Dendritic Cells: A Spot on Sialic Acid

PubMed Central

Crespo, Hélio J.; Lau, Joseph T. Y.; Videira, Paula A.

2013-01-01

Glycans decorating cell surface and secreted proteins and lipids occupy the juncture where critical host–host and host-pathogen interactions occur. The role of glycan epitopes in cell–cell and cell-pathogen adhesive events is already well-established, and cell surface glycan structures change rapidly in response to stimulus and inflammatory cues. Despite the wide acceptance that glycans are centrally implicated in immunity, exactly how glycans and their changes contribute to the overall immune response remains poorly defined. Sialic acids are unique sugars that usually occupy the terminal position of the glycan chains and may be modified by external factors, such as pathogens, or upon specific physiological cellular events. At cell surface, sialic acid-modified structures form the key fundamental determinants for a number of receptors with known involvement in cellular adhesiveness and cell trafficking, such as the Selectins and the Siglec families of carbohydrate recognizing receptors. Dendritic cells (DCs) preside over the transition from innate to the adaptive immune repertoires, and no other cell has such relevant role in antigen screening, uptake, and its presentation to lymphocytes, ultimately triggering the adaptive immune response. Interestingly, sialic acid-modified structures are involved in all DC functions, such as antigen uptake, DC migration, and capacity to prime T cell responses. Sialic acid content changes along DC differentiation and activation and, while, not yet fully understood, these changes have important implications in DC functions. This review focuses on the developmental regulation of DC surface sialic acids and how manipulation of DC surface sialic acids can affect immune-critical DC functions by altering antigen endocytosis, pathogen and tumor cell recognition, cell recruitment, and capacity for T cell priming. The existing evidence points to a potential of DC surface sialylation as a therapeutic target to improve and diversify DC-based therapies. PMID:24409183

Dendritic Cell Transmigration through Brain Microvessel Endothelium Is Regulated by MIP-1α Chemokine and Matrix Metalloproteinases1

PubMed Central

Zozulya, Alla L.; Reinke, Emily; Baiu, Dana C.; Karman, Jozsef; Sandor, Matyas; Fabry, Zsuzsanna

2007-01-01

Dendritic cells (DCs) accumulate in the CNS during inflammatory diseases, but the exact mechanism regulating their traffic into the CNS remains to be defined. We now report that MIP-1α increases the transmigration of bone marrow-derived, GFP-labeled DCs across brain microvessel endothelial cell monolayers. Furthermore, occludin, an important element of endothelial tight junctions, is reorganized when DCs migrate across brain capillary endothelial cell monolayers without causing significant changes in the barrier integrity as measured by transendothelial electrical resistance. We show that DCs produce matrix metalloproteinases (MMP) -2 and -9 and GM6001, an MMP inhibitor, decreases both baseline and MIP-1α -induced DC transmigration. These observations suggest that DC transmigration across brain endothelial cell monolayers is partly MMP dependent. The migrated DCs express higher levels of CD40, CD80, and CD86 costimulatory molecules and induce T cell proliferation, indicating that the transmigration of DCs across brain endothelial cell monolayers contributes to the maintenance of DC Ag-presenting function. The MMP dependence of DC migration across brain endothelial cell monolayers raises the possibility that MMP blockers may decrease the initiation of T cell recruitment and neuroinflammation in the CNS. PMID:17182592

Sexual Victimization and the Military Environment: Contributing Factors, Vocational, Psychological, and Medical Sequelae

DTIC Science & Technology

1997-10-01

social attitudes are an important causative factor in sexual victimization. A multicultural study found that acceptance of rape myths ("all women want...included attempted or completed sexual penetration of the victim’s vagina , mouth or rectum. Physical assault was defined as any act not occurring during...before the 95th Congress, 2nd Session), Jan. 10-12. Washington, DC, Government Printing Office. Burt, M. R. (1980). "Cultural myths and supports for

A Competitive Infection Model of Hematogenously Disseminated Candidiasis in Mice Redefines the Role of Candida albicans IRS4 in Pathogenesis

PubMed Central

Raman, Suresh B.; Nguyen, M. Hong; Cheng, Shaoji; Badrane, Hassan; Iczkowski, Kenneth A.; Wegener, Marilyn; Gaffen, Sarah L.; Mitchell, Aaron P.

2013-01-01

Candida albicans IRS4 encodes a protein that regulates phosphatidylinositol-(4,5)-bisphosphate, which was shown to contribute to hematogenously disseminated candidiasis (DC) after several days in the standard mouse model. Our objective was to more accurately define the temporal contributions of IRS4 to pathogenesis. During competition assays in vitro, an irs4-null (Δirs4) mutant exhibited wild-type fitness. In DC experiments, mice were infected intravenously with the Δirs4 mutant, strain CAI-12 (1 × 105 CFU), or a mixture of the strains (0.5 × 105 CFU each). In single-strain infections, quantitative PCR revealed reduced Δirs4 mutant burdens within kidneys at days 1, 4, and 7 but not 6 h. In competitive infections, the Δirs4 mutant was outcompeted by CAI-12 in each mouse at ≥6 h (competitive indices, P ≤ 0.0001). At 4 and 7 days, the Δirs4 mutant burdens during competitive infections were significantly lower than those during single-strain infections (P = 0.01 and P < 0.001, respectively), suggesting increased susceptibility to inflammatory responses. Phagocytic infiltration of kidneys in response to CAI-12 or competitive infections was significantly greater than that in response to Δirs4 mutant infection at days 1 and 4 (P < 0.001), and the Δirs4 mutant was more susceptible to phagocytosis and killing by human polymorphonuclear cells (P = 0.01 and P = 0.006, respectively) and mouse macrophages in vitro (P = 0.04 and P = 0.01, respectively). Therefore, IRS4 contributes to tissue invasion at early stages of DC and mediates resistance to phagocytosis as DC progresses. Microarray analysis revealed remarkably similar gene expression by the Δirs4 mutant and reference strain CAI-12 within blood, suggesting that IRS4 is not significantly involved in the hematogenous stage of disease. A competitive DC model detects attenuated virulence that is not evident with the standard model. PMID:23429534

CD11c(hi) Dendritic Cells Regulate Ly-6C(hi) Monocyte Differentiation to Preserve Immune-privileged CNS in Lethal Neuroinflammation.

PubMed

Kim, Jin Hyoung; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Patil, Ajit Mahadev; Han, Young Woo; Park, Sang-Youel; Lee, John Hwa; Kim, Koanhoi; Eo, Seong Kug

2015-12-02

Although the roles of dendritic cells (DCs) in adaptive defense have been defined well, the contribution of DCs to T cell-independent innate defense and subsequent neuroimmunopathology in immune-privileged CNS upon infection with neurotropic viruses has not been completely defined. Notably, DC roles in regulating innate CD11b(+)Ly-6C(hi) monocyte functions during neuroinflammation have not yet been addressed. Using selective ablation of CD11c(hi)PDCA-1(int/lo) DCs without alteration in CD11c(int)PDCA-1(hi) plasmacytoid DC number, we found that CD11c(hi) DCs are essential to control neuroinflammation caused by infection with neurotropic Japanese encephalitis virus, through early and increased infiltration of CD11b(+)Ly-6C(hi) monocytes and higher expression of CC chemokines. More interestingly, selective CD11c(hi) DC ablation provided altered differentiation and function of infiltrated CD11b(+)Ly-6C(hi) monocytes in the CNS through Flt3-L and GM-CSF, which was closely associated with severely enhanced neuroinflammation. Furthermore, CD11b(+)Ly-6C(hi) monocytes generated in CD11c(hi) DC-ablated environment had a deleterious rather than protective role during neuroinflammation, and were more quickly recruited into inflamed CNS, depending on CCR2, thereby exacerbating neuroinflammation via enhanced supply of virus from the periphery. Therefore, our data demonstrate that CD11c(hi) DCs provide a critical and unexpected role to preserve the immune-privileged CNS in lethal neuroinflammation via regulating the differentiation, function, and trafficking of CD11b(+)Ly-6C(hi) monocytes.

Pension Plan Types and Financial Literacy in Later Life.

PubMed

Li, Yang; Burr, Jeffrey A; Miller, Edward Alan

2017-09-09

The ongoing shift from defined benefit (DB) to defined contribution (DC) pension plans means that middle-aged and older adults are increasingly being called upon to manage their own fiscal security in retirement. Yet, half of older Americans are financially illiterate, lacking the knowledge and skills to manage financial resources. This study investigates whether pension plan types are associated with varying levels of financial literacy among older Americans. Cross-sectional analyses of the 2010 Health and Retirement Study (HRS) (n = 1,281) using logistic and linear regression models were employed to investigate the association between different pension plans and multiple indicators of financial literacy. The potential moderating effect of gender was also examined. Respondents with DC plans, with or without additional DB plans, were more likely to correctly answer various financial literacy questions, in comparison with respondents with DB plans only. Men with both DC and DB plans scored significantly higher on the financial literacy index than women with both types of plans, relative to respondents with DB plans only. Middle-aged and older adults, who are incentivized by participation in DC plans to manage financial resources and decide where to invest pension funds, tend to self-educate to improve financial knowledge and skills, thereby resulting in greater financial literacy. This finding suggests that traditional financial education programs may not be the only means of achieving financial literacy. Further consideration should be given to providing older adults with continued, long-term exposure to financial decision-making opportunities. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Macrophage-Inducible C-Type Lectin Mincle-Expressing Dendritic Cells Contribute to Control of Splenic Mycobacterium bovis BCG Infection in Mice

PubMed Central

Behler, Friederike; Maus, Regina; Bohling, Jennifer; Knippenberg, Sarah; Kirchhof, Gabriele; Nagata, Masahiro; Jonigk, Danny; Izykowski, Nicole; Mägel, Lavinia; Welte, Tobias; Yamasaki, Sho

2014-01-01

The macrophage-inducible C-type lectin Mincle has recently been identified to be a pattern recognition receptor sensing mycobacterial infection via recognition of the mycobacterial cell wall component trehalose-6′,6-dimycolate (TDM). However, its role in systemic mycobacterial infections has not been examined so far. Mincle-knockout (KO) mice were infected intravenously with Mycobacterium bovis BCG to mimic the systemic spread of mycobacteria under defined experimental conditions. After intravenous infection with M. bovis BCG, Mincle-KO mice responded with significantly higher numbers of mycobacterial CFU in spleen and liver, while reduced granuloma formation was observed only in the spleen. At the same time, reduced Th1 cytokine production and decreased numbers of gamma interferon-producing T cells were observed in the spleens of Mincle-KO mice relative to the numbers in the spleens of wild-type (WT) mice. The effect of adoptive transfer of defined WT leukocyte subsets generated from bone marrow cells of zDC+/DTR mice (which bear the human diphtheria toxin receptor [DTR] under the control of the classical dendritic cell-specific zinc finger transcription factor zDC) to specifically deplete Mincle-expressing classical dendritic cells (cDCs) but not macrophages after diphtheria toxin application on the numbers of splenic and hepatic CFU and T cell subsets was then determined. Adoptive transfer experiments revealed that Mincle-expressing splenic cDCs rather than Mincle-expressing macrophages contributed to the reconstitution of attenuated splenic antimycobacterial immune responses in Mincle-KO mice after intravenous challenge with BCG. Collectively, we show that expression of Mincle, particularly by cDCs, contributes to the control of splenic M. bovis BCG infection in mice. PMID:25332121

A Cryogenic Dc-Dc Power Converter for a 100 kW Synchronous HTS Generator at Liquid Nitrogen Temperatures

NASA Astrophysics Data System (ADS)

Bailey, Wendell; Wen, Hauming; Yang, Yifeng; Forsyth, Andrew; Jia, Chungjiang

A dc-dc converter has been developed for retrofitting inside the vacuum space of the HTS rotor of a synchronous generator. The heavy copper sections of the current leads used for energising the HTS field winding were replaced by cryogenic power electronics; consisting of the converter and a rotor control unit. The converter board was designed using an H-bridge configuration with two 5A rated wires connecting the cryogenic boards to the stator control board located on the outside of the generator and drawing power from a (5A, 50 V) dc power source. The robustness of converter board was well demonstrated when it was powered up from a cold start at 82K. When charging the field winding with moderate currents (30A), the heat in-leak to the 'cold' rotor core was only 2W. It continued to function down to 74K, surviving several quenches. However, the quench protection function failed when injecting 75A into the field winding, resulting in the burn out of one of the DC-link capacitors. The magnitudes of the critical currents measured with the original current leads were compared to the quench currents, which was defined as the current which triggered quench protection protocol. The difference between the two currents was rather large, (∼20A). However, additional measurements using a single HTS coil in liquid nitrogen found that this reduction should not be so dramatic and in the region of 4A. Our conclusions identified the converter's switching voltage and its operating frequency as two parameters, which could have contributed to lowering the quench current. Magnetic fields and eddy currents are expected to be more prominent the field winding and its impact on the converter also need further investigation.

The Ampere and Electrical Standards

PubMed Central

Elmquist, Randolph E.; Cage, Marvin E.; Tang, Yi-hua; Jeffery, Anne-Marie; Kinard, Joseph R.; Dziuba, Ronald F.; Oldham, Nile M.; Williams, Edwin R.

2001-01-01

This paper describes some of the major contributions to metrology and physics made by the NIST Electricity Division, which has existed since 1901. It was one of the six original divisions of the National Bureau of Standards. The Electricity Division provides dc and low-frequency calibrations for industrial, scientific, and research organizations, and conducts research on topics related to electrical metrology and fundamental constants. The early work of the Electricity Division staff included the development of precision standards, such as Rosa and Thomas standard resistors and the ac-dc thermal converter. Research contributions helped define the early international system of measurement units and bring about the transition to absolute units based on fundamental principles and physical and dimensional measurements. NIST research has helped to develop and refine electrical standards using the quantum Hall effect and the Josephson effect, which are both based on quantum physics. Four projects covering a number of voltage and impedance measurements are described in detail. Several other areas of current research at NIST are described, including the use of the Internet for international compatibility in metrology, determination of the fine-structure and Planck constants, and construction of the electronic kilogram. PMID:27500018

Dendritic Cell Immune Responses in HIV-1 Controllers.

PubMed

Martin-Gayo, Enrique; Yu, Xu G

2017-02-01

Robust HIV-1-specific CD8 T cell responses are currently regarded as the main correlate of immune defense in rare individuals who achieve natural, drug-free control of HIV-1; however, the mechanisms that support evolution of such powerful immune responses are not well understood. Dendritic cells (DCs) are specialized innate immune cells critical for immune recognition, immune regulation, and immune induction, but their possible contribution to HIV-1 immune defense in controllers remains ill-defined. Recent studies suggest that myeloid DCs from controllers have improved abilities to recognize HIV-1 through cytoplasmic immune sensors, resulting in more potent, cell-intrinsic type I interferon secretion in response to viral infection. This innate immune response may facilitate DC-mediated induction of highly potent antiviral HIV-1-specific T cells. Moreover, protective HLA class I isotypes restricting HIV-1-specific CD8 T cells may influence DC function through specific interactions with innate myelomonocytic MHC class I receptors from the leukocyte immunoglobulin-like receptor family. Bi-directional interactions between dendritic cells and HIV-1-specific T cells may contribute to natural HIV-1 immune control, highlighting the importance of a fine-tuned interplay between innate and adaptive immune activities for effective antiviral immune defense.

Plasmacytoid dendritic cells: no longer an enigma and now key to transplant tolerance?

PubMed Central

Rogers, NM; Isenberg, JS; Thomson, AW

2014-01-01

Plasmacytoid (p) dendritic cells (DC) are a specialized subset of DC whose primary role was initially defined by the production of type I interferons in response to viral infection. They are now known to also possess a repertoire of functions capable of determining T cell fate and activation. Under homeostatic conditions, non-lymphoid tissue-resident pDC play a critical role in the regulation of mucosal immunity, as well as the development of central and peripheral tolerance. Although these cells display a number of characteristics that differ from conventional DC, particularly altered costimulatory molecule expression and poor allostimulatory capacity when interacting with T cells, this phenotype favors the generation of alloantigen-specific regulatory CD4+ or CD8+ T cells critical to the development of graft tolerance. In this minireview we discuss pDC ontogeny, functional biology and the emerging data that demonstrate the importance of pDC in the induction of tolerance, as well as recent studies that define mechanisms underlying pDC-mediated tolerance to both solid organ and hematopoietic stem cell transplantats. We also highlight their use in clinical settings and the potential of pDC both as targets and cellular therapeutic agents to improve the outcome of organ transplantation. PMID:23617754

Global Noise Studies for CMS Tracker Upgrade

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

Arteche, F.; /Zaragoza, ITA; Esteban, C.

The characterization of the noise emissions of DC-DC converters at system level is critical to optimize the design of the detector and define rules for the integration strategy. This paper presents the impedance effects on the noise emissions of DC-DC converters at system level. Conducted and radiated noise emissions at the input and at the output from DC-DC converters have been simulated for different types of power network and FEE impedances. System aspects as granularity, stray capacitances of the system and different working conditions of the DC-DC converters are presented too. This study has been carried out using simulation modelsmore » of noise emissions of DC-DC converters in the real scenario. The results of these studies show important recommendations and criteria to be applied to integrate the DC-DC converters and decrease the system noise level.« less

Protective Mechanisms of Mitochondria and Heart Function in Diabetes

PubMed Central

Tocchetti, Carlo G.; Bhatt, Niraj; Paolocci, Nazareno; Cortassa, Sonia

2015-01-01

Abstract Significance: The heart depends on continuous mitochondrial ATP supply and maintained redox balance to properly develop force, particularly under increased workload. During diabetes, however, myocardial energetic-redox balance is perturbed, contributing to the systolic and diastolic dysfunction known as diabetic cardiomyopathy (DC). Critical Issues: How these energetic and redox alterations intertwine to influence the DC progression is still poorly understood. Excessive bioavailability of both glucose and fatty acids (FAs) play a central role, leading, among other effects, to mitochondrial dysfunction. However, where and how this nutrient excess affects mitochondrial and cytoplasmic energetic/redox crossroads remains to be defined in greater detail. Recent Advances: We review how high glucose alters cellular redox balance and affects mitochondrial DNA. Next, we address how lipid excess, either stored in lipid droplets or utilized by mitochondria, affects performance in diabetic hearts by influencing cardiac energetic and redox assets. Finally, we examine how the reciprocal energetic/redox influence between mitochondrial and cytoplasmic compartments shapes myocardial mechanical activity during the course of DC, focusing especially on the glutathione and thioredoxin systems. Future Directions: Protecting mitochondria from losing their ability to generate energy, and to control their own reactive oxygen species emission is essential to prevent the onset and/or to slow down DC progression. We highlight mechanisms enforced by the diabetic heart to counteract glucose/FAs surplus-induced damage, such as lipid storage, enhanced mitochondria-lipid droplet interaction, and upregulation of key antioxidant enzymes. Learning more on the nature and location of mechanisms sheltering mitochondrial functions would certainly help in further optimizing therapies for human DC. Antioxid. Redox Signal. 22, 1563–1586. PMID:25674814

NASA DC-8 Pilots Craig Bomben and Bill Brockett explain the DC-8 cockpit to Chilean students onboard the DC-8 aircraft in Punta Arenas, Chile

NASA Image and Video Library

2004-03-17

NASA DC-8 Pilots Craig Bomben and Bill Brockett explain the DC-8 cockpit to Chilean students onboard the DC-8 aircraft at Carlos Ibanez del Campo International Airport in Punta Arenas, Chile. AirSAR 2004 is a three-week expedition by an international team of scientists that is using an all-weather imaging tool, called the Airborne Synthetic Aperture Radar (AirSAR) which is located onboard NASA's DC-8 airborne laboratory. Scientists from many parts of the world including NASA's Jet Propulsion Laboratory are combining ground research done in several areas in Central and South America with NASA's AirSAR technology to improve and expand on the quality of research they are able to conduct. In South America and Antarctica, AirSAR will collect imagery and data to help determine the contribution of Southern Hemisphere glaciers to sea level rise due to climate change. In Patagonia, researchers found this contribution had more than doubled from 1995 to 2000, compared to the previous 25 years. AirSAR data will make it possible to determine whether that trend is decreasing, continuing or accelerating. AirSAR will also provide reliable information on ice shelf thickness to measure the contribution of the glaciers to sea level.

Factors associated with NO2 and NOX concentration gradients near a highway.

PubMed

Richmond-Bryant, J; Snyder, M G; Owen, R C; Kimbrough, S

2017-11-21

The objective of this research is to learn how the near-road gradient, in which NO 2 and NO X (NO + NO 2 ) concentrations are elevated, varies with changes in meteorological and traffic variables. Measurements of NO 2 and NO X were obtained east of I-15 in Las Vegas and fit to functions whose slopes (dC NO 2 /dx and dC NO X /dx, respectively) characterize the size of the near-road zone where NO 2 and NO X concentrations from mobile sources on the highway are elevated. These metrics were used to learn about the near-road gradient by modeling dC NO 2 /dx and dC NO X /dx as functions of meteorological variables (e.g., wind direction, wind speed), traffic (vehicle count), NO X concentration upwind of the road, and O 3 concentration at two fixed-site ambient monitors. Generalized additive models (GAM) were used to model dC NO 2 /dx and dC NO X /dx versus the independent variables because they allowed for nonlinearity of the variables being compared. When data from all wind directions were included in the analysis, variability in O 3 concentration comprised the largest proportion of variability in dC NO 2 /dx, followed by variability in wind direction. In a second analysis constrained to winds from the west, variability in O 3 concentration remained the largest contributor to variability in dC NO 2 /dx, but the relative contribution of variability in wind speed to variability in dC NO 2 /dx increased relative to its contribution for the all-wind analysis. When data from all wind directions were analyzed, variability in wind direction was by far the largest contributor to variability in dC NO X /dx, with smaller contributions from hour of day and upwind NO X concentration. When only winds from the west were analyzed, variability in upwind NO X concentration, wind speed, hour of day, and traffic count all were associated with variability in dC NO X /dx. Increases in O 3 concentration were associated with increased magnitude near-road dC NO 2 /dx, possibly shrinking the zone of elevated concentrations occurring near roads. Wind direction parallel to the highway was also related to an increased magnitude of both dC NO 2 /dx and dC NO X /dx, again likely shrinking the zone of elevated concentrations occurring near roads. Wind direction perpendicular to the road decreased the magnitude of dC NO 2 /dx and dC NO X /dx and likely contributed to growth of the zone of elevated concentrations occurring near roads. Thus, variability in near-road concentrations is influenced by local meteorology and ambient O 3 concentration.

Characterization and Long-Term Prognosis of Postmyocarditic Dilated Cardiomyopathy Compared With Idiopathic Dilated Cardiomyopathy.

PubMed

Merlo, Marco; Anzini, Marco; Bussani, Rossana; Artico, Jessica; Barbati, Giulia; Stolfo, Davide; Gigli, Marta; Muça, Matilda; Naso, Paola; Ramani, Federica; Di Lenarda, Andrea; Pinamonti, Bruno; Sinagra, Gianfranco

2016-09-15

Dilated cardiomyopathy (DC) is the final common pathway of different pathogenetic processes and presents a significant prognostic heterogeneity, possibly related to its etiologic variety. The characterization and long-term prognosis of postmyocarditic dilated cardiomyopathy (PM-DC) remain unknown. This study assesses the clinical-instrumental evolution and long-term prognosis of a large cohort of patients with PM-DC. We analyzed 175 patients affected with DC consecutively enrolled from 1993 to 2008 with endomyocardial biopsy (EMB) data available. PM-DC was defined in the presence of borderline myocarditis at EMB or persistent left ventricular dysfunction 1 year after diagnosis of active myocarditis at EMB. Other patients were defined as affected by idiopathic dilated cardiomyopathy (IDC). Analysis of follow-up evaluations was performed at 24, 60, and 120 months. We found 72 PM-DC of 175 enrolled patients (41%). Compared with IDC, patients with PM-DC were more frequently females and less frequently presented a familial history of DC. No other baseline significant differences were found. During the long-term follow-up (median 154, first to third interquartile range 78 to 220 months), patients with PM-DC showed a trend toward slower disease progression. Globally, 18 patients with PM-DC (25%) versus 49 with IDC (48%) experienced death/heart transplantation (p = 0.045). The prognostic advantage for patients with PM-DC became significant beyond 40 months of follow-up. At multivariable time-dependent Cox analysis, PM-DC was confirmed to have a global independent protective role (hazard ratio 0.53, 95% confidence interval 0.28 to 0.97, p = 0.04). In conclusion, PM-DC is characterized by better long-term prognosis compared with IDC. An exhaustive etiologic characterization appears relevant in the prognostic assessment of DC. Copyright © 2016 Elsevier Inc. All rights reserved.

Defining essential processes in plant pathogenesis with Pseudomonas syringae pv. tomato DC3000 disarmed polymutants and a subset of key type III effectors.

PubMed

Wei, Hai-Lei; Collmer, Alan

2017-12-25

Pseudomonas syringae pv. tomato DC3000 and its derivatives cause disease in tomato, Arabidopsis and Nicotiana benthamiana. The primary virulence factors include a repertoire of 29 effector proteins injected into plant cells by the type III secretion system and the phytotoxin coronatine. The complete repertoire of effector genes and key coronatine biosynthesis genes have been progressively deleted and minimally reassembled to reconstitute basic pathogenic ability in N. benthamiana, and in Arabidopsis plants that have mutations in target genes that mimic effector actions. This approach and molecular studies of effector activities and plant immune system targets have highlighted a small subset of effectors that contribute to essential processes in pathogenesis. Most notably, HopM1 and AvrE1 redundantly promote an aqueous apoplastic environment, and AvrPtoB and AvrPto redundantly block early immune responses, two conditions that are sufficient for substantial bacterial growth in planta. In addition, disarmed DC3000 polymutants have been used to identify the individual effectors responsible for specific activities of the complete repertoire and to more effectively study effector domains, effector interplay and effector actions on host targets. Such work has revealed that AvrPtoB suppresses cell death elicitation in N. benthamiana that is triggered by another effector in the DC3000 repertoire, highlighting an important aspect of effector interplay in native repertoires. Disarmed DC3000 polymutants support the natural delivery of test effectors and infection readouts that more accurately reveal effector functions in key pathogenesis processes, and enable the identification of effectors with similar activities from a broad range of other pathogens that also defeat plants with cytoplasmic effectors. © 2017 BSPP AND JOHN WILEY & SONS LTD.

Dendritic Cells Promote Macrophage Infiltration and Comprise a Substantial Proportion of Obesity-Associated Increases in CD11c+ Cells in Adipose Tissue and Liver

PubMed Central

Stefanovic-Racic, Maja; Yang, Xiao; Turner, Michael S.; Mantell, Benjamin S.; Stolz, Donna B.; Sumpter, Tina L.; Sipula, Ian J.; Dedousis, Nikolaos; Scott, Donald K.; Morel, Penelope A.; Thomson, Angus W.; O’Doherty, Robert M.

2012-01-01

Obesity-associated increases in adipose tissue (AT) CD11c+ cells suggest that dendritic cells (DC), which are involved in the tissue recruitment and activation of macrophages, may play a role in determining AT and liver immunophenotype in obesity. This study addressed this hypothesis. With the use of flow cytometry, electron microscopy, and loss-and-gain of function approaches, the contribution of DC to the pattern of immune cell alterations and recruitment in obesity was assessed. In AT and liver there was a substantial, high-fat diet (HFD)–induced increase in DC. In AT, these increases were associated with crown-like structures, whereas in liver the increase in DC constituted an early and reversible response to diet. Notably, mice lacking DC had reduced AT and liver macrophages, whereas DC replacement in DC-null mice increased liver and AT macrophage populations. Furthermore, delivery of bone marrow–derived DC to lean wild-type mice increased AT and liver macrophage infiltration. Finally, mice lacking DC were resistant to the weight gain and metabolic abnormalities of an HFD. Together, these data demonstrate that DC are elevated in obesity, promote macrophage infiltration of AT and liver, contribute to the determination of tissue immunophenotype, and play a role in systemic metabolic responses to an HFD. PMID:22851575

GMP-Grade mRNA Electroporation of Dendritic Cells for Clinical Use.

PubMed

Derdelinckx, Judith; Berneman, Zwi N; Cools, Nathalie

2016-01-01

mRNA-electroporated dendritic cells (DC) are demonstrating clinical benefit in patients in many therapeutic areas, including cancer and infectious diseases. According to current good manufacturing guidelines, cell-based medicinal products have to be defined for identity, purity, potency, stability, and viability. In order to comply with the directives and guidelines defined by the regulatory authorities, we report here a standardized and reproducible method for the manufacturing of clinical-grade mRNA-transfected DC.

A Review of Microgrid Architectures and Control Strategy

NASA Astrophysics Data System (ADS)

Jadav, Krishnarajsinh A.; Karkar, Hitesh M.; Trivedi, I. N.

2017-12-01

In this paper microgrid architecture and various converters control strategies are reviewed. Microgrid is defined as interconnected network of distributed energy resources, loads and energy storage systems. This emerging concept realizes the potential of distributed generators. AC microgrid interconnects various AC distributed generators like wind turbine and DC distributed generators like PV, fuel cell using inverter. While in DC microgrid output of an AC distributed generator must be converted to DC using rectifiers and DC distributed generator can be directly interconnected. Hybrid microgrid is the solution to avoid this multiple reverse conversions AC-DC-AC and DC-AC-DC that occur in the individual AC-DC microgrid. In hybrid microgrid all AC distributed generators will be connected in AC microgrid and DC distributed generators will be connected in DC microgrid. Interlinking converter is used for power balance in both microgrids, which transfer power from one microgrid to other if any microgrid is overloaded. At the end, review of interlinking converter control strategies is presented.

Type I interferon regulates pDC maturation and Ly49Q expression.

PubMed

Toma-Hirano, Makiko; Namiki, Sahori; Miyatake, Shoichiro; Arai, Ken-Ichi; Kamogawa-Schifter, Yumiko

2007-10-01

Ly49Q is expressed on peripheral mouse plasmacytoid dendritic cells (pDC). Immature Ly49Q-negative pDC precursors acquire Ly49Q in the bone marrow and then migrate into the periphery. While searching for molecules that regulate pDC maturation, we found that type I interferon (IFN) inhibited Ly49Q acquisition in vitro. Infections that induce type I IFN production by cells other than pDC (a condition mimicked by poly(I:C) injection in vivo) increase the prevalence of Ly49Q(-) pDC in the bone marrow and peripheral lymphoid organs in wild-type but not IFN-alpha/beta receptor knockout BALB/c mice. Moreover, in vivo exposure to type I IFN causes some Ly49Q(-), but not Ly49Q(+), pDC to convert to conventional DC, defined as B220(-) CD11c(+) CD11b(+) cells. These data suggest that type I IFN regulates pDC development and affects their distribution in the body.

