous auricle twitches, unless the average absorbed power was high enough to produce preparation heating. Treatment of the preparation with saline containing (0.6--3.0) 10{sup {minus}5} M of propranolol or (0.5--1.5) 10{sup {minus}7} M of atropine altered neither its pacemaker nor its contractile functions; these drugs also had no effect when they were combined with nonthermal microwave irradiation.more » Caffeine (1 mM) strongly increased the average heart power, which was calculated as the product of twitch rate ad amplitude. The caffeine effect appeared to be significantly augmented (by about 15%, P<0.02) under exposure to burst-type pulsed microwaves (pulse width, 1.5 msec; pause, 2.5 msec; 8 pulses/burst, 16 bursts/s; average SAR, 8--10 W/kg). By itself, this modulation was not effective; the heating of the preparation and saline during exposure was approximately 0.1 C, which could not account for the detected changes. The experimental results demonstrate that caffeine treatment increases the microwave sensitivity of the frog auricle preparation and reveals primarily subthreshold, nonthermal microwave effect.« less

Natriuretic factor, a lasting enigma.

PubMed

Licht, A; Fine, L G; Bourgoignie, J J

1978-01-01

A gel filtration fraction of urine from patients with chronic uremia (natriuretic factor) decreases potential difference, net sodium flux and lumen to peritubular flux of sodium across the isolated rabbit cortical collecting tubule. These effects are consistent with the possibility that natriuretic factor represents a modulator of sodium excretion in the mammalian nephron. Natriuretic factor induces a dose-dependent inhibition of short-circuit current in the isolated toad bladder. By comparing the effects of natriuretic factor to those of a standard unit of reference, it may be possible to develop a quantitative assay for natriuretic factor. The acidic nature of natriuretic factor was confirmed by cation exchange column in a high pressure liquid chromatography system.

Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota.

PubMed

Chang, Chih-Jung; Lin, Chuan-Sheng; Lu, Chia-Chen; Martel, Jan; Ko, Yun-Fei; Ojcius, David M; Tseng, Shun-Fu; Wu, Tsung-Ru; Chen, Yi-Yuan Margaret; Young, John D; Lai, Hsin-Chih

2015-06-23

Obesity is associated with low-grade chronic inflammation and intestinal dysbiosis. Ganoderma lucidum is a medicinal mushroom used in traditional Chinese medicine with putative anti-diabetic effects. Here, we show that a water extract of Ganoderma lucidum mycelium (WEGL) reduces body weight, inflammation and insulin resistance in mice fed a high-fat diet (HFD). Our data indicate that WEGL not only reverses HFD-induced gut dysbiosis-as indicated by the decreased Firmicutes-to-Bacteroidetes ratios and endotoxin-bearing Proteobacteria levels-but also maintains intestinal barrier integrity and reduces metabolic endotoxemia. The anti-obesity and microbiota-modulating effects are transmissible via horizontal faeces transfer from WEGL-treated mice to HFD-fed mice. We further show that high molecular weight polysaccharides (>300 kDa) isolated from the WEGL extract produce similar anti-obesity and microbiota-modulating effects. Our results indicate that G. lucidum and its high molecular weight polysaccharides may be used as prebiotic agents to prevent gut dysbiosis and obesity-related metabolic disorders in obese individuals.

Maesopsin 4-O-beta-D-glucoside, a natural compound isolated from the leaves of Artocarpus tonkinensis, inhibits proliferation and up-regulates HMOX1, SRXN1 and BCAS3 in acute myeloid leukemia.

PubMed

Pozzesi, N; Pierangeli, S; Vacca, C; Falchi, L; Pettorossi, V; Martelli, M P; Thuy, T T; Ninh, P T; Liberati, A M; Riccardi, C; Sung, T V; Delfino, D V

2011-06-01

The leaves of Artocarpus tonkinensis are used in Vietnamese traditional medicine for treatment of arthritis, and the compound maesopsin 4-O-β-D-glucoside (TAT-2), isolated from them, inhibits the proliferation of activated T cells. Our goal was to test the anti-proliferative activity of TAT-2 on the T-cell leukemia, Jurkat, and on the acute myeloid leukemia, OCI-AML. TAT-2 inhibited the growth of OCI-AML (and additional acute myeloid leukemia cells) but not Jurkat cells. Growth inhibition was shown to be due to inhibition of proliferation rather than increase in cell death. Analysis of cytokine release showed that TAT-2 stimulated the release of TGF-β, yet TGF-β neutralization did not reverse the maesopsin-dependent effect. Gene expression profiling determined that maesopsin modulated 19 identifiable genes. Transcription factor CP2 was the gene most significantly modulated. Real-time PCR validated that up-regulation of sulphiredoxin 1 homolog (SRXN1), hemeoxygenase 1 (HMOX1), and breast carcinoma amplified sequence 3 (BCAS3) were consistently modulated.

Comparison of the Effects of the Selective Estrogen Receptor Modulators Ospemifene, Raloxifene, and Tamoxifen on Breast Tissue in Ex Vivo Culture.

PubMed

Eigeliene, Natalija; Erkkola, Risto; Härkönen, Pirkko

2016-01-01

Explant tissue culture provides a model for studying the direct effects of steroid hormones, their analogs, and novel hormonally active compounds on normal freshly isolated human breast tissues (HBTs). For this purpose, pre- and postmenopausal HBTs can be maintained in this culture system. The results demonstrate that the morphological integrity of HBT explants can be maintained in tissue culture up to 2 weeks and expression of differentiation markers, steroid hormone receptors, proliferation and apoptosis ratios can be evaluated as a response to hormonal stimulation. This chapter describes an ex vivo culture model that we have applied to study the effects of various hormonally active substances, including 17β-estradiol and selective estrogen receptor modulators (SERMs), on normal human breast tissues.

Module degradation catalyzed by metal-encapsulation reactions

NASA Technical Reports Server (NTRS)

Gallagher, B. D.

1983-01-01

Four major properties are considered to be relevant in determining service life of a photovoltaic module: (1) Mechanical: creep resistance, modulus, tensile strength; (2) Optical: integrated transmission at 0.4 to 1.1 m wavelength; (3) Chemical: inertness with respect to metals and other components, retention of stabilizers, etc. and (4) Electrical; maintaining effective isolation of conductive components. These properties were measured after exposing polymer specimens to three types of accelerated stress: thermal, ultraviolet radiation and metal catalysts. These conditions give rise to a large number of complex interrelated free-radical reactions that result in the deterioration of polymeric materials.

Physics of frequency-modulated comb generation in quantum-well diode lasers

NASA Astrophysics Data System (ADS)

Dong, Mark; Cundiff, Steven T.; Winful, Herbert G.

2018-05-01

We investigate the physical origin of frequency-modulated combs generated from single-section semiconductor diode lasers based on quantum wells, isolating the essential physics necessary for comb generation. We find that the two effects necessary for comb generation—spatial hole burning (leading to multimode operation) and four-wave mixing (leading to phase locking)—are indeed present in some quantum-well systems. The physics of comb generation in quantum wells is similar to that in quantum dot and quantum cascade lasers. We discuss the nature of the spectral phase and some important material parameters of these diode lasers.

Reparation and Immunomodulating Properties of Bacillus sp. Metabolites from Permafrost.

PubMed

Kalenova, L F; Melnikov, V P; Besedin, I M; Bazhin, A S; Gabdulin, M A; Kolyvanova, S S

2017-09-01

An ointment containing metabolites of Bacillus sp. microorganisms isolated from permafrost samples was applied onto the skin wound of BALB/c mice. Metabolites isolated during culturing of Bacillus sp. at 37°C produced a potent therapeutic effect and promoted wound epithelialization by 30% in comparison with the control (ointment base) and by 20% in comparison with Solcoseryl. Treatment with Bacillus sp. metabolites stimulated predominantly humoral immunity, reduced the time of wound contraction and the volume of scar tissue, and promoted complete hair recovery. These metabolites can be considered as modulators of the wound process with predominance of regeneration mechanisms.

Flexible, reconfigurable, power efficient transmitter and method

NASA Technical Reports Server (NTRS)

Bishop, James W. (Inventor); Zaki, Nazrul H. Mohd (Inventor); Newman, David Childress (Inventor); Bundick, Steven N. (Inventor)

2011-01-01

A flexible, reconfigurable, power efficient transmitter device and method is provided. In one embodiment, the method includes receiving outbound data and determining a mode of operation. When operating in a first mode the method may include modulation mapping the outbound data according a modulation scheme to provide first modulation mapped digital data, converting the first modulation mapped digital data to an analog signal that comprises an intermediate frequency (IF) analog signal, upconverting the IF analog signal to produce a first modulated radio frequency (RF) signal based on a local oscillator signal, amplifying the first RF modulated signal to produce a first RF output signal, and outputting the first RF output signal via an isolator. In a second mode of operation method may include modulation mapping the outbound data according a modulation scheme to provide second modulation mapped digital data, converting the second modulation mapped digital data to a first digital baseband signal, conditioning the first digital baseband signal to provide a first analog baseband signal, modulating one or more carriers with the first analog baseband signal to produce a second modulated RF signal based on a local oscillator signal, amplifying the second RF modulated signal to produce a second RF output signal, and outputting the second RF output signal via the isolator. The digital baseband signal may comprise an in-phase (I) digital baseband signal and a quadrature (Q) baseband signal.

Non-reciprocal optical mirrors based on spatio-temporal acousto-optic modulation

NASA Astrophysics Data System (ADS)

Fleury, R.; Sounas, D. L.; Alù, A.

2018-03-01

Here, we investigate a scheme to realize free-space isolators and highly non-reciprocal mirrors with weak modulation imparted by an acoustic wave. We propose a strategy to dramatically break time-reversal symmetry by exploiting resonant interactions between a travelling acoustic wave and highly resonant Fabry-Pérot modes, inducing total reflection of an optical beam at a given angle, and no reflection at the negative angle. Different from conventional acousto-optic isolators, which are based on non-resonant frequency conversion and filtering, our proposal operates at the frequency of the optical signal by tailoring the resonant properties of the structure as well as the acoustic wave frequency and intensity, enabling 50 dB isolation with modest modulation requirements. Operation in the reflection mode allows for close-to-zero insertion loss, enabling disruptive opportunities in our ability to control and manipulate photons.

Individual Battery-Power Control for a Battery Energy Storage System Using a Modular Multilevel Cascade Converter

NASA Astrophysics Data System (ADS)

Yamagishi, Tsukasa; Maharjan, Laxman; Akagi, Hirofumi

This paper focuses on a battery energy storage system that can be installed in a 6.6-kV power distribution system. This system comprises a combination of a modular multilevel cascade converter based on single-star bridge-cells (MMCC-SSBC) and multiple battery modules. Each battery module is connected to the dc side of each bridge-cell, where the battery modules are galvanically isolated from each other. Three-phase multilevel line-to-line voltages with extremely low voltage steps on the ac side of the converter help in solving problems related to line harmonic currents and electromagnetic interference (EMI) issues. This paper proposes a control method that allows each bridge-cell to independently adjust the battery power flowing into or out of each battery module. A three-phase energy storage system using nine nickel-metal-hydride (NiMH) battery modules, each rated at 72V and 5.5Ah, is designed, constructed, and tested to verify the viability and effectiveness of the proposed control method.

Photocontrol of Voltage-Gated Ion Channel Activity by Azobenzene Trimethylammonium Bromide in Neonatal Rat Cardiomyocytes

PubMed Central

Frolova, Sheyda R.; Gaiko, Olga; Tsvelaya, Valeriya A.; Pimenov, Oleg Y.; Agladze, Konstantin I.

2016-01-01

The ability of azobenzene trimethylammonium bromide (azoTAB) to sensitize cardiac tissue excitability to light was recently reported. The dark, thermally relaxed trans- isomer of azoTAB suppressed spontaneous activity and excitation propagation speed, whereas the cis- isomer had no detectable effect on the electrical properties of cardiomyocyte monolayers. As the membrane potential of cardiac cells is mainly controlled by activity of voltage-gated ion channels, this study examined whether the sensitization effect of azoTAB was exerted primarily via the modulation of voltage-gated ion channel activity. The effects of trans- and cis- isomers of azoTAB on voltage-dependent sodium (INav), calcium (ICav), and potassium (IKv) currents in isolated neonatal rat cardiomyocytes were investigated using the whole-cell patch-clamp technique. The experiments showed that azoTAB modulated ion currents, causing suppression of sodium (Na+) and calcium (Ca2+) currents and potentiation of net potassium (K+) currents. This finding confirms that azoTAB-effect on cardiac tissue excitability do indeed result from modulation of voltage-gated ion channels responsible for action potential. PMID:27015602

Optical isolation based on space-time engineered asymmetric photonic band gaps

NASA Astrophysics Data System (ADS)

Chamanara, Nima; Taravati, Sajjad; Deck-Léger, Zoé-Lise; Caloz, Christophe

2017-10-01

Nonreciprocal electromagnetic devices play a crucial role in modern microwave and optical technologies. Conventional methods for realizing such systems are incompatible with integrated circuits. With recent advances in integrated photonics, the need for efficient on-chip magnetless nonreciprocal devices has become more pressing than ever. This paper leverages space-time engineered asymmetric photonic band gaps to generate optical isolation. It shows that a properly designed space-time modulated slab is highly reflective/transparent for opposite directions of propagation. The corresponding design is magnetless, accommodates low modulation frequencies, and can achieve very high isolation levels. An experimental proof of concept at microwave frequencies is provided.

Component isolation for multi-component signal analysis using a non-parametric gaussian latent feature model

NASA Astrophysics Data System (ADS)

Yang, Yang; Peng, Zhike; Dong, Xingjian; Zhang, Wenming; Clifton, David A.

2018-03-01

A challenge in analysing non-stationary multi-component signals is to isolate nonlinearly time-varying signals especially when they are overlapped in time and frequency plane. In this paper, a framework integrating time-frequency analysis-based demodulation and a non-parametric Gaussian latent feature model is proposed to isolate and recover components of such signals. The former aims to remove high-order frequency modulation (FM) such that the latter is able to infer demodulated components while simultaneously discovering the number of the target components. The proposed method is effective in isolating multiple components that have the same FM behavior. In addition, the results show that the proposed method is superior to generalised demodulation with singular-value decomposition-based method, parametric time-frequency analysis with filter-based method and empirical model decomposition base method, in recovering the amplitude and phase of superimposed components.

Conductive connection induced speed-up of localized-surface-plasmon dynamics

NASA Astrophysics Data System (ADS)

Cun, Peng; Wang, Meng; Huang, Cuiying; Huang, Pei; He, Xinkui; Wei, Zhiyi; Zhang, Xinping

2018-01-01

Conductive connection of localized surface plasmons (LSPs) was achieved by depositing a layer of continuous gold film onto the top surface of a matrix of randomly distributed gold nanoparticles (AuNPs) that were originally isolated on a glass substrate. Ultrafast spectroscopic response of such plasmonic nanostructures was investigated by femtosecond pump-probe detection technique. The transient-absorption data showed large redshift and broadening of the resonance spectrum of the conductively connected AuNPs with respect to the isolated ones. Such effects led to modulation on the evolution dynamics of LSPs in a transient transition spectral band. Making use of the temporal and spectral dislocation between the edges of transition band, we achieved much increased speed of the plasmonic optical switching effect.

Antileishmanial Activity and Immunomodulatory Effects of Tricin Isolated from Leaves of Casearia arborea (Salicaceae).

PubMed

Santos, Augusto L; Yamamoto, Eduardo S; Passero, Luiz Felipe D; Laurenti, Márcia D; Martins, Ligia F; Lima, Marta L; Uemi, Miriam; Soares, Marisi G; Lago, João Henrique G; Tempone, Andre G; Sartorelli, Patricia

2017-05-01

Bioactivity-guided fractionation of antileishmanial active extract from leaves of Casearia arborea led to isolation of three metabolites: tricin (1), 1',6'-di-O-β-d-vanilloyl glucopyranoside (2) and vanillic acid (3). Compound 1 demonstrated the highest activity against the intracellular amastigotes of Leishmania infantum, with an IC 50 value of 56 μm. Tricin (1) demonstrated selectivity in mammalian cells (SI > 7) and elicited immunomodulatory effect on host cells. The present work suggests that tricin modulated the respiratory burst of macrophages to a leishmanicidal state, contributing to the parasite elimination. Therefore, the natural compound tricin could be further explored in drug design studies for leishmaniasis treatment. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Umbilical Stiffness Matrix Characterization and Testing for Microgravity Science Payloads

NASA Technical Reports Server (NTRS)

Engberg, Robert C.

2003-01-01

This paper describes efforts of testing and analysis of various candidate cables and umbilicals for International Space Station microgravity science payloads. The effects of looping, large vs. small displacements, and umbilical mounting configurations were assessed. A 3-DOF stepper motor driven fixture was used to excite the umbilicals. Forces and moments were directly measured in all three axes with a 6-DOF load cell in order to derive suitable stiffness matrices for design and analysis of vibration isolation controllers. Data obtained from these tests were used to help determine the optimum type and configuration of umbilical cables for the International Space Station microgravity science glovebox (MSG) vibration isolation platform. The data and procedures can also be implemented into control algorithm simulations to assist in validation of actively controlled vibration isolation systems. The experimental results of this work are specific in support of the Glovebox Integrated Microgravity Isolation Technology (g-LIMIT) isolation platform, to be located in the microgravity science glovebox aboard the U.S. Destiny Laboratory Module.

Design and Implementation of a Characterization Test Rig for Evaluating High Bandwidth Liquid Fuel Flow Modulators

NASA Technical Reports Server (NTRS)

Saus, Joseph R.; Chang, Clarence T.; DeLaat, John C.; Vrnak, Daniel R.

2010-01-01

A test rig was designed and developed at the NASA Glenn Research Center (GRC) for the purpose of characterizing high bandwidth liquid fuel flow modulator candidates to determine their suitability for combustion instability control research. The test rig is capable of testing flow modulators at up to 600 psia supply pressure and flows of up to 2 gpm. The rig is designed to provide a quiescent flow into the test section in order to isolate the dynamic flow modulations produced by the test article. Both the fuel injector orifice downstream of the test article and the combustor are emulated. The effect of fuel delivery line lengths on modulator dynamic performance can be observed and modified to replicate actual fuel delivery systems. For simplicity, water is currently used as the working fluid, although future plans are to use jet fuel. The rig is instrumented for dynamic pressures and flows and a high-speed data system is used for dynamic data acquisition. Preliminary results have been obtained for one candidate flow modulator.

Orion MPCV Service Module Avionics Ring Pallet Testing, Correlation, and Analysis

NASA Technical Reports Server (NTRS)

Staab, Lucas; Akers, James; Suarez, Vicente; Jones, Trevor

2012-01-01

The NASA Orion Multi-Purpose Crew Vehicle (MPCV) is being designed to replace the Space Shuttle as the main manned spacecraft for the agency. Based on the predicted environments in the Service Module avionics ring, an isolation system was deemed necessary to protect the avionics packages carried by the spacecraft. Impact, sinusoidal, and random vibration testing were conducted on a prototype Orion Service Module avionics pallet in March 2010 at the NASA Glenn Research Center Structural Dynamics Laboratory (SDL). The pallet design utilized wire rope isolators to reduce the vibration levels seen by the avionics packages. The current pallet design utilizes the same wire rope isolators (M6-120-10) that were tested in March 2010. In an effort to save cost and schedule, the Finite Element Models of the prototype pallet tested in March 2010 were correlated. Frequency Response Function (FRF) comparisons, mode shape and frequency were all part of the correlation process. The non-linear behavior and the modeling the wire rope isolators proved to be the most difficult part of the correlation process. The correlated models of the wire rope isolators were taken from the prototype design and integrated into the current design for future frequency response analysis and component environment specification.

Antibiotic modulation of the plasminogen binding ability of viridans group streptococci.

PubMed

Teles, Cristina; Smith, Andrew; Lang, Sue

2012-01-01

The ability of viridans group streptococci to bind human plasminogen and its subsequent activation into plasmin may contribute to the pathogenesis of infective endocarditis (IE) by leading to a decreased stability of the streptococcal vegetation and facilitating dehiscence of emboli. At levels greater than or equal to their MICs, penicillin, vancomycin, and linezolid are efficacious in the treatment of streptococcal endocarditis. However, at sub-MICs, antibiotics can modulate the expression of bacterial genes, including virulence-associated genes, which can have counterproductive effects on the treatment of endocarditis. The effects of 1/8× and 1/4× MICs of penicillin, vancomycin, and linezolid on the plasminogen binding ability of IE isolates Streptococcus mitis 881/956, Streptococcus oralis 12601, and Streptococcus sanguinis 12403 were assessed phenotypically and the expression of plasminogen receptors α-enolase and glyceraldehyde 3-phosphate dehydrogenase of S. oralis 12601 when exposed to 1/4× MIC of penicillin, was analyzed through quantitative reverse transcription (qRT)-PCR. The plasminogen binding ability of S. mitis 881/956 and S. sanguinis 12403 remained unaffected by exposure to sub-MICs of all of the antibiotics tested, while that of S. oralis 12601 was significantly enhanced by all of the antibiotics tested at sub-MICs. qRT-PCR analysis of S. oralis 12601 demonstrated an upregulation of the eno and gapdh genes, indicating an overexpression of plasminogen receptors. These findings suggest that for some endocarditis isolates, the effect of antibiotic sub-MICs, in addition to a reduced antibacterial effect, may influence the clinical response to nonsurgical therapy. It remains difficult to accurately predict isolate responses to sub-MIC antimicrobials since there appears to be interspecies variation.

Novel approaches to determine contractile function of the isolated adult zebrafish ventricular cardiac myocyte.

PubMed

Dvornikov, Alexey V; Dewan, Sukriti; Alekhina, Olga V; Pickett, F Bryan; de Tombe, Pieter P

2014-05-01

The zebrafish (Danio rerio) has been used extensively in cardiovascular biology, but mainly in the study of heart development. The relative ease of its genetic manipulation may indicate the suitability of this species as a cost-effective model system for the study of cardiac contractile biology. However, whether the zebrafish heart is an appropriate model system for investigations pertaining to mammalian cardiac contractile structure-function relationships remains to be resolved. Myocytes were isolated from adult zebrafish hearts by enzymatic digestion, attached to carbon rods, and twitch force and intracellular Ca(2+) were measured. We observed the modulation of twitch force, but not of intracellular Ca(2+), by both extracellular [Ca(2+)] and sarcomere length. In permeabilized cells/myofibrils, we found robust myofilament length-dependent activation. Moreover, modulation of myofilament activation-relaxation and force redevelopment kinetics by varied Ca(2+) activation levels resembled that found previously in mammalian myofilaments. We conclude that the zebrafish is a valid model system for the study of cardiac contractile structure-function relationships.

Differential Effect of Lactobacillus johnsonii BFE 6128 on Expression of Genes Related to TLR Pathways and Innate Immunity in Intestinal Epithelial Cells.

PubMed

Seifert, Stephanie; Rodriguez Gómez, Manuel; Watzl, Bernhard; Holzapfel, Wilhelm H; Franz, Charles M A P; Vizoso Pinto, María G

2010-12-01

Probiotics have been shown to enhance immune defenses, but their mechanisms of action are only partially understood. We investigated the modulation of signal pathways involved in innate immunity in enterocytes by Lactobacillus johnsonii BFE 6128 isolated from 'Kule naoto', a Maasai traditional fermented milk product. This lactobacillus sensitized HT29 intestinal epithelial cells toward recognition of Salmonella enterica serovar Typhimurium by increasing the IL-8 levels released after challenge with this pathogen and by differentially modulating genes related to toll-like receptor (TLR) pathways and innate immunity. Thus, the modulation of pro-inflammatory mediators and TLR-pathway-related molecules may be an important mechanism contributing to the potential stimulation of innate immunity by lactobacilli at the intestinal epithelial level.

Environmental isolation task

NASA Technical Reports Server (NTRS)

Coulbert, C. D.

1982-01-01

The failure-analysis process was organized into a more specific set of long-term degradation steps so that material property change can be differentiated from module damage and module failure. Increasing module performance and life are discussed. A polymeric aging computer model is discussed. Early detection of polymer surface reactions due to aging is reported.

Fault detection monitor circuit provides ''self-heal capability'' in electronic modules - A concept

NASA Technical Reports Server (NTRS)

Kennedy, J. J.

1970-01-01

Self-checking technique detects defective solid state modules used in electronic test and checkout instrumentation. A ten bit register provides failure monitor and indication for 1023 comparator circuits, and the automatic fault-isolation capability permits the electronic subsystems to be repaired by replacing the defective module.

Agmatine Modulation of Noradrenergic Neurotransmission in Isolated Rat Blood Vessels.

PubMed

Török, Jozef; Zemančíková, Anna

2016-06-30

Agmatine, a vasoactive metabolite of L-arginine, is widely distributed in mammalian tissues including blood vessels. Agmatine binding to imidazoline and α₂-adrenoceptors induces a variety of physiological and pharmacological effects. We investigated the effect of agmatine on contractile responses of the rat pulmonary artery and portal vein induced by electrical stimulation of perivascular nerves and by exogenous adrenergic substances. Experiments were performed on isolated segments of rat main pulmonary artery and its extralobular branches, and portal vein suspended in organ bath containing modified Krebs bicarbonate solution and connected to a force-displacement transducer for isometric tension recording. Electrical field stimulation (EFS) produced tetrodotoxin-sensitive contractile responses of pulmonary artery and portal vein. Besides the well known vasorelaxant actions, we found that agmatine also produced a concentration-dependent inhibition of neurogenic contractions induced by EFS in pulmonary arteries; however, the agmatine treatment did not influence the responses to exogenous noradrenaline. The inhibitory effect on EFS-induced contractions was not abolished by the α₂-adrenoceptor antagonist rauwolscine. In portal vein, in contrast, agmatine increased spontaneous mechanical contractions and enhanced the contractions induced by EFS. The results suggest that agmatine can significantly influence vascular function of pulmonary arteries and portal veins by modulating sympathetically mediated vascular contractions by pre- and postsynaptic mechanisms.

Estrogenic status modulates the effect of soy on hepatic responses to 7,12-dimethylbenz(a)anthracene (DMBA)

USDA-ARS?s Scientific Manuscript database

We examined the influence of estradiol (E2) status and soy protein isolate (SPI) intake on the hepatic responses altered by 7,12-dimethylbenz(a)anthracene (DMBA, a polycyclic aromatic hydrocarbon [PAH]). Sprague–Dawley rats were ovariectomized (OVX) at PND50 and infused with E2 or vehicle for 14 d a...

Estrogenic status modulates the effect of soy on hepatic responses to 7,12- dimethylbenz(a)anthracene

USDA-ARS?s Scientific Manuscript database

We examined the influence of estradiol (E2) status and soy protein isolate (SPI) intake on the hepatic responses altered by 7,12-dimethylbenz(a)anthracene (DMBA, a polycyclic aromatic hydrocarbon [PAH]). Sprague-Dawley rats were ovariectomized (OVX) at PND50 and infused with E2 or vehicle for 14d an...

Peptidase modulation of the pulmonary effects of tachykinins.

PubMed

Martins, M A; Shore, S A; Drazen, J M

1991-01-01

The physiological effects of the tachykinin peptides substance P (SP) and neurokinin A (NKA) are limited by their microenvironmental degradation. We used the isolated tracheally superfused guinea pig lung to examine the importance of various degradative enzymes in limiting the physiological effects of exogenously administered and endogenously released tachykinins. When SP and NKA are administered via the airway epithelium, neutral endopeptidase (NEP; EC 3.4.24.11) is the major degradative enzyme as indicated by the effects of NEP inhibitors alone compared to the effects of a NEP inhibitor along with a cocktail of other peptidase inhibitors. The effects of enzyme inhibitors on physiological responses is mirrored in the amounts of peptide recovered from lung perfusates as determined using an enzyme-linked immunosorbent assay. We found similar effects when SP and NKA were released endogenously by the acute infusion of capsaicin. These data indicate that NEP is the predominant degradative enzyme modulating the effects of SP and NKA administered via the airways.

Design of the high voltage isolation transmission module with low delay for ECRH system on J-TEXT

NASA Astrophysics Data System (ADS)

Haiyan, MA; Donghui, XIA; Zhijiang, WANG; Fangtai, CUI; Zhenxiong, YU; Yikun, JIN; Changhai, LIU

2018-02-01

As a flexible auxiliary heating method, the electron cyclotron resonance heating (ECRH) has been widely used in many tokamaks and also will be applied for the J-TEXT tokamak. To meet requirements of protection and fault analysis for the ECRH system on J-TEXT, signals of gyrotrons such as the cathode voltage and current, the anode voltage and current, etc should be transmitted to the control and data acquisition system. Considering the high voltage environment of gyrotrons, isolation transmission module based on FPGA and optical fiber communication has been designed and tested. The test results indicate that the designed module has strong anti-noise ability, low error rate and high transmission speed. The delay of the module is no more than 5 μs which can fulfill the requirements.

Compact diode laser module at 1116 nm with an integrated optical isolation and a PM-SMF output

NASA Astrophysics Data System (ADS)

Jedrzejczyk, Daniel; Hofmann, Julian; Werner, Nils; Sahm, Alexander; Paschke, Katrin

2017-02-01

In this work, a fiber-coupled diode laser module emitting around 1116 nm with an output power P < 60 mW is realized. As a laser light source a distributed Bragg reflector (DBR) ridge waveguide diode laser is applied. The module comprises temperature stabilizing components, a micro-lens system as well as an optical micro-isolator. At the output, a polarization-maintaining single-mode fiber (PM-SMF) with a core diameter of 5.5 μm and a standard FC/APC connector are utilized. The generated diffraction limited beam is characterized by a narrow linewidth ( δν < 10 MHz) and a high polarization extinction ratio (PER > 25 dB).

Effects of permafrost microorganisms on skin wound reparation.

PubMed

Kalenova, L F; Novikova, M A; Subbotin, A M

2015-02-01

Local application of ointment with Bacillus spp. strain MG8 (15,000-20,000 living bacterial cells), isolated from permafrost specimens, on the skin wound of about 60 mm(2) stimulated the reparation processes in experimental mice. A possible mechanism stimulating the regeneration of the damaged tissues under the effect of MG8 could be modulation of the immune system reactivity with more rapid switchover to humoral immunity anti-inflammatory mechanisms aimed at de novo synthesis of protein.

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

Harvey, Steven P.; Moseley, John; Norman, Andrew

We investigated the potential-induced degradation (PID) shunting mechanism in multicrystalline-silicon photovoltaic modules by using a multiscale, multitechnique characterization approach. Both field-stressed modules and laboratory-stressed mini modules were studied. We used photoluminescence, electroluminescence, and dark lock-in thermography imaging to identify degraded areas at the module scale. Small samples were then removed from degraded areas, laser marked, and imaged by scanning electron microscopy. We used simultaneous electron-beam induced current imaging and focused ion beam milling to mark around PID shunts for chemical analysis by time-of-flight secondary-ion mass spectrometry or to isolate individual shunt defects for transmission electron microscopy and atom-probe tomography analysis.more » By spanning a range of 10 orders of magnitude in size, this approach enabled us to investigate the root-cause mechanisms for PID shunting. We observed a direct correlation between recombination active shunts and sodium content. The sodium content in shunted areas peaks at the SiNX/Si interface and is consistently observed at a concentration of 0.1% to 2% in shunted areas. Analysis of samples subjected to PID recovery, either activated by electron beam or thermal effects only, reveals that recovery of isolated shunts correlates with diffusion of sodium out of the structural defects to the silicon surface. We observed the role of oxygen and chlorine in PID shunting and found that those species - although sometimes present in structural defects where PID shunting was observed - do not play a consistent role in PID shunting.« less

Design, analysis, and test verification of advanced encapsulation systems

NASA Technical Reports Server (NTRS)

Garcia, A.; Minning, C.

1981-01-01

Thermal, optical, structural, and electrical isolation analyses are decribed. Major factors in the design of terrestrial photovoltaic modules are discussed. Mechanical defects in the different layers of an encapsulation system, it was found, would strongly influence the minimum pottant thickness required for electrical isolation. Structural, optical, and electrical properties, a literature survey indicated, are hevily influenced by the presence of moisture. These items, identified as technology voids, are discussed. Analyses were based upon a 1.2 meter square module using 10.2 cm (4-inch) square cells placed 1.3 mm apart as shown in Figure 2-2. Sizing of the structural support member of a module was determined for a uniform, normal pressure load of 50 psf, corresponding to the pressure difference generated between the front and back surface of a module by a 100 mph wind. Thermal and optical calculations were performed for a wind velocity of 1 meter/sec parallel to the ground and for module tilt (relative to the local horizontal) of 37 deg. Placement of a module in a typical array field is illustrated.

Design, analysis, and test verification of advanced encapsulation systems

NASA Astrophysics Data System (ADS)

Garcia, A.; Minning, C.

1981-11-01

Thermal, optical, structural, and electrical isolation analyses are decribed. Major factors in the design of terrestrial photovoltaic modules are discussed. Mechanical defects in the different layers of an encapsulation system, it was found, would strongly influence the minimum pottant thickness required for electrical isolation. Structural, optical, and electrical properties, a literature survey indicated, are hevily influenced by the presence of moisture. These items, identified as technology voids, are discussed. Analyses were based upon a 1.2 meter square module using 10.2 cm (4-inch) square cells placed 1.3 mm apart as shown in Figure 2-2. Sizing of the structural support member of a module was determined for a uniform, normal pressure load of 50 psf, corresponding to the pressure difference generated between the front and back surface of a module by a 100 mph wind. Thermal and optical calculations were performed for a wind velocity of 1 meter/sec parallel to the ground and for module tilt (relative to the local horizontal) of 37 deg. Placement of a module in a typical array field is illustrated.

Methylene chloride protects against cecal ligation and puncture-induced acute lung injury by modulating inflammatory mediators.

PubMed

Pang, Qingfeng; Dou, Lidong; Pan, Xiuhua; Zeng, Si; He, Jun; Xu, Wenli; Zeng, Yinming

2010-08-01

Recent studies suggest that exogenously administered CO is beneficial for the resolution of acute pulmonary inflammation. In this study, we assessed the role of CO donor, methylene chloride (MC), on modulation of lung inflammation during sepsis. Acute lung injury in Sprague-Dawley rats was induced by cecal ligation and perforation (CLP). MC (100mg/kg) was intragastrically administered 2h before CLP induction. Lung tissues and lavage samples were isolated for biochemical determinations and histological measurements 10h after CLP operation. In addition, we investigated survival rate with the other 40 rats. Intragastric administration with MC significantly decreased morbidity and mortality of CLP-induced ALI as confirmed by blinded histological changes, myeloperoxidase activity, mortality, and the content of TNF-alpha and IL-10. This protective effect could be abolished by an MC inhibitor, disulfiram. These results suggested that MC has obvious protective effects against CLP-induced ALI in rats. The mechanism of the protective effects partly involves modulating inflammatory mediators. (c) 2010 Elsevier B.V. All rights reserved.

Barratt with TVIS in Service module

NASA Image and Video Library

2009-04-23

ISS019-E-009818 (23 April 2009) --- Astronaut Michael Barratt, Expedition 19/20 flight engineer, performs in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

Barratt with TVIS in Service module

NASA Image and Video Library

2009-04-23

ISS019-E-009857 (23 April 2009) --- Astronaut Michael Barratt, Expedition 19/20 flight engineer, performs in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

Barratt with TVIS in Service module

NASA Image and Video Library

2009-04-23

ISS019-E-009840 (23 April 2009) --- Astronaut Michael Barratt, Expedition 19/20 flight engineer, performs in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

Barratt with TVIS in Service module

NASA Image and Video Library

2009-04-23

ISS019-E-009856 (23 April 2009) --- Astronaut Michael Barratt, Expedition 19/20 flight engineer, performs in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

Barratt with TVIS in Service module

NASA Image and Video Library

2009-04-23

ISS019-E-009819 (23 April 2009) --- Astronaut Michael Barratt, Expedition 19/20 flight engineer, performs in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

Improved intersection operations during detector failures.

DOT National Transportation Integrated Search

2010-03-01

The objective of this project was to develop three modules that would improve the efficiency of : intersection operations at isolated signalized intersections. The motivation for these modules was to use the : existing detectors more efficiently. Thi...

Epigenetic silencing of CYP24 in the tumor microenvironment

PubMed Central

Johnson, Candace S.; Chung, Ivy; Trump, Donald L.

2010-01-01

Calcitriol (1,25 dihydroxycholecalciferol) has significant antitumor activity in vitro and in vivo in a number of tumor model systems. We developed a system for isolation of fresh endothelial cells from tumors and Matrigel environments which demonstrate that CYP24, the catabolic enzyme involved in vitamin D signaling, is epigenetically silenced selectively in tumor-derived endothelial cells (TDEC). TDEC maintain phenotypic characteristics which are distinct from endothelial cells isolated from normal tissues and from Matrigel plugs (MDEC). In TDEC, calcitriol induces G0/G1 arrest, modulates p27 and p21, and induces apoptotic cell death and decreases P-Erk and P-Akt. In contrast, endothelial cells isolated from normal tissues and MDEC are unresponsive to calcitriol-mediated anti-proliferative effects despite intact signaling through the vitamin D receptor (VDR). In TDEC, which is sensitive to calcitriol, the CYP24 promoter is hypermethylated in two CpG island regions located at the 5′end; this hypermethylation may contribute to gene silencing of CYP24. The extent of methylation in these two regions is significantly less in MDEC. Lastly, treatment of TDEC with a DNA methyltransferase inhibitor restores calcitriol-mediated induction of CYP24 and resistance to calcitriol. These data suggest that epigenetic silencing of CYP24 modulates cellular responses to calcitriol. PMID:20304059

Deletion of African swine fever virus interferon inhibitors from the genome of a virulent isolate reduces virulence in domestic pigs and induces a protective response.

PubMed

Reis, Ana Luisa; Abrams, Charles C; Goatley, Lynnette C; Netherton, Chris; Chapman, Dave G; Sanchez-Cordon, Pedro; Dixon, Linda K

2016-09-07

African swine fever virus (ASFV) encodes multiple copies of MGF360 and MGF530/505 gene families. These genes have been implicated in the modulation of the type I interferon (IFN) response. We investigated the effect of modulating the IFN response on virus attenuation and induction of protective immunity by deleting genes MGF360 (MGF360-10L, 11L, 12L, 13L, 14L) and MGF530/505 (MGF530/505-1R, 2R and 3R) and interrupting genes (MGF360-9L and MGF530/505-4R) in the genome of the virulent ASFV isolate Benin 97/1. Replication of this deletion mutant, BeninΔMGF, in porcine macrophages in vitro was similar to that of the parental virulent virus Benin 97/1 and the natural attenuated isolate OURT88/3, which has a similar deletion of MGF360 and 530/505 genes. Levels of IFN-β mRNA in macrophages infected with virulent Benin 97/1 isolate were barely detectable but high levels were detected in macrophages infected with OURT88/3 and intermediate levels in macrophages infected with BeninΔMGF. The data confirms that these MGF360 and MGF530/505 genes have roles in suppressing induction of type I IFN. Immunisation and boost of pigs with BeninΔMGF showed that the virus was attenuated and all pigs (5/5) were protected against challenge with a lethal dose of virulent Benin 97/1. A short transient fever was observed at day 5 or 6 post-immunisation but no other clinical signs. Following immunisation and boost with the OURT88/3 isolate 3 of 4 pigs were protected against challenge. Differences were observed in the cellular and antibody responses in pigs immunised with BeninΔMGF compared to OURT88/3. Deletion of IFN modulators is a promising route for construction of rationally attenuated ASFV candidate vaccine strains. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Acidic pH modulation of Na+ channels in trigeminal mesencephalic nucleus neurons.

PubMed

Kang, In-Sik; Cho, Jin-Hwa; Choi, In-Sun; Kim, Do-Yeon; Jang, Il-Sung

2016-12-07

Cell bodies of trigeminal mesencephalic nucleus (Vmes) neurons are located within the central nervous system, and therefore, peripheral as well as central acidosis can modulate the excitability of Vmes neurons. Here, we report the effect of acidic pH on voltage-gated Na channels in acutely isolated rat Vmes neurons using a conventional whole-cell patch clamp technique. Acidic pH (pH 6.0) slightly but significantly shifted both the activation and steady-state fast inactivation relationships toward depolarized potentials. However, acidic pH (pH 6.0) had a minor effect on the inactivation kinetics of voltage-gated Na channels. Less sensitivity of voltage-gated Na channels to acidic pH may allow Vmes neurons to transduce the precise proprioceptive information even under acidic pH conditions.

Sphingosine-1-phosphate receptor expression in cardiac fibroblasts is modulated by in vitro culture conditions.

PubMed

Landeen, Lee K; Aroonsakool, Nakon; Haga, Jason H; Hu, Betty S; Giles, Wayne R

2007-06-01

The bioactive molecule sphingosine-1-phosphate (S1P) binds with high affinity to five recognized receptors (S1P(1-5)) to affect various tissues, including cellular responses of cardiac fibroblasts (CFbs) and myocytes. CFbs are essential components of myocardium, and detailed study of their cell signaling and physiology is required for a number of emerging disciplines. Meaningful studies on CFbs, however, necessitate methods for selective, reproducible cell isolations. Macrophages reside within normal cardiac tissues and often are isolated with CFbs. A protocol was therefore developed that significantly reduces macrophage levels and utilizes more CFb-specific markers (discoidin domain receptor-2) instead of, or in addition to, more commonly used cytoskeletal markers. Our results demonstrate that primary isolated, purified CFbs express predominantly S1P(1-3); however, the relative levels of these receptor subtypes are modulated with time and by culture conditions. In coculture experiments, macrophages altered CFb S1P receptor levels relative to controls. Further investigations using known macrophage-secreted factors showed that S1P and H(2)O(2) had minimal effects on CFb S1P(1-3) expression, whereas transforming growth factor-beta1, TNF-alpha, and PDGF-BB significantly altered all S1P receptor subtypes. Lowering FBS concentrations from 10% to 0.1% increased S1P(2), whereas supplementation with either PDGF-BB or Rho-associated protein kinase inhibitor Y-27632 significantly elevated S1P(3) levels. S1P(2) and S1P(3) receptor levels are known to regulate cell migration. Using cells isolated from either normal or S1P(3)-null mice, we demonstrate that S1P(3) is important and necessary for CFb migration. These results highlight the importance of demonstrating CFb culture purity in functional studies of S1P and also identify conditions that modulate S1P receptor expression in CFbs.

Extracting binaural information from simultaneous targets and distractors: Effects of amplitude modulation and asynchronous envelopes

PubMed Central

Stellmack, Mark A.; Byrne, Andrew J.; Viemeister, Neal F.

2010-01-01

When different components of a stimulus carry different binaural information, processing of binaural information in a target component is often affected. The present experiments examine whether such interference is affected by amplitude modulation and the relative phase of modulation of the target and distractors. In all experiments, listeners attempted to discriminate interaural time differences of a target stimulus in the presence of distractor stimuli with ITD=0. In Experiment 1, modulation of the distractors but not the target reduced interference between components. In Experiment 2, synthesized musical notes exhibited little binaural interference when there were slight asynchronies between different streams of notes (31 or 62 ms). The remaining experiments suggested that the reduction in binaural interference in the previous experiments was due neither to the complex spectra of the synthesized notes nor to greater detectability of the target in the presence of modulated distractors. These data suggest that this interference is reduced when components are modulated in ways that result in the target appearing briefly in isolation, not because of segregation cues. These data also suggest that modulation and asynchronies between modulators that might be encountered in real-world listening situations are adequate to reduce binaural interference to inconsequential levels. PMID:20815459

Garlic compounds modulate macrophage and T-lymphocyte functions.

PubMed

Lau, B H; Yamasaki, T; Gridley, D S

1991-06-01

Organosulfur compounds of garlic have been shown to inhibit growth of animal tumors and to modulate the activity of diverse chemical carcinogens. There is also evidence that garlic may modulate antitumor immunity. In this study, we determined the effects of an aqueous garlic extract and a protein fraction isolated from the extract on the chemiluminescent oxidative burst of the murine J774 macrophage cell line and thioglycollate-elicited peritoneal macrophages obtained from BALB/c mice. T-lymphocyte activity was determined using mouse splenocytes incubated with phytohemagglutinin, labeled with [3H]-thymidine and assayed for lymphoproliferation. Significant dose-related augmentation of oxidative burst was observed with garlic extract and the protein fraction. The protein fraction also enhanced the T-lymphocyte blastogenesis. The data suggest that garlic compounds may serve as biological response modifiers by augmenting macrophage and T-lymphocyte functions.

The acai flavonoid velutin is a potent anti-inflammatory agent: Blockade of LPS-mediated TNF-alpha and IL-6 production through inhibiting NF-kappa B activation and MAPK pathway

USDA-ARS?s Scientific Manuscript database

Recent studies have shown that some flavonoids are modulators for pro-inflammatory cytokine production. In this study, velutin, an unique flavone isolated from the pulp of acai fruit (Euterpe oleracea Mart.), was examined for its effects in reducing lipopolysaccharide-induced pro-inflammatory cytoki...

Volkov exercises on TVIS in Service Module

NASA Image and Video Library

2011-11-08

ISS029-E-040701 (8 Nov. 2011) --- Russian cosmonaut Sergei Volkov, Expedition 29 flight engineer, equipped with a bungee harness, exercises on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

Long-Term Haloperidol Treatment Prolongs QT Interval and Increases Expression of Sigma 1 and IP3 Receptors in Guinea Pig Hearts.

PubMed

Stracina, Tibor; Slaninova, Iva; Polanska, Hana; Axmanova, Martina; Olejnickova, Veronika; Konecny, Petr; Masarik, Michal; Krizanova, Olga; Novakova, Marie

2015-07-01

Haloperidol is a neuroleptic drug used for a medication of various psychoses and deliria. Its administration is frequently accompanied by cardiovascular side effects, expressed as QT interval prolongation and occurrence of even lethal arrhythmias. Despite these side effects, haloperidol is still prescribed in Europe in clinical practice. Haloperidol binds to sigma receptors that are coupled with inositol 1,4,5-trisphosphate (IP3) receptors. Sigma receptors are expressed in various tissues, including heart muscle, and they modulate potassium channels. Together with IP3 receptors, sigma receptors are also involved in calcium handling in various tissues. Therefore, the present work aimed to study the effects of long-term haloperidol administration on the cardiac function. Haloperidol (2 mg/kg once a day) or vehiculum was administered by intraperitoneal injection to guinea pigs for 21 consecutive days. We measured the responsiveness of the hearts isolated from the haloperidol-treated animals to additional application of haloperidol. Expression of the sigma 1 receptor and IP3 receptors was studied by real time-PCR and immunohistochemical analyses. Haloperidol treatment caused the significant decrease in the relative heart rate and the prolongation of QT interval of the isolated hearts from the haloperidol-treated animals, compared to the hearts isolated from control animals. The expression of sigma 1 and IP3 type 1 and type 2 receptors was increased in both atria of the haloperidol-treated animals but not in ventricles. The modulation of sigma 1 and IP3 receptors may lead to altered calcium handling in cardiomyocytes and thus contribute to changed sensitivity of cardiac cells to arrhythmias.

The effects of atropine and oxotremorine on acetylcholine release in rat phrenic nerve-diaphragm preparations.

PubMed Central

Abbs, E. T.; Joseph, D. N.

1981-01-01

1 Atropine (10(-5) M) enhanced the release of [3H]-acetylcholine from rat isolated hemidiaphragms, previously incubated with [3H-methyl]-choline, stimulated via their phrenic nerves. 2 Oxotremorine (10(-5) M) did not affect the stimulated release of [3H]-acetylcholine but antagonized the facilitatory effects of atropine (10(-5) M). 3 It is suggested that there are presynaptic inhibitory muscarinic receptors that modulate the release of acetylcholine in the phrenic nerves of the rat. PMID:7236997

Value conditioning modulates visual working memory processes.

PubMed

Thomas, Paul M J; FitzGibbon, Lily; Raymond, Jane E

2016-01-01

Learning allows the value of motivationally salient events to become associated with stimuli that predict those events. Here, we asked whether value associations could facilitate visual working memory (WM), and whether such effects would be valence dependent. Our experiment was specifically designed to isolate value-based effects on WM from value-based effects on selective attention that might be expected to bias encoding. In a simple associative learning task, participants learned to associate the color of tinted faces with gaining or losing money or neither. Tinted faces then served as memoranda in a face identity WM task for which previously learned color associations were irrelevant and no monetary outcomes were forthcoming. Memory was best for faces with gain-associated tints, poorest for faces with loss-associated tints, and average for faces with no-outcome-associated tints. Value associated with 1 item in the WM array did not modulate memory for other items in the array. Eye movements when studying faces did not depend on the valence of previously learned color associations, arguing against value-based biases being due to differential encoding. This valence-sensitive value-conditioning effect on WM appears to result from modulation of WM maintenance processes. (c) 2015 APA, all rights reserved).

Strain-dependent release of cytokines modulated by Lactobacillus salivarius human isolates in an in vitro model

PubMed Central

2010-01-01

Background Oral administration of probiotics is known to modulate cytokines profile not only locally, but also systemically. Four strains of Lactobacillus salivarius, LDR0723, BNL1059, RGS1746 and CRL1528, were evaluated for their ability to modulate release of pro- and anti-inflammatory cytokines. Findings Strains were assessed for effects on production of Interleukin-12 (IL-12), Interferon-γ (IFN-γ), Interleukin-4 (IL-4) and Interleukin-5 (IL-5) by incubating bacterial suspensions with THP-1 macrophage like cells. Cytokines were determined by means of specific quantitative enzyme-linked immunosorbent assays. LDR0723 and CRL1528 led to a sustained increment in production of IL-12 and IFN-γ and to a decrease in release of IL-4 and IL-5, while BNL1059 and RGS1746 favoured Th2 response, leading to a decrease in Th1/Th2 ratio with respect to unstimulated cells. Conclusions In conclusion, capability of L. salivarius to modulate immune response was strictly strain dependent and strains of the same species might have opposite effects. Therefore, a careful evaluation of anti-inflammatory properties of lactobacilli should be performed on single strain, before any consideration on potential probiotic use. PMID:20184725

Wakata with TVIS in Service module

NASA Image and Video Library

2009-04-23

ISS019-E-009824 (23 April 2009) --- Japan Aerospace Exploration Agency (JAXA) astronaut Koichi Wakata, Expedition 19/20 flight engineer, performs in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

Wakata with TVIS in Service module

NASA Image and Video Library

2009-04-23

ISS019-E-009853 (23 April 2009) --- Japan Aerospace Exploration Agency (JAXA) astronaut Koichi Wakata, Expedition 19/20 flight engineer, performs in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

Barratt with TVIS in Service module

NASA Image and Video Library

2009-04-22

ISS019-E-009491 (22 April 2009) --- Astronaut Michael Barratt, Expedition 19/20 flight engineer, poses for a photo with the Treadmill Vibration Isolation System (TVIS) during in-flight maintenance operations in the Zvezda Service Module of the International Space Station.

Characterizing isolated attosecond pulses with angular streaking

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

Li, Siqi; Guo, Zhaoheng; Coffee, Ryan N.

Here, we present a reconstruction algorithm for isolated attosecond pulses, which exploits the phase dependent energy modulation of a photoelectron ionized in the presence of a strong laser field. The energy modulation due to a circularly polarized laser field is manifest strongly in the angle-resolved photoelectron momentum distribution, allowing for complete reconstruction of the temporal and spectral profile of an attosecond burst. We show that this type of reconstruction algorithm is robust against counting noise and suitable for single-shot experiments. This algorithm holds potential for a variety of applications for attosecond pulse sources.

Characterizing isolated attosecond pulses with angular streaking

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

Li, Sigi; Guo, Zhaoheng; Coffee, Ryan N.

We present a reconstruction algorithm for isolated attosecond pulses, which exploits the phase dependent energy modulation of a photoelectron ionized in the presence of a strong laser field. The energy modulation due to a circularly polarized laser field is manifest strongly in the angle-resolved photoelectron momentum distribution, allowing for complete reconstruction of the temporal and spectral profile of an attosecond burst. We show that this type of reconstruction algorithm is robust against counting noise and suitable for single-shot experiments. This algorithm holds potential for a variety of applications for attosecond pulse sources.

Characterizing isolated attosecond pulses with angular streaking

DOE PAGES

Li, Siqi; Guo, Zhaoheng; Coffee, Ryan N.; ...

2018-02-12

Here, we present a reconstruction algorithm for isolated attosecond pulses, which exploits the phase dependent energy modulation of a photoelectron ionized in the presence of a strong laser field. The energy modulation due to a circularly polarized laser field is manifest strongly in the angle-resolved photoelectron momentum distribution, allowing for complete reconstruction of the temporal and spectral profile of an attosecond burst. We show that this type of reconstruction algorithm is robust against counting noise and suitable for single-shot experiments. This algorithm holds potential for a variety of applications for attosecond pulse sources.

Characterizing isolated attosecond pulses with angular streaking

DOE PAGES

Li, Sigi; Guo, Zhaoheng; Coffee, Ryan N.; ...

2018-02-13

We present a reconstruction algorithm for isolated attosecond pulses, which exploits the phase dependent energy modulation of a photoelectron ionized in the presence of a strong laser field. The energy modulation due to a circularly polarized laser field is manifest strongly in the angle-resolved photoelectron momentum distribution, allowing for complete reconstruction of the temporal and spectral profile of an attosecond burst. We show that this type of reconstruction algorithm is robust against counting noise and suitable for single-shot experiments. This algorithm holds potential for a variety of applications for attosecond pulse sources.

The effects of acute social isolation on long-term social recognition memory.

PubMed

Leser, Noam; Wagner, Shlomo

2015-10-01

The abilities to recognize individual animals of the same species and to distinguish them from other individuals are the basis for all mammalian social organizations and relationships. These abilities, termed social recognition memory, can be explored in mice and rats using their innate tendency to investigate novel social stimuli more persistently than familiar ones. Using this methodology it was found that social recognition memory is mediated by a specific neural network in the brain, the activity of which is modulated by several molecules, such the neuropeptides oxytocin and vasopressin. During the last 15 years several independent studies have revealed that social recognition memory of mice and rats depends upon their housing conditions. Specifically, long-term social recognition memory cannot be formed as shortly as few days following social isolation of the animal. This rapid and reversible impairment caused by acute social isolation seems to be specific to social memory and has not been observed in other types of memory. Here we review these studies and suggest that this unique system may serve for exploring of the mechanisms underlying the well-known negative effects of partial or perceived social isolation on human mental health. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of Subinhibitory Concentrations of Antibiotics on Alpha-Toxin (hla) Gene Expression of Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureus Isolates

PubMed Central

Ohlsen, Knut; Ziebuhr, Wilma; Koller, Klaus-Peter; Hell, Wolfgang; Wichelhaus, Thomas A.; Hacker, Jörg

1998-01-01

Concentrations of antibiotics below the MIC are able to modulate the expression of virulence-associated genes. In this study, the influence of subinhibitory doses of 31 antibiotics on the expression of the gene encoding the staphylococcal alpha-toxin (hla), a major virulence factor of Staphylococcus aureus, was investigated with a novel gene fusion protocol. The most striking observation was a strong induction of hla expression by subinhibitory concentrations of β-lactams and an almost complete inhibition of alpha-toxin expression by clindamycin. Whereas glycopeptide antibiotics had no effect, the macrolide erythromycin and several aminoglycosides reduced and fluoroquinolones slightly stimulated hla expression. Furthermore, Northern blot analysis of hla mRNA and Western blot (immunoblot) analysis of culture supernatants of both methicillin-sensitive and methicillin-resistant S. aureus strains revealed that methicillin-induced alpha-toxin expression is a common phenomenon of alpha-toxin-producing strains. Some methicillin-resistant S. aureus isolates produced up to 30-fold more alpha-toxin in the presence of 10 μg of methicillin per ml than in its absence. The results indicate that the novel gene fusion technique is a useful tool for studying the modulation of virulence gene expression by antibiotics. Moreover, the results suggest that the effects of certain antibiotics on virulence properties may be relevant for the management of S. aureus infections. PMID:9797209

Influence of Bovine Whey Protein Concentrate and Hydrolysate Preparation Methods on Motility in the Isolated Rat Distal Colon

PubMed Central

Dalziel, Julie E.; Anderson, Rachel C.; Bassett, Shalome A.; Lloyd-West, Catherine M.; Haggarty, Neill W.; Roy, Nicole C.

2016-01-01

Whey protein concentrate (WPC) and hydrolysate (WPH) are protein ingredients used in sports, medical and pediatric formulations. Concentration and hydrolysis methods vary for whey sourced from cheese and casein co-products. The purpose of this research was to investigate the influence of whey processing methods on in vitro gastrointestinal (GI) health indicators for colonic motility, epithelial barrier integrity and immune modulation. WPCs from casein or cheese processing and WPH (11% or 19% degree of hydrolysis, DH) were compared for their effects on motility in a 1 cm section of isolated rat distal colon in an oxygenated tissue bath. Results showed that WPC decreased motility irrespective of whether it was a by-product of lactic acid or mineral acid casein production, or from cheese production. This indicated that regardless of the preparation methodology, the whey protein contained components that modulate aspects of motility within the distal colon. WPH (11% DH) increased contractile frequency by 27% in a delayed manner and WPH (19% DH) had an immediate effect on contractile properties, increasing tension by 65% and frequency by 131%. Increased motility was associated with increased hydrolysis that may be attributed to the abundance of bioactive peptides. Increased frequency of contractions by WPH (19% DH) was inhibited (by 44%) by naloxone, implicating a potential involvement of opioid receptors in modulation of motility. Trans-epithelial electrical resistance and cytokine expression assays revealed that the WPC proteins studied did not alter intestinal barrier integrity or elicit any discernible immune response. PMID:27983629

Dielectric magnetic microparticles as photomagnonic cavities: Enhancing the modulation of near-infrared light by spin waves

NASA Astrophysics Data System (ADS)

Almpanis, Evangelos

2018-05-01

The coupling between spin waves and optical Mie resonances inside a dielectric magnetic spherical particle, which acts simultaneously as a photonic and magnonic (photomagnonic) cavity, is investigated by means of numerical calculations accurate to arbitrary order in the magnetooptical coupling coefficient. Isolated dielectric magnetic particles with diameters of just a few microns support high-Q optical Mie resonances at near-infrared frequencies and localized spin waves, providing an ultrasmall and compact platform in the emerging field of cavity optomagnonics. Our results predict the occurrence of strong interaction effects, beyond the linear-response approximation, which lead to enhanced modulation of near-infrared light by spin waves through multimagnon absorption and emission mechanisms.

Williams with TVIS hardware in Zvezda Service module

NASA Image and Video Library

2007-02-26

ISS014-E-15136 (26 Feb. 2007) --- Astronaut Sunita L. Williams, Expedition 14 flight engineer, performs maintenance work on the Treadmill Vibration Isolation System (TVIS) during routine in-flight maintenance (IFM) in the Zvezda Service Module of the International Space Station.

Voss on TVIS equipment in Zvezda module

NASA Image and Video Library

2001-05-15

ISS002-E-06677 (15 May 2001) --- James S. Voss, Expedition Two flight engineer, wearing a safety harness, exercises on the Treadmill Vibration Isolation System (TVIS) equipment in the Zvezda Service Module. This image was taken with a digital still camera.

Usachev performs maintenance on TVIS in Zvezda module

NASA Image and Video Library

2001-04-26

ISS002-E-7015 (26 April 2001) --- Cosmonaut Yury V. Usachev, Expedition Two commander representing Rosaviakosmos, conducts maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda/Service Module. A digital still camera was used to record this image.

Gentiana asclepiadea and Armoracia rusticana can modulate the adaptive response induced by zeocin in human lymphocytes.

PubMed

Hudecova, A; Hasplova, K; Kellovska, L; Ikreniova, M; Miadokova, E; Galova, E; Horvathova, E; Vaculcikova, D; Gregan, F; Dusinska, M

2012-01-01

Zeocin is a member of bleomycin/phleomycin family of antibiotics isolated from Streptomyces verticullus. This unique radiomimetic antibiotic is known to bind to DNA and induce oxidative stress in different organisms producing predominantly single- and double- strand breaks, as well as a DNA base loss resulting in apurinic/apyrimidinic (AP) sites. The aim of this study was to induce an adaptive response (AR) by zeocin in freshly isolated human lymphocytes from blood and to observe whether plant extracts could modulate this response. The AR was evaluated by the comet assay. The optimal conditions for the AR induction and modulation were determined as: 2 h-intertreatment time (in PBS, at 4°C) given after a priming dose (50 µg/ml) of zeocin treatment. Genotoxic impact of zeocin to lymphocytes was modulated by plant extracts isolated from Gentiana asclepiadea (methanolic and aqueous haulm extracts, 0.25 mg/ml) and Armoracia rusticana (methanolic root extract, 0.025 mg/ml). These extracts enhanced the AR and also decreased DNA damage caused by zeocin (after 0, 1 and 4 h-recovery time after the test dose of zeocin application) to more than 50%. These results support important position of plants containing many biologically active compounds in the field of pharmacology and medicine.

The application of "double isolation" in Fourier transform ion cyclotron resonance sustained off-resonance irradiation collisionally-induced dissociation tandem mass spectrometry to remove labile isobaric impurities.

PubMed

Gates, Paul J; Lopes, Norberto P; Pinto, Emani; Colepicolo, Pio; Cardozo, Karina H M

2011-01-01

This study reports the application of "double isolation" in sustained off-resonance irradiation collisionally-induced dissociation tandem mass spectrometry (SORI-CID-MS/MS) to remove radio- frequency (RF) fragment ions of very close mass isobaric ions (0.02 m/z apart). Analyses were performed with a fraction of a biological extract isolated from a macroalgae containing the mycosporine-like amino acid asterina-330. Direct isolation of the precursor ion by narrowing the isolation window proved ineffective as it impinged upon the required ion thus substantially reducing its intensity. By increasing the correlated sweep time, ejection efficiency of the isolation was improved, but caused the unwanted side-effect of RF fragmentation of labile ions. Finally, by skipping the ion activation step and performing a second isolation (in the MS(3) module) the RF fragments from the first isolation were removed leaving a very pure isolation of the required precursor ion and allowed a very clean CID fragmentation. We demonstrated that the m/z 272.1351 ion is derived from the loss of NH(3) from m/z 289.1620 isobaric impurity and is not related to asterina-330. This application represents a powerful tool to remove unwanted ions in the MS/MS spectrum that result from fragmentation of isobaric ions.

Antiproliferative, Antibacterial and Antifungal Activity of the Lichen Xanthoria parietina and Its Secondary Metabolite Parietin

PubMed Central

Basile, Adriana; Rigano, Daniela; Loppi, Stefano; Di Santi, Annalisa; Nebbioso, Angela; Sorbo, Sergio; Conte, Barbara; Paoli, Luca; De Ruberto, Francesca; Molinari, Anna Maria; Altucci, Lucia; Bontempo, Paola

2015-01-01

Lichens are valuable natural resources used for centuries throughout the world as medicine, food, fodder, perfume, spices and dyes, as well as for other miscellaneous purposes. This study investigates the antiproliferative, antibacterial and antifungal activity of the acetone extract of the lichen Xanthoria parietina (Linnaeus) Theodor Fries and its major secondary metabolite, parietin. The extract and parietin were tested for antimicrobial activity against nine American Type Culture Collection standard and clinically isolated bacterial strains, and three fungal strains. Both showed strong antibacterial activity against all bacterial strains and matched clinical isolates, particularly against Staphylococcus aureus from standard and clinical sources. Among the fungi tested, Rhizoctonia solani was the most sensitive. The antiproliferative effects of the extract and parietin were also investigated in human breast cancer cells. The extract inhibited proliferation and induced apoptosis, both effects being accompanied by modulation of expression of cell cycle regulating genes such as p16, p27, cyclin D1 and cyclin A. It also mediated apoptosis by activating extrinsic and intrinsic cell death pathways, modulating Tumor Necrosis Factor-related apoptosis-inducing ligand (TRAIL) and B-cell lymphoma 2 (Bcl-2), and inducing Bcl-2-associated agonist of cell death (BAD) phosphorylation. Our results indicate that Xanthoria parietina is a major potential source of antimicrobial and anticancer substances. PMID:25860944

ENSO Modulations due to Interannual Variability of Freshwater Forcing and Ocean Biology-induced Heating in the Tropical Pacific

PubMed Central

Zhang, Rong-Hua; Gao, Chuan; Kang, Xianbiao; Zhi, Hai; Wang, Zhanggui; Feng, Licheng

2015-01-01

Recent studies have identified clear climate feedbacks associated with interannual variations in freshwater forcing (FWF) and ocean biology-induced heating (OBH) in the tropical Pacific. The interrelationships among the related anomaly fields are analyzed using hybrid coupled model (HCM) simulations to illustrate their combined roles in modulating the El Niño-Southern Oscillation (ENSO). The HCM-based supporting experiments are performed to isolate the related feedbacks, with interannually varying FWF and OBH being represented individually or collectively, which allows their effects to be examined in a clear way. It is demonstrated that the interannual freshwater forcing enhances ENSO variability and slightly prolongs the simulated ENSO period, while the interannual OBH reduces ENSO variability and slightly shortens the ENSO period, with their feedback effects tending to counteract each other. PMID:26678931

Calcium modulates the ATP and ADP hydrolysis in human placental mitochondria.

