SacB-SacR gene cassette as the negative selection marker to suppress Agrobacterium overgrowth in Agrobacterium-mediated plant transformation

Science.gov (United States)

Agrobacterium overgrowth is a common problem in Agrobacterium-mediated plant transformation. To suppress the Agrobacterium overgrowth, various antibiotics have been used during plant tissue culture steps. The antibiotics are expensive and may adversely affect plant cell differentiation and reduce ...

Jasmonic acid-mediated defense suppresses brassinosteroid-mediated susceptibility to Rice black streaked dwarf virus infection in rice.

Science.gov (United States)

He, Yuqing; Zhang, Hehong; Sun, Zongtao; Li, Junmin; Hong, Gaojie; Zhu, Qisong; Zhou, Xuebiao; MacFarlane, Stuart; Yan, Fei; Chen, Jianping

2017-04-01

Plant hormones play a vital role in plant immune responses. However, in contrast to the relative wealth of information on hormone-mediated immunity in dicot plants, little information is available on monocot-virus defense systems. We used a high-throughput-sequencing approach to compare the global gene expression of Rice black-streaked dwarf virus (RBSDV)-infected rice plants with that of healthy plants. Exogenous hormone applications and transgenic rice were used to test RBSDV infectivity and pathogenicity. Our results revealed that the jasmonic acid (JA) pathway was induced while the brassinosteroid (BR) pathway was suppressed in infected plants. Foliar application of methyl jasmonate (MeJA) or brassinazole (BRZ) resulted in a significant reduction in RBSDV incidence, while epibrassinolide (BL) treatment increased RBSDV infection. Infection studies using coi1-13 and Go mutants demonstrated JA-mediated resistance and BR-mediated susceptibility to RBSDV infection. A mixture of MeJA and BL treatment resulted in a significant reduction in RBSDV infection compared with a single BL treatment. MeJA application efficiently suppressed the expression of BR pathway genes, and this inhibition depended on the JA coreceptor OsCOI1. Collectively, our results reveal that JA-mediated defense can suppress the BR-mediated susceptibility to RBSDV infection. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Sulforaphane inhibits osteoclast differentiation by suppressing the cell-cell fusion molecules DC-STAMP and OC-STAMP

International Nuclear Information System (INIS)

Takagi, Tomohiro; Inoue, Hirofumi; Takahashi, Nobuyuki; Katsumata-Tsuboi, Rie; Uehara, Mariko

2017-01-01

Sulforaphane (SFN), a kind of isothiocyanate, is derived from broccoli sprouts. It has anti-tumor, anti-inflammatory, and anti-oxidation activity. The molecular function of SFN in the inhibition of osteoclast differentiation is not well-documented. In this study, we assessed the effect of SFN on osteoclast differentiation in vitro. SFN inhibited osteoclast differentiation in both bone marrow cells and RAW264.7 cells. Key molecules involved in the inhibitory effects of SFN on osteoclast differentiation were determined using a microarray analysis, which showed that SFN inhibits osteoclast-associated genes, such as osteoclast-associated receptor (OSCAR), nuclear factor of activated T cells cytoplasmic-1, tartrate-resistant acid phosphatase, and cathepsin K. Moreover, the mRNA expression levels of the cell-cell fusion molecules dendritic cell specific transmembrane protein (DC-STAMP) and osteoclast stimulatory transmembrane protein (OC-STAMP) were strongly suppressed in cells treated with SFN. Furthermore, SFN increased the phosphorylation of signal transducer and activator of transcription 1 (STAT1), a regulator of macrophage and osteoclast cell fusion. Thus, our data suggested that SFN significantly inhibits the cell-cell fusion molecules DC-STAMP and OC-STAMP by inducing the phosphorylation of STAT1 (Tyr701), which might be regulated by interactions with OSCAR. - Highlights: • Sulforaphane inhibited osteoclast differentiation and osteoclast cell-fusion. • Sulforaphane suppressed not only NFATc1, but also cell-cell fusion molecules, DC-STAMP and OC-STAMP. • Sulforaphane decreased multinucleated osteoclasts, whereas increased mono-nucleated osteoclasts. • Sulforaphane inhibits the cell-cell fusion by inducing the phosphorylation of STAT1 (Tyr701).

Arctigenin suppresses unfolded protein response and sensitizes glucose deprivation-mediated cytotoxicity of cancer cells.

Science.gov (United States)

Sun, Shengrong; Wang, Xiong; Wang, Changhua; Nawaz, Ahmed; Wei, Wen; Li, Juanjuan; Wang, Lijun; Yu, De-Hua

2011-01-01

The involvement of unfolded protein response (UPR) activation in tumor survival and resistance to chemotherapies suggests a new anticancer strategy targeting UPR pathway. Arctigenin, a natural product, has been recently identified for its antitumor activity with selective toxicity against cancer cells under glucose starvation with unknown mechanism. Here we found that arctigenin specifically blocks the transcriptional induction of two potential anticancer targets, namely glucose-regulated protein-78 (GRP78) and its analog GRP94, under glucose deprivation, but not by tunicamycin. The activation of other UPR pathways, e.g., XBP-1 and ATF4, by glucose deprivation was also suppressed by arctigenin. A further transgene experiment showed that ectopic expression of GRP78 at least partially rescued arctigenin/glucose starvation-mediated cell growth inhibition, suggesting the causal role of UPR suppression in arctigenin-mediated cytotoxicity under glucose starvation. These observations bring a new insight into the mechanism of action of arctigenin and may lead to the design of new anticancer therapeutics. © Georg Thieme Verlag KG Stuttgart · New York.

Vorinostat, a histone deacetylase inhibitor, suppresses dendritic cell function and ameliorates experimental autoimmune encephalomyelitis.

Science.gov (United States)

Ge, Zhenzhen; Da, Yurong; Xue, Zhenyi; Zhang, Kai; Zhuang, Hao; Peng, Meiyu; Li, Yan; Li, Wen; Simard, Alain; Hao, Junwei; Yao, Zhi; Zhang, Rongxin

2013-03-01

Vorinostat, a histone deacetylase inhibitor, has been used clinically as an anticancer drug and also has immunosuppressive properties. However, the underlying mechanisms of effects of vorinostat on central nervous system (CNS) inflammatory diseases remain incomplete. Here, this study investigates the effects of vorinostat on human CD14(+) monocyte-derived dendritic cells (DCs) and mouse immature DC in vitro. Furthermore, we explore the therapeutic effects and cellular mechanisms of vorinostat on animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) in vivo. Our findings demonstrate that vorinostat inhibited human CD14(+) monocyte-derived DCs differentiation, maturation, endocytosis, and further inhibited mDCs' stimulation of allogeneic T-cell proliferation. In addition, vorinostat inhibited DC-directed Th1- (Type 1T helper) and Th17-polarizing cytokine production. Furthermore, vorinostat ameliorated Th1- and Th17-mediated EAE by reducing CNS inflammation and demyelination. What's more, Th1 and Th17 cell functions were suppressed in vorinostat-treated EAE mice. Finally, vorinostat suppressed expression of costimulatory molecules of DC in EAE mice. These suggest therapeutic effects of vorinostat on EAE which may by suppress DCs and DCs-mediated Th1 and Th17 cell functions. Our findings warrant further investigation in the potential of vorinostat for the treatment of human multiple sclerosis. Copyright © 2012. Published by Elsevier Inc.

DC-SIGN mediates avian H5N1 influenza virus infection in cis and in trans

International Nuclear Information System (INIS)

Wang, S.-F.; Huang, Jason C.; Lee, Y.-M.; Liu, S.-J.; Chan, Yu-Jiun; Chau, Y.-P.; Chong, P.; Chen, Y.-M.A.

2008-01-01

DC-SIGN, a C-type lectin receptor expressed in dendritic cells (DCs), has been identified as a receptor for human immunodeficiency virus type 1, hepatitis C virus, Ebola virus, cytomegalovirus, dengue virus, and the SARS coronavirus. We used H5N1 pseudotyped and reverse-genetics (RG) virus particles to study their ability to bind with DC-SIGN. Electronic microscopy and functional assay results indicate that pseudotyped viruses containing both HA and NA proteins express hemagglutination and are capable of infecting cells expressing α-2,3-linked sialic acid receptors. Results from a capture assay show that DC-SIGN-expressing cells (including B-THP-1/DC-SIGN and T-THP-1/DC-SIGN) and peripheral blood dendritic cells are capable of transferring H5N1 pseudotyped and RG virus particles to target cells; this action can be blocked by anti-DC-SIGN monoclonal antibodies. In summary, (a) DC-SIGN acts as a capture or attachment molecule for avian H5N1 virus, and (b) DC-SIGN mediates infections in cis and in trans

DC8 and DC13 var genes associated with severe malaria bind avidly to diverse endothelial cells.

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Marion Avril

Full Text Available During blood stage infection, Plasmodium falciparum infected erythrocytes (IE bind to host blood vessels. This virulence determinant enables parasites to evade spleen-dependent killing mechanisms, but paradoxically in some cases may reduce parasite fitness by killing the host. Adhesion of infected erythrocytes is mediated by P. falciparum erythrocyte membrane protein 1 (PfEMP1, a family of polymorphic adhesion proteins encoded by var genes. Whereas cerebral binding and severe malaria are associated with parasites expressing DC8 and DC13 var genes, relatively little is known about the non-brain endothelial selection on severe malaria adhesive types. In this study, we selected P. falciparum-IEs on diverse endothelial cell types and demonstrate that DC8 and DC13 var genes were consistently among the major var transcripts selected on non-brain endothelial cells (lung, heart, bone marrow. To investigate the molecular basis for this avid endothelial binding activity, recombinant proteins were expressed from the predominant upregulated DC8 transcript, IT4var19. In-depth binding comparisons revealed that multiple extracellular domains from this protein bound brain and non-brain endothelial cells, and individual domains largely did not discriminate between different endothelial cell types. Additionally, we found that recombinant DC8 and DC13 CIDR1 domains exhibited a widespread endothelial binding activity and could compete for DC8-IE binding to brain endothelial cells, suggesting they may bind the same host receptor. Our findings provide new insights into the interaction of severe malaria adhesive types and host blood vessels and support the hypothesis that parasites causing severe malaria express PfEMP1 variants with a superior ability to adhere to diverse endothelial cell types, and may therefore endow these parasites with a growth and transmission advantage.

Why expressive suppression does not pay? Cognitive costs of negative emotion suppression: The mediating role of subjective tense-arousal

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Szczygieł Dorota

2015-09-01

Full Text Available The aim of this paper was to contribute to a broader understanding of the cognitive consequences of expressive suppression. Specifically, we examined whether the deteriorating effect of expressive suppression on cognitive functioning is caused by tense arousal enhanced by suppression. Two experiments were performed in order to test this prediction. In both studies we tested the effect of expressive suppression on working memory, as measured with a backwards digit-span task (Study 1, N = 43 and anagram problem-solving task (Study 2, N = 60. In addition, in Study 2 we tested whether expressive suppression degrades memory of the events that emerged during the period of expressive suppression. Both studies were conducted in a similar design: Participants watched a film clip which evoked negative emotions (i.e. disgust in Study 1 and a combination of sadness and anxiety in Study 2 under the instruction to suppress those negative emotions or (in the control condition to simply watch the film. The results of these experiments lead to three conclusions. First, the results reveal that expressive suppression degrades memory of the events that emerged during the period of expressive suppression and leads to poorer performance on working memory tasks, as measured with a backwards digit-span task and anagram problem-solving task. Second, the results indicate that expressive suppression leads to a significant increase in subjective tense arousal. Third, the results support our prediction that expressive suppression decreases cognitive performance through its effects on subjective tense arousal. The results of the Study 1 show that tense arousal activated during expressive suppression of disgust fully mediates the negative effect of suppression on working memory as measured with a backwards digit-span task. The results of Study 2 reveal that subjective tense arousal elicited while suppressing sadness and anxiety mediates both the effect of suppression on

High-Voltage DC-DC Converter Topology for PV Energy Utilization - Investigation and Implementation

DEFF Research Database (Denmark)

Sanjeevikumar, Padmanaban; Blaabjerg, Frede; Wheeler, Patrick

2017-01-01

This paper exploited the utilization of photovoltaic (PV) energy system with high-voltage (HV) output DC-DC converter. Classical boost converters are used for both renewable energy integration and HV applications, but limited by reducing output/efficiency in performance. Moreover, as parasitic...... elements suppress the power transfer ratio, converter needs to maximize the PV energy utilization. This investigation study focused to include additional parasitic elements (voltage-lift technique) to a standard DC-DC buck converter and to overcome all the above drawbacks to maximize the PV power...

DC-Compensated Current Transformer.

Science.gov (United States)

Ripka, Pavel; Draxler, Karel; Styblíková, Renata

2016-01-20

Instrument current transformers (CTs) measure AC currents. The DC component in the measured current can saturate the transformer and cause gross error. We use fluxgate detection and digital feedback compensation of the DC flux to suppress the overall error to 0.15%. This concept can be used not only for high-end CTs with a nanocrystalline core, but it also works for low-cost CTs with FeSi cores. The method described here allows simultaneous measurements of the DC current component.

Beliefs about emotions mediate the relationship between emotional suppression and quality of life in irritable bowel syndrome.

Science.gov (United States)

Bowers, Hannah; Wroe, Abigail

2016-01-01

Cross-sectional and experimental research has demonstrated an association between emotional suppression and IBS. However, the relationship is not well understood. To examine the relationships between emotional suppression, we compare the measures of beliefs about emotions and quality of life in irritable bowel syndrome (IBS) with healthy controls. Online questionnaires measured beliefs about emotions, emotional suppression and IBS-related quality of life in participants with (n = 87) and without (n = 37) IBS. Mediation analyses and group comparisons were used to explore the role of emotional suppression and beliefs about emotions in this sample. IBS participants held significantly more beliefs about the unacceptability of emotions compared to healthy controls despite no differences in emotional suppression. The relationship between beliefs about emotions and quality of life was not mediated by emotional suppression. However, the relationship between emotional suppression and quality of life was mediated by beliefs about emotions. The findings suggest a role of beliefs about emotions and emotional suppression in IBS, where emotional suppression may relate to changes in beliefs about emotions and consequently quality of life. This is discussed in relation to the cognitive-behavioural model of medically unexplained symptoms.

Histamine H2 Receptor-Mediated Suppression of Intestinal Inflammation by Probiotic Lactobacillus reuteri.

Science.gov (United States)

Gao, Chunxu; Major, Angela; Rendon, David; Lugo, Monica; Jackson, Vanessa; Shi, Zhongcheng; Mori-Akiyama, Yuko; Versalovic, James

2015-12-15

Probiotics and commensal intestinal microbes suppress mammalian cytokine production and intestinal inflammation in various experimental model systems. Limited information exists regarding potential mechanisms of probiotic-mediated immunomodulation in vivo. In this report, we demonstrate that specific probiotic strains of Lactobacillus reuteri suppress intestinal inflammation in a trinitrobenzene sulfonic acid (TNBS)-induced mouse colitis model. Only strains that possess the hdc gene cluster, including the histidine decarboxylase and histidine-histamine antiporter genes, can suppress colitis and mucosal cytokine (interleukin-6 [IL-6] and IL-1β in the colon) gene expression. Suppression of acute colitis in mice was documented by diminished weight loss, colonic injury, serum amyloid A (SAA) protein concentrations, and reduced uptake of [(18)F]fluorodeoxyglucose ([(18)F]FDG) in the colon by positron emission tomography (PET). The ability of probiotic L. reuteri to suppress colitis depends on the presence of a bacterial histidine decarboxylase gene(s) in the intestinal microbiome, consumption of a histidine-containing diet, and signaling via the histamine H2 receptor (H2R). Collectively, luminal conversion of l-histidine to histamine by hdc(+) L. reuteri activates H2R, and H2R signaling results in suppression of acute inflammation within the mouse colon. Probiotics are microorganisms that when administered in adequate amounts confer beneficial effects on the host. Supplementation with probiotic strains was shown to suppress intestinal inflammation in patients with inflammatory bowel disease and in rodent colitis models. However, the mechanisms of probiosis are not clear. Our current studies suggest that supplementation with hdc(+) L. reuteri, which can convert l-histidine to histamine in the gut, resulted in suppression of colonic inflammation. These findings link luminal conversion of dietary components (amino acid metabolism) by gut microbes and probiotic-mediated

Controlling DC-DC converters by chaos-based pulse width modulation to reduce EMI

International Nuclear Information System (INIS)

Li Hong; Zhang Bo; Li Zhong; Halang, Wolfgang A.; Chen Guanrong

2009-01-01

In this paper, periodic and chaotic behaviors of DC-DC converters under certain parametric conditions are simulated, experimentally verified, and analyzed. Motivated by the work of J.H.B. Deane and D.C. Hamill in 1996, where chaotic phenomena are useful in suppressing electromagnetic interference (EMI) by adjusting the parameters of the DC-DC converter and making it operate in chaos, a chaos-based pulse width modulation (CPWM) is proposed to distribute the harmonics of the DC-DC converters continuously and evenly over a wide frequency range, thereby reducing the EMI. The output waves and spectral properties of the EMI are simulated and analyzed as the carrier frequency or amplitude changes with regard to different chaotic maps. Simulation and experimental results are given to illustrate the effectiveness of the proposed CPWM, which provides a good example of applying chaos theory in engineering practice.

Analysis of the Coupling Behavior of PEM Fuel Cells and DC-DC Converters

Directory of Open Access Journals (Sweden)

Achim Kienle

2009-03-01

Full Text Available The connection between PEM fuel cells and common DC-DC converters is examined. The analysis is model-based and done for boost, buck and buck-boost converters. In a first step, the effect of the converter ripples upon the PEM fuel cell is shown. They introduce oscillations in the fuel cell. Their appearance is explained, discussed and possibilities for their suppression are given. After that, the overall behaviors of the coupled fuel cell-converter systems are analyzed. It is shown, that neither stationary multiplicities nor oscillations can be introduced by the couplings and therefore separate control approaches for both the PEMFC and the DC-DC converters are applicable.

Test Results of Selected Commercial DC/DC Converters under Cryogenic Temperatures - A Digest

Science.gov (United States)

Patterson, Richard; Hammoud, Ahmad

2010-01-01

DC/DC converters are widely used in space power systems in the areas of power management and distribution, signal conditioning, and motor control. Design of DC/DC converters to survive cryogenic temperatures will improve the power system performance, simplify design, and reduce development and launch costs. In this work, the performance of nine COTS modular, low-tomedium power DC/DC converters was investigated under cryogenic temperatures. The converters were evaluated in terms of their output regulation, efficiency, and input and output currents. At a given temperature, these properties were obtained at various input voltages and at different load levels. A summary on the performance of the tested converters was given. More comprehensive testing and in-depth analysis of performance under long-term exposure to extreme temperatures are deemed necessary to establish the suitability of these and other devices for use in the harsh environment of space exploration missions.

DC/DC converters for integration of double-layer condensers in onboard power supply; DC/DC-Wandler zur Einbindung von Doppelschichtkondensatoren in das Fahrzeugenergiebordnetz

Energy Technology Data Exchange (ETDEWEB)

Polenov, Dieter

2010-01-15

The paper discusses DC/DC converters for integration of double layer condensers into the onboard power system. First, requirements on DC/DC converters are listed and compared on the basis of three exemplary applications. A DC/DC converter concept is developed for decoupling transient high-power loads like electric steering systems. Three different topologies are compared using a specially developed method in order to find the best solution for the given application. In order to establish adequate criteria for selecting the switching frequency and inductivities of storage throttles, the influence of the trottle power change on the switching characteristics of the MOSFETs and on certain ranges of EMP interference emissions is investigated. As methods of optimising the operation of the synchronous rectifiers, parallel connection of Schottky diodes and synchronous rectifiers as well as the variation of the shut-off dead times of synchronous rectifiers were investigated. Further, a concept for converter control was developed in consideration of the intended application and topology. Finally, selected aspects for implementation of the DC/DC converter concept are presented as well as the results of experimental investigations.

DC-Compensated Current Transformer †

Science.gov (United States)

Ripka, Pavel; Draxler, Karel; Styblíková, Renata

2016-01-01

Instrument current transformers (CTs) measure AC currents. The DC component in the measured current can saturate the transformer and cause gross error. We use fluxgate detection and digital feedback compensation of the DC flux to suppress the overall error to 0.15%. This concept can be used not only for high-end CTs with a nanocrystalline core, but it also works for low-cost CTs with FeSi cores. The method described here allows simultaneous measurements of the DC current component. PMID:26805830

Acetylation Is Crucial for p53-Mediated Ferroptosis and Tumor Suppression

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Shang-Jui Wang

2016-10-01

Full Text Available Although previous studies indicate that loss of p53-mediated cell cycle arrest, apoptosis, and senescence does not completely abrogate its tumor suppression function, it is unclear how the remaining activities of p53 are regulated. Here, we have identified an acetylation site at lysine K98 in mouse p53 (or K101 for human p53. Whereas the loss of K98 acetylation (p53K98R alone has very modest effects on p53-mediated transactivation, simultaneous mutations at all four acetylation sites (p534KR: K98R+ 3KR[K117R+K161R+K162R] completely abolish its ability to regulate metabolic targets, such as TIGAR and SLC7A11. Notably, in contrast to p533KR, p534KR is severely defective in suppressing tumor growth in mouse xenograft models. Moreover, p534KR is still capable of inducing the p53-Mdm2 feedback loop, but p53-dependent ferroptotic responses are markedly abrogated. Together, these data indicate the critical role of p53 acetylation in ferroptotic responses and its remaining tumor suppression activity.

Multi Bus DC-DC Converter in Electric Hybrid Vehicles

Science.gov (United States)

Krithika, V.; Subramaniam, C.; Sridharan, R.; Geetha, A.

2018-04-01

This paper is cotncerned with the design, simulation and fabrication of the prototype of a Multi bus DC- DC converter operating from 42V DC and delivering 14V DC and 260V DC. As a result, three DC buses are interconnected through a single power electronic circuitry. Such a requirement is energized in the development of a hybrid electric automobile which uses the technology of fuel cell. This is implemented by using a Bidirectional DC-DC converter configuration which is ideally suitable for multiple outputs with mutual electrical isolation. For the sake of reduced size and cost of step-up transformer, selection of a high frequency switching cycle at 10 KHz was done.

Volatile-mediated suppression of plant pathogens is related to soil properties and microbial community composition

NARCIS (Netherlands)

Van Agtmaal, M.; Straathof, A.L.; Termorshuizen, Aad J; Lievens, Bart; Hoffland, Ellis; De Boer, W.

2018-01-01

There is increasing evidence that the soil microbial community produces a suite of volatile organic compounds that suppress plant pathogens. However, it remains unknown which soil properties and management practices influence volatile-mediated pathogen suppression. The aim of this study was to

Volatile-mediated suppression of plant pathogens is related to soil properties and microbial community composition

NARCIS (Netherlands)

Agtmaal, van Maaike; Straathof, Angela L.; Termorshuizen, Aad; Lievens, Bart; Hoffland, Ellis; Boer, de Wietse

2018-01-01

There is increasing evidence that the soil microbial community produces a suite of volatile organic compounds that suppress plant pathogens. However, it remains unknown which soil properties and management practices influence volatile-mediated pathogen suppression. The aim of this study was to

groE mutants of Escherichia coli are defective in umuDC-dependent UV mutagenesis

International Nuclear Information System (INIS)

Donnelly, C.E.; Walker, G.C.

1989-01-01

Overexpression of the SOS-inducible umuDC operon of Escherichia coli results in the inability of these cells to grow at 30 degrees C. Mutations in several heat shock genes suppress this cold sensitivity. Suppression of umuD+C+-dependent cold sensitivity appears to occur by two different mechanisms. We show that mutations in lon and dnaK heat shock genes suppress cold sensitivity in a lexA-dependent manner. In contrast, mutations in groES, groEL, and rpoH heat shock genes suppress cold sensitivity regardless of the transcriptional regulation of the umuDC genes. We have also found that mutations in groES and groEL genes are defective in umuDC-dependent UV mutagenesis. This defect can be suppressed by increased expression of the umuDC operon. The mechanism by which groE mutations affect umuDC gene product function may be related to the stability of the UmuC protein, since the half-life of this protein is shortened because of mutations at the groE locus

Attentional selection and suppression in children and adults.

Science.gov (United States)

Sun, Meirong; Wang, Encong; Huang, Jing; Zhao, Chenguang; Guo, Jialiang; Li, Dongwei; Sun, Li; Du, Boqi; Ding, Yulong; Song, Yan

2018-05-15

The fundamental role of covert spatial attention is to enhance the processing of attended items while simultaneously ignoring irrelevant items. However, relatively little is known about how brain electrophysiological activities associated with target selection and distractor suppression are involved as they develop and become fully functional. The current study aimed to identify the neurophysiological bases of the development of covert spatial attention, focusing on electroencephalographic (EEG) markers of attentional selection (N2pc) and suppression (P D ). EEG data were collected from healthy young adults and typically developing children (9-15 years old) as they searched for a shape singleton target in either the absence or the presence of a salient-but-irrelevant color singleton distractor. The ERP results showed that a lateral shape target elicited a smaller N2pc in children compared with adults regardless of whether a distractor was present or not. Moreover, the target-elicited N2pc was always followed by a similar positivity in both age groups. Counterintuitively, a lateral salient-but-irrelevant distractor elicited a large P D in children with low behavioral accuracy, whereas high-accuracy children exhibited a small and "adult-like" P D . More importantly, we found no evidence for a correlation between the target-elicited N2pc and the distractor-elicited P D in either age group. Our results provide neurophysiological evidence for the developmental differences between target selection and distractor suppression. Compared with adults, 9-15-year-old children deploy insufficient attentional selection resources to targets but use "adult-like" or even more attentional suppression resources to resist irrelevant distractors. A video abstract of this article can be viewed at: https://www.youtube.com/watch?v=NhWapx0d75I. © 2018 John Wiley & Sons Ltd.

Effect of arc suppression on the physical properties of low temperature dc magnetron sputtered tantalum thin films

International Nuclear Information System (INIS)

Subrahmanyam, A.; Valleti, Krishna; Joshi, Srikant V.; Sundararajan, G.

2007-01-01

Arcing is a common phenomenon in the sputtering process. Arcs and glow discharges emit electrons which may influence the physical properties of films. This article reports the properties of tantalum (Ta) thin films prepared by continuous dc magnetron sputtering in normal and arc-suppression modes. The substrate temperature was varied in the range of 300-673 K. The tantalum films were ∼1.8 μm thick and have good adherence to 316 stainless steel and single-crystal silicon substrates. The phase of the Ta thin film determines the electrical and tribological properties. The films deposited at 300 K using both methods were crystallized in a tetragonal structure (β phase) with a smooth surface (grain size of ∼10 nm) and exhibited an electrical resistivity of ∼194 μΩ cm and a hardness of ∼20 GPa. When the substrate temperature was 473 K and higher, the arc-suppression mode appears to influence the films to crystallize in the α phase with a grain size of ∼40 nm, whereas the normal power mode gave mixed phases β and α beyond 473 K, the arc-suppression mode yields larger grain sizes in the Ta thin films and the hardness decreases. These changes in the physical properties in arc-suppression mode are attributed to either the change in plasma characteristics or the energetic particle bombardment onto the substrate, or both

Egr2 induced during DC development acts as an intrinsic negative regulator of DC immunogenicity.

Science.gov (United States)

Miah, Mohammad Alam; Byeon, Se Eun; Ahmed, Md Selim; Yoon, Cheol-Hee; Ha, Sang-Jun; Bae, Yong-Soo

2013-09-01

Early growth response gene 2 (Egr2), which encodes a zinc finger transcription factor, is rapidly and transiently induced in various cell types independently of de novo protein synthesis. Although a role for Egr2 is well established in T-cell development, Egr2 expression and its biological function in dendritic cells (DCs) have not yet been described. Here, we demonstrate Egr2 expression during DC development, and its role in DC-mediated immune responses. Egr2 is expressed in the later stage of DC development from BM precursor cells. Even at steady state, Egr2 is highly expressed in mouse splenic DCs. Egr2-knockdown (Egr2-KD) DCs showed increased levels of major histocompatability complex (MHC) class I and II and co-stimulatory molecules, and enhanced antigen uptake and migratory capacities. Furthermore, Egr2-KD abolished SOCS1 expression and signal transducer and activator of transcription 5 (STAT5) activation during DC development, probably resulting in the enhancement of IL-12 expression and Th1 immunogenicity of a DC vaccine. DC-mediated cytotoxic T lymphocyte (CTL) activation and antitumor immunity were significantly enhanced by Egr2-KD, and impaired by Egr2 overexpression in antigen-pulsed DC vaccines. These data suggest that Egr2 acts as an intrinsic negative regulator of DC immunogenicity and can be an attractive molecular target for DC vaccine development. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Glechoma hederacea Suppresses RANKL-mediated Osteoclastogenesis.

Science.gov (United States)

Hwang, J K; Erkhembaatar, M; Gu, D R; Lee, S H; Lee, C H; Shin, D M; Lee, Y R; Kim, M S

2014-07-01

Glechoma hederacea (GH), commonly known as ground-ivy or gill-over-the-ground, has been extensively used in folk remedies for relieving symptoms of inflammatory disorders. However, the molecular mechanisms underlying the therapeutic action of GH are poorly understood. Here, we demonstrate that GH constituents inhibit osteoclastogenesis by abrogating receptor activator of nuclear κ-B ligand (RANKL)-induced free cytosolic Ca(2+) ([Ca(2+)]i) oscillations. To evaluate the effect of GH on osteoclastogenesis, we assessed the formation of multi-nucleated cells (MNCs), enzymatic activity of tartrate-resistant acidic phosphatase (TRAP), expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), and [Ca(2+)]i alterations in response to treatment with GH ethanol extract (GHE) in primarily cultured bone marrow-derived macrophages (BMMs). Treatment of RANKL-stimulated or non-stimulated BMMs with GHE markedly suppressed MNC formation, TRAP activity, and NFATc1 expression in a dose-dependent manner. Additionally, GHE treatment induced a large transient elevation in [Ca(2+)]i while suppressing RANKL-induced [Ca(2+)]i oscillations, which are essential for NFATc1 activation. GHE-evoked increase in [Ca(2+)]i was dependent on extracellular Ca(2+) and was inhibited by 1,4-dihydropyridine (DHP), inhibitor of voltage-gated Ca(2+) channels (VGCCs), but was independent of store-operated Ca(2+) channels. Notably, after transient [Ca(2+)] elevation, treatment with GHE desensitized the VGCCs, resulting in an abrogation of RANKL-induced [Ca(2+)]i oscillations and MNC formation. These findings demonstrate that treatment of BMMs with GHE suppresses RANKL-mediated osteoclastogenesis by activating and then desensitizing DHP-sensitive VGCCs, suggesting potential applications of GH in the treatment of bone disorders, such as periodontitis, osteoporosis, and rheumatoid arthritis. © International & American Associations for Dental Research.

Endoglin-mediated suppression of prostate cancer invasion is regulated by activin and bone morphogenetic protein type II receptors.

Directory of Open Access Journals (Sweden)

Michael J Breen

Full Text Available Mortality from prostate cancer (PCa is due to the formation of metastatic disease. Understanding how that process is regulated is therefore critical. We previously demonstrated that endoglin, a type III transforming growth factor β (TGFβ superfamily receptor, suppresses human PCa cell invasion and metastasis. Endoglin-mediated suppression of invasion was also shown by us to be dependent upon the type I TGFβ receptor, activin receptor-like kinase 2 (ALK2, and the downstream effector, Smad1. In this study we demonstrate for the first time that two type II TGFβ receptors are required for endoglin-mediated suppression of invasion: activin A receptor type IIA (ActRIIA and bone morphogenetic protein receptor type II (BMPRII. Downstream signaling through these receptors is predominantly mediated by Smad1. ActRIIA stimulates Smad1 activation in a kinase-dependent manner, and this is required for suppression of invasion. In contrast BMPRII regulates Smad1 in a biphasic manner, promoting Smad1 signaling through its kinase domain but suppressing it through its cytoplasmic tail. BMPRII's Smad1-regulatory effects are dependent upon its expression level. Further, its ability to suppress invasion is independent of either kinase function or tail domain. We demonstrate that ActRIIA and BMPRII physically interact, and that each also interacts with endoglin. The current findings demonstrate that both BMPRII and ActRIIA are necessary for endoglin-mediated suppression of human PCa cell invasion, that they have differential effects on Smad1 signaling, that they make separate contributions to regulation of invasion, and that they functionally and physically interact.

Multitarget Tracking with Spatial Nonmaximum Suppressed Sensor Selection

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Liang Ma

2015-01-01

Full Text Available Multitarget tracking is one of the most important applications of sensor networks, yet it is an extremely challenging problem since multisensor multitarget tracking itself is nontrivial and the difficulty is further compounded by sensor management. Recently, random finite set based Bayesian framework has opened doors for multitarget tracking with sensor management, which is modelled in the framework of partially observed Markov decision process (POMDP. However, sensor management posed as a POMDP is in essence a combinatorial optimization problem which is NP-hard and computationally unacceptable. In this paper, we propose a novel sensor selection method for multitarget tracking. We first present the sequential multi-Bernoulli filter as a centralized multisensor fusion scheme for multitarget tracking. In order to perform sensor selection, we define the hypothesis information gain (HIG of a sensor to measure its information quantity when the sensor is selected alone. Then, we propose spatial nonmaximum suppression approach to select sensors with respect to their locations and HIGs. Two distinguished implementations have been provided using the greedy spatial nonmaximum suppression. Simulation results verify the effectiveness of proposed sensor selection approach for multitarget tracking.

Transcriptional Dynamics Driving MAMP-Triggered Immunity and Pathogen Effector-Mediated Immunosuppression in Arabidopsis Leaves Following Infection with Pseudomonas syringae pv tomato DC3000.

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Lewis, Laura A; Polanski, Krzysztof; de Torres-Zabala, Marta; Jayaraman, Siddharth; Bowden, Laura; Moore, Jonathan; Penfold, Christopher A; Jenkins, Dafyd J; Hill, Claire; Baxter, Laura; Kulasekaran, Satish; Truman, William; Littlejohn, George; Prusinska, Justyna; Mead, Andrew; Steinbrenner, Jens; Hickman, Richard; Rand, David; Wild, David L; Ott, Sascha; Buchanan-Wollaston, Vicky; Smirnoff, Nick; Beynon, Jim; Denby, Katherine; Grant, Murray

2015-11-01

Transcriptional reprogramming is integral to effective plant defense. Pathogen effectors act transcriptionally and posttranscriptionally to suppress defense responses. A major challenge to understanding disease and defense responses is discriminating between transcriptional reprogramming associated with microbial-associated molecular pattern (MAMP)-triggered immunity (MTI) and that orchestrated by effectors. A high-resolution time course of genome-wide expression changes following challenge with Pseudomonas syringae pv tomato DC3000 and the nonpathogenic mutant strain DC3000hrpA- allowed us to establish causal links between the activities of pathogen effectors and suppression of MTI and infer with high confidence a range of processes specifically targeted by effectors. Analysis of this information-rich data set with a range of computational tools provided insights into the earliest transcriptional events triggered by effector delivery, regulatory mechanisms recruited, and biological processes targeted. We show that the majority of genes contributing to disease or defense are induced within 6 h postinfection, significantly before pathogen multiplication. Suppression of chloroplast-associated genes is a rapid MAMP-triggered defense response, and suppression of genes involved in chromatin assembly and induction of ubiquitin-related genes coincide with pathogen-induced abscisic acid accumulation. Specific combinations of promoter motifs are engaged in fine-tuning the MTI response and active transcriptional suppression at specific promoter configurations by P. syringae. © 2015 American Society of Plant Biologists. All rights reserved.

The role of inducer cells in mediating in vitro suppression of feline immunodeficiency virus replication

International Nuclear Information System (INIS)

Phadke, Anagha P.; Choi, In-Soo; Li Zhongxia; Weaver, Eric; Collisson, Ellen W.

2004-01-01

CD8 + T-cell-mediated suppression of feline immunodeficiency virus (FIV) replication has been described by several groups, although the mechanisms of activation and conditions for viral suppression vary with the methodologies. We have previously reported that CD8 + T-cell-mediated suppression of FIV replication required inducer cell stimulation of the effector cells. The focus of the present study was to examine the essential role of inducer cells required for the induction of this soluble anti-FIV activity. Both FIV-PPR-infected T cells and feline skin fibroblasts (FSF) infected with an alphavirus vector expressing FIV capsid or the irrelevant antigen lacZ, stimulated autologous or heterologous effector cells to produce supernatants that suppressed FIV replication. Thus, induction of this suppression of FIV replication did not strictly require autologous inducer cells and did not require the presence of FIV antigen. Anti-viral activity correlated with the presence of CD8 + T cells. Suppression was maximal when the inducer cells and the effector cells were in contact with each other, because separation of the inducer and effector cells by a 0.45-μm membrane reduced FIV suppression by approximately 50%. These findings emphasize the importance for membrane antigen interactions and cytokines in the optimal induction of effector cell synthesis of the soluble anti-FIV activity

Acoustic noise alters selective attention processes as indicated by direct current (DC) brain potential changes.

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Trimmel, Karin; Schätzer, Julia; Trimmel, Michael

2014-09-26

Acoustic environmental noise, even of low to moderate intensity, is known to adversely affect information processing in animals and humans via attention mechanisms. In particular, facilitation and inhibition of information processing are basic functions of selective attention. Such mechanisms can be investigated by analyzing brain potentials under conditions of externally directed attention (intake of environmental information) versus internally directed attention (rejection of environmental stimuli and focusing on memory/planning processes). This study investigated brain direct current (DC) potential shifts-which are discussed to represent different states of cortical activation-of tasks that require intake and rejection of environmental information under noise. It was hypothesized that without background noise rejection tasks would show more positive DC potential changes compared to intake tasks and that under noise both kinds of tasks would show positive DC shifts as an expression of cortical inhibition caused by noise. DC potential shifts during intake and rejection tasks were analyzed at 16 standard locations in 45 persons during irrelevant speech or white noise vs. control condition. Without noise, rejection tasks were associated with more positive DC potential changes compared to intake tasks. During background noise, however, this difference disappeared and both kinds of tasks led to positive DC shifts. Results suggest-besides some limitations-that noise modulates selective attention mechanisms by switching to an environmental information processing and noise rejection mode, which could represent a suggested "attention shift". Implications for fMRI studies as well as for public health in learning and performance environments including susceptible persons are discussed.

Acoustic Noise Alters Selective Attention Processes as Indicated by Direct Current (DC Brain Potential Changes

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Karin Trimmel

2014-09-01

Full Text Available Acoustic environmental noise, even of low to moderate intensity, is known to adversely affect information processing in animals and humans via attention mechanisms. In particular, facilitation and inhibition of information processing are basic functions of selective attention. Such mechanisms can be investigated by analyzing brain potentials under conditions of externally directed attention (intake of environmental information versus internally directed attention (rejection of environmental stimuli and focusing on memory/planning processes. This study investigated brain direct current (DC potential shifts—which are discussed to represent different states of cortical activation—of tasks that require intake and rejection of environmental information under noise. It was hypothesized that without background noise rejection tasks would show more positive DC potential changes compared to intake tasks and that under noise both kinds of tasks would show positive DC shifts as an expression of cortical inhibition caused by noise. DC potential shifts during intake and rejection tasks were analyzed at 16 standard locations in 45 persons during irrelevant speech or white noise vs. control condition. Without noise, rejection tasks were associated with more positive DC potential changes compared to intake tasks. During background noise, however, this difference disappeared and both kinds of tasks led to positive DC shifts. Results suggest—besides some limitations—that noise modulates selective attention mechanisms by switching to an environmental information processing and noise rejection mode, which could represent a suggested “attention shift”. Implications for fMRI studies as well as for public health in learning and performance environments including susceptible persons are discussed.

Immunotherapy: Shifting the Balance of Cell-Mediated Immunity and Suppression in Human Prostate Cancer

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Tucker, Jo A.; Jochems, Caroline [Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Gulley, James L. [Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Schlom, Jeffrey, E-mail: js141c@nih.gov; Tsang, Kwong Y. [Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

2012-12-11

Active immunotherapy is dependent on the ability of the immune system to recognize and respond to tumors. Despite overwhelming evidence to support a cell-mediated immune response to prostate cancer, it is insufficient to eradicate the disease. This is likely due to a high level of suppression at the tumor site from a variety of sources, including immunosuppressive cells. Immune cells entering the tumor microenvironment may be inhibited directly by the tumor, stromal cells or other immune cells that have been induced to adopt a suppressive phenotype. The resurgence of interest in immunotherapy following the approval of sipuleucel-T and ipilimumab by the Food and Drug Administration has brought about new strategies for overcoming tumor-mediated suppression and bolstering anti-tumor responses. Improved understanding of the immune response to prostate cancer can lead to new combination therapies, such as the use of vaccine with small molecule and checkpoint inhibitors or other immunotherapies.

Immunotherapy: Shifting the Balance of Cell-Mediated Immunity and Suppression in Human Prostate Cancer

International Nuclear Information System (INIS)

Tucker, Jo A.; Jochems, Caroline; Gulley, James L.; Schlom, Jeffrey; Tsang, Kwong Y.

2012-01-01

Active immunotherapy is dependent on the ability of the immune system to recognize and respond to tumors. Despite overwhelming evidence to support a cell-mediated immune response to prostate cancer, it is insufficient to eradicate the disease. This is likely due to a high level of suppression at the tumor site from a variety of sources, including immunosuppressive cells. Immune cells entering the tumor microenvironment may be inhibited directly by the tumor, stromal cells or other immune cells that have been induced to adopt a suppressive phenotype. The resurgence of interest in immunotherapy following the approval of sipuleucel-T and ipilimumab by the Food and Drug Administration has brought about new strategies for overcoming tumor-mediated suppression and bolstering anti-tumor responses. Improved understanding of the immune response to prostate cancer can lead to new combination therapies, such as the use of vaccine with small molecule and checkpoint inhibitors or other immunotherapies

Suppression of immune-mediated liver injury after vaccination with attenuated pathogenic cells.

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Mei, Yunhua; Wang, Ying; Xu, Lingyun

2007-05-15

Cell vaccination via immunization with attenuated pathogenic cells is an effective preventive method that has been successfully applied in several animal models of inflammatory or autoimmune diseases. Concanavalin A (Con A)-induced hepatitis (CIH) is a commonly used experimental model to study immune-mediated liver injury. Multiple cell types including T lymphocytes, macrophages and neutrophils have been found to be involved in the pathogenesis of CIH. In this study, we used attenuated spleen lymphocytes or peripheral blood lymphocytes as vaccines to investigate whether they could induce protective immune responses to prevent mice from developing CIH. We found that mice receiving such vaccination before CIH induction developed much milder diseases, exhibited a lower level of alanine aminotransferase (ALT) released into their plasma and had less inflammatory lesions in their livers. Such CIH-suppression is dose- and frequency-dependent. The suppressive effect was associated with inhibition of several major inflammatory mediators, pro-inflammatory cytokines and chemokines.

Neisseria meningitidis expressing lgtB lipopolysaccharide targets DC-SIGN and modulates dendritic cell function.

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Steeghs, Liana; van Vliet, Sandra J; Uronen-Hansson, Heli; van Mourik, Andries; Engering, Anneke; Sanchez-Hernandez, Martha; Klein, Nigel; Callard, Robin; van Putten, Jos P M; van der Ley, Peter; van Kooyk, Yvette; van de Winkel, Jan G J

2006-02-01

Neisseria meningitidis lipopolysaccharide (LPS) has been identified as a major determinant of dendritic cell (DC) function. Here we report that one of a series of meningococcal mutants with defined truncations in the lacto-N-neotetraose outer core of the LPS exhibited unique strong adhesion and internalization properties towards DC. These properties were mediated by interaction of the GlcNAc(beta1-3)-Gal(beta1-4)-Glc-R oligosaccharide outer core of lgtB LPS with the dendritic-cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) lectin receptor. Activation of DC-SIGN with this novel oligosaccharide ligand skewed T-cell responses driven by DC towards T helper type 1 activity. Thus, the use of lgtB LPS may provide a powerful instrument to selectively induce the desired arm of the immune response and potentially increase vaccine efficacy.

Glycogen synthase kinase-3 inhibitors suppress the AR-V7-mediated transcription and selectively inhibit cell growth in AR-V7-positive prostate cancer cells.

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Nakata, Daisuke; Koyama, Ryokichi; Nakayama, Kazuhide; Kitazawa, Satoshi; Watanabe, Tatsuya; Hara, Takahito

2017-06-01

Recent evidence suggests that androgen receptor (AR) splice variants, including AR-V7, play a pivotal role in resistance to androgen blockade in prostate cancer treatment. The development of new therapeutic agents that can suppress the transcriptional activities of AR splice variants has been anticipated as the next generation treatment of castration-resistant prostate cancer. High-throughput screening of AR-V7 signaling inhibitors was performed using an AR-V7 reporter system. The effects of a glycogen synthase kinase-3 (GSK3) inhibitor, LY-2090314, on endogenous AR-V7 signaling were evaluated in an AR-V7-positive cell line, JDCaP-hr, by quantitative reverse transcription polymerase chain reaction. The relationship between AR-V7 signaling and β-catenin signaling was assessed using RNA interference. The effect of LY-2090314 on cell growth in various prostate cancer cell lines was also evaluated. We identified GSK3 inhibitors as transcriptional suppressors of AR-V7 using a high-throughput screen with an AR-V7 reporter system. LY-2090314 suppressed the reporter activity and endogenous AR-V7 activity in JDCaP-hr cells. Because silencing of β-catenin partly rescued the suppression, it was evident that the suppression was mediated, at least partially, via the activation of β-catenin signaling. AR-V7 signaling and β-catenin signaling reciprocally regulate each other in JDCaP-hr cells, and therefore, GSK3 inhibition can repress AR-V7 transcriptional activity by accumulating intracellular β-catenin. Notably, LY-2090314 selectively inhibited the growth of AR-V7-positive prostate cancer cells in vitro. Our findings demonstrate the potential of GSK3 inhibitors in treating advanced prostate cancer driven by AR splice variants. In vivo evaluation of AR splice variant-positive prostate cancer models will help illustrate the overall significance of GSK3 inhibitors in treating prostate cancer. © 2017 Wiley Periodicals, Inc.

Multifaceted effects of synthetic TLR2 ligand and Legionella pneumophilia on Treg-mediated suppression of T cell activation

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Sutmuller Roger PM

2011-03-01

Full Text Available Abstract Background Regulatory T cells (Treg play a crucial role in maintaining immune homeostasis and self-tolerance. The immune suppressive effects of Tregs should however be limited in case effective immunity is required against pathogens or cancer cells. We previously found that the Toll-like receptor 2 (TLR2 agonist, Pam3CysSK4, directly stimulated Tregs to expand and temporarily abrogate their suppressive capabilities. In this study, we evaluate the effect of Pam3CysSK4 and Legionella pneumophila, a natural TLR2 containing infectious agent, on effector T (Teff cells and dendritic cells (DCs individually and in co-cultures with Tregs. Results TLR2 agonists can directly provide a co-stimulatory signal inducing enhanced proliferation and cytokine production of naive CD4+ Teff cells. With respect to cytokine production, DCs appear to be most sensitive to low amounts of TLR agonists. Using wild type and TLR2-deficient cells in Treg suppression assays, we accordingly show that all cells (e.g. Treg, Teff cells and DCs contributed to overcome Treg-mediated suppression of Teff cell proliferation. Furthermore, while TLR2-stimulated Tregs readily lost their ability to suppress Teff cell proliferation, cytokine production by Teff cells was still suppressed. Similar results were obtained upon stimulation with TLR2 ligand containing bacteria, Legionella pneumophila. Conclusions These findings indicate that both synthetic and natural TLR2 agonists affect DCs, Teff cells and Treg directly, resulting in multi-modal modulation of Treg-mediated suppression of Teff cells. Moreover, Treg-mediated suppression of Teff cell proliferation is functionally distinct from suppression of cytokine secretion.

Nonequilibrium response of an electron-mediated charge density wave ordered material to a large dc electric field

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Matveev, O. P.; Shvaika, A. M.; Devereaux, T. P.; Freericks, J. K.

2016-01-01

Using the Kadanoff-Baym-Keldysh formalism, we employ nonequilibrium dynamical mean-field theory to exactly solve for the nonlinear response of an electron-mediated charge-density-wave-ordered material. We examine both the dc current and the order parameter of the conduction electrons as the ordered system is driven by the electric field. Although the formalism we develop applies to all models, for concreteness, we examine the charge-density-wave phase of the Falicov-Kimball model, which displays a number of anomalous behaviors including the appearance of subgap density of states as the temperature increases. These subgap states should have a significant impact on transport properties, particularly the nonlinear response of the system to a large dc electric field.

The Chaotic-Based Control of Three-Port Isolated Bidirectional DC/DC Converters for Electric and Hybrid Vehicles

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Zheng Wang

2016-01-01

Full Text Available Three-port isolated (TPI bidirectional DC/DC converters have three energy ports and offer advantages of large voltage gain, galvanic isolation ability and high power density. For this reason this kind of converters are suitable to connect different energy sources and loads in electric and hybrid vehicles. The purpose of this paper is to propose chaotic modulation and the related control scheme for TPI bidirectional DC/DC converters, in such a way that the switching harmonic peaks can be suppressed in spectrum and the conducted electromagnetic interference (EMI is reduced. Two chaotic modulation strategies, namely the continuously chaotic modulation and the discretely chaotic modulation are presented. These two chaotic modulation strategies are applied for TPI bidirectional DC/DC converters with shifted-phase angle based control and phase-shifted PWM control. Both simulation and experiments are given to verify the validity of the proposed chaotic modulation-based control schemes.

Role of the carbohydrate-binding sites of griffithsin in the prevention of DC-SIGN-mediated capture and transmission of HIV-1.

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Bart Hoorelbeke

Full Text Available BACKGROUND: The glycan-targeting C-type DC-SIGN lectin receptor is implicated in the transmission of the human immunodeficiency virus (HIV by binding the virus and transferring the captured HIV-1 to CD4(+ T lymphocytes. Carbohydrate binding agents (CBAs have been reported to block HIV-1 infection. We have now investigated the potent mannose-specific anti-HIV CBA griffithsin (GRFT on its ability to inhibit the capture of HIV-1 to DC-SIGN, its DC-SIGN-directed transmission to CD4(+ T-lymphocytes and the role of the three carbohydrate-binding sites (CBS of GRFT in these processes. FINDINGS: GRFT inhibited HIV-1(IIIB infection of CEM and HIV-1(NL4.3 infection of C8166 CD4(+ T-lymphocytes at an EC50 of 0.059 and 0.444 nM, respectively. The single mutant CBS variants of GRFT (in which a key Asp in one of the CBS was mutated to Ala were about ∼20 to 60-fold less potent to prevent HIV-1 infection and ∼20 to 90-fold less potent to inhibit syncytia formation in co-cultures of persistently HIV-1 infected HuT-78 and uninfected C8166 CD4(+ T-lymphocytes. GRFT prevents DC-SIGN-mediated virus capture and HIV-1 transmission to CD4(+ T-lymphocytes at an EC50 of 1.5 nM and 0.012 nM, respectively. Surface plasmon resonance (SPR studies revealed that wild-type GRFT efficiently blocked the binding between DC-SIGN and immobilized gp120, whereas the point mutant CBS variants of GRFT were ∼10- to 15-fold less efficient. SPR-analysis also demonstrated that wild-type GRFT and its single mutant CBS variants have the capacity to expel bound gp120 from the gp120-DC-SIGN complex in a dose dependent manner, a property that was not observed for HHA, another mannose-specific potent anti-HIV-1 CBA. CONCLUSION: GRFT is inhibitory against HIV gp120 binding to DC-SIGN, efficiently prevents DC-SIGN-mediated transfer of HIV-1 to CD4(+ T-lymphocytes and is able to expel gp120 from the gp120-DC-SIGN complex. Functionally intact CBS of GRFT are important for the optimal action of

Dopamine agonist suppression of rapid-eye-movement sleep is secondary to sleep suppression mediated via limbic structures

International Nuclear Information System (INIS)

Miletich, R.S.

1985-01-01

The effects of pergolide, a direct dopamine receptor agonist, on sleep and wakefulness, motor behavior and 3 H-spiperone specific binding in limbic structures and striatum in rats was studied. The results show that pergolide induced a biphasic dose effect, with high doses increasing wakefulness and suppressing sleep while low dose decreased wakefulness, but increased sleep. It was shown that pergolide-induced sleep suppression was blocked by α-glupenthixol and pimozide, two dopamine receptor antagonists. It was further shown that pergolide merely delayed the rebound resulting from rapid-eye-movement (REM) sleep deprivation, that dopamine receptors stimulation had no direct effect on the period, phase or amplitude of the circadian rhythm of REM sleep propensity and that there was no alteration in the coupling of REM sleep episodes with S 2 episodes. Rapid-eye-movement sleep deprivation resulted in increased sensitivity to the pergolide-induced wakefulness stimulation and sleep suppression and pergolide-induced motor behaviors of locomotion and head bobbing. 3 H-spiperone specific binding to dopamine receptors was shown to be altered by REM sleep deprivation in the subcortical limbic structures. It is concluded that the REM sleep suppressing action of dopamine receptor stimulation is secondary to sleep suppression per se and not secondary to a unique effect on the REM sleep. Further, it is suggested that the wakefulness stimulating action of dopamine receptor agonists is mediated by activation of the dopamine receptors in the terminal areas of the mesolimbocortical dopamine projection system

Suppressive effects of lysozyme on polyphosphate-mediated vascular inflammatory responses

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Chung, Jiwoo [College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu 41566 (Korea, Republic of); Ku, Sae-Kwang [Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610 (Korea, Republic of); Lee, Suyeon [College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu 41566 (Korea, Republic of); Bae, Jong-Sup, E-mail: baejs@knu.ac.kr [College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu 41566 (Korea, Republic of)

2016-06-10

Lysozyme, found in relatively high concentration in blood, saliva, tears, and milk, protects us from the ever-present danger of bacterial infection. Previous studies have reported proinflammatory responses of endothelial cells to the release of polyphosphate(PolyP). In this study, we examined the anti-inflammatory responses and mechanisms of lysozyme and its effects on PolyP-induced septic activities in human umbilical vein endothelial cells (HUVECs) and mice. The survival rates, septic biomarker levels, behavior of human neutrophils, and vascular permeability were determined in PolyP-activated HUVECs and mice. Lysozyme suppressed the PolyP-mediated vascular barrier permeability, upregulation of inflammatory biomarkers, adhesion/migration of leukocytes, and activation and/or production of nuclear factor-κB, tumor necrosis factor-α, and interleukin-6. Furthermore, lysozyme demonstrated protective effects on PolyP-mediated lethal death and the levels of the related septic biomarkers. Therefore, these results indicated the therapeutic potential of lysozyme on various systemic inflammatory diseases, such as sepsis or septic shock. -- Highlights: •PolyP is shown to be an important mediator of vascular inflammation. •Lysozyme inhibited PolyP-mediated hyperpermeability. •Lysozyme inhibited PolyP-mediated septic response. •Lysozyme reduced PolyP-induced septic mortality.

Suppressive effects of lysozyme on polyphosphate-mediated vascular inflammatory responses

International Nuclear Information System (INIS)

Chung, Jiwoo; Ku, Sae-Kwang; Lee, Suyeon; Bae, Jong-Sup

2016-01-01

Lysozyme, found in relatively high concentration in blood, saliva, tears, and milk, protects us from the ever-present danger of bacterial infection. Previous studies have reported proinflammatory responses of endothelial cells to the release of polyphosphate(PolyP). In this study, we examined the anti-inflammatory responses and mechanisms of lysozyme and its effects on PolyP-induced septic activities in human umbilical vein endothelial cells (HUVECs) and mice. The survival rates, septic biomarker levels, behavior of human neutrophils, and vascular permeability were determined in PolyP-activated HUVECs and mice. Lysozyme suppressed the PolyP-mediated vascular barrier permeability, upregulation of inflammatory biomarkers, adhesion/migration of leukocytes, and activation and/or production of nuclear factor-κB, tumor necrosis factor-α, and interleukin-6. Furthermore, lysozyme demonstrated protective effects on PolyP-mediated lethal death and the levels of the related septic biomarkers. Therefore, these results indicated the therapeutic potential of lysozyme on various systemic inflammatory diseases, such as sepsis or septic shock. -- Highlights: •PolyP is shown to be an important mediator of vascular inflammation. •Lysozyme inhibited PolyP-mediated hyperpermeability. •Lysozyme inhibited PolyP-mediated septic response. •Lysozyme reduced PolyP-induced septic mortality.

Id1 suppresses anti-tumour immune responses and promotes tumour progression by impairing myeloid cell maturation.

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Papaspyridonos, Marianna; Matei, Irina; Huang, Yujie; do Rosario Andre, Maria; Brazier-Mitouart, Helene; Waite, Janelle C; Chan, April S; Kalter, Julie; Ramos, Ilyssa; Wu, Qi; Williams, Caitlin; Wolchok, Jedd D; Chapman, Paul B; Peinado, Hector; Anandasabapathy, Niroshana; Ocean, Allyson J; Kaplan, Rosandra N; Greenfield, Jeffrey P; Bromberg, Jacqueline; Skokos, Dimitris; Lyden, David

2015-04-29

A central mechanism of tumour progression and metastasis involves the generation of an immunosuppressive 'macroenvironment' mediated in part through tumour-secreted factors. Here we demonstrate that upregulation of the Inhibitor of Differentiation 1 (Id1), in response to tumour-derived factors, such as TGFβ, is responsible for the switch from dendritic cell (DC) differentiation to myeloid-derived suppressor cell expansion during tumour progression. Genetic inactivation of Id1 largely corrects the myeloid imbalance, whereas Id1 overexpression in the absence of tumour-derived factors re-creates it. Id1 overexpression leads to systemic immunosuppression by downregulation of key molecules involved in DC differentiation and suppression of CD8 T-cell proliferation, thus promoting primary tumour growth and metastatic progression. Furthermore, advanced melanoma patients have increased plasma TGFβ levels and express higher levels of ID1 in myeloid peripheral blood cells. This study reveals a critical role for Id1 in suppressing the anti-tumour immune response during tumour progression and metastasis.

On and off controlled resonant dc-dc power converter

DEFF Research Database (Denmark)

2015-01-01

The present invention relates to a resonant DC-DC power converter comprising an input side circuit comprising a positive and a negative input terminal for receipt of an input voltage or current and an output side circuit comprising positive and negative output terminals for supply of a converter...... output voltage and connection to a converter load. The resonant DC-DC power converter further comprises a rectification circuit connected between an output of a resonant network and the output side circuit. The resonant network is configured for alternatingly being charged from the input voltage...... or current and discharged through the rectification circuit by a first controllable switch arrangement in accordance with a first switch control signal. A second controllable switch arrangement of the resonant DC-DC power converter is configured to select a first impedance characteristic of the resonant...

Weight Suppression Predicts Bulimic Symptoms at 20-year Follow-up: The Mediating Role of Drive for Thinness

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Bodell, Lindsay P.; Brown, Tiffany A.; Keel, Pamela K.

2016-01-01

Weight suppression predicts the onset and maintenance of bulimic syndromes. Despite this finding, no study has examined psychological mechanisms contributing to these associations using a longitudinal design. Given societal pressures to be thin and an actual history of higher weight, it is possible that greater weight suppression contributes to increased fear of gaining weight and preoccupation with being thin, which increase vulnerability to eating disorders. The present study investigated whether greater drive for thinness mediates associations between weight suppression and bulimic symptoms over long-term follow-up. Participants were women (n = 1190) and men (n = 509) who completed self-report surveys in college and 10- and 20- years later. Higher weight suppression at baseline predicted higher bulimic symptoms at 20-year follow-up (p symptoms, body mass index, and drive for thinness. Increased drive for thinness at 10-year follow-up mediated this effect. Findings highlight the long-lasting effect of weight suppression on bulimic symptoms and suggest that preoccupation with thinness may help maintain this association. Future studies would benefit from incorporating other hypothesized consequences of weight suppression, including biological factors, into risk models. PMID:27808544

Escape of HIV-1-infected dendritic cells from TRAIL-mediated NK cell cytotoxicity during NK-DC cross-talk--a pivotal role of HMGB1.

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Marie-Thérèse Melki

2010-04-01

Full Text Available Early stages of Human Immunodeficiency Virus-1 (HIV-1 infection are associated with local recruitment and activation of important effectors of innate immunity, i.e. natural killer (NK cells and dendritic cells (DCs. Immature DCs (iDCs capture HIV-1 through specific receptors and can disseminate the infection to lymphoid tissues following their migration, which is associated to a maturation process. This process is dependent on NK cells, whose role is to keep in check the quality and the quantity of DCs undergoing maturation. If DC maturation is inappropriate, NK cells will kill them ("editing process" at sites of tissue inflammation, thus optimizing the adaptive immunity. In the context of a viral infection, NK-dependent killing of infected-DCs is a crucial event required for early elimination of infected target cells. Here, we report that NK-mediated editing of iDCs is impaired if DCs are infected with HIV-1. We first addressed the question of the mechanisms involved in iDC editing, and we show that cognate NK-iDC interaction triggers apoptosis via the TNF-related apoptosis-inducing ligand (TRAIL-Death Receptor 4 (DR4 pathway and not via the perforin pathway. Nevertheless, once infected with HIV-1, DC(HIV become resistant to NK-induced TRAIL-mediated apoptosis. This resistance occurs despite normal amounts of TRAIL released by NK cells and comparable DR4 expression on DC(HIV. The escape of DC(HIV from NK killing is due to the upregulation of two anti-apoptotic molecules, the cellular-Flice like inhibitory protein (c-FLIP and the cellular inhibitor of apoptosis 2 (c-IAP2, induced by NK-DC(HIV cognate interaction. High-mobility group box 1 (HMGB1, an alarmin and a key mediator of NK-DC cross-talk, was found to play a pivotal role in NK-dependent upregulation of c-FLIP and c-IAP2 in DC(HIV. Finally, we demonstrate that restoration of DC(HIV susceptibility to NK-induced TRAIL killing can be obtained either by silencing c-FLIP and c-IAP2 by specific

Peripheral and central mediators of lipopolysaccharide induced suppression of defensive rage behavior in the cat.

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Bhatt, S; Bhatt, R S; Zalcman, S S; Siegel, A

2009-11-10

Based upon recent findings in our laboratory that cytokines microinjected into the medial hypothalamus or periaqueductal gray (PAG) powerfully modulate defensive rage behavior in cat, the present study determined the effects of peripherally released cytokines following lipopolysaccharide (LPS) challenge upon defensive rage. The study involved initial identification of the effects of peripheral administration of LPS upon defensive rage by electrical stimulation from PAG and subsequent determination of the peripheral and central mechanisms governing this process. The results revealed significant elevation in response latencies for defensive rage from 60 to 300 min, post LPS injection, with no detectable signs of sickness behavior present at 60 min. In contrast, head turning behavior elicited by stimulation of adjoining midbrain sites was not affected by LPS administration, suggesting a specificity of the effects of LPS upon defensive rage. Direct administration of LPS into the medial hypothalamus had no effect on defensive rage, suggesting that the effects of LPS were mediated by peripheral cytokines rather than by any direct actions upon hypothalamic neurons. Complete blockade of the suppressive effects of LPS by peripheral pretreatment with an Anti-tumor necrosis factor-alpha (TNFalpha) antibody but not with an anti- interleukin-1 (IL-1) antibody demonstrated that the effects of LPS were mediated through TNF-alpha rather than through an IL-1 mechanism. A determination of the central mechanisms governing LPS suppression revealed that pretreatment of the medial hypothalamus with PGE(2) or 5-HT(1A) receptor antagonists each completely blocked the suppressive effects of LPS, while microinjections of a TNF-alpha antibody into the medial hypothalamus were ineffective. Microinjections of -Iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) benzamide monohydrochloride (p-MPPI) into lateral hypothalamus (to test for anatomical specificity) had no effect upon

Probiotics-mediated suppression of cancer.