National Systematic Legal Review of State Policies on Emergency Medical Services Licensure Levels' Authority to Administer Opioid Antagonists.

PubMed

Kinsman, Jeremiah M; Robinson, Kathy

2018-02-27

Previous research conducted in November 2013 found there were a limited number of states and territories in the United States (US) that authorize emergency medical technicians (EMTs) and emergency medical responders (EMRs) to administer opioid antagonists. Given the continued increase in the number of opioid-related overdoses and deaths, many states have changed their policies to authorize EMTs and EMRs to administer opioid antagonists. The goal of this study is to provide an updated description of policy on EMS licensure levels' authority to administer opioid antagonists for all 50 US states, the District of Columbia (DC), and the Commonwealth of Puerto Rico (PR). State law and scopes of practice were systematically reviewed using a multi-tiered approach to determine each state's legally-defined EMS licensure levels and their authority to administer an opioid antagonist. State law, state EMS websites, and state EMS scope of practice documents were identified and searched using Google Advanced Search with Boolean Search Strings. Initial results of the review were sent to each state office of EMS for review and comment. As of September 1, 2017, 49 states and DC authorize EMTs to administer an opioid antagonist. Among the 40 US jurisdictions (39 states and DC) that define the EMR or a comparable first responder licensure level in state law, 37 states and DC authorize their EMRs to administer an opioid antagonist. Paramedics are authorized to administer opioid antagonists in all 50 states, DC, and PR. All 49 of the US jurisdictions (48 states and DC) that define the advanced emergency medical technician (AEMT) or a comparable intermediate EMS licensure level in state law authorize their AEMTs to administer an opioid antagonist. 49 out of 52 US jurisdictions (50 states, DC, and PR) authorize all existing levels of EMS licensure levels to administer an opioid antagonist. Expanding access to this medication can save lives, especially in communities that have limited advanced life support coverage.

Power flow in normal human voice production

NASA Astrophysics Data System (ADS)

Krane, Michael

2016-11-01

The principal mechanisms of energy utilization in voicing are quantified using a simplified model, in order to better define voice efficiency. A control volume analysis of energy utilization in phonation is presented to identify the energy transfer mechanisms in terms of their function. Conversion of subglottal airstream potential energy into useful work done (vocal fold vibration, flow work, sound radiation), and into heat (sound radiation absorbed by the lungs, glottal jet dissipation) are described. An approximate numerical model is used to compute the contributions of each of these mechanisms, as a function of subglottal pressure, for normal phonation. Acknowledge support of NIH Grant 2R01DC005642-10A1.

Tissue-specific differentiation of a circulating CCR9- pDC-like common dendritic cell precursor.

PubMed

Schlitzer, Andreas; Heiseke, Alexander F; Einwächter, Henrik; Reindl, Wolfgang; Schiemann, Matthias; Manta, Calin-Petru; See, Peter; Niess, Jan-Hendrik; Suter, Tobias; Ginhoux, Florent; Krug, Anne B

2012-06-21

The ontogenic relationship between the common dendritic cell (DC) progenitor (CDP), the committed conventional DC precursor (pre-cDC), and cDC subpopulations in lymphoid and nonlymphoid tissues has been largely unraveled. In contrast, the sequential steps of plasmacytoid DC (pDC) development are less defined, and it is unknown at which developmental stage and location final commitment to the pDC lineage occurs. Here we show that CCR9(-) pDCs from murine BM which enter the circulation and peripheral tissues have a common DC precursor function in vivo in the steady state, in contrast to CCR9(+) pDCs which are terminally differentiated. On adoptive transfer, the fate of CCR9(-) pDC-like precursors is governed by the tissues they enter. In the BM and liver, most transferred CCR9(-) pDC-like precursors differentiate into CCR9(+) pDCs, whereas in peripheral lymphoid organs, lung, and intestine, they additionally give rise to cDCs. CCR9(-) pDC-like precursors which are distinct from pre-cDCs can be generated from the CDP. Thus, CCR9(-) pDC-like cells are novel CDP-derived circulating DC precursors with pDC and cDC potential. Their final differentiation into functionally distinct pDCs and cDCs depends on tissue-specific factors allowing adaptation to local requirements under homeostatic conditions.

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

NASA Astrophysics Data System (ADS)

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.

Hepatitis B virus surface antigen impairs myeloid dendritic cell function: a possible immune escape mechanism of hepatitis B virus

PubMed Central

Op den Brouw, Marjoleine L; Binda, Rekha S; van Roosmalen, Mark H; Protzer, Ulrike; Janssen, Harry L A; van der Molen, Renate G; Woltman, Andrea M

2009-01-01

Chronic hepatitis B virus (HBV) infection is the result of an inadequate immune response towards the virus. Myeloid dendritic cells (mDC) of patients with chronic HBV are impaired in their maturation and function, resulting in more tolerogenic rather than immunogenic responses, which may contribute to viral persistence. The mechanism responsible for altered mDC function remains unclear. The HBV-infected patients display large amounts of HBV particles and viral proteins in their circulation, especially the surface antigen HBsAg, which allows multiple interactions between the virus, its viral proteins and DC. To assess whether HBV directly influences mDC function, the effects of HBV and HBsAg on human mDC maturation and function were investigated in vitro. As already described for internalization of HBV by DC, the present study shows that peripheral blood-derived mDC of healthy controls also actively take up HBsAg in a time-dependent manner. Cytokine-induced maturation in the presence of HBV or HBsAg resulted in a significantly more tolerogenic mDC phenotype as demonstrated by a diminished up-regulation of costimulatory molecules and a decreased T-cell stimulatory capacity, as assessed by T-cell proliferation and interferon-γ production. In addition, the presence of HBV significantly reduced interleukin-12 production by mDC. These results show that both HBV particles and purified HBsAg have an immune modulatory capacity and may directly contribute to the dysfunction of mDC in patients with chronic HBV. The direct immune regulatory effect of HBV and circulating HBsAg particles on the function of DC can be considered as part of the mechanism by which HBV escapes immunity. PMID:18624732

EGFR-driven up-regulation of decoy receptor 3 in keratinocytes contributes to the pathogenesis of psoriasis.

PubMed

Wu, Nan-Lin; Huang, Duen-Yi; Hsieh, Shie-Liang; Hsiao, Cheng-Hsiang; Lee, Te-An; Lin, Wan-Wan

2013-10-01

Decoy receptor 3 (DcR3) is a soluble receptor of Fas ligand (FasL), LIGHT (TNFSF14) and TNF-like molecule 1A (TL1A) and plays pleiotropic roles in many inflammatory and autoimmune disorders and malignant diseases. In cutaneous biology, DcR3 is expressed in primary human epidermal keratinocytes and is upregulated in skin lesions in psoriasis, which is characterized by chronic inflammation and angiogenesis. However, the regulatory mechanisms of DcR3 over-expression in skin lesions of psoriasis are unknown. Here, we demonstrate that DcR3 can be detected in both dermal blood vessels and epidermal layers of psoriatic skin lesions. Analysis of serum samples showed that DcR3 was elevated, but FasL was downregulated in psoriatic patients compared with normal individuals. Additional cell studies revealed a central role of epidermal growth factor receptor (EGFR) in controlling the basal expression of DcR3 in keratinocytes. Activation of EGFR by epidermal growth factor (EGF) and transforming growth factor (TGF)-α strikingly upregulated DcR3 production. TNF-αenhanced DcR3 expression in both keratinocytes and endothelial cells compared with various inflammatory cytokines involved in psoriasis. Additionally, TNF-α-enhanced DcR3 expression in keratinocytes was inhibited when EGFR was knocked down or EGFR inhibitor was used. The NF-κB pathway was critically involved in the molecular mechanisms underlying the action of EGFR and inflammatory cytokines. Collectively, the novel regulatory mechanisms of DcR3 expression in psoriasis, particularly in keratinocytes and endothelial cells, provides new insight into the pathogenesis of psoriasis and may also contribute to the understanding of other diseases that involve DcR3 overexpression. Copyright © 2013 Elsevier B.V. All rights reserved.

NASA DC-8 Ground Support Technician Joe Niquette performs routine maintenance on the DC-8 aircraft in Punta Arenas, Chile

NASA Image and Video Library

2004-03-17

NASA DC-8 Ground Support Technician Joe Niquette performs routine maintenance on the DC-8 aircraft at Carlos Ibanez del Campo International Airport in Punta Arenas, Chile. AirSAR 2004 is a three-week expedition by an international team of scientists that is using an all-weather imaging tool, called the Airborne Synthetic Aperture Radar (AirSAR) which is located onboard NASA's DC-8 airborne laboratory. Scientists from many parts of the world including NASA's Jet Propulsion Laboratory are combining ground research done in several areas in Central and South America with NASA's AirSAR technology to improve and expand on the quality of research they are able to conduct. In South America and Antarctica, AirSAR will collect imagery and data to help determine the contribution of Southern Hemisphere glaciers to sea level rise due to climate change. In Patagonia, researchers found this contribution had more than doubled from 1995 to 2000, compared to the previous 25 years. AirSAR data will make it possible to determine whether that trend is decreasing, continuing or accelerating. AirSAR will also provide reliable information on ice shelf thickness to measure the contribution of the glaciers to sea level.

Direct current modulation of spin-Hall-induced spin torque ferromagnetic resonance in platinum/permalloy bilayer thin films

NASA Astrophysics Data System (ADS)

Hirayama, Shigeyuki; Mitani, Seiji; Otani, YoshiChika; Kasai, Shinya

2018-06-01

We examined the spin-Hall-induced spin torque ferromagnetic resonance (ST-FMR) in platinum/permalloy bilayer thin films under bias direct current (DC). The bias DC modulated the symmetric components of the ST-FMR spectra, while no dominant modulation was found in the antisymmetric components. A detailed analysis in combination with simple model calculations clarified that the major origin of the modulation can be attributed to the DC resistance change under the precessional motion of magnetization. This effect is the second order contribution for the precession angle, even though the contribution can be comparable to the rectification voltage under some specific conditions.

The Pseudorabies Virus Glycoprotein gE/gI Complex Suppresses Type I Interferon Production by Plasmacytoid Dendritic Cells

PubMed Central

Lamote, Jochen A. S.; Kestens, Manon; Van Waesberghe, Cliff; Delva, Jonas; De Pelsmaeker, Steffi; Devriendt, Bert

2017-01-01

ABSTRACT Plasmacytoid dendritic cells (pDC) play a central role in the antiviral immune response, both in the innate response and in shaping the adaptive response, mainly because of their ability to produce massive amounts of type I interferon (TI-IFN). Here, we report that cells infected with the live attenuated Bartha vaccine strain of porcine alphaherpesvirus pseudorabies virus (PRV) trigger a dramatically increased TI-IFN response by porcine primary pDC compared to cells infected with wild-type PRV strains (Becker and Kaplan). Since Bartha is one of the relatively few examples of a highly successful alphaherpesvirus vaccine, identification of factors that may contribute to its efficacy may provide insights for the rational design of other alphaherpesvirus vaccines. The Bartha vaccine genome displays several mutations compared to the genome of wild-type PRV strains, including a large deletion in the unique short (US) region, encompassing the glycoprotein E (gE), gI, US9, and US2 genes. Using recombinant PRV Becker strains harboring the entire Bartha US deletion or single mutations in the four affected US genes, we demonstrate that the absence of the viral gE/gI complex contributes to the observed increased IFN-α response. Furthermore, we show that the absence of gE leads to an enhanced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation in pDC, which correlates with a higher TI-IFN production by pDC. In conclusion, the PRV Bartha vaccine strain triggers strongly increased TI-IFN production by porcine pDC. Our data further indicate that the gE/gI glycoprotein complex suppresses TI-IFN production by pDC, which represents the first alphaherpesvirus factor that suppresses pDC activity. IMPORTANCE Several alphaherpesviruses, including herpes simpex virus, still lack effective vaccines. However, the highly successful Bartha vaccine has contributed substantially to eradication of the porcine alphaherpesvirus pseudorabies virus (PRV) in several countries. The impact of Bartha on the immune response is still poorly understood. Type I interferon (TI-IFN)-producing plasmacytoid dendritic cells (pDC) may play an important role in vaccine development. Here, we show that Bartha elicits a dramatically increased type I interferon (TI-IFN) response in primary porcine pDC compared to wild-type strains. In addition, we found that the gE/gI complex, which is absent in Bartha, inhibits the pDC TI-IFN response. This is the first description of an immune cell type that is differentially affected by Bartha versus wild-type PRV and is the first report describing an alphaherpesvirus protein that inhibits the TI-IFN response by pDC. These data may therefore contribute to the rational design of other alphaherpesvirus vaccines. PMID:28122975

The Pseudorabies Virus Glycoprotein gE/gI Complex Suppresses Type I Interferon Production by Plasmacytoid Dendritic Cells.

PubMed

Lamote, Jochen A S; Kestens, Manon; Van Waesberghe, Cliff; Delva, Jonas; De Pelsmaeker, Steffi; Devriendt, Bert; Favoreel, Herman W

2017-04-01

Plasmacytoid dendritic cells (pDC) play a central role in the antiviral immune response, both in the innate response and in shaping the adaptive response, mainly because of their ability to produce massive amounts of type I interferon (TI-IFN). Here, we report that cells infected with the live attenuated Bartha vaccine strain of porcine alphaherpesvirus pseudorabies virus (PRV) trigger a dramatically increased TI-IFN response by porcine primary pDC compared to cells infected with wild-type PRV strains (Becker and Kaplan). Since Bartha is one of the relatively few examples of a highly successful alphaherpesvirus vaccine, identification of factors that may contribute to its efficacy may provide insights for the rational design of other alphaherpesvirus vaccines. The Bartha vaccine genome displays several mutations compared to the genome of wild-type PRV strains, including a large deletion in the unique short (US) region, encompassing the glycoprotein E (gE), gI, US9, and US2 genes. Using recombinant PRV Becker strains harboring the entire Bartha US deletion or single mutations in the four affected US genes, we demonstrate that the absence of the viral gE/gI complex contributes to the observed increased IFN-α response. Furthermore, we show that the absence of gE leads to an enhanced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation in pDC, which correlates with a higher TI-IFN production by pDC. In conclusion, the PRV Bartha vaccine strain triggers strongly increased TI-IFN production by porcine pDC. Our data further indicate that the gE/gI glycoprotein complex suppresses TI-IFN production by pDC, which represents the first alphaherpesvirus factor that suppresses pDC activity. IMPORTANCE Several alphaherpesviruses, including herpes simpex virus, still lack effective vaccines. However, the highly successful Bartha vaccine has contributed substantially to eradication of the porcine alphaherpesvirus pseudorabies virus (PRV) in several countries. The impact of Bartha on the immune response is still poorly understood. Type I interferon (TI-IFN)-producing plasmacytoid dendritic cells (pDC) may play an important role in vaccine development. Here, we show that Bartha elicits a dramatically increased type I interferon (TI-IFN) response in primary porcine pDC compared to wild-type strains. In addition, we found that the gE/gI complex, which is absent in Bartha, inhibits the pDC TI-IFN response. This is the first description of an immune cell type that is differentially affected by Bartha versus wild-type PRV and is the first report describing an alphaherpesvirus protein that inhibits the TI-IFN response by pDC. These data may therefore contribute to the rational design of other alphaherpesvirus vaccines. Copyright © 2017 American Society for Microbiology.

Analysis, Simulation, and Fabrication of Current Mode Controlled DC-DC Power Converters

DTIC Science & Technology

1999-12-01

susceptibility), vou/ vin . 3 . The output impedance including the load. 22 The crossover frequency, coc, appears in all poles and is defined as: oo... VIN - 3 0 VIN - 3 V Delay to Outputs (TJ=25*C, (Note 2) 200 500 200 500 ns ( Current Limit Adjust Section Current Limit Offset

Power and Energy Management Strategy for Solid State Transformer Interfaced DC Microgrid

NASA Astrophysics Data System (ADS)

Yu, Xunwei

As a result of more and more applications of renewable energy into our ordinary life, how to construct a microgrid (MG) based on the distributed renewable energy resources and energy storages, and then to supply a reliable and flexible power to the conventional power system are the hottest topics nowadays. Comparing to the AC microgrid (AC MG), DC microgrid (DC MG) gets more attentions, because it has its own advantages, such as high efficiency, easy to integrate the DC energy sources and energy storages, and so on. Furthermore, the interaction between DC MG system and the distribution system is also an important and practical issue. In Future Renewable Electric Energy Delivery and Management Systems Center (FREEDM), the Solid State Transformer (SST) is built, which can transform the distribution system to the low AC and DC system directly (usually home application level). Thus, the SST gives a new promising solution for low voltage level MG to interface the distribution level system instead of the traditional transformer. So a SST interfaced DC MG is proposed. However, it also brings new challenges in the design and control fields for this system because the system gets more complicated, which includes distributed energy sources and storages, load, and SST. The purpose of this dissertation is to design a reliable and flexible SST interfaced DC MG based on the renewable energy sources and energy storages, which can operate in islanding mode and SST-enabled mode. Dual Half Bridge (DHB) is selected as the topology for DC/DC converter in DC MG. The DHB operation procedure and average model are analyzed, which is the basis for the system modeling, control and operation. Furthermore, two novel power and energy management strategies are proposed. The first one is a distributed energy management strategy for the DC MG operating in the SST-enabled mode. In this method, the system is not only in distributed control to increase the system reliability, but the power sharing between DC MG and SST, State of Charge (SOC) for battery, are both considered in the system energy management strategy. Then the DC MG output power is controllable and the battery is autonomous charged and discharged based on its SOC and system information without communication. The system operation modes are defined, analyzed and the simulation results verify the strategy. The second power and energy management strategy is the hierarchical control. In this control strategy, three-layer control structure is presented and defined. The first layer is the primary control for the DC MG in islanding mode, which is to guarantee the DC MG system power balance without communication to increase the system reliability. The second control layer is to implement the seamless switch for DC MG system from islanding mode to SST-enabled mode. The third control layer is the tertiary control for the system energy management and the communication is also involved. The tertiary layer not only controls the whole DC MG output power, but also manages battery module charge and discharge statuses based on its SOC. The simulation and experimental results verify the methods. Some practical issues for the SST interfaced DC MG are also investigated. Power unbalance issue of SST is analyzed and a distributed control strategy is presented to solve this problem. Simulation and experimental results verify it. Furthermore, the control strategy for SST interfaced DC MG blackout is presented and the simulation results are shown to valid it. Also a plug and play SST interfaced DC MG is constructed and demonstrated. Several battery and PV modules construct a typical DC MG and a DC source is adopted to simulate the SST. The system is in distributed control and can operate in islanding mode and SST-enabled mode. The experimental results verify that individual module can plug into and unplug from the DC MG randomly without affecting the system stability. Furthermore, the communication ports are embedded into the system and a universal communication protocol is proposed to implement the plug and play function. Specified ID is defined for individual PV and battery for system recognition. A database is built to store the whole system date for visual display, monitor and history query.

Study of the physical discharge properties of a Ar/O2 DC plasma jet

NASA Astrophysics Data System (ADS)

Barkhordari, A.; Ganjovi, A.; Mirzaei, I.; Falahat, A.

2018-03-01

In this paper, the physical properties of plasma discharge in a manufactured DC plasma jet operating with the Ar/O2 gaseous mixture are studied. Moreover, the optical emission spectroscopy technique is used to perform the experimental measurements. The obtained emission spectra are analyzed and, the plasma density, rotational, vibrational and electronic temperature are calculated. The NO emission lines from {NO }γ( A2 Σ^{+} \\to {X}2 Πr ) electronic transition are observed. It is seen that, at the higher argon contributions in Ar/O2 gaseous mixture, the emission intensities from argon ions will increase. Moreover, while the vibrational and excitation temperatures are increased at the higher input DC currents, they will decrease at the higher Ar percentages in the Ar/O2 gaseous mixture. Furthermore, at the higher DC currents and Ar contributions, both the plasma electron density and dissociation fraction of oxygen atoms are increased.

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

PubMed

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.

Dissociative complexity: Antecedents and clinical correlates of a new construct.

PubMed

Briere, John; Dietrich, Anne; Semple, Randye J

2016-09-01

To the extent that dissociation is a multidimensional phenomenon, and given a growing literature on complex posttraumatic outcomes, we hypothesized a new construct: dissociative complexity (DC). DC is defined as the tendency to simultaneously endorse multiple, relatively independent dissociative dimensions into their clinical ranges, and therefore represents the overall breadth or complexity of an individual's dissociative response. DC was evaluated in general population and prison participants using the Multiscale Dissociation Inventory (MDI; Briere, 2002). DC was higher among prisoners and women, and, as hypothesized, was associated with cumulative trauma and serious comorbidities (suicidality and substance abuse), even when controlling for generally elevated dissociation. DC appears to be a meaningful clinical construct that is phenomenologically and empirically different from a unidimensional index of dissociative severity. DC may serve as a clinical marker for multiple trauma exposures, complex dissociative outcomes, and risk of problematic comorbidities. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Technical advance: Generation of human pDC equivalents from primary monocytes using Flt3-L and their functional validation under hypoxia.

PubMed

Sekar, Divya; Brüne, Bernhard; Weigert, Andreas

2010-08-01

The division of labor between DC subsets is evolutionarily well-defined. mDC are efficient in antigen presentation, whereas pDC act as rheostats of the immune system. They activate NK cells, cause bystander activation of mDC, and interact with T cells to induce tolerance. This ambiguity positions pDC at the center of inflammatory diseases, such as cancer, arthritis, and autoimmune diseases. The ability to generate human mDC ex vivo made it possible to engineer them to suit therapy needs. Unfortunately, a similar, easily accessible system to generate human pDC is not available. We describe a method to generate human pDC equivalents ex vivo, termed mo-pDC from peripheral blood monocytes using Flt3-L. mo-pDC showed a characteristic pDC profile, such as high CD123 and BDCA4, but low CD86 and TLR4 surface expression and a low capacity to induce autologous lymphocyte proliferation and to phagocytose apoptotic debris in comparison with mDC. Interestingly, mo-pDC up-regulated the pDC lineage-determining transcription factor E2-2 as well as expression of BDCA2, which is under the transcriptional control of E2-2 but not its inhibitor ID2, during differentiation. mo-pDC produced high levels of IFN-alpha when pretreated overnight with TNF-alpha. Under hypoxia, E2-2 was down-regulated, and ID2 was induced in mo-pDC, whereas surface expression of MHCI, CD86, and BDCA2 was decreased. Furthermore, mo-pDC produced high levels of inflammatory cytokines when differentiated under hypoxia compared with normoxia. Hence, mo-pDC can be used to study differentiation and functions of human pDC under microenvironmental stimuli.

Stability testing and analysis of a PMAD dc test bed for the Space Station Freedom

NASA Technical Reports Server (NTRS)

Button, Robert M.; Brush, Andrew S.

1992-01-01

The Power Management and Distribution (PMAD) dc Test Bed at the NASA Lewis Research Center is introduced. Its usefulness to the Space Station Freedom Electrical Power (EPS) development and design are discussed in context of verifying system stability. Stability criteria developed by Middlebrook and Cuk are discussed as they apply to constant power dc to dc converters exhibiting negative input impedance at low frequencies. The utility-type Secondary Subsystem is presented and each component is described. The instrumentation used to measure input and output impedance under load is defined. Test results obtained from input and output impedance measurements of test bed components are presented. It is shown that the PMAD dc Test Bed Secondary Subsystem meets the Middlebrook stability criterion for certain loading conditions.

Stability Testing and Analysis of a PMAD DC Test Bed for the Space Station Freedom

NASA Technical Reports Server (NTRS)

Button, Robert M.; Brush, Andrew S.

1992-01-01

The Power Management and Distribution (PMAD) DC Test Bed at the NASA Lewis Research Center is introduced. Its usefulness to the Space Station Freedom Electrical Power (EPS) development and design are discussed in context of verifying system stability. Stability criteria developed by Middlebrook and Cuk are discussed as they apply to constant power DC to DC converters exhibiting negative input impedance at low frequencies. The utility-type Secondary Subsystem is presented and each component is described. The instrumentation used to measure input and output impedance under load is defined. Test results obtained from input and output impedance measurements of test bed components are presented. It is shown that the PMAD DC Test Bed Secondary Subsystem meets the Middlebrook stability criterion for certain loading conditions.

The evolution of Japanese employer-sponsored retirement plans.

PubMed

Rajnes, David

2007-01-01

This article examines the development of Japanese voluntary employer-sponsored retirement plans with an emphasis on recent trends. Until 2001, companies in Japan offered retirement benefits as lump-sum severance payments and/or benefits from one of two types of defined benefit (DB) pension plans. One type of DB plan was based on the occupational pension model used in the United States before the adoption of the Employee Retirement Income Security Act of 1974 (ERISA), but lacked the funding, vesting, and other protective features contained in ERISA. The other type of DB plan allowed companies to opt out of the earnings-related portion of social security, commonly referred to as "contracting out." Landmark laws passed in 2001 introduced a new generation of occupational retirement plans to employers and employees. One law increased funding requirements and enhanced employee protections for employer-sponsored DB plans, while a second law introduced defined contribution (DC) plans for several reasons, chiefly to increase retirement savings and help boost Japanese financial markets. These laws complemented earlier changes in the tax code and financial accounting standards already affecting employer-sponsored retirement plans. As a result, new retirement plan designs will replace most prereform era company retirement plans by 2012. In 2001, the experience of 401(k) plans in the United States, where 42 million participants had accumulated more than $1.8 trillion in assets over 20 years, attracted considerable attention among Japanese lawmakers finalizing provisions of the DC pension law. Even with government support and encouragement from the financial services industry, Japanese companies have not adopted these new DC plans in large numbers. As a result, occupational retirement plans in Japan have remained predominantly DB-a surprising development in light of the shift in a number of countries from DB to DC plans observed in recent decades. However, recent proposals to make DC plans more attractive to employers in Japan are likely to be implemented in the near future. This article summarizes the Japanese retirement system, with an emphasis on private-sector employees, and the complementary role played by voluntary employer-sponsored retirement plans; describes the financial pressures that faced retirement plan sponsors in the late twentieth century and the factors motivating the reform of Japanese voluntary retirement plans; examines the 2001 legislative changes that have transformed company retirement plans; and concludes with a review of trends and recent developments in employer-sponsored retirement plans since the implementation of the 2001 pension laws.

HIV-1 Env and Nef Cooperatively Contribute to Plasmacytoid Dendritic Cell Activation via CD4-Dependent Mechanisms.

PubMed

Reszka-Blanco, Natalia J; Sivaraman, Vijay; Zhang, Liguo; Su, Lishan

2015-08-01

Plasmacytoid dendritic cells (pDCs) are the major source of type I IFN (IFN-I) in response to human immunodeficiency virus type 1 (HIV-1) infection. pDCs are rapidly activated during HIV-1 infection and are implicated in reducing the early viral load, as well as contributing to HIV-1-induced pathogenesis. However, most cell-free HIV-1 isolates are inefficient in activating human pDCs, and the mechanisms of HIV-1 recognition by pDCs and pDC activation are not clearly defined. In this study, we report that two genetically similar HIV-1 variants (R3A and R3B) isolated from a rapid progressor differentially activated pDCs to produce alpha interferon (IFN-α). The highly pathogenic R3A efficiently activated pDCs to induce robust IFN-α production, while the less pathogenic R3B did not. The viral determinant for efficient pDC activation was mapped to the V1V2 region of R3A Env, which also correlated with enhanced CD4 binding activity. Furthermore, we showed that the Nef protein was also required for the activation of pDCs by R3A. Analysis of a panel of R3A Nef functional mutants demonstrated that Nef domains involved in CD4 downregulation were necessary for R3A to activate pDCs. Our data indicate that R3A-induced pDC activation depends on (i) the high affinity of R3A Env for binding the CD4 receptor and (ii) Nef activity, which is involved in CD4 downregulation. Our findings provide new insights into the mechanism by which HIV-1 induces IFN-α in pDCs, which contributes to pathogenesis. Plasmacytoid dendritic cells (pDCs) are the major type I interferon (IFN-I)-producing cells, and IFN-I actually contributes to pathogenesis during chronic viral infections. How HIV-1 activates pDCs and the roles of pDCs/IFN-I in HIV-1 pathogenesis remain unclear. We report here that the highly pathogenic HIV R3A efficiently activated pDCs to induce IFN-α production, while most HIV-1 isolates are inefficient in activating pDCs. We have discovered that R3A-induced pDC activation depends on (i) the high affinity of R3A Env for binding the CD4 receptor and (ii) Nef activity, which is involved in CD4 downregulation. Our findings thus provide new insights into the mechanism by which HIV-1 induces IFN-α in pDCs and contributes to HIV-1 pathogenesis. These novel findings will be of great interest to those working on the roles of IFN and pDCs in HIV-1 pathogenesis in general and on the interaction of HIV-1 with pDCs in particular. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

NASA DC-8 airborne research laboratory

NASA Technical Reports Server (NTRS)

Degreef, Leo H.

1991-01-01

Since the summer of 1987, NASA Ames Research Center has been operating a DC-8 equipped with CFM 56 engines as a flying research laboratory. In this relatively short time, the DC-8, with its tremendous capabilities, has made significant contributions to numerous scientific fields. Capable of staying aloft for over 12 hours, the DC-8 has flown directly over both the North and South Poles, gathering data relating to the ozone hole. Operating from a few thousand feet to over 40,000 feet above sea level the interchangeable payload capability of the DC-8 has made it a versatile scientific tool. The DC-8 also plays a vital role in the development of new satellite-borne sensors as very often those sensors are test-flown on the DC-8 before they are launched into space. The tremendous range and instrument carrying capability make the DC-8 an ideal flying laboratory. A few of the programs the DC-8 has participated in as well as a sampling of the instruments carried are outlined.

Ion trap device

DOEpatents

Ibrahim, Yehia M.; Smith, Richard D.

2016-01-26

An ion trap device is disclosed. The device includes a series of electrodes that define an ion flow path. A radio frequency (RF) field is applied to the series of electrodes such that each electrode is phase shifted approximately 180 degrees from an adjacent electrode. A DC voltage is superimposed with the RF field to create a DC gradient to drive ions in the direction of the gradient. A second RF field or DC voltage is applied to selectively trap and release the ions from the device. Further, the device may be gridless and utilized at high pressure.