PubMed

Martínez, Federico; Uribe, Aida; Espinosa-García, M Teresa; Flores-Herrera, Oscar; García-Pérez, Cecilia; Milán, Rebeca

2002-08-01

This study evaluated the effect of Ca2+ on the extramitochondrial hydrolysis of ATP and ADP by the extramitochondrial ATPase in isolated mitochondria and submitochondrial particles (SMPs) from human term placenta. The effect of different oxidizable substrates on the hydrolysis of ATP and ADP in the presence of sucrose or K+ was evaluated. Ca2+ increased phosphate release from ATP and ADP, but this stimulation showed different behavior depending on the oxidizable substrate present in the incubation media. Ca2+ stimulated the hydrolysis of ATP and ADP in the presence of sucrose. However, Ca2+ did not stimulate the hydrolysis of ADP in the medium containing K+. Ca2+ showed inhibition depending on the respiratory substrate. This study suggests that the energetic state of mitochondria controls the extramitochondrial ATPase activity, which is modulated by Ca2+ and respiratory substrates.

Low-dose radiation modulates human mesenchymal stem cell proliferation through regulating CDK and Rb.

PubMed

Yang, Lei; Liu, Ziling; Chen, Chen; Cong, Xiaofeng; Li, Zhi; Zhao, Shasha; Ren, Meng

2017-01-01

Low-dose radiation (LDR) has been known to stimulate cell proliferation. The effect of LDR on human bone marrow mesenchymal stem cells (BMSCs), however, remains to be determined. The current study, therefore, aimed to investigate the effect of LDR on human BMSC proliferation and its mechanisms. To accomplish this, human BMSCs were isolated from ribs and cultured with or without exposition to LDR (75 mGy) for 24 h. Cell proliferation was assessed by MTT assay, the cytokines secreted by the BMSCs were quantified by ELISA, and the proteins associated with cell proliferation and cell cycle were evaluated by immunoblot analysis. BMSCs isolated from human ribs were capable of differentiating into osteoblasts and adipocytes. LDR stimulated human BMSC proliferation (0.580 ± 0.106 vs 0.419 ± 0.026 on day 4, P < 0.05; 0.794 ± 0.025 vs 0.689 ± 0.047 on day 7, P < 0.05) and increased S-phase proportion. LDR significantly enhanced the production of SCF, GM-CSF, and IL-11. Moreover, BMSCs modulated T-cell proliferation, and LDR further augmented the modulatory effect of BMSCs on T-cell proliferation. Cell cycle-associated proteins, such as Rb, CDK1, and CDC25B, appeared to mediate the stimulatory effect of LDR on BMSC proliferation. The findings of the current study indicate that physical stimulants, such as LDR, could be used for the large-scale expansion of human BMSCs, and thus may be used for MSC cellular therapy in clinic.

Anti-Wrinkle and Anti-Inflammatory Effects of Active Garlic Components and the Inhibition of MMPs via NF-κB Signaling

PubMed Central

Kim, So Ra; Jung, Yu Ri; An, Hye Jin; Kim, Dae Hyun; Jang, Eun Ji; Choi, Yeon Ja; Moon, Kyoung Mi; Park, Min Hi; Park, Chan Hum; Chung, Ki Wung; Bae, Ha Ram; Choi, Yung Whan; Kim, Nam Deuk; Chung, Hae Young

2013-01-01

Skin aging is a multisystem degenerative process caused by several factors, such as, UV irradiation, stress, and smoke. Furthermore, wrinkle formation is a striking feature of photoaging and is associated with oxidative stress and inflammatory response. In the present study, we investigated whether caffeic acid, S-allyl cysteine, and uracil, which were isolated from garlic, modulate UVB-induced wrinkle formation and effect the expression of matrix-metalloproteinase (MMP) and NF-κB signaling. The results obtained showed that all three compounds significantly inhibited the degradation of type І procollagen and the expressions of MMPs in vivo and attenuated the histological collagen fiber disorder and oxidative stress in vivo. Furthermore, caffeic acid and S-allyl cysteine were found to decrease oxidative stress and inflammation by modulating the activities of NF-κB and AP-1, and uracil exhibited an indirect anti-oxidant effect by suppressing cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions levels and downregulating transcriptional factors. These results suggest that the anti-wrinkle effects of caffeic acid, S-allyl cysteine, and uracil are due to anti-oxidant and/or anti-inflammatory effects. Summarizing, caffeic acid, S-allyl cysteine, and uracil inhibited UVB-induced wrinkle formation by modulating MMP via NF-κB signaling. PMID:24066081

Microwave effects on isolated chick embryo hearts

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

Caddemi, A.; Tamburello, C.C.; Zanforlin, L.

1986-01-01

This study was designed to examine the effects of microwaves on the electric activity of hearts as a means of elucidating interactive mechanisms of nonionizing radiation with cardiac tissue. Experiments were performed on isolated hearts of 9-12-day-old chick embryos placed in small petri dishes. Oxygenated isotonic Ringer's solution at 37 degrees C permitted heart survival. Samples were irradiated at 2.45 GHz with a power density of 3 mW/cm2. The heart signal was detected with a glass micropipet inserted into the sinoatrial node and examined by means of a Berg-Fourier analyzer. Pulsed microwaves caused the locking of the heartbeat to themore » modulation frequency, whereas continuous wave irradiation might have induced slight bradycardia. Pulsed fields induced stimulation or regularization of the heartbeat in arrhythmia, fibrillation, or arrest of the heart.« less

A Detailed Analysis of Visible Defects Formed in Commercial Silicon Thin-Film Modules During Outdoor Exposure

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

Gerber, Andreas; Johnston, Steve; Olivera-Pimentel, Guillermo

We analyzed defects in silicon thin-film tandem (a-Si:H/..mu..c-Si:H) modules from an outdoor installation in India. The inspection of several affected modules reveals that most of the defects -- which optically appear as bright spots -- were formed primarily nearby the separation and series connection laser lines. Cross-sectional SEM analysis reveals that the bright spots emerge due to electrical isolation, caused by a delamination of the cell from the front TCO in the affected area. In addition, the morphology of the a-Si:H top cell differs in the delaminated area compared to the surrounding unaffected area. We propose that these effects aremore » potentially caused by an explosive and thermally triggered liberation of hydrogen from the a-Si:H layer. Electrical and thermal measurements reveal that these defects can impact the cell performance significantly.« less

Pentameric procyanidins isolated from Theobroma cacao seeds selectively downregulate ErbB2 in human aortic endothelial cells.

PubMed

Kenny, Thomas P; Keen, Carl L; Jones, Paul; Kung, Hsing-Jien; Schmitz, Harold H; Gershwin, M Eric

2004-03-01

Flavonoids isolated from cocoa have biological activities relevant to oxidant defenses, vascular health, tumor suppression, and immune function. The intake of certain dietary flavonoids, along with other dietary substances such as tocopherols, ascorbate, and carotenoids, is epidemiologically associated with a reduced risk of cardiovascular disease. Flavonoids have also been shown to modulate tumor pathology in vitro and in animal models. We took advantage of the conserved sequences found in tyrosine kinases to study the influence of cocoa fractions and controls on gene expression. We report that the pentameric procyanidin (molecular weight of 1442 daltons) fraction isolated from cocoa was a potent inhibitor of tyrosine kinase ErbB2 expression, a receptor important in angiogenesis regulation. Consistent with this primary observation, the cocoa flavonoid fraction also suppressed human aortic endothelial cell (HAEC) growth and decreased expression of two tyrosine kinases responsive to ErbB2 modulation, namely VEGFR-2/KDR and MapK 11/p38beta2. These inhibitory effects were observed when HAECs were treated with the flavonol fraction (molecular weight 280 daltons) isolated from cocoa, which comprise the structural subunits from which the procyanidin flavonoid subclass is biosynthetically constructed. Down-regulation of ErbB2 and inhibition of HAEC growth by cocoa procyanidins may have several downstream implications, including reduced vascular endothelial growth factor (VEGF) activity and angiogenic activity associated with tumor pathology. These results suggest specific dietary flavonoids are capable of selectively inhibiting ErbB2 and therefore may offer important insight into the design of therapeutic agents that target tumors overexpressing ErbB2.

Usachev performs maintenance on TVIS system in Service module

NASA Image and Video Library

2001-04-01

ISS002-E-5137 (April 2001) --- Cosmonaut Yury V. Usachev, Expedition Two mission commander, performs routine maintenance on the International Space Station's (ISS) Treadmill Vibration Isolation System (TVIS) in the Zvezda / Service Module. This image was recorded with a digital still camera.

Phytochemical Analysis and Modulation of Antibiotic Activity by Luehea paniculata Mart. & Zucc. (Malvaceae) in Multiresistant Clinical Isolates of Candida Spp.

PubMed Central

Calixto Júnior, João T.; Morais, Selene M.; Martins, Clécio G.; Vieira, Larissa G.; Morais-Braga, Maria Flaviana B.; Carneiro, Joara N. P.; Machado, Antonio J. P.; Menezes, Irwin R. A.; Tintino, Saulo R.; Coutinho, Henrique D. M.

2015-01-01

The high incidence of fungal infections has led to the continuous search for new drugs. Extracts of Luehea paniculata, a tree of multiple medicinal uses, were evaluated for anti-Candida activity, as well as its modulator potential of the Fluconazole antibiotic. Chemical prospecting of ethanol extracts of leaf and bark was carried out, the quantification of total phenols and flavonoids, characterized by the HPLC-DAD technique. The rosmarinic acid and the vitexin flavonoid were observed as major constituents in ELELP and ESWELP, respectively. Antioxidant activity was also evaluated by the method of scavenging the free radical DPPH, and quercetin was used as standard, obtaining IC50 values: 0.341 (mg/mL) for ELELP and 0.235 (mg/mL) for ESWELP. The microdilution assay was performed for antifungal activity against strains of Candida albicans, C. krusei, and C. tropicalis and showed minimum inhibitory concentrations values ≥1024 μg/mL. In the modulator action of extracts on Fluconazole against multiresistant clinical isolates of Candida (subinhibitory concentration minimum of 128 μg/mL), a significant synergism was observed, indicating that the extracts potentiated the antifungal effect against C. tropicalis, where antioxidant flavonoids could be responsible. This is the first report about modifying activity of the antibiotic action of a species of the genus Luehea. PMID:25821822

Hierarchical cortical transcriptome disorganization in autism.

PubMed

Lombardo, Michael V; Courchesne, Eric; Lewis, Nathan E; Pramparo, Tiziano

2017-01-01

Autism spectrum disorders (ASD) are etiologically heterogeneous and complex. Functional genomics work has begun to identify a diverse array of dysregulated transcriptomic programs (e.g., synaptic, immune, cell cycle, DNA damage, WNT signaling, cortical patterning and differentiation) potentially involved in ASD brain abnormalities during childhood and adulthood. However, it remains unclear whether such diverse dysregulated pathways are independent of each other or instead reflect coordinated hierarchical systems-level pathology. Two ASD cortical transcriptome datasets were re-analyzed using consensus weighted gene co-expression network analysis (WGCNA) to identify common co-expression modules across datasets. Linear mixed-effect models and Bayesian replication statistics were used to identify replicable differentially expressed modules. Eigengene network analysis was then utilized to identify between-group differences in how co-expression modules interact and cluster into hierarchical meta-modular organization. Protein-protein interaction analyses were also used to determine whether dysregulated co-expression modules show enhanced interactions. We find replicable evidence for 10 gene co-expression modules that are differentially expressed in ASD cortex. Rather than being independent non-interacting sources of pathology, these dysregulated co-expression modules work in synergy and physically interact at the protein level. These systems-level transcriptional signals are characterized by downregulation of synaptic processes coordinated with upregulation of immune/inflammation, response to other organism, catabolism, viral processes, translation, protein targeting and localization, cell proliferation, and vasculature development. Hierarchical organization of meta-modules (clusters of highly correlated modules) is also highly affected in ASD. These findings highlight that dysregulation of the ASD cortical transcriptome is characterized by the dysregulation of multiple coordinated transcriptional programs producing synergistic systems-level effects that cannot be fully appreciated by studying the individual component biological processes in isolation.

Proceedings of the 21st Project Integration Meeting

NASA Technical Reports Server (NTRS)

1983-01-01

Progress made by the Flat Plate Solar Array Project during the period April 1982 to January 1983 is described. Reports on polysilicon refining, thin film solar cell and module technology development, central station electric utility activities, silicon sheet growth and characteristics, advanced photovoltaic materials, cell and processes research, module technology, environmental isolation, engineering sciences, module performance and failure analysis and project analysis and integration are included.

Immunomodulation and Anti-Inflammatory Effects of Garlic Compounds

PubMed Central

Arreola, Rodrigo; Quintero-Fabián, Saray; López-Roa, Rocío Ivette; Flores-Gutiérrez, Enrique Octavio; Reyes-Grajeda, Juan Pablo; Carrera-Quintanar, Lucrecia; Ortuño-Sahagún, Daniel

2015-01-01

The benefits of garlic to health have been proclaimed for centuries; however, only recently have Allium sativum and its derivatives been proposed as promising candidates for maintaining the homeostasis of the immune system. The complex biochemistry of garlic makes it possible for variations in processing to yield different preparations with differences in final composition and compound proportion. In this review, we assess the most recent experimental results, which indicate that garlic appears to enhance the functioning of the immune system by stimulating certain cell types, such as macrophages, lymphocytes, natural killer (NK) cells, dendritic cells, and eosinophils, by mechanisms including modulation of cytokine secretion, immunoglobulin production, phagocytosis, and macrophage activation. Finally, because immune dysfunction plays an important role in the development and progress of several diseases, we critically examined immunoregulation by garlic extracts and compounds isolated, which can contribute to the treatment and prevention of pathologies such as obesity, metabolic syndrome, cardiovascular disorders, gastric ulcer, and even cancer. We concluded that A. sativum modulates cytokine secretion and that such modulation may provide a mechanism of action for many of their therapeutic effects. PMID:25961060

Immunomodulation and anti-inflammatory effects of garlic compounds.

PubMed

Arreola, Rodrigo; Quintero-Fabián, Saray; López-Roa, Rocío Ivette; Flores-Gutiérrez, Enrique Octavio; Reyes-Grajeda, Juan Pablo; Carrera-Quintanar, Lucrecia; Ortuño-Sahagún, Daniel

2015-01-01

The benefits of garlic to health have been proclaimed for centuries; however, only recently have Allium sativum and its derivatives been proposed as promising candidates for maintaining the homeostasis of the immune system. The complex biochemistry of garlic makes it possible for variations in processing to yield different preparations with differences in final composition and compound proportion. In this review, we assess the most recent experimental results, which indicate that garlic appears to enhance the functioning of the immune system by stimulating certain cell types, such as macrophages, lymphocytes, natural killer (NK) cells, dendritic cells, and eosinophils, by mechanisms including modulation of cytokine secretion, immunoglobulin production, phagocytosis, and macrophage activation. Finally, because immune dysfunction plays an important role in the development and progress of several diseases, we critically examined immunoregulation by garlic extracts and compounds isolated, which can contribute to the treatment and prevention of pathologies such as obesity, metabolic syndrome, cardiovascular disorders, gastric ulcer, and even cancer. We concluded that A. sativum modulates cytokine secretion and that such modulation may provide a mechanism of action for many of their therapeutic effects.

Evidence for a possible role for nitric oxide in the modulation of heart activity in Achatina fulica and Helix aspersa.

PubMed

White, A R; Curtis, S A; Walker, R J

2004-02-01

The effects of nitric oxide (NO) donors, S-nitroso-N-acetylpenicillamine, S-nitroso-l-glutathione, sodium nitroprusside and sodium nitrite were investigated on the activity of the isolated hearts of Achatina fulica and Helix aspersa. NO donors inhibited heart activity in a concentration-dependent manner. The only exception was sodium nitroprusside, which excited H. aspersa heart. The inhibitory effects of these NO donors were reduced by the NO scavenger, methylene blue, the guanylyl cyclase inhibitor, 1H-(1,2,4) Oxadiazolo(4,3-a)quinoxalin-1-one (ODQ), and potentiated by 8-Br-cGMP and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Acetylcholine also inhibited the heart activity, and this inhibition was reduced by methylene blue and ODQ. Positive NADPH-diaphorase staining was located in the outer pericardial layer of the heart of A. fulica. The present results provide evidence that NO may modulate the activity of gastropod hearts, and this modulation may modify the inhibitory action of acetylcholine on heart activity.

The postantifungal effect and phospholipase production of oral Candida albicans from smokers, diabetics, asthmatics, denture wearers and healthy individuals following brief exposure to subtherapeutic concentrations of chlorhexidine gluconate.

PubMed

Ellepola, Arjuna N B; Joseph, Bobby K; Khan, Z U

2014-09-01

Candida albicans is the major aetiological agent of oral candidosis and one of its important virulent factors is the production of extracellular phospholipases, which can be modulated by subtherapeutic concentrations of antifungal agents thus decreasing their pathogenicity. Hence, considering that chlorhexidine gluconate (CG) is a common antimicrobial mouthwash used in dentistry and that its concentration in the mouth reaches subtherapeutic levels during dosage intervals due to the diluent effect of saliva and cleansing effect of the oral musculature, the postantifungal effect (PAFE) and the phospholipase production of oral C. albicans following brief exposure to subtherapeutic concentrations of CG was studied. Fifty C. albicans planktonic oral isolates obtained from smokers, diabetics, asthmatics using steroid inhalers, partial denture wearers and healthy individuals were exposed to three subtherapeutic concentrations of CG (0.005%, 0.0025% and 0.00125%) for 1 h. Isolates unexposed to CG was the control group. Thereafter the antiseptic was removed and the PAFE and phospholipase production was determined by a turbidometric method and a plate assay using an egg yolk agar medium respectively. Mean PAFE (hours) of 50 oral isolates of C. albicans following 1-h exposure to 0.005%, 0.0025% and 0.00125% CG was 6.97, 1.85 and 0.62 respectively. The phospholipase production of these isolates was significantly suppressed with a percentage reduction of 21.68, 18.20 and 14.04% following exposure to 0.005%, 0.0025% and 0.00125% CG respectively. Brief exposure of C. albicans isolates to subtherapeutic concentrations of CG would wield an antifungal effect by suppressing growth and phospholipase production, thereby quelling its pathogenicity. © 2014 Blackwell Verlag GmbH.

Tickling during adolescence alters fear-related and cognitive behaviors in rats after prolonged isolation.

PubMed

Hori, Miyo; Yamada, Kazuo; Ohnishi, Junji; Sakamoto, Shigeko; Furuie, Hiroki; Murakami, Kazuo; Ichitani, Yukio

2014-05-28

Social interactions during adolescence are important especially for neuronal development and behavior. We recently showed that positive emotions induced by repeated tickling could modulate fear-related behaviors and sympatho-adrenal stress responses. In the present study, we examined whether tickling during early to late adolescence stage could reverse stress vulnerability induced by socially isolated rearing. Ninety-five male Fischer rats were reared under different conditions from postnatal day (PND) 21 to 53: group-housed (three rats/cage), isolated-nontickled (one rat/cage) and isolated-tickled (received tickling stimulation for 5min a day). Auditory fear conditioning was then performed on the rats at PND 54. Isolated-tickled rats exhibited significantly lower freezing compared with group-housed rats in the first retention test performed 48h after conditioning and compared with isolated-nontickled rats in the second retention test performed 96h after conditioning. Moreover, group-housed and isolated-tickled rats tended to show a significant decrease in freezing responses in the second retention test; however, isolated-nontickled rats did not. In the Morris water maze task that was trained in adulthood (PND 88), but not in adolescence (PND 56), isolated-nontickled rats showed slower decrease of escape latency compared to group-housed rats; however, tickling treatment significantly improved this deficit. These results suggest that tickling stimulation can alleviate the detrimental effects of isolated rearing during adolescence on fear responses and spatial learning. Copyright © 2014 Elsevier Inc. All rights reserved.

Assembly of opto-electronic module with improved heat sink

DOEpatents

Chan, Benson; Fortier, Paul Francis; Freitag, Ladd William; Galli, Gary T.; Guindon, Francois; Johnson, Glen Walden; Letourneau, Martial; Sherman, John H.; Tetreault, Real

2004-11-23

A heat sink for a transceiver optoelectronic module including dual direct heat paths and a structure which encloses a number of chips having a central web which electrically isolates transmitter and receiver chips from each other. A retainer for an optical coupler having a port into which epoxy is poured. An overmolded base for an optoelectronic module having epoxy flow controller members built thereon. Assembly methods for an optoelectronic module including gap setting and variation of a TAB bonding process.

Reduced Sleep During Social Isolation Leads to Cellular Stress and Induction of the Unfolded Protein Response.

PubMed

Brown, Marishka K; Strus, Ewa; Naidoo, Nirinjini

2017-07-01

Social isolation has a multitude of negative consequences on human health including the ability to endure challenges to the immune system, sleep amount and efficiency, and general morbidity and mortality. These adverse health outcomes are conserved in other social species. In the fruit fly Drosophila melanogaster, social isolation leads to increased aggression, impaired memory, and reduced amounts of daytime sleep. There is a correlation between molecules affected by social isolation and those implicated in sleep in Drosophila. We previously demonstrated that acute sleep loss in flies and mice induced the unfolded protein response (UPR), an adaptive signaling pathway. One mechanism indicating UPR upregulation is elevated levels of the endoplasmic reticular chaperone BiP/GRP78. We previously showed that BiP overexpression in Drosophila led to increased sleep rebound. Increased rebound sleep has also been demonstrated in socially isolated (SI) flies. D. melanogaster were used to study the effect of social isolation on cellular stress. SI flies displayed an increase in UPR markers; there were higher BiP levels, increased phosphorylation of the translation initiation factor eIF2α, and increased splicing of xbp1. These are all indicators of UPR activation. In addition, the effects of isolation on the UPR were reversible; pharmacologically and genetically altering sleep in the flies modulated the UPR. The reduction in sleep observed in SI flies is a cellular stressor that results in UPR induction. © Sleep Research Society 2017. Published by Oxford University Press [on behalf of the Sleep Research Society]. All rights reserved. For permissions, please email: journals.permissions@oup.com

Thrombopoietin modulates cardiac contractility in vitro and contributes to myocardial depressing activity of septic shock serum.

PubMed

Lupia, Enrico; Spatola, Tiziana; Cuccurullo, Alessandra; Bosco, Ornella; Mariano, Filippo; Pucci, Angela; Ramella, Roberta; Alloatti, Giuseppe; Montrucchio, Giuseppe

2010-09-01

Thrombopoietin (TPO) is a humoral growth factor that has been shown to increase platelet activation in response to several agonists. Patients with sepsis have increased circulating TPO levels, which may enhance platelet activation, potentially participating to the pathogenesis of multi-organ failure. Aim of this study was to investigate whether TPO affects myocardial contractility and participates to depress cardiac function during sepsis. We showed the expression of the TPO receptor c-Mpl on myocardial cells and tissue by RT-PCR, immunofluorescence and western blotting. We then evaluated the effect of TPO on the contractile function of rat papillary muscle and isolated heart. TPO did not change myocardial contractility in basal conditions, but, when followed by epinephrine (EPI) stimulation, it blunted the enhancement of contractile force induced by EPI both in papillary muscle and isolated heart. An inhibitor of TPO prevented TPO effect on cardiac inotropy. Treatment of papillary muscle with pharmacological inhibitors of phosphatidylinositol 3-kinase, NO synthase, and guanilyl cyclase abolished TPO effect, indicating NO as the final mediator. We finally studied the role of TPO in the negative inotropic effect exerted by human septic shock (HSS) serum and TPO cooperation with TNF-alpha and IL-1beta. Pre-treatment with the TPO inhibitor prevented the decrease in contractile force induced by HSS serum. Moreover, TPO significantly amplified the negative inotropic effect induced by TNF-alpha and IL-1beta in papillary muscle. In conclusion, TPO negatively modulates cardiac inotropy in vitro and contributes to the myocardial depressing activity of septic shock serum.

Comprehensive Evaluation of the MBT STAR-BL Module for Simultaneous Bacterial Identification and β-Lactamase-Mediated Resistance Detection in Gram-Negative Rods from Cultured Isolates and Positive Blood Cultures.

PubMed

Lee, Annie W T; Lam, Johnson K S; Lam, Ricky K W; Ng, Wan H; Lee, Ella N L; Lee, Vicky T Y; Sze, Po P; Rajwani, Rahim; Fung, Kitty S C; To, Wing K; Lee, Rodney A; Tsang, Dominic N C; Siu, Gilman K H

2018-01-01

Objective: This study evaluated the capability of a MALDI Biotyper system equipped with the newly introduced MBT STAR-BL module to simultaneously perform species identification and β-lactamase-mediated resistance detection in bacteremia -causing bacteria isolated from cultured isolates and patient-derived blood cultures (BCs). Methods: Two hundred retrospective cultured isolates and 153 prospective BCs containing Gram-negative rods (GNR) were collected and subjected to direct bacterial identification, followed by the measurement of β-lactamase activities against ampicillin, piperacillin, cefotaxime, ceftazidime, and meropenem using the MBT STAR-BL module. The results and turnaround times were compared with those of routine microbiological processing. All strains were also characterized by beta-lactamase PCR and sequencing. Results: Using the saponin-based extraction method, MALDI-TOF MS correctly identified bacteria in 116/134 (86.6%) monomicrobial BCs. The detection sensitivities for β-lactamase activities against ampicillin, piperacillin, third-generation cephalosporin and meropenem were 91.3, 100, 97.9, and 100% for cultured isolates, and 80.4, 100, 68.8, and 40% for monomicrobial BCs ( n = 134) respectively. The overall specificities ranged from 91.5 to 100%. Furthermore, the MBT STAR-BL and conventional drug susceptibility test results were concordant in 14/19 (73.7%) polymicrobial cultures. Reducing the logRQ cut-off value from 0.4 to 0.2 increased the direct detection sensitivities for β-lactamase activities against ampicillin, cefotaxime and meropenem in BCs to 85.7, 87.5, and 100% respectively. The MBT STAR-BL test enabled the reporting of β-lactamase-producing GNR at 14.16 and 47.64 h before the interim and final reports of routine BCs processing, respectively, were available. Conclusion: The MALDI Biotyper system equipped with the MBT STAR-BL module enables the simultaneous rapid identification of bacterial species and β-lactamase-mediated resistance from BCs and cultured isolates. Adjustment of the logRQ cut-off value to 0.2 significantly increased the detection sensitivities for clinically important drug-resistant pathogens.

Comprehensive Evaluation of the MBT STAR-BL Module for Simultaneous Bacterial Identification and β-Lactamase-Mediated Resistance Detection in Gram-Negative Rods from Cultured Isolates and Positive Blood Cultures

PubMed Central

Lee, Annie W. T.; Lam, Johnson K. S.; Lam, Ricky K. W.; Ng, Wan H.; Lee, Ella N. L.; Lee, Vicky T. Y.; Sze, Po P.; Rajwani, Rahim; Fung, Kitty S. C.; To, Wing K.; Lee, Rodney A.; Tsang, Dominic N. C.; Siu, Gilman K. H.

2018-01-01

Objective: This study evaluated the capability of a MALDI Biotyper system equipped with the newly introduced MBT STAR-BL module to simultaneously perform species identification and β-lactamase-mediated resistance detection in bacteremia -causing bacteria isolated from cultured isolates and patient-derived blood cultures (BCs). Methods: Two hundred retrospective cultured isolates and 153 prospective BCs containing Gram-negative rods (GNR) were collected and subjected to direct bacterial identification, followed by the measurement of β-lactamase activities against ampicillin, piperacillin, cefotaxime, ceftazidime, and meropenem using the MBT STAR-BL module. The results and turnaround times were compared with those of routine microbiological processing. All strains were also characterized by beta-lactamase PCR and sequencing. Results: Using the saponin-based extraction method, MALDI-TOF MS correctly identified bacteria in 116/134 (86.6%) monomicrobial BCs. The detection sensitivities for β-lactamase activities against ampicillin, piperacillin, third-generation cephalosporin and meropenem were 91.3, 100, 97.9, and 100% for cultured isolates, and 80.4, 100, 68.8, and 40% for monomicrobial BCs (n = 134) respectively. The overall specificities ranged from 91.5 to 100%. Furthermore, the MBT STAR-BL and conventional drug susceptibility test results were concordant in 14/19 (73.7%) polymicrobial cultures. Reducing the logRQ cut-off value from 0.4 to 0.2 increased the direct detection sensitivities for β-lactamase activities against ampicillin, cefotaxime and meropenem in BCs to 85.7, 87.5, and 100% respectively. The MBT STAR-BL test enabled the reporting of β-lactamase-producing GNR at 14.16 and 47.64 h before the interim and final reports of routine BCs processing, respectively, were available. Conclusion: The MALDI Biotyper system equipped with the MBT STAR-BL module enables the simultaneous rapid identification of bacterial species and β-lactamase-mediated resistance from BCs and cultured isolates. Adjustment of the logRQ cut-off value to 0.2 significantly increased the detection sensitivities for clinically important drug-resistant pathogens. PMID:29527202

Dihydro-β-agarofuran sesquiterpenes from celastraceae species as anti-tumour-promoting agents: Structure-activity relationship.

PubMed

Núñez, Marvin J; Jiménez, Ignacio A; Mendoza, Cristina R; Chavez-Sifontes, Marvin; Martinez, Morena L; Ichiishi, Eiichiro; Tokuda, Ryo; Tokuda, Harukuni; Bazzocchi, Isabel L

2016-03-23

Inhibition of tumour promotion in multistage chemical carcinogenesis is considered a promising strategy for cancer chemoprevention. In an ongoing investigation of bioactive secondary metabolites from Celastraceae species, five new dihydro-β-agarofuran sesquiterpenes (1-5), named Chiapens A-E, and seventeen known ones, were isolated from Maytenus chiapensis. Their structures were elucidated by extensive NMR spectroscopic and mass spectrometric techniques, and their absolute configurations were determined by circular dichroism studies, chemical correlations and biogenic means. The isolated compounds, along with twenty known sesquiterpenes, previously isolated from Zinowiewia costaricensis, have been tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorpol-13-acetate (TPA). Thirty three compounds from this series showed stronger effects than that of β-carotene, the reference inhibitor. The structure-activity relationship (SAR) analysis revealed that the type of substituent, in particular at the C-1 position of the sesquiterpene scaffold, was able to modulate the anti-tumour promoting activity. Compounds 3, 6, and 33 showed significant effects in an in vivo two-stage mouse-skin carcinogenesis model. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Transcriptional control in Alicyclobacillus acidocaldarius and associated genes, proteins, and methods

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

Lee, Brady D.; Thompson, David N.; Apel, William A.

Isolated and/or purified polypeptides and nucleic acid sequences encoding polypeptides from Alicyclobacillus acidocaldarius are provided. Further provided are methods of modulating transcription or transcription or transcriptional control using isolated and/or purified polypeptides and nucleic acid sequences from Alicyclobacillus acidocaldarius.

Transcriptional control in Alicyclobacillus acidocaldarius and associated genes, proteins, and methods

DOEpatents

Lee, Brady Deneys; Thompson, David N; Apel, William A.; Thompson, Vicki Slavchev; Reed, David W; Lacey, Jeffrey A

2014-05-06

Isolated and/or purified polypeptides and nucleic acid sequences encoding polypeptides from Alicyclobacillus acidocaldarius are provided. Further provided are methods of modulating transcription or transcription or transcriptional control using isolated and/or purified polypeptides and nucleic acid sequences from Alicyclobacillus acidocaldarius.

Transcriptional control in Alicyclobacillus acidocaldarius and associated genes, proteins, and methods

DOEpatents

Lee, Brady D.; Thompson, David N.; Apel, William A.; Thompson, Vicki S.; Reed, David W.; Lacey, Jeffrey A.

2015-11-17

Isolated and/or purified polypeptides and nucleic acid sequences encoding polypeptides from Alicyclobacillus acidocaldarius are provided. Further provided are methods of modulating transcription or transcription or transcriptional control using isolated and/or purified polypeptides and nucleic acid sequences from Alicyclobacillus acidocaldarius.

Transcriptional control in alicyclobacillus acidocaldarius and associated genes, proteins, and methods

DOEpatents

Lee, Brady D; Thompson, David N; Apel, William A; Thompson, Vicki S; Reed, David W; Lacey, Jeffrey A

2016-11-22

Isolated and/or purified polypeptides and nucleic acid sequences encoding polypeptides from Alicyclobacillus acidocaldarius are provided. Further provided are methods of modulating transcription or transcription or transcriptional control using isolated and/or purified polypeptides and nucleic acid sequences from Alicyclobacillus acidocaldarius.

Nitric oxide-mediated modulation of the murine locomotor network

PubMed Central

Foster, Joshua D.; Dunford, Catherine; Sillar, Keith T.

2013-01-01

Spinal motor control networks are regulated by neuromodulatory systems to allow adaptability of movements. The present study aimed to elucidate the role of nitric oxide (NO) in the modulation of mammalian spinal locomotor networks. This was investigated with isolated spinal cord preparations from neonatal mice in which rhythmic locomotor-related activity was induced pharmacologically. Bath application of the NO donor diethylamine NONOate (DEA/NO) decreased the frequency and modulated the amplitude of locomotor-related activity recorded from ventral roots. Removal of endogenous NO with coapplication of a NO scavenger (PTIO) and a nitric oxide synthase (NOS) blocker [nitro-l-arginine methyl ester (l-NAME)] increased the frequency and decreased the amplitude of locomotor-related activity. This demonstrates that endogenously derived NO can modulate both the timing and intensity of locomotor-related activity. The effects of DEA/NO were mimicked by the cGMP analog 8-bromo-cGMP. In addition, the soluble guanylyl cyclase (sGC) inhibitor ODQ blocked the effects of DEA/NO on burst amplitude and frequency, although the frequency effect was only blocked at low concentrations of DEA/NO. This suggests that NO-mediated modulation involves cGMP-dependent pathways. Sources of NO were studied within the lumbar spinal cord during postnatal development (postnatal days 1–12) with NADPH-diaphorase staining. NOS-positive cells in the ventral horn exhibited a rostrocaudal gradient, with more cells in rostral segments. The number of NOS-positive cells was also found to increase during postnatal development. In summary, we have shown that NO, derived from sources within the mammalian spinal cord, modulates the output of spinal motor networks and is therefore likely to contribute to the fine-tuning of locomotor behavior. PMID:24259545

Inhibition of α-amylase and glucoamylase by tannins extracted from cocoa, pomegranates, cranberries, and grapes.

PubMed

Barrett, Ann; Ndou, Tshinanne; Hughey, Christine A; Straut, Christine; Howell, Amy; Dai, Zifei; Kaletunc, Gonul

2013-02-20

Proanthocyanidins and ellagitannins, referred to as "tannins", exist in many plant sources. These compounds interact with proteins due to their numerous hydroxyl groups, which are suitable for hydrophobic associations. It was hypothesized that tannins could bind to the digestive enzymes α-amylase and glucoamylase, thereby inhibiting starch hydrolysis. Slowed starch digestion can theoretically increase satiety by modulating glucose "spiking" and depletion that occurs after carbohydrate-rich meals. Tannins were isolated from extracts of pomegranate, cranberry, grape, and cocoa and these isolates tested for effectiveness to inhibit the activity of α-amylase and glucoamylase in vitro. The compositions of the isolates were confirmed by NMR and LC/MS analysis, and tannin-protein interactions were investigated using relevant enzyme assays and differential scanning calorimetry (DSC). The results demonstrated inhibition of each enzyme by each tannin, but with variation in magnitude. In general, larger and more complex tannins, such as those in pomegranate and cranberry, more effectively inhibited the enzymes than did less polymerized cocoa tannins. Interaction of the tannins with the enzymes was confirmed through calorimetric measurements of changes in enzyme thermal stability.

Integrated optical isolators using magnetic surface plasmon (Presentation Recording)

NASA Astrophysics Data System (ADS)

Shimizu, Hiromasa; Kaihara, Terunori; Umetsu, Saori; Hosoda, Masashi

2015-09-01

Optical isolators are one of the essential components to protect semiconductor laser diodes (LDs) from backward reflected light in integrated optics. In order to realize optical isolators, nonreciprocal propagation of light is necessary, which can be realized by magnetic materials. Semiconductor optical isolators have been strongly desired on Si and III/V waveguides. We have developed semiconductor optical isolators based on nonreciprocal loss owing to transverse magneto-optic Kerr effect, where the ferromagnetic metals are deposited on semiconductor optical waveguides1). Use of surface plasmon polariton at the interface of ferromagnetic metal and insulator leads to stronger optical confinement and magneto-optic effect. It is possible to modulate the optical confinement by changing the magnetic field direction, thus optical isolator operation is proposed2, 3). We have investigated surface plasmons at the interfaces between ferrimagnetic garnet/gold film, and applications to waveguide optical isolators. We assumed waveguides composed of Au/Si(38.63nm)/Ce:YIG(1700nm)/Si(220nm)/Si , and calculated the coupling lengths between Au/Si(38.63nm)/Ce:YIG plasmonic waveguide and Ce:YIG/Si(220nm)/Si waveguide for transversely magnetized Ce:YIG with forward and backward directions. The coupling length was calculated to 232.1um for backward propagating light. On the other hand, the coupling was not complete, and the length was calculated to 175.5um. The optical isolation by using the nonreciprocal coupling and propagation loss was calculated to be 43.7dB when the length of plasmonic waveguide is 700um. 1) H. Shimizu et al., J. Lightwave Technol. 24, 38 (2006). 2) V. Zayets et al., Materials, 5, 857-871 (2012). 3) J. Montoya, et al, J. Appl. Phys. 106, 023108, (2009).

Study of curved glass photovoltaic module and module electrical isolation design requirements

NASA Technical Reports Server (NTRS)

1980-01-01

The design of a 1.2 by 2.4 m curved glass superstrate and support clip assembly is presented, along with the results of finite element computer analysis and a glass industry survey conducted to assess the technical and economic feasibility of the concept. Installed costs for four curved glass module array configurations are estimated and compared with cost previously reported for comparable flat glass module configurations. Electrical properties of candidate module encapsulation systems are evaluated along with present industry practice for the design and testing of electrical insulation systems. Electric design requirements for module encapsulation systems are also discussed.

Study of curved glass photovoltaic module and module electrical isolation design requirements

NASA Astrophysics Data System (ADS)

1980-06-01

The design of a 1.2 by 2.4 m curved glass superstrate and support clip assembly is presented, along with the results of finite element computer analysis and a glass industry survey conducted to assess the technical and economic feasibility of the concept. Installed costs for four curved glass module array configurations are estimated and compared with cost previously reported for comparable flat glass module configurations. Electrical properties of candidate module encapsulation systems are evaluated along with present industry practice for the design and testing of electrical insulation systems. Electric design requirements for module encapsulation systems are also discussed.

Shizukaol D, a Dimeric Sesquiterpene Isolated from Chloranthus serratus, Represses the Growth of Human Liver Cancer Cells by Modulating Wnt Signalling Pathway.

PubMed

Tang, Lisha; Zhu, Hengrui; Yang, Xianmei; Xie, Fang; Peng, Jingtao; Jiang, Deke; Xie, Jun; Qi, Meiyan; Yu, Long

2016-01-01

Natural products have become sources of developing new drugs for the treatment of cancer. To seek candidate compounds that inhibit the growth of liver cancer, components of Chloranthus serratus were tested. Here, we report that shizukaol D, a dimeric sesquiterpene from Chloranthus serratus, exerted a growth inhibition effect on liver cancer cells in a dose- and time-dependent manner. We demonstrated that shizukaol D induced cells to undergo apoptosis. More importantly, shizukaol D attenuated Wnt signalling and reduced the expression of endogenous Wnt target genes, which resulted in decreased expression of β-catenin. Collectively, this study demonstrated that shizukaol D inhibited the growth of liver cancer cells by modulating Wnt pathway.

Type II restriction modification system methylation subunit of Alicyclobacillus acidocaldarius

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

Lee, Brady D.; Newby, Deborah T.; Lacey, Jeffrey A.

2018-02-13

Isolated and/or purified polypeptides and nucleic acid sequences encoding polypeptides from Alicyclobacillus acidocaldarius are provided. Further provided are methods for modulating or altering recombination inside or outside of a cell using isolated and/or purified polypeptides and/or nucleic acid sequences from Alicyclobacillus acidocaldarius.

Type II restriction-modification system methylation subunit of Alicyclobacillus acidocaldarius

DOEpatents

Lee, Brady D; Newby, Deborah T; Lacey, Jeffrey A; Thompson, David N; Thompson, Vicki S; Apel, William A; Roberto, Francisco F; Reed, David W

2013-10-29

Isolated and/or purified polypeptides and nucleic acid sequences encoding polypeptides from Alicyclobacillus acidocaldarius are provided. Further provided are methods for modulating or altering recombination inside or outside of a cell using isolated and/or purified polypeptides and/or nucleic acid sequences from Alicyclobacillus acidocaldarius.

Type II restriction-modification system methylation subunit of Alicyclobacillus acidocaldarius

DOEpatents

Lee, Brady D; Newby, Deborah T; Lacey, Jeffrey A; Thompson, David N; Thompson, Vicki S; Apel, William A; Roberto, Francisco F; Reed, David W

2015-05-12

Isolated and/or purified polypeptides and nucleic acid sequences encoding polypeptides from Alicyclobacillus acidocaldarius are provided. Further provided are methods for modulating or altering recombination inside or outside of a cell using isolated and/or purified polypeptides and/or nucleic acid sequences from Alicyclobacillus acidocaldarius.

Type II restriction modification system methylation subunit of Alicyclobacillus acidocaldarius

DOEpatents

Lee, Brady D.; Newby, Deborah T.; Lacey, Jeffrey A.; Thompson, David N.; Thompson, Vicki S.; Apel, William A.; Roberto, Francisco F.; Reed, David W.

2017-02-14

Isolated and/or purified polypeptides and nucleic acid sequences encoding polypeptides from Alicyclobacillus acidocaldarius are provided. Further provided are methods for modulating or altering recombination inside or outside of a cell using isolated and/or purified polypeptides and/or nucleic acid sequences from Alicyclobacillus acidocaldarius.

Thermophilic and thermoacidophilic metabolism genes and enzymes from alicyclobacillus acidocaldarius and related organisms, methods

DOEpatents

Thompson, Vicki S.; Apel, William A.; Reed, David William; Lee, Brady D.; Thompson, David N.; Roberto, Francisco F.; Lacey, Jeffrey A.

2015-12-29

Isolated and/or purified polypeptides and nucleic acid sequences encoding polypeptides from Alicyclobacillus acidocaldarius are provided. Further provided are methods for modulating or altering metabolism in a cell using isolated and/or purified polypeptides and nucleic acid sequences from Alicyclobacillus acidocaldarius.

Thermophilic and thermoacidophilic metabolism genes and enzymes from Alicyclobacillus acidocaldarius and related organisms, methods

DOEpatents

Thompson, Vicki S; Apel, William A; Reed, David W; Lee, Brady D; Thompson, David N; Roberto, Francisco F; Lacey, Jeffrey A

2014-05-20

Isolated and/or purified polypeptides and nucleic acid sequences encoding polypeptides from Alicyclobacillus acidocaldarius are provided. Further provided are methods for modulating or altering metabolism in a cell using isolated and/or purified polypeptides and nucleic acid sequences from Alicyclobacillus acidocaldarius.

Thermophilic and thermoacidophilic metabolism genes and enzymes from Alicyclobacillus acidocaldarius and related organisms, methods

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

Thompson, Vicki S.; Apel, William A.; Lacey, Jeffrey A.

Isolated and/or purified polypeptides and nucleic acid sequences encoding polypeptides from Alicyclobacillus acidocaldarius are provided. Further provided are methods for modulating or altering metabolism in a cell using isolated and/or purified polypeptides and nucleic acid sequences from Alicyclobacillus acidocaldarius.

Osthole inhibits histamine-dependent itch via modulating TRPV1 activity.

PubMed

Yang, Niu-Niu; Shi, Hao; Yu, Guang; Wang, Chang-Ming; Zhu, Chan; Yang, Yan; Yuan, Xiao-Lin; Tang, Min; Wang, Zhong-Li; Gegen, Tana; He, Qian; Tang, Kehua; Lan, Lei; Wu, Guan-Yi; Tang, Zong-Xiang

2016-05-10

Osthole, an active coumarin isolated from Cnidium monnieri (L.) Cusson, has long been used in China as an antipruritic herbal medicine; however, the antipruitic mechanism of osthole is unknown. We studied the molecular mechanism of osthole in histamine-dependent itch by behavioral test, Ca(2+) imaging, and electrophysiological experiments. First, osthole clearly remitted the scratching behaviors of mice induced with histamine, HTMT, and VUF8430. Second, in cultured dorsal root ganglion (DRG) neurons, osthole showed a dose-dependent inhibitory effect to histamine. On the same neurons, osthole also decreased the response to capsaicin and histamine. In further tests, the capsaicin-induced inward currents were inhibited by osthole. These results revealed that osthole inhibited histamine-dependent itch by modulating TRPV1 activity. This study will be helpful in understanding how osthole exerts anti-pruritus effects and suggests that osthole may be a useful treatment medicine for histamine-dependent itch.

Osthole inhibits histamine-dependent itch via modulating TRPV1 activity

PubMed Central

Yang, Niu-Niu; Shi, Hao; Yu, Guang; Wang, Chang-Ming; Zhu, Chan; Yang, Yan; Yuan, Xiao-Lin; Tang, Min; Wang, Zhong-li; Gegen, Tana; He, Qian; Tang, Kehua; Lan, Lei; Wu, Guan-Yi; Tang, Zong-Xiang

2016-01-01

Osthole, an active coumarin isolated from Cnidium monnieri (L.) Cusson, has long been used in China as an antipruritic herbal medicine; however, the antipruitic mechanism of osthole is unknown. We studied the molecular mechanism of osthole in histamine-dependent itch by behavioral test, Ca2+ imaging, and electrophysiological experiments. First, osthole clearly remitted the scratching behaviors of mice induced with histamine, HTMT, and VUF8430. Second, in cultured dorsal root ganglion (DRG) neurons, osthole showed a dose-dependent inhibitory effect to histamine. On the same neurons, osthole also decreased the response to capsaicin and histamine. In further tests, the capsaicin-induced inward currents were inhibited by osthole. These results revealed that osthole inhibited histamine-dependent itch by modulating TRPV1 activity. This study will be helpful in understanding how osthole exerts anti-pruritus effects and suggests that osthole may be a useful treatment medicine for histamine-dependent itch. PMID:27160770

A protein isolated from human oviductal tissue in vitro secretion, identified as human lactoferrin, interacts with spermatozoa and oocytes and modulates gamete interaction.

PubMed

Zumoffen, C M; Gil, R; Caille, A M; Morente, C; Munuce, M J; Ghersevich, S A

2013-05-01

Is lactoferrin (LF) (detected in oviductal secretion) able to bind to oocytes and sperm and modulate gamete interaction? LF binds to zona pellucida (ZP) and spermatozoa (depending upon the capacitation stage and acrosome status) and inhibits gamete interaction in vitro. Proteins from human oviductal tissue secretion modulate gamete interaction and parameters of sperm function in vitro and some of them bind to sperm, but they remain to be isolated and identified. Proteins were isolated from human oviductal tissue secretion using their sperm membrane binding ability. One of the isolated proteins was identified as human LF and immunolocalized in tubal tissues. LF expression was analyzed in native oviductal fluid and oviduct epithelial cells (at different phases of the menstrual cycle: proliferative, periovulatory and secretory). In addition, the LF binding sites on spermatozoa (at different capacitation and acrosome reaction stages) and on ZP and the dose-dependent effect of LF on gamete interaction were investigated. All experiments were performed at least three times. Tubal tissues obtained from premenopausal patients (scheduled for hysterectomy, n = 23) were cultured in DMEM/Ham's F12 medium and conditioned media (CM) were collected. Motile spermatozoa were obtained by swim-up from normozoospermic semen samples from healthy donors (n = 4). An affinity chromatography with sperm membrane extracts was used to isolate proteins from CM. Isolated proteins were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophresis and further identified by nano liquid chromatography tandem mass spectrometry peptide sequencing. The presence of LF in oviductal tissue was investigated by immunohistochemistry and immunofluorescence and was detected in native oviductal fluid and oviduct epithelial cells homogenates by western blot. LF binding sites on gametes were investigated by incubating gametes with the protein coupled to fluorescein isothiocyanate (FITC). The acrosome reaction was assessed with Pisum sativum agglutinin conjugated with rhodamine. The effect of increasing concentrations of LF (0.1-100 µg/ml) on gamete interaction was evaluated by a sperm-ZP binding assay, using human oocytes donated by women undergoing IVF procedures. A protein isolated by the affinity column was identified as human LF. LF was immunolocalized in human oviductal tissue and detected in oviductal fluid and oviduct epithelial cell homogenates. In the latter case, LF expression was highest at the periovulatory phase of the menstrual cycle (P < 0.01). Different LF binding patterns were observed on spermatozoa depending upon capacitation stage and if the acrosome reaction had occurred. Unstained sperm were most prevalent before capacitation, but after incubation for 6 h under capacitating conditions and in acrosome-reacted sperm LF binding was observed, mainly localized in the equatorial segment and post-acrosomal region of the sperm head. LF binding studies on ZP showed homogenous staining. LF caused a dose-dependent significant inhibition of sperm-ZP interaction, and the effect was already significant (P < 0.01) with the lowest LF concentration used. This study has investigated the effect of LF only on human gamete interaction in vitro and thus has some limitations. Further investigations of the potential mechanisms involved in LF action both on gamete function in vitro and in vivo in animal models are needed to confirm the role of this protein in the reproductive process. The present data indicate that human oviductal LF expression is cycle dependent and inhibited gamete interaction in vitro. No previous data were available about potential direct effects of LF on gamete interaction. It could be thought that the protein is involved in the regulation of the reproductive process, perhaps contributing to prevent polyspermy. Thus, further research is needed to clarify the potential role of LF in the regulation of the fertilization process. This study was supported by grants from FONCYT (PICT 01095, S.A.G., M.J.M) and SECyT UNR (PIDBIO238, S.A.G). The authors have no conflict of interest to declare.

In Vitro Activities of Iboga Alkaloid Congeners Coronaridine and 18-Methoxycoronaridine against Leishmania amazonensis

PubMed Central

Delorenzi, Jan Carlo; Freire-de-Lima, Leonardo; Gattass, Cerli R.; de Andrade Costa, Deise; He, Liwen; Kuehne, Martin E.; Saraiva, Elvira M. B.

2002-01-01

In previous studies, we demonstrated the leishmanicide effect of coronaridine, a natural indole alkaloid isolated from stem bark of Peschiera australis (Delorenzi et al., Antimicrob. Agents Chemother. 45:1349-1354, 2001). In this study we show the leishmanicidal effect of the synthetic coronaridine and its racemic 18-methoxylated analog, 18-methoxycoronaridine. Both alkaloids revealed a potent leishmanicide effect against Leishmania amazonensis, a causative agent of cutaneous and diffuse cutaneous leishmaniasis in the New World. Despite their potent leishmanicide effect, both alkaloids were neither toxic to murine macrophages nor did they modulate their oxidative or cytokine production responses. PMID:12069962

Anti-inflammatory activity of p-coumaryl alcohol-γ-O-methyl ether is mediated through modulation of interferon-γ production in Th cells

PubMed Central

Yu, E-S; Min, H-J; Lee, K; Lee, M-S; Nam, J-W; Seo, E-K; Hong, J-H; Hwang, E-S

2009-01-01

Background and purpose: p-Coumaryl alcohol-γ-O-methyl ether (CAME) was isolated from Alpinia galanga and shown to contain a phenylpropanoid structure similar to p-coumaryl diacetate (CDA). CDA is known to have antioxidant and anti-inflammatory activity, but the biochemical activities of CAME are unknown. Inflammation is mediated by inflammatory cytokine production, in particular, by CD4+ T helper cells (Th cells), but it is unclear whether phenylpropanoids affect cytokine production in Th cells. In this study, we decided to investigate the functions of CAME and CDA in CD4+ Th cells. Experimental approach: Mouse CD4+ Th cells were isolated from C57BL6 mice and stimulated with an antibody against T cell receptors in the presence of phenylpropanoids. Cytokine production was measured by elisa and intracellular cytokine staining. Gene knockout mice and tetracycline-inducible transgenic mice were used to examine the molecular mechanisms of phenylpropanoids on modulation of cytokine production. Key results: CAME potently reduced intracellular reactive oxygen species in Th cells, as does CDA. However, although CDA was cytotoxic, CAME selectively and potently suppresses interferon-γ (IFNγ) production in CD4+ Th cells, without toxicity. This effect was caused by attenuated expression of the transcription factor, T-box protein expressed in T cells (T-bet), and T-bet was essential for CAME to inhibit IFNγ production in CD4+ Th cells. Conclusions and implications: CAME selectively and substantially suppresses IFNγ production in CD4+ Th cells by decreasing T-bet expression. As increased IFNγ production by CD4+ Th cells can mediate inflammatory immune responses, a selective IFNγ suppressor, such as CAME may be an effective, naturally occurring, compound for modulating inflammatory immune disorders. PMID:19226286

Neurotransmitter modulation of extracellular H+ fluxes from isolated retinal horizontal cells of the skate

PubMed Central

Molina, Anthony J A; Verzi, Michael P; Birnbaum, Andrea D; Yamoah, Ebenezer N; Hammar, Katherine; Smith, Peter J S; Malchow, Robert Paul

2004-01-01

Self-referencing H+-selective microelectrodes were used to measure extracellular H+ fluxes from horizontal cells isolated from the skate retina. A standing H+ flux was detected from quiescent cells, indicating a higher concentration of free hydrogen ions near the extracellular surface of the cell as compared to the surrounding solution. The standing H+ flux was reduced by removal of extracellular sodium or application of 5-(N-ethyl-N-isopropyl) amiloride (EIPA), suggesting activity of a Na+–H+ exchanger. Glutamate decreased H+ flux, lowering the concentration of free hydrogen ions around the cell. AMPA/kainate receptor agonists mimicked the response, and the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) eliminated the effects of glutamate and kainate. Metabotropic glutamate agonists were without effect. Glutamate-induced alterations in H+ flux required extracellular calcium, and were abolished when cells were bathed in an alkaline Ringer solution. Increasing intracellular calcium by photolysis of the caged calcium compound NP-EGTA also altered extracellular H+ flux. Immunocytochemical localization of the plasmalemma Ca2+–H+-ATPase (PMCA pump) revealed intense labelling within the outer plexiform layer and on isolated horizontal cells. Our results suggest that glutamate modulation of H+ flux arises from calcium entry into cells with subsequent activation of the plasmalemma Ca2+–H+-ATPase. These neurotransmitter-induced changes in extracellular pH have the potential to play a modulatory role in synaptic processing in the outer retina. However, our findings argue against the hypothesis that hydrogen ions released by horizontal cells normally act as the inhibitory feedback neurotransmitter onto photoreceptor synaptic terminals to create the surround portion of the centre-surround receptive fields of retinal neurones. PMID:15272044

NS309 decreases rat detrusor smooth muscle membrane potential and phasic contractions by activating SK3 channels

PubMed Central

Parajuli, Shankar P; Hristov, Kiril L; Soder, Rupal P; Kellett, Whitney F; Petkov, Georgi V

2013-01-01

Background and Purpose Overactive bladder (OAB) is often associated with abnormally increased detrusor smooth muscle (DSM) contractions. We used NS309, a selective and potent opener of the small or intermediate conductance Ca2+-activated K+ (SK or IK, respectively) channels, to evaluate how SK/IK channel activation modulates DSM function. Experimental Approach We employed single-cell RT-PCR, immunocytochemistry, whole cell patch-clamp in freshly isolated rat DSM cells and isometric tension recordings of isolated DSM strips to explore how the pharmacological activation of SK/IK channels with NS309 modulates DSM function. Key Results We detected SK3 but not SK1, SK2 or IK channels expression at both mRNA and protein levels by RT-PCR and immunocytochemistry in DSM single cells. NS309 (10 μM) significantly increased the whole cell SK currents and hyperpolarized DSM cell resting membrane potential. The NS309 hyperpolarizing effect was blocked by apamin, a selective SK channel inhibitor. NS309 inhibited the spontaneous phasic contraction amplitude, force, frequency, duration and tone of isolated DSM strips in a concentration-dependent manner. The inhibitory effect of NS309 on spontaneous phasic contractions was blocked by apamin but not by TRAM-34, indicating no functional role of the IK channels in rat DSM. NS309 also significantly inhibited the pharmacologically and electrical field stimulation-induced DSM contractions. Conclusions and Implications Our data reveal that SK3 channel is the main SK/IK subtype in rat DSM. Pharmacological activation of SK3 channels with NS309 decreases rat DSM cell excitability and contractility, suggesting that SK3 channels might be potential therapeutic targets to control OAB associated with detrusor overactivity. PMID:23145946

Negative Inotropic Effects of High Mobility Box Group 1 Protein in Isolated Contracting Cardiac Myocytes

PubMed Central

Tzeng, Huei-Ping; Fan, Jinping; Vallejo, Jesus G.; Dong, Jian Wen; Chen, Xiongwen; Houser, Steven R.; Mann, Douglas L.

2013-01-01

HMGB1 released from necrotic cells or macrophages functions as a late inflammatory mediator, and has been shown to induce cardiovascular collapse during sepsis. Thus far, however, the effect(s) of HMGB1 in the heart are not known. We determined the effects of HMGB1 on isolated feline cardiac myocytes by measuring sarcomere shortening in contracting cardiac myocytes, intracellular Ca2+ transients using fluo-3, and L-type calcium currents using whole cell perforate configuration of the patch clamp technique. Treatment of isolated myocytes with HMGB1 (100 ng/ml) resulted in a 70% decrease in sarcomere shortening and a 50% decrease in the height of the peak Ca++ transient within 5 min (p <0.01). The immediate negative inotropic effects HMGB1 on cell contractility and calcium homeostasis were partially reversible upon washout of HMGB1. A significant inhibition of the inward L-type calcium currents also was documented by the patch clamp technique. HMGB1 induced the PKCε translocation and a PKC inhibitor significantly attenuated the negative inotropic effects of HMGB1. These studies show for the first time that HMGB1 impairs sarcomere shortening by decreasing calcium availability in cardiac myocytes through modulating membrane calcium influx, and suggest that HMGB1 maybe act as a novel myocardial depressant factor during cardiac injury. PMID:18223193

Fluid Properties Measurements Using Wavelength Modulation Spectroscopy with First Harmonic Detection

NASA Technical Reports Server (NTRS)

Silver, Joel A. (Inventor); Chen, Shin-Juh (Inventor)

2014-01-01

An apparatus and method for monitoring gas velocity, temperature, and pressure in combustion systems and flow devices, in particular at inlets and isolators of scramjet engines. The invention employs wavelength modulation spectroscopy with first harmonic detection and without the need to scan the full absorption spectra.

Chronic social isolation and chronic variable stress during early development induce later elevated ethanol intake in adult C57BL/6J mice.

PubMed

Lopez, Marcelo F; Doremus-Fitzwater, Tamara L; Becker, Howard C

2011-06-01

Experience with stress situations during early development can have long-lasting effects on stress- and anxiety-related behaviors. Importantly, this can also favor drug self-administration. These studies examined the effects of chronic social isolation and/or variable stress experiences during early development on subsequent voluntary ethanol intake in adult male and female C57BL/6J mice. The experiments were conducted to evaluate the effect of chronic isolation between weaning and adulthood (Experiment 1), chronic isolation during adulthood (Experiment 2), and chronic variable stress (CVS) alone or in combination with chronic social isolation between weaning and adulthood (Experiment 3) on subsequent voluntary ethanol intake. Mice were born in our facility and were separated into two housing conditions: isolate housed (one mouse/cage) or group housed (four mice/cage) according to sex. Separate groups were isolated for 40 days starting either at time of weaning postnatal day 21 (PD 21) (early isolation, Experiments 1 and 3) or at adulthood (PD 60: late isolation, Experiment 2). The effects of housing condition on subsequent ethanol intake were assessed starting at around PD 65 in Experiments 1 and 3 or PD 105 days in Experiment 2. In Experiment 3, starting at PD 32, isolate-housed and group-housed mice were either subjected to CVS or left undisturbed. CVS groups experienced random presentations of mild stressors for 14 days, including exposure to an unfamiliar open field, restraint, physical shaking, and forced swim, among others. All mice were tested for ethanol intake for 14 days using a two-bottle choice (ethanol 15% vol/vol vs. water) for a 2-h limited access procedure. Early social isolation resulted in greater ethanol intake compared with the corresponding group-housed mice (Experiment 1). In contrast, social isolation during adulthood (late isolation) did not increase subsequent ethanol intake compared with the corresponding group-housed mice (Experiment 2). For mice that did not experience CVS, early social isolation resulted in greater ethanol intake compared with group-housed mice (Experiment 3). CVS subsequently resulted in a significant increase in ethanol intake in group-housed mice, but CVS failed to further increase ethanol intake in mice that experienced chronic social isolation early in life (Experiment 3). Overall, female mice consumed more ethanol than males, whether isolated (early or late) or group housed. These results indicate that early but not late social isolation can subsequently influence ethanol consumption in C57BL/6J mice. Thus, the developmental timing of chronic social isolation appears to be an important factor in defining later effects on ethanol self-administration behavior. In addition, experience with CVS early in life results in elevated ethanol intake later in adulthood. Taken together, these results emphasize the important role of early stress experiences that modulate later voluntary ethanol intake during adulthood. Copyright © 2011 Elsevier Inc. All rights reserved.

The International Society for Extracellular Vesicles launches the first massive open online course on extracellular vesicles.

PubMed

Lässer, Cecilia; Théry, Clotilde; Buzás, Edit I; Mathivanan, Suresh; Zhao, Weian; Gho, Yong Song; Lötvall, Jan

2016-01-01

The International Society for Extracellular Vesicles (ISEV) has organised its first educational online course for students and beginners in the field of extracellular vesicles (EVs). This course, "Basics of Extracellular Vesicles," uses recorded lectures from experts in the field and will be open for an unlimited number of participants. The course is divided into 5 modules and can be accessed at www.coursera.org/learn/extracellular-vesicles. The first module is an introduction to the field covering the nomenclature and history of EVs. Module 2 focuses on the biogenesis and uptake mechanisms of EVs, as well as their RNA, protein and lipid cargo. Module 3 covers the collection and processing of cell culture media and body fluids such as blood, breast milk, cerebrospinal fluid and urine prior to isolation of EVs. Modules 4 and 5 present different isolation methods and characterisation techniques utilised in the EV field. Here, differential ultracentrifugation, size-exclusion chromatography, density gradient centrifugation, kit-based precipitation, electron microscopy, cryo-electron microscopy, flow cytometry, atomic-force microscopy and nanoparticle-tracking analysis are covered. This first massive open online course (MOOC) on EVs was launched on 15 August 2016 at the platform "Coursera" and is free of charge.

Jack bean (Canavalia ensiformis) urease induces eicosanoid-modulated hemocyte aggregation in the Chagas' disease vector Rhodnius prolixus.