Science.gov (United States)

So, Stephanie S Y; Wan, Murphy L Y; El-Nezami, Hani

2017-01-01

Probiotics can be used as an adjuvant for cancer prevention or/and treatment through their abilities to modulate intestinal microbiota and host immune response. Although most of the recent reviews have focused on the potential role of probiotics against colon cancer, only few of them include the probiotic effect on extraintestinal cancers. The present review covers the most important findings from the literature published during the past 20 months (from January 2015 to August 2016) regarding the probiotics-mediated suppression of both gastrointestinal and extraintestinal cancers and the underlying mechanisms. A comprehensive literature search in Pubmed, Science direct and Google scholar databases was conducted to locate all relevant articles that investigated the effect of probiotics on prevention/treatment of both gastrointestinal and extraintestinal cancers. Different mechanisms for the beneficial effects of probiotics against cancer were also discussed, mainly via modulation of gut microbiota which thereby influences host metabolism and immunity. Despite laboratory-based studies having demonstrated encouraging outcomes that probiotics possess antitumor effects, the benefits should not be exaggerated before we get more results from human clinical trials. These are very important before the medical community can accept the use of probiotics as an alternative therapy for cancer control.

The effector SPRYSEC-19 of Globodera rostochiensis suppresses CC-NB-LRR-mediated disease resistance in plants.

Science.gov (United States)

Postma, Wiebe J; Slootweg, Erik J; Rehman, Sajid; Finkers-Tomczak, Anna; Tytgat, Tom O G; van Gelderen, Kasper; Lozano-Torres, Jose L; Roosien, Jan; Pomp, Rikus; van Schaik, Casper; Bakker, Jaap; Goverse, Aska; Smant, Geert

2012-10-01

The potato cyst nematode Globodera rostochiensis invades roots of host plants where it transforms cells near the vascular cylinder into a permanent feeding site. The host cell modifications are most likely induced by a complex mixture of proteins in the stylet secretions of the nematodes. Resistance to nematodes conferred by nucleotide-binding-leucine-rich repeat (NB-LRR) proteins usually results in a programmed cell death in and around the feeding site, and is most likely triggered by the recognition of effectors in stylet secretions. However, the actual role of these secretions in the activation and suppression of effector-triggered immunity is largely unknown. Here we demonstrate that the effector SPRYSEC-19 of G. rostochiensis physically associates in planta with the LRR domain of a member of the SW5 resistance gene cluster in tomato (Lycopersicon esculentum). Unexpectedly, this interaction did not trigger defense-related programmed cell death and resistance to G. rostochiensis. By contrast, agroinfiltration assays showed that the coexpression of SPRYSEC-19 in leaves of Nicotiana benthamiana suppresses programmed cell death mediated by several coiled-coil (CC)-NB-LRR immune receptors. Furthermore, SPRYSEC-19 abrogated resistance to Potato virus X mediated by the CC-NB-LRR resistance protein Rx1, and resistance to Verticillium dahliae mediated by an unidentified resistance in potato (Solanum tuberosum). The suppression of cell death and disease resistance did not require a physical association of SPRYSEC-19 and the LRR domains of the CC-NB-LRR resistance proteins. Altogether, our data demonstrated that potato cyst nematodes secrete effectors that enable the suppression of programmed cell death and disease resistance mediated by several CC-NB-LRR proteins in plants.

NADPH oxidase-2 derived ROS dictates murine DC cytokine-mediated cell fate decisions during CD4 T helper-cell commitment.

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Meghan A Jendrysik

Full Text Available NADPH oxidase-2 (Nox2/gp91(phox and p47(phox deficient mice are prone to hyper-inflammatory responses suggesting a paradoxical role for Nox2-derived reactive oxygen species (ROS as anti-inflammatory mediators. The molecular basis for this mode of control remains unclear. Here we demonstrate that IFNγ/LPS matured p47(phox-/--ROS deficient mouse dendritic cells (DC secrete more IL-12p70 than similarly treated wild type DC, and in an in vitro co-culture model IFNγ/LPS matured p47(phox-/- DC bias more ovalbumin-specific CD4(+ T lymphocytes toward a Th1 phenotype than wild type (WT DC through a ROS-dependent mechanism linking IL-12p70 expression to regulation of p38-MAPK activation. The Nox2-dependent ROS production in DC negatively regulates proinflammatory IL-12 expression in DC by constraining p38-MAPK activity. Increasing endogenous H(2O(2 attenuates p38-MAPK activity in IFNγ/LPS stimulated WT and p47(phox-/- DC, which suggests that endogenous Nox 2-derived ROS functions as a secondary messenger in the activated p38-MAPK signaling pathway during IL-12 expression. These findings indicate that ROS, generated endogenously by innate and adaptive immune cells, can function as important secondary messengers that can regulate cytokine production and immune cell cross-talk to control during the inflammatory response.

Wild Carrot Differentiation in Europe and Selection at DcAOX1 Gene?

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Tânia Nobre

Full Text Available By definition, the domestication process leads to an overall reduction of crop genetic diversity. This lead to the current search of genomic regions in wild crop relatives (CWR, an important task for modern carrot breeding. Nowadays massive sequencing possibilities can allow for discovery of novel genetic resources in wild populations, but this quest could be aided by the use of a surrogate gene (to first identify and prioritize novel wild populations for increased sequencing effort. Alternative oxidase (AOX gene family seems to be linked to all kinds of abiotic and biotic stress reactions in various organisms and thus have the potential to be used in the identification of CWR hotspots of environment-adapted diversity. High variability of DcAOX1 was found in populations of wild carrot sampled across a West-European environmental gradient. Even though no direct relation was found with the analyzed climatic conditions or with physical distance, population differentiation exists and results mainly from the polymorphisms associated with DcAOX1 exon 1 and intron 1. The relatively high number of amino acid changes and the identification of several unusually variable positions (through a likelihood ratio test, suggests that DcAOX1 gene might be under positive selection. However, if positive selection is considered, it only acts on some specific populations (i.e. is in the form of adaptive differences in different population locations given the observed high genetic diversity. We were able to identify two populations with higher levels of differentiation which are promising as hot spots of specific functional diversity.

Dopamine agonist suppression of rapid-eye-movement sleep is secondary to sleep suppression mediated via limbic structures

Energy Technology Data Exchange (ETDEWEB)

Miletich, R.S.

1985-01-01

The effects of pergolide, a direct dopamine receptor agonist, on sleep and wakefulness, motor behavior and /sup 3/H-spiperone specific binding in limbic structures and striatum in rats was studied. The results show that pergolide induced a biphasic dose effect, with high doses increasing wakefulness and suppressing sleep while low dose decreased wakefulness, but increased sleep. It was shown that pergolide-induced sleep suppression was blocked by ..cap alpha..-glupenthixol and pimozide, two dopamine receptor antagonists. It was further shown that pergolide merely delayed the rebound resulting from rapid-eye-movement (REM) sleep deprivation, that dopamine receptors stimulation had no direct effect on the period, phase or amplitude of the circadian rhythm of REM sleep propensity and that there was no alteration in the coupling of REM sleep episodes with S/sub 2/ episodes. Rapid-eye-movement sleep deprivation resulted in increased sensitivity to the pergolide-induced wakefulness stimulation and sleep suppression and pergolide-induced motor behaviors of locomotion and head bobbing. /sup 3/H-spiperone specific binding to dopamine receptors was shown to be altered by REM sleep deprivation in the subcortical limbic structures. It is concluded that the REM sleep suppressing action of dopamine receptor stimulation is secondary to sleep suppression per se and not secondary to a unique effect on the REM sleep. Further, it is suggested that the wakefulness stimulating action of dopamine receptor agonists is mediated by activation of the dopamine receptors in the terminal areas of the mesolimbocortical dopamine projection system.

Evidence that shock-induced immune suppression is mediated by adrenal hormones and peripheral beta-adrenergic receptors.

Science.gov (United States)

Cunnick, J E; Lysle, D T; Kucinski, B J; Rabin, B S

1990-07-01

Our previous work has demonstrated that presentations of mild foot-shock to Lewis rats induces a suppression of splenic and peripheral blood lymphocyte responses to nonspecific T-cell mitogens. The present study demonstrated that adrenalectomy prevented the shock-induced suppression of the mitogenic response of peripheral blood T-cells but did not attenuate the suppression of splenic T-cells. Conversely, the beta-adrenergic receptor antagonists, propranolol and nadolol, attenuated the shock-induced suppression of splenic T-cells in a dose-dependent manner but did not attenuate suppression of the blood mitogen response. These data indicate that distinct mechanisms mediate the shock-induced suppression of T-cell responsiveness to mitogens in the spleen and the peripheral blood. The results indicate that the peripheral release of catecholamines is responsible for splenic immune suppression and that adrenal hormones, which do not interact with beta-adrenergic receptors, are responsible for shock-induced suppression of blood mitogenic responses.

TRIM45 negatively regulates NF-κB-mediated transcription and suppresses cell proliferation

International Nuclear Information System (INIS)

Shibata, Mio; Sato, Tomonobu; Nukiwa, Ryota; Ariga, Tadashi; Hatakeyama, Shigetsugu

2012-01-01

Highlights: ► NF-κB plays an important role in cell survival and carcinogenesis. ► TRIM45 negatively regulates TNFα-induced NF-κB-mediated transcription. ► TRIM45 overexpression suppresses cell growth. ► TRIM45 acts as a repressor for the NF-κB signal and regulates cell growth. -- Abstract: The NF-κB signaling pathway plays an important role in cell survival, immunity, inflammation, carcinogenesis, and organogenesis. Activation of NF-κB is regulated by several posttranslational modifications including phosphorylation, neddylation and ubiquitination. The NF-κB signaling pathway is activated by two distinct signaling mechanisms and is strictly modulated by the ubiquitin–proteasome system. It has been reported that overexpression of TRIM45, one of the TRIM family ubiquitin ligases, suppresses transcriptional activities of Elk-1 and AP-1, which are targets of the MAPK signaling pathway. In this study, we showed that TRIM45 also negatively regulates TNFα-induced NF-κB-mediated transcription by a luciferase reporter assay and that TRIM45 lacking a RING domain also has an activity to inhibit the NF-κB signal. Moreover, we found that TRIM45 overexpression suppresses cell growth. These findings suggest that TRIM45 acts as a repressor for the NF-κB signal and regulates cell growth.

Targeting acceptance in the management of food craving: The mediating roles of eating styles and thought suppression.

Science.gov (United States)

Coffino, Jaime A; Heiss, Sydney; Hormes, Julia M

2018-04-01

Food craving is now widely considered to be a cognitively motivated state. Acceptance-based treatments are effective in reducing the adverse impact of food cravings on consumption, via a hypothesized decrease in experiential avoidance. The mechanisms that drive the success of acceptance-based management of craving remain to be empirically tested. This study examined the role of eating styles and thought suppression as mediators in the relationship between experiential avoidance and craving. Participants (n = 298, 51.5% female) completed the Food Craving Acceptance and Awareness Questionnaire (FAAQ), the Dutch Eating Behavior Questionnaire (DEBQ), the White Bear Suppression Inventory (WBSI; a measure of thought suppression), and the reduced version of the Food Craving Questionnaire- Trait (FCQ-T-r). Scores on the FAAQ were inversely associated with scores on the FCQ-T-r, DEBQ, and WBSI; FCQ-T-r scores were positively correlated with scores on the DEBQ and WBSI (all p styles and thought suppression, acceptance remained a significant predictor of craving. Results thus provide initial evidence that eating styles and thought suppression mediate the relationship between food-specific experiential avoidance and food craving. Findings lay the foundation for future study of the proximal antecedents of food cravings and lend preliminary support for targeting thought suppression and eating styles in acceptance-based approaches to the management of craving. Copyright © 2018 Elsevier Ltd. All rights reserved.

Understanding the social effects of emotion regulation: the mediating role of authenticity for individual differences in suppression.

Science.gov (United States)

English, Tammy; John, Oliver P

2013-04-01

Individuals differ in the strategies they use to regulate their emotions (e.g., suppression, reappraisal), and these regulatory strategies can differentially influence social outcomes. However, the mechanisms underlying these social effects remain to be specified. We examined one potential mediator that arises directly from emotion-regulatory effort (expression of positive emotion), and another mediator that does not involve emotion processes per se, but instead results from the link between regulation and self-processes (subjective inauthenticity). Across three studies, only inauthenticity mediated the link between habitual use of suppression and poor social functioning (lower relationship satisfaction, lower social support). These findings replicated across individuals socialized in Western and East Asian cultural contexts, younger and older adults, when predicting social functioning concurrently and a decade later, and even when broader adjustment was controlled. Thus, the social costs of suppression do not seem to be due to reduced positive emotion expression but rather the incongruence between inner-self and outer-behavior. Reappraisal was not consistently related to social functioning. Implications of these findings for emotion processes, self processes, and interpersonal relationships are discussed. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Peroxisome Proliferator-Activated Receptor-γ Inhibits Transformed Growth of Non-Small Cell Lung Cancer Cells through Selective Suppression of Snail

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Rashmi Choudhary

2010-03-01

Full Text Available Work from our laboratory and others has demonstrated that activation of the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ inhibits transformed growth of non-small cell lung cancer (NSCLC cell lines in vitro and in vivo. We have demonstrated that activation of PPARγ promotes epithelial differentiation of NSCLC by increasing expression of E-cadherin, as well as inhibiting expression of COX-2 and nuclear factor-κB. The Snail family of transcription factors, which includes Snail (Snail1, Slug (Snail2, and ZEB1, is an important regulator of epithelial-mesenchymal transition, as well as cell survival. The goal of this study was to determine whether the biological responses to rosiglitazone, a member of the thiazolidinedione family of PPARγ activators, are mediated through the regulation of Snail family members. Our results indicate that, in two independent NSCLC cell lines, rosiglitazone specifically decreased expression of Snail, with no significant effect on either Slug or ZEB1. Suppression of Snail using short hairpin RNA silencing mimicked the effects of PPARγ activation, in inhibiting anchorage-independent growth, promoting acinar formation in three-dimensional culture, and inhibiting invasiveness. This was associated with the increased expression of E-cadherin and decreased expression of COX-2 and matrix metaloproteinases. Conversely, overexpression of Snail blocked the biological responses to rosiglitazone, increasing anchorage-independent growth, invasiveness, and promoting epithelial-mesenchymal transition. The suppression of Snail expression by rosiglitazone seemed to be independent of GSK-3 signaling but was rather mediated through suppression of extracellular signal-regulated kinase activity. These findings suggest that selective regulation of Snail may be critical in mediating the antitumorigenic effects of PPARγ activators.

Gambogic acid inhibits multiple myeloma mediated osteoclastogenesis through suppression of chemokine receptor CXCR4 signaling pathways.

Science.gov (United States)

Pandey, Manoj K; Kale, Vijay P; Song, Chunhua; Sung, Shen-shu; Sharma, Arun K; Talamo, Giampaolo; Dovat, Sinisa; Amin, Shantu G

2014-10-01

Bone disease, characterized by the presence of lytic lesions and osteoporosis is the hallmark of multiple myeloma (MM). Stromal cell-derived factor 1α (SDF-1α) and its receptor, CXC chemokine receptor 4 (CXCR4), has been implicated as a regulator of bone resorption, suggesting that agents that can suppress SDF1α/CXCR4 signaling might inhibit osteoclastogenesis, a process closely linked to bone resorption. We, therefore, investigated whether gambogic acid (GA), a xanthone, could inhibit CXCR4 signaling and suppress osteoclastogenesis induced by MM cells. Through docking studies we predicted that GA directly interacts with CXCR4. This xanthone down-regulates the expression of CXCR4 on MM cells in a dose- and time-dependent manner. The down-regulation of CXCR4 was not due to proteolytic degradation, but rather GA suppresses CXCR4 mRNA expression by inhibiting nuclear factor-kappa B (NF-κB) DNA binding. This was further confirmed by quantitative chromatin immunoprecipitation assay, as GA inhibits p65 binding at the CXCR4 promoter. GA suppressed SDF-1α-induced chemotaxis of MM cells and downstream signaling of CXCR4 by inhibiting phosphorylation of Akt, p38, and Erk1/2 in MM cells. GA abrogated the RANKL-induced differentiation of macrophages to osteoclasts in a dose- and time-dependent manner. In addition, we found that MM cells induced differentiation of macrophages to osteoclasts, and that GA suppressed this process. Importantly, suppression of osteoclastogenesis by GA was mediated through IL-6 inhibition. Overall, our results show that GA is a novel inhibitor of CXCR4 expression and has a strong potential to suppress osteoclastogenesis mediated by MM cells. Published by Elsevier Inc.

In vitro suppression of dendritic cells by Helicobacter pylori OipA.

Science.gov (United States)

Teymournejad, Omid; Mobarez, Ashraf M; Hassan, Zuhair M; Moazzeni, Seyed M; Ahmadabad, Hassan N

2014-04-01

Outer inflammatory protein A (OipA) has an important role in Helicobacter pylori pathogenesis. In this study, we purified the outer membrane protein and evaluated the effects of this protein on maturation and cytokine production by dendritic cells (DCs). The oipA gene was inserted into pET28a, and this construct was transformed into Escherichia coli BL21 (DE3). Purification of the recombinant protein was performed by Ni-NTA affinity chromatography. Immature DCs were purified from spleen of C57BL/6 mice with more than 90% purity and were treated with several concentrations of OipA (1-20 μg/mL) overnight. Expression of maturation markers (CD86, CD40, and MHC-II) on the surface of DCs and production of IL-10 and IL-12 were assessed by flow cytometry and ELISA, respectively. The expression of DC maturation markers CD40, CD86, and MHC-II was downregulated on the surface of OipA-treated DCs at concentrations of 10 and 20 μg/mL compared with negative control. Production of IL-10 decreases with increasing OipA concentration at a concentration of 5 μg/mL, but we detected no change in IL-12 production. Inability to eliminate H. pylori from stomach is partly due to the evasion of the bacteria from the immune response. DCs are central mediators between innate and adaptive immunity, and DC cytokines direct the types of adaptive immune response. This study indicated that OipA of H. pylori is a DC maturation suppression factor. Previous studies have shown that H. pylori manage tolerogenic programming in DCs leading to long-time gastric colonization. In conclusion, H. pylori OipA helps the establishment of chronic infection with reduction in IL-10 and suppression of DC maturation. © 2014 John Wiley & Sons Ltd.

Androgen Receptor-Mediated Growth Suppression of HPr-1AR and PC3-Lenti-AR Prostate Epithelial Cells.

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Young-Chae Kim

Full Text Available The androgen receptor (AR mediates the developmental, physiologic, and pathologic effects of androgens including 5α-dihydrotestosterone (DHT. However, the mechanisms whereby AR regulates growth suppression and differentiation of luminal epithelial cells in the prostate gland and proliferation of malignant versions of these cells are not well understood, though they are central to prostate development, homeostasis, and neoplasia. Here, we identify androgen-responsive genes that restrain cell cycle progression and proliferation of human prostate epithelial cell lines (HPr-1AR and PC3-Lenti-AR, and we investigate the mechanisms through which AR regulates their expression. DHT inhibited proliferation of HPr-1AR and PC3-Lenti-AR, and cell cycle analysis revealed a prolonged G1 interval. In the cell cycle, the G1/S-phase transition is initiated by the activity of cyclin D and cyclin-dependent kinase (CDK complexes, which relieve growth suppression. In HPr-1AR, cyclin D1/2 and CDK4/6 mRNAs were androgen-repressed, whereas CDK inhibitor, CDKN1A, mRNA was androgen-induced. The regulation of these transcripts was AR-dependent, and involved multiple mechanisms. Similar AR-mediated down-regulation of CDK4/6 mRNAs and up-regulation of CDKN1A mRNA occurred in PC3-Lenti-AR. Further, CDK4/6 overexpression suppressed DHT-inhibited cell cycle progression and proliferation of HPr-1AR and PC3-Lenti-AR, whereas CDKN1A overexpression induced cell cycle arrest. We therefore propose that AR-mediated growth suppression of HPr-1AR involves cyclin D1 mRNA decay, transcriptional repression of cyclin D2 and CDK4/6, and transcriptional activation of CDKN1A, which serve to decrease CDK4/6 activity. AR-mediated inhibition of PC3-Lenti-AR proliferation occurs through a similar mechanism, albeit without down-regulation of cyclin D. Our findings provide insight into AR-mediated regulation of prostate epithelial cell proliferation.

Punica granatum L. Fruit Aqueous Extract Suppresses Reactive Oxygen Species-Mediated p53/p65/miR-145 Expressions followed by Elevated Levels of irs-1 in Alloxan-Diabetic Rats.

Science.gov (United States)

Gharib, Ehsan; Montasser Kouhsari, Shideh; Izad, Maryam

2018-01-01

Reactive oxygen species (ROS) is an apoptosis inducer in pancreatic β-cells that stimulates p53/p65 mediated microRNA (miR)-145 expression. Punica granatum L. (pomegranate) is an antioxidant fruit that attenuates ROS generation. This study examines the effects of pomegranate fruit aqueous extract (PGE) on the levels of ROS, p53, p65, miR-145, and its target insulin receptor substrate 1 (irs-1) mRNA in Alloxan-diabetic male Wistar rats. In this experimental study, diabetic rats received different doses of PGE. The effects of the PGE polyphenols were examined through a long-term PGE treatment period model, followed by an evaluation of the plasma and tissue contents of free fatty acids (FFAs), triglycerides (TG), and glycogen compared with diabetic controls (DC) and normal controls (NC). We used real-time polymerase chain reaction (PCR) to investigate the modulation of p53, p65, miR-145, and irs-1 expression levels. There was a noticeable reduction in fasting blood glucose (FBG) and ROS generation compared to DC. We observed marked decreases in p53, p65, miR-145 expression levels followed by an elevated level of irs-1, which contributed to improvement in insulin sensitivity. PGE administration downregulated miR-145 levels in Alloxan-diabetic Wistar rats by suppression of ROS-mediated p53 and p65 overexpression. Copyright© by Royan Institute. All rights reserved.

GP2 is selectively expressed by small intestinal CD103⁺CD11b⁺ cDC

DEFF Research Database (Denmark)

Müller-Luda, Katarzyna; Ahmadi, Fatemeh; Ohno, Hiroshi

DC in the small intestine. Moreover, GP2 expressing cDC in the small intestine were dramatically reduced in the setting of intestinal inflammation. We have previously shown that mice with an IRF4 deletion in CD11c+ cells (Cd11c-cre.Irf4 fl/fl mice) have reduced numbers of small intestinal CD103+CD11b+ c......DC. Interesting, we found that GP2+ CD103+CD11b+ cDC were dramatically reduced in these mice. Finally, to address the in vivo role of GP2 expression by cDC, we have generated mice with a selective deletion of GP2 in CD103+CD11b+ cDC (huLangerin-cre.gp2 fl/fl  mice). Results from these ongoing studies...

Critical role of heme oxygenase-1 in Foxp3-mediated immune suppression

International Nuclear Information System (INIS)

Choi, Byung-Min; Pae, Hyun-Ock; Jeong, Young-Ran; Kim, Young-Myeong; Chung, Hun-Taeg

2005-01-01

Foxp3, which encodes the transcription factor scurfin, is indispensable for the development and function of CD4 + CD25 + regulatory T cells (Treg). Recent data suggest conversion of peripheral CD4 + CD25 - naive T cells to CD4 + CD25 + Treg by acquisition of Foxp3 through costimulation with TCR and TGF-β or forced expression of the gene. One critical question is how Foxp3 causes T cells to become regulatory. In the present work, we demonstrate that Foxp3 can induce heme oxygenase-1 (HO-1) expression and subsequently such regulatory phenotypes as the suppression of nontransfected cells in a cell-cell contact-dependent manner as well as impaired proliferation and production of cytokines upon stimulation in Jurkat T cells. Moreover, we confirm the expression of both Foxp3 and HO-1 in peripheral CD4 + CD25 + Treg and suppressive function of the cells are relieved by the inhibition of HO-1 activity. In summary, we demonstrate that Foxp3 induces HO-1 expression and HO-1 engages in Foxp3-mediated immune suppression

Weight loss in obese men by caloric restriction and high-dose diazoxide-mediated insulin suppression.

NARCIS (Netherlands)

Boekel, G.A.J van; Loves, S.; Sorge, A.A. van; Ruinemans-Koerts, J.; Rijnders, T.; Boer, H. de

2008-01-01

OBJECTIVE: To examine the concept whether high-dose diazoxide (DZX)-mediated insulin suppression, in combination with moderate caloric restriction and increased physical activity, can establish a weight loss of at least 15% in obese hyperinsulinaemic men. DESIGN: Open, uncontrolled, 6-month pilot

InterProScan Result: DC435847 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available DC435847 DC435847_2_ORF2 B865BD96179C9173 PANTHER PTHR10082 INTEGRIN BETA SUBUNIT 0...-matrix adhesion (GO:0007160)|Biological Process: integrin-mediated signaling pathway (GO:0007229)|Cellular Component: integrin complex (GO:0008305) ...

Baicalein suppresses the androgen receptor (AR)-mediated prostate cancer progression via inhibiting the AR N-C dimerization and AR-coactivators interaction.

Science.gov (United States)

Xu, Defeng; Chen, Qiulu; Liu, Yalin; Wen, Xingqiao

2017-12-01

Androgen receptor (AR) plays a critical role in prostate cancer (PCa) development and progression. Androgen deprivation therapy with antiandrogens to reduce androgen biosynthesis or prevent androgens from binding to AR are widely used to suppress AR-mediated PCa growth. However, most of ADT may eventually fail with development of the castration resistance after 12-24 months. Here we found that a natural product baicalein can effectively suppress the PCa progression via targeting the androgen-induced AR transactivation with little effect to AR protein expression. PCa cells including LNCaP, CWR22Rv1, C4-2, PC-3, and DU145, were treated with baicalein and luciferase assay was used to evaluate their effect on the AR transactivation. Cell growth and IC 50 were determined by MTT assay after 48 hrs treatment. RT-PCR was used to evaluate the mRNA levels of AR target genes including PSA, TMPRSS2, and TMEPA1. Western blot was used to determine AR and PSA protein expression. The natural product of baicalein can selectively inhibit AR transactivation with little effect on the other nuclear receptors, including ERα, and GR. At a low concentration, 2.5 μM of baicalein effectively suppresses the growth of AR-positive PCa cells, and has little effect on AR-negative PCa cells. Mechanism dissection suggest that baicalein can suppress AR target genes (PSA, TMPRSS2, and TMEPA1) expression in both androgen responsive LNCaP cells and castration resistant CWR22Rv1 cells, that may involve the inhibiting the AR N/C dimerization and AR-coactivators interaction. Baicalein may be developed as an effective anti-AR therapy via its ability to inhibit AR transactivation and AR-mediated PCa cell growth.

Assessing the Role of ETHYLENE RESPONSE FACTOR Transcriptional Repressors in Salicylic Acid-Mediated Suppression of Jasmonic Acid-Responsive Genes.

Science.gov (United States)

Caarls, Lotte; Van der Does, Dieuwertje; Hickman, Richard; Jansen, Wouter; Verk, Marcel C Van; Proietti, Silvia; Lorenzo, Oscar; Solano, Roberto; Pieterse, Corné M J; Van Wees, Saskia C M

2017-02-01

Salicylic acid (SA) and jasmonic acid (JA) cross-communicate in the plant immune signaling network to finely regulate induced defenses. In Arabidopsis, SA antagonizes many JA-responsive genes, partly by targeting the ETHYLENE RESPONSE FACTOR (ERF)-type transcriptional activator ORA59. Members of the ERF transcription factor family typically bind to GCC-box motifs in the promoters of JA- and ethylene-responsive genes, thereby positively or negatively regulating their expression. The GCC-box motif is sufficient for SA-mediated suppression of JA-responsive gene expression. Here, we investigated whether SA-induced ERF-type transcriptional repressors, which may compete with JA-induced ERF-type activators for binding at the GCC-box, play a role in SA/JA antagonism. We selected ERFs that are transcriptionally induced by SA and/or possess an EAR transcriptional repressor motif. Several of the 16 ERFs tested suppressed JA-dependent gene expression, as revealed by enhanced JA-induced PDF1.2 or VSP2 expression levels in the corresponding erf mutants, while others were involved in activation of these genes. However, SA could antagonize JA-induced PDF1.2 or VSP2 in all erf mutants, suggesting that the tested ERF transcriptional repressors are not required for SA/JA cross-talk. Moreover, a mutant in the co-repressor TOPLESS, that showed reduction in repression of JA signaling, still displayed SA-mediated antagonism of PDF1.2 and VSP2. Collectively, these results suggest that SA-regulated ERF transcriptional repressors are not essential for antagonism of JA-responsive gene expression by SA. We further show that de novo SA-induced protein synthesis is required for suppression of JA-induced PDF1.2, pointing to SA-stimulated production of an as yet unknown protein that suppresses JA-induced transcription. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Transgene IL-6 Enhances DC-Stimulated CTL Responses by Counteracting CD4+25+Foxp3+ Regulatory T Cell Suppression via IL-6-Induced Foxp3 Downregulation

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Kalpana Kalyanasundaram Bhanumathy

2014-03-01

Full Text Available Dendritic cells (DCs, the most potent antigen-presenting cells have been extensively applied in clinical trials for evaluation of antitumor immunity. However, the efficacy of DC-mediated cancer vaccines is still limited as they are unable to sufficiently break the immune tolerance. In this study, we constructed a recombinant adenoviral vector (AdVIL-6 expressing IL-6, and generated IL-6 transgene-engineered DC vaccine (DCOVA/IL-6 by transfection of murine bone marrow-derived ovalbumin (OVA-pulsed DCs (DCOVA with AdVIL-6. We then assessed DCOVA/IL-6-stimulated cytotoxic T-lymphocyte (CTL responses and antitumor immunity in OVA-specific animal tumor model. We demonstrate that DCOVA/IL-6 vaccine up-regulates expression of DC maturation markers, secretes transgene-encoded IL-6, and more efficiently stimulates OVA-specific CTL responses and therapeutic immunity against OVA-expressing B16 melanoma BL6-10OVA in vivo than the control DCOVA/Null vaccine. Moreover, DCOVA/IL-6-stimulated CTL responses were relatively maintained in mice with transfer of CD4+25+Foxp3+ Tr-cells, but significantly reduced when treated with anti-IL-6 antibody. In addition, we demonstrate that IL-6 down-regulates Foxp3-expression of CD4+25+Foxp3+ Tr-cells in vitro. Taken together, our results demonstrate that AdV-mediated IL-6 transgene-engineered DC vaccine stimulates potent CTL responses and antitumor immunity by counteracting CD4+25+ Tr immunosuppression via IL-6-induced Foxp3 down-regulation. Thus, IL-6 may be a good candidate for engineering DCs for cancer immunotherapy.

InterProScan Result: DC567196 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available DC567196 DC567196_6_ORF1 3D5CCF80D25D4770 PANTHER PTHR10082 INTEGRIN BETA SUBUNIT 6...-matrix adhesion (GO:0007160)|Biological Process: integrin-mediated signaling pathway (GO:0007229)|Cellular Component: integrin complex (GO:0008305) ...

Design of a -1 MV dc UHV power supply for ITER NBI

Science.gov (United States)

Watanabe, K.; Yamamoto, M.; Takemoto, J.; Yamashita, Y.; Dairaku, M.; Kashiwagi, M.; Taniguchi, M.; Tobari, H.; Umeda, N.; Sakamoto, K.; Inoue, T.

2009-05-01

Procurement of a dc -1 MV power supply system for the ITER neutral beam injector (NBI) is shared by Japan and the EU. The Japan Atomic Energy Agency as the Japan Domestic Agency (JADA) for ITER contributes to the procurement of dc -1 MV ultra-high voltage (UHV) components such as a dc -1 MV generator, a transmission line and a -1 MV insulating transformer for the ITER NBI power supply. The inverter frequency of 150 Hz in the -1 MV power supply and major circuit parameters have been proposed and adopted in the ITER NBI. The dc UHV insulation has been carefully designed since dc long pulse insulation is quite different from conventional ac insulation or dc short pulse systems. A multi-layer insulation structure of the transformer for a long pulse up to 3600 s has been designed with electric field simulation. Based on the simulation the overall dimensions of the dc UHV components have been finalized. A surge energy suppression system is also essential to protect the accelerator from electric breakdowns. The JADA contributes to provide an effective surge suppression system composed of core snubbers and resistors. Input energy into the accelerator from the power supply can be reduced to about 20 J, which satisfies the design criteria of 50 J in total in the case of breakdown at -1 MV.

InterProScan Result: DC567196 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available DC567196 DC567196_6_ORF1 3D5CCF80D25D4770 PRINTS PR01186 INTEGRINB 1.3e-27 T IPR015812 Integri...0)|Biological Process: integrin-mediated signaling pathway (GO:0007229)|Cellular Component: integrin complex (GO:0008305) ...

Identification of a regulatory T cell specific cell surface molecule that mediates suppressive signals and induces Foxp3 expression.

Science.gov (United States)

Wang, Rui; Wan, Qi; Kozhaya, Lina; Fujii, Hodaka; Unutmaz, Derya

2008-07-16

Regulatory T (T(reg)) cells control immune activation and maintain tolerance. How T(regs) mediate their suppressive function is unclear. Here we identified a cell surface molecule, called GARP, (or LRRC32), which within T cells is specifically expressed in T(regs) activated through the T cell receptor (TCR). Ectopic expression of GARP in human naïve T (T(N)) cells inhibited their proliferation and cytokine secretion upon TCR activation. Remarkably, GARP over-expression in T(N) cells induced expression of T(reg) master transcription factor Foxp3 and endowed them with a partial suppressive function. The extracellular but not the cytoplasmic region of GARP, was necessary for these functions. Silencing Foxp3 in human T(reg) cells reduced expression of GARP and attenuated their suppressive function. However, GARP function was not affected when Foxp3 was downregulated in GARP-overexpressing cells, while silencing GARP in Foxp3-overexpressing cells reduced their suppressive activity. These findings reveal a novel cell surface molecule-mediated regulatory mechanism, with implications for modulating aberrant immune responses.

Identification of a regulatory T cell specific cell surface molecule that mediates suppressive signals and induces Foxp3 expression.

Directory of Open Access Journals (Sweden)

Rui Wang

2008-07-01

Full Text Available Regulatory T (T(reg cells control immune activation and maintain tolerance. How T(regs mediate their suppressive function is unclear. Here we identified a cell surface molecule, called GARP, (or LRRC32, which within T cells is specifically expressed in T(regs activated through the T cell receptor (TCR. Ectopic expression of GARP in human naïve T (T(N cells inhibited their proliferation and cytokine secretion upon TCR activation. Remarkably, GARP over-expression in T(N cells induced expression of T(reg master transcription factor Foxp3 and endowed them with a partial suppressive function. The extracellular but not the cytoplasmic region of GARP, was necessary for these functions. Silencing Foxp3 in human T(reg cells reduced expression of GARP and attenuated their suppressive function. However, GARP function was not affected when Foxp3 was downregulated in GARP-overexpressing cells, while silencing GARP in Foxp3-overexpressing cells reduced their suppressive activity. These findings reveal a novel cell surface molecule-mediated regulatory mechanism, with implications for modulating aberrant immune responses.

Cadmium-mediated disruption of cortisol biosynthesis involves suppression of corticosteroidogenic genes in rainbow trout

International Nuclear Information System (INIS)

Sandhu, Navdeep; Vijayan, Mathilakath M.

2011-01-01

Cadmium is widely distributed in the aquatic environment and is toxic to fish even at sublethal concentrations. This metal is an endocrine disruptor, and one well established role in teleosts is the suppression of adrenocorticotrophic hormone (ACTH)-stimulated cortisol biosynthesis by the interrenal tissue. However the mechanism(s) leading to this steroid suppression is poorly understood. We tested the hypothesis that cadmium targets genes encoding proteins critical for corticosteroid biosynthesis, including melanocortin 2 receptor (MC2R), steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage enzyme (P450scc), in rainbow trout (Oncorhynchus mykiss). To test this, head kidney slices (containing the interrenal tissues) were incubated in vitro with cadmium chloride (0, 10, 100 and 1000 nM) for 4 h either in the presence or absence of ACTH (0.5 IU/mL). In the unstimulated head kidney slices, cadmium exposure did not affect basal cortisol secretion and the mRNA levels of MC2R and P450scc, while StAR gene expression was significantly reduced. Cadmium exposure significantly suppressed ACTH-stimulated cortisol production in a dose-related fashion. This cadmium-mediated suppression in corticosteroidogenesis corresponded with a significant reduction in MC2R, StAR and P450scc mRNA levels in trout head kidney slices. The inhibition of ACTH-stimulated cortisol production and suppression of genes involved in corticosteroidogenesis by cadmium were completely abolished in the presence of 8-Bromo-cAMP (a cAMP analog). Overall, cadmium disrupts the expression of genes critical for corticosteroid biosynthesis in rainbow trout head kidney slices. However, the rescue of cortisol production as well as StAR and P450scc gene expressions by cAMP analog suggests that cadmium impact occurs upstream of cAMP production. We propose that MC2R signaling, the primary step in ACTH-induced cortocosteroidogenesis, is a key target for cadmium-mediated disruption of

Cadmium-mediated disruption of cortisol biosynthesis involves suppression of corticosteroidogenic genes in rainbow trout

Energy Technology Data Exchange (ETDEWEB)

Sandhu, Navdeep [Department of Biology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1 (Canada); Vijayan, Mathilakath M., E-mail: mvijayan@uwaterloo.ca [Department of Biology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1 (Canada)

2011-05-15

Cadmium is widely distributed in the aquatic environment and is toxic to fish even at sublethal concentrations. This metal is an endocrine disruptor, and one well established role in teleosts is the suppression of adrenocorticotrophic hormone (ACTH)-stimulated cortisol biosynthesis by the interrenal tissue. However the mechanism(s) leading to this steroid suppression is poorly understood. We tested the hypothesis that cadmium targets genes encoding proteins critical for corticosteroid biosynthesis, including melanocortin 2 receptor (MC2R), steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage enzyme (P450scc), in rainbow trout (Oncorhynchus mykiss). To test this, head kidney slices (containing the interrenal tissues) were incubated in vitro with cadmium chloride (0, 10, 100 and 1000 nM) for 4 h either in the presence or absence of ACTH (0.5 IU/mL). In the unstimulated head kidney slices, cadmium exposure did not affect basal cortisol secretion and the mRNA levels of MC2R and P450scc, while StAR gene expression was significantly reduced. Cadmium exposure significantly suppressed ACTH-stimulated cortisol production in a dose-related fashion. This cadmium-mediated suppression in corticosteroidogenesis corresponded with a significant reduction in MC2R, StAR and P450scc mRNA levels in trout head kidney slices. The inhibition of ACTH-stimulated cortisol production and suppression of genes involved in corticosteroidogenesis by cadmium were completely abolished in the presence of 8-Bromo-cAMP (a cAMP analog). Overall, cadmium disrupts the expression of genes critical for corticosteroid biosynthesis in rainbow trout head kidney slices. However, the rescue of cortisol production as well as StAR and P450scc gene expressions by cAMP analog suggests that cadmium impact occurs upstream of cAMP production. We propose that MC2R signaling, the primary step in ACTH-induced cortocosteroidogenesis, is a key target for cadmium-mediated disruption of

A soft-switching coupled inductor bidirectional DC-DC converter with high-conversion ratio

Science.gov (United States)

Chao, Kuei-Hsiang; Jheng, Yi-Cing

2018-01-01

A soft-switching bidirectional DC-DC converter is presented herein as a way to improve the conversion efficiency of a photovoltaic (PV) system. Adoption of coupled inductors enables the presented converter not only to provide a high-conversion ratio but also to suppress the transient surge voltage via the release of the energy stored in leakage flux of the coupled inductors, and the cost can kept down consequently. A combined use of a switching mechanism and an auxiliary resonant branch enables the converter to successfully perform zero-voltage switching operations on the main switches and improves the efficiency accordingly. It was testified by experiments that our proposed converter works relatively efficiently in full-load working range. Additionally, the framework of the converter intended for testifying has high-conversion ratio. The results of a test, where a generating system using PV module array coupled with batteries as energy storage device was used as the low-voltage input side, and DC link was used as high-voltage side, demonstrated our proposed converter framework with high-conversion ratio on both high-voltage and low-voltage sides.

A fast novel soft-start circuit for peak current-mode DC—DC buck converters

International Nuclear Information System (INIS)

Li Jie; Yang Miao; Sun Weifeng; Lu Xiaoxia; Xu Shen; Lu Shengli

2013-01-01

A fully integrated soft-start circuit for DC—DC buck converters is presented. The proposed high speed soft-start circuit is made of two sections: an overshoot suppression circuit and an inrush current suppression circuit. The overshoot suppression circuit is presented to control the input of the error amplifier to make output voltage limit increase in steps without using an external capacitor. A variable clock signal is adopted in the inrush current suppression circuit to increase the duty cycle of the system and suppress the inrush current. The DC—DC converter with the proposed soft-start circuit has been fabricated with a standard 0.13 μm CMOS process. Experimental results show that the proposed high speed soft-start circuit has achieved less than 50 μs start-up time. The inductor current and the output voltage increase smoothly over the whole load range. (semiconductor integrated circuits)

DC electric springs with DC/DC converters

DEFF Research Database (Denmark)

Wang, Qingsong; Cheng, Ming; Jiang, Yunlei

2016-01-01

The concept of DC electric spring (DCES) was recently proposed to solve the stability issue caused by integrating intermittent renewable energy sources (RESs) to DC microgrids. In this paper, a new topology of DCES is proposed based on DC/DC converters. The proposed DCES consists of a bi-directio......The concept of DC electric spring (DCES) was recently proposed to solve the stability issue caused by integrating intermittent renewable energy sources (RESs) to DC microgrids. In this paper, a new topology of DCES is proposed based on DC/DC converters. The proposed DCES consists of a bi...... and/or constant discharging for batteries is adopted and four operating modes are analyzed as charging-positive, charging-negative, discharging-positive and discharging-negative modes. An additional mechanism for fast charging or fast discharging is also designed to secure normal operation...... of batteries. With the proposed DCES, the power fluctuations due to intermittent RESs can be passed to non-critical loads (NCLs) and batteries while power on critical loads (CLs) is kept stable. This is possibly the first attempt to design a DCES with only DC/DC converters. The performances of the proposed...

An active role for endogenous beta-1,3-glucanase genes in transgene-mediated co-suppression in tobacco.

Science.gov (United States)

Sanders, Matthew; Maddelein, Wendy; Depicker, Anna; Van Montagu, Marc; Cornelissen, Marc; Jacobs, John

2002-11-01

Post-transcriptional gene silencing (PTGS) is characterized by the accumulation of short interfering RNAs that are proposed to mediate sequence-specific degradation of cognate and secondary target mRNAs. In plants, it is unclear to what extent endogenous genes contribute to this process. Here, we address the role of the endogenous target genes in transgene-mediated PTGS of beta-1,3-glucanases in tobacco. We found that mRNA sequences of the endogenous glucanase glb gene with varying degrees of homology to the Nicotiana plumbaginifolia gn1 transgene are targeted by the silencing machinery, although less efficiently than corresponding transgene regions. Importantly, we show that endogene-specific nucleotides in the glb sequence provide specificity to the silencing process. Consistent with this finding, small sense and antisense 21- to 23-nucleotide RNAs homologous to the endogenous glb gene were detected. Combined, these data demonstrate that a co-suppressed endogenous glucan ase gene is involved in signal amplification and selection of homologous targets, and show that endogenous genes can actively participate in PTGS in plants. The findings are introduced as a further sophistication of the post-transciptional silencing model.

Interleukin 35: A Key Mediator of Suppression and the Propagation of Infectious Tolerance

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Brian M Olson

2013-10-01

Full Text Available The importance of regulatory T cells in balancing the effector arm of the immune system is well documented, playing a central role in preventing autoimmunity, facilitating graft tolerance following organ transplantation, and having a detrimental impact on the development of anti-tumor immunity. These regulatory responses use a variety of mechanisms to mediate suppression, including soluble factors. While IL-10 and TGF-β are the most commonly studied immunosuppressive cytokines, the recently identified IL-35 has been shown to have potent suppressive function in vitro and in vivo. Furthermore, not only does IL-35 have the ability to directly suppress effector T cell responses, it is also able to expand regulatory responses by propagating infectious tolerance and generating a potent population of IL-35-expressing inducible regulatory T cells. In this review, we summarize research characterizing the structure and function of IL-35, examine its role in disease, and discuss how it can contribute to the induction of a distinct population of inducible regulatory T cells.

Novel DC Bias Suppression Device Based on Adjustable Parallel Resistances

DEFF Research Database (Denmark)

Wang, Zhixun; Xie, Zhicheng; Liu, Chang

2018-01-01

resistances is designed. The mathematical model for global optimal switching of CBDs is established by field-circuit coupling method with the equivalent resistance network of ac system along with the location of substations and ground electrodes. The optimal switching scheme to minimize the global maximum dc...

Selective Attention in Inattentional Blindness: Selection is Specific but Suppression is Not

OpenAIRE

Wood, Katherine; Simons, Daniel J.

2017-01-01

When we selectively attend to one set of objects and ignore another, we often fail to notice unexpected events. The likelihood of noticing varies depending on the similarity of an unexpected object to other items in the display, a process thought to be controlled by the attention set that we create for the attended and ignored objects. It remains unclear, though, how attention sets are formed and structured. Do they enhance features of attended objects (“white”) and suppress features of ignor...

Advanced DC/DC converters

CERN Document Server

Luo, Fang Lin

2003-01-01

DC/DC conversion techniques have undergone rapid development in recent decades. With the pioneering work of these authors, DC/DC converters have now moved into their sixth generation. This book offers a concise, practical presentation of DC/DC converters, summarizing the spectrum of conversion tecnologies and presentingmany new ideas and more than 100 new topologies. Nowhere else in the literature are DC/DC converters so logically sorted and systematically introduced, and nowhere else can readers find detailed information on prototype topologies that represent a major contribution to modern power engineering. More than 320 figures, 60 tables, and 500 formulae facilitate understand and provide precise data.

Active superconducting DC fault current limiter based on flux compensation

International Nuclear Information System (INIS)

Shi Jing; Tang Yuejin; Wang, Chen; Zhou Yusheng; Li Jingdong; Ren Li; Chen Shijie

2006-01-01

With the extensive application of DC power systems, suppression of DC fault current is an important subject that guarantees system security. This paper presents an active superconducting DC fault current limiter (DC-SFCL) based on flux compensation. The DC-SFCL is composed of two superconducting windings wound on a single iron core, the primary winding is in series with DC power system, and the second winding is connected with AC power system through a PWM converter. In normal operating state, the flux in the iron core is compensated to zero, and the SFCL has no influence on DC power system. In the case of DC system accident, through regulating the active power exchange between the SFCL's second winding and the AC power system, the current on the DC side can be limited to different level complying with the system demand. Moreover, the PWM converter that interface the DC system and AC system can be controlled as a reactive power source to supply voltage support for the AC side, which has little influence on the performance of SFCL. Using MATLAB SIMULINK, the mathematic model of the DC-SFCL is created, simulation results validate the dynamics of system, and the performance of DC-SFCL is confirmed

Recombinant adenovirus-mediated gene transfer suppresses experimental arthritis

Directory of Open Access Journals (Sweden)

E. Quattrocchi

2011-09-01

Full Text Available Collagen Induced Arthritis (CIA is a widely studied animal model to develop and test novel therapeutic approaches for treating Rheumatoid Arthritis (RA in humans. Soluble Cytotoxic T-Lymphocyte Antigen 4 (CTLA4-Ig, which binds B7 molecule on antigen presenting cells and blocks CD28 mediated T-lymphocyte activation, has been shown to ameliorate experimental autoimmune diseases such as lupus, diabetes and CIA. Objective of our research was to investigate in vivo the effectiveness of blocking the B7/CD28 T-lymphocyte co-stimulatory pathway, utilizing a gene transfer technology, as a therapeutic strategy against CIA. Replication-deficient adenoviruses encoding a chimeric CTLA4-Ig fusion protein, or β-galactosidase as control, have been injected intravenously once at arthritis onset. Disease activity has been monitored by the assessment of clinical score, paw thickness and type II collagen (CII specific cellular and humoral immune responses for 21 days. The adenovirally delivered CTLA4-Ig fusion protein at a dose of 2×108 pfu suppressed established CIA, whereas the control β-galactosidase did not significantly affect the disease course. CII-specific lymphocyte proliferation, IFNg production and anti-CII antibodies were significantly reduced by CTLA4-Ig treatment. Our results demonstrate that blockade of the B7/CD28 co-stimulatory pathway by adenovirus-mediated CTLA4-Ig gene transfer is effective in treating established CIA suggesting its potential in treating RA.

Intestinal colonization of IL-2 deficient mice with non-colitogenic B. vulgatus prevents DC maturation and T-cell polarization.

Directory of Open Access Journals (Sweden)

Martina Müller

Full Text Available BACKGROUND: IL-2 deficient (IL-2(-/- mice mono-colonized with E. coli mpk develop colitis whereas IL-2(-/--mice mono-colonized with B. vulgatus mpk do not and are even protected from E. coli mpk induced colitis. METHODOLOGY/PRINCIPAL FINDINGS: We investigated if mono-colonization with E. coli mpk or B. vulgatus mpk differentially modulates distribution, activation and maturation of intestinal lamina propria (LP dendritic cells (DC. LP DC in mice mono-colonized with protective B. vulgatus mpk or co-colonized with E. coli mpk/B. vulgatus mpk featured a semi-mature LP DC phenotype (CD40(loCD80(loMHC-II(hi whereas mono-colonization with colitogenic E. coli mpk induced LP DC activation and maturation prior to onset of colitis. Accordingly, chemokine receptor (CCR 7 surface expression was more strikingly enhanced in mesenteric lymph node DC from E. coli mpk than B. vulgatus mpk mono- or co-colonized mice. Mature but not semi-mature LP DC promoted Th1 polarization. As B. vulgatus mpk promotes differentiation of semi-mature DC presumably by IL-6, mRNA and protein expression of IL-6 was investigated in LP DC. The data demonstrated that IL-6 mRNA and protein was increased in LP DC of B. vulgatus mpk as compared to E. coli mpk mono-colonized IL-2(-/--mice. The B. vulgatus mpk mediated suppression of CCR7 expression and DC migration was abolished in IL-6(-/--DC in vitro. CONCLUSIONS/SIGNIFICANCE: From this data we conclude that the B. vulgatus triggered IL-6 secretion by LP DC in absence of proinflammatory cytokines such as IL-12 or TNF-alpha induces a semi-mature LP DC phenotype, which might prevent T-cell activation and thereby the induction of colitis in IL-2(-/--mice. The data provide new evidence that IL-6 might act as an immune regulatory cytokine in the mucosa by targeting intestinal DC.

Using built-in functions of Adobe Acrobat Pro DC to help the selection process in systematic reviews of randomised trials.

Science.gov (United States)

Nur, Selin; Adams, Clive E; Brailsford, David F

2016-02-18

This letter describes a simple way of using Adobe Acrobat Pro DC to help select and auto-extract data from Portable Document Format (PDFs) of randomised trials in order to assist swift early selection of trials for a systematic review.

A Unidirectional DC-DC Autotransformer for DC Grid Application

Directory of Open Access Journals (Sweden)

Meng Zhou

2018-03-01

Full Text Available Conventional unidirectional DC-DC converters for DC grid application employ DC-AC-DC two-stage conversion technology and suffer from high converter cost and power loss. To solve these issues, a unidirectional step-up DC-DC autotransformer (UUDAT and a unidirectional step-down DC-DC autotransformer (DUDAT are studied. The UUDAT and DUDAT are composed of a series connection of diode bridges and voltage source converters. Topologies of UUDAT and DUDAT are detailed. The harmonic and un-controllability issues are discussed. Control and possible application scenarios for UUDAT and DUDAT are depicted. DC fault isolation mechanism and the methods of dimensioning the voltage and power ratings of the components in UUDAT and DUDAT are studied. Extensive simulations on power system level and experiments on a UUDAT and DUDAT prototype verified their technical feasibility.

Pharmacological approach to the mechanisms of transcranial DC-stimulation-induced after-effects of human motor cortex excitability.

Science.gov (United States)

Liebetanz, David; Nitsche, Michael A; Tergau, Frithjof; Paulus, Walter

2002-10-01

Weak transcranial direct current stimulation (tDCS) induces persisting excitability changes in the human motor cortex. These plastic excitability changes are selectively controlled by the polarity, duration and current strength of stimulation. To reveal the underlying mechanisms of direct current (DC)-induced neuroplasticity, we combined tDCS of the motor cortex with the application of Na(+)-channel-blocking carbamazepine (CBZ) and the N-methyl-D-aspartate (NMDA)-receptor antagonist dextromethorphan (DMO). Monitored by transcranial magnetic stimulation (TMS), motor cortical excitability changes of up to 40% were achieved in the drug-free condition. Increase of cortical excitability could be selected by anodal stimulation, and decrease by cathodal stimulation. Both types of excitability change lasted several minutes after cessation of current stimulation. DMO suppressed the post-stimulation effects of both anodal and cathodal DC stimulation, strongly suggesting the involvement of NMDA receptors in both types of DC-induced neuroplasticity. In contrast, CBZ selectively eliminated anodal effects. Since CBZ stabilizes the membrane potential voltage-dependently, the results reveal that after-effects of anodal tDCS require a depolarization of membrane potentials. Similar to the induction of established types of short- or long-term neuroplasticity, a combination of glutamatergic and membrane mechanisms is necessary to induce the after-effects of tDCS. On the basis of these results, we suggest that polarity-driven alterations of resting membrane potentials represent the crucial mechanisms of the DC-induced after-effects, leading to both an alteration of spontaneous discharge rates and to a change in NMDA-receptor activation.

Selective harmonic elimination strategy in eleven level inverter for PV system with unbalanced DC sources

Science.gov (United States)

Ghoudelbourk, Sihem.; Dib, D.; Meghni, B.; Zouli, M.

2017-02-01

The paper deals with the multilevel converters control strategy for photovoltaic system integrated in distribution grids. The objective of the proposed work is to design multilevel inverters for solar energy applications so as to reduce the Total Harmonic Distortion (THD) and to improve the power quality. The multilevel inverter power structure plays a vital role in every aspect of the power system. It is easier to produce a high-power, high-voltage inverter with the multilevel structure. The topologies of multilevel inverter have several advantages such as high output voltage, lower total harmonic distortion (THD) and reduction of voltage ratings of the power semiconductor switching devices. The proposed control strategy ensures an implementation of selective harmonic elimination (SHE) modulation for eleven levels. SHE is a very important and efficient strategy of eliminating selected harmonics by judicious selection of the firing angles of the inverter. Harmonics elimination technique eliminates the need of the expensive low pass filters in the system. Previous research considered that constant and equal DC sources with invariant behavior; however, this research extends earlier work to include variant DC sources, which are typical of lead-acid batteries when used in system PV. This Study also investigates methods to minimize the total harmonic distortion of the synthesized multilevel waveform and to help balance the battery voltage. The harmonic elimination method was used to eliminate selected lower dominant harmonics resulting from the inverter switching action.

The Effector SPRYSEC-19 of Globodera rostochiensis Suppresses CC-NB-LRR-Mediated Disease Resistance in Plants1[C][W][OA

Science.gov (United States)

Postma, Wiebe J.; Slootweg, Erik J.; Rehman, Sajid; Finkers-Tomczak, Anna; Tytgat, Tom O.G.; van Gelderen, Kasper; Lozano-Torres, Jose L.; Roosien, Jan; Pomp, Rikus; van Schaik, Casper; Bakker, Jaap; Goverse, Aska; Smant, Geert

2012-01-01

The potato cyst nematode Globodera rostochiensis invades roots of host plants where it transforms cells near the vascular cylinder into a permanent feeding site. The host cell modifications are most likely induced by a complex mixture of proteins in the stylet secretions of the nematodes. Resistance to nematodes conferred by nucleotide-binding-leucine-rich repeat (NB-LRR) proteins usually results in a programmed cell death in and around the feeding site, and is most likely triggered by the recognition of effectors in stylet secretions. However, the actual role of these secretions in the activation and suppression of effector-triggered immunity is largely unknown. Here we demonstrate that the effector SPRYSEC-19 of G. rostochiensis physically associates in planta with the LRR domain of a member of the SW5 resistance gene cluster in tomato (Lycopersicon esculentum). Unexpectedly, this interaction did not trigger defense-related programmed cell death and resistance to G. rostochiensis. By contrast, agroinfiltration assays showed that the coexpression of SPRYSEC-19 in leaves of Nicotiana benthamiana suppresses programmed cell death mediated by several coiled-coil (CC)-NB-LRR immune receptors. Furthermore, SPRYSEC-19 abrogated resistance to Potato virus X mediated by the CC-NB-LRR resistance protein Rx1, and resistance to Verticillium dahliae mediated by an unidentified resistance in potato (Solanum tuberosum). The suppression of cell death and disease resistance did not require a physical association of SPRYSEC-19 and the LRR domains of the CC-NB-LRR resistance proteins. Altogether, our data demonstrated that potato cyst nematodes secrete effectors that enable the suppression of programmed cell death and disease resistance mediated by several CC-NB-LRR proteins in plants. PMID:22904163

Selective suppression of high-order harmonics within phase-matched spectral regions.

Science.gov (United States)

Lerner, Gavriel; Diskin, Tzvi; Neufeld, Ofer; Kfir, Ofer; Cohen, Oren

2017-04-01

Phase matching in high-harmonic generation leads to enhancement of multiple harmonics. It is sometimes desired to control the spectral structure within the phase-matched spectral region. We propose a scheme for selective suppression of high-order harmonics within the phase-matched spectral region while weakly influencing the other harmonics. The method is based on addition of phase-mismatched segments within a phase-matched medium. We demonstrate the method numerically in two examples. First, we show that one phase-mismatched segment can significantly suppress harmonic orders 9, 15, and 21. Second, we show that two phase-mismatched segments can efficiently suppress circularly polarized harmonics with one helicity over the other when driven by a bi-circular field. The new method may be useful for various applications, including the generation of highly helical bright attosecond pulses.

Cell-mediated immune suppression effect of rocket kerosene through dermal exposure in mice

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Bing-xin XU

2015-10-01

Full Text Available Objective　To study the effect of cell-mediated immune suppression effect of rocket kerosene (RK through dermal application in mice. Methods　Skin delayed type hypersensitivity (DTH was used to observe the relation of the RK amount the skin exposed and the cellular immune inhibitory function. Different amount of the undiluted fuel was smeared directly onto the dorsal skin of mice. Mice in negative and positive control groups were treated with acetone. After the last exposure, all the mice except those in negative control group were allergized by evenly smearing with 1% dinitrofluorobenzene (DNFB solution on their dorsum. Five days after allergy, 1% DNFB solution was smeared onto right ear of all mice to stimulate the allergic reaction. Twenty-four hours after attack, the auricle swelling, spleen index and thymus index in corresponding mice were determined. In the first series of experiments, different dosages of RK were applied once, and the ICR mice were randomly divided into negative control group, positive control group and experimental group (0.5ml/kg.BW×1, 1ml/kg.BW×1 and 2ml/kg.BW×1 group. In the second series of experiments, the certain and same dosage of RK was applied for different times, and the ICR mice were randomly divided into negative control group, positive control group and experimental group (0.5ml/kg.BW×1, 0.5mL/kg.BW×2, 0.5ml/kg.BW×3, 0.5ml/kg.BW×4 and 0.5mL/kg.BW×5 group. In the third series of experiments, the different dosages of RK were applied more than once, and the ICR mice were randomly divided into negative control group, positive control group and experimental group (0.5ml/kg.BW×5, 1ml/kg.BW×5 and 2ml/kg.BW×5 group. Lymphocyte proliferation experiment in vitrowas conducted to observe the persistent time of the cell-mediated immune suppression in mice by RK dermal exposure. The lymphocyte proliferation induced by concanavalin A (Con A was analyzed by MTT assay, and T lymphocyte subsets (CD3+, CD4+ and CD

Acetylation-mediated suppression of transcription-independent memory: bidirectional modulation of memory by acetylation.

Directory of Open Access Journals (Sweden)

Katja Merschbaecher

Full Text Available Learning induced changes in protein acetylation, mediated by histone acetyl transferases (HATs, and the antagonistic histone deacetylases (HDACs play a critical role in memory formation. The status of histone acetylation affects the interaction between the transcription-complex and DNA and thus regulates transcription-dependent processes required for long-term memory (LTM. While the majority of studies report on the role of elevated acetylation in memory facilitation, we address the impact of both, increased and decreased acetylation on formation of appetitive olfactory memory in honeybees. We show that learning-induced changes in the acetylation of histone H3 at aminoacid-positions H3K9 and H3K18 exhibit distinct and different dynamics depending on the training strength. A strong training that induces LTM leads to an immediate increase in acetylation at H3K18 that stays elevated for hours. A weak training, not sufficient to trigger LTM, causes an initial increase in acetylation at H3K18, followed by a strong reduction in acetylation at H3K18 below the control group level. Acetylation at position H3K9 is not affected by associative conditioning, indicating specific learning-induced actions on the acetylation machinery. Elevating acetylation levels by blocking HDACs after conditioning leads to an improved memory. While memory after strong training is enhanced for at least 2 days, the enhancement after weak training is restricted to 1 day. Reducing acetylation levels by blocking HAT activity after strong training leads to a suppression of transcription-dependent LTM. The memory suppression is also observed in case of weak training, which does not require transcription processes. Thus, our findings demonstrate that acetylation-mediated processes act as bidirectional regulators of memory formation that facilitate or suppress memory independent of its transcription-requirement.

A new phase modulated binomial-like selective-inversion sequence for solvent signal suppression in NMR.