Pulmonary stromal cells induce the generation of regulatory DC attenuating T-cell-mediated lung inflammation.

PubMed

Li, Qian; Guo, Zhenhong; Xu, Xiongfei; Xia, Sheng; Cao, Xuetao

2008-10-01

The tissue microenvironment may affect the development and function of immune cells such as DC. Whether and how the pulmonary stromal microenvironment can affect the development and function of lung DC need to be investigated. Regulatory DC (DCreg) can regulate T-cell response. We wondered whether such regulatory DC exist in the lung and what is the effect of the pulmonary stromal microenvironment on the generation of DCreg. Here we demonstrate that murine pulmonary stromal cells can drive immature DC, which are regarded as being widely distributed in the lung, to proliferate and differentiate into a distinct subset of DCreg, which express high levels of CD11b but low levels of MHC class II (I-A), CD11c, secrete high amounts of IL-10, NO and prostaglandin E2 (PGE2) and suppress T-cell proliferation. The natural counterpart of DCreg in the lung with similar phenotype and regulatory function has been identified. Pulmonary stroma-derived TGF-beta is responsible for the differentiation of immature DC to DCreg, and DCreg-derived PGE2 contributes to their suppression of T-cell proliferation. Moreover, DCreg can induce the generation of CD4+CD25+Foxp3+ Treg. Importantly, infusion with DCreg attenuates T-cell-mediated eosinophilic airway inflammation in vivo. Therefore, the pulmonary microenvironment may drive the generation of DCreg, thus contributing to the maintenance of immune homoeostasis and the control of inflammation in the lung.

Diverse Functional Outcomes of Plasmodium falciparum Ligation of EPCR: Potential Implications for Malarial Pathogenesis

PubMed Central

Gillrie, Mark R.; Avril, Marion; Brazier, Andrew J.; Davis, Shevaun P.; Stins, Monique F.; Smith, Joseph D.; Ho, May

2015-01-01

Summary P. falciparum-infected erythrocytes (IRBC) expressing the domain cassettes (DC) 8 and 13 of the cytoadherent ligand PfEMP1 adhere to the endothelial protein C receptor (EPCR). By interfering with EPCR anti-coagulant and pro-endothelial barrier functions, IRBC adhesion could promote coagulation and vascular permeability that contribute to the pathogenesis of cerebral malaria. In this study, we examined adhesion of DC8- and DC13-expressing parasite lines to endothelial cells from different microvasculature, and the consequences of EPCR engagement on endothelial cell function. We found that IRBC from IT4var19 (DC8) and IT4var07 (DC13) parasite lines adhered to human brain, lung, and dermal endothelial cells under shear stress. However, the relative contribution of EPCR to parasite cytoadherence on the different types of endothelial cell varied. We also observed divergent functional outcomes for DC8 CIDRα1.1 and DC13 CIDRα1.4 domains. IT4var07 CIDRα1.4 inhibited generation of activated protein C (APC) on lung and dermal endothelial cells and blocked the APC-EPCR binding interaction on brain endothelial cells. IT4var19 CIDRα1.1 inhibited thrombin-induced endothelial barrier dysfunction in lung endothelial cells, while IT4var07 CIDRα1.4- inhibited the protective effect of APC on thrombin-induced permeability. Overall, these findings reveal a much greater complexity of how CIDRα1-expressing parasites may modulate malaria pathogenesis through EPCR adhesion. PMID:26119044

The Differential Contribution of the Innate Immune System to a Good Pathological Response in the Breast and Axillary Lymph Nodes Induced by Neoadjuvant Chemotherapy in Women with Large and Locally Advanced Breast Cancers

PubMed Central

Verma, Chandan; Eremin, Jennifer M.; Cowley, Gerard; Ilyas, Mohammad; Satthaporn, Sukchai; Eremin, Oleg

2017-01-01

The tumour microenvironment consists of malignant cells, stroma, and immune cells. The role of adaptive immunity in inducing a pathological complete response (pCR) in breast cancer with neoadjuvant chemotherapy (NAC) is well studied. The contribution of innate immunity, however, is poorly documented. Breast tumours and axillary lymph nodes (ALNs) from 33 women with large and locally advanced breast cancers (LLABCs) undergoing NAC were immunohistochemically assessed for tumour-infiltrating macrophages (TIMs: M1 and M2), neutrophils (TINs), and dendritic cells (TIDCs) using labelled antibodies and semiquantitative methods. Patients' blood neutrophils (n = 108), DCs (mDC1 and pDC), and their costimulatory molecules (n = 30) were also studied. Pathological results were classified as pCR, good (GPR) or poor (PRR). In breast and metastatic ALNs, high levels of CD163+ TIMs were significantly associated with a pCR. In blood, high levels of neutrophils were significantly associated with pCR in metastatic ALNs, whilst the % of mDC1 and pDC and expression of HLA-DR, mDC1 CD40, and CD83 were significantly reduced. NAC significantly reduced tumour DCs but increased blood DCs. PPRs to NAC had significantly reduced HLA-DR, CD40, and CD86 expression. Our study demonstrated novel findings documenting the differential but important contributions of innate immunity to pCRs in patients with LLABCs undergoing NAC. PMID:28913366

Electrical Behavior of Copper Mine Tailings During EKR with Modified Electric Fields.

PubMed

Rojo, Adrian; Hansen, Henrik K; Monárdez, Omara; Jorquera, Carlos; Santis, Paulina; Inostroza, Paula

2017-03-01

Electro-kinetic remediation (EKR) with sinusoidal electric field obtained simultaneously with DC/AC voltage reduce the polarization of the EKR with DC voltage. The DC voltage value defines the presence of a periodic polarity reversal of the cell and the electrical charge for electro-kinetic transport. In this case, the AC frequency favors the breaking of polarization conditions resulting from the EKR with DC voltage. However, with high frequencies a negative effect occurs where the tailings behave as a filter circuit, discriminating frequencies of an electric signal. The goal of this work is to analyse the electrical behaviour of tailings in EKR experiments. The conditions selected were: DC/AC voltages: 10/15 and 20/25 V (peak values), and AC voltage frequencies 50-2000 Hz. When the AC frequency reaches 2000 Hz, the copper removal tends to zero, indicating that the tailing behaves as a high-pass filter in which the DC voltage was filtered out.

Silencing of decoy receptor 3 (DcR3) expression by siRNA in pancreatic carcinoma cells induces Fas ligand-mediated apoptosis in vitro and in vivo.

PubMed

Zhou, Jian; Song, Shiduo; He, Songbin; Wang, Zhenxin; Zhang, Bing; Li, Dechun; Zhu, Dongming

2013-09-01

Decoy receptor 3 (DcR3) is abundantly expressed in human tumors and protects cells from a wide range of apoptotic stimuli. In this study, we demonstrate that DcR3 is overexpressed in pancreatic carcinoma cells, and that the pancreatic carcinoma cell lines, Panc-1 and SW1990, are resistant to Fas ligand (FasL)-mediated apoptosis. To further define the function of DcR3 in cell growth and apoptosis, we used small interfering RNA (siRNA) to knockdown the expression of the DcR3 gene in Panc-1 and SW1990 cells. Our results revealed that the silencing of DcR3 expression enhanced the inhibitory effects of FasL and reduced the capabiltiy of the cells for proliferation and colony formation in vitro. In addition, the downregulation of DcR3 modulated the cell apoptotic regulators, Fas-associated death domain (FADD), caspase‑3 and caspase‑8, thus triggering cell apoptosis. Furthermore, the knockdown of DcR3 inhibited the growth of Panc-1 tumor xenografts. Taken together, our findings indicate that DcR3 is important in cancer progression and may be a used as a potential therapeutic target for the gene therapy of pancreatic carcinoma.

The Clinical Value of Deflation Cough in Chronic Coughers With Reflux Symptoms.

PubMed

Lavorini, Federico; Chellini, Elisa; Bigazzi, Francesca; Surrenti, Elisabetta; Fontana, Giovanni A

2016-06-01

Patients with deflation cough (DC), the cough-like expulsive effort(s) evoked by maximal lung emptying during a slow vital capacity maneuver, also present symptoms of gastroesophageal reflux. DC can be inhibited by prior intake of antacids. We wished to assess DC prevalence and association between DC and chemical characteristics of refluxate in patients with gastroesophageal reflux symptoms. A total of 157 consecutive outpatients underwent DC assessment and 24-h multichannel intraluminal impedance pH (MII-pH) monitoring; 93/157 also had chronic cough. Patients performed two to four slow vital capacity maneuvers and DC was detected aurally. Subsequently, they underwent 24-h MII-pH monitoring, the outcomes of which were defined as abnormal when acid or non-acid reflux events were > 73. DC occurred in 46/157 patients, 18 of whom had abnormal MII-pH outcomes; 28 of the remaining 111 patients without DC also had abnormal MII-pH findings. Thus, in the patients as a group, there was no association between DC and MII-pH outcomes. DC occurred in 40/93 of the chronic coughers; 15 of whom had acid reflux. All but 2 of the 53 patients without DC had normal MII-pH outcomes (P < .001), and the negative predictive value of DC for excluding acid reflux was 96.2%. At follow-up, 65% of coughers showed significant improvement after treatment. The overall prevalence of DC was 29%, increasing to 43% in chronic coughers in whom the absence of DC virtually excludes acid reflux. Therefore, DC assessment may represent a useful screening test for excluding acid reflux in chronic coughers with reflux symptoms. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Wake-Induced Aerodynamics on a Trailing Aircraft

NASA Technical Reports Server (NTRS)

Mendenhall, Michael R.; Lesieutre, Daniel J.; Kelly, Michael J.

2016-01-01

NASA conducted flight tests to measure the exhaust products from alternative fuels using a DC-8 transport aircraft and a Falcon business jet. An independent analysis of the maximum vortex-induced loads on the Falcon in the DC-8 wake was conducted for pre-flight safety analysis and to define safe trail distances for the flight tests. Static and dynamic vortex-induced aerodynamic loads on the Falcon were predicted at a matrix of locations aft of the DC-8 under flight-test conditions, and the maximum loads were compared with design limit loads to assess aircraft safety. Trajectory simulations for the Falcon during close encounters with the DC-8 wake were made to study the vortex-induced loads during traverses of the DC-8 primary trailing vortex. A parametric study of flight traverses through the trailing vortex was conducted to assess Falcon flight behavior and motion characteristics.

DC-8 Airborne Laboratory in flight

NASA Image and Video Library

1998-02-20

The NASA DC-8 in a right bank over the rugged Sierra Nevada Mountains. The former airliner is a "dash-72" model and has a range of 5,500 miles. The craft can stay airborne for 12 hours and has an operational speed range between 300 and 500 knots. The research flights are made at between 500 and 41,000 feet. The aircraft can carry up to 30,000 lbs of research/science payload equipment installed in 15 mission-definable spaces. In this photo, the aircraft is shown in flight from below, with the DC-8 silhouetted against a blue sky.

Sets of spectral lines for spectrographic thermometry and manometry in d.c. arcs of geologic materials

USGS Publications Warehouse

Golightly, D.W.; Dorrzapf, A.F.; Thomas, C.P.

1977-01-01

Sets of 5 Fe(I) lines and 3 Ti(I)Ti(II) line pairs have been characterized for precise spectrographic thermometry and manometry, respectively, in d.c. arcs of geologic materials. The recommended lines are free of spectral interferences, exhibit minimal self absorption within defined concentration intervals, and are useful for chemically-unaltered silicate rocks, arced in an argon-oxygen stream. The functional character of these lines in thermometry and manometry of d.c. arcs for evaluations of electrical parameter effects, for temporal studies, and for matrix-effect investigations on real samples is illustrated. ?? 1977.

An assessment of the Space Station Freedom program's leakage current requirement

NASA Technical Reports Server (NTRS)

Nagy, Michael

1991-01-01

The Space Station Freedom Program requires leakage currents to be limited to less than human perception level, which NASA presently defines as 5 mA for dc. The origin of this value is traced, and the literature for other dc perception threshold standards is surveyed. It is shown that while many varying standards exist, very little experimental data is available to support them.

Crystal Structure of the Complex of Human FasL and Its Decoy Receptor DcR3.

PubMed

Liu, Weifeng; Ramagopal, Udupi; Cheng, Huiyong; Bonanno, Jeffrey B; Toro, Rafael; Bhosle, Rahul; Zhan, Chenyang; Almo, Steven C

2016-11-01

The apoptotic effect of FasL:Fas signaling is disrupted by DcR3, a unique secreted member of the tumor necrosis factor receptor superfamily, which also binds and neutralizes TL1A and LIGHT. DcR3 is highly elevated in patients with various tumors and contributes to mechanisms by which tumor cells to evade host immune surveillance. Here we report the crystal structure of FasL in complex with DcR3. Comparison of FasL:DcR3 structure with our earlier TL1A:DcR3 and LIGHT:DcR3 structures supports a paradigm involving the recognition of invariant main-chain and conserved side-chain functionalities, which is responsible for the recognition of multiple TNF ligands exhibited by DcR3. The FasL:DcR3 structure also provides insight into the FasL:Fas recognition surface. We demonstrate that the ability of recombinant FasL to induce Jurkat cell apoptosis is significantly enhanced by native glycosylation or by structure-inspired mutations, both of which result in reduced tendency to aggregate. All of these activities are efficiently inhibited by recombinant DcR3. Copyright © 2016 Elsevier Ltd. All rights reserved.

High-Hall-Mobility Al-Doped ZnO Films Having Textured Polycrystalline Structure with a Well-Defined (0001) Orientation

NASA Astrophysics Data System (ADS)

Nomoto, Junichi; Makino, Hisao; Yamamoto, Tetsuya

2016-06-01

Five hundred-nanometer-thick ZnO-based textured polycrystalline films consisting of 490-nm-thick Al-doped ZnO (AZO) films deposited on 10-nm-thick Ga-doped ZnO (GZO) films exhibited a high Hall mobility ( μ H) of 50.1 cm2/Vs with a carrier concentration ( N) of 2.55 × 1020 cm-3. Firstly, the GZO films were prepared on glass substrates by ion plating with dc arc discharge, and the AZO films were then deposited on the GZO films by direct current magnetron sputtering (DC-MS). The GZO interface layers with a preferential c-axis orientation play a critical role in producing AZO films with texture development of a well-defined (0001) orientation, whereas 500-nm-thick AZO films deposited by only DC-MS showed a mixture of the c-plane and the other plane orientation, to exhibit a μ H of 38.7 cm2/Vs with an N of 2.22 × 1020 cm-3.

High strength undiffused brushless machine and method

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

Hsu, John S

2009-04-14

A method and apparatus in which a rotor (11) and a stator (17) define a radial air gap (20) for receiving AC flux and at least one DC excitation coil (23, 24) positioned near the stator end turn to produce DC flux in axial air gaps (21, 22) additive to the AC flux. Side magnets (16) and flux-guiding magnets (14) are provided as boundaries separating the side poles (12a, 12b) of opposite polarity from other portions of the rotor (11) and from each other to define PM poles (12a, 12b) for conveying the DC flux to or from the primarymore » air gap (20) and for inhibiting flux from leaking from said pole portions prior to reaching the primary air gap (20). Side magnets (16), side poles (12a and 12b), flux-guiding magnets (14), ferromagnetic end plates (11c), non-magnetic end plates (12c), and ring bands (37) are optionally provided for performance improvement.« less

Cutaneous myeloid dendritic cell dyscrasia: A cutaneous clonal monocytosis associated with chronic myeloproliferative disorders and peripheral blood monocytosis.

PubMed

Magro, Cynthia M; Momtahen, Shabnam; Verma, Shalini; Abraham, Ronnie M; Friedman, Constantin; Nuovo, Gerard J; Tam, Wayne

2016-12-01

Monocytes are critical components of the innate immune system and they can differentiate into dendritic cells (DCs). Cutaneous neoplasms of dendritic cell origin are uncommon and mostly represented by histiocytic lesions derived primarily from Langerhans cells. The myeloid DC (mDC) while recognized in the immunology literature does not have a well-defined neoplastic cutaneous counterpart. Eleven patients with a diagnosis of cutaneous mDC dyscrasia were evaluated. Routine hematoxylin and eosin stain were performed followed by selective phenotypic studies. The patients were older without a gender predilection and exhibited an asymptomatic papular skin rash with a waxing and waning course. The biopsies demonstrated a dermal based monomorphic small mononuclear cell infiltrate. The cells expressed CD14, CD11c, HLA-DR, as well as granzyme and lysozyme that defines terminally differentiated monocyte/dendritic cells. Expression of BDCA-3 (CD141) by the tumor cells indicated that they were myeloid dendritic cells (mDC2). Each patient had a prior or subsequent diagnosis of an abnormal bone marrow biopsy that included myelodysplastic syndrome, myelofibrosis, chronic myelomonocytic leukemia, and acute myelogenous leukemia. We propose the term cutaneous mDC cell dyscrasia for distinctive infiltrates of differentiated mDCs reflective of underlying myeloproliferative disease. The clinical course is variable and can be indolent although it is strongly correlated with myelodysplastic syndrome that included leukemia. Copyright © 2016 Elsevier Inc. All rights reserved.

Decoy receptor 3: a pleiotropic immunomodulator and biomarker for inflammatory diseases, autoimmune diseases and cancer.

PubMed

Lin, Wan-Wan; Hsieh, Shie-Liang

2011-04-01

Recently, several decoy molecules belonging to tumor necrosis factor receptor superfamily (TNFRSF) have been identified, including decoy receptor 1 (DcR1), decoy receptor 2 (DcR2), and decoy receptor 3 (DcR3). One of the tumor necrosis factor superfamily (TNFSF) members, TNF-related apoptosis-inducing ligand (TRAIL), binds to DcR1 and DcR2, which are membranous receptors with a truncated cytoplasmic domain, thus unable to transduce TRAIL-mediated signaling. In contrast to DcR1 and DcR2, DcR3 is a soluble receptor capable of neutralizing the biological effects of three other TNFSF members: Fas ligand (FasL/TNFSF6/CD95L), LIGHT (TNFSF14) and TNF-like molecule 1A (TL1A/TNFSF15). Since FasL is a potent apoptosis- and inflammation-inducing factor, LIGHT is involved in apoptosis and inflammation, and TL1A is a T cell costimulator and is involved in gut inflammation, DcR3 can be defined as an immunomodulator on the basis of its neutralizing effects on FasL, LIGHT, and TL1A. Initial studies demonstrated that DcR3 expression is elevated in tumors cells; however, later work showed that DcR3 expression is also upregulated in inflammatory diseases, where serum DcR3 levels correlate with disease progression. In addition to its neutralizing effect, DcR3 also acts as an effector molecule to modulate cell function via 'non-decoy' activities. This review focuses on the immunomodulatory effects of DcR3 via 'decoy' and 'non-decoy' functions, and discusses the potential of DcR3 as a biomarker to predict cancer invasion and inflammation progression. We also discuss the possible utility of recombinant DcR3 as a therapeutic agent to control autoimmune diseases, as well as the potential to attenuate tumor progression by inhibiting DcR3 expression. Copyright © 2011 Elsevier Inc. All rights reserved.

Plasmacytoid Dendritic Cells: Neglected Regulators of the Immune Response to Staphylococcus aureus

PubMed Central

Bekeredjian-Ding, Isabelle; Greil, Johann; Ammann, Sandra; Parcina, Marijo

2014-01-01

Plasmacytoid dendritic cells (pDC) are a rare subset of leukocytes equipped with Fcγ and Fcε receptors, which exert contrary effects on sensing of microbial nucleic acids by endosomal Toll-like receptors. In this article, we explain how pDC contribute to the immune response to Staphylococcus aureus. Under normal circumstances the pDC participates in the memory response to the pathogen: pDC activation is initiated by uptake of staphylococcal immune complexes with IgG or IgE. However, protein A-expressing S. aureus strains additionally trigger pDC activation in the absence of immunoglobulin. In this context, staphylococci exploit the pDC to induce antigen-independent differentiation of IL-10 producing plasmablasts, an elegant means to propagate immune evasion. We further discuss the role of type I interferons in infection with S. aureus and the implications of these findings for the development of immune based therapies and vaccination. PMID:24904586

Role of Dendritic Cells in Immune Dysfunction

NASA Technical Reports Server (NTRS)

Savary, Cherylyn A.

1998-01-01

The specific aims of the project were: (1) Application of the NASA bioreactor to enhance cytokine-regulated proliferation and maturation of dendritic cells (DC). (2) Compare the frequency and function of DC in normal donors and immunocompromised cancer patients. (3) Analyze the effectiveness of cytokine therapy and DC-assisted immunotherapy (using bioreactor-expanded DC) in a murine model of experimental fungal disease. Our investigations have provided new insight into DC immunobiology and have led to the development of methodology to evaluate DC in blood of normal donors and patients. Information gained from these studies has broadened our understanding of possible mechanisms involved in the immune dysfunction of space travelers and earth-bound cancer patients, and could contribute to the design of novel therapies to restore/preserve immunity in these individuals. Several new avenues of investigation were also revealed. The results of studies completed during Round 2 are summarized.

Host genetics contributes to the effectiveness of dendritic cell-based HIV immunotherapy.

PubMed

Reis, Edione C; da Silva, Lais T; da Silva, Wanessa C; Rios, Alexandre; Duarte, Alberto J; Oshiro, Telma M; Crovella, Sergio; Pontillo, Alessandra

2018-04-11

Systems biological analysis has recently revealed how innate immune variants as well as gut microbiota impact the individual response to immunization. HIV-infected (HIV+) patients have a worse response rate after standard vaccinations, possibly due to the immune exhaustion, increased gut permeability and microbial translocation. In the last decade, dendritic cells (DC)-based immunotherapy has been proposed as an alternative approach to control HIV plasma viral load, however clinical trials showed a heterogeneity of immunization response. Hypothesizing that host genetics may importantly affects the outcome of immunotherapy in HIV+ patients, genetic polymorphisms' distribution and gene expression modulation were analyzed in a phase I/II clinical trial of DC-based immunotherapy according to immunization response, and quality of vaccine product (DC). Polymorphisms in genes previously associated with progression of HIV infection to AIDS (i.e.: PARD3B, CCL5) contribute to a better response to immunotherapy in HIV+ individuals, possibly through a systemic effect on host immune system, but also directly on vaccine product. Genes expression profile after immunization correlates with different degrees of immune chronic activation/exhaustion of HIV+ patients (i.e. PD1, IL7RA, EOMES), but also with anti-viral response and DC quality (i.e.: APOBEC3G, IL8, PPIA), suggested that an incompetent individual would have a better vaccine response. These findings showed once more that host genetics can affect the response to DC-based immunotherapy in HIV+ individuals, contributing to the heterogeneity of response observed in concluded trials; and it can be used as predictor of immunization success.

Role of Dendritic Cells in the Pathogenesis of Whipple's Disease

PubMed Central

Schinnerling, Katina; Geelhaar-Karsch, Anika; Allers, Kristina; Friebel, Julian; Conrad, Kristina; Loddenkemper, Christoph; Kühl, Anja A.; Erben, Ulrike; Ignatius, Ralf; Schneider, Thomas

2014-01-01

Accumulation of Tropheryma whipplei-stuffed macrophages in the duodenum, impaired T. whipplei-specific Th1 responses, and weak secretion of interleukin-12 (IL-12) are hallmarks of classical Whipple's disease (CWD). This study addresses dendritic cell (DC) functionality during CWD. We documented composition, distribution, and functionality of DC ex vivo or after in vitro maturation by fluorescence-activated cell sorting (FACS) and by immunohistochemistry in situ. A decrease in peripheral DC of untreated CWD patients compared to healthy donors was due to reduced CD11chigh myeloid DC (M-DC). Decreased maturation markers CD83, CD86, and CCR7, as well as low IL-12 production in response to stimulation, disclosed an immature M-DC phenotype. In vitro-generated monocyte-derived DC from CWD patients showed normal maturation and T cell-stimulatory capacity under proinflammatory conditions but produced less IL-12 and failed to activate T. whipplei-specific Th1 cells. In duodenal and lymphoid tissues, T. whipplei was found within immature DC-SIGN+ DC. DC and proliferating lymphocytes were reduced in lymph nodes of CWD patients compared to levels in controls. Our results indicate that dysfunctional IL-12 production by DC provides suboptimal conditions for priming of T. whipplei-specific T cells during CWD and that immature DC carrying T. whipplei contribute to the dissemination of the bacterium. PMID:25385798

Improvement in lifetime of color DC PDP K, Maezawa, T. Akeyoshi, and T. Mizutani

NASA Astrophysics Data System (ADS)

Motoyama, Y.; Ushirozawa, M.; Sakai, T.

1995-05-01

An important subject for the color DC PDP is how to extend its lifetime (defined by the decrease of luminance). The empirical equations for lifetime in He-Xe, Ne-Xe gas mixture have been obtained. These equations indicate that high pressure and a current limiting resistor built into each cell can secure a lifetime over 10,000 hours, which is long enough for practical use.

Distinct DC subsets regulate adaptive Th1 and 2 responses during Trichuris muris infection.

PubMed

Demiri, M; Müller-Luda, K; Agace, W W; Svensson-Frej, M

2017-10-01

Low- and high-dose infections with the murine large intestinal nematode Trichuris muris are associated with induction of adaptive Th1 and Th2 responses, respectively, in mesenteric lymph nodes (MLN). Classical dendritic cells (cDC) accumulate in the large intestinal mucosa and MLN upon T. muris infection, yet their role in driving adaptive responses to infection remains largely unknown. We performed low- and high-dose T. muris infections of mice deficient in defined cDC subsets to investigate their role in induction of adaptive immune responses. Mice lacking IRF4-dependent cDC failed to clear a high-dose infection and displayed impaired Th2 responses. Conversely, mice lacking IRF8-dependent cDC cleared a low-dose infection and displayed an impaired Th1 response while increased production of Th2 cytokines. Finally, mice lacking both IRF4- and IRF8-dependent cDC were able to generate a Th2 response and clear a low-dose infection. Collectively, these results suggest that IRF4- and IRF8-dependent cDC act antagonistically during T. muris infection, and demonstrate that intestinal Th2 responses can be generated towards T. muris in the absence of IRF4-dependent cDC. © 2017 John Wiley & Sons Ltd.

In Vitro Activity of DC-159a, a New Broad-Spectrum Fluoroquinolone, Compared with That of Other Agents against Drug-Susceptible and -Resistant Pneumococci▿

PubMed Central

Clark, Catherine; Smith, Kathy; Ednie, Lois; Bogdanovich, Tatiana; Dewasse, Bonifacio; McGhee, Pamela; Appelbaum, Peter C.

2008-01-01

DC-159a yielded MICs of ≤1 μg/ml against 316 strains of both quinolone-susceptible and -resistant pneumococci (resistance was defined as a levofloxacin MIC ≥4 μg/ml). Although the MICs for DC-159a against quinolone-susceptible pneumococci were a few dilutions higher than those of gemifloxacin, the MICs of these two compounds against 28 quinolone-resistant pneumococci were identical. The DC-159a MICs against quinolone-resistant strains did not appear to depend on the number or the type of mutations in the quinolone resistance-determining region. DC-159a, as well as the other quinolones tested, was bactericidal after 24 h at 2× MIC against 11 of 12 strains tested. Two of the strains were additionally tested at 1 and 2 h, and DC-159a at 4× MIC showed significant killing as early as 2 h. Multistep resistance selection studies showed that even after 50 consecutive subcultures of 10 strains in the presence of sub-MICs, DC-159a produced only two mutants with maximum MICs of 1 μg/ml. PMID:17938189

Magnetic characteristics and AC losses of DC type-II superconductors under oscillating magnetic fields

NASA Astrophysics Data System (ADS)

Robert, B. C.; Ruiz, H. S.

2018-07-01

Remarkable features on the magnetic moment of type-II superconducting (SC) wires of cylindrical shape, subjected to direct current conditions (DC) and transverse oscillating (AC) magnetic fields, are reported. We show how for relatively low amplitudes of the applied magnetic field, B a , the superconducting wire rapidly develops a saturation state, | {M}p| , characterizing the limits of magnetization loops that exhibit a Boolean-like behaviour. Regardless of the premagnetization state of the SC wire, we show how after two cycles of magnetic relaxation, boolean-like ±M p states can be measured during the entire period of time from which the external magnetic field B 0 ranges from 0 to ±B a , with the signs rule defined by the sign of the slope ΔB 0y (t). In addition, for the practical implementation of SC DC wires sharing the right of way with AC lines, we report that for relatively low values of magnetic field, {B}a≤slant {B}P/2, being B P the analytical value for the full penetration field in absence of transport current, I tr, the use of semi-analytical approaches for the calculation of AC losses leads to a significant underestimation of the actual contribution of the induction losses. This phenomena is particularly relevant at dimensionless fields {b}a< 1-{i}a2/3, being b a = B a /B P and, i a = I a /I c the amplitude of an AC or DC transport current, due to the local motion of flux front profiles being dominated by the occurrence of transport current. On the other hand, we have found that regardless of the nature of the transport current, either be DC or AC, when a transverse oscillating magnetic field greater than the classical limit b a = (1 - i a ) is applied to the SC wire, the difference between the obtained AC losses in both situations results to be negligible indistinctly of the approach used, semi-analytical or numerical. Thus, the actual limits from which the estimation of the AC losses can be used as an asset for the deployment of DC SC wires sharing the right of way with AC lines, against the sole use of SC wires for the transmission of AC transport current, are established.

Vasopressor use after initial damage control laparotomy increases risk for anastomotic disruption in the management of destructive colon injuries.

PubMed

Fischer, Peter E; Nunn, Andrew M; Wormer, Blair A; Christmas, A Britton; Gibeault, Lindsay A; Green, John M; Sing, Ronald F

2013-12-01

Management of destructive colon injuries during damage control (DC) laparotomy is debated. The authors reviewed a single institution's experience with destructive colon injuries to identify risk factors for anastomotic failure after colon reconstruction. The authors identified all trauma patients sustaining destructive colon injuries between 2002 and 2011 from their medical center's trauma registry. Anastomotic leak was defined as suture or staple line disruption or enteral fistula formation. Of 171 identified patients, 68 had DC procedures, 41 (60%) had subsequent anastomoses performed during the same hospitalization, and 27 (40%) were diverted. The colon anastomotic leak rate in patients who underwent DC laparotomy was higher than in patients who were reconstructed at the primary operation in a non-DC setting (17% vs 6%, P = .09). The use of vasopressors after the initial DC operation more than quadrupled the leak rate to 50% (P = .02). Colonic anastomotic disruptions yield deadly consequences, and diversion rather than anastomosis should be used in patients who require vasopressor support after the initial DC procedure. Copyright © 2013 Elsevier Inc. All rights reserved.