PubMed

Defferrari, M S; da Silva, R; Orchard, I; Carlini, C R

2014-05-01

Ureases are multifunctional proteins that display biological activities independently of their enzymatic function, such as induction of exocytosis and insecticidal effects. Rhodnius prolixus, a major vector of Chagas' disease, is a model for studies on the entomotoxicity of jack bean urease (JBU). We have previously shown that JBU induces the production of eicosanoids in isolated tissues of R. prolixus. In insects, the immune response comprises cellular and humoral reactions, and is centrally modulated by eicosanoids. Cyclooxygenase products signal immunity in insects, mainly cellular reactions, such as hemocyte aggregation. In searching for a link between JBU's toxic effects and immune reactions in insects, we have studied the effects of this toxin on R. prolixus hemocytes. JBU triggers aggregation of hemocytes after injection into the hemocoel and when applied to isolated cells. On in vitro assays, the eicosanoid synthesis inhibitors dexamethasone (phospholipase A2 indirect inhibitor) and indomethacin (cyclooxygenase inhibitor) counteracted JBU's effect, indicating that eicosanoids, more specifically cyclooxygenase products, are likely to mediate the aggregation response. Contrarily, the inhibitors esculetin and baicalein were inactive, suggesting that lipoxygenase products are not involved in JBU's effect. Extracellular calcium was also necessary for JBU's effect, in agreement to other cell models responsive to ureases. A progressive darkening of the medium of JBU-treated hemocytes was observed, suggestive of a humoral response. JBU was immunolocalized in the cultured cells upon treatment along with cytoskeleton damage. The highest concentration of JBU tested on cultured cells also led to nuclei aggregation of adherent hemocytes. This is the first time urease has been shown to affect insect hemocytes, contributing to our understanding of the entomotoxic mechanisms of action of this protein. Copyright © 2014 Elsevier Ltd. All rights reserved.

In vivo treatment by diallyl disulfide increases histone acetylation in rat colonocytes

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

Druesne-Pecollo, Nathalie; Chaumontet, Catherine; Pagniez, Anthony

2007-03-02

Diallyl disulfide (DADS) is an organosulfur compound from garlic which exhibits various anticarcinogenic properties including inhibition of tumor cell proliferation. DADS antiproliferative effects were previously associated with an increase in histone acetylation in two human tumor colon cell lines, suggesting that DADS-induced histone hyperacetylation could be one of the mechanisms involved in its protective properties on colon carcinogenesis. The effects of DADS on histone H4 and H3 acetylation levels were investigated in vivo in colonocytes isolated from non-tumoral rat. Administrated by intracaecal perfusion or gavage, DADS increases histone H4 and H3 acetylation in colonocytes. Moreover, data generated using cDNA expressionmore » arrays suggest that DADS could modulate the expression of a subset of genes. These results suggest the involvement of histone acetylation in modulation of gene expression by DADS in normal rat colonocytes, which might play a role in its biological effects as well as in its anticarcinogenic properties in vivo.« less

Six Month Report on Tissue Cultured Avian Skeletal Myofibers in the STL/A Module Aboard STS-77

NASA Technical Reports Server (NTRS)

Vandenburgh, Herman H.

1997-01-01

Space travel is know to effect skeletal muscle, causing rapid and pronounced atrophy in humans and animals, even when strenuous exercise is used as a countermeasure. The cellular and molecular bases of this atrophy are unknown. Space travel may cause muscle atrophy by a direct effect on the muscle fibers and/or indirectly by reducing circulating levels of growth factors such as growth hormone. The recent development of a tissue culture incubator system for Shuttle Middeck basic science experiments [Space Tissue Loss (STL) Module] by the Walter Reed Army Institute of Research (WRAIR) allows the study of the effects of space travel directly on isolated skeletal myofibers. Avian bioartificial skeletal muscle 'organoids' containing differentiated skeletal myofibers and connective tissue fibroblasts were flown aboard the Space Shuttle (Space Transportation System, STS) on Flight STS-77, a repeat of a similar experiment flown on STS-66. The results from these two flight experiments show for the first time that space travel has a direct effect on skeletal muscle cells separate from any systemic effects resulting from altered circulating growth factors.

Pharmacological comparison of the effect of ibogaine and 18-methoxycoronaridine on isolated smooth muscle from the rat and guinea-pig.

PubMed

Mundey, M K; Blaylock, N A; Mason, R; Glick, S D; Maisonneuve, I M; Wilson, V G

2000-04-01

Ibogaine and 18-methoxycoronaridine are naturally occurring alkaloids reported to possess antiaddictive properties in several models of drug dependence. We have examined their effect at mu-opioid receptors regulating neurogenic contractions of several smooth muscle preparations and also against spontaneous contractions of the rat isolated portal vein. Ibogaine (pIC(50) 5.28) and 18-methoxycoronaridine (pIC(50) 5.05) caused a concentration-dependent inhibition of cholinergic contractions of the guinea-pig ileum which was not affected by the opioid receptor antagonist naloxone (1 microM). In the rat isolated vas deferens ibogaine and 18-methoxycoronaridine caused a concentration-dependent enhancement of purinergic contractions. Both agents (30 microM) caused a 3 - 5 fold rightward displacement of DAMGO-induced inhibition of purinergic contractions, but similar effects were observed for ibogaine against alpha(2)-adrenoceptor-mediated inhibition of neurogenic responses. In the guinea-pig isolated bladder both ibogaine (10 microM) and 18-methoxycoronaridine (10 microM) caused a 2 fold increase in the purinergic component of neurogenic contractions without significantly altering cholinergic contractions or responses to exogenous ATP. In contrast, ibogaine (1 - 30 microM), but not 18-methoxycoronaridine, caused a concentration-dependent enhancement of spontaneous contractions of the rat isolated portal vein. In summary, while ibogaine and 18-methoxycoronaridine modulated electrically-evoked contractions in the three preparations examined, we have no evidence for a selective interaction with pre-junctional mu-opioid receptors. The pronounced enhancement of purinergic contractions produced by both agents is a novel finding and worthy of further investigation.

A high-resolution thermoelectric module-based calorimeter for measuring the energetics of isolated ventricular trabeculae at body temperature.

PubMed

Johnston, Callum M; Han, June-Chiew; Ruddy, Bryan P; Nielsen, Poul M F; Taberner, Andrew J

2015-07-15

Isolated ventricular trabeculae are the most common experimental preparations used in the study of cardiac energetics. However, the experiments have been conducted at subphysiological temperatures. We have overcome this limitation by designing and constructing a novel calorimeter with sufficiently high thermal resolution for simultaneously measuring the heat output and force production of isolated, contracting, ventricular trabeculae at body temperature. This development was largely motivated by the need to better understand cardiac energetics by performing such measurements at body temperature to relate tissue performance to whole heart behavior in vivo. Our approach uses solid-state thermoelectric modules, tailored for both temperature sensing and temperature control. The thermoelectric modules have high sensitivity and low noise, which, when coupled with a multilevel temperature control system, enable an exceptionally high temperature resolution with a noise-equivalent power an order of magnitude greater than those of other existing muscle calorimeters. Our system allows us to rapidly and easily change the experimental temperature without disturbing the state of the muscle. Our calorimeter is useful in many experiments that explore the energetics of normal physiology as well as pathophysiology of cardiac muscle. Copyright © 2015 the American Physiological Society.

T Cell Stimulatory Effects of Korean Red Ginseng through Modulation of Myeloid-Derived Suppressor Cells.

PubMed

Jeon, Chanoh; Kang, Soowon; Park, Seungbeom; Lim, Kyungtaek; Hwang, Kwang Woo; Min, Hyeyoung

2011-11-01

Myeloid-derived suppressor cells (MDSCs) actively suppress immune cells and have been considered as an impediment to successful cancer immunotherapy. Many approaches have been made to overcome such immunosuppressive factors and to exert effective anti-tumor effects, but the possibility of using medicinal plants for this purpose has been overlooked. Korean red ginseng (KRG) is widely known to possess a variety of pharmacological properties, including immunoboosting and anti-tumor activities. However, little has been done to assess the anti-tumor activity of KRG on MDSCs. Therefore, we examined the effects of KRG on MDSCs in tumor-bearing mice and evaluated immunostimulatory and anti-tumor activities of KRG through MDSC modulation. The data show that intraperitoneal administration of KRG compromises MDSC function and induces T cell proliferation and the secretion of IL-2 and IFN-γ, while it does not exhibit direct cytotoxicity on tumor cells and reduced MDSC accumulation. MDSCs isolated from KRG-treated mice also express significantly lower levels of inducible nitric oxide synthase and IL-10 accompanied by a decrease in nitric oxide production compared with control. Taken together, the present study demonstrates that KRG enhances T cell function by inhibiting the immunosuppressive activity of MDSCs and suggests that although KRG alone does not exhibit direct anti-tumor effects, the use of KRG together with conventional chemo- or immunotherapy may provide better outcomes to cancer patients through MDSC modulation.

Spacelab flight simulated by two monkeys at CERMA

NASA Technical Reports Server (NTRS)

Langereux, P.

1980-01-01

A semiautomatic module for two monkeys was designed. The module shelters two Rhesus monkeys seated side by side in a compartment, reducing the emotional stresses caused by isolation. Food pellets, water, and air are supplied and body wastes are automatically removed. Physiological and environmental parameters are continually monitored, making possible the performance of experiments concerning the pathophysiological mechanisms of the disorders of weightlessness. A ten day flight of the module in Spacelab was simulated.

G-protein βγ subunits in vasorelaxing and anti-endothelinergic effects of calcitonin gene-related peptide.

PubMed

Meens, M J P M T; Mattheij, N J A; van Loenen, P B; Spijkers, L J A; Lemkens, P; Nelissen, J; Compeer, M G; Alewijnse, A E; De Mey, J G R

2012-05-01

Calcitonin gene-related peptide (CGRP) has been proposed to relax vascular smooth muscle cells (VSMC) via cAMP and can promote dissociation of endothelin-1 (ET-1) from ET(A) receptors. The latter is not mimicked by other stimuli of adenylate cyclases. Therefore, we evaluated the involvement of G-protein βγ subunits (Gβγ) in the arterial effects of CGRP receptor stimulation. To test the hypothesis that instead of α subunits of G-proteins (Gαs), Gβγ mediates the effects of CGRP receptor activation, we used (i) rat isolated mesenteric resistance arteries (MRA), (ii) pharmacological modulators of cyclic nucleotides; and (iii) low molecular weight inhibitors of the functions of Gβγ, gallein and M119. To validate these tools with respect to CGRP receptor function, we performed organ bath studies with rat isolated MRA, radioligand binding on membranes from CHO cells expressing human CGRP receptors and cAMP production assays in rat cultured VSMC. In isolated arteries contracted with K(+) or ET-1, IBMX (PDE inhibitor) increased sodium nitroprusside (SNP)- and isoprenaline (ISO)- but not CGRP-induced relaxations. While fluorescein (negative control) was without effects, gallein increased binding of [(125) I]-CGRP in the absence and presence of GTPγS. Gallein also increased CGRP-induced cAMP production in VSMC. Despite these stimulating effects, gallein and M119 selectively inhibited the relaxing and anti-endothelinergic effects of CGRP in isolated arteries while not altering contractile responses to K(+) or ET-1 or relaxing responses to ISO or SNP. Activated CGRP receptors induce cyclic nucleotide-independent relaxation of VSMC and terminate arterial effects of ET-1 via Gβγ. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Isolated and modulated effects of topology and material type on the mechanical properties of additively manufactured porous biomaterials.

PubMed

Hedayati, R; Ahmadi, S M; Lietaert, K; Pouran, B; Li, Y; Weinans, H; Rans, C D; Zadpoor, A A

2018-03-01

In this study, we tried to quantify the isolated and modulated effects of topological design and material type on the mechanical properties of AM porous biomaterials. Towards this aim, we assembled a large dataset comprising the mechanical properties of AM porous biomaterials with different topological designs (i.e. different unit cell types and relative densities) and material types. Porous structures were additively manufactured from Co-Cr using a selective laser melting (SLM) machine and tested under quasi-static compression. The normalized mechanical properties obtained from those structures were compared with mechanical properties available from our previous studies for porous structures made from Ti-6Al-4V and pure titanium as well as with analytical solutions. The normalized values of elastic modulus and yield stress were found to be relatively close to each other as well as in agreement with analytical solutions regardless of material type. However, the material type was found to systematically affect the mechanical properties of AM porous biomaterials in general and the post-elastic/post-yield range (plateau stress and energy absorption capacity) in particular. To put this in perspective, topological design could cause up to 10-fold difference in the mechanical properties of AM porous biomaterials while up to 2-fold difference was observed as a consequence of changing the material type. Copyright © 2017 Elsevier Ltd. All rights reserved.

Collaborative remembering revisited: Study context access modulates collaborative inhibition and later benefits for individual memory.

PubMed

Abel, Magdalena; Bäuml, Karl-Heinz T

2017-11-01

Collaborating groups typically show reduced recall relative to nominal groups, i.e., to the cumulated non-redundant recall of the same number of people remembering in isolation-a finding termed collaborative inhibition. Motivated by the results of several previous studies, this study examined in two experiments whether access to study context at test influences the effects of collaboration. In both experiments, subjects collaborated in triads or recalled previously studied material in isolation. Experiment 1 applied short versus prolonged retention intervals to vary access to study context at test, whereas Experiment 2 used the list-method directed forgetting task and applied remember versus forget instructions to modulate context access. In both experiments, collaborative inhibition was present when access to study context at test was intact (i.e., after the short delay and the remember instruction) but was eliminated when the access was impaired (i.e., after the prolonged delay and the forget instruction). Also, post-collaborative gains for individual recall were greater when context access was impaired and collaborative inhibition was eliminated. The findings demonstrate a critical role of access to study context at test for collaborative inhibition, indicating that impaired context access may reflect a general boundary condition for the recall impairment. The possible role of context reactivation processes for beneficial effects of social recall is discussed.

Development of a High Fidelity Dynamic Module of the Advanced Resistive Exercise Device (ARED) Using Adams

NASA Technical Reports Server (NTRS)

Humphreys, B. T.; Thompson, W. K.; Lewandowski, B. E.; Cadwell, E. E.; Newby, N. J.; Fincke, R. S.; Sheehan, C.; Mulugeta, L.

2012-01-01

NASA's Digital Astronaut Project (DAP) implements well-vetted computational models to predict and assess spaceflight health and performance risks, and enhance countermeasure development. DAP provides expertise and computation tools to its research customers for model development, integration, or analysis. DAP is currently supporting the NASA Exercise Physiology and Countermeasures (ExPC) project by integrating their biomechanical models of specific exercise movements with dynamic models of the devices on which the exercises were performed. This presentation focuses on the development of a high fidelity dynamic module of the Advanced Resistive Exercise Device (ARED) on board the ISS. The ARED module, illustrated in the figure below, was developed using the Adams (MSC Santa Ana, California) simulation package. The Adams package provides the capabilities to perform multi rigid body, flexible body, and mixed dynamic analyses of complex mechanisms. These capabilities were applied to accurately simulate: Inertial and mass properties of the device such as the vibration isolation system (VIS) effects and other ARED components, Non-linear joint friction effects, The gas law dynamics of the vacuum cylinders and VIS components using custom written differential state equations, The ARED flywheel dynamics, including torque limiting clutch. Design data from the JSC ARED Engineering team was utilized in developing the model. This included solid modeling geometry files, component/system specifications, engineering reports and available data sets. The Adams ARED module is importable into LifeMOD (Life Modeler, Inc., San Clemente, CA) for biomechanical analyses of different resistive exercises such as squat and dead-lift. Using motion capture data from ground test subjects, the ExPC developed biomechanical exercise models in LifeMOD. The Adams ARED device module was then integrated with the exercise subject model into one integrated dynamic model. This presentation will describe the development of the Adams ARED module including its capabilities, limitations, and assumptions. Preliminary results, validation activities, and a practical application of the module to inform the relative effect of the flywheels on exercise will be discussed.

Multiple Mutations Modulate the Function of Dihydrofolate Reductase in Trimethoprim-Resistant Streptococcus pneumoniae

PubMed Central

Maskell, Jeffrey P.; Sefton, Armine M.; Hall, Lucinda M. C.

2001-01-01

Trimethoprim resistance in Streptococcus pneumoniae can be conferred by a single amino acid substitution (I100-L) in dihydrofolate reductase (DHFR), but resistant clinical isolates usually carry multiple DHFR mutations. DHFR genes from five trimethoprim-resistant isolates from the United Kingdom were compared to susceptible isolates and used to transform a susceptible control strain (CP1015). All trimethoprim-resistant isolates and transformants contained the I100-L mutation. The properties of DHFRs from transformants with different combinations of mutations were compared. In a transformant with only the I100-L mutation (R12/T2) and a D92-A mutation also found in the DHFRs of susceptible isolates, the enzyme was much more resistant to trimethoprim inhibition (50% inhibitory concentration [IC50], 4.2 μM) than was the DHFR from strain CP1015 (IC50, 0.09 μM). However, Km values indicated a lower affinity for the enzyme's natural substrates (Km for dihydrofolate [DHF], 3.1 μM for CP1015 and 27.5 μM for R12/T2) and a twofold decrease in the specificity constant. In transformants with additional mutations in the C-terminal portion of the enzyme, Km values for DHF were reduced (9.2 to 15.2 μM), indicating compensation for the lower affinity generated by I100-L. Additional mutations in the N-terminal portion of the enzyme were associated with up to threefold-increased resistance to trimethoprim (IC50 of up to 13.7 μM). It is postulated that carriage of the mutation M53-I—which, like I100-L, corresponds to a trimethoprim binding site in the Escherichia coli DHFR—is responsible for this increase. This study demonstrates that although the I100-L mutation alone may give rise to trimethoprim resistance, additional mutations serve to enhance resistance and modulate the effects of existing mutations on the affinity of DHFR for its natural substrates. PMID:11257022

Design and operating experience of a 40 MW, highly-stabilized power supply

NASA Astrophysics Data System (ADS)

Boenig, Heinrich J.; Ferner, James A.; Bogdan, Ferenc; Morris, Gary C.; Rumrill, Ron S.

Four 10 MW, highly-stabilized power supply modules have been installed at the National High Magnetic Field Laboratory in Tallahassee, FL, to energize water-cooled, resistive, high-field research magnets. The power supply modules achieve a long term current stability if 10 ppM over a 12 h period with a short term ripple and noise variation of less than 10 ppM over a time period of one cycle. The power supply modules can operate independently, feeding four separate magnets, or two, three or four modules can operate in parallel. Each power supply module consists of a 12.5 kV vacuum circuit breaker, two three-winding, step-down transformers, a 24-pulse rectifier with interphase reactors, and a passive and an active filter. Two different transformer tap settings allow rated dc supply output voltages of 400 and 500 V. The rated current of a supply module is 17 kA and each supply module has a one-hour overload capability of 20 kA. The isolated output terminals of each power supply module are connected to a reversing switch. An extensive high-current bus system allows the modules to be connected to 16 magnet cells. This paper presents the detailed design of the power supply components. Various test results taken during the commissioning phase with a 10 MW resistive load and results taken with the research magnets are shown. The effects of the modules on the electrical supply system and the operational behavior of the power factor correction/harmonic filters are described. Included also are results of a power supply module feeding a superconducting magnet during quench propagation tests. Problems with the power supply design and solutions are presented. Some suggestions on how to improve the performance of these supplies are outlined.

In Vitro Morphogenesis of Arabidopsis to Search for Novel Endophytic Fungi Modulating Plant Growth.

PubMed

Dovana, Francesco; Mucciarelli, Marco; Mascarello, Maurizio; Fusconi, Anna

2015-01-01

Fungal endophytes have shown to affect plant growth and to confer stress tolerance to the host; however, effects of endophytes isolated from water plants have been poorly investigated. In this study, fungi isolated from stems (stem-E) and roots (root-E) of Mentha aquatica L. (water mint) were identified, and their morphogenetic properties analysed on in vitro cultured Arabidopsis (L.) Heynh., 14 and 21 days after inoculation (DAI). Nineteen fungi were analysed and, based on ITS analysis, 17 isolates showed to be genetically distinct. The overall effect of water mint endophytes on Arabidopsis fresh (FW) and dry weight (DW) was neutral and positive, respectively, and the increased DW, mainly occurring 14 DAI, was possibly related to plant defence mechanism. Only three fungi increased both FW and DW of Arabidopsis at 14 and 21 DAI, thus behaving as plant growth promoting (PGP) fungi. E-treatment caused a reduction of root depth and primary root length in most cases and inhibition-to-promotion of root area and lateral root length, from 14 DAI. Only Phoma macrostoma, among the water mint PGP fungi, increased both root area and depth, 21 DAI. Root depth and area 14 DAI were shown to influence DWs, indicating that the extension of the root system, and thus nutrient uptake, was an important determinant of plant dry biomass. Reduction of Arabidopsis root depth occurred to a great extent when plants where treated with stem-E while root area decreased or increased under the effects of stem-E and root-E, respectively, pointing to an influence of the endophyte origin on root extension. M. aquatica and many other perennial hydrophytes have growing worldwide application in water pollution remediation. The present study provided a model for directed screening of endophytes able to modulate plant growth in the perspective of future field applications of these fungi.

Functional integrity of the habenula is necessary for social play behaviour in rats

PubMed Central

van Kerkhof, Linda W. M.; Damsteegt, Ruth; Trezza, Viviana; Voorn, Pieter; Vanderschuren, Louk J. M. J.

2013-01-01

During post-weaning development, a marked increase in peer–peer interactions is observed in all mammals, including humans, which is signified by the abundance of social play behaviour. Social play is highly rewarding, and known to be modulated through monoaminergic neurotransmission. Recently, the habenula has received widespread attention because of its role in the regulation of monoaminergic neurotransmission as well as in a variety of emotional and cognitive functions. Therefore, in the present study, we investigated the involvement of the habenula in social play behaviour. Using the neuronal activity maker c-fos, we showed that the habenula was activated after 24 h of social isolation in adolescent rats, and that a subsequent social play interaction reduced c-fos activity in the medial part of the lateral habenula. This suggested that habenula activity modulated the aversive properties of social isolation, which was alleviated by the positive effects of social play. Furthermore, after functional inactivation of the habenula, using a mixture of the GABA receptor agonists baclofen and muscimol, social play behaviour was markedly reduced, whereby responsiveness to play solicitation was more sensitive to habenula inactivation than play solicitation itself. Together, our data indicated an important role for the habenula in the processing of positive (i.e. social play behaviour) and negative (i.e. social isolation) social information in adolescent rats. Altered habenula function might therefore be related to the social impairments in childhood and adolescent psychiatric disorders such as autism, attention deficit/hyperactivity disorder and early-onset schizophrenia. PMID:24103016

Short Term, Low Dose Simvastatin Pretreatment Alters Memory Immune Function Following Secondary Staphylococcus aureus Infection.

PubMed

Smelser, Lisa K; Walker, Callum; Burns, Erin M; Curry, Michael; Black, Nathanael; Metzler, Jennifer A; McDowell, Susan A; Bruns, Heather A

Statins are potent modulators of immune responses, resulting in their ability to enhance host survival from primary bacterial infections. Alterations in primary immune responses that may be beneficial for survival following infection may also result in alterations in the generation of the immunologic memory response and subsequently affect immune responses mounted during secondary bacterial infection. In this study, we report that levels of total serum IgG2c, following primary infection, were decreased in simvastatin pretreated mice, and investigate the effect of simvastatin treatment, prior to primary infection, on immune responses activated during secondary S. aureus infection. A secondary infection model was implemented whereby simvastatin pretreated and control mice were reinfected with S. aureus 14 days after primary infection, with no additional simvastatin treatment, and assessed for survival and alterations in immune function. While survivability to secondary S. aureus infection was not different between simvastatin pretreated and control mice, memory B and T lymphocyte functions were altered. Memory B cells, isolated 14 days after secondary infection, from simvastatin pretreated mice and stimulated ex vivo produced increased levels of IgG1 compared to memory B cells isolated from control mice, while levels of IgM and IgG2c remained similar. Furthermore, memory B and T lymphocytes from simvastatin pretreated mice exhibited a decreased proliferative response when stimulated ex vivo compared to memory cells isolated from control mice. These findings demonstrate the ability of a short term, low dose simvastatin treatment to modulate memory immune function.

Some failure modes and analysis techniques for terrestrial solar cell modules

NASA Technical Reports Server (NTRS)

Shumka, A.; Stern, K. H.

1978-01-01

Analysis data are presented on failed/defective silicon solar cell modules of various types and produced by different manufacturers. The failure mode (e.g., internal short and open circuits, output power degradation, isolation resistance degradation, etc.) are discussed in detail and in many cases related to the type of technology used in the manufacture of the modules; wherever applicable, appropriate corrective actions are recommended. Consideration is also given to some failure analysis techniques that are applicable to such modules, including X-ray radiography, capacitance measurement, cell shunt resistance measurement by the shadowing technique, steady-state illumination test station for module performance illumination, laser scanning techniques, and the SEM.

Flat Plate Solar Array Project: Proceedings of the 20th Project Integration Meeting

NASA Technical Reports Server (NTRS)

Mcdonald, R. R.

1982-01-01

Progress made by the Flat-Plate Solar Array Project during the period November 1981 to April 1982 is reported. Project analysis and integration, technology research in silicon material, large-area silicon sheet and environmental isolation, cell and module formation, engineering sciences, and module performance and failure analysis are covered.

Williams with TVIS hardware in Zvezda Service module

NASA Image and Video Library

2007-02-27

ISS014-E-15349 (27 Feb. 2007) --- Assisted by the weightlessness of space, astronaut Sunita L. Williams, Expedition 14 flight engineer, hoists the Treadmill Vibration Isolation System (TVIS). She took a moment to pose for a photo during routine in-flight maintenance (IFM) on TVIS in the Zvezda Service Module of the International Space Station.

Lopez-Alegria exercises in the Zvezda Service module

NASA Image and Video Library

2006-11-05

ISS014-E-07115 (2 Nov. 2006) --- Astronaut Michael E. Lopez-Alegria, Expedition 14 commander and NASA space station science officer, equipped with a bungee harness, exercises on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station. In this close-up view, the TVIS is out of frame.

Flat-plate solar array progress and plans

NASA Technical Reports Server (NTRS)

Callaghan, W. T.

1984-01-01

The results of research into the technology of flat-plate solar arrays undertaken in the Flat-Plate Solar Array Project under the sponsorship of the U.S. Department of Energy are surveyed. Topics examined include Si refinement, ribbon-sheet substrate formation, module process sequences, environmental isolation, module engineering and testing, and photovoltaic-array economics.

Relaxant Effects of the Selective Estrogen Receptor Modulator, Bazedoxifene, and Estrogen Receptor Agonists in Isolated Rabbit Basilar Artery.

PubMed

Castelló-Ruiz, María; Salom, Juan B; Fernández-Musoles, Ricardo; Burguete, María C; López-Morales, Mikahela A; Arduini, Alessandro; Jover-Mengual, Teresa; Hervás, David; Torregrosa, Germán; Alborch, Enrique

2016-10-01

We have previously shown that the selective estrogen receptor modulator, bazedoxifene, improves the consequences of ischemic stroke. Now we aimed to characterize the effects and mechanisms of action of bazedoxifene in cerebral arteries. Male rabbit isolated basilar arteries were used for isometric tension recording and quantitative polymerase chain reaction. Bazedoxifene relaxed cerebral arteries, as 17-β-estradiol, 4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol [estrogen receptor (ER) α agonist], and G1 [G protein-coupled ER (GPER) agonist] did it (4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol > bazedoxifene = G1 > 17-β-estradiol). 2,3-Bis(4-hydroxyphenyl)-propionitrile (ERβ agonist) had no effect. Expression profile of genes encoding for ERα (ESR1), ERβ (ESR2), and GPER was GPER > ESR1 > ESR2. As to the endothelial mechanisms, endothelium removal, N-nitro-L-arginine methyl ester, and indomethacin, did not modify the relaxant responses to bazedoxifene. As to the K channels, both a high-K medium and the Kv blocker, 4-aminopyridine, inhibited the bazedoxifene-induced relaxations, whereas tetraethylammonium (nonselective K channel blocker), glibenclamide (selective KATP blocker) or iberiotoxin (selective KCa blocker) were without effect. Bazedoxifene also inhibited both Ca- and Bay K8644-elicited contractions. Therefore, bazedoxifene induces endothelium-independent relaxations of cerebral arteries through (1) activation of GPER and ERα receptors; (2) increase of K conductance through Kv channels; and (3) inhibition of Ca entry through L-type Ca channels. Such a profile is compatible with the beneficial effects of estrogenic compounds (eg, SERMs) on vascular function and, specifically, that concerning the brain. Therefore, bazedoxifene could be useful in the treatment of cerebral disorders in which the cerebrovascular function is compromised (eg, stroke).

Facilitation of face recognition through the retino-tectal pathway.

PubMed

Nakano, Tamami; Higashida, Noriko; Kitazawa, Shigeru

2013-08-01

Humans can shift their gazes faster to human faces than to non-face targets during a task in which they are required to choose between face and non-face targets. However, it remains unclear whether a direct projection from the retina to the superior colliculus is specifically involved in this facilitated recognition of faces. To address this question, we presented a pair of face and non-face pictures to participants modulated in greyscale (luminance-defined stimuli) in one condition and modulated in a blue-yellow scale (S-cone-isolating stimuli) in another. The information of the S-cone-isolating stimuli is conveyed through the retino-geniculate pathway rather than the retino-tectal pathway. For the luminance stimuli, the reaction time was shorter towards a face than towards a non-face target. The facilitatory effect while choosing a face disappeared with the S-cone stimuli. Moreover, fearful faces elicited a significantly larger facilitatory effect relative to neutral faces, when the face (with or without emotion) and non-face stimuli were presented in greyscale. The effect of emotional expressions disappeared with the S-cone stimuli. In contrast to the S-cone stimuli, the face facilitatory effect was still observed with negated stimuli that were prepared by reversing the polarity of the original colour pictures and looked as unusual as the S-cone stimuli but still contained luminance information. These results demonstrate that the face facilitatory effect requires the facial and emotional information defined by luminance, suggesting that the luminance information conveyed through the retino-tectal pathway is responsible for the faster recognition of human faces. Copyright © 2013 Elsevier Ltd. All rights reserved.

Wakata uses Treadmill Vibration Isolation and Stabilization (TVIS)

NASA Image and Video Library

2009-03-22

ISS018-E-042662 (22 March 2009) --- Japan Aerospace Exploration Agency (JAXA) astronaut Koichi Wakata, Expedition 18 flight engineer, equipped with a bungee harness, exercises on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station while Space Shuttle Discovery (STS-119) remains docked with the station.

Onboard Nonlinear Engine Sensor and Component Fault Diagnosis and Isolation Scheme

NASA Technical Reports Server (NTRS)

Tang, Liang; DeCastro, Jonathan A.; Zhang, Xiaodong

2011-01-01

A method detects and isolates in-flight sensor, actuator, and component faults for advanced propulsion systems. In sharp contrast to many conventional methods, which deal with either sensor fault or component fault, but not both, this method considers sensor fault, actuator fault, and component fault under one systemic and unified framework. The proposed solution consists of two main components: a bank of real-time, nonlinear adaptive fault diagnostic estimators for residual generation, and a residual evaluation module that includes adaptive thresholds and a Transferable Belief Model (TBM)-based residual evaluation scheme. By employing a nonlinear adaptive learning architecture, the developed approach is capable of directly dealing with nonlinear engine models and nonlinear faults without the need of linearization. Software modules have been developed and evaluated with the NASA C-MAPSS engine model. Several typical engine-fault modes, including a subset of sensor/actuator/components faults, were tested with a mild transient operation scenario. The simulation results demonstrated that the algorithm was able to successfully detect and isolate all simulated faults as long as the fault magnitudes were larger than the minimum detectable/isolable sizes, and no misdiagnosis occurred

Photovoltaic module encapsulation design and materials section, volume 2

NASA Technical Reports Server (NTRS)

Cuddihy, E. F.

1984-01-01

Tests for chemical structure, material properties, water absorption, aging and curing agent of Ethylene Vinyl Acetate (EVA) and UV absorption studies are carried out. A computer model was developed for thermal optical modeling, to investigate dependence between module operating temperature and solar insolation, and heat dissapation behavior. Structural analyses were performed in order to determine the stress distribution under wind and heat conditions. Curves are shown for thermal loading conditions. An electrical isolation was carried out to investigate electrical stress aging of non-metallic encapsulation materials and limiting material flaws, and to develop a computer model of electrical fields and stresses in encapsulation materials. In addition, a mathematical model was developed and tests were conducted to predict hygroscopic and thermal expansion and contraction on a plastic coated wooden substrate. Thermal cycle and humidity freezing cycle tests, partial discharge tests, and hail impact tests were also carried out. Finally, the effects of soiling on the surface of photovoltaic modules were investigated. Two antisoiling coatings, a fluorinated silane and perflourodecanoic acid were considered.

Strong G-Protein-Mediated Inhibition of Sodium Channels.

PubMed

Mattheisen, Glynis B; Tsintsadze, Timur; Smith, Stephen M

2018-05-29

Voltage-gated sodium channels (VGSCs) are strategically positioned to mediate neuronal plasticity because of their influence on action potential waveform. VGSC function may be strongly inhibited by local anesthetic and antiepileptic drugs and modestly modulated via second messenger pathways. Here, we report that the allosteric modulators of the calcium-sensing receptor (CaSR) cinacalcet, calindol, calhex, and NPS 2143 completely inhibit VGSC current in the vast majority of cultured mouse neocortical neurons. This form of VGSC current block persisted in CaSR-deficient neurons, indicating a CaSR-independent mechanism. Cinacalcet-mediated blockade of VGSCs was prevented by the guanosine diphosphate (GDP) analog GDPβs, indicating that G-proteins mediated this effect. Cinacalcet inhibited VGSCs by increasing channel inactivation, and block was reversed by prolonged hyperpolarization. Strong cinacalcet inhibition of VGSC currents was also present in acutely isolated mouse cortical neurons. These data identify a dynamic signaling pathway by which G-proteins regulate VGSC current to indirectly modulate central neuronal excitability. Published by Elsevier Inc.

Diffraction leveraged modulation of X-ray pulses using MEMS-based X-ray optics

DOEpatents

Lopez, Daniel; Shenoy, Gopal; Wang, Jin; Walko, Donald A.; Jung, Il-Woong; Mukhopadhyay, Deepkishore

2016-08-09

A method and apparatus are provided for implementing Bragg-diffraction leveraged modulation of X-ray pulses using MicroElectroMechanical systems (MEMS) based diffractive optics. An oscillating crystalline MEMS device generates a controllable time-window for diffraction of the incident X-ray radiation. The Bragg-diffraction leveraged modulation of X-ray pulses includes isolating a particular pulse, spatially separating individual pulses, and spreading a single pulse from an X-ray pulse-train.

Elderberry and Elderflower Extracts, Phenolic Compounds, and Metabolites and Their Effect on Complement, RAW 264.7 Macrophages and Dendritic Cells

PubMed Central

Ho, Giang Thanh Thi; Wangensteen, Helle; Barsett, Hilde

2017-01-01

Modulation of complement activity and inhibition of nitric oxide (NO) production by macrophages and dendritic cells may have therapeutic value in inflammatory diseases. Elderberry and elderflower extracts, constituents, and metabolites were investigated for their effects on the complement system, and on NO production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages and murine dendritic D2SC/I cells. The EtOH crude extracts from elderberry and elderflower and the isolated anthocyanins and procyanidins possessed strong complement fixating activity and strong inhibitory activity on NO production in RAW cells and dendritic cells. Phenolic compounds in the range of 0.1–100 µM showed a dose-dependent inhibition of NO production, with quercetin, rutin, and kaempferol as the most potent ones. Among the metabolites, caffeic acid and 3,4-dihydroxyphenylacetic acid showed the strongest inhibitory effects on NO production in both cell lines, without having cytotoxic effect. Only 4-methylcatechol was cytotoxic at the highest tested concentration (100 µM). Elderberry and elderflower constituents may possess inflammatory modulating activity, which increases their nutritional value. PMID:28282861

Elderberry and Elderflower Extracts, Phenolic Compounds, and Metabolites and Their Effect on Complement, RAW 264.7 Macrophages and Dendritic Cells.

PubMed

Ho, Giang Thanh Thi; Wangensteen, Helle; Barsett, Hilde

2017-03-08

Modulation of complement activity and inhibition of nitric oxide (NO) production by macrophages and dendritic cells may have therapeutic value in inflammatory diseases. Elderberry and elderflower extracts, constituents, and metabolites were investigated for their effects on the complement system, and on NO production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages and murine dendritic D2SC/I cells. The EtOH crude extracts from elderberry and elderflower and the isolated anthocyanins and procyanidins possessed strong complement fixating activity and strong inhibitory activity on NO production in RAW cells and dendritic cells. Phenolic compounds in the range of 0.1-100 µM showed a dose-dependent inhibition of NO production, with quercetin, rutin, and kaempferol as the most potent ones. Among the metabolites, caffeic acid and 3,4-dihydroxyphenylacetic acid showed the strongest inhibitory effects on NO production in both cell lines, without having cytotoxic effect. Only 4-methylcatechol was cytotoxic at the highest tested concentration (100 µM). Elderberry and elderflower constituents may possess inflammatory modulating activity, which increases their nutritional value.

Cascaded Converters for Integration and Management of Grid Level Energy Storage Systems

NASA Astrophysics Data System (ADS)

Alaas, Zuhair

This research work proposes two cascaded multilevel inverter structures for BESS. The gating and switching control of switching devices in both inverter typologies are done by using a phase-shifted PWM scheme. The first proposed isolated multilevel inverter is made up of three-phase six-switch inverter blocks with a reduced number of power components compared with traditional isolated CHB. The suggested isolated converter has only one battery string for three-phase system that can be used for high voltage and high power applications such as grid connected BESS and alternative energy systems. The isolated inverter enables dq frame based simple control and eliminates the issues of single-phase pulsating power, which can cause detrimental impacts on certain dc sources. Simulation studies have been carried out to compare the proposed isolated multi-level inverter with an H-bridge cascaded transformer inverter. The simulation results verified the performance of the isolated inverter. The second proposed topology is a Hierarchal Cascaded Multilevel Converter (HCMC) with phase to phase SOC balancing capability which also for high voltage and high power battery energy storage systems. The HCMC has a hybrid structure of half-bridge converters and H-bridge inverters and the voltage can be hierarchically cascaded to reach the desired value at the half-bridge and the H-bridge levels. The uniform SOC battery management is achieved by controlling the half-bridge converters that are connected to individual battery modules/cells. Simulation studies and experimental results have been carried on a large scale battery system under different operating conditions to verify the effectiveness of the proposed inverters. Moreover, this dissertation presents a new three-phase SOC equalizing circuit, called six-switch energy-level balancing circuit (SSBC), which can be used to realize uniform SOC operation for full utilization of the battery capacity in proposed HCMC or any CMI inverter while keeping balanced three-phase operation. A sinusoidal PWM modulation technique is used to control power transferring between phases. Simulation results have been carried out to verify the performance of the proposed SSBC circuit of uniform three-phase SOC balancing.

Evolution of African swine fever virus genes related to evasion of host immune response.

PubMed

Frączyk, Magdalena; Woźniakowski, Grzegorz; Kowalczyk, Andrzej; Bocian, Łukasz; Kozak, Edyta; Niemczuk, Krzysztof; Pejsak, Zygmunt

2016-09-25

African swine fever (ASF) is a notifiable and one of the most complex and devastating infectious disease of pigs, wild boars and other representatives of Suidae family. African swine fever virus (ASFV) developed various molecular mechanisms to evade host immune response including alteration of interferon production by multigene family protein (MGF505-2R), inhibition of NF-κB and nuclear activating factor in T-cells by the A238L protein, or modulation of host defense by CD2v lectin-like protein encoded by EP402R and EP153R genes. The current situation concerning ASF in Poland seems to be stable in comparison to other eastern European countries but up-to-date in total 106 ASF cases in wild boar and 5 outbreaks in pigs were identified. The presented study aimed to reveal and summarize the genetic variability of genes related to inhibition or modulation of infected host response among 67 field ASF isolates collected from wild boar and pigs. The nucleotide sequences derived from the analysed A238L and EP153R regions showed 100% identity. However, minor but remarkable genetic diversity was found within EP402R and MGF505-2R genes suggesting slow molecular evolution of circulating ASFV isolates and the important role of this gene in modulation of interferon I production and hemadsorption phenomenon. The obtained nucleotide sequences of Polish ASFV isolates were closely related to Georgia 2007/1 and Odintsovo 02/14 isolates suggesting their common Caucasian origin. In the case of EP402R and partially in MGF505-2R gene the identified genetic variability was related to spatio-temporal occurrence of particular cases and outbreaks what may facilitate evolution tracing of ASFV isolates. This is the first report indicating identification of genetic variability within the genes related to evasion of host immune system which may be used to trace the direction of ASFV isolates molecular evolution. Copyright © 2016 Elsevier B.V. All rights reserved.

A novel role for the Bombyx Slbo homologue, BmC/EBP, in insect choriogenesis.

PubMed

Sourmeli, S; Papantonis, A; Lecanidou, R

2005-11-18

One previously unidentified cDNA clone coding for a C/EBP factor, BmC/EBP, was isolated from Bombyx mori follicular cells. This is the first time that a C/EBP factor has been isolated and characterized in Lepidoptera. We provide information concerning structural features and developmental specificity, as well as in vitro interaction properties with chorion gene promoter modules. BmC/EBP was capable of effectively recognizing homologous binding sites from chorion gene promoters derived from flies and other moths, despite significant diversity of chorion structure, gene organization, and gene expression profiles. We propose that the relative concentration of BmC/EBP, in relation to its differential binding affinity for promoter cis-elements, results in activation or repression of silkmoth chorion gene expression.

A practical implementation of multi-frequency widefield frequency-domain FLIM

PubMed Central

Chen, Hongtao

2013-01-01

Widefield frequency-domain fluorescence lifetime imaging microscopy (FD-FLIM) is a fast and accurate method to measure the fluorescence lifetime, especially in kinetic studies in biomedical researches. However, the small range of modulation frequencies available in commercial instruments makes this technique limited in its applications. Here we describe a practical implementation of multi-frequency widefield FD-FLIM using a pulsed supercontinuum laser and a direct digital synthesizer. In this instrument we use a pulse to modulate the image intensifier rather than the more conventional sine wave modulation. This allows parallel multi-frequency FLIM measurement using the Fast Fourier Transform and the cross-correlation technique, which permits precise and simultaneous isolation of individual frequencies. In addition, the pulse modulation at the cathode of image intensifier restored the loss of optical resolution caused by the defocusing effect when the voltage at the cathode is sinusoidally modulated. Furthermore, in our implementation of this technique, data can be graphically analyzed by the phasor method while data are acquired, which allows easy fit-free lifetime analysis of FLIM images. Here our measurements of standard fluorescent samples and a Föster resonance energy transfer pair demonstrate that the widefield multi-frequency FLIM system is a valuable and simple tool in fluorescence imaging studies. PMID:23296945

Plant growth and resistance promoted by Streptomyces spp. in tomato.

PubMed

Dias, Maila P; Bastos, Matheus S; Xavier, Vanessa B; Cassel, Eduardo; Astarita, Leandro V; Santarém, Eliane R

2017-09-01

Plant Growth Promoting Rhizobacteria (PGPR) represent an alternative to improve plant growth and yield as well as to act as agents of biocontrol. This study characterized isolates of Streptomyces spp. (Stm) as PGPR, determined the antagonism of these isolates against Pectobacterium carotovorum subsp. brasiliensis (Pcb), evaluated the ability of Stm on promoting growth and modulating the defense-related metabolism of tomato plants, and the potential of Stm isolates on reducing soft rot disease in this species. The VOC profile of Stm was also verified. Promotion of plant growth was assessed indirectly through VOC emission and by direct interaction with Stm isolates in the roots. Evaluation of soft rot disease was performed in vitro on plants treated with Stm and challenged with Pcb. Enzymes related to plant defense were then analyzed in plants treated with three selected isolates of Stm, and PM1 was chosen for further Pcb-challenging experiment. Streptomyces spp. isolates displayed characteristics of PGPR. PM3 was the isolate with efficient antagonism against Pcb by dual-culture. Most of the isolates promoted growth of root and shoot of tomato plants by VOC, and PM5 was the isolate that most promoted growth by direct interaction with Stm. Soft rot disease and mortality of plants were significantly reduced when plants were treated with StmPM1. Modulation of secondary metabolism was observed with Stm treatment, and fast response of polyphenoloxidases was detected in plants pretreated with StmPM1 and challenged with Pcb. Peroxidase was significantly activated three days after infection with Pcb in plants pretreated with StmPM1. Results suggest that Streptomyces sp. PM1 and PM5 have the potential to act as PGPR. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Role of taurine in the vasculature: an overview of experimental and human studies

PubMed Central

Abebe, Worku; Mozaffari, Mahmood S

2011-01-01

Taurine is a sulfur-containing amino acid-like endogenous compound found in substantial amounts in mammalian tissues. It exerts a diverse array of biological effects, including cardiovascular regulation, antioxidation, modulation of ion transport, membrane stabilization, osmoregulation, modulation of neurotransmission, bile acid conjugation, hypolipidemia, antiplatelet activity and modulation of fetal development. This brief review summarizes the role of taurine in the vasculature and modulation of blood pressure, based on experimental and human studies. Oral supplementation of taurine induces antihypertensive effects in various animal models of hypertension. These effects of taurine have been shown to be both centrally and peripherally mediated. Consistent with this, taurine produces endothelium-dependent and independent relaxant effects in isolated vascular tissue preparations. Oral administration of taurine also ameliorates impairment of vascular reactivity, intimal thickening, arteriosclerosis, endothelial apoptosis, oxidative stress and inflammation, associated primarily with diabetes and, to a lesser extent with obesity, hypertension and nicotine-induced vascular adverse events. In rat aortic vascular smooth muscle cells (VSMCs), taurine acts as an antiproliferative and antioxidant agent. In endothelial cells, taurine inhibits apoptosis, inflammation, oxidative stress and cell death while increasing NO generation. Oral taurine in hypertensive human patients alleviates the symptoms of hypertension and also reverses arterial stiffness and brachial artery reactivity in type 1 diabetic patients. However, despite these favorable findings, there is a need to further establish certain aspects of the reported results and also consider addressing unresolved related issues. In addition, the molecular mechanism (s) involved in the vascular effects of taurine is largely unknown and requires further investigations. Elucidation of the mechanisms through which taurine affects the vasculature could facilitate the development of therapeutic and/or diet-based strategies to reduce the burdens of vascular diseases. PMID:22254206

Botryorhodines A-D, antifungal and cytotoxic depsidones from Botryosphaeria rhodina, an endophyte of the medicinal plant Bidens pilosa.

PubMed

Abdou, Randa; Scherlach, Kirstin; Dahse, Hans-Martin; Sattler, Isabel; Hertweck, Christian

2010-01-01

An endophytic fungus (Botryosphaeria rhodina) was isolated from the stems of the medicinal plant Bidens pilosa (Asteraceae) that is known for its anti-inflammatory, antiseptic and antifungal effects. The ethyl acetate extract of the fungal isolate exhibits significant antifungal activity as well as potent cytotoxic and antiproliferative effects against several cancer cell lines. Activity-guided fractionation resulted in the isolation of a complex of four depsidones, botryorhodines A-D and the auxin indole carboxylic acid. Botryorhodine A and B show moderate to weak cytotoxic activities against HeLa cell lines with a CC(50) of 96.97 microM and 36.41 microM, respectively. In addition, they also show antifungal activity against a range of pathogenic fungi such as Aspergillus terreus (MIC 26.03 microM for botryorhodine A and 49.70 microM for B) and the plant pathogen Fusarium oxysporum (MIC 191.60 microM for botryorhodine A and 238.80 microM for B). A potential role of the endophyte in modulating fungal populations living within or attacking the host plant is discussed. 2009 Elsevier Ltd. All rights reserved.

The International Society for Extracellular Vesicles launches the first massive open online course on extracellular vesicles

PubMed Central

Lässer, Cecilia; Théry, Clotilde; Buzás, Edit I.; Mathivanan, Suresh; Zhao, Weian; Gho, Yong Song; Lötvall, Jan

2016-01-01

The International Society for Extracellular Vesicles (ISEV) has organised its first educational online course for students and beginners in the field of extracellular vesicles (EVs). This course, “Basics of Extracellular Vesicles,” uses recorded lectures from experts in the field and will be open for an unlimited number of participants. The course is divided into 5 modules and can be accessed at www.coursera.org/learn/extracellular-vesicles. The first module is an introduction to the field covering the nomenclature and history of EVs. Module 2 focuses on the biogenesis and uptake mechanisms of EVs, as well as their RNA, protein and lipid cargo. Module 3 covers the collection and processing of cell culture media and body fluids such as blood, breast milk, cerebrospinal fluid and urine prior to isolation of EVs. Modules 4 and 5 present different isolation methods and characterisation techniques utilised in the EV field. Here, differential ultracentrifugation, size-exclusion chromatography, density gradient centrifugation, kit-based precipitation, electron microscopy, cryo-electron microscopy, flow cytometry, atomic-force microscopy and nanoparticle-tracking analysis are covered. This first massive open online course (MOOC) on EVs was launched on 15 August 2016 at the platform “Coursera” and is free of charge. PMID:27989272

Modélisation des charges d'espace dans les isolants solides par une analyse spectrale

NASA Astrophysics Data System (ADS)

Haas, V.; Scouarnec, Ch.; Franceschi, J. L.

1998-01-01

A mathematical method based on spectral algebra is developped for the thermal modulation method. These methods permit to measure the space charge distribution in solid insulators. The modelling presented permits to evaluate the performances and the limitations of the measurement method. Une linéarisation par l'algèbre spectrale a été développée dans une méthode de modulation thermique pour mesurer la distribution des charges électriques dans les isolants solides. La modélisation présentée permet d'évaluer les performances et les limites tant numériques que physiques de la méthode de mesure.

Lipid membrane modulation and pigmentation: A cryoprotection mechanism in Arctic pigmented bacteria.

PubMed

Singh, Archana; Krishnan, Kottekattu P; Prabaharan, Dharmar; Sinha, Rupesh K

2017-09-01

The present study aims to address the effect of gradual change in temperature (15-4 °C) followed by freeze-thaw on pigmented bacterial strains - Leeuwenhoekiella aequorea, Pseudomonas pelagia, Halomonas boliviensis, Rhodococcus yunnanensis, and Algoriphagus ratkwoskyi, isolated from Kongsfjorden (an Arctic fjord) to understand their survival in present climate change scenario. The total cell count and retrievability of the isolates were not affected despite the variation in temperature. In all the isolates, the saturated fatty acids, particularly stearic and palmitic acid were predominant at higher temperature, while at 4 °C, the unsaturated fatty acids, primarily cis-10-pentadecenoic, palmitoleic, and oleic acid, were major constituents, confirming homeoviscous adaptation. Even after freeze-thaw, the unsaturated fatty acid composition was retained in all the isolates except A. ratkwoskyi. The increase in unsaturated fatty acids was at the expense of their saturated analogs, probably by desaturase activity. The major pigment in the isolates resembled Zeaxanthin, whose concentration was found to be 26-65% higher after freeze-thaw, suggesting its vital role as a cryoprotective agent in regulating membrane fluidity. Such experimental simulations related to freeze-thaw in polar bacterial isolates are helpful in understanding the physiological plasticity adaptations, which could be critical for survival in harsh and rapidly changing polar environments. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pharmacological comparison of the effect of ibogaine and 18-methoxycoronaridine on isolated smooth muscle from the rat and guinea-pig

PubMed Central

Mundey, M K; Blaylock, N A; Mason, R; Glick, S D; Maisonneuve, I M; Wilson, V G

2000-01-01

Ibogaine and 18-methoxycoronaridine are naturally occurring alkaloids reported to possess antiaddictive properties in several models of drug dependence. We have examined their effect at μ-opioid receptors regulating neurogenic contractions of several smooth muscle preparations and also against spontaneous contractions of the rat isolated portal vein.Ibogaine (pIC50 5.28) and 18-methoxycoronaridine (pIC50 5.05) caused a concentration-dependent inhibition of cholinergic contractions of the guinea-pig ileum which was not affected by the opioid receptor antagonist naloxone (1 μM).In the rat isolated vas deferens ibogaine and 18-methoxycoronaridine caused a concentration-dependent enhancement of purinergic contractions. Both agents (30 μM) caused a 3–5 fold rightward displacement of DAMGO-induced inhibition of purinergic contractions, but similar effects were observed for ibogaine against α2-adrenoceptor-mediated inhibition of neurogenic responses.In the guinea-pig isolated bladder both ibogaine (10 μM) and 18-methoxycoronaridine (10 μM) caused a 2 fold increase in the purinergic component of neurogenic contractions without significantly altering cholinergic contractions or responses to exogenous ATP. In contrast, ibogaine (1–30 μM), but not 18-methoxycoronaridine, caused a concentration-dependent enhancement of spontaneous contractions of the rat isolated portal vein.In summary, while ibogaine and 18-methoxycoronaridine modulated electrically-evoked contractions in the three preparations examined, we have no evidence for a selective interaction with pre-junctional μ-opioid receptors. The pronounced enhancement of purinergic contractions produced by both agents is a novel finding and worthy of further investigation. PMID:10780959

Regulatory Organizations and Their Requirements. MAS-113. Waste Isolation Division (WID). Management and Supervisor Training (MAST) Program.

ERIC Educational Resources Information Center

Westinghouse Electric Corp., Carlsbad, NM.

This learning module, which is part of a management and supervisor training program for managers and supervisors employed at the Department of Energy's Waste Isolation Division, is designed to enable trainees to identify regulatory organizations and oversight groups and monitor and provide guidance in the implementation of the requirements of…

A fiber-coupled 9xx module with tap water cooling

NASA Astrophysics Data System (ADS)

Schleuning, D.; Anthon, D.; Chryssis, A.; Ryu, G.; Liu, G.; Winhold, H.; Fan, L.; Xu, Z.; Tanbun-Ek, T.; Lehkonen, S.; Acklin, B.

2016-03-01

A novel, 9XX nm fiber-coupled module using arrays of highly reliable laser diode bars has been developed. The module is capable of multi-kW output power in a beam parameter product of 80 mm-mrad. The module incorporates a hard-soldered, isolated stack package compatible with tap-water cooling. Using extensive, accelerated multi-cell life-testing, with more than ten million device hours of test, we have demonstrated a MTTF for emitters of >500,000 hrs. In addition we have qualified the module in hard-pulse on-off cycling and stringent environmental tests. Finally we have demonstrated promising results for a next generation 9xx nm chip design currently in applications and qualification testing

A compensation method of lever arm effect for tri-axis hybrid inertial navigation system based on fiber optic gyro

NASA Astrophysics Data System (ADS)

Liu, Zengjun; Wang, Lei; Li, Kui; Gao, Jiaxin

2017-05-01

Hybrid inertial navigation system (HINS) is a new kind of inertial navigation system (INS), which combines advantages of platform INS, strap-down INS and rotational INS. HINS has a physical platform to isolate the angular motion as platform INS does, HINS also uses strap-down attitude algorithms and applies rotation modulation technique. Tri-axis HINS has three gimbals to isolate the angular motion in the dynamic base, in which way the system can reduce the effects of angular motion and improve the positioning precision. However, the angular motion will affect the compensation of some error parameters, especially for the lever arm effect. The lever arm effect caused by position errors between the accelerometers and rotation center cannot be ignored due to the rapid rotation of inertial measurement unit (IMU) and it will cause fluctuation and stage in velocity in HINS. The influences of angular motion on the lever arm effect compensation are analyzed firstly in this paper, and then the compensation method of lever arm effect based on the photoelectric encoders in dynamic base is proposed. Results of experiments on turntable show that after compensation, the fluctuations and stages in velocity curve disappear.

Neonatal isolation impairs neurogenesis in the dentate gyrus of the guinea pig.

PubMed

Rizzi, Simona; Bianchi, Patrizia; Guidi, Sandra; Ciani, Elisabetta; Bartesaghi, Renata

2007-01-01

In the current study we examined the effects of early isolation rearing on cell proliferation, survival and differentiation in the dentate gyrus of the guinea pig. Animals were assigned to either a standard (control) or an isolated environment a few days after birth (P5-P6), taking advantage of the precocious independence from maternal care of the guinea pig. On P14-P17 animals received one daily bromodeoxyuridine injection, to label dividing cells, and were sacrificed either on P18, to evaluate cell proliferation or on P45, to evaluate cell survival and differentiation. In P18 isolated animals we found a reduced cell proliferation (-35%) compared to controls and a lower expression of brain-derived neurotrophic factor (BDNF). Though in absolute terms P45 isolated animals had less surviving cells, they showed no differences in survival rate and phenotype percent distribution compared to controls. Looking at the location of the new neurons, we found that while in control animals 76% of them had migrated to the granule cell layer, in isolated animals only 55% of the new neurons had reached this layer. Examination of radial glia cells of P18 and P45 animals by vimentin immunohistochemistry showed that in isolated animals radial glia cells were reduced in density and had less and shorter processes. Granule cell count revealed that P45 isolated animals had less (-42%) granule cells than controls. Results show that isolation rearing reduces hippocampal cell proliferation, likely by reducing BDNF expression and hampers migration of the new neurons to the granule cell layer, likely by altering density/morphology of radial glia cells. The large reduction in granule cell number following isolation rearing emphasizes the role of environmental cues as relevant modulators of neurogenesis.

Leptin modulates enteric neurotransmission in the rat proximal colon: an in vitro study.

PubMed

Florian, Voinot; Caroline, Fischer; Francis, Crenner; Camille, Schmidt; Fabielle, Angel

2013-08-10

Leptin has been shown to modulate gastrointestinal functions including nutrient absorption, growth, and inflammation and to display complex effects on gut motility. Leptin receptors have also been identified within the enteric nervous system (ENS), which plays a crucial role in digestive functions. Although leptin has recently been shown to activate neurons in the ENS, the precise mechanisms involved are so far unknown. Therefore, the aim of the present study was to determine the effects of leptin on rat proximal colon smooth muscle and enteric neuron activities. The effects of exogenous leptin on tone and on responses to transmural nerve stimulation (TNS) of isolated circular smooth muscle of proximal colon in rats were investigated using an organ bath technique. The effects of a physiological concentration (0.1 μM) of leptin were also studied on tone and TNS-induced relaxation in the presence of atropine, hexamethonium, L-N(G)-nitroarginine methyl ester (L-NAME) and capsazepine. Leptin caused a slight but significant decrease in tone, TNS-induced relaxation and contraction in a concentration-dependent manner in colonic preparations. Cholinergic antagonists abolished the effects of 0.1 μM leptin on TNS-induced relaxation. This concentration of leptin had no further effect on relaxation in the presence of L-NAME. In the presence of capsazepine, leptin had no further effect either on tone or relaxation compared to the drug alone. In conclusion, leptin modulates the activity of enteric inhibitory and excitatory neurons in proximal colon. These effects may be mediated through nitrergic neurons. Intrinsic primary afferent neurons may be involved. © 2013.

Sex-specific effects of docosahexaenoic acid (DHA) on the microbiome and behavior of socially-isolated mice.

PubMed

Davis, Daniel J; Hecht, Patrick M; Jasarevic, Eldin; Beversdorf, David Q; Will, Matthew J; Fritsche, Kevin; Gillespie, Catherine H

2017-01-01

Dietary supplementation with the long-chain omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) has been shown to have a beneficial effect on reducing the symptoms associated with several neuropsychiatric conditions including anxiety and depression. However, the mechanisms underlying this effect remain largely unknown. Increasing evidence suggests that the vast repertoire of commensal bacteria within the gut plays a critical role in regulating various biological processes in the brain and may contribute to neuropsychiatric disease risk. The present study determined the contribution of DHA on anxiety and depressive-like behaviors through modulation of the gut microbiota in a paradigm of social isolation. Adult male and female mice were subjected to social isolation for 28days and then placed either on a control diet or a diet supplemented with 0.1% or 1.0% DHA. Fecal pellets were collected both 24h and 7days following the introduction of the new diets. Behavioral testing revealed that male mice fed a DHA diet, regardless of dose, exhibited reduced anxiety and depressive-like behaviors compared to control fed mice while no differences were observed in female mice. As the microbiota-brain-axis has been recently implicated in behavior, composition of microbial communities were analyzed to examine if these sex-specific effects of DHA may be associated with changes in the gut microbiota (GM). Clear sex differences were observed with males and females showing distinct microbial compositions prior to DHA supplementation. The introduction of DHA into the diet also induced sex-specific interactions on the GM with the fatty acid producing a significant effect on the microbial profiles in males but not in females. Interestingly, levels of Allobaculum and Ruminococcus were found to significantly correlate with the behavioral changes observed in the male mice. Predictive metagenome analysis using PICRUSt was performed on the fecal samples collected from males and identified enrichment in functional KEGG pathway terms relevant to processes such as the biosynthesis of unsaturated fatty acids and antioxidant metabolism. These results indicate that DHA alters commensal community composition and produces beneficial effects on anxiety and depressive-like behaviors in a sex-specific manner. The present study provides insight into the mechanistic role that gut microbes may play in the regulation of anxiety and depressive-like behaviors and how dietary intervention can modulate these effects. Copyright © 2016 Elsevier Inc. All rights reserved.

CrossTalk, The Journal of Defense Software Engineering. Volume 27, Number 4. July/August 2014

DTIC Science & Technology

2014-07-01

hires him for the work.” To do this with a development project, isolate parts of the sys- tem the development of which is not obvious and develop...class. Coupling makes it more difficult to isolate units of code for testing. The interdependence also makes code comprehension more difficult and...coupled, it is more difficult or impossible to isolate the module under test to ensure the test is focusing only on the desired code and producing

Alpha2-Adrenergic Receptors and Breast Tumor Stroma: A Novel Pathway Driving Breast Cancer Growth and Metastasis

DTIC Science & Technology

2014-10-01

TAF ) were isolated to determine if α2−AR activation directly modulates collagen microstructure. 15. SUBJECT TERMS Alpha2-adrenergic receptors, breast...group. 15 3) Significant results/key outcomes: Here we demonstrate the isolation of tumor associated fibroblasts ( TAF ) from 4T1 tumors. The goal...of these experiments was to determine the optimal conditions and appropriate markers for isolation of TAF and to optimize yield and purity of the

T Cell Stimulatory Effects of Korean Red Ginseng through Modulation of Myeloid-Derived Suppressor Cells

PubMed Central

Jeon, Chanoh; Kang, Soowon; Park, Seungbeom; Lim, Kyungtaek; Hwang, Kwang Woo; Min, Hyeyoung

2011-01-01

Myeloid-derived suppressor cells (MDSCs) actively suppress immune cells and have been considered as an impediment to successful cancer immunotherapy. Many approaches have been made to overcome such immunosuppressive factors and to exert effective anti-tumor effects, but the possibility of using medicinal plants for this purpose has been overlooked. Korean red ginseng (KRG) is widely known to possess a variety of pharmacological properties, including immunoboosting and anti-tumor activities. However, little has been done to assess the anti-tumor activity of KRG on MDSCs. Therefore, we examined the effects of KRG on MDSCs in tumor-bearing mice and evaluated immunostimulatory and anti-tumor activities of KRG through MDSC modulation. The data show that intraperitoneal administration of KRG compromises MDSC function and induces T cell proliferation and the secretion of IL-2 and IFN-γ, while it does not exhibit direct cytotoxicity on tumor cells and reduced MDSC accumulation. MDSCs isolated from KRG-treated mice also express significantly lower levels of inducible nitric oxide synthase and IL-10 accompanied by a decrease in nitric oxide production compared with control. Taken together, the present study demonstrates that KRG enhances T cell function by inhibiting the immunosuppressive activity of MDSCs and suggests that although KRG alone does not exhibit direct anti-tumor effects, the use of KRG together with conventional chemo- or immunotherapy may provide better outcomes to cancer patients through MDSC modulation. PMID:23717093

Isolation, characterization and hypolipidemic activity of ferulic acid in high-fat-diet-induced hyperlipidemia in laboratory rats

PubMed Central

Jain, Pankaj G.; Surana, Sanjay J.