Science.gov (United States)

Chen, Johnny; Zheng, Gang; Price, William S

2017-02-01

A new 8-pulse Phase Modulated binomial-like selective inversion pulse sequence, dubbed '8PM', was developed by optimizing the nutation and phase angles of the constituent radio-frequency pulses so that the inversion profile resembled a target profile. Suppression profiles were obtained for both the 8PM and W5 based excitation sculpting sequences with equal inter-pulse delays. Significant distortions were observed in both profiles because of the offset effect of the radio frequency pulses. These distortions were successfully reduced by adjusting the inter-pulse delays. With adjusted inter-pulse delays, the 8PM and W5 based excitation sculpting sequences were tested on an aqueous lysozyme solution. The 8 PM based sequence provided higher suppression selectivity than the W5 based sequence. Two-dimensional nuclear Overhauser effect spectroscopy experiments were also performed on the lysozyme sample with 8PM and W5 based water signal suppression. The 8PM based suppression provided a spectrum with significantly increased (~ doubled) cross-peak intensity around the suppressed water resonance compared to the W5 based suppression. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Selective Attention in Inattentional Blindness: Selection is Specific but Suppression is Not

Directory of Open Access Journals (Sweden)

Katherine Wood

2017-08-01

Full Text Available When we selectively attend to one set of objects and ignore another, we often fail to notice unexpected events. The likelihood of noticing varies depending on the similarity of an unexpected object to other items in the display, a process thought to be controlled by the attention set that we create for the attended and ignored objects. It remains unclear, though, how attention sets are formed and structured. Do they enhance features of attended objects (“white” and suppress features of ignored objects (“black”, or do they distinguish objects based on relations or categories (“darker” versus “lighter,” or “dark objects” versus “light objects”? In previous work, these explanations are confounded; the objects would be partitioned into the same groups regardless the structure of the attention set. In the present three experiments, the attended or ignored set of objects was a constant color while the other set was variable. When people attended white and ignored a multicolored set of objects (Experiment 1, novel colors were suppressed just as much as display colors, suggesting nonselective filtering of nonwhite objects. When the color of one set of objects varied across displays but was constant within them (Experiments 2 and 3, we again found as much suppression for task-irrelevant and novel colors as for actively ignored ones. Whenever people ignored a set of objects that varied in color, they suppressed unexpected objects that matched the ignored colors and that differed from the actively ignored items on the critical trial. In contrast, when people attended a varying set, noticing was enhanced only for unexpected objects that matched the currently attended color. In this task, attentional filtering is category-based and did not depend on the features of the individual objects.

Induction of osteoblast differentiation by selective activation of kinase-mediated actions of the estrogen receptor.

Science.gov (United States)

Kousteni, Stavroula; Almeida, Maria; Han, Li; Bellido, Teresita; Jilka, Robert L; Manolagas, Stavros C

2007-02-01

Estrogens control gene transcription by cis or trans interactions of the estrogen receptor (ER) with target DNA or via the activation of cytoplasmic kinases. We report that selective activation of kinase-mediated actions of the ER with 4-estren-3alpha,17beta-diol (estren) or an estradiol-dendrimer conjugate, each a synthetic compound that stimulates kinase-mediated ER actions 1,000 to 10,000 times more potently than direct DNA interactions, induced osteoblastic differentiation in established cell lines of uncommitted osteoblast precursors and primary cultures of osteoblast progenitors by stimulating Wnt and BMP-2 signaling in a kinase-dependent manner. In sharp contrast, 17beta-estradiol (E(2)) suppressed BMP-2-induced osteoblast progenitor commitment and differentiation. Consistent with the in vitro findings, estren, but not E(2), stimulated Wnt/beta-catenin-mediated transcription in T-cell factor-lacZ transgenic mice. Moreover, E(2) stimulated BMP signaling in mice in which ERalpha lacks DNA binding activity and classical estrogen response element-mediated transcription (ERalpha(NERKI/-)) but not in wild-type controls. This evidence reveals for the first time the existence of a large signalosome in which inputs from the ER, kinases, bone morphogenetic proteins, and Wnt signaling converge to induce differentiation of osteoblast precursors. ER can either induce it or repress it, depending on whether the activating ligand (and presumably the resulting conformation of the receptor protein) precludes or accommodates ERE-mediated transcription.

Assessing the role of STAT3 in DC differentiation and autologous DC immunotherapy in mouse models of GBM.

Directory of Open Access Journals (Sweden)

Hikmat Assi

Full Text Available Cellular microenvironments, particularly those found in tumors, elicit a tolerogenic DC phenotype which can attenuate immune responses. Central to this process is the STAT3-mediated signaling cascade. As a transcription factor and oncogene, STAT3 promotes the expression of genes which allow tumor cells to proliferate, migrate and evade apoptosis. More importantly, activation of STAT3 in tumor infiltrating immune cells has been shown to be responsible, in part, for their immune-suppressed phenotype. The ability of STAT3 to orchestrate a diverse set of immunosuppressive instructions has made it an attractive target for cancer vaccines. Using a conditional hematopoietic knockout mouse model of STAT3, we evaluated the impact of STAT3 gene ablation on the differentiation of dendritic cells from bone marrow precursors. We also assessed the impact of STAT3 deletion on phagocytosis, maturation, cytokine secretion and antigen presentation by GM-CSF derived DCs in vitro. In addition to in vitro studies, we compared the therapeutic efficacy of DC vaccination using STAT3 deficient DCs to wild type counterparts in an intracranial mouse model of GBM. Our results indicated the following pleiotropic functions of STAT3: hematopoietic cells which lacked STAT3 were unresponsive to Flt3L and failed to differentiate as DCs. In contrast, STAT3 was not required for GM-CSF induced DC differentiation as both wild type and STAT3 null bone marrow cells gave rise to similar number of DCs. STAT3 also appeared to regulate the response of GM-CSF derived DCs to CpG. STAT3 null DCs expressed high levels of MHC-II, secreted more IL-12p70, IL-10, and TNFα were better antigen presenters in vitro. Although STAT3 deficient DCs displayed an enhanced activated phenotype in culture, they elicited comparable therapeutic efficacy in vivo compared to their wild type counterparts when utilized in vaccination paradigms in mice bearing intracranial glioma tumors.

Assessing the role of STAT3 in DC differentiation and autologous DC immunotherapy in mouse models of GBM.

Science.gov (United States)

Assi, Hikmat; Espinosa, Jaclyn; Suprise, Sarah; Sofroniew, Michael; Doherty, Robert; Zamler, Daniel; Lowenstein, Pedro R; Castro, Maria G

2014-01-01

Cellular microenvironments, particularly those found in tumors, elicit a tolerogenic DC phenotype which can attenuate immune responses. Central to this process is the STAT3-mediated signaling cascade. As a transcription factor and oncogene, STAT3 promotes the expression of genes which allow tumor cells to proliferate, migrate and evade apoptosis. More importantly, activation of STAT3 in tumor infiltrating immune cells has been shown to be responsible, in part, for their immune-suppressed phenotype. The ability of STAT3 to orchestrate a diverse set of immunosuppressive instructions has made it an attractive target for cancer vaccines. Using a conditional hematopoietic knockout mouse model of STAT3, we evaluated the impact of STAT3 gene ablation on the differentiation of dendritic cells from bone marrow precursors. We also assessed the impact of STAT3 deletion on phagocytosis, maturation, cytokine secretion and antigen presentation by GM-CSF derived DCs in vitro. In addition to in vitro studies, we compared the therapeutic efficacy of DC vaccination using STAT3 deficient DCs to wild type counterparts in an intracranial mouse model of GBM. Our results indicated the following pleiotropic functions of STAT3: hematopoietic cells which lacked STAT3 were unresponsive to Flt3L and failed to differentiate as DCs. In contrast, STAT3 was not required for GM-CSF induced DC differentiation as both wild type and STAT3 null bone marrow cells gave rise to similar number of DCs. STAT3 also appeared to regulate the response of GM-CSF derived DCs to CpG. STAT3 null DCs expressed high levels of MHC-II, secreted more IL-12p70, IL-10, and TNFα were better antigen presenters in vitro. Although STAT3 deficient DCs displayed an enhanced activated phenotype in culture, they elicited comparable therapeutic efficacy in vivo compared to their wild type counterparts when utilized in vaccination paradigms in mice bearing intracranial glioma tumors.

A resonant dc-dc power converter assembly

DEFF Research Database (Denmark)

2015-01-01

The present invention relates to a resonant DC-DC power converter assembly comprising a first resonant DC-DC power converter and a second resonant DC-DC power converter having identical circuit topologies. A first inductor of the first resonant DC-DC power converter and a second inductor of the s......The present invention relates to a resonant DC-DC power converter assembly comprising a first resonant DC-DC power converter and a second resonant DC-DC power converter having identical circuit topologies. A first inductor of the first resonant DC-DC power converter and a second inductor...... of the second resonant DC-DC power converter are configured for magnetically coupling the first and second resonant DC-DC power converters to each other to forcing substantially 180 degrees phase shift, or forcing substantially 0 degree phase shift, between corresponding resonant voltage waveforms of the first...

Faraday-Shielded dc Stark-Shift-Free Optical Lattice Clock

Science.gov (United States)

Beloy, K.; Zhang, X.; McGrew, W. F.; Hinkley, N.; Yoon, T. H.; Nicolodi, D.; Fasano, R. J.; Schäffer, S. A.; Brown, R. C.; Ludlow, A. D.

2018-05-01

We demonstrate the absence of a dc Stark shift in an ytterbium optical lattice clock. Stray electric fields are suppressed through the introduction of an in-vacuum Faraday shield. Still, the effectiveness of the shielding must be experimentally assessed. Such diagnostics are accomplished by applying high voltage to six electrodes, which are grounded in normal operation to form part of the Faraday shield. Our measurements place a constraint on the dc Stark shift at the 10-20 level, in units of the clock frequency. Moreover, we discuss a potential source of error in strategies to precisely measure or cancel nonzero dc Stark shifts, attributed to field gradients coupled with the finite spatial extent of the lattice-trapped atoms. With this consideration, we find that Faraday shielding, complemented with experimental validation, provides both a practically appealing and effective solution to the problem of dc Stark shifts in optical lattice clocks.

DC Stark addressing for quantum memory in Tm:YAG

Science.gov (United States)

Gerasimov, Konstantin; Minnegaliev, Mansur; Urmancheev, Ravil; Moiseev, Sergey

2017-10-01

We observed a linear DC Stark effect for 3H6 - 3H4 optical transition of Tm3+ ions in Y3Al5O12. We observed that application of electric field pulse suppresses the two-pulse photon echo signal. If we then apply a second electric pulse of opposite polarity the echo signal is restored again, which indicates the linear nature of the observed effect. The effect is present despite the D2 symmetry of the Tm3+ sites that prohibits a linear Stark effect. Experimental data analysis shows that the observed electric field influence can be attributed to defects that break the local crystal field symmetry near Tm3+ ions. Using this effect we demonstrate selective retrieval of light pulses in two-pulse photon echo.

Step-Up DC-DC converters

DEFF Research Database (Denmark)

Forouzesh, Mojtaba; Siwakoti, Yam P.; Gorji, Saman A.

2017-01-01

on the general law and framework of the development of next-generation step-up dc-dc converters, this paper aims to comprehensively review and classify various step-up dc-dc converters based on their characteristics and voltage-boosting techniques. In addition, the advantages and disadvantages of these voltage......DC-DC converters with voltage boost capability are widely used in a large number of power conversion applications, from fraction-of-volt to tens of thousands of volts at power levels from milliwatts to megawatts. The literature has reported on various voltage-boosting techniques, in which......-boosting techniques and associated converters are discussed in detail. Finally, broad applications of dc-dc converters are presented and summarized with comparative study of different voltage-boosting techniques....

A resonant dc-dc power converter assembly

OpenAIRE

Madsen, Mickey Pierre

2015-01-01

The present invention relates to a resonant DC-DC power converter assembly comprising a first resonant DC-DC power converter and a second resonant DC-DC power converter having identical circuit topologies. A first inductor of the first resonant DC-DC power converter and a second inductor of the second resonant DC-DC power converter are configured for magnetically coupling the first and second resonant DC-DC power converters to each other to forcing substantially 180 degrees phase shift, or fo...

Mucuna pruriens (L.) DC chemo sensitize human breast cancer cells via downregulation of prolactin-mediated JAK2/STAT5A signaling.

Science.gov (United States)

Sinha, Sonam; Sharma, Sonal; Vora, Jaykant; Shah, Heta; Srivastava, Anshu; Shrivastava, Neeta

2018-05-10

Mucuna pruriens (L.) DC (MP) is an ancient Indian medicinal plant traditionally used to treat Parkinson's disease. L-Dopa (LD), precursor of dopamine is abundantly found in the seeds of MP. L-dopa is a natural inhibitor of prolactin (PRL) hormone which is required to maintain lactation in women but it's over production (hyperprolactinemia) plays critical role in advancement of breast cancer. We aim to examine the pharmacological effect of LD and MP on this hyperprolactinemia associated breast cancer and related signaling for effective management of the disease. We also investigated chemo-sensitizing effect of MP on hyperprolactinemia-mediated cisplatin resistance. Methanolic seed extract of MP were prepared and analysed using HPLC. Effect of LD and MP on the cellular viability of breast cancer cells (T47D, MCF-7, MDA-MB-468 and MDA-MB-231) were evaluated using MTT assay. Further, effect of LD and MP on colony forming potential, DNA damage, cell cycle distribution and apoptosis was determined using agar/agarose method, comet assay and annexin and PI method followed by FACS analysis. To reveal the molecular mechanism involved in the anti-cancer activity of MP, transcriptional and translational level analysis of the key proteins involved in the PRL-mediated signaling, was performed using RT-PCR and western blot analysis. The effect of MP extract on PRL-mediated signaling was validated using dopaminergic agonist bromocriptine. MP extract and cisplatin was given in different combination with appropriate controls to check their effect on chemo-resistivity of breast cancer cells. Our results demonstrated that MP seed extract has the potential to inhibit cellular proliferation of PRL expressing T47D and MCF-7 breast cancer cells via induction of DNA damage, G1 phase of cell cycle arrest and apoptosis more effectively as compare to LD. Further, MP-mediated anti-cancerous effect was associated with the downregulation of PRL expression, further suppressing the JAK2/STAT5A

Tumor-Mediated Suppression of Dendritic Cell Vaccines

National Research Council Canada - National Science Library

Akporiaye, Emmanuel

2004-01-01

.... One of these factors is Transforming Growth Factor-beta (TGF-beta). TGF-beta is produced in large quantities by different types of cancer including breast cancer and inhibits the actions of several immune cells including dendritic cells (DC...

Influence of DC arc jets on flow fields analyzed by an integrated numerical model for a DC-RF hybrid plasma

International Nuclear Information System (INIS)

Seo, Jun Ho; Park, Jin Myung; Hong, Sang Hee

2008-01-01

The influence of DC arc jets on the flow fields in a hybrid plasma torch is numerically analyzed by an integrated direct current-radio frequency (DC-RF) plasma model based on magneto-hydrodynamic formulations. The calculated results reveal that the increase in DC arc gas flow rate raises the axial flow velocity along the central column of the DC-RF hybrid plasma together with the enhanced backflow streams in the peripheral wall region. The temperature profiles on the torch exit plane are little affected due to the reheating process of the central column by the combined RF plasma. Accordingly, the exit enthalpy emitted from the DC-RF hybrid torch can be concentrated to the central column of the plasma and controlled by adjusting the DC arc gas flow rate. The swirl in the sheath gas flow turns out to have the opposite effect on the DC arc gas flow rate. The swirling motion of the sheath gas can reduce the back flows near the induction tube wall as well as the axial velocities in the central column of the plasma. Accordingly, the swirl in the sheath gas flow can be used for the functional operation of the DC-RF hybrid plasma along with the DC arc gas flow rate to suppress the back flows at the wall region and to reduce the excessive interactions between the DC arc jet and the ambient RF plasmas. The effects of DC input current on the flow fields of hybrid plasma are similar to those of the DC arc gas flow rate, but the axial velocities for the higher current relatively quickly decay along the centerline. This is in contrast to the increase in the axial velocity remaining in proportion to the increase in the DC arc gas flow rate all the way up to the exit of the DC-RF hybrid plasma. Accordingly, the present integrated numerical analysis suggests that the hybrid plasma field profiles and the entrainment of ambient air from the torch exit are controllable by adjusting the DC arc gas flow rate, the DC input current and swirl in the sheath gas flow taking advantage of

Tetherin Suppresses Type I Interferon Signaling by Targeting MAVS for NDP52-Mediated Selective Autophagic Degradation in Human Cells.

Science.gov (United States)

Jin, Shouheng; Tian, Shuo; Luo, Man; Xie, Weihong; Liu, Tao; Duan, Tianhao; Wu, Yaoxing; Cui, Jun

2017-10-19

Tetherin (BST2/CD317) is an interferon-inducible antiviral factor known for its ability to block the release of enveloped viruses from infected cells. Yet its role in type I interferon (IFN) signaling remains poorly defined. Here, we demonstrate that Tetherin is a negative regulator of RIG-I like receptor (RLR)-mediated type I IFN signaling by targeting MAVS. The induction of Tetherin by type I IFN accelerates MAVS degradation via ubiquitin-dependent selective autophagy in human cells. Moreover, Tetherin recruits E3 ubiquitin ligase MARCH8 to catalyze K27-linked ubiquitin chains on MAVS at lysine 7, which serves as a recognition signal for NDP52-dependent autophagic degradation. Taken together, our findings reveal a negative feedback loop of RLR signaling generated by Tetherin-MARCH8-MAVS-NDP52 axis and provide insights into a better understanding of the crosstalk between selective autophagy and optimal deactivation of type I IFN signaling. Copyright © 2017 Elsevier Inc. All rights reserved.

Suppression of Oncolytic Adenovirus-Mediated Hepatotoxicity by Liver-Specific Inhibition of NF-κB

Directory of Open Access Journals (Sweden)

Mitsuhiro Machitani

2017-12-01

Full Text Available Telomerase-specific replication-competent adenoviruses (Ads, i.e., TRADs, which possess an E1 gene expression cassette driven by the human telomerase reverse transcriptase promoter, are promising agents for cancer treatment. However, even though oncolytic Ads, including TRAD, are intratumorally administered, they are disseminated from the tumor to systemic circulation, causing concern about oncolytic Ad-mediated hepatotoxicity (due mainly to leaky expression of Ad genes in liver. We reported that inhibition of nuclear factor-κB (NF-κB leads to the suppression of replication-incompetent Ad vector-mediated hepatotoxicity via reduction of the leaky expression of Ad genes in liver. Here, to develop a TRAD with an improved safety profile, we designed a TRAD that carries a liver-specific promoter-driven dominant-negative IκBα (DNIκBα expression cassette (TRAD-DNIκBα. Compared with a conventional TRAD, TRAD-DNIκBα showed hepatocyte-specific inhibition of NF-κB signaling and significantly reduced Ad gene expression and replication in the normal human hepatocyte cell line. TRAD-induced hepatotoxicity was largely suppressed in mice following intravenous administration of TRAD-DNIκBα. However, the replication profiles and oncolytic activities of TRAD-DNIκBα were comparable with those of the conventional TRAD in human non-hepatic tumor cells. These results indicate that oncolytic Ads containing the liver-specific DNIκBα expression cassette have improved safety profiles without inhibiting oncolytic activities.

Selecting a model of supersymmetry breaking mediation

International Nuclear Information System (INIS)

AbdusSalam, S. S.; Allanach, B. C.; Dolan, M. J.; Feroz, F.; Hobson, M. P.

2009-01-01

We study the problem of selecting between different mechanisms of supersymmetry breaking in the minimal supersymmetric standard model using current data. We evaluate the Bayesian evidence of four supersymmetry breaking scenarios: mSUGRA, mGMSB, mAMSB, and moduli mediation. The results show a strong dependence on the dark matter assumption. Using the inferred cosmological relic density as an upper bound, minimal anomaly mediation is at least moderately favored over the CMSSM. Our fits also indicate that evidence for a positive sign of the μ parameter is moderate at best. We present constraints on the anomaly and gauge mediated parameter spaces and some previously unexplored aspects of the dark matter phenomenology of the moduli mediation scenario. We use sparticle searches, indirect observables and dark matter observables in the global fit and quantify robustness with respect to prior choice. We quantify how much information is contained within each constraint.

Curcumin inhibits urothelial tumor development by suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway.

Science.gov (United States)

Tian, Binqiang; Zhao, Yingmei; Liang, Tao; Ye, Xuxiao; Li, Zuowei; Yan, Dongliang; Fu, Qiang; Li, Yonghui

2017-08-01

We have previously reported that curcumin inhibits urothelial tumor development in a rat bladder carcinogenesis model. In this study, we report that curcumin inhibits urothelial tumor development by suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway. Curcumin inhibits IGF2 expression at the transcriptional level and decreases the phosphorylation levels of IGF1R and IRS-1 in bladder cancer cells and N-methyl-N-nitrosourea (MNU)-induced urothelial tumor tissue. Ectopic expression of IGF2 and IGF1R, but not IGF1, in bladder cancer cells restored this process, suggesting that IGF2 is a target of curcumin. Moreover, introduction of constitutively active AKT1 abolished the inhibitory effect of curcumin on cell proliferation, migration, and restored the phosphorylation levels of 4E-BP1 and S6K1, suggesting that curcumin functions via suppressing IGF2-mediated AKT/mTOR signaling pathway. In summary, our results reveal that suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway is one of the mechanisms of action of curcumin. Our findings suggest a new therapeutic strategy against human bladder cancer caused by aberrant activation of IGF2, which are useful for translational application of curcumin.

Integrated Three-Voltage-Booster DC-DC Converter to Achieve High Voltage Gain with Leakage-Energy Recycling for PV or Fuel-Cell Power Systems

Directory of Open Access Journals (Sweden)

Chih-Lung Shen

2015-09-01

Full Text Available In this paper, an integrated three-voltage-booster DC-DC (direct current to direct current converter is proposed to achieve high voltage gain for renewable-energy generation systems. The proposed converter integrates three voltage-boosters into one power stage, which is composed of an active switch, a coupled-inductor, five diodes, and five capacitors. As compared with conventional high step-up converters, it has a lower component count. In addition, the features of leakage-energy recycling and switching loss reduction can be accomplished for conversion efficiency improvement. While the active switch is turned off, the converter can inherently clamp the voltage across power switch and suppress voltage spikes. Moreover, the reverse-recovery currents of all diodes can be alleviated by leakage inductance. A 200 W prototype operating at 100 kHz switching frequency with 36 V input and 400 V output is implemented to verify the theoretical analysis and to demonstrate the feasibility of the proposed high step-up DC-DC converter.

Step-Up DC-DC converters

DEFF Research Database (Denmark)

Forouzesh, Mojtaba; Siwakoti, Yam P.; Gorji, Saman A.

2017-01-01

on the general law and framework of the development of next-generation step-up dc-dc converters, this paper aims to comprehensively review and classify various step-up dc-dc converters based on their characteristics and voltage-boosting techniques. In addition, the advantages and disadvantages of these voltage...

Role of aryl hydrocarbon receptor polymorphisms on TCDD-mediated CYP1B1 induction and IgM suppression by human B cells

Energy Technology Data Exchange (ETDEWEB)

Kovalova, Natalia, E-mail: kovalova@msu.edu [Department of Pharmacology and Toxicology, Michigan State University, Lansing, MI 48824 (United States); Institute for Integrative Toxicology, Michigan State University, Lansing, MI 48824 (United States); Manzan, Maria, E-mail: ale.manzan@gmail.com [Institute for Integrative Toxicology, Michigan State University, Lansing, MI 48824 (United States); Crawford, Robert, E-mail: crawfo28@msu.edu [Institute for Integrative Toxicology, Michigan State University, Lansing, MI 48824 (United States); Kaminski, Norbert, E-mail: kamins11@msu.edu [Department of Pharmacology and Toxicology, Michigan State University, Lansing, MI 48824 (United States); Institute for Integrative Toxicology, Michigan State University, Lansing, MI 48824 (United States)

2016-10-15

Previous studies have demonstrated that most of the intraspecies variation in sensitivity to the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), including suppression of antibody responses, in murine models is due to single nucleotide polymorphisms (SNPs) within the aryl hydrocarbon receptor (AhR) gene. The underlying reason for variation in sensitivity to TCDD-induced suppression of IgM responses among humans is not well understood, but is thought, in part, to be a result of different polymorphic forms of the AhR expressed by different individuals. In this study, the functional properties of six (P517S, R554K, V570I, V570I + P517S, R554K + V570I and P517S + R554K + V570I) human AhR variants were examined in the human B cell line, SKW 6.4. TCDD-induced Cyp1B1 and Cyp1A2 mRNA expression levels and Cyp1B1-regulated reporter gene activity, used for comparative purposes, were markedly lower in SKW cells containing the R554K SNP than in SKW-AHR{sup +} (control AhR) cells. Furthermore, all AhR variants were able to mediate TCDD-induced suppression of the IgM response; however, a combined P517S + R554K + V570I variant partially reduced sensitivity to TCDD-mediated suppression of IgM secretion. Collectively, our findings show that the R554K human AhR SNP alone altered sensitivity of human B cells to TCDD-mediated induction of Cyp1B1 and Cyp1A2. By contrast, attenuation of TCDD-induced IgM suppression required a combination of all three SNPs P517S, R554K, and V570I. - Highlights: • Mouse, rat and SKW-AHR{sup +} B cells have a similar window of sensitivity to TCDD. • R554K AhR SNP alters B cell sensitivity to TCDD-mediated Cyp1B1 and Cyp1A2 induction. • Combination of P517S, R554K, and V570I SNPs attenuates TCDD-induced IgM suppression.

Emotion regulation mediates age differences in emotions.

Science.gov (United States)

Yeung, Dannii Y; Wong, Carmen K M; Lok, David P P

2011-04-01

This study aimed at testing the proposition of socioemotional selectivity theory whether older people would use more antecedent-focused emotion regulatory strategies like cognitive reappraisal but fewer response-focused strategies like suppression. It also aimed at investigating the mediating role of emotion regulation on the relationship between age and emotions. The sample consisted of 654 younger and older adults aged between 18 and 64. Results showed that age was significantly associated with positive emotions and cognitive reappraisal. No difference was found in negative emotions and suppression between younger and older adults. Cognitive reappraisal partially mediated the effect of age on positive emotions. Findings of this study contribute to our understanding of the underlying mechanism of age variations in emotional experiences.

Pathogenesis of herpes simplex virus in B cell-suppressed mice: the relative roles of cell-mediated and humoral immunity.

Science.gov (United States)

Kapoor, A K; Nash, A A; Wildy, P

1982-07-01

B cell responses of Balb/c mice were suppressed using sheep anti-mouse IgM serum. At 4 weeks, both B cell-suppressed and normal littermates were infected in the ear pinna with herpes simplex virus type 1 (HSV-1). The B cell-suppressed mice failed to produce neutralizing herpes antibodies in their sera but had a normal cell-mediated immunity (CMI) response as measured by a delayed hypersensitivity skin test. Although the infection was eliminated from the ear in both B cell-suppressed and normal mice by day 10 after infection, there was an indication that B cell-suppressed mice had a more florid primary infection of the peripheral and central nervous system and also a higher incidence of a latent infection. These results support the hypothesis that antibody is important in restricting the spread of virus to the central nervous system, whereas CMI is important in clearing the primary infection in the ear pinna.

Power Quality in DC Power Distribution Systems and Microgrids

Directory of Open Access Journals (Sweden)

Stephen Whaite

2015-05-01

Full Text Available This review paper discusses power quality considerations for direct current (DC electric power distribution systems, particularly DC microgrids. First, four selected sample DC architectures are discussed to provide motivation for the consideration of power quality in DC systems. Second, a brief overview of power quality challenges in conventional alternating current (AC distribution systems is given to establish the field of power quality. Finally, a survey of literature addressing power quality issues in DC systems is presented, and necessary power quality considerations in DC distribution system design and operation are discussed.

3-bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth.

Science.gov (United States)

Wang, Ting-An; Zhang, Xiao-Dong; Guo, Xing-Yu; Xian, Shu-Lin; Lu, Yun-Fei

2016-03-01

Glycolysis is the primary method utilized by cancer cells to produce the energy (adenosine triphosphate, ATP) required for cell proliferation. Therefore, inhibition of glycolysis may inhibit tumor growth. We previously found that both 3-bromopyruvate (3-BrPA) and sodium citrate (SCT) can inhibit glycolysis in vitro; however, the underlying inhibitory mechanisms remain unclear. In the present study, we used a human gastric cancer cell line (SGC-7901) and an orthotopic transplantation tumor model in nude mice to explore the specific mechanisms of 3-BrPA and SCT. We found that both 3-BrPA and SCT effectively suppressed cancer cell proliferation, arrested the cell cycle, induced apoptosis, and decreased the production of lactate and ATP. 3-BrPA significantly reduced the glycolytic enzyme hexokinase activity, while SCT selectively inhibited phosphofructokinase-1 activity. Furthermore, 3-BrPA and SCT upregulated the expression of pro-apoptotic proteins (Bax, cytochrome c, and cleaved caspase-3) and downregulated the expression of anti-apoptotic proteins (Bcl-2 and survivin). Finally, our animal model of gastric cancer indicated that intraperitoneal injection of 3-BrPA and SCT suppressed orthotopic transplantation tumor growth and induced tumor apoptosis. Taken together, these results suggest that 3-BrPA and SCT selectively suppress glycolytic enzymes, decrease ATP production, induce mitochondrial-mediated apoptosis, downregulate survivin, and inhibit tumor growth. Moreover, an intraperitoneal injection is an effective form of administration of 3-BrPA and SCT.

Simian virus 40 inhibits differentiation and maturation of rhesus macaque DC-SIGN+-dendritic cells

Directory of Open Access Journals (Sweden)

Changyong G

2010-09-01

Full Text Available Abstract Dendritic cells (DC are the initiators and modulators of the immune responses. Some species of pathogenic microorganisms have developed immune evasion strategies by controlling antigen presentation function of DC. Simian virus 40 (SV40 is a DNA tumor virus of rhesus monkey origin. It can induce cell transformation and tumorigenesis in many vertebrate species, but often causes no visible effects and persists as a latent infection in rhesus monkeys under natural conditions. To investigate the interaction between SV40 and rhesus monkey DC, rhesus monkey peripheral blood monocyte-derived DC were induced using recombinant human Interleukin-4 (rhIL-4 and infective SV40, the phenotype and function of DC-specific intracellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN+ DC were analyzed by flow cytometry (FCM and mixed lymphocyte reaction (MLR. Results showed that SV40 can down-regulate the expression of CD83 and CD86 on DC and impair DC-induced activation of T cell proliferation. These findings suggest that SV40 might also cause immune suppression by influencing differentiation and maturation of DC.

DC KIDS COUNT e-Databook Indicators

Science.gov (United States)

DC Action for Children, 2012

2012-01-01

This report presents indicators that are included in DC Action for Children's 2012 KIDS COUNT e-databook, their definitions and sources and the rationale for their selection. The indicators for DC KIDS COUNT represent a mix of traditional KIDS COUNT indicators of child well-being, such as the number of children living in poverty, and indicators of…

Adeno-associated virus-mediated doxycycline-regulatable TRAIL expression suppresses growth of human breast carcinoma in nude mice

International Nuclear Information System (INIS)

Zheng, Liu; Weilun, Zhang; Minghong, Jiang; Yaxi, Zhang; Shilian, Liu; Yanxin, Liu; Dexian, Zheng

2012-01-01

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) functions as a cytokine to selectively kill various cancer cells without toxicity to most normal cells. Numerous studies have demonstrated the potential use of recombinant soluble TRAIL as a cancer therapeutic agent. We have showed previous administration of a recombinant adeno-associated virus (rAAV) vector expressing soluble TRAIL results in an efficient suppression of human tumor growth in nude mice. In the present study, we introduced Tet-On gene expression system into the rAAV vector to control the soluble TRAIL expression and evaluate the efficiency of the system in cancer gene therapy. Controllability of the Tet-On system was determined by luciferase activity assay, and Western blotting and enzyme-linked immunoabsorbent assay. Cell viability was determined by MTT assay. The breast cancer xenograft animal model was established and recombinant virus was administrated through tail vein injection to evaluate the tumoricidal activity. The expression of soluble TRAIL could be strictly controlled by the Tet-On system in both normal and cancer cells. Transduction of human cancer cell lines with rAAV-TRE-TRAIL&rAAV-Tet-On under the presence of inducer doxycycline resulted in a considerable cell death by apoptosis. Intravenous injection of the recombinant virus efficiently suppressed the growth of human breast carcinoma in nude mice when activated by doxycycline. These data suggest that rAAV-mediated soluble TRAIL expression under the control of the Tet-On system is a promising strategy for breast cancer therapy

75 FR 23571 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-10-10, DC-10-10F, DC-10-15, DC...

Science.gov (United States)

2010-05-04

... Airworthiness Directives; McDonnell Douglas Corporation Model DC- 10-10, DC-10-10F, DC-10-15, DC-10-30, DC-10... amends Sec. 39.13 by adding the following new AD: 2010-09-12 McDonnell Douglas Corporation: Amendment 39... to McDonnell Douglas Corporation Model DC- 10-10, DC-10-10F, DC-10-15, DC-10-30, DC-10-30F (KC-10A...

Discharge Characteristic of VHF-DC Superimposed Magnetron Sputtering System

Science.gov (United States)

Toyoda, Hirotaka; Fukuoka, Yushi; Fukui, Takashi; Takada, Noriharu; Sasai, Kensuke

2014-10-01

Magnetron plasmas are one of the most important tools for sputter deposition of thin films. However, energetic particles from the sputtered target such as backscattered rare gas atoms or oxygen negative ions from oxide targets sometimes induce physical and chemical damages as well as surface roughening to the deposited film surface during the sputtering processes. To suppress kinetic energy of such particles, superposition of RF or VHF power to the DC power has been investigated. In this study, influence of the VHF power superposition on the DC target voltage, which is important factor to determine kinetic energy of high energy particles, is investigated. In the study, 40 MHz VHF power was superimposed to an ITO target and decrease in the target DC voltage was measured as well as deposited film deposition properties such as deposition rate or electrical conductivity. From systematic measurement of the target voltage, it was revealed that the target voltage can be determined by a very simple parameter, i.e., a ratio of VHF power to the total input power (DC and VHF powers) in spite of the DC discharge current. Part of this work was supported by ASTEP, JST.

Sensitivity to Sunburn Is Associated with Susceptibility to Ultraviolet Radiation–Induced Suppression of Cutaneous Cell–Mediated Immunity

Science.gov (United States)

Kelly, Deirdre A.; Young, Antony R.; McGregor, Jane M.; Seed, Paul T.; Potten, Christopher S.; Walker, Susan L.

2000-01-01

Skin cancer incidence is highest in white-skinned people. Within this group, skin types I/II (sun sensitive/tan poorly) are at greater risk than skin types III/IV (sun tolerant/tan well). Studies in mice demonstrate that ultraviolet radiation (UVR)-induced suppression of cell-mediated immune function plays an important role in the development of skin cancer and induces a susceptibility to infectious disease. A similar role is suspected in humans, but we lack quantitative human data to make risk assessments of ambient solar exposure on human health. This study demonstrates that ambient levels of solar UVR, typically experienced within 1 h of exposure to noonday summer sunlight, can suppress contact hypersensitivity (CHS) responses in healthy white-skinned humans in vivo (n = 93). There was a linear relationship between increase in erythema and suppression of CHS (P sunburn (two minimal erythema doses [2 MED]) was sufficient to suppress CHS in all volunteers by 93%. However, a single suberythemal exposure of either 0.25 or 0.5 MED suppressed CHS responses by 50 and 80%, respectively, in skin types I/II, whereas 1 MED only suppressed CHS by 40% in skin types III/IV. The two- to threefold greater sensitivity of skin types I/II for a given level of sunburn may play a role in their greater sensitivity to skin cancer. PMID:10662801

Arctigenin suppresses receptor activator of nuclear factor κB ligand (RANKL)-mediated osteoclast differentiation in bone marrow-derived macrophages.

Science.gov (United States)

Kim, A-Ram; Kim, Hyuk Soon; Lee, Jeong Min; Choi, Jung Ho; Kim, Se Na; Kim, Do Kyun; Kim, Ji Hyung; Mun, Se Hwan; Kim, Jie Wan; Jeon, Hyun Soo; Kim, Young Mi; Choi, Wahn Soo

2012-05-05

Osteoclasts, multinucleated bone-resorbing cells, are closely associated with bone diseases such as rheumatoid arthritis and osteoporosis. Osteoclasts are derived from hematopoietic precursor cells, and their differentiation is mediated by two cytokines, including macrophage colony stimulating factor and receptor activator of nuclear factor κB ligand (RANKL). Previous studies have shown that arctigenin exhibits an anti-inflammatory effect. However, the effect of arctigenin on osteoclast differentiation is yet to be elucidated. In this study, we found that arctigenin inhibited RANKL-mediated osteoclast differentiation in bone marrow macrophages in a dose-dependent manner and suppressed RANKL-mediated bone resorption. Additionally, the expression of typical marker proteins, such as NFATc1, c-Fos, TRAF6, c-Src, and cathepsin K, were significantly inhibited. Arctigenin inhibited the phosphorylation of Erk1/2, but not p38 and JNK, in a dose-dependent manner. Arctigenin also dramatically suppressed immunoreceptor tyrosine-based activation motif-mediated costimulatory signaling molecules, including Syk and PLCγ2, and Gab2. Notably, arctigenin inhibited the activation of Syk through RANKL stimulation. Furthermore, arctigenin prevented osteoclast differentiation in the calvarial bone of mice following stimulation with lipopolysaccharide. Our results show that arctigenin inhibits osteoclast differentiation in vitro and in vivo. Therefore, arctigenin may be useful for treating rheumatoid arthritis and osteoporosis. Copyright © 2012 Elsevier B.V. All rights reserved.

R5 human immunodeficiency virus type 1 with efficient DC-SIGN use is not selected for early after birth in vertically infected children.

Science.gov (United States)

Borggren, Marie; Navér, Lars; Casper, Charlotte; Ehrnst, Anneka; Jansson, Marianne

2013-04-01

The binding of human immunodeficiency virus (HIV) to C-type lectin receptors may result in either enhanced trans-infection of T-cells or virus degradation. We have investigated the efficacy of HIV-1 utilization of DC-SIGN, a C-type lectin receptor, in the setting of intrauterine or intrapartum mother-to-child transmission (MTCT). Viruses isolated from HIV-1-infected mothers at delivery and from their vertically infected children both shortly after birth and later during the progression of the disease were analysed for their use of DC-SIGN, binding and ability to trans-infect. DC-SIGN use of a child's earlier virus isolate tended to be reduced as compared with that of the corresponding maternal isolate. Furthermore, the children's later isolate displayed enhanced DC-SIGN utilization compared with that of the corresponding earlier virus. These results were also supported in head-to-head competition assays and suggest that HIV-1 variants displaying efficient DC-SIGN use are not selected for during intrauterine or intrapartum MTCT. However, viruses with increased DC-SIGN use may evolve later in paediatric HIV-1 infections.

Performance analysis of pulse analog control schemes for LLC resonant DC/DC converters suitable in portable applications

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P. Kowstubha

2016-12-01

Full Text Available Performance Analysis of Pulse Analog Control Schemes, predominantly Pulse-Width Modulation (PWM and Pulse-Position Modulation (PPM for LLC resonant DC/DC converter suitable in portable applications is addressed in this paper. The analysis is done for closed loop performance, frequency domain performance, primary and secondary side conduction losses and soft commutation using PSIM 6.0 software and observed that PPM scheme provides better performance at high input voltage with a good selectivity of frequency over a wide range of line and load variations. The performance of LLC resonant DC/DC converter is demonstrated using PPM scheme for a design specifications of 12 V, 5 A output.

Disruption of Ethylene Responses by Turnip mosaic virus Mediates Suppression of Plant Defense against the Green Peach Aphid Vector.

Science.gov (United States)

Casteel, Clare L; De Alwis, Manori; Bak, Aurélie; Dong, Haili; Whitham, Steven A; Jander, Georg

2015-09-01

Plants employ diverse responses mediated by phytohormones to defend themselves against pathogens and herbivores. Adapted pathogens and herbivores often manipulate these responses to their benefit. Previously, we demonstrated that Turnip mosaic virus (TuMV) infection suppresses callose deposition, an important plant defense induced in response to feeding by its aphid vector, the green peach aphid (Myzus persicae), and increases aphid fecundity compared with uninfected control plants. Further, we determined that production of a single TuMV protein, Nuclear Inclusion a-Protease (NIa-Pro) domain, was responsible for changes in host plant physiology and increased green peach aphid reproduction. To characterize the underlying molecular mechanisms of this phenomenon, we examined the role of three phytohormone signaling pathways, jasmonic acid, salicylic acid, and ethylene (ET), in TuMV-infected Arabidopsis (Arabidopsis thaliana), with or without aphid herbivory. Experiments with Arabidopsis mutants ethylene insensitive2 and ethylene response1, and chemical inhibitors of ET synthesis and perception (aminoethoxyvinyl-glycine and 1-methylcyclopropene, respectively), show that the ET signaling pathway is required for TuMV-mediated suppression of Arabidopsis resistance to the green peach aphid. Additionally, transgenic expression of NIa-Pro in Arabidopsis alters ET responses and suppresses aphid-induced callose formation in an ET-dependent manner. Thus, disruption of ET responses in plants is an additional function of NIa-Pro, a highly conserved potyvirus protein. Virus-induced changes in ET responses may mediate vector-plant interactions more broadly and thus represent a conserved mechanism for increasing transmission by insect vectors across generations. © 2015 American Society of Plant Biologists. All Rights Reserved.

Social exclusion impairs distractor suppression but not target enhancement in selective attention.

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Xu, Mengsi; Li, Zhiai; Diao, Liuting; Fan, Lingxia; Zhang, Lijie; Yuan, Shuge; Yang, Dong

2017-11-01

Social exclusion has been thought to weaken one's ability to exert inhibitory control. Existing studies have primarily focused on the relationship between exclusion and behavioral inhibition, and have reported that exclusion impairs behavioral inhibition. However, whether exclusion also affects selective attention, another important aspect of inhibitory control, remains unknown. Therefore, the current study aimed to explore whether social exclusion impairs selective attention, and to specifically examine its effect on two hypothesized mechanisms of selective attention: target enhancement and distractor suppression. The Cyberball game was used to manipulate social exclusion. Participants then performed a visual search task while event-related potentials were recorded. In the visual search task, target and salient distractor were either both presented laterally or one was presented on the vertical midline and the other laterally. Results showed that social exclusion differentially affected target and distractor processing. While exclusion impaired distractor suppression, reflected as smaller distractor-positivity (Pd) amplitudes for the exclusion group compared to the inclusion group, it did not affect target enhancement, reflected as similar target-negativity (Nt) amplitudes for both the exclusion and inclusion groups. Together, these results extend our understanding of the relationship between exclusion and inhibitory control, and suggest that social exclusion affects selective attention in a more complex manner than previously thought. Copyright © 2017. Published by Elsevier B.V.

Propolin C Inhibited Migration and Invasion via Suppression of EGFR-Mediated Epithelial-to-Mesenchymal Transition in Human Lung Cancer Cells

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Jih-Tung Pai

2018-01-01

Full Text Available Controlling lung cancer cell migration and invasion via epithelial-to-mesenchymal transition (EMT through the regulation of epidermal growth factor receptor (EGFR signaling pathway has been demonstrated. Searching biological active phytochemicals to repress EGFR-regulated EMT might prevent lung cancer progression. Propolis has been used as folk medicine in many countries and possesses anti-inflammatory, antioxidant, and anticancer activities. In this study, the antimigration and anti-invasion activities of propolin C, a c-prenylflavanone from Taiwanese propolis, were investigated on EGFR-regulated EMT signaling pathway. Cell migration and invasion activities were dose-dependently suppressed by noncytotoxic concentration of propolin C. Downregulations of vimentin and snail as well as upregulation of E-cadherin expressions were through the inhibition of EGFR-mediated phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt and extracellular signal-regulated kinase (ERK signaling pathway in propolin C-treated cells. In addition, EGF-induced migration and invasion were suppressed by propolin C-treated A549 lung cancer cells. No significant differences in E-cadherin expression were observed in EGF-stimulated cells. Interestingly, EGF-induced expressions of vimentin, snail, and slug were suppressed through the inhibition of PI3K/Akt and ERK signaling pathway in propolin C-treated cells. Inhibition of cell migration and invasion by propolin C was through the inhibition of EGF/EGFR-mediated signaling pathway, followed by EMT suppression in lung cancer.

BET Bromodomain Inhibition Releases the Mediator Complex from Select cis-Regulatory Elements.

Science.gov (United States)

Bhagwat, Anand S; Roe, Jae-Seok; Mok, Beverly Y L; Hohmann, Anja F; Shi, Junwei; Vakoc, Christopher R

2016-04-19

The bromodomain and extraterminal (BET) protein BRD4 can physically interact with the Mediator complex, but the relevance of this association to the therapeutic effects of BET inhibitors in cancer is unclear. Here, we show that BET inhibition causes a rapid release of Mediator from a subset of cis-regulatory elements in the genome of acute myeloid leukemia (AML) cells. These sites of Mediator eviction were highly correlated with transcriptional suppression of neighboring genes, which are enriched for targets of the transcription factor MYB and for functions related to leukemogenesis. A shRNA screen of Mediator in AML cells identified the MED12, MED13, MED23, and MED24 subunits as performing a similar regulatory function to BRD4 in this context, including a shared role in sustaining a block in myeloid maturation. These findings suggest that the interaction between BRD4 and Mediator has functional importance for gene-specific transcriptional activation and for AML maintenance. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Behavioral performance follows the time course of neural facilitation and suppression during cued shifts of feature-selective attention.

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Andersen, S K; Müller, M M

2010-08-03

A central question in the field of attention is whether visual processing is a strictly limited resource, which must be allocated by selective attention. If this were the case, attentional enhancement of one stimulus should invariably lead to suppression of unattended distracter stimuli. Here we examine voluntary cued shifts of feature-selective attention to either one of two superimposed red or blue random dot kinematograms (RDKs) to test whether such a reciprocal relationship between enhancement of an attended and suppression of an unattended stimulus can be observed. The steady-state visual evoked potential (SSVEP), an oscillatory brain response elicited by the flickering RDKs, was measured in human EEG. Supporting limited resources, we observed both an enhancement of the attended and a suppression of the unattended RDK, but this observed reciprocity did not occur concurrently: enhancement of the attended RDK started at 220 ms after cue onset and preceded suppression of the unattended RDK by about 130 ms. Furthermore, we found that behavior was significantly correlated with the SSVEP time course of a measure of selectivity (attended minus unattended) but not with a measure of total activity (attended plus unattended). The significant deviations from a temporally synchronized reciprocity between enhancement and suppression suggest that the enhancement of the attended stimulus may cause the suppression of the unattended stimulus in the present experiment.

DC Home Appliances for DC Distribution System

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MUHAMMAD KAMRAN

2017-10-01

Full Text Available This paper strengthens the idea of DC distribution system for DC microgrid consisting of a building of 50 apartments. Since the war of currents AC system has been dominant because of the paucity of research in the protection of the DC system. Now with the advance research in power electronics material and components, generation of electricity is inherently DC as by solar PV, fuel cell and thermoelectric generator that eliminates the rectification process. Transformers are replaced by the power electronics buck-boost converters. DC circuit breakers have solved the protection problems for both DC transmission and distribution system. In this paper 308V DC microgrid is proposed and home appliances (DC internal are modified to operate on 48V DC from DC distribution line. Instead of using universal and induction motors in rotary appliances, BLDC (Brushless DC motors are proposed that are highly efficient with minimum electro-mechanical and no commutation losses. Proposed DC system reduces the power conversion stages, hence diminishes the associated power losses and standby losses that boost the overall system efficiency. So in view of all this a conventional AC system can be replaced by a DC system that has many advantages by cost as well as by performance

Dissociating the influence of response selection and task anticipation on corticospinal suppression during response preparation.

Science.gov (United States)

Duque, Julie; Labruna, Ludovica; Cazares, Christian; Ivry, Richard B

2014-12-01

Motor behavior requires selecting between potential actions. The role of inhibition in response selection has frequently been examined in tasks in which participants are engaged in some advance preparation prior to the presentation of an imperative signal. Under such conditions, inhibition could be related to processes associated with response selection, or to more general inhibitory processes that are engaged in high states of anticipation. In Experiment 1, we manipulated the degree of anticipatory preparation. Participants performed a choice reaction time task that required choosing between a movement of the left or right index finger, and used transcranial magnetic stimulation (TMS) to elicit motor evoked potentials (MEPs) in the left hand agonist. In high anticipation blocks, a non-informative cue (e.g., fixation marker) preceded the imperative; in low anticipation blocks, there was no cue and participants were required to divide their attention between two tasks to further reduce anticipation. MEPs were substantially reduced before the imperative signal in high anticipation blocks. In contrast, in low anticipation blocks, MEPs remained unchanged before the imperative signal but showed a marked suppression right after the onset of the imperative. This effect occurred regardless of whether the imperative had signalled a left or right hand response. After this initial inhibition, left MEPs increased when the left hand was selected and remained suppressed when the right hand was selected. We obtained similar results in Experiment 2 except that the persistent left MEP suppression when the left hand was not selected was attenuated when the alternative response involved a non-homologous effector (right foot). These results indicate that, even in the absence of an anticipatory period, inhibitory mechanisms are engaged during response selection, possibly to prevent the occurrence of premature and inappropriate responses during a competitive selection process. Copyright

Dissociating the Influence of Response Selection and Task Anticipation on Corticospinal Suppression During Response Preparation

Science.gov (United States)

Duque, Julie; Labruna, Ludovica; Cazares, Christian; Ivry, Richard B.

2014-01-01

Motor behavior requires selecting between potential actions. The role of inhibition in response selection has frequently been examined in tasks in which participants are engaged in some advance preparation prior to the presentation of an imperative signal. Under such conditions, inhibition could be related to processes associated with response selection, or to more general inhibitory processes that are engaged in high states of anticipation. In Experiment 1, we manipulated the degree of anticipatory preparation. Participants performed a choice reaction time task that required choosing between a movement of the left or right index finger, and used transcranial magnetic stimulation (TMS) to elicit motor evoked potentials (MEPs) in the left hand agonist. In high anticipation blocks, a non-informative cue (e.g., fixation marker) preceded the imperative; in low anticipation blocks, there was no cue and participants were required to divide their attention between two tasks to further reduce anticipation. MEPs were substantially reduced before the imperative signal in high anticipation blocks. In contrast, in low anticipation blocks, MEPs remained unchanged before the imperative signal but showed a marked suppression right after the onset of the imperative. This effect occurred regardless of whether the imperative had signaled a left or right hand response. After this initial inhibition, left MEPs increased when the left hand was selected and remained suppressed when the right hand was selected. We obtained similar results in Experiment 2 except that the persistent left MEP suppression when the left hand was not selected was attenuated when the alternative response involved a non-homologous effector (right foot). These results indicate that, even in the absence of an anticipatory period, inhibitory mechanisms are engaged during response selection, possibly to prevent the occurrence of premature and inappropriate responses during a competitive selection process. PMID

Family of multiport bidirectional DC-DC converters

NARCIS (Netherlands)

Tao, H.; Kotsopoulos, A.; Duarte, J.L.; Hendrix, M.A.M.

2006-01-01

Multiport DC-DC converters are of potential interest in applications such as generation systems utilising multiple sustainable energy sources. A family of multiport bidirectional DC-DC converters derived from a general topology is presented. The topology shows a combination of DC-link and magnetic

Quinacrine induces apoptosis in human leukemia K562 cells via p38 MAPK-elicited BCL2 down-regulation and suppression of ERK/c-Jun-mediated BCL2L1 expression

International Nuclear Information System (INIS)

Changchien, Jung-Jung; Chen, Ying-Jung; Huang, Chia-Hui; Cheng, Tian-Lu; Lin, Shinne-Ren; Chang, Long-Sen

2015-01-01

Although previous studies have revealed the anti-cancer activity of quinacrine, its effect on leukemia is not clearly resolved. We sought to explore the cytotoxic effect and mechanism of quinacrine action in human leukemia K562 cells. Quinacrine induced K562 cell apoptosis accompanied with ROS generation, mitochondrial depolarization, and down-regulation of BCL2L1 and BCL2. Upon exposure to quinacrine, ROS-mediated p38 MAPK activation and ERK inactivation were observed in K562 cells. Quinacrine-induced cell death and mitochondrial depolarization were suppressed by the p38MAPK inhibitor SB202190 and constitutively active MEK1 over-expression. Activation of p38 MAPK was shown to promote BCL2 degradation. Further, ERK inactivation suppressed c-Jun-mediated transcriptional expression of BCL2L1. Over-expression of BCL2L1 and BCL2 attenuated quinacrine-evoked mitochondrial depolarization and rescued the viability of quinacrine-treated cells. Taken together, our data indicate that quinacrine-induced K562 cell apoptosis is mediated through mitochondrial alterations triggered by p38 MAPK-mediated BCL2 down-regulation and suppression of ERK/c-Jun-mediated BCL2L1 expression. - Highlights: • Quinacrine induces K562 cell apoptosis via down-regulation of BCL2 and BCL2L1. • Quinacrine induces p38 MAPK activation and ERK inactivation in K562 cells. • Quinacrine elicits p38 MAPK-mediated BCL2 down-regulation. • Quinacrine suppresses ERK/c-Jun-mediated BCL2L1 expression

Enduring neurobehavioral effects of early life trauma mediated through learning and corticosterone suppression

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Stephanie Moriceau

2009-09-01

Full Text Available Early life trauma alters later life emotions, including fear. To better understand mediating mechanisms, we subjected pups to either predictable or unpredictable trauma, in the form of paired or unpaired odor-0.5mA shock conditioning which, during a sensitive period, produces an odor preference and no learning respectively. Fear conditioning and its neural correlates were then assessed after the sensitive period at postnatal day (PN13 or in adulthood, ages when amygdala-dependent fear occurs. Our results revealed that paired odor-shock conditioning starting during the sensitive period (PN8-12 blocked fear conditioning in older infants (PN13 and pups continued to express olfactory bulb-dependent odor preference learning. This PN13 fear learning inhibition was also associated with suppression of shock-induced corticosterone, although the age appropriate amygdala-dependent fear learning was reinstated with systemic corticosterone (3mg/kg during conditioning. On the other hand, sensitive period odor-shock conditioning did not prevent adult fear conditioning, although freezing, amygdala and hippocampal 2-DG uptake and corticosterone levels were attenuated compared to adult conditioning without infant conditioning. Normal levels of freezing, amygdala and hippocampal 2-DG uptake were induced with systemic corticosterone (5mg/kg during adult conditioning. These results suggest that the contingency of early life trauma mediates at least some effects of early life stress through learning and suppression of corticosterone levels. However, developmental differences between infants and adults are expressed with PN13 infants’ learning consistent with the original learned preference, while adult conditioning overrides the original learned preference with attenuated amygdala-dependent fear learning.

The Fusarium oxysporum effector Six6 contributes to virulence and suppresses I-2-mediated cell death.

Science.gov (United States)

Gawehns, F; Houterman, P M; Ichou, F Ait; Michielse, C B; Hijdra, M; Cornelissen, B J C; Rep, M; Takken, F L W

2014-04-01

Plant pathogens secrete effectors to manipulate their host and facilitate colonization. Fusarium oxysporum f. sp. lycopersici is the causal agent of Fusarium wilt disease in tomato. Upon infection, F. oxysporum f. sp. lycopersici secretes numerous small proteins into the xylem sap (Six proteins). Most Six proteins are unique to F. oxysporum, but Six6 is an exception; a homolog is also present in two Colletotrichum spp. SIX6 expression was found to require living host cells and a knockout of SIX6 in F. oxysporum f. sp. lycopersici compromised virulence, classifying it as a genuine effector. Heterologous expression of SIX6 did not affect growth of Agrobacterium tumefaciens in Nicotiana benthamiana leaves or susceptibility of Arabidopsis thaliana toward Verticillium dahliae, Pseudomonas syringae, or F. oxysporum, suggesting a specific function for F. oxysporum f. sp. lycopersici Six6 in the F. oxysporum f. sp. lycopersici- tomato pathosystem. Remarkably, Six6 was found to specifically suppress I-2-mediated cell death (I2CD) upon transient expression in N. benthamiana, whereas it did not compromise the activity of other cell-death-inducing genes. Still, this I2CD suppressing activity of Six6 does not allow the fungus to overcome I-2 resistance in tomato, suggesting that I-2-mediated resistance is independent from cell death.

Chronic restraint stress impairs endocannabinoid mediated suppression of GABAergic signaling in the hippocampus of adult male rats.

Science.gov (United States)

Hu, Wen; Zhang, Mingyue; Czéh, Boldizsár; Zhang, Weiqi; Flügge, Gabriele

2011-07-15

Chronic stress, a risk factor for the development of psychiatric disorders, is known to induce alterations in neuronal networks in many brain areas. Previous studies have shown that chronic stress changes the expression of the cannabinoid receptor 1 (CB1) in the brains of adult rats, but neurophysiological consequences of these changes remained unclear. Here we demonstrate that chronic restraint stress causes a dysfunction in CB1 mediated modulation of GABAergic transmission in the hippocampus. Using an established protocol, adult male Sprague Dawley rats were daily restrained for 21 days and whole-cell voltage clamp was performed at CA1 pyramidal neurons. When recording carbachol-evoked inhibitory postsynaptic currents (IPSCs) which presumably originate from CB1 expressing cholecystokinin (CCK) interneurons, we found that depolarization-induced suppression of inhibition (DSI) was impaired by the stress. DSI is a form of short-term plasticity at GABAergic synapses that is known to be CB1 mediated and has been suggested to be involved in hippocampal information encoding. Chronic stress attenuated the depolarization-induced suppression of the frequency of carbachol-evoked IPSCs. Incubation with a CB1 receptor antagonist prevented this DSI effect in control but not in chronically stressed animals. The stress-induced impairment of CB1-mediated short-term plasticity at GABAergic synapses may underlie cognitive deficits which are commonly observed in animal models of stress as well as in patients with stress-related psychiatric disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

Investigating category- and shape-selective neural processing in ventral and dorsal visual stream under interocular suppression.

Science.gov (United States)

Ludwig, Karin; Kathmann, Norbert; Sterzer, Philipp; Hesselmann, Guido

2015-01-01

Recent behavioral and neuroimaging studies using continuous flash suppression (CFS) have suggested that action-related processing in the dorsal visual stream might be independent of perceptual awareness, in line with the "vision-for-perception" versus "vision-for-action" distinction of the influential dual-stream theory. It remains controversial if evidence suggesting exclusive dorsal stream processing of tool stimuli under CFS can be explained by their elongated shape alone or by action-relevant category representations in dorsal visual cortex. To approach this question, we investigated category- and shape-selective functional magnetic resonance imaging-blood-oxygen level-dependent responses in both visual streams using images of faces and tools. Multivariate pattern analysis showed enhanced decoding of elongated relative to non-elongated tools, both in the ventral and dorsal visual stream. The second aim of our study was to investigate whether the depth of interocular suppression might differentially affect processing in dorsal and ventral areas. However, parametric modulation of suppression depth by varying the CFS mask contrast did not yield any evidence for differential modulation of category-selective activity. Together, our data provide evidence for shape-selective processing under CFS in both dorsal and ventral stream areas and, therefore, do not support the notion that dorsal "vision-for-action" processing is exclusively preserved under interocular suppression. © 2014 Wiley Periodicals, Inc.

Thomson scattering measurements on an atmospheric Ar dc discharge lamp

NARCIS (Netherlands)

Zhu, Xiao-Yan; Redwitz, M.; Kieft, E.R.; Sande, van de M.J.; Mullen, van der J.J.A.M.

2004-01-01

Thomson scattering (TS) experiments have been performed in the region near the electrodes of a dc powered model lamp filled with 1-2 bar argon gas. In order to suppress the false stray light and Rayleigh scattered photons, a triple grating spectrograph was used. In this way the electron density and

A Compact Band-Pass Filter with High Selectivity and Second Harmonic Suppression.

Science.gov (United States)

Hadarig, Ramona Cosmina; de Cos Gomez, Maria Elena; Las-Heras, Fernando

2013-12-03

The design of a novel band-pass filter with narrow-band features based on an electromagnetic resonator at 6.4 GHz is presented. A prototype is manufactured and characterized in terms of transmission and reflection coefficient. The selective passband and suppression of the second harmonic make the filter suitable to be used in a C band frequency range for radar systems and satellite/terrestrial applications. To avoid substantial interference for this kind of applications, passive components with narrow band features and small dimensions are required. Between 3.6 GHz and 4.2 GHz the band-pass filter with harmonic suppression should have an attenuation of at least 35 dB, whereas for a passband, less than 10% is sufficient.

Positive-negative-selection-mediated gene targeting in rice

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Zenpei eShimatani

2015-01-01

Full Text Available Gene targeting (GT refers to the designed modification of genomic sequence(s through homologous recombination (HR. GT is a powerful tool both for the study of gene function and for molecular breeding. However, in transformation of higher plants, non-homologous end joining (NHEJ occurs overwhelmingly in somatic cells, masking HR-mediated GT. Positive-negative selection (PNS is an approach for finding HR-mediated GT events because it can eliminate NHEJ effectively by expression of a negative-selection marker gene. In rice—a major crop worldwide—reproducible PNS-mediated GT of endogenous genes has now been successfully achieved. The procedure is based on strong PNS using diphtheria toxin A-fragment as a negative marker, and has succeeded in the directed modification of several endogenous rice genes in various ways. In addition to gene knock-outs and knock-ins, a nucleotide substitution in a target gene was also achieved recently. This review presents a summary of the development of the rice PNS system, highlighting its advantages. Different types of gene modification and gene editing aimed at developing new plant breeding technology (NPBT based on PNS are discussed.

Rapid Exercise-Induced Mobilization of Dendritic Cells Is Potentially Mediated by a Flt3L- and MMP-9-Dependent Process in Multiple Sclerosis

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Nathalie Deckx

2015-01-01

Full Text Available In healthy individuals, one exercise bout induces a substantial increase in the number of circulating leukocytes, while their function is transiently suppressed. The effect of one exercise bout in multiple sclerosis (MS is less studied. Since recent evidence suggests a role of dendritic cells (DC in the pathogenesis of MS, we investigated the effect of one combined endurance/resistance exercise bout on the number and function of DC in MS patients and healthy controls. Our results show a rapid increase in the number of DC in response to physical exercise in both MS patients and controls. Further investigation revealed that in particular DC expressing the migratory molecules CCR5 and CD62L were increased upon acute physical activity. This may be mediated by Flt3L- and MMP-9-dependent mobilization of DC, as demonstrated by increased circulating levels of Flt3L and MMP-9 following one exercise bout. Circulating DC display reduced TLR responsiveness after acute exercise, as evidenced by a less pronounced upregulation of activation markers, HLA-DR and CD86, on plasmacytoid DC and conventional DC, respectively. Our results indicate mobilization of DC, which may be less prone to drive inflammatory processes, following exercise. This may present a negative feedback mechanism for exercise-induced tissue damage and inflammation.

Design and Testing of Boost Type DC/DC Converter for DC Motor Control Applications

OpenAIRE

Samman, Faizal Arya; Akil, Yusri Syam; Noor, Nirwan A.

2017-01-01

in The Proceeding of The 2nd International Symposium on Smart Material and Mechatronics 2015 This paper presents the design and testing of a boost type DC/DC converter circuit, which can be used for DC motor control applications. The Boost converter is designed using DC chopper and DC chopper cascade configurations. The experimental setup was made by connecting the boost converter circuit with four types of DC motor, i.e. self-excited DC motor shunt, series, compound and separately exci...