The Larsen Ice Shelf in Antarctica viewed from NASA's DC-8 aircraft during the AirSAR 2004 campaign

NASA Image and Video Library

2004-03-16

The Larsen Ice Shelf in Antarctica viewed from NASA's DC-8 aircraft during the AirSAR 2004 campaign. AirSAR 2004 is a three-week expedition in Central and South America by an international team of scientists that is using an all-weather imaging tool, called the Airborne Synthetic Aperture Radar (AirSAR), located onboard NASA's DC-8 airborne laboratory. Scientists from many parts of the world are combining ground research with NASA's AirSAR technology to improve and expand on the quality of research they are able to conduct. These photos are from the DC-8 aircraft while flying an AirSAR mission over Antarctica. The Antarctic Peninsula is more similar to Alaska and Patagonia than to the rest of the Antarctic continent. It is drained by fast glaciers, receives abundant precipitation, and melts significantly in the summer months. In recent decades, the Peninsula has experienced significant atmospheric warming (about 2 degrees C since 1950), which has triggered a vast and spectacular retreat of its floating ice shelves, glacier reduction, a decrease in permanent snow cover and a lengthening of the melt season. As a result, the contribution to sea level from this region could be rapid and substantial. With an area of 120,000 km, or ten times the Patagonia ice fields, the Peninsula could contribute as much as 0.4mm/yr sea level rise, which would be the largest single contribution to sea level from anywhere in the world. This region is being studied by NASA using a DC-8 equipped with the Airborne Synthetic Aperture Radar developed by scientists from NASA’s Jet Propulsion Laboratory. AirSAR will provide a baseline model and unprecedented mapping of the region. This data will make it possible to determine whether the warming trend is slowing, continuing or accelerating. AirSAR will also provide reliable information on ice shelf thickness to measure the contribution of the glaciers to sea level.

The Larsen Ice Shelf in Antarctica viewed from NASA's DC-8 aircraft during the AirSAR 2004 campaign

NASA Image and Video Library

2004-03-13

The Larsen Ice Shelf in Antarctica viewed from NASA's DC-8 aircraft during the AirSAR 2004 campaign. AirSAR 2004 is a three-week expedition in Central and South America by an international team of scientists that is using an all-weather imaging tool, called the Airborne Synthetic Aperture Radar (AirSAR), located onboard NASA's DC-8 airborne laboratory. Scientists from many parts of the world are combining ground research with NASA's AirSAR technology to improve and expand on the quality of research they are able to conduct. These photos are from the DC-8 aircraft while flying an AirSAR mission over Antarctica. The Antarctic Peninsula is more similar to Alaska and Patagonia than to the rest of the Antarctic continent. It is drained by fast glaciers, receives abundant precipitation, and melts significantly in the summer months. In recent decades, the Peninsula has experienced significant atmospheric warming (about 2 degrees C since 1950), which has triggered a vast and spectacular retreat of its floating ice shelves, glacier reduction, a decrease in permanent snow cover and a lengthening of the melt season. As a result, the contribution to sea level from this region could be rapid and substantial. With an area of 120,000 km, or ten times the Patagonia ice fields, the Peninsula could contribute as much as 0.4mm/yr sea level rise, which would be the largest single contribution to sea level from anywhere in the world. This region is being studied by NASA using a DC-8 equipped with the Airborne Synthetic Aperture Radar developed by scientists from NASA’s Jet Propulsion Laboratory. AirSAR will provide a baseline model and unprecedented mapping of the region. This data will make it possible to determine whether the warming trend is slowing, continuing or accelerating. AirSAR will also provide reliable information on ice shelf thickness to measure the contribution of the glaciers to sea level.

The Larsen Ice Shelf in Antarctica viewed from NASA's DC-8 aircraft during the AirSAR 2004 campaign

NASA Image and Video Library

2004-03-16

The Larsen Ice Shelf in Antarctica viewed from NASA's DC-8 aircraft during the AirSAR 2004 campaign. AirSAR 2004 is a three-week expedition in Central and South America by an international team of scientists that is using an all-weather imaging tool, called the Airborne Synthetic Aperture Radar (AirSAR), located onboard NASA's DC-8 airborne laboratory. Scientists from many parts of the world are combining ground research with NASA's AirSAR technology to improve and expand on the quality of research they are able to conduct. These photos are from the DC-8 aircraft while flying an AirSAR mission over Antarctica. The Antarctic Peninsula is more similar to Alaska and Patagonia than to the rest of the Antarctic continent. It is drained by fast glaciers, receives abundant precipitation, and melts significantly in the summer months. In recent decades, the Peninsula has experienced significant atmospheric warming (about 2 degrees C since 1950), which has triggered a vast and spectacular retreat of its floating ice shelves, glacier reduction, a decrease in permanent snow cover and a lengthening of the melt season. As a result, the contribution to sea level from this region could be rapid and substantial. With an area of 120,000 km, or ten times the Patagonia ice fields, the Peninsula could contribute as much as 0.4mm/yr sea level rise, which would be the largest single contribution to sea level from anywhere in the world. This region is being studied by NASA using a DC-8 equipped with an Airborne Synthetic Aperture Radar (AirSAR) developed by scientists from NASA’s Jet Propulsion Laboratory. AirSAR will provide a baseline model and unprecedented mapping of the region. This data will make it possible to determine whether the warming trend is slowing, continuing or accelerating. AirSAR will also provide reliable information on ice shelf thickness to measure the contribution of the glaciers to sea level.

36 CFR 1251.3 - What definitions apply to this part?

Code of Federal Regulations, 2014 CFR

2014-07-01

... authorization of a court of competent jurisdiction. See Doe v. Digenova, 779 F.2d 74 (D.C. Cir. 1985); Stiles v... defined above in this section; (3) All documents and materials which are NARA agency records under the.... 2201; historical materials as defined in 44 U.S.C. 2101; records as defined in 44 U.S.C. 2107 and 44 U...

36 CFR 1251.3 - What definitions apply to this part?

Code of Federal Regulations, 2012 CFR

2012-07-01

... authorization of a court of competent jurisdiction. See Doe v. Digenova, 779 F.2d 74 (D.C. Cir. 1985); Stiles v... defined above in this section; (3) All documents and materials which are NARA agency records under the.... 2201; historical materials as defined in 44 U.S.C. 2101; records as defined in 44 U.S.C. 2107 and 44 U...

36 CFR 1251.3 - What definitions apply to this part?

Code of Federal Regulations, 2010 CFR

2010-07-01

... authorization of a court of competent jurisdiction. See Doe v. Digenova, 779 F.2d 74 (D.C. Cir. 1985); Stiles v... defined above in this section; (3) All documents and materials which are NARA agency records under the.... 2201; historical materials as defined in 44 U.S.C. 2101; records as defined in 44 U.S.C. 2107 and 44 U...

36 CFR 1251.3 - What definitions apply to this part?

Code of Federal Regulations, 2011 CFR

2011-07-01

... authorization of a court of competent jurisdiction. See Doe v. Digenova, 779 F.2d 74 (D.C. Cir. 1985); Stiles v... defined above in this section; (3) All documents and materials which are NARA agency records under the.... 2201; historical materials as defined in 44 U.S.C. 2101; records as defined in 44 U.S.C. 2107 and 44 U...

36 CFR § 1251.3 - What definitions apply to this part?

Code of Federal Regulations, 2013 CFR

2013-07-01

... authorization of a court of competent jurisdiction. See Doe v. Digenova, 779 F.2d 74 (D.C. Cir. 1985); Stiles v... defined above in this section; (3) All documents and materials which are NARA agency records under the.... 2201; historical materials as defined in 44 U.S.C. 2101; records as defined in 44 U.S.C. 2107 and 44 U...

B and T Lymphocyte Attenuator Down-regulation by HIV-1 Depends on Type I Interferon and Contributes to T-Cell Hyperactivation

PubMed Central

Zhang, Zheng; Xu, Xiangsheng; Lu, Jiyun; Zhang, Shuye; Gu, Lanlan; Fu, Junliang; Jin, Lei; Li, Haiying; Zhao, Min; Zhang, Jiyuan; Wu, Hao; Su, Lishan; Fu, Yang-Xin

2011-01-01

Background. Nonspecific T-cell hyperactivation is the main driving force for human immunodeficiency virus (HIV)–1 disease progression, but the reasons why the excess immune response is not properly shut off are poorly defined. Methods. Eighty-five HIV-1–infected individuals were enrolled to characterize B and T lymphocyte attenuator (BTLA) expression and function. Infection and blockade assays were used to dissect the factors that influenced BTLA signaling in vitro. Results. BTLA expression on overall CD4+ and CD8+ T cells was progressively decreased in HIV-1 infection, which was directly correlated with disease progression and CD4+ T-cell differentiation and activation. BTLA+CD4+ T cells from HIV-1–infected patients also displayed an altered immune status, which was indicated by reduced expression of naive markers but increased activation and exhaustion markers. Cross-linking of BTLA can substantially decrease CD4+ T-cell activation in vitro. This responsiveness of CD4+ T cells to BTLA-mediated inhibitory signaling was further found to be impaired in HIV-1–infected patients. Furthermore, HIV-1 NL4-3 down-regulated BTLA expression on CD4+ T cells dependent on plasmacytoid dendritic cell (pDC)-derived interferon (IFN)-α. Blockade of IFN-α or depletion of pDCs prevents HIV-1-induced BTLA down-regulation. Conclusions. HIV-1 infection potentially impairs BTLA-mediated signaling dependent on pDC-derived IFN-α, which may contribute to broad T-cell hyperactivation induced by chronic HIV-1 infection. PMID:21592997

A new method of converter transformer protection without commutation failure

NASA Astrophysics Data System (ADS)

Zhang, Jiayu; Kong, Bo; Liu, Mingchang; Zhang, Jun; Guo, Jianhong; Jing, Xu

2018-01-01

With the development of AC / DC hybrid transmission technology, converter transformer as nodes of AC and DC conversion of HVDC transmission technology, its reliable safe and stable operation plays an important role in the DC transmission. As a common problem of DC transmission, commutation failure poses a serious threat to the safe and stable operation of power grid. According to the commutation relation between the AC bus voltage of converter station and the output DC voltage of converter, the generalized transformation ratio is defined, and a new method of converter transformer protection based on generalized transformation ratio is put forward. The method uses generalized ratio to realize the on-line monitoring of the fault or abnormal commutation components, and the use of valve side of converter transformer bushing CT current characteristics of converter transformer fault accurately, and is not influenced by the presence of commutation failure. Through the fault analysis and EMTDC/PSCAD simulation, the protection can be operated correctly under the condition of various faults of the converter.

Effect of sialic acid loss on dendritic cell maturation

PubMed Central

Crespo, Hélio J; Guadalupe Cabral, M; Teixeira, Alexandra V; Lau, Joseph T Y; Trindade, Hélder; Videira, Paula A

2009-01-01

Sialic acids are key structural determinants and contribute to the functionality of a number of immune cell receptors. Previously, we demonstrated that differentiation of human dendritic cells (DCs) is accompanied by an increased expression of sialylated cell surface structures, putatively through the activity of the ST3Gal.I and ST6Gal.I sialyltransferases. Furthermore, DC endocytosis was reduced upon removal of the cell surface sialic acid residues by neuraminidase. In the present work, we evaluate the contribution of the sialic acid modifications in DC maturation. We demonstrate that neuraminidase-treated human DCs have increased expression of major histocompatibility complex (MHC) and costimulatory molecules, increased gene expression of specific cytokines and induce a higher proliferative response of T lymphocytes. Together, the data suggest that clearance of cell surface sialic acids contributes to the development of a T helper type 1 proinflammatory response. This postulate is supported by mouse models, where elevated MHC class II and increased maturation of specific DC subsets were observed in DCs harvested from ST3Gal.I−/− and ST6Gal.I−/− mice. Moreover, important qualitative differences, particularly in the extent of reduced endocytosis and in the peripheral distribution of DC subsets, existed between the ST3Gal.I−/− and ST6Gal.I−/− strains. Together, the data strongly suggest not only a role of cell surface sialic acid modifications in maturation and functionality of DCs, but also that the sialic acid linkages created by different sialyltransferases are functionally distinct. Consequently, with particular relevance to DC-based therapies, cell surface sialylation, mediated by individual sialyltransferases, can influence the immunogenicity of DCs upon antigen loading. PMID:19740323

Plasmacytoid Dendritic Cell Dynamics Tune Interferon-Alfa Production in SIV-Infected Cynomolgus Macaques

PubMed Central

Bruel, Timothée; Dupuy, Stéphanie; Démoulins, Thomas; Rogez-Kreuz, Christine; Dutrieux, Jacques; Corneau, Aurélien; Cosma, Antonio; Cheynier, Rémi; Dereuddre-Bosquet, Nathalie; Le Grand, Roger; Vaslin, Bruno

2014-01-01

IFN-I production is a characteristic of HIV/SIV primary infections. However, acute IFN-I plasma concentrations rapidly decline thereafter. Plasmacytoid dendritic cells (pDC) are key players in this production but primary infection is associated with decreased responsiveness of pDC to TLR 7 and 9 triggering. IFNα production during primary SIV infection contrasts with increased pDC death, renewal and dysfunction. We investigated the contribution of pDC dynamics to both acute IFNα production and the rapid return of IFNα concentrations to pre-infection levels during acute-to-chronic transition. Nine cynomolgus macaques were infected with SIVmac251 and IFNα-producing cells were quantified and characterized. The plasma IFN-I peak was temporally associated with the presence of IFNα+ pDC in tissues but IFN-I production was not detectable during the acute-to-chronic transition despite persistent immune activation. No IFNα+ cells other than pDC were detected by intracellular staining. Blood-pDC and peripheral lymph node-pDC both lost IFNα− production ability in parallel. In blood, this phenomenon correlated with an increase in the counts of Ki67+-pDC precursors with no IFNα production ability. In tissues, it was associated with increase of both activated pDC and KI67+-pDC precursors, none of these being IFNα+ in vivo. Our findings also indicate that activation/death-driven pDC renewal rapidly blunts acute IFNα production in vivo: pDC sub-populations with no IFNα-production ability rapidly increase and shrinkage of IFNα production thus involves both early pDC exhaustion, and increase of pDC precursors. PMID:24497833

Dielectric Breakdown Characteristics of Oil-pressboard Insulation System against AC/DC Superposed Voltage

NASA Astrophysics Data System (ADS)

Ebisawa, Yoshihito; Yamada, Shin; Mori, Shigekazu; Ikeda, Masami

This paper describes breakdown characteristics of an oil-pressboard insulation system to a superposition voltage of AC and DC voltages. Although AC electric field is decided by the ratio of the relative permittivity of a pressboard and insulating oil, DC electric field is decided by ratio α of volume resistivities. From the measurement in this study, 13—78 and 1.8—5.7 are obtained as the volume resistivity ratios α at temperature of 30°C and 80°C, respectively. The breakdown voltages against AC, DC, and those superposition voltages are surveyed to insulation models. In normal temperature, the breakdown voltage to the superposition voltage of AC and DC is determined by AC electric field applied to the oil duct. Since the α becomes as low as 2-3 at temperature of 80°C, AC and DC voltages almost equally contribute to the electric field of the oil duct as a result. That is, it became clear that superposed DC voltage boosts the electric field across oil ducts at operating high temperature.

AFM force spectroscopy reveals how subtle structural differences affect the interaction strength between Candida albicans and DC-SIGN.

PubMed

te Riet, Joost; Reinieren-Beeren, Inge; Figdor, Carl G; Cambi, Alessandra

2015-11-01

The fungus Candida albicans is the most common cause of mycotic infections in immunocompromised hosts. Little is known about the initial interactions between Candida and immune cell receptors, such as the C-type lectin dendritic cell-specific intracellular cell adhesion molecule-3 (ICAM-3)-grabbing non-integrin (DC-SIGN), because a detailed characterization at the structural level is lacking. DC-SIGN recognizes specific Candida-associated molecular patterns, that is, mannan structures present in the cell wall of Candida. The molecular recognition mechanism is however poorly understood. We postulated that small differences in mannan-branching may result in considerable differences in the binding affinity. Here, we exploit atomic force microscope-based dynamic force spectroscopy with single Candida cells to gain better insight in the carbohydrate recognition capacity of DC-SIGN. We demonstrate that slight differences in the N-mannan structure of Candida, that is, the absence or presence of a phosphomannan side chain, results in differences in the recognition by DC-SIGN as follows: (i) it contributes to the compliance of the outer cell wall of Candida, and (ii) its presence results in a higher binding energy of 1.6 kB T. The single-bond affinity of tetrameric DC-SIGN for wild-type C. albicans is ~10.7 kB T and a dissociation constant kD of 23 μM, which is relatively strong compared with other carbohydrate-protein interactions described in the literature. In conclusion, this study shows that DC-SIGN specifically recognizes mannan patterns on C. albicans with high affinity. Knowledge on the binding pocket of DC-SIGN and its pathogenic ligands will lead to a better understanding of how fungal-associated carbohydrate structures are recognized by receptors of the immune system and can ultimately contribute to the development of new anti-fungal drugs. Copyright © 2015 John Wiley & Sons, Ltd.

The Neck Region of the C-type Lectin DC-SIGN Regulates Its Surface Spatiotemporal Organization and Virus-binding Capacity on Antigen-presenting Cells*

PubMed Central

Manzo, Carlo; Torreno-Pina, Juan A.; Joosten, Ben; Reinieren-Beeren, Inge; Gualda, Emilio J.; Loza-Alvarez, Pablo; Figdor, Carl G.; Garcia-Parajo, Maria F.; Cambi, Alessandra

2012-01-01

The C-type lectin DC-SIGN expressed on dendritic cells (DCs) facilitates capture and internalization of a plethora of different pathogens. Although it is known that DC-SIGN organizes in nanoclusters at the surface of DCs, the molecular mechanisms responsible for this well defined nanopatterning and role in viral binding remain enigmatic. By combining biochemical and advanced biophysical techniques, including optical superresolution and single particle tracking, we demonstrate that DC-SIGN intrinsic nanoclustering strictly depends on its molecular structure. DC-SIGN nanoclusters exhibited free, Brownian diffusion on the cell membrane. Truncation of the extracellular neck region, known to abrogate tetramerization, significantly reduced nanoclustering and concomitantly increased lateral diffusion. Importantly, DC-SIGN nanocluster dissolution exclusively compromised binding to nanoscale size pathogens. Monte Carlo simulations revealed that heterogeneity on nanocluster density and spatial distribution confers broader binding capabilities to DC-SIGN. As such, our results underscore a direct relationship between spatial nanopatterning, driven by intermolecular interactions between the neck regions, and receptor diffusion to provide DC-SIGN with the exquisite ability to dock pathogens at the virus length scale. Insight into how virus receptors are organized prior to virus binding and how they assemble into functional platforms for virus docking is helpful to develop novel strategies to prevent virus entry and infection. PMID:23019323

Dendritic cells in chronic myelomonocytic leukaemia.

PubMed

Vuckovic, S; Fearnley, D B; Gunningham, S; Spearing, R L; Patton, W N; Hart, D N

1999-06-01

Blood dendritic cells (DC) differentiate in vitro via two separate pathways: either directly from blood DC precursors (DCp) or from CD14+ monocytes. In chronic myelomonocytic leukaemia (CMML) abnormal bone marrow precursors contribute to blood monocyte development but DC development has not been studied previously. Monocytes comprised 60% of blood MNC in 15 CMML patients studied, compared with 20% in 16 age-matched controls. The increase in blood monocytes was accompanied by a reciprocal decrease in mean blood DC percentage (from 0.42% of MNC in normal individuals to 0.16% of MNC in CMML patients). Absolute blood DC numbers showed a minimal (non-significant) reduction from 9.8 x 10(6)/l in normal individuals to 7.5 x 10(6)/l in CMML patients. The CD14(low) WCD16+ monocyte subpopulation was not found in CMML patients. After culture in GM-CSF/IL-4, CMML CD14+ monocytes acquired the phenotype of immature monocyte derived DC (Mo-DC) with similar yields to normal blood Mo-DC generation. Addition of TNF-alpha or LPS induced both normal and CMML Mo-DC to express prominent dendritic processes, the CMRF44+ and CD83+ antigens and high levels of HLA-DR, CD80 and CD86. Treatment either with TNF-alpha or LPS increased the allostimulatory activity of normal Mo-DC, but had little effect on the allostimulatory activity of CMML Mo-DC, perhaps reflecting the underlying neoplastic changes in monocyte precursors. We conclude that the blood DC numbers are relatively unaffected in CMML, suggesting discrete regulation of monocyte and DC production.

[Electrophysiological markers of middle cerebral artery blood flow velocity in healthy subjects].

PubMed

Fokin, V F; Ponomareva, N V; Kuntsevich, G I

2013-01-01

to determine electrophysiological markers of middle cerebral artery blood flow velocity (BFV). transcranial Doppler registration of middle cerebral artery BFV and direct current (DC) potentials recording from surface of head were performed in 30 healthy volunteers. Analysis of correlation between the BFV and DC potentials was used. significant correlation between BFV and DC potential characteristics was observed. The highest correlation was found between BFV in middle cerebral artery and the difference of DC potentials between central and temporal areas of head (r = 0,55; p = 0,003). These areas coincide with the location of middle cerebral artery and the correlation observed may be connected with streaming potential generated by the blood flow in middle cerebral artery. If electrode placement did not coincide with blood current, DC potentials and BFV were not correlated. it is assumed that electrical field created BFV in middle cerebral artery may contribute to the generation of DC potentials registered from the head.

Model Based Optimization of Integrated Low Voltage DC-DC Converter for Energy Harvesting Applications

NASA Astrophysics Data System (ADS)

Jayaweera, H. M. P. C.; Muhtaroğlu, Ali

2016-11-01

A novel model based methodology is presented to determine optimal device parameters for the fully integrated ultra low voltage DC-DC converter for energy harvesting applications. The proposed model feasibly contributes to determine the maximum efficient number of charge pump stages to fulfill the voltage requirement of the energy harvester application. The proposed DC-DC converter based power consumption model enables the analytical derivation of the charge pump efficiency when utilized simultaneously with the known LC tank oscillator behavior under resonant conditions, and voltage step up characteristics of the cross-coupled charge pump topology. The verification of the model has been done using a circuit simulator. The optimized system through the established model achieves more than 40% maximum efficiency yielding 0.45 V output with single stage, 0.75 V output with two stages, and 0.9 V with three stages for 2.5 kΩ, 3.5 kΩ and 5 kΩ loads respectively using 0.2 V input.

A Study of 4-level DC-DC Boost Inverter with Passive Component Reduction Consideration

NASA Astrophysics Data System (ADS)

Kasiran, A. N.; Ponniran, A.; Harimon, M. A.; Hamzah, H. H.

2018-04-01

This study is to analyze design principles of boost inductor and capacitor used in the 4-level DC-DC boost converter to realize size reduction of passive component referring to their attributes. The important feature of this circuit is that most of the boost-up energy is transferred from the capacitor-clamped to the output side which the small inductance can be used at the input side. The inductance of the boost inductor is designed by referring the inductor current ripple. On the other hand, the capacitance of the capacitor-clamped is designed by considering voltage stress on semiconductor devices and also the used switching frequency. Besides that, according to the design specifications, the required inductance in 4-level DC-DC boost converter is decreased compared to a conventional conventional DC-DC boost converter. Meanwhile, voltage stress on semiconductor device is depending on the maximum voltage ripple of the capacitor-clamped. A 50 W 4-level DC-DC boost converter prototype has been constructed. The results show that the inductor current ripple was 1.15 A when the inductors, 1 mH and 0.11 mH were used in the conventional and 4-level DC-DC boost converters, respectively. Thus, based on the experimental results, it shows that the reduction of passive components by referring to their attributes in 4-level DC-DC boost converter is achieved. Moreover, the decreasing of voltage stress on the semiconductor devices is an advantage for the selection of low ON-resistance of the devices which will contribute to the reduction of the semiconductor conduction loss. The integration result of boost converter and H-bridge inverter is also shown.

Approches pour la reduction de l'impact de defaut dans le transport d'energie du parc eolien offshore via VSC-HVDC =

NASA Astrophysics Data System (ADS)

Benadja, Mounir

Dans ce travail est presente un systeme de generation d'energie d'un parc eolien offshore et un systeme de transport utilisant les stations VSC-HVDC connectees au reseau principal AC onshore. Trois configurations ont ete etudiees, modelisees et validees par simulation. Dans chacune des configurations, des contributions ameliorant les cotes techniques et economiques sont decrites ci-dessous : La premiere contribution concerne un nouvel algorithme MPPT (Maximum Power Point Tracking) utilise pour l'extraction de la puissance maximale disponible dans les eoliennes des parcs offshores. Cette technique d'extraction du MPPT ameliore le rendement energetique de la chaine de conversion des energies renouvelables notamment l'energie eolienne a petite et a grande echelles (parc eolien offshore) qui constitue un probleme pour les constructeurs qui se trouvent confrontes a developper des dispositifs MPPT simples, moins couteux, robustes, fiables et capable d'obtenir un rendement energetique maximal. La deuxieme contribution concerne la reduction de la taille, du cout et de l'impact des defauts electriques (AC et DC) dans le systeme construit pour transporter l'energie d'un parc eolien offshore (OWF) vers le reseau principal AC onshore via deux stations 3L-NPC VSCHVDC. La solution developpee utilise des observateurs non-lineaires bases sur le filtre de Kalman etendu (EKF). Ce filtre permet d'estimer la vitesse de rotation et la position du rotor de chacune des generatrices du parc eolien offshore et de la tension du bus DC de l'onduleur DC-AC offshore et des deux stations 3L-NPC-VSC-HVDC (offshore et onshore). De plus, ce developpement du filtre de Kalman etendu a permis de reduire l'impact des defauts AC et DC. Deux commandes ont ete utilisees, l'une (commande indirect dans le plan abc) avec EKF integre destinee pour controler le convertisseur DC-AC offshore et l'autre (commande d-q) avec EKF integre pour controler les convertisseurs des deux stations AC-DC et DC-AC tout en tenant compte des entrees de chacune des stations. L'integration des observateurs non-lineaires (EKF) dans le controle des convertisseurs permet de resoudre le probleme des incertitudes de mesure, des incertitudes dans la modelisation, en cas du dysfonctionnement ou de panne des capteurs de mesure ainsi que le probleme de l'impact des defauts (AC et DC) sur la qualite d'energie dans les systemes de transmission. Ces estimations contribuent a rendre le cout global du systeme moins cher et sa taille moins encombrante ainsi que la reduction de l'impact des defauts (AC et DC) sur le systeme. La troisieme contribution concerne la reduction de la taille, du cout et de l'impact des defauts electriques (AC et DC) dans le systeme construit pour transporter l'energie d'un parc eolien offshore (OWF) vers le reseau principal AC onshore via deux stations VSC-HVDC. La solution developpee utilise des observateurs non-lineaires bases sur le filtre de Kalman etendu (EKF). Ce filtre permet d'estimer la vitesse de rotation et la position du rotor de chacune des generatrices du parc eolien et de la tension du bus DC de l'onduleur DC-AC offshore. La contribution porte surtout sur le developpement des deux commandes des deux stations. La premiere, la commande non-lineaire modifiee pour controler le premier convertisseur de la station VSC-HVDC offshore assurant le transfert de la puissance generee par le parc eolien vers la station VSC-HVDC onshore. La deuxieme commande non-lineaire modifiee avec integration de la regulation de la tension du bus DC et de la commande a modele de reference adaptative (MRAC) pour la compensation des surintensites et surtensions durant les defauts AC et DC. On peut constater que lors d'un defaut AC au PCC (Point of Common Coupling) du cote reseau onshore, la profondeur de l'impact du defaut AC sur l'amplitude des courants du reseau principal AC onshore qui etait reduit a 60% par les travaux de recherche (Erlich, Feltes et Shewarega, 2014), comparativement a la nouvelle commande proposee MRAC qui reduit la profondeur de l'impact a 35%. Lors de l'apparition des defauts AC et DC, une reduction de l'impact des defauts sur l'amplitude des courants de reseau AC terrestre et du temps de reponse a ete observee et la stabilite du systeme a ete renforcee par l'utilisation de la commande adaptative basee sur le modele de reference MRAC. La quatrieme contribution concerne une nouvelle commande basee sur le mode de glissement (SM) appliquee pour la station VSC-HVDC qui relie le parc eolien offshore (OWF) au reseau principal AC. Ce parc est compose de dix eoliennes basees sur des generatrices synchrones a aimant permanent (VSWT/PMSGs) connectees en parallele et chacune est controlee par son propre convertisseur DC-DC. Une comparaison des performances entre la commande SM et de la commande non-lineaire avec des controleurs PI pour les deux conditions (presence et absence de defaut DC) a ete analysee et montre la superiorite de la commande par SM. Un prototype du systeme etudie a echelle reduite a ete realise et teste au laboratoire GREPCI en utilisant la carte dSPACE-DS1104 pour la validation experimentale. L'analyse et la simulation des systemes etudies sont developpees sous l'environnement Matlab/Simulink/Simpowersystem. Les resultats obtenus a partir des configurations developpees sont valides par simulation et par experimentation. Les performances sont tres satisfaisantes du point de vue reponse dynamique, reponse en regime permanent, stabilite du systeme et qualite de l'energie.

[Nursing diagnosis sedentary lifestyle in individuals with hypertension: an analysis of accuracy].

PubMed

Martins, Larissa Castelo Guedes; Lopes, Marcos Venícios de Oliveira; Guedes, Nirla Gomes; Teixeira, Iane Ximenes; Souza, Vanessa Emille Carvalho de; Montoril, Michelle Helcias

2014-10-01

Assessing the accuracy of the defining characteristics (DC) of the nursing diagnosis Sedentary Lifestyle (SL) in people with hypertension. A cross-sectional study carried out in a referral center in the outpatient care of people with hypertension and diabetes, with a sample of 285 individuals. The form used in the study was designed from operational definitions constructed for each DC of the diagnosis. Four nurses with training to carry out diagnostic inferences did the clinical assessment for the presence of SL. The prevalence of SL was 55.8%. Regarding measures of accuracy, the main DC for SL was chooses a daily routine lacking physical exercise, with sensitivity of 100% and specificity of 84.13%. Two DC stood out in the logistic regression, namely: reports preference for activities low in physical activity and poor performance in instrumental activities of daily living (IADL). The results allowed identifying the best clinical indicators for SL in hypertensive adults.