2016-01-01

Prosopis cineraria (L.) Druce (Leguminosae) (syn. Prosopis spicigera L.) has antidiabetic and antioxidant potential. Earlier we reported its hypolipidemic activity obtained from ethanol extract (ET-PCF). Object of this work was to isolate ferulic acid (FA) from ET-PCF and evaluate hypolipidemic activity against high-fat diet (HFD)-induced hyperlipidemic laboratory rats. ET-PCF was subjected to flash column chromatography to isolate FA. The chemical structure of the isolated compound was elucidated by UV, IR, 1H NMR,13C NMR and LC-MS. Further, the antihyperlipidemic effect of FA (10, 20 and 40 mg/kg, p.o.) in HFD-induced hyperlipidemic rats was investigated. Hyperlipidemia was induced in male Sprague-Dawley rats by feeding with HFD for 60 days. Lipid parameters such as total cholesterol (TC), Low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) levels were measured in serum and hepatic tissue. Hepatic oxido-nitrosative stress (SOD, GSH, MDA and NO) were also determined. Histological evaluation of liver tissue was carried out. The structure of the isolated compound was characterized based on spectral data and confirmed as FA. HFD induced an alteration in serum, and hepatic lipid profile (triglyceride, cholesterol, HDL, and LDL) was significantly restored (p < 0.001) by administration of FA (20 and 40 mg/kg, p.o.). The elevated level of oxido-nitrosative stress in liver was significantly reduced (p < 0.001) by FA (20 and 40 mg/kg, p.o.). Histological aberration induced in the liver after HFD ingestion were restored by FA administration. Ferulic acid isolated from ET-PCF showed hypolipidemic effects in HFD-induced hyperlipidemic rats via modulation of elevated oxido-nitrosative stress. PMID:28096790

Jaceosidin, isolated from dietary mugwort (Artemisia princeps), induces G2/M cell cycle arrest by inactivating cdc25C-cdc2 via ATM-Chk1/2 activation.

PubMed

Lee, Jong-Gyu; Kim, Ji-Hyun; Ahn, Ji-Hye; Lee, Kyung-Tae; Baek, Nam-In; Choi, Jung-Hye

2013-05-01

Jaceosidin, a flavonoid derived from Artemisia princeps (Japanese mugwort), has been shown to inhibit the growth of several human cancer cells, However, the exact mechanism for the cytotoxic effect of jaceosidin is not completely understood. In this study, we investigated the molecular mechanism involved in the antiproliferative effect of jaceosidin in human endometrial cancer cells. We demonstrated that jaceosidin is a more potent inhibitor of cell growth than cisplatin in human endometrial cancer cells. In contrast, jaceosidin-induced cytotoxicity in normal endometrial cells was lower than that observed for cisplatin. Jaceosidin induced G2/M phase cell cycle arrest and modulated the levels of cyclin B and p-Cdc2 in Hec1A cells. Knockdown of p21 using specific siRNAs partially abrogated jaceosidin-induced cell growth inhibition. Additional mechanistic studies revealed that jaceosidin treatment resulted in an increase in phosphorylation of Cdc25C and ATM-Chk1/2. Ku55933, an ATM inhibitor, reversed jaceosidin-induced cell growth inhibition, in part. Moreover, jaceosidin treatment resulted in phosphorylation of ERK, and pretreatment with the ERK inhibitor, PD98059, attenuated cell growth inhibition by jaceosidin. These data suggest that jaceosidin, isolated from Japanese mugwort, modulates the ERK/ATM/Chk1/2 pathway, leading to inactivation of the Cdc2-cyclin B1 complex, followed by G2/M cell cycle arrest in endometrial cancer cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cell-specific modulation of surfactant proteins by ambroxol treatment

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

Seifart, Carola; Clostermann, Ursula; Seifart, Ulf

2005-02-15

Ambroxol [trans-4-(2-amino-3,5-dibromobenzylamino)-cyclohexanole hydrochloride], a mucolytic agent, was postulated to provide surfactant stimulatory properties and was previously used to prevent surfactant deficiency. Currently, the underlying mechanisms are not exactly clear. Because surfactant homeostasis is regulated by surfactant-specific proteins (SP), we analyzed protein amount and mRNA expression in whole lung tissue, isolated type II pneumocytes and bronchoalveolar lavage of Sprague-Dawley rats treated with ambroxol i.p. (75 mg/kg body weight, twice a day [every 12 h]). The methods used included competitive polymerase chain reaction (RT-PCR), Northern blotting, Western immunoblotting, and immunohistochemistry. In isolated type II pneumocytes of ambroxol-treated animals, SP-C protein and mRNAmore » content were increased, whereas SP-A, -B and -D protein, mRNA, and immunoreactivity remained unaffected. However, ambroxol treatment resulted in a significant increase of SP-B and in a decrease of SP-D in whole lung tissue with enhanced immunostaining for SP-B in Clara Cells. SP-A and SP-D were significantly decreased in BAL fluid of ambroxol-treated animals. The data suggest that surfactant protein expression is modulated in a cell-specific manner by ambroxol, as type II pneumocytes exhibited an increase in SP-C, whereas Clara cells exhibited an increase in the immunoreactivity for SP-B accounting for the increased SP-B content of whole lung tissue. The results indicate that ambroxol may exert its positive effects, observed in the treatment of diseases related to surfactant deficiency, via modulation of surfactant protein expression.« less

Pulse-Width-Modulating Driver for Brushless dc Motor

NASA Technical Reports Server (NTRS)

Salomon, Phil M.

1991-01-01

High-current pulse-width-modulating driver for brushless dc motor features optical coupling of timing signals from low-current control circuitry to high-current motor-driving circuitry. Provides high electrical isolation of motor-power supply, helping to prevent fast, high-current motor-driving pulses from being coupled through power supplies into control circuitry, where they interfere with low-current control signals.

The 19th Project Integration Meeting

NASA Technical Reports Server (NTRS)

Mcdonald, R. R.

1981-01-01

The Flat-Plate Solar Array Project is described. Project analysis and integration is discussed. Technology research in silicon material, large-area silicon sheet and environmental isolation; cell and module formation; engineering sciences, and module performance and failure analysis. It includes a report on, and copies of visual presentations made at, the 19th Project Integration Meeting held at Pasadena, California, on November 11, 1981.

Phonological and syntactic competition effects in spoken word recognition: evidence from corpus-based statistics.

PubMed

Zhuang, Jie; Devereux, Barry J

2017-02-07

As spoken language unfolds over time the speech input transiently activates multiple candidates at different levels of the system - phonological, lexical, and syntactic - which in turn leads to short-lived between-candidate competition. In an fMRI study, we investigated how different kinds of linguistic competition may be modulated by the presence or absence of a prior context (Tyler 1984; Tyler et al. 2008). We found significant effects of lexico-phonological competition for isolated words, but not for words in short phrases, with high competition yielding greater activation in left inferior frontal gyrus (LIFG) and posterior temporal regions. This suggests that phrasal contexts reduce lexico-phonological competition by eliminating form-class inconsistent cohort candidates. A corpus-derived measure of lexico-syntactic competition was associated with greater activation in LIFG for verbs in phrases, but not for isolated verbs, indicating that lexico-syntactic information is boosted by the phrasal context. Together, these findings indicate that LIFG plays a general role in resolving different kinds of linguistic competition.

A Lactobacillus plantarum strain isolated from kefir protects against intestinal infection with Yersinia enterocolitica O9 and modulates immunity in mice.

PubMed

De Montijo-Prieto, Soumi; Moreno, Encarnación; Bergillos-Meca, Triana; Lasserrot, Agustín; Ruiz-López, María-Dolores; Ruiz-Bravo, Alfonso; Jiménez-Valera, María

2015-10-01

Lactobacillus plantarum C4, previously isolated from kefir and characterized as a potential probiotic strain, was tested for its protective and immunomodulatory capacity in a murine model of yersiniosis. The inoculation of BALB/c mice with a low pathogenicity serotype O9 strain of Yersinia enterocolitica results in a prolonged intestinal infection with colonization of Peyer's patches. Pretreatment with C4 was without effect on fecal excretion of yersiniae, but shortened the colonization of Peyer's patches. This protective effect was associated with pro-inflammatory status in the intestinal mucosa (TNF-α production in infected mice was increased by C4) and an increase in total IgA secretion. At a systemic level, C4 did not promote a pro-inflammatory response, although production of the immunoregulatory cytokine IFN-γ was enhanced. These findings suggest that L. plantarum C4 can increase resistance to intestinal infections through its immunomodulatory activity. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Neutral endopeptidase inhibitors potentiate substance P-induced contraction in gut smooth muscle.

PubMed

Djokic, T D; Sekizawa, K; Borson, D B; Nadel, J A

1989-01-01

To determine the role of endogenous neutral endopeptidase (NEP), also called enkephalinase (EC 3.4.24.11), in regulating tachykinin-induced contraction of gut smooth muscle, we studied the effects of NEP inhibitors on the contractile responses to substance P (SP) in isolated longitudinal strips of ileum or duodenum in rats and ferrets. Leucine-thiorphan and phosphoramidon shifted the concentration-response curves of SP to lower concentrations in all tissues studied, but the sensitivity to SP was greater and the effect of leucine-thiorphan was less in the ferret, a finding that correlated with the observation that the ferret ileum contained substantially less NEP activity than rat ileum. Captopril, bestatin, MGTA, leupeptin, and physostigmine did not alter contractile responses to SP, suggesting that kininase II, aminopeptidases, carboxypeptidase N, serine proteinases, and acetylcholinesterase do not modulate the SP-induced effects. These studies suggest that, in the ileum and duodenum, NEP modulates the actions of SP and, furthermore, that the sensitivity of tissues may be determined, at least in part, by the amount of enzymatically active NEP present.

N-Acetylcysteine Selectively Antagonizes the Activity of Imipenem in Pseudomonas aeruginosa by an OprD-Mediated Mechanism

PubMed Central

Rodríguez-Beltrán, Jerónimo; Cabot, Gabriel; Valencia, Estela Ynés; Costas, Coloma; Bou, German; Oliver, Antonio

2015-01-01

The modulating effect of N-acetylcysteine (NAC) on the activity of different antibiotics has been studied in Pseudomonas aeruginosa. Our results demonstrate that, in contrast to previous reports, only the activity of imipenem is clearly affected by NAC. MIC and checkerboard determinations indicate that the NAC-based modulation of imipenem activity is dependent mainly on OprD. SDS-PAGE of outer membrane proteins (OMPs) after NAC treatments demonstrates that NAC does not modify the expression of OprD, suggesting that NAC competitively inhibits the uptake of imipenem through OprD. Similar effects on imipenem activity were obtained with P. aeruginosa clinical isolates. Our results indicate that imipenem-susceptible P. aeruginosa strains become resistant upon simultaneous treatment with NAC and imipenem. Moreover, the generality of the observed effects of NAC on antibiotic activity was assessed with two additional bacterial species, Escherichia coli and Acinetobacter baumannii. Caution should be taken during treatments, as the activity of imipenem may be modified by physiologically attainable concentrations of NAC, particularly during intravenous and nebulized regimes. PMID:25801561

N-acetylcysteine selectively antagonizes the activity of imipenem in Pseudomonas aeruginosa by an OprD-mediated mechanism.

PubMed

Rodríguez-Beltrán, Jerónimo; Cabot, Gabriel; Valencia, Estela Ynés; Costas, Coloma; Bou, German; Oliver, Antonio; Blázquez, Jesús

2015-01-01

The modulating effect of N-acetylcysteine (NAC) on the activity of different antibiotics has been studied in Pseudomonas aeruginosa. Our results demonstrate that, in contrast to previous reports, only the activity of imipenem is clearly affected by NAC. MIC and checkerboard determinations indicate that the NAC-based modulation of imipenem activity is dependent mainly on OprD. SDS-PAGE of outer membrane proteins (OMPs) after NAC treatments demonstrates that NAC does not modify the expression of OprD, suggesting that NAC competitively inhibits the uptake of imipenem through OprD. Similar effects on imipenem activity were obtained with P. aeruginosa clinical isolates. Our results indicate that imipenem-susceptible P. aeruginosa strains become resistant upon simultaneous treatment with NAC and imipenem. Moreover, the generality of the observed effects of NAC on antibiotic activity was assessed with two additional bacterial species, Escherichia coli and Acinetobacter baumannii. Caution should be taken during treatments, as the activity of imipenem may be modified by physiologically attainable concentrations of NAC, particularly during intravenous and nebulized regimes. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Functional integrity of the habenula is necessary for social play behaviour in rats.

PubMed

van Kerkhof, Linda W M; Damsteegt, Ruth; Trezza, Viviana; Voorn, Pieter; Vanderschuren, Louk J M J

2013-11-01

During post-weaning development, a marked increase in peer-peer interactions is observed in mammals, including humans, which is signified by the abundance of social play behaviour. Social play is highly rewarding, and known to be modulated through monoaminergic neurotransmission. Recently, the habenula has received widespread attention because of its role in the regulation of monoaminergic neurotransmission as well as in a variety of emotional and cognitive functions. Therefore, in the present study, we investigated the involvement of the habenula in social play behaviour. Using the neuronal activity maker c-fos, we showed that the habenula was activated after 24 h of social isolation in adolescent rats, and that a subsequent social play interaction reduced c-fos activity in the medial part of the lateral habenula. This suggested that habenula activity modulated the aversive properties of social isolation, which was alleviated by the positive effects of social play. Furthermore, after functional inactivation of the habenula, using a mixture of the GABA receptor agonists baclofen and muscimol, social play behaviour was markedly reduced, whereby responsiveness to play solicitation was more sensitive to habenula inactivation than play solicitation itself. Together, our data indicate an important role for the habenula in the processing of positive (i.e., social play behaviour) and negative (i.e., social isolation) social information in adolescent rats. Altered habenula function might therefore be related to the social impairments in childhood and adolescent psychiatric disorders such as autism, attention deficit/hyperactivity disorder and early-onset schizophrenia. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Color of scents: chromatic stimuli modulate odor responses in the human brain.

PubMed

Osterbauer, Robert A; Matthews, Paul M; Jenkinson, Mark; Beckmann, Christian F; Hansen, Peter C; Calvert, Gemma A

2005-06-01

Color has a profound effect on the perception of odors. For example, strawberry-flavored drinks smell more pleasant when colored red than green and descriptions of the "nose" of a wine are dramatically influenced by its color. Using functional magnetic resonance imaging, we demonstrate a neurophysiological correlate of these cross-modal visual influences on olfactory perception. Subjects were scanned while exposed either to odors or colors in isolation or to color-odor combinations that were rated on the basis of how well they were perceived to match. Activity in caudal regions of the orbitofrontal cortex and in the insular cortex increased progressively with the perceived congruency of the odor-color pairs. These findings demonstrate the neuronal correlates of olfactory response modulation by color cues in brain areas previously identified as encoding the hedonic value of smells.

Isolation Mounting for Charge-Coupled Devices

NASA Technical Reports Server (NTRS)

Goss, W. C.; Salomon, P. M.

1985-01-01

CCD's suspended by wires under tension. Remote thermoelectric cooling of charge coupled device allows vibration isolating mounting of CCD assembly alone, without having to suspend entire mass and bulk of thermoelectric module. Mounting hardware simple and light. Developed for charge-coupled devices (CCD's) in infrared telescope support adaptable to sensors in variety of environments, e.g., sensors in nuclear reactors, engine exhausts and plasma chambers.

Complete Genome Sequence of Nitrosomonas cryotolerans ATCC 49181, a Phylogenetically Distinct Ammonia-Oxidizing Bacterium Isolated from Arctic Waters

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

Rice, Marlen C.; Norton, Jeanette M.; Stein, Lisa Y.

ABSTRACT Nitrosomonas cryotoleransATCC 49181 is a cold-tolerant marine ammonia-oxidizing bacterium isolated from seawater collected in the Gulf of Alaska. The high-quality complete genome contains a 2.87-Mbp chromosome and a 56.6-kbp plasmid. Chemolithoautotrophic modules encoding ammonia oxidation and CO 2 fixation were identified.

Optical voltage reference

DOEpatents

Rankin, Richard; Kotter, Dale

1994-01-01

An optical voltage reference for providing an alternative to a battery source. The optical reference apparatus provides a temperature stable, high precision, isolated voltage reference through the use of optical isolation techniques to eliminate current and impedance coupling errors. Pulse rate frequency modulation is employed to eliminate errors in the optical transmission link while phase-lock feedback is employed to stabilize the frequency to voltage transfer function.

Pirin-like proteins are regulated by oxidative stress and iron in bacteroides fragilis and involved in the modulation of central energy metabolism and metronidazole susceptibility

USDA-ARS?s Scientific Manuscript database

Bacteroides fragilis is the most frequent anaerobe isolated from human infections. Clinical isolates of B. fragilis are among the highest aerotolerant anaerobic bacteria. The oxidative stress response (OSR) in B. fragilis induces an array of genes enabling them to survive prolonged oxygen exposure i...

Complete Genome Sequence of Nitrosomonas cryotolerans ATCC 49181, a Phylogenetically Distinct Ammonia-Oxidizing Bacterium Isolated from Arctic Waters

DOE PAGES

Rice, Marlen C.; Norton, Jeanette M.; Stein, Lisa Y.; ...

2017-03-16

ABSTRACT Nitrosomonas cryotoleransATCC 49181 is a cold-tolerant marine ammonia-oxidizing bacterium isolated from seawater collected in the Gulf of Alaska. The high-quality complete genome contains a 2.87-Mbp chromosome and a 56.6-kbp plasmid. Chemolithoautotrophic modules encoding ammonia oxidation and CO 2 fixation were identified.

Neonatal isolation delays the developmental decline of long-term depression in the CA1 region of rat hippocampus.

PubMed

Ku, Hsiao-Yun; Huang, Yu-Fei; Chao, Pei-Hsuan; Huang, Chiung-Chun; Hsu, Kuei-Sen

2008-11-01

Activity-dependent alterations of synaptic efficacy or connectivity are essential for the development, signal processing, and learning and memory functions of the nervous system. It was observed that, in particular in the CA1 region of the hippocampus, low-frequency stimulation (LFS) became progressively less effective at inducing long-term depression (LTD) with advancing developmental age. The physiological factors regulating this developmental plasticity change, however, have not yet been elucidated. Here we examined the hypothesis that neonatal isolation (once per day for 1 h from postnatal days 1-7) is able to alter processes underlying the developmental decline of LTD. We confirm that the magnitude of LTD induced by LFS (900 stimuli at 1 Hz) protocol correlates negatively with developmental age and illustrates that neonatal isolation delays this developmental decline via the activation of corticotrophin-releasing factor (CRF) system. Furthermore, this modulation appears to be mediated by an increased transcription of N-methyl-D-aspartate receptor NR2B subunits. We also demonstrate that intracerebroventricular injection of CRF postnatally mimicked the effect of neonatal isolation to increase the expression of NR2B subunits and delayed the developmental decline of LTD, which was specifically blocked by CRF receptor 1 antagonist NBI27914 pretreatment. These results suggest a novel role for CRF in regulating developmental events in the hippocampus and indicate that although maternal deprivation is stressful for neonate, appropriate neonatal isolation can serve to promote an endocrine state that may regulate the gradual developmental change in the induction rules for synaptic plasticity in the hippocampal CA1 region.

Ciprofloxacin and Trimethoprim Cause Phage Induction and Virulence Modulation in Staphylococcus aureus

PubMed Central

Goerke, Christiane; Köller, Johanna; Wolz, Christiane

2006-01-01

In Staphylococcus aureus strains of human origin, phages which integrate into the chromosomal gene coding for β-hemolysin (hlb) are widely distributed. Most of them encode accessory virulence determinants such as staphylokinase (sak) or enterotoxins. Here, we analyzed the effects of ciprofloxacin and trimethoprim on phage induction and expression of phage-encoded virulence factors by using isolates from patients with cystic fibrosis for which the induction of hlb-converting phages was demonstrated in vivo (C. Goerke, S. Matias y Papenberg, S. Dasbach, K. Dietz, R. Ziebach, B. C. Kahl, and C. Wolz, J. Infect. Dis. 189:724-734, 2004) as well as a φ13 lysogen of phage-cured strain 8325-4. Treatment of lysogens with subinhibitory concentrations of either antibiotic resulted in (i) delysogenization of strains resembling the isolates picked up after chronic lung infection and (ii) replication of phages in the bacterial host in a dose-dependent manner. Ciprofloxacin treatment resulted in enhanced recA transcription, indicating involvement of the SOS response in phage mobilization. Induction of φ13 was linked to elevated expression of the phage-encoded virulence gene sak, chiefly due to the activation of latent phage promoters. In summary, we could show the induction of hlb-converting phages and a subsequent virulence modulation of the host bacterium by ciprofloxacin and trimethoprim. PMID:16377683

The Effects of Carbohydrates, in Isolation and Combined with Caffeine, on Cognitive Performance and Mood—Current Evidence and Future Directions

PubMed Central

Lawton, Clare Louise

2018-01-01

This review examines the effects of carbohydrates, delivered individually and in combination with caffeine, on a range of cognitive domains and subjective mood. There is evidence for beneficial effects of glucose at a dose of 25 g on episodic memory, but exploration of dose effects has not been systematic and the effects on other cognitive domains is not known. Factors contributing to the differential sensitivity to glucose facilitation include age, task difficulty/demand, task domain, and glucoregulatory control. There is modest evidence to suggest modulating glycemic response may impact cognitive function. The evidence presented in this review identifies dose ranges of glucose and caffeine which improve cognition, but fails to find convincing consistent synergistic effects of combining caffeine and glucose. Whilst combining glucose and caffeine has been shown to facilitate cognitive performance and mood compared to placebo or glucose alone, the relative contribution of caffeine and glucose to the observed effects is difficult to ascertain, due to the paucity of studies that have appropriately compared the effects of these ingredients combined and in isolation. This review identifies a number of methodological challenges which need to be considered in the design of future hypothesis driven research in this area. PMID:29425182

Increased excitability of spinal pain reflexes and altered frequency-dependent modulation in the dopamine D3-receptor knockout mouse.

PubMed

Keeler, Benjamin E; Baran, Christine A; Brewer, Kori L; Clemens, Stefan

2012-12-01

Frequency-dependent modulation and dopamine (DA) receptors strongly modulate neural circuits in the spinal cord. Of the five known DA receptor subtypes, the D3 receptor has the highest affinity to DA, and D3-mediated actions are mainly inhibitory. Using an animal model of spinal sensorimotor dysfunction, the D3 receptor knockout mouse (D3KO), we investigated the physiological consequences of D3 receptor dysfunction on pain-associated signaling pathways in the spinal cord, the initial integration site for the processing of pain signaling. In the D3KO spinal cord, inhibitory actions of DA on the proprioceptive monosynaptic stretch reflex are converted from depression to facilitation, but its effects on longer-latency and pain-associated reflex responses and the effects of FM have not been studied. Using behavioral approaches in vivo, we found that D3KO animals exhibit reduced paw withdrawal latencies to thermal pain stimulation (Hargreaves' test) over wild type (WT) controls. Electrophysiological and pharmacological approaches in the isolated spinal cord in vitro showed that constant current stimulation of dorsal roots at a pain-associated frequency was associated with a significant reduction in the frequency-dependent modulation of longer-latency reflex (LLRs) responses but not monosynaptic stretch reflexes (MSRs) in D3KO. Application of the D1 and D2 receptor agonists and the voltage-gated calcium-channel ligand, pregabalin, but not DA, was able to restore the frequency-dependent modulation of the LLR in D3KO to WT levels. Thus we demonstrate that nociception-associated LLRs and proprioceptive MSRs are differentially modulated by frequency, dopaminergics and the Ca(2+) channel ligand, pregabalin. Our data suggest a role for the DA D3 receptor in pain modulation and identify the D3KO as a possible model for increased nociception. Copyright © 2012 Elsevier Inc. All rights reserved.

Module Extraction for Efficient Object Queries over Ontologies with Large ABoxes

PubMed Central

Xu, Jia; Shironoshita, Patrick; Visser, Ubbo; John, Nigel; Kabuka, Mansur

2015-01-01

The extraction of logically-independent fragments out of an ontology ABox can be useful for solving the tractability problem of querying ontologies with large ABoxes. In this paper, we propose a formal definition of an ABox module, such that it guarantees complete preservation of facts about a given set of individuals, and thus can be reasoned independently w.r.t. the ontology TBox. With ABox modules of this type, isolated or distributed (parallel) ABox reasoning becomes feasible, and more efficient data retrieval from ontology ABoxes can be attained. To compute such an ABox module, we present a theoretical approach and also an approximation for SHIQ ontologies. Evaluation of the module approximation on different types of ontologies shows that, on average, extracted ABox modules are significantly smaller than the entire ABox, and the time for ontology reasoning based on ABox modules can be improved significantly. PMID:26848490

Empirical testing of an analytical model predicting electrical isolation of photovoltaic models

NASA Astrophysics Data System (ADS)

Garcia, A., III; Minning, C. P.; Cuddihy, E. F.

A major design requirement for photovoltaic modules is that the encapsulation system be capable of withstanding large DC potentials without electrical breakdown. Presented is a simple analytical model which can be used to estimate material thickness to meet this requirement for a candidate encapsulation system or to predict the breakdown voltage of an existing module design. A series of electrical tests to verify the model are described in detail. The results of these verification tests confirmed the utility of the analytical model for preliminary design of photovoltaic modules.

Concentrating photovoltaic solar panel

DOEpatents

Cashion, Steven A; Bowser, Michael R; Farrelly, Mark B; Hines, Braden E; Holmes, Howard C; Johnson, Jr., Richard L; Russell, Richard J; Turk, Michael F

2014-04-15

The present invention relates to photovoltaic power systems, photovoltaic concentrator modules, and related methods. In particular, the present invention features concentrator modules having interior points of attachment for an articulating mechanism and/or an articulating mechanism that has a unique arrangement of chassis members so as to isolate bending, etc. from being transferred among the chassis members. The present invention also features adjustable solar panel mounting features and/or mounting features with two or more degrees of freedom. The present invention also features a mechanical fastener for secondary optics in a concentrator module.

Volterra equalization of complex modulation utilizing frequency chirp in directly modulated lasers

NASA Astrophysics Data System (ADS)

Hu, Shaohua; Yi, Xingwen; Zhang, Jing; Song, Yang; Zhu, Mingyue; Qiu, Kun

2018-02-01

We apply Volterra-based equalization for complex modulated optical signals utilizing the frequency chirp in DMLs. We experimentally demonstrate that the higher order Volterra filter is necessary in the higher speed transmissions. For further study, we isolate the adiabatic chirp by injection locking and realize the optical PM transmission. We make a comparison among IM, FM and PM with Volterra equalization, finding that PM and FM are more power insensitive and suitable for high speed, power limited fiber transmission. The performance can be further improved by exploiting the diversity gain.

Apollo 12 crewmen participate in water egress training

NASA Image and Video Library

1969-09-20

S69-52990 (20 Sept. 1969) --- The three prime crew men of the Apollo 12 lunar landing mission participate in water egress training in the Gulf of Mexico. They have just egressed the Apollo Command Module (CM) trainer. The man standing at left is a Manned Spacecraft Center's (MSC) swimmer. The crew men await in life raft for helicopter pickup. All four persons are wearing biological isolation garments. Participating in the training exercise were astronauts Charles Conrad Jr., commander; Richard F. Gordon Jr., command module pilot; and Alan L. Bean, lunar module pilot.

Effects of St John's wort and its active constituents, hypericin and hyperforin, on isolated rat urinary bladder.

PubMed

Valeri, Aurora; Capasso, Raffaele; Valoti, Massimo; Pessina, Federica

2012-12-01

To investigate the effect of St John's wort (SJW) and its active constituents hypericin and hyperforin on detrusor smooth muscle contractility and their possible neuroprotective role against ischaemic-like conditions, which could arise during overactive bladder disease. In whole bladders, intrinsic nerves underwent electrical field stimulation (EFS). The effect of drugs on the contractile response and its recovery in reperfusion phase (R) was monitored at different concentrations during 1 or 2 h of anoxia-glucopenia (A-G) and the first 30 min of R. The effects of the drugs were also investigated on rat detrusor muscle strips contracted with carbachol, KCl and electrically. SJW has spasmolytic activity, which increases with increasing concentration and it worsens the damage induced by A-G/R on rat urinary bladder. Hypericin and hyperforin had no effect during ischemic-like conditions but they both exert a dual modulation of rat detrusor strips contraction. At high micromolar concentrations they showed a relaxing effect, but at submicromolar range hypericin increased the plasma membrane depolarisation and hyperforin showed a stimulatory effect on the cholinergic system. The results of our study showed that SJW and its constituents could modulate urinary bladder contractility and even worsen A-G/R injury. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

CovR Regulates Streptococcus mutans Susceptibility To Complement Immunity and Survival in Blood

PubMed Central

Alves, Lívia A.; Nomura, Ryota; Mariano, Flávia S.; Harth-Chu, Erika N.; Stipp, Rafael N.; Nakano, Kazuhiko

2016-01-01

Streptococcus mutans, a major pathogen of dental caries, may promote systemic infections after accessing the bloodstream from oral niches. In this study, we investigate pathways of complement immunity against S. mutans and show that the orphan regulator CovR (CovRSm) modulates susceptibility to complement opsonization and survival in blood. S. mutans blood isolates showed reduced susceptibility to C3b deposition compared to oral isolates. Reduced expression of covRSm in blood strains was associated with increased transcription of CovRSm-repressed genes required for S. mutans interactions with glucans (gbpC, gbpB, and epsC), sucrose-derived exopolysaccharides (EPS). Consistently, blood strains showed an increased capacity to bind glucan in vitro. Deletion of covRSm in strain UA159 (UAcov) impaired C3b deposition and binding to serum IgG and C-reactive protein (CRP) as well as phagocytosis through C3b/iC3b receptors and killing by neutrophils. Opposite effects were observed in mutants of gbpC, epsC, or gtfBCD (required for glucan synthesis). C3b deposition on UA159 was abolished in C1q-depleted serum, implying that the classical pathway is essential for complement activation on S. mutans. Growth in sucrose-containing medium impaired the binding of C3b and IgG to UA159, UAcov, and blood isolates but had absent or reduced effects on C3b deposition in gtfBCD, gbpC, and epsC mutants. UAcov further showed increased ex vivo survival in human blood in an EPS-dependent way. Consistently, reduced survival was observed for the gbpC and epsC mutants. Finally, UAcov showed an increased ability to cause bacteremia in a rat model. These results reveal that CovRSm modulates systemic virulence by regulating functions affecting S. mutans susceptibility to complement opsonization. PMID:27572331

μ-Opioid receptor activation inhibits N- and P-type Ca2+ channel currents in magnocellular neurones of the rat supraoptic nucleus

PubMed Central

Soldo, Brandi L; Moises, Hylan C

1998-01-01

The whole-cell voltage-clamp technique was used to examine opioid regulation of Ba2+ currents (IBa) through voltage-sensitive Ca2+ channels in isolated magnocellular supraoptic neurones (MNCs). The effects of local application of μ-, δ- or κ-opioid receptor selective agonists were examined on specific components of high voltage-activated (HVA) IBa, pharmacologically isolated by use of Ca2+ channel-subtype selective antagonists. The μ-opioid receptor selective agonist, DAMGO, suppressed HVA IBa (in 64/71 neurones) in a naloxone-reversible and concentration-dependent manner (EC50 = 170 nm, Emax = 19.5 %). The DAMGO-induced inhibition was rapid in onset, associated with kinetic slowing and voltage dependent, being reversed by strong depolarizing prepulses. Low-voltage activated (LVA) IBa was not modulated by DAMGO. Administration of κ- (U69 593) or δ-selective (DPDPE) opioid receptor agonists did not affect IBa. However, immunostaining of permeabilized MNCs with an antibody specific for κ1-opioid receptors revealed the presence of this opioid receptor subtype in a large number of isolated somata. μ-Opioid-induced inhibition in IBa was largely abolished after blockade of N-type and P-type channel currents by ω-conotoxin GVIA (1 μm) and ω-agatoxin IVA (100 nm), respectively. Quantitation of antagonist effects on DAMGO-induced reductions in IBa revealed that N- and P-type channels contributed roughly equally to the μ-opioid sensitive portion of total IBa. These results indicate that μ-opioid receptors are negatively coupled to N- and P-type Ca2+ channels in the somatodendritic regions of MNCs, possibly via a membrane-delimited G-protein-dependent pathway. They also support a scheme in which opioids may act in part to modulate cellular activity and regulate neurosecretory function by their direct action on the neuroendocrine neurones of the hypothalamic supraoptic neucleus. PMID:9824718

Effects of a Spirulina-based dietary supplement on cytokine production from allergic rhinitis patients.

PubMed

Mao, T K; Van de Water, J; Gershwin, M E

2005-01-01

Spirulina represents a blue-green alga that is widely produced and commercialized as a dietary supplement for modulating immune functions, as well as ameliorating a variety of diseases. We have previously shown that the in vitro culture of Spirulina with human peripheral blood mononuclear cells (PBMCs) modulated the production of cytokines. In the present study, we evaluated the impact of a Spirulina-based dietary supplement (Earthrise Nutritionals, Inc., Irvine, CA) on patients with allergic rhinitis by assessing the production of cytokines [interleukin (IL)-4, interferon (IFN)-gamma, and IL-2] critical in regulating immunoglobulin E-mediated allergy. In a randomized double-blinded crossover study versus placebo, allergic individuals were fed daily with either placebo or Spirulina, at 1,000 mg or 2,000 mg, for 12 weeks. PBMCs isolated before and after the Spirulina feeding were stimulated with phytohemagglutinin (PHA) prior to determining the levels of cytokine from cell culture supernatants. Although Spirulina seemed to be ineffective at modulating the secretion of Th1 cytokines (IFN-gamma and IL-2), we discovered that Spirulina, administered at 2,000 mg/day, significantly reduced IL-4 levels by 32% from PHA-stimulated cells. These results indicate that Spirulina can modulate the Th profile in patients with allergic rhinitis by suppressing the differentiation of Th2 cells mediated, in part, by inhibiting the production of IL-4. To our knowledge, this is the first human feeding study that demonstrates the protective effects of Spirulina towards allergic rhinitis.

GABA-A Receptor Modulation and Anticonvulsant, Anxiolytic, and Antidepressant Activities of Constituents from Artemisia indica Linn

PubMed Central

Khan, Imran; Karim, Nasiara; Ahmad, Waqar; Abdelhalim, Abeer; Chebib, Mary

2016-01-01

Artemisia indica, also known as “Mugwort,” has been widely used in traditional medicines. However, few studies have investigated the effects of nonvolatile components of Artemisia indica on central nervous system's function. Fractionation of Artemisia indica led to the isolation of carnosol, ursolic acid, and oleanolic acid which were evaluated for their effects on GABA-A receptors in electrophysiological studies in Xenopus oocytes and were subsequently investigated in mouse models of acute toxicity, convulsions (pentylenetetrazole induced seizures), depression (tail suspension and forced swim tests), and anxiety (elevated plus maze and light/dark box paradigms). Carnosol, ursolic acid, and oleanolic acid were found to be positive modulators of α1β2γ2L GABA-A receptors and the modulation was antagonized by flumazenil. Carnosol, ursolic acid, and oleanolic acid were found to be devoid of any signs of acute toxicity (50–200 mg/kg) but elicited anticonvulsant, antidepressant, and anxiolytic activities. Thus carnosol, ursolic acid, and oleanolic acid demonstrated CNS activity in mouse models of anticonvulsant, antidepressant, and anxiolysis. The anxiolytic activity of all three compounds was ameliorated by flumazenil suggesting a mode of action via the benzodiazepine binding site of GABA-A receptors. PMID:27143980

Nanoscale phase engineering of thermal transport with a Josephson heat modulator.

PubMed

Fornieri, Antonio; Blanc, Christophe; Bosisio, Riccardo; D'Ambrosio, Sophie; Giazotto, Francesco

2016-03-01

Macroscopic quantum phase coherence has one of its pivotal expressions in the Josephson effect, which manifests itself both in charge and energy transport. The ability to master the amount of heat transferred through two tunnel-coupled superconductors by tuning their phase difference is the core of coherent caloritronics, and is expected to be a key tool in a number of nanoscience fields, including solid-state cooling, thermal isolation, radiation detection, quantum information and thermal logic. Here, we show the realization of the first balanced Josephson heat modulator designed to offer full control at the nanoscale over the phase-coherent component of thermal currents. Our device provides magnetic-flux-dependent temperature modulations up to 40 mK in amplitude with a maximum of the flux-to-temperature transfer coefficient reaching 200 mK per flux quantum at a bath temperature of 25 mK. Foremost, it demonstrates the exact correspondence in the phase engineering of charge and heat currents, breaking ground for advanced caloritronic nanodevices such as thermal splitters, heat pumps and time-dependent electronic engines.

Exploring the Role of CYP3A4 Mediated Drug Metabolism in the Pharmacological Modulation of Nitric Oxide Production

PubMed Central

Pérez-del Palacio, José; Díaz, Caridad; Vergara, Noemí; Algieri, Francesca; Rodríguez-Nogales, Alba; de Pedro, Nuria; Rodríguez-Cabezas, M. Elena; Genilloud, Olga; Gálvez, Julio; Vicente, Francisca

2017-01-01

Nitric-oxide synthase, the enzyme responsible for mammalian nitric oxide generation, and cytochrome P450, the major enzymes involved in drug metabolism, share striking similarities. Therefore, it makes sense that cytochrome P450 drug mediated biotransformations might play an important role in the pharmacological modulation of nitric oxide synthase. In this work, we have undertaken an integrated in vitro assessment of the hepatic metabolism and nitric oxide modulation of previously described dual inhibitors (imidazoles and macrolides) of these enzymes in order assess the implication of CYP450 activities over production of nitric oxide. In vitro systems based in human liver microsomes and activated mouse macrophages were developed for these purposes. Additionally in vitro production the hepatic metabolites of dual inhibitor, roxithromycin, was investigated achieving the identification and isolation of main hepatic biotransformation products. Our results suggested that for some macrolide compounds, the cytochrome P450 3A4 derived drug metabolites have an important effect on nitric oxide production and might critically contribute to the pharmacological immunomodulatory activity observed. PMID:28446877

Nanoscale phase engineering of thermal transport with a Josephson heat modulator

NASA Astrophysics Data System (ADS)

Fornieri, Antonio; Blanc, Christophe; Bosisio, Riccardo; D'Ambrosio, Sophie; Giazotto, Francesco

2016-03-01

Macroscopic quantum phase coherence has one of its pivotal expressions in the Josephson effect, which manifests itself both in charge and energy transport. The ability to master the amount of heat transferred through two tunnel-coupled superconductors by tuning their phase difference is the core of coherent caloritronics, and is expected to be a key tool in a number of nanoscience fields, including solid-state cooling, thermal isolation, radiation detection, quantum information and thermal logic. Here, we show the realization of the first balanced Josephson heat modulator designed to offer full control at the nanoscale over the phase-coherent component of thermal currents. Our device provides magnetic-flux-dependent temperature modulations up to 40 mK in amplitude with a maximum of the flux-to-temperature transfer coefficient reaching 200 mK per flux quantum at a bath temperature of 25 mK. Foremost, it demonstrates the exact correspondence in the phase engineering of charge and heat currents, breaking ground for advanced caloritronic nanodevices such as thermal splitters, heat pumps and time-dependent electronic engines.

Effect of social odor context on the emission of isolation-induced ultrasonic vocalizations in the BTBR T+tf/J mouse model for autism

PubMed Central

Wöhr, Markus

2015-01-01

An important diagnostic criterion for social communication deficits in autism spectrum disorders (ASD) are difficulties in adjusting behavior to suit different social contexts. While the BTBR T+tf/J (BTBR) inbred strain of mice is one of the most commonly used mouse models for ASD, little is known about whether BTBR mice display deficits in detecting changes in social context and their ability to adjust to them. Here, it was tested therefore whether the emission of isolation-induced ultrasonic vocalizations (USV) in BTBR mouse pups is affected by the social odor context, in comparison to the standard control strain with high sociability, C57BL/6J (B6). It is known that the presence of odors from mothers and littermates leads to a calming of the isolated mouse pup, and hence to a reduction in isolation-induced USV emission. In accordance with their behavioral phenotypes with relevance to all diagnostic core symptoms of ASD, it was predicted that BTBR mouse pups would not display a calming response when tested under soiled bedding conditions with home cage bedding material containing maternal odors, and that similar isolation-induced USV emission rates would be seen in BTBR mice tested under clean and soiled bedding conditions. Unexpectedly, however, the present findings show that BTBR mouse pups display such a calming response and emit fewer isolation-induced USV when tested under soiled as compared to clean bedding conditions, similar to B6 mouse pups. Yet, in contrast to B6 mouse pups, which emitted isolation-induced USV with shorter call durations and lower levels of frequency modulation under soiled bedding conditions, social odor context had no effect on acoustic call features in BTBR mouse pups. This indicates that the BTBR mouse model for ASD does not display deficits in detecting changes in social context, but has a limited ability and/or reduced motivation to adjust to them. PMID:25852455

Optical voltage reference

DOEpatents

Rankin, R.; Kotter, D.

1994-04-26

An optical voltage reference for providing an alternative to a battery source is described. The optical reference apparatus provides a temperature stable, high precision, isolated voltage reference through the use of optical isolation techniques to eliminate current and impedance coupling errors. Pulse rate frequency modulation is employed to eliminate errors in the optical transmission link while phase-lock feedback is employed to stabilize the frequency to voltage transfer function. 2 figures.

Enriched environment increases neurogenesis and improves social memory persistence in socially isolated adult mice.

PubMed

Monteiro, Brisa M M; Moreira, Fabrício A; Massensini, André R; Moraes, Márcio F D; Pereira, Grace S

2014-02-01

Social memory consists of the information necessary to identify and recognize cospecifics and is essential to many forms of social interaction. Social memory persistence is strongly modulated by the animal's experiences. We have shown in previous studies that social isolation (SI) in adulthood impairs social memory persistence and that an enriched environment (EE) prevents this impairment. However, the mechanisms involved in the effects of SI and EE on social memory persistence remain unknown. We hypothesized that the mechanism by which SI and EE affect social memory persistence is through their modulation of neurogenesis. To investigate this hypothesis, adult mice were submitted to 7 days of one of the following conditions: group-housing in a standard (GH) or enriched environment (GH+EE); social isolation in standard (SI) or enriched environment (SI+EE). We observed an increase in the number of newborn neurons in the dentate gyrus of the hippocampus (DG) and glomerular layer of the olfactory bulb (OB) in both GH+EE and SI+EE mice. However, this increase of newborn neurons in the granule cell layer of the OB was restricted to the GH+EE group. Furthermore, both SI and SI+EE groups showed less neurogenesis in the mitral layer of the OB. Interestingly, the performance of the SI mice in the buried food-finding task was inferior to that of the GH mice. To further analyze whether increased neurogenesis is in fact the mechanism by which the EE improves social memory persistence in SI mice, we administered the mitotic inhibitor AraC or saline directly into the lateral ventricles of the SI+EE mice. We found that the AraC treatment decreased cell proliferation in both the DG and OB, and impaired social memory persistence in the SI+EE mice. Taken together, our results strongly suggest that neurogenesis is what supports social memory persistence in socially isolated mice. © 2013 Wiley Periodicals, Inc.

A Pseudopterane Diterpene Isolated From the Octocoral Pseudopterogorgia acerosa Inhibits the Inflammatory Response Mediated by TLR-Ligands and TNF-Alpha in Macrophages

PubMed Central

González, Yisett; Doens, Deborah; Santamaría, Ricardo; Ramos, Marla; Restrepo, Carlos M.; Barros de Arruda, Luciana; Lleonart, Ricardo; Gutiérrez, Marcelino; Fernández, Patricia L.

2013-01-01

Several diterpenoids isolated from terrestrial and marine environments have been identified as important anti-inflammatory agents. Although considerable progress has been made in the area of anti-inflammatory treatment, the search for more effective and safer compounds is a very active field of research. In this study we investigated the anti-inflammatory effects of a known pseudopterane diterpene (referred here as compound 1) isolated from the octocoral Pseudopterogorgia acerosa on the tumor necrosis factor- alpha (TNF-α) and TLRs- induced response in macrophages. Compound 1 inhibited the expression and secretion of the inflammatory mediators TNF-α, interleukin (IL)-6, IL-1β, nitric oxide (NO), interferon gamma-induced protein 10 (IP-10), ciclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) and monocyte chemoattractant protein-1 (MCP-1) induced by LPS in primary murine macrophages. This effect was associated with the inhibition of IκBα degradation and subsequent activation of NFκB. Compound 1 also inhibited the expression of the co-stimulatory molecules CD80 and CD86, which is a hallmark of macrophage activation and consequent initiation of an adaptive immune response. The anti-inflammatory effect was not exclusive to LPS because compound 1 also inhibited the response of macrophages to TNF-α and TLR2 and TLR3 ligands. Taken together, these results indicate that compound 1 is an anti-inflammatory molecule, which modulates a variety of processes occurring in macrophage activation. PMID:24358331

Biological effects of novel bovine milk fractions.

PubMed

Lönnerdal, Bo

2011-01-01

Novel dairy fractions have been isolated and are now commercially available. Several of them have been shown to have biological activities in various test systems. α-Lactalbumin was first isolated to provide a good source of tryptophan, often the first limiting amino acid in infant formulas, but has then been shown to be digested into smaller peptides with antimicrobial and prebiotic activities, immunostimulatory effect and acting as enhancers of mineral absorption. Lactoferrin bioactivities include antibacterial and antiviral effects, regulation of immune function, stimulation of intestinal proliferation and differentiation and facilitating iron absorption, but these activities may have been limited due to earlier contamination with LPS. Lactoferrin free of lipopolysaccharide may prove to be more effective with regard to exerting these activities. Osteopontin is a heavily phosphorylated and glycosylated protein that modulates immune function and stimulates Th1/Th2 switching, and, possibly, also affects bone mineralization and growth. Biological activities of lactoferrin may be facilitated by osteopontin. Milk fat globule membranes are a fraction that has previously been excluded from infant formulas, but components of this fraction have been shown to exhibit antimicrobial activities and to prevent infection. Further clinical studies are needed on infants fed formulas with these components incorporated. Copyright © 2011 S. Karger AG, Basel.

Diadenosine Polyphosphates Suppress the Effects of Sympathetic Nerve Stimulation in Rabbit Heart Pacemaker.

PubMed

Abramochkin, D V; Pustovit, K B; Kuz'min, V S

2017-09-01

The modulatory influence of diadenosine tetraphosphate (Ap4A) and diadenosine pentaphosphate (Ap5A) on the effect of intramural autonomic nerve stimulation in isolated rabbit sinoatrial node were examined. Electrical activity of the sinoatrial node was recorded intracellularly. Against the background of blockade of adrenergic effects with propranolol (3×10 -6 M) or in preparations isolated 2 h after injection of reserpine (2 mg/kg), nerve stimulation induced short-term membrane hyperpolarization and diminished the sinus node firing rate. These phenomena were not affected by Ap4A or Ap5A (10 -5 M). Under the action of atropine (3×10 -6 M) that completely eliminated the cholinergic influences, nerve stimulation enhanced the sinus node firing rate by 17.30±3.45% from the initial rate. Both Ap4A and Ap5A moderated the stimulation-induced elevation of firing rate to 9.9±2.8 and 10.5±2.9%, respectively. The data suggest that diadenosine polyphosphates significantly modulate the sympathetic influences on the heart rhythm, but have no effect on the parasympathetic control over activity of sinoatrial node.

Inhibitory Effects of Honokiol on the Voltage-Gated Potassium Channels in Freshly Isolated Mouse Dorsal Root Ganglion Neurons.

PubMed

Sheng, Anqi; Zhang, Yan; Li, Guang; Zhang, Guangqin

2018-02-01

Voltage-gated potassium (K V ) currents, subdivided into rapidly inactivating A-type currents (I A ) and slowly inactivating delayed rectifier currents (I K ), play a fundamental role in modulating pain by controlling neuronal excitability. The effects of Honokiol (Hon), a natural biphenolic compound derived from Magnolia officinalis, on K V currents were investigated in freshly isolated mouse dorsal root ganglion neurons using the whole-cell patch clamp technique. Results showed that Hon inhibited I A and I K in concentration-dependent manner. The IC 50 values for block of I A and I K were 30.5 and 25.7 µM, respectively. Hon (30 µM) shifted the steady-state activation curves of I A and I K to positive potentials by 17.6 and 16.7 mV, whereas inactivation and recovery from the inactivated state of I A were unaffected. These results suggest that Hon preferentially interacts with the active states of the I A and I K channels, and has no effect on the resting state and inactivated state of the I A channel. Blockade on K + channels by Hon may contribute to its antinociceptive effect, especially anti-inflammatory pain.

Oral Serum-Derived Bovine Immunoglobulin/Protein Isolate Has Immunomodulatory Effects on the Colon of Mice that Spontaneously Develop Colitis.

PubMed

Pérez-Bosque, Anna; Miró, Lluïsa; Maijó, Mònica; Polo, Javier; Campbell, Joy M; Russell, Louis; Crenshaw, Joe D; Weaver, Eric; Moretó, Miquel

2016-01-01

Dietary immunoglobulin concentrates prepared from animal plasma can modulate the immune response of gut-associated lymphoid tissue (GALT). Previous studies have revealed that supplementation with serum-derived bovine immunoglobulin/protein isolate (SBI) ameliorates colonic barrier alterations in the mdr1a-/- genetic mouse model of IBD. Here, we examine the effects of SBI on mucosal inflammation in mdr1a-/- mice that spontaneously develop colitis. Wild type (WT) mice and mice lacking the mdr1a gene (KO) were fed diets supplemented with either SBI (2% w/w) or milk proteins (Control diet), from day 21 (weaning) until day 56. Leucocytes in mesenteric lymph nodes (MLN) and in lamina propria were determined, as was mucosal cytokine production. Neutrophil recruitment and activation in MLN and lamina propria of KO mice were increased, but were significantly reduced in both by SBI supplementation (p < 0.05). The increased neutrophil recruitment and activation observed in KO mice correlated with increased colon oxidative stress (p < 0.05) and SBI supplementation reduced this variable (p < 0.05). The Tact/Treg lymphocyte ratios in MLN and lamina propria were also increased in KO animals, but SBI prevented these changes (both p < 0.05). In the colon of KO mice, there was an increased production of mucosal pro-inflammatory cytokines such as IL-2 (2-fold), IL-6 (26-fold) and IL-17 (19-fold), and of chemokines MIP-1β (4.5-fold) and MCP-1 (7.2-fold). These effects were significantly prevented by SBI (p < 0.05). SBI also significantly increased TGF-β secretion in the colon mucosa, suggesting a role of this anti-inflammatory cytokine in the modulation of GALT and the reduction of the severity of the inflammatory response during the onset of colitis.

Prefrontal cortical glutathione-dependent defense and proinflammatory mediators in chronically isolated rats: Modulation by fluoxetine or clozapine.

PubMed

Todorović, Nevena; Filipović, Dragana

2017-07-04

Chronic psychosocial stress modulates brain antioxidant systems and causes neuroinflammation that plays a role in the pathophysiology of depression. Although the antidepressant fluoxetine (FLX) represents the first-line treatment for depression and the atypical antipsychotic clozapine (CLZ) is considered as a second-line treatment for psychotic disorders, the downstream mechanisms of action of these treatments, beyond serotonergic or dopaminergic signaling, remain elusive. We examined behavioral changes, glutathione (GSH)-dependent defense and levels of proinflammatory mediators in the prefrontal cortex (PFC) of adult male Wistar rats exposed to 21days of chronic social isolation (CSIS). We also tested the ability of FLX (15mg/kg/day) or CLZ (20mg/kg/day), applied during CSIS, to prevent stress-induced changes. CSIS caused depressive- and anxiety-like behaviors, compromised GSH-dependent defense, and induced nuclear factor-kappa B (NF-κB) activation with a concomitant increase in cytosolic levels of proinflammatory mediators cyclooxigenase-2, interleukin-1beta and tumor necrosis factor-alpha in the PFC. NF-κB activation and proinflammatory response in the PFC were not found in CSIS rats treated with FLX or CLZ. In contrast, only FLX preserved GSH content in CSIS rats. CLZ not only failed to protect against CSIS-induced GSH depletion, but it diminished its levels when applied to non-stressed rats. In conclusion, prefrontal cortical GSH depletion and the proinflammatory response underlying depressive- and anxiety-like states induced by CSIS were prevented by FLX. The protective effect of CLZ, which was equally effective as FLX on the behavioral level, was limited to proinflammatory components. Hence, different mechanisms underlie the protective effects of these two drugs in CSIS rats. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

High-Throughput, Motility-Based Sorter for Microswimmers such as C. elegans

PubMed Central

Yuan, Jinzhou; Zhou, Jessie; Raizen, David M.; Bau, Haim H.

2015-01-01

Animal motility varies with genotype, disease, aging, and environmental conditions. In many studies, it is desirable to carry out high throughput motility-based sorting to isolate rare animals for, among other things, forward genetic screens to identify genetic pathways that regulate phenotypes of interest. Many commonly used screening processes are labor-intensive, lack sensitivity, and require extensive investigator training. Here, we describe a sensitive, high throughput, automated, motility-based method for sorting nematodes. Our method is implemented in a simple microfluidic device capable of sorting thousands of animals per hour per module, and is amenable to parallelism. The device successfully enriches for known C. elegans motility mutants. Furthermore, using this device, we isolate low-abundance mutants capable of suppressing the somnogenic effects of the flp-13 gene, which regulates C. elegans sleep. By performing genetic complementation tests, we demonstrate that our motility-based sorting device efficiently isolates mutants for the same gene identified by tedious visual inspection of behavior on an agar surface. Therefore, our motility-based sorter is capable of performing high throughput gene discovery approaches to investigate fundamental biological processes. PMID:26008643

Revealing the Hidden Relationship by Sparse Modules in Complex Networks with a Large-Scale Analysis

PubMed Central

Jiao, Qing-Ju; Huang, Yan; Liu, Wei; Wang, Xiao-Fan; Chen, Xiao-Shuang; Shen, Hong-Bin

2013-01-01

One of the remarkable features of networks is module that can provide useful insights into not only network organizations but also functional behaviors between their components. Comprehensive efforts have been devoted to investigating cohesive modules in the past decade. However, it is still not clear whether there are important structural characteristics of the nodes that do not belong to any cohesive module. In order to answer this question, we performed a large-scale analysis on 25 complex networks with different types and scales using our recently developed BTS (bintree seeking) algorithm, which is able to detect both cohesive and sparse modules in the network. Our results reveal that the sparse modules composed by the cohesively isolated nodes widely co-exist with the cohesive modules. Detailed analysis shows that both types of modules provide better characterization for the division of a network into functional units than merely cohesive modules, because the sparse modules possibly re-organize the nodes in the so-called cohesive modules, which lack obvious modular significance, into meaningful groups. Compared with cohesive modules, the sizes of sparse ones are generally smaller. Sparse modules are also found to have preferences in social and biological networks than others. PMID:23762457

Single-Chip T/R Module for 1.2 GHz

NASA Technical Reports Server (NTRS)

Moussessian, Alina; Mojarradi, Mohammad; Johnson, Travis; Davis, John; Grigorian, Edwin; Hoffman, James; Caro, Edward; Kuhn, William

2006-01-01

A single-chip CMOS-based (complementary-metal-oxide-semiconductorbased) transmit/receive (T/R) module is being developed for L-band radar systems. Previous T/R module implementations required multiple chips employing different technologies (GaAs, Si, and others) combined with off-chip transmission lines and discrete components including circulators. The new design eliminates the bulky circulator, significantly reducing the size and mass of the T/R module. Compared to multi-chip designs, the single-chip CMOS can be implemented with lower cost. These innovations enable cost-effective realization of advanced phased array and synthetic aperture radar systems that require integration of thousands of T/R modules. The circulator is a ferromagnetic device that directs the flow of the RF (radio frequency) power during transmission and reception. During transmission, the circulator delivers the transmitted power from the amplifier to the antenna, while preventing it from damaging the sensitive receiver circuitry. During reception, the circulator directs the energy from the antenna to the low-noise amplifier (LNA) while isolating the output of the power amplifier (PA). In principle, a circulator could be replaced by series transistors acting as electronic switches. However, in practice, the integration of conventional series transistors into a T/R chip introduces significant losses and noise. The prototype single-chip T/R module contains integrated transistor switches, but not connected in series; instead, they are connected in a shunt configuration with resonant circuits (see figure). The shunt/resonant circuit topology not only reduces the losses associated with conventional semiconductor switches but also provides beneficial transformation of impedances for the PA and the LNA. It provides full singlepole/ double-throw switching for the antenna, isolating the LNA from the transmitted signal and isolating the PA from the received signal. During reception, the voltage on control line RX/TX (raised bar) is high, causing the field-effect transistor (FET) switch S1 to be closed, forming a parallel resonant tank circuit L1||C1. This circuit presents high impedance to the left of the antenna, so that the received signal is coupled to the LNA. At the same time, FET switches S2 and S3 are open, so that C2 is removed from the circuit (except for a small parasitic capacitance). The combination of L2 and C3 forms a matching network that transforms the antenna impedance of 50 ohms to a higher value from the perspective of the LNA input terminal. This transformation of impedance improves LNA noise figure by increasing the received voltage delivered to the input transistor. This allows lower transconductance and therefore a smaller transistor, which makes it possible to design the CMOS LNA for low power consumption. During transmission, the voltage on control line RX/TX (raised bar) is low, causing switch S1 to be open. In this configuration, the combination of L1 and C1 transforms the antenna impedance to a lower value from the perspective of the PA. This low impedance is helpful in producing a relatively high output power compatible with the low CMOS operating potential. At the same time, switches S2 and S3 are closed, forming the parallel resonant tank circuit L2||C2. This circuit presents high impedance to the right of the antenna, directing the PA output signal to the antenna and away from the LNA. During this time, S3 presents a short circuit across the LNA input terminals to guarantee that the voltage seen by the LNA is small enough to prevent damage.

Pre-treatment of soybean plants with calcium stimulates ROS responses and mitigates infection by Sclerotinia sclerotiorum.

PubMed

Arfaoui, Arbia; El Hadrami, Abdelbasset; Daayf, Fouad

2018-01-01

Considering the high incidence of white mold caused by Sclerotinia sclerotiorum in a variety of field crops and vegetables, different control strategies are needed to keep the disease under economical threshold. This study assessed the effect of foliar application of a calcium formulation on disease symptoms, oxalic acid production, and on the oxidative stress metabolism in soybean plants inoculated with each of two isolates of the pathogen that have contrasting aggressiveness (HA, highly-aggressive versus WA, weakly-aggressive). Changes in reactive oxygen species (ROS) levels in soybean plants inoculated with S. sclerotiorum isolates were assessed at 6, 24, 48 and 72 h post inoculation (hpi). Generation of ROS including hydrogen peroxide (H 2 O 2 ), anion superoxide (O 2 - ) and hydroxyl radical (OH) was evaluated. Inoculation with the WA isolate resulted in more ROS accumulation compared to the HA isolate. Pre-treatment with the calcium formulation restored ROS production in plants inoculated with the HA isolate. We also noted a marked decrease in oxalic acid content in the leaves inoculated with the HA isolate in presence of calcium, which coincided with an increase in plant ROS production. The expression patterns of genes involved in ROS detoxification in response to the calcium treatments and/or inoculation with S. Sclerotiorum isolates were monitored by RT-qPCR. All of the tested genes showed a higher expression in response to inoculation with the WA isolate. The expression of most genes tested peaked at 6 hpi, which preceded ROS accumulation in the soybean leaves. Overall, these data suggest that foliar application of calcium contributes to a decrease in oxalic acid production and disease, arguably via modulation of the ROS metabolism. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Modulation of human multidrug-resistance MDR-1 gene by natural curcuminoids

PubMed Central

Limtrakul, Pornngarm; Anuchapreeda, Songyot; Buddhasukh, Duang

2004-01-01

Background Multidrug resistance (MDR) is a phenomenon that is often associated with decreased intracellular drug accumulation in patient's tumor cells resulting from enhanced drug efflux. It is related to the overexpression of a membrane protein, P-glycoprotein (Pgp-170), thereby reducing drug cytotoxicity. A variety of studies have tried to find MDR modulators which increase drug accumulation in cancer cells. Methods In this study, natural curcuminoids, pure curcumin, demethoxycurcumin and bisdemethoxycurcumin, isolated from turmeric (Curcuma longa Linn), were compared for their potential ability to modulate the human MDR-1 gene expression in multidrug resistant human cervical carcinoma cell line, KB-V1 by Western blot analysis and RT-PCR. Results Western blot analysis and RT-PCR showed that all the three curcuminoids inhibited MDR-1 gene expression, and bisdemethoxycurcumin produced maximum effect. In additional studies we found that commercial grade curcuminoid (approximately 77% curcumin, 17% demethoxycurcumin and 3% bisdemthoxycurcumin) decreased MDR-1 gene expression in a dose dependent manner and had about the same potent inhibitory effect on MDR-1 gene expression as our natural curcuminoid mixtures. Conclusion These results indicate that bisdemethoxycurcumin is the most active of the curcuminoids present in turmeric for modulation of MDR-1 gene. Treatment of drug resistant KB-V1 cells with curcumin increased their sensitivity to vinblastine, which was consistent with a decreased MDR-1 gene product, a P-glycoprotein, on the cell plasma membrane. Although many drugs that prevent the P-glycoprotein function have been reported, this report describes the inhibition of MDR-1 expression by a phytochemical. The modulation of MDR-1 expression may be an attractive target for new chemosensitizing agents. PMID:15090070

The effect of zinc diffusion on extinction ratio of MQW electroabsorption modulator integrated with DFB laser

NASA Astrophysics Data System (ADS)

Zhou, Daibing; Zhang, Ruikang; Wang, Huitao; Wang, Baojun; Bian, Jing; An, Xin; Zhao, Lingjuan; Zhu, Hongliang; Ji, Chen; Wang, Wei

2014-11-01

Monolithically integrated electroabsorption modulated lasers (EML) are widely being used in the optical fiber communication systems, due to their low chip, compact size and good compatible with the current communication systems. In this paper, we investigated the effect of Zinc diffusion on extinction ratio of electroabsorption modulator (EAM) integrated with distributed feedback laser (DFB). EML was fabricated by selective area growth (SAG) technology. The MQW structure of different quantum energy levels was grown on n-type InP buffer layer with 150nm thick SiO2 parallel stripes mask by selective area metal-organic chemical vapor deposition (MOCVD). A 35nm photoluminescence wavelength variation was observed between the laser area (λPL=1535nm) and modulator area (λPL=1500nm) by adjusting the dimension of parallel stripes. The grating (λ=1550nm) was fabricated in the selective area. The device was mesa ridge structure, which was constituted of the DFB laser, isolation gap and modulator. The length of every part is 300μm, 50μm, and 150μm respectively. Two samples were fabricated with the same structure and different p-type Zn-doped concentration, the extinction ratio of heavy Zn-doped device is 12.5dB at -6V. In contrast, the extinction ratio of light Zn-doped device is 20dB at -6V, that was improved for approximate 60%. The different Zn diffusion depth into the MQW absorption layer was observed by Secondary ion mass spectrometer (SIMS). The heavy Zn-doped device diffused into absorption layer deeper than the light Zn-doped device, which caused the large non-uniformity of the electric field in the MQW layer. So the extinction ratio characteristics can be improved by optimizing the Zn-doped concentration of p-type layer.

Wise retained in the endoplasmic reticulum inhibits Wnt signaling by reducing cell surface LRP6.

PubMed

Guidato, Sonia; Itasaki, Nobue

2007-10-15

The Wnt signaling pathway is tightly regulated by extracellular and intracellular modulators. Wise was isolated as a secreted protein capable of interacting with the Wnt co-receptor LRP6. Studies in Xenopus embryos revealed that Wise either enhances or inhibits the Wnt pathway depending on the cellular context. Here we show that the cellular localization of Wise has distinct effects on the Wnt pathway readout. While secreted Wise either synergizes or inhibits the Wnt signals depending on the partner ligand, ER-retained Wise consistently blocks the Wnt pathway. ER-retained Wise reduces LRP6 on the cell surface, making cells less susceptible to the Wnt signal. This study provides a cellular mechanism for the action of Wise and introduces the modulation of cellular susceptibility to Wnt signals as a novel mechanism of the regulation of the Wnt pathway.

Reward acts on the pFC to enhance distractor resistance of working memory representations.

PubMed

Fallon, Sean James; Cools, Roshan

2014-12-01

Working memory and reward processing are often thought to be separate, unrelated processes. However, most daily activities involve integrating these two types of information, and the two processes rarely, if ever, occur in isolation. Here, we show that working memory and reward interact in a task-dependent manner and that this task-dependent interaction involves modulation of the pFC by the ventral striatum. Specifically, BOLD signal during gains relative to losses in the ventral striatum and pFC was associated not only with enhanced distractor resistance but also with impairment in the ability to update working memory representations. Furthermore, the effect of reward on working memory was accompanied by differential coupling between the ventral striatum and ignore-related regions in the pFC. Together, these data demonstrate that reward-related signals modulate the balance between cognitive stability and cognitive flexibility by altering functional coupling between the ventral striatum and the pFC.