Protocatechuic aldehyde attenuates cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation

Directory of Open Access Journals (Sweden)

Li Gao

2016-12-01

Full Text Available Cisplatin is a classic chemotherapeutic agent widely used to treat different types of cancers including ovarian, head and neck, testicular and uterine cervical carcinomas. However, cisplatin induces acute kidney injury by directly triggering an excessive inflammatory response, oxidative stress and programmed cell death of renal tubular epithelial cells. All of which lead to higher mortality rates in patients. In this study we examined the protective effect of protocatechuic aldehyde (PA in vitro in cisplatin-treated tubular epithelial cells and in vivo in cisplatin nephropathy. PA is a monomer of Traditional Chinese Medicine isolated from the root of S. miltiorrhiza. Results show that PA prevented cisplatin-induced decline of renal function and histological damage, which was confirmed by attenuation of KIM1 in both mRNA and protein levels. Moreover, PA reduced renal inflammation by suppressing oxidative stress and programmed cell death in response to cisplatin, which was further evidenced by in vitro data. Of note, PA suppressed NAPDH oxidases, including Nox2 and Nox4, in a dosage-dependent manner. Moreover, silencing Nox4, but not Nox2, removed the inhibitory effect of PA on cisplatin-induced renal injury, indicating that Nox4 may play a pivotal role in mediating the protective effect of PA in cisplatin-induced acute kidney injury. Collectively, our data indicate that PA largely blocked cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation without compromising anti-tumor activity of cisplatin. These findings suggest that PA and its derivatives may serve as potential protective agents for cancer patients with cisplatin treatment.

Adeno-associated virus-mediated doxycycline-regulatable TRAIL expression suppresses growth of human breast carcinoma in nude mice

Directory of Open Access Journals (Sweden)

Zheng Liu

2012-04-01

Full Text Available Abstract Background Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL functions as a cytokine to selectively kill various cancer cells without toxicity to most normal cells. Numerous studies have demonstrated the potential use of recombinant soluble TRAIL as a cancer therapeutic agent. We have showed previous administration of a recombinant adeno-associated virus (rAAV vector expressing soluble TRAIL results in an efficient suppression of human tumor growth in nude mice. In the present study, we introduced Tet-On gene expression system into the rAAV vector to control the soluble TRAIL expression and evaluate the efficiency of the system in cancer gene therapy. Methods Controllability of the Tet-On system was determined by luciferase activity assay, and Western blotting and enzyme-linked immunoabsorbent assay. Cell viability was determined by MTT assay. The breast cancer xenograft animal model was established and recombinant virus was administrated through tail vein injection to evaluate the tumoricidal activity. Results The expression of soluble TRAIL could be strictly controlled by the Tet-On system in both normal and cancer cells. Transduction of human cancer cell lines with rAAV-TRE-TRAIL&rAAV-Tet-On under the presence of inducer doxycycline resulted in a considerable cell death by apoptosis. Intravenous injection of the recombinant virus efficiently suppressed the growth of human breast carcinoma in nude mice when activated by doxycycline. Conclusion These data suggest that rAAV-mediated soluble TRAIL expression under the control of the Tet-On system is a promising strategy for breast cancer therapy.

DC-DC Converter Topology Assessment for Large Scale Distributed Photovoltaic Plant Architectures

Energy Technology Data Exchange (ETDEWEB)

Agamy, Mohammed S; Harfman-Todorovic, Maja; Elasser, Ahmed; Sabate, Juan A; Steigerwald, Robert L; Jiang, Yan; Essakiappan, Somasundaram

2011-07-01

Distributed photovoltaic (PV) plant architectures are emerging as a replacement for the classical central inverter based systems. However, power converters of smaller ratings may have a negative impact on system efficiency, reliability and cost. Therefore, it is necessary to design converters with very high efficiency and simpler topologies in order not to offset the benefits gained by using distributed PV systems. In this paper an evaluation of the selection criteria for dc-dc converters for distributed PV systems is performed; this evaluation includes efficiency, simplicity of design, reliability and cost. Based on this evaluation, recommendations can be made as to which class of converters is best fit for this application.

Social hierarchy and depression: the role of emotion suppression.

Science.gov (United States)

Langner, Carrie A; Epel, Elissa S; Matthews, Karen A; Moskowitz, Judith T; Adler, Nancy E

2012-01-01

Position in the social hierarchy is a major determinant of health outcomes. We examined the associations between aspects of social hierarchy and depressive symptoms with a specific focus on one potential psychological mechanism: emotion suppression. Suppressing negative emotion has mental health costs, but individuals with low social power and low social status may use these strategies to avoid conflict. Study 1 assessed perceived social power, tendency to suppress negative emotion, and depressive symptoms in a community sample of women. Low social power was related to greater depressive symptoms, and this relationship was partially mediated by emotion suppression. Study 2 examined education as a proxy for social hierarchy position, anger suppression, and depressive symptoms in a national, longitudinal cohort study (The coronary artery risk development in young adults [CARDIA] study; Cutter et al., 1991). Much as in study 1, low education levels were correlated with greater depressive symptoms, and this relationship was partially mediated by anger suppression. Further, suppression mediated the relationship between low education and subsequent depression up to 15 years later. These findings support the theory that social hierarchy affects mental health in part through a process of emotion suppression.

Five-Level Active-Neutral-Point-Clamped DC/DC Converter for Medium-Voltage DC Grids

DEFF Research Database (Denmark)

Liu, Dong; Deng, Fujin; Chen, Zhe

2017-01-01

This paper proposes a five-level active-neutralpoint- clamped (5L-ANPC) dc/dc converter for applications in medium voltage dc (MVDC) grids. A modulation strategy is proposed for the 5L-ANPC dc/dc converter to generate multilevel voltage waveforms, which can effectively reduce voltage change rate dv...... effectively eliminate high voltage leaps caused by the dead time effect. In addition, a capacitor voltage control strategy is proposed for the 5L-ANPC dc/dc converter to ensure the balanced flying capacitor voltage and desired five-level voltage waveforms. Finally, simulation and experimental studies...

Acupuncture suppresses intravenous methamphetamine self-administration through GABA receptor's mediation.

Science.gov (United States)

Choi, Yi Jeong; Kim, Nam Jun; Zhao, Rong Jie; Kim, Da Hye; Yang, Chae Ha; Kim, Hee Young; Gwak, Young S; Jang, Eun Young; Kim, Jae Su; Lee, Yun Kyu; Lee, Hyun Jong; Lee, Sang Nam; Lim, Sung Chul; Lee, Bong Hyo

2018-01-01

Methamphetamine is one of the widely abused drugs. In spite of a number of studies, there is still little successful therapy to suppress the methamphetamine abuse. Acupuncture has shown to attenuate the reinforcing effects of psychostimulant. Based on, the present study investigated if acupuncture could suppress intravenous methamphetamine self-administration behavior. In addition, a possible neuronal mechanism was investigated. Male Sprague-Dawley rats weighing 270-300g were trained to intake food pellet. After catheter implantation, animal was trained to self-administer methamphetamine (0.05mg/kg) intravenously using fixed ratio 1 schedule in daily 2h session during 3 weeks. After training, rats who established baseline (infusion variation less than 20% of the mean for 3 consecutive days) received acupuncture treatment on the next day. Acupuncture was performed at each acupoint manually. In the second experiment, the selective antagonists of GABA A or GABA B receptor were given before acupuncture to investigate the possible neuronal involvement of GABA receptor pathway in the acupuncture effects. C-Fos expression was examined in the nucleus accumbens to support behavioral data. Acupuncture at HT7, but not at control acupoint LI5, reduced the self-administration behavior significantly. Also, the effects of acupuncture were blocked by the GABA receptor antagonists. C-Fos expression was shown to be parallel with the behavioral data. Results of this study have shown that acupuncture at HT7 suppressed methamphetamine self-administration through GABA receptor system, suggesting that acupuncture at HT7 can be a useful therapy for the treatment of methamphetamine abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

Control of improved full-bridge three-level DC/DC converter for wind turbines in a DC grid

DEFF Research Database (Denmark)

Deng, Fujin; Chen, Zhe

2013-01-01

transformer in the IFBTL dc/dc converter. A modulation strategy, including two operation modes, is proposed for the IFBTL dc/dc converter. Then, a voltage balancing control strategy is proposed for the IFBTL dc/dc converter. Furthermore, the control of the wind turbine based on the IFBTL dc/dc converter......This paper presents an improved full-bridge three-level (IFBTL) dc/dc converter for a wind turbine in a dc grid by inserting a passive filter into the dc/dc converter to improve the performance of the converter. The passive filter can effectively reduce the voltage stress of the medium frequency...

IGBT Based DC/DC Converter

Directory of Open Access Journals (Sweden)

M. Akherraz

1997-12-01

Full Text Available This paper presents an in-depth analytical and experimental investigation of an indirect DC-DC converter. The DC-AC conversion is a full bridge based on IGBT power modules, and the AC-DC conversion is done via a high  frequency AC link and a first diode bridge. The AC link, which consists of snubbing capacitors and a variable air-gap transformer, is analytically designed to fulfill Zero Voltage commutation requirement. The proposed converter is simulated using PSPICE and a prototype is designed built and tested in the laboratory. PSPICE simulation and experimental results are presented and compared.

Nuclear DAMP complex-mediated RAGE-dependent macrophage cell death

Energy Technology Data Exchange (ETDEWEB)

Chen, Ruochan [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Department of Infectious Diseases and State Key Lab of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008 (China); Fu, Sha; Fan, Xue-Gong [Department of Infectious Diseases and State Key Lab of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008 (China); Lotze, Michael T.; Zeh, Herbert J. [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Tang, Daolin, E-mail: tangd2@upmc.edu [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Kang, Rui, E-mail: kangr@upmc.edu [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 (United States)

2015-03-13

High mobility group box 1 (HMGB1), histone, and DNA are essential nuclear components involved in the regulation of chromosome structure and function. In addition to their nuclear function, these molecules act as damage-associated molecular patterns (DAMPs) alone or together when released extracellularly. The synergistic effect of these nuclear DNA-HMGB1-histone complexes as DAMP complexes (nDCs) on immune cells remains largely unexplored. Here, we demonstrate that nDCs limit survival of macrophages (e.g., RAW264.7 and peritoneal macrophages) but not cancer cells (e.g., HCT116, HepG2 and Hepa1-6). nDCs promote production of inflammatory tumor necrosis factor α (TNFα) release, triggering reactive oxygen species-dependent apoptosis and necrosis. Moreover, the receptor for advanced glycation end products (RAGE), but not toll-like receptor (TLR)-4 and TLR-2, was required for Akt-dependent TNFα release and subsequent cell death following treatment with nDCs. Genetic depletion of RAGE by RNAi, antioxidant N-Acetyl-L-cysteine, and TNFα neutralizing antibody significantly attenuated nDC-induced cell death. These findings provide evidence supporting novel signaling mechanisms linking nDCs and inflammation in macrophage cell death. - Highlights: • Nuclear DAMP complexes (nDCs) selectively induce cell death in macrophages, but not cancer cells. • TNFα-mediated oxidative stress is required for nDC-induced death. • RAGE-mediated Akt activation is required for nDC-induced TNFα release. • Blocking RAGE and TNFα inhibits nDC-induced macrophage cell death.

Three-port DC-DC converter with new integrated transformer for DC Distribution Systems

DEFF Research Database (Denmark)

Ouyang, Ziwei; Andersen, Michael A. E.

2014-01-01

A new integrated transformer for three-port dc-dc converter is proposed to overcome the power coupling effect existed in some known multiple inputs dc-dc converters. Orthogonal primary windings arrangement and in series connection of diagonal secondary Windings enables a fully power decoupling...

Three new DC-to-DC Single-Switch Converters

Directory of Open Access Journals (Sweden)

Barry W. Williams

2017-06-01

Full Text Available This paper presents a new family of three previously unidentified dc-to-dc converters, buck, boost, and buck-boost voltage-transfer-function topologies, which offer advantageous transformer coupling features and low capacitor dc voltage stressing. The three single-switch, single-diode, converters offer the same features as basic dc-to-dc converters, such as the buck function with continuous output current and the boost function with continuous input current. Converter time-domain simulations and experimental results (including transformer coupling support and extol the dc-to-dc converter concepts and analysis presented.

Selective suppression of antibody production with the aid of radiolabelled birch pollen allergen

International Nuclear Information System (INIS)

Filipp, G.; Biro, G.; Hartung, W.D.; Lehmann, G.

1981-01-01

In accordance with the clonal selection theory we intended to prevent the development of artificially induced birch pollen allergy in rabbits with the aid of of the radiolabelled pollen allergen (75-1000 μCi 125 I-pollen/animal) intravenously administered prior to pollen sensitization. The birch pollen allergen, in accordance with Burnet's working hypothesis, reacts only with a genetically determining B cell subpopulation. The fixation of the radiolabelled birch pollen allergen to the receptors of the competent B cell clone causes the lesion of the latter. Compared with the control group, this group of rabbits showed an extensive suppression of anaphylactic reagin-like PCA-antibodies, and haemagglutinating antibodies in the blood as well as in nasal secretion. In addition, we tried to influence the already ongoing synthesis of the antibodies with the aid of a subsequent intravenously administered radiolabelled birch pollen allergen (750-1000μCi 125 I-pollen/animal). An intensive suppression of the synthesis of antibodies could also be proved in this case. The simultaneous immunization of the control rabbits with birch pollen and egg albumin resulted in the production of antibodies against both antigens, as expected. The hot-labelled birch pollen antigen intravenously injected before or after immunization with egg albumin and birch pollen led selectively to suppression of anti-birch-pollen PCA antibodies. The synthesis of anti-egg albumin PCA antibodies was unaffected. (author)

Hsp90 inhibitor 17-AAG sensitizes Bcl-2 inhibitor (-)-gossypol by suppressing ERK-mediated protective autophagy and Mcl-1 accumulation in hepatocellular carcinoma cells.

Science.gov (United States)

Wang, Bin; Chen, Linfeng; Ni, Zhenhong; Dai, Xufang; Qin, Liyan; Wu, Yaran; Li, Xinzhe; Xu, Liang; Lian, Jiqin; He, Fengtian

2014-11-01

Natural BH3-memitic (-)-gossypol shows promising antitumor efficacy in several kinds of cancer. However, our previous studies have demonstrated that protective autophagy decreases the drug sensitivities of Bcl-2 inhibitors in hepatocellular carcinoma (HCC) cells. In the present study, we are the first to report that Hsp90 inhibitor 17-AAG enhanced (-)-gossypol-induced apoptosis via suppressing (-)-gossypol-triggered protective autophagy and Mcl-1 accumulation. The suppression effect of 17-AAG on autophagy was mediated by inhibiting ERK-mediated Bcl-2 phosphorylation while was not related to Beclin1 or LC3 protein instability. Meanwhile, 17-AAG downregulated (-)-gossypol-triggered Mcl-1 accumulation by suppressing Mcl-1(Thr163) phosphorylation and promoting protein degradation. Collectively, our study indicates that Hsp90 plays an important role in tumor maintenance and inhibition of Hsp90 may become a new strategy for sensitizing Bcl-2-targeted chemotherapies in HCC cells. Copyright © 2014 Elsevier Inc. All rights reserved.

A bacterial cysteine protease effector protein interferes with photosynthesis to suppress plant innate immune responses.

Science.gov (United States)

Rodríguez-Herva, José J; González-Melendi, Pablo; Cuartas-Lanza, Raquel; Antúnez-Lamas, María; Río-Alvarez, Isabel; Li, Ziduo; López-Torrejón, Gema; Díaz, Isabel; Del Pozo, Juan C; Chakravarthy, Suma; Collmer, Alan; Rodríguez-Palenzuela, Pablo; López-Solanilla, Emilia

2012-05-01

The bacterial pathogen Pseudomonas syringae pv tomato DC3000 suppresses plant innate immunity with effector proteins injected by a type III secretion system (T3SS). The cysteine protease effector HopN1, which reduces the ability of DC3000 to elicit programmed cell death in non-host tobacco, was found to also suppress the production of defence-associated reactive oxygen species (ROS) and callose when delivered by Pseudomonas fluorescens heterologously expressing a P. syringae T3SS. Purified His(6) -tagged HopN1 was used to identify tomato PsbQ, a member of the oxygen evolving complex of photosystem II (PSII), as an interacting protein. HopN1 localized to chloroplasts and both degraded PsbQ and inhibited PSII activity in chloroplast preparations, whereas a HopN1(D299A) non-catalytic mutant lost these abilities. Gene silencing of NtPsbQ in tobacco compromised ROS production and programmed cell death by DC3000. Our data reveal PsbQ as a contributor to plant immunity responses and a target for pathogen suppression. © 2012 Blackwell Publishing Ltd.

Hypericin-mediated selective photomodification of connective tissues

Science.gov (United States)

Hovhannisyan, V.; Hovhannisyan, A.; Ghukasyan, V.; Guo, H. W.; Lin, Hung-Ming; Chen, S. J.; Chen, Yang-Fang; Dong, Chen-Yuan

2017-02-01

Hypericin (Hyp) has received attention due to its high phototoxicity against viruses and anti-tumor photoactivity. Using two-photon imaging, we demonstrated that Hyp induced photosensitized modification of collagen fibers in native tissues. Dynamics of photo-processes was monitored by time-lapse multiphoton imaging. We showed that Hyp-mediated processes in collagen tissues may be used for the selective modification of collagen fibers.

Adaptive single-antenna transmit selection with interference suppression

KAUST Repository

Radaydeh, Redha Mahmoud Mesleh

2011-10-01

This paper studies the performance of adaptive transmit selection with co-channel interference suppression in multipath fading channels. The adaptive selection algorithms are configured for single-antenna bandwidth-efficient or power-efficient transmission with as low transmit channel estimations as possible. Due to the fact that the number of active co-channel interfering signals and their corresponding powers experience random behavior, the adaptation to channels conditions, assuming uniform buffer and traffic loading, is proposed to be jointly based on the transmit channels instantaneous signal-to-noise ratios (SNRs) and signal-to-interference-plus-noise ratios (SINRs). Two interference cancelation algorithms are considered. The first algorithm assumes that the receiver eliminates the impact of the strongest subset of interferers, whereas the second algorithm suggests random cancelation of interferers to further reduce processing complexity. The impact of outdated ordering of interferers powers on the efficiency of interference cancelation, and the effect of imperfect prediction of transmit channels for desired user adaptation are investigated. Analytical formulations for various performance measures and comparisons between the performance and processing complexity of different adaptation schemes are presented. © 2011 IEEE.

Lewis X component in human milk binds DC-SIGN and inhibits HIV-1 transfer to CD4(+) T lymphocytes

NARCIS (Netherlands)

Naarding, Marloes A.; Ludwig, Irene S.; Groot, Fedde; Berkhout, Ben; Geijtenbeek, Teunis B. H.; Pollakis, Georgios; Paxton, William A.

2005-01-01

DC-specific ICAM3-grabbing non-integrin (DC-SIGN), which is expressed on DCs, can interact with a variety of pathogens such as HIV-1, hepatitis C, Ebola, cytomegalovirus, Dengue virus, Mycobacterium, Leisbmania, and Candida albicans. We demonstrate that human milk can inhibit the DC-SIGN-mediated

DcR3 induces epithelial-mesenchymal transition through activation of the TGF-β3/SMAD signaling pathway in CRC.

Science.gov (United States)

Liu, Yan-Ping; Zhu, Hui-Fang; Liu, Ding-Li; Hu, Zhi-Yan; Li, Sheng-Nan; Kan, He-Ping; Wang, Xiao-Yan; Li, Zu-Guo

2016-11-22

Decoy receptor 3 (DcR3), a novel member of the tumor necrosis factor receptor (TNFR) family, was recently reported to be associated with tumorigenesis and metastasis. However, the role of DcR3 in human colorectal cancer (CRC) has not been fully elucidated. In this study, we found that DcR3 expression was significantly higher in human colorectal cancer tissues than in paired normal tissues, and that DcR3 expression was strongly correlated with tumor invasion, lymph node metastases and poor prognoses. Moreover, DcR3 overexpression significantly enhanced CRC cell proliferation and migration in vitro and tumorigenesis in vivo. Conversely, DcR3 knockdown significantly repressed CRC cell proliferation and migration in vitro, and DcR3 deficiency also attenuated CRC tumorigenesis and metastasis in vivo. Functionally, DcR3 was essential for TGF-β3/SMAD-mediated epithelial-mesenchymal transition (EMT) of CRC cells. Importantly, cooperation between DcR3 and TGF-β3/SMAD-EMT signaling-related protein expression was correlated with survival and survival time in CRC patients. In conclusion, our results demonstrate that DcR3 may be a prognostic biomarker for CRC and that this receptor facilitates CRC development and metastasis by participating in TGF-β3/SMAD-mediated EMT of CRC cells.

Suppression of TLR4-mediated inflammatory response by macrophage class A scavenger receptor (CD204)

Energy Technology Data Exchange (ETDEWEB)

Ohnishi, Koji; Komohara, Yoshihiro; Fujiwara, Yukio; Takemura, Kenichi [Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Lei, XiaoFeng [Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Department of Biochemistry, Showa University School of Medicine, Tokyo (Japan); Nakagawa, Takenobu [Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Sakashita, Naomi [Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Department of Human Pathology, Institute of Health Biosciences, The University of Tokushima, Tokushima (Japan); Takeya, Motohiro, E-mail: takeya@kumamoto-u.ac.jp [Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan)

2011-08-05

Highlights: {yields} We focused on the interaction between SR-A and TLR4 signaling in this study. {yields} SR-A deletion promoted NF{kappa}B activation in macrophages in septic model mouse. {yields} SR-A suppresses both MyD88-dependent and -independent TLR4 signaling in vitro. {yields} SR-A clears LPS binding to TLR4 which resulting in the suppression of TLR4 signals. -- Abstract: The class A scavenger receptor (SR-A, CD204), one of the principal receptors expressed on macrophages, has been found to regulate inflammatory response and attenuate septic endotoxemia. However, the detailed mechanism of this process has not yet been well characterized. To clarify the regulative mechanisms of lipopolysaccharide (LPS)-induced macrophage activation by SR-A, we evaluated the activation of Toll-like receptor 4 (TLR4)-mediated signaling molecules in SR-A-deficient (SR-A{sup -/-}) macrophages. In a septic shock model, the blood levels of tumor necrosis factor (TNF)-{alpha}, interleukin (IL)-6 and interferon (IFN)-{beta} were significantly increased in SR-A{sup -/-} mice compared to wild-type mice, and elevated nuclear factor kappa B (NF{kappa}B) activation was detected in SR-A{sup -/-} macrophages. SR-A deletion increased the production of pro-inflammatory cytokines, and the phosphorylation of mitogen-activated protein kinase (MAPK) and NF{kappa}B in vitro. SR-A deletion also promoted the nuclear translocation of NF{kappa}B and IFN regulatory factor (IRF)-3. In addition, a competitive binding assay with acetylated low-density lipoprotein, an SR-A-specific ligand, and anti-SR-A antibody induced significant activation of TLR4-mediated signaling molecules in wild-type macrophages but not in SR-A{sup -/-} macrophages. These results suggest that SR-A suppresses the macrophage activation by inhibiting the binding of LPS to TLR4 in a competitive manner and it plays a pivotal role in the regulation of the LPS-induced inflammatory response.

γ-Oryzanol suppresses COX-2 expression by inhibiting reactive oxygen species-mediated Erk1/2 and Egr-1 signaling in LPS-stimulated RAW264.7 macrophages.

Science.gov (United States)

Shin, Soon Young; Kim, Heon-Woong; Jang, Hwan-Hee; Hwang, Yu-Jin; Choe, Jeong-Sook; Kim, Jung-Bong; Lim, Yoongho; Lee, Young Han

2017-09-16

Cyclooxygenase (COX)-2 produces prostanoids, which contribute to inflammatory responses. Nuclear factor (NF)-κB is a key transcription factor mediating COX-2 expression. γ-Oryzanol is an active component in rice bran oil, which inhibits lipopolysaccharide (LPS)-mediated COX-2 expression by inhibiting NF-κB. However, the inhibition of COX-2 expression by γ-oryzanol independently of NF-κB is poorly understood. We found that LPS upregulated Egr-1 expression at the transcriptional level. Forced expression of Egr-1 trans-activated the Cox-2 promoter independently of NF-κB. In contrast, silencing of Egr-1 abrogated LPS-mediated COX-2 expression. LPS produced reactive oxygen species (ROS), which, in turn, induced Egr-1 expression via the Erk1/2 MAPK pathway. ROS scavenging activity of γ-oryzanol suppressed Egr-1 expression by inhibiting the Erk1/2 MAPK pathway. Our results suggest that γ-oryzanol inhibits LPS-mediated COX-2 expression by suppressing Erk1/2-mediated Egr-1 expression. This study supports that γ-oryzanol may be useful for ameliorating LPS-mediated inflammatory responses. Copyright © 2017 Elsevier Inc. All rights reserved.

75 FR 60602 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-10-10, DC-10-10F, DC-10-15, DC...

Science.gov (United States)

2010-10-01

... Airworthiness Directives; McDonnell Douglas Corporation Model DC- 10-10, DC-10-10F, DC-10-15, DC-10-30, DC-10... adding the following new AD: 2010-20-14 McDonnell Douglas Corporation: Amendment 39-16449. Docket No. FAA... the airplanes identified in paragraphs (c)(1) and (c)(2) of this AD. (1) McDonnell Douglas Corporation...

75 FR 38943 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-10-10, DC-10-10F, DC-10-30, DC...

Science.gov (United States)

2010-07-07

...-0672; Directorate Identifier 2010-NM-047-AD] RIN 2120-AA64 Airworthiness Directives; McDonnell Douglas...: McDonnell Douglas Corporation: Docket No. FAA-2010-0672; Directorate Identifier 2010-NM-047-AD. Comments Due... applies to McDonnell Douglas Corporation Model DC- 10-10, DC-10-10F, DC-10-30, DC-10-30F (KDC-10), DC-10...

Establishment of functional requirements to DC-connected wind turbine and their use in concept selection

DEFF Research Database (Denmark)

Dincan, Catalin Gabriel; Kjær, Philip Carne; Chen, Yu-Hsing

2017-01-01

, but they are all still at an immature technology level, as no substantial experience from full-scale detailed design exists. By employing a functional failure mode and effects analysis (F-FMEA) with a decision making tool (Pugh Matrix), the paper presents a structured set of functionalities and design drivers...... required from the turbine DC converter and uses these to compare 6 distinct candidate circuit topologies. The end goal is not to select the best topology, but to narrow down from a vast list of options and give a method that will increase confidence and guide towards the characteristics of reliable design....

Suppression of Mediator is regulated by Cdk8-dependent Grr1 turnover of the Med3 coactivator.

Science.gov (United States)

Gonzalez, Deyarina; Hamidi, Nurul; Del Sol, Ricardo; Benschop, Joris J; Nancy, Thomas; Li, Chao; Francis, Lewis; Tzouros, Manuel; Krijgsveld, Jeroen; Holstege, Frank C P; Conlan, R Steven

2014-02-18

Mediator, an evolutionary conserved large multisubunit protein complex with a central role in regulating RNA polymerase II-transcribed genes, serves as a molecular switchboard at the interface between DNA binding transcription factors and the general transcription machinery. Mediator subunits include the Cdk8 module, which has both positive and negative effects on activator-dependent transcription through the activity of the cyclin-dependent kinase Cdk8, and the tail module, which is required for positive and negative regulation of transcription, correct preinitiation complex formation in basal and activated transcription, and Mediator recruitment. Currently, the molecular mechanisms governing Mediator function remain largely undefined. Here we demonstrate an autoregulatory mechanism used by Mediator to repress transcription through the activity of distinct components of different modules. We show that the function of the tail module component Med3, which is required for transcription activation, is suppressed by the kinase activity of the Cdk8 module. Med3 interacts with, and is phosphorylated by, Cdk8; site-specific phosphorylation triggers interaction with and degradation by the Grr1 ubiquitin ligase, thereby preventing transcription activation. This active repression mechanism involving Grr1-dependent ubiquitination of Med3 offers a rationale for the substoichiometric levels of the tail module that are found in purified Mediator and the corresponding increase in tail components seen in cdk8 mutants.

75 FR 6160 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-10-10, DC-10-10F, DC-10-15, DC...

Science.gov (United States)

2010-02-08

...-0032; Directorate Identifier 2009-NM-213-AD] RIN 2120-AA64 Airworthiness Directives; McDonnell Douglas...: McDonnell Douglas Corporation: Docket No. FAA-2010-0032; Directorate Identifier 2009-NM-213-AD. Comments Due... applies to McDonnell Douglas Corporation Model DC- 10-10, DC-10-10F, DC-10-15, DC-10-30, DC-10-30F (KC-10A...

Protectin DX suppresses hepatic gluconeogenesis through AMPK-HO-1-mediated inhibition of ER stress.

Science.gov (United States)

Jung, Tae Woo; Kim, Hyung-Chun; Abd El-Aty, A M; Jeong, Ji Hoon

2017-06-01

Several studies have shown that protectins, which are ω-3 fatty acid-derived proresolution mediators, may improve insulin resistance. Recently, protectin DX (PDX) was documented to attenuate insulin resistance by stimulating IL-6 expression in skeletal muscle, thereby regulating hepatic gluconeogenesis. These findings made us investigate the direct effects of PDX on hepatic glucose metabolism in the context of diabetes. In the current study, we show that PDX regulates hepatic gluconeogenesis in a manner distinct from its indirect glucoregulatory activity via IL-6. We found that PDX stimulated AMP-activated protein kinase (AMPK) phosphorylation, thereby inducing heme oxygenase 1 (HO-1) expression. This induction blocked hepatic gluconeogenesis by suppressing endoplasmic reticulum (ER) stress in hepatocytes under hyperlipidemic conditions. These effects were significantly dampened by silencing AMPK or HO-1 expression with small interfering RNA (siRNA). We also demonstrated that administration of PDX to high fat diet (HFD)-fed mice resulted in increased hepatic AMPK phosphorylation and HO-1 expression, whereas hepatic ER stress was substantially attenuated. Furthermore, PDX treatment suppressed the expression of gluconeogenic genes, thereby decreasing blood glucose levels in HFD-fed mice. In conclusion, our findings suggest that PDX inhibits hepatic gluconeogenesis via AMPK-HO-1-dependent suppression of ER stress. Thus, PDX may be an effective therapeutic target for the treatment of insulin resistance and type 2 diabetes through the regulation of hepatic gluconeogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

75 FR 61989 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-8-31, DC-8-32, DC-8-33, DC-8-41...

Science.gov (United States)

2010-10-07

... Airworthiness Directives; McDonnell Douglas Corporation Model DC- 8-31, DC-8-32, DC-8-33, DC-8-41, DC-8-42, and... to all of the McDonnell Douglas Corporation airplanes identified above. The existing AD currently... the following new airworthiness directive (AD): 2010-21-03 McDonnell Douglas Corporation: Amendment 39...

Gut Microbiota Promotes Obesity-Associated Liver Cancer through PGE2-Mediated Suppression of Antitumor Immunity.

Science.gov (United States)

Loo, Tze Mun; Kamachi, Fumitaka; Watanabe, Yoshihiro; Yoshimoto, Shin; Kanda, Hiroaki; Arai, Yuriko; Nakajima-Takagi, Yaeko; Iwama, Atsushi; Koga, Tomoaki; Sugimoto, Yukihiko; Ozawa, Takayuki; Nakamura, Masaru; Kumagai, Miho; Watashi, Koichi; Taketo, Makoto M; Aoki, Tomohiro; Narumiya, Shuh; Oshima, Masanobu; Arita, Makoto; Hara, Eiji; Ohtani, Naoko

2017-05-01

Obesity increases the risk of cancers, including hepatocellular carcinomas (HCC). However, the precise molecular mechanisms through which obesity promotes HCC development are still unclear. Recent studies have shown that gut microbiota may influence liver diseases by transferring its metabolites and components. Here, we show that the hepatic translocation of obesity-induced lipoteichoic acid (LTA), a Gram-positive gut microbial component, promotes HCC development by creating a tumor-promoting microenvironment. LTA enhances the senescence-associated secretory phenotype (SASP) of hepatic stellate cells (HSC) collaboratively with an obesity-induced gut microbial metabolite, deoxycholic acid, to upregulate the expression of SASP factors and COX2 through Toll-like receptor 2. Interestingly, COX2-mediated prostaglandin E 2 (PGE 2 ) production suppresses the antitumor immunity through a PTGER4 receptor, thereby contributing to HCC progression. Moreover, COX2 overexpression and excess PGE 2 production were detected in HSCs in human HCCs with noncirrhotic, nonalcoholic steatohepatitis (NASH), indicating that a similar mechanism could function in humans. Significance: We showed the importance of the gut-liver axis in obesity-associated HCC. The gut microbiota-driven COX2 pathway produced the lipid mediator PGE 2 in senescent HSCs in the tumor microenvironment, which plays a pivotal role in suppressing antitumor immunity, suggesting that PGE 2 and its receptor may be novel therapeutic targets for noncirrhotic NASH-associated HCC. Cancer Discov; 7(5); 522-38. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 443 . ©2017 American Association for Cancer Research.

Borehole DC-12 hydrostratigraphic chart

International Nuclear Information System (INIS)

Gephart, R.E.

1981-09-01

This hydrostratigraphic chart identifies the basic stratigraphy and preliminary hydrologic testing results for Borehole DC-12. This borehole was cored through the Saddle Mountains and Wanapum basalt formations and into the Grande Ronde. Selected zones were hydrologically tested during coring

Borehole DC-14 hydrostratigraphic chart

International Nuclear Information System (INIS)

Gephart, R.E.

1981-09-01

This hydrostratigraphic chart identifies the basic stratigraphy and preliminary hydrologic testing results for Borehole DC-14. This borehole was cored through the Saddle Mountains and Wanapum basalt formations and into the Grande Ronde. Selected zones were hydrologically tested during coring

Borehole DC-15 hydrostratigraphic chart

International Nuclear Information System (INIS)

Gephart, R.E.

1981-09-01

This hydrostratigraphic chart identifies the basic stratigraphy and preliminary hydrologic testing results for Borehole DC-15. This borehole was cored through the Saddle Mountains and Wanapum basalt formations and into the Grande Ronde. Selected zones were hydrologically tested during coring

Step-Up DC-DC Power Converter

DEFF Research Database (Denmark)

2015-01-01

The present invention relates to a step-up DC-DC power converter which comprises a primary side circuit and a secondary side circuit coupled through a galvanic isolation barrier. The primary side circuit comprises a positive and a negative input terminal for receipt of an input voltage and an input...... being charged from the input voltage and discharged to the output capacitor through the galvanic isolation barrier in accordance with a switch control signal to produce the converter output voltage. The step-up DC-DC power converter comprises an electrical short-circuit connection across the galvanic...

AC-DC PFC Converter Using Combination of Flyback Converter and Full-bridge DC-DC Converter

Directory of Open Access Journals (Sweden)

Moh. Zaenal Efendi

2014-06-01

Full Text Available This paper presents a combination of power factor correction converter using Flyback converter and Full-bridge dc-dc converter in series connection. Flyback converter is operated in discontinuous conduction mode so that it can serve as a power factor correction converter and meanwhile Full-bridge dc-dc converter is used for dc regulator. This converter system is designed to produce a 86 Volt of output voltage and 2 A of output current. Both simulation and experiment results show that the power factor of this converter achieves up to 0.99 and meets harmonic standard of IEC61000-3-2. Keywords: Flyback Converter, Full-bridge DC-DC Converter, Power Factor Correction.

Early Oscillation Detection for DC/DC Converter Fault Diagnosis

Science.gov (United States)

Wang, Bright L.

2011-01-01

The electrical power system of a spacecraft plays a very critical role for space mission success. Such a modern power system may contain numerous hybrid DC/DC converters both inside the power system electronics (PSE) units and onboard most of the flight electronics modules. One of the faulty conditions for DC/DC converter that poses serious threats to mission safety is the random occurrence of oscillation related to inherent instability characteristics of the DC/DC converters and design deficiency of the power systems. To ensure the highest reliability of the power system, oscillations in any form shall be promptly detected during part level testing, system integration tests, flight health monitoring, and on-board fault diagnosis. The popular gain/phase margin analysis method is capable of predicting stability levels of DC/DC converters, but it is limited only to verification of designs and to part-level testing on some of the models. This method has to inject noise signals into the control loop circuitry as required, thus, interrupts the DC/DC converter's normal operation and increases risks of degrading and damaging the flight unit. A novel technique to detect oscillations at early stage for flight hybrid DC/DC converters was developed.

Negative affect, negative urgency, thought suppression, and bulimic symptoms: a moderated mediation analysis in a sample at-risk for bulimic symptoms.

Science.gov (United States)

Lavender, Jason M; Green, Daniel; Anestis, Michael D; Tull, Matthew T; Gratz, Kim L

2015-05-01

Research suggests that negative affect, negative urgency, and thought suppression are related to bulimic symptoms, either directly or indirectly. This study examined associations between these constructs in a sample at-risk for bulimic symptoms. Participants (N = 80) recruited from a residential substance abuse treatment facility completed self-report questionnaires. A regression-based bootstrapping approach was used to examine the indirect effect of negative affect on bulimic symptoms through negative urgency and the moderating role of thought suppression in the association between negative affect and negative urgency. Results revealed a significant indirect effect, significant moderation, and a significant moderated mediation effect, with an indirect effect of negative affect on bulimic symptoms through negative urgency, conditional upon low to moderate (but not high) levels of thought suppression. These findings suggest that negative affect may promote rash actions, particularly in the context of low to moderate thought suppression, leading to increased risk of bulimic symptoms. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

Superconducting energy stabilizer with charging and discharging DC-DC converters

International Nuclear Information System (INIS)

Kim, S.H.; Kostecki, E.L.; DeWinkel, C.C.

1992-01-01

This patent describes a superconducting energy stabilizer having multiple load connections and employing DC-DC conversion for storing energy in a superconducting inductive energy storage device having a first end and a second end, and for releasing the stored energy from the superconducting inductive energy storage device to a load or loads or to a utility or an industrial electrical distribution system, the superconducting energy stabilizer having multiple load connections and employing DC-DC conversion. It comprises: energy storage cell means for supplying energy to the load, discharging DC-DC converter means for releasing energy from the superconducting inductive energy storage device to the energy storage cell means, the discharging DC-DC converter means having input terminals, output terminals, and a discharging control line means for carrying signals controlling the operation of the discharging DC-DC converter means, one of the input terminals of the discharging DC-DC converter means coupled to the first end of the superconducting energy storage device

25 CFR 291.11 - What must the Secretary do upon receiving the proposal selected by the mediator?

Science.gov (United States)

2010-04-01

... selected by the mediator? 291.11 Section 291.11 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE... receiving the proposal selected by the mediator? Within 60 days of receiving the proposal selected by the mediator, the Secretary must do one of the following: (a) Notify the Indian tribe, the Governor and the...

A Phytophthora sojae effector PsCRN63 forms homo-/hetero-dimers to suppress plant immunity via an inverted association manner.

Science.gov (United States)

Li, Qi; Zhang, Meixiang; Shen, Danyu; Liu, Tingli; Chen, Yanyu; Zhou, Jian-Min; Dou, Daolong

2016-05-31

Oomycete pathogens produce a large number of effectors to promote infection. Their mode of action are largely unknown. Here we show that a Phytophthora sojae effector, PsCRN63, suppresses flg22-induced expression of FRK1 gene, a molecular marker in pathogen-associated molecular patterns (PAMP)-triggered immunity (PTI). However, PsCRN63 does not suppress upstream signaling events including flg22-induced MAPK activation and BIK1 phosphorylation, indicating that it acts downstream of MAPK cascades. The PsCRN63-transgenic Arabidopsis plants showed increased susceptibility to bacterial pathogen Pseudomonas syringae pathovar tomato (Pst) DC3000 and oomycete pathogen Phytophthora capsici. The callose deposition were suppressed in PsCRN63-transgenic plants compared with the wild-type control plants. Genes involved in PTI were also down-regulated in PsCRN63-transgenic plants. Interestingly, we found that PsCRN63 forms an dimer that is mediated by inter-molecular interactions between N-terminal and C-terminal domains in an inverted association manner. Furthermore, the N-terminal and C-terminal domains required for the dimerization are widely conserved among CRN effectors, suggesting that homo-/hetero-dimerization of Phytophthora CRN effectors is required to exert biological functions. Indeed, the dimerization was required for PTI suppression and cell death-induction activities of PsCRN63.

dc Arc Fault Effect on Hybrid ac/dc Microgrid

Science.gov (United States)

Fatima, Zahra

The advent of distributed energy resources (DER) and reliability and stability problems of the conventional grid system has given rise to the wide spread deployment of microgrids. Microgrids provide many advantages by incorporating renewable energy sources and increasing the reliability of the grid by isolating from the main grid in case of an outage. AC microgrids have been installed all over the world, but dc microgrids have been gaining interest due to the advantages they provide over ac microgrids. However the entire power network backbone is still ac and dc microgrids require expensive converters to connect to the ac power network. As a result hybrid ac/dc microgrids are gaining more attention as it combines the advantages of both ac and dc microgrids such as direct integration of ac and dc systems with minimum number of conversions which increases the efficiency by reducing energy losses. Although dc electric systems offer many advantages such as no synchronization and no reactive power, successful implementation of dc systems requires appropriate protection strategies. One unique protection challenge brought by the dc systems is dc arc faults. A dc arc fault is generated when there is a gap in the conductor due to insulation degradation and current is used to bridge the gap, resulting in an arc with very high temperature. Such a fault if it goes undetected and is not extinguished can cause damage to the entire system and cause fires. The purpose of the research is to study the effect of the dc arc fault at different locations in the hybrid ac/dc microgrid and provide insight on the reliability of the grid components when it is impacted by arc faults at various locations in the grid. The impact of dc arc fault at different locations on the performance of the PV array, wind generation, and constant power loads (CPL) interfaced with dc/dc converters is studied. MATLAB/Simulink is used to model the hybrid ac/dc microgrid and arc fault.

STING activation enhances cetuximab-mediated NK cell activation and DC maturation and correlates with HPV+ status in head and neck cancer.

Science.gov (United States)

Lu, Shanhong; Concha-Benavente, Fernando; Shayan, Gulidanna; Srivastava, Raghvendra M; Gibson, Sandra P; Wang, Lin; Gooding, William E; Ferris, Robert L

2018-03-01

The intracellular DNA sensor stimulator of interferon genes (STING) has recently been shown to play a vital role in anti-viral and anti-tumor immune responses stimulating cytokine production. While human papillomavirus (HPV) is a causative agent for a subset of head and neck squamous cell carcinoma (HNSCC) with unique etiology and clinical outcome, how the STING pathway is regulated in a virus-induced tumor microenvironment is not well understood. Since STING inactivation likely reflects immunoescape via innate immunity, we hypothesized that its restoration would improve efficacy of the immune modulatory monoclonal antibody (mAb), cetuximab. We correlated STING protein expression with clinical parameters by immunohistochemistry (n = 106) and its mRNA expression from The Cancer Genome Atlas (TCGA) in HNSCC tissue specimens. STING protein expression was tested for association with cancer-specific survival (CSS). We further examined the impact of STING activation on cetuximab-mediated immunity using an in vitro NK:DC:tumor cells co-culture system. In this study, we found that expression of STING both at the protein and mRNA level was higher in HPV positive (HPV + ) specimens but unrelated to TNM stage or cancer-specific survival. Our in vitro studies verified that STING activation enhanced cetuximab mediated NK cell activation and DC maturation. Our findings suggest a novel role of STING in HPV-related carcinogenesis, in which activation of the STING signaling pathway may facilitate anti-tumor response in HNSCC patients, particularly in combination with therapeutic monoclonal antibodies (mAbs) such as cetuximab, an epidermal growth factor receptor (EGFR) inhibitor. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Suppression of cancer growth in mice by adeno-associated virus vector-mediated IFN-beta expression driven by hTERT promoter.

Science.gov (United States)

He, Ling Feng; Wang, Yi Gang; Xiao, Tian; Zhang, Kang Jiang; Li, Gong Chu; Gu, Jin Fa; Chu, Liang; Tang, Wen Hao; Tan, Wen-Song; Liu, Xin Yuan

2009-12-28

Adeno-associated virus (AAV) has rapidly become a promising gene delivery vehicle for its excellent advantages of non-immunogenic, low pathogenicity and long-term gene expression in vivo. However, a major obstacle in development of effective AAV vector is the lack of tissue specificity, which caused low efficiency of AAV transfer to target cells. The application of human telomerase reverse transcriptase (hTERT) promoter is a prior targeting strategy for AAV in cancer gene therapy as hTERT activity is transcriptionally upregulated in most cancer cells. In the present work, we investigated whether AAV-mediated human interferon beta (IFN-beta) gene driven by hTERT promoter could specifically express in tumor cells and suppress tumor cell growth. Our data demonstrated that hTERT promoter-driven IFN-beta expression was the tumor-specific, decreased the cell viability of tumor cells but not normal cells, and induced tumor cell apoptosis via activation of caspase pathway and release of cytochrome c. AAV-mediated IFN-beta expression driven by hTERT promoter significantly suppressed the growth of colorectal cancer and lung cancer xenograft in mice and resulted in tumor cells death in vivo. These data suggested that AAVs in combination with hTERT-mediated IFN-beta expression could exert potential antitumor activity and provide a novel targeting approach to clinical gene therapy of varieties of cancers.

Milliwatt dc/dc Inverter

Science.gov (United States)

Mclyman, C. W.

1983-01-01

Compact dc/dc inverter uses single integrated-circuit package containing six inverter gates that generate and amplify 100-kHz square-wave switching signal. Square-wave switching inverts 10-volt local power to isolated voltage at another desired level. Relatively high operating frequency reduces size of filter capacitors required, resulting in small package unit.

Deconstructing continuous flash suppression.

Science.gov (United States)

Yang, Eunice; Blake, Randolph

2012-03-08

In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in contrast detection thresholds) as a function of the visual features of the stimulus being suppressed and the stimulus evoking suppression, namely, the popular "Mondrian" CFS stimulus (N. Tsuchiya & C. Koch, 2005). First, we found that CFS differentially suppresses the spatial components of the suppressed stimulus: Observers' sensitivity for stimuli of relatively low spatial frequency or cardinally oriented features was more strongly impaired in comparison to high spatial frequency or obliquely oriented stimuli. Second, we discovered that this feature-selective bias primarily arises from the spatiotemporal structure of the CFS stimulus, particularly within information residing in the low spatial frequency range and within the smooth rather than abrupt luminance changes over time. These results imply that this CFS stimulus operates by selectively attenuating certain classes of low-level signals while leaving others to be potentially encoded during suppression. These findings underscore the importance of considering the contribution of low-level features in stimulus-driven effects that are reported under CFS.

75 FR 63040 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-10-10, DC-10-10F, DC-10-30, DC...

Science.gov (United States)

2010-10-14

... Airworthiness Directives; McDonnell Douglas Corporation Model DC- 10-10, DC-10-10F, DC-10-30, DC-10-30F (KDC-10... following new airworthiness directive (AD): 2010-21-13 McDonnell Douglas Corporation: Amendment 39-16473... November 18, 2010. Affected ADs (b) None. Applicability (c) This AD applies to McDonnell Douglas...

75 FR 68246 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-10-10, DC-10-10F, DC-10-15, DC...

Science.gov (United States)

2010-11-05

...-1044; Directorate Identifier 2010-NM-033-AD] RIN 2120-AA64 Airworthiness Directives; McDonnell Douglas..., 2007) and adding the following new AD: McDonnell Douglas Corporation: Docket No. FAA-2010-1044.... Applicability (c) This AD applies to all McDonnell Douglas Corporation Model DC-10-10, DC-10-10F, DC-10-15, DC...

Genomic structural variation-mediated allelic suppression causes hybrid male sterility in rice.

Science.gov (United States)

Shen, Rongxin; Wang, Lan; Liu, Xupeng; Wu, Jiang; Jin, Weiwei; Zhao, Xiucai; Xie, Xianrong; Zhu, Qinlong; Tang, Huiwu; Li, Qing; Chen, Letian; Liu, Yao-Guang

2017-11-03

Hybrids between divergent populations commonly show hybrid sterility; this reproductive barrier hinders hybrid breeding of the japonica and indica rice (Oryza sativa L.) subspecies. Here we show that structural changes and copy number variation at the Sc locus confer japonica-indica hybrid male sterility. The japonica allele, Sc-j, contains a pollen-essential gene encoding a DUF1618-domain protein; the indica allele, Sc-i, contains two or three tandem-duplicated ~ 28-kb segments, each carrying an Sc-j-homolog with a distinct promoter. In Sc-j/Sc-i hybrids, the high-expression of Sc-i in sporophytic cells causes suppression of Sc-j expression in pollen and selective abortion of Sc-j-pollen, leading to transmission ratio distortion. Knocking out one or two of the three Sc-i copies by CRISPR/Cas9 rescues Sc-j expression and male fertility. Our results reveal the gene dosage-dependent allelic suppression as a mechanism of hybrid incompatibility, and provide an effective approach to overcome the reproductive barrier for hybrid breeding.

Cysteine protease antigens cleave CD123, the α subunit of murine IL-3 receptor, on basophils and suppress IL-3-mediated basophil expansion

International Nuclear Information System (INIS)

Nishikado, Hideto; Fujimura, Tsutomu; Taka, Hikari; Mineki, Reiko; Ogawa, Hideoki; Okumura, Ko; Takai, Toshiro

2015-01-01

Th2 type immune responses are essential for protective immunity against parasites and play crucial roles in allergic disorders. Helminth parasites secrete a variety of proteases for their infectious cycles including for host entry, tissue migration, and suppression of host immune effector cell function. Furthermore, a number of pathogen-derived antigens, as well as allergens such as papain, belong to the family of cysteine proteases. Although the link between protease activity and Th2 type immunity is well documented, the mechanisms by which proteases regulate host immune responses are largely unknown. Here, we demonstrate that the cysteine proteases papain and bromelain selectively cleave the α subunit of the IL-3 receptor (IL-3Rα/CD123) on the surface of murine basophils. The decrease in CD123 expression on the cell surface, and the degradation of the extracellular domain of recombinant CD123 were dependent on the protease activity of papain and bromelain. Pre-treatment of murine basophils with papain resulted in inhibition of IL-3-IL-3R signaling and suppressed IL-3- but not thymic stromal lymphopoietin-induced expansion of basophils in vitro. Our unexpected findings illuminate a novel mechanism for the regulation of basophil functions by protease antigens. Because IL-3 plays pivotal roles in the activation and proliferation of basophils and in protective immunity against helminth parasites, pathogen-derived proteases might contribute to the pathogenesis of infections by regulating IL-3-mediated functions in basophils. - Highlights: • We identified the murine IL3R as a novel target of papain-family cysteine proteases. • Papain-family cysteine proteases cleaved IL3Rα/CD123 on murine basophils. • Papain suppressed IL3- but not TSLP-induced expansion of murine basophils. • The inactivation of IL3R might be a strategy for pathogens to suppress host immunity

Cysteine protease antigens cleave CD123, the α subunit of murine IL-3 receptor, on basophils and suppress IL-3-mediated basophil expansion

Energy Technology Data Exchange (ETDEWEB)

Nishikado, Hideto [Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo (Japan); Fujimura, Tsutomu; Taka, Hikari; Mineki, Reiko [Laboratory of Proteomics and Biomolecular Science, BioMedical Research Center, Juntendo University Graduate School of Medicine, Tokyo (Japan); Ogawa, Hideoki; Okumura, Ko [Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo (Japan); Takai, Toshiro, E-mail: t-takai@juntendo.ac.jp [Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo (Japan)

2015-05-01

Th2 type immune responses are essential for protective immunity against parasites and play crucial roles in allergic disorders. Helminth parasites secrete a variety of proteases for their infectious cycles including for host entry, tissue migration, and suppression of host immune effector cell function. Furthermore, a number of pathogen-derived antigens, as well as allergens such as papain, belong to the family of cysteine proteases. Although the link between protease activity and Th2 type immunity is well documented, the mechanisms by which proteases regulate host immune responses are largely unknown. Here, we demonstrate that the cysteine proteases papain and bromelain selectively cleave the α subunit of the IL-3 receptor (IL-3Rα/CD123) on the surface of murine basophils. The decrease in CD123 expression on the cell surface, and the degradation of the extracellular domain of recombinant CD123 were dependent on the protease activity of papain and bromelain. Pre-treatment of murine basophils with papain resulted in inhibition of IL-3-IL-3R signaling and suppressed IL-3- but not thymic stromal lymphopoietin-induced expansion of basophils in vitro. Our unexpected findings illuminate a novel mechanism for the regulation of basophil functions by protease antigens. Because IL-3 plays pivotal roles in the activation and proliferation of basophils and in protective immunity against helminth parasites, pathogen-derived proteases might contribute to the pathogenesis of infections by regulating IL-3-mediated functions in basophils. - Highlights: • We identified the murine IL3R as a novel target of papain-family cysteine proteases. • Papain-family cysteine proteases cleaved IL3Rα/CD123 on murine basophils. • Papain suppressed IL3- but not TSLP-induced expansion of murine basophils. • The inactivation of IL3R might be a strategy for pathogens to suppress host immunity.

Spatial variation in pollinator-mediated selection on phenology, floral display and spur length in the orchid Gymnadenia conopsea.

Science.gov (United States)

Chapurlat, Elodie; Ågren, Jon; Sletvold, Nina

2015-12-01

Spatial variation in plant-pollinator interactions may cause variation in pollinator-mediated selection on floral traits, but to establish this link conclusively experimental studies are needed. We quantified pollinator-mediated selection on flowering phenology and morphology in four populations of the fragrant orchid Gymnadenia conopsea, and compared selection mediated by diurnal and nocturnal pollinators in two of the populations. Variation in pollinator-mediated selection explained most of the among-population variation in the strength of directional and correlational selection. Pollinators mediated correlational selection on pairs of display traits, and on one display trait and spur length, a trait affecting pollination efficiency. Only nocturnal pollinators selected for longer spurs, and mediated stronger selection on the number of flowers compared with diurnal pollinators in one population. The two types of pollinators caused correlational selection on different pairs of traits and selected for different combinations of spur length and number of flowers. The results demonstrate that spatial variation in interactions with pollinators may result in differences in directional and correlational selection on floral traits in a plant with a semi-generalized pollination system, and suggest that differences in the relative importance of diurnal and nocturnal pollinators can cause variation in selection. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Overview of Multi-DC-Bus Solutions for DC Microgrids

DEFF Research Database (Denmark)

Ricchiuto, D.; Mastromauro, R.A.; Liserre, Marco

2013-01-01

DC Microgrids have recently received a lot of attention in the last years due to high penetration of renewable energy sources as well as distributed energy storage systems. In the future DC microgrids could be preferable respect to AC microgrids in terms of redundancy since multi-DC-Bus solutions...... could provide a continuative power supply to the loads. An overview of Multi-DC-Bus solutions is presented in this paper. The performances are compared on the basis of possible DC microgrid configurations, redundancy, different DC voltage levels....

Let-7b-mediated suppression of basigin expression and metastasis in mouse melanoma cells

International Nuclear Information System (INIS)

Fu, Tzu-Yen; Chang, Chia-Che; Lin, Chun-Ting; Lai, Cong-Hao; Peng, Shao-Yu; Ko, Yi-Ju; Tang, Pin-Chi

2011-01-01

Basigin (Bsg), also called extracellular matrix metalloproteinase inducer (EMMPRIN), is highly expressed on the surface of tumor cells and stimulates adjacent fibroblasts or tumor cells to produce matrix metalloproteinases (mmps). It has been shown that Bsg plays an important role in growth, development, cell differentiation, and tumor progression. MicroRNAs (miRNAs) are a class of short endogenous non-protein coding RNAs of 20-25 nucleotides (nt) that function as post-transcriptional regulators of gene expression by base-pairing to their target mRNAs and thereby mediate cleavage of target mRNAs or translational repression. In this study, let-7b, one of the let-7 family members, was investigated for its effect on the growth and invasiveness of the mouse melanoma cell line B16-F10. We have shown that let-7b can suppress the expression of Bsg in B16-F10 cells and also provided evidence that this suppression could result in the indirect suppression of mmp-9. The ability of B16-F10 cells transfected with let-7b to invade or migrate was significantly reduced. In addition, let-7b transfected B16-F10 cells displayed an inhibition of both cellular proliferation and colony formation. Furthermore, it was shown that the overexpression of let-7b in B16-F10 cells could reduce lung metastasis. Taken together, the present study identifies let-7b as a tumor suppressor that represses cancer cell proliferation and migration as well as tumor metastasis in mouse melanoma cells.

Let-7b-mediated suppression of basigin expression and metastasis in mouse melanoma cells

Energy Technology Data Exchange (ETDEWEB)

Fu, Tzu-Yen [Department of Animal Science, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China); Chang, Chia-Che [Institute of Biomedical Sciences, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China); Graduate Institute of Basic Medical Science, China Medical University, 91 Hsueh Shih Road, Taichung 40402, Taiwan (China); Lin, Chun-Ting [Department of Animal Science, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China); Lai, Cong-Hao [Institute of Biomedical Sciences, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China); Department of Life Sciences, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China); Peng, Shao-Yu; Ko, Yi-Ju [Department of Animal Science, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China); Tang, Pin-Chi, E-mail: pctang@dragon.nchu.edu.tw [Department of Animal Science, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China)

2011-02-15

Basigin (Bsg), also called extracellular matrix metalloproteinase inducer (EMMPRIN), is highly expressed on the surface of tumor cells and stimulates adjacent fibroblasts or tumor cells to produce matrix metalloproteinases (mmps). It has been shown that Bsg plays an important role in growth, development, cell differentiation, and tumor progression. MicroRNAs (miRNAs) are a class of short endogenous non-protein coding RNAs of 20-25 nucleotides (nt) that function as post-transcriptional regulators of gene expression by base-pairing to their target mRNAs and thereby mediate cleavage of target mRNAs or translational repression. In this study, let-7b, one of the let-7 family members, was investigated for its effect on the growth and invasiveness of the mouse melanoma cell line B16-F10. We have shown that let-7b can suppress the expression of Bsg in B16-F10 cells and also provided evidence that this suppression could result in the indirect suppression of mmp-9. The ability of B16-F10 cells transfected with let-7b to invade or migrate was significantly reduced. In addition, let-7b transfected B16-F10 cells displayed an inhibition of both cellular proliferation and colony formation. Furthermore, it was shown that the overexpression of let-7b in B16-F10 cells could reduce lung metastasis. Taken together, the present study identifies let-7b as a tumor suppressor that represses cancer cell proliferation and migration as well as tumor metastasis in mouse melanoma cells.

Suppression sours sacrifice: emotional and relational costs of suppressing emotions in romantic relationships.

Science.gov (United States)

Impett, Emily A; Kogan, Aleksandr; English, Tammy; John, Oliver; Oveis, Christopher; Gordon, Amie M; Keltner, Dacher

2012-06-01

What happens when people suppress their emotions when they sacrifice for a romantic partner? This multimethod study investigates how suppressing emotions during sacrifice shapes affective and relationship outcomes. In Part 1, dating couples came into the laboratory to discuss important romantic relationship sacrifices. Suppressing emotions was associated with emotional costs for the partner discussing his or her sacrifice. In Part 2, couples participated in a 14-day daily experience study. Within-person increases in emotional suppression during daily sacrifice were associated with decreases in emotional well-being and relationship quality as reported by both members of romantic dyads. In Part 3, suppression predicted decreases in relationship satisfaction and increases in thoughts about breaking up with a romantic partner 3 months later. In the first two parts of the study, authenticity mediated the costly effects of suppression. Implications for research on close relationships and emotion regulation are discussed.

Select phytochemicals suppress human T-lymphocytes and mouse splenocytes suggesting their use in autoimmunity and transplantation

Science.gov (United States)

Hushmendy, Shazaan; Jayakumar, Lalithapriya; Hahn, Amy B.; Bhoiwala, Devang; Bhoiwala, Dipti L.; Crawford, Dana R.

2009-01-01

We have considered a novel “rational” gene targeting approach for treating pathologies whose genetic bases are defined using select phytochemicals. We reason that one such potential application of this approach would be conditions requiring immunosuppression such as autoimmune disease and transplantation, where the genetic target is clearly defined; i.e., interleukin-2 and associated T-cell activation. Therefore, we hypothesized that select phytochemicals can suppress T-lymphocyte proliferation both in vitro and in vivo. The immunosuppressive effects of berry extract, curcumin, quercetin, sulforaphane, epigallocatechin gallate (EGCG), resveratrol, α-tocopherol, vitamin C and sucrose were tested on anti-CD3 plus anti-CD28-activated primary human T-lymphocytes in culture. Curcumin, sulforaphane, quercetin, berry extract and EGCG all significantly inhibited T-cell proliferation, and this effect was not due to toxicity. IL-2 production was also reduced by these agents, implicating this important T-cell cytokine in proliferation suppression. Except for berry extract, these same agents also inhibited mouse splenic T-cell proliferation and IL-2 production. Subsequent in vivo studies revealed that quercetin (but not sulforaphane) modestly suppressed mouse splenocyte proliferation following supplementation of BALB/c mice diets. This effect was especially prominent if corrected for the loss of supplement “recall” as observed in cultured T-cells. These results suggest the potential use of these select phytochemicals for treating autoimmune and transplant patients, and support our strategy of using select phytochemicals to treat genetically-defined pathologies, an approach that we believe is simple, healthy, and cost-effective. PMID:19761891

Wnt/β-catenin signaling mediates the suppressive effects of diallyl trisulfide on colorectal cancer stem cells.

Science.gov (United States)

Zhang, Qi; Li, Xiao-Ting; Chen, Yue; Chen, Jia-Qi; Zhu, Jian-Yun; Meng, Yu; Wang, Xiao-Qian; Li, Yuan; Geng, Shan-Shan; Xie, Chun-Feng; Wu, Jie-Shu; Zhong, Cai-Yun; Han, Hong-Yu

2018-06-01

Cancer stem cells (CSCs) are responsible for colorectal cancer (CRC) initiation, growth, and metastasis. Garlic-derived organosulfur compound diallyl trisulfide (DATS) possesses cancer suppressive properties. Wnt/β-catenin signaling is a key target for CSCs inhibition. However, the interventional effect of DATS on colorectal CSCs has not been clarified. We aimed to illustrate the regulation of Wnt/β-catenin in DATS-induced colorectal CSCs inhibition. Serum-free medium culture was used to enrich colorectal CSCs. SW480 and DLD-1 sphere-forming cells were treated with different concentrations of DATS for 5 days; LiCl and β-catenin plasmids were used to stimulate the activity of Wnt/β-catenin pathway. The size and number of colonspheres were detected by tumorsphere formation assay; the expression of colorectal CSCs-related genes was detected by Western blotting and qRT-PCR; the capacities of colorectal CSCs proliferation and apoptosis were detected by Cell Counting Kit-8, Hoechst 33258 cell staining and flow cytometry, respectively. The levels of colorectal CSCs markers were elevated in the tumorspheres cells. DATS efficiently suppressed the activity of colorectal CSCs, as evidenced by reducing the size and number of colonspheres, decreasing the expression of colorectal CSCs markers, promoting apoptosis and inhibiting the proliferation of colorectal CSCs. Moreover, DATS suppressed the activity of Wnt/β-catenin pathway, while upregulation of Wnt/β-catenin diminished the inhibitory effect of DATS on colorectal CSCs. Wnt/β-catenin pathway mediates DATS-induced colorectal CSCs suppression. These findings support the use of DATS for targeting colorectal CSCs.

Dietary, nondigestible oligosaccharides and Bifidobacterium breve M-16V suppress allergic inflammation in intestine via targeting dendritic cell maturation.