Der p 1-pulsed myeloid and plasmacytoid dendritic cells from house dust mite-sensitized allergic patients dysregulate the T cell response.

PubMed

Charbonnier, Anne-Sophie; Hammad, Hamida; Gosset, Philippe; Stewart, Geoffrey A; Alkan, Sefik; Tonnel, André-Bernard; Pestel, Joël

2003-01-01

Although reports suggest that dendritic cells (DC) are involved in the allergic reaction characterized by a T helper cell type 2 (Th2) profile, the role of myeloid (M-DC) and plasmacytoid DC (P-DC), controlling the balance Th1/Th2, remains unknown. Here, we showed that in Dermatophagoides pteronyssinus (Dpt)-sensitized allergic patients and in healthy donors, M-DC displayed a higher capacity to capture Der p 1, a major allergen of Dpt, than did P-DC. However, Der p 1-pulsed M-DC from healthy subjects overexpressed CD80 and secreted interleukin (IL)-10, whereas M-DC from allergic patients did not. In contrast, with Der p 1-pulsed P-DC from both groups, no increase in human leukocyte antigen-DR, CD80, and CD86 and no IL-10 secretion were detected. When cocultured with allogeneic naive CD4(+) T cells from healthy donors, Der p 1-pulsed M-DC from allergic patients favored a Th1 profile [interferon (IFN)-gamma(high)/IL-4(low)] and Der p 1-pulsed P-DC, a Th2 profile (IFN-gamma(low)/IL-4(high)). In healthy donors, no T cell polarization (IFN-gamma(low)/IL-4(low)) was induced by Der p 1-pulsed M-DC or P-DC, but in response to Der p 1-pulsed M-DC, T cells secreted IL-10. The neutralization of IL-10 produced by Der p 1-pulsed M-DC from healthy donors led to an inhibition of IL-10 production by T cells and a polarization toward a type 1. Thus, IL-10 produced by M-DC might be an essential mediator controlling the balance between tolerance and allergic status. In addition, P-DC could contribute to the steady state in healthy donors or to the development of a Th2 response in allergic donors.

Binding of HIV-1 gp120 to DC-SIGN Promotes ASK-1-Dependent Activation-Induced Apoptosis of Human Dendritic Cells

PubMed Central

Chan, Vera S. F.; Chung, Nancy P. Y.; Wang, Shu-Rong; Li, Zhongye; Ma, Jing; Lin, Chia-Wei; Hsieh, Ya-Ju; Chang, Kao-Ping; Kung, Sui-Sum; Wu, Yi-Chia; Chu, Cheng-Wei; Tai, Hsiao-Ting; Gao, George F.; Zheng, Bojian; Yokoyama, Kazunari K.; Austyn, Jonathan M.; Lin, Chen-Lung S.

2013-01-01

During disease progression to AIDS, HIV-1 infected individuals become increasingly immunosuppressed and susceptible to opportunistic infections. It has also been demonstrated that multiple subsets of dendritic cells (DC), including DC-SIGN(+) cells, become significantly depleted in the blood and lymphoid tissues of AIDS patients, which may contribute to the failure in initiating effective host immune responses. The mechanism for DC depletion, however, is unclear. It is also known that vast quantities of viral envelope protein gp120 are shed from maturing HIV-1 virions and form circulating immune complexes in the serum of HIV-1-infected individuals, but the pathological role of gp120 in HIV-1 pathogenesis remains elusive. Here we describe a previously unrecognized mechanism of DC death in chronic HIV-1 infection, in which ligation of DC-SIGN by gp120 sensitizes DC to undergo accelerated apoptosis in response to a variety of activation stimuli. The cultured monocyte-derived DC and also freshly-isolated DC-SIGN(+) blood DC that were exposed to either cross-linked recombinant gp120 or immune-complex gp120 in HIV(+) serum underwent considerable apoptosis after CD40 ligation or exposure to bacterial lipopolysaccharide (LPS) or pro-inflammatory cytokines such as TNFα and IL-1β. Furthermore, circulating DC-SIGN(+) DC that were isolated directly from HIV-1(+) individuals had actually been pre-sensitized by serum gp120 for activation-induced exorbitant apoptosis. In all cases the DC apoptosis was substantially inhibited by DC-SIGN blockade. Finally, we showed that accelerated DC apoptosis was a direct consequence of excessive activation of the pro-apoptotic molecule ASK-1 and transfection of siRNA against ASK-1 significantly prevented the activation-induced excessive DC death. Our study discloses a previously unknown mechanism of immune modulation by envelope protein gp120, provides new insights into HIV immunopathogenesis, and suggests potential therapeutic approaches to prevent DC depletion in chronic HIV infection. PMID:23382671

Influence of DC-biasing on the performance of graphene spin valve

NASA Astrophysics Data System (ADS)

Iqbal, Muhammad Zahir; Hussain, Ghulam; Siddique, Salma; Hussain, Tassadaq; Iqbal, Muhammad Javaid

2018-04-01

Generating and controlling the spin valve signal are key factors in 'spintronics', which aims to utilize the spin degree of electrons. For this purpose, spintronic devices are constructed that can detect the spin signal. Here we investigate the effect of direct current (DC) on the magnetoresistance (MR) of graphene spin valve. The DC input not only decreases the magnitude of MR but also distorts the spin valve signal at higher DC inputs. Also, low temperature measurements revealed higher MR for the device, while the magnitude is noticed to decrease at higher temperatures. Furthermore, the spin polarization associated with NiFe electrodes is continuously increased at low DC bias and low temperatures. We also demonstrate the ohmic behavior of graphene spin valve by showing linear current-voltage (I-V) characteristics of the junction. Our findings may contribute significantly in modulating and controlling the spin transport properties of vertical spin valve structures.

Distributed control system for parallel-connected DC boost converters

DOEpatents

Goldsmith, Steven

2017-08-15

The disclosed invention is a distributed control system for operating a DC bus fed by disparate DC power sources that service a known or unknown load. The voltage sources vary in v-i characteristics and have time-varying, maximum supply capacities. Each source is connected to the bus via a boost converter, which may have different dynamic characteristics and power transfer capacities, but are controlled through PWM. The invention tracks the time-varying power sources and apportions their power contribution while maintaining the DC bus voltage within the specifications. A central digital controller solves the steady-state system for the optimal duty cycle settings that achieve a desired power supply apportionment scheme for a known or predictable DC load. A distributed networked control system is derived from the central system that utilizes communications among controllers to compute a shared estimate of the unknown time-varying load through shared bus current measurements and bus voltage measurements.

Redefining Myeloid Cell Subsets in Murine Spleen

PubMed Central

Hey, Ying-Ying; Tan, Jonathan K. H.; O’Neill, Helen C.

2016-01-01

Spleen is known to contain multiple dendritic and myeloid cell subsets, distinguishable on the basis of phenotype, function and anatomical location. As a result of recent intensive flow cytometric analyses, splenic dendritic cell (DC) subsets are now better characterized than other myeloid subsets. In order to identify and fully characterize a novel splenic subset termed “L-DC” in relation to other myeloid cells, it was necessary to investigate myeloid subsets in more detail. In terms of cell surface phenotype, L-DC were initially characterized as a CD11bhiCD11cloMHCII−Ly6C−Ly6G− subset in murine spleen. Their expression of CD43, lack of MHCII, and a low level of CD11c was shown to best differentiate L-DC by phenotype from conventional DC subsets. A complete analysis of all subsets in spleen led to the classification of CD11bhiCD11cloMHCII−Ly6CloLy6G− cells as monocytes expressing CX3CR1, CD43 and CD115. Siglec-F expression was used to identify a specific eosinophil population, distinguishable from both Ly6Clo and Ly6Chi monocytes, and other DC subsets. L-DC were characterized as a clear subset of CD11bhiCD11cloMHCII−Ly6C−Ly6G− cells, which are CD43+, Siglec-F− and CD115−. Changes in the prevalence of L-DC compared to other subsets in spleens of mutant mice confirmed the phenotypic distinction between L-DC, cDC and monocyte subsets. L-DC development in vivo was shown to occur independently of the BATF3 transcription factor that regulates cDC development, and also independently of the FLT3L and GM-CSF growth factors which drive cDC and monocyte development, so distinguishing L-DC from these commonly defined cell types. PMID:26793192

Electric Motors Everywhere: Most Forms of Energy Go through Some Conversion Process to Do Useful Work for Us

ERIC Educational Resources Information Center

Deal, Walter F., III

2004-01-01

This article discusses electric motors and the many ways in which they are used. Selecting the most appropriate miniature DC electric motor wisely will contribute toward success and satisfaction in designing and building motorized projects and activities. Typical parts suppliers stock a variety of miniature DC motors and provide sufficient…

Healthy School Environment and Enhanced Educational Performance: The Case of Charles Young Elementary School, Washington, DC.

ERIC Educational Resources Information Center

Berry, Michael A.

This report presents a case study of the renovation of Charles Young Elementary School in Washington, DC, focusing on how an improved school environment contributed to higher levels of educational performance. The school was chosen as a school revitalization demonstration project for the Urban Schools Initiative. The objective of the project was…

Permanent Magnet Machine And Method With Reluctance Poles For High Strength Undiffused Brushless Operation.

DOEpatents

Hsu, John S [Oak Ridge, TN

2005-12-06

A method and apparatus in which a rotor (11) and a stator (17) define a radial air gap (20) for receiving AC flux and at least one, and preferably two, DC excitation assemblies (23, 24) are positioned at opposite ends of the rotor (20) to define secondary air gaps (21, 22). Portions of PM material (14a, 14b) are provided as boundaries separating the rotor pole portions (12a, 12b) of opposite polarity from other portions of the rotor (11) and from each other to define PM poles (12a, 12b) for conveying the DC flux to or from the primary air gap (20) and for inhibiting flux from leaking from the pole portions prior to reaching the primary air gap (20). The portions of PM material (14a, 14b) are spaced from each other so as to include reluctance poles (15) of ferromagnetic material between the PM poles (12a, 12b) to interact with the AC flux in the primary-air gap (20).

The nuclear electric quadrupole moment of antimony from the molecular method.

PubMed

Haiduke, Roberto L A; da Silva, Albérico B F; Visscher, Lucas

2006-08-14

Relativistic Dirac-Coulomb (DC) Hartree-Fock calculations are employed to obtain the analytic electric field gradient (EFG) on the antimony nucleus in the SbN, SbP, SbF, and SbCl molecules. The electronic correlation contribution to the EFGs is included with the DC-CCSD(T) and DC-CCSD-T approaches, also in the four-component framework, using a finite-difference method. The total EFG results, along with the experimental nuclear quadrupole coupling constants from microwave spectroscopy, allow to derive the nuclear quadrupole moments of (121)Sb and (123)Sb, respectively, as -543(11) and -692(14) mb.

Key issues in application of composites to transport aircraft

NASA Technical Reports Server (NTRS)

Stone, M.

1978-01-01

The application of composite materials to transport aircraft was identified and reviewed including the major contributing disciplines of design, manufacturing, and processing. Factors considered include: crashworthiness considerations (structural integrity, postcrash fires, and structural fusing), electrical/avionics subsystems integration, lightning, and P-static protection design; manufacturing development, evaluation, selection, and refining of tooling and curing procedures; and major joint design considerations. Development of the DC-10 rudder, DC-10 vertical stabilizer, and the DC-9 wing study project was reviewed. The Federal Aviation Administration interface and the effect on component design of compliance with Federal Aviation Regulation 25 Composite Guidelines are discussed.

IL-27 Production and STAT3-Dependent Upregulation of B7-H1 Mediate Immune Regulatory Functions of Liver Plasmacytoid DC1

PubMed Central

Matta, Benjamin M.; Raimondi, Giorgio; Rosborough, Brian R.; Sumpter, Tina L.; Thomson, Angus W.

2012-01-01

Plasmacytoid (p) dendritic cells (DC) are highly-specialized APC that, in addition to their well-recognized role in anti-viral immunity, also regulate immune responses. Liver-resident pDC are considerably less immunostimulatory than those from secondary lymphoid tissues and are equipped to promote immune tolerance/regulation through various mechanisms. IL-27 is an IL-12-family cytokine that regulates the function of both APC and T cells, although little is known about its role in pDC immunobiology. In this study, we show that mouse liver pDC express higher levels of IL-27p28 and EBV-induced protein (Ebi)3 compared to splenic pDC. Both populations of pDC express the IL-27Rα/WSX-1; however, only liver pDC significantly upregulate expression of the co-regulatory molecule B7 homolog-1 (B7-H1) in response to IL-27. Inhibition of STAT3 activation completely abrogates IL-27-induced upregulation of B7-H1 expression on liver pDC. Liver pDC treated with IL-27 increase the percentage of CD4+Foxp3+ T cells in MLR, which is dependent upon expression of B7-H1. pDC from Ebi3-deficient mice lacking functional IL-27, show increased capacity to stimulate allogeneic T cell proliferation and IFN-γ production in MLR. Liver but not spleen pDC suppress delayed-type hypersensitivity responses to OVA, an effect that is lost with Ebi3−/− and B7-H1−/− liver pDC compared to wild-type (WT) liver pDC. These data suggest that IL-27 signaling in pDC promotes their immunoregulatory function and that IL-27 produced by pDC contributes to their capacity to regulate immuneresponses in vitro and in vivo. PMID:22508931

A complete dc characterization of a constant-frequency, clamped-mode, series-resonant converter

NASA Technical Reports Server (NTRS)

Tsai, Fu-Sheng; Lee, Fred C.

1988-01-01

The dc behavior of a clamped-mode series-resonant converter is characterized systematically. Given a circuit operating condition, the converter's mode of operation is determined and various circuit parameters are calculated, such as average inductor current (load current), rms inductor current, peak capacitor voltage, rms switch currents, average diode currents, switch turn-on currents, and switch turn-off currents. Regions of operation are defined, and various circuit characteristics are derived to facilitate the converter design.

Test and treat DC: forecasting the impact of a comprehensive HIV strategy in Washington DC.

PubMed

Walensky, Rochelle P; Paltiel, A David; Losina, Elena; Morris, Bethany L; Scott, Callie A; Rhode, Erin R; Seage, George R; Freedberg, Kenneth A

2010-08-15

The United States and international agencies have signaled their commitment to containing the human immunodeficiency virus (HIV) epidemic via early case identification and linkage to antiretroviral therapy (ART) immediately at diagnosis. We forecast outcomes of this approach if implemented in Washington DC. Using a mathematical model of HIV case detection and treatment, we evaluated combinations of HIV screening and ART initiation strategies. We define current practice as no regular screening program and ART at CD4 counts < or = 350 cells/microL, and we define test and treat as annual screening and administration of ART at diagnosis. Outcomes include life expectancy of HIV-infected persons and changes in the population time with transmissible HIV RNA levels. Data, largely from Washington DC, include undiagnosed HIV prevalence of 0.6%, annual incidence of 0.13%, 31% rate of test offer, 60% rate of acceptance, and 50% linkage to care. Input parameters, including optimized ART efficacy, are varied in sensitivity analyses. Projected life expectancies, from an initial mean age of 41 years, are 23.9, 25.0, and 25.6 years for current practice, test and treat, and test and treat with optimized ART, respectively. Compared with current practice, test and treat leads to a 14.7% reduction in time spent with transmissible HIV RNA level in the next 5 years; test and treat with optimized ART results in a 27.3% reduction. An expanded HIV test and treat program in Washington DC will increase life expectancy of HIV-infected patients but will have a modest impact on HIV transmission over the next 5 years and is unlikely to halt the HIV epidemic.

Antigen presenting capacity of murine splenic myeloid cells.

PubMed

Hey, Ying-Ying; Quah, Benjamin; O'Neill, Helen C

2017-01-11

The spleen is an important site for hematopoiesis. It supports development of myeloid cells from bone marrow-derived precursors entering from blood. Myeloid subsets in spleen are not well characterised although dendritic cell (DC) subsets are clearly defined in terms of phenotype, development and functional role. Recently a novel dendritic-like cell type in spleen named 'L-DC' was distinguished from other known dendritic and myeloid cells by its distinct phenotype and developmental origin. That study also redefined splenic eosinophils as well as resident and inflammatory monocytes in spleen. L-DC are shown to be distinct from known splenic macrophages and monocyte subsets. Using a new flow cytometric procedure, it has been possible to identify and isolate L-DC in order to assess their functional competence and ability to activate T cells both in vivo and in vitro. L-DC are readily accessible to antigen given intravenously through receptor-mediated endocytosis. They are also capable of CD8 + T cell activation through antigen cross presentation, with subsequent induction of cytotoxic effector T cells. L-DC are MHCII - cells and unable to activate CD4 + T cells, a property which clearly distinguishes them from conventional DC. The myeloid subsets of resident monocytes, inflammatory monocytes, neutrophils and eosinophils, were found to have varying capacities to take up antigen, but were uniformly unable to activate either CD4 + T cells or CD8 + T cells. The results presented here demonstrate that L-DC in spleen are distinct from other myeloid cells in that they can process antigen for CD8 + T cell activation and induction of cytotoxic effector function, while both L-DC and myeloid subsets remain unable to activate CD4 + T cells. The L-DC subset in spleen is therefore distinct as an antigen presenting cell.

Targeting Toll-like receptor 7/8 enhances uptake of apoptotic leukemic cells by monocyte-derived dendritic cells but interferes with subsequent cytokine-induced maturation.

PubMed

van den Ancker, Willemijn; van Luijn, Marvin M; Ruben, Jurjen M; Westers, Theresia M; Bontkes, Hetty J; Ossenkoppele, Gert J; de Gruijl, Tanja D; van de Loosdrecht, Arjan A

2011-01-01

Therapeutic vaccination with dendritic cells (DC) is an emerging investigational therapy for eradication of minimal residual disease in acute myeloid leukemia. Various strategies are being explored in manufacturing DC vaccines ex vivo, e.g., monocyte-derived DC (MoDC) loaded with leukemia-associated antigens (LAA). However, the optimal source of LAA and the choice of DC-activating stimuli are still not well defined. Here, loading with leukemic cell preparations (harboring both unknown and known LAA) was explored in combination with a DC maturation-inducing cytokine cocktail (CC; IL-1β, IL-6, TNF-α, and PGE(2)) and Toll-like receptor ligands (TLR-L) to optimize uptake. Since heat shock induced apoptotic blasts were more efficiently taken up than lysates, we focused on uptake of apoptotic leukemic cells. Uptake of apoptotic blast was further enhanced by the TLR7/8-L R848 (20-30%); in contrast, CC-induced maturation inhibited uptake. CC, and to a lesser extent R848, enhanced the ability of MoDC to migrate and stimulate T cells. Furthermore, class II-associated invariant chain peptide expression was down-modulated after R848- or CC-induced maturation, indicating enhanced processing and presentation of antigenic peptides. To improve both uptake and maturation, leukemic cells and MoDC were co-incubated with R848 for 24 h followed by addition of CC. However, this approach interfered with CC-mediated MoDC maturation as indicated by diminished migratory and T cell stimulatory capacity, and the absence of IL-12 production. Taken together, our data demonstrate that even though R848 improved uptake of apoptotic leukemic cells, the sequential use of R848 and CC is counter-indicated due to its adverse effects on MoDC maturation.

NASA Dryden Mission Manager Walter Klein poses with school children that visited the DC-8 during AirSAR 2004 in Punta Arenas, Chile

NASA Image and Video Library

2004-03-10

NASA Dryden Mission Manager Walter Klein poses with school children that visited the DC-8 during AirSAR 2004 in Punta Arenas, Chile. AirSAR 2004 is a three-week expedition by an international team of scientists that uses an all-weather imaging tool, called the Airborne Synthetic Aperture Radar (AirSAR) which is located onboard NASA's DC-8 airborne laboratory. Scientists from many parts of the world including NASA's Jet Propulsion Laboratory are combining ground research done in several areas in Central and South America with NASA's AirSAR technology to improve and expand on the quality of research they are able to conduct. In South America and Antarctica, AirSAR collected imagery and data to help determine the contribution of Southern Hemisphere glaciers to sea level rise due to climate change. In Patagonia, researchers found this contribution had more than doubled from 1995 to 2000, compared to the previous 25 years. AirSAR data will make it possible to determine whether that trend is continuing or accelerating. AirSAR will also provide reliable information on ice shelf thickness to measure the contribution of the glaciers to sea level.

76 FR 79714 - Premium Changes Based On Recharacterization of Contributions

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-22

... PENSION BENEFIT GUARANTY CORPORATION Premium Changes Based On Recharacterization of Contributions AGENCY: Pension Benefit Guaranty Corporation. ACTION: Policy statement. SUMMARY: This policy statement..., Legislative and Regulatory Department, Pension Benefit Guaranty Corporation, 1200 K Street NW., Washington DC...

Poor allostimulatory function of liver plasmacytoid DC is associated with pro-apoptotic activity, dependent on regulatory T cells

PubMed Central

Tokita, Daisuke; Sumpter, Tina L.; Raimondi, Giorgio; Zahorchak, Alan F.; Wang, Zhiliang; Nakao, Atsunori; Mazariegos, George V.; Abe, Masanori; Thomson, Angus W.

2008-01-01

Background/Aims The liver is comparatively rich in plasmacytoid (p) dendritic cells (DC),- innate immune effector cells that are also thought to play key roles in the induction and regulation of adaptive immunity. Methods Liver and spleen pDC were purified from fms-like tyrosine kinase ligand-reated control or lipopolysaccharide-injected C57BL/10 mice. Flow cytometric and molecular biologic assays were used to characterize their function and interaction with naturally-occurring regulatory T cells (Treg). Results While IL-10 production was greater for freshly-isolated liver compared with splenic pDC, the former produced less bioactive IL-12p70. Moreover, liver pDC expressed a low Delta4/Jagged1 Notch ligand ratio, skewed towards T helper 2 cell differentiation/cytokine production, and promoted allogeneic CD4+ T cell apoptosis. T cell proliferation in response to liver pDC was, however, enhanced by blocking IL-10 function at the initiation of cultures. In the absence of naturally occurring CD4+CD25+ regulatory T cells, similar levels of T cell proliferation were induced by liver and spleen pDC and the pro-apoptotic activity of liver pDC was reversed. Conclusion The inferior T cell allostimulatory activity of in vivo-stimulated liver pDC may depend on the presence and function of Treg, a property that may contribute to inherent liver tolerogenicity. PMID:18926588

MicroRNA-Mediated Down-Regulation of M-CSF Receptor Contributes to Maturation of Mouse Monocyte-Derived Dendritic Cells

PubMed Central

Riepsaame, Joey; van Oudenaren, Adri; den Broeder, Berlinda J. H.; van IJcken, Wilfred F. J.; Pothof, Joris; Leenen, Pieter J. M.

2013-01-01

Dendritic cell (DC) maturation is a tightly regulated process that requires coordinated and timed developmental cues. Here we investigate whether microRNAs are involved in this process. We identify microRNAs in mouse GM-CSF-generated, monocyte-related DC (GM-DC) that are differentially expressed during both spontaneous and LPS-induced maturation and characterize M-CSF receptor (M-CSFR), encoded by the Csf1r gene, as a key target for microRNA-mediated regulation in the final step toward mature DC. MicroRNA-22, -34a, and -155 are up-regulated in mature MHCIIhi CD86hi DC and mediate Csf1r mRNA and protein down-regulation. Experimental inhibition of Csf1r-targeting microRNAs in vitro results not only in sustained high level M-CSFR protein expression but also in impaired DC maturation upon stimulation by LPS. Accordingly, over-expression of Csf1r in GM-DC inhibits terminal differentiation. Taken together, these results show that developmentally regulated microRNAs control Csf1r expression, supplementing previously identified mechanisms that regulate its transcription and protein surface expression. Furthermore, our data indicate a novel function for Csf1r in mouse monocyte-derived DC, showing that down-regulation of M-CSFR expression is essential for final DC maturation. PMID:24198819

Design and modelling of high gain DC-DC converters for fuel cell hybrid electric vehicles

NASA Astrophysics Data System (ADS)

Elangovan, D.; Karthigeyan, V.; Subhanu, B.; Ashwin, M.; Arunkumar, G.

2017-11-01

Transportation (Diesel and petrol internal combustion engine vehicles) approximately contributes to 25.5% of total CO2 emission. Thus diesel and petrol engine vehicles are the most dominant contributors of CO2 emission which leads global warming which causes climate change. The problem of CO2 emission and global warming can be reduced by focusing on renewable energy vehicles. Out of the available renewable energy sources fuel cell is the only source which has reasonable efficiency and can be used in vehicles. But the main disadvantage of fuel cell is its slow response time. So energy storage systems like batteries and super capacitors are used in parallel with the fuel cell. Fuel cell is used during steady state vehicle operation while during transient conditions like starting, acceleration and braking batteries and super capacitors can supply or absorb energy. In this paper a unidirectional fuel cell DC-DC converter and bidirectional energy storage system DC-DC converter is proposed, which can interface dc sources at different voltage levels to the dc bus and also it can independently control the power flow from each energy source to the dc bus and vice versa. The proposed converters are designed and simulated using PSIM version 9.1.1 and gate pulse pattern, input and output voltage waveforms of the converters for steady state operation are studied.

Fasciola hepatica glycoconjugates immuneregulate dendritic cells through the Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin inducing T cell anergy

PubMed Central

Rodríguez, Ernesto; Kalay, Hakan; Noya, Verónica; Brossard, Natalie; Giacomini, Cecilia; van Kooyk, Yvette; García-Vallejo, Juan J.; Freire, Teresa

2017-01-01

Dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) expressed on a variety of DCs, is a C-type lectin receptor that recognizes glycans on a diverse range of pathogens, including parasites. The interaction of DC-SIGN with pathogens triggers specific signaling events that modulate DC-maturation and activity and regulate T-cell activation by DCs. In this work we evaluate whether F. hepatica glycans can immune modulate DCs via DC-SIGN. We demonstrate that DC-SIGN interacts with F. hepatica glycoconjugates through mannose and fucose residues. We also show that mannose is present in high-mannose structures, hybrid and trimannosyl N-glycans with terminal GlcNAc. Furthermore, we demonstrate that F. hepatica glycans induce DC-SIGN triggering leading to a strong production of TLR-induced IL-10 and IL-27p28. In addition, parasite glycans induced regulatory DCs via DC-SIGN that decrease allogeneic T cell proliferation, via the induction of anergic/regulatory T cells, highlighting the role of DC-SIGN in the regulation of innate and adaptive immune responses by F. hepatica. Our data confirm the immunomodulatory properties of DC-SIGN triggered by pathogen-derived glycans and contribute to the identification of immunomodulatory glyans of helminths that might eventually be useful for the design of vaccines against fasciolosis. PMID:28436457

Fasciola hepatica glycoconjugates immuneregulate dendritic cells through the Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin inducing T cell anergy.

PubMed

Rodríguez, Ernesto; Kalay, Hakan; Noya, Verónica; Brossard, Natalie; Giacomini, Cecilia; van Kooyk, Yvette; García-Vallejo, Juan J; Freire, Teresa

2017-04-24

Dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) expressed on a variety of DCs, is a C-type lectin receptor that recognizes glycans on a diverse range of pathogens, including parasites. The interaction of DC-SIGN with pathogens triggers specific signaling events that modulate DC-maturation and activity and regulate T-cell activation by DCs. In this work we evaluate whether F. hepatica glycans can immune modulate DCs via DC-SIGN. We demonstrate that DC-SIGN interacts with F. hepatica glycoconjugates through mannose and fucose residues. We also show that mannose is present in high-mannose structures, hybrid and trimannosyl N-glycans with terminal GlcNAc. Furthermore, we demonstrate that F. hepatica glycans induce DC-SIGN triggering leading to a strong production of TLR-induced IL-10 and IL-27p28. In addition, parasite glycans induced regulatory DCs via DC-SIGN that decrease allogeneic T cell proliferation, via the induction of anergic/regulatory T cells, highlighting the role of DC-SIGN in the regulation of innate and adaptive immune responses by F. hepatica. Our data confirm the immunomodulatory properties of DC-SIGN triggered by pathogen-derived glycans and contribute to the identification of immunomodulatory glyans of helminths that might eventually be useful for the design of vaccines against fasciolosis.

Efficient Design in a DC to DC Converter Unit

NASA Technical Reports Server (NTRS)

Bruemmer, Joel E.; Williams, Fitch R.; Schmitz, Gregory V.

2002-01-01

Space Flight hardware requires high power conversion efficiencies due to limited power availability and weight penalties of cooling systems. The International Space Station (ISS) Electric Power System (EPS) DC-DC Converter Unit (DDCU) power converter is no exception. This paper explores the design methods and tradeoffs that were utilized to accomplish high efficiency in the DDCU. An isolating DC to DC converter was selected for the ISS power system because of requirements for separate primary and secondary grounds and for a well-regulated secondary output voltage derived from a widely varying input voltage. A flyback-current-fed push-pull topology or improved Weinberg circuit was chosen for this converter because of its potential for high efficiency and reliability. To enhance efficiency, a non-dissipative snubber circuit for the very-low-Rds-on Field Effect Transistors (FETs) was utilized, redistributing the energy that could be wasted during the switching cycle of the power FETs. A unique, low-impedance connection system was utilized to improve contact resistance over a bolted connection. For improved consistency in performance and to lower internal wiring inductance and losses a planar bus system is employed. All of these choices contributed to the design of a 6.25 KW regulated dc to dc converter that is 95 percent efficient. The methodology used in the design of this DC to DC Converter Unit may be directly applicable to other systems that require a conservative approach to efficient power conversion and distribution.

Dendritic cell based vaccines: progress in immunotherapy studies for prostate cancer.