Selection of specific interactors from phage display library based on sea lamprey variable lymphocyte receptor sequences.

PubMed

Wezner-Ptasinska, Magdalena; Otlewski, Jacek

2015-12-01

Variable lymphocyte receptors (VLRs) are non-immunoglobulin components of adaptive immunity in jawless vertebrates. These proteins composed of leucine-rich repeat modules offer some advantages over antibodies in target binding and therefore are attractive candidates for biotechnological applications. In this paper we report the design and characterization of a phage display library based on a previously proposed dVLR scaffold containing six LRR modules [Wezner-Ptasinska et al., 2011]. Our library was designed based on a consensus approach in which the randomization scheme reflects the frequencies of amino acids naturally occurring in respective positions responsible for antigen recognition. We demonstrate general applicability of the scaffold by selecting dVLRs specific for lysozyme and S100A7 protein with KD values in the micromolar range. The dVLR library could be used as a convenient alternative to antibodies for effective isolation of high affinity binders.

Defibrotide modulates prostaglandin production in the rat mesenteric vascular bed.

PubMed

Peredo, H A

2002-10-01

Defibrotide 1 microM, a polydeoxyribonucleotide extracted from mammalian organs, reduced the contractile responses to noradrenaline (NA) in the rat isolated and perfused mesenteric vascular bed, in intact as well as in de-endothelialized preparations. Defibrotide was without effect on the acetylcholine-induced relaxations of U-46619-precontracted mesenteric vascular beds. Moreover, defibrotide increased 6-keto prostaglandin (PG) F(2alpha) (stable metabolite of prostacyclin) release sixfold in the presence, but not in the absence of the endothelium, with no modification on the release of other prostanoids. Defibrotide also inhibited the NA-induced increase in PGF(2alpha) release, in both intact and de-endothelialized mesenteric vascular beds. In conclusion, the present results show that defibrotide modulates PG production in the mesenteric bed and that the observed inhibition of the contractile responses should be due to the impairment of the NA-induced increase in PGF(2alpha) release.

The Structure–Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation

PubMed Central

Bow, Eric W.; Rimoldi, John M.

2016-01-01

The cannabinoids are members of a deceptively simple class of terpenophenolic secondary metabolites isolated from Cannabis sativa highlighted by (−)-Δ9-tetrahydrocannabinol (THC), eliciting distinct pharmacological effects mediated largely by cannabinoid receptor (CB1 or CB2) signaling. Since the initial discovery of THC and related cannabinoids, synthetic and semisynthetic classical cannabinoid analogs have been evaluated to help define receptor binding modes and structure–CB1/CB2 functional activity relationships. This perspective will examine the classical cannabinoids, with particular emphasis on the structure–activity relationship of five regions: C3 side chain, phenolic hydroxyl, aromatic A-ring, pyran B-ring, and cyclohexenyl C-ring. Cumulative structure–activity relationship studies to date have helped define the critical structural elements required for potency and selectivity toward CB1 and CB2 and, more importantly, ushered the discovery and development of contemporary nonclassical cannabinoid modulators with enhanced physicochemical and pharmacological profiles. PMID:27398024

PV modules for ground testing

NASA Technical Reports Server (NTRS)

1986-01-01

The main objective was to design and build a minimum of three photovoltaic test panels for plasma interaction experiments. These experiments are intended to provide data on the interactions between high-voltage solar arrays and the space plasma environment. Data gathered will significantly contribute to the development of design criteria for the space station solar arrays. Electrical isolation between the solar cell strings and the module mounting plate is required for high-voltage bias.

Differential Inhibition of Water and Ion Channel Activities of Mammalian Aquaporin-1 by Two Structurally Related Bacopaside Compounds Derived from the Medicinal Plant Bacopa monnieri.

PubMed

Pei, Jinxin V; Kourghi, Mohamad; De Ieso, Michael L; Campbell, Ewan M; Dorward, Hilary S; Hardingham, Jennifer E; Yool, Andrea J

2016-10-01

Aquaporin-1 (AQP1) is a major intrinsic protein that facilitates flux of water and other small solutes across cell membranes. In addition to its function as a water channel in maintaining fluid homeostasis, AQP1 also acts as a nonselective cation channel gated by cGMP, a property shown previously to facilitate rapid cell migration in a AQP1-expressing colon cancer cell line. Here we report two new modulators of AQP1 channels, bacopaside I and bacopaside II, isolated from the medicinal plant Bacopa monnieri Screening was conducted in the Xenopus oocyte expression system, using quantitative swelling and two-electrode voltage clamp techniques. Results showed bacopaside I blocked both the water (IC50 117 μM) and ion channel activities of AQP1 but did not alter AQP4 activity, whereas bacopaside II selectively blocked the AQP1 water channel (IC50 18 μM) without impairing the ionic conductance. These results fit with predictions from in silico molecular modeling. Both bacopasides were tested in migration assays using HT29 and SW480 colon cancer cell lines, with high and low levels of AQP1 expression, respectively. Bacopaside I (IC50 48 μM) and bacopaside II (IC50 14 μM) impaired migration of HT29 cells but had minimal effect on SW480 cell migration. Our results are the first to identify differential AQP1 modulators isolated from a medicinal plant. Bacopasides could serve as novel lead compounds for pharmaceutic development of selective aquaporin modulators. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Floquet topological insulators for sound

NASA Astrophysics Data System (ADS)

Fleury, Romain; Khanikaev, Alexander B.; Alù, Andrea

2016-06-01

The unique conduction properties of condensed matter systems with topological order have recently inspired a quest for the similar effects in classical wave phenomena. Acoustic topological insulators, in particular, hold the promise to revolutionize our ability to control sound, allowing for large isolation in the bulk and broadband one-way transport along their edges, with topological immunity against structural defects and disorder. So far, these fascinating properties have been obtained relying on moving media, which may introduce noise and absorption losses, hindering the practical potential of topological acoustics. Here we overcome these limitations by modulating in time the acoustic properties of a lattice of resonators, introducing the concept of acoustic Floquet topological insulators. We show that acoustic waves provide a fertile ground to apply the anomalous physics of Floquet topological insulators, and demonstrate their relevance for a wide range of acoustic applications, including broadband acoustic isolation and topologically protected, nonreciprocal acoustic emitters.

Dynamic protein coronas revealed as a modulator of silver nanoparticle sulphidation in vitro

NASA Astrophysics Data System (ADS)

Miclăuş, Teodora; Beer, Christiane; Chevallier, Jacques; Scavenius, Carsten; Bochenkov, Vladimir E.; Enghild, Jan J.; Sutherland, Duncan S.

2016-06-01

Proteins adsorbing at nanoparticles have been proposed as critical toxicity mediators and are included in ongoing efforts to develop predictive tools for safety assessment. Strongly attached proteins can be isolated, identified and correlated to changes in nanoparticle state, cellular association or toxicity. Weakly attached, rapidly exchanging proteins are also present at nanoparticles, but are difficult to isolate and have hardly been examined. Here we study rapidly exchanging proteins and show for the first time that they have a strong modulatory effect on the biotransformation of silver nanoparticles. Released silver ions, known for their role in particle toxicity, are found to be trapped as silver sulphide nanocrystals within the protein corona at silver nanoparticles in serum-containing cell culture media. The strongly attached corona acts as a site for sulphidation, while the weakly attached proteins reduce nanocrystal formation in a serum-concentration-dependent manner. Sulphidation results in decreased toxicity of Ag NPs.

Floquet topological insulators for sound

PubMed Central

Fleury, Romain; Khanikaev, Alexander B; Alù, Andrea

2016-01-01

The unique conduction properties of condensed matter systems with topological order have recently inspired a quest for the similar effects in classical wave phenomena. Acoustic topological insulators, in particular, hold the promise to revolutionize our ability to control sound, allowing for large isolation in the bulk and broadband one-way transport along their edges, with topological immunity against structural defects and disorder. So far, these fascinating properties have been obtained relying on moving media, which may introduce noise and absorption losses, hindering the practical potential of topological acoustics. Here we overcome these limitations by modulating in time the acoustic properties of a lattice of resonators, introducing the concept of acoustic Floquet topological insulators. We show that acoustic waves provide a fertile ground to apply the anomalous physics of Floquet topological insulators, and demonstrate their relevance for a wide range of acoustic applications, including broadband acoustic isolation and topologically protected, nonreciprocal acoustic emitters. PMID:27312175

Signal Processing for Wireless Communication MIMO System with Nano- Scaled CSDG MOSFET based DP4T RF Switch.

PubMed

Srivastava, Viranjay M

2015-01-01

In the present technological expansion, the radio frequency integrated circuits in the wireless communication technologies became useful because of the replacement of increasing number of functions, traditional hardware components by modern digital signal processing. The carrier frequencies used for communication systems, now a day, shifted toward the microwave regime. The signal processing for the multiple inputs multiple output wireless communication system using the Metal- Oxide-Semiconductor Field-Effect-Transistor (MOSFET) has been done a lot. In this research the signal processing with help of nano-scaled Cylindrical Surrounding Double Gate (CSDG) MOSFET by means of Double- Pole Four-Throw Radio-Frequency (DP4T RF) switch, in terms of Insertion loss, Isolation, Reverse isolation and Inter modulation have been analyzed. In addition to this a channel model has been presented. Here, we also discussed some patents relevant to the topic.

Voltage-dependent neuromodulation of Na+ channels by D1-like dopamine receptors in rat hippocampal neurons.

PubMed

Cantrell, A R; Scheuer, T; Catterall, W A

1999-07-01

Activation of D1-like dopamine (DA) receptors reduces peak Na+ current in acutely isolated hippocampal neurons through phosphorylation of the alpha subunit of the Na+ channel by cAMP-dependent protein kinase (PKA). Here we report that neuromodulation of Na+ currents by DA receptors via PKA is voltage-dependent in the range of -110 to -70 mV and is also sensitive to concurrent activation of protein kinase C (PKC). Depolarization enhanced the ability of D1-like DA receptors to reduce peak Na+ currents via the PKA pathway. Similar voltage-dependent modulation was observed when PKA was activated directly with the membrane-permeant PKA activator DCl-cBIMPS (cBIMPS; 20 microM), indicating that the membrane potential dependence occurs downstream of PKA. PKA activation caused only a small (-2.9 mV) shift in the voltage dependence of steady-state inactivation and had no effect on slow inactivation or on the rates of entry into the fast or slow inactivated states, suggesting that another mechanism is responsible for coupling of membrane potential changes to PKA modulation. Activation of PKC with a low concentration of the membrane-permeant diacylglycerol analog oleylacetyl glycerol also potentiated modulation by SKF 81297 or cBIMPS, and these effects were most striking at hyperpolarized membrane potentials where PKA modulation was not stimulated by membrane depolarization. Thus, activation of D1-like DA receptors causes a strong reduction in Na+ current via the PKA pathway, but it is effective primarily when it is combined with depolarization or activation of PKC. The convergence of these three distinct signaling modalities on the Na+ channel provides an intriguing mechanism for integration of information from multiple signaling pathways in the hippocampus and CNS.

The α2C-adrenoceptor antagonist, ORM-10921, has antipsychotic-like effects in social isolation reared rats and bolsters the response to haloperidol.

PubMed

Uys, Madeleine; Shahid, Mohammed; Sallinen, Jukka; Dreyer, Walter; Cockeran, Marike; Harvey, Brian H

2016-11-03

Early studies suggest that selective α2C-adrenoceptor (AR)-antagonism has anti-psychotic-like and pro-cognitive properties. However, this has not been demonstrated in an animal model of schizophrenia with a neurodevelopmental construct. The beneficial effects of clozapine in refractory schizophrenia and associated cognitive deficits have, among others, been associated with its α2C-AR modulating activity. Altered brain-derived neurotrophic factor (BDNF) has been linked to schizophrenia and cognitive deficits. We investigated whether the α2C-AR antagonist, ORM-10921, could modulate sensorimotor gating and cognitive deficits, as well as alter striatal BDNF levels in the social isolation reared (SIR) model of schizophrenia, comparing its effects to clozapine and the typical antipsychotic, haloperidol, the latter being devoid of α2C-AR-activity. Moreover, the ability of ORM-10921 to augment the effects of haloperidol on the above parameters was also investigated. Animals received subcutaneous injection of either ORM-10921 (0.01mg/kg), clozapine (5mg/kg), haloperidol (0.2mg/kg), haloperidol (0.2mg/kg)+ORM-10921 (0.01mg/kg) or vehicle once daily for 14days, followed by assessment of novel object recognition (NOR), prepulse inhibition (PPI) of startle response and striatal BDNF levels. SIR significantly attenuated NOR memory as well as PPI, and reduced striatal BDNF levels vs. social controls. Clozapine, ORM-10921 and haloperidol+ORM-10921, but not haloperidol alone, significantly improved SIR-associated deficits in PPI and NOR, with ORM-10921 also significantly improving PPI deficits vs. haloperidol-treated SIR animals. Haloperidol+ORM-10921 significantly reversed reduced striatal BDNF levels in SIR rats. α2C-AR-antagonism improves deficits in cognition and sensorimotor gating in a neurodevelopmental animal model of schizophrenia and bolsters the effects of a typical antipsychotic, supporting a therapeutic role for α2C-AR-antagonism in schizophrenia. Copyright © 2016 Elsevier Inc. All rights reserved.

Novel Insights about Class 2 Integrons from Experimental and Genomic Epidemiology▿

PubMed Central

Ramírez, María Soledad; Piñeiro, Silvia; Centrón, Daniela

2010-01-01

In order to contribute to the knowledge of the architecture and epidemiology of class 2 integrons, we performed a class 2 integron molecular survey in which we analyzed 726 isolates in two bacterial populations from environmental and nonepidemiologically related clinical samples, respectively, collected from 1982 to 2007. We recovered the intI2 gene from 130 of 726 isolates, most of which were clinical isolates, and only 1 (a psychrophilic Pseudomonas sp.) was from a water sample. Unlike the widespread distribution of class 1 integrons within Gram-negative bacilli, only Acinetobacter baumannii and Enterobacter cloacae harbored class 2 integrons at a high frequency in our collection. Class 2 integrons with six novel cassette arrays were documented. Characterization of the transposition module of Tn7, the genetic platform in which class 2 integrons have always been reported, showed tns modules with a mosaic genetic structure. A bioinformatic analysis performed with the tns genes present in sequence databases, the finding of intI2 not associated with tns genes, and the genetic examination of novel tns-like genes found in three isolates indicated the possibility of the independent evolution of the two components related to horizontal gene transfer, the class 2 integrons and the Tn7 transposons. PMID:19917745

Fluoxetine reverses behavior changes in socially isolated rats: role of the hippocampal GSH-dependent defense system and proinflammatory cytokines.

PubMed

Perić, Ivana; Stanisavljević, Andrijana; Gass, Peter; Filipović, Dragana

2017-12-01

Exposure of an organism to chronic social isolation (CSIS) has been shown to have an important role in depression. Fluoxetine (Flx) is a first-line treatment for depression; however, its downstream mechanisms of action beyond serotonergic signaling remain ill-defined. We investigated the effect of 3 weeks of Flx (15 mg/kg/day) treatment on behavioral changes and protein expression/activity of the GSH-dependent defense system, including reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GLR), and glutathione S-transferase (GST), as well as catalase (CAT), in the hippocampus of rats exposed to 6 weeks of CSIS. The subcellular distributions of nuclear factor-κB (NF-κB), as well as, cytosolic IL-1β and IL-6 protein expression, were also determined. CSIS induced depressive- and anxiety-like behaviors, evidenced by a decrease in sucrose preference and an increase in the number of buried marbles. Moreover, CSIS compromised redox homeostasis, targeting enzymes such as GPx, CAT, GST, and caused NF-κB nuclear translocation with a concomitant increase in IL-6 protein expression, without an effect on IL-1β. Flx treatment reversed CSIS-induced depressive- and anxiety-like behaviors, modulated GSH-dependent defense by increasing GLR and GST activity, and suppressed NF-κB activation and cytosolic IL-6 protein expression in socially isolated rats. The present study suggests that changes in the GSH-dependent defense system, NF-κB activation and increased IL-6 protein expression may have a role in social isolation-induced changes in a rat model of depression and anxiety, and contributes to our understanding of the mechanisms that underlie the antidepressant and anti-inflammatory activity of Flx in socially isolated rats.

Evaluation of Isolated Fractions of Aloe vera Gel Materials on Indinavir Pharmacokinetics: In vitro and in vivo Studies.

PubMed

Wallis, Lonette; Malan, Maides; Gouws, Chrisna; Steyn, Dewald; Ellis, Suria; Abay, Efrem; Wiesner, Lubbe; Otto, Daniel P; Hamman, Josias

2016-01-01

Aloe vera is a plant with a long history of traditional medicinal use and is consumed in different products, sometimes in conjunction with prescribed medicines. A. vera gel has shown the ability to modulate drug absorption in vitro. The aim of this study was to fractionate the precipitated polysaccharide component of A. vera gel based on molecular weight and to compare their interactions with indinavir pharmacokinetics. Crude polysaccharides were precipitated from a solution of A. vera gel and was fractionated by means of centrifugal filtration through membranes with different molecular weight cut-off values (i.e. 300 KDa, 100 KDa and 30 KDa). Marker molecules were quantified in the aloe leaf materials by means of nuclear magnetic resonance spectroscopy and the average molecular weight was determined by means of gel filtration chromatography linked to multi-angle-laser-light scattering and refractive index detection. The effect of the aloe leaf materials on the transepithelial electrical resistance (TEER) of Caco-2 cell monolayers as well as indinavir metabolism in LS180 cells was measured. The bioavailability of indinavir in the presence and absence of the aloe leaf materials was determined in Sprague-Dawley rats. All the aloe leaf materials investigated in this study reduced the TEER of Caco-2 cell monolayers, inhibited indinavir metabolism in LS 180 cells to different extents and changed the bioavailability parameters of indinavir in rats compared to that of indinavir alone. These indinavir pharmacokinetic modulation effects were not dependent on the presence of aloverose and also not on the average molecular weight of the isolated fractions.

Differential Regulation of Native Estrogen Receptor-Regulatory Elements by Estradiol, Tamoxifen, and Raloxifene

PubMed Central

Levy, Nitzan; Tatomer, Dierdre; Herber, Candice B.; Zhao, Xiaoyue; Tang, Hui; Sargeant, Toby; Ball, Lonnele J.; Summers, Jonathan; Speed, Terence P.; Leitman, Dale C.

2008-01-01

Estrogen receptors (ERs) regulate gene transcription by interacting with regulatory elements. Most information regarding how ER activates genes has come from studies using a small set of target genes or simple consensus sequences such as estrogen response element, activator protein 1, and Sp1 elements. However, these elements cannot explain the differences in gene regulation patterns and clinical effects observed with estradiol (E2) and selective estrogen receptor modulators. To obtain a greater understanding of how E2 and selective estrogen receptor modulators differentially regulate genes, it is necessary to investigate their action on a more comprehensive set of native regulatory elements derived from ER target genes. Here we used chromatin immunoprecipitation-cloning and sequencing to isolate 173 regulatory elements associated with ERα. Most elements were found in the introns (38%) and regions greater than 10 kb upstream of the transcription initiation site (38%); 24% of the elements were found in the proximal promoter region (<10 kb). Only 11% of the elements contained a classical estrogen response element; 23% of the elements did not have any known response elements, including one derived from the naked cuticle homolog gene, which was associated with the recruitment of p160 coactivators. Transfection studies found that 80% of the 173 elements were regulated by E2, raloxifene, or tamoxifen with ERα or ERβ. Tamoxifen was more effective than raloxifene at activating the elements with ERα, whereas raloxifene was superior with ERβ. Our findings demonstrate that E2, tamoxifen, and raloxifene differentially regulate native ER-regulatory elements isolated by chromatin immunoprecipitation with ERα and ERβ. PMID:17962382

The Role of Mesenchymal Stem Cells in the Regenerative Wound Healing Phenotype.

PubMed

Balaji, Swathi; Keswani, Sundeep G; Crombleholme, Timothy M

2012-08-01

Mesenchymal stem cells (MSCs) are key to regenerative wound healing. MSCs have spatial memory and respond to local environment. MSCs orchestrate wound repair by: (1) structural repair via cellular differentiation; (2) immune-modulation; (3) secretion of growth factors that drive neovascularization and re-epithelialization; and (4) mobilization of resident stem cells. Autologous bone-marrow-derived cells and MSCs demonstrate improved healing and tissue-integrity in animal models and clinical trials. However, the effects are variable and the mechanisms of MSC-mediated wound healing are not fully understood. The mammalian MSC niche and signaling sequences and factors affecting their homing, differentiation, viability, and safety need to be characterized to get full benefits of MSC cellular therapy. MSCs can be isolated from bone-marrow, and less-invasive tissues such as adipose, gingiva, muscle, and umbilical cord, with similar functional effects. However, isolation, culture conditions, and markers used to identify and trace the lineage of these MSCs have not been standardized, which is crucial to determine the extent to which MSCs act as multipotent stem cells or sources of secreted factors in wounds. In chronic nonhealing wounds, where efficacy of conventional therapies is unsatisfactory, autotransplantation of MSCs could accelerate wound healing, promote regeneration and restoration of tissue integrity, and reduce recurrence of wounds at characteristically predisposed sites. Regenerative medicine and novel wound therapies using autologous stem cells holds great promise for clinical management of difficult wounds. The ideal candidate stem cells can be used to repopulate the wound bed to mediate appropriate epidermal and dermal regeneration and promote efficient wound repair, while modulating the immune system to prevent infection.

beta2-Agonist modulates epithelial gene expression involved in the T- and B-cell chemotaxis and induces airway sensitization in human isolated bronchi.

PubMed

Faisy, Christophe; Pinto, Francisco M; Blouquit-Laye, Sabine; Danel, Claire; Naline, Emmanuel; Buenestado, Amparo; Grassin Delyle, Stanislas; Burgel, Pierre-Régis; Chapelier, Alain; Advenier, Charles; Candenas, Maria-Luz; Devillier, Philippe

2010-02-01

Regular use of beta(2)-adrenoceptor agonists may enhance non-specific airway responsiveness and inflammation. In earlier experimental studies, we showed that prolonged in vitro fenoterol exposure induced airway sensitization via perturbed epithelial regulation of bronchoconstriction. The aim of the present work was to examine the involvement of inflammatory mediator genes and proinflammatory cells and to investigate the role of the bronchial epithelium in these untoward effects. Bronchial tissues were surgically removed from 17 ex-smokers. Bronchial rings and primary cultures of bronchial epithelial cells were incubated with 0.1microM fenoterol for 15h. Levels of mRNA-expression were analyzed using a real-time quantitative reverse transcription-polymerase chain reaction array. Bronchial rings were contracted with endothelin-1 and immune cell infiltration was assessed by immunohistochemistry. Compared to paired controls, fenoterol up-regulated the mRNAs of cytokines/proteins implicated in the recruitment of T and B cells or the activation and proliferation of bronchial epithelial cells (CCL20/MIP-3alpha, FOXA2, PPAR-gamma) in isolated bronchi and in cultured epithelial cells. Fenoterol exposure significantly enhanced CD8(+)-T and differentiated CD138(+)-B-cells infiltration into the bronchi, especially the subepithelial area. Increase in CD8 or CD138 labeling-intensity strongly correlated with rise in maximal contraction to endothelin-1 induced by fenoterol exposure. In summary, our results show that fenoterol modulates the T and B cells chemotaxis possibly via the epithelial chemokine secretion in isolated bronchi from ex-smokers. They also suggest that the infiltration of resident T and B cells into the subepithelial area is associated with an increase in airway responsiveness due to fenoterol exposure. Copyright 2009 Elsevier Ltd. All rights reserved.

Low-level and high-level modulations of fixational saccades and high frequency oscillatory brain activity in a visual object classification task

PubMed Central

Kosilo, Maciej; Wuerger, Sophie M.; Craddock, Matt; Jennings, Ben J.; Hunt, Amelia R.; Martinovic, Jasna

2013-01-01

Until recently induced gamma-band activity (GBA) was considered a neural marker of cortical object representation. However, induced GBA in the electroencephalogram (EEG) is susceptible to artifacts caused by miniature fixational saccades. Recent studies have demonstrated that fixational saccades also reflect high-level representational processes. Do high-level as opposed to low-level factors influence fixational saccades? What is the effect of these factors on artifact-free GBA? To investigate this, we conducted separate eye tracking and EEG experiments using identical designs. Participants classified line drawings as objects or non-objects. To introduce low-level differences, contours were defined along different directions in cardinal color space: S-cone-isolating, intermediate isoluminant, or a full-color stimulus, the latter containing an additional achromatic component. Prior to the classification task, object discrimination thresholds were measured and stimuli were scaled to matching suprathreshold levels for each participant. In both experiments, behavioral performance was best for full-color stimuli and worst for S-cone isolating stimuli. Saccade rates 200–700 ms after stimulus onset were modulated independently by low and high-level factors, being higher for full-color stimuli than for S-cone isolating stimuli and higher for objects. Low-amplitude evoked GBA and total GBA were observed in very few conditions, showing that paradigms with isoluminant stimuli may not be ideal for eliciting such responses. We conclude that cortical loops involved in the processing of objects are preferentially excited by stimuli that contain achromatic information. Their activation can lead to relatively early exploratory eye movements even for foveally-presented stimuli. PMID:24391611

Color selectivity of the spatial congruency effect: evidence from the focused attention paradigm.

PubMed

Makovac, Elena; Gerbino, Walter

2014-01-01

The multisensory response enhancement (MRE), occurring when the response to a visual target integrated with a spatially congruent sound is stronger than the response to the visual target alone, is believed to be mediated by the superior colliculus (SC) (Stein & Meredith, 1993). Here, we used a focused attention paradigm to show that the spatial congruency effect occurs with red (SC-effective) but not blue (SC-ineffective) visual stimuli, when presented with spatially congruent sounds. To isolate the chromatic component of SC-ineffective targets and to demonstrate the selectivity of the spatial congruency effect we used the random luminance modulation technique (Experiment 1) and the tritanopic technique (Experiment 2). Our results indicate that the spatial congruency effect does not require the distribution of attention over different sensory modalities and provide correlational evidence that the SC mediates the effect.

Electrical insulation design requirements and reliability goals

NASA Astrophysics Data System (ADS)

Ross, R. G., Jr.

1983-11-01

The solar cells in a photovoltaic module which must be electrically isolated from module exterior surfaces to satisfy a variety of safety and operating considerations are discussed. The performance and reliability of the insulation system are examined. Technical requirements involve the capability of withstanding the differential voltage from the solar cells to the module frame. The maximum system voltage includes consideration of maximum open circuit array voltages achieved under low-temperature, high-irradiance conditions, and transient overvoltages due to system feedback of lightning transients. The latter is bounded by the characteristics of incorporated voltage limiting devices such as MOVs.

Modulation response characteristics of optical injection-locked cascaded microring laser

NASA Astrophysics Data System (ADS)

Yu, Shaowei; Pei, Li; Liu, Chao; Wang, Yiqun; Weng, Sijun

2014-09-01

Modulation bandwidth and frequency chirping of the optical injection-locked (OIL) microring laser (MRL) in the cascaded configuration are investigated. The unidirectional operation of the MRL under strong injection allows simple and cost-saving monolithic integration of the OIL system on one chip as it does not need the use of isolators between the master and slave lasers. Two cascading schemes are discussed in detail by focusing on the tailorable modulation response. The chip-to-power ratio of the cascaded optical injection-locked configuration has decreased by up to two orders of magnitude, compared with the single optical injection-locked configuration.

Home Care Nursing via Computer Networks: Justification and Design Specifications

PubMed Central

Brennan, Patricia Flatley

1988-01-01

High-tech home care includes the use of information technologies, such as computer networks, to provide direct care to patients in the home. This paper presents the justification and design of a project using a free, public access computer network to deliver home care nursing. The intervention attempts to reduce isolation and improve problem solving among home care patients and their informal caregivers. Three modules comprise the intervention: a decision module, a communications module, and an information data base. This paper describes the experimental evaluation of the project, and discusses issues in the delivery of nursing care via computers.

Pharmacologic properties of brewery dust extracts in vitro.

PubMed

Schachter, E N; Zuskin, E; Rienzi, N; Goswami, S; Castranova, V; Whitmer, M; Siegel, P

2001-06-01

To study the effects of extracts of brewery dust on isolated guinea pig tracheal smooth muscle in vitro. Parallel pharmacologic intervention on guinea pig tracheal rings that were obtained from the same animal. Mount Sinai School of Medicine, Department of Pulmonary Medicine. The isolated guinea pig tracheal tissue of 18 guinea pigs. Pretreatment of guinea pig rings by mediator-modifying agents before challenge with the brewery dust extracts. The effect of brewery dust extracts on isolated guinea pig tracheal smooth muscle was studied using water-soluble extracts of dust obtained from brewery materials, including hops, barley, and brewery yeast. Dust extracts were prepared as a 1:10 (wt/vol) aqueous solution. Dose-related contractions of nonsensitized guinea pig tracheas were demonstrated using these extracts. The dust extracts contained significant quantities of bacterial components (eg, endotoxin and n-formyl-methionyl-leucyl-phenylalanine), but these agents were not thought to contribute directly to the constrictor effect of the dusts. Pharmacologic studies were performed by pretreating guinea pig tracheal tissue with the following drugs known to modulate smooth muscle contraction: atropine; indomethacin; pyrilamine; LY171883; nordihydroguaiaretic acid; captopril; thiorphan; verapamil; and TMB8. The constrictor effects of the dust extracts were inhibited by a wide variety of agents, the patterns of which depended on the dust extract. Atropine consistently and strikingly reduced the contractile effects of these extracts. These observations may suggest an interaction of the extracts with parasympathetic nerves or, more directly, with muscarinic receptors. The inhibition of contraction by the blocking of other mediators was less effective and varied with the dust extract. We suggest that brewery dust extracts cause a dose-related airway smooth muscle constriction by nonimmunologic mechanisms involving a variety of airway mediators and, possibly, cholinergic receptors. This effect is not dependent on presensitization of the guinea pigs.

TVIS Inflight Maintenance

NASA Image and Video Library

2011-07-01

ISS028-E-013757 (1 July 2011) --- Russian cosmonaut Andrey Borisenko, Expedition 28 commander, performs in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

Electrical isolation of component cells in monolithically interconnected modules

DOEpatents

Wanlass, Mark W.

2001-01-01

A monolithically interconnected photovoltaic module having cells which are electrically connected which comprises a substrate, a plurality of cells formed over the substrate, each cell including a primary absorber layer having a light receiving surface and a p-region, formed with a p-type dopant, and an n-region formed with an n-type dopant adjacent the p-region to form a single pn-junction, and a cell isolation diode layer having a p-region, formed with a p-type dopant, and an n-region formed with an n-type dopant adjacent the p-region to form a single pn-junction, the diode layer intervening the substrate and the absorber layer wherein the absorber and diode interfacial regions of a same conductivity type orientation, the diode layer having a reverse-breakdown voltage sufficient to prevent inter-cell shunting, and each cell electrically isolated from adjacent cells with a vertical trench trough the pn-junction of the diode layer, interconnects disposed in the trenches contacting the absorber regions of adjacent cells which are doped an opposite conductivity type, and electrical contacts.

Neural Repetition Effects in the Medial Temporal Lobe Complex are Modulated by Previous Encoding Experience

PubMed Central

Greene, Ciara M.; Soto, David

2012-01-01

It remains an intriguing question why the medial temporal lobe (MTL) can display either attenuation or enhancement of neural activity following repetition of previously studied items. To isolate the role of encoding experience itself, we assessed neural repetition effects in the absence of any ongoing task demand or intentional orientation to retrieve. Experiment 1 showed that the hippocampus and surrounding MTL regions displayed neural repetition suppression (RS) upon repetition of past items that were merely attended during an earlier study phase but this was not the case following re-occurrence of items that had been encoded into working memory (WM). In this latter case a trend toward neural repetition enhancement (RE) was observed, though this was highly variable across individuals. Interestingly, participants with a higher degree of neural RE in the MTL complex displayed higher memory sensitivity in a later, surprise recognition test. Experiment 2 showed that massive exposure at encoding effected a change in the neural architecture supporting incidental repetition effects, with regions of the posterior parietal and ventral-frontal cortex in addition to the hippocampus displaying neural RE, while no neural RS was observed. The nature of encoding experience therefore modulates the expression of neural repetition effects in the MTL and the neocortex in the absence of memory goals. PMID:22829892

Meta-analysis of the effects of forest fragmentation on interspecific interactions.

PubMed

Magrach, Ainhoa; Laurance, William F; Larrinaga, Asier R; Santamaria, Luis

2014-10-01

Forest fragmentation dramatically alters species persistence and distribution and affects many ecological interactions among species. Recent studies suggest that mutualisms, such as pollination and seed dispersal, are more sensitive to the negative effects of forest fragmentation than antagonisms, such as predation or herbivory. We applied meta-analytical techniques to evaluate this hypothesis and quantified the relative contributions of different components of the fragmentation process (decreases in fragment size, edge effects, increased isolation, and habitat degradation) to the overall effect. The effects of fragmentation on mutualisms were primarily driven by habitat degradation, edge effects, and fragment isolation, and, as predicted, they were consistently more negative on mutualisms than on antagonisms. For the most studied interaction type, seed dispersal, only certain components of fragmentation had significant (edge effects) or marginally significant (fragment size) effects. Seed size modulated the effect of fragmentation: species with large seeds showed stronger negative impacts of fragmentation via reduced dispersal rates. Our results reveal that different components of the habitat fragmentation process have varying impacts on key mutualisms. We also conclude that antagonistic interactions have been understudied in fragmented landscapes, most of the research has concentrated on particular types of mutualistic interactions such as seed dispersal, and that available studies of interspecific interactions have a strong geographical bias (arising mostly from studies carried out in Brazil, Chile, and the United States). © 2014 Society for Conservation Biology.

Protective effects of ψ taraxasterol 3-O-myristate and arnidiol 3-O-myristate isolated from Calendula officinalis on epithelial intestinal barrier.

PubMed

Dall'Acqua, Stefano; Catanzaro, Daniela; Cocetta, Veronica; Igl, Nadine; Ragazzi, Eugenio; Giron, Maria Cecilia; Cecconello, Laura; Montopoli, Monica

2016-03-01

The triterpene esters ᴪ taraxasterol-3-O-myristate (1) and arnidiol-3-O-myristate (2) were tested for their ability to protect epithelial intestinal barrier in an in vitro model. Their effects on ROS production and on trans-epithelial resistance were investigated on CaCo-2 cell monolayers both in basal and stress-induced conditions. Both compounds were able to modulate the stress damage induced by H2O2 and INFγ+TNFα, showing a potential use as model compounds for the study of new therapeutic agents for intestinal inflammations. Copyright © 2016 Elsevier B.V. All rights reserved.

Performance degradation of grid-tied photovoltaic modules in a hot-dry climatic condition

NASA Astrophysics Data System (ADS)

Suleske, Adam; Singh, Jaspreet; Kuitche, Joseph; Tamizh-Mani, Govindasamy

2011-09-01

The crystalline silicon photovoltaic (PV) modules under open circuit conditions typically degrade at a rate of about 0.5% per year. However, it is suspected that the modules in an array level may degrade, depending on equipment/frame grounding and array grounding, at higher rates because of higher string voltage and increased module mismatch over the years of operation in the field. This paper compares and analyzes the degradation rates of grid-tied photovoltaic modules operating over 10-17 years in a desert climatic condition of Arizona. The nameplate open-circuit voltages of the arrays ranged between 400 and 450 V. Six different types/models of crystalline silicon modules with glass/glass and glass/polymer constructions were evaluated. About 1865 modules were inspected using an extended visual inspection checklist and infrared (IR) scanning. The visual inspection checklist included encapsulant discoloration, cell/interconnect cracks, delamination and corrosion. Based on the visual inspection and IR studies, a large fraction of these modules were identified as allegedly healthy and unhealthy modules and they were electrically isolated from the system for currentvoltage (I-V) measurements of individual modules. The annual degradation rate for each module type is determined based on the I-V measurements.

Phyto-SERM Constitutes from Flemingia macrophylla

PubMed Central

Lai, Wan-Chun; Tsui, Ya-Ting; Singab, Abdel Nasser B.; El-Shazly, Mohamed; Du, Ying-Chi; Hwang, Tsong-Long; Wu, Chin-Chung; Yen, Ming-Hong; Lee, Ching-Kuo; Hou, Ming-Feng; Wu, Yang-Chang; Chang, Fang-Rong

2013-01-01

The methanolic extract of Flemingia macrophylla roots exhibited significant estrogenic activity in the transgenic plant assay system which was comparable to the activity of soybean extract. Utilizing estrogenic activity-guided fractionation, one new compound, fleminigin, together with 23 known compounds were isolated from F. macrophylla roots’ methanolic extract. The structure of the new compound was identified based on intensive spectroscopic analysis and the full spectral data for one of the isolated compounds, flemichin E, was introduced for the first time in the current investigation. The estrogenic and anti-estrogenic activities of the isolated compounds were evaluated revealing that the isolated isoflavonoids may act as partial estrogen agonists, as well as antagonists. Additionally, the anti-inflammatory and the cytotoxic activities of the isolated compounds were studied. These results suggested the potential applications of F. macrophylla extract and its isolated compounds as selective estrogen receptor modulators (SERMs). PMID:23896592

iss051e029335

NASA Image and Video Library

2017-04-30

iss051e029335 (April 30, 2017) --- European Space Agency astronaut Thomas Pesquet exercises on the Cycle Ergometer with Vibration Isolation and Stabilization System (CEVIS), the station’s exercise bike, inside the Destiny laboratory module.

Hydroalcoholic extract from Nerium oleander L. (Apocynaceae) elicits arrhythmogenic activity.

PubMed

Botelho, Ana Flávia Machado; Santos-Miranda, Artur; Joca, Humberto Cavalcante; Mattoso, Cláudio Roberto Scabelo; de Oliveira, Maira Souza; Pierezan, Felipe; Cruz, Jader Santos; Soto-Blanco, Benito; Melo, Marília Martins

2017-07-12

Nerium oleander L. (OLE) has been used medicinally and is reported to possess a wide range of pharmacological activities. OLE effects are caused by different cardiac glycosides (CG), primarily oleandrin, found within the plant. CG can potentially impair sodium-potassium ATPase (NKA) pump activity and cause positive inotropic effects on the heart. The aim of this study was to investigate the potential arrhythmogenic effects of hydroalcoholic extracts from N. oleander (OLE). OLE hydroalcoholic extracts were obtained from N. oleander leaves and analyzed by HPLC. In vivo experiments with guinea pigs consisted if oral administration of water, 150mg/kg and 300mg/kg OLE extract. Clinical signs and ECG analysis were evaluated. Sample tissues from the heart were processed for histopathological and ultra-structural analysis. Autonomic effects were assessed through pharmacological blockade and ECG monitoring. In vitro experiments were conducted with isolated ventricular myocytes from adult mice. The effects of OLE extract on cardiac excitability, Na + /K + pump current and global Ca 2+ transients were evaluated. Our results demonstrated that OLE hydroalcoholic extract elicited severe cardiac arrhythmias that can lead to death with minimal tissue damage. In vitro experiments suggest that OLE causes electromechanical disturbances in the heart due to inhibition of Na + /K + pump, mitochondrial swelling, and modulation of the sarco(endo)plasmic Ca 2+ ATPase without interfering with the autonomic nervous system. Thus, arrhythmias and electrical conduction disturbances promoted by OLE are mainly associated with impaired cardiomyocyte dysfunction, rather than anatomical tissue remodeling and/or autonomic modulation. Our data revealed the potential cardiotoxicity and positive inotropic effect of OLE and its important role in modulation of electrophysiology in cardiomyocytes. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Modulating the Effects of the Bacterial Chaperonin GroEL on Fibrillogenic Polypeptides through Modification of Domain Hinge Architecture.

PubMed

Fukui, Naoya; Araki, Kiho; Hongo, Kunihiro; Mizobata, Tomohiro; Kawata, Yasushi

2016-11-25

The isolated apical domain of the Escherichia coli GroEL subunit displays the ability to suppress the irreversible fibrillation of numerous amyloid-forming polypeptides. In previous experiments, we have shown that mutating Gly-192 (located at hinge II that connects the apical domain and the intermediate domain) to a tryptophan results in an inactive chaperonin whose apical domain is disoriented. In this study, we have utilized this disruptive effect of Gly-192 mutation to our advantage, by substituting this residue with amino acid residues of varying van der Waals volumes with the intent to modulate the affinity of GroEL toward fibrillogenic peptides. The affinities of GroEL toward fibrillogenic polypeptides such as Aβ(1-40) (amyloid-β(1-40)) peptide and α-synuclein increased in accordance to the larger van der Waals volume of the substituent amino acid side chain in the G192X mutants. When we compared the effects of wild-type GroEL and selected GroEL G192X mutants on α-synuclein fibril formation, we found that the effects of the chaperonin on α-synuclein fibrillation were different; the wild-type chaperonin caused changes in both the initial lag phase and the rate of fibril extension, whereas the effects of the G192X mutants were more specific toward the nucleus-forming lag phase. The chaperonins also displayed differential effects on α-synuclein fibril morphology, suggesting that through mutation of Gly-192, we may induce changes to the intermolecular affinities between GroEL and α-synuclein, leading to more efficient fibril suppression, and in specific cases, modulation of fibril morphology. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Effects of temperature on the nitric oxide-dependent modulation of the Frank-Starling mechanism: the fish heart as a case study.

PubMed

Amelio, D; Garofalo, F; Capria, C; Tota, B; Imbrogno, S

2013-02-01

The Frank-Starling law is a fundamental property of the vertebrate myocardium which allows, when the end-diastolic volume increases, that the consequent stretch of the myocardial fibers generates a more forceful contraction. It has been shown that in the eel (Anguilla anguilla) heart, nitric oxide (NO) exerts a direct myocardial relaxant effect, increasing the sensitivity of the Frank-Starling response (Garofalo et al., 2009). With the use of isolated working heart preparations, this study investigated the relationship between NO modulation of Frank-Starling response and temperature challenges in the eel. The results showed that while, in long-term acclimated fish (spring animals perfused at 20 °C and winter animals perfused at 10 °C) the inhibition of NO production by L-N5 (1-iminoethyl)ornithine (L-NIO) significantly reduced the Frank-Starling response, under thermal shock conditions (spring animals perfused at 10 or 15 °C and winter animals perfused at 15 or 20 °C) L-NIO treatment resulted without effect. Western blotting analysis revealed a decrease of peNOS and pAkt expressions in samples subjected to thermal shock. Moreover, an increase in Hsp90 protein levels was observed under heat thermal stress. Together, these data suggest that the NO synthase/NO-dependent modulation of the Frank-Starling mechanism in fish is sensitive to thermal stress. Copyright © 2012 Elsevier Inc. All rights reserved.

Hydrostatic pressure modulates mRNA expressions for matrix proteins in human meniscal cells.

PubMed

Suzuki, Toru; Toyoda, Takashi; Suzuki, Hiroshi; Hisamori, Noriyuki; Matsumoto, Hideo; Toyama, Yoshiaki

2006-01-01

There have been few reports describing the effects of mechanical loading on the metabolism of meniscal cells. The aim of this study was to investigate the effects of hydrostatic pressure on meniscal cell metabolism. Human meniscal cells were cultured in alginate beads for 3 days. They were then subjected to 4 MPa hydrostatic pressure for 4 hours in either a static or cyclic (1 Hz) mode using a specially designed and constructed system. Immediately after the pressure application, the messenger RNA levels for aggrecan, type I collagen, matrix metalloproteinases (MMP) -1, -3, -9, -13 and tissue inhibitors of metalloproteinases (TIMP) -1 and -2 were measured. It was found that the application of static hydrostatic pressure caused a significant decrease in mRNA expression for MMP-1 and -13 (p<0.05). In contrast, the application of cyclic hydrostatic pressure was associated with a significant increase in type I collagen (p<0.01), TIMP-1 and -2 mRNA expression (p<0.01). These results would suggest that hydrostatic pressure in isolation can modulate mRNA expressions for matrix proteins in meniscal cells.

Oridonin's therapeutic effect: suppressing Th1/Th17 simultaneously in a mouse model of Crohn's disease.

PubMed

Wang, Shubei; Zhang, Yong; Saas, Philippe; Wang, Haili; Xu, Ying; Chen, Ke; Zhong, Jie; Yuan, Yaozong; Wang, Ying; Sun, Yunwei

2015-03-01

Crohn's disease is a chronic inflammatory bowel disease. Oridonin is an effective component isolated from Rabdosia rubescens. It can inhibit the activation of transcription factor nuclear factor-kappa B and suppress the over expression of cytokines. We postulated that oridonin may be a potential therapeutic candidate for Crohn's disease. To confirm the postulation, we investigated clinical and immunologic modulations of oridonin in a mouse model of trinitrobenzene sulfonic acid-induced colitis. It was found that oridonin attenuated trinitrobenzene sulfonic acid-induced colitis as represented by a reduction in colonic interferon-γ/inteleukin-17 secretion and a decrement in splenic Th1/Th17 cells and effector memory CD4(+) T cells. Oridonin treatment inhibited the proliferation of CD4(+) T cells and upregulated the apoptosis of lymphocytes by inhibiting nuclear translocation of transcription factor nuclear factor-kappa B. Oridonin is a potential modulator for trinitrobenzene sulfonic acid-induced colitis and other Th1/Th17 mediated inflammatory diseases. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Driving Sodium/Potassium Pumps with an Oscillating Electric field: Effects on Muscle Fatigue

NASA Astrophysics Data System (ADS)

Lanes, Olivia; Bovyn, Matthew; Chen, Wei

2013-03-01

Dr. Chen has developed a technique called Synchronization Modulation, which has already been proven to be an effective tool in synchronizing and speeding up the sodium/potassium pumps in cell membranes. When synchronized, it is thought that these pumps are more efficient because they require less ATP. We hypothesized that if this was correct, this technique may be used to reduce muscle fatigue. To test our hypothesis, we had multiple test subjects hold a 15 lb weight for as long as they could while isolating the bicep muscle and applying an oscillating electric field. We compared the EMG data we took during these trials to the control, which was done the same way but without applying the electric field. To compare how fatigued subjects were, we did a Fast Fourier Transform on the first and last 10 seconds of each trial to measure the Fatigue Index. Our preliminary results suggest that the Fatigue Index decreased at a slower rate in the trials where the subject held the weight with Synchronization Modulation.

Effective delivery of recombinant proteins to rod photoreceptors via lipid nanovesicles

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

Asteriti, Sabrina; Dal Cortivo, Giuditta; Pontelli, Valeria

2015-06-12

The potential of liposomes to deliver functional proteins in retinal photoreceptors and modulate their physiological response was investigated by two experimental approaches. First, we treated isolated mouse retinas with liposomes encapsulating either recoverin, an important endogenous protein operating in visual phototransduction, or antibodies against recoverin. We then intravitrally injected in vivo liposomes encapsulating either rhodamin B or recoverin and we investigated the distribution in retina sections by confocal microscopy. The content of liposomes was found to be released in higher amount in the photoreceptor layer than in the other regions of the retina and the functional effects of the release weremore » in line with the current model of phototransduction. Our study sets the basis for quantitative investigations aimed at assessing the potential of intraocular protein delivery via biocompatible nanovesicles, with promising implications for the treatment of retinal diseases affecting the photoreceptor layer. - Highlights: • Recombinant proteins encapsulated in nano-sized liposomes injected intravitreally reach retinal photoreceptors. • The phototransduction cascade in rods is modulated by the liposome content. • Mathematical modeling predicts the alteration of the photoresponses following liposome fusion.« less

Chemoprotective potentials of homoisoflavonoids and chalcones of Dracaena cinnabari: modulations of drug-metabolizing enzymes and antioxidant activity.

PubMed

Machala, M; Kubínová, R; Horavová, P; Suchý, V

2001-03-01

A series of homoisoflavonoids and chalcones, isolated from the endemic tropical plant Dracaena cinnabari Balf. (Agavaceae), were tested for their potential to inhibit cytochrome P4501A (CYP1A) enzymes and Fe-enhanced in vitro peroxidation of microsomal lipids in C57B1/6 mouse liver. The effects of the polyphenolic compounds were compared with those of prototypal flavonoid modulators of CYP1A and the well-known antioxidant, butylated hydroxytoluene. 2-Hydroxychalcone and partly 4,6-dihydroxychalcone were found to be strong inhibitors of CYP1A-dependent 7-ethoxyresorufin O-deethylase (EROD) activity in vitro comparable to the effects of quercetin and chrysin. The first screening of flavonoids and chalcones of Dracaena cinnabari for antioxidant activity was done in an in vitro microsomal peroxidation assay. While chalcones were shown to be poor antioxidants, 7,8-methylenedioxy-3(4-hydroxybenzyl) chromane, as one of the tested homoisoflavonoids, exhibited a strong antioxidant activity comparable to that of the strongest flavonol antioxidant, quercetin. Copyright 2001 John Wiley & Sons, Ltd.

Observations of ELM stabilization during neutral beam injection in DIII-D

NASA Astrophysics Data System (ADS)

Bortolon, Alessandro; Kramer, Gerrit; Diallo, Ahmed; Knolker, Matthias; Maingi, Rajesh; Nazikian, Raffi; Degrassie, John; Osborne, Thomas

2017-10-01

Edge localized modes (ELMs) are generally interpreted as peeling-ballooning instabilities, driven by the pedestal current and pressure gradient, with other subdominant effects possibly relevant close to marginal stability. We report observations of transient stabilization of type-I ELMs during neutral beam injection (NBI), emerging from a combined dataset of DIII-D ELMy H-mode plasmas with moderate heating obtained through pulsed NBI waveforms. Statistical analysis of ELM onset times indicates that, in the selected dataset, the likelihood of onset of an ELM lowers significantly during NBI modulation pulses, with the stronger correlation found with counter-current NBI. The effect is also found in rf-heated H-modes, where ELMs appear inhibited when isolated diagnostic beam pulses are applied. Coherent average analysis is used to determine how plasma density, temperature, rotation as well as beam ion quantities evolve during a NB modulation cycle, finding relatively small changes ( 3%) of pedestal Te and ne and toroidal and poloidal rotation variations up to 5 km/s. The effect of these changes on pedestal stability will be discussed. Work supported by US DOE under DE-FC02-04ER54698, DE-AC02-09CH11466.

Down-regulation of NR2B receptors partially contributes to analgesic effects of Gentiopicroside in persistent inflammatory pain.

PubMed

Chen, Lei; Liu, Jin-cheng; Zhang, Xiao-nan; Guo, Yan-yan; Xu, Zhao-hui; Cao, Wei; Sun, Xiao-li; Sun, Wen-ji; Zhao, Ming-Gao

2008-06-01

Gentiopicroside is one of the secoiridoid compound isolated from Gentiana lutea. It exhibits analgesic activities in the mice. The anterior cingulate cortex (ACC) is a forebrain structure known for its roles in pain transmission and modulation. Painful stimuli potentiate the prefrontal synaptic transmission and induce glutamate NMDA NR2B receptor expression in the ACC. But little is known about Gentiopicroside on the persistent inflammatory pain and chronic pain-induced synaptic transmission changes in the ACC. The present study was undertaken to investigate its analgesic activities and central synaptic modulation to the peripheral painful inflammation. Gentiopicroside produced significant analgesic effects against persistent inflammatory pain stimuli in mice. Systemic administration of Gentiopicroside significantly reversed NR2B over-expression during the chronic phases of persistent inflammation caused by hind-paw administration of complete Freunds adjuvant (CFA) in mice. Whole-cell patch clamp recordings revealed that Gentiopicroside significantly reduced NR2B receptors mediated postsynaptic currents in the ACC. Our findings provide strong evidence that analgesic effects of Gentiopicroside involve down-regulation of NR2B receptors in the ACC to persistent inflammatory pain.

Startling sweet temptations: hedonic chocolate deprivation modulates experience, eating behavior, and eyeblink startle.

PubMed

Blechert, Jens; Naumann, Eva; Schmitz, Julian; Herbert, Beate M; Tuschen-Caffier, Brunna

2014-01-01

Many individuals restrict their food intake to prevent weight gain. This restriction has both homeostatic and hedonic effects but their relative contribution is currently unclear. To isolate hedonic effects of food restriction, we exposed regular chocolate eaters to one week of chocolate deprivation but otherwise regular eating. Before and after this hedonic deprivation, participants viewed images of chocolate and images of high-calorie but non-chocolate containing foods, while experiential, behavioral and eyeblink startle responses were measured. Compared to satiety, hedonic deprivation triggered increased chocolate wanting, liking, and chocolate consumption but also feelings of frustration and startle potentiation during the intertrial intervals. Deprivation was further characterized by startle inhibition during both chocolate and food images relative to the intertrial intervals. Individuals who responded with frustration to the manipulation and those who scored high on a questionnaire of impulsivity showed more relative startle inhibition. The results reveal the profound effects of hedonic deprivation on experiential, behavioral and attentional/appetitive response systems and underscore the role of individual differences and state variables for startle modulation. Implications for dieting research and practice as well as for eating and weight disorders are discussed.

Startling Sweet Temptations: Hedonic Chocolate Deprivation Modulates Experience, Eating Behavior, and Eyeblink Startle

PubMed Central

Blechert, Jens; Naumann, Eva; Schmitz, Julian; Herbert, Beate M.; Tuschen-Caffier, Brunna

2014-01-01

Many individuals restrict their food intake to prevent weight gain. This restriction has both homeostatic and hedonic effects but their relative contribution is currently unclear. To isolate hedonic effects of food restriction, we exposed regular chocolate eaters to one week of chocolate deprivation but otherwise regular eating. Before and after this hedonic deprivation, participants viewed images of chocolate and images of high-calorie but non-chocolate containing foods, while experiential, behavioral and eyeblink startle responses were measured. Compared to satiety, hedonic deprivation triggered increased chocolate wanting, liking, and chocolate consumption but also feelings of frustration and startle potentiation during the intertrial intervals. Deprivation was further characterized by startle inhibition during both chocolate and food images relative to the intertrial intervals. Individuals who responded with frustration to the manipulation and those who scored high on a questionnaire of impulsivity showed more relative startle inhibition. The results reveal the profound effects of hedonic deprivation on experiential, behavioral and attentional/appetitive response systems and underscore the role of individual differences and state variables for startle modulation. Implications for dieting research and practice as well as for eating and weight disorders are discussed. PMID:24416437

Distributed reconfigurable control strategies for switching topology networked multi-agent systems.

PubMed

Gallehdari, Z; Meskin, N; Khorasani, K

2017-11-01

In this paper, distributed control reconfiguration strategies for directed switching topology networked multi-agent systems are developed and investigated. The proposed control strategies are invoked when the agents are subject to actuator faults and while the available fault detection and isolation (FDI) modules provide inaccurate and unreliable information on the estimation of faults severities. Our proposed strategies will ensure that the agents reach a consensus while an upper bound on the team performance index is ensured and satisfied. Three types of actuator faults are considered, namely: the loss of effectiveness fault, the outage fault, and the stuck fault. By utilizing quadratic and convex hull (composite) Lyapunov functions, two cooperative and distributed recovery strategies are designed and provided to select the gains of the proposed control laws such that the team objectives are guaranteed. Our proposed reconfigurable control laws are applied to a team of autonomous underwater vehicles (AUVs) under directed switching topologies and subject to simultaneous actuator faults. Simulation results demonstrate the effectiveness of our proposed distributed reconfiguration control laws in compensating for the effects of sudden actuator faults and subject to fault diagnosis module uncertainties and unreliabilities. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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.

Barrett during TVIS maintenance

NASA Image and Video Library

2009-04-21

ISS019-E-008750 (21 April 2009) --- Astronaut Michael Barratt, Expedition 19/20 flight engineer, performs in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

Barrett during TVIS maintenance

NASA Image and Video Library

2009-04-21

ISS019-E-008752 (21 April 2009) --- Astronaut Michael Barratt, Expedition 19/20 flight engineer, performs in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

SM, TVIS Chassis Assembly, Treadmill Belt Assembly, Top

NASA Image and Video Library

2002-01-01

jsc2002e38738 (2002) --- Top view of the Treadmill Belt Assembly on the Treadmill Vibration Isolation System (TVIS) Chassis Assembly for use in the International Space Station (ISS) Service Module (SM).

Barrett during TVIS maintenance

NASA Image and Video Library

2009-04-21

ISS019-E-008767 (21 April 2009) --- Astronaut Michael Barratt, Expedition 19/20 flight engineer, performs in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

Barrett during TVIS maintenance

NASA Image and Video Library

2009-04-21

ISS019-E-008764 (21 April 2009) --- Astronaut Michael Barratt, Expedition 19/20 flight engineer, performs in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

Persistent changes in the initial rate of pyruvate transport by isolated rat liver mitochondria after preincubation with adenine nucleotides and calcium ions.

PubMed

Vaartjes, W J; den Breejen, J N; Geelen, M J; van den Bergh, S G

1980-08-05

1. Preincubation of isolated rat-liver mitochondria in the presence of adenine nucleotides or Ca2+ results in definite and persistent changes in the initial rate of pyruvate transport. 2. These changes in the rate of pyruvate transport are accompanied by equally persistent changes in the opposite direction of the activity of pyruvate dehydrogenase (EC 1.2.4.1). 3. Changes of the transmembrane pH gradient and of the membrane potential, brought about by the pretreatments of the mitochondria, cannot account for the observed changes in the rate of pyruvate transport. 4. It is proposed that the pretreatment of the mitochondria directly modulates the activity of the mitochondrial pyruvate carrier. The possible regulatory role of such a modulation system is discussed.

Emotion modulates activity in the 'what' but not 'where' auditory processing pathway.

PubMed

Kryklywy, James H; Macpherson, Ewan A; Greening, Steven G; Mitchell, Derek G V

2013-11-15

Auditory cortices can be separated into dissociable processing pathways similar to those observed in the visual domain. Emotional stimuli elicit enhanced neural activation within sensory cortices when compared to neutral stimuli. This effect is particularly notable in the ventral visual stream. Little is known, however, about how emotion interacts with dorsal processing streams, and essentially nothing is known about the impact of emotion on auditory stimulus localization. In the current study, we used fMRI in concert with individualized auditory virtual environments to investigate the effect of emotion during an auditory stimulus localization task. Surprisingly, participants were significantly slower to localize emotional relative to neutral sounds. A separate localizer scan was performed to isolate neural regions sensitive to stimulus location independent of emotion. When applied to the main experimental task, a significant main effect of location, but not emotion, was found in this ROI. A whole-brain analysis of the data revealed that posterior-medial regions of auditory cortex were modulated by sound location; however, additional anterior-lateral areas of auditory cortex demonstrated enhanced neural activity to emotional compared to neutral stimuli. The latter region resembled areas described in dual pathway models of auditory processing as the 'what' processing stream, prompting a follow-up task to generate an identity-sensitive ROI (the 'what' pathway) independent of location and emotion. Within this region, significant main effects of location and emotion were identified, as well as a significant interaction. These results suggest that emotion modulates activity in the 'what,' but not the 'where,' auditory processing pathway. Copyright © 2013 Elsevier Inc. All rights reserved.

Immunomodulatory potencies of isolated compounds from Crataegus azarolus through their antioxidant activities.

PubMed

Mustapha, Nadia; Mokdad-Bzéouich, Imèn; Sassi, Aicha; Abed, Besma; Ghedira, Kamel; Hennebelle, Thierry; Chekir-Ghedira, Leila

2016-06-01

The search of natural immunomodulatory agents has become an area of great interest in order to reduce damage to the human body. In this study, the immunomodulatory potential of Crataegus azarolus and its isolated hyperoside on mouse lymphocytes and macrophages in vitro was assessed. The effect of C. azarolus natural compounds on splenocytes proliferation, natural killer (NK) and cytotoxic T lymphocytes (CTL) activities, and on macrophage-mediated cytotoxicity were assessed by MTT test. Phagocytic activity and inhibition of nitric oxide (NO) release by macrophages were also evaluated. The antioxidant capacity of these products was evaluated by determining their cellular antioxidant activity (CAA) in splenocytes and macrophages. Depending on the concentrations, both ethyl acetate (EA) extract and hyperoside (Hyp) from C. azarolus affect macrophage functions by modulating their lysosomal enzyme activity and nitric oxide release. Whereas, the above-mentioned products significantly promote LPS and lectin-stimulated splenocyte proliferation, implying a potential activation of lymphocytes B and T enhancing humoral and cellular immune responses. Moreover, EA extract and Hyp could enhance the activity of NK and T lymphocytes cells, as well as the macrophages-mediated cytotoxicity against B16F10 cells. The anti-inflammatory activity was concomitant with the cellular antioxidant effect of the tested compounds against macrophages and splenocytes. Collectively, C. azarolus and its isolated hyperoside exhibited an immunomodulatory effect through their antioxidant activity. These findings suggest that C. azarolus should be explored as a novel potential immunomodulatory agent for the treatment of inflammatory diseases.

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

PubMed

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.

Characterization of fungi isolated from the equipment used in the International Space Station or Space Shuttle.

PubMed

Satoh, Kazuo; Yamazaki, Takashi; Nakayama, Takako; Umeda, Yoshiko; Alshahni, Mohamed Mahdi; Makimura, Miho; Makimura, Koichi

2016-05-01

As a part of a series of studies regarding the microbial biota in manned space environments, fungi were isolated from six pieces of equipment recovered from the Japanese Experimental Module "KIBO" of the International Space Station and from a space shuttle. Thirty-seven strains of fungi were isolated, identified and investigated with regard to morphological phenotypes and antifungal susceptibilities. The variety of fungi isolated in this study was similar to that of several previous reports. The dominant species belonged to the genera Penicillium, Aspergillus and Cladosporium, which are potential causative agents of allergy and opportunistic infections. The morphological phenotypes and antifungal susceptibilities of the strains isolated from space environments were not significantly different from those of reference strains on Earth. © 2016 The Societies and John Wiley & Sons Australia, Ltd.

Single-cell isolation using a DVD optical pickup

PubMed Central

Kasukurti, A.; Potcoava, M.; Desai, S.A.; Eggleton, C.; Marr, D. W. M.

2011-01-01

A low-cost single-cell isolation system incorporating a digital versatile disc burner (DVD RW) optical pickup has been developed. We show that these readily available modules have the required laser power and focusing optics to provide a steady Gaussian beam capable of optically trapping micron-sized colloids and red blood cells. Utility of the pickup is demonstrated through the non-destructive isolation of such particles in a laminar-flow based microfluidic device that captures and translates single microscale objects across streamlines into designated channel exits. In this, the integrated objective lens focusing coils are used to steer the optical trap across the channel, resulting in the isolation of colloids and red blood cells using a very inexpensive off-the-shelf optical component. PMID:21643294

Variable Bandwidth Filtering for Improved Sensitivity of Cross-Frequency Coupling Metrics

PubMed Central

McDaniel, Jonathan; Liu, Song; Cornew, Lauren; Gaetz, William; Roberts, Timothy P.L.; Edgar, J. Christopher

2012-01-01

Abstract There is an increasing interest in examining cross-frequency coupling (CFC) between groups of oscillating neurons. Most CFC studies examine how the phase of lower-frequency brain activity modulates the amplitude of higher-frequency brain activity. This study focuses on the signal filtering that is required to isolate the higher-frequency neuronal activity which is hypothesized to be amplitude modulated. In particular, previous publications have used a filter bandwidth fixed to a constant for all assessed modulation frequencies. The present article demonstrates that fixed bandwidth filtering can destroy amplitude modulation and create false-negative CFC measures. To overcome this limitation, this study presents a variable bandwidth filter that ensures preservation of the amplitude modulation. Simulated time series data were created with theta-gamma, alpha-gamma, and beta-gamma phase-amplitude coupling. Comparisons between filtering methods indicate that the variable bandwidth approach presented in this article is preferred when examining amplitude modulations above the theta band. The variable bandwidth method of filtering an amplitude modulated signal is proposed to preserve amplitude modulation and enable accurate CFC measurements. PMID:22577870

AMPK modulatory activity of olive-tree leaves phenolic compounds: Bioassay-guided isolation on adipocyte model and in silico approach.