Science.gov (United States)

de Kivit, Sander; Kostadinova, Atanaska I; Kerperien, JoAnn; Morgan, Mary E; Muruzabal, Veronica Ayechu; Hofman, Gerard A; Knippels, Leon M J; Kraneveld, Aletta D; Garssen, Johan; Willemsen, Linette E M

2017-07-01

Dietary intervention with short-chain galacto-oligosaccharides (scGOS), long-chain fructo-oligosaccharides (lcFOS) and Bifidobacterium breve M-16V ( Bb ) (GF/ Bb ) suppresses food allergic symptoms in mice, potentially via intestinal epithelial cell (IEC)-derived galectin-9. Furthermore, in vitro studies showed galacto- and fructo-oligosaccharides (GF) to enhance the immunomodulatory capacity of a TLR9 ligand representing bacterial CpG DNA when exposed to IEC. In this study, we investigated whether GF/ Bb modulates dendritic cells (DCs) and subsequent Th2 and regulatory T cell (T reg ) frequency in the small intestinal lamina propria (SI-LP). BALB/c mice were fed GF/ Bb during oral OVA sensitization. DC and T cell phenotype were determined in SI-LP mononuclear cells using flow cytometry. Murine bone marrow-derived DCs (BMDCs) were exposed to recombinant galectin-9 or human monocyte-derived DCs (moDCs) and were cultured in IEC-conditioned medium from GF and TLR9 ligand-exposed HT-29 cells. GF/ Bb reduced allergic symptoms and enhanced serum galectin-9 levels, while suppressing activation, restoring phagocytic capacity, and normalizing CD103 expression of SI-LP DCs of OVA-allergic mice. In vitro, galectin-9 suppressed LPS-induced activation markers and cytokine secretion by BMDCs, and IEC-conditioned medium suppressed moDC activation in a galectin-9-dependent manner. Besides suppression of SI-LP DC activation, dietary GF/ Bb also lowered the frequency of activated Th2 cells, while enhancing T reg in the SI-LP of OVA-allergic mice compared to the control diet. Dietary intervention with GF/ Bb enhances galectin-9 and suppresses allergic symptoms of OVA-allergic mice in association with reduced intestinal DC and Th2 activation and increased T reg frequency in these mice. © Society for Leukocyte Biology.

DC to DC power converters and methods of controlling the same

Science.gov (United States)

Steigerwald, Robert Louis; Elasser, Ahmed; Sabate, Juan Antonio; Todorovic, Maja Harfman; Agamy, Mohammed

2012-12-11

A power generation system configured to provide direct current (DC) power to a DC link is described. The system includes a first power generation unit configured to output DC power. The system also includes a first DC to DC converter comprising an input section and an output section. The output section of the first DC to DC converter is coupled in series with the first power generation unit. The first DC to DC converter is configured to process a first portion of the DC power output by the first power generation unit and to provide an unprocessed second portion of the DC power output of the first power generation unit to the output section.

Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

International Nuclear Information System (INIS)

Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng

2015-01-01

Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice. �

Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

Energy Technology Data Exchange (ETDEWEB)

Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng, E-mail: zhouqs@suda.edu.cn

2015-10-15

Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice. �

Practical Design Guidelines of qZSI Based Step-Up DC/DC Converter

Science.gov (United States)

Zakis, Janis; Vinnikov, Dmitri; Roasto, Indrek; Jalakas, Tanel

2010-01-01

This paper presents some design guidelines for a new voltage fed step-up DC/DC isolated converter. The most significant advantage of proposed converter is voltage buck-boost operation on single stage. The most promising application for proposed converter is in the field of distributed power generation e.g. fuel cells or photovoltaic. The most sensitive issues - such as power losses caused by high currents in the input side of converter and high transient overvoltages across the inverter bridge caused by stray inductances were discussed and solved. The proposals and recommendations to overcome these issues are given in the paper. The Selection and design guidelines of converter elements are proposed and explained. The prototype of proposed converter was built and experimentally tested. Some results are presented and evaluated.

Does suppression of oscillatory synchronisation mediate some of the therapeutic effects of DBS in patients with Parkinson’s disease?

Directory of Open Access Journals (Sweden)

Alexandre eEusebio

2012-07-01

Full Text Available There is growing evidence for exaggerated oscillatory neuronal synchronisation in patients with Parkinson’s disease. In particular, oscillations at around 20 Hz, in the so-called beta frequency band, relate to the cardinal symptoms of bradykinesia and rigidity. Deep brain stimulation of the subthalamic nucleus can significantly improve these motor impairments. Recent evidence has demonstrated reduction of beta oscillations concurrent with alleviation of PD motor symptoms, raising the possibility that suppression of aberrant activity may mediate the effects of DBS. Here we review the evidence supporting suppression of pathological oscillations during stimulation and discuss how this might underlie the efficacy of DBS. We also consider how beta activity may provide a feedback signal suitable for next generation closed loop and intelligent stimulators.

Hierarchical Velocity Control Based on Differential Flatness for a DC/DC Buck Converter-DC Motor System

Directory of Open Access Journals (Sweden)

R. Silva-Ortigoza

2014-01-01

Full Text Available This paper presents a hierarchical controller that carries out the angular velocity trajectory tracking task for a DC motor driven by a DC/DC Buck converter. The high level control is related to the DC motor and the low level control is dedicated to the DC/DC Buck converter; both controls are designed via differential flatness. The high level control provides a desired voltage profile for the DC motor to achieve the tracking of a desired angular velocity trajectory. Then, a low level control is designed to ensure that the output voltage of the DC/DC Buck converter tracks the voltage profile imposed by the high level control. In order to experimentally verify the hierarchical controller performance, a DS1104 electronic board from dSPACE and Matlab-Simulink are used. The switched implementation of the hierarchical average controller is accomplished by means of pulse width modulation. Experimental results of the hierarchical controller for the velocity trajectory tracking task show good performance and robustness against the uncertainties associated with different system parameters.

Cord blood mesenchymal stem cells suppress DC-T Cell proliferation via prostaglandin B2

NARCIS (Netherlands)

Berk, L.C.J. van den; Jansen, B.J.H.; Snowden, S.; Siebers-Vermeulen, K.G.C.; Gilissen, C.; Kogler, G.; Figdor, C.G.; Wheelock, C.E.; Torensma, R.

2014-01-01

Immune suppression is a very stable property of multipotent stromal cells also known as mesenchymal stem cells (MSCs). All cell lines tested showed robust immune suppression not affected by a long culture history. Several mechanisms were described to account for this capability. Since several of the

An indoxyl compound 5-bromo-4-chloro-3-indolyl 1,3-diacetate, CAC-0982, suppresses activation of Fyn kinase in mast cells and IgE-mediated allergic responses in mice

Energy Technology Data Exchange (ETDEWEB)

Lee, Jun Ho [Department of Immunology, School of Medicine, Konkuk University, Chungju 380-701 (Korea, Republic of); College of Medicine, Korea University, Seoul 136-701 (Korea, Republic of); Kim, Tae Hyung [College of Pharmacy, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Kim, Hyuk Soon; Kim, A-Ram [Department of Immunology, School of Medicine, Konkuk University, Chungju 380-701 (Korea, Republic of); Kim, Do-Kyun [Department of Immunology, School of Medicine, Konkuk University, Chungju 380-701 (Korea, Republic of); Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Nam, Seung Taek; Kim, Hyun Woo; Park, Young Hwan; Her, Erk; Park, Yeong Min [Department of Immunology, School of Medicine, Konkuk University, Chungju 380-701 (Korea, Republic of); Kim, Hyung Sik [College of Pharmacy, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Kim, Young Mi [College of Pharmacy, Duksung Women' s University, Seoul 132-714 (Korea, Republic of); Choi, Wahn Soo, E-mail: wahnchoi@kku.ac.kr [Department of Immunology, School of Medicine, Konkuk University, Chungju 380-701 (Korea, Republic of)

2015-06-15

Mast cells, constituents of virtually all organs and tissues, are critical cells in IgE-mediated allergic responses. The aim of this study was to investigate the effect and mechanism of an indoxyl chromogenic compound, 5-bromo-4-chloro-3-indolyl 1,3-diacetate, CAC-0982, on IgE-mediated mast cell activation and allergic responses in mice. CAC-0982 reversibly suppressed antigen-stimulated degranulation in murine mast cells (IC{sub 50}, ~ 3.8 μM) and human mast cells (IC{sub 50}, ~ 3.0 μM). CAC-0982 also inhibited the expression and secretion of IL-4 and TNF-α in mast cells. Furthermore, CAC-0982 suppressed the mast cell-mediated allergic responses in mice in a dose-dependent manner (ED{sub 50} 27.9 mg/kg). As for the mechanism, CAC-0982 largely suppressed the phosphorylation of Syk and its downstream signaling molecules, including LAT, Akt, Erk1/2, p38, and JNK. Notably, the tyrosine kinase assay of antigen-stimulated mast cells showed that CAC-0982 inhibited Fyn kinase, one of the upstream tyrosine kinases for Syk activation in mast cells. Taken together, these results suggest that CAC-0982 may be used as a new treatment for regulating IgE-mediated allergic diseases through the inhibition of the Fyn/Syk pathway in mast cells. - Highlights: • The anti-allergic effect of 5-bromo-4-chloro-3-indolyl 1,3-diacetate, CAC-0982, was measured. • CAC-0982 reversibly suppressed the activation of mast cells by IgE and antigen. • CAC-0982 inhibited passive cutaneous anaphylaxis in mice. • CAC-0982 suppresses mast cells through inhibition of Fyn activation in mast cells.

An indoxyl compound 5-bromo-4-chloro-3-indolyl 1,3-diacetate, CAC-0982, suppresses activation of Fyn kinase in mast cells and IgE-mediated allergic responses in mice

International Nuclear Information System (INIS)

Lee, Jun Ho; Kim, Tae Hyung; Kim, Hyuk Soon; Kim, A-Ram; Kim, Do-Kyun; Nam, Seung Taek; Kim, Hyun Woo; Park, Young Hwan; Her, Erk; Park, Yeong Min; Kim, Hyung Sik; Kim, Young Mi; Choi, Wahn Soo

2015-01-01

Mast cells, constituents of virtually all organs and tissues, are critical cells in IgE-mediated allergic responses. The aim of this study was to investigate the effect and mechanism of an indoxyl chromogenic compound, 5-bromo-4-chloro-3-indolyl 1,3-diacetate, CAC-0982, on IgE-mediated mast cell activation and allergic responses in mice. CAC-0982 reversibly suppressed antigen-stimulated degranulation in murine mast cells (IC 50 , ~ 3.8 μM) and human mast cells (IC 50 , ~ 3.0 μM). CAC-0982 also inhibited the expression and secretion of IL-4 and TNF-α in mast cells. Furthermore, CAC-0982 suppressed the mast cell-mediated allergic responses in mice in a dose-dependent manner (ED 50 27.9 mg/kg). As for the mechanism, CAC-0982 largely suppressed the phosphorylation of Syk and its downstream signaling molecules, including LAT, Akt, Erk1/2, p38, and JNK. Notably, the tyrosine kinase assay of antigen-stimulated mast cells showed that CAC-0982 inhibited Fyn kinase, one of the upstream tyrosine kinases for Syk activation in mast cells. Taken together, these results suggest that CAC-0982 may be used as a new treatment for regulating IgE-mediated allergic diseases through the inhibition of the Fyn/Syk pathway in mast cells. - Highlights: • The anti-allergic effect of 5-bromo-4-chloro-3-indolyl 1,3-diacetate, CAC-0982, was measured. • CAC-0982 reversibly suppressed the activation of mast cells by IgE and antigen. • CAC-0982 inhibited passive cutaneous anaphylaxis in mice. • CAC-0982 suppresses mast cells through inhibition of Fyn activation in mast cells

DC systems design and research of Hainan Changjiang nuclear power plant

International Nuclear Information System (INIS)

Jiang Qingshui; Wang Yuhan

2014-01-01

Hainan Changjiang nuclear power plant is different from the referent power plant, the DC and 220 V AC uninterrupted systems of the nuclear island have been changed since the control system use DCS. It has different design on DC systems, power supply, selectivity of breakers, capacity of equipments and layout. We optimize the design of DC systems at the basement of Fuqing and Fangjiashan project. These are good experiments for the three generation nuclear power project about DC systems design of ACP1000. (authors)

Possible neuroimmunomodulation therapy in T-cell-mediated oral diseases

Directory of Open Access Journals (Sweden)

Tsuyoshi Sato

2015-01-01

Full Text Available Introduction: Recurrent aphthous stomatitis and oral lichen planus are local chronic inflammatory diseases which are implicated in T cell-mediated immunity. According to the systematic review, there is insufficient evidence to support any specific treatment for T-cell mediated oral diseases. The hypothesis: In this paper, we propose a hypothesis that recurrent aphthous stomatitis and oral lichen planus can be treated with selective α7 subunit of nicotinic acetylcholine receptor (α7 -nAChR agonists. Our hypothesis is supported by the following two facts. First, the pathophysiological conditions, T h 1/T h 17 cell activation and autonomic nervous system dysfunction, are observed in T-cell mediated oral diseases as well as in T-cell mediated systemic diseases such as rheumatoid arthritis. Second, the cholinergic anti-inflammatory pathway is inhibited in systemic T-cell mediated chronic inflammatory diseases. On the other hand, treatment with α7 -nAChR agonists which activate the cholinergic anti-inflammatory pathway suppresses neuroinflammation via inhibition of T h 1/T h 17 responses in animal model of systemic T-cell mediated chronic inflammatory diseases. We thus expect that selective α7 -nAChR agonists will be effective for the treatment of T-cell mediated oral diseases. Evaluation of the hypothesis: To test our hypothesis, we need to develop in vivo mouse model of T-cell mediated oral diseases. To evaluate the therapeutic effect of a selective α7 -nAChR agonist, we choose ABT-107 because of its safety and tolerability. We believe that the selective α7 -nAChR agonist, especially ABT-107, may be a therapeutic drug to treat T-cell mediated oral diseases.

Perceptual Color Space Representations in the Oculomotor System Are Modulated by Surround Suppression and Biased Selection

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Devin H. Kehoe

2018-01-01

Full Text Available The oculomotor system utilizes color extensively for planning saccades. Therefore, we examined how the oculomotor system actually encodes color and several factors that modulate these representations: attention-based surround suppression and inherent biases in selecting and encoding color categories. We measured saccade trajectories while human participants performed a memory-guided saccade task with color targets and distractors and examined whether oculomotor target selection processing was functionally related to the CIE (x,y color space distances between color stimuli and whether there were hierarchical differences between color categories in the strength and speed of encoding potential saccade goals. We observed that saccade planning was modulated by the CIE (x,y distances between stimuli thus demonstrating that color is encoded in perceptual color space by the oculomotor system. Furthermore, these representations were modulated by (1 cueing attention to a particular color thereby eliciting surround suppression in oculomotor color space and (2 inherent selection and encoding biases based on color category independent of cueing and perceptual discriminability. Since surround suppression emerges from recurrent feedback attenuation of sensory projections, observing oculomotor surround suppression suggested that oculomotor encoding of behavioral relevance results from integrating sensory and cognitive signals that are pre-attenuated based on task demands and that the oculomotor system therefore does not functionally contribute to this process. Second, although perceptual discriminability did partially account for oculomotor processing differences between color categories, we also observed preferential processing of the red color category across various behavioral metrics. This is consistent with numerous previous studies and could not be simply explained by perceptual discriminability. Since we utilized a memory-guided saccade task, this

Perceptual Color Space Representations in the Oculomotor System Are Modulated by Surround Suppression and Biased Selection.

Science.gov (United States)

Kehoe, Devin H; Rahimi, Maryam; Fallah, Mazyar

2018-01-01

The oculomotor system utilizes color extensively for planning saccades. Therefore, we examined how the oculomotor system actually encodes color and several factors that modulate these representations: attention-based surround suppression and inherent biases in selecting and encoding color categories. We measured saccade trajectories while human participants performed a memory-guided saccade task with color targets and distractors and examined whether oculomotor target selection processing was functionally related to the CIE ( x , y ) color space distances between color stimuli and whether there were hierarchical differences between color categories in the strength and speed of encoding potential saccade goals. We observed that saccade planning was modulated by the CIE ( x , y ) distances between stimuli thus demonstrating that color is encoded in perceptual color space by the oculomotor system. Furthermore, these representations were modulated by (1) cueing attention to a particular color thereby eliciting surround suppression in oculomotor color space and (2) inherent selection and encoding biases based on color category independent of cueing and perceptual discriminability. Since surround suppression emerges from recurrent feedback attenuation of sensory projections, observing oculomotor surround suppression suggested that oculomotor encoding of behavioral relevance results from integrating sensory and cognitive signals that are pre-attenuated based on task demands and that the oculomotor system therefore does not functionally contribute to this process. Second, although perceptual discriminability did partially account for oculomotor processing differences between color categories, we also observed preferential processing of the red color category across various behavioral metrics. This is consistent with numerous previous studies and could not be simply explained by perceptual discriminability. Since we utilized a memory-guided saccade task, this indicates that

An Integrated Multifunctional Bidirectional AC/DC and DC/DC Converter for Electric Vehicles Applications

OpenAIRE

Liwen Pan; Chengning Zhang

2016-01-01

This paper presents an on-board vehicular battery charger that integrates bidirectional AC/DC converter and DC/DC converter to achieve high power density for application in electric vehicles (EVs). The integrated charger is able to transfer electrical energy between the battery pack and the electric traction system and to function as an AC/DC battery charger. The integrated charger topology is presented and the design of passive components is discussed. The control schemes are developed for m...

PENGGUNAAN FUZZY LOGIC UNTUK KONTROL PARALLEL CONVERTER DC-DC

Directory of Open Access Journals (Sweden)

Bambang Prio Hartono

2012-09-01

Full Text Available Abstract: Using system fuzzy logic as control  technology have been used on low load dc-dc converter with combined parallel compiled  dc-dc converter can  obtain big load.   With existence of differrence of component parameter and each parallel compiled converter can obtained different current  and voltage output.  Function of controller  for to do adjustment, so that current which is applied  to  load by each converter  can be obtained  difference error as small as possible or same. The object of research is developing design of large signal dc-dc converter which is  combined with using  FLC so that  obtain  better performance.  To get better performance have been made plant model and simulation with CDE method.  The more systematic  system and design is needed to overcome bigger load  on dc-dc converter, so that parallel  compiled current master slave control system on dc-dc converter with using fuzzy logic  controller is used. Result of  research showed that error or difference of  current  which is applied to load can handled by fuzzy logic  controller.  Technic of current and voltage controller co to do adjustment current and voltage distribution  equally to load.  Distribution of iL1,iL2 and  output voltage Vo on dc-dc  converter with load 2,25 until  7,875 and voltage  100  until 120 volt,  load current beetwen  12 until 48, % relatif  error  Vo  0,4% until  0,9%.

Stimulation of cannabinoid receptor 2 (CB2 suppresses microglial activation

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Fernandez Francisco

2005-12-01

Full Text Available Abstract Background Activated microglial cells have been implicated in a number of neurodegenerative disorders, including Alzheimer's disease (AD, multiple sclerosis (MS, and HIV dementia. It is well known that inflammatory mediators such as nitric oxide (NO, cytokines, and chemokines play an important role in microglial cell-associated neuron cell damage. Our previous studies have shown that CD40 signaling is involved in pathological activation of microglial cells. Many data reveal that cannabinoids mediate suppression of inflammation in vitro and in vivo through stimulation of cannabinoid receptor 2 (CB2. Methods In this study, we investigated the effects of a cannabinoid agonist on CD40 expression and function by cultured microglial cells activated by IFN-γ using RT-PCR, Western immunoblotting, flow cytometry, and anti-CB2 small interfering RNA (siRNA analyses. Furthermore, we examined if the stimulation of CB2 could modulate the capacity of microglial cells to phagocytise Aβ1–42 peptide using a phagocytosis assay. Results We found that the selective stimulation of cannabinoid receptor CB2 by JWH-015 suppressed IFN-γ-induced CD40 expression. In addition, this CB2 agonist markedly inhibited IFN-γ-induced phosphorylation of JAK/STAT1. Further, this stimulation was also able to suppress microglial TNF-α and nitric oxide production induced either by IFN-γ or Aβ peptide challenge in the presence of CD40 ligation. Finally, we showed that CB2 activation by JWH-015 markedly attenuated CD40-mediated inhibition of microglial phagocytosis of Aβ1–42 peptide. Taken together, these results provide mechanistic insight into beneficial effects provided by cannabinoid receptor CB2 modulation in neurodegenerative diseases, particularly AD.

Full range ZVS DC-DC converter

International Nuclear Information System (INIS)

Upadhyay, Rinki; Badapanda, M.K.; Hannurkar, P.R.

2011-01-01

A 500 V, 24 Amp DC-DC converter with digital signal processor (DSP) based control and protection has been designed, fabricated and tested. Its power circuit consists of IGBT based single phase inverter bridge, ferrite transformer and diode rectifier. All IGBTs in the inverter bridge are operated in zero voltage switching (ZVS) mode to minimize switching losses thereby increasing the efficiency of the converter significantly. The efficiency of this converter is measured to be greater than 97% at full load. In a conventional full bridge inverter, typically ZVS is achieved under full load condition while at light load ZVS is lost. An auxiliary LC circuit has been intentionally incorporated in this converter to achieve ZVS even at light loaded conditions. Detailed simulation of the converter circuit is carried out and crucial waveforms have been presented in this paper. Microchip make dsPIC30F2020 DSP is employed to provide phase shifted PWMs to IGBTs in the inverter bridge. All the crucial parameters are also monitored by this DSP and in case of any unfavorable conditions, the converter is tripped off. Suitable experiments were carried out in this DC-DC converter under different loaded conditions and a close match between the simulated and experimental results were obtained. Such DC-DC converters can be connected in series or parallel for the development of solid state modular power supplies for various applications. (author)

Research on key technology of planning and design for AC/DC hybrid distribution network

Science.gov (United States)

Shen, Yu; Wu, Guilian; Zheng, Huan; Deng, Junpeng; Shi, Pengjia

2018-04-01

With the increasing demand of DC generation and DC load, the development of DC technology, AC and DC distribution network integrating will become an important form of future distribution network. In this paper, the key technology of planning and design for AC/DC hybrid distribution network is proposed, including the selection of AC and DC voltage series, the design of typical grid structure and the comprehensive evaluation method of planning scheme. The research results provide some ideas and directions for the future development of AC/DC hybrid distribution network.

Perceptual Color Space Representations in the Oculomotor System Are Modulated by Surround Suppression and Biased Selection

OpenAIRE

Kehoe, Devin H.; Rahimi, Maryam; Fallah, Mazyar

2018-01-01

The oculomotor system utilizes color extensively for planning saccades. Therefore, we examined how the oculomotor system actually encodes color and several factors that modulate these representations: attention-based surround suppression and inherent biases in selecting and encoding color categories. We measured saccade trajectories while human participants performed a memory-guided saccade task with color targets and distractors and examined whether oculomotor target selection processing was...

TOPOLOGICAL REVIEW AND ANALYSIS OF DC-DC BOOST CONVERTERS

Directory of Open Access Journals (Sweden)

V. INDRA GANDHI

2017-06-01

Full Text Available DC voltage boost up is essential in numerous applications; especially considering Photovoltaic (PV based renewable power generation system. The conventional DC-DC boost converter is the most admired configuration for this scheme, even if the converter efficiency is restricted at duty cycle near to maximum value. In order to find solution to the problem and improve its conversion capability, many converter configurations have been implemented so far. With this circumstance, this research work proposes to give overview of a few most imperative research works related to DC-DC boost converters. Some configurations are covered and classified basically based on the application. The major benefits and disadvantages related to the available techniques are also briefly conveyed. At last, a proper evaluation is recognized among the important types of DC-DC boost converters in terms of efficiency, number of components, and stability.

Transient phenomena analysis of a DC-1 MV power supply for the ITER NBI

International Nuclear Information System (INIS)

Yamamoto, Masanori; Watanabe, Kazuhiro; Yamanaka, Haruhiko; Takemoto, Jumpei; Inoue, Takashi; Yamashita, Yasuo

2010-08-01

A power supply for the ITER Neutral Beam Injector (NBI) is a DC ultra-high voltage (UHV) power supply to accelerate negative ion beams of 40 A up to an energy of 1 MeV. Japan Atomic Energy Agency as the Japan Domestic Agency for ITER contributes procurement of dc -1 MV main components such as step-up -1 MV transformers rectifiers, a high voltage deck 2, a -1 MV insulating transformer, a transmission line, a surge reduction system and equipments for site test. Design of the surge suppression in the NBI power supply is one of the key issues to obtain the stable injector performance. This report describes the design study using EMTDC code on the surge suppression by optimizing the core snubber and additional elements in the -1 MV power supply. The results show that the input energy from the stray capacitance to the accelerator at the breakdown can be reduced to about 25 J that is smaller than design criteria for ITER. (author)

Experimental power reactor dc generator energy storage study

International Nuclear Information System (INIS)

Heck, F.M.; Smeltzer, G.S.; Myers, E.H.; Kilgore, L.

1978-01-01

This study covers the use of dc generators for meeting the Experimental Power Reactor Ohmic Heating Energy Storage Requirements. The dc generators satisfy these requirements which are the same as defined in WFPS-TME-038 which covered the use of ac generators and homopolar generators. The costs of the latter two systems have been revised to eliminate first-of-a-kind factors. The cost figures for dc generators indicate a need to develop larger machines in order to take advantage of the economy-of-scale that the large ac machines have. Each of the systems has its own favorable salient features on which to base a system selection

Andrographolide suppresses the migratory ability of human glioblastoma multiforme cells by targeting ERK1/2-mediated matrix metalloproteinase-2 expression.

Science.gov (United States)

Yang, Shih-Liang; Kuo, Fu-Hsuan; Chen, Pei-Ni; Hsieh, Yi-Hsien; Yu, Nuo-Yi; Yang, Wei-En; Hsieh, Ming-Ju; Yang, Shun-Fa

2017-12-01

Glioblastoma multiforme (GBM) can be a fatal tumor because of difficulties in treating the related metastasis. Andrographolide is the bioactive component of the Andrographis paniculata . Andrographolide possesses the anti-inflammatory activity and inhibits the growth of various cancers; however, its effect on GBM cancer motility remains largely unknown. In this study, we examined the antimetastatic properties of andrographolide in human GBM cells. Our results revealed that andrographolide inhibited the invasion and migration abilities of GBM8401 and U251 cells. Furthermore, andrographolide inhibited matrix metalloproteinase (MMP)-2 activity and expression. Real-time PCR and promoter activity assays indicated that andrographolide inhibited MMP-2 expression at the transcriptional level. Such inhibitory effects were associated with the suppression of CREB DNA-binding activity and CREB expression. Mechanistically, andrographolide inhibited the cell motility of GBM8401 cells through the extracellular-regulated kinase (ERK) 1/2 pathway, and the blocking of the ERK 1/2 pathway could reverse MMP-2-mediated cell motility. In conclusion, CREB is a crucial target of andrographolide for suppressing MMP-2-mediated cell motility in GBM cells. Therefore, a combination of andrographolide and an ERK inhibitor might be a good strategy for preventing GBM metastasis.

The Aversive Agent Lithium Chloride Suppresses Phasic Dopamine Release Through Central GLP-1 Receptors.

Science.gov (United States)

Fortin, Samantha M; Chartoff, Elena H; Roitman, Mitchell F

2016-02-01

Unconditioned rewarding stimuli evoke phasic increases in dopamine concentration in the nucleus accumbens (NAc) while discrete aversive stimuli elicit pauses in dopamine neuron firing and reductions in NAc dopamine concentration. The unconditioned effects of more prolonged aversive states on dopamine release dynamics are not well understood and are investigated here using the malaise-inducing agent lithium chloride (LiCl). We used fast-scan cyclic voltammetry to measure phasic increases in NAc dopamine resulting from electrical stimulation of dopamine cell bodies in the ventral tegmental area (VTA). Systemic LiCl injection reduced electrically evoked dopamine release in the NAc of both anesthetized and awake rats. As some behavioral effects of LiCl appear to be mediated through glucagon-like peptide-1 receptor (GLP-1R) activation, we hypothesized that the suppression of phasic dopamine by LiCl is GLP-1R dependent. Indeed, peripheral pretreatment with the GLP-1R antagonist exendin-9 (Ex-9) potently attenuated the LiCl-induced suppression of dopamine. Pretreatment with Ex-9 did not, however, affect the suppression of phasic dopamine release by the kappa-opioid receptor agonist, salvinorin A, supporting a selective effect of GLP-1R stimulation in LiCl-induced dopamine suppression. By delivering Ex-9 to either the lateral or fourth ventricle, we highlight a population of central GLP-1 receptors rostral to the hindbrain that are involved in the LiCl-mediated suppression of NAc dopamine release.

Glutaminase 2 is a novel negative regulator of small GTPase Rac1 and mediates p53 function in suppressing metastasis

Science.gov (United States)

Zhang, Cen; Liu, Juan; Zhao, Yuhan; Yue, Xuetian; Zhu, Yu; Wang, Xiaolong; Wu, Hao; Blanco, Felix; Li, Shaohua; Bhanot, Gyan; Haffty, Bruce G; Hu, Wenwei; Feng, Zhaohui

2016-01-01

Glutaminase (GLS) isoenzymes GLS1 and GLS2 are key enzymes for glutamine metabolism. Interestingly, GLS1 and GLS2 display contrasting functions in tumorigenesis with elusive mechanism; GLS1 promotes tumorigenesis, whereas GLS2 exhibits a tumor-suppressive function. In this study, we found that GLS2 but not GLS1 binds to small GTPase Rac1 and inhibits its interaction with Rac1 activators guanine-nucleotide exchange factors, which in turn inhibits Rac1 to suppress cancer metastasis. This function of GLS2 is independent of GLS2 glutaminase activity. Furthermore, decreased GLS2 expression is associated with enhanced metastasis in human cancer. As a p53 target, GLS2 mediates p53’s function in metastasis suppression through inhibiting Rac1. In summary, our results reveal that GLS2 is a novel negative regulator of Rac1, and uncover a novel function and mechanism whereby GLS2 suppresses metastasis. Our results also elucidate a novel mechanism that contributes to the contrasting functions of GLS1 and GLS2 in tumorigenesis. DOI: http://dx.doi.org/10.7554/eLife.10727.001 PMID:26751560

Jinggangmycin-suppressed reproduction in the small brown planthopper (SBPH), Laodelphax striatellus (Fallen), is mediated by glucose dehydrogenase (GDH).

Science.gov (United States)

Ding, Jun; Wu, You; You, Lin-Lin; Xu, Bin; Ge, Lin-Quan; Yang, Guo-Qing; Wu, Jin-Cai

2017-06-01

The small brown planthopper (SBPH), Laodelphax striatellus (Fallen), is a serious pest insect of rice, wheat, and maize in China. SBPH not only sucks plant sap but also transmits plant disease viruses, causing serious damage. These viruses include rice striped virus disease (RSV disease), black streaked dwarf, and maize rough disease virus. SBPH outbreaks are related to the overuse of pesticides in China. Some pesticides, such as triazophos, stimulate the reproduction of SBPH, but an antibiotic fungicide jinggangmycin (JGM) suppresses its reproduction. However, mechanisms of decreased reproduction of SBPH induced by JGM remain unclear. The present findings show that JGM suppressed reproduction of SBPH (↓approximately 35.7%) and resulted in the down-regulated expression of glucose dehydrogenase (GDH). GDH-silenced control females (control+dsGDH) show that the number of eggs laid was reduced by 48.6% compared to control females. Biochemical tests show that the total lipid and fatty acid contents in JGM-treated and control+dsGDH females decreased significantly. Thus, we propose that the suppression of reproduction in SBPH induced by JGM is mediated by GDH via metabolic pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Modular Study of the Type III Effector Repertoire in Pseudomonas syringae pv. tomato DC3000 Reveals a Matrix of Effector Interplay in Pathogenesis.

Science.gov (United States)

Wei, Hai-Lei; Zhang, Wei; Collmer, Alan

2018-05-08

The bacterial pathogen Pseudomonas syringae pv. tomato DC3000 suppresses the two-tiered innate immune system of Nicotiana benthamiana and other plants by injecting a complex repertoire of type III secretion effector (T3E) proteins. Effectorless polymutant DC3000D36E was used with a modularized system for native delivery of the 29 DC3000 T3Es singly and in pairs. Assays of the performance of this T3E library in N. benthamiana leaves revealed a matrix of T3E interplay, with six T3Es eliciting death and eight others variously suppressing the death activity of the six. The T3E library was also interrogated for effects on DC3000D36E elicitation of a reactive oxygen species burst, for growth in planta, and for T3Es that reversed these effects. Pseudomonas fluorescens and Agrobacterium tumefaciens heterologous delivery systems yielded notably different sets of death-T3Es. The DC3000D36E T3E library system highlights the importance of 13 T3Es and their interplay in interactions with N. benthamiana. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Full wave dc-to-dc converter using energy storage transformers

Science.gov (United States)

Moore, E. T.; Wilson, T. G.

1969-01-01

Full wave dc-to-dc converter, for an ion thrustor, uses energy storage transformers to provide a method of dc-to-dc conversion and regulation. The converter has a high degree of physical simplicity, is lightweight and has high efficiency.

Pulsewidth modulated DC-to-DC power conversion circuits, dynamics, and control designs

CERN Document Server

Choi, Byungcho

2013-01-01

This is the definitive reference for anyone involved in pulsewidth modulated DC-to-DC power conversion Pulsewidth Modulated DC-to-DC Power Conversion: Circuits, Dynamics, and Control Designs provides engineers, researchers, and students in the power electronics field with comprehensive and complete guidance to understanding pulsewidth modulated (PWM) DC-to-DC power converters. Presented in three parts, the book addresses the circuitry and operation of PWM DC-to-DC converters and their dynamic characteristics, along with in-depth discussions of control design of PWM DC-to

Type I interferons as stimulators of DC-mediated cross-priming: impact on anti-tumor response

Directory of Open Access Journals (Sweden)

Giovanna eSchiavoni

2013-12-01

Full Text Available Induction of potent tumor-specific cytotoxic T-cell responses is a fundamental objective in anticancer therapeutic strategies. This event requires that antigen-presenting cells (APC present tumor-associated antigens (Ag on their MHC class-I molecule, in a process termed cross-presentation. Dendritic cells (DC are particularly keen on this task and can induce the cross-priming of CD8+ T cells, when exposed to danger or inflammatory signals that stimulate their activation. Type I interferons (IFN-I, a family of long-known immunostimulatory cytokines, have been proven to produce optimal activation signal for DC-induced cross-priming. Recent in vitro and in vivo evidences have suggested that IFN-I -stimulated cross-priming by DC against tumor-associated Ag is a key mechanism for cancer immunosurveillance and may be usefully exploited to boost anti-tumor CD8+ T-cell responses. Here, we will review the cross-presentation properties of different DC subsets, with special focus on cell-associated and tumor Ag, and discuss how IFN-I can modify this function, with the aim of identifying more specific and effective strategies for improving anticancer responses.

Modular Study of the Type III Effector Repertoire in Pseudomonas syringae pv. tomato DC3000 Reveals a Matrix of Effector Interplay in Pathogenesis

Directory of Open Access Journals (Sweden)

Hai-Lei Wei

2018-05-01

Full Text Available Summary: The bacterial pathogen Pseudomonas syringae pv. tomato DC3000 suppresses the two-tiered innate immune system of Nicotiana benthamiana and other plants by injecting a complex repertoire of type III secretion effector (T3E proteins. Effectorless polymutant DC3000D36E was used with a modularized system for native delivery of the 29 DC3000 T3Es singly and in pairs. Assays of the performance of this T3E library in N. benthamiana leaves revealed a matrix of T3E interplay, with six T3Es eliciting death and eight others variously suppressing the death activity of the six. The T3E library was also interrogated for effects on DC3000D36E elicitation of a reactive oxygen species burst, for growth in planta, and for T3Es that reversed these effects. Pseudomonas fluorescens and Agrobacterium tumefaciens heterologous delivery systems yielded notably different sets of death-T3Es. The DC3000D36E T3E library system highlights the importance of 13 T3Es and their interplay in interactions with N. benthamiana. : Wei et al. used a Pseudomonas syringae strain lacking all known type III effectors with a modularized library expressing the 29 active effectors in the strain’s native repertoire, individually and in pairs, to comprehensively determine effector actions and interplay in inducing and suppressing responses associated with plant pathogenesis and immunity. Keywords: effector-triggered-immunity, pattern-triggered-immunity, Hop proteins, plant immunity, mini-Tn7

Triple voltage dc-to-dc converter and method

Science.gov (United States)

Su, Gui-Jia

2008-08-05

A circuit and method of providing three dc voltage buses and transforming power between a low voltage dc converter and a high voltage dc converter, by coupling a primary dc power circuit and a secondary dc power circuit through an isolation transformer; providing the gating signals to power semiconductor switches in the primary and secondary circuits to control power flow between the primary and secondary circuits and by controlling a phase shift between the primary voltage and the secondary voltage. The primary dc power circuit and the secondary dc power circuit each further comprising at least two tank capacitances arranged in series as a tank leg, at least two resonant switching devices arranged in series with each other and arranged in parallel with the tank leg, and at least one voltage source arranged in parallel with the tank leg and the resonant switching devices, said resonant switching devices including power semiconductor switches that are operated by gating signals. Additional embodiments having a center-tapped battery on the low voltage side and a plurality of modules on both the low voltage side and the high voltage side are also disclosed for the purpose of reducing ripple current and for reducing the size of the components.

Design of double DC motor control system based on DSP

Directory of Open Access Journals (Sweden)

Suo WANG

2017-10-01

Full Text Available Aiming at the problems of speed control, commutation and so on in the multi-motor synchronous control system, based on automatic control technology, a control system with PC as principal computer and DSP as slave computer is designed, which can change dual DC motor speed and steering, as well as select work drive motors. Related hardware and software design of the control system are given. Through serial communication between DSP and PC using PC serial port software, digital control command is sent to the slave computer for controlling dual DC motor to do a series of preset functions. PWM pulse width modulation is used for motor speed regulation, photoelectric encoder is used to measure motor speed by T method, and the motor speed is displayed by the actual waveform. Experimental results show that the system can not only realize the synchronization of dual DC motor speed and steering adjustment, but also select the motor and achieve the dual DC motors synchronization control effect. The control system has certain reliability and effectiveness.

Tris(2-ethylhexyl)phosphine oxide as an effective solvent mediator for constructing a serotonin-selective membrane electrode

International Nuclear Information System (INIS)

Ueda, Keisuke; Yonemoto, Rei; Komagoe, Keiko; Masuda, Kazufumi; Hanioka, Nobumitsu; Narimatsu, Shizuo; Katsu, Takashi

2006-01-01

A series of solvent mediators containing a phosphoryl (P=O) group, such as tris(2-ethylhexyl)phosphate, bis(2-ethylhexyl) 2-ethylhexylphosphonate, 2-ethylhexyl bis(2-ethylhexyl)phosphinate, and tris(2-ethylhexyl)phosphine oxide, were used to construct serotonin-selective membrane electrodes. We found that replacing the alkoxy groups attached to phosphorus atoms in P=O groups with alkyl groups strengthened the response of the electrode to serotonin, suppressing remarkably interference from inorganic cations, such as Na + . Thus, an electrode combining tris(2-ethylhexyl)phosphine oxide with an ion-exchanger, sodium tetrakis[3,5-bis(2-methoxyhexafluoro-2-propyl)phenyl]borate, gave a detection limit of 9 x 10 -6 M with a slope of 55.2 mV per concentration decade in physiological saline containing 150 mM NaCl and 10 mM NaH 2 PO 4 /Na 2 HPO 4 (pH 7.4). This is the best detection limit of any serotonin-selective electrode developed to date. The selectivity of this electrode for serotonin was over 10 3 times that for inorganic cations, such as Na + and K + , and lipophilic quaternary ammonium ions, such as acetylcholine and (C 2 H 5 ) 4 N + . Using the electrode, we measured the amount of serotonin released from platelets and found that the results agreed well with those obtained by a conventional fluorimetric assay of serotonin

Selection Demands and Working Memory Mediate Interference during Naming

Directory of Open Access Journals (Sweden)

Julie W Hughes

2015-05-01

Analyzing RTs, we replicated previous SI effects in BCN in healthy subjects and patients (reported effects’ p’s < .05. Subjects responded more slowly to items in semantically related vs. unrelated groups, and this interference increased across cycles (evidence of increasing selection demands; Figures 1a/c. Indicative of WM, healthy subjects were faster to name items as the number of unrelated items to be named (i.e., remembered decreased. However, this was attenuated by selection demand, as there was no decrease in RTs across repeated related items (Figure 1b. Converging evidence from patients demonstrated more impaired selection capacity produced increasingly slower RTs across item positions within the related condition (high selection demand (Figure 1d. Larger WM capacity (rhyme probe but not category probe, p = .54 produced increasingly faster RTs across items positions in the unrelated condition (low selection demand (Figure 1e. Together, these findings suggest that both selection demand and phonological WM processes mediate interference during naming.

Switching coordination of distributed dc-dc converters for highly efficient photovoltaic power plants

Science.gov (United States)

Agamy, Mohammed; Elasser, Ahmed; Sabate, Juan Antonio; Galbraith, Anthony William; Harfman Todorovic, Maja

2014-09-09

A distributed photovoltaic (PV) power plant includes a plurality of distributed dc-dc converters. The dc-dc converters are configured to switch in coordination with one another such that at least one dc-dc converter transfers power to a common dc-bus based upon the total system power available from one or more corresponding strings of PV modules. Due to the coordinated switching of the dc-dc converters, each dc-dc converter transferring power to the common dc-bus continues to operate within its optimal efficiency range as well as to optimize the maximum power point tracking in order to increase the energy yield of the PV power plant.

The performance of the DC motor by the PID controlling PWM DC-DC boost converter

OpenAIRE

Can, Erol; Sayan, Hasan Hüseyin

2017-01-01

This paper presents the PID controlling direct current (DC) to the direct current boost converter feds DC motor which has a 3.68 kW and 240 V of DC voltage input on its characteristics. What is first formed is the boost converter mathematical model at the design stage. Secondly, a mathematical model of the DC motor is created so that the boost converter with the machine can be established and modeled at the Matlab Simulink. The PID controller is considered for arranging a pulse width modulati...

NF-κB functions as a molecular link between tumor cells and Th1/Tc1 T cells in the tumor microenvironment to exert radiation-mediated tumor suppression

Science.gov (United States)

Simon, Priscilla S.; Bardhan, Kankana; Chen, May R.; Paschall, Amy V.; Lu, Chunwan; Bollag, Roni J.; Kong, Feng-Chong; Jin, JianYue; Kong, Feng-Ming; Waller, Jennifer L.; Pollock, Raphael E.; Liu, Kebin

2016-01-01

Radiation modulates both tumor cells and immune cells in the tumor microenvironment to exert its anti-tumor activity; however, the molecular connection between tumor cells and immune cells that mediates radiation-exerted tumor suppression activity in the tumor microenvironment is largely unknown. We report here that radiation induces rapid activation of the p65/p50 and p50/p50 NF-κB complexes in human soft tissue sarcoma (STS) cells. Radiation-activated p65/p50 and p50/p50 bind to the TNFα promoter to activate its transcription in STS cells. Radiation-induced TNFα induces tumor cell death in an autocrine manner. A sublethal dose of Smac mimetic BV6 induces cIAP1 and cIAP2 degradation to increase tumor cell sensitivity to radiation-induced cell death in vitro and to enhance radiation-mediated suppression of STS xenografts in vivo. Inhibition of caspases, RIP1, or RIP3 blocks radiation/TNFα-induced cell death, whereas inhibition of RIP1 blocks TNFα-induced caspase activation, suggesting that caspases and RIP1 act sequentially to mediate the non-compensatory cell death pathways. Furthermore, we determined in a syngeneic sarcoma mouse model that radiation up-regulates IRF3, IFNβ, and the T cell chemokines CCL2 and CCL5 in the tumor microenvironment, which are associated with activation and increased infiltration of Th1/Tc1 T cells in the tumor microenvironment. Moreover, tumor-infiltrating T cells are in their active form since both the perforin and FasL pathways are activated in irradiated tumor tissues. Consequently, combined BV6 and radiation completely suppressed tumor growth in vivo. Therefore, radiation-induced NF-κB functions as a molecular link between tumor cells and immune cells in the tumor microenvironment for radiation-mediated tumor suppression. PMID:27014915

The Topologies Research of a Soft Switching Bidirectional DC/DC Converter

DEFF Research Database (Denmark)

Zhang, Qi; Zhang, Yongping; Sun, Xiangdong

2017-01-01

A soft-switching solution implemented to the traditional bidirectional DC/DC converter is developed. The soft-switching cell, which composed of three auxiliary switches, one resonant capacitor and one resonant inductor, is equipped in the traditional bidirectional DC/DC converter to realize circuit...... circle. And the proposed topology of bidirectional soft-switching dc-dc converter(TASBC) performs ideal soft switching at boost operations. The characteristics of the proposed converter has been verified by MATLAB simulations and experimental results....

75 FR 27401 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-9-30, DC-9-40, and DC-9-50...

Science.gov (United States)

2010-05-17

... Airworthiness Directives; McDonnell Douglas Corporation Model DC- 9-30, DC-9-40, and DC-9-50 Series Airplanes... airworthiness directive (AD) for certain Model DC-9-30, DC-9-40, and DC-9-50 series airplanes. This AD requires... this AD to detect and correct the potential for an arc/spark condition to occur within the fuel boost...

A Virtual Inertia Control Strategy for DC Microgrids Analogized with Virtual Synchronous Machines

DEFF Research Database (Denmark)

Wu, Wenhua; Chen, Yandong; Luo, An

2017-01-01

In a DC microgrid (DC-MG), the dc bus voltage is vulnerable to power fluctuation derived from the intermittent distributed energy or local loads variation. In this paper, a virtual inertia control strategy for DC-MG through bidirectional grid-connected converters (BGCs) analogized with virtual...... synchronous machine (VSM) is proposed to enhance the inertia of the DC-MG, and to restrain the dc bus voltage fluctuation. The small-signal model of the BGC system is established, and the small-signal transfer function between the dc bus voltage and the dc output current of the BGC is deduced. The dynamic...... for the BGC is introduced to smooth the dynamic response of the dc bus voltage. By analyzing the control system stability, the appropriate virtual inertia control parameters are selected. Finally, simulations and experiments verified the validity of the proposed control strategy....

A Feed-Forward Control Realizing Fast Response for Three-Branch Interleaved DC-DC Converter in DC Microgrid

Directory of Open Access Journals (Sweden)

Haojie Wang

2016-07-01

Full Text Available It is a common practice for storage batteries to be connected to DC microgrid buses through DC-DC converters for voltage support on islanded operation mode. A feed-forward control based dual-loop constant voltage PI control for three-branch interleaved DC-DC converters (TIDC is proposed for storage batteries in DC microgrids. The working principle of TIDC is analyzed, and the factors influencing the response rate based on the dual-loop constant voltage control for TIDC are discussed, and then the method of feed-forward control for TIDC is studied to improve the response rate for load changing. A prototype of the TIDC is developed and an experimental platform is built. The experiment results show that DC bus voltage sags or swells caused by load changing can be reduced and the time for voltage recovery can be decreased significantly with the proposed feed-forward control.

A Feed-Forward Control Realizing Fast Response for Three-Branch Interleaved DC-DC Converter in DC Microgrid

DEFF Research Database (Denmark)

Wang, Haojie; Han, Minxiao; Yan, Wenli

2016-01-01

It is a common practice for storage batteries to be connected to DC microgrid buses through DC-DC converters for voltage support on islanded operation mode. A feed-forward control based dual-loop constant voltage PI control for three-branch interleaved DC-DC converters (TIDC) is proposed...... for storage batteries in DC microgrids. The working principle of TIDC is analyzed, and the factors influencing the response rate based on the dual-loop constant voltage control for TIDC are discussed, and then the method of feed-forward control for TIDC is studied to improve the response rate for load...... changing. A prototype of the TIDC is developed and an experimental platform is built. The experiment results show that DC bus voltage sags or swells caused by load changing can be reduced and the time for voltage recovery can be decreased significantly with the proposed feed-forward control....

Deconstructing continuous flash suppression

OpenAIRE

Yang, Eunice; Blake, Randolph

2012-01-01

In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in co...

Virus-mediated suppression of host non-self recognition facilitates horizontal transmission of heterologous viruses.

Directory of Open Access Journals (Sweden)

Songsong Wu

2017-03-01

Full Text Available Non-self recognition is a common phenomenon among organisms; it often leads to innate immunity to prevent the invasion of parasites and maintain the genetic polymorphism of organisms. Fungal vegetative incompatibility is a type of non-self recognition which often induces programmed cell death (PCD and restricts the spread of molecular parasites. It is not clearly known whether virus infection could attenuate non-self recognition among host individuals to facilitate its spread. Here, we report that a hypovirulence-associated mycoreovirus, named Sclerotinia sclerotiorum mycoreovirus 4 (SsMYRV4, could suppress host non-self recognition and facilitate horizontal transmission of heterologous viruses. We found that cell death in intermingled colony regions between SsMYRV4-infected Sclerotinia sclerotiorum strain and other tested vegetatively incompatible strains was markedly reduced and inhibition barrage lines were not clearly observed. Vegetative incompatibility, which involves Heterotrimeric guanine nucleotide-binding proteins (G proteins signaling pathway, is controlled by specific loci termed het (heterokaryon incompatibility loci. Reactive oxygen species (ROS plays a key role in vegetative incompatibility-mediated PCD. The expression of G protein subunit genes, het genes, and ROS-related genes were significantly down-regulated, and cellular production of ROS was suppressed in the presence of SsMYRV4. Furthermore, SsMYRV4-infected strain could easily accept other viruses through hyphal contact and these viruses could be efficiently transmitted from SsMYRV4-infected strain to other vegetatively incompatible individuals. Thus, we concluded that SsMYRV4 is capable of suppressing host non-self recognition and facilitating heterologous viruses transmission among host individuals. These findings may enhance our understanding of virus ecology, and provide a potential strategy to utilize hypovirulence-associated mycoviruses to control fungal diseases.

Selective epidemic broadcast algorithm to suppress broadcast storm in vehicular ad hoc networks

Directory of Open Access Journals (Sweden)

M. Chitra

2018-03-01

Full Text Available Broadcasting in Vehicular Ad Hoc Networks is the best way to spread emergency messages all over the network. With the dynamic nature of vehicular ad hoc networks, simple broadcast or flooding faces the problem called as Broadcast Storm Problem (BSP. The issue of the BSP will degrade the performance of a message broadcasting process like increased overhead, collision and dissemination delay. The paper is motivated to solve the problems in the existing Broadcast Strom Suppression Algorithms (BSSAs like p-Persistence, TLO, VSPB, G-SAB and SIR. This paper proposes to suppress the Broadcast Storm Problem and to improve the Emergency Safety message dissemination rate through a new BSSA based on Selective Epidemic Broadcast Algorithm (SEB. The simulation results clearly show that the SEB outperforms the existing algorithms in terms of ESM Delivery Ratio, Message Overhead, Collision Ratio, Broadcast Storm Ratio and Redundant Rebroadcast Ratio with decreased Dissemination Delay.

Suppression of Aflatoxin Production in Aspergillus Species by Selected Peanut (Arachis hypogaea) Stilbenoids.

Science.gov (United States)

Sobolev, Victor; Arias, Renee; Goodman, Kerestin; Walk, Travis; Orner, Valerie; Faustinelli, Paola; Massa, Alicia

2018-01-10

Aspergillus flavus is a soil fungus that commonly invades peanut seeds and often produces carcinogenic aflatoxins. Under favorable conditions, the fungus-challenged peanut plant produces and accumulates resveratrol and its prenylated derivatives in response to such an invasion. These prenylated stilbenoids are considered peanut antifungal phytoalexins. However, the mechanism of peanut-fungus interaction has not been sufficiently studied. We used pure peanut stilbenoids arachidin-1, arachidin-3, and chiricanine A to study their effects on the viability of and metabolite production by several important toxigenic Aspergillus species. Significant reduction or virtually complete suppression of aflatoxin production was revealed in feeding experiments in A. flavus, Aspergillus parasiticus, and Aspergillus nomius. Changes in morphology, spore germination, and growth rate were observed in A. flavus exposed to the selected peanut stilbenoids. Elucidation of the mechanism of aflatoxin suppression by peanut stilbenoids could provide strategies for preventing plant invasion by the fungi that produce aflatoxins.

Attentional Selection and Suppression in Children With Attention-Deficit/Hyperactivity Disorder.

Science.gov (United States)

Wang, Encong; Sun, Li; Sun, Meirong; Huang, Jing; Tao, Ye; Zhao, Xixi; Wu, Zhanliang; Ding, Yulong; Newman, Daniel P; Bellgrove, Mark A; Wang, Yufeng; Song, Yan

2016-07-01

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with prominent impairments in directing and sustaining attention. The aim of this study was to identify the neurophysiologic bases of attention deficits in ADHD, focusing on electroencephalography markers of attentional selection (posterior contralateral N2 [N2pc]) and suppression (distractor positivity [P D ]). The electroencephalography data were collected from 135 children 9-15 years old with and without ADHD while they searched for a shape target in either the absence (experiment 1) or the presence (experiment 2) of a salient but irrelevant color distractor. In experiment 1, the shape target elicited a smaller N2pc in children with ADHD (n = 38) compared with typically developing children (n = 36). The smaller N2pc amplitude predicted higher levels of inattentive symptoms in children with ADHD. Moreover, the target-elicited N2pc was followed by a positivity in typically developing children but not in children with ADHD. In experiment 2, the salient but irrelevant color distractor elicited a smaller P D component in children with ADHD (n = 32) compared with typically developing children (n = 29). The smaller P D predicted higher inattentive symptom severity as well as lower behavioral accuracy in children with ADHD. The correlation between N2pc/P D amplitudes and ADHD symptom severity suggests that these signals of attentional selection and suppression may serve as potential candidates for neurophysiologic markers of ADHD. Our findings provide a neurophysiologic basis for the subjective reports of attention deficits in children with ADHD and highlight the importance of spatial attention impairments in ADHD. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Controlling DC permeability in cast steels

Energy Technology Data Exchange (ETDEWEB)

Sumner, Aaran, E-mail: aaran.sumner@nottingham.ac.uk [University of Nottingham, Nottingham University Park Campus, Nottingham NG7 2RD, England (United Kingdom); Gerada, Chris, E-mail: chris.gerada@nottingham.ac.uk [Electrical Machines, University of Nottingham, Tower Building, Nottingham NG7 2RD, England (United Kingdom); Brown, Neil, E-mail: neil.brown@cummins.com [Advanced Electrical Machines Research and Technology at Cummins Power Generation, Peterborough PE2 6FZ, England (United Kingdom); Clare, Adam, E-mail: adam.clare@nottingham.ac.uk [Advanced Manufacturing, University of Nottingham, University Park Campus, Nottingham NG7 2RD, England (United Kingdom)

2017-05-01

Annealing (at multiple cooling rates) and quenching (with tempering) was performed on specimens of cast steel of varying composition. The aim was to devise a method for selecting the steel with the highest permeability, from any given range of steels, and then increasing the permeability by heat treatment. Metallographic samples were imaged using optical microscopy to show the effect of the applied heat treatments on the microstructure. Commonly cast steels can have DC permeability altered by the careful selection of a heat treatment. Increases of up to 381% were achieved by annealing using a cooling rate of 6.0 °C/min. Annealing was found to cause the carbon present in the steel to migrate from grain boundaries and from within ferrite crystals into adjacent pearlite crystals. The migration of the carbon resulted in less carbon at grain boundaries and within ferrite crystals reducing the number of pinning sites between magnetic domains. This gives rise to a higher permeability. Quenching then tempering was found to cause the formation of small ferrite crystals with the carbon content of the steel predominately held in the martensitic crystal structures. The results show that with any given range of steel compositions the highest baseline DC permeability will be found with the steel that has the highest iron content and the lowest carbon content. For the samples tested in this paper a cooling rate of 4.5 °C/min resulted in the relative permeability of the sample with the highest baseline permeability, AS4, increasing from 783 to 1479 at 0.5 T. This paper shows how heat treatments commonly applied to hypoeutectoid cast steels, to improve their mechanical performance, can be used to also enhance electromagnetic properties of these alloys. The use of cast steels allows the creation of DC components for electrical machines not possible by the widely used method of stacking of electrical grade sheet steels. - Highlights: • A range of structural steels had their

Controlling DC permeability in cast steels

International Nuclear Information System (INIS)

Sumner, Aaran; Gerada, Chris; Brown, Neil; Clare, Adam

2017-01-01

Annealing (at multiple cooling rates) and quenching (with tempering) was performed on specimens of cast steel of varying composition. The aim was to devise a method for selecting the steel with the highest permeability, from any given range of steels, and then increasing the permeability by heat treatment. Metallographic samples were imaged using optical microscopy to show the effect of the applied heat treatments on the microstructure. Commonly cast steels can have DC permeability altered by the careful selection of a heat treatment. Increases of up to 381% were achieved by annealing using a cooling rate of 6.0 °C/min. Annealing was found to cause the carbon present in the steel to migrate from grain boundaries and from within ferrite crystals into adjacent pearlite crystals. The migration of the carbon resulted in less carbon at grain boundaries and within ferrite crystals reducing the number of pinning sites between magnetic domains. This gives rise to a higher permeability. Quenching then tempering was found to cause the formation of small ferrite crystals with the carbon content of the steel predominately held in the martensitic crystal structures. The results show that with any given range of steel compositions the highest baseline DC permeability will be found with the steel that has the highest iron content and the lowest carbon content. For the samples tested in this paper a cooling rate of 4.5 °C/min resulted in the relative permeability of the sample with the highest baseline permeability, AS4, increasing from 783 to 1479 at 0.5 T. This paper shows how heat treatments commonly applied to hypoeutectoid cast steels, to improve their mechanical performance, can be used to also enhance electromagnetic properties of these alloys. The use of cast steels allows the creation of DC components for electrical machines not possible by the widely used method of stacking of electrical grade sheet steels. - Highlights: • A range of structural steels had their

Using PBL to Improve Educational Outcomes and Student Satisfaction in the Teaching of DC/DC and DC/AC Converters

Science.gov (United States)

Martinez-Rodrigo, Fernando; Herrero-De Lucas, Luis Carlos; de Pablo, Santiago; Rey-Boue, Alexis B.

2017-01-01

This paper examines the question of how to use project-based learning to increase student performance and satisfaction in a power electronics course addressing the topics of dc/dc and dc/ac converters, the assembly of a dc/dc converter, and the use of a commercial speed drive. A detailed presentation of the methodology is shown, and the results…

Improved Control Strategy for T-type Isolated DC/DC Converters

DEFF Research Database (Denmark)

Liu, Dong; Deng, Fujin; Wang, Yanbo

2017-01-01

T-type isolated DC/DC converters have recently attracted attention due to their numerous advantages, including few components, low cost, and symmetrical operation of transformers. This study proposes an improved control strategy for increasing the efficiency of T-type isolated DC/DC converters....... Under the proposed strategy, the primary circulating current flows through the auxiliary switches (metal–oxide–semiconductor field-effect transistors) instead of their body diodes in free-wheeling periods. Such feature can reduce conduction losses, thereby improving the efficiency of T-type isolated DC...

Selective DNA-Mediated Assembly of Gold Nanoparticles on Electroded Substrates

Science.gov (United States)

2008-06-01

might use the Watson - Crick base-pairing of DNA as a means for ultrahigh-precision engineering is well- known.5,6 The idea is to use the highly specific...Selective DNA -Mediated Assembly of Gold Nanoparticles on Electroded Substrates K. E. Sapsford,†,‡,∇ D. Park,§ E. R. Goldman,‡ E. E. Foos,| S. A...electrodes via DNA hybridization. Protocols are demonstrated for maximizing selectivity and coverage using 15mers as the active binding agents. Detailed

The role of autophagy in chloroplast degradation and chlorophagy in immune defenses during Pst DC3000 (AvrRps4 infection.

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Junjian Dong

Full Text Available BACKGROUND: Chlorosis of leaf tissue normally observed during pathogen infection may result from the degradation of chloroplasts. There is a growing evidence to suggest that the chloroplast plays a significant role during pathogen infection. Although most degradation of the organelles and cellular structures in plants is mediated by autophagy, its role in chloroplast catabolism during pathogen infection is largely unknown. RESULTS: In this study, we investigated the function of autophagy in chloroplast degradation during avirulent Pst DC3000 (AvrRps4 infection. We examined the expression of defensive marker genes and suppression of bacterial growth using the electrolyte leakage assay in normal light (N and low light (L growing environments of wild-type and atg5-1 plants during pathogen treatment. Stroma-targeted GFP proteins (CT-GFP were observed with LysoTracker Red (LTR staining of autophagosome-like structures in the vacuole. The results showed that Arabidopsis expressed a significant number of small GFP-labeled bodies when infected with avirulent Pst DC3000 (AvrRps4. While barely detectable, there were small GFP-labeled bodies in plants with the CT-GFP expressing atg5-1 mutation. The results showed that chloroplast degradation depends on autophagy and this may play an important role in inhibiting pathogen growth. CONCLUSION: Autophagy plays a role in chloroplast degradation in Arabidopsis during avirulent Pst DC3000 (AvrRps4 infection. Autophagy dependent chloroplast degradation may be the primary source of reactive oxygen species (ROS as well as the pathogen-response signaling molecules that induce the defense response.

DHA suppresses Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages.

Science.gov (United States)

Choi, Eun-Young; Jin, Ji-Young; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

2014-04-14

Several reports have indicated that dietary intake of DHA is associated with lower prevalence of periodontitis. In the present study, we investigated the effect of DHA on the production of proinflammatory mediators in murine macrophage-like RAW264.7 cells stimulated with lipopolysaccharide (LPS) isolated from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. LPS was isolated from lyophilised P. intermedia ATCC 25,611 cells using the standard hot-phenol-water protocol. Culture supernatants were collected and assayed for NO, IL-1β and IL-6. Real-time PCR analysis was carried out to detect the expression of inducible NO synthase (iNOS), IL-1β, IL-6 and haeme oxygenase-1 (HO-1) mRNA. Immunoblot analysis was carried out to quantify the expression of iNOS and HO-1 protein and concentrations of signalling proteins. DNA-binding activities of NF-κB subunits were determined using an ELISA-based assay kit. DHA significantly attenuated the production of NO, IL-1β and IL-6 at both gene transcription and translation levels in P. intermedia LPS-activated RAW264.7 cells. DHA induced the expression of HO-1 in cells treated with P. intermedia LPS. Selective inhibition of HO-1 activity by tin protoporphyrin IX significantly mitigated the inhibitory effects of DHA on LPS-induced NO production. DHA significantly attenuated the phosphorylation of c-Jun N-terminal kinase induced by LPS. In addition, DHA suppressed the transcriptional activity of NF-κB by regulating the nuclear translocation and DNA-binding activity of NF-κB p50 subunit and inhibited the phosphorylation of signal transducer and activator of transcription 1. Further in vivo studies are needed to better evaluate the potential of DHA in humans as a therapeutic agent to treat periodontal disease.