PubMed

Ragde, Haakon; Cavanagh, William A; Tjoa, Benjamin A

2004-12-01

No effective treatment is currently available for metastatic prostate cancer. Dendritic cell (DC) based cancer vaccine research has emerged from the laboratories to human clinical trials. We describe progress in the development of DC based prostate cancer vaccine. The literature was reviewed for major contributions to a growing number of studies that demonstrate the potential of DC based immunotherapeutics for prostate cancer. Background topics relating to DC based immunotherapy theory and practice are also addressed. DCs have been recognized as the most efficient antigen presenting cells that have the capacity to initiate naive T cell response in vitro and in vivo. During their differentiation and maturation pathways, dendritic cells can efficiently capture, process and present antigens for T cell activation. These characteristics make DC an attractive choice as the cellular adjuvant for cancer vaccines. Advances in DC generation, loading, and maturation methodologies have made it possible to generate clinical grade vaccines for various human trials. More than 100 DC vaccine trials, including 7 studies of patients with advanced prostate cancer have been reported to date. These vaccines were generally well tolerated with no significant adverse toxicity reported. Clinical responders have been identified in these studies. The new prospects opened by DC based vaccines for prostate cancer are fascinating. When compared to conventional treatments, DC vaccinations have few side effects. Improvements in patient selection, vaccine delivery strategies, immune monitoring and vaccine manufacturing will be crucial in moving DC based prostate cancer vaccines closer to the clinics.

NASA DC-8 Mission Manager Walter Klein and Chilean Air Force Advisor Captain Saez review maps of the Antarctic Peninsula during an AirSAR 2004 mission

NASA Image and Video Library

2004-03-13

NASA DC-8 Mission Manager Walter Klein and Chilean Air Force Advisor Captain Saez review maps of the Antarctic Peninsula during an AirSAR 2004 mission. AirSAR 2004 is a three-week expedition in Central and South America by an international team of scientists that is using an all-weather imaging tool, called the Airborne Synthetic Aperture Radar (AirSAR), located onboard NASA's DC-8 airborne laboratory. Scientists from many parts of the world are combining ground research with NASA's AirSAR technology to improve and expand on the quality of research they are able to conduct. These photos are from the DC-8 aircraft while flying an AirSAR mission over Antarctica. The Antarctic Peninsula is more similar to Alaska and Patagonia than to the rest of the Antarctic continent. It is drained by fast glaciers, receives abundant precipitation, and melts significantly in the summer months. In recent decades, the Peninsula has experienced significant atmospheric warming (about 2 degrees C since 1950), which has triggered a vast and spectacular retreat of its floating ice shelves, glacier reduction, a decrease in permanent snow cover and a lengthening of the melt season. As a result, the contribution to sea level from this region could be rapid and substantial. With an area of 120,000 km, or ten times the Patagonia ice fields, the Peninsula could contribute as much as 0.4mm/yr sea level rise, which would be the largest single contribution to sea level from anywhere in the world. This region is being studied by NASA using a DC-8 equipped with the Airborne Synthetic Aperture Radar developed by scientists from NASA’s Jet Propulsion Laboratory. AirSAR will provide a baseline model and unprecedented mapping of the region. This data will make it possible to determine whether the warming trend is slowing, continuing or accelerating. AirSAR will also provide reliable information on ice shelf thickness to measure the contribution of the glaciers to sea level.

An AirSAR 2004 view from the DC-8 as it approaches the Larsen Ice Shelf, which is part of the Antarctic Peninsula

NASA Image and Video Library

2004-03-13

An AirSAR 2004 view from the DC-8 as it approaches the Larsen Ice Shelf, which is part of the Antarctic Peninsula. AirSAR 2004 is a three-week expedition in Central and South America by an international team of scientists that is using an all-weather imaging tool, called the Airborne Synthetic Aperture Radar (AirSAR), located onboard NASA's DC-8 airborne laboratory. Scientists from many parts of the world are combining ground research with NASA's AirSAR technology to improve and expand on the quality of research they are able to conduct. These photos are from the DC-8 aircraft while flying an AirSAR mission over Antarctica. The Antarctic Peninsula is more similar to Alaska and Patagonia than to the rest of the Antarctic continent. It is drained by fast glaciers, receives abundant precipitation, and melts significantly in the summer months. In recent decades, the Peninsula has experienced significant atmospheric warming (about 2 degrees C since 1950), which has triggered a vast and spectacular retreat of its floating ice shelves, glacier reduction, a decrease in permanent snow cover and a lengthening of the melt season. As a result, the contribution to sea level from this region could be rapid and substantial. With an area of 120,000 km, or ten times the Patagonia ice fields, the Peninsula could contribute as much as 0.4mm/yr sea level rise, which would be the largest single contribution to sea level from anywhere in the world. This region is being studied by NASA using a DC-8 equipped with the Airborne Synthetic Aperture Radar developed by scientists from NASA’s Jet Propulsion Laboratory. AirSAR will provide a baseline model and unprecedented mapping of the region. This data will make it possible to determine whether the warming trend is slowing, continuing or accelerating. AirSAR will also provide reliable information on ice shelf thickness to measure the contribution of the glaciers to sea level.

TCF4-Targeting miR-124 is Differentially Expressed amongst Dendritic Cell Subsets

PubMed Central

Han, Sun Murray; Na, Hye Young; Ham, Onju; Choi, Wanho; Sohn, Moah; Ryu, Seul Hye; In, Hyunju; Hwang, Ki-Chul

2016-01-01

Dendritic cells (DCs) are professional antigen-presenting cells that sample their environment and present antigens to naïve T lymphocytes for the subsequent antigen-specific immune responses. DCs exist in a range of distinct subpopulations including plasmacytoid DCs (pDCs) and classical DCs (cDCs), with the latter consisting of the cDC1 and cDC2 lineages. Although the roles of DC-specific transcription factors across the DC subsets have become understood, the posttranscriptional mechanisms that regulate DC development are yet to be elucidated. MicroRNAs (miRNAs) are pivotal posttranscriptional regulators of gene expression in a myriad of biological processes, but their contribution to the immune system is just beginning to surface. In this study, our in-house probe collection was screened to identify miRNAs possibly involved in DC development and function by targeting the transcripts of relevant mouse transcription factors. Examination of DC subsets from the culture of mouse bone marrow with Flt3 ligand identified high expression of miR-124 which was able to target the transcript of TCF4, a transcription factor critical for the development and homeostasis of pDCs. Further expression profiling of mouse DC subsets isolated from in vitro culture as well as via ex vivo purification demonstrated that miR-124 was outstandingly expressed in CD24+ cDC1 cells compared to in pDCs and CD172α+ cDC2 cells. These results imply that miR-124 is likely involved in the processes of DC subset development by posttranscriptional regulation of a transcription factor(s). PMID:26937233

The "critical limits for crystallinity" in nanoparticles of the elements: A combined thermodynamic and crystallographic critique

NASA Astrophysics Data System (ADS)

Pelegrina, J. L.; Guillermet, A. Fernández

2018-03-01

The theme of the present work is the procedure for evaluating the minimum size for the stability of a crystalline particle with respect to the same group of atoms but in the amorphous state. A key goal of the study is the critical analysis of an extensively quoted paper by F.G. Shi [J. Mater. Res. 9 (1994) 1307-1313], who presented a criterion for evaluating a "crystallinity distance" (h) through its relation with the "critical diameter" (dC) of a particle, i.e., the diameter below which no particles with the crystalline structure are expected to exist at finite temperatures. Key assumptions of Shi's model are a direct proportionality relation between h and dC , and a prescription for estimating h from crystallographic information. In the present work the accuracy of the Shi model is assessed with particular reference to nanoparticles of the elements. To this end, an alternative way to obtain h, that better realizes Shi's idea of this quantity as "the height of a monolayer of atoms on the bulk crystal surface", is explored. Moreover, a thermodynamic calculation of dC , which involves a description of the bulk- and the surface contributions to the crystalline/amorphous relative phase stability for nanoparticles, is performed. It is shown that the Shi equation does not account for the key features of the h vs. dC relation established in the current work. Consequently, it is concluded that the parameter h obtained only from information about the structure of the crystalline phase, does not provide an accurate route to estimate the quantity dC . In fact, a key result of the current study is that dC crucially depends on the relation between bulk- and surface contributions to the crystalline/amorphous relative thermodynamic stability.

Characterization of colonic dendritic cells in normal and colitic mice.

PubMed

Cruickshank, Sheena M; English, Nicholas R; Felsburg, Peter J; Carding, Simon R

2005-10-28

Recent studies demonstrating the direct involvement of dendritic cells (DC) in the activation of pathogenic T cells in animal models of inflammatory bowel disease identify DC as important antigen presenting cells in the colon. However, very little is known about the properties of colonic DC. Using immunohistochemistry, electron microscopy and flow cytometry we have characterized and compared colonic DC in the colon of healthy animals and interleukin-2-deficient (IL2(-/-)) mice that develop colitis. In the healthy colon, DC resided within the lamina propria and in close association with the basement membrane of colonic villi. Type 1 myeloid (CD11c(+), CD11b(+), B220(-), CD8alpha(-)) DC made up the largest (40-45%) population and all DC expressed low levels of CD80, CD86, and CD40, and had high endocytic activity consistent with an immature phenotype. In colitic IL2(-/-) mice, colonic DC numbers increased four- to five-fold and were localized within the epithelial layer and within aggregates of T and B cells. They were also many more DC in mesenteric lymph nodes (MLN). The majority (>85%) of DC in the colon and MLN of IL2(-/-) mice were type 1 myeloid, and expressed high levels of MHC class II, CD80, CD86, CD40, DEC 205, and CCR5 molecules and were of low endocytic activity consistent with mature DC. These findings demonstrate striking changes in the number, distribution and phenotype of DC in the inflamed colon. Their intimate association with lymphocytes in the colon and draining lymph nodes suggest that they may contribute directly to the ongoing inflammation in the colon.

Characterization of colonic dendritic cells in normal and colitic mice

PubMed Central

Cruickshank, Sheena M; English, Nicholas R; Felsburg, Peter J; Carding, Simon R

2005-01-01

AIM: Recent studies demonstrating the direct involvement of dendritic cells (DC) in the activation of pathogenic T cells in animal models of inflammatory bowel disease identify DC as important antigen presenting cells in the colon. However, very little is known about the properties of colonic DC. METHODS: Using immunohistochemistry, electron microscopy and flow cytometry we have characterized and compared colonic DC in the colon of healthy animals and interleukin-2-deficient (IL2-/-) mice that develop colitis. RESULTS: In the healthy colon, DC resided within the lamina propria and in close association with the basement membrane of colonic villi. Type 1 myeloid (CD11c+, CD11b+, B220-, CD8α-) DC made up the largest (40-45%) population and all DC expressed low levels of CD80, CD86, and CD40, and had high endocytic activity consistent with an immature phenotype. In colitic IL2-/- mice, colonic DC numbers increased four- to five-fold and were localized within the epithelial layer and within aggregates of T and B cells. They were also many more DC in mesenteric lymph nodes (MLN). The majority (>85%) of DC in the colon and MLN of IL2-/- mice were type 1 myeloid, and expressed high levels of MHC class II, CD80, CD86, CD40, DEC 205, and CCR5 molecules and were of low endocytic activity consistent with mature DC. CONCLUSION: These findings demonstrate striking changes in the number, distribution and phenotype of DC in the inflamed colon. Their intimate association with lymphocytes in the colon and draining lymph nodes suggest that they may contribute directly to the ongoing inflammation in the colon. PMID:16419163

Effect of DC Offset on the T-Wave Residuum Parameter

NASA Technical Reports Server (NTRS)

Scott, N.; Greco, E. C.; Schlegel, Todd T.

2006-01-01

The T-wave residuum (TWR) is a relatively new 12-lead ECG parameter that may reflect cardiac repolarization heterogeneity. TWR shows clinical promise and may become an important diagnostic tool if accurate, consistent, and convenient methods for its calculation can be developed. However, there are discrepancies between the methods that various investigators have used to calculate TWR, as well as some questions about basic methodology and assumptions that require resolution. The presence of a DC offset or very low frequency AC component to the ECG is often observed. Many researchers have attempted to compensate for these by high pass filters and by median beat techniques. These techniques may help minimize the contribution of a low frequency AC component to the TWR, but they will not eliminate a DC offset inherent within the instrumentation. The present study examined the presence of DC offsets in the ECG record, and their effect on TWR. Specifically, in healthy individuals, a DC offset was added to all 8 channels collectively or to each channel selectively. Even with offsets that were relatively small compared to T-wave amplitude, the addition of either collectively or individually applied offsets was observed to produce very significant changes in the TWR, affecting its value by as much as an order of magnitude. These DC offsets may arise from at least two possible sources: a transient artifact from EMG or electrode movement resulting in a transient baseline offset in one or more channels. Since highpass filters have a settling time of several seconds, these artifacts will contribute to a transitory baseline offset lasting 1020 cycles. The machine hardware may also introduce an offset. Regardless of the cause or source of a DC offset, this study demonstrates that offsets have a very significant impact on TWR, and that future studies must not ignore their presence, but rather more appropriately compensate for them.

Defining and Measuring the Success of Service Contracts

DTIC Science & Technology

2012-06-01

group has its own representative professional certification (Garrett, 2010). Project management is defined as the centralized, coordinated management...and to the Office of Management and Budget, Paperwork Reduction Project (0704-0188) Washington DC 20503. 1. AGENCY USE ONLY (Leave blank) 2...for this project . Additionally, we would like to thank the Acquisition Research Program, especially Ms. Tera Yoder, for providing funding and

Cell-Intrinsic Glycogen Metabolism Supports Early Glycolytic Reprogramming Required for Dendritic Cell Immune Responses.

PubMed

Thwe, Phyu M; Pelgrom, Leonard; Cooper, Rachel; Beauchamp, Saritha; Reisz, Julie A; D'Alessandro, Angelo; Everts, Bart; Amiel, Eyal

2017-09-05

Dendritic cell (DC) activation by Toll-like receptor (TLR) agonists causes rapid glycolytic reprogramming that is required to meet the metabolic demands of their immune activation. Recent efforts in the field have identified an important role for extracellular glucose sourcing to support DC activation. However, the contributions of intracellular glucose stores to these processes have not been well characterized. We demonstrate that DCs possess intracellular glycogen stores and that cell-intrinsic glycogen metabolism supports the early effector functions of TLR-activated DCs. Inhibition of glycogenolysis significantly attenuates TLR-mediated DC maturation and impairs their ability to initiate lymphocyte activation. We further report that DCs exhibit functional compartmentalization of glucose- and glycogen-derived carbons, where these substrates preferentially contribute to distinct metabolic pathways. This work provides novel insights into nutrient homeostasis in DCs, demonstrating that differential utilization of glycogen and glucose metabolism regulates their optimal immune function. Copyright © 2017 Elsevier Inc. All rights reserved.

Heavy rainfall in Mediterranean cyclones. Part I: contribution of deep convection and warm conveyor belt

NASA Astrophysics Data System (ADS)

Flaounas, Emmanouil; Kotroni, Vassiliki; Lagouvardos, Konstantinos; Gray, Suzanne L.; Rysman, Jean-François; Claud, Chantal

2018-04-01

In this study, we provide an insight to the role of deep convection (DC) and the warm conveyor belt (WCB) as leading processes to Mediterranean cyclones' heavy rainfall. To this end, we use reanalysis data, lighting and satellite observations to quantify the relative contribution of DC and the WCB to cyclone rainfall, as well as to analyse the spatial and temporal variability of these processes with respect to the cyclone centre and life cycle. Results for the period 2005-2015 show that the relationship between cyclone rainfall and intensity has high variability and demonstrate that even intense cyclones may produce low rainfall amounts. However, when considering rainfall averages for cyclone intensity bins, a linear relationship was found. We focus on the 500 most intense tracked cyclones (responsible for about 40-50% of the total 11-year Mediterranean rainfall) and distinguish between the ones producing high and low rainfall amounts. DC and the WCB are found to be the main cause of rainfall for the former (producing up to 70% of cyclone rainfall), while, for the latter, DC and the WCB play a secondary role (producing up to 50% of rainfall). Further analysis showed that rainfall due to DC tends to occur close to the cyclones' centre and to their eastern sides, while the WCBs tend to produce rainfall towards the northeast. In fact, about 30% of rainfall produced by DC overlaps with rainfall produced by WCBs but this represents only about 8% of rainfall produced by WCBs. This suggests that a considerable percentage of DC is associated with embedded convection in WCBs. Finally, DC was found to be able to produce higher rain rates than WCBs, exceeding 50 mm in 3-h accumulated rainfall compared to a maximum of the order of 40 mm for WCBs. Our results demonstrate in a climatological framework the relationship between cyclone intensity and processes that lead to heavy rainfall, one of the most prominent environmental risks in the Mediterranean. Therefore, we set perspectives for a deeper analysis of the favourable atmospheric conditions that yield high impact weather.

Impact of Toxoplasma gondii on Dendritic Cell Subset Function in the Intestinal Mucosa.

PubMed

Cohen, Sara B; Denkers, Eric Y

2015-09-15

The function of mucosal dendritic cell (DC) subsets in immunity and inflammation is not well understood. In this study, we define four DC subsets present within the lamina propria and mesenteric lymph node compartments based on expression of CD103 and CD11b. Using IL-12p40 YFP (Yet40) reporter mice, we show that CD103(+)CD11b(-) mucosal DCs are primary in vivo sources of IL-12p40; we also identified CD103(-)CD11b(-) mucosal DCs as a novel population producing this cytokine. Infection was preferentially found in CD11b(+) DCs that were negative for CD103. Lamina propria DCs containing parasites were negative for IL-12p40. Instead, production of the cytokine was strictly a property of noninfected cells. We also show that vitamin A metabolism, as measured by ALDH activity, was preferentially found in CD103(+)CD11b(+) DC and was strongly downregulated in all mucosal DC subsets during infection. Finally, overall apoptosis of lamina propria DC subsets was increased during infection. Combined, these results highlight the ability of intestinal Toxoplasma infection to alter mucosal DC activity at both the whole population level and at the level of individual subsets. Copyright © 2015 by The American Association of Immunologists, Inc.

Electromigration failures under bidirectional current stress

NASA Astrophysics Data System (ADS)

Tao, Jiang; Cheung, Nathan W.; Hu, Chenming

1998-01-01

Electromigration failure under DC stress has been studied for more than 30 years, and the methodologies for accelerated DC testing and design rules have been well established in the IC industry. However, the electromigration behavior and design rules under time-varying current stress are still unclear. In CMOS circuits, as many interconnects carry pulsed-DC (local VCC and VSS lines) and bidirectional AC current (clock and signal lines), it is essential to assess the reliability of metallization systems under these conditions. Failure mechanisms of different metallization systems (Al-Si, Al-Cu, Cu, TiN/Al-alloy/TiN, etc.) and different metallization structures (via, plug and interconnect) under AC current stress in a wide frequency range (from mHz to 500 MHz) has been study in this paper. Based on these experimental results, a damage healing model is developed, and electromigration design rules are proposed. It shows that in the circuit operating frequency range, the "design-rule current" is the time-average current. The pure AC component of the current only contributes to self-heating, while the average (DC component) current contributes to electromigration. To ensure longer thermal-migration lifetime under high frequency AC stress, an additional design rule is proposed to limit the temperature rise due to self-joule heating.

Interplay of foot-and-mouth disease virus, antibodies and plasmacytoid dendritic cells: virus opsonization under non-neutralizing conditions results in enhanced interferon-alpha responses

PubMed Central

2012-01-01

Foot-and-mouth disease virus (FMDV) is a highly infectious member of the Picornaviridae inducing an acute disease of cloven-hoofed species. Vaccine-induced immune protection correlates with the presence of high levels of neutralizing antibodies but also opsonising antibodies have been proposed as an important mechanism of the immune response contributing to virus clearance by macrophages and leading to the production of type-I interferon (IFN) by plasmacytoid dendritic cells (pDC). The present study demonstrates that the opsonising antibody titres mediating enhanced IFN-α responses in pDC were similar to neutralizing titres, when antigenically related viruses from the same serotype were employed. However, sera cross-reacted also with non-neutralized isolates of multiple serotypes, when tested in this assay. Both uncomplexed virus and immune complexed virus stimulated pDC via Toll-like receptor 7. An additional finding of potential importance for strain-specific differences in virulence and/or immunogenicity was that pDC activation by FMDV strongly differed between viral isolates. Altogether, our results indicate that opsonising antibodies can have a broader reactivity than neutralizing antibodies and may contribute to antiviral responses induced against antigenically distant viruses. PMID:22934974

Effects of forward motion on jet and core noise

NASA Technical Reports Server (NTRS)

Low, J. K. C.

1977-01-01

A study was conducted to investigate the effects of forward motion on both jet and core noise. Measured low-frequency noise from static-engine and from flyover tests with a DC-9-30 powered by JT8D-109 turbofan engines and with a DC-10-40 powered by JT9D-59A turbofan engines was separated into jet- and core noise components. Comparisons of the static and the corresponding in-flight jet- and core-noise components are presented. The results indicate that for the DC-9 airplane at low power settings, where core noise is predominant, the effect of convective amplification on core-noise levels is responsible for the higher in-flight low-frequency noise levels in the inlet quadrant. Similarly, it was found that for the DC-10 airplane with engines mounted under the wings and flaps and flap deflection greater than 30 degrees, the contribution from jet-flap-interaction noise is as much as 5 dB in the inlet quadrant and is responsible for higher in-flight low-frequency noise levels during approach conditions. Those results indicate that to properly investigate flight effects, it is important to consider the noise contributions from other low-frequency sources, such as the core and the jet-flap interaction.

Precision cancer immunotherapy: optimizing dendritic cell-based strategies to induce tumor antigen-specific T-cell responses against individual patient tumors.

PubMed

Osada, Takuya; Nagaoka, Koji; Takahara, Masashi; Yang, Xiao Yi; Liu, Cong-Xiao; Guo, Hongtao; Roy Choudhury, Kingshuk; Hobeika, Amy; Hartman, Zachary; Morse, Michael A; Lyerly, H Kim

2015-05-01

Most dendritic cell (DC)-based vaccines have loaded the DC with defined antigens, but loading with autologos tumor-derived antigens would generate DCs that activate personalized tumor-specific T-cell responses. We hypothesized that DC matured with an optimized combination of reagents and loaded with tumor-derived antigens using a clinically feasible electroporation strategy would induce potent antitumor immunity. We first studied the effects on DC maturation and antigen presentation of the addition of picibanil (OK432) to a combination of zoledronic acid, tumor necrosis factor-α, and prostaglandin E2. Using DC matured with the optimized combination, we tested 2 clinically feasible sources of autologous antigen for electroloading, total tumor mRNA or total tumor lysate, to determine which stimulated more potent antigen-specific T cells in vitro and activated more potent antitumor immunity in vivo. The combination of tumor necrosis factor-α/prostaglandin E2/zoledronic acid/OK432 generated DC with high expression of maturation markers and antigen-specific T-cell stimulatory function in vitro. Mature DC electroloaded with tumor-derived mRNA [mRNA electroporated dendritic cell (EPDC)] induced greater expansion of antigen-specific T cells in vitro than DC electroloaded with tumor lysate (lysate EPDC). In a therapeutic model of MC38-carcinoembryonic antigen colon cancer-bearing mice, vaccination with mRNA EPDC induced the most efficient anti-carcinoembryonic antigen cellular immune response, which significantly suppressed tumor growth. In conclusion, mature DC electroloaded with tumor-derived mRNA are a potent cancer vaccine, especially useful when specific tumor antigens for vaccination have not been identified, allowing autologous tumor, and if unavailable, allogeneic cell lines to be used as an unbiased source of antigen. Our data support clinical testing of this strategy.

Developmental regulation by cytokines of bone marrow-derived dendritic cells and epidermal Langerhans cells.

PubMed

Yamaguchi, Y

1998-01-01

Dendritic cells (DC) are specialized antigen-presenting cells involved in T cell-mediated immune responses. Differentiation and functional maturation of the DC are now known to be regulated by various cytokines, including TGF-beta1. The experiments of this study examined the effect of other cytokines, such as IL-4, IL-10 and IL-6, on the differentiation and maturation of bone marrow (BM)-derived DC (BM-DC) and epidermal Langerhans cells (LC). When IL-6 or IL-10 was added to cultures of BM cells in the presence of GM-CSF, both cytokines, as in the case of TGF-beta1, suppressed the maturation of DC in terms of the expression of adhesion and costimulatory molecules and T cell-stimulating activity. In contrast, IL-4 was not suppressive but rather supportive for the differentiation of DC. However, these suppressive cytokines hardly counteracted the maturation-inducing activity of TNF-alpha when added to cultures of immature DC. In addition, they appeared to block the overmaturation of DC, which is characterized by a loss of MHC class II molecules. Regarding LC maturation in epidermal cell cultures, IL-6 and IL-10 were inhibitory for the expression of CD86 and CD80 in a dose-dependent fashion. Unlike BM-DC, LC maturation was slightly enhanced by TGF-beta1. The protein antigen-presentation by LC to Th1 clone was not affected by IL-6, but slightly reduced by IL-10. These results suggest that each cytokine contributes to regulate the differentiation and maturation of DC at a different developmental stage.

Galectin-9 Produced by Intestinal Epithelial Cells Enhances Aldehyde Dehydrogenase Activity in Dendritic Cells in a PI3K- and p38-Dependent Manner.

PubMed

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

2017-01-01

Intestinal epithelial cells (IEC) drive regulatory T cell (Treg) responses by promoting the differentiation of aldehyde dehydrogenase (ALDH)-expressing CD103+ dendritic cells (DC). Apical stimulation of TLR9 by CpG DNA on IEC supports galectin-9 expression by IEC, which is promoted by short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (GF). While galectin-9 can induce the maturation of monocyte-derived DC (moDC), the contribution of galectin-9 on the induction of ALDH activity in DC is not known. To this end, DC were stimulated with galectin-9, and ALDH activity and the expression of CD103 were assessed. ALDH activity was increased by moDC exposed to galectin-9, while the expression of CD103 remained unaltered. Galectin-9 secreted by IEC apically exposed to CpG DNA and GF enhanced ALDH activity, but not CD103 expression by moDC, which was abrogated upon galectin-9 neutralization. Similar observations were found in murine GM-CSF-cultured bone marrow-derived DC (BMDC). Using Flt3L-cultured BMDC and ex vivo murine splenic DC, it was observed that galectin-9 only enhanced ALDH activity in the presence of GM-CSF in CD103- cells. The induction of ALDH activity in BMDC was dependent on p38 and PI3K signaling. These data indicate a novel role for galectin-9 in modulating innate immunity by inducing ALDH activity in DC. © 2017 S. Karger AG, Basel.

Critical Role of Plasmacytoid Dendritic Cells in Regulating Gene Expression and Innate Immune Responses to Human Rhinovirus-16

PubMed Central

Xi, Yang; Troy, Niamh M.; Anderson, Denise; Pena, Olga M.; Lynch, Jason P.; Phipps, Simon; Bosco, Anthony; Upham, John W.

2017-01-01

Though human rhinoviruses (HRVs) are usually innocuous viruses, they can trigger serious consequences in certain individuals, especially in the setting of impaired interferon (IFN) synthesis. Plasmacytoid dendritic cells (pDCs) are key IFN producing cells, though we know little about the role of pDC in HRV-induced immune responses. Herein, we used gene expression microarrays to examine HRV-activated peripheral blood mononuclear cells (PBMCs) from healthy people, in combination with pDC depletion, to assess whether observed gene expression patterns were pDC dependent. As expected, pDC depletion led to a major reduction in IFN-α release. This was associated with profound differences in gene expression between intact PBMC and pDC-depleted PBMC, and major changes in upstream regulators: 70–80% of the HRV activated genes appeared to be pDC dependent. Real-time PCR confirmed key changes in gene expression, in which the following selected genes were shown to be highly pDC dependent: the transcription factor IRF7, both IL-27 chains (IL-27p28 and EBI3), the alpha chain of the IL-15 receptor (IL-15RA) and the IFN-related gene IFI27. HRV-induced IL-6, IFN-γ, and IL-27 protein synthesis were also highly pDC dependent. Supplementing pDC-depleted cultures with recombinant IL-15, IFN-γ, IL-27, or IL-6 was able to restore the IFN-α response, thereby compensating for the absence of pDC. Though pDC comprise only a minority population of migratory leukocytes, our findings highlight the profound extent to which these cells contribute to the immune response to HRV. PMID:29118754

Double Chooz and a history of reactor θ 13 experiments

DOE PAGES

Suekane, Fumihiko; Junqueira de Castro Bezerra, Thiago

2016-04-11

This is a contribution paper from the Double Chooz (DC) experiment to the special issue of Nuclear Physics B on the topics of neutrino oscillations, celebrating the recent Nobel prize to Profs. T. Kajita and A.B. McDonald. DC is a reactor neutrino experiment which measures the last neutrino mixing angle θ 13. In addition, the DC group presented an indication of disappearance of the reactor neutrinos at a baseline of similar to 1 km for the first time in 2011 and is improving the measurement of θ 13. DC is a pioneering experiment of this research field. In accordance withmore » the nature of this special issue, physics and history of the reactor-θ 13 experiments, as well as the Double Chooz experiment and its neutrino oscillation analyses, are reviewed.« less

Double Chooz and a history of reactor θ 13 experiments

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

Suekane, Fumihiko; Junqueira de Castro Bezerra, Thiago

This is a contribution paper from the Double Chooz (DC) experiment to the special issue of Nuclear Physics B on the topics of neutrino oscillations, celebrating the recent Nobel prize to Profs. T. Kajita and A.B. McDonald. DC is a reactor neutrino experiment which measures the last neutrino mixing angle θ 13. In addition, the DC group presented an indication of disappearance of the reactor neutrinos at a baseline of similar to 1 km for the first time in 2011 and is improving the measurement of θ 13. DC is a pioneering experiment of this research field. In accordance withmore » the nature of this special issue, physics and history of the reactor-θ 13 experiments, as well as the Double Chooz experiment and its neutrino oscillation analyses, are reviewed.« less

Low CD1c + myeloid dendritic cell counts correlated with a high risk of rapid disease progression during early HIV-1 infection.

PubMed

Diao, Yingying; Geng, Wenqing; Fan, Xuejie; Cui, Hualu; Sun, Hong; Jiang, Yongjun; Wang, Yanan; Sun, Amy; Shang, Hong

2015-08-19

During early HIV-1 infection (EHI), the interaction between the immune response and the virus determines disease progression. Although CD1c + myeloid dendritic cells (mDCs) can trigger the immune response, the relationship between CD1c + mDC alteration and disease progression has not yet been defined. EHI changes in CD1c + mDC counts, surface marker (CD40, CD86, CD83) expression, and IL-12 secretion were assessed by flow cytometry in 29 patients. When compared with the normal controls, patients with EHI displayed significantly lower CD1c + mDC counts and IL-12 secretion and increased surface markers. CD1c + mDC counts were positively correlated with CD4+ T cell counts and inversely associated with viral loads. IL-12 secretion was only positively associated with CD4+ T cell counts. Rapid progressors had lower counts, CD86 expression, and IL-12 secretion of CD1c + mDCs comparing with typical progressors. Kaplan-Meier analysis and Cox regression models suggested patients with low CD1c + mDC counts (<10 cells/μL) had a 4-fold higher risk of rapid disease progression than those with high CD1c + mDC counts. However, no relationship was found between surface markers or IL-12 secretion and disease progression. During EHI, patients with low CD1c + mDC counts were more likely to experience rapid disease progression than those with high CD1c + mDC counts.