PubMed

Jiménez-Sánchez, Cecilia; Olivares-Vicente, Mariló; Rodríguez-Pérez, Celia; Herranz-López, María; Lozano-Sánchez, Jesús; Segura-Carretero, Antonio; Fernández-Gutiérrez, Alberto; Encinar, José Antonio; Micol, Vicente

2017-01-01

Olive-tree polyphenols have demonstrated potential for the management of obesity-related pathologies. We aimed to explore the capacity of Olive-tree leaves extract to modulate triglyceride accumulation and AMP-activated protein kinase activity (AMPK) on a hypertrophic adipocyte model. Intracellular triglycerides and AMPK activity were measured on the hypertrophic 3T3-L1 adipocyte model by AdipoRed and immunofluorescence microscopy, respectively. Reverse phase high performance liquid chromatography coupled to time-of-flight mass detection with electrospray ionization (RP-HPLC-ESI-TOF/MS) was used for the fractionation of the extract and the identification of the compounds. In-silico molecular docking of the AMPK alpha-2, beta and gamma subunits with the identified compounds was performed. Olive-tree leaves extract decreased the intracellular lipid accumulation through AMPK-dependent mechanisms in hypertrophic adipocytes. Secoiridoids, cinnamic acids, phenylethanoids and phenylpropanoids, flavonoids and lignans were the candidates predicted to account for this effect. Molecular docking revealed that some compounds may be AMPK-gamma modulators. The modulatory effects of compounds over the alpha and beta AMPK subunits appear to be less probable. Olive-tree leaves polyphenols modulate AMPK activity, which may become a therapeutic aid in the management of obesity-associated disturbances. The natural occurrence of these compounds may have important nutritional implications for the design of functional ingredients.

AMPK modulatory activity of olive–tree leaves phenolic compounds: Bioassay-guided isolation on adipocyte model and in silico approach

PubMed Central

Jiménez-Sánchez, Cecilia; Olivares-Vicente, Mariló; Rodríguez-Pérez, Celia; Herranz-López, María; Lozano-Sánchez, Jesús; Segura-Carretero, Antonio; Fernández-Gutiérrez, Alberto; Encinar, José Antonio; Micol, Vicente

2017-01-01

Scope Olive-tree polyphenols have demonstrated potential for the management of obesity-related pathologies. We aimed to explore the capacity of Olive-tree leaves extract to modulate triglyceride accumulation and AMP-activated protein kinase activity (AMPK) on a hypertrophic adipocyte model. Methods Intracellular triglycerides and AMPK activity were measured on the hypertrophic 3T3-L1 adipocyte model by AdipoRed and immunofluorescence microscopy, respectively. Reverse phase high performance liquid chromatography coupled to time-of-flight mass detection with electrospray ionization (RP-HPLC-ESI-TOF/MS) was used for the fractionation of the extract and the identification of the compounds. In-silico molecular docking of the AMPK alpha-2, beta and gamma subunits with the identified compounds was performed. Results Olive-tree leaves extract decreased the intracellular lipid accumulation through AMPK-dependent mechanisms in hypertrophic adipocytes. Secoiridoids, cinnamic acids, phenylethanoids and phenylpropanoids, flavonoids and lignans were the candidates predicted to account for this effect. Molecular docking revealed that some compounds may be AMPK-gamma modulators. The modulatory effects of compounds over the alpha and beta AMPK subunits appear to be less probable. Conclusions Olive-tree leaves polyphenols modulate AMPK activity, which may become a therapeutic aid in the management of obesity-associated disturbances. The natural occurrence of these compounds may have important nutritional implications for the design of functional ingredients. PMID:28278224

Interactions of Top-Down and Bottom-Up Mechanisms in Human Visual Cortex

PubMed Central

McMains, Stephanie; Kastner, Sabine

2011-01-01

Multiple stimuli present in the visual field at the same time compete for neural representation by mutually suppressing their evoked activity throughout visual cortex, providing a neural correlate for the limited processing capacity of the visual system. Competitive interactions among stimuli can be counteracted by top-down, goal-directed mechanisms such as attention, and by bottom-up, stimulus-driven mechanisms. Because these two processes cooperate in everyday life to bias processing toward behaviorally relevant or particularly salient stimuli, it has proven difficult to study interactions between top-down and bottom-up mechanisms. Here, we used an experimental paradigm in which we first isolated the effects of a bottom-up influence on neural competition by parametrically varying the degree of perceptual grouping in displays that were not attended. Second, we probed the effects of directed attention on the competitive interactions induced with the parametric design. We found that the amount of attentional modulation varied linearly with the degree of competition left unresolved by bottom-up processes, such that attentional modulation was greatest when neural competition was little influenced by bottom-up mechanisms and smallest when competition was strongly influenced by bottom-up mechanisms. These findings suggest that the strength of attentional modulation in the visual system is constrained by the degree to which competitive interactions have been resolved by bottom-up processes related to the segmentation of scenes into candidate objects. PMID:21228167

Modulation of desensitization at glutamate receptors in isolated crucian carp horizontal cells by concanavalin A, cyclothiazide, aniracetam and PEPA.

PubMed

Shen, Y; Lu, T; Yang, X L

1999-03-01

In horizontal cells freshly dissociated from crucian carp (Carassius auratus) retina, we examined the effects of modulators of glutamate receptor desensitization, concanavalin A, cyclothiazide, aniracetam and 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluoro-phenoxyacetam ide (PEPA), on responses to rapid application of glutamate and kainate, using whole-cell voltage-clamp techniques. Incubation of concanavalin A suppressed the peak response but weakly potentiated the equilibrium response of horizontal cells to glutamate. Cyclothiazide blocked glutamate-induced desensitization in a dose-dependent manner, which resulted in a steady increase of the equilibrium current. The concentration of cyclothiazide causing a half-maximal potentiation for the equilibrium response was 85 microM. Furthermore, cyclothiazide shifted the dose-response relationship of the equilibrium current to the right, but slightly suppressed the kainate-induced sustained current. These effects of concanavalin A and cyclothiazide are consistent with the supposition that glutamate receptors of carp horizontal cells may be an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-preferring subtype. In order to further characterize the AMPA receptors of horizontal cells, modulation by aniracetam and PEPA of glutamate- and kainate-induced currents was studied. Aniracetam, a preferential modulator of flop variants of AMPA receptors, considerably blocked desensitization of glutamate-induced currents, but only slightly potentiated kainate-induced currents. It was further found that PEPA, a flop-preferring allosteric modulator of AMPA receptor desensitization, slightly suppressed the peak current, while it dramatically potentiated the equilibrium current induced by glutamate in a dose-dependent manner. PEPA was much potent than aniracetam at these receptors and showed the effect on glutamate-induced desensitization even at a concentration as low as 3 microM. PEPA also potentiated non-desensitizing currents induced by kainate, but with much less extent. These modulatory effects of concanavalin A, cyclothiazide, aniracetam and PEPA on AMPA receptors in carp horizontal cells were rather similar to those obtained at AMPA receptors assembled from flop variants expressed in Xenopus oocyte and HEK cell. Consequently, we speculate that the AMPA receptor on carp horizontal cells may predominantly carry the flop splice variants.

Pyridostigmine bromide modulates topical irritant-induced cytokine release from human epidermal keratinocytes and isolated perfused porcine skin.

PubMed

Monteiro-Riviere, Nancy A; Baynes, Ronald E; Riviere, Jim E

2003-02-01

Gulf War personnel were given pyridostigmine bromide (PB) as a prophylactic treatment against organophosphate nerve agent exposure, and were exposed to the insecticide permethrin and the insect repellent N,N-diethyl-m-toluamide (DEET). The purpose of this study was to assess the effects of PB to modulate release of inflammatory biomarkers after topical chemical exposure to chemical mixtures containing permethrin and DEET applied in ethanol or water vehicles. Treatments were topically applied to isolated perfused porcine skin flaps (IPPSFs). Concentrations of interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E(2) (PGE(2)) were assayed in perfusate to probe for potential inflammatory effects after complex mixture application. IPPSFs (n=4/treatment) were topically dosed with mixtures of permethrin, DEET, and permethrin/DEET, in ethanol. Each treatment was repeated with perfusate spiked with 50 ng/ml of PB. Perfusate was also spiked with 30 ng/ml diisopropylfluorophosphate to simulate low level organophosphate nerve agent exposure. Timed IPPSF venous effluent samples (0.5,1,2,4, and 8 h) were assayed by ELISA for IL-8 and TNF-alpha and by EIA for PGE(2). Overall, PB infusion caused a decrease or IL-8 and PGE(2) release. Effects on TNF-alpha were vehicle dependent. To probe the potential mechanism of this PB effect, human epidermal keratinocyte HEK cell cultures were exposed to permethrin DEET permethrin/DEET, with and without PB in DMSO. IL-8 was assayed at 1, 2, 4, 8, 12 and 24 h. PB suppressed IL-8 in permethrin and ethanol treatment from 4 to 24 h confirming the IPPSF results. In conclusion, these studies suggest that systemic exposure to PB suppressed IL-8 release at multiple time points in two skin model systems. This interaction merits further study.

Modulation of experimental atopic dermatitis by topical application of Gami-Cheongyeul-Sodok-Eum

PubMed Central

2013-01-01

Background Gami-Cheongyeul-Sodok-Eum (GCSE), an herbal formula of traditional Korean medicine, comprises nine herb components. GCSE has various biological activities such as anti-inflammatory, anti-bacterial and anti-viral activities. However, it is still unclear whether GCSE has any immunomodulatory effect on atopic dermatitis (AD). Methods GCSE was treated to primary B cells and CD4+ T cells isolated from atopic mice to compare its inhibitory effects on IgE secretion and cytokine expression. Experimental AD was established by alternative treatment of 2, 4-dinitrochlorobenzene (DNCB) and house dust mite extract to the ears of BALB/c mice. GCSE was topically applied to ears of atopic mice every day for 3 weeks. AD progression was analyzed by measuring ear thickness, serum IgE level, histological examination of ear tissue by H&E staining and cytokine profile of CD4+ T cells and CD19+ B cells by real time PCR and ELISA. Results Treatment of GCSE significantly reduced IgE production and expression of AD associated pathogenic cytokines such as IL-4, IL-5, IL-10, IL-13, IL-17, TNF-α, and IFN-γ by lymphocytes isolated from AD-induced mice. Topical application of GCSE on the ears of AD-induced mice significantly reduced ear thickness, clinical score and lymphocytes infiltration to ears as compared to control group. GCSE treatment also reduced serum IgE level and the levels of major pathogenic cytokines such as IL-4, IL-5, IL-10, IL-13 and IL-17. In addition, GCSE treatment significantly increased Foxp3 expression level. Conclusions The protective effect of GCSE in experimental AD is mediated by inhibition of IgE production, by reduction in the levels of pathogenic cytokines and by induction of Foxp3, all of which are suggesting the beneficial effect of GCSE on modulating atopic dermatitis. PMID:24499290

Propagation of maternal behavior across generations is associated with changes in non-maternal cognitive and behavioral processes.

PubMed

Lovic, Vedran; Fleming, Alison S

2015-08-01

Over a number of years we have studied the phenomenology of maternal behavior from endocrine, neural, experiential, and ontogenetic perspectives. Here, we focus on the effects of early life experiences with and without the mother on subsequent maternal and non-maternal behaviors of the offspring. We have used an artificial rearing procedure, which entails removing rat pups from their mother and raising them in isolation, while controlling and manipulating several aspects of their upbringing. As adults, mother-reared (MR) and artificially-reared (AR) rats are assessed on their own maternal behavior, as well several other behaviors. While both AR and MR rats nurse and successfully wean their young, the AR rats spend less time licking, grooming, and crouching over their young. Hence, being raised in social isolation does not seem to affect primary maternal motivational dynamics. Instead, isolation rearing produces alterations in the ongoing execution of the behavior and its effective organization. Here, we present evidence that changes in maternal behavior, as a result of social isolation from mother and siblings, are due to changes in top-down (e.g., sustained attention, flexibility) and bottom-up process (e.g., increased stimulus-driven behavior). These changes are likely due to alterations in brain dopamine systems, which are sensitive to early life manipulations and are modulators of bottom-up and top-down processes. Finally, we draw parallels between the rat and human maternal behavior. This article is part of a Special Issue entitled: In Honor of Jerry Hogan. Copyright © 2015 Elsevier B.V. All rights reserved.

Aerobic Microbial Community of Insectary Population of Phlebotomus papatasi

PubMed Central

Maleki-Ravasan, Naseh; Oshaghi, Mohammad Ali; Hajikhani, Sara; Saeidi, Zahra; Akhavan, Amir Ahmad; Gerami-Shoar, Mohsen; Shirazi, Mohammad Hasan; Yakhchali, Bagher; Rassi, Yavar; Afshar, Davoud

2014-01-01

Background: Microbes particularly bacteria presenting in the gut of haematophagous insects may have an important role in the epidemiology of human infectious disease. Methods: The microbial flora of gut and surrounding environmental of a laboratory strain of Phlebotomus papatasi, the main vector of Zoonotic Cutaneous Leishmaniasis (ZCL) in the old world, was investigated. Biochemical reactions and 16s rDNA sequencing of the isolated bacteria against 24 sugars and amino acids were used for bacteria species identification. Common mycological media used for fungi identification as well. Results: Most isolates belonged to the Enterobacteriaceae, a large, heterogeneous group of gram-negative rods whose natural habitat is the intestinal tract of humans and animals. Enterobacteriaceae groups included Edwardsiella, Enterobacter, Escherichia, Klebsiella, Kluyvera, Leminorella, Pantoea, Proteus, Providencia, Rahnella, Serratia, Shigella, Tatumella, and Yersinia and non Enterobacteriaceae groups included Bacillus, Staphylococcus and Pseudomonas. The most prevalent isolates were Proteus mirabilis and P. vulgaris. These saprophytic and swarming motile bacteria were isolated from all immature, pupae, and mature fed or unfed male or female sand flies as well as from larval and adult food sources. Five fungi species were also isolated from sand flies, their food sources and colonization materials where Candida sp. was common in all mentioned sources. Conclusion: Midgut microbiota are increasingly seen as an important factor for modulating vector competence in insect vectors so their possible effects of the mirobiota on the biology of P. papatasi and their roles in the sandfly-Leishmania interaction are discussed. PMID:25629067

Predation risk determines breeding territory choice in a Mediterranean cavity-nesting bird community.

PubMed

Parejo, Deseada; Avilés, Jesús M

2011-01-01

Non-direct effects of predation can be an important component of the total effect of predation, modulating animal population and community dynamics. The isolated effects of predation risk on the spatial organisation of the breeding bird community, however, remains poorly studied. We investigated whether an experimentally increased predation risk prior to reproduction affected breeding territory selection and subsequent reproductive strategies in three Mediterranean cavity-nesting birds, i.e., the little owl Athene noctua, European roller Coracias garrulus and scops owl Otus scops. We found that territories used the previous year were more likely to be re-occupied when they belonged to the safe treatment rather than to the risky treatment. The first choice of breeders of all three species was for safe territories over risky ones. When all breeding attempts in the season (i.e., final occupation) were considered, breeders also preferred safe to risky sites. In addition, little owls laid larger eggs in risky territories than in safe territories. Our study provides experimental evidence of a rapid preventive response of the three most abundant species in a cavity-nesting bird community to a short-term manipulation of predation risk. This response highlights the key role of the non-direct effects of predation in modulating avian community organisation.

Effects of modulators of AMP-activated protein kinase on TASK-1/3 and intracellular Ca(2+) concentration in rat carotid body glomus cells.

PubMed

Kim, Donghee; Kang, Dawon; Martin, Elizabeth A; Kim, Insook; Carroll, John L

2014-05-01

Acute hypoxia depolarizes carotid body chemoreceptor (glomus) cells and elevates intracellular Ca(2+) concentration ([Ca(2+)]i). Recent studies suggest that AMP-activated protein kinase (AMPK) mediates these effects of hypoxia by inhibiting the background K(+) channels such as TASK. Here we studied the effects of modulators of AMPK on TASK activity in cell-attached patches. Activators of AMPK (1mM AICAR and 0.1-0.5mM A769662) did not inhibit TASK activity or cause depolarization during acute (10min) or prolonged (2-3h) exposure. Hypoxia inhibited TASK activity by ∼70% in cells pretreated with AICAR or A769662. Both AICAR and A769662 (15-40min) failed to increase [Ca(2+)]i in glomus cells. Compound C (40μM), an inhibitor of AMPK, showed no effect on hypoxia-induced inhibition of TASK. AICAR and A769662 phosphorylated AMPKα in PC12 cells, and Compound C blocked the phosphorylation. Our results suggest that AMPK does not affect TASK activity and is not involved in hypoxia-induced elevation of intracellular [Ca(2+)] in isolated rat carotid body glomus cells. Copyright © 2014 Elsevier B.V. All rights reserved.

Chamitoff works on TVIS in the SM during Expedition 17

NASA Image and Video Library

2008-08-01

ISS017-E-012105 (1 Aug. 2008) --- NASA astronaut Greg Chamitoff, Expedition 17 flight engineer, works with the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

[Normalizing effect of the pineal gland peptides on the daily melatonin rhythm in old monkeys and elderly people].

PubMed

Korkushko, O V; Lapin, B A; Goncharova, N D; Khavinson, V Kh; Shatilo, V B; Vengerin, A A; Antoniuk-Shcheglova, I A; Magdich, L V

2007-01-01

In the course of aging both monkeys and people reveal decreased night and average daily level of melatonin in the blood plasma and reduced hormone circadian rhythm amplitude, which evidence the disorder of the pineal gland melatonin releasing function. Peptide preparations of the pineal gland (Epithalamin--a complex of peptides isolated from the pineal gland and Epitalon--synthetic tetrapeptide) recover night release of endogenous melatonin and lead to the normalization of the hormone circadian rhythm in the blood plasma. In elderly people Epithalamin and Epitalon modulate pineal gland functional state: people with pineal gland functional insufficiency report an increase of night melatonin level. The preparations of the pineal gland, effectively increasing melatonin concentration and having no side effects, can be used in clinical geriatric practice.

Isolation of lactobacillus reuteri from Peyer's patches and their effects on sIgA production and gut microbiota diversity.

PubMed

Wang, Panpan; Li, Ya; Xiao, Hang; Shi, Yonghui; Le, Guo-Wei; Sun, Jin

2016-09-01

We previously reported that specific Lactobacillus reuteri colonized within mouse Peyer's patches (PP) effectively prevented high fat diet induced obesity and low-grade chronic inflammation. We further investigated the role of PP Lactobacillus reuteri on sIgA production in rats in this study. Lactobacilli were isolated from rat PP. All isolates were L. reuteri and belonged to three phenotypes according to amplified fragment length polymorphism analysis. Typical strains of two main clusters, PP1 and PP2, were used to treat control and vitamin A deficient (VAD) rats, respectively. The feeding of PP1 and PP2 affected sIgA and Lactobacillus diversity by strain-specific manner. Free sIgA was significantly increased by PP1 (p = 0.069) and PP2 (p < 0.05) in the control rats but not in the VAD rats. Only PP1 significantly changed PP Lactobacillus diversity in the control rats (p < 0.05). However, PP2 specifically changed ileal Lactobacillus diversity in both control and VAD rats. Fecal sIgA was correlated with PP Lactobacillus diversity (R(2) = 0.7958, p = 0.011). Modulation of sIgA production by PP L. reuteri of rat is dependent on vitamin A and change of Lactobacillus diversity in PP. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Application Specific Electronic Module Program (ASEM), Final Technical Report.

DTIC Science & Technology

1994-12-14

relatively high temperatures , may induce a metal break or other continuity problems. Secondly, the improved electrical environment at the module level vs...wafer probe can permit higher speed tests to be applied, isolating marginal die. Thirdly, high reliability screens, such as temperature cycling, bum-in...The high temperature aging is done at 150’ C for 500 hours. The thermal cycle treatments are from 0- 100 0 C and 3 cycles per hour are done. The

A versatile, non genetically modified organism (GMO)-based strategy for controlling low-producer mutants in Bordetella pertussis cultures using antigenic modulation.

PubMed

Goffin, Philippe; Slock, Thomas; Smessaert, Vincent; De Rop, Philippe; Dehottay, Philippe

2015-08-01

The uncontrolled presence of non-producer mutants negatively affects bioprocesses. In Bordetella pertussis cultures, avirulent mutants emerge spontaneously and accumulate. We characterized the dynamics of accumulation using high-throughput growth assays and competition experiments between virulent and avirulent (bvg(-) ) isolates. A fitness advantage of bvg(-) cells was identified as the main driver for bvg(-) accumulation under conditions of high virulence factor production. Conversely, under conditions that reduce their expression (antigenic modulation), bvg(-) takeover could be avoided. A control strategy was derived, which consists in applying modulating conditions whenever virulence factor production is not required. It has a wide range of applications, from routine laboratory operations to vaccine manufacturing, where pertussis toxin yields were increased 1.4-fold by performing early pre-culture steps in modulating conditions. Because it only requires subtle modifications of the culture medium and does not involve genetic modifications, this strategy is applicable to any B. pertussis isolate, and should facilitate regulatory acceptance of process changes for vaccine production. Strategies based on the same concept, could be derived for other industrially relevant micro-organisms. This study illustrates how a sound scientific understanding of physiological principles can be turned into a practical application for the bioprocess industry, in alignment with Quality by Design principles. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Red wine induced modulation of vascular function: separating the role of polyphenols, ethanol, and urates.

PubMed

Boban, Mladen; Modun, Darko; Music, Ivana; Vukovic, Jonatan; Brizic, Ivica; Salamunic, Ilza; Obad, Ante; Palada, Ivan; Dujic, Zeljko

2006-05-01

By using red wine (RW), dealcoholized red wine (DARW), polyphenols-stripped red wine (PSRW), ethanol-water solution (ET), and water (W), the role of wine polyphenols, ethanol, and urate on vascular function was examined in humans (n = 9 per beverage) and on isolated rat aortic rings (n = 9). Healthy males randomly consumed each beverage in a cross-over design. Plasma ethanol, catechin, and urate concentrations were measured before and 30, 60 and 120 minutes after beverage intake. Endothelial function was assessed before and 60 minutes after beverage consumption by normalized flow-mediated dilation (FMD). RW and DARW induced similar vasodilatation in the isolated vessels whereas PSRW, ET, and W did not. All ethanol-containing beverages induced similar basal vasodilatation of brachial artery. Only intake of RW resulted in enhancement of endothelial response, despite similar plasma catechin concentration after DARW. The borderline effect of RW on FMD (P = 0.0531) became significant after FMD normalization (P = 0.0043) that neutralized blunting effect of ethanol-induced basal vasodilatation. Effects of PSRW and ET did not differ although plasma urate increased after PSRW and not after ET, indicating lack of urate influence on endothelial response. Acute vascular effects of RW, mediated by polyphenols, cannot be predicted by plasma catechin concentration only.

Metformin repositioning as antitumoral agent: selective antiproliferative effects in human glioblastoma stem cells, via inhibition of CLIC1-mediated ion current

PubMed Central

Barbieri, Federica; Peretti, Marta; Pizzi, Erika; Pattarozzi, Alessandra; Carra, Elisa; Sirito, Rodolfo; Daga, Antonio; Curmi, Paul M.G.; Mazzanti, Michele; Florio, Tullio

2014-01-01

Epidemiological and preclinical studies propose that metformin, a first-line drug for type-2 diabetes, exerts direct antitumor activity. Although several clinical trials are ongoing, the molecular mechanisms of this effect are unknown. Here we show that chloride intracellular channel-1 (CLIC1) is a direct target of metformin in human glioblastoma cells. Metformin exposure induces antiproliferative effects in cancer stem cell-enriched cultures, isolated from three individual WHO grade IV human glioblastomas. These effects phenocopy metformin-mediated inhibition of a chloride current specifically dependent on CLIC1 functional activity. CLIC1 ion channel is preferentially active during the G1-S transition via transient membrane insertion. Metformin inhibition of CLIC1 activity induces G1 arrest of glioblastoma stem cells. This effect was time-dependent, and prolonged treatments caused antiproliferative effects also for low, clinically significant, metformin concentrations. Furthermore, substitution of Arg29 in the putative CLIC1 pore region impairs metformin modulation of channel activity. The lack of drugs affecting cancer stem cell viability is the main cause of therapy failure and tumor relapse. We identified CLIC1 not only as a modulator of cell cycle progression in human glioblastoma stem cells but also as the main target of metformin's antiproliferative activity, paving the way for novel and needed pharmacological approaches to glioblastoma treatment. PMID:25361004

Metformin repositioning as antitumoral agent: selective antiproliferative effects in human glioblastoma stem cells, via inhibition of CLIC1-mediated ion current.

PubMed

Gritti, Marta; Würth, Roberto; Angelini, Marina; Barbieri, Federica; Peretti, Marta; Pizzi, Erika; Pattarozzi, Alessandra; Carra, Elisa; Sirito, Rodolfo; Daga, Antonio; Curmi, Paul M G; Mazzanti, Michele; Florio, Tullio

2014-11-30

Epidemiological and preclinical studies propose that metformin, a first-line drug for type-2 diabetes, exerts direct antitumor activity. Although several clinical trials are ongoing, the molecular mechanisms of this effect are unknown. Here we show that chloride intracellular channel-1 (CLIC1) is a direct target of metformin in human glioblastoma cells. Metformin exposure induces antiproliferative effects in cancer stem cell-enriched cultures, isolated from three individual WHO grade IV human glioblastomas. These effects phenocopy metformin-mediated inhibition of a chloride current specifically dependent on CLIC1 functional activity. CLIC1 ion channel is preferentially active during the G1-S transition via transient membrane insertion. Metformin inhibition of CLIC1 activity induces G1 arrest of glioblastoma stem cells. This effect was time-dependent, and prolonged treatments caused antiproliferative effects also for low, clinically significant, metformin concentrations. Furthermore, substitution of Arg29 in the putative CLIC1 pore region impairs metformin modulation of channel activity. The lack of drugs affecting cancer stem cell viability is the main cause of therapy failure and tumor relapse. We identified CLIC1 not only as a modulator of cell cycle progression in human glioblastoma stem cells but also as the main target of metformin's antiproliferative activity, paving the way for novel and needed pharmacological approaches to glioblastoma treatment.

Effect of fusimotor stimulation on Ia discharge during shortening of cat soleus muscle at different speeds

PubMed Central

Appenteng, K.; Prochazka, A.; Proske, U.; Wand, P.

1982-01-01

1. In barbiturate-anaesthetized cats, the L7 and S1 dorsal and ventral roots were dissected to isolate functionally single afferents identified as primary endings of soleus muscle spindles, and motor filaments which exerted a fusimotor action on the afferents with limited action on extrafusal muscle. Up to seven filaments, with an action on a given primary ending, could be isolated and each was classified as exerting either a predominantly dynamic or static action. 2. Combined stimulation of these filaments, at rates up to 200 impulses/s could maintain afferent firing during muscle shortenings at speeds up to 200 mm/s. 3. Fusimotor stimulation could also maintain afferent firing at a target frequency of 100 impulses/s during muscle shortenings up to 200 mm/s. The timing, in relation to the onset of shortening, and the rates of fusimotor stimulation were found to be critical in achieving the target frequency. 4. Sinusoidal modulation of the frequency of fusimotor stimulation was used to study the conditions required to achieve constant afferent firing in the face of imposed sinusoidal length changes. 5. For given depths of modulation, the phase advance of fusimotor stimulation needed to produce minimum modulation of afferent firing (best compensation) increased with increasing frequency of the sinusoids. The compensation deteriorated with an increase in the frequency of the sinusoids and a change in the mean muscle lengths, although in some cases it could be restored by adjustments to the depth of modulation of fusimotor rate. This suggests that for movements of varying speeds and amplitudes, settings which are appropriate for shortening at a given velocity and mean muscle length, do not apply if either of these two variables are altered. 6. These findings demonstrate that the fusimotor system is potentially capable of eliciting constant afferent firing as envisaged in the `servo-assistance' hypothesis (Matthews, 1964, 1972; Stein, 1974). This, and the fact that constant afferent firing is not seen during normal unobstructed shortenings at velocities greater than 0·2 resting length/s (Prochazka, 1981), are used to argue that it is by choice rather than necessity that `servo-assistance' (as defined above) is not employed during normal movements. However, servo-assistance of a different form (involving modulated spindle afferent feed-back from both agonists and antagonists) remains a viable alternative. PMID:6216336

The effects of voluntary running exercise coincidence with social isolation after early weaning on monoaminergic axonal development.

PubMed

Ishikawa, J; Ishikawa, A

2013-01-29

The axonal development of serotonin (5-HT)-, noradrenaline (NA)-, or tyrosine hydroxylase (TH)-containing monoaminergic neurons is affected by rearing conditions during the juvenile period. Impaired monoaminergic axonal development is implicated in the pathophysiology of emotional and cognitive dysfunction. On the other hand, exercise may have beneficial effects on emotional and learning performance in adults. We have examined whether voluntary running exercise during social isolation after early weaning (early weaning/social isolation; EI) from postnatal day (PD) 14-28 could prevent the impaired monoaminergic axonal development associated with EI. Compared with control animals reared with their dam and siblings until PD28, the EI animals showed lower density of 5-HT and NA axons in the dorsal-medial prefrontal cortex (mPFC) and basolateral nucleus of the amygdala and of NA- and TH-containing axons in the ventral-mPFC. These adverse effects of EI were not observed in rats taking part in voluntary running (EI+R) when these animals were compared to controls. The 5-HT axon density in the ventral-mPFC was significantly higher in the EI+R rats than that in the EI rats, although both these values were significantly lower than those in the control rats. The density of monoaminergic axons in the dentate gyrus and CA3 of the hippocampus was not affected by either EI or EI+R. These results suggest that the beneficial effects of voluntary running may be because of the modulation of monoaminergic axonal morphology. Our findings will hopefully provide the basis for future research into the beneficial effects of voluntary exercise during the juvenile period on brain development and emotional and cognitive performance. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Isolation of hydroxyoctaprenyl-1',4'-hydroquinone, a new octaprenylhydroquinone from the marine sponge Sarcotragus spinosulus and evaluation of its pharmacological activity on acetylcholine and glutamate release in the rat central nervous system.

PubMed

Bisio, Angela; Fedele, Ernesto; Pittaluga, Anna; Olivero, Guendalina; Grilli, Massimo; Chen, Jiayang; Mele, Giacomo; Malafronte, Nicola; De Tommasi, Nunziatina; Leddae, Fabio; Manconi, Renata; Pronzato, Roberto; Marchi, Mario

2014-11-01

Three polyprenyl-1',4'-hydroquinone derivatives, heptaprenyl-1',4'-hydroquinone (1), octaprenyl-1',4'-hydroquinone (2), and hydroxyoctaprenyl-1',4'- hydroquinone (3) were isolated from the marine sponge Sarcotragus spinosulus collected at Baia di Porto Conte, Alghero (Italy). Our findings indicate that the compounds isolated from S. spinosulus can significantly modulate the release of glutamate and acetylcholine in the rat hippocampus and cortex and might, therefore, represent the prototype of a new class of drugs regulating glutamatergic and cholinergic transmission in the mammalian central nervous system.

Inhibition of p38 MAPK during cellular activation modulate gene expression of head kidney leukocytes isolated from Atlantic salmon (Salmo salar) fed soy bean oil or fish oil based diets.

PubMed

Holen, E; Winterthun, S; Du, Z-Y; Krøvel, A V

2011-01-01

Head kidney leukocytes isolated from Atlantic salmon fed either a diet based on fish oil (FO) or soy bean oil (VO) were used in order to evaluate if different lipid sources could contribute to cellular activation of the salmon innate immune system. A specific inhibitor of p38 MAPK, SB202190, was used to investigate the effect of lipopolysaccharide (LPS) signalling in the head kidney leukocytes. The results show that LPS up regulate IL-1β, TNF-α, Cox2 expression in leukocytes isolated from fish fed either diet. The p38 MAPK inhibitor, SB202190, reduced the LPS induced expression of these genes in both dietary groups. In LPS stimulated leukocytes isolated from VO fed fish, SB202190 showed a clear dose dependent inhibitory effect on IL-1β, TNF-α and Cox2 expression. This effect was also observed for Cox2 in leukocytes isolated from FO fed fish. Furthermore, there was a stronger mean induction of Cox2 in LPS stimulated leucocytes isolated from the VO-group compared to LPS stimulated leukocytes isolated from the FO-group. In both dietary groups, LPS stimulation of salmon head kidney leukocytes increased the induction of CD83, a dendrite cell marker, while the inhibitor reduced CD83 expression in the VO fed fish only. The inhibitor also clearly reduced hsp27 expression in VO fed fish. Indicating a p38 MAPK feedback loop, LPS significantly inhibited the expression of p38MAPK itself in both diets, while SB202190 increased p38MAPK expression especially in the VO diet group. hsp70 expression was not affected by any treatment or feed composition. There were also differences in p38MAPK protein phosphorylation comparing treatment groups but no obvious difference comparing the two dietary groups. The results indicate that dietary fatty acids have the ability to modify signalling through p38 MAPK which may have consequences for the fish's ability to handle infections and stress. Signalling through p38MAPK is ligand dependent and affects gene and protein expression differently. Copyright © 2010 Elsevier Ltd. All rights reserved.

A quantitative method for photovoltaic encapsulation system optimization

NASA Technical Reports Server (NTRS)

Garcia, A., III; Minning, C. P.; Cuddihy, E. F.

1981-01-01

It is pointed out that the design of encapsulation systems for flat plate photovoltaic modules requires the fulfillment of conflicting design requirements. An investigation was conducted with the objective to find an approach which will make it possible to determine a system with optimum characteristics. The results of the thermal, optical, structural, and electrical isolation analyses performed in the investigation indicate the major factors in the design of terrestrial photovoltaic modules. For defect-free materials, minimum encapsulation thicknesses are determined primarily by structural considerations. Cell temperature is not strongly affected by encapsulant thickness or thermal conductivity. The emissivity of module surfaces exerts a significant influence on cell temperature. Encapsulants should be elastomeric, and ribs are required on substrate modules. Aluminum is unsuitable as a substrate material. Antireflection coating is required on cell surfaces.

Power module assembly

DOEpatents

Campbell, Jeremy B [Torrance, CA; Newson, Steve [Redondo Beach, CA

2011-11-15

A power module assembly of the type suitable for deployment in a vehicular power inverter, wherein the power inverter has a grounded chassis, is provided. The power module assembly comprises a conductive base layer electrically coupled to the chassis, an insulating layer disposed on the conductive base layer, a first conductive node disposed on the insulating layer, a second conductive node disposed on the insulating layer, wherein the first and second conductive nodes are electrically isolated from each other. The power module assembly also comprises a first capacitor having a first electrode electrically connected to the conductive base layer, and a second electrode electrically connected to the first conductive node, and further comprises a second capacitor having a first electrode electrically connected to the conductive base layer, and a second electrode electrically connected to the second conductive node.

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

NASA Technical Reports Server (NTRS)

Coulbert, C. D.

1983-01-01

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

Electrical system for pulse-width modulated control of a power inverter using phase-shifted carrier signals and related operating methods

DOEpatents

Welchko, Brian A [Torrance, CA

2012-02-14

Systems and methods are provided for pulse-width modulated control of power inverter using phase-shifted carrier signals. An electrical system comprises an energy source and a motor. The motor has a first set of windings and a second set of windings, which are electrically isolated from each other. An inverter module is coupled between the energy source and the motor and comprises a first set of phase legs coupled to the first set of windings and a second set of phase legs coupled to the second set of windings. A controller is coupled to the inverter module and is configured to achieve a desired power flow between the energy source and the motor by modulating the first set of phase legs using a first carrier signal and modulating the second set of phase legs using a second carrier signal. The second carrier signal is phase-shifted relative to the first carrier signal.

Neuropeptide Y is a prejunctional inhibitor of vagal but not sympathetic inotropic responses in guinea-pig isolated left atria

PubMed Central

Serone, Adrian P; Angus, James A

1999-01-01

The effects of NPY and related peptides were examined on basal contractile force and nerve-mediated inotropic responses to electrical field stimulation of the guinea-pig isolated left atrium.Electrical field stimulus (EFS)-inotropic response curves were constructed by applying 1-64 trains of four field pulses (200 Hz, 0.1 ms duration, 100 V) across isolated left atria (paced at 4 Hz, 2 ms, 1–4 V) within the atrial refractory period. Curves were constructed in presence of vehicle, propranolol (1 μM) or atropine (1 μM) to determine appropriate stimulus conditions.The effects of PYY (1–10,000 nM), NPY (0.01–10 μM), N-Ac-[Leu28,31]NPY(24–36) (N-A[L]NPY(24–36); 0.01–10 μM) and clonidine (0.1–1000 nM) were examined on the positive and negative inotropic responses to EFS (eight trains, four pulses per refractory period).NPY-related peptides had no effect on basal force of contraction nor on the inotropic concentration-response curves to bethanechol or isoprenaline. All three peptides inhibited vagally-mediated negative inotropic responses; rank order of potency PYY>NPY⩾N-A[L]NPY(24–36) was consistent with an action at prejunctional Y2-receptors. Clonidine concentration-dependently inhibited sympathetic inotropic responses. However, PYY, NPY and N-A[L]NPY(24–36) failed to mediate any significant inhibition of the positive inotropic response to EFS.These data demonstrate that NPY is an effective inhibitor of vagal but not sympathetically-mediated inotropic responses in the guinea-pig isolated left atria. This may suggest that endogenously co-released NPY is important in mediating cross talk between efferent components of the autonomic nervous system modulating cardiac contractility, acting overall to sustain positive inotropic responses. PMID:10385237

iss002e6675

NASA Image and Video Library

2001-05-15

ISS002-E-6675 (15 May 2001) --- James S. Voss, Expedition Two flight engineer, wearing a safety harness, exercises on the Treadmill Vibration Isolation System (TVIS) equipment in the Zvezda Service Module. This image was taken with a digital still camera.

Williams exercises on TVIS in Zvezda

NASA Image and Video Library

2007-12-28

ISS014-E-10591 (28 Dec. 2006) --- Astronaut Sunita L. Williams, Expedition 14 flight engineer, equipped with a bungee harness, exercises on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

Wakata during TVIS maintenance

NASA Image and Video Library

2009-04-21

ISS019-E-008758 (21 April 2009) --- Japan Aerospace Exploration Agency (JAXA) astronaut Koichi Wakata, Expedition 19/20 flight engineer, performs in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

Chamitoff performs maintenance on the TVIS during Expedition 17

NASA Image and Video Library

2008-08-12

ISS017-E-012864 (12 Aug. 2008) --- NASA astronaut Greg Chamitoff, Expedition 17 flight engineer, performs in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

Novitskiy performs in-flight maintenance on the TVIS

NASA Image and Video Library

2013-01-23

ISS034-E-033549 (23 Jan. 2013) --- Russian cosmonaut Oleg Novitskiy, Expedition 34 flight engineer, performs routine in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

Power module assembly with reduced inductance

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

Ward, Terence G.; Stancu, Constantin C.; Jaksic, Marko

A power module assembly has a plurality of electrically conducting layers, including a first layer and a third layer. One or more electrically insulating layers are operatively connected to each of the plurality of electrically conducting layers. The electrically insulating layers include a second layer positioned between and configured to electrically isolate the first and the third layers. The first layer is configured to carry a first current flowing in a first direction. The third layer is configured to carry a second current flowing in a second direction opposite to the first direction, thereby reducing an inductance of the assembly.more » The electrically insulating layers may include a fourth layer positioned between and configured to electrically isolate the third layer and a fifth layer. The assembly results in a combined substrate and heat sink structure. The assembly eliminates the requirements for connections between separate substrate and heat sink structures.« less

Lupin protein isolate versus casein modifies cholesterol excretion and mRNA expression of intestinal sterol transporters in a pig model

PubMed Central

2014-01-01

Background Lupin proteins exert hypocholesterolemic effects in man and animals, although the underlying mechanism remains uncertain. Herein we investigated whether lupin proteins compared to casein modulate sterol excretion and mRNA expression of intestinal sterol transporters by use of pigs as an animal model with similar lipid metabolism as humans, and cellular cholesterol-uptake by Caco-2 cells. Methods Two groups of pigs were fed cholesterol-containing diets with either 230 g/kg of lupin protein isolate from L. angustifolius or 230 g/kg casein, for 4 weeks. Faeces were collected quantitatively over a 5 d period for analysis of neutral sterols and bile acids by gas chromatographically methods. The mRNA abundances of intestinal lipid transporters were analysed by real-time RT-PCR. Cholesterol-uptake studies were performed with Caco-2 cells that were incubated with lupin conglutin γ, phytate, ezetimibe or albumin in the presence of labelled [4-14C]-cholesterol. Results Pigs fed the lupin protein isolate revealed lower cholesterol concentrations in total plasma, LDL and HDL than pigs fed casein (P < 0.05). Analysis of faeces revealed a higher output of cholesterol in pigs that were fed lupin protein isolate compared to pigs that received casein (+57.1%; P < 0.05). Relative mRNA concentrations of intestinal sterol transporters involved in cholesterol absorption (Niemann-Pick C1-like 1, scavenger receptor class B, type 1) were lower in pigs fed lupin protein isolate than in those who received casein (P < 0.05). In vitro data showed that phytate was capable of reducing the uptake of labelled [4-14C]-cholesterol into the Caco-2 cells to the same extend as ezetimibe when compared to control (−20.5% vs. −21.1%; P < 0.05). Conclusions Data reveal that the cholesterol-lowering effect of lupin protein isolate is attributable to an increased faecal output of cholesterol and a reduced intestinal uptake of cholesterol. The findings indicate phytate as a possible biofunctional ingredient of lupin protein isolate. PMID:24490902

Anti-Inflammatory benefits of antibiotic-induced neutrophil apoptosis: tulathromycin induces caspase-3-dependent neutrophil programmed cell death and inhibits NF-kappaB signaling and CXCL8 transcription.

PubMed

Fischer, Carrie D; Beatty, Jennifer K; Zvaigzne, Cheryl G; Morck, Douglas W; Lucas, Merlyn J; Buret, A G

2011-01-01

Clearance of apoptotic neutrophils is a central feature of the resolution of inflammation. Findings indicate that immuno-modulation and induction of neutrophil apoptosis by macrolide antibiotics generate anti-inflammatory benefits via mechanisms that remain obscure. Tulathromycin (TUL), a new antimicrobial agent for bovine respiratory disease, offers superior clinical efficacy for reasons not fully understood. The aim of this study was to identify the immuno-modulating effects of tulathromycin and, in this process, to establish tulathromycin as a new model for characterizing the novel anti-inflammatory properties of antibiotics. Bronchoalveolar lavage specimens were collected from Holstein calves 3 and 24 h postinfection, challenged intratracheally with live Mannheimia haemolytica (2 × 10(7) CFU), and treated with vehicle or tulathromycin (2.5 mg/kg body weight). Terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) staining and enzyme-linked immunosorbent assay (ELISA) revealed that tulathromycin treatment significantly increased leukocyte apoptosis and reduced levels of proinflammatory leukotriene B(4) in M. haemolytica-challenged calves. In vitro, tulathromycin concentration dependently induced apoptosis in freshly isolated bovine neutrophils from healthy steers in a capase-3-dependent manner but failed to induce apoptosis in bovine fibroblasts, epithelial cells, and endothelial cells, as well as freshly isolated bovine blood monocytes and monocyte-derived macrophages. The proapoptotic effects of TUL were also, in part, drug specific; equimolar concentrations of penicillin G, oxytetracycline, and ceftiofur failed to cause apoptosis in bovine neutrophils. In addition, tulathromycin significantly reduced levels of phosphorylated IκBα, nuclear translocation of NF-κB p65, and mRNA levels of proinflammatory interleukin-8 in lipopolysaccharide (LPS)-stimulated bovine neutrophils. The findings illustrate novel mechanisms through which tulathromycin confers anti-inflammatory benefits.

Doxorubicin-induced nitrosative stress is mitigated by vitamin C via the modulation of nitric oxide synthases.

PubMed

Akolkar, Gauri; Bagchi, Ashim K; Ayyappan, Prathapan; Jassal, Davinder S; Singal, Pawan K

2017-04-01

An increase in oxidative stress is suggested to be the main cause in Doxorubicin (Dox)-induced cardiotoxicity. However, there is now evidence that activation of inducible nitric oxide synthase (iNOS) and nitrosative stress are also involved. The role of vitamin C (Vit C) in the regulation of nitric oxide synthase (NOS) and reduction of nitrosative stress in Dox-induced cardiotoxicity is unknown. The present study investigated the effects of Vit C in the mitigation of Dox-induced changes in the levels of nitric oxide (NO), NOS activity, protein expression of NOS isoforms, and nitrosative stress as well as cytokines TNF-α and IL-10 in isolated cardiomyocytes. Cardiomyocytes isolated from adult Sprague-Dawley rats were segregated into four groups: 1 ) control, 2 ) Vit C (25 µM), 3 ) Dox (10 µM), and 4 ) Vit C + Dox. Dox caused a significant increase in the generation of superoxide radical (O 2 ·- ), peroxynitrite, and NO, and these effects of Dox were blunted by Vit C. Dox increased the expression of iNOS and altered protein expression as well as activation of endothelial NOS (eNOS). These changes were prevented by Vit C. Dox induced an increase in the ratio of monomeric/dimeric eNOS, promoting the production of O 2 ·- , which was prevented by Vit C by increasing the stability of the dimeric form of eNOS. Vit C protected against the Dox-induced increase in TNFα as well as a reduction in IL-10. These results suggest that Vit C provides cardioprotection by reducing oxidative/nitrosative stress and inflammation via a modulation of Dox-induced increase in the NO levels and NOS activity. Copyright © 2017 the American Physiological Society.

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

PubMed

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

2012-03-01

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

Dorsal Raphe Dopamine Neurons Represent the Experience of Social Isolation

PubMed Central

Matthews, Gillian A.; Nieh, Edward H.; Vander Weele, Caitlin M.; Halbert, Sarah A.; Pradhan, Roma V.; Yosafat, Ariella S.; Glober, Gordon F.; Izadmehr, Ehsan M.; Thomas, Rain E.; Lacy, Gabrielle D.; Wildes, Craig P.; Ungless, Mark A.; Tye, Kay M.

2016-01-01

Summary The motivation to seek social contact may arise from either positive or negative emotional states, as social interaction can be rewarding and social isolation can be aversive. While ventral tegmental area (VTA) dopamine (DA) neurons may mediate social reward, a cellular substrate for the negative affective state of loneliness has remained elusive. Here, we identify a functional role for DA neurons in the dorsal raphe nucleus (DRN), in which we observe synaptic changes following acute social isolation. DRN DA neurons show increased activity upon social contact following isolation, revealed by in vivo calcium imaging. Optogenetic activation of DRN DA neurons increases social preference but causes place avoidance. Furthermore, these neurons are necessary for promoting rebound sociability following an acute period of isolation. Finally, the degree to which these neurons modulate behavior is predicted by social rank, together supporting a role for DRN dopamine neurons in mediating a loneliness-like state. PaperClip PMID:26871628

Pathogenicity Island O-122 in enteropathogenic Escherichia coli strains is associated with diarrhea severity in children from Lima Peru

PubMed Central

Mercado, Erik H.; Piscoche, Cristian; Contreras, Carmen; Durand, David; Riveros, Maribel; Ruiz, Joaquim; Ochoa, Theresa J.

2016-01-01

EPEC is an attaching and effacing diarrheal pathogen that carries a large pathogenicity island, locus for enterocyte effacement (LEE). Recently, the pathogenicity island PAI O-122 was described among non-LEE effectors and found to be associated with diarrhea among atypical EPEC strains. It is unknown if incomplete PAI O-122 could be associated with diarrhea duration and severity. To identify these virulence determinants we analyzed 379 EPEC strains isolated from Peruvian children. EPEC was diagnosed by PCR(eae+, stx−) and classified as typical(t-EPEC) or atypical(a-EPEC). To characterize PAI O-122 we amplified three modules by PCR: Module 1(pagC), Module 2(senA, nleB and nleE) and Module 3(lifA/efa-1). To characterize the large ORF lifA/efa-1 we amplified the regions known as efa-N, efa-M and efa-C. Clinical information was obtained from the cohort study. A total of 379 EPEC strains were able to analyze PAI O-122 genes, 128 (10.4%) EPEC strains were isolated from 1235 diarrhea episodes and 251(9.2%) from 2734 healthy controls. t-EPEC strains were isolated from 14.8% (19/128) of children with diarrhea and 25/251(10.0%) from healthy controls. The most frequent PAI O-122 genes were nleE(37.7%), senA(34.6%) and nleB(37.5%), with similar prevalence among diarrhea and control samples. However, lifA/efa-1 was more common among diarrhea cases than healthy control cases (30.5% vs. 21.1%, p<0.05). The presence of complete PAI O-122 was associated with diarrhea episodes of higher severity among single pathogen infection (33.3% vs. 1.8%, p<0.05) mainly due to the presence of a complete lifA/efa-1 gene. In summary, the gene lifA/efa-1 is significantly associated with diarrheal episodes of higher severity, suggesting to be an important virulent factor. PMID:27236730

Phenotypic Modulation of the Virulent Bvg Phase Is Not Required for Pathogenesis and Transmission of Bordetella bronchiseptica in Swine

PubMed Central

Brockmeier, Susan L.; Loving, Crystal L.; Register, Karen B.; Kehrli, Marcus E.; Stibitz, Scott E.; Shore, Sarah M.

2012-01-01

The majority of virulence gene expression in Bordetella is regulated by a two-component sensory transduction system encoded by the bvg locus. In response to environmental cues, the BvgAS regulatory system controls expression of a spectrum of phenotypic phases, transitioning between a virulent (Bvg+) phase and a nonvirulent (Bvg−) phase, a process referred to as phenotypic modulation. We hypothesized that the ability of Bordetella bronchiseptica to undergo phenotypic modulation is required at one or more points during the infectious cycle in swine. To investigate the Bvg phase-dependent contribution to pathogenesis of B. bronchiseptica in swine, we constructed a series of isogenic mutants in a virulent B. bronchiseptica swine isolate and compared each mutant to the wild-type isolate for its ability to colonize and cause disease. We additionally tested whether a BvgAS system capable of modulation is required for direct or indirect transmission. The Bvg− phase-locked mutant was never recovered from any respiratory tract site at any time point examined. An intermediate phase-locked mutant (Bvgi) was found in numbers lower than the wild type at all respiratory tract sites and time points examined and caused limited to no disease. In contrast, colonization of the respiratory tract and disease caused by the Bvg+ phase-locked mutant and the wild-type strain were indistinguishable. The Bvg+ phase-locked mutant transmitted to naïve pigs by both direct and indirect contact with efficiency equal to that of the wild-type isolate. These results indicate that while full activation of the BvgAS regulatory system is required for colonization and severe disease, it is not deleterious to direct and indirect transmission. Overall, our results demonstrate that the Bvg+ phase is sufficient for respiratory infection and host-to-host transmission of B. bronchiseptica in swine. PMID:22158743

Haberlea rhodopensis: pharmaceutical and medical potential as a food additive.

PubMed

Todorova, Roumiana; Atanasov, Atanas T

2016-01-01

This review discusses the potential of Haberlea rhodopensis as a food additive. The following are described: plant distribution, reproduction, cultivation, propagation and resurrection properties; extraction, isolation and screening of biologically active compounds; metabolite changes during dehydration; phytotherapy-related properties such as antioxidant potential and free radical-scavenging activities, antioxidant skin effect, antibacterial activity, cytotoxic activity and cancer-modulating effect, radioprotective effect, chemoprotective effect, immunologic effect; present use in homoeopathy and cosmetics, pharmacological and economical importance; perspectives based on the ethnobotanical data for medicinal, cosmetic or ritual attributes. H. rhodopensis showed unique medical and pharmaceutical potential, related to antioxidant, antimicrobial, antimutagenic, anticancer, radioprotective, chemoprotective and immunological properties. H. rhodopensis extracts lack any cytotoxic activity and could be used in phytotherapy. The metabolic profiling of H. rhodopensis extracts revealed the presence of biologically active compounds, possessing antiradical and other physiological activities, useful for design of in vitro synthesised analogues and drugs.

Digital transmitter for data bus communications system

NASA Technical Reports Server (NTRS)

Proch, G. E. (Inventor)

1975-01-01

An improved digital transmitter for transmitting serial pulse code modulation (pcm) data at high bit rates over a transmission line is disclosed. When not transmitting, the transmitter features a high output impedance which prevents the transmitter from loading the transmission line. The pcm input is supplied to a logic control circuit which produces two discrete logic level signals which are supplied to an amplifier. The amplifier, which is transformer coupled to the output isolation circuitry, converts the discrete logic level signals to two high current level, ground isolated signals in the secondary windings of the coupling transformer. The latter signals are employed as inputs to the isolation circuitry which includes two series transistor pairs operating into a hybrid transformer functioning to isolate the transmitter circuitry from the transmission line.

Uterine responses to feeding soy protein isolate and treatment with 17β-estradiol differ in ovariectomized female rats

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

Ronis, Martin J., E-mail: mronis@lsuhsc.edu; Gomez-Acevedo, Horacio; Blackburn, Michael L.

There are concerns regarding reproductive toxicity from consumption of soy foods, including an increased risk of endometriosis and endometrial cancer, as a result of phytoestrogen consumption. In this study, female rats were fed AIN-93G diets made with casein (CAS) or soy protein isolate (SPI) from postnatal day (PND) 30, ovariectomized on PND 50 and infused with 5 μg/kg/d 17β-estradiol (E2) or vehicle. E2 increased uterine wet weight (P < 0.05). RNAseq analysis revealed that E2 significantly altered expression of 1991 uterine genes (P < 0.05). SPI feeding had no effect on uterine weight and altered expression of far fewer genesmore » than E2 at 152 genes (P < 0.05). Overlap between E2 and SPI genes was limited to 67 genes. Functional annotation analysis indicated significant differences in uterine biological processes affected by E2 and SPI and little evidence for recruitment of estrogen receptor (ER)α to the promoters of ER-responsive genes after SPI feeding. The major E2 up-regulated uterine pathways were carcinogenesis and extracellular matrix organization, whereas SPI feeding up-regulated uterine peroxisome proliferator activated receptor (PPAR) signaling and fatty acid metabolism. The combination of E2 and SPI resulted in significant regulation of 504 fewer genes relative to E2 alone. The ability of E2 to induce uterine proliferation in response to the carcinogen dimethybenz(a)anthracene (DMBA) as measured by expression of PCNA and Ki67 mRNA was suppressed by feeding SPI (P < 0.05). These data suggest that SPI is a selective estrogen receptor modulator (SERM) interacting with a small sub-set of E2-regulated genes and is anti-estrogenic in the presence of endogenous estrogens. - Highlights: • Concerns exist regarding risk of uterine cancer from consumption of soy products. • These concerns are related to potential estrogenicity. • Estradiol and soy protein isolate effects on uterine gene expression were compared. • Soy acts as a selective estrogen receptor modulator not a weak estrogen. • Soy feeding blocked uterine proliferation after treatment with estradiol and DMBA.« less

Quantitative and qualitative microbiological profiles of the Apollo 10 and 11 spacecraft.

PubMed

Puleo, J R; Oxborrow, G S; Fields, N D; Hall, H E

1970-09-01

Microbiological profiles were determined for surfaces of the command module, lunar module (ascent and descent stages), instrument unit, Saturn S-4B stage, and the spacecraft lunar module adapter of the Apollo 10 and 11 spacecraft. Average levels of contamination of the command module were 2.1 x 10(4) and 2.7 x 10(4) microorganisms per ft(2) for Apollo 10 and 11, respectively. With the exception of the exterior surfaces of the ascent stage of the lunar module and the interior surfaces of the command module, average levels of microbial contamination on all components of the Apollo 11 were found to be lower than those observed on Apollo 10. For each Apollo mission, approximately 2,000 colonies were picked from a variety of media and identified. The results showed that approximately 95% of all isolates were those considered indigenous to humans; the remaining were associated with soil and dust in the environment. However, the ratio of these two general groups varied depending on the degrees of personnel density and environmental control associated with each module.

Glucocorticoid-dependent induction of interleukin-6 receptor expression in human hepatocytes facilitates interleukin-6 stimulation of amino acid transport.

PubMed

Fischer, C P; Bode, B P; Takahashi, K; Tanabe, K K; Souba, W W

1996-05-01

The authors studied the effects of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) on glutamine and alanine transport in isolated human hepatocytes. They also evaluated the role of dexamethasone in modulating this response and its effects on the expression of the plasma membrane high-affinity IL-6 receptor. Animal studies indicate that cytokines are important mediators of the increased hepatic amino acid uptake that occurs during cancer and sepsis, but studies in human tissues are lacking. The control of transport by cytokines and cytokine receptor expression in the liver may provide a mechanism by which hepatocytes can modulate amino acid availability during catabolic disease states. Human hepatocytes were isolated from wedge biopsy specimens and plated in 24-well trays. Interleukin-6 and TNF-alpha, in combination with the synthetic glucocorticoid dexamethasone, were added to hepatocytes in culture, and the transport of radiolabeled glutamine and alanine was measured. Fluorescent-activated cell sorter (FACS) analysis was used to study the effects of dexamethasone on IL-6 receptor number in the well-differentiated human hepatoma HepG2. Both IL-6 and TNF-alpha exerted a small stimulatory effect on alanine and glutamine transport. Dexamethasone alone did not alter transport rates, but pretreatment of cells augmented the effects of both cytokines on carrier-mediated amino acid uptake. Dexamethasone pretreatment and a combination of IL-6 and TNF-alpha resulted in a greater than twofold increase in transport activity. Fluorescent-activated cell sorter analysis demonstrated that dexamethasone induced a threefold increase in the expression of high-affinity IL-6 receptors. Interleukin-6 and TNF-alpha work coordinately with glucocorticoids to stimulate amino acid uptake in human hepatocytes. Dexamethasone exerts a permissive effect on cytokine-mediated increases in transport by increasing IL-6 receptor expression on the cell surface. It is likely that this upregulation of IL-6 receptors "primes" human liver cells for subsequent stimulation by cytokines. The resulting increase in hepatic amino acid transport provides the liver with substrate to support key metabolic pathways during catabolic states.

Proceedings of the 22nd Project Integration Meeting

NASA Technical Reports Server (NTRS)

1983-01-01

This report describes progress made by the Flat-Plate Solar Array Project during the period January to September 1983. It includes reports on silicon sheet growth and characterization, module technology, silicon material, cell processing and high-efficiency cells, environmental isolation, engineering sciences, module performance and failure analysis and project analysis and integration. It includes a report on, and copies of visual presentations made at the 22nd Project Integration Meeting held at Pasadena, California, on September 28 and 29, 1983.

What the cerveau isolé preparation tells us nowadays about sleep-wake mechanisms?

PubMed

Gottesmann, C

1988-01-01

The intercollicular transected preparation opened a rich field for investigations of sleep-wake mechanisms. Initial results showed that brain stem ascending influences are essential for maintaining an activated cortex. It was subsequently shown that the forebrain also develops activating influences, since EEG desynchronization of the cortex reappears in the chronic cerveau isolé preparation, and continuous or almost continuous theta rhythm is able to occur in the acute cerveau isolé preparation. A brief "intermediate stage" of sleep occurs during natural sleep just prior to and after paradoxical sleep. It is characterized by cortical spindle bursts, hippocampal low frequency theta activity (two patterns of the acute cerveau isolé preparation) and is accompanied by a very low thalamic transmission level, suggesting a cerveau isolé-like state. The chronic cerveau isolé preparation also demonstrates that the executive processes of paradoxical sleep are located in the lower brain stem, while the occurrence of this sleep stage seems to be modulated by forebrain structures.

Social influences on microglial reactivity and neuronal damage after cardiac arrest/cardiopulmonary resuscitation.

PubMed

Gaudier-Diaz, Monica M; Haines, Adam H; Zhang, Ning; Courtney DeVries, A

2018-06-19

Social isolation presents a risk factor and worsens outcome to cerebrovascular diseases; however, the underlying mechanisms remain underspecified. This study examines the effect of social environment on microglial reactivity after global cerebral ischemia, to test the hypothesis that social isolation leads to greater microglial responses. Adult female and male mice were pair-housed or socially isolated for one week prior to cardiac arrest/cardiopulmonary resuscitation (CA/CPR) or the sham procedure, and following either 2 or 24 h of reperfusion, microglia samples were enriched and analyzed for gene expression. At the 2-hour time point, microglia from both females and males exhibited ischemia-induced inflammation, characterized by the gene expression increase of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6), regardless of the housing conditions. However, at 24 h post-ischemia, social housing attenuated microglial pro-inflammatory gene expression in a sex-specific manner. At this time point, the ischemia-induced increased expression of IL-1β and IL-6 was attenuated by social interaction in microglia from male mice, while among female mice social attenuation of the inflammatory response was observed in the microglial expression of cell surface protein major histocompatibility complex II (MHC II). A second study examined behavioral and physiological measures 96 h after ischemic injury. At this time point, female and male mice displayed increased locomotion and exploratory behavior following CA/CPR relative to controls. Regardless of sex, ischemia also elicited neuroinflammation and neurodegeneration, both of which were modulated by the social environment. Hippocampal nitric oxide (iNOS), cortical TNF-α, and counts of Fluoro-Jade C positive stained cells in the CA1 region of the hippocampus, were increased in the isolated CA/CPR group relative to sham controls and the pair-housed CA/CPR groups. Together, these data indicate that female and male mice exhibit similar outcome measures and social modulation at 96 h post-ischemic injury, nonetheless, that social environment influences microglial reactivity to global cerebral ischemia in a sex-specific manner. Copyright © 2017. Published by Elsevier Inc.

Enkephalinase inhibitor potentiates substance P- and electrically induced contraction in ferret trachea.

PubMed

Sekizawa, K; Tamaoki, J; Nadel, J A; Borson, D B

1987-10-01

To determine the role of endogenous enkephalinase (EC 3.4.24.11) in regulating peptide-induced contraction of airway smooth muscle, we studied the effect of the enkephalinase inhibitor, leucine-thiorphan (Leu-thiorphan), on responses of isolated ferret tracheal smooth muscle segments to substance P (SP) and to electrical field stimulation (EFS). Leu-thiorphan shifted the dose-response curve to SP to lower concentrations. Atropine or the SP antagonist [D-Pro2,D-Trp7,9]SP significantly inhibited SP-induced contractions in the presence of Leu-thiorphan. Leu-thiorphan increased the contractile responses to EFS dose dependently, an effect that was significantly inhibited by the SP antagonist [D-Pro2,D-Trp7,9]SP. SP, in a concentration that did not cause contraction, increased the contractile responses to EFS. This effect was augmented by Leu-thiorphan dose dependently and was not inhibited by hexamethonium or by phentolamine but was inhibited by atropine. Because contractile responses to acetylcholine were not significantly affected by SP or by Leu-thiorphan, the potentiating effects of SP were probably on presynaptic-postganglionic cholinergic neurotransmission. Captopril, bestatin, or leupeptin did not augment contractions, suggesting that enkephalinase was responsible for the effects. These results suggest that endogenous tachykinins modulate smooth muscle contraction and endogenous enkephalinase modulates contractions produced by endogenous or exogenous tachykinins and tachykinin-induced facilitation of cholinergic neurotransmission.

Cardiac effects of 3-iodothyronamine: a new aminergic system modulating cardiac function.

PubMed

Chiellini, Grazia; Frascarelli, Sabina; Ghelardoni, Sandra; Carnicelli, Vittoria; Tobias, Sandra C; DeBarber, Andrea; Brogioni, Simona; Ronca-Testoni, Simonetta; Cerbai, Elisabetta; Grandy, David K; Scanlan, Thomas S; Zucchi, Riccardo

2007-05-01

3-Iodothyronamine T1AM is a novel endogenous thyroid hormone derivative that activates the G protein-coupled receptor known as trace anime-associated receptor 1 (TAAR1). In the isolated working rat heart and in rat cardiomyocytes, T1AM produced a reversible, dose-dependent negative inotropic effect (e.g., 27+/-5, 51+/-3, and 65+/-2% decrease in cardiac output at 19, 25, and 38 microM concentration, respectively). An independent negative chronotropic effect was also observed. The hemodynamic effects of T1AM were remarkably increased in the presence of the tyrosine kinase inhibitor genistein, whereas they were attenuated in the presence of the tyrosine phosphatase inhibitor vanadate. No effect was produced by inhibitors of protein kinase A, protein kinase C, calcium-calmodulin kinase II, phosphatidylinositol-3-kinase, or MAP kinases. Tissue cAMP levels were unchanged. In rat ventricular tissue, Western blot experiments with antiphosphotyrosine antibodies showed reduced phosphorylation of microsomal and cytosolic proteins after perfusion with synthetic T1AM; reverse transcriptase-polymerase chain reaction experiments revealed the presence of transcripts for at least 5 TAAR subtypes; specific and saturable binding of [125I]T1AM was observed, with a dissociation constant in the low micromolar range (5 microM); and endogenous T1AM was detectable by tandem mass spectrometry. In conclusion, our findings provide evidence for the existence of a novel aminergic system modulating cardiac function.