An Integrated Multifunctional Bidirectional AC/DC and DC/DC Converter for Electric Vehicles Applications

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Liwen Pan

2016-06-01

Full Text Available This paper presents an on-board vehicular battery charger that integrates bidirectional AC/DC converter and DC/DC converter to achieve high power density for application in electric vehicles (EVs. The integrated charger is able to transfer electrical energy between the battery pack and the electric traction system and to function as an AC/DC battery charger. The integrated charger topology is presented and the design of passive components is discussed. The control schemes are developed for motor drive system and battery-charging system with a power pulsation reduction circuit. Simulation results in MATLAB/Simulink and experiments on a 30-kW motor drive and 3.3-kW AC/DC charging prototype validate the performance of the proposed technology. In addition, power losses, efficiency comparison and thermal stress for the integrated charger are illustrated. The results of the analyses show the validity of the advanced integrated charger for electric vehicles.

β3-adrenoceptor mediates β3-selective agonist-induced effects on ...

African Journals Online (AJOL)

β3-adrenoceptor mediates β3-selective agonist-induced effects on energy expenditure, insulin secrtion and food ... Journal of the Ghana Science Association ... is usually associated with obesity, also involves defective energy expenditure, ...

Two photon microscopy intravital study of DC-mediated anti-tumor response of NK cells

Science.gov (United States)

Caccia, Michele; Gorletta, Tatiana; Sironi, Laura; Zanoni, Ivan; Salvetti, Cristina; Collini, Maddalena; Granucci, Francesca; Chirico, Giuseppe

2010-02-01

Recent studies have demonstrated that dendritic cells (DCs) play a crucial role in the activation of Natural Killer cells (NKs) that are responsible for anti-tumor innate immune responses. The focus of this report is on the role of pathogen associated molecular pattern (PAMP) activated-DCs in inducing NK cell-mediated anti-tumor responses. Mice transplanted sub-cute (s.c.) with AK7 cells, a mesothelioma cell line sensitive to NK cell responses, are injected with fluorescent NK cells and DC activation is then induced by s.c. injection of Lipopolysaccharide (LPS). Using 4 dimensional tracking we follow the kinetic behavior of NK cells at the Draining Lymph-Node (DLN). As control, noninflammatory conditions are also evaluated. Our data suggest that NK cells are recruited to the DLN where they can interact with activated-DCs with a peculiar kinetic behavior: short lived interactions interleaved by rarer longer ones. We also found that the changes in the NK dynamic behavior in inflammatory conditions clearly affect relevant motility parameters such as the instantaneous and average velocity and the effective diffusion coefficient. This observation suggests that NK cells and activated-DCs might efficiently interact in the DLN, where cells could be activated. Therefore the interaction between activated-DCs and NK cells in DLN is not only a reality but it may be also crucial for the start of the immune response of the NKs.

Selected Food Consumption Mediates the Association between Education Level and Metabolic Syndrome in Korean Adults.

Science.gov (United States)

Kim, Oh Yoen; Kwak, So-Young; Kim, Boeun; Kim, Young-Sun; Kim, Hye Young; Shin, Min-Jeong

2017-01-01

Low socioeconomic status (SES) is linked to higher incidence/mortality of cardiovascular disease, but emerging evidence inconsistently reported that education level, a proxy for SES, is related to cardiovascular risk and metabolic syndrome (MetS) in Koreans. Furthermore, limited information is available on whether dietary components would mediate the relationship between education level and cardiovascular risk. We hypothesized that selected food consumption mediates the association between education level and MetS prevalence. Data from the Korea National Health and Nutritional Examination Survey (2008-2011) were included in cross-sectional analyses (n = 11,029, 30-64 years). The possible mediating effect of selected food groups (fruits, raw vegetables, red meat, milk, and soft drinks) on the association between education level and MetS was tested using a multiple mediation model. Education level was negatively associated with MetS prevalence. The association between lower education level and higher MetS prevalence was partially mediated by selected food consumption (lower intakes of fruit, red meat and milk; higher intakes of vegetable and soft drink) after adjusted for covariates. Gender also modified the association between education level and MetS prevalence that was more prominent in women than in men. Selected food consumption substantially contributes to the association between education level and MetS in Korean adults, especially among women. © 2017 S. Karger AG, Basel.

RESONANT STEP-DOWN DC-DC POWER CONVERTERS

DEFF Research Database (Denmark)

2015-01-01

The present invention relates to a resonant step-down DC-DC power converter which comprises a primary side circuit and a secondary side circuit coupled through a galvanic isolation barrier. The primary side circuit comprises a positive and a negative input terminal for receipt of an input voltage...... charged from the input voltage and discharged to the output capacitor through the galvanic isolation barrier by a semiconductor switch arrangement in accordance with a switch control signal to produce the converter output voltage. The resonant step-down DC-DC power converter comprises an electrical short......-circuit connection across the galvanic isolation barrier connecting, in a first case, the second negative electrode of the output capacitor to the positive input terminal of the primary side circuit or, in a second case, connecting the second positive electrode of the output capacitor to the negative input terminal...

Mechanism of acetylcholine receptor cluster formation induced by DC electric field.

Directory of Open Access Journals (Sweden)

Hailong Luke Zhang

Full Text Available BACKGROUND: The formation of acetylcholine receptor (AChR cluster is a key event during the development of the neuromuscular junction. It is induced through the activation of muscle-specific kinase (MuSK by the heparan-sulfate proteoglycan agrin released from the motor axon. On the other hand, DC electric field, a non-neuronal stimulus, is also highly effective in causing AChRs to cluster along the cathode-facing edge of muscle cells. METHODOLOGY/PRINCIPAL FINDINGS: To understand its molecular mechanism, quantum dots (QDs were used to follow the movement of AChRs as they became clustered under the influence of electric field. From analyses of trajectories of AChR movement in the membrane, it was concluded that diffuse receptors underwent Brownian motion until they were immobilized at sites of cluster formation. This supports the diffusion-mediated trapping model in explaining AChR clustering under the influence of this stimulus. Disrupting F-actin cytoskeleton assembly and interfering with rapsyn-AChR interaction suppressed this phenomenon, suggesting that these are integral components of the trapping mechanism induced by the electric field. Consistent with the idea that signaling pathways are activated by this stimulus, the localization of tyrosine-phosphorylated forms of AChR β-subunit and Src was observed at cathodal AChR clusters. Furthermore, disrupting MuSK activity through the expression of a kinase-dead form of this enzyme abolished electric field-induced AChR clustering. CONCLUSIONS: These results suggest that DC electric field as a physical stimulus elicits molecular reactions in muscle cells in the form of cathodal MuSK activation in a ligand-free manner to trigger a signaling pathway that leads to cytoskeletal assembly and AChR clustering.

Atmel Microcontroller Based Soft Switched PWM ZVS Full Bridge DC to DC Converter

Directory of Open Access Journals (Sweden)

DEEPAK KUMAR NAYAK

2010-12-01

Full Text Available This paper deals with the simulation and implementation of soft switched PWM ZVS full bridge DC to DC converter. The 48V DC is efficiently reduced to 12V DC using a DC to DC converter. This converter has advantages like reduced switching losses, stresses and EMI. Input DC is converted into high frequency AC and it is stepped down to 12V level. Later it is rectified using a full wave rectifier. Laboratory model of microcontroller based DC to DC converter is fabricated and tested. The experimental results are compared with the simulation results.

Quasi-Z-Source Half-Bridge DC-DC Converter for Photovoltaic Applications

OpenAIRE

Vinnikov, D; Chub, A; Husev, O; Zaķis, J

2015-01-01

This paper presents a novel quasi-Z-source halfbridge galvanically isolated DC-DC converter intended for the photovoltaic applications. The topology could be envisioned as an alternative to the boost half-bridge DC-DC converter but the benefit of its symmetric structure reduces the threat of transformer saturation due to the dc flux. The proposed converter features the continuous input current and could be used either with one or two input voltage sources.

High sintering resistance of size-selected platinum cluster catalysts by suppressed ostwald ripening

DEFF Research Database (Denmark)

Wettergren, Kristina; Schweinberger, Florian F.; Deiana, Davide

2014-01-01

on different supports exhibit remarkable intrinsic sintering resistance even under reaction conditions. The observed stability is related to suppression of Ostwald ripening by elimination of its main driving force via size-selection. This study thus constitutes a general blueprint for the rational design...... of sintering resistant catalyst systems and for efficient experimental strategies to determine sintering mechanisms. Moreover, this is the first systematic experimental investigation of sintering processes in nanoparticle systems with an initially perfectly monomodal size distribution under ambient conditions....

DC motor operation controlled from a DC/DC power converter in pulse mode with low duty cycle

OpenAIRE

Stefanov, Goce; Kukuseva, Maja; Citkuseva Dimitrovska, Biljana

2016-01-01

In this paper pulse mode of operation of DC motor controlled by DC/DC power converter is analyzed. DC motor operation with time intervals in which the motor operates without output load is of interest. In this mode it is possible the motor to restore energy. Also, in the paper are represented calculations for the amount of the restored energy in the pulse mode operation of the motor for different duty cycles.

A crucial role of activin A-mediated growth hormone suppression in mouse and human heart failure.

Directory of Open Access Journals (Sweden)

Noritoshi Fukushima

Full Text Available Infusion of bone marrow-derived mononuclear cells (BMMNC has been reported to ameliorate cardiac dysfunction after acute myocardial infarction. In this study, we investigated whether infusion of BMMNC is also effective for non-ischemic heart failure model mice and the underlying mechanisms. Intravenous infusion of BMMNC showed transient cardioprotective effects on animal models with dilated cardiomyopathy (DCM without their engraftment in heart, suggesting that BMMNC infusion improves cardiac function via humoral factors rather than their differentiation into cardiomyocytes. Using conditioned media from sorted BMMNC, we found that the cardioprotective effects were mediated by growth hormone (GH secreted from myeloid (Gr-1(+ cells and the effects was partially mediated by signal transducer and activator of transcription 3 in cardiomyocytes. On the other hand, the GH expression in Gr-1(+ cells was significantly downregulated in DCM mice compared with that in healthy control, suggesting that the environmental cue in heart failure might suppress the Gr-1(+ cells function. Activin A was upregulated in the serum of DCM models and induced downregulation of GH levels in Gr-1(+ cells and serum. Furthermore, humoral factors upregulated in heart failure including angiotensin II upregulated activin A in peripheral blood mononuclear cells (PBMNC via activation of NFκB. Similarly, serum activin A levels were also significantly higher in DCM patients with heart failure than in healthy subjects and the GH levels in conditioned medium from PBMNC of DCM patients were lower than that in healthy subjects. Inhibition of activin A increased serum GH levels and improved cardiac function of DCM model mice. These results suggest that activin A causes heart failure by suppressing GH activity and that inhibition of activin A might become a novel strategy for the treatment of heart failure.

Performance evaluation of directly photovoltaic powered DC PM (direct current permanent magnet) motor – propeller thrust system

International Nuclear Information System (INIS)

Atlam, Ozcan; Kolhe, Mohan

2013-01-01

Photovoltaic (PV) powered directly coupled electro-mechanical system has wide applications (e.g. PV powered cooling fans in green houses, PV water pumping system, solar vehicles). The objective of this work is to analyse the operation of directly PV powered DC PM (direct current permanent magnet) motor – propeller system for selection of motor parameters. The performance of such system mainly depends on the incident solar radiation, operating cell temperature, DC motor and propeller load parameters. It is observed that the operating points of the PV DC PM motor – propeller system matches very closely with the maximum power points (MPPs) of the PV array, if the DC PM motor – propeller parameters have been properly selected. It is found that for a specific application of such type of system, matching of torque–speed operating points with respect to the maximum power points of PV array are very important. It is ascertained through results that the DC PM motor's armature resistance, magnetic field constant, starting current to overcome the starting torque and torque coefficient are the main parameters. In designing a PV powered DC PM motor for a specific application, selection of these parameters are important for maximum utilization of the PV array output. The results of this system are useful for designing of directly PV powered DC PM motor's for aerodynamic applications. - Highlights: • We analyse the performance of directly PV powered DC PM motor – propeller system. • We examine PV electro-mechanical system for selection of DC motor parameters. • Matching of torque–speed curve to maximum power points of PV array is important

Hypericin-mediated selective photomodification of connective tissues

International Nuclear Information System (INIS)

Hovhannisyan, V.; Guo, H. W.; Chen, Y. F.; Hovhannisyan, A.; Ghukasyan, V.; Dong, C. Y.

2014-01-01

Controllable modification of biological molecules and supramolecular components of connective tissue are important for biophysical and biomedical applications. Through the use of second harmonic generation imaging, two-photon fluorescence microscopy, and spectrofluorimetry, we found that hypericin, a natural pigment, induces photosensitized destruction of collagen fibers but does not affect elastic fibers and lipids in chicken tendon, skin, and blood vessels. We demonstrated the dynamics and efficiency of collagen photomodification and investigated mechanisms of this processes. Our results suggest that hypericin–mediated photoprocesses in biological tissues may be useful in biomedical applications that require selective modification of connective tissues

Hypericin-mediated selective photomodification of connective tissues

Energy Technology Data Exchange (ETDEWEB)

Hovhannisyan, V., E-mail: hovv@phys.ntu.edu.tw; Guo, H. W.; Chen, Y. F., E-mail: yfchen@phys.ntu.edu.tw [Department of Physics, National Taiwan University, Taipei 106, Taiwan (China); Hovhannisyan, A. [Multimedia and Programming, European Regional Education Academy, Yerevan 0037 (Armenia); Ghukasyan, V. [Neuroscience Center, University of North Carolina at Chapel Hill, North Carolina 27514 (United States); Dong, C. Y., E-mail: cydong@phys.ntu.edu.tw [Department of Physics, National Taiwan University, Taipei 106, Taiwan (China); Center for Quantum Science and Engineering, National Taiwan University, Taipei 106, Taiwan (China)

2014-12-29

Controllable modification of biological molecules and supramolecular components of connective tissue are important for biophysical and biomedical applications. Through the use of second harmonic generation imaging, two-photon fluorescence microscopy, and spectrofluorimetry, we found that hypericin, a natural pigment, induces photosensitized destruction of collagen fibers but does not affect elastic fibers and lipids in chicken tendon, skin, and blood vessels. We demonstrated the dynamics and efficiency of collagen photomodification and investigated mechanisms of this processes. Our results suggest that hypericin–mediated photoprocesses in biological tissues may be useful in biomedical applications that require selective modification of connective tissues.

Control of the DC-DC Converter used into Energy Generation System

International Nuclear Information System (INIS)

Bizon, Nicu; Oproescu, Mihai

2006-01-01

This paper presents an investigation of the DC-DC Converter controller used into Energy Generation System. The full bridge is used into an Energy Generation System (EGS) as second power interface between the energy source and the high DC bus. The simulation results show that the DC-DC Converter behavior can be improved using a well designed PI control surface. The used Simulink models for the EGS blocks and some design considerations are presented, too. (authors)

Myeloid-derived suppressor cells mediate immune suppression in spinal cord injury.

Science.gov (United States)

Wang, Lei; Yu, Wei-bo; Tao, Lian-yuan; Xu, Qing

2016-01-15

Spinal cord injury (SCI) is characterized by the loss of motor and sensory functions in areas below the level of the lesion and numerous accompanying deficits. Previous studies have suggested that myeloid-derived suppressor cell (MDSC)-induced immune depression may play a pivotal role in the course of SCI. However, the concrete mechanism of these changes regarding immune suppression remains unknown. Here, we created an SCI mouse model to gain further evidence regarding the relationship between MDSCs following SCI and T lymphocyte suppression. We showed that in the SCI mouse model, the expanding MDSCs have the capacity to suppress T cell proliferation, and this suppression could be reversed by blocking the arginase. Copyright © 2015 Elsevier B.V. All rights reserved.

Wind-driven SEIG supplying DC microgrid through a single-stage power converter

Directory of Open Access Journals (Sweden)

Vellapatchi Nayanar

2016-09-01

Full Text Available Nowadays, there is an increased emphasis on utilizing the renewable energy sources and selection of suitable power converters for supplying dc microgrid. Among the various renewable energy sources, wind energy stands first in terms of installed capacity. So, an attempt is made in this paper for supplying dc microgrid utilizing wind energy. A self-excited induction generator has been used in the proposed wind energy conversion system (WECS. A single-stage power converter, namely, semi-converter is connected between the SEIG and dc grid terminals for closed-loop control of the proposed system. A perturb and observe (P&O based maximum power point tracking (MPPT algorithm has been developed and implemented using a dsPIC30F4011 digital controller. In this MPPT algorithm, the firing angle of the converter is adjusted by continuously monitoring the dc grid current for a given wind velocity. For analyzing the proposed system, a MATLAB/Simulink model has been developed by selecting the various components starting from wind-turbine model to the power converter supplying dc microgrid. Successful working of the proposed WECS has also been shown through experimental results obtained on a prototype model developed in the laboratory.

Different efficiency of UmuDC and MucAB proteins in UV light induced mutagenesis in Escherichia coli

International Nuclear Information System (INIS)

Blanco, M.; Herrera, G.; Aleixandre, V.

1986-01-01

Two multicopy plasmids carrying either the umuDC or the mucAB operon were used to compare the efficiency of UmuDC and MucAB proteins in UV mutagenesis of Escherichia coli K12. It was found that in recA + uvr + bacteria, plasmid pIC80, mucAB + mediated UV mutagenesis more efficiently than did plasmid pSE 117, umuDC + . A similar result was obtained in lex A51(Def) cells, excluding the possibility that this was due to a differential regulation by LexA of the umuDC and mucAB operons. We conclude that some structural characteristic of the UmuDC and MucAB proteins determines their different efficiency in UV mutagenesis. This characteristic could be also responsible for the observation that in the recA430 mutant, pIC80 but no pSE117 can mediate UV mutagenesis. In the recAS142 mutant pIC80 also promoted UV mutagenesis more efficiently than pSE117. In this mutant, the recombination proficiency, the protease activity toward LexA and the mutation frequency were increased by the presence of adenine in the medium. In recA + uvrB5 bacteria, plasmid pSE117, umuDC caused both an increase in UV sensitivity as well as a reduction in the mutation frequency. These negative effects resulting from the overproduction of UmuDC proteins were higher in recA142 uvrB5 than in recA + uvrB5 cells. In contrast, overproduction of MucAB proteins in excision-deficient bacteria containing pIC80 led to a large increase in the mutation frequency. We suggest that the functional differences between UmuDC and MucAB proteins might be due to their different dependence on the direct role of RecA protease in UV mutagenesis. (orig.)

Mechanisms of RhoGDI2 Mediated Lung Cancer Epithelial-Mesenchymal Transition Suppression

Directory of Open Access Journals (Sweden)

Huiyan Niu

2014-11-01

Full Text Available Background: The aim of this study was to evaluate the function of RhoGDI2 in lung cancer epithelial-mesenchymal transition (EMT process and to illustrate the underlying mechanisms that will lead to improvement of lung cancer treatment. Methods: The RhoGDI2 knock-down and overexpressing A549 cell lines were first constructed. The influence of RhoGDI2 on cytoskeleton in A549 cells was studied using two approaches: G-LISA-based Rac1 activity measurement and immunostaining-based F-actin distribution. The expression levels of key EMT genes were analyzed using real time quantitative polymerase chain reaction (RT-qPCR, western blot and immunostaining in untreated and RhoGDI2 knock-down or overexpressing A549 cells in both in vivo and in vitro experimental settings. Results: Our study showed that the activity of Rac1, a key gene that is crucial for the initiation and metastasis of human lung adenocarcinoma, causing the redistribution of F-actin with partial loss of cell-cell adhesions and stress fibers, was significantly suppressed by RhoGDI2. RhoGDI2 promoted the expression of EMT marker gene E-cadherin and repressed EMT promoting genes Slug, Snail, α-SMA in both A549 cells and lung and liver organs derived from the mouse models. Knocking-down RhoGDI2 induced abnormal morphology for lung organs. Conclusion: These findings indicate that RhoGDI2 repressed the activity of Rac1 and may be involved in the rearrangement of cytoskeleton in lung cancer cells. RhoGDI2 suppresses the metastasis of lung cancer mediated through EMT by regulating the expression of key genes such as E-cadherin, Slug, Snail and α-SMA in both in vivo and in vitro models.

Antigen-driven C–C Chemokine-mediated HIV-1 Suppression by CD4+ T Cells from Exposed Uninfected Individuals Expressing the Wild-type CCR-5 Allele

Science.gov (United States)

Furci, Lucinda; Scarlatti, Gabriella; Burastero, Samuele; Tambussi, Giuseppe; Colognesi, Claudia; Quillent, Caroline; Longhi, Renato; Loverro, Patrizia; Borgonovo, Barbara; Gaffi, Davide; Carrow, Emily; Malnati, Mauro; Lusso, Paolo; Siccardi, Antonio G.; Lazzarin, Adriano; Beretta, Alberto

1997-01-01

Despite repeated exposure to HIV-1, certain individuals remain persistently uninfected. Such exposed uninfected (EU) people show evidence of HIV-1–specific T cell immunity and, in rare cases, selective resistance to infection by macrophage-tropic strains of HIV-1. The latter has been associated with a 32–base pair deletion in the C–C chemokine receptor gene CCR-5, the major coreceptor of macrophage-tropic strains of HIV-1. We have undertaken an analysis of the HIV-specific T cell responses in 12 EU individuals who were either homozygous for the wild-type CCR-5 allele or heterozygous for the deletion allele (CCR-5Δ32). We have found evidence of an oligoclonal T cell response mediated by helper T cells specific for a conserved region of the HIV-1 envelope. These cells produce very high levels of C–C chemokines when stimulated by the specific antigen and suppress selectively the replication of macrophage-tropic, but not T cell–tropic, strains of HIV-1. These chemokine-producing helper cells may be part of a protective immune response that could be potentially exploited for vaccine development. PMID:9236198

Regulatory Eosinophils Suppress T Cells Partly through Galectin-10.

Science.gov (United States)

Lingblom, Christine; Andersson, Jennie; Andersson, Kerstin; Wennerås, Christine

2017-06-15

Eosinophils have the capacity to regulate the function of T cell subsets. Our aim was to test the hypothesis of the existence of a regulatory subset of eosinophils. Human eosinophils were incubated with T cells that were stimulated with allogeneic leukocytes or CD3/CD28 cross-linking. After 2 d of coculture, 11% of the eosinophils gained CD16 expression. A CD16 hi subset of eosinophils, encompassing 1-5% of all eosinophils, was also identified in the blood of healthy subjects. FACS sorting showed that these CD16 hi eosinophils were significantly stronger suppressors of T cell proliferation than were conventional CD16 neg eosinophils. Human eosinophils contain stores of the immunoregulatory protein galectin-10. We found that Ab-mediated neutralization of galectin-10 partially abrogated the suppressive function of the eosinophils. Moreover, recombinant galectin-10 by itself was able to suppress T cell proliferation. Finally, we detected galectin-10-containing immune synapses between eosinophils and lymphocytes. To conclude, we describe a subset of suppressive eosinophils expressing CD16 that may escape detection because CD16-based negative selection is the standard procedure for the isolation of human eosinophils. Moreover, we show that galectin-10 functions as a T cell-suppressive molecule in eosinophils. Copyright © 2017 by The American Association of Immunologists, Inc.

Novel composite resonance DC-DC converter with voltage doubler rectifier

OpenAIRE

Kato, Hisatsugu; Matsuo, Hirohumi; Eguchi, Masaki; Sakamoto, Yukitaka; Nakaishi, Masaki

2009-01-01

This paper deals with a novel composite resonance DC-DC converter with the voltage doubler rectifier, which is developed to be applied to the power conditioner of the photovoltaic generation system. The proposed DC-DC converter has the current and voltage resonance functions. Therefore, the output voltage regulation can be achieved for the large variations of the input voltage and load. Also, this converter has the high power efficiency. The maximum power efficiency 96.1% can be realized.

Ultra-high Efficiency DC-DC Converter using GaN Devices

DEFF Research Database (Denmark)

Ramachandran, Rakesh

2016-01-01

properties of GaN devices can be utilized in power converters to make them more compact and highly efficient. This thesis entitled “Ultra-high Efficiency DC-DC Converter using GaN devices” focuses on achieving ultra-high conversion efficiency in an isolated dc-dc converter by the optimal utilization of Ga...... for many decades. However, the rate of improvement slowed as the silicon power materials asymptotically approached its theoretical bounds. Compared to Si, wideband gap materials such as Silicon Carbide (SiC) and Gallium Nitride (GaN) are promising semiconductors for power devices due to their superior...... in this thesis. Efficiency measurements from the hardware prototype of both the topologies are also presented in this thesis. Finally, the bidirectional operation of an optimized isolated dc-dc converter is presented. The optimized converter has achieved an ultra-high efficiency of 98.8% in both directions...

75 FR 61352 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-10-30, DC-10-30F, DC-10-30F (KC...

Science.gov (United States)

2010-10-05

... Airworthiness Directives; McDonnell Douglas Corporation Model DC- 10-30, DC-10-30F, DC-10-30F (KC-10A and KDC-10...-13 McDonnell Douglas Corporation: Amendment 39-16448; Docket No. FAA-2010-0553; Directorate.... Applicability (c) This AD applies to McDonnell Douglas Corporation Model DC- 10-30, DC-10-30F, DC-10-30F (KC-10A...

Sitagliptin, An Anti-diabetic Drug, Suppresses Estrogen Deficiency-Induced OsteoporosisIn Vivo and Inhibits RANKL-Induced Osteoclast Formation and Bone Resorption In Vitro

Directory of Open Access Journals (Sweden)

Chuandong Wang

2017-06-01

Full Text Available Postmenopausal osteoporosis is a disease characterized by excessive osteoclastic bone resorption. Some anti-diabetic drugs were demonstrated for anti-osteoclastic bone-loss effects. The present study investigated the skeletal effects of chronic administration of sitagliptin, a dipeptidyl peptidase IV (DPP IV inhibitor that is increasingly used for type 2 diabetes treatments, in an estrogen deficiency-induced osteoporosis and elucidated the associated mechanisms. This study indicated that sitagliptin effectively prevented ovariectomy-induced bone loss and reduced osteoclast numbers in vivo. It was also indicated that sitagliptin suppressed receptor activator of nuclear factor-κB ligand (RANKL-mediated osteoclast differentiation, bone resorption, and F-actin ring formation in a manner of dose-dependence. In addition, sitagliptin significantly reduced the expression of osteoclast-specific markers in mouse bone-marrow-derived macrophages, including calcitonin receptor (Calcr, dendrite cell-specific transmembrane protein (Dc-stamp, c-Fos, and nuclear factor of activated T-cells cytoplasmic 1 (Nfatc1. Further study indicated that sitagliptin inhibited osteoclastogenesis by suppressing AKT and ERK signaling pathways, scavenging ROS activity, and suppressing the Ca2+ oscillation that consequently affects the expression and/or activity of the osteoclast-specific transcription factors, c-Fos and NFATc1. Collectively, these findings suggest that sitagliptin possesses beneficial effects on bone and the suppression of osteoclast number implies that the effect is exerted directly on osteoclastogenesis.

Antibody-mediated suppression of grafted lymphoma. III. Evaluation of the role of thymic function, non-thymus-derived lymphocytes, macrophages, platelets, and polymorphonuclear leukocytes in syngeneic and allogeneic hosts

International Nuclear Information System (INIS)

Shin, H.S.; Hayden, M.; Langley, S.; Kaliss, N.; Smith, M.R.

1975-01-01

Syngeneic or allogeneic mice pretreated with sublethal whole-body irradiation were rendered incapable of suppressing the growth of grafted tumor cells sensitized with alloantibody. The growth of sensitized tumor cells was suppressed when they were mixed with donor effector cells from mice syngeneic or allogeneic to the recipients and then were inoculated in irradiated recipients. Three donor-host combinations were used to study the suppression of the murine lymphoma 6C3HED indigenous to C3H mice. These were C3H donor cells in C3H recipients, C57BL/6 donor cells in C3H recipients, or C57BL/6 donor cells in C57BL/6 recipients. In all three combinations, macrophages obtained from an inflammatory exudate, exudate lymphocytes not bearing theta antigen, and platelets were, in descending order of effectiveness, consistently active in restoring antibody-mediated suppression of tumor growth in irradiated hosts. Prior irradiation of the transferred lymphocytes somewhat diminished their effectiveness. Freeze-thawed or heat-killed macrophages (but not freeze-thawed platelets or lymphocytes) were effective in restoration. Peripheral blood mononuclear leukocytes and splenic lymphoid cells were not active in the recipients syngeneic to the donor cells but were active in recipients allogeneic to the donor cells. Polymorphonuclear leukocytes isolated from peripheral blood or an inflammatory exudate were not active. Intact thymic function seems unimportant since antibody-mediated suppression took place as effectively in thymectomized mice as in normal controls. (U.S.)

Sliding-Mode Control of a Charger/Discharger DC/DC Converter for DC-Bus Regulation in Renewable Power Systems

Directory of Open Access Journals (Sweden)

Sergio Ignacio Serna-Garcés

2016-03-01

Full Text Available Stand-alone power systems based on renewable energy sources are used to replace generators based on fossil fuels. Those renewable power systems also require Energy Storage Devices (ESD interfaced by a charger/discharger power converter, which consist of a bidirectional DC/DC converter, and a DC bus. This paper proposes a single sliding-mode controller (SMC for the charger/discharger DC/DC converter to provide a stable DC bus voltage in any operation condition: charging or discharging the ESD, or even without any power exchange between the ESD and the DC bus. Due to the non-linear nature of the power converter, the SMC parameters are adapted on-line to ensure global stability in any operation condition. Such stability of the adaptive SMC is mathematically demonstrated using analytical expressions for the transversality, reachability and equivalent control conditions. Moreover, a design procedure for the adaptive SMC parameters is provided in order to ensure the dynamic response required for the correct operation of the load. Finally, simulations and experimental tests validate the proposed controller and design procedure.

Xanomeline suppresses excessive pro-inflammatory cytokine responses through neural signal-mediated pathways and improves survival in lethal inflammation

Science.gov (United States)

Rosas-Ballina, Mauricio; Ferrer, Sergio Valdés; Dancho, Meghan; Ochani, Mahendar; Katz, David; Cheng, Kai Fan; Olofsson, Peder S.; Chavan, Sangeeta S.; Al-Abed, Yousef; Tracey, Kevin J.; Pavlov, Valentin A.

2014-01-01

Inflammatory conditions characterized by excessive immune cell activation and cytokine release, are associated with bidirectional immune system-brain communication, underlying sickness behavior and other physiological responses. The vagus nerve has an important role in this communication by conveying sensory information to the brain, and brain-derived immunoregulatory signals that suppress peripheral cytokine levels and inflammation. Brain muscarinic acetylcholine receptor (mAChR)-mediated cholinergic signaling has been implicated in this regulation. However, the possibility of controlling inflammation by peripheral administration of centrally-acting mAChR agonists is unexplored. To provide insight we used the centrally-acting M1 mAChR agonist xanomeline, previously developed in the context of Alzheimer’s disease and schizophrenia. Intraperitoneal administration of xanomeline significantly suppressed serum and splenic TNF levels, alleviated sickness behavior, and increased survival during lethal murine endotoxemia. The anti-inflammatory effects of xanomeline were brain mAChR-mediated and required intact vagus nerve and splenic nerve signaling. The anti-inflammatory efficacy of xanomeline was retained for at least 20h, associated with alterations in splenic lymphocyte, and dendritic cell proportions, and decreased splenocyte responsiveness to endotoxin. These results highlight an important role of the M1 mAChR in a neural circuitry to spleen in which brain cholinergic activation lowers peripheral pro-inflammatory cytokines to levels favoring survival. The therapeutic efficacy of xanomeline was also manifested by significantly improved survival in preclinical settings of severe sepsis. These findings are of interest for strategizing novel therapeutic approaches in inflammatory diseases. PMID:25063706

Design and Analysis of Two-Phase Boost DC-DC Converter

OpenAIRE

Taufik Taufik; Tadeus Gunawan; Dale Dolan; Makbul Anwari

2010-01-01

Multiphasing of dc-dc converters has been known to give technical and economical benefits to low voltage high power buck regulator modules. A major advantage of multiphasing dc-dc converters is the improvement of input and output performances in the buck converter. From this aspect, a potential use would be in renewable energy where power quality plays an important factor. This paper presents the design of a 2-phase 200W boost converter for battery charging application. Analysis of results fr...

SCM Handbooks for dc-to-dc Converters

Science.gov (United States)

Lee, F.; Mohmoud, M.; Yu, Y.

1984-01-01

Two documents aid in design of control modules for dc-to-dc converters. Features of SCM include: Adaptive stability, power component stress limiting, implementation of various control laws, unified design approach. Analysis and quidelines contained in handbooks enable engineer to design SCM circuit and confidently predict resulting overall performance.

Isolated step-down DC -DC converter for electric vehicles

Science.gov (United States)

Kukovinets, O. V.; Sidorov, K. M.; Yutt, V. E.

2018-02-01

Modern motor-vehicle industrial sector is moving rapidly now towards the electricity-driving cars production, improving their range and efficiency of components, and in particular the step-down DC/DC converter to supply the onboard circuit 12/24V of electric vehicle from the high-voltage battery. The purpose of this article - to identify the best circuitry topology to design an advanced step-down DC/DC converters with the smallest mass, volume, highest efficiency and power. And this will have a positive effect on driving distance of electric vehicle (EV). On the basis of computational research of existing and implemented circuit topologies of step-down DC/DC converters (serial resonant converter, full bridge with phase-shifting converter, LLC resonant converter) a comprehensive analysis was carried out on the following characteristics: specific volume, specific weight, power, efficiency. The data obtained was the basis for the best technical option - LLC resonant converter. The results can serve as a guide material in the process of components design of the traction equipment for electric vehicles, providing for the best technical solutions in the design and manufacturing of converting equipment, self-contained power supply systems and advanced driver assistance systems.

Hotair mediates hepatocarcinogenesis through suppressing miRNA-218 expression and activating P14 and P16 signaling.

Science.gov (United States)

Fu, Wei-Ming; Zhu, Xiao; Wang, Wei-Mao; Lu, Ying-Fei; Hu, Bao-Guang; Wang, Hua; Liang, Wei-Cheng; Wang, Shan-Shan; Ko, Chun-Hay; Waye, Mary Miu-Yee; Kung, Hsiang-Fu; Li, Gang; Zhang, Jin-Fang

2015-10-01

Long non-coding RNA Hotair has been considered as a pro-oncogene in multiple cancers. Although there is emerging evidence that reveals its biological function and the association with clinical prognosis, the precise mechanism remains largely elusive. We investigated the function and mechanism of Hotair in hepatocellular carcinoma (HCC) cell models and a xenograft mouse model. The regulatory network between miR-218 and Hotair was elucidated by RNA immunoprecipitation and luciferase reporter assays. Finally, the correlation between Hotair, miR-218 and the target gene Bmi-1 were evaluated in 52 paired HCC specimens. In this study, we reported that Hotair negatively regulated miR-218 expression in HCC, which might be mediated through an EZH2-targeting-miR-218-2 promoter regulatory axis. Further investigation revealed that Hotair knockdown dramatically inhibited cell viability and induced G1-phase arrest in vitro and suppressed tumorigenicity in vivo by promoting miR-218 expression. Oncogene Bmi-1 was shown to be a functional target of miR-218, and the main downstream targets signaling, P16(Ink4a) and P14(ARF), were activated in Hotair-suppressed tumorigenesis. In primary human HCC specimens, Hotair and Bmi-1 were concordantly upregulated whereas miR-218 was downregulated in these tissues. Furthermore, Hotair was inversely associated with miR-218 expression and positively correlated with Bmi-1 expression in these clinical tissues. Hotair silence activates P16(Ink4a) and P14(ARF) signaling by enhancing miR-218 expression and suppressing Bmi-1 expression, resulting in the suppression of tumorigenesis in HCC. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Suppressive Effects of Bee Venom Acupuncture on Paclitaxel-Induced Neuropathic Pain in Rats: Mediation by Spinal α2-Adrenergic Receptor

Directory of Open Access Journals (Sweden)

Jiho Choi

2017-10-01

Full Text Available Paclitaxel, a chemotherapy drug for solid tumors, induces peripheral painful neuropathy. Bee venom acupuncture (BVA has been reported to have potent analgesic effects, which are known to be mediated by activation of spinal α-adrenergic receptor. Here, we investigated the effect of BVA on mechanical hyperalgesia and spinal neuronal hyperexcitation induced by paclitaxel. The role of spinal α-adrenergic receptor subtypes in the analgesic effect of BVA was also observed. Administration of paclitaxel (total 8 mg/kg, intraperitoneal on four alternate days (days 0, 2, 4, and 6 induced significant mechanical hyperalgesic signs, measured using a von Frey filament. BVA (1 mg/kg, ST36 relieved this mechanical hyperalgesia for at least two hours, and suppressed the hyperexcitation in spinal wide dynamic range neurons evoked by press or pinch stimulation. Both melittin (0.5 mg/kg, ST36 and phospholipase A2 (0.12 mg/kg, ST36 were shown to play an important part in this analgesic effect of the BVA, as they significantly attenuated the pain. Intrathecal pretreatment with the α2-adrenergic receptor antagonist (idazoxan, 50 µg, but not α1-adrenergic receptor antagonist (prazosin, 30 µg, blocked the analgesic effect of BVA. These results suggest that BVA has potent suppressive effects against paclitaxel-induced neuropathic pain, which were mediated by spinal α2-adrenergic receptor.

Suppressive Effects of Bee Venom Acupuncture on Paclitaxel-Induced Neuropathic Pain in Rats: Mediation by Spinal α₂-Adrenergic Receptor.

Science.gov (United States)

Choi, Jiho; Jeon, Changhoon; Lee, Ji Hwan; Jang, Jo Ung; Quan, Fu Shi; Lee, Kyungjin; Kim, Woojin; Kim, Sun Kwang

2017-10-31

Paclitaxel, a chemotherapy drug for solid tumors, induces peripheral painful neuropathy. Bee venom acupuncture (BVA) has been reported to have potent analgesic effects, which are known to be mediated by activation of spinal α-adrenergic receptor. Here, we investigated the effect of BVA on mechanical hyperalgesia and spinal neuronal hyperexcitation induced by paclitaxel. The role of spinal α-adrenergic receptor subtypes in the analgesic effect of BVA was also observed. Administration of paclitaxel (total 8 mg/kg, intraperitoneal) on four alternate days (days 0, 2, 4, and 6) induced significant mechanical hyperalgesic signs, measured using a von Frey filament. BVA (1 mg/kg, ST36) relieved this mechanical hyperalgesia for at least two hours, and suppressed the hyperexcitation in spinal wide dynamic range neurons evoked by press or pinch stimulation. Both melittin (0.5 mg/kg, ST36) and phospholipase A2 (0.12 mg/kg, ST36) were shown to play an important part in this analgesic effect of the BVA, as they significantly attenuated the pain. Intrathecal pretreatment with the α₂-adrenergic receptor antagonist (idazoxan, 50 µg), but not α₁-adrenergic receptor antagonist (prazosin, 30 µg), blocked the analgesic effect of BVA. These results suggest that BVA has potent suppressive effects against paclitaxel-induced neuropathic pain, which were mediated by spinal α₂-adrenergic receptor.

Reduction of DC-link Capacitor in Case of Cascade Multilevel Converters by means of Reactive Power Control

DEFF Research Database (Denmark)

Gohil, Ghanshyamsinh Vijaysinh; Wang, Huai; Liserre, Marco

2014-01-01

A method to selectively control the amount of dc link voltage ripple by processing desired reactive power by a DC/DC converter in isolated AC/DC or AC/DC/AC system is proposed. The concept can reduce the dc link capacitors used for balancing the input and output power and thereby limiting...... the voltage ripple. It allows the use of smaller dc link capacitor and hence a longer lifetime and at the same time high power density and low cost can be achieved. The isolated DC/DC converter is controlled to process the desired reactive power in addition to the active power. The control system to achieve...

Assessment of ptxD gene as an alternative selectable marker for Agrobacterium-mediated maize transformation.

Science.gov (United States)

Nahampun, Hartinio N; López-Arredondo, Damar; Xu, Xing; Herrera-Estrella, Luis; Wang, Kan

2016-05-01

Bacterial phosphite oxidoreductase gene and chemical phosphite can be used as a selection system for Agrobacterium -mediated maize transformation. Application of phosphite (Phi) on plants can interfere the plant metabolic system leading to stunted growth and lethality. On the other hand, ectopic expression of the ptxD gene in tobacco and Arabidopsis allowed plants to grow in media with Phi as the sole phosphorous source. The phosphite oxidoreductase (PTXD) enzyme catalyzes the conversion of Phi into phosphate (Pi) that can then be metabolized by plants and utilized as their essential phosphorous source. Here we assess an alternative selectable marker based on a bacterial ptxD gene for Agrobacterium-mediated maize transformation. We compared the transformation frequencies of maize using either the ptxD/Phi selection system or a standard herbicide bar/bialaphos selection system. Two maize genotypes, a transformation amenable hybrid Hi II and an inbred B104, were tested. Transgene presence, insertion copy numbers, and ptxD transcript levels were analyzed and compared. This work demonstrates that the ptxD/Phi selection system can be used for Agrobacterium-mediated maize transformation of both type I and type II callus culture and achieve a comparable frequency as that of the herbicide bar/bialaphos selection system.

75 FR 75872 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-9-30, DC-9-40, and DC-9-50...

Science.gov (United States)

2010-12-07

... Airworthiness Directives; McDonnell Douglas Corporation Model DC- 9-30, DC-9-40, and DC-9-50 Series Airplanes...: We are adopting a new airworthiness directive (AD) for the McDonnell Douglas Corporation airplanes... to include an airworthiness directive (AD) that would apply to certain McDonnell Douglas Model DC-9...

B cells exposed to enterobacterial components suppress development of experimental colitis

DEFF Research Database (Denmark)

Schmidt, Esben Gjerløff Wedebye; Larsen, Hjalte List; Kristensen, Nanna Ny

2012-01-01

). RESULTS: We demonstrate that splenic B cells exposed to ebx produce large amounts of IL-10 in vitro and express CD1d and CD5 previously known to be associated with regulatory B cells. In SCID mice transplanted with colitogenic CD4(+) CD25(-) T cells, co-transfer of ebx-B cells significantly suppressed...... development of colitis. Suppression was dependent on B cell-derived IL-10, as co-transfer of IL-10 knockout ebx-B cells failed to suppress colitis. Ebx-B cell-mediated suppression of colitis was associated with a decrease in interferon gamma (IFN-¿)-producing T(H) 1 cells and increased frequencies of Foxp3......-expressing T cells. CONCLUSIONS: These data demonstrate that splenic B cells exposed to enterobacterial components acquire immunosuppressive functions by which they can suppress development of experimental T cell-mediated colitis in an IL-10-dependent way. (Inflamm Bowel Dis 2011;)....

A Component-Reduced Zero-Voltage Switching Three-Level DC-DC Converter

DEFF Research Database (Denmark)

Qin, Zian; Pang, Ying; Wang, Huai

2016-01-01

The basic Zero-Voltage Switching (ZVS) three-level DC-DC converter has one clamping capacitor to realize the ZVS of the switches, and two clamping diodes to clamp the voltage of the clamping capacitor. In order to reduce the reverse recovery loss of the diode as well as its cost, this paper...... proposes to remove one of the clamping diodes in basic ZVS three-level DC-DC converter. With less components, the proposed converter can still have a stable clamping capacitor voltage, which is clamped at half of the dc link voltage. Moreover, the ZVS performance will be influenced by removing the clamping...

mTOR signaling promotes stem cell activation via counterbalancing BMP-mediated suppression during hair regeneration.

Science.gov (United States)

Deng, Zhili; Lei, Xiaohua; Zhang, Xudong; Zhang, Huishan; Liu, Shuang; Chen, Qi; Hu, Huimin; Wang, Xinyue; Ning, Lina; Cao, Yujing; Zhao, Tongbiao; Zhou, Jiaxi; Chen, Ting; Duan, Enkui

2015-02-01

Hair follicles (HFs) undergo cycles of degeneration (catagen), rest (telogen), and regeneration (anagen) phases. Anagen begins when the hair follicle stem cells (HFSCs) obtain sufficient activation cues to overcome suppressive signals, mainly the BMP pathway, from their niche cells. Here, we unveil that mTOR complex 1 (mTORC1) signaling is activated in HFSCs, which coincides with the HFSC activation at the telogen-to-anagen transition. By using both an inducible conditional gene targeting strategy and a pharmacological inhibition method to ablate or inhibit mTOR signaling in adult skin epithelium before anagen initiation, we demonstrate that HFs that cannot respond to mTOR signaling display significantly delayed HFSC activation and extended telogen. Unexpectedly, BMP signaling activity is dramatically prolonged in mTOR signaling-deficient HFs. Through both gain- and loss-of-function studies in vitro, we show that mTORC1 signaling negatively affects BMP signaling, which serves as a main mechanism whereby mTORC1 signaling facilitates HFSC activation. Indeed, in vivo suppression of BMP by its antagonist Noggin rescues the HFSC activation defect in mTORC1-null skin. Our findings reveal a critical role for mTOR signaling in regulating stem cell activation through counterbalancing BMP-mediated repression during hair regeneration. © The Author (2015). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

The Fbw7 tumor suppressor targets KLF5 for ubiquitin-mediated degradation and suppresses breast cell proliferation.

Science.gov (United States)

Zhao, Dong; Zheng, Han-Qiu; Zhou, Zhongmei; Chen, Ceshi

2010-06-01

Fbw7 is a tumor suppressor frequently inactivated in cancers. The KLF5 transcription factor promotes breast cell proliferation and tumorigenesis through upregulating FGF-BP. The KLF5 protein degrades rapidly through the ubiquitin proteasome pathway. Here, we show that the Skp1-CUL1-Fbw7 E3 ubiquitin ligase complex (SCF(Fbw7)) targets KLF5 for ubiquitin-mediated degradation in a GSK3beta-mediated KLF5 phosphorylation-dependent manner. Mutation of the critical S303 residue in the KLF5 Cdc4 phospho-degrons motif ((303)SPPSS) abolishes the protein interaction, ubiquitination, and degradation by Fbw7. Inactivation of endogenous Fbw7 remarkably increases the endogenous KLF5 protein abundances. Endogenous Fbw7 suppresses the FGF-BP gene expression and breast cell proliferation through targeting KLF5 for degradation. These findings suggest that Fbw7 inhibits breast cell proliferation at least partially through targeting KLF5 for proteolysis. This new regulatory mechanism of KLF5 degradation may result in useful diagnostic and therapeutic targets for breast cancer and other cancers. Copyright 2010 AACR.

Active pre-filters for dc/dc Boost regulators

Directory of Open Access Journals (Sweden)

Carlos Andrés Ramos-Paja

2014-05-01

Full Text Available This paper proposes an active pre-filter to mitigate the current harmonics generated by classical dc/dc Boost regulators, which generate current ripples proportional to the duty cycle. Therefore, high output voltage conditions, i.e., high voltage conversion ratios, produce high current harmonics that must be filtered to avoid damage or source losses. Traditionally, these current components are filtered using electrolytic capacitors, which introduce reliability problems because of their high failure rate. The solution introduced in this paper instead uses a dc/dc converter based on the parallel connection of the Boost canonical cells to filter the current ripples generated by the Boost regulator, improving the system reliability. This solution provides the additional benefits of improving the overall efficiency and the voltage conversion ratio. Finally, the solution is validated with simulations and experimental results.

Laboratory manual for pulse-width modulated DC-DC power converters

CERN Document Server

Kazimierczuk, Marian K

2015-01-01

Designed to complement a range of power electronics study resources, this unique lab manual helps students to gain a deep understanding of the operation, modeling, analysis, design, and performance of pulse-width modulated (PWM) DC-DC power converters.  Exercises focus on three essential areas of power electronics: open-loop power stages; small-signal modeling, design of feedback loops and PWM DC-DC converter control schemes; and semiconductor devices such as silicon, silicon carbide and gallium nitride. Meeting the standards required by industrial employers, the lab manual combines program

A Novel PPFHB Bidirectional DC-DC Converter for Supercapacitor Application

DEFF Research Database (Denmark)

Zhang, Zhe; Thomsen, Ole Cornelius; Andersen, Michael Andreas E.

2009-01-01

This paper presents a novel bidirectional DC-DC converter for the supercapacitor application. In the proposed converter, push-pull forward with half bridge (PPFHB) voltage doubler structure is used to reduce the number of the power switches and get higher voltage gain. Based on phase-shift modula......This paper presents a novel bidirectional DC-DC converter for the supercapacitor application. In the proposed converter, push-pull forward with half bridge (PPFHB) voltage doubler structure is used to reduce the number of the power switches and get higher voltage gain. Based on phase...

A moving pole-placement compensation design method to increase the bandwidth of RC-damper-based dual “Buck-Boost” AC/DC converter

DEFF Research Database (Denmark)

Wu, Weimin; Qin, Weibo; Wang, Houqin

2017-01-01

the “Buck” mode, the control-to-grid current transfer function of this dual “Buck-Boost” AC/DC converter has a movable zero, which is related to the input power and the output DC voltage. When the input power increases, the movable zero will slide to the lower frequency range. And then, the gain between...... the cut-off frequency point and the resonant frequency of LCL filter will swell up, resulting in reduced amplitude margin and suppressed bandwidth of system. Based on the theoretical analysis, a new dynamic pole placement compensation control design method is proposed for this dual AC/DC converter...

Decentralized Interleaving of Paralleled Dc-Dc Buck Converters: Preprint

Energy Technology Data Exchange (ETDEWEB)

Johnson, Brian B [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Rodriguez, Miguel [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Sinha, Mohit [University of Minnesota; Dhople, Sairaj [University of Minnesota; Poon, Jason [University of California at Berkeley

2017-09-01

We present a decentralized control strategy that yields switch interleaving among parallel connected dc-dc buck converters without communication. The proposed method is based on the digital implementation of the dynamics of a nonlinear oscillator circuit as the controller. Each controller is fully decentralized, i.e., it only requires the locally measured output current to synthesize the pulse width modulation (PWM) carrier waveform. By virtue of the intrinsic electrical coupling between converters, the nonlinear oscillator-based controllers converge to an interleaved state with uniform phase-spacing across PWM carriers. To the knowledge of the authors, this work represents the first fully decentralized strategy for switch interleaving of paralleled dc-dc buck converters.

Suppression of polymorphonuclear (PMN) and monocyte-mediated inhibition of Candida albicans growth by delta-9-tetrahydrocannabinol

International Nuclear Information System (INIS)

Djeu, J.Y.; Parapanios, A.; Halkias, D.; Friedman, H.

1986-01-01

This study was an in vitro attempt to identify the effector cells responsible for growth inhibition of the opportunistic fungus, candida albicans, and to determine if THC or another marijuana derivatives, 11-hydroxyTHC, would adversely affect their function. Using a 24h radiolabel assay, the authors found that growth inhibition of C. albicans was primarily mediated by PMN and monocytes that could be isolated normal human peripheral blood. Both effector cell types caused almost complete inhibition of Candida growth at effector/target ratio of 300/1 and inhibition was often still seen at 30/1-. Incubation of PMN, PBL, or monocytes for 1 hr at 37C with THC or 11-hydroxyTHC caused a marked suppression of function in all 3 cell populations. Maximal suppression was obtained with 7.5-10μg/ml of the drugs in medium containing 10% fetal bovine serum (FBS) or with 2-4μg/ml in 1% FBS. These drug concentrations did not affect lymphoid cell viability or candida growth in the absence of lymphoid effector cells. Marijuana derivatives, therefore, are doubly dangerous in that opportunistic fungi such as C. albicans can grow in their presence while the effector cells that control fungal growth are readily inactivated

Quantitative disease resistance: to better understand parasite-mediated selection on major histocompatibility complex.

Science.gov (United States)

Westerdahl, Helena; Asghar, Muhammad; Hasselquist, Dennis; Bensch, Staffan

2012-02-07

We outline a descriptive framework of how candidate alleles of the immune system associate with infectious diseases in natural populations of animals. Three kinds of alleles can be separated when both prevalence of infection and infection intensity are measured--qualitative disease resistance, quantitative disease resistance and susceptibility alleles. Our descriptive framework demonstrates why alleles for quantitative resistance and susceptibility cannot be separated based on prevalence data alone, but are distinguishable on infection intensity. We then present a case study to evaluate a previous finding of a positive association between prevalence of a severe avian malaria infection (GRW2, Plasmodium ashfordi) and a major histocompatibility complex (MHC) class I allele (B4b) in great reed warblers Acrocephalus arundinaceus. Using the same dataset, we find that individuals with allele B4b have lower GRW2 infection intensities than individuals without this allele. Therefore, allele B4b provides quantitative resistance rather than increasing susceptibility to infection. This implies that birds carrying B4b can mount an immune response that suppresses the acute-phase GRW2 infection, while birds without this allele cannot and may die. We argue that it is important to determine whether MHC alleles related to infections are advantageous (quantitative and qualitative resistance) or disadvantageous (susceptibility) to obtain a more complete picture of pathogen-mediated balancing selection.

DIAGNOSTIC CLASSIFICATION OF MENTAL HEALTH AND DEVELOPMENTAL DISORDERS OF INFANCY AND EARLY CHILDHOOD DC:0-5: SELECTIVE REVIEWS FROM A NEW NOSOLOGY FOR EARLY CHILDHOOD PSYCHOPATHOLOGY.

Science.gov (United States)

Zeanah, Charles H; Carter, Alice S; Cohen, Julie; Egger, Helen; Gleason, Mary Margaret; Keren, Miri; Lieberman, Alicia; Mulrooney, Kathleen; Oser, Cindy

2016-09-01

The Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood: Revised Edition (DC:0-5; ZERO TO THREE) is scheduled to be published in 2016. The articles in this section are selective reviews that have been undertaken as part of the process of refining and updating the nosology. They provide the rationales for new disorders, for disorders that had not been included previously in the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood: Revised Edition (DC:0-3R; ZERO TO THREE, 2005), and for changes in how certain types of disorders are conceptualized. © 2016 Michigan Association for Infant Mental Health.

A Bidirectional Multi-Port DC-DC Converter Integrating Voltage Equalizer

DEFF Research Database (Denmark)

Chen, Jianfei; Hou, Shiying; Deng, Fujin

2015-01-01

A novel bidirectional multi-port dc-dc converter integrating voltage equalizer based on switched-capacitor voltage accumulator (SCVA) is proposed. It has two operating modes of charging and discharging for battery modules. All battery modules are connected in series indirectly and can be equalize...... battery modules with different voltages. Simulation results has shown the feasibility of the proposed converter.......A novel bidirectional multi-port dc-dc converter integrating voltage equalizer based on switched-capacitor voltage accumulator (SCVA) is proposed. It has two operating modes of charging and discharging for battery modules. All battery modules are connected in series indirectly and can be equalized...

Suppression of APOBEC3-mediated restriction of HIV-1 by Vif

Directory of Open Access Journals (Sweden)

Yuqing eFeng

2014-08-01

Full Text Available The APOBEC3 restriction factors are a family of deoxycytidine deaminases that are able to suppress replication of viruses with a single-stranded DNA intermediate by inducing mutagenesis and functional inactivation of the virus. Of the seven human APOBEC3 enzymes, only APOBEC3-D, -F, -G, and -H appear relevant to restriction of HIV-1 in CD4+ T cells and will be the focus of this review. The restriction of HIV-1 occurs most potently in the absence of HIV-1 Vif that induces polyubiquitination and degradation of APOBEC3 enzymes through the proteasome pathway. To restrict HIV-1, APOBEC3 enzymes must be encapsidated into budding virions. Upon infection of the target cell during reverse transcription of the HIV-1 RNA into (-DNA APOBEC3 enzymes deaminate cytosines to forms uracils in single-stranded (- DNA regions. Upon replication of the (-DNA to (+DNA, the HIV-1 reverse transcriptase incorporates adenines opposite the uracils thereby inducing C/G to T/A mutations that can functionally inactivate HIV-1. APOBEC3G is the most studied APOBEC3 enzyme and it is known that Vif attempts to thwart APOBEC3 function not only by inducing its proteasomal degradation but by several degradation-independent mechanisms such as inhibiting APOBEC3G virion encapsidation, mRNA translation, and for those APOBEC3G molecules that still become virion encapsidated, Vif can inhibit APOBEC3G mutagenic activity. Although most Vif variants can induce efficient degradation of APOBEC3-D, -F, and -G, there appears to be differential sensitivity to Vif-mediated degradation for APOBEC3H. This review examines APOBEC3-mediated HIV restriction mechanisms, how Vif acts as a substrate receptor for a Cullin5 ubiquitin ligase complex to induce degradation of APOBEC3s, and the determinants and functional consequences of the APOBEC3 and Vif interaction from a biological and biochemical perspective.

In vivo evolution of HIV-1 co-receptor usage and sensitivity to chemokine-mediated suppression.

Science.gov (United States)

Scarlatti, G; Tresoldi, E; Björndal, A; Fredriksson, R; Colognesi, C; Deng, H K; Malnati, M S; Plebani, A; Siccardi, A G; Littman, D R; Fenyö, E M; Lusso, P

1997-11-01

Following the identification of the C-C chemokines RANTES, MIP-1alpha and MIP-1beta as major human immunodeficiency virus (HIV)-suppressive factors produced by CD8+ T cells, several chemokine receptors were found to serve as membrane co-receptors for primate immunodeficiency lentiretroviruses. The two most widely used co-receptors thus far recognized, CCR5 and CXCR4, are expressed by both activated T lymphocytes and mononuclear phagocytes. CCR5, a specific RANTES, MIP-1alpha and MIP-1 receptor, is used preferentially by non-MT2-tropic HIV-1 and HIV-2 strains and by simian immunodeficiency virus (SIV), whereas CXCR4, a receptor for the C-X-C chemokine SDF-1, is used by MT2-tropic HIV-1 and HIV-2, but not by SIV. Other receptors with a more restricted cellular distribution, such as CCR2b, CCR3 and STRL33, can also function as co-receptors for selected viral isolates. The third variable region (V3) of the gp120 envelope glycoprotein of HIV-1 has been fingered as a critical determinant of the co-receptor choice. Here, we document a consistent pattern of evolution of viral co-receptor usage and sensitivity to chemokine-mediated suppression in a longitudinal follow-up of children with progressive HIV-1 infection. Viral isolates obtained during the asymptomatic stages generally used only CCR5 as a co-receptor and were inhibited by RANTES, MIP-1alpha and MIP-1beta, but not by SDF-1. By contrast, the majority of the isolates derived after the progression of the disease were resistant to C-C chemokines, having acquired the ability to use CXCR4 and, in some cases, CCR3, while gradually losing CCR5 usage. Surprisingly, most of these isolates were also insensitive to SDF-1, even when used in combination with RANTES. An early acquisition of CXCR4 usage predicted a poor prognosis. In children who progressed to AIDS without a shift to CXCR4 usage, all the sequential isolates were CCR5-dependent but showed a reduced sensitivity to C-C chemokines. Discrete changes in the V3 domain

Role of the hinge region of glucocorticoid receptor for HEXIM1-mediated transcriptional repression

International Nuclear Information System (INIS)

Yoshikawa, Noritada; Shimizu, Noriaki; Sano, Motoaki; Ohnuma, Kei; Iwata, Satoshi; Hosono, Osamu; Fukuda, Keiichi; Morimoto, Chikao

2008-01-01

We previously reported that HEXIM1 (hexamethylene bisacetamide-inducible protein 1), which suppresses transcription elongation via sequestration of positive transcription elongation factor b (P-TEFb) using 7SK RNA as a scaffold, directly associates with glucocorticoid receptor (GR) to suppress glucocorticoid-inducible gene activation. Here, we revealed that the hinge region of GR is essential for its interaction with HEXIM1, and that oxosteroid receptors including GR show sequence homology in their hinge region and interact with HEXIM1, whereas the other members of nuclear receptors do not. We also showed that HEXIM1 suppresses GR-mediated transcription in two ways: sequestration of P-TEFb by HEXIM1 and direct interaction between GR and HEXIM1. In contrast, peroxisome proliferator-activated receptor γ-dependent gene expression is negatively modulated by HEXIM1 solely via sequestration of P-TEFb. We, therefore, conclude that HEXIM1 may act as a gene-selective transcriptional regulator via direct interaction with certain transcriptional regulators including GR and contribute to fine-tuning of, for example, glucocorticoid-mediated biological responses

A Current-Fed Isolated Bidirectional DC-DC Converter

DEFF Research Database (Denmark)

Sun, Xiaofeng; Wu, Xiaoying; Shen, Yanfeng

2017-01-01

This paper proposes a current-fed isolated bidirectional DC-DC converter (CF-IBDC) which has the advantages of wide input voltage range, low input current ripple, low conduction losses, and soft switching over the full operating range. Compared with conventional CF-IBDCs, the voltage spikes...

Peptide-Based Selective Inhibitors of Matrix Metalloproteinase-Mediated Activities

Directory of Open Access Journals (Sweden)

Margaret W. Ndinguri

2012-11-01

Full Text Available The matrix metalloproteinases (MMPs exhibit a broad array of activities, some catalytic and some non-catalytic in nature. An overall lack of selectivity has rendered small molecule, active site targeted MMP inhibitors problematic in execution. Inhibitors that favor few or individual members of the MMP family often take advantage of interactions outside the enzyme active site. We presently focus on peptide-based MMP inhibitors and probes that do not incorporate conventional Zn2+ binding groups. In some cases, these inhibitors and probes function by binding only secondary binding sites (exosites, while others bind both exosites and the active site. A myriad of MMP mediated-activities beyond selective catalysis can be inhibited by peptides, particularly cell adhesion, proliferation, motility, and invasion. Selective MMP binding peptides comprise highly customizable, unique imaging agents. Areas of needed improvement for MMP targeting peptides include binding affinity and stability.

Bi-Directional DC-DC Converter for PHEV Applications

Energy Technology Data Exchange (ETDEWEB)

Abas Goodarzi

2011-01-31

Plug-In Hybrid Electric Vehicles (PHEV) require high power density energy storage system (ESS) for hybrid operation and high energy density ESS for Electric Vehicle (EV) mode range. However, ESS technologies to maximize power density and energy density simultaneously are not commercially feasible. The use of bi-directional DC-DC converter allows use of multiple energy storage, and the flexible DC-link voltages can enhance the system efficiency and reduce component sizing. This will improve fuel consumption, increase the EV mode range, reduce the total weight, reduce battery initial and life cycle cost, and provide flexibility in system design.

Selective regulation of YB-1 mRNA translation by the mTOR signaling pathway is not mediated by 4E-binding protein.

Science.gov (United States)

Lyabin, D N; Ovchinnikov, L P

2016-03-02

The Y-box binding protein 1 (YB-1) is a key regulator of gene expression at the level of both translation and transcription. The mode of its action on cellular events depends on its subcellular distribution and the amount in the cell. So far, the regulatory mechanisms of YB-1 synthesis have not been adequately studied. Our previous finding was that selective inhibition of YB-1 mRNA translation was caused by suppression of activity of the mTOR signaling pathway. It was suggested that this event may be mediated by phosphorylation of the 4E-binding protein (4E-BP). Here, we report that 4E-BP alone can only slightly inhibit YB-1 synthesis both in the cell and in vitro, although it essentially decreases binding of the 4F-group translation initiation factors to mRNA. With inhibited mTOR kinase, the level of mRNA binding to the eIF4F-group factors was decreased, while that to 4E-BP1 was increased, as was observed for both mTOR kinase-sensitive mRNAs and those showing low sensitivity. This suggests that selective inhibition of translation of YB-1 mRNA, and probably some other mRNAs as well, by mTOR kinase inhibitors is not mediated by the action of the 4E-binding protein upon functions of the 4F-group translation initiation factors.