Decoy Receptor DcR1 Is Induced in a p50/Bcl3-Dependent Manner and Attenuates the Efficacy of Temozolomide.

PubMed

Mansour, Nassir M; Bernal, Giovanna M; Wu, Longtao; Crawley, Clayton D; Cahill, Kirk E; Voce, David J; Balyasnikova, Irina V; Zhang, Wei; Spretz, Ruben; Nunez, Luis; Larsen, Gustavo F; Weichselbaum, Ralph R; Yamini, Bakhtiar

2015-05-15

Temozolomide is used widely to treat malignant glioma, but the overall response to this agent is generally poor. Resistance to DNA-damaging drugs such as temozolomide has been related to the induction of antiapoptotic proteins. Specifically, the transcription factor NF-κB has been suggested to participate in promoting the survival of cells exposed to chemotherapy. To identify factors that modulate cytotoxicity in the setting of DNA damage, we used an unbiased strategy to examine the NF-κB-dependent expression profile induced by temozolomide. By this route, we defined the decoy receptor DcR1 as a temozolomide response gene induced by a mechanism relying upon p50/NF-κB1. A conserved NF-κB-binding sequence (κB-site) was identified in the proximal promoter and was demonstrated to be required for DcR1 induction by temozolomide. Loss-of-function and gain-of-function studies reveal that the atypical IκB protein, Bcl3, is also required for induction of DcR1 by temozolomide. Mechanistically, DcR1 attenuates temozolomide efficacy by blunting activation of the Fas receptor pathway in p53(+/+) glioma cells. Intracranial xenograft studies show that DcR1 depletion in glioma cells enhances the efficacy of temozolomide. Taken together, our results show how DcR1 upregulation mediates temozolomide resistance and provide a rationale for DcR1 targeting as a strategy to sensitize gliomas to this widely used chemotherapy. ©2015 American Association for Cancer Research.

Does cocoa/dark chocolate supplementation have favorable effect on body weight, body mass index and waist circumference? A systematic review, meta-analysis and dose-response of randomized clinical trials.

PubMed

Kord-Varkaneh, Hamed; Ghaedi, Ehsan; Nazary-Vanani, Ali; Mohammadi, Hamed; Shab-Bidar, Sakineh

2018-03-19

Cocoa and dark chocolate (DC) have been reported to be effective for health promotion; however the exact effect of cocoa/DC on anthropometric measures have not been yet defined. A comprehensive search to identify randomized clinical trials investigating the impact of cocoa/DC on body weight, body mass index (BMI) and waist circumference (WC) was performed up to December 2017. A meta-analysis of eligible studies was performed using random effects model to estimate pooled effect size. Fractional polynominal modeling was used to explore dose-response relationships. A total of 35 RCTs investigated the effects of cocoa/DC on weight, BMI and WC were included. Meta-analysis did not suggest any significant effect of cocoa/DC supplementation on body weight (-0.108 kg, 95% CI -0.262, 0.046 P = 0.168), BMI (-0.014 kg/m 2 95% CI -0.105, 0.077, P: 0.759,) and WC (0.025 cm 95% CI -0.083, 0.129, P = 0.640). Subgroup analysis revealed that that weight and BMI were reduced with cocoa/DC supplementation ≥ 30 g chocolate per day in trials between 4-8 weeks. Cocoa/DC consumption resulted in WC reduction in non-linear fashion (r = 0.042, P-nonlinearity = 0.008). Cocoa/DC supplementation does not reduce anthropometric measures significantly. However subgroup analysis regarding dose (≥ 30 g/day) and duration (between 4 to 8 weeks) revealed significant reduction of body weight and BMI.

Hepatitis B Virus Lacks Immune Activating Capacity, but Actively Inhibits Plasmacytoid Dendritic Cell Function

PubMed Central

Woltman, Andrea M.; Shi, Cui C.; Janssen, Harry L. A.

2011-01-01

Chronic hepatitis B virus (HBV) infection is caused by inadequate anti-viral immunity. Activation of plasmacytoid dendritic cells (pDC) leading to IFNα production is important for effective anti-viral immunity. Hepatitis B virus (HBV) infection lacks IFNα induction in animal models and patients and chronic HBV patients display impaired IFNα production by pDC. Therefore, HBV and HBV-derived proteins were examined for their effect on human pDC in vitro. In addition, the in vitro findings were compared to the function of pDC derived from chronic HBV patients ex vivo. In contrast to other viruses, HBV did not activate pDC. Moreover, HBV and HBsAg abrogated CpG-A/TLR9-induced, but not Loxoribine/TLR7-induced, mTOR-mediated S6 phosphorylation, subsequent IRF7 phosphorylation and IFNα gene transcription. HBV/HBsAg also diminished upregulation of co-stimulatory molecules, production of TNFα, IP-10 and IL-6 and pDC-induced NK cell function, whereas TLR7-induced pDC function was hardly affected. In line, HBsAg preferentially bound to TLR9-triggered pDC demonstrating that once pDC are able to bind HBV/HBsAg, the virus exerts its immune regulatory effect. HBV not only directly interfered with pDC function, but also indirectly by interfering with monocyte-pDC interaction. Also HBeAg diminished pDC function to a certain extent, but via another unknown mechanism. Interestingly, patients with HBeAg-positive chronic hepatitis B displayed impaired CpG-induced IFNα production by pDC without significant alterations in Loxoribine-induced pDC function compared to HBeAg-negative patients and healthy controls. The lack of activation and the active inhibition of pDC by HBV may both contribute to HBV persistence. The finding that the interaction between pDC and HBV may change upon activation may aid in the identification of a scavenging receptor supporting immunosuppressive effects of HBV and also in the design of novel treatment strategies for chronic HBV. PMID:21246041

Partitioning Algorithms for Simultaneously Balancing Iterative and Direct Methods

DTIC Science & Technology

2004-03-03

is defined as 57698&:&;=<$>?8A@B8 DC E & /F <G8H IJ0 K L 012 1NM? which is the ratio of the highest partition weight over the average...OQPSR , 57698T:;=<$>U8T@B8 DC E & /VXWZYK[\\O , and E :^] E_CU`4ab /V is minimized. The load imbalance is the constraint we have to satisfy, and...that the initial partitioning can be improved [16, 19, 20]. 3 Problem Definition and Challenges Consider a graph )c2 with d e f vertices

Report of the NIH Panel to Define Principles of Therapy of HIV Infection and Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents. Vol. 47/No. RR-5.

DTIC Science & Technology

1998-04-25

MA David Cooper, M.D. National Center for HIV Epidemiology and Clinical Research Sydney, NSW, Australia Stephen Follansbee, M.D. Davies...National Association of People with AIDS Washington, DC David Barr, J.D. Forum for Collaborative HIV Research Washington, DC Samuel Bozzette, M.D...Mellors, M.D. University of Pittsburgh Pittsburgh, PA David Nash, M.D. Thomas Jefferson University Philadelphia, PA Sallie Perryman New York

Defining a Quality Education. Proceedings of the Annual Conference of the North East Association for Institutional Research (19th, Washington, D.C., November 14-17, 1992).

ERIC Educational Resources Information Center

Price, Jane, Ed.

This publication contains 25 papers from a conference on defining quality higher education. Opening sections cover the conference program and members of the conference's steering committee. A representative sampling of papers includes the following: "The College Student Experiences Questionnaire: A Follow-Up Study of Academic and Social…

High glucose disrupts oligosaccharide recognition function via competitive inhibition: a potential mechanism for immune dysregulation in diabetes mellitus.

PubMed

Ilyas, Rebecca; Wallis, Russell; Soilleux, Elizabeth J; Townsend, Paul; Zehnder, Daniel; Tan, Bee K; Sim, Robert B; Lehnert, Hendrik; Randeva, Harpal S; Mitchell, Daniel A

2011-01-01

Diabetic complications include infection and cardiovascular disease. Within the immune system, host-pathogen and regulatory host-host interactions operate through binding of oligosaccharides by C-type lectin. A number of C-type lectins recognise oligosaccharides rich in mannose and fucose - sugars with similar structures to glucose. This raises the possibility that high glucose conditions in diabetes affect protein-oligosaccharide interactions via competitive inhibition. Mannose-binding lectin, soluble DC-SIGN and DC-SIGNR, and surfactant protein D, were tested for carbohydrate binding in the presence of glucose concentrations typical of diabetes, via surface plasmon resonance and affinity chromatography. Complement activation assays were performed in high glucose. DC-SIGN and DC-SIGNR expression in adipose tissues was examined via immunohistochemistry. High glucose inhibited C-type lectin binding to high-mannose glycoprotein and binding of DC-SIGN to fucosylated ligand (blood group B) was abrogated in high glucose. Complement activation via the lectin pathway was inhibited in high glucose and also in high trehalose - a nonreducing sugar with glucoside stereochemistry. DC-SIGN staining was seen on cells with DC morphology within omental and subcutaneous adipose tissues. We conclude that high glucose disrupts C-type lectin function, potentially illuminating new perspectives on susceptibility to infectious and inflammatory disease in diabetes. Mechanisms involve competitive inhibition of carbohydrate binding within sets of defined proteins, in contrast to broadly indiscriminate, irreversible glycation of proteins. Copyright © 2010 Elsevier GmbH. All rights reserved.

Dr. Tom Mace talks with a student from Punta Arenas, Chile, during a tour of the DC-8 aircraft

NASA Image and Video Library

2004-03-10

Dr. Tom Mace, NASA DFRC Director of Airborne Sciences, talks with a student from Punta Arenas, Chile, during a tour of the DC-8 aircraft while it was in the country supporting the AirSAR 2004 campaign. AirSAR 2004 is a three-week expedition by an international team of scientists that uses an all-weather imaging tool, called the Airborne Synthetic Aperture Radar (AirSAR) which is located onboard NASA's DC-8 airborne laboratory. Scientists from many parts of the world including NASA's Jet Propulsion Laboratory are combining ground research done in several areas in Central and South America with NASA's AirSAR technology to improve and expand on the quality of research they are able to conduct. In South America and Antarctica, AirSAR collected imagery and data to help determine the contribution of Southern Hemisphere glaciers to sea level rise due to climate change. In Patagonia, researchers found this contribution had more than doubled from 1995 to 2000, compared to the previous 25 years. AirSAR data will make it possible to determine whether that trend is continuing or accelerating. AirSAR will also provide reliable information on ice shelf thickness to measure the contribution of the glaciers to sea level.

NASA DC-8 Ground Support Technicians Mark Corlew and Mike Lakowski perform routine maintenance on the aircraft in Punta Arenas, Chile

NASA Image and Video Library

2004-03-17

NASA DC-8 Ground Support Technicians Mark Corlew and Mike Lakowski perform routine maintenance on the aircraft at Carlos Ibanez del Campo International Airport in Punta Arenas, Chile. AirSAR 2004 is a three-week expedition by an international team of scientists that is using an all-weather imaging tool, called the Airborne Synthetic Aperture Radar (AirSAR) which is located onboard NASA's DC-8 airborne laboratory. Scientists from many parts of the world including NASA's Jet Propulsion Laboratory are combining ground research done in several areas in Central and South America with NASA's AirSAR technology to improve and expand on the quality of research they are able to conduct. In South America and Antarctica, AirSAR will collect imagery and data to help determine the contribution of Southern Hemisphere glaciers to sea level rise due to climate change. In Patagonia, researchers found this contribution had more than doubled from 1995 to 2000, compared to the previous 25 years. AirSAR data will make it possible to determine whether that trend is decreasing, continuing or accelerating. AirSAR will also provide reliable information on ice shelf thickness to measure the contribution of the glaciers to sea level.

Pilot Bill Brockett (left) and Chilean Air Force Captain Saez with school children in the cockpit of NASA Dryden's DC-8 flying laboratory

NASA Image and Video Library

2004-03-10

Pilot Bill Brockett (left) and Chilean Air Force Captain Saez with school children in the cockpit of NASA Dryden's DC-8 flying laboratory. Brockett explained NASA's AirSAR 2004 mission in Chile. AirSAR 2004 is a three-week expedition by an international team of scientists that uses an all-weather imaging tool, called the Airborne Synthetic Aperture Radar (AirSAR) which is located onboard NASA's DC-8 airborne laboratory. Scientists from many parts of the world including NASA's Jet Propulsion Laboratory are combining ground research done in several areas in Central and South America with NASA's AirSAR technology to improve and expand on the quality of research they are able to conduct. In South America and Antarctica, AirSAR collected imagery and data to help determine the contribution of Southern Hemisphere glaciers to sea level rise due to climate change. In Patagonia, researchers found this contribution had more than doubled from 1995 to 2000, compared to the previous 25 years. AirSAR data will make it possible to determine whether that trend is continuing or accelerating. AirSAR will also provide reliable information on ice shelf thickness to measure the contribution of the glaciers to sea level.

NASA DC-8 Mission Manager Walter Klein poses with a group of Chilean Students onboard the aircraft in Punta Arenas, Chile

NASA Image and Video Library

2004-03-17

NASA DC-8 Mission Manager Walter Klein poses with a group of Chilean Students onboard the aircraft at Carlos Ibanez del Campo International Airport in Punta Arenas, Chile. AirSAR 2004 is a three-week expedition by an international team of scientists that is using an all-weather imaging tool, called the Airborne Synthetic Aperture Radar (AirSAR) which is located onboard NASA's DC-8 airborne laboratory. Scientists from many parts of the world including NASA's Jet Propulsion Laboratory are combining ground research done in several areas in Central and South America with NASA's AirSAR technology to improve and expand on the quality of research they are able to conduct. In South America and Antarctica, AirSAR will collect imagery and data to help determine the contribution of Southern Hemisphere glaciers to sea level rise due to climate change. In Patagonia, researchers found this contribution had more than doubled from 1995 to 2000, compared to the previous 25 years. AirSAR data will make it possible to determine whether that trend is decreasing, continuing or accelerating. AirSAR will also provide reliable information on ice shelf thickness to measure the contribution of the glaciers to sea level.

NASA Dryden Mission Manager Walter Klein talks with school children from Punta Arenas, Chile, during a tour of the DC-8 aircraft

NASA Image and Video Library

2004-03-10

NASA Dryden Mission Manager Walter Klein talks with school children from Punta Arenas, Chile, during a tour of the DC-8 aircraft while it was in the country supporting the AirSAR 2004 campaign. AirSAR 2004 is a three-week expedition by an international team of scientists that uses an all-weather imaging tool, called the Airborne Synthetic Aperture Radar (AirSAR) which is located onboard NASA's DC-8 airborne laboratory. Scientists from many parts of the world including NASA's Jet Propulsion Laboratory are combining ground research done in several areas in Central and South America with NASA's AirSAR technology to improve and expand on the quality of research they are able to conduct. In South America and Antarctica, AirSAR collected imagery and data to help determine the contribution of Southern Hemisphere glaciers to sea level rise due to climate change. In Patagonia, researchers found this contribution had more than doubled from 1995 to 2000, compared to the previous 25 years. AirSAR data will make it possible to determine whether that trend is continuing or accelerating. AirSAR will also provide reliable information on ice shelf thickness to measure the contribution of the glaciers to sea level.

Chilean Air Force Captain Saez and Dr. Tom Mace discuss airborne science during a DC-8 ferry flight from Santiago to Punta Arenas, Chile

NASA Image and Video Library

2004-03-10

Chilean Air Force Captain Saez and Dr. Tom Mace, DFRC Director of Airborne Sciences, discuss airborne science during a DC-8 ferry flight from Santiago to Punta Arenas, Chile. AirSAR 2004 is a three-week expedition by an international team of scientists that uses an all-weather imaging tool, called the Airborne Synthetic Aperture Radar (AirSAR) which is located onboard NASA's DC-8 airborne laboratory. Scientists from many parts of the world including NASA's Jet Propulsion Laboratory are combining ground research done in several areas in Central and South America with NASA's AirSAR technology to improve and expand on the quality of research they are able to conduct. In South America and Antarctica, AirSAR collected imagery and data to help determine the contribution of Southern Hemisphere glaciers to sea level rise due to climate change. In Patagonia, researchers found this contribution had more than doubled from 1995 to 2000, compared to the previous 25 years. AirSAR data will make it possible to determine whether that trend is continuing or accelerating. AirSAR will also provide reliable information on ice shelf thickness to measure the contribution of the glaciers to sea level.

Fast Charging Electric Vehicle Research & Development Project

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

Heny, Michael

The research and development project supported the engineering, design and implementation of on-road Electric Vehicle (“EV”) charging technologies. It included development of potential solutions for DC fast chargers (“DCFC”) capable of converting high voltage AC power to the DC power required by EVs. Additional development evaluated solutions related to the packaging of power electronic components and enclosure design, as well as for the design and evaluation of EV charging stations. Research compared different charging technologies to identify optimum applications in a municipal fleet. This project collected EV usage data and generated a report demonstrating that EVs, when supported by adequatemore » charging infrastructure, are capable of replacing traditional internal combustion vehicles in many municipal applications. The project’s period of performance has demonstrated various methods of incorporating EVs into a municipal environment, and has identified three general categories for EV applications: Short Commute: Defined as EVs performing in limited duration, routine commutes. - Long Commute: Defined as tasks that require EVs to operate in longer daily mileage patterns. - Critical Needs: Defined as the need for EVs to be ready at every moment for indefinite periods. Together, the City of Charlottesville, VA (the “City”) and Aker Wade Power Technologies, LLC (“Aker Wade”) concluded that the EV has a viable position in many municipal fleets but with limited recommendation for use in Critical Needs applications such as Police fleets. The report also documented that, compared to internal combustion vehicles, BEVs have lower vehicle-related greenhouse gas (“GHG”) emissions and contribute to a reduction of air pollution in urban areas. The enhanced integration of EVs in a municipal fleet can result in reduced demand for imported oil and reduced municipal operating costs. The conclusions indicated in the project’s Engineering Report (see Attachment A) are intended to assist future implementation of electric vehicle technology. They are based on the cited research and on the empirical data collected and presented. The report is not expected to represent the entire operating conditions of any of the equipment under consideration within this project, and tested equipment may operate differently under other conditions.« less

The McAndrews Leadership Lecture: February 2015, by Dr Scott Haldeman. Challenges of the Past, Challenges of the Present

PubMed Central

Haldeman, Scott; McAndrews, George P.; Goertz, Christine; Sportelli, Louis; Hamm, Anthony W.; Johnson, Claire

2015-01-01

The McAndrews Leadership Lecture was developed by the American Chiropractic Association to honor the legacy of Jerome F. McAndrews, DC, and George P. McAndrews, JD, and their contributions to the chiropractic profession. This article is a transcription of the presentation made by Dr Scott Haldeman on February 28, 2015, in Washington, DC, at the National Chiropractic Leadership Conference. PMID:26770177

Trichuris suis-induced modulation of human dendritic cell function is glycan-mediated.

PubMed

Klaver, Elsenoor J; Kuijk, Loes M; Laan, Lisa C; Kringel, Helene; van Vliet, Sandra J; Bouma, Gerd; Cummings, Richard D; Kraal, Georg; van Die, Irma

2013-03-01

Human monocyte-derived dendritic cells (DCs) show remarkable phenotypic changes upon direct contact with soluble products (SPs) of Trichuris suis, a pig whipworm that is experimentally used in therapies to ameliorate inflammation in patients with Crohn's disease and multiple sclerosis. These changes may contribute to the observed induction of a T helper 2 (Th2) response and the suppression of Toll-like receptor (TLR)-induced Th1 and Th17 responses by human DCs primed with T. suis SPs. Here it is demonstrated that glycans of T. suis SPs contribute significantly to the suppression of the lipopolysaccharide (LPS)-induced expression in DCs of a broad variety of cytokines and chemokines, including important pro-inflammatory mediators such as TNF-α, IL-6, IL-12, lymphotoxin α (LTA), C-C Motif Ligand (CCL)2, C-X-C Motif Ligands (CXCL)9 and CXCL10. In addition, the data show that human DCs strongly bind T. suis SP-glycans via the C-type lectin receptors (CLRs) mannose receptor (MR) and DC-specific ICAM-3-grabbing non-integrin (DC-SIGN). The interaction of DCs with T. suis glycans likely involves mannose-type glycans, rather than fucosylated glycans, which differs from DC binding to soluble egg antigens of the human worm parasite, Schistosoma mansoni. In addition, macrophage galactose-type lectin (MGL) recognises T. suis SPs, which may contribute to the interaction with immature DCs or other MGL-expressing immune cells such as macrophages. The interaction of T. suis glycans with CLRs of human DCs may be essential for the ability of T. suis to suppress a pro-inflammatory phenotype of human DCs. The finding that the T. suis-induced modulation of human DC function is glycan-mediated is novel and indicates that helminth glycans contribute to the dampening of inflammation in a wide range of human inflammatory diseases. Copyright © 2012 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

A malaria protein factor induces IL-4 production by dendritic cells via PI3K-Akt-NF-κB signaling independent of MyD88/TRIF and promotes Th2 response.

PubMed

Wu, Xianzhu; Gowda, Nagaraj M; Kawasawa, Yuka I; Gowda, D Channe

2018-04-17

Dendritic cells (DC) and cytokines produced by DC play crucial roles in inducing and regulating pro-/anti-inflammatory and Th1/Th2 responses. DC are known to produce Th1-promoting cytokine, IL-12, in response to malaria and other pathogenic infections, but it is thought that DC do not produce Th2-promoting cytokine, IL-4. Here, we show that a protein factor of malaria parasites induces IL-4 responses by CD11c hi MHCII hi CD3ε - CD49b - CD19 - FcεRI - DC via PI3K-Akt-NF-κB signaling independent of TLR-MyD88/TRIF. Malaria parasite-activated DC induced IL-4 responses by T cells both in vitro and in vivo , favoring Th2, and il-4 deficient DC were unable to induce IL-4 expression by T cell.  Interestingly, lethal parasites, Plasmodium falciparum and P. berghei ANKA, induced IL-4 response primarily by CD8a - DC, whereas nonlethal P. yoelii induced IL-4 by both CD8α + and CD8α - DC. In both P. berghei ANKA- and P. yoelii -infected mice, IL-4-expressing CD8α - DC did not express IL-12, but a distinct CD8α - DC subset expressed IL-12. In P. berghei ANKA infection, CD8α + DC expressed IL-12 but not IL-4, whereas in P. yoelii infection CD8α + DC expressed IL-4 but not IL-12. This differential IL-4 and IL-12 responses by DC subsets may contribute to different Th1/Th2 development and clinical outcomes in lethal and nonlethal malaria. Our results for the first time demonstrate that a malaria protein factor induces IL-4 production by DC via PI3K-Akt-NF-κB signaling, revealing signaling and molecular mechanisms that initiate and promote Th2 development. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

The bacterial preparation OK432 induces IL-12p70 secretion in human dendritic cells in a TLR3 dependent manner.

PubMed

Hovden, Arnt-Ove; Karlsen, Marie; Jonsson, Roland; Appel, Silke

2012-01-01

Dendritic cells (DC) used in therapeutic cancer immunotherapy have to be able to stimulate T cells resulting in an immune response that can efficiently target the cancer cells. One of the critical hurdles has been the lack of IL-12p70 production when maturating the DC, which is rectified by using the bacterial preparation OK432 (trade name Picibanil) to mature the cells. In order to identify the mechanism behind OK432 stimulation of DC, we investigated the contribution of different TLR to examine their involvement in IL-12p70 production. By combining different inhibitors of TLR signaling, we demonstrate here that TLR3 is responsible for the IL-12p70 production of DC induced by OK432. Moreover, our data suggest that the ligand triggering IL-12p70 secretion upon TLR3 stimulation is sensitive to proteinase and partly also RNAse treatment. The fact that a bacterial compound like OK432 can activate the TLR3 pathway in human DC is a novel finding. OK432 demonstrates a critical ability to induce IL-12p70 production, which is of great relevance in DC based cancer immunotherapy.

The Bacterial Preparation OK432 Induces IL-12p70 Secretion in Human Dendritic Cells in a TLR3 Dependent Manner

PubMed Central

Hovden, Arnt-Ove; Karlsen, Marie; Jonsson, Roland; Appel, Silke

2012-01-01

Dendritic cells (DC) used in therapeutic cancer immunotherapy have to be able to stimulate T cells resulting in an immune response that can efficiently target the cancer cells. One of the critical hurdles has been the lack of IL-12p70 production when maturating the DC, which is rectified by using the bacterial preparation OK432 (trade name Picibanil) to mature the cells. In order to identify the mechanism behind OK432 stimulation of DC, we investigated the contribution of different TLR to examine their involvement in IL-12p70 production. By combining different inhibitors of TLR signaling, we demonstrate here that TLR3 is responsible for the IL-12p70 production of DC induced by OK432. Moreover, our data suggest that the ligand triggering IL-12p70 secretion upon TLR3 stimulation is sensitive to proteinase and partly also RNAse treatment. The fact that a bacterial compound like OK432 can activate the TLR3 pathway in human DC is a novel finding. OK432 demonstrates a critical ability to induce IL-12p70 production, which is of great relevance in DC based cancer immunotherapy. PMID:22363584

Mitochondrial transcription factor A serves as a danger signal by augmenting plasmacytoid dendritic cell responses to DNA.

PubMed

Julian, Mark W; Shao, Guohong; Bao, Shengying; Knoell, Daren L; Papenfuss, Tracey L; VanGundy, Zachary C; Crouser, Elliott D

2012-07-01

Plasmacytoid dendritic cells (pDC) are potent APCs known to regulate immune responses to self-Ags, particularly DNA. The mitochondrial fraction of necrotic cells was found to most potently promote human pDC activation, as reflected by type I IFN release, which was dependent upon the presence of mitochondrial DNA and involved TLR9 and receptors for advanced glycation end products. Mitochondrial transcription factor A (TFAM), a highly abundant mitochondrial protein that is functionally and structurally homologous to high mobility group box protein 1, was observed to synergize with CpG-containing oligonucleotide, type A, DNA to promote human pDC activation. pDC type I IFN responses to TFAM and CpG-containing oligonucleotide, type A, DNA indicated their engagement with receptors for advanced glycation end products and TLR9, respectively, and were dependent upon endosomal processing and PI3K, ERK, and NF-κB signaling. Taken together, these results indicate that pDC contribute to sterile immune responses by recognizing the mitochondrial component of necrotic cells and further incriminate TFAM and mitochondrial DNA as likely mediators of pDC activation under these circumstances.

Involvement of tumour necrosis factor-α-related apoptosis-inducing ligand in enhanced cytotoxicity of lipopolysaccharide-stimulated dendritic cells to activated T cells

PubMed Central

Yu, Yizhi; Liu, Shuxun; Wang, Wenya; Song, Wengang; Zhang, Minghui; Zhang, Weiping; Qin, Zhihai; Cao, Xuetao

2002-01-01

Dendritic cells (DC) are potent antigen-presenting cells (APC) specialized in T-cell mediated immune responses, and also play critical roles in the homeostasis of T cells for controlling immune responses. In the present study, we demonstrated that during mouse bone-marrow-derived DC activation of ovalbumin (OVA)-specific Ia-kb-restricted T hybridoma cells, MF2.2D9 and OVA257–264-specific H-2kb-restricted RF33.70 T cells, respectively, both hybridomas undergo cell death, partially mediated via apoptotic ligand–tumour necrosis factor-α (TNF-α)-related apoptosis-inducing ligand (TRAIL). Lipopolysaccharide enhanced the cytotoxic effect on the two activated T hybridoma cells, which was correlated with up-regulation of TRAIL-expression on DC to some extent. The activation of caspase-3 in activated T hybridoma cells cocultured with DC contributed to the programmed cell death pathway T cells underwent. Therefore, our results show that activation-induced cell death of T hybridoma cells can be influenced by DC, suggesting that DC may be involved in elimination of activated T cells at the end of primary immune responses. PMID:12100718

Involvement of tumour necrosis factor-alpha-related apoptosis-inducing ligand in enhanced cytotoxicity of lipopolysaccharide-stimulated dendritic cells to activated T cells.

PubMed

Yu, Yizhi; Liu, Shuxun; Wang, Wenya; Song, Wengang; Zhang, Minghui; Zhang, Weiping; Qin, Zhihai; Cao, Xuetao

2002-07-01

Dendritic cells (DC) are potent antigen-presenting cells (APC) specialized in T-cell mediated immune responses, and also play critical roles in the homeostasis of T cells for controlling immune responses. In the present study, we demonstrated that during mouse bone-marrow-derived DC activation of ovalbumin (OVA)-specific Ia-kb-restricted T hybridoma cells, MF2.2D9 and OVA257-264-specific H-2kb-restricted RF33.70 T cells, respectively, both hybridomas undergo cell death, partially mediated via apoptotic ligand-tumour necrosis factor-alpha (TNF-alpha)-related apoptosis-inducing ligand (TRAIL). Lipopolysaccharide enhanced the cytotoxic effect on the two activated T hybridoma cells, which was correlated with up-regulation of TRAIL-expression on DC to some extent. The activation of caspase-3 in activated T hybridoma cells cocultured with DC contributed to the programmed cell death pathway T cells underwent. Therefore, our results show that activation-induced cell death of T hybridoma cells can be influenced by DC, suggesting that DC may be involved in elimination of activated T cells at the end of primary immune responses.