Impact of Feed Supplementation with Antimicrobial Agents on Growth Performance of Broiler Chickens, Clostridium perfringens and Enterococcus Counts, and Antibiotic Resistance Phenotypes and Distribution of Antimicrobial Resistance Determinants in Escherichia coli Isolates▿

PubMed Central

Diarra, Moussa S.; Silversides, Fred G.; Diarrassouba, Fatoumata; Pritchard, Jane; Masson, Luke; Brousseau, Roland; Bonnet, Claudie; Delaquis, Pascal; Bach, Susan; Skura, Brent J.; Topp, Edward

2007-01-01

The effects of feed supplementation with the approved antimicrobial agents bambermycin, penicillin, salinomycin, and bacitracin or a combination of salinomycin plus bacitracin were evaluated for the incidence and distribution of antibiotic resistance in 197 commensal Escherichia coli isolates from broiler chickens over 35 days. All isolates showed some degree of multiple antibiotic resistance. Resistance to tetracycline (68.5%), amoxicillin (61.4%), ceftiofur (51.3%), spectinomycin (47.2%), and sulfonamides (42%) was most frequent. The levels of resistance to streptomycin, chloramphenicol, and gentamicin were 33.5, 35.5, and 25.3%, respectively. The overall resistance levels decreased from day 7 to day 35 (P < 0.001). Comparing treatments, the levels of resistance to ceftiofur, spectinomycin, and gentamicin (except for resistance to bacitracin treatment) were significantly higher in isolates from chickens receiving feed supplemented with salinomycin than from the other feeds (P < 0.001). Using a DNA microarray analysis capable of detecting commonly found antimicrobial resistance genes, we characterized 104 tetracycline-resistant E. coli isolates from 7- to 28-day-old chickens fed different growth promoters. Results showed a decrease in the incidence of isolates harboring tet(B), blaTEM, sulI, and aadA and class 1 integron from days 7 to 35 (P < 0.01). Of the 84 tetracycline-ceftiofur-resistant E. coli isolates, 76 (90.5%) were positive for blaCMY-2. The proportions of isolates positive for sulI, aadA, and integron class 1 were significantly higher in salinomycin-treated chickens than in the control or other treatment groups (P < 0.05). These data demonstrate that multiantibiotic-resistant E. coli isolates can be found in broiler chickens regardless of the antimicrobial growth promoters used. However, the phenotype and the distribution of resistance determinants in E. coli can be modulated by feed supplementation with some of the antimicrobial agents used in broiler chicken production. PMID:17827305

Pulse Wave Velocity Predicts Response to Renal Denervation in Isolated Systolic Hypertension.

PubMed

Fengler, Karl; Rommel, Karl-Philipp; Hoellriegel, Robert; Blazek, Stephan; Besler, Christian; Desch, Steffen; Schuler, Gerhard; Linke, Axel; Lurz, Philipp

2017-05-17

Renal sympathetic denervation seems to be less effective as a treatment for hypertension in patients with isolated systolic hypertension, a condition associated with elevated central arterial stiffness. Because isolated systolic hypertension can also be caused by wave reflection or increased cardiac output, a more differentiated approach might improve patient preselection for renal sympathetic denervation. We sought to evaluate the additional predictive value of invasive pulse wave velocity for response to renal sympathetic denervation in patients with combined versus isolated systolic hypertension. Patients scheduled for renal sympathetic denervation underwent additional invasive measurement of pulse wave velocity and pulse pressure before denervation. Blood pressure was assessed via ambulatory measurement at baseline and after 3 months. In total 109 patients (40 patients with isolated systolic hypertension) were included in our analysis. After 3 months, blood pressure reduction was more pronounced among patients with combined hypertension compared with patients with isolated systolic hypertension (systolic 24-hour average 9.3±10.5 versus 5.0±11.5 mm Hg, P =0.046). However, when stratifying patients with isolated systolic hypertension by invasive pulse wave velocity, patients in the lowest tertile of pulse wave velocity had comparable blood pressure reduction (12.1±12.6 mm Hg, P =0.006) despite lower baseline blood pressure than patients with combined hypertension (systolic 24-hour average 154.8±12.5 mm Hg in combined hypertension versus 141.2±8.1, 148.4±10.9, and 150.5±12.7 mm Hg, respectively, by tertiles of pulse wave velocity, P =0.002). Extended assessment of arterial stiffness can help improve patient preselection for renal sympathetic denervation and identify a subgroup of isolated systolic hypertension patients who benefit from sympathetic modulation. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Surveyor 3: Bacterium isolated from lunar retrieved television camera

NASA Technical Reports Server (NTRS)

Mitchell, F. J.; Ellis, W. L.

1972-01-01

Microbial analysis was the first of several studies of the retrieved camera and was performed immediately after the camera was opened. The emphasis of the analysis was placed upon isolating microorganisms that could be potentially pathogenic for man. Every step in the retrieval of the Surveyor 3 television camera was analyzed for possible contamination sources, including camera contact by the astronauts, ingassing in the lunar and command module during the mission or at splashdown, and handling during quarantine, disassembly, and analysis at the Lunar Receiving Laboratory

Chiao holds an Electronic Box Assembly from the TVIS in the SM during Expedition 10

NASA Image and Video Library

2005-02-17

ISS010-E-18164 (17 February 2005) --- Astronaut Leroy Chiao, Expedition 10 commander and NASA ISS science officer, holds an Electronic Box Assembly, and Violation Isolation and Stabilization (VIS) Controller Assembly, which is part of the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station (ISS). Also in view is a VIS/TM data cable and VIS/TM power cable. This box receives power and distributes it between the treadmill and the VIS subassemblies.

A soft actuation system for segmented reflector articulation and isolation

NASA Technical Reports Server (NTRS)

Agronin, Michael L.; Jandura, Louise

1990-01-01

Segmented reflectors have been proposed for space based applications such as optical communication and large diameter telescopes. An actuation system for mirrors in a space based segmented mirror array was developed as part of NASA's Precision Segmented Reflector program. The actuation system, called the Articulated Panel Module (APM), provides 3 degrees of freedom mirror articulation, gives isolation from structural motion, and simplifies space assembly of the mirrors to the reflector backup truss. A breadboard of the APM was built and is described.

Eyharts performs TVIS maintenance

NASA Image and Video Library

2008-03-03

ISS016-E-030559 (4 March 2008) --- European Space Agency (ESA) astronaut Leopold Eyharts, Expedition 16 flight engineer, works with the Treadmill Vibration Isolation System (TVIS) removed from the Zvezda Service Module floor during in-flight maintenance (IFM) on the International Space Station.

Williams in Node 1 / Unity module

NASA Image and Video Library

2007-03-01

ISS014-E-15830 (4 March 2007) --- Astronaut Sunita L. Williams, Expedition 14 flight engineer, works with a portion of the Treadmill Vibration Isolation System (TVIS) during in-flight maintenance (IFM) in the Unity node of the International Space Station.

Volkov performs maintenance on the TVIS during Expedition 17

NASA Image and Video Library

2008-08-12

ISS017-E-012861 (12 Aug. 2008) --- Russian Federal Space Agency cosmonaut Sergei Volkov, Expedition 17 commander, performs in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

Notice of Violation of IEEE Publication PrinciplesJoint Redundant Residue Number Systems and Module Isolation for Mitigating Single Event Multiple Bit Upsets in Datapath

NASA Astrophysics Data System (ADS)

Li, Lei; Hu, Jianhao

2010-12-01

Notice of Violation of IEEE Publication Principles"Joint Redundant Residue Number Systems and Module Isolation for Mitigating Single Event Multiple Bit Upsets in Datapath"by Lei Li and Jianhao Hu,in the IEEE Transactions on Nuclear Science, vol.57, no.6, Dec. 2010, pp. 3779-3786After careful and considered review of the content and authorship of this paper by a duly constituted expert committee, this paper has been found to be in violation of IEEE's Publication Principles.This paper contains substantial duplication of original text from the paper cited below. The original text was copied without attribution (including appropriate references to the original author(s) and/or paper title) and without permission.Due to the nature of this violation, reasonable effort should be made to remove all past references to this paper, and future references should be made to the following articles:"Multiple Error Detection and Correction Based on Redundant Residue Number Systems"by Vik Tor Goh and M.U. Siddiqi,in the IEEE Transactions on Communications, vol.56, no.3, March 2008, pp.325-330"A Coding Theory Approach to Error Control in Redundant Residue Number Systems. I: Theory and Single Error Correction"by H. Krishna, K-Y. Lin, and J-D. Sun, in the IEEE Transactions on Circuits and Systems II: Analog and Digital Signal Processing, vol.39, no.1, Jan 1992, pp.8-17In this paper, we propose a joint scheme which combines redundant residue number systems (RRNS) with module isolation (MI) for mitigating single event multiple bit upsets (SEMBUs) in datapath. The proposed hardening scheme employs redundant residues to improve the fault tolerance for datapath and module spacings to guarantee that SEMBUs caused by charge sharing do not propagate among the operation channels of different moduli. The features of RRNS, such as independence, parallel and error correction, are exploited to establish the radiation hardening architecture for the datapath in radiation environments. In the proposed scheme, all of the residues can be processed independently, and most of the soft errors in datapath can be corrected with the redundant relationship of the residues at correction module, which is allocated at the end of the datapath. In the back-end implementation, module isolation technique is used to improve the soft error rate performance for RRNS by physically separating the operation channels of different moduli. The case studies show at least an order of magnitude decrease on the soft error rate (SER) as compared to the NonRHBD designs, and demonstrate that RRNS+MI can reduce the SER from 10-12 to 10-17 when the processing steps of datapath are 106. The proposed scheme can even achieve less area and latency overheads than that without radiation hardening, since RRNS can reduce the operational complexity in datapath.

Lacosamide modulates interictal spiking and high-frequency oscillations in a model of mesial temporal lobe epilepsy

PubMed Central

Behr, Charles; Lévesque, Maxime; Ragsdale, David; Avoli, Massimo

2016-01-01

Objective Nearly one third of patients presenting with mesial temporal lobe epilepsy (MTLE), the most prevalent lesion-related epileptic disorder in adulthood, do not respond to currently available antiepileptic medications. Thus, there is a need to identify and characterize new antiepileptic drugs. In this study, we used the pilocarpine model of MTLE to establish the effects of a third generation drug, lacosamide (LCM), on seizures, interictal spikes and high-frequency oscillations (HFOs, ripples: 80–200 Hz, fast ripples: 250–500 Hz). Methods Sprague–Dawley rats (250–300 g) were injected with pilocarpine to induce a status epilepticus (SE) that was pharmacologically terminated after 1 h. Eight pilocarpine-treated rats were then injected with LCM (30 mg/kg, i.p.) 4 h after SE and daily for 14 days. Eight pilocarpine-treated rats were used as controls and treated with saline. Three days after SE, all rats were implanted with bipolar electrodes in the hippocampal CA3 region, entorhinal cortex (EC), dentate gyrus (DG) and subiculum and EEG-video monitored from day 4 to day 14 after SE. Results LCM-treated animals showed lower rates of seizures (0.21 (±0.11) seizures/day) than controls (2.6 (±0.57), p < 0.05), and a longer latent period (LCM: 11 (±1) days, controls: 6.25 (±1), p < 0.05). Rates of interictal spikes in LCM-treated rats were significantly lower than in controls in CA3 and subiculum (p < 0.05). Rates of ripples and fast ripples associated with interictal spikes in CA3 and subiculum as well as rates of fast ripples occurring outside of interictal spikes in CA3 were also significantly lower in LCM-treated animals. In controls, interictal spikes and associated HFOs correlated to seizure clustering, while this was not the case for isolated HFOs. Significance Our findings show that early treatment with LCM has powerful anti-ictogenic properties in the pilocarpine model of MTLE. These effects are accompanied by decreased rates of interictal spikes and associated HFOs. Isolated HFOs were also modulated by LCM, in a manner that appeared to be unrelated to its antiictogenic effects. These results thus suggest that distinct mechanisms may underlie interictal-associated and isolated HFOs in the pilocarpine model of MTLE. PMID:26220372

Coffee consumption modulates inflammatory processes in an individual fashion.

PubMed

Muqaku, Besnik; Tahir, Ammar; Klepeisz, Philip; Bileck, Andrea; Kreutz, Dominique; Mayer, Rupert L; Meier, Samuel M; Gerner, Marlene; Schmetterer, Klaus; Gerner, Christopher

2016-12-01

Anti-inflammatory effects of coffee consumption have been reported to be caused by caffeine and adenosine receptor signaling. However, contradictory effects have been observed. Many kinds of chronic diseases are linked to inflammation; therefore a profound understanding of potential effects of coffee consumption is desirable. We performed ex vivo experiments with eight individuals investigating peripheral blood mononuclear cells isolated from venous blood before and after coffee consumption, as well as in vitro experiments applying caffeine on isolated cells. After in vitro inflammatory stimulation of the cells, released cytokines, chemokines, and eicosanoids were determined and quantified using targeted mass spectrometric methods. Remarkably, the release of inflammation mediators IL6, IL8, GROA, CXCL2, CXCL5 as well as PGA2, PGD2, prostaglandin E2 (PGE2), LTC4, LTE4, and 15S-HETE was significantly affected after coffee consumption. While in several individuals coffee consumption or caffeine treatment caused significant downregulation of most inflammation mediators, in other healthy individuals exactly the opposite effects were observed. Ruling out age, sex, coffee consumption habits, the metabolic kinetics of caffeine in blood and the individual amount of regulatory T cells or CD39 expression as predictive parameters, we demonstrated here that coffee consumption may have significant pro- or anti-inflammatory effects in an individual fashion. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

West African Sorghum bicolor Leaf Sheaths Have Anti-Inflammatory and Immune-Modulating Properties In Vitro

PubMed Central

Benson, Kathleen F.; Beaman, Joni L.; Ou, Boxin; Okubena, Ademola; Okubena, Olajuwon

2013-01-01

Abstract The impact of chronic inflammatory conditions on immune function is substantial, and the simultaneous application of anti-inflammatory and immune modulating modalities has potential for reducing inflammation-induced immune suppression. Sorghum-based foods, teas, beers, and extracts are used in traditional medicine, placing an importance on obtaining an increased understanding of the biological effects of sorghum. This study examined selected anti-inflammatory and immune-modulating properties in vitro of Jobelyn™, containing the polyphenol-rich leaf sheaths from a West African variant of Sorghum bicolor (SBLS). Freshly isolated primary human polymorphonuclear (PMN) and mononuclear cell subsets were used to test selected cellular functions in the absence versus presence of aqueous and ethanol extracts of SBLS. Both aqueous and nonaqueous compounds contributed to reduced reactive oxygen species formation by inflammatory PMN cells, and reduced the migration of these cells in response to the inflammatory chemoattractant leukotriene B4. Distinct effects were seen on lymphocyte and monocyte subsets in cultures of peripheral blood mononuclear cells. The aqueous extract of SBLS triggered robust upregulation of the CD69 activation marker on CD3− CD56+ natural killer (NK) cells, whereas the ethanol extract of SBLS triggered similar upregulation of CD69 on CD3+ CD56+ NKT cells, CD3+ T lymphocytes, and monocytes. This was accompanied by many-fold increases in the chemokines RANTES/CCL5, Mip-1α/CCL3, and MIP-1β/CCL4. Both aqueous and nonaqueous compounds contribute to anti-inflammatory effects, combined with multiple effects on immune cell activation status. These observations may help suggest mechanisms of action that contribute to the traditional use of sorghum-based products, beverages, and extracts for immune support. PMID:23289787

Purinergic and muscarinic modulation of ATP release from the urothelium and its paracrine actions

PubMed Central

Sui, Guiping; Fry, Chris H.; Montgomery, Bruce; Roberts, Max; Wu, Rui

2013-01-01

The urothelium is a newly recognized sensory structure that detects bladder fullness. Pivotal to this sensory role is the release of ATP from the urothelium. However, the routes for urothelial ATP release, its modulation by receptor-mediated pathways, and the autocrine/paracrine role of ATP are poorly understood, especially in native tissue. We examined the action of key neurotransmitters: purinergic and muscarinic agonists on ATP release and its paracrine effect. Guinea pig and human urothelial mucosa were mounted in a perfusion trough; superfusate ATP was measured using a luciferin-luciferase assay, and tissue contractions were recorded with a tension transducer. Intracellular Ca2+ was measured in isolated urothelial cells with fura-2. The P2Y agonist UTP but not the P2X agonist α,β-methylene-ATP generated ATP release. The muscarinic agonist carbachol and the M2-preferential agonist oxotremorine also generated ATP release, which was antagonized by the M2-specific agent methoctramine. Agonist-evoked ATP release was accompanied by mucosal contractions. Urothelial ATP release was differentially mediated by intracellular Ca2+ release, cAMP, exocytosis, or connexins. Urothelium-attached smooth muscle exhibited spontaneous contractions that were augmented by subthreshold concentrations of carbachol, which had little direct effect on smooth muscle. This activity was attenuated by desensitizing P2X receptors on smooth muscle. Urothelial ATP release was increased in aging bladders. Purinergic and muscarinic agents produced similar effects in human urothelial tissue. This is the first demonstration of specific modulation of urothelial ATP release in native tissue by purinergic and muscarinic neurotransmitters via distinct mechanisms. Released ATP produces paracrine effects on underlying tissues. This process is altered during aging and has relevance to human bladder pathologies. PMID:24285497

Purinergic and muscarinic modulation of ATP release from the urothelium and its paracrine actions.

PubMed

Sui, Guiping; Fry, Chris H; Montgomery, Bruce; Roberts, Max; Wu, Rui; Wu, Changhao

2014-02-01

The urothelium is a newly recognized sensory structure that detects bladder fullness. Pivotal to this sensory role is the release of ATP from the urothelium. However, the routes for urothelial ATP release, its modulation by receptor-mediated pathways, and the autocrine/paracrine role of ATP are poorly understood, especially in native tissue. We examined the action of key neurotransmitters: purinergic and muscarinic agonists on ATP release and its paracrine effect. Guinea pig and human urothelial mucosa were mounted in a perfusion trough; superfusate ATP was measured using a luciferin-luciferase assay, and tissue contractions were recorded with a tension transducer. Intracellular Ca²⁺ was measured in isolated urothelial cells with fura-2. The P2Y agonist UTP but not the P2X agonist α,β-methylene-ATP generated ATP release. The muscarinic agonist carbachol and the M₂-preferential agonist oxotremorine also generated ATP release, which was antagonized by the M₂-specific agent methoctramine. Agonist-evoked ATP release was accompanied by mucosal contractions. Urothelial ATP release was differentially mediated by intracellular Ca²⁺ release, cAMP, exocytosis, or connexins. Urothelium-attached smooth muscle exhibited spontaneous contractions that were augmented by subthreshold concentrations of carbachol, which had little direct effect on smooth muscle. This activity was attenuated by desensitizing P2X receptors on smooth muscle. Urothelial ATP release was increased in aging bladders. Purinergic and muscarinic agents produced similar effects in human urothelial tissue. This is the first demonstration of specific modulation of urothelial ATP release in native tissue by purinergic and muscarinic neurotransmitters via distinct mechanisms. Released ATP produces paracrine effects on underlying tissues. This process is altered during aging and has relevance to human bladder pathologies.

AT1 Receptor Modulator Attenuates the Hypercholesterolemia-Induced Impairment of the Myocardial Ischemic Post-Conditioning Benefits.

PubMed

Li, Yun-Wei; Li, Yan-Ming; Hon, Yan; Wan, Qi-Lin; He, Rui-Li; Wang, Zhi-Zhong; Zhao, Cui-Hua

2017-03-01

Ischemic post-conditioning (PostC) has been demonstrated as a novel strategy to harness nature's protection against myocardial ischemia-reperfusion (I/R). Hypercholesterolemia (HC) has been reported to block the effect of PostC on the heart. Angiotensin II type-1 (AT1) modulators have shown benefits in myocardial ischemia. The present study investigates the effect of a novel inhibitor of AT1, azilsartan in PostC of the heart of normocholesterolemic (NC) and HC rats. HC was induced by the administration of high-fat diet to the animals for eight weeks. Isolated Langendorff's perfused NC and HC rat hearts were exposed to global ischemia for 30 min and reperfusion for 120 min. I/R-injury had been assessed by cardiac hemodynamic parameters, myocardial infarct size, release of tumor necrosis factor-alpha troponin I, lactate dehydrogenase, creatine kinase, nitrite in coronary effluent, thiobarbituric acid reactive species, a reduced form of glutathione, superoxide anion, and left ventricle collagen content in normal and HC rat hearts. Azilsartan post-treatment and six episodes of PostC (10 sec each) afforded cardioprotection against I/R-injury in normal rat hearts. PostC protection against I/R-injury was abolished in HC rat hearts. Azilsartan prevented the HC-mediated impairment of the beneficial effects of PostC in I/R-induced myocardial injury, which was inhibited by L-N 5 -(1-Iminoethyl)ornithinehydrochloride, a potent inhibitor of endothelial nitric oxide synthase (eNOS). Azilsartan treatment has attenuated the HC-induced impairment of beneficial effects of PostC in I/R-injury of rat hearts, by specifically modulating eNOS. Azilsartan may be explored further in I/R-myocardial injury, both in NC and HC conditions, with or without PostC.

AT1 Receptor Modulator Attenuates the Hypercholesterolemia-Induced Impairment of the Myocardial Ischemic Post-Conditioning Benefits

PubMed Central

Li, Yun-Wei; Hon, Yan; Wan, Qi-Lin; He, Rui-Li; Wang, Zhi-Zhong; Zhao, Cui-Hua

2017-01-01

Background and Objectives Ischemic post-conditioning (PostC) has been demonstrated as a novel strategy to harness nature's protection against myocardial ischemia-reperfusion (I/R). Hypercholesterolemia (HC) has been reported to block the effect of PostC on the heart. Angiotensin II type-1 (AT1) modulators have shown benefits in myocardial ischemia. The present study investigates the effect of a novel inhibitor of AT1, azilsartan in PostC of the heart of normocholesterolemic (NC) and HC rats. Materials and Methods HC was induced by the administration of high-fat diet to the animals for eight weeks. Isolated Langendorff's perfused NC and HC rat hearts were exposed to global ischemia for 30 min and reperfusion for 120 min. I/R-injury had been assessed by cardiac hemodynamic parameters, myocardial infarct size, release of tumor necrosis factor-alpha troponin I, lactate dehydrogenase, creatine kinase, nitrite in coronary effluent, thiobarbituric acid reactive species, a reduced form of glutathione, superoxide anion, and left ventricle collagen content in normal and HC rat hearts. Results Azilsartan post-treatment and six episodes of PostC (10 sec each) afforded cardioprotection against I/R-injury in normal rat hearts. PostC protection against I/R-injury was abolished in HC rat hearts. Azilsartan prevented the HC-mediated impairment of the beneficial effects of PostC in I/R-induced myocardial injury, which was inhibited by L-N5-(1-Iminoethyl)ornithinehydrochloride, a potent inhibitor of endothelial nitric oxide synthase (eNOS). Conclusion Azilsartan treatment has attenuated the HC-induced impairment of beneficial effects of PostC in I/R-injury of rat hearts, by specifically modulating eNOS. Azilsartan may be explored further in I/R-myocardial injury, both in NC and HC conditions, with or without PostC. PMID:28382073

Attosecond transient absorption of argon atoms in the vacuum ultraviolet region: line energy shifts versus coherent population transfer

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

Cao, Wei; Warrick, Erika R.; Neumark, Daniel M.

Using attosecond transient absorption, the dipole response of an argon atom in the vacuum ultraviolet (VUV) region is studied when an external electromagnetic field is present. An isolated attosecond VUV pulse populates Rydberg states lying 15 eV above the argon ground state. A synchronized few-cycle near infrared (NIR) pulse modifies the oscillating dipoles of argon impulsively, leading to alterations in the VUV absorption spectra. As the NIR pulse is delayed with respect to the VUV pulse, multiple features in the absorption profile emerge simultaneously including line broadening, sideband structure, sub-cycle fast modulations, and 5-10 fs slow modulations. These features indicatemore » the coexistence of two general processes of the light-matter interaction: the energy shift of individual atomic levels and coherent population transfer between atomic eigenstates, revealing coherent superpositions. Finally, an intuitive formula is derived to treat both effects in a unifying framework, allowing one to identify and quantify the two processes in a single absorption spectrogram.« less

Attosecond transient absorption of argon atoms in the vacuum ultraviolet region: line energy shifts versus coherent population transfer

NASA Astrophysics Data System (ADS)

Cao, Wei; Warrick, Erika R.; Neumark, Daniel M.; Leone, Stephen R.

2016-01-01

Using attosecond transient absorption, the dipole response of an argon atom in the vacuum ultraviolet (VUV) region is studied when an external electromagnetic field is present. An isolated attosecond VUV pulse populates Rydberg states lying 15 eV above the argon ground state. A synchronized few-cycle near infrared (NIR) pulse modifies the oscillating dipoles of argon impulsively, leading to alterations in the VUV absorption spectra. As the NIR pulse is delayed with respect to the VUV pulse, multiple features in the absorption profile emerge simultaneously including line broadening, sideband structure, sub-cycle fast modulations, and 5-10 fs slow modulations. These features indicate the coexistence of two general processes of the light-matter interaction: the energy shift of individual atomic levels and coherent population transfer between atomic eigenstates, revealing coherent superpositions. An intuitive formula is derived to treat both effects in a unifying framework, allowing one to identify and quantify the two processes in a single absorption spectrogram.

Attosecond transient absorption of argon atoms in the vacuum ultraviolet region: line energy shifts versus coherent population transfer

DOE PAGES

Cao, Wei; Warrick, Erika R.; Neumark, Daniel M.; ...

2016-01-18

Using attosecond transient absorption, the dipole response of an argon atom in the vacuum ultraviolet (VUV) region is studied when an external electromagnetic field is present. An isolated attosecond VUV pulse populates Rydberg states lying 15 eV above the argon ground state. A synchronized few-cycle near infrared (NIR) pulse modifies the oscillating dipoles of argon impulsively, leading to alterations in the VUV absorption spectra. As the NIR pulse is delayed with respect to the VUV pulse, multiple features in the absorption profile emerge simultaneously including line broadening, sideband structure, sub-cycle fast modulations, and 5-10 fs slow modulations. These features indicatemore » the coexistence of two general processes of the light-matter interaction: the energy shift of individual atomic levels and coherent population transfer between atomic eigenstates, revealing coherent superpositions. Finally, an intuitive formula is derived to treat both effects in a unifying framework, allowing one to identify and quantify the two processes in a single absorption spectrogram.« less

High-affinity monoclonal IgA regulates gut microbiota and prevents colitis in mice.

PubMed

Okai, Shinsaku; Usui, Fumihito; Yokota, Shuhei; Hori-I, Yusaku; Hasegawa, Makoto; Nakamura, Toshinobu; Kurosawa, Manabu; Okada, Seiji; Yamamoto, Kazuya; Nishiyama, Eri; Mori, Hiroshi; Yamada, Takuji; Kurokawa, Ken; Matsumoto, Satoshi; Nanno, Masanobu; Naito, Tomoaki; Watanabe, Yohei; Kato, Tamotsu; Miyauchi, Eiji; Ohno, Hiroshi; Shinkura, Reiko

2016-07-04

Immunoglobulin A (IgA) is the main antibody isotype secreted into the intestinal lumen. IgA plays a critical role in the defence against pathogens and in the maintenance of intestinal homeostasis. However, how secreted IgA regulates gut microbiota is not completely understood. In this study, we isolated monoclonal IgA antibodies from the small intestine of healthy mouse. As a candidate for an efficient gut microbiota modulator, we selected a W27 IgA, which binds to multiple bacteria, but not beneficial ones such as Lactobacillus casei. W27 could suppress the cell growth of Escherichia coli but not L. casei in vitro, indicating an ability to improve the intestinal environment. Indeed W27 oral treatment could modulate gut microbiota composition and have a therapeutic effect on both lymphoproliferative disease and colitis models in mice. Thus, W27 IgA oral treatment is a potential remedy for inflammatory bowel disease, acting through restoration of host-microbial symbiosis.

A Non-Invasive NMR Method Based on Histidine Imidazoles to Analyze the pH-Modulation of Protein-Nucleic Acid Interfaces.

PubMed

Cruz-Gallardo, Isabel; Del Conte, Rebecca; Velázquez-Campoy, Adrián; García-Mauriño, Sofía M; Díaz-Moreno, Irene

2015-05-11

A useful (2) J(N-H) coupling-based NMR spectroscopic approach is proposed to unveil, at the molecular level, the contribution of the imidazole groups of histidines from RNA/DNA-binding proteins on the modulation of binding to nucleic acids by pH. Such protonation/deprotonation events have been monitored on the single His96 located at the second RNA/DNA recognition motif (RRM2) of T-cell intracellular antigen-1 (TIA-1) protein. The pKa values of the His96 ionizable groups were substantially higher in the complexes with short U-rich RNA and T-rich DNA oligonucleotides than those of the isolated TIA-1 RRM2. Herein, the methodology applied to determine changes in pKa of histidine side chains upon DNA/RNA binding, gives valuable information to understand the pH effect on multidomain DNA/RNA-binding proteins that shuttle among different cellular compartments. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

NeuroGrid: recording action potentials from the surface of the brain.

PubMed

Khodagholy, Dion; Gelinas, Jennifer N; Thesen, Thomas; Doyle, Werner; Devinsky, Orrin; Malliaras, George G; Buzsáki, György

2015-02-01

Recording from neural networks at the resolution of action potentials is critical for understanding how information is processed in the brain. Here, we address this challenge by developing an organic material-based, ultraconformable, biocompatible and scalable neural interface array (the 'NeuroGrid') that can record both local field potentials(LFPs) and action potentials from superficial cortical neurons without penetrating the brain surface. Spikes with features of interneurons and pyramidal cells were simultaneously acquired by multiple neighboring electrodes of the NeuroGrid, allowing for the isolation of putative single neurons in rats. Spiking activity demonstrated consistent phase modulation by ongoing brain oscillations and was stable in recordings exceeding 1 week's duration. We also recorded LFP-modulated spiking activity intraoperatively in patients undergoing epilepsy surgery. The NeuroGrid constitutes an effective method for large-scale, stable recording of neuronal spikes in concert with local population synaptic activity, enhancing comprehension of neural processes across spatiotemporal scales and potentially facilitating diagnosis and therapy for brain disorders.

ROVER: A prototype active vision system

NASA Astrophysics Data System (ADS)

Coombs, David J.; Marsh, Brian D.

1987-08-01

The Roving Eyes project is an experiment in active vision. We present the design and implementation of a prototype that tracks colored balls in images from an on-line charge coupled device (CCD) camera. Rover is designed to keep up with its rapidly changing environment by handling best and average case conditions and ignoring the worst case. This allows Rover's techniques to be less sophisticated and consequently faster. Each of Rover's major functional units is relatively isolated from the others, and an executive which knows all the functional units directs the computation by deciding which jobs would be most effective to run. This organization is realized with a priority queue of jobs and their arguments. Rover's structure not only allows it to adapt its strategy to the environment, but also makes the system extensible. A capability can be added to the system by adding a functional module with a well defined interface and by modifying the executive to make use of the new module. The current implementation is discussed in the appendices.

Neurophysiological Effects of Trait Empathy in Music Listening

PubMed Central

Wallmark, Zachary; Deblieck, Choi; Iacoboni, Marco

2018-01-01

The social cognitive basis of music processing has long been noted, and recent research has shown that trait empathy is linked to musical preferences and listening style. Does empathy modulate neural responses to musical sounds? We designed two functional magnetic resonance imaging (fMRI) experiments to address this question. In Experiment 1, subjects listened to brief isolated musical timbres while being scanned. In Experiment 2, subjects listened to excerpts of music in four conditions (familiar liked (FL)/disliked and unfamiliar liked (UL)/disliked). For both types of musical stimuli, emotional and cognitive forms of trait empathy modulated activity in sensorimotor and cognitive areas: in the first experiment, empathy was primarily correlated with activity in supplementary motor area (SMA), inferior frontal gyrus (IFG) and insula; in Experiment 2, empathy was mainly correlated with activity in prefrontal, temporo-parietal and reward areas. Taken together, these findings reveal the interactions between bottom-up and top-down mechanisms of empathy in response to musical sounds, in line with recent findings from other cognitive domains. PMID:29681804

Different Classes of Glutamate Receptors Mediate Distinct Behaviors in a Single Brainstem Nucleus

NASA Astrophysics Data System (ADS)

Dye, John; Heiligenberg, Walter; Keller, Clifford H.; Kawasaki, Masashi

1989-11-01

We have taken advantage of the increasing understanding of glutamate neuropharmacology to probe mechanisms of well-defined vertebrate behaviors. Here we report a set of experiments that suggests distinct roles for two major classes of glutamate receptors in a discrete premotor nucleus of the brainstem. The medullary pacemaker nucleus of weakly electric fish is an endogenous oscillator that controls the electric organ discharge (EOD). Its regular frequency of firing is modulated during several distinct behaviors. The pacemaker nucleus continues firing regularly when isolated in vitro, and modulatory behaviors can be reproduced by stimulating the descending input pathway. Glutamate agonists applied to the pacemaker in vitro produced increases in frequency, while glutamate antagonists selectively blocked stimulus-induced modulations. Experiments with glutamate antagonists in the intact animal resulted in specific effects on two well-characterized behaviors. Our data indicate that these behaviors are separately mediated in the pacemaker by receptors displaying characteristics of the kainate/quisqualate and N-methyl-D-aspartate subtypes of glutamate receptor, respectively.

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

Holley, W.H. Jr.; Agro, S.C.; Galica, J.P.

The problem of browning in a number of EVA encapsulated flat plate photovoltaic modules has led to the questioning of EVA as a suitable material for such applications. By isolating the variables that could possibly lead to EVA browning, such as module construction, types of glass superstrates, additives, and processing conditions, the authors have been able to determine those significant specific variables that seem to have the most influence on discoloration.When standard-cure EVA-based laminates were exposed to accelerated UV aging, measurable yellowing of those laminates was evident after only one to two weeks exposure, and visual discoloration was observed aftermore » four to six weeks. Some samples yellowed quickly and some not at all, and there were significant differences in the rates of discoloration between standard-cure and fast-cure EVA. This paper looks at the results of these studies, especially focusing on the effect of additives in the EVA on the rate of yellowing, and discusses how preliminary results can be used to reformulate EVA encapsulants.« less

Systematic Identification of MCU Modulators by Orthogonal Interspecies Chemical Screening.

PubMed

Arduino, Daniela M; Wettmarshausen, Jennifer; Vais, Horia; Navas-Navarro, Paloma; Cheng, Yiming; Leimpek, Anja; Ma, Zhongming; Delrio-Lorenzo, Alba; Giordano, Andrea; Garcia-Perez, Cecilia; Médard, Guillaume; Kuster, Bernhard; García-Sancho, Javier; Mokranjac, Dejana; Foskett, J Kevin; Alonso, M Teresa; Perocchi, Fabiana

2017-08-17

The mitochondrial calcium uniporter complex is essential for calcium (Ca 2+ ) uptake into mitochondria of all mammalian tissues, where it regulates bioenergetics, cell death, and Ca 2+ signal transduction. Despite its involvement in several human diseases, we currently lack pharmacological agents for targeting uniporter activity. Here we introduce a high-throughput assay that selects for human MCU-specific small-molecule modulators in primary drug screens. Using isolated yeast mitochondria, reconstituted with human MCU, its essential regulator EMRE, and aequorin, and exploiting a D-lactate- and mannitol/sucrose-based bioenergetic shunt that greatly minimizes false-positive hits, we identify mitoxantrone out of more than 600 clinically approved drugs as a direct selective inhibitor of human MCU. We validate mitoxantrone in orthogonal mammalian cell-based assays, demonstrating that our screening approach is an effective and robust tool for MCU-specific drug discovery and, more generally, for the identification of compounds that target mitochondrial functions. Copyright © 2017 Elsevier Inc. All rights reserved.

Visual evoked potential assessment of the effects of glaucoma on visual subsystems.

PubMed

Greenstein, V C; Seliger, S; Zemon, V; Ritch, R

1998-06-01

The purpose of this study is to test the hypothesis that glaucoma leads to selective deficits in parallel pathways or channels. Sweep VEPs were obtained to isolated-check stimuli that were modulated sinusoidally in either isoluminant chromatic contrast or in positive and negative luminance contrast. Response functions were obtained from 14 control subjects, 15 patients with open-angle glaucoma, and seven glaucoma suspects. For all three groups of subjects we found characteristic differences between the VEP response functions to isoluminant chromatic contrast stimuli and to luminance contrast stimuli. The isoluminant chromatic stimulus conditions appeared to favor activity of the P-pathway, whereas the luminance contrast stimuli at low depths of modulation favored M-pathway activity. VEP responses for patients with OAG were significantly reduced for chromatic contrast and luminance contrast conditions, whereas VEP responses for glaucoma suspects were significantly reduced only for the 15-Hz positive luminance contrast condition. Our results suggest that both M- and P-pathways are affected by glaucoma.

Neurophysiological Effects of Trait Empathy in Music Listening.

PubMed

Wallmark, Zachary; Deblieck, Choi; Iacoboni, Marco

2018-01-01

The social cognitive basis of music processing has long been noted, and recent research has shown that trait empathy is linked to musical preferences and listening style. Does empathy modulate neural responses to musical sounds? We designed two functional magnetic resonance imaging (fMRI) experiments to address this question. In Experiment 1, subjects listened to brief isolated musical timbres while being scanned. In Experiment 2, subjects listened to excerpts of music in four conditions (familiar liked (FL)/disliked and unfamiliar liked (UL)/disliked). For both types of musical stimuli, emotional and cognitive forms of trait empathy modulated activity in sensorimotor and cognitive areas: in the first experiment, empathy was primarily correlated with activity in supplementary motor area (SMA), inferior frontal gyrus (IFG) and insula; in Experiment 2, empathy was mainly correlated with activity in prefrontal, temporo-parietal and reward areas. Taken together, these findings reveal the interactions between bottom-up and top-down mechanisms of empathy in response to musical sounds, in line with recent findings from other cognitive domains.

New immunomodulatory role of neuropeptide Y (NPY) in Salmo salar leucocytes.

PubMed

González-Stegmaier, Roxana; Villarroel-Espíndola, Franz; Manríquez, René; López, Mauricio; Monrás, Mónica; Figueroa, Jaime; Enríquez, Ricardo; Romero, Alex

2017-11-01

Neuropeptide Y (NPY) plays different roles in mammals such as: regulate food intake, memory retention, cardiovascular functions, and anxiety. It has also been shown in the modulation of chemotaxis, T lymphocyte differentiation, and leukocyte migration. In fish, NPY expression and functions have been studied but its immunomodulatory role remains undescribed. This study confirmed the expression and synthesis of NPY in S. salar under inflammation, and validated a commercial antibody for NPY detection in teleost. Additionally, immunomodulatory effects of NPY were assayed in vitro and in vivo. Phagocytosis and superoxide anion production in leukocytes and SHK cells were induced under stimulation with a synthetic peptide. IL-8 mRNA was selectively and strongly induced in the spleen, head kidney, and isolated cells, after in vivo challenge with NPY. All together suggest that NPY is expressed in immune tissues and modulates the immune response in teleost fish. Copyright © 2017 Elsevier Ltd. All rights reserved.

Task-dependent changes of corticospinal excitability during observation and motor imagery of balance tasks.

PubMed

Mouthon, A; Ruffieux, J; Wälchli, M; Keller, M; Taube, W

2015-09-10

Non-physical balance training has demonstrated to be efficient to improve postural control in young people. However, little is known about the potential to increase corticospinal excitability by mental simulation in lower leg muscles. Mental simulation of isolated, voluntary contractions of limb muscles increase corticospinal excitability but more automated tasks like walking seem to have no or only minor effects on motor-evoked potentials (MEPs) evoked by transcranial magnetic stimulation (TMS). This may be related to the way of performing the mental simulation or the task itself. Therefore, the present study aimed to clarify how corticospinal excitability is modulated during AO+MI, MI and action observation (AO) of balance tasks. For this purpose, MEPs and H-reflexes were elicited during three different mental simulations (a) AO+MI, (b) MI and (c) passive AO. For each condition, two balance tasks were evaluated: (1) quiet upright stance (static) and (2) compensating a medio-lateral perturbation while standing on a free-swinging platform (dynamic). AO+MI resulted in the largest facilitation of MEPs followed by MI and passive AO. MEP facilitation was significantly larger in the dynamic perturbation than in the static standing task. Interestingly, passive observation resulted in hardly any facilitation independent of the task. H-reflex amplitudes were not modulated. The current results demonstrate that corticospinal excitability during mental simulation of balance tasks is influenced by both the type of mental simulation and the task difficulty. As H-reflexes and background EMG were not modulated, it may be argued that changes in excitability of the primary motor cortex were responsible for the MEP modulation. From a functional point of view, our findings suggest best training/rehabilitation effects when combining MI with AO during challenging postural tasks. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

PubMed

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

2013-08-01

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

Extracellular Protein Kinase A Modulates Intracellular Calcium/Calmodulin-Dependent Protein Kinase II, Nitric Oxide Synthase, and the Glutamate-Nitric Oxide-cGMP Pathway in Cerebellum. Differential Effects in Hyperammonemia.

PubMed

Cabrera-Pastor, Andrea; Llansola, Marta; Felipo, Vicente

2016-12-21

Extracellular protein kinases, including cAMP-dependent protein kinase (PKA), modulate neuronal functions including N-methyl-d-aspartate (NMDA) receptor-dependent long-term potentiation. NMDA receptor activation increases calcium, which binds to calmodulin and activates nitric oxide synthase (NOS), increasing nitric oxide (NO), which activates guanylate cyclase, increasing cGMP, which is released to the extracellular fluid, allowing analysis of this glutamate-NO-cGMP pathway in vivo by microdialysis. The function of this pathway is impaired in hyperammonemic rats. The aims of this work were to assess (1) whether the glutamate-NO-cGMP pathway is modulated in cerebellum in vivo by an extracellular PKA, (2) the role of phosphorylation and activity of calcium/calmodulin-dependent protein kinase II (CaMKII) and NOS in the pathway modulation by extracellular PKA, and (3) whether the effects are different in hyperammonemic and control rats. The pathway was analyzed by in vivo microdialysis. The role of extracellular PKA was analyzed by inhibiting it with a membrane-impermeable inhibitor. The mechanisms involved were analyzed in freshly isolated cerebellar slices from control and hyperammonemic rats. In control rats, inhibiting extracellular PKA reduces the glutamate-NO-cGMP pathway function in vivo. This is due to reduction of CaMKII phosphorylation and activity, which reduces NOS phosphorylation at Ser1417 and NOS activity, resulting in reduced guanylate cyclase activation and cGMP formation. In hyperammonemic rats, under basal conditions, CaMKII phosphorylation and activity are increased, increasing NOS phosphorylation at Ser847, which reduces NOS activity, guanylate cyclase activation, and cGMP. Inhibiting extracellular PKA in hyperammonemic rats normalizes CaMKII phosphorylation and activity, NOS phosphorylation, NOS activity, and cGMP, restoring normal function of the pathway.

Immunomodulatory effect of an isolated fraction from Tinospora crispa on intracellular expression of INF-γ, IL-6 and IL-8

PubMed Central

2014-01-01

Background Immunomodulators are substances that modify immune system response to a threat. Immunomodulators modulate and potentiate the immune system, keeping it highly prepared for any threat. The immunomodulatory effect of the traditional medicine Tinospora crispa is investigated in this work. Methods T. crispa ethanol extract was fractionated by using different solvents. The ethanol extract and effective isolated fraction were used to investigate the potential immunomodulatory effect of different T. crispa doses ranging from 25 μg/mL to 1000 μg/mL on RAW 246.7 cells by detecting intracellular INF-γ, IL-6, and IL-8 expressions. The antioxidant activity of T. crispa was evaluated through FRAP and DPPH. The total phenolic and total flavonoid contents were also quantified. Results Results show that T. crispa extract has higher antioxidant potential than ascorbic acid. The FRAP value of T. crispa extract is 11011.11 ± 1145.42 μmol Fe+2/g, and its DPPH inhibition percentage is 55.79 ± 7.9, with 22 μg/mL IC50. The results also reveal that the total phenolic content of T. crispa extract is 213.16- ± 1.31 mg GAE/g dry stem weight, and the total flavonoid content is 62.07- ± 39.76 mg QE/g dry stem weight. T. crispa crude extract and its isolated fraction significantly stimulate RAW264.7 cell viability (P ≤ 0.05) and intracellular INF-γ, IL-6, and IL-8 expressions. The results of LC-MS show that four of the active compounds detected in the T. crispa isolated fraction are cordioside, quercetin, eicosenoic acid (paullinic acid), and boldine. Conclusions The results of this study obviously indicate that T. crispa has immunomodulatory effects through the stimulation of INF-γ, IL-6, and IL-8 expressions. LC-MS phytochemical analysis showed that the T. crispa fraction has cordioside, quercetin, eicosenoic acid (paullinic acid), and boldine, which may be responsible for the immunostimulator effect of T. crispa. PMID:24969238

Immunomodulatory effect of an isolated fraction from Tinospora crispa on intracellular expression of INF-γ, IL-6 and IL-8.

PubMed

Abood, Walaa Najm; Fahmi, Iman; Abdulla, Mahmood Ameen; Ismail, Salmah

2014-06-27

Immunomodulators are substances that modify immune system response to a threat. Immunomodulators modulate and potentiate the immune system, keeping it highly prepared for any threat. The immunomodulatory effect of the traditional medicine Tinospora crispa is investigated in this work. T. crispa ethanol extract was fractionated by using different solvents. The ethanol extract and effective isolated fraction were used to investigate the potential immunomodulatory effect of different T. crispa doses ranging from 25 μg/mL to 1000 μg/mL on RAW 246.7 cells by detecting intracellular INF-γ, IL-6, and IL-8 expressions. The antioxidant activity of T. crispa was evaluated through FRAP and DPPH. The total phenolic and total flavonoid contents were also quantified. Results show that T. crispa extract has higher antioxidant potential than ascorbic acid. The FRAP value of T. crispa extract is 11011.11 ± 1145.42 μmol Fe(+2)/g, and its DPPH inhibition percentage is 55.79 ± 7.9, with 22 μg/mL IC50. The results also reveal that the total phenolic content of T. crispa extract is 213.16- ± 1.31 mg GAE/g dry stem weight, and the total flavonoid content is 62.07- ± 39.76 mg QE/g dry stem weight. T. crispa crude extract and its isolated fraction significantly stimulate RAW264.7 cell viability (P ≤ 0.05) and intracellular INF-γ, IL-6, and IL-8 expressions. The results of LC-MS show that four of the active compounds detected in the T. crispa isolated fraction are cordioside, quercetin, eicosenoic acid (paullinic acid), and boldine. The results of this study obviously indicate that T. crispa has immunomodulatory effects through the stimulation of INF-γ, IL-6, and IL-8 expressions. LC-MS phytochemical analysis showed that the T. crispa fraction has cordioside, quercetin, eicosenoic acid (paullinic acid), and boldine, which may be responsible for the immunostimulator effect of T. crispa.

A Design of a Modular GPHS-Stirling Power System for a Lunar Habitation Module

NASA Technical Reports Server (NTRS)

Schmitz, Paul C.; Penswick, L. Barry; Shaltens, Richard K.

2005-01-01

Lunar habitation modules need electricity and potentially heat to operate. Because of the low amounts of radiation emitted by General Purpose Heat Source (GPHS) modules, power plants incorporating these as heat sources could be placed in close proximity to habitation modules. A design concept is discussed for a high efficiency power plant based on a GPHS assembly integrated with a Stirling convertor. This system could provide both electrical power and heat, if required, for a lunar habitation module. The conceptual GPHS/Stirling system is modular in nature and made up of a basic 5.5 KWe Stirling convertor/GPHS module assembly, convertor controller/PMAD electronics, waste heat radiators, and associated thermal insulation. For the specific lunar application under investigation eight modules are employed to deliver 40 KWe to the habitation module. This design looks at three levels of Stirling convertor technology and addresses the issues of integrating the Stirling convertors with the GPHS heat sources assembly using proven technology whenever possible. In addition, issues related to the high-temperature heat transport system, power management, convertor control, vibration isolation, and potential system packaging configurations to ensure safe operation during all phases of deployment will be discussed.

First Materials Science Research Facility Rack Capabilities and Design Features

NASA Technical Reports Server (NTRS)

Cobb, S.; Higgins, D.; Kitchens, L.; Curreri, Peter (Technical Monitor)

2002-01-01

The first Materials Science Research Rack (MSRR-1) is the primary facility for U.S. sponsored materials science research on the International Space Station. MSRR-1 is contained in an International Standard Payload Rack (ISPR) equipped with the Active Rack Isolation System (ARIS) for the best possible microgravity environment. MSRR-1 will accommodate dual Experiment Modules and provide simultaneous on-orbit processing operations capability. The first Experiment Module for the MSRR-1, the Materials Science Laboratory (MSL), is an international cooperative activity between NASA's Marshall Space Flight Center (MSFC) and the European Space Agency's (ESA) European Space Research and Technology Center (ESTEC). The MSL Experiment Module will accommodate several on-orbit exchangeable experiment-specific Module Inserts which provide distinct thermal processing capabilities. Module Inserts currently planned for the MSL are a Quench Module Insert, Low Gradient Furnace, and a Solidification with Quench Furnace. The second Experiment Module for the MSRR-1 configuration is a commercial device supplied by MSFC's Space Products Development (SPD) Group. Transparent furnace assemblies include capabilities for vapor transport processes and annealing of glass fiber preforms. This Experiment Module is replaceable on-orbit. This paper will describe facility capabilities, schedule to flight and research opportunities.

Immune responses to novel allergens and modulation of inflammation by vitamin K3 analogue: a ROS dependent mechanism.

PubMed

Kohli, Vineet; Sharma, Deepak; Sandur, Santosh Kumar; Suryavanshi, Shweta; Sainis, Krishna B

2011-02-01

The possibility of newer allergens being responsible for atopy needs to be explored at regional level due to environmental variables. Current studies were undertaken to identify common environmental allergens causing atopy in a defined population of India and to correlate the presence of various risk factors with the clinical presentation of allergy. Newer allergens like human dander and rice grain dust were identified and reported as the most common cause of atopy in this region. Atopy, elevated serum total IgE and familial tendency, was observed in 88%, 69% and 58% of allergic patients respectively. Further, allergen-specific immune responses like lymphocyte proliferation and cytokine secretion were studied in vitro using peripheral blood mononuclear cells (PBMC) isolated from both allergic and non-allergic individuals. Although, some allergens induced significant lymphocyte proliferation in vitro, allergen-induced cytokine secretion except that of TNF-α was not seen. Significantly higher ratio of secreted IL-4/IFN-γ cytokines was observed in PBMC isolated from allergic subjects in response to PHA. Plumbagin (vitamin K3 analogue) completely inhibited PHA-induced cytokine production in PBMC, in both allergic and non-allergic individuals. Plumbagin modulated the levels of intracellular reactive oxygen species and glutathione and suppressed PHA induced activation of NF-κB in human PBMC. The results thus show in human PMBC, for the first time, the anti-allergic and anti-inflammatory effects of plumbagin and underscore its therapeutic potential. Copyright © 2010 Elsevier B.V. All rights reserved.

The SSM/PMAD automated test bed project

NASA Technical Reports Server (NTRS)

Lollar, Louis F.

1991-01-01

The Space Station Module/Power Management and Distribution (SSM/PMAD) autonomous subsystem project was initiated in 1984. The project's goal has been to design and develop an autonomous, user-supportive PMAD test bed simulating the SSF Hab/Lab module(s). An eighteen kilowatt SSM/PMAD test bed model with a high degree of automated operation has been developed. This advanced automation test bed contains three expert/knowledge based systems that interact with one another and with other more conventional software residing in up to eight distributed 386-based microcomputers to perform the necessary tasks of real-time and near real-time load scheduling, dynamic load prioritizing, and fault detection, isolation, and recovery (FDIR).

A novel approach for studying the temporal modulation of embryonic skeletal development using organotypic bone cultures and microcomputed tomography.

PubMed

Kanczler, Janos M; Smith, Emma L; Roberts, Carol A; Oreffo, Richard O C

2012-10-01

Understanding the structural development of embryonic bone in a three dimensional framework is fundamental to developing new strategies for the recapitulation of bone tissue in latter life. We present an innovative combined approach of an organotypic embryonic femur culture model, microcomputed tomography (μCT) and immunohistochemistry to examine the development and modulation of the three dimensional structures of the developing embryonic femur. Isolated embryonic chick femurs were organotypic (air/liquid interface) cultured for 10 days in either basal, chondrogenic, or osteogenic supplemented culture conditions. The growth development and modulating effects of basal, chondrogenic, or osteogenic culture media of the embryonic chick femurs was investigated using μCT, immunohistochemistry, and histology. The growth and development of noncultured embryonic chick femur stages E10, E11, E12, E13, E15, and E17 were very closely correlated with increased morphometric indices of bone formation as determined by μCT. After 10 days in the organotpyic culture set up, the early aged femurs (E10 and E11) demonstrated a dramatic response to the chondrogenic or osteogenic culture conditions compared to the basal cultured femurs as determined by a change in μCT morphometric indices and modified expression of chondrogenic and osteogenic markers. Although the later aged femurs (E12 and E13) increased in size and structure after 10 days organotpypic culture, the effects of the osteogenic and chondrogenic organotypic cultures on these femurs were not significantly altered compared to basal conditions. We have demonstrated that the embryonic chick femur organotpyic culture model combined with the μCT and immunohistochemical analysis can provide an integral methodology for investigating the modulation of bone development in an ex vivo culture setting. Hence, these interdisciplinary techniques of μCT and whole organ bone cultures will enable us to delineate some of the temporal, structural developmental paradigms and modulation of bone tissue formation to underpin innovative skeletal regenerative technology for clinical therapeutic strategies in musculoskeletal trauma and diseases.

High-Throughput, Motility-Based Sorter for Microswimmers and Gene Discovery Platform

NASA Astrophysics Data System (ADS)

Yuan, Jinzhou; Raizen, David; Bau, Haim

2015-11-01

Animal motility varies with genotype, disease progression, aging, and environmental conditions. In many studies, it is desirable to carry out high throughput motility-based sorting to isolate rare animals for, among other things, forward genetic screens to identify genetic pathways that regulate phenotypes of interest. Many commonly used screening processes are labor-intensive, lack sensitivity, and require extensive investigator training. Here, we describe a sensitive, high throughput, automated, motility-based method for sorting nematodes. Our method was implemented in a simple microfluidic device capable of sorting many thousands of animals per hour per module, and is amenable to parallelism. The device successfully enriched for known C. elegans motility mutants. Furthermore, using this device, we isolated low-abundance mutants capable of suppressing the somnogenic effects of the flp-13 gene, which regulates sleep-like quiescence in C. elegans. Subsequent genomic sequencing led to the identification of a flp-13-suppressor gene. This research was supported, in part, by NIH NIA Grant 5R03AG042690-02.

Archaeal MCM has separable processivity, substrate choice and helicase domains

PubMed Central

Barry, Elizabeth R.; McGeoch, Adam T.; Kelman, Zvi; Bell, Stephen D.

2007-01-01

The mini-chromosome maintenance (MCM) complex is the principal candidate for the replicative helicase of archaea and eukaryotes. Here, we describe a functional dissection of the roles of the three principal structural modules of the homomultimeric MCM of the hyperthermophilic archaeon Sulfolobus solfataricus. Our results include the first analysis of the central AAA+ domain in isolation. This domain possesses ATPase and helicase activity, defining this as the minimal helicase domain. Reconstitution experiments show that the helicase activity of the AAA+ domain can be stimulated by addition of the isolated N-terminal half in trans. Addition of the N-terminus influences both the processivity of the helicase and the choice of substrate that can be melted by the ATPase domain. The degenerate helix-turn-helix domain at the C-terminus of MCM exerts a negative effect on the helicase activity of the complex. These results provide the first evidence for extensive regulatory inter-domain communication within the MCM complex. PMID:17259218

Dihydrotestosterone activates the MAPK pathway and modulates maximum isometric force through the EGF receptor in isolated intact mouse skeletal muscle fibres.

PubMed

Hamdi, M M; Mutungi, G

2010-02-01

It is generally believed that steroid hormones have both genomic and non-genomic (rapid) actions. Although the latter form an important component of the physiological response of these hormones, little is known about the cellular signalling pathway(s) mediating these effects and their physiological functions in adult mammalian skeletal muscle fibres. Therefore, the primary aim of this study was to investigate the non-genomic actions of dihydrotestosterone (DHT) and their physiological role in isolated intact mammalian skeletal muscle fibre bundles. Our results show that treating the fibre bundles with physiological concentrations of DHT increases both twitch and tetanic contractions in fast twitch fibres. However, it decreases them in slow twitch fibres. These changes in force are accompanied by an increase in the phosphorylation of MAPK/ERK1/2 in both fibre types and that of regulatory myosin light chains in fast twitch fibres. Both effects were insensitive to inhibitors of Src kinase, androgen receptor, insulin-like growth factor 1 receptor and platelet-derived growth factor receptor. However, they were abolished by the MAPK/ERK1/2 kinase inhibitor PD98059 and the epidermal growth factor (EGF) receptor inhibitor tyrphostin AG 1478. In contrast, testosterone had no effect on force and increased the phosphorylation of ERK1/2 in slow twitch fibres only. From these results we conclude that sex steroids have non-genomic actions in isolated intact mammalian skeletal muscle fibres. These are mediated through the EGF receptor and one of their main physiological functions is the enhancement of force production in fast twitch skeletal muscle fibres.

Free Fatty Acid Effects on the Atrial Myocardium: Membrane Ionic Currents Are Remodeled by the Disruption of T-Tubular Architecture

PubMed Central

O’Connell, Ryan P.; Musa, Hassan; Gomez, Mario San Martin; Avula, Uma Mahesh; Herron, Todd J.; Kalifa, Jerome; Anumonwo, Justus M. B.

2015-01-01

Background Epicardial adiposity and plasma levels of free fatty acids (FFAs) are elevated in atrial fibrillation, heart failure and obesity, with potentially detrimental effects on myocardial function. As major components of epicardial fat, FFAs may be abnormally regulated, with a potential to detrimentally modulate electro-mechanical function. The cellular mechanisms underlying such effects of FFAs are unknown. Objective To determine the mechanisms underlying electrophysiological effects of palmitic (PA), stearic (SA) and oleic (OA) FFAs on sheep atrial myocytes. Methods We used electrophysiological techniques, numerical simulations, biochemistry and optical imaging to examine the effects of acutely (≤ 15 min), short-term (4–6 hour) or 24-hour application of individual FFAs (10 μM) on isolated ovine left atrial myocytes (LAMs). Results Acute and short-term incubation in FFAs resulted in no differences in passive or active properties of isolated left atrial myocytes (LAMs). 24-hour application had differential effects depending on the FFA. PA did not affect cellular passive properties but shortened (p<0.05) action potential duration at 30% repolarization (APD30). APD50 and APD80 were unchanged. SA had no effect on resting membrane potential but reduced membrane capacitance by 15% (p<0.05), and abbreviated APD at all values measured (p≤0.001). OA did not significantly affect passive or active properties of LAMs. Measurement of the major voltage-gated ion channels in SA treated LAMs showed a ~60% reduction (p<0.01) of the L-type calcium current (ICa-L) and ~30% reduction (p<0.05) in the transient outward potassium current (ITO). A human atrial cell model recapitulated SA effects on APD. Optical imaging showed that SA incubated for 24 hours altered t-tubular structure in isolated cells (p<0.0001). Conclusions SA disrupts t-tubular architecture and remodels properties of membrane ionic currents in sheep atrial myocytes, with potential implications in arrhythmogenesis. PMID:26274906

Free Fatty Acid Effects on the Atrial Myocardium: Membrane Ionic Currents Are Remodeled by the Disruption of T-Tubular Architecture.

PubMed

O'Connell, Ryan P; Musa, Hassan; Gomez, Mario San Martin; Avula, Uma Mahesh; Herron, Todd J; Kalifa, Jerome; Anumonwo, Justus M B

2015-01-01

Epicardial adiposity and plasma levels of free fatty acids (FFAs) are elevated in atrial fibrillation, heart failure and obesity, with potentially detrimental effects on myocardial function. As major components of epicardial fat, FFAs may be abnormally regulated, with a potential to detrimentally modulate electro-mechanical function. The cellular mechanisms underlying such effects of FFAs are unknown. To determine the mechanisms underlying electrophysiological effects of palmitic (PA), stearic (SA) and oleic (OA) FFAs on sheep atrial myocytes. We used electrophysiological techniques, numerical simulations, biochemistry and optical imaging to examine the effects of acutely (≤ 15 min), short-term (4-6 hour) or 24-hour application of individual FFAs (10 μM) on isolated ovine left atrial myocytes (LAMs). Acute and short-term incubation in FFAs resulted in no differences in passive or active properties of isolated left atrial myocytes (LAMs). 24-hour application had differential effects depending on the FFA. PA did not affect cellular passive properties but shortened (p<0.05) action potential duration at 30% repolarization (APD30). APD50 and APD80 were unchanged. SA had no effect on resting membrane potential but reduced membrane capacitance by 15% (p<0.05), and abbreviated APD at all values measured (p≤0.001). OA did not significantly affect passive or active properties of LAMs. Measurement of the major voltage-gated ion channels in SA treated LAMs showed a ~60% reduction (p<0.01) of the L-type calcium current (ICa-L) and ~30% reduction (p<0.05) in the transient outward potassium current (ITO). A human atrial cell model recapitulated SA effects on APD. Optical imaging showed that SA incubated for 24 hours altered t-tubular structure in isolated cells (p<0.0001). SA disrupts t-tubular architecture and remodels properties of membrane ionic currents in sheep atrial myocytes, with potential implications in arrhythmogenesis.

Effects of norepinephrine on alpha-subtype receptors in the feline pulmonary vascular bed.

PubMed

Kaye, Alan D; Hoover, Jason M; Baber, Syed R; Ibrahim, Ikhlass N; Fields, Aaron M

2004-11-01

To test the hypothesis that norepinephrine induces a pressor response in the pulmonary vascular bed of the cat and identify the alpha-(1)adrenoceptor subtypes involved in the mediation or modulation of these effects. Prospective vehicle controlled study. University research laboratory. Intact chest preparation, adult mongrel cats. In separate experiments, the effects of 5-methyl-urapidil, a selective alpha-(1)A-subtype adrenoceptor antagonist, chloroethylclonidine, an alpha-(1)B-subtype and -(1)D-subtype adrenoceptor antagonist, and BMY 7378, the selective alpha-(1)D-subtype adrenoceptor antagonist, were investigated on pulmonary arterial responses to norepinephrine and other agonists in the pulmonary vascular bed of the cat. The systemic pressure and lobar arterial perfusion pressure were continuously monitored, electronically averaged, and permanently recorded. In the feline pulmonary vascular bed of the isolated left lower lobe, norepinephrine induced a dose-dependent vasoconstrictor response that was not significantly altered after administration of BMY 7378. However, the responses to norepinephrine were significantly attenuated following administration of 5-methyl-urapidil and chloroethylclonidine. The results of the present study suggest that norepinephrine has potent vasopressor activity in the pulmonary vascular bed of the cat and that this response may be mediated or modulated by both alpha-(1)A-subtype and -(1)B-subtype adrenoceptor sensitive pathways.

Recovery - Apollo 11

NASA Image and Video Library

1969-07-24

S69-21698 (24 July 1969) --- The three Apollo 11 crew men await pickup by a helicopter from the USS Hornet, prime recovery ship for the historic Apollo 11 lunar landing mission. The fourth man in the life raft is a United States Navy underwater demolition team swimmer. All four men are wearing biological isolation garments. Apollo 11, with astronauts Neil A. Armstrong, commander; Michael Collins, command module pilot; and Edwin E. Aldrin Jr., lunar module pilot, onboard, splashed down at 11:49 a.m. (CDT), July 24, 1969, about 812 nautical miles southwest of Hawaii and only 12 nautical miles from the USS Hornet. While astronauts Armstrong and Aldrin descended in the Lunar Module (LM) "Eagle" to explore the Sea of Tranquility region of the moon, astronaut Collins remained with the Command and Service Modules (CSM) "Columbia" in lunar orbit.