Design of resonant converter based DC power supply for RF amplifier

International Nuclear Information System (INIS)

Mohan, Kartik; Suthar, Gajendra; Dalicha, Hrushikesh; Agarwal, Rohit; Trivedi, R.G.; Mukherjee, Aparajita

2017-01-01

ITER require 20 MW of RF power to a large variety of plasmas in the Ion Cyclotron frequency range for heating and driving plasma current. Nine RF sources of 2.5MW RF power level each collectively will accomplish the above requirement. Each RF source consists of SSPA, driver and end stage, above which driver and end stage amplifier are tube (Tetrode/Diacrode) based which requires auxiliary DC power source viz. filament, screen grid and control grid DC power supply. DC power supply has some stringent requirements like low stored energy, fast turn off, and low ripple value, etc. This paper will focus only on Zero Current Switching (ZCS) resonant converter based buck converter. This can serve the purpose of control grid and screen grid DC power supply for above requirement. IGBT switch will be used at 20 kHz so as to lower the filter requirement hence low stored energy and ripple in the output voltage. ZCS operation will also assist us in reducing EMI/EMC effect. Design of resonant tank circuit is important aspect of the converter as it forms the backbone of the complete system and basis of selection of other important parameters as well hence mathematical model analysis with the help of circuit equations for various modes have been shown as a part of selection criteria. Peak current through the switch, duty cycle, switching frequency will be the design parameters for selecting resonant tank circuit

Determination of input/output characteristics of full-bridge AC/DC/DC converter for arc welding

OpenAIRE

Stefanov, Goce; Karadzinov, Ljupco; Sarac, Vasilija; Cingoski, Vlatko; Gelev, Saso

2016-01-01

This paper describes the design and practical implementation of AC/DC/DC converter in mode of arc welding. An analysis of the operation of AC/DC/DC converter and its input/output characteristics are determined with computer simulations. The practical part is consisted of AC/DC/DC converter prototype for arc welding with output power of 3 kW and switching frequency of 64 kHz. The operation of AC/DC/DC converter is validated with experimental measurements.

ITAR Free Commercial-of-the-Shelf DC/DC Converter

Science.gov (United States)

Denzinger, Wolfgang; Hintze, Thomas

2014-08-01

A commercial-of-the-shelf (COTS) DC/DC converter for digital space equipment has been developed by ASP under ESA contract with special emphasis on low cost, no use of ITAR listed EEE parts like Mosfets, minimum number of rad-hard digital IC's and a design tolerance against single event effects by appropriate filtering. However, the intention to qualify this discrete converter design for a low cost FM series production was difficult due to the high up-sceening cost of EEE-parts with one lot guarantee and minimum-by. To overcome this problem, in a next step a redesign of the DC/DC converter was performed with all semiconductors like bipolar transistors, rectifiers and zener diodes packaged into hybrids. With this approach it was possible to buy a high number of less expensive wafers or dies from one lot, to perform a lot acceptance test and to integrate the dies into hybrid packages with further up- screening for FM use. The semiconductors have been packaged into three signal hybrids with 44 pins and one power hybrid with 24 pins for the dissipating transistors and rectifiers. The design of the hybrids is such, that all integrated semiconductors can be tested individually. The qualification of four EQM DC/DC converters with different combinations of output voltages has been successfully performed and two FM's have been manufactured and tested.

Behavioral performance follows the time course of neural facilitation and suppression during cued shifts of feature-selective attention

OpenAIRE

Andersen, S. K.; Müller, M. M.

2010-01-01

A central question in the field of attention is whether visual processing is a strictly limited resource, which must be allocated by selective attention. If this were the case, attentional enhancement of one stimulus should invariably lead to suppression of unattended distracter stimuli. Here we examine voluntary cued shifts of feature-selective attention to either one of two superimposed red or blue random dot kinematograms (RDKs) to test whether such a reciprocal relationship between enhanc...

Categorization difficulty modulates the mediated route for response selection in task switching.

Science.gov (United States)

Schneider, Darryl W

2017-12-22

Conflict during response selection in task switching is indicated by the response congruency effect: worse performance for incongruent targets (requiring different responses across tasks) than for congruent targets (requiring the same response). The effect can be explained by dual-task processing in a mediated route for response selection, whereby targets are categorized with respect to both tasks. In the present study, the author tested predictions for the modulation of response congruency effects by categorization difficulty derived from a relative-speed-of-processing hypothesis. Categorization difficulty was manipulated for the relevant and irrelevant task dimensions in a novel spatial task-switching paradigm that involved judging the locations of target dots in a grid, without repetition of dot configurations. Response congruency effects were observed and they varied systematically with categorization difficulty (e.g., being larger when irrelevant categorization was easy than when it was hard). These results are consistent with the relative-speed-of-processing hypothesis and suggest that task-switching models that implement variations of the mediated route for response selection need to address the time course of categorization.

Performance of 22.4-kW nonlaminated-frame dc series motor with chopper controller. [a dc to dc voltage converter

Science.gov (United States)

Schwab, J. R.

1979-01-01

Performance data obtained through experimental testing of a 22.4 kW traction motor using two types of excitation are presented. Ripple free dc from a motor-generator set for baseline data and pulse width modulated dc as supplied by a battery pack and chopper controller were used for excitation. For the same average values of input voltage and current, the motor power output was independent of the type of excitation. However, at the same speeds, the motor efficiency at low power output (corresponding to low duty cycle of the controller) was 5 to 10 percentage points lower on chopped dc than on ripple free dc. The chopped dc locked-rotor torque was approximately 1 to 3 percent greater than the ripple free dc torque for the same average current.

Characterising and modelling extended conducted electromagnetic interference in densely packed DC-DC converter

CSIR Research Space (South Africa)

Grobler, Inus

2013-09-01

Full Text Available . The military specified DC-DC converters are applicable, spanning from 100 W handheld power managers up to 2 kW DC-DC battery chargers. Circuit layout high frequency effects as well as high frequency impedances of the power components were characterised...

A New Sliding Mode Controller for DC/DC Converters in Photovoltaic Systems

Directory of Open Access Journals (Sweden)

M. Sarvi

2013-01-01

Full Text Available DC/DC converters are widely used in many industrial and electrical systems. As DC/DC converters are nonlinear and time-variant systems, the application of linear control techniques for the control of these converters is not suitable. In this paper, a new sliding mode controller is proposed as the indirect control method and compared to a simple direct control method in order to control a buck converter in photovoltaic applications. The solar arrays are dependent power sources with nonlinear voltage-current characteristics under different environmental conditions (insolation and temperature. From this point of view, the DC/DC converter is particularly suitable for the application of the sliding mode control in photovoltaic application, because of its controllable states. Simulations are performed in Matlab/Simulink software. The simulation results are presented for a step change in reference voltage and input voltage as well as step load variations. The simulations results of proposed method are compared with the conventional PID controller. The results show the good performance of the proposed sliding mode controller. The proposed method can be used for the other DC/DC converter.

Very High Frequency Half Bridge DC/DC Converter

DEFF Research Database (Denmark)

Madsen, Mickey Pierre; Knott, Arnold; Andersen, Michael A. E.

2014-01-01

This paper presents the first, off chip, class DE (resonant half bridge) converter working in the Very High Frequency (VHF) range. The benefits of using half bridge circuits both in the inverter and rectifier part of a VHF resonant dc/dc converter are analyzed and design equations for all...

Sheppard-Taylor Isolated High Boost DC-DC Converter

DEFF Research Database (Denmark)

Chub, Andrii; Siwakoti, Yam Prasad; Vinnikov, Dmitri

2017-01-01

This paper presents a new galvanically isolated step-up dc-dc converter intended for low-power but high step-up applications. The proposed converter is capable of regulating output voltage within a wide range of the input voltage or load variations. In contrast to competitors, the converter can...

Studies of ZVS soft switching of dual-active-bridge isolated bidirectional DC-DC converters

Science.gov (United States)

Xu, Fei; Zhao, Feng; Shi, Qibiao; Wen, Xuhui

2018-05-01

To operate dual-active-bridge isolated bidirectional dc- dc converter (DAB) at high efficiency, the two bridge switches must operate with Zero-Voltage-Switching (ZVS) over as wide an operating range as possible. This paper proposes a new perspective on realizing ZVS in dead-time. An exact theoretical analysis and mathematical mode is built to explain the process of ZVS switching in dead-time under Single Phase Shift (SPS) control strategy. In order to assure the two bridge switches operate on soft switching, every SPS switching point is analyzed. Generally, dead-time will be determined when the power electronic devices is selected. The key factor to realizing ZVS is the size of the end time of resonance comparing to dead-time. Through detailed analysis, it can obtain the conditions of all switches achieving ZVS turn-on and turn-off. Finally, simulation validates the theoretical analysis and some advice are given to realize the ZVS soft switching.

Inflammatory cytokine tumor necrosis factor α suppresses neuroprotective endogenous erythropoietin from astrocytes mediated by hypoxia-inducible factor-2α.

Science.gov (United States)

Nagaya, Yoshiaki; Aoyama, Mineyoshi; Tamura, Tetsuya; Kakita, Hiroki; Kato, Shin; Hida, Hideki; Saitoh, Shinji; Asai, Kiyofumi

2014-12-01

Interest in erythropoietin (EPO) as a neuroprotective mediator has grown since it was found that systemically administered EPO is protective in several animal models of disease. However, given that the blood-brain barrier limits EPO entry into the brain, alternative approaches that induce endogenous EPO production in the brain may be more effective clinically and associated with fewer untoward side-effects. Astrocytes are the main source of EPO in the central nervous system. In the present study we investigated the effect of the inflammatory cytokine tumor necrosis factor α (TNFα) on hypoxia-induced upregulation of EPO in rat brain. Hypoxia significantly increased EPO mRNA expression in the brain and kidney, and this increase was suppressed by TNFα in vivo. In cultured astrocytes exposed to hypoxic conditions for 6 and 12 h, TNFα suppressed the hypoxia-induced increase in EPO mRNA expression in a concentration-dependent manner. TNFα inhibition of hypoxia-induced EPO expression was mediated primarily by hypoxia-inducible factor (HIF)-2α rather than HIF-1α. The effects of TNFα in reducing hypoxia-induced upregulation of EPO mRNA expression probably involve destabilization of HIF-2α, which is regulated by the nuclear factor (NF)-κB signaling pathway. TNFα treatment attenuated the protective effects of astrocytes on neurons under hypoxic conditions via EPO signaling. The effective blockade of TNFα signaling may contribute to the maintenance of the neuroprotective effects of EPO even under hypoxic conditions with an inflammatory response. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Assessment of an Average Controller for a DC/DC Converter via Either a PWM or a Sigma-Delta-Modulator

Directory of Open Access Journals (Sweden)

R. Silva-Ortigoza

2014-01-01

Full Text Available Sliding mode control is a discontinuous control technique that is, by its nature, appropriate for controlling variable structure systems, such as the switch regulated systems employed in power electronics. However, when designing control laws based on the average models of these systems a modulator is necessary for their experimental implementation. Among the most widely used modulators in power electronics are the pulse width modulation (PWM and, more recently, the sigma-delta-modulator (Σ-Δ-modulator. Based on the importance of achieving an appropriate implementation of average control laws and the relevance of the trajectory tracking task in DC/DC power converters, for the first time, this research presents the assessment of the experimental results obtained when one of these controllers is implemented through either a PWM or a Σ-Δ-modulator to perform such a task. A comparative assessment based on the integral square error (ISE index shows that, at frequencies with similar efficiency, the Σ-Δ-modulator provides a better tracking performance for the DC/DC Buck converter. In this paper, an average control based on differential flatness was used to perform the experiments. It is worth mentioning that a different trajectory tracking controller could have been selected for this research.

Hepatitis C Virus Frameshift/Alternate Reading Frame Protein Suppresses Interferon Responses Mediated by Pattern Recognition Receptor Retinoic-Acid-Inducible Gene-I.

Directory of Open Access Journals (Sweden)

Seung Bum Park

Full Text Available Hepatitis C virus (HCV actively evades host interferon (IFN responses but the mechanisms of how it does so are not completely understood. In this study, we present evidence for an HCV factor that contributes to the suppression of retinoic-acid-inducible gene-I (RIG-I-mediated IFN induction. Expression of frameshift/alternate reading frame protein (F/ARFP from HCV -2/+1 frame in Huh7 hepatoma cells suppressed type I IFN responses stimulated by HCV RNA pathogen-associated molecular pattern (PAMP and poly(IC. The suppression occurred independently of other HCV factors; and activation of interferon stimulated genes, TNFα, IFN-λ1, and IFN-λ2/3 was likewise suppressed by HCV F/ARFP. Point mutations in the full-length HCV sequence (JFH1 genotype 2a strain were made to introduce premature termination codons in the -2/+1 reading frame coding for F/ARFP while preserving the original reading frame, which enhanced IFNα and IFNβ induction by HCV. The potentiation of IFN response by the F/ARFP mutations was diminished in Huh7.5 cells, which already have a defective RIG-I, and by decreasing RIG-I expression in Huh7 cells. Furthermore, adding F/ARFP back via trans-complementation suppressed IFN induction in the F/ARFP mutant. The F/ARFP mutants, on the other hand, were not resistant to exogenous IFNα. Finally, HCV-infected human liver samples showed significant F/ARFP antibody reactivity, compared to HCV-uninfected control livers. Therefore, HCV F/ARFP likely cooperates with other viral factors to suppress type I and III IFN induction occurring through the RIG-I signaling pathway. This study identifies a novel mechanism of pattern recognition receptor modulation by HCV and suggests a biological function of the HCV alternate reading frame in the modulation of host innate immunity.

A saponin-detoxifying enzyme mediates suppression of plant defences

Science.gov (United States)

Bouarab, K.; Melton, R.; Peart, J.; Baulcombe, D.; Osbourn, A.

2002-08-01

Plant disease resistance can be conferred by constitutive features such as structural barriers or preformed antimicrobial secondary metabolites. Additional defence mechanisms are activated in response to pathogen attack and include localized cell death (the hypersensitive response). Pathogens use different strategies to counter constitutive and induced plant defences, including degradation of preformed antimicrobial compounds and the production of molecules that suppress induced plant defences. Here we present evidence for a two-component process in which a fungal pathogen subverts the preformed antimicrobial compounds of its host and uses them to interfere with induced defence responses. Antimicrobial saponins are first hydrolysed by a fungal saponin-detoxifying enzyme. The degradation product of this hydrolysis then suppresses induced defence responses by interfering with fundamental signal transduction processes leading to disease resistance.

A DC-DC Conversion Powering Scheme for the CMS Phase-1 Pixel Upgrade

CERN Document Server

Feld, Lutz Werner; Marcel Friedrichs; Richard Hensch; Karpinski, Waclaw; Klein, Katja; Sammet, Jan Domenik; Wlochal, Michael

2012-01-01

The powering scheme of the CMS pixel detector will be described, and the performance of prototype DC-DC buck converters will be presented, including power efficiency, system tests with DC-DC converters and pixel modules, thermal management, reliability at low temperature, and studies of potential frequency locking betwe...

Study on the Control Algorithm of Two-Stage DC-DC Converter for Electric Vehicles

Directory of Open Access Journals (Sweden)

Changhao Piao

2014-01-01

Full Text Available The fast response, high efficiency, and good reliability are very important characteristics to electric vehicles (EVs dc/dc converters. Two-stage dc-dc converter is a kind of dc-dc topologies that can offer those characteristics to EVs. Presently, nonlinear control is an active area of research in the field of the control algorithm of dc-dc converters. However, very few papers research on two-stage converter for EVs. In this paper, a fixed switching frequency sliding mode (FSFSM controller and double-integral sliding mode (DISM controller for two-stage dc-dc converter are proposed. And a conventional linear control (lag is chosen as the comparison. The performances of the proposed FSFSM controller are compared with those obtained by the lag controller. In consequence, the satisfactory simulation and experiment results show that the FSFSM controller is capable of offering good large-signal operations with fast dynamical responses to the converter. At last, some other simulation results are presented to prove that the DISM controller is a promising method for the converter to eliminate the steady-state error.

The interleukin-15 system suppresses T cell-mediated autoimmunity by regulating negative selection and nT(H)17 cell homeostasis in the thymus.

Science.gov (United States)

Hou, Mau-Sheng; Huang, Shih-Ting; Tsai, Ming-Han; Yen, Ching-Cheng; Lai, Yein-Gei; Liou, Yae-Huei; Lin, Chih-Kung; Liao, Nan-Shih

2015-01-01

The interleukin-15 (IL-15) system is important for regulating both innate and adaptive immune responses, however, its role in autoimmune disease remained unclear. Here we found that Il15(-/-) and Il15ra(-/-) mice spontaneously developed late-onset autoimmune phenotypes. CD4(+) T cells of the knockout mice showed elevated autoreactivity as demonstrated by the induction of lymphocyte infiltration in the lacrimal and salivary glands when transferred into nude mice. The antigen-presenting cells in the thymic medullary regions expressed IL-15 and IL-15Rα, whose deficiency resulted in insufficient negative selection and elevated number of natural IL-17A-producing CD4(+) thymocytes. These findings reveal previously unknown functions of the IL-15 system in thymocyte development, and thus a new layer of regulation in T cell-mediated autoimmunity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Selective serotonin reuptake inhibitor suppression of HIV infectivity and replication.

Science.gov (United States)

Benton, Tami; Lynch, Kevin; Dubé, Benoit; Gettes, David R; Tustin, Nancy B; Ping Lai, Jian; Metzger, David S; Blume, Joshua; Douglas, Steven D; Evans, Dwight L

2010-11-01

To test the hypothesis that the selective serotonin reuptake inhibitor (SSRI) citalopram would down-regulate human immunodeficiency virus (HIV) infectivity and that the greatest effects would be seen in people with depression. Depression is a risk factor for morbidity and mortality in HIV/acquired immune deficiency syndrome. Serotonin (5-HT) neurotransmission has been implicated in the pathobiology of depression, and pharmacologic therapies for depression target this system. The 5-HT transporter and 5-HT receptors are widely distributed throughout the central nervous and immune systems. Depression has been associated with suppression of natural killer cells and CD8(+) lymphocytes, key regulators of HIV infection. Ex vivo models for acute and chronic HIV infection were used to study the effects of citalopram on HIV viral infection and replication in 48 depressed and nondepressed women. For both the acute and chronic infection models, HIV reverse transcriptase activity was measured in the citalopram treatment condition and the control condition. The SSRI significantly down-regulated the reverse transcriptase response in both the acute and chronic infection models. Specifically, citalopram significantly decreased the acute HIV infectivity of macrophages. Citalopram also significantly decreased HIV viral replication in the latently infected T-cell line and in the latently infected macrophage cell line. There was no difference in down-regulation by depression status. These studies suggest that an SSRI enhances natural killer/CD8 noncytolytic HIV suppression in HIV/acquired immune deficiency syndrome and decreases HIV viral infectivity of macrophages, ex vivo, suggesting the need for in vivo studies to determine a potential role for agents targeting serotonin in the host defense against HIV.

Suppression of NFAT5-mediated Inflammation and Chronic Arthritis by Novel κB-binding Inhibitors

Directory of Open Access Journals (Sweden)

Eun-Jin Han

2017-04-01

Full Text Available Nuclear factor of activated T cells 5 (NFAT5 has been implicated in the pathogenesis of various human diseases, including cancer and arthritis. However, therapeutic agents inhibiting NFAT5 activity are currently unavailable. To discover NFAT5 inhibitors, a library of >40,000 chemicals was screened for the suppression of nitric oxide, a direct target regulated by NFAT5 activity, through high-throughput screening. We validated the anti-NFAT5 activity of 198 primary hit compounds using an NFAT5-dependent reporter assay and identified the novel NFAT5 suppressor KRN2, 13-(2-fluoro-benzylberberine, and its derivative KRN5. KRN2 inhibited NFAT5 upregulation in macrophages stimulated with lipopolysaccharide and repressed the formation of NF-κB p65-DNA complexes in the NFAT5 promoter region. Interestingly, KRN2 selectively suppressed the expression of pro-inflammatory genes, including Nos2 and Il6, without hampering high-salt-induced NFAT5 and its target gene expressions. Moreover, KRN2 and KRN5, the latter of which exhibits high oral bioavailability and metabolic stability, ameliorated experimentally induced arthritis in mice without serious adverse effects, decreasing pro-inflammatory cytokine production. Particularly, orally administered KRN5 was stronger in suppressing arthritis than methotrexate, a commonly used anti-rheumatic drug, displaying better potency and safety than its original compound, berberine. Therefore, KRN2 and KRN5 can be potential therapeutic agents in the treatment of chronic arthritis.

Decentralized control of the COFS-I Mast using linear dc motors

Science.gov (United States)

Lindner, Douglas K.; Celano, Tom; Ide, Eric

1989-01-01

Consideration is given to a decentralized control design for vibration suppression in the COFS-I Mast using linear dc motors for actuators. The decentralized control design is based results from power systems using root locus techniques that are not well known. The approach is effective because the loop gain is low due to low actuator authority. The frequency-dependent nonlinearities of the actuator are taken into account. Because of the tendency of the transients to saturate the the stroke length of the actuator, its effectiveness is limited.

A novel analog/digital reconfigurable automatic gain control with a novel DC offset cancellation circuit

Energy Technology Data Exchange (ETDEWEB)

He Xiaofeng; Ye Tianchun [Institute of Microelectronics, Chinese Academy of Science, Beijing 100029 (China); Mo Taishan; Ma Chengyan, E-mail: hexiaofeng@casic.ac.cn [Hangzhou Zhongke Microelectronics Co, Ltd, Hangzhou 310053 (China)

2011-02-15

An analog/digital reconfigurable automatic gain control (AGC) circuit with a novel DC offset cancellation circuit for a direct-conversion receiver is presented. The AGC is analog/digital reconfigurable in order to be compatible with different baseband chips. What's more, a novel DC offset cancellation (DCOC) circuit with an HPCF (high pass cutoff frequency) less than 10 kHz is proposed. The AGC is fabricated by a 0.18 {mu}m CMOS process. Under analog control mode, the AGC achieves a 70 dB dynamic range with a 3 dB-bandwidth larger than 60 MHz. Under digital control mode, through a 5-bit digital control word, the AGC shows a 64 dB gain control range by 2 dB each step with a gain error of less than 0.3 dB. The DC offset cancellation circuits can suppress the output DC offset voltage to be less than 1.5 mV, while the offset voltage of 40 mV is introduced into the input. The overall power consumption is less than 3.5 mA, and the die area is 800 x 300 {mu}m{sup 2}. (semiconductor integrated circuits)

Suppression of Thyroid Hormone Receptor-Mediated Transcription ...

African Journals Online (AJOL)

TH)-induced TR-mediated transcription. We further examined the effects of methamidophos on TR-thyroid hormone response element (TRE) binding using the liquid chemiluminescent DNA pull-down assay (LCDPA), and found no dissociation of ...

EPHA2 is a mediator of vemurafenib resistance and a novel therapeutic target in melanoma.

Science.gov (United States)

Miao, Benchun; Ji, Zhenyu; Tan, Li; Taylor, Michael; Zhang, Jianming; Choi, Hwan Geun; Frederick, Dennie T; Kumar, Raj; Wargo, Jennifer A; Flaherty, Keith T; Gray, Nathanael S; Tsao, Hensin

2015-03-01

BRAF(V600E) is the most common oncogenic lesion in melanoma and results in constitutive activation of the MAPK pathway and uncontrolled cell growth. Selective BRAF inhibitors such as vemurafenib have been shown to neutralize oncogenic signaling, restrain cellular growth, and improve patient outcome. Although several mechanisms of vemurafenib resistance have been described, directed solutions to overcome these resistance lesions are still lacking. Herein, we found that vemurafenib resistance can be (i) mediated by EPHA2, a member of the largest receptor tyrosine kinases (RTK) subfamily erythropoietin-producing hepatocellular (EPH) receptors, and (ii) associated with a greater phenotypic dependence on EPHA2. Furthermore, we developed a series of first-in-class EPHA2 inhibitors and show that these new compounds potently induce apoptosis, suppress viability, and abrogate tumorigenic growth of melanoma cells, including those that are resistant to vemurafenib. These results provide proof of concept that RTK-guided growth, and therapeutic resistance, can be prospectively defined and selectively targeted. In this study, we show that resistance to selective BRAF inhibitors can be mediated by the RTK EPHA2. Furthermore, direct targeting of EPHA2 can successfully suppress melanoma growth and mitigate therapeutic resistance. ©2014 American Association for Cancer Research.

Ubiquitin carboxyl terminal hydrolase L1 negatively regulates TNFα-mediated vascular smooth muscle cell proliferation via suppressing ERK activation

International Nuclear Information System (INIS)

Ichikawa, Tomonaga; Li, Jinqing; Dong, Xiaoyu; Potts, Jay D.; Tang, Dong-Qi; Li, Dong-Sheng; Cui, Taixing

2010-01-01

Deubiquitinating enzymes (DUBs) appear to be critical regulators of a multitude of processes such as proliferation, apoptosis, differentiation, and inflammation. We have recently demonstrated that a DUB of ubiquitin carboxyl terminal hydrolase L1 (UCH-L1) inhibits vascular lesion formation via suppressing inflammatory responses in vasculature. However, the precise underlying mechanism remains to be defined. Herein, we report that a posttranscriptional up-regulation of UCH-L1 provides a negative feedback to tumor necrosis factor alpha (TNFα)-mediated activation of extracellular signal-regulated kinases (ERK) and proliferation in vascular smooth muscle cells (VSMCs). In rat adult VSMCs, adenoviral over-expression of UCH-L1 inhibited TNFα-induced activation of ERK and DNA synthesis. In contrast, over-expression of UCH-L1 did not affect platelet derived growth factor (PDGF)-induced VSMC proliferation and activation of growth stimulating cascades including ERK. TNFα hardly altered UCH-L1 mRNA expression and stability; however, up-regulated UCH-L1 protein expression via increasing UCH-L1 translation. These results uncover a novel mechanism by which UCH-L1 suppresses vascular inflammation.

Optimal Constant DC Link Voltage Operation of aWave Energy Converter

Directory of Open Access Journals (Sweden)

Mats Leijon

2013-04-01

Full Text Available This article proposes a simple and reliable damping strategy for wave powerfarm operation of small-scale point-absorber converters. The strategy is based on passiverectification onto a constant DC-link, making it very suitable for grid integration of the farm.A complete model of the system has been developed in Matlab Simulink, and uses real sitedata as input. The optimal constant DC-voltage is evaluated as a function of the significantwave height and energy period of the waves. The total energy output of the WEC is derivedfor one year of experimental site data. The energy output is compared for two cases, onewhere the optimal DC-voltage is determined and held constant at half-hour basis throughoutthe year, and one where a selected value of the DC-voltage is kept constant throughout theyear regardless of sea state.

Elimination of output voltage oscillations in DC-DC converter using PWM with PI controller

Directory of Open Access Journals (Sweden)

Sreenivasappa Veeranna Bhupasandra

2010-01-01

Full Text Available In this paper the SIMULINK model of a PWM controlled DC-DC converter is modeled using switching function concept to control the speed of the DC motor. The presence of the voltage oscillation cycles due to higher switching frequency in the DC-DC converter is identified. The effect of these oscillations on the output voltage of the converter, Armature current, Developed torque and Speed of the DC motor is analyzed. In order to minimize the oscillation cycles the PI controller is proposed in the PWM controller.

Analysis of high voltage step-up nonisolated DC-DC boost converters

Science.gov (United States)

Alisson Alencar Freitas, Antônio; Lessa Tofoli, Fernando; Junior, Edilson Mineiro Sá; Daher, Sergio; Antunes, Fernando Luiz Marcelo

2016-05-01

A high voltage step-up nonisolated DC-DC converter based on coupled inductors suitable to photovoltaic (PV) systems applications is proposed in this paper. Considering that numerous approaches exist to extend the voltage conversion ratio of DC-DC converters that do not use transformers, a detailed comparison is also presented among the proposed converter and other popular topologies such as the conventional boost converter and the quadratic boost converter. The qualitative analysis of the coupled-inductor-based topology is developed so that a design procedure can be obtained, from which an experimental prototype is implemented to validate the theoretical assumptions.

Common mode noise in three-level DC-DC converters

CSIR Research Space (South Africa)

Grobler, Inus

2009-09-01

Full Text Available that three-level buck DC-DC converters in general generate much lower common mode currents than conventional two-level buck converters. Further, reductions in common mode currents are achieved by using the improved three-level topologies that have been...

Selective Mitochondrial Uptake of MKT-077 Can Suppress Medullary Thyroid Carcinoma Cell Survival and

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Dmytro Starenki

2015-12-01

Full Text Available BackgroundMedullary thyroid carcinoma (MTC is a neuroendocrine tumor mainly caused by mutations in the rearranged during transfection (RET proto-oncogene. Not all patients with progressive MTC respond to current therapy inhibiting RET, demanding additional therapeutic strategies. We recently demonstrated that disrupting mitochondrial metabolism using a mitochondria-targeted agent or by depleting a mitochondrial chaperone effectively suppressed human MTC cells in culture and in mouse xenografts by inducing apoptosis and RET downregulation. These observations led us to hypothesize that mitochondria are potential therapeutic targets for MTC. This study further tests this hypothesis using1-ethyl-2-[[3-ethyl-5-(3-methylbenzothiazolin-2-yliden]-4-oxothiazolidin-2-ylidenemethyl] pyridinium chloride (MKT-077, a water-soluble rhodocyanine dye analogue, which can selectively accumulate in mitochondria.MethodsThe effects of MKT-077 on cell proliferation, survival, expression of RET and tumor protein 53 (TP53, and mitochondrial activity were determined in the human MTC lines in culture and in mouse xenografts.ResultsMKT-077 induced cell cycle arrest in TT and MZ-CRC-1. Intriguingly, MKT-077 also induced RET downregulation and strong cell death responses in TT cells, but not in MZ-CRC-1 cells. This discrepancy was mainly due to the difference between the capacities of these cell lines to retain MKT-077 in mitochondria. The cytotoxicity of MKT-077 in TT cells was mainly attributed to oxidative stress while being independent of TP53. MKT-077 also effectively suppressed tumor growth of TT xenografts.ConclusionMKT-077 can suppress cell survival of certain MTC subtypes by accumulating in mitochondria and interfering with mitochondrial activity although it can also suppress cell proliferation via other mechanisms. These results consistently support the hypothesis that mitochondrial targeting has therapeutic potential for MTC.

Analysis and Design of Bi-Directional DC-DC Converter in the Extended Run Time DC UPS System Based on Fuel Cell and Supercapacitor

DEFF Research Database (Denmark)

Zhang, Zhe; Thomsen, Ole Cornelius; Andersen, Michael A. E.

2009-01-01

Abstract-In this paper, an extended run time DC UPS system structure with fuel cell and supercapacitor is investigated. A wide input range bi-directional dc-dc converter is described along with the phase-shift modulation scheme and phase-shift with duty cycle control, in different modes. The deli......Abstract-In this paper, an extended run time DC UPS system structure with fuel cell and supercapacitor is investigated. A wide input range bi-directional dc-dc converter is described along with the phase-shift modulation scheme and phase-shift with duty cycle control, in different modes...

Mode of ATM-dependent suppression of chromosome translocation

Energy Technology Data Exchange (ETDEWEB)

Yamauchi, Motohiro, E-mail: motoyama@nagasaki-u.ac.jp [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Suzuki, Keiji; Oka, Yasuyoshi; Suzuki, Masatoshi; Kondo, Hisayoshi; Yamashita, Shunichi [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)

2011-12-09

Highlights: Black-Right-Pointing-Pointer We addressed how ATM suppresses frequency of chromosome translocation. Black-Right-Pointing-Pointer We found ATM/p53-dependent G1 checkpoint suppresses translocation frequency. Black-Right-Pointing-Pointer We found ATM and DNA-PKcs function in a common pathway to suppress translocation. -- Abstract: It is well documented that deficiency in ataxia telangiectasia mutated (ATM) protein leads to elevated frequency of chromosome translocation, however, it remains poorly understood how ATM suppresses translocation frequency. In the present study, we addressed the mechanism of ATM-dependent suppression of translocation frequency. To know frequency of translocation events in a whole genome at once, we performed centromere/telomere FISH and scored dicentric chromosomes, because dicentric and translocation occur with equal frequency and by identical mechanism. By centromere/telomere FISH analysis, we confirmed that chemical inhibition or RNAi-mediated knockdown of ATM causes 2 to 2.5-fold increase in dicentric frequency at first mitosis after 2 Gy of gamma-irradiation in G0/G1. The FISH analysis revealed that ATM/p53-dependent G1 checkpoint suppresses dicentric frequency, since RNAi-mediated knockdown of p53 elevated dicentric frequency by 1.5-fold. We found ATM also suppresses dicentric occurrence independently of its checkpoint role, as ATM inhibitor showed additional effect on dicentric frequency in the context of p53 depletion and Chk1/2 inactivation. Epistasis analysis using chemical inhibitors revealed that ATM kinase functions in the same pathway that requires kinase activity of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to suppress dicentric frequency. From the results in the present study, we conclude that ATM minimizes translocation frequency through its commitment to G1 checkpoint and DNA double-strand break repair pathway that requires kinase activity of DNA-PKcs.

DC-DC power converter research for Orbiter/Station power exchange

Science.gov (United States)

Ehsani, M.

1993-01-01

This project was to produce innovative DC-DC power converter concepts which are appropriate for the power exchange between the Orbiter and the Space Station Freedom (SSF). The new converters must interface three regulated power buses on SSF, which are at different voltages, with three fuel cell power buses on the Orbiter which can be at different voltages and should be tracked independently. Power exchange is to be bi-directional between the SSF and the Orbiter. The new converters must satisfy the above operational requirements with better weight, volume, efficiency, and reliability than is available from the present conventional technology. Two families of zero current DC-DC converters were developed and successfully adapted to this application. Most of the converters developed are new and are presented.

Analysis of dc-Link Voltage Switching Ripple in Three-Phase PWM Inverters

Directory of Open Access Journals (Sweden)

Marija Vujacic

2018-02-01

Full Text Available The three-phase voltage source inverter (VSI is de facto standard in power conversion systems. To realize high power density systems, one of the items to be correctly addressed is the design and selection of the dc-link capacitor in relation to the voltage switching ripple. In this paper, effective formulas for designing the dc-link capacitor as a function of the switching voltage ripple amplitude are obtained, considering the operating conditions such as the modulation index and the output current amplitude. The calculations are obtained considering the requirements and restrictions referring to the high (switching-frequency dc-link voltage ripple component. Analyses have been performed considering the dc source impedance (non-ideal dc voltage source at the switching frequency and a balanced load. Analytical expressions are derived for the dc-link voltage switching ripple amplitude and its maximum value over the fundamental period. Different values of modulation index and output phase angle have been considered and different diagrams are presented. Analytical results were validated both by simulations and comprehensive experimental tests.

Contribution of Ruminal Fungi, Archaea, Protozoa, and Bacteria to the Methane Suppression Caused by Oilseed Supplemented Diets

OpenAIRE

Wang, Shaopu; Giller, Katrin; Kreuzer, Michael; Ulbrich, Susanne E.; Braun, Ueli; Schwarm, Angela

2017-01-01

Dietary lipids can suppress methane emission from ruminants, but effects are variable. Especially the role of bacteria, archaea, fungi and protozoa in mediating the lipid effects is unclear. In the present in vitro study, archaea, fungi and protozoa were selectively inhibited by specific agents. This was fully or almost fully successful for fungi and protozoa as well as archaeal activity as determined by the methyl-coenzyme M reductase alpha subunit gene. Five different microbial treatments w...

Sliding-mode control of single input multiple output DC-DC converter

Science.gov (United States)

Zhang, Libo; Sun, Yihan; Luo, Tiejian; Wan, Qiyang

2016-10-01

Various voltage levels are required in the vehicle mounted power system. A conventional solution is to utilize an independent multiple output DC-DC converter whose cost is high and control scheme is complicated. In this paper, we design a novel SIMO DC-DC converter with sliding mode controller. The proposed converter can boost the voltage of a low-voltage input power source to a controllable high-voltage DC bus and middle-voltage output terminals, which endow the converter with characteristics of simple structure, low cost, and convenient control. In addition, the sliding mode control (SMC) technique applied in our converter can enhance the performances of a certain SIMO DC-DC converter topology. The high-voltage DC bus can be regarded as the main power source to the high-voltage facility of the vehicle mounted power system, and the middle-voltage output terminals can supply power to the low-voltage equipment on an automobile. In the respect of control algorithm, it is the first time to propose the SMC-PID (Proportion Integration Differentiation) control algorithm, in which the SMC algorithm is utilized and the PID control is attended to the conventional SMC algorithm. The PID control increases the dynamic ability of the SMC algorithm by establishing the corresponding SMC surface and introducing the attached integral of voltage error, which endow the sliding-control system with excellent dynamic performance. At last, we established the MATLAB/SIMULINK simulation model, tested performance of the system, and built the hardware prototype based on Digital Signal Processor (DSP). Results show that the sliding mode control is able to track a required trajectory, which has robustness against the uncertainties and disturbances.

Inefficient HIV-1 trans infection of CD4+ T cells by macrophages from HIV-1 nonprogressors is associated with altered membrane cholesterol and DC-SIGN.

Science.gov (United States)

DeLucia, Diana C; Rinaldo, Charles R; Rappocciolo, Giovanna

2018-04-11

Professional antigen presenting cells (APC: myeloid dendritic cells (DC) and macrophages (MΦ); B lymphocytes) mediate highly efficient HIV-1 infection of CD4 + T cells, termed trans infection, that could contribute to HIV-1 pathogenesis. We have previously shown that lower cholesterol content in DC and B lymphocytes is associated with a lack of HIV-1 trans infection in HIV-1 infected nonprogressors (NP). Here we assessed whether HIV-1 trans infection mediated by another major APC, MΦ, is deficient in NP due to altered cholesterol metabolism. When comparing healthy HIV-1 seronegatives (SN), rapid progressors (PR), and NP, we found that monocyte-derived MΦ from NP did not mediate HIV-1 trans infection of autologous CD4 + T cells, in contrast to efficient trans infection mediated by SN and PR MΦ. MΦ trans infection efficiency was directly associated with the number of DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN)-expressing MΦ. Significantly fewer NP MΦ expressed DC-SIGN. Unesterified (free) cholesterol in MΦ cell membranes and lipid rafting was significantly lower in NP than PR, as well as virus internalization in early endosomes. Furthermore, simvastatin (SIMV), decreased the subpopulation of DC-SIGN + MΦ, as well as MΦ cis and trans infection. Notably, SIMV decreased cell membrane cholesterol and led to lipid raft dissociation, effectively mimicking the incompetent APC trans infection environment characteristic of NP. Our data support that DC-SIGN and membrane cholesterol are central to MΦ trans infection, and a lack of these limits HIV-1 disease progression. Targeting the ability of MΦ to drive HIV-1 dissemination in trans could enhance HIV-1 therapeutic strategies. IMPORTANCE Despite the success of combination anti-retroviral therapy, neither a vaccine nor a cure for HIV infection has been developed, demonstrating a need for novel prophylactic and therapeutic strategies. Here we show that efficiency of macrophage (M�

Y-Source Boost DC/DC Converter for Distributed Generation

DEFF Research Database (Denmark)

Siwakoti, Yam P.; Loh, Poh Chiang; Blaabjerg, Frede

2015-01-01

This paper introduces a versatile Y-source boost dc/dc converter intended for distributed power generation, where high gain is often demanded. The proposed converter uses a Y-source impedance network realized with a tightly coupled three-winding inductor for high voltage boosting that is presently...

Influence of DC plasma modification on the selected properties and the geometrical surface structure of polylactide prior to autocatalytic metallization

Energy Technology Data Exchange (ETDEWEB)

Moraczewski, Krzysztof, E-mail: kmm@ukw.edu.pl [Kazimierz Wielki University, Chodkiewicza 30, 85-064 Bydgoszcz (Poland); Rytlewski, Piotr [Kazimierz Wielki University, Chodkiewicza 30, 85-064 Bydgoszcz (Poland); Malinowski, Rafał [Institute for Engineering of Polymer Materials and Dyes, Marii Skłodowskiej-Curie 55, 87-100 Toruń (Poland); Tracz, Adam [Centre for Molecular and Macromolecular Studies of the Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź (Poland); Żenkiewicz, Marian [Institute for Engineering of Polymer Materials and Dyes, Marii Skłodowskiej-Curie 55, 87-100 Toruń (Poland)

2015-03-01

The paper presents the results of studies to determine the applicability of plasma modification in the process of polylactide (PLA) surface preparation prior to the autocatalytic metallization. The polylactide plasma modification was carried out in an oxygen or nitrogen chemistry. The samples were tested with the following methods: scanning electron microscopy (SEM), atomic force microscopy (AFM), goniometry and electron spectrophotometry (XPS). Scanning electron microscopy and atomic force microscopy images were demonstrated. The results of surface free energy calculations, performed based on the results of the contact angle measurements have been presented. The results of the qualitative (degree of oxidation or nitridation) and quantitative analysis of the chemical composition of the polylactide surface layer have also been described. The results of the studies show that the DC plasma modification performed in the proposed condition is a suitable as a method of surface preparation for the polylactide metallization. - Highlights: • We modified polylactide surface layer with plasma generated in oxygen or nitrogen. • We tested selected properties and surface structure of modified samples. • DC plasma modification can be used to prepare the PLA surface for metallization. • For better results metallization should be preceded by sonication process.

SUBCONTRACT REPORT: DC-DC Converter for Fuel Cell and Hybrid Vehicles

Energy Technology Data Exchange (ETDEWEB)

Marlino, Laura D [ORNL; Zhu, Lizhi [Ballard Power Systems/Siemens VDO

2007-07-01

The goal of this project is to develop and fabricate a 5kW dc-dc converter with a baseline 14V output capability for fuel cell and hybrid vehicles. The major objectives for this dc-dc converter technology are to meet: Higher efficiency (92%); High coolant temperature,e capability (105 C); High reliability (15 Years/150,000miles); Smaller volume (5L); Lower weight (6kg); and Lower cost ($75/kW). The key technical challenge for these converters is the 105 C coolant temperatures. The power switches and magnetics must be designed to sustain these operating temperatures reliably, without a large cost/mass/volume penalty.

Multi-level cascaded DC/DC converters for PV applications

Directory of Open Access Journals (Sweden)

Ahmed A.A. Hafez

2015-12-01

Full Text Available A robust multi-level cascaded DC/DC system for Photovoltaic (PV application is advised in this article. There are three PV generators, each is coupled to a half-bridge buck cell. Each PV-generator–buck-converter channel is controlled such that maximum power is captured independently under different irradiation and temperature levels. The system operation under normal and abnormal conditions was comprehensively investigated. Internal Model Control (IMC technique was adopted for tuning the controllers. An elaborate switching modulation strategy was used to reduce the current ripple and inductor size, while maintaining high efficiency. Annotative, simple and robust remedial strategies were proposed to mitigate different anticipated faults. Comprehensive simulation results in Matlab environment were illustrated for corroborating the performance of the advised cascaded DC/DC system under normal/abnormal conditions. The proposed system enjoys the merits of independency, reduced volumetric dimensions and improved efficiency. Furthermore, the system is inherently fault-tolerant.

Selective suppression of endothelial cytokine production by progesterone receptor.

Science.gov (United States)

Goddard, Lauren M; Ton, Amy N; Org, Tõnis; Mikkola, Hanna K A; Iruela-Arispe, M Luisa

2013-01-01

Steroid hormones are well-recognized suppressors of the inflammatory response, however, their cell- and tissue-specific effects in the regulation of inflammation are far less understood, particularly for the sex-related steroids. To determine the contribution of progesterone in the endothelium, we have characterized and validated an in vitro culture system in which human umbilical vein endothelial cells constitutively express human progesterone receptor (PR). Using next generation RNA-sequencing, we identified a selective group of cytokines that are suppressed by progesterone both under physiological conditions and during pathological activation by lipopolysaccharide. In particular, IL-6, IL-8, CXCL2/3, and CXCL1 were found to be direct targets of PR, as determined by ChIP-sequencing. Regulation of these cytokines by progesterone was also confirmed by bead-based multiplex cytokine assays and quantitative PCR. These findings provide a novel role for PR in the direct regulation of cytokine levels secreted by the endothelium. They also suggest that progesterone-PR signaling in the endothelium directly impacts leukocyte trafficking in PR-expressing tissues. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

PR-957, a selective inhibitor of immunoproteasome subunit low-MW polypeptide 7, attenuates experimental autoimmune neuritis by suppressing Th17-cell differentiation and regulating cytokine production.

Science.gov (United States)

Liu, Haijie; Wan, Chunxiao; Ding, Yanan; Han, Ranran; He, Yating; Xiao, Jinting; Hao, Junwei

2017-04-01

Experimental autoimmune neuritis (EAN) is a CD4 + T-cell-mediated autoimmune inflammatory demyelinating disease of the peripheral nervous system. It has been replicated in an animal model of human inflammatory demyelinating polyradiculoneuropathy, Guillain-Barré syndrome. In this study, we evaluated the therapeutic efficacy of a selective inhibitor of the immunoproteasome subunit, low-MW polypeptide 7 (PR-957) in rats with EAN. Our results showed that PR-957 significantly delayed onset day, reduced severity and shortened duration of EAN, and alleviated demyelination and inflammatory infiltration in sciatic nerves. In addition to significantly regulating expression of the cytokine profile, PR-957 treatment down-regulated the proportion of proinflammatory T-helper (T h )17 cells in sciatic nerves and spleens of rats with EAN. Data presented show the role of PR-957 in the signal transducer and activator of transcription 3 (STAT3) pathway. PR-957 not only decreased expression of IL-6 and IL-23 but also led to down-regulation of STAT3 phosphorylation in CD4 + T cells. Regulation of the STAT3 pathway led to a reduction in retinoid-related orphan nuclear receptor γ t and IL-17 production. Furthermore, reduction of STAT3 phosphorylation may have directly suppressed T h 17-cell differentiation. Therefore, our study demonstrates that PR-957 could potently alleviate inflammation in rats with EAN and that it may be a likely candidate for treating Guillain-Barré syndrome.-Liu, H., Wan, C., Ding, Y., Han, R., He, Y., Xiao, J., Hao, J. PR-957, a selective inhibitor of immunoproteasome subunit low-MW polypeptide 7, attenuates experimental autoimmune neuritis by suppressing T h 17-cell differentiation and regulating cytokine production. © FASEB.

Development of a DC-DC conversion powering scheme for the CMS Phase-1 pixel upgrade

CERN Document Server

Feld, Lutz Werner; Karpinski, Waclaw; Klein, Katja; Lipinski, Martin; Preuten, Marius; Max Rauch; Rittich, David Michael; Sammet, Jan Domenik; Wlochal, Michael

2014-01-01

A novel powering scheme based on the DC-DC conversion technique will be exploited to power the CMS Phase-1 pixel detector. DC-DC buck converters for the CMS pixel project have been developed, based on the AMIS5 ASIC designed by CERN. The powering system of the Phase-1 pixel detector is described and the performance of the converter prototypes is detailed, including power efficiency, stability of the output voltage, shielding, and thermal management. Results from a test of the magnetic field tolerance of the DC-DC converters are reported. System tests with pixel modules using many components of the future pixel barrel system are summarized. Finally first impressions from a pre-series of 200 DC-DC converters are presented.

Antibody-mediated immunity to the obligate intracellular bacterial pathogen Coxiella burnetii is Fc receptor- and complement-independent

Directory of Open Access Journals (Sweden)

Heinzen Robert A

2009-05-01

Full Text Available Abstract Background The obligate intracellular bacterial pathogen Coxiella burnetii causes the zoonosis Q fever. The intracellular niche of C. burnetii has led to the assumption that cell-mediated immunity is the most important immune component for protection against this pathogen. However, passive immunization with immune serum can protect naïve animals from challenge with virulent C. burnetii, indicating a role for antibody (Ab in protection. The mechanism of this Ab-mediated protection is unknown. Therefore, we conducted a study to determine whether Fc receptors (FcR or complement contribute to Ab-mediated immunity (AMI to C. burnetii. Results Virulent C. burnetii infects and replicates within human dendritic cells (DC without inducing their maturation or activation. We investigated the effects of Ab opsonized C. burnetii on human monocyte-derived and murine bone marrow-derived DC. Infection of DC with Ab-opsonized C. burnetii resulted in increased expression of maturation markers and inflammatory cytokine production. Bacteria that had been incubated with naïve serum had minimal effect on DC, similar to virulent C. burnetii alone. The effect of Ab opsonized C. burnetii on DC was FcR dependent as evidenced by a reduced response of DC from FcR knockout (FcR k/o compared to C57Bl/6 (B6 mice. To address the potential role of FcR in Ab-mediated protection in vivo, we compared the response of passively immunized FcR k/o mice to the B6 controls. Interestingly, we found that FcR are not essential for AMI to C. burnetii in vivo. We subsequently examined the role of complement in AMI by passively immunizing and challenging several different strains of complement-deficient mice and found that AMI to C. burnetii is also complement-independent. Conclusion Despite our data showing FcR-dependent stimulation of DC in vitro, Ab-mediated immunity to C. burnetii in vivo is FcR-independent. We also found that passive immunity to this pathogen is independent of

Auxiliary resonant DC tank converter

Science.gov (United States)

Peng, Fang Z.

2000-01-01

An auxiliary resonant dc tank (ARDCT) converter is provided for achieving soft-switching in a power converter. An ARDCT circuit is coupled directly across a dc bus to the inverter to generate a resonant dc bus voltage, including upper and lower resonant capacitors connected in series as a resonant leg, first and second dc tank capacitors connected in series as a tank leg, and an auxiliary resonant circuit comprising a series combination of a resonant inductor and a pair of auxiliary switching devices. The ARDCT circuit further includes first clamping means for holding the resonant dc bus voltage to the dc tank voltage of the tank leg, and second clamping means for clamping the resonant dc bus voltage to zero during a resonant period. The ARDCT circuit resonantly brings the dc bus voltage to zero in order to provide a zero-voltage switching opportunity for the inverter, then quickly rebounds the dc bus voltage back to the dc tank voltage after the inverter changes state. The auxiliary switching devices are turned on and off under zero-current conditions. The ARDCT circuit only absorbs ripples of the inverter dc bus current, thus having less current stress. In addition, since the ARDCT circuit is coupled in parallel with the dc power supply and the inverter for merely assisting soft-switching of the inverter without participating in real dc power transmission and power conversion, malfunction and failure of the tank circuit will not affect the functional operation of the inverter; thus a highly reliable converter system is expected.

Pollinator-mediated selection on nectary depth in Urophysa (Ranunculaceae

Directory of Open Access Journals (Sweden)

Li Sun

2016-04-01

Full Text Available Pollinator-mediated selection has been considered to be one of major factors that shapes the evolution of flowers by matching flowers to their pollinators on traits associated with attraction of pollinators or mechanical fit. The match between nectary depth, which means the length of the tubular structure formed in many plant species to hide the nectary and store nectar, and the mouthparts length of its major nectar-foraging pollinators has been repeatedly demonstrated as an example, because this trait have shown a positive relationship with pollen removal and deposition in experimental manipulations in many synpetalous plants and orchid family. However, it remains unclear how pollinator-mediated selection affects the evolution of nectary depth in choripetalous and actinomorphic flowers, such as most flowers in Ranunculaceae. Here we investigated floral characteristics and pollinators in Urophysa rockii Ulbr. and U. henryi (Oliv. Ulbr., as they are quite the same in habitat, anthesis and morphological characteristics except for nectary depth. Both of these species have flat white sepals and yellow petals each has a spatial structure at the base that contains nectar, but the nectary depth of U. rockii is deeper than that of U. henryi, for the former petals are shortly spurred about 3-4mm in length while the latter are saccate. Meanwhile, the flowers of both species are most frequently visited by Apis cerana, the Chinese honey bee, and one or two species of hover fly, Syrphidae, but only A. cerana was able to forage nectar in U. rockii while all visitors can forage nectar in U. henryi. A. cerana always lands on the center of a flower and projects its proboscis into each petal when its thorax touches anthers and stigmas. The difference between two species is that U. rockii was visited by A. cerana with a higher frequency, longer visiting time per flower and more activities on flowers than U. henryi. Besides, the petal width and its nectary depth of

Interaction and inhibition of dengue envelope glycoprotein with mammalian receptor DC-sign, an in-silico approach.

Directory of Open Access Journals (Sweden)

Masaud Shah

Full Text Available Membrane fusion is the central molecular event during the entry of enveloped viruses into cells. The critical agents of this process are viral surface proteins, primed to facilitate cell bilayer fusion. The important role of Dendritic-cell-specific ICAM3-grabbing non-integrin (DC-SIGN in Dengue virus transmission makes it an attractive target to interfere with Dengue virus Propagation. Receptor mediated endocytosis allows the entry of virions due to the presence of endosomal membranes and low pH-induced fusion of the virus. DC-SIGN is the best characterized molecule among the candidate protein receptors and is able to mediate infection with the four serotypes of dengue virus (DENV. Unrestrained pair wise docking was used for the interaction of dengue envelope protein with DC-SIGN and monoclonal antibody 2G12. Pre-processed the PDB coordinates of dengue envelope glycoprotein and other candidate proteins were prepared and energy minimized through AMBER99 force field distributed in MOE software. Protein-protein interaction server, ZDOCK was used to find molecular interaction among the candidate proteins. Based on these interactions it was found that antibody successfully blocks the glycosylation site ASN 67 and other conserved residues present at DC-SIGN-Den-E complex interface. In order to know for certain, the exact location of the antibody in the envelope protein, co-crystallize of the envelope protein with these compounds is needed so that their exact docking locations can be identified with respect to our results.

Capsaicin Suppresses Cell Proliferation, Induces Cell Cycle Arrest and ROS Production in Bladder Cancer Cells through FOXO3a-Mediated Pathways

Directory of Open Access Journals (Sweden)

Kaiyu Qian

2016-10-01

Full Text Available Capsaicin (CAP, a highly selective agonist for transient receptor potential vanilloid type 1 (TRPV1, has been widely reported to exhibit anti-oxidant, anti-inflammation and anticancer activities. Currently, several therapeutic approaches for bladder cancer (BCa are available, but accompanied by unfavorable outcomes. Previous studies reported a potential clinical effect of CAP to prevent BCa tumorigenesis. However, its underlying molecular mechanism still remains unknown. Our transcriptome analysis suggested a close link among calcium signaling pathway, cell cycle regulation, ROS metabolism and FOXO signaling pathway in BCa. In this study, several experiments were performed to investigate the effects of CAP on BCa cells (5637 and T24 and NOD/SCID mice. Our results showed that CAP could suppress BCa tumorigenesis by inhibiting its proliferation both in vitro and in vivo. Moreover, CAP induced cell cycle arrest at G0/G1 phase and ROS production. Importantly, our studies revealed a strong increase of FOXO3a after treatment with CAP. Furthermore, we observed no significant alteration of apoptosis by CAP, whereas Catalase and SOD2 were considerably upregulated, which could clear ROS and protect against cell death. Thus, our results suggested that CAP could inhibit viability and tumorigenesis of BCa possibly via FOXO3a-mediated pathways.

Dc-To-Dc Converter Uses Reverse Conduction Of MOSFET's

Science.gov (United States)

Gruber, Robert P.; Gott, Robert W.

1991-01-01

In modified high-power, phase-controlled, full-bridge, pulse-width-modulated dc-to-dc converters, switching devices power metal oxide/semiconductor field-effect transistors (MOSFET's). Decreases dissipation of power during switching by eliminating approximately 0.7-V forward voltage drop in anti-parallel diodes. Energy-conversion efficiency increased.

Platelet activating factor receptor binding plays a critical role in jet fuel-induced immune suppression

International Nuclear Information System (INIS)

Ramos, Gerardo; Kazimi, Nasser; Nghiem, Dat X.; Walterscheid, Jeffrey P.; Ullrich, Stephen E.

2004-01-01

Applying military jet fuel (JP-8) or commercial jet fuel (Jet-A) to the skin of mice suppresses the immune response in a dose-dependant manner. The release of biological response modifiers, particularly prostaglandin E 2 (PGE 2 ), is a critical step in activating immune suppression. Previous studies have shown that injecting selective cyclooxygenase-2 inhibitors into jet fuel-treated mice blocks immune suppression. Because the inflammatory phospholipid mediator, platelet-activating factor (PAF), up-regulates cyclooxygenase-2 production and PGE 2 synthesis by keratinocytes, we tested the hypothesis that PAF-receptor binding plays a role in jet fuel-induced immune suppression. Treating keratinocyte cultures with PAF and/or jet fuel (JP-8 and Jet-A) stimulates PGE 2 secretion. Jet fuel-induced PGE 2 production was suppressed by treating the keratinocytes with specific PAF-receptor antagonists. Injecting mice with PAF, or treating the skin of the mice with JP-8, or Jet-A, induced immune suppression. Jet fuel-induced immune suppression was blocked when the jet fuel-treated mice were injected with PAF-receptor antagonists before treatment. Jet fuel treatment has been reported to activate oxidative stress and treating the mice with anti-oxidants (Vitamins C, or E or beta-hydroxy toluene), before jet fuel application, interfered with immune suppression. These findings confirm previous studies showing that PAF-receptor binding can modulate immune function. Furthermore, they suggest that PAF-receptor binding may be an early event in the induction of immune suppression by immunotoxic environmental agents that target the skin

Gauge mediated mini-split

Energy Technology Data Exchange (ETDEWEB)

Cohen, Timothy [Institute of Theoretical Science, University of Oregon,Eugene, OR 97403 (United States); Craig, Nathaniel [Department of Physics, University of California,Santa Barbara, CA 93106 (United States); Knapen, Simon [Berkeley Center for Theoretical Physics,University of California, Berkeley, CA 94720 (United States); Theoretical Physics Group,Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States)

2016-03-15

We propose a simple model of split supersymmetry from gauge mediation. This model features gauginos that are parametrically a loop factor lighter than scalars, accommodates a Higgs boson mass of 125 GeV, and incorporates a simple solution to the μ−b{sub μ} problem. The gaugino mass suppression can be understood as resulting from collective symmetry breaking. Imposing collider bounds on μ and requiring viable electroweak symmetry breaking implies small a-terms and small tan β — the stop mass ranges from 10{sup 5} to 10{sup 8} GeV. In contrast with models with anomaly + gravity mediation (which also predict a one-loop loop suppression for gaugino masses), our gauge mediated scenario predicts aligned squark masses and a gravitino LSP. Gluinos, electroweakinos and Higgsinos can be accessible at the LHC and/or future colliders for a wide region of the allowed parameter space.

4-Chlorotetrazolo[1,5-a]quinoxaline inhibits activation of Syk kinase to suppress mast cells in vitro and mast cell-mediated passive cutaneous anaphylaxis in mice

Energy Technology Data Exchange (ETDEWEB)

Park, Kui Lea [Center for Drug Development Assistance, National Institute of Food Drug Safety Evaluation (NIFDS), KFDA, Cheongwon-gun (Korea, Republic of); Ko, Na Young; Lee, Jun Ho; Kim, Do Kyun; Kim, Hyuk Soon; Kim, A-Ram; Her, Erk; Kim, Bokyung [Department of Immunology and physiology, College of Medicine, Konkuk University, Chungju (Korea, Republic of); Kim, Hyung Sik [College of Pharmacy, Pusan National University, Busan (Korea, Republic of); Moon, Eun-Yi [Department of Bioscience and Biotechnology, College of Biological Science, Sejong University, Seoul (Korea, Republic of); Kim, Young Mi [College of Pharmacy, Duksung Women' s University, Seoul (Korea, Republic of); Kim, Hang-Rae, E-mail: hangrae2@snu.ac.kr [Department of Anatomy, Seoul National University College of Medicine, Seoul (Korea, Republic of); Choi, Wahn Soo, E-mail: wahnchoi@kku.ac.kr [Department of Immunology and physiology, College of Medicine, Konkuk University, Chungju (Korea, Republic of)

2011-12-15

4-Chlorotetrazolo[1,5-a]quinoxaline is a quinoxaline derivative. We aimed to study the effects of 4-chlorotetrazolo[1,5-a]quinoxaline on activation of mast cells in vitro and in mice. 4-Chlorotetrazolo[1,5-a]quinoxaline reversibly inhibited degranulation of mast cells in a dose-dependent manner, and also suppressed the expression and secretion of TNF-{alpha} and IL-4 in mast cells. Mechanistically, 4-chlorotetrazolo[1,5-a]quinoxaline inhibited activating phosphorylation of Syk and LAT, which are crucial for early Fc{epsilon}RI-mediated signaling events, as well as Akt and MAP kinases, which play essential roles in the production of various pro-inflammatory cytokines in mast cells. Notably, although 4-chlorotetrazolo[1,5-a]quinoxaline inhibited the activation of Fyn and Syk, minimal inhibition was observed in mast cells in the case of Lyn. Furthermore, consistent with its in vitro activity, 4-chlorotetrazolo[1,5-a]quinoxaline significantly suppressed mast cell-mediated passive cutaneous anaphylaxis in mice. In summary, the results from this study demonstrate that 4-chlorotetrazolo[1,5-a]quinoxaline shows an inhibitory effect on mast cells in vitro and in vivo, and that this is mediated by inhibiting the activation of Syk in mast cells. Therefore, 4-chlorotetrazolo[1,5-a]quinoxaline could be useful in the treatment of mast cell-mediated allergic diseases. -- Highlights: Black-Right-Pointing-Pointer 4-chlorotetrazolo[1,5-a]quinoxaline is a quinoxaline derivative. Black-Right-Pointing-Pointer The effect of 4-chlorotetrazolo[1,5-a]quinoxaline on mast cells was investigated. Black-Right-Pointing-Pointer 4-chlorotetrazolo[1,5-a]quinoxaline reversibly inhibited Syk activation. Black-Right-Pointing-Pointer 4-chlorotetrazolo[1,5-a]quinoxaline could be useful for IgE-mediated allergy.

4-Chlorotetrazolo[1,5-a]quinoxaline inhibits activation of Syk kinase to suppress mast cells in vitro and mast cell-mediated passive cutaneous anaphylaxis in mice

International Nuclear Information System (INIS)

Park, Kui Lea; Ko, Na Young; Lee, Jun Ho; Kim, Do Kyun; Kim, Hyuk Soon; Kim, A-Ram; Her, Erk; Kim, Bokyung; Kim, Hyung Sik; Moon, Eun-Yi; Kim, Young Mi; Kim, Hang-Rae; Choi, Wahn Soo

2011-01-01

4-Chlorotetrazolo[1,5-a]quinoxaline is a quinoxaline derivative. We aimed to study the effects of 4-chlorotetrazolo[1,5-a]quinoxaline on activation of mast cells in vitro and in mice. 4-Chlorotetrazolo[1,5-a]quinoxaline reversibly inhibited degranulation of mast cells in a dose-dependent manner, and also suppressed the expression and secretion of TNF-α and IL-4 in mast cells. Mechanistically, 4-chlorotetrazolo[1,5-a]quinoxaline inhibited activating phosphorylation of Syk and LAT, which are crucial for early FcεRI-mediated signaling events, as well as Akt and MAP kinases, which play essential roles in the production of various pro-inflammatory cytokines in mast cells. Notably, although 4-chlorotetrazolo[1,5-a]quinoxaline inhibited the activation of Fyn and Syk, minimal inhibition was observed in mast cells in the case of Lyn. Furthermore, consistent with its in vitro activity, 4-chlorotetrazolo[1,5-a]quinoxaline significantly suppressed mast cell-mediated passive cutaneous anaphylaxis in mice. In summary, the results from this study demonstrate that 4-chlorotetrazolo[1,5-a]quinoxaline shows an inhibitory effect on mast cells in vitro and in vivo, and that this is mediated by inhibiting the activation of Syk in mast cells. Therefore, 4-chlorotetrazolo[1,5-a]quinoxaline could be useful in the treatment of mast cell-mediated allergic diseases. -- Highlights: ► 4-chlorotetrazolo[1,5-a]quinoxaline is a quinoxaline derivative. ► The effect of 4-chlorotetrazolo[1,5-a]quinoxaline on mast cells was investigated. ► 4-chlorotetrazolo[1,5-a]quinoxaline reversibly inhibited Syk activation. ► 4-chlorotetrazolo[1,5-a]quinoxaline could be useful for IgE-mediated allergy.