The Physiological Effects of Deleting the Mouse Slc30a8 Gene Encoding Zinc Transporter-8 Are Influenced by Gender and Genetic Background

PubMed Central

Pound, Lynley D.; Sarkar, Suparna A.; Ustione, Alessandro; Dadi, Prasanna K.; Shadoan, Melanie K.; Lee, Catherine E.; Walters, Jay A.; Shiota, Masakazu; McGuinness, Owen P.; Jacobson, David A.; Piston, David W.; Hutton, John C.; Powell, David R.; O’Brien, Richard M.

2012-01-01

Objective The SLC30A8 gene encodes the islet-specific transporter ZnT-8, which is hypothesized to provide zinc for insulin-crystal formation. A polymorphic variant in SLC30A8 is associated with altered susceptibility to type 2 diabetes. Several groups have examined the effect of global Slc30a8 gene deletion but the results have been highly variable, perhaps due to the mixed 129SvEv/C57BL/6J genetic background of the mice studied. We therefore sought to remove the conflicting effect of 129SvEv-specific modifier genes. Methods The impact of Slc30a8 deletion was examined in the context of the pure C57BL/6J genetic background. Results Male C57BL/6J Slc30a8 knockout (KO) mice had normal fasting insulin levels and no change in glucose-stimulated insulin secretion (GSIS) from isolated islets in marked contrast to the ∼50% and ∼35% decrease, respectively, in both parameters observed in male mixed genetic background Slc30a8 KO mice. This observation suggests that 129SvEv-specific modifier genes modulate the impact of Slc30a8 deletion. In contrast, female C57BL/6J Slc30a8 KO mice had reduced (∼20%) fasting insulin levels, though this was not associated with a change in fasting blood glucose (FBG), or GSIS from isolated islets. This observation indicates that gender also modulates the impact of Slc30a8 deletion, though the physiological explanation as to why impaired insulin secretion is not accompanied by elevated FBG is unclear. Neither male nor female C57BL/6J Slc30a8 KO mice showed impaired glucose tolerance. Conclusions Our data suggest that, despite a marked reduction in islet zinc content, the absence of ZnT-8 does not have a substantial impact on mouse physiology. PMID:22829903

Topics in electrochemical degradation of photovoltaic modules

NASA Technical Reports Server (NTRS)

Mon, G. R.

1984-01-01

Electrochemical degradation of photovoltaic modules was examined. It is found that the extent of electrochemical damage is dependent on the integrated leakage current. The PV electrochemical degradation mechanisms in the two polarities are different: (1) degradation rates in the two polarities are of the same order of magnitude; (2) center tapped grounded arrays are a preferred system configuration to minimize electrochemical degradation. The use of thicker pottant layers and polymer substrate films to reduce equilibrium leakage current values is suggested. A metallized substrate layer, if used, should be isolated from the pottant and the frame by polyester layers, and EVA modules appear to be consistent with 30 year life allocation levels for electrochemical damage. Temperature acceleration factors are well behaved and moderately well understood; humidity acceleration factors vary radically with module construction and materials and require additional research.

Fluid pumping apparatus

DOEpatents

West, Phillip B.

2006-01-17

A method and apparatus suitable for coupling seismic or other downhole sensors to a borehole wall in high temperature and pressure environments. In one embodiment, one or more metal bellows mounted to a sensor module are inflated to clamp the sensor module within the borehole and couple an associated seismic sensor to a borehole wall. Once the sensing operation is complete, the bellows are deflated and the sensor module is unclamped by deflation of the metal bellows. In a further embodiment, a magnetic drive pump in a pump module is used to supply fluid pressure for inflating the metal bellows using borehole fluid or fluid from a reservoir. The pump includes a magnetic drive motor configured with a rotor assembly to be exposed to borehole fluid pressure including a rotatable armature for driving an impeller and an associated coil under control of electronics isolated from borehole pressure.

Deoxycholic acid inhibits smooth muscle contraction via protein kinase C-dependent modulation of L-type Ca2+ channels in rat proximal colon.

PubMed

Hu, Liu-Dan; Yu, Bao-Ping; Yang, Bin

2012-10-01

The aim of this study was to investigate the effects of deoxycholic acid (DCA) on the contractions of rat proximal colonic smooth muscle (PCSM) in vitro. The contractile response of rat PCSM strips was tested using a polyphysio-graph. The whole cell patch-clamp technique was also used in rat colonic smooth muscle cells (SMCs) isolated by an enzymatic procedure to record the L-type calcium current (I(Ca-L)) prior to and following the application of various concentrations of DCA. The application of DCA (10(-6)-10(-4) M) decreased the amplitude of spontaneous contractions of the PCSM strips in a dose-dependent manner. The administration of DCA (10(-5) M) caused the relaxation of isolated smooth muscle strips pre-contracted by acetylcholine (Ach) or KCl (by 12.2±1.5 and 16.3±6.9%, respectively). The concentration-response curve of CaCl2 was shifted to the right. Pre-treatment of the strips with the protein kinase C (PKC) inhibitor chelerythrine (1 µM) significantly attenuated the effects of DCA on the strips pre-contracted by Ach. DCA reduced the peak I(Ca-L) by 6.02±0.87% at 10(-6) M, 15.02±1.73% at 10(-5) M and 47.14±3.79% at 10(-4) M. DCA shifted the current-voltage (I-V) curve of ICa-L upward, but the contour of the I-V curve was unchanged, and the peak current-induced voltage remained at 0 mV. Pre-treatment with chelerythrine (1 µM) blocked the actions of DCA on the I(Ca-L). Taken together, the actions of DCA on I(Ca-L) in rat colonic SMCs contributed to a negative inotropic effect. These actions appear to be mediated through protein kinase C. Furthermore, this study suggests another possible mechanism for the DCA-related modulation of gastrointestinal motility.

Effect of interconnection between cervical vagus trunk, epicardial fat pad on sinus node function, and atrial fibrillation.

PubMed

Zhou, Qina; Zhang, Ling; Wang, Kun; Xu, Xiaoxia; Ji, Meng; Zhang, Feng; Wang, Hongli; Hou, Yuemei

2014-03-01

The epicardial fat pad (FP) integrates the autonomic innervation between the extrinsic and intrinsic cardiac autonomic nervous system and affects atrial electrophysiology and pathophysiology. Eighteen dogs were divided into two groups: sequential ablation of sinoatrial node FP (SAN-FP) and atrioventricular node FP (AVN-FP). Sinus rate (SR), atrial fibrillation (AF) inducibility, and effective refractory period (ERP) changes during electrical stimulation of the vagus trunk were detected before and after ablation. In the SAN-FP group, the SR slowing, increasing AF inducibility, and ERP shortening that induced by vagus trunk stimulation were significantly attenuated by isolated SAN-FP ablation, compared with the same group prior to ablation (all P < 0.05). Subsequent AVN-FP ablation following SAN-FP ablation almost cannot produce further attenuation during vagus trunk stimulation, compared with isolated SAN-FP ablation (P > 0.05). In the AVN-FP group, SR slowing, increasing AF inducibility, and ERP shortening that induced by vagus trunk stimulation were completely eliminated by isolated AVN-FP ablation, compared with the same group prior to ablation (all P < 0.05). Subsequent SAN-FP ablation following AVN-FP ablation produced no further attenuation, compared with isolated AVN-FP ablation (P > 0.05). A neural pathway from the cervical vagus trunk to the sinus node and atrium runs through the SAN-FP, but eventually converges at the AVN-FP and also suggested that the AVN-FP serves as an "integration center" for the SAN-FP to modulate sinus node function. The AVN-FP may play a more critical role in the initiation and maintenance of AF. ©2013 First Affilated Hospital of Xingiang Medical University Pacing and Clinical Electrophysiology ©2013 Wiley Periodicals, Inc.

Extrafoveally applied flashing light affects contrast thresholds of achromatic and S-cone isolating, but not L-M cone modulated stimuli.

PubMed

Őze, A; Puszta, A; Buzás, P; Kóbor, P; Braunitzer, G; Nagy, A

2018-06-21

Flashing light stimulation is often used to investigate the visual system. However, the magnitude of the effect of this stimulus on the various subcortical pathways is not well investigated. The signals of conscious vision are conveyed by the magnocellular, parvocellular and koniocellular pathways. Parvocellular and koniocellular pathways (or more precisely, the L-M opponent and S-cone isolating channels) can be accessed by isoluminant red-green (L-M) and S-cone isolating stimuli, respectively. The main goal of the present study was to explore how costimulation with strong white extrafoveal light flashes alters the perception of stimuli specific to these pathways. Eleven healthy volunteers with negative neurological and ophthalmological history were enrolled for the study. Isoluminance of L-M and S-cone isolating sine-wave gratings was set individually, using the minimum motion procedure. The contrast thresholds for these stimuli as well as for achromatic gratings were determined by an adaptive staircase procedure where subjects had to indicate the orientation (horizontal, oblique or vertical) of the gratings. Thresholds were then determined again while a strong white peripheral light flash was presented 50 ms before each trial. Peripheral light flashes significantly (p < 0.05) increased the contrast thresholds of the achromatic and S-cone isolating stimuli. The threshold elevation was especially marked in case of the achromatic stimuli. However, the contrast threshold for the L-M stimuli was not significantly influenced by the light flashes. We conclude that extrafoveally applied light flashes influence predominantly the perception of achromatic stimuli. Copyright © 2018 Elsevier B.V. All rights reserved.

Therapeutic potential of octyl gallate isolated from fruits of Terminalia bellerica in streptozotocin-induced diabetic rats.

PubMed

Latha, R Cecily Rosemary; Daisy, P

2013-06-01

Medicinal plants are a potential source of antidiabetic drugs. Terminalia bellerica Roxb. (Combretaceae) is used in Indian traditional systems of medicine to treat diabetes mellitus. The aim of this study was to isolate and identify antihyperglycemic principle(s) from the fruits of T. bellerica and assess the bioactivity in streptozotocin (STZ)-induced diabetic rats. Bioassay-guided fractionation was followed to isolate the active compound(s), structure was elucidated using (1)H and (13)C NMR, IR and mass spectrometry and administered intragastrically to diabetic Wistar rats at different doses (5, 10 and 20 mg/kg, body weight) for 28 d. Plasma glucose, insulin, C-peptide and other biochemical parameters were studied. Octyl gallate (OG) isolated first time from the fruit rind of T. bellerica significantly (p < 0.05) reduced plasma glucose to near normal values (108.47 ± 6.9 mg/dl) after 14 d at the dose of 20 mg/kg. In addition, OG significantly increased plasma insulin, C-peptide, total protein, albumin, tissue glycogen, body weight and markedly decreased serum total cholesterol, triglyceride, LDL-cholesterol, urea, uric acid and creatinine in diabetic rats. Also OG restored the altered regulatory enzymes of carbohydrate metabolism. OG might have augmented the secretion of insulin by the modulation of cAMP and intracellular calcium levels in the β cells of the pancreas. Our findings indicate that OG isolated first time from the fruit rind of T. bellerica has potential antidiabetic effect as it augments insulin secretion and normalizes the altered biochemical parameters in experimental diabetic rat models.

FE Thirsk exercises on the TVIS in the SM

NASA Image and Video Library

2009-11-11

ISS021-E-024162 (11 Nov. 2009) --- Canadian Space Agency astronaut Robert Thirsk, Expedition 21 flight engineer, equipped with a bungee harness, exercises on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

Krikalev with TVIS hardware in Zvezda

NASA Image and Video Library

2005-09-07

ISS011-E-12601 (7 September 2005) --- Cosmonaut Sergei K. Krikalev, Expedition 11 commander representing Russia's Federal Space Agency, works with the Treadmill Vibration Isolation System (TVIS) during In-Flight Maintenance (IFM) in the Zvezda Service Module of the International Space Station.

TVIS Inflight Maintenance

NASA Image and Video Library

2011-07-01

ISS028-E-013758 (1 July 2011) --- Russian cosmonauts Sergei Volkov, Expedition 28 flight engineer; and Andrey Borisenko (mostly out of frame at left), commander, perform in-flight maintenance on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

Krikalev during TVIS IFM

NASA Image and Video Library

2005-05-16

ISS011-E-06188 (16 May 2005) --- Cosmonaut Sergei K. Krikalev, Expedition 11 commander representing Russia's Federal Space Agency, works with the Treadmill Vibration Isolation System (TVIS) removed from the Zvezda Service Module floor during In-Flight Maintenance (IFM) on the International Space Station (ISS).

Williams Exercises in Zvezda

NASA Image and Video Library

2007-01-13

ISS014-E-11786 (13 Jan. 2007) --- Surrounded by hardware, astronaut Sunita L. Williams, Expedition 14 flight engineer, equipped with a bungee harness, exercises on the Treadmill Vibration Isolation System (TVIS) (out of frame) in the Zvezda Service Module of the International Space Station.

Krikalev with TVIS hardware in Zvezda

NASA Image and Video Library

2005-09-07

ISS011-E-12494 (7 September 2005) --- Cosmonaut Sergei K. Krikalev, Expedition 11 commander representing Russia's Federal Space Agency, works with the Treadmill Vibration Isolation System (TVIS) during In-Flight Maintenance (IFM) in the Zvezda Service Module of the International Space Station.

Williams Exercises in Zvezda

NASA Image and Video Library

2007-01-13

ISS014-E-11784 (13 Jan. 2007) --- Surrounded by hardware, astronaut Sunita L. Williams, Expedition 14 flight engineer, equipped with a bungee harness, exercises on the Treadmill Vibration Isolation System (TVIS) (out of frame) in the Zvezda Service Module of the International Space Station.

Validation of a novel CARTOSEG™ segmentation module software for contrast-enhanced computed tomography-guided radiofrequency ablation in patients with atrial fibrillation.

PubMed

Imanli, Hasan; Bhatty, Shaun; Jeudy, Jean; Ghzally, Yousra; Ume, Kiddy; Vunnam, Rama; Itah, Refael; Amit, Mati; Duell, John; See, Vincent; Shorofsky, Stephen; Dickfeld, Timm M

2017-11-01

Visualization of left atrial (LA) anatomy using image integration modules has been associated with decreased radiation exposure and improved procedural outcome when used for guidance of pulmonary vein isolation (PVI) in atrial fibrillation (AF) ablation. We evaluated the CARTOSEG™ CT Segmentation Module (Biosense Webster, Inc.) that offers a new CT-specific semiautomatic reconstruction of the atrial endocardium. The CARTOSEG™ CT Segmentation Module software was assessed prospectively in 80 patients undergoing AF ablation. Using preprocedural contrast-enhanced computed tomography (CE-CT), cardiac chambers, coronary sinus (CS), and esophagus were semiautomatically segmented. Segmentation quality was assessed from 1 (poor) to 4 (excellent). The reconstructed structures were registered with the electroanatomic map (EAM). PVI was performed using the registered 3D images. Semiautomatic reconstruction of the heart chambers was successfully performed in all 80 patients with AF. CE-CT DICOM file import, semiautomatic segmentation of cardiac chambers, esophagus, and CS was performed in 185 ± 105, 18 ± 5, 119 ± 47, and 69 ± 19 seconds, respectively. Average segmentation quality was 3.9 ± 0.2, 3.8 ± 0.3, and 3.8 ± 0.2 for LA, esophagus, and CS, respectively. Registration accuracy between the EAM and CE-CT-derived segmentation was 4.2 ± 0.9 mm. Complications consisted of one perforation (1%) which required pericardiocentesis, one increased pericardial effusion treated conservatively (1%), and one early termination of ablation due to thrombus formation on the ablation sheath without TIA/stroke (1%). All targeted PVs (n  =  309) were successfully isolated. The novel CT- CARTOSEG™ CT Segmentation Module enables a rapid and reliable semiautomatic 3D reconstruction of cardiac chambers and adjacent anatomy, which facilitates successful and safe PVI. © 2017 Wiley Periodicals, Inc.

Muscarinic Stimulation Facilitates Sarcoplasmic Reticulum Ca Release by Modulating Ryanodine Receptor 2 Phosphorylation Through Protein Kinase G and Ca/Calmodulin-Dependent Protein Kinase II.

PubMed

Ho, Hsiang-Ting; Belevych, Andriy E; Liu, Bin; Bonilla, Ingrid M; Radwański, Przemysław B; Kubasov, Igor V; Valdivia, Héctor H; Schober, Karsten; Carnes, Cynthia A; Györke, Sándor

2016-11-01

Although the effects and the underlying mechanism of sympathetic stimulation on cardiac Ca handling are relatively well established both in health and disease, the modes of action and mechanisms of parasympathetic modulation are poorly defined. Here, we demonstrate that parasympathetic stimulation initiates a novel mode of excitation-contraction coupling that enhances the efficiency of cardiac sarcoplasmic reticulum Ca store utilization. This efficient mode of excitation-contraction coupling involves reciprocal changes in the phosphorylation of ryanodine receptor 2 at Ser-2808 and Ser-2814. Specifically, Ser-2808 phosphorylation was mediated by muscarinic receptor subtype 2 and activation of PKG (protein kinase G), whereas dephosphorylation of Ser-2814 involved activation of muscarinic receptor subtype 3 and decreased reactive oxygen species-dependent activation of CaMKII (Ca/calmodulin-dependent protein kinase II). The overall effect of these changes in phosphorylation of ryanodine receptor 2 is an increase in systolic Ca release at the low sarcoplasmic reticulum Ca content and a paradoxical reduction in aberrant Ca leak. Accordingly, cholinergic stimulation of cardiomyocytes isolated from failing hearts improved Ca cycling efficiency by restoring altered ryanodine receptor 2 phosphorylation balance. © 2016 American Heart Association, Inc.

Non-covalent pomegranate (Punica granatum) hydrolyzable tannin-protein complexes modulate antigen uptake, processing and presentation by a T-cell hybridoma line co-cultured with murine peritoneal macrophages.

PubMed

Madrigal-Carballo, Sergio; Haas, Linda; Vestling, Martha; Krueger, Christian G; Reed, Jess D

2016-12-01

In this work we characterize the interaction of pomegranate hydrolyzable tannins (HT) with hen egg-white lysozyme (HEL) and determine the effects of non-covalent tannin-protein complexes on macrophage endocytosis, processing and presentation of antigen. We isolated HT from pomegranate and complex to HEL, the resulting non-covalent tannin-protein complex was characterized by gel electrophoresis and MALDI-TOF MS. Finally, cell culture studies and confocal microscopy imaging were conducted on the non-covalent pomegranate HT-HEL protein complexes to evaluate its effect on macrophage antigen uptake, processing and presentation to T-cell hybridomas. Our results indicate that non-covalent pomegranate HT-HEL protein complexes modulate uptake, processing and antigen presentation by mouse peritoneal macrophages. After 4 h of pre-incubation, only trace amounts of IL-2 were detected in the co-cultures treated with HEL alone, whereas a non-covalent pomegranate HT-HEL complex had already reached maximum IL-2 expression. Pomegranate HT may increase rate of endocytose of HEL and subsequent expression of IL-2 by the T-cell hybridomas.

Sympathetic Nervous System Modulation of Inflammation and Remodeling in the Hypertensive Heart

PubMed Central

Levick, Scott P.; Murray, David B.; Janicki, Joseph S.; Brower, Gregory L.

2010-01-01

Chronic activation of the sympathetic nervous system (SNS) is a key component of cardiac hypertrophy and fibrosis. However, previous studies have provided evidence to also implicate inflammatory cells, including mast cells, in the development of cardiac fibrosis. The current study investigated the potential interaction of cardiac mast cells with the SNS. Eight week old male SHR were sympathectomized to establish the effect of the SNS on cardiac mast cell density, myocardial remodeling and cytokine production in the hypertensive heart. Age-matched WKY served as controls. Cardiac fibrosis and hypertension were significantly attenuated and left ventricular mass normalized while cardiac mast cell density was markedly increased in sympathectomized SHR. Sympathectomy normalized myocardial levels of IFN-γ, IL-6 and IL-10, but had no effect on IL-4. The effect of norepinephrine and substance P on isolated cardiac mast cell activation was investigated as potential mechanisms of interaction between the two. Only substance P elicited mast cell degranulation. Substance P was also shown to induce the production of angiotensin II by a mixed population of isolated cardiac inflammatory cells, including mast cells, lymphocytes and macrophages. These results demonstrate the ability of neuropeptides to regulate inflammatory cell function, providing a potential mechanism by which the SNS and afferent nerves may interact with inflammatory cells in the hypertensive heart. PMID:20048196

Mode and site of acupuncture modulation in the human brain: 3D (124-ch) EEG power spectrum mapping and source imaging.

PubMed

Chen, Andrew C N; Liu, Feng-Jun; Wang, Li; Arendt-Nielsen, Lars

2006-02-15

This study determined: (a) if acupuncture stimulation at a traditional site might modulate ongoing EEG as compared with stimulation of a control site; (b) if high-frequency vs. low-frequency stimulation could exert differential effects of acupuncture; (c) if the observed effects of acupuncture were specific to certain EEG bands; and (d) if the acupuncture effect could be isolated at a specific scalp field, with its putative underlying intracranial source. Twelve healthy male volunteers (age range 22-35) participated in two experimental sessions separated by 1 week, which involved transcutaneous acupoint stimulation at selected acupoint (Li 4, HeGu) vs. a mock point at the fourth interosseous muscle area on the left hand in high (HF: 100 Hz) vs. low-frequency (LF: 2 Hz) stimulation by counter-balanced order. 124-ch EEG data were used to analyze the Delta, Theta, Alpha-1, Alpha-2, Beta, and Gamma bands. The absolute EEG powers (muv2) at focal maxima across three stages (baseline, stimulation, post) were examined by two-way (condition, stage) repeated measures ANOVA. The activity of the Theta power significantly decreased (P = 0.02), compared with control during HF but not LF stimulation at acupoint stimulation, however, there was no study effect at the mock point. A decreased Theta EEG power was prominent at the frontal midline sites (FCz, Fz) and the contralateral right hemisphere front site (FCC2h). In contrast, the Theta power of low-frequency stimulation showed an increase from the baseline as those in both controlled mock point stimulations. The observed high-frequency acupoint stimulation effects of Theta EEG were only present during, but not after, simulation. The topographic Theta activity was tentatively identified to originate from the intracranial current source in cingulate cortex, likely ACC. It is likely that short-term cortical plasticity occurs during high-frequency but not low-frequency stimulation at the HeGu point, but not mock point. We suggest that HeGu acupuncture stimulation modulates limbic cingulum by a frequency modulation mode, which then may damp nociceptive processing in the brain.

Lactic acid bacteria and bifidobacteria attenuate the proinflammatory response in intestinal epithelial cells induced by Salmonella enterica serovar Typhimurium.

PubMed

Carey, Christine M; Kostrzynska, Magdalena

2013-01-01

Inflammation is a physiological response to infections and tissue injury; however, abnormal immune responses can give rise to chronic inflammation and contribute to disease progression. Various dietary components, including probiotic lactic acid bacteria and prebiotics, have the potential to modulate intestinal inflammatory responses. One factor in particular, the chemokine interleukin-8 (IL-8, CXCL-8), is one of the major mediators of the inflammatory response. The purpose of this study was to investigate modulation of the inflammatory host response induced by Salmonella enterica serovar Typhimurium DT104 in the presence of selected probiotics and lactic acid bacteria (LAB) isolated from human sources, dairy products, and farm animals. IL-8 gene expression and protein production in HT-29 cells were evaluated by real-time PCR and ELISA, respectively. Pre-incubation of HT-29 cells with Lactobacillus kefir IM002, Bifidobacterium adolescentis FRP 61, Bifidobacterium longum FRP 68 and FRP 69, Bifidobacterium breve FRP 334, and Leuconostoc mesenteroides IM080 significantly inhibited IL-8 secretion induced by Salmonella Typhimurium DT104. Co-culture of selected probiotics and Salmonella Typhimurium DT104 reduced IL-8 production, while potential probiotics and LAB had no effect on IL-8 secretion in HT-29 cells preincubated with Salmonella Typhimurium DT104 prior to adding probiotics. Lactobacillus kefir IM002 supernatant also significantly reduced IL-8 production. In conclusion, our study suggests that probiotic bifidobacteria and LAB modulate cytokine induction and possess anti-inflammatory properties; however, the effectiveness is strain dependent.

Circuit-Host Coupling Induces Multifaceted Behavioral Modulations of a Gene Switch.

PubMed

Blanchard, Andrew E; Liao, Chen; Lu, Ting

2018-02-06

Quantitative modeling of gene circuits is fundamentally important to synthetic biology, as it offers the potential to transform circuit engineering from trial-and-error construction to rational design and, hence, facilitates the advance of the field. Currently, typical models regard gene circuits as isolated entities and focus only on the biochemical processes within the circuits. However, such a standard paradigm is getting challenged by increasing experimental evidence suggesting that circuits and their host are intimately connected, and their interactions can potentially impact circuit behaviors. Here we systematically examined the roles of circuit-host coupling in shaping circuit dynamics by using a self-activating gene switch as a model circuit. Through a combination of deterministic modeling, stochastic simulation, and Fokker-Planck equation formalism, we found that circuit-host coupling alters switch behaviors across multiple scales. At the single-cell level, it slows the switch dynamics in the high protein production regime and enlarges the difference between stable steady-state values. At the population level, it favors cells with low protein production through differential growth amplification. Together, the two-level coupling effects induce both quantitative and qualitative modulations of the switch, with the primary component of the effects determined by the circuit's architectural parameters. This study illustrates the complexity and importance of circuit-host coupling in modulating circuit behaviors, demonstrating the need for a new paradigm-integrated modeling of the circuit-host system-for quantitative understanding of engineered gene networks. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Optical modulation from an electro-optic polymer based hybrid Fabry-Perot etalon using transparent conducting oxides

NASA Astrophysics Data System (ADS)

Gan, Haiyong; Zhang, Hongxi; DeRose, Christopher T.; Norwood, Robert A.; Fallahi, Mahmoud; Luo, Jingdong; Jen, Alex K.-Y.; Liu, Boyang; Ho, Seng-Tiong; Peyghambarian, Nasser

2007-02-01

Fabry-Perot etalons using electro-optic (EO) organic materials can be used for devices such as tunable filters and spatial light modulators (SLM's) for wavelength division multiplexing (WDM) communication systems 1-5 and ultrafast imaging systems. For these applications the SLM's need to have: (i) low insertion loss, (ii) high speed operation, and (iii) large modulation depth with low drive voltage. Recently, there have been three developments which together can enhance the SLM performance to a higher level. First, low loss distributed Bragg reflector (DBR) mirrors are now used in SLM's to replace thin metal mirrors, resulting in reduced transmission loss, high reflectivity (>99%) and high finesse. Second, EO polymer materials have shown excellent properties for wide bandwidth optical modulation for information technology due to their fabrication flexibility, compatibility with high speed operation, and large EO coefficients at telecommunication wavelengths. For instance, the EO polymer AJL8/APC (AJL8: nonlinear optical chromophore, and APC: amorphous polycarbonate has recently been incorporated into waveguide modulators and achieved good performance for optical modulation. Finally, very low loss transparent conducting oxide (TCO) electrodes have drawn increasing attention for applications in optoelectronic devices. Here we will address how the low loss indium oxide (In IIO 3) electrodes with an absorption coefficient ~1000/cm and conductivity ~204 S/cm can help improve the modulation performance of EO polymer Fabry-Pérot étalons using the advanced electro-optic (EO) polymer material (AJL8/APC). A hybrid etalon structure with one highly conductive indium tin oxide (ITO) electrode outside the etalon cavity and one low-absorption In IIO 3 electrode inside etalon cavity has been demonstrated. High finesse (~234), improved effective applied voltage ratio (~0.25), and low insertion loss (~4 dB) have been obtained. A 10 dB isolation ratio and ~10% modulation depth at 200 kHz with only 5 V applied voltage have been achieved. These results indicate that such etalons are very promising candidates for ultrafast spatial light modulation in information technology.

Spatially tuned normalization explains attention modulation variance within neurons.

PubMed

Ni, Amy M; Maunsell, John H R

2017-09-01

Spatial attention improves perception of attended parts of a scene, a behavioral enhancement accompanied by modulations of neuronal firing rates. These modulations vary in size across neurons in the same brain area. Models of normalization explain much of this variance in attention modulation with differences in tuned normalization across neurons (Lee J, Maunsell JHR. PLoS One 4: e4651, 2009; Ni AM, Ray S, Maunsell JHR. Neuron 73: 803-813, 2012). However, recent studies suggest that normalization tuning varies with spatial location both across and within neurons (Ruff DA, Alberts JJ, Cohen MR. J Neurophysiol 116: 1375-1386, 2016; Verhoef BE, Maunsell JHR. eLife 5: e17256, 2016). Here we show directly that attention modulation and normalization tuning do in fact covary within individual neurons, in addition to across neurons as previously demonstrated. We recorded the activity of isolated neurons in the middle temporal area of two rhesus monkeys as they performed a change-detection task that controlled the focus of spatial attention. Using the same two drifting Gabor stimuli and the same two receptive field locations for each neuron, we found that switching which stimulus was presented at which location affected both attention modulation and normalization in a correlated way within neurons. We present an equal-maximum-suppression spatially tuned normalization model that explains this covariance both across and within neurons: each stimulus generates equally strong suppression of its own excitatory drive, but its suppression of distant stimuli is typically less. This new model specifies how the tuned normalization associated with each stimulus location varies across space both within and across neurons, changing our understanding of the normalization mechanism and how attention modulations depend on this mechanism. NEW & NOTEWORTHY Tuned normalization studies have demonstrated that the variance in attention modulation size seen across neurons from the same cortical area can be largely explained by between-neuron differences in normalization strength. Here we demonstrate that attention modulation size varies within neurons as well and that this variance is largely explained by within-neuron differences in normalization strength. We provide a new spatially tuned normalization model that explains this broad range of observed normalization and attention effects. Copyright © 2017 the American Physiological Society.

In vitro activities of kappa-carrageenan isolated from red marine alga Hypnea musciformis: Antimicrobial, anticancer and neuroprotective potential.

PubMed

Souza, Ricardo Basto; Frota, Annyta Fernandes; Silva, Joana; Alves, Celso; Neugebauer, Agnieszka Zofia; Pinteus, Susete; Rodrigues, José Ariévilo Gurgel; Cordeiro, Edna Maria Silva; de Almeida, Raimundo Rafael; Pedrosa, Rui; Benevides, Norma Maria Barros

2018-06-01

This study assessed the antioxidant, antimicrobial, anticancer and neuroprotective activities of the kappa(k)-carrageenan isolated from the red alga Hypnea musciformis (Hm-SP). The chemical spectrum of the k-carrageenan from Hm-SP was confirmed by Fourier transform infrared (FT-IR) spectroscopy. Hm-SP revealed an antibacterial and antifungal action against Staphylococcus aureus and Candida albicans, respectively. Hm-SP did not promoted cytotoxic effects against Human breast cancer (MCF-7) and Human neuroblastoma (SH-SY5Y) cell-lines. However, it was observed a significant reduction of the cellular proliferation capacity in these cancer cells in presence of the Hm-SP. Furthermore, Hm-SP showed neuroprotective activity in 6-hydroxydopamine-induced neurotoxicity on SH-SY5Y cells by modulation of the mitochondria transmembrane potential and reducing Caspase 3 activity. In addition, Hm-SP demonstrates low antioxidant potential and did not induce significant cytotoxic effects or changes in the cell proliferation on Balb/c 3T3 mouse fibroblast cell-line. In summary, our data suggest that Hm-SP shows antimicrobial, anticancer and neuprotective activities. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of acylation on the functional properties and in vitro trypsin digestibility of red kidney bean (Phaseolus vulgaris L.) protein isolate.

PubMed

Yin, Shou-Wei; Tang, Chuan-He; Wen, Qi-Biao; Yang, Xiao-Quan

2009-01-01

The effects of succinylation and acetylation on some functional properties and the in vitro trypsin digestibility of kidney bean protein isolate (KPI) were investigated. The extent of succinylation or acetylation progressively increased from 0% to 96% to 97%, as the anhydride-to-protein ratio increased from 0 to 1 g/g. Polyacrylamide gel electrophoresis (PAGE) and zeta potential analyses indicated that acylation, especially succinylation, considerably increased the net charge and hydrodynamic radius of the proteins in KPI, especially vicilin. Acylation treatment at various anhydride-to-protein ratios (0.05 to 1 g/g) remarkably improved the protein solubility (PS) and emulsifying activity index (EAI) at neutral pH, but the improvement by succinylation was much better than that by acetylation. Succinylation resulted in a marked decrease in mechanical moduli of heat-induced gels of KPI, while the mechanical moduli were, on the contrary, increased by acetylation. Additionally, in vitro trypsin digestibility was improved by the acylation in an anhydride-type and level-dependent manner. The results suggest that the functional properties of KPI could be modulated by the chemical acylation treatment, using succinic or acetic anhydride at appropriate anhydride-to-protein ratios.

36 kDa glycoprotein isolated from Rhus verniciflua stokes inhibits G/GO-induced mitochondrial apoptotic signal pathways in BNL CL.2 cells.

PubMed

Lee, Sei-Jung; Oh, Phil-Sun; Lim, Kwang; Lim, Kye-Taek

2005-12-01

Rhus verniciflua Stokes is one of the medicinal plants traditionally used to heal and treat hepatic and inflammatory diseases. We found that a glycoprotein isolated from the fruit has a molecular weight of 36 kDa and consists of a carbohydrate component (38.75%) and a protein (61.25%), and that the glycoprotein has a strong scavenging activity against hydroxyl radicals without any pro-oxidant activity in the cell-free system. In glucose/glucose oxidase (G/GO)-induced BNL CL.2 cells, the results showed that Rhus verniciflua Stokes glycoprotein has dose-dependent blocking activities against G/GO-induced cytotoxicity and apoptosis, increasing the glutathione (GSH) peroxidase activity. In the activity of the mitochondrial apoptotic mediators (cytochrome c, caspases and poly(ADP-ribose)polymerase (PARP)), the glycoprotein (100 microg/ml) showed an inhibitory effect on cytochrome c release, caspase-9/3 activation, and PARP cleavage. Moreover, Rhus verniciflua Stokes glycoprotein has a stimulating effect on the nitric oxide production. Here, we speculate that this glycoprotein is one of the natural antioxidants and of the modulators of apoptotic signal pathways in BNL CL.2 cells.

Mechanisms involved in the cytotoxic action of Brazilian propolis and caffeic acid against HEp-2 cells and modulation of P-glycoprotein activity.

PubMed

da Silva, Lívia M; Frión-Herrera, Yahima; Bartolomeu, Ariane R; Gorgulho, Carolina Mendonça; Sforcin, José M

2017-11-01

The effects of propolis and phenolic compounds (caffeic acid - Caf; dihydrocinnamic acid - Cin; p-coumaric acid - Cou) in the same quantity found in our propolis sample were investigated on human laryngeal epidermoid carcinoma (HEp-2) cells. Cell viability, apoptosis/necrosis and cell cycle arrest, P53 and CASPASE-3 gene expression, generation of reactive oxygen species (ROS) and the ability of propolis to induce doxorubicin (DOX) efflux using a P-glycoprotein (P-gp) inhibitor (verapamil) were assayed. Propolis exerted a cytotoxic effect on HEp-2 cells, whereas isolated compounds had no effect on cell viability. Higher concentrations were tested and Caf induced late apoptosis or necrosis in HEp-2 cells, while propolis induced apoptosis, both probably due to ROS generation. P53 expression was downregulated by propolis but not by Caf. CASPASE-3 expression was correlated with induction of both early and late apoptosis, with both propolis and Caf alone upregulating its expression. Propolis induced cell cycle arrest at G2/M phase and Caf at S phase. Propolis but not Caf may act as a P-gp inhibitor by modulating P-gp activity and inhibiting DOX efflux. Propolis exerted cytotoxic effects on HEp-2 cells, and the mechanisms are discussed, showing its potential as an antitumour drug. © 2017 Royal Pharmaceutical Society.

Low levels of lipopolysaccharide modulate mitochondrial oxygen consumption in skeletal muscle

PubMed Central

Frisard, Madlyn I.; Wu, Yaru; McMillan, Ryan P.; Voelker, Kevin A.; Wahlberg, Kristin A.; Anderson, Angela S.; Boutagy, Nabil; Resendes, Kyle; Ravussin, Eric; Hulver, Matthew W.

2014-01-01

Objective We have previously demonstrated that activation of toll-like receptor 4 (TLR4) in skeletal muscle results in an increased reliance on glucose as an energy source and a concomitant decrease in fatty acid oxidation under basal conditions. Herein, we examined the effects of lipopolysaccharide (LPS), the primary ligand for TLR4, on mitochondrial oxygen consumption in skeletal muscle cell culture and isolated mitochondria. Materials/ methods Skeletal muscle cell cultures were exposed to LPS and oxygen consumption was assessed using a Seahorse Bioscience extracellular flux analyzer. Mice were also exposed to LPS and oxygen consumption was assessed in mitochondria isolated from skeletal muscle. Results Acute LPS exposure resulted in significant reductions in cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP)-stimulated maximal respiration (state 3u) and increased oligomycin induced state 4 (state 4O) respiration in C2C12 and human primary myotubes. These findings were observed in conjunction with increased mRNA of uncoupling protein 3 (UCP3), superoxide dismutase 2 (SOD2), and pyruvate dehydrogenase activity. The LPS-mediated changes in substrate oxidation and maximal mitochondrial respiration were prevented in the presence of the antioxidants N-acetylcysteine and catalase, suggesting a potential role of reactive oxygen species in mediating these effects. Mitochondria isolated from red gastrocnemius and quadriceps femoris muscle from mice injected with LPS also demonstrated reduced respiratory control ratio (RCR), and ADP- and FCCP-stimulated respiration. Conclusion LPS exposure in skeletal muscle alters mitochondrial oxygen consumption and substrate preference, which is absent when antioxidants are present. PMID:25528444

Cardiotoxicity of acetogenins from Persea americana occurs through the mitochondrial permeability transition pore and caspase-dependent apoptosis pathways.

PubMed

Silva-Platas, Christian; García, Noemí; Fernández-Sada, Evaristo; Dávila, Daniel; Hernández-Brenes, Carmen; Rodríguez, Dariana; García-Rivas, Gerardo

2012-08-01

Acetogenins are cell-membrane permeable, naturally occurring secondary metabolites of plants such as Annonaceae, Lauraceae and other related phylogenic families. They belong to the chemical derivatives of polyketides, which are synthesized from fatty acid precursors. Although acetogenins have displayed diverse biological activities, the anti-proliferative effect on human cancer cells has been widely reported. Acetogenins are inhibitors of complex I in the electron transport chain therefore they interrupt ATP synthesis in mitochondria. We tested a new acetogenins-enriched extract from the seed of Persea americana in order to investigate if any toxicity was induced on cardiac tissue and determine the involved mechanism. In isolated perfused heart we found that contractility was completely inhibited at an accumulative dose of 77 μg/ml. In isolated cardiomyocytes, the acetogenins-enriched extract induced apoptosis through the activation of the intrinsic pathway at 43 μg/ml. In isolated mitochondria, it inhibited complex I activity on NADH-linked respiration, as would be expected, but also induced permeability transition on succinate-linked respiration. Cyclosporine A, a known blocker of permeability transition, significantly prevented the permeability transition triggered by the acetogenins-enriched extract. In addition, our acetogenins-enriched extract inhibited ADP/ATP exchange, suggesting that an important element in phosphate or adenylate transport was affected. In this manner we suggest that acetogenins-enriched extract from Persea americana could directly modulate permeability transition, an entity not yet associated with the acetogenins' direct effects, resulting in cardiotoxicity.

Development of an Inertial Measurement Unit for Unmanned Aerial Vehicles

DTIC Science & Technology

2011-02-01

Tri-axis accelerometers Dual Angular rate gyros Micro-Controller board Battery Rubber isolation stands wireless comunication module (XBee...University. Special thanks to Mr. Jesse McAvoy & Mr. Laith Sahawneh for all the support and valuable scientific contributions. gxk gyk gzk gxb

Kotov Exercising on the TVIS during Expedition 15

NASA Image and Video Library

2007-05-06

ISS015-E-07005 (6 May 2007) --- Cosmonaut Oleg V. Kotov, Expedition 15 flight engineer representing Russia's Federal Space Agency, equipped with a bungee harness, exercises on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

TVIS belt inspection on Expedition 12

NASA Image and Video Library

2006-02-13

ISS012-E-18210 (13 Feb. 2006) --- Astronaut William S. (Bill) McArthur, Expedition 12 commander and NASA space station science officer, works with the Treadmill Vibration Isolation System (TVIS) during in-flight maintenance (IFM) in the Zvezda Service Module of the International Space Station.

Flight Engineer Donald R. Pettit exercises on the TVIS in the SM during Expedition Six

NASA Image and Video Library

2003-03-20

ISS006-E-45265 (20 March 2003) --- Astronaut Donald R. Pettit, Expedition 6 NASA ISS science officer, exercises on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module on the International Space Station (ISS).

Kotov Exercising on the TVIS during Expedition 15

NASA Image and Video Library

2007-05-06

ISS015-E-07003 (6 May 2007) --- Cosmonaut Oleg V. Kotov, Expedition 15 flight engineer representing Russia's Federal Space Agency, equipped with a bungee harness, exercises on the Treadmill Vibration Isolation System (TVIS) in the Zvezda Service Module of the International Space Station.

CALCIUM RELEASE FROM NERVOUS TISSUE - EXPERIMENTAL RESULTS AND POSSIBLE MECHANISMS

EPA Science Inventory

The research discussed in this paper was first conceived following a report by Bawin et al (1975) which demonstrated that amplitude-modulated radiofrequency (RF) fields could preferentially cause a biochemical change in isolated brain tissue depending on the specific frequency of...

High voltage power supply with modular series resonant inverters

DOEpatents

Dreifuerst, Gary R.; Merritt, Bernard T.

1995-01-01

A relatively small and compact high voltage, high current power supply for a laser utilizes a plurality of modules containing series resonant half bridge inverters. A pair of reverse conducting thyristors are incorporated in each series resonant inverter module such that the series resonant inverter modules are sequentially activated in phases 360.degree./n apart, where n=number of modules for n>2. Selective activation of the modules allows precise output control reducing ripple and improving efficiency. Each series resonant half bridge inverter module includes a transformer which has a cooling manifold for actively circulating a coolant such as water, to cool the transformer core as well as selected circuit elements. Conductors connecting and forming various circuit components comprise hollow, electrically conductive tubes such as copper. Coolant circulates through the tubes to remove heat. The conductive tubes act as electrically conductive lines for connecting various components of the power supply. Where it is desired to make electrical isolation breaks, tubes comprised of insulating material such as nylon are used to provide insulation and continue the fluid circuit.

High voltage power supply with modular series resonant inverters

DOEpatents

Dreifuerst, G.R.; Merritt, B.T.

1995-07-18

A relatively small and compact high voltage, high current power supply for a laser utilizes a plurality of modules containing series resonant half bridge inverters. A pair of reverse conducting thyristors are incorporated in each series resonant inverter module such that the series resonant inverter modules are sequentially activated in phases 360{degree}/n apart, where n=number of modules for n>2. Selective activation of the modules allows precise output control reducing ripple and improving efficiency. Each series resonant half bridge inverter module includes a transformer which has a cooling manifold for actively circulating a coolant such as water, to cool the transformer core as well as selected circuit elements. Conductors connecting and forming various circuit components comprise hollow, electrically conductive tubes such as copper. Coolant circulates through the tubes to remove heat. The conductive tubes act as electrically conductive lines for connecting various components of the power supply. Where it is desired to make electrical isolation breaks, tubes comprised of insulating material such as nylon are used to provide insulation and continue the fluid circuit. 11 figs.

Using Next-Generation Sequencing to Explore Genetics and Race in the High School Classroom

PubMed Central

Yang, Xinmiao; Hartman, Mark R.; Harrington, Kristin T.; Etson, Candice M.; Fierman, Matthew B.; Slonim, Donna K.; Walt, David R.

2017-01-01

With the development of new sequencing and bioinformatics technologies, concepts relating to personal genomics play an increasingly important role in our society. To promote interest and understanding of sequencing and bioinformatics in the high school classroom, we developed and implemented a laboratory-based teaching module called “The Genetics of Race.” This module uses the topic of race to engage students with sequencing and genetics. In the experimental portion of this module, students isolate their own mitochondrial DNA using standard biotechnology techniques and collect next-generation sequencing data to determine which of their classmates are most and least genetically similar to themselves. We evaluated the efficacy of this module by administering a pretest/posttest evaluation to measure student knowledge related to sequencing and bioinformatics, and we also conducted a survey at the conclusion of the module to assess student attitudes. Upon completion of our Genetics of Race module, students demonstrated significant learning gains, with lower-performing students obtaining the highest gains, and developed more positive attitudes toward scientific research. PMID:28408407

Triterpene esters from Uncaria rhynchophylla drive potent IL-12-dependent Th1 polarization.

PubMed

Umeyama, Akemi; Yahisa, Yoshinori; Okada, Minori; Okayama, Eriko; Uda, Ayaka; Shoji, Noboru; Lee, Je-Jung; Takei, Masao; Hashimoto, Toshihiro

2010-10-01

Dendritic cells (DC) are key antigen-presenting cells that link innate and adaptive immunity and ultimately activate antigen-specific T cells. In the current study, we demonstrated that two triterpene esters, uncarinic acid C (1) and uncarinic acid D (2), which are isolated from the hooks of Uncaria rhynchophylla, activate phenotypic and cytokine production alterations in DC. We also show that 1 and 2 modulate human DC function in a fashion that favors Th1 cell polarization. The effect of 1 (E configuration at the 2' position) was approximately 20 times more potent than that of 2 (Z configuration at 2'). These results indicated that the configuration of the 2' double bond greatly effects activity. Thus, 1 and 2 may prove useful as DC-based vaccines for cancer immunotherapy.

Integrins as Modulators of Transforming Growth Factor Beta Signaling in Dermal Fibroblasts During Skin Regeneration After Injury.

PubMed

Boo, Stellar; Dagnino, Lina

2013-06-01

Abnormal wound repair results from disorders in granulation tissue remodeling, and can lead to hypertrophic scarring and fibrosis. Excessive scarring can compromise tissue function and decrease tissue resistance to additional injuries. The development of potential therapies to minimize scarring is, thus, necessary to address an important clinical problem. It has been clearly established that multiple cytokines and growth factors participate in the regulation of cutaneous wound healing. More recently, it has become apparent that these factors do not necessarily activate isolated signaling pathways. Rather, in some cases, there is cross-modulation of several cellular pathways involved in this process. Two of the key pathways that modulate each other during wound healing are activated by transforming growth factor-β and by extracellular matrix proteins acting through integrins. The pathogenesis of excessive scarring upon wound healing is not fully understood, as a result of the complexity of this process. However, the fact that many pathways combine to produce fibrosis provides multiple potential therapeutic targets. Some of them have been identified, such as focal adhesion kinase and integrin-linked kinase. Currently, a major challenge is to develop pharmacological inhibitors of these proteins with therapeutic value to promote efficient wound repair. The ability to better understand how different pathways crosstalk during wound repair and to identify and pharmacologically modulate key factors that contribute to the regulation of multiple wound-healing pathways could potentially provide effective therapeutic targets to decrease or prevent excessive scar formation and/or development of fibrosis.

Particle separation by phase modulated surface acoustic waves.

PubMed

Simon, Gergely; Andrade, Marco A B; Reboud, Julien; Marques-Hueso, Jose; Desmulliez, Marc P Y; Cooper, Jonathan M; Riehle, Mathis O; Bernassau, Anne L

2017-09-01

High efficiency isolation of cells or particles from a heterogeneous mixture is a critical processing step in lab-on-a-chip devices. Acoustic techniques offer contactless and label-free manipulation, preserve viability of biological cells, and provide versatility as the applied electrical signal can be adapted to various scenarios. Conventional acoustic separation methods use time-of-flight and achieve separation up to distances of quarter wavelength with limited separation power due to slow gradients in the force. The method proposed here allows separation by half of the wavelength and can be extended by repeating the modulation pattern and can ensure maximum force acting on the particles. In this work, we propose an optimised phase modulation scheme for particle separation in a surface acoustic wave microfluidic device. An expression for the acoustic radiation force arising from the interaction between acoustic waves in the fluid was derived. We demonstrated, for the first time, that the expression of the acoustic radiation force differs in surface acoustic wave and bulk devices, due to the presence of a geometric scaling factor. Two phase modulation schemes are investigated theoretically and experimentally. Theoretical findings were experimentally validated for different mixtures of polystyrene particles confirming that the method offers high selectivity. A Monte-Carlo simulation enabled us to assess performance in real situations, including the effects of particle size variation and non-uniform acoustic field on sorting efficiency and purity, validating the ability to separate particles with high purity and high resolution.

Second LDEF Post-Retrieval Symposium interim results of experiment A0034

NASA Technical Reports Server (NTRS)

Linton, Roger C.; Kamenetzky, Rachel R.

1993-01-01

Thermal control coatings and contaminant collector mirrors were exposed on the leading and trailing edge modules of Long Duration Exposure Facility (LDEF) experiment A0034 to provide a basis of comparison for investigating the role of atomic oxygen in the stimulation of volatile outgassing products. The exposure of identical thermal coatings on both the leading and trailing edges of the LDEF and the additional modified exposure of identical coatings under glass windows and metallic covers in each of the flight modules provided multiple combinations of space environmental exposure to the coatings and the contaminant collector mirrors. Investigations were made to evaluate the effects of the natural space and the induced environments on the thermal coatings and the collector mirrors to differentiate the sources of observed material degradation. Two identical flight units were fabricated for the LDEF mission, each of which included twenty-five thermal control coatings mounted in isolated compartments, each with an adjacent contaminant collector mirror mounted on the wall. The covers of the flight units included apertures for each compartment, exposing the thermal coatings directly to the space environment. Six of these compartments were sealed with ultraviolet-grade transmitting quartz windows and four other compartments were sealed with aluminum covers. One module of this passive LDEF experiment, occupying one-sixth of a full tray, was mounted in Tray C9 (leading edge), while the other identical module was mounted in Tray C3 (trailing edge).

Proanthocyanidins Modulate MicroRNA Expression in Human HepG2 Cells

PubMed Central

Arola-Arnal, Anna; Bladé, Cinta

2011-01-01

Mi(cro)RNAs are small non-coding RNAs of 18-25 nucleotides in length that modulate gene expression at the post-transcriptional level. These RNAs have been shown to be involved in a several biological processes, human diseases and metabolic disorders. Proanthocyanidins, which are the most abundant polyphenol class in the human diet, have positive health effects on a variety of metabolic disorders such as inflammation, obesity, diabetes and insulin resistance. The present study aimed to evaluate whether proanthocyanidin-rich natural extracts modulate miRNA expression. Using microarray analysis and Q-PCR, we investigated miRNA expression in HepG2 cells treated with proanthocyanidins. Our results showed that when HepG2 cells were treated with grape seed proanthocyanidin extract (GSPE), cocoa proanthocyanidin extract (CPE) or pure epigallocatechin gallate isolated from green tea (EGCG), fifteen, six and five differentially expressed miRNAs, respectively, were identified out of 904 mRNAs. Specifically, miR-30b* was downregulated by the three treatments, and treatment with GSPE or CPE upregulated miR-1224-3p, miR-197 and miR-532-3p. Therefore, these results provide evidence of the capacity of dietary proanthocyanidins to influence microRNA expression, suggesting a new mechanism of action of proanthocyanidins. PMID:21998738

The peripheral clock regulates human pigmentation.

PubMed

Hardman, Jonathan A; Tobin, Desmond J; Haslam, Iain S; Farjo, Nilofer; Farjo, Bessam; Al-Nuaimi, Yusur; Grimaldi, Benedetto; Paus, Ralf

2015-04-01

Although the regulation of pigmentation is well characterized, it remains unclear whether cell-autonomous controls regulate the cyclic on-off switching of pigmentation in the hair follicle (HF). As human HFs and epidermal melanocytes express clock genes and proteins, and given that core clock genes (PER1, BMAL1) modulate human HF cycling, we investigated whether peripheral clock activity influences human HF pigmentation. We found that silencing BMAL1 or PER1 in human HFs increased HF melanin content. Furthermore, tyrosinase expression and activity, as well as TYRP1 and TYRP2 mRNA levels, gp100 protein expression, melanocyte dendricity, and the number gp100+ HF melanocytes, were all significantly increased in BMAL1 and/or PER1-silenced HFs. BMAL1 or PER1 silencing also increased epidermal melanin content, gp100 protein expression, and tyrosinase activity in human skin. These effects reflect direct modulation of melanocytes, as BMAL1 and/or PER1 silencing in isolated melanocytes increased tyrosinase activity and TYRP1/2 expression. Mechanistically, BMAL1 knockdown reduces PER1 transcription, and PER1 silencing induces phosphorylation of the master regulator of melanogenesis, microphthalmia-associated transcription factor, thus stimulating human melanogenesis and melanocyte activity in situ and in vitro. Therefore, the molecular clock operates as a cell-autonomous modulator of human pigmentation and may be targeted for future therapeutic strategies.

Auditory Selective Attention to Speech Modulates Activity in the Visual Word Form Area

PubMed Central

Yoncheva, Yuliya N.; Zevin, Jason D.; Maurer, Urs

2010-01-01

Selective attention to speech versus nonspeech signals in complex auditory input could produce top-down modulation of cortical regions previously linked to perception of spoken, and even visual, words. To isolate such top-down attentional effects, we contrasted 2 equally challenging active listening tasks, performed on the same complex auditory stimuli (words overlaid with a series of 3 tones). Instructions required selectively attending to either the speech signals (in service of rhyme judgment) or the melodic signals (tone-triplet matching). Selective attention to speech, relative to attention to melody, was associated with blood oxygenation level–dependent (BOLD) increases during functional magnetic resonance imaging (fMRI) in left inferior frontal gyrus, temporal regions, and the visual word form area (VWFA). Further investigation of the activity in visual regions revealed overall deactivation relative to baseline rest for both attention conditions. Topographic analysis demonstrated that while attending to melody drove deactivation equivalently across all fusiform regions of interest examined, attending to speech produced a regionally specific modulation: deactivation of all fusiform regions, except the VWFA. Results indicate that selective attention to speech can topographically tune extrastriate cortex, leading to increased activity in VWFA relative to surrounding regions, in line with the well-established connectivity between areas related to spoken and visual word perception in skilled readers. PMID:19571269

Modulation of drug resistance and biofilm formation of Staphylococcus aureus isolated from the oral cavity of Tunisian children.

PubMed

Zmantar, Tarek; Ben Slama, Rihab; Fdhila, Kais; Kouidhi, Bochra; Bakhrouf, Amina; Chaieb, Kamel

This study aims to investigate the antimicrobial and the anti-biofilm activities of Lactobacillus plantarum extract (LPE) against a panel of oral Staphylococcus aureus (n=9) and S. aureus ATCC 25923. The in vitro ability of LPE to modulate bacterial resistance to tetracycline, benzalchonium chloride, and chlorhexidine were tested also. The minimum inhibitory concentrations (MICs) and the minimal bactericidal concentrations of Lactobacillus plantarum extract, tetracycline, benzalchonium chloride and clohrhexidine were determined in absence and in presence of a sub-MIC doses of LPE (1/2 MIC). In addition, the LPE potential to inhibit biofilm formation was assessed by microtiter plate and atomic force microscopy assays. Statistical analysis was performed on SPSS v. 17.0 software using Friedman test and Wilcoxon signed ranks test. These tests were used to assess inter-group difference (p<0.05). Our results revealed that LPE exhibited a significant antimicrobial and anti-biofilm activities against the tested strains. A synergistic effect of LPEs and drug susceptibility was observed with a 2-8-fold reduction. LPE may be considered to have resistance-modifying activity. A more detailed investigation is necessary to determine the active compound responsible for therapeutic and disinfectant modulation. Copyright © 2016 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

Determinants of genetic structure in a nonequilibrium metapopulation of the plant Silene latifolia.

PubMed

Fields, Peter D; Taylor, Douglas R

2014-01-01

Population genetic differentiation will be influenced by the demographic history of populations, opportunities for migration among neighboring demes and founder effects associated with repeated extinction and recolonization. In natural populations, these factors are expected to interact with each other and their magnitudes will vary depending on the spatial distribution and age structure of local demes. Although each of these effects has been individually identified as important in structuring genetic variance, their relative magnitude is seldom estimated in nature. We conducted a population genetic analysis in a metapopulation of the angiosperm, Silene latifolia, from which we had more than 20 years of data on the spatial distribution, demographic history, and extinction and colonization of demes. We used hierarchical Bayesian methods to disentangle which features of the populations contributed to among population variation in allele frequencies, including the magnitude and direction of their effects. We show that population age, long-term size and degree of connectivity all combine to affect the distribution of genetic variance; small, recently-founded, isolated populations contributed most to increase FST in the metapopulation. However, the effects of population size and population age are best understood as being modulated through the effects of connectivity to other extant populations, i.e. FST diminishes as populations age, but at a rate that depends how isolated the population is. These spatial and temporal correlates of population structure give insight into how migration, founder effect and within-deme genetic drift have combined to enhance and restrict genetic divergence in a natural metapopulation.

Myeloid Cell Prostaglandin E2 Receptor EP4 Modulates Cytokine Production but Not Atherogenesis in a Mouse Model of Type 1 Diabetes.

PubMed

Vallerie, Sara N; Kramer, Farah; Barnhart, Shelley; Kanter, Jenny E; Breyer, Richard M; Andreasson, Katrin I; Bornfeldt, Karin E

2016-01-01

Type 1 diabetes mellitus (T1DM) is associated with cardiovascular complications induced by atherosclerosis. Prostaglandin E2 (PGE2) is often raised in states of inflammation, including diabetes, and regulates inflammatory processes. In myeloid cells, a key cell type in atherosclerosis, PGE2 acts predominately through its Prostaglandin E Receptor 4 (EP4; Ptger4) to modulate inflammation. The effect of PGE2-mediated EP4 signaling specifically in myeloid cells on atherosclerosis in the presence and absence of diabetes is unknown. Because diabetes promotes atherosclerosis through increased arterial myeloid cell accumulation, we generated a myeloid cell-targeted EP4-deficient mouse model (EP4M-/-) of T1DM-accelerated atherogenesis to investigate the relationship between myeloid cell EP4, inflammatory phenotypes of myeloid cells, and atherogenesis. Diabetic mice exhibited elevated plasma PGE metabolite levels and elevated Ptger4 mRNA in macrophages, as compared with non-diabetic littermates. PGE2 increased Il6, Il1b, Il23 and Ccr7 mRNA while reducing Tnfa mRNA through EP4 in isolated myeloid cells. Consistently, the stimulatory effect of diabetes on peritoneal macrophage Il6 was mediated by PGE2-EP4, while PGE2-EP4 suppressed the effect of diabetes on Tnfa in these cells. In addition, diabetes exerted effects independent of myeloid cell EP4, including a reduction in macrophage Ccr7 levels and increased early atherogenesis characterized by relative lesional macrophage accumulation. These studies suggest that this mouse model of T1DM is associated with increased myeloid cell PGE2-EP4 signaling, which is required for the stimulatory effect of diabetes on IL-6, markedly blunts the effect of diabetes on TNF-α and does not modulate diabetes-accelerated atherogenesis.

Myeloid Cell Prostaglandin E2 Receptor EP4 Modulates Cytokine Production but Not Atherogenesis in a Mouse Model of Type 1 Diabetes

PubMed Central

Vallerie, Sara N.; Kramer, Farah; Barnhart, Shelley; Kanter, Jenny E.; Breyer, Richard M.; Andreasson, Katrin I.; Bornfeldt, Karin E.

2016-01-01

Type 1 diabetes mellitus (T1DM) is associated with cardiovascular complications induced by atherosclerosis. Prostaglandin E2 (PGE2) is often raised in states of inflammation, including diabetes, and regulates inflammatory processes. In myeloid cells, a key cell type in atherosclerosis, PGE2 acts predominately through its Prostaglandin E Receptor 4 (EP4; Ptger4) to modulate inflammation. The effect of PGE2-mediated EP4 signaling specifically in myeloid cells on atherosclerosis in the presence and absence of diabetes is unknown. Because diabetes promotes atherosclerosis through increased arterial myeloid cell accumulation, we generated a myeloid cell-targeted EP4-deficient mouse model (EP4M-/-) of T1DM-accelerated atherogenesis to investigate the relationship between myeloid cell EP4, inflammatory phenotypes of myeloid cells, and atherogenesis. Diabetic mice exhibited elevated plasma PGE metabolite levels and elevated Ptger4 mRNA in macrophages, as compared with non-diabetic littermates. PGE2 increased Il6, Il1b, Il23 and Ccr7 mRNA while reducing Tnfa mRNA through EP4 in isolated myeloid cells. Consistently, the stimulatory effect of diabetes on peritoneal macrophage Il6 was mediated by PGE2-EP4, while PGE2-EP4 suppressed the effect of diabetes on Tnfa in these cells. In addition, diabetes exerted effects independent of myeloid cell EP4, including a reduction in macrophage Ccr7 levels and increased early atherogenesis characterized by relative lesional macrophage accumulation. These studies suggest that this mouse model of T1DM is associated with increased myeloid cell PGE2-EP4 signaling, which is required for the stimulatory effect of diabetes on IL-6, markedly blunts the effect of diabetes on TNF-α and does not modulate diabetes-accelerated atherogenesis. PMID:27351842

Synchronized conductivity modulation to realize broadband lossless magnetic-free non-reciprocity.

PubMed

Dinc, Tolga; Tymchenko, Mykhailo; Nagulu, Aravind; Sounas, Dimitrios; Alu, Andrea; Krishnaswamy, Harish

2017-10-06

Recent research has explored the spatiotemporal modulation of permittivity to break Lorentz reciprocity in a manner compatible with integrated-circuit fabrication. However, permittivity modulation is inherently weak and accompanied by loss due to carrier injection, particularly at higher frequencies, resulting in large insertion loss, size, and/or narrow operation bandwidths. Here, we show that the presence of absorption in an integrated electronic circuit may be counter-intuitively used to our advantage to realize a new generation of magnet-free non-reciprocal components. We exploit the fact that conductivity in semiconductors provides a modulation index several orders of magnitude larger than permittivity. While directly associated with loss in static systems, we show that properly synchronized conductivity modulation enables loss-free, compact and extremely broadband non-reciprocity. We apply these concepts to obtain a wide range of responses, from isolation to gyration and circulation, and verify our findings by realizing a millimeter-wave (25 GHz) circulator fully integrated in complementary metal-oxide-semiconductor technology.Optical non-reciprocity achieved through refractive index modulation can have its challenges and limitations. Here, Dinc et al. introduce the concept of non-reciprocity based on synchronized spatio-temporal modulation of conductivity to achieve different types of non-reciprocal functionality.

Development of versatile non-homologous end joining-based knock-in module for genome editing.

PubMed

Sawatsubashi, Shun; Joko, Yudai; Fukumoto, Seiji; Matsumoto, Toshio; Sugano, Shigeo S

2018-01-12

CRISPR/Cas9-based genome editing has dramatically accelerated genome engineering. An important aspect of genome engineering is efficient knock-in technology. For improved knock-in efficiency, the non-homologous end joining (NHEJ) repair pathway has been used over the homology-dependent repair pathway, but there remains a need to reduce the complexity of the preparation of donor vectors. We developed the versatile NHEJ-based knock-in module for genome editing (VIKING). Using the consensus sequence of the time-honored pUC vector to cut donor vectors, any vector with a pUC backbone could be used as the donor vector without customization. Conditions required to minimize random integration rates of the donor vector were also investigated. We attempted to isolate null lines of the VDR gene in human HaCaT keratinocytes using knock-in/knock-out with a selection marker cassette, and found 75% of clones isolated were successfully knocked-in. Although HaCaT cells have hypotetraploid genome composition, the results suggest multiple clones have VDR null phenotypes. VIKING modules enabled highly efficient knock-in of any vectors harboring pUC vectors. Users now can insert various existing vectors into an arbitrary locus in the genome. VIKING will contribute to low-cost genome engineering.