Myostatin Suppression of Akirin1 Mediates Glucocorticoid-Induced Satellite Cell Dysfunction

Science.gov (United States)

Dong, Yanjun; Pan, Jenny S.; Zhang, Liping

2013-01-01

Glucocorticoids production is increased in many pathological conditions that are associated with muscle loss, but their role in causing muscle wasting is not fully understood. We have demonstrated a new mechanism of glucocorticoid-induced muscle atrophy: Dexamethasone (Dex) suppresses satellite cell function contributing to the development of muscle atrophy. Specifically, we found that Dex decreases satellite cell proliferation and differentiation in vitro and in vivo. The mechanism involved Dex-induced upregulation of myostatin and suppression of Akirin1, a promyogenic gene. When myostatin was inhibited in Dex-treated mice, Akirin1 expression increased as did satellite cell activity, muscle regeneration and muscle growth. In addition, silencing myostatin in myoblasts or satellite cells prevented Dex from suppressing Akirin1 expression and cellular proliferation and differentiation. Finally, overexpression of Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation, theses improvements were no longer suppressed by Dex. We conclude that glucocorticoids stimulate myostatin which inhibits Akirin1 expression and the reparative functions of satellite cells. These responses attribute to muscle atrophy. Thus, inhibition of myostatin or increasing Akirin1 expression could lead to therapeutic strategies for improving satellite cell activation and enhancing muscle growth in diseases associated with increased glucocorticoid production. PMID:23516508

Myostatin suppression of Akirin1 mediates glucocorticoid-induced satellite cell dysfunction.

Directory of Open Access Journals (Sweden)

Yanjun Dong

Full Text Available Glucocorticoids production is increased in many pathological conditions that are associated with muscle loss, but their role in causing muscle wasting is not fully understood. We have demonstrated a new mechanism of glucocorticoid-induced muscle atrophy: Dexamethasone (Dex suppresses satellite cell function contributing to the development of muscle atrophy. Specifically, we found that Dex decreases satellite cell proliferation and differentiation in vitro and in vivo. The mechanism involved Dex-induced upregulation of myostatin and suppression of Akirin1, a promyogenic gene. When myostatin was inhibited in Dex-treated mice, Akirin1 expression increased as did satellite cell activity, muscle regeneration and muscle growth. In addition, silencing myostatin in myoblasts or satellite cells prevented Dex from suppressing Akirin1 expression and cellular proliferation and differentiation. Finally, overexpression of Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation, theses improvements were no longer suppressed by Dex. We conclude that glucocorticoids stimulate myostatin which inhibits Akirin1 expression and the reparative functions of satellite cells. These responses attribute to muscle atrophy. Thus, inhibition of myostatin or increasing Akirin1 expression could lead to therapeutic strategies for improving satellite cell activation and enhancing muscle growth in diseases associated with increased glucocorticoid production.

Development of a green mode DC/DC converter available to portable nuclear instrument

International Nuclear Information System (INIS)

Gao Feiyan; Wu Longxiong; Tan Wei; Tang Yaogeng

2010-01-01

A green mode DC/DC converter was developed which suitable to the portable nuclear instrument which is powered by battery and is sometime at stand-by mode. Some updated control approaches such as pseudo-resonant type power supply control and synchronous rectification were adopted to makethe DC/DC converter operate with low power consumption and high efficiency. The test results the battery can be prolonged with this converter. (authors)

Piperlongumine selectively suppresses ABC-DLBCL through inhibition of NF-κB p65 subunit nuclear import

Energy Technology Data Exchange (ETDEWEB)

Niu, Mingshan [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Shen, Yangling; Xu, Xiaoyu [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Yao, Yao; Fu, Chunling [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Yan, Zhiling [Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Wu, Qingyun [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Cao, Jiang; Sang, Wei [Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Zeng, Lingyu [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Li, Zhenyu [Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Liu, Xuejiao, E-mail: liuxuejiao0923@126.com [Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu (China); and others

2015-07-10

Constitutive NF-κB activation is required for survival of activated B cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). However, current NF-κB targeting strategies lack cancer cell specificity. Here, we identified a novel inhibitor, piperlongumine, features direct binding to NF-κB p65 subunit and suppression of p65 nuclear import. This was accompanied by NF-κB reporter activity suppression and NF-κB target gene downregulation. Moreover, mutation of Cys{sup 38} to Ser in p65 abolished this effect of piperlongumine on inhibition of p65 nuclear import. Furthermore, we show that piperlongumine selectively inhibited proliferation and induced apoptosis of ABC-DLBCL cells. Most notably, it has been reported that piperlongumine did not affect normal cells even at high doses and was nontoxic to animals. Hence, our current study provides new insight into piperlongumine's mechanism of action and novel approach to ABC-DLBCL target therapy. - Highlights: • Current NF-κB targeting strategies lack cancer cell specificity. • Piperlongumine inhibits NF-κB p65 subunit nuclear import via directly binding to p65. • Piperlongumine selectively inhibits proliferation of ABC-DLBCL cells. • This study provides a novel approach to ABC-DLBCL target therapy.

Piperlongumine selectively suppresses ABC-DLBCL through inhibition of NF-κB p65 subunit nuclear import

International Nuclear Information System (INIS)

Niu, Mingshan; Shen, Yangling; Xu, Xiaoyu; Yao, Yao; Fu, Chunling; Yan, Zhiling; Wu, Qingyun; Cao, Jiang; Sang, Wei; Zeng, Lingyu; Li, Zhenyu; Liu, Xuejiao

2015-01-01

Constitutive NF-κB activation is required for survival of activated B cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). However, current NF-κB targeting strategies lack cancer cell specificity. Here, we identified a novel inhibitor, piperlongumine, features direct binding to NF-κB p65 subunit and suppression of p65 nuclear import. This was accompanied by NF-κB reporter activity suppression and NF-κB target gene downregulation. Moreover, mutation of Cys 38 to Ser in p65 abolished this effect of piperlongumine on inhibition of p65 nuclear import. Furthermore, we show that piperlongumine selectively inhibited proliferation and induced apoptosis of ABC-DLBCL cells. Most notably, it has been reported that piperlongumine did not affect normal cells even at high doses and was nontoxic to animals. Hence, our current study provides new insight into piperlongumine's mechanism of action and novel approach to ABC-DLBCL target therapy. - Highlights: • Current NF-κB targeting strategies lack cancer cell specificity. • Piperlongumine inhibits NF-κB p65 subunit nuclear import via directly binding to p65. • Piperlongumine selectively inhibits proliferation of ABC-DLBCL cells. • This study provides a novel approach to ABC-DLBCL target therapy

A Dual-Buck–Boost AC/DC Converter for DC Nanogrid With Three Terminal Outputs

DEFF Research Database (Denmark)

Wu, Weimin; Wang, Houqing; Liu, Yuan

2017-01-01

Due to the widely used dc characterized loads and more distributed power generation sources, the dc nanogrid becomes more and more popular, and it is seen as an alternative to the ac grid. For safety considerations, the dc nanogrid should provide reliable grounding for the residential loads...... such as the low-voltage ac power system. There are three typical grounding configurations for a dc nanogrid: the united grounding, the unidirectional grounding, and the virtual isolated grounding. Each grounding configuration has its own specifications to ac/dc converters. In this paper, a dual-buck-boost ac/dc...... converter for use in the united-grounding-configuration-based dc nanogrid with three terminal outputs is proposed. The working principle of this converter is presented in detail through analyzing the equivalent circuits. Experiments are carried out to verify the theoretical analysis....

DESIGN OPTIMIZATION OF RESONANT DC-DC CONVERTERS

OpenAIRE

Belqasem Aljafari

2016-01-01

Resonant DC/DC converters are the class of converters, which have L-C resonant tank serving as a major part of the power conversion process. The fundamental concept of the resonant converter is that the circulating energy in an L-C resonant circuit is manageable by changing the operating frequency, and therefore the converter can condition the input power to the desired output voltage. The development in power conversion technology is steady demand for high power efficiency and high power den...

PLZF mediates the PTEN/AKT/FOXO3a signaling in suppression of prostate tumorigenesis.

Directory of Open Access Journals (Sweden)

JingPing Cao

Full Text Available Promyelocytic leukemia zinc finger (PLZF protein expression is closely related to the progression of human cancers, including prostate cancer (PCa. However, the according context of a signaling pathway for PLZF to suppress prostate tumorigenesis remains greatly unknown. Here we report that PLZF is a downstream mediator of the PTEN signaling pathway in PCa. We found that PLZF expression is closely correlated with PTEN expression in a cohort of prostate cancer specimens. Interestingly, both PTEN rescue and phosphoinositide 3-kinase (PI3K inhibitor LY294002 treatment increase the PLZF expression in prostate cancer cell lines. Further, luciferase reporter assay and chromatin immunoprecipitation assay demonstrate that FOXO3a, a transcriptional factor phosphorylated by PI3K/AKT, could directly bind to the promoter of PLZF gene. These results indicate that PTEN regulates PLZF expression by AKT/FOXO3a. Moreover, our animal experiments also demonstrate that PLZF is capable of inhibiting prostate tumorigenesis in vivo. Taken together, our study defines a PTEN/PLZF pathway and would shed new lights for developing therapeutic strategy of prostate cancer.

High Voltage Coil Current Sensor for DC-DC Converters Employing DDCC

Directory of Open Access Journals (Sweden)

M. Drinovsky

2015-12-01

Full Text Available Current sensor is an integral part of every switching converter. It is used for over-current protection, regulation and in case of multiphase converters for balancing. A new high voltage current sensor for coil-based current sensing in DC-DC converters is presented. The sensor employs DDCC with high voltage input stage and gain trimming. The circuit has been simulated and implemented in 0.35 um BCD technology as part of a multiphase DC-DC converter where its function has been verified. The circuit is able to sustain common mode voltage on the input up to 40 V, it occupies 0.387*0.345 mm2 and consumes 3.2 mW typically.

The relation of weight suppression and BMI to bulimic symptoms.

Science.gov (United States)

Butryn, Meghan L; Juarascio, Adrienne; Lowe, Michael R

2011-11-01

High levels of weight suppression have been associated with greater binge eating and weight gain as well as poorer treatment outcome in bulimia nervosa. This study examined the relationship between weight suppression and bulimia nervosa symptoms and explored how weight suppression might interact with body mass index (BMI) in accounting for level of symptomatology at presentation for treatment. Participants were 64 women with threshold or sub-threshold bulimia nervosa. A clinical interview assessed binge eating and purging. Weight suppression and the interaction between BMI and weight suppression predicted frequency of binge eating such that participants with low BMI and high weight suppression engaged in the most binge eating. High levels of weight suppression also predicted more frequent purging. Additional research is warranted to examine mediators of these relationships. Copyright © 2010 Wiley Periodicals, Inc.

Global inhibition of DC priming capacity in the spleen of self-antigen vaccinated mice requires IL-10

Directory of Open Access Journals (Sweden)

Douglas Matthew Marvel

2014-02-01

Full Text Available DC in the spleen are highly activated following intravenous vaccination with a foreign antigen, promoting expansion of effector T cells, but remain phenotypically and functionally immature after vaccination with a self-antigen. Up-regulation or suppression of expression of a cohort of pancreatic enzymes 24-72 hours post-vaccination can be used as a biomarker of stimulatory versus toleragenic DC, respectively. Here we show, using MUC1 transgenic mice (MUC1.Tg and a vaccine based on the MUC1 peptide which these mice perceive as a self-antigen, that the difference in enzyme expression that predicts whether DC will promote immune response or immune tolerance, is seen as early as 4-8 hours following vaccination. We also identify early production of IL-10 as a predominant factor that both correlates with this early time point and controls DC function. Pre-treating mice with an antibody against the IL-10 receptor (IL-10R prior to vaccination results in DC that up-regulate CD40, CD80, and CD86 and promote stronger IFNγ+ T cell responses. This study suggests that transient inhibition of IL-10 prior to vaccination could improve responses to cancer vaccines that utilize self-tumor antigens.

DC-159a Shows Inhibitory Activity against DNA Gyrases of Mycobacterium leprae.

Science.gov (United States)

Yamaguchi, Tomoyuki; Yokoyama, Kazumasa; Nakajima, Chie; Suzuki, Yasuhiko

2016-09-01

Fluoroquinolones are a class of antibacterial agents used for leprosy treatment. Some new fluoroquinolones have been attracting interest due to their remarkable potency that is reportedly better than that of ofloxacin, the fluoroquinolone currently recommended for treatment of leprosy. For example, DC-159a, a recently developed 8-methoxy fluoroquinolone, has been found to be highly potent against various bacterial species. Nonetheless, the efficacy of DC-159a against Mycobacterium leprae is yet to be examined. To gather data that can support highly effective fluoroquinolones as candidates for new remedies for leprosy treatment, we conducted in vitro assays to assess and compare the inhibitory activities of DC-159a and two fluoroquinolones that are already known to be more effective against M. leprae than ofloxacin. The fluoroquinolone-inhibited DNA supercoiling assay using recombinant DNA gyrases of wild type and ofloxacin-resistant M. leprae revealed that inhibitory activities of DC-159a and sitafloxacin were at most 9.8- and 11.9-fold higher than moxifloxacin. Also the fluoroquinolone-mediated cleavage assay showed that potencies of those drugs were at most 13.5- and 9.8-fold higher than moxifloxacin. In addition, these two drugs retained their inhibitory activities even against DNA gyrases of ofloxacin-resistant M. leprae. The results indicated that DC-159a and sitafloxacin are more effective against wild type and mutant M. leprae DNA gyrases than moxifloxacin, suggesting that these antibacterial drugs can be good candidates that may supersede current fluoroquinolone remedies. DC-159a in particular is very promising because it is classified in a subgroup of fluoroquinolones that is known to be less likely to cause adverse effects. Our results implied that DC-159a is well worth further investigation to ascertain its in vivo effectiveness and clinical safety for humans.

On the modelling of linear-assisted DC-DC voltage regulators for photovoltaic solar energy systems

Science.gov (United States)

Martínez-García, Herminio; García-Vílchez, Encarna

2017-11-01

This paper shows the modelling of linear-assisted or hybrid (linear & switching) DC/DC voltage regulators. In this kind of regulators, an auxiliary linear regulator is used, which objective is to cancel the ripple at the output voltage and provide fast responses for load variations. On the other hand, a switching DC/DC converter, connected in parallel with the linear regulator, allows to supply almost the whole output current demanded by the load. The objective of this topology is to take advantage of the suitable regulation characteristics that series linear voltage regulators have, but almost achieving the high efficiency that switching DC/DC converters provide. Linear-assisted DC/DC regulators are feedback systems with potential instability. Therefore, their modelling is mandatory in order to obtain design guidelines and assure stability of the implemented power supply system.

Rituximab selectively suppresses specific islet antibodies.

Science.gov (United States)

Yu, Liping; Herold, Kevan; Krause-Steinrauf, Heidi; McGee, Paula L; Bundy, Brian; Pugliese, Alberto; Krischer, Jeff; Eisenbarth, George S

2011-10-01

The TrialNet Study Group evaluated rituximab, a B-cell-depleting monoclonal antibody, for its effect in new-onset patients with type 1A diabetes. Rituximab decreased the loss of C-peptide over the first year of follow-up and markedly depleted B lymphocytes for 6 months after administration. This article analyzes the specific effect of rituximab on multiple islet autoantibodies. A total of 87 patients between the ages of 8 and 40 years received either rituximab or a placebo infusion weekly for four doses close to the onset of diabetes. Autoantibodies to insulin (IAAs), GAD65 (GADAs), insulinoma-associated protein 2 (IA2As), and ZnT8 (ZnT8As) were measured with radioimmunoassays. The primary outcome for this autoantibody analysis was the mean level of autoantibodies during follow-up. Rituximab markedly suppressed IAAs compared with the placebo injection but had a much smaller effect on GADAs, IA2As, and ZnT8As. A total of 40% (19 of 48) of rituximab-treated patients who were IAA positive became IAA negative versus 0 of 29 placebo-treated patients (P 1 year in insulin-treated patients. For the patients receiving insulin for >2 weeks prior to rituximab administration, we cannot assess whether rituximab not only blocks the acquisition of insulin antibodies induced by insulin administration and/or also suppresses preformed insulin autoantibodies. Studies in prediabetic non-insulin-treated patients will likely be needed to evaluate the specific effects of rituximab on levels of IAAs.

A Feedback Passivation Design for DC Microgrid and Its DC/DC Converters

Directory of Open Access Journals (Sweden)

Feifan Ji

2016-12-01

Full Text Available There are difficulties in analyzing the stability of microgrids since they are located on various network structures. However, considering that the network often consists of passive elements, the passivity theory is applied in this paper to solve the above-mentioned problem. It has been formerly shown that when the network is weakly strictly positive real (WSPR, the DC microgrid is stable if all interfaces between the microgrid and converters are made to be passive, which is called interface passivity. Then, the feedback passivation method is proposed for the controller design of various DC–DC converters to achieve the interface passivity. The interface passivity is different from the passivity of closed-loop systems on which the passivity based control (PBC concentrates. The feedback passivation design is detailed for typical buck converters and boost converters in terms of conditions that the controller parameters should satisfy. The theoretical results are verified by a hardware-in-loop real-time labotray (RTLab simulation of a DC microgrid with four generators.

Weak surround suppression of the attentional focus characterizes visual selection in the ventral stream in autism

Directory of Open Access Journals (Sweden)

Luca Ronconi

Full Text Available Neurophysiological findings in the typical population demonstrate that spatial scrutiny for visual selection determines a center-surround profile of the attentional focus, which is the result of recurrent processing in the visual system. Individuals with autism spectrum disorder (ASD manifest several anomalies in their visual selection, with strengths in detail-oriented tasks, but also difficulties in distractor inhibition tasks. Here, we asked whether contradictory aspects of perception in ASD might be due to a different center-surround profile of their attentional focus. In two experiments, we tested two independent samples of children with ASD, comparing them with typically developing (TD peers. In Experiment 1, we used a psychophysical task that mapped the entire spatial profile of the attentional focus. In Experiment 2, we used dense-array electroencephalography (EEG to explore its neurophysiological underpinnings. Experiment 1 results showed that the suppression, surrounding the attentional focus, was markedly reduced in children with ASD. Experiment 2 showed that the center-surround profile in TD children resulted in a modulation of the posterior N2 ERP component, with cortical sources in the lateral-occipital and medial/inferior temporal areas. In contrast, children with ASD did not show modulation of the N2 and related activations in the ventral visual stream. Furthermore, behavioural and neurophysiological measures of weaker suppression predicted more severe autistic symptomatology. The present findings, showing an altered center-surround profile during attentional selection, give an important insight to understand superior visual processing in autism as well as the experiencing of sensory overload. Keywords: EEG, Source analysis, Ventral visual stream, Perception, Rehabilitation

Genome-wide scans between two honeybee populations reveal putative signatures of human-mediated selection.

Science.gov (United States)

Parejo, M; Wragg, D; Henriques, D; Vignal, A; Neuditschko, M

2017-12-01

Human-mediated selection has left signatures in the genomes of many domesticated animals, including the European dark honeybee, Apis mellifera mellifera, which has been selected by apiculturists for centuries. Using whole-genome sequence information, we investigated selection signatures in spatially separated honeybee subpopulations (Switzerland, n = 39 and France, n = 17). Three different test statistics were calculated in windows of 2 kb (fixation index, cross-population extended haplotype homozygosity and cross-population composite likelihood ratio) and combined into a recently developed composite selection score. Applying a stringent false discovery rate of 0.01, we identified six significant selective sweeps distributed across five chromosomes covering eight genes. These genes are associated with multiple molecular and biological functions, including regulation of transcription, receptor binding and signal transduction. Of particular interest is a selection signature on chromosome 1, which corresponds to the WNT4 gene, the family of which is conserved across the animal kingdom with a variety of functions. In Drosophila melanogaster, WNT4 alleles have been associated with differential wing, cross vein and abdominal phenotypes. Defining phenotypic characteristics of different Apis mellifera ssp., which are typically used as selection criteria, include colour and wing venation pattern. This signal is therefore likely to be a good candidate for human mediated-selection arising from different applied breeding practices in the two managed populations. © 2017 The Authors. Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics.

A Bidirectional Resonant DC-DC Converter Suitable for Wide Voltage Gain Range

DEFF Research Database (Denmark)

Shen, Yanfeng; Wang, Huai; Al-Durra, Ahmed

2018-01-01

This paper proposes a new bidirectional resonant dc-dc converter suitable for wide voltage gain range applications (e.g., energy storage systems). The proposed converter overcomes the narrow voltage gain range of conventional resonant dc-dc converters, and meanwhile achieves high efficiency...... losses. The operation principles and characteristics of the proposed converter are firstly analyzed in this paper. Then the analytical solutions for the voltage gain, soft-switching, and rms currents are derived, which facilitates the parameters design and optimization. Finally, the proposed topology...... and analysis are verified with experimental results obtained from a 1-kW converter prototype....

Ethylene signaling renders the jasmonate response of Arabidopsis insensitive to future suppression by salicylic Acid.

Science.gov (United States)

Leon-Reyes, Antonio; Du, Yujuan; Koornneef, Annemart; Proietti, Silvia; Körbes, Ana P; Memelink, Johan; Pieterse, Corné M J; Ritsema, Tita

2010-02-01

Cross-talk between jasmonate (JA), ethylene (ET), and Salicylic acid (SA) signaling is thought to operate as a mechanism to fine-tune induced defenses that are activated in response to multiple attackers. Here, 43 Arabidopsis genotypes impaired in hormone signaling or defense-related processes were screened for their ability to express SA-mediated suppression of JA-responsive gene expression. Mutant cev1, which displays constitutive expression of JA and ET responses, appeared to be insensitive to SA-mediated suppression of the JA-responsive marker genes PDF1.2 and VSP2. Accordingly, strong activation of JA and ET responses by the necrotrophic pathogens Botrytis cinerea and Alternaria brassicicola prior to SA treatment counteracted the ability of SA to suppress the JA response. Pharmacological assays, mutant analysis, and studies with the ET-signaling inhibitor 1-methylcyclopropene revealed that ET signaling renders the JA response insensitive to subsequent suppression by SA. The APETALA2/ETHYLENE RESPONSE FACTOR transcription factor ORA59, which regulates JA/ET-responsive genes such as PDF1.2, emerged as a potential mediator in this process. Collectively, our results point to a model in which simultaneous induction of the JA and ET pathway renders the plant insensitive to future SA-mediated suppression of JA-dependent defenses, which may prioritize the JA/ET pathway over the SA pathway during multi-attacker interactions.

Zingerone suppresses liver inflammation induced by antibiotic mediated endotoxemia through down regulating hepatic mRNA expression of inflammatory markers in Pseudomonas aeruginosa peritonitis mouse model.

Directory of Open Access Journals (Sweden)

Lokender Kumar

Full Text Available Antibiotic-induced endotoxin release is associated with high mortality rate even when appropriate antibiotics are used for the treatment of severe infections in intensive care units. Since liver is involved in systemic clearance and detoxification of endotoxin hence it becomes a primary target organ for endotoxin mediated inflammation. Currently available anti-inflammatory drugs give rise to serious side effects. Hence, there is an urgent need for safe and effective anti-inflammatory therapy. It is likely that anti-inflammatory phytochemicals and neutraceutical agents may have the potential to reduce the endotoxin mediated inflammation and complications associated with endotoxin release. Keeping this in mind, the present study was planned to evaluate the hepatoprotective potential of zingerone (active compound of zingiber officinale against liver inflammation induced by antibiotic mediated endotoxemia. The selected antibiotics capable of releasing high content of endotoxin were employed for their in vivo efficacy in P.aeruginosa peritonitis model. Released endotoxin induced inflammation and zingerone as co-anti-inflammatory therapy significantly reduced inflammatory response. Improved liver histology and reduced inflammatory markers MDA, RNI, MPO, tissue damage markers (AST, ALT, ALP and inflammatory cytokines (MIP-2, IL-6 and TNF-α were indicative of therapeutic potential of zingerone. The mechanism of action of zingerone may be related to significant inhibition of the mRNA expression of inflammatory markers (TLR4, RelA, NF-kB2, TNF- α, iNOS, COX-2 indicating that zingerone interferes with cell signalling pathway and suppresses hyper expression of cell signaling molecules of inflammatory pathway. Zingerone therapy significantly protected liver from endotoxin induced inflammatory damage by down regulating biochemical as well as molecular markers of inflammation. In conclusion, this study provides evidence that zingerone is a potent anti

Zingerone suppresses liver inflammation induced by antibiotic mediated endotoxemia through down regulating hepatic mRNA expression of inflammatory markers in Pseudomonas aeruginosa peritonitis mouse model.

Science.gov (United States)

Kumar, Lokender; Chhibber, Sanjay; Harjai, Kusum

2014-01-01

Antibiotic-induced endotoxin release is associated with high mortality rate even when appropriate antibiotics are used for the treatment of severe infections in intensive care units. Since liver is involved in systemic clearance and detoxification of endotoxin hence it becomes a primary target organ for endotoxin mediated inflammation. Currently available anti-inflammatory drugs give rise to serious side effects. Hence, there is an urgent need for safe and effective anti-inflammatory therapy. It is likely that anti-inflammatory phytochemicals and neutraceutical agents may have the potential to reduce the endotoxin mediated inflammation and complications associated with endotoxin release. Keeping this in mind, the present study was planned to evaluate the hepatoprotective potential of zingerone (active compound of zingiber officinale) against liver inflammation induced by antibiotic mediated endotoxemia. The selected antibiotics capable of releasing high content of endotoxin were employed for their in vivo efficacy in P.aeruginosa peritonitis model. Released endotoxin induced inflammation and zingerone as co-anti-inflammatory therapy significantly reduced inflammatory response. Improved liver histology and reduced inflammatory markers MDA, RNI, MPO, tissue damage markers (AST, ALT, ALP) and inflammatory cytokines (MIP-2, IL-6 and TNF-α) were indicative of therapeutic potential of zingerone. The mechanism of action of zingerone may be related to significant inhibition of the mRNA expression of inflammatory markers (TLR4, RelA, NF-kB2, TNF- α, iNOS, COX-2) indicating that zingerone interferes with cell signalling pathway and suppresses hyper expression of cell signaling molecules of inflammatory pathway. Zingerone therapy significantly protected liver from endotoxin induced inflammatory damage by down regulating biochemical as well as molecular markers of inflammation. In conclusion, this study provides evidence that zingerone is a potent anti

Anti-inflammatory activity of chloroquine and amodiaquine through p21-mediated suppression of T cell proliferation and Th1 cell differentiation

International Nuclear Information System (INIS)

Oh, Sera; Shin, Ji Hyun; Jang, Eun Jung; Won, Hee Yeon; Kim, Hyo Kyeong; Jeong, Mi- Gyeong; Kim, Kwang Soo; Hwang, Eun Sook

2016-01-01

Chloroquine (CQ) and amodiaquine (AQ) have been used for treating or preventing malaria for decades, and their application has expanded into treating inflammatory disease in humans. CQ and AQ are applicable for controlling rheumatoid arthritis, but their molecular mechanisms of anti-inflammatory activity remain to be elucidated. In this study, we examined the effects of CQ and AQ on T cell activation and T cell-mediated immune response. CQ had no significant effect on T cell numbers, but decreased the population of T cells with a high division rate. However, AQ treatment significantly increased the number of cells with low division rates and eliminated cells with high division rates, resulting in the inhibition of T cell proliferation triggered by T cell receptor stimulation, of which inhibition occurred in developing effector T helper and regulatory T cells, regardless of the different exogenous cytokines. Interestingly, the cyclin-dependent kinase inhibitor p21 was significantly and dose-dependently increased by CQ, and more potently by AQ, while other cell cycle regulators were unchanged. Both CQ and AQ elevated the transcription level of p21 though the activation of p53, but also blocked p21 protein degradation in the presence of cycloheximide, causing p21 protein accumulation mainly in the nucleus. Sustained treatment of developing T cells with either CQ or AQ suppressed IFN-γ production in a dose dependent manner and potently inhibited the differentiation of IFN-γ-producing Th1 cells. These results demonstrate that CQ and AQ increase the expression level of p21 and inhibit T cell proliferation and the development of IFN-γ-producing Th1 cells, thereby revealing beneficial roles in treating a wide range of chronic inflammatory diseases mediated by inflammatory T cells. -- Highlights: •T cell division rates are suppressed by chloroquine and amodiaquine treatment. •Chloroquine and amodiaquine potently increased the p21 expression. •The p21 induction is

Anti-inflammatory activity of chloroquine and amodiaquine through p21-mediated suppression of T cell proliferation and Th1 cell differentiation

Energy Technology Data Exchange (ETDEWEB)

Oh, Sera; Shin, Ji Hyun; Jang, Eun Jung; Won, Hee Yeon; Kim, Hyo Kyeong; Jeong, Mi- Gyeong [College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750 (Korea, Republic of); Kim, Kwang Soo [Molecular Neurobiology Laboratory, Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478 (United States); Hwang, Eun Sook, E-mail: eshwang@ewha.ac.kr [College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750 (Korea, Republic of)

2016-05-27

Chloroquine (CQ) and amodiaquine (AQ) have been used for treating or preventing malaria for decades, and their application has expanded into treating inflammatory disease in humans. CQ and AQ are applicable for controlling rheumatoid arthritis, but their molecular mechanisms of anti-inflammatory activity remain to be elucidated. In this study, we examined the effects of CQ and AQ on T cell activation and T cell-mediated immune response. CQ had no significant effect on T cell numbers, but decreased the population of T cells with a high division rate. However, AQ treatment significantly increased the number of cells with low division rates and eliminated cells with high division rates, resulting in the inhibition of T cell proliferation triggered by T cell receptor stimulation, of which inhibition occurred in developing effector T helper and regulatory T cells, regardless of the different exogenous cytokines. Interestingly, the cyclin-dependent kinase inhibitor p21 was significantly and dose-dependently increased by CQ, and more potently by AQ, while other cell cycle regulators were unchanged. Both CQ and AQ elevated the transcription level of p21 though the activation of p53, but also blocked p21 protein degradation in the presence of cycloheximide, causing p21 protein accumulation mainly in the nucleus. Sustained treatment of developing T cells with either CQ or AQ suppressed IFN-γ production in a dose dependent manner and potently inhibited the differentiation of IFN-γ-producing Th1 cells. These results demonstrate that CQ and AQ increase the expression level of p21 and inhibit T cell proliferation and the development of IFN-γ-producing Th1 cells, thereby revealing beneficial roles in treating a wide range of chronic inflammatory diseases mediated by inflammatory T cells. -- Highlights: •T cell division rates are suppressed by chloroquine and amodiaquine treatment. •Chloroquine and amodiaquine potently increased the p21 expression. •The p21 induction is

Y-source impedance-network-based isolated boost DC/DC converter

DEFF Research Database (Denmark)

Siwakoti, Yam P.; Town, Graham; Loh, Poh Chiang

2014-01-01

A dc-dc converter with very high voltage gain is proposed in this paper for any medium-power application requiring a high voltage boost with galvanic isolation. The proposed converter topology can be realized using only two switches. With this topology a very high voltage boost can be achieved even...... with a relatively low duty cycle of the switches, and the gain obtainable is presently not matched by any existing impedance network based converter operated at the same duty ratio. The proposed converter has a Y-source impedance network to boost the voltage at the intermediate dc-link side and a push......-pull transformer for square-wave AC inversion and isolation. The voltage-doubler rectifier provides a constant dc voltage at the output stage. A theoretical analysis of the converter is presented, supported by simulation and experimental results. A 250 W down-scaled prototype was implemented in the laboratory...

Multilevel DC link inverter

Science.gov (United States)

Su, Gui-Jia

2003-06-10

A multilevel DC link inverter and method for improving torque response and current regulation in permanent magnet motors and switched reluctance motors having a low inductance includes a plurality of voltage controlled cells connected in series for applying a resulting dc voltage comprised of one or more incremental dc voltages. The cells are provided with switches for increasing the resulting applied dc voltage as speed and back EMF increase, while limiting the voltage that is applied to the commutation switches to perform PWM or dc voltage stepping functions, so as to limit current ripple in the stator windings below an acceptable level, typically 5%. Several embodiments are disclosed including inverters using IGBT's, inverters using thyristors. All of the inverters are operable in both motoring and regenerating modes.

Stability analysis of a high-step-Up DC grid-connected two-stage boost DC-DC converter

Directory of Open Access Journals (Sweden)

El Aroudi A.

2014-01-01

Full Text Available High conversion ratio switching converters are used whenever there is a need to step-up dc source voltage level to a much higher output dc voltage level such as in photovoltaic systems, telecommunications and in some medical applications. A simple solution for achieving this high conversion ratio is by cascading different stages of dc-dc boost converters. The individual converters in such a cascaded system are usually designed separately applying classical design criteria. However these criteria may not be applicable for the complete cascaded system . This paper first presents a glimpse on the bifurcation behavior that a cascade connection of two boost converters can exhibit. It is shown that the desired periodic orbit can undergo period doubling leading to subharmonic oscillations and chaotic regimes. Then, in order to simplify the analysis the second stage is considered as constant current sink and design-oriented analysis is carried out to obtain stability boundaries in the parameter space by taking into account slope interactions between the state variables in the two-different stages.

Appetite Suppression and Altered Food Preferences Coincide with Changes in Appetite-Mediating Hormones During Energy Deficit at High Altitude, But Are Not Affected by Protein Intake.

Science.gov (United States)

Karl, J Philip; Cole, Renee E; Berryman, Claire E; Finlayson, Graham; Radcliffe, Patrick N; Kominsky, Matthew T; Murphy, Nancy E; Carbone, John W; Rood, Jennifer C; Young, Andrew J; Pasiakos, Stefan M

2018-02-12

Karl, J. Philip, Renee E. Cole, Claire E. Berryman, Graham Finlayson, Patrick N. Radcliffe, Matthew T. Kominsky, Nancy E. Murphy, John W. Carbone, Jennifer C. Rood, Andrew J. Young, and Stefan M. Pasiakos. Appetite Suppression and Altered Food Preferences Coincide with Changes in Appetite-Mediating Hormones During Energy Deficit at High Altitude, But Are Not Affected by Protein Intake. High Alt Med Biol. 00:000-000, 2018.-Anorexia and unintentional body weight loss are common during high altitude (HA) sojourn, but underlying mechanisms are not fully characterized, and the impact of dietary macronutrient composition on appetite regulation at HA is unknown. This study aimed to determine the effects of a hypocaloric higher protein diet on perceived appetite and food preferences during HA sojourn and to examine longitudinal changes in perceived appetite, appetite mediating hormones, and food preferences during acclimatization and weight loss at HA. Following a 21-day level (SL) period, 17 unacclimatized males ascended to and resided at HA (4300 m) for 22 days. At HA, participants were randomized to consume measured standard-protein (1.0 g protein/kg/d) or higher protein (2.0 g/kg/d) hypocaloric diets (45% carbohydrate, 30% energy restriction) and engaged in prescribed physical activity to induce an estimated 40% energy deficit. Appetite, food preferences, and appetite-mediating hormones were measured at SL and at the beginning and end of HA. Diet composition had no effect on any outcome. Relative to SL, appetite was lower during acute HA (days 0 and 1), but not different after acclimatization and weight loss (HA day 18), and food preferences indicated an increased preference for sweet- and low-protein foods during acute HA, but for high-fat foods after acclimatization and weight loss. Insulin, leptin, and cholecystokinin concentrations were elevated during acute HA, but not after acclimatization and weight loss, whereas acylated ghrelin concentrations were

Studi Komparasi Fungsi Keanggotaan Fuzzy sebagai Kontroler Bidirectional DC-DC Converter pada Sistem Penyimpan Energi

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Eka Prasetyono

2015-09-01

Full Text Available Bidirectional DC-DC converter is needed in the energy storage system. The converter topology used in this paper was a non-isolated bidirectional DC-DC buck-boost converter. This converter worked in two ways, which the charging mode stored energy into battery when load current was less than nominal main DC current (set point and discharging mode transferred energy from battery to the load when its current exceeded set point value. Both of these modes worked automatically according to the load current. The charging and discharging currents were controlled by fuzzy logic controller which was implemented on microcontroller ARM Cortex-M4F STM32F407VG. This paper compares two types of fuzzy membership function (triangular and sigmoid in controlling bidirectional DC-DC converter. The results showed that fuzzy logic controller with triangle membership function and sigmoid as control bidirectional DC-DC converter had no significant different response, both had an average error for charging and discharging process under 4% with ripple current on the main DC bus around 0.5%. The computing time of program for fuzzy logic controller with triangular membership functions had 19.01% faster than sigmoid, and fuzzy logic computation time on a microcontroller with hardware floating point was 60% faster than software floating point.

A High-Efficiency Isolated LCLC Multi-Resonant Three-Port Bidirectional DC-DC Converter

Directory of Open Access Journals (Sweden)

Cheng-Shan Wang

2017-07-01

Full Text Available In this paper, an isolated multi-resonant three-port bidirectional direct current-direct current (DC-DC converter is proposed, which is composed of three full bridges, two inductor-capacitor-inductor-capacitor (LCLC multi-resonant tanks and a three-winding transformer. The phase shift control method is employed to manage the power transmission among three ports. Relying on the appropriate parameter selection, both of the fundamental and the third order power can be delivered through the multi-element LCLC resonant tanks, and consequently, it contributes to restrained circulating energy and the desirable promoted efficiency. Besides, by adjusting the driving frequency under different load conditions, zero-voltage-switching (ZVS characteristics of all the switches of three ports are guaranteed. Therefore, lower switching loss and higher efficiency are achieved in full load range. In order to verify the feasibility of the proposed topology, a 1.5 kW prototype is established, of which the maximum efficiencies under forward and reverse operating conditions are 96.7% and 96.9% respectively. In addition, both of the bidirectional efficiencies maintain higher than 95.5% when the power level is above 0.5 kW.

Digitally intensive DC-DC converter for extreme space environments, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — The Space Micro-Arizona State University (ASU) team will develop an all-digitally controlled, wide temperature range point-of-load switch-mode DC-DC regulator core...

Pokemon siRNA Delivery Mediated by RGD-Modified HBV Core Protein Suppressed the Growth of Hepatocellular Carcinoma.

Science.gov (United States)

Kong, Jing; Liu, Xiaoping; Jia, Jianbo; Wu, Jinsheng; Wu, Ning; Chen, Jun; Fang, Fang

2015-10-01

Hepatocellular carcinoma (HCC) is a deadly human malignant tumor that is among the most common cancers in the world, especially in Asia. Hepatitis B virus (HBV) infection has been well established as a high risk factor for hepatic malignance. Studies have shown that Pokemon is a master oncogene for HCC growth, suggesting it as an ideal therapeutic target. However, efficient delivery system is still lacking for Pokemon targeting treatment. In this study, we used core proteins of HBV, which is modified with RGD peptides, to construct a biomimetic vector for the delivery of Pokemon siRNAs (namely, RGD-HBc-Pokemon siRNA). Quantitative PCR and Western blot assays revealed that RGD-HBc-Pokemon siRNA possessed the highest efficiency of Pokemon suppression in HCC cells. In vitro experiments further indicated that RGD-HBc-Pokemon-siRNA exerted a higher tumor suppressor activity on HCC cell lines, evidenced by reduced proliferation and attenuated invasiveness, than Pokemon-siRNA or RGD-HBc alone. Finally, animal studies demonstrated that RGD-HBc-Pokemon siRNA suppressed the growth of HCC xenografts in mice by a greater extent than Pokemon-siRNA or RGD-HBc alone. Based on the above results, Pokemon siRNA delivery mediated by RGD-modified HBV core protein was shown to be an effective strategy of HCC gene therapy.

Influence of a transverse magnetic field on arc root movements in a dc plasma torch: Diamagnetic effect of arc column

International Nuclear Information System (INIS)

Kim, Keun Su

2009-01-01

The effect of a transverse magnetic field on the anodic arc root movement inside a dc plasma torch has been investigated. The arc voltage fluctuation, which represents the degree of the arc instability, was reduced to 28.6% of the original value and the high frequency components in the voltage signal also decreased in their magnitudes. The inherent arc instability in a dc thermal plasma torch seems to be suppressed by a diamagnetic effect of the arc column. Furthermore, the measured voltage wave forms indicated that the arc root attachment mode would be controllable by a transverse magnetic field

Zero-voltage DC/DC converter with asymmetric pulse-width modulation for DC micro-grid system

Science.gov (United States)

Lin, Bor-Ren

2018-04-01

This paper presents a zero-voltage switching DC/DC converter for DC micro-grid system applications. The proposed circuit includes three half-bridge circuit cells connected in primary-series and secondary-parallel in order to lessen the voltage rating of power switches and current rating of rectifier diodes. Thus, low voltage stress of power MOSFETs can be adopted for high-voltage input applications with high switching frequency operation. In order to achieve low switching losses and high circuit efficiency, asymmetric pulse-width modulation is used to turn on power switches at zero voltage. Flying capacitors are used between each circuit cell to automatically balance input split voltages. Therefore, the voltage stress of each power switch is limited at Vin/3. Finally, a prototype is constructed and experiments are provided to demonstrate the circuit performance.

A Fixed-Frequency Bidirectional Resonant DC-DC Converter Suitable for Wide Voltage Gain Range

DEFF Research Database (Denmark)

Shen, Yanfeng; Wang, Huai; Blaabjerg, Frede

2017-01-01

This paper proposes a new bidirectional resonant dc-dc converter suitable for wide voltage gain range applications (e.g., energy storage systems). The proposed converter overcomes the narrow voltage gain range of conventional resonant DC-DC converters, and meanwhile achieves high efficiency...... and characteristics of the proposed converter are analyzed. Finally, a 1-kW converter prototype is built and the experimental results verify the theoretical analyses....

Frequency of interaction-mediated triggering of antibiotic production among soil bacteria

Directory of Open Access Journals (Sweden)

Olaf eTyc

2014-10-01

Full Text Available Certain bacterial species produce antimicrobial compounds only in the presence of a competing species. However little is known on the frequency of interaction-mediated induction of antibiotic compound production in natural communities of soil bacteria. Here we developed a high-throughput method to screen for the production of antimicrobial activity by monocultures and pair-wise combinations of 146 phylogenetically different bacteria isolated from similar soil habitats. Growth responses of two human pathogenic model organisms, Escherichia coli WA321 and Staphylococcus aureus 533R4, were used to monitor antimicrobial activity. From all isolates, 33% showed antimicrobial activity only in monoculture and 42% showed activity only when tested in interactions. More bacterial isolates were active against S. aureus than against E. coli. The frequency of interaction-mediated induction of antimicrobial activity was 6% (154 interactions out of 2798 indicating that only a limited set of species combinations showed such activity. The screening revealed also interaction-mediated suppression of antimicrobial activity for 22% of all combinations tested. Whereas all patterns of antimicrobial activity (non-induced production, induced production and suppression were seen for various bacterial classes, interaction-mediated induction of antimicrobial activity was more frequent for combinations of Flavobacteria and alpha- Proteobacteria. The results of our study give a first indication on the frequency of interference competitive interactions in natural soil bacterial communities which may forms a basis for selection of bacterial groups that are promising for the discovery of novel, cryptic antibiotics.

Time course of dichoptic masking in normals and suppression in amblyopes.

Science.gov (United States)

Zhou, Jiawei; McNeal, Suzanne; Babu, Raiju J; Baker, Daniel H; Bobier, William R; Hess, Robert F

2014-04-17

To better understand the relationship between dichoptic masking in normal vision and suppression in amblyopia we address three questions: First, what is the time course of dichoptic masking in normals and amblyopes? Second, is interocular suppression low-pass or band-pass in its spatial dependence? And third, in the above two regards, is dichoptic masking in normals different from amblyopic suppression? We measured the dependence of dichoptic masking in normal controls and amblyopes on the temporal duration of presentation under three conditions; monocular (the nontested eye-i.e., dominant eye of normals or nonamblyopic eye of amblyopes, being patched), dichoptic-luminance (the nontested eye seeing a mean luminance-i.e., a DC component) and dichoptic-contrast (the nontested eye seeing high-contrast visual noise). The subject had to detect a letter in the other eye, the contrast of which was varied. We found that threshold elevation relative to the patched condition occurred in both normals and amblyopes when the nontested eye saw either 1/f or band-pass filtered noise, but not just mean luminance (i.e., there was no masking from the DC component that corresponds to a channel responsive to a spatial frequency of 0 cyc/deg); longer presentation of the target (corresponding to lower temporal frequencies) produced greater threshold elevation. Dichoptic masking exhibits similar properties in both subject groups, being low-pass temporally and band-pass spatially, so that masking was greatest at the longest presentation durations and was not greatly affected by mean luminance in the nontested eye. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Pulse-width modulated DC-DC power converters

CERN Document Server

Kazimierczuk, Marian K

2008-01-01

This book studies switch-mode power supplies (SMPS) in great detail. This type of converter changes an unregulated DC voltage into a high-frequency pulse-width modulated (PWM) voltage controlled by varying the duty cycle, then changes the PWM AC voltage to a regulated DC voltage at a high efficiency by rectification and filtering. Used to supply electronic circuits, this converter saves energy and space in the overall system. With concept-orientated explanations, this book offers state-of-the-art SMPS technology and promotes an understanding of the principle operations of PWM converters,

Digitally intensive DC-DC converter for extreme space environments, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — The Space Micro –Arizona State University (ASU) team will develop an all-digitally controlled, wide temperature range point-of-load switch-mode DC-DC regulator core...

DC Voltage Droop Control Implementation in the AC/DC Power Flow Algorithm: Combinational Approach

DEFF Research Database (Denmark)

Akhter, F.; Macpherson, D.E.; Harrison, G.P.

2015-01-01

of operational flexibility, as more than one VSC station controls the DC link voltage of the MTDC system. This model enables the study of the effects of DC droop control on the power flows of the combined AC/DC system for steady state studies after VSC station outages or transient conditions without needing...... to use its complete dynamic model. Further, the proposed approach can be extended to include multiple AC and DC grids for combined AC/DC power flow analysis. The algorithm is implemented by modifying the MATPOWER based MATACDC program and the results shows that the algorithm works efficiently....

Computer Simulation of Phase Shifted Series Resonant DC to DC Converter

Directory of Open Access Journals (Sweden)

P. PARVATHY

2016-01-01

Full Text Available This paper deals with digital simulation of phase shifted series resonant DC to DC converter using Matlab Simulink. The Simulink models for open loop and closed loop systems are developed and they are used for simulation studies. This converter is capable of producing ripple free DC output. Switching losses and switching stresses are reduced by using soft switching. This converter has advantages like high power density and low switching losses. Theoretical predictions are well supported by the simulation results.

Power flow analysis for DC voltage droop controlled DC microgrids

DEFF Research Database (Denmark)

Li, Chendan; Chaudhary, Sanjay; Dragicevic, Tomislav

2014-01-01

This paper proposes a new algorithm for power flow analysis in droop controlled DC microgrids. By considering the droop control in the power flow analysis for the DC microgrid, when compared with traditional methods, more accurate analysis results can be obtained. The algorithm verification is ca...

Light weight, high power, high voltage dc/dc converter technologies

Science.gov (United States)

Kraus, Robert; Myers, Ira; Baumann, Eric

1990-01-01

Power-conditioning weight reductions by orders of magnitude will be required to enable the megawatt-power-level space systems envisioned by the Strategic Defense Initiative, the Air Force, and NASA. An interagency program has been initiated to develop an 0.1-kg/kW dc/dc converter technology base for these future space applications. Three contractors are in the first phase of a competitive program to develop a megawatt dc/dc converter. Researchers at NASA Lewis Research Center are investigating innovative converter topology control. Three different converter subsystems based on square wave, resonant, and super-resonant topologies are being designed. The components required for the converter designs cover a wide array of technologies. Two different switches, one semiconductor and the other gas, are under development. Issues related to thermal management and material reliability for inductors, transformers, and capacitors are being investigated in order to maximize power density. A brief description of each of the concepts proposed to meet the goals of this program is presented.

Digital peak current mode control with adaptive slope compensation for DC-DC converters

DEFF Research Database (Denmark)

Andersen, Karsten Holm; Nymand, Morten

2017-01-01

performance and stability of current mode control. The presented method adapt to DC-DC converter operating conditions by estimating the rising and falling inductor current slopes, to apply a current slope compensation value to obtain a constant quality factor. The experimental results verifies the theoretical......This paper presents an adaptive slope compensation method for peak current mode control of digital controlled DC-DC converters, which controls the quality factor of the complex conjugated poles at half the switching frequency. Using quality factor control enables optimization of the dynamic...

DC-Link Compensation Method for Slim DC Link Drives Fed by Soft Grid

DEFF Research Database (Denmark)

Mathe, Laszlo; Rosendahl Andersen, Henrik; Lazar, Radu

2010-01-01

Slim DC-link PWM (AC) drives for lowperformance applications are emerging on the market. Such drives equipped with a small DC-link capacitance exhibit instability tendencies, if installed on a soft line, giving a degraded performance. The total harmonic distortion (THD) and the partially weighted...... harmonic distortion (PWHD) of the line current are degraded, if resonance between the line impedance and the DC-link capacitance occurs. Likewise, the motor performance is affected negatively giving extra torque ripple, vibration and acoustic-noise emission. This paper proposes a novel DC-link compensation...

Activated T cells sustain myeloid-derived suppressor cell-mediated immune suppression

Science.gov (United States)

Damuzzo, Vera; Francescato, Samuela; Pozzuoli, Assunta; Berizzi, Antonio; Mocellin, Simone; Rossi, Carlo Riccardo; Bronte, Vincenzo; Mandruzzato, Susanna

2016-01-01

The expansion of myeloid derived suppressor cells (MDSCs), a suppressive population able to hamper the immune response against cancer, correlates with tumor progression and overall survival in several cancer types. We have previously shown that MDSCs can be induced in vitro from precursors present in the bone marrow and observed that these cells are able to actively proliferate in the presence of activated T cells, whose activation level is critical to drive the suppressive activity of MDSCs. Here we investigated at molecular level the mechanisms involved in the interplay between MDSCs and activated T cells. We found that activated T cells secrete IL-10 following interaction with MDSCs which, in turn, activates STAT3 phosphorylation on MDSCs then leading to B7-H1 expression. We also demonstrated that B7-H1+ MDSCs are responsible for immune suppression through a mechanism involving ARG-1 and IDO expression. Finally, we show that the expression of ligands B7-H1 and MHC class II both on in vitro-induced MDSCs and on MDSCs in the tumor microenvironment of cancer patients is paralleled by an increased expression of their respective receptors PD-1 and LAG-3 on T cells, two inhibitory molecules associated with T cell dysfunction. These findings highlight key molecules and interactions responsible for the extensive cross-talk between MDSCs and activated T cells that are at the basis of immune suppression. PMID:26700461

High-power three-port three-phase bidirectional DC-DC converter

NARCIS (Netherlands)

Tao, H.; Duarte, J.L.; Hendrix, M.A.M.

2007-01-01

This paper proposes a three-port three-phase bidirectional dc-dc converter suitable for high-power applications. The converter combines a slow primary source and a fast storage to power a common load (e.g., an inverter). Since this type of system is gaining popularity in sustainable energy

Interleukin-4 Supports the Suppressive Immune Responses Elicited by Regulatory T Cells

Directory of Open Access Journals (Sweden)

Wei-Cheng Yang

2017-11-01

Full Text Available Interleukin-4 (IL-4 has been considered as one of the tolerogenic cytokines in many autoimmune animal models and clinical settings. Despite its role in antagonizing pathogenic Th1 responses, little is known about whether IL-4 possesses functions that affect regulatory T cells (Tregs. Tregs are specialized cells responsible for the maintenance of peripheral tolerance through their immune modulatory capabilities. Interestingly, it has been suggested that IL-4 supplement at a high concentration protects responder T cells (Tresps from Treg-mediated immune suppression. In addition, such supplement also impedes TGF-β-induced Treg differentiation in vitro. However, these phenomena may contradict the tolerogenic role of IL-4, and the effects of IL-4 on Tregs are therefore needed to be further elucidated. In this study, we utilized IL-4 knockout (KO mice to validate the role of IL-4 on Treg-mediated immune suppression. Although IL-4 KO and control animals harbor similar frequencies of Tregs, Tregs from IL-4 KO mice weakly suppressed autologous Tresp activation. In addition, IL-4 deprivation impaired the ability of Tregs to modulate immune response, whereas IL-4 supplementation reinforced IL-4 KO Tregs in their function in suppressing Tresps. Finally, the presence of IL-4 was associated with increased cell survival and granzyme expression of Tregs. These results suggest the essential role of IL-4 in supporting Treg-mediated immune suppression, which may benefit the development of therapeutic strategies for autoimmune diseases.

Precharge strategies for isolated modular DC-DC converters under two different start-up conditions

DEFF Research Database (Denmark)

Zhang, Yi; Wang, Huai; Li, Binbin

2017-01-01

The isolated modular DC-DC converter (IMDCC) is a new topology designed to connect high-voltage direct current (HVDC) lines with different voltage levels, which ties two DC grids by using two modular multilevel converters (MMCs) via a medium-frequency transformer. Due to the large value of capaci......The isolated modular DC-DC converter (IMDCC) is a new topology designed to connect high-voltage direct current (HVDC) lines with different voltage levels, which ties two DC grids by using two modular multilevel converters (MMCs) via a medium-frequency transformer. Due to the large value...... of capacitance in the IMDCC, proper precharge strategies before the start-up are significant for the safety and reliability of the whole system. This paper presents two closed-loop precharge control strategies to fully charge the sub-module (SM) capacitors of the IMDCC, considering two different start...

Modeling and analysis of fractional order DC-DC converter.

Science.gov (United States)

Radwan, Ahmed G; Emira, Ahmed A; AbdelAty, Amr M; Azar, Ahmad Taher

2017-07-11

Due to the non-idealities of commercial inductors, the demand for a better model that accurately describe their dynamic response is elevated. So, the fractional order models of Buck, Boost and Buck-Boost DC-DC converters are presented in this paper. The detailed analysis is made for the two most common modes of converter operation: Continuous Conduction Mode (CCM) and Discontinuous Conduction Mode (DCM). Closed form time domain expressions are derived for inductor currents, voltage gain, average current, conduction time and power efficiency where the effect of the fractional order inductor is found to be strongly present. For example, the peak inductor current at steady state increases with decreasing the inductor order. Advanced Design Systems (ADS) circuit simulations are used to verify the derived formulas, where the fractional order inductor is simulated using Valsa Constant Phase Element (CPE) approximation and Generalized Impedance Converter (GIC). Different simulation results are introduced with good matching to the theoretical formulas for the three DC-DC converter topologies under different fractional orders. A comprehensive comparison with the recently published literature is presented to show the advantages and disadvantages of each approach. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

CD40L induces functional tunneling nanotube networks exclusively in dendritic cells programmed by mediators of type 1 immunity.

Science.gov (United States)

Zaccard, Colleen R; Watkins, Simon C; Kalinski, Pawel; Fecek, Ronald J; Yates, Aarika L; Salter, Russell D; Ayyavoo, Velpandi; Rinaldo, Charles R; Mailliard, Robbie B

2015-02-01

The ability of dendritic cells (DC) to mediate CD4(+) T cell help for cellular immunity is guided by instructive signals received during DC maturation, as well as the resulting pattern of DC responsiveness to the Th signal, CD40L. Furthermore, the professional transfer of antigenic information from migratory DC to lymph node-residing DC is critical for the effective induction of cellular immune responses. In this study we report that, in addition to their enhanced IL-12p70 producing capacity, human DC matured in the presence of inflammatory mediators of type 1 immunity are uniquely programmed to form networks of tunneling nanotube-like structures in response to CD40L-expressing Th cells or rCD40L. This immunologic process of DC reticulation facilitates intercellular trafficking of endosome-associated vesicles and Ag, but also pathogens such HIV-1, and is regulated by the opposing roles of IFN-γ and IL-4. The initiation of DC reticulation represents a novel helper function of CD40L and a superior mechanism of intercellular communication possessed by type 1 polarized DC, as well as a target for exploitation by pathogens to enhance direct cell-to-cell spread. Copyright © 2015 by The American Association of Immunologists, Inc.

Thermal activation and macroscopic quantum tunneling in a DC SQUID

International Nuclear Information System (INIS)

Sharifi, F.; Gavilano, J.L.; VanHarlingen, D.J.

1989-01-01

The authors report measurements of the transition rate from metastable minima in the two-dimensional 1 of a dc SQUID as a function of applied flux temperature. The authors observe a crossover from energy-activated escape to macroscopic quantum tunneling at a critical temperature. The macroscopic quantum tunneling rate is substantially reduced by damping, and also broadens the crossover region. Most interestingly, the authors observe thermal rates that are suppressed from those predicted by the two-dimensional thermal activation model. The authors discuss possible explanations for this based on the interaction of the macroscopic degree of freedom in the device and energy level effects

Magnetically coupled high-gain Y-source isolated DC/DC converter

DEFF Research Database (Denmark)

Siwakoti, Yam P.; Loh, Poh Chiang; Blaabjerg, Frede

2014-01-01

A new form of magnetically coupled DC/DC converter is proposed for medium power applications (250 W to 2 kW), requiring a high-voltage gain, short inductive charging time and galvanic isolation. The proposed converter can be realised using a unique Y-source impedance network and a two-switch push...

DC-SIGN activation mediates the differential effects of SAP and CRP on the innate immune system and inhibits fibrosis in mice.

Science.gov (United States)

Cox, Nehemiah; Pilling, Darrell; Gomer, Richard H

2015-07-07

Fibrosis is caused by scar tissue formation in internal organs and is associated with 45% of deaths in the United States. Two closely related human serum proteins, serum amyloid P (SAP) and C-reactive protein (CRP), strongly affect fibrosis. In multiple animal models, and in Phase 1 and Phase 2 clinical trials, SAP affects several aspects of the innate immune system to reduce fibrosis, whereas CRP appears to potentiate fibrosis. However, SAP and CRP bind the same Fcγ receptors (FcγR) with similar affinities, and why SAP and CRP have opposing effects is unknown. Here, we report that SAP but not CRP binds the receptor DC-SIGN (SIGN-R1) to affect the innate immune system, and that FcγR are not necessary for SAP function. A polycyclic aminothiazole DC-SIGN ligand and anti-DC-SIGN antibodies mimic SAP effects in vitro. In mice, the aminothiazole reduces neutrophil accumulation in a model of acute lung inflammation and, at 0.001 mg/kg, alleviates pulmonary fibrosis by increasing levels of the immunosuppressant IL-10. DC-SIGN (SIGN-R1) is present on mouse lung epithelial cells, and SAP and the aminothiazole potentiate IL-10 production from these cells. Our data suggest that SAP activates DC-SIGN to regulate the innate immune system differently from CRP, and that DC-SIGN is a target for antifibrotics.

A high voltage ratio and low ripple interleaved DC-DC converter for fuel cell applications.

Science.gov (United States)

Chang, Long-Yi; Chao, Kuei-Hsiang; Chang, Tsang-Chih

2012-01-01

This paper proposes a high voltage ratio and low ripple interleaved boost DC-DC converter, which can be used to reduce the output voltage ripple. This converter transfers the low DC voltage of fuel cell to high DC voltage in DC link. The structure of the converter is parallel with two voltage-doubler boost converters by interleaving their output voltages to reduce the voltage ripple ratio. Besides, it can lower the current stress for the switches and inductors in the system. First, the PSIM software was used to establish a proton exchange membrane fuel cell and a converter circuit model. The simulated and measured results of the fuel cell output characteristic curve are made to verify the correctness of the established simulation model. In addition, some experimental results are made to validate the effectiveness in improving output voltage ripple of the proposed high voltage ratio interleaved boost DC-DC converters.

'Isn't it ironic?' Beliefs about the unacceptability of emotions and emotional suppression relate to worse outcomes in fibromyalgia.

Science.gov (United States)

Bowers, Hannah; Wroe, Abigail L; Pincus, Tamar

2017-05-01

Beliefs about the unacceptability of experiencing and expressing emotions have been found to be related to worse outcomes in people with persistent physical symptoms. The current study tested mediation models regarding emotional suppression, beliefs about emotions, support-seeking and global impact in fibromyalgia. One hundred eighty-two participants took part in an online questionnaire testing potential mechanisms of this relationship using mediation analysis. The model tested emotional suppression and affective distress as serial mediators of the relationship between beliefs about emotions and global impact. In parallel paths, two forms of support-seeking were tested (personal/emotional and symptom-related support-seeking) as mediators. Emotional suppression and affective distress significantly serially mediated the relationship between beliefs about emotions and global impact. Neither support-seeking variable significantly mediated this relationship. Results indicate a potential mechanism through which beliefs about emotions and global impact might relate which might provide a theoretical basis for future research on treatments for fibromyalgia.

DC Rocks! Using Place-Based Learning to Introduce Washington DC's K-12 Students to the Geosciences

Science.gov (United States)

Mayberry, G. C.; Mattietti, G. K.

2017-12-01

The Washington DC area has interesting geology and a multitude of agencies that deal with the geosciences, yet K-12 public school students in DC, most of whom are minorities, have limited exposure to the geosciences. Geoscience agencies in the DC area have a unique opportunity to address this by introducing the geosciences to local students who otherwise may not have such an opportunity, by highlighting the geology in the students' "backyard," and by leveraging partnerships among DC-based geoscience-related agencies. The USGS and George Mason University are developing a project called DC Rocks, which will give DC's students an exciting introduction into the world of geoscience with place-based learning opportunities that will make geoscience relevant to their lives and their futures. Both the need in DC and the potential for lasting impact are great; the geosciences have the lowest racial diversity of all the science, technology, engineering, and math (STEM) fields, 89% of students in DC public schools are minorities, and there is no dedicated geoscience curriculum in DC. DC Rocks aims to give these students early exposure to the earth sciences, and encourage them to consider careers in the profession. DC Rocks will work with partner agencies to apply several methods that are recommended by researchers to increase the participation of minority students in the geosciences, including providing profoundly positive experiences that spark interest in the geosciences (Levine et al., 2007); increasing students' sense of belonging in the geosciences (Huntoon, et al, 2016); and place-based teaching practices that emphasize the study of local sites (Semken, 2005), such as DC's Rock Creek Park. DC Rocks will apply these methods by coordinating local geoscientists and resources to provide real-world examples of the geosciences' impact on students' lives. Through the DC Rocks website, educators will be able to request geoscience-related resources such as class presentations by