Modulation of dendritic cell maturation and function by the Tax protein of human T cell leukemia virus type 1

PubMed Central

Jain, Pooja; Ahuja, Jaya; Khan, Zafar K.; Shimizu, Saori; Meucci, Olimpia; Jennings, Stephen R.; Wigdahl, Brian

2009-01-01

Human T cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is characterized by the generation of an intense CTL cell response directed against the viral transactivator protein Tax. In addition, patients diagnosed with HAM/TSP exhibit rapid activation and maturation of dendritic cells (DC), likely contributing to the robust, Tax-specific CTL response. In this study, extracellular Tax has been shown to induce maturation and functional alterations in human monocyte-derived DC, critical observations being confirmed in freshly isolated myeloid DC. Tax was shown to promote the production of proinflammatory cytokines and chemokines involved in the DC activation process in a dose- and time-dependent manner. Furthermore, Tax induced the expression of DC activation (CD40, CD80, and CD86) and maturation (CD83) markers and enhanced the T cell proliferation capability of DC. Heat inactivation of Tax resulted in abrogation of these effects, indicating a requirement for the native structure of Tax, which was found to bind efficiently to the DC membrane and was internalized within a few hours, suggesting that extracellular Tax may possess an intracellular mechanism of action subsequent to entry. Finally, inhibitors of cellular signaling pathways, NF-κB, protein kinase, tyrosine kinase, and phospholipase C, were shown to inhibit Tax-mediated DC activation. This is the first study reporting the immunomodulatory effects of extracellular Tax in the DC compartment. These results suggest that DC, once exposed to Tax by uptake from the extracellular environment, can undergo activation, providing constant antigen presentation and costimulation to T cells, leading to the intense T cell proliferation and inflammatory responses underlying HAM/TSP. PMID:17442856

Piezoelectric two-dimensional nanosheets/anionic layer heterojunction for efficient direct current power generation.

PubMed

Kim, Kwon-Ho; Kumar, Brijesh; Lee, Keun Young; Park, Hyun-Kyu; Lee, Ju-Hyuck; Lee, Hyun Hwi; Jun, Hoin; Lee, Dongyun; Kim, Sang-Woo

2013-01-01

Direct current (DC) piezoelectric power generator is promising for the miniaturization of a power package and self-powering of nanorobots and body-implanted devices. Hence, we report the first use of two-dimensional (2D) zinc oxide (ZnO) nanostructure and an anionic nanoclay layer to generate piezoelectric DC output power. The device, made from 2D nanosheets and an anionic nanoclay layer heterojunction, has potential to be the smallest size power package, and could be used to charge wireless nano/micro scale systems without the use of rectifier circuits to convert alternating current into DC to store the generated power. The combined effect of buckling behaviour of the ZnO nanosheets, a self-formed anionic nanoclay layer, and coupled semiconducting and piezoelectric properties of ZnO nanosheets contributes to efficient DC power generation. The networked ZnO nanosheets proved to be structurally stable under huge external mechanical loads.

Spontaneous Eruption of Premolar Associated with a Dentigerous Cyst.

PubMed

de Carvalho, Irla Karlinne Ferreira; Luna, Anibal Henrique Barbosa

2016-01-01

Dentigerous cyst (DC) is the second most common odontogenic cyst with greater incidence in young patients. It presents as a unilocular, asymptomatic radiolucency involving the crown of an impacted tooth, commonly noticed in X-rays to investigate absence, wrong tooth position, or delay in the chronology of eruption. Decompression/marsupialization (D/M) is the most implemented treatment, especially when preserving the tooth involved is advised. The aim of this study is to discuss the DC characteristics that contribute to spontaneous eruption of premolars, by reporting the case of a conservative treatment of DC. This eruption depends on factors such as age, angulation of inclusion, rate of root formation, depth of inclusion, and eruption space. This paper reports the case of a 10-year-old patient with a radiolucent lesion diagnosed as DC involving element 35, which erupted as a result of treatment. The patient was observed during 1 year and 6 months.

Spontaneous Eruption of Premolar Associated with a Dentigerous Cyst

PubMed Central

Luna, Anibal Henrique Barbosa

2016-01-01

Dentigerous cyst (DC) is the second most common odontogenic cyst with greater incidence in young patients. It presents as a unilocular, asymptomatic radiolucency involving the crown of an impacted tooth, commonly noticed in X-rays to investigate absence, wrong tooth position, or delay in the chronology of eruption. Decompression/marsupialization (D/M) is the most implemented treatment, especially when preserving the tooth involved is advised. The aim of this study is to discuss the DC characteristics that contribute to spontaneous eruption of premolars, by reporting the case of a conservative treatment of DC. This eruption depends on factors such as age, angulation of inclusion, rate of root formation, depth of inclusion, and eruption space. This paper reports the case of a 10-year-old patient with a radiolucent lesion diagnosed as DC involving element 35, which erupted as a result of treatment. The patient was observed during 1 year and 6 months. PMID:27313912

Electronics for Deep Space Cryogenic Applications

NASA Technical Reports Server (NTRS)

Patterson, R. L.; Hammond, A.; Dickman, J. E.; Gerber, S. S.; Elbuluk, M. E.; Overton, E.

2002-01-01

Deep space probes and planetary exploration missions require electrical power management and control systems that are capable of efficient and reliable operation in very cold temperature environments. Typically, in deep space probes, heating elements are used to keep the spacecraft electronics near room temperature. The utilization of power electronics designed for and operated at low temperature will contribute to increasing efficiency and improving reliability of space power systems. At NASA Glenn Research Center, commercial-off-the-shelf devices as well as developed components are being investigated for potential use at low temperatures. These devices include semiconductor switching devices, magnetics, and capacitors. Integrated circuits such as digital-to-analog and analog-to-digital converters, DC/DC converters, operational amplifiers, and oscillators are also being evaluated. In this paper, results will be presented for selected analog-to-digital converters, oscillators, DC/DC converters, and pulse width modulation (PWM) controllers.

Stable-Carbon Isotope Ratios for Sourcing the Nerve-Agent Precursor Methylphosphonic Dichloride and Its Products

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

Moran, James J.; Fraga, Carlos G.; Nims, Megan K.

The ability to connect a chemical threat agent to a specific batch of a synthetic precursor can provide a fingerprint to contribute to effective forensic investigations. Stable isotope analysis can leverage intrinsic, natural isotopic variability within the molecules of a threat agent to unlock embedded chemical fingerprints in the material. Methylphosphonic dichloride (DC) is a chemical precursor to the nerve agent sarin. DC is converted to methylphosphonic difluoride (DF) as part of the sarin synthesis process. We used a suite of commercially available DC stocks to both evaluate the potential for δ 13C analysis to be used as a fingerprintingmore » tool in sarin-related investigations and to develop sample preparation techniques (using chemical hydrolysis) that can simplify isotopic analysis of DC and its synthetic products. We demonstrate that natural isotopic variability in DC results in at least three distinct, isotope-resolved clusters within the thirteen stocks we analyzed. Isotopic variability in the carbon feedstock (i.e., methanol) used for DC synthesis is likely inherited by the DC samples we measured. Here, we demonstrate that the hydrolysis of DC and DF to methylphosphonic acid (MPA) can be used as a preparative step for isotopic analysis because the reaction does not impart a significant isotopic fractionation. MPA is more chemically stable, less toxic, and easier to handle than DC or DF. Further, the hydrolysis method we demonstrated can be applied to a suite of other precursors or to sarin itself, thereby providing a potentially valuable forensic tool.« less

Stable-Carbon Isotope Ratios for Sourcing the Nerve-Agent Precursor Methylphosphonic Dichloride and Its Products

DOE PAGES

Moran, James J.; Fraga, Carlos G.; Nims, Megan K.

2018-04-01

The ability to connect a chemical threat agent to a specific batch of a synthetic precursor can provide a fingerprint to contribute to effective forensic investigations. Stable isotope analysis can leverage intrinsic, natural isotopic variability within the molecules of a threat agent to unlock embedded chemical fingerprints in the material. Methylphosphonic dichloride (DC) is a chemical precursor to the nerve agent sarin. DC is converted to methylphosphonic difluoride (DF) as part of the sarin synthesis process. We used a suite of commercially available DC stocks to both evaluate the potential for δ 13C analysis to be used as a fingerprintingmore » tool in sarin-related investigations and to develop sample preparation techniques (using chemical hydrolysis) that can simplify isotopic analysis of DC and its synthetic products. We demonstrate that natural isotopic variability in DC results in at least three distinct, isotope-resolved clusters within the thirteen stocks we analyzed. Isotopic variability in the carbon feedstock (i.e., methanol) used for DC synthesis is likely inherited by the DC samples we measured. Here, we demonstrate that the hydrolysis of DC and DF to methylphosphonic acid (MPA) can be used as a preparative step for isotopic analysis because the reaction does not impart a significant isotopic fractionation. MPA is more chemically stable, less toxic, and easier to handle than DC or DF. Further, the hydrolysis method we demonstrated can be applied to a suite of other precursors or to sarin itself, thereby providing a potentially valuable forensic tool.« less

Exploring the Interaction Mechanism Between Cyclopeptide DC3 and Androgen Receptor Using Molecular Dynamics Simulations and Free Energy Calculations

PubMed Central

Zhang, Huimin; Song, Tianqing; Yang, Yizhao; Fu, Chenggong; Li, Jiazhong

2018-01-01

Androgen receptor (AR) is a key target in the discovery of anti-PCa (Prostate Cancer) drugs. Recently, a novel cyclopeptide Diffusa Cyclotide-3 (DC3), isolated from Hedyotisdiffusa, has been experimentally demonstrated to inhibit the survival and growth of LNCap cells, which typically express T877A-mutated AR, the most frequently detected point mutation of AR in castration-resistant prostate cancer (CRPC). But the interaction mechanism between DC3 and AR is not clear. Here in this study we aim to explore the possible binding mode of DC3 to T877A-mutated AR from molecular perspective. Firstly, homology modeling was employed to construct the three-dimensional structure of the cyclopeptide DC3 using 2kux.1.A as the template. Then molecular docking, molecular dynamics (MD) simulations, and molecular mechanics/generalized Born surface area (MM-GBSA) methods were performed to determine the bind site and explore the detailed interaction mechanism of DC3-AR complex. The obtained results suggested that the site formed by H11, loop888-893, and H12 (site 2) was the most possible position of DC3 binding to AR. Besides, hydrogen bonds, hydrophobic, and electrostatic interactions play dominant roles in the recognition and combination of DC3-AR complex. The essential residues dominant in each interaction were specifically revealed. This work facilitates our understanding of the interaction mechanism of DC3 binding to AR at the molecular level and contributes to the rational cyclopeptide drug design for prostate cancer. PMID:29755968

Exploring the Interaction Mechanism between Cyclopeptide DC3 and Androgen Receptor Using Molecular Dynamics Simulations and Free Energy Calculations

NASA Astrophysics Data System (ADS)

Zhang, Huimin; Song, Tianqing; Yang, Yizhao; Fu, Chenggong; Li, Jiazhong

2018-04-01

Androgen receptor (AR) is a key target in the discovery of anti-PCa (Prostate Cancer) drugs. Recently, a novel cyclopeptide Diffusa Cyclotide-3 (DC3), isolated from Hedyotisdiffusa, has been experimentally demonstrated to inhibit the survival and growth of LNCap cells, which typically express T877A-mutated AR, the most frequently detected point mutation of AR in castration-resistant prostate cancer (CRPC). But the interaction mechanism between DC3 and AR is not clear. Here in this study we aim to explore the possible binding mode of DC3 to T877A-mutated AR from molecular perspective. Firstly, homology modeling was employed to construct the three-dimensional structure of the cyclopeptide DC3 using 2kux.1.A as the template. Then molecular docking, molecular dynamics (MD) simulations and molecular mechanics/generalized Born surface area (MM-GBSA) methods were performed to determine the bind site and explore the detailed interaction mechanism of DC3-AR complex. The obtained results suggested that the site formed by H11, loop888-893 and H12 (site 2) was the most possible position of DC3 binding to AR. Besides, hydrogen bonds, hydrophobic and electrostatic interactions play dominant roles in the recognition and combination of DC3-AR complex. The essential residues dominant in each interaction were specifically revealed. This work facilitates our understanding of the interaction mechanism of DC3 binding to AR at the molecular level and contributes to the rational cyclopeptide drug design for prostate cancer.

Exploring the Interaction Mechanism Between Cyclopeptide DC3 and Androgen Receptor Using Molecular Dynamics Simulations and Free Energy Calculations.

PubMed

Zhang, Huimin; Song, Tianqing; Yang, Yizhao; Fu, Chenggong; Li, Jiazhong

2018-01-01

Androgen receptor (AR) is a key target in the discovery of anti-PCa (Prostate Cancer) drugs. Recently, a novel cyclopeptide Diffusa Cyclotide-3 (DC3), isolated from Hedyotisdiffusa , has been experimentally demonstrated to inhibit the survival and growth of LNCap cells, which typically express T877A-mutated AR, the most frequently detected point mutation of AR in castration-resistant prostate cancer (CRPC). But the interaction mechanism between DC3 and AR is not clear. Here in this study we aim to explore the possible binding mode of DC3 to T877A-mutated AR from molecular perspective. Firstly, homology modeling was employed to construct the three-dimensional structure of the cyclopeptide DC3 using 2kux.1.A as the template. Then molecular docking, molecular dynamics (MD) simulations, and molecular mechanics/generalized Born surface area (MM-GBSA) methods were performed to determine the bind site and explore the detailed interaction mechanism of DC3-AR complex. The obtained results suggested that the site formed by H11, loop888-893, and H12 (site 2) was the most possible position of DC3 binding to AR. Besides, hydrogen bonds, hydrophobic, and electrostatic interactions play dominant roles in the recognition and combination of DC3-AR complex. The essential residues dominant in each interaction were specifically revealed. This work facilitates our understanding of the interaction mechanism of DC3 binding to AR at the molecular level and contributes to the rational cyclopeptide drug design for prostate cancer.

Stable-carbon isotope ratios for sourcing the nerve-agent precursor methylphosphonic dichloride and its products.

PubMed

Moran, James J; Fraga, Carlos G; Nims, Megan K

2018-08-15

The ability to connect a chemical threat agent to a specific batch of a synthetic precursor can provide a fingerprint to contribute to effective forensic investigations. Stable isotope analysis can leverage intrinsic, natural isotopic variability within the molecules of a threat agent to unlock embedded chemical fingerprints in the material. Methylphosphonic dichloride (DC) is a chemical precursor to the nerve agent sarin. DC is converted to methylphosphonic difluoride (DF) as part of the sarin synthesis process. We used a suite of commercially available DC stocks to both evaluate the potential for δ 13 C analysis to be used as a fingerprinting tool in sarin-related investigations and to develop sample preparation techniques (using chemical hydrolysis) that can simplify isotopic analysis of DC and its synthetic products. We demonstrate that natural isotopic variability in DC results in at least three distinct, isotope-resolved clusters within the thirteen stocks we analyzed. Isotopic variability in the carbon feedstock (i.e., methanol) used for DC synthesis is likely inherited by the DC samples we measured. We demonstrate that the hydrolysis of DC and DF to methylphosphonic acid (MPA) can be used as a preparative step for isotopic analysis because the reaction does not impart a significant isotopic fractionation. MPA is more chemically stable, less toxic, and easier to handle than DC or DF. Further, the hydrolysis method we demonstrated can be applied to a suite of other precursors or to sarin itself, thereby providing a potentially valuable forensic tool. Copyright © 2018. Published by Elsevier B.V.

Station Blackout at Browns Ferry Unit One - accident sequence analysis. Volume 1

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

Cook, D.H.; Harrington, R.M.; Greene, S.R.

1981-11-01

This study describes the predicted response of Unit 1 at the Browns Ferry Nuclear Plant to Station Blackout, defined as a loss of offsite power combined with failure of all onsite emergency diesel-generators to start and load. Every effort has been made to employ the most realistic assumptions during the process of defining the sequence of events for this hypothetical accident. DC power is assumed to remain available from the unit batteries during the initial phase and the operator actions and corresponding events during this period are described using results provided by an analysis code developed specifically for this purpose.more » The Station Blackout is assumed to persist beyond the point of battery exhaustion and the events during this second phase of the accident in which dc power would be unavailable were determined through use of the MARCH code. Without dc power, cooling water could no longer be injected into the reactor vessel and the events of the second phase include core meltdown and subsequent containment failure. An estimate of the magnitude and timing of the concomitant release of the noble gas, cesium, and iodine-based fission products to the environment is provided in Volume 2 of this report. 58 refs., 75 figs., 8 tabs.« less

Efficiency optimization of a photovoltaic water pumping system for irrigation in Ouargla, Algeria

NASA Astrophysics Data System (ADS)

Louazene, M. L.; Garcia, M. C. Alonso; Korichi, D.

2017-02-01

This work is technical study to contribute to the optimization of pumping systems powered by solar energy (clean) and used in the field of agriculture. To achieve our goals, we studied the techniques that must be entered on a photovoltaic system for maximum energy from solar panels. Our scientific contribution in this research is the realization of an efficient photovoltaic pumping system for irrigation needs. To achieve this and extract maximum power from the PV generator, two axes have been optimized: 1. Increase in the uptake of solar radiation by choice an optimum tilt angle of the solar panels, and 2. it is necessary to add an adaptation device, MPPT controller with a DC-DC converter, between the source and the load.

Porphyromonas gingivalis evasion of autophagy and intracellular killing by human myeloid dendritic cells involves DC-SIGN-TLR2 crosstalk.

PubMed

El-Awady, Ahmed R; Miles, Brodie; Scisci, Elizabeth; Kurago, Zoya B; Palani, Chithra D; Arce, Roger M; Waller, Jennifer L; Genco, Caroline A; Slocum, Connie; Manning, Matthew; Schoenlein, Patricia V; Cutler, Christopher W

2015-02-01

Signaling via pattern recognition receptors (PRRs) expressed on professional antigen presenting cells, such as dendritic cells (DCs), is crucial to the fate of engulfed microbes. Among the many PRRs expressed by DCs are Toll-like receptors (TLRs) and C-type lectins such as DC-SIGN. DC-SIGN is targeted by several major human pathogens for immune-evasion, although its role in intracellular routing of pathogens to autophagosomes is poorly understood. Here we examined the role of DC-SIGN and TLRs in evasion of autophagy and survival of Porphyromonas gingivalis in human monocyte-derived DCs (MoDCs). We employed a panel of P. gingivalis isogenic fimbriae deficient strains with defined defects in Mfa-1 fimbriae, a DC-SIGN ligand, and FimA fimbriae, a TLR2 agonist. Our results show that DC-SIGN dependent uptake of Mfa1+P. gingivalis strains by MoDCs resulted in lower intracellular killing and higher intracellular content of P. gingivalis. Moreover, Mfa1+P. gingivalis was mostly contained within single membrane vesicles, where it survived intracellularly. Survival was decreased by activation of TLR2 and/or autophagy. Mfa1+P. gingivalis strain did not induce significant levels of Rab5, LC3-II, and LAMP1. In contrast, P. gingivalis uptake through a DC-SIGN independent manner was associated with early endosomal routing through Rab5, increased LC3-II and LAMP-1, as well as the formation of double membrane intracellular phagophores, a characteristic feature of autophagy. These results suggest that selective engagement of DC-SIGN by Mfa-1+P. gingivalis promotes evasion of antibacterial autophagy and lysosome fusion, resulting in intracellular persistence in myeloid DCs; however TLR2 activation can overcome autophagy evasion and pathogen persistence in DCs.

The integrin effector PINCH regulates JNK activity and epithelial migration in concert with Ras suppressor 1

PubMed Central

Kadrmas, Julie L.; Smith, Mark A.; Clark, Kathleen A.; Pronovost, Stephen M.; Muster, Nemone; Yates, John R.; Beckerle, Mary C.

2004-01-01

Cell adhesion and migration are dynamic processes requiring the coordinated action of multiple signaling pathways, but the mechanisms underlying signal integration have remained elusive. Drosophila embryonic dorsal closure (DC) requires both integrin function and c-Jun amino-terminal kinase (JNK) signaling for opposed epithelial sheets to migrate, meet, and suture. Here, we show that PINCH, a protein required for integrin-dependent cell adhesion and actin–membrane anchorage, is present at the leading edge of these migrating epithelia and is required for DC. By analysis of native protein complexes, we identify RSU-1, a regulator of Ras signaling in mammalian cells, as a novel PINCH binding partner that contributes to PINCH stability. Mutation of the gene encoding RSU-1 results in wing blistering in Drosophila, demonstrating its role in integrin-dependent cell adhesion. Genetic interaction analyses reveal that both PINCH and RSU-1 antagonize JNK signaling during DC. Our results suggest that PINCH and RSU-1 contribute to the integration of JNK and integrin functions during Drosophila development. PMID:15596544

Space Station Crew Discusses Life in Space with Students in Washington, D.C.

NASA Image and Video Library

2017-09-27

Aboard the International Space Station, Expedition 53 Commander Randy Bresnik of NASA discussed life and research on the orbital outpost during an educational in-flight event Sept. 27 with students gathered at the National Air and Space Museum in Washington, D.C. The so-called “STEM in 30” group of students is focused on investigations regarding station science and Bresnik’s contributions to the research being conducted in orbit.

Modelling ac ripple currents in HTS coated conductors

NASA Astrophysics Data System (ADS)

Xu, Zhihan; Grilli, Francesco

2015-10-01

Dc transmission using high temperature superconducting (HTS) coated conductors (CCs) offers a promising solution to the globally growing demand for effective, reliable and economic transmission of green energy up to the gigawatt level over very long distances. The credible estimation of the losses and thereby the heat dissipation involved, where ac ripples (introduced in rectification/ac-dc conversion) are viewed as a potential source of notable contribution, is highly essential for the rational design of practical HTS dc transmission cables and corresponding cryogenic systems to fulfil this demand. Here we report a targeted modelling study into the ac losses in a HTS CC subject to dc and ac ripple currents simultaneously, by solving Maxwell’s equations using the finite element method (FEM) in the commercial software package COMSOL. It is observed that the instantaneous loss exhibits only one peak per cycle in the HTS CC subject to sinusoidal ripples, given that the amplitude of the ac ripples is smaller than approximately 20% of that of the dc current. This is a distinct contrast to the usual observation of two peaks per cycle in a HTS CC subject to ac currents only. The unique mechanism is also revealed, which is directly associated with the finding that, around any local minima of the applied ac ripples, the critical state of -J c is never reached at the edges of the HTS CC, as it should be according to the Bean model. When running further into the longer term, it is discovered that the ac ripple loss of the HTS CC in full-wave rectification decays monotonically, at a speed which is found to be insensitive to the frequency of the applied ripples within our targeted situations, to a relatively low level of approximately 1.38 × 10-4 W m-1 in around 1.7 s. Comparison between this level and other typical loss contributions in a HTS dc cable implies that ac ripple currents in HTS CCs should only be considered as a minor source of dissipation in superconducting dc transmission.

Social representations of obstetricians and neonatologists about fetal and early neonatal death certificate in the city of São Paulo.

PubMed

Schoeps, Daniela; Lefevre, Fernando; Silva, Zilda Pereira; Novaes, Hillegonda Maria Dutilh; Raspantini, Priscila Ribeiro; de Almeida, Márcia Furquim

2014-01-01

The insatisfactory completeness of the variables in the Death Certificate (DC) makes it difficult to obtain specific perinatal mortality indicators. To assess the social representation of physicians about the perinatal DC. Twenty-five physicians were interviewed in 15 hospitals in the city of São Paulo, in 2009. Qualitative analysis was performed with the Collective Subject Discourse technique. The DC is primarily considered according to its legal aspect. Physicians feel responsible for fulfilling the cause of death. The majority of them reported receiving help from other professionals to complete information on maternal characteristics and identification variables. There is lack of information on the mother's pre-natal conditions, which can make it difficult to identify the perinatal cause of death, mainly in the Unified Health System (SUS) hospitals. Some participants received specific DC training only when attending medical schools. The organization of medical work may affect the completion of the DC, especially in hospitals from SUS. Other professionals contributed to this task and their training can improve the quality of information.

In vitro immunization of patient T cells with autologous bone marrow antigen presenting cells pulsed with tumor lysates.

PubMed

Coulon, V; Ravaud, A; Gaston, R; Delaunay, M; Pariente, J L; Verdier, D; Scrivante, V; Gualde, N

2000-12-01

Presentation of cell-associated antigen to T cells is a critical event in the initiation of an anti-tumor immune response but it appears to often be deficient or limiting. Here we report an experimental system for stimulation of human T lymphocytes using autologous antigen presenting cells (APCs) and autologous tumor cells. Two types of APCs were prepared from human bone marrow: MC and DC. MC were produced by using GM-CSF and SCF. DC were obtained with the same cytokines plus IL-4. DC and MC were generated in parallel from the same patients and their phenotypes and capacities to prime T lymphocytes were analyzed and compared. MC were CD14+, CD1a-, CD33+ and HLA-DR+. Two populations of DC were defined: immature DC were uniformly CD1a-; mature DC expressed CD1a, CD80, CD86, HLA-DR, CD54 and CD58 but lacked surface CD14. Stimulation of autologous T lymphocytes was studied by measuring their proliferation and cytotoxic function. In more than 80% of our experiments the proliferation of autologous T lymphocytes cocultured with APC pulsed or not with tumor cell lysates was higher than that of T cells cultured alone. DC were more effective than MC in stimulating proliferation of lymphocytes. The capacity of a patient's autologous bone marrow-derived APC to stimulate T cells when exposed to autologous tumor cell lysates suggest that such antigen-exposed APC may be useful in specific anti-tumor immunotherapy protocols. Copyright 2000 Wiley-Liss, Inc.

DC-8 Airborne Laboratory in flight over Palmdale, CA

NASA Image and Video Library

1998-02-20

The DC-8 Airborne Laboratory in a left banking turn above the airport at Palmdale, California. The right wing is silhouetted against the blue sky, while the left wing contrasts with the desert terrain. The former airliner is a "dash-72" model and has a range of 5,400 miles. The craft can stay airborne for 12 hours and has an operational speed range between 300 and 500 knots. The research flights are made at between 500 and 41,000 feet. The aircraft can carry up to 30,000 lbs of research/science payload equipment installed in 15 mission-definable spaces.

Giant Permittivity in Epitaxial Ferroelectric Heterostructures

NASA Astrophysics Data System (ADS)

Erbil, A.; Kim, Y.; Gerhardt, R. A.

1996-08-01

A giant permittivity associated with the motion of domain walls is reported in epitaxial hetero- structures having alternating layers of ferroelectric and nonferroelectric oxides. At low frequencies, permittivities as high as 420 000 are found. Real and imaginary parts of the dielectric constant show large dispersion at high frequencies. In dc measurements, a nonlinear resistance is observed with a well-defined threshold field correlated with the dc bias-field dependence of ac permittivities. We interpret the observations as a result of the motion of a pinned domain wall lattice at low electric fields and sliding-mode motion at high electric fields.

Characterization of blood dendritic and regulatory T cells in asymptomatic adults with sub-microscopic Plasmodium falciparum or Plasmodium vivax infection.

PubMed

Kho, Steven; Marfurt, Jutta; Handayuni, Irene; Pava, Zuleima; Noviyanti, Rintis; Kusuma, Andreas; Piera, Kim A; Burdam, Faustina H; Kenangalem, Enny; Lampah, Daniel A; Engwerda, Christian R; Poespoprodjo, Jeanne R; Price, Ric N; Anstey, Nicholas M; Minigo, Gabriela; Woodberry, Tonia

2016-06-21

Plasmodium falciparum and Plasmodium vivax infections compromise dendritic cell (DC) function and expand regulatory T (Treg) cells in both clinical disease (malaria) and experimental human sub-microscopic infection. Conversely, in asymptomatic microscopy-positive (patent) P. falciparum or P. vivax infection in endemic areas, blood DC increase or retain HLA-DR expression and Treg cells exhibit reduced activation, suggesting that DC and Treg cells contribute to the control of patent asymptomatic infection. The effect of sub-microscopic (sub-patent) asymptomatic Plasmodium infection on DC and Treg cells in malaria-endemic area residents remains unclear. In a cross-sectional household survey conducted in Papua, Indonesia, 162 asymptomatic adults were prospectively evaluated for DC and Treg cells using field-based flow cytometry. Of these, 161 individuals (99 %) were assessed retrospectively by polymerase chain reaction (PCR), 19 of whom had sub-microscopic infection with P. falciparum and 15 with sub-microscopic P. vivax infection. Flow cytometric data were re-analysed after re-grouping asymptomatic individuals according to PCR results into negative controls, sub-microscopic and microscopic parasitaemia to examine DC and Treg cell phenotype in sub-microscopic infection. Asymptomatic adults with sub-microscopic P. falciparum or P. vivax infection had DC HLA-DR expression and Treg cell activation comparable to PCR-negative controls. Sub-microscopic P. falciparum infection was associated with lower peripheral CD4(+) T cells and lymphocytes, however sub-microscopic Plasmodium infection had no apparent effect on DC sub-set number or Treg cell frequency. In contrast to the impairment of DC maturation/function and the activation of Treg cells seen with sub-microscopic parasitaemia in primary experimental human Plasmodium infection, no phenotypic evidence of dysregulation of DC and Treg cells was observed in asymptomatic sub-microscopic Plasmodium infection in Indonesian adults. This is consistent with DC and Treg cells retaining their functional capacity in sub-microscopic asymptomatic infection with P. falciparum or P. vivax in malaria-endemic areas.

Instrument Pointing Capabilities: Past, Present, and Future

NASA Technical Reports Server (NTRS)

Blackmore, Lars; Murray, Emmanuell; Scharf, Daniel P.; Aung, Mimi; Bayard, David; Brugarolas, Paul; Hadaegh, Fred; Lee, Allan; Milman, Mark; Sirlin, Sam;

A general theory of DC electromagnetic launchers

NASA Astrophysics Data System (ADS)

Engel, Thomas G.; Timpson, Erik J.

2015-08-01

The non-linear, transient operation of DC electromagnetic launchers (EMLs) complicates their theoretical understanding and prevents scaling studies and performance comparisons without the aid of detailed numerical models. This paper presents a general theory for DC electromagnetic launchers that has simplified these tasks by identifying critical EML parameters and relationships affecting the EML's voltage, current, and power scaling, as well as its performance and energy conversion efficiency. EML parameters and relationships discussed in this paper include the specific force, the operating mode, the launcher constant, the launcher characteristic velocity, the contact characteristic velocity, the energy conversion efficiency, and the kinetic power and voltage-current scaling relationship. The concepts of the ideal EML, same-scale comparisons, and EML impedance are discussed. This paper defines conditions needed for the EML to operate in the steady-state. A comparison of the general theory with experimental results of several different types of DC (i.e., non-induction) electromagnetic launchers ranging from medium velocity (100's m/s) to high velocity (1000's m/s) is performed. There is good agreement between the general theory and the experimental results.

Steady State Dendritic Cells Present Parenchymal Self-Antigen and Contribute to, but Are Not Essential for, Tolerization of Naive and Th1 Effector CD4 Cells1

PubMed Central

Hagymasi, Adam T.; Slaiby, Aaron M.; Mihalyo, Marianne A.; Qui, Harry Z.; Zammit, David J.; Lefrançois, Leo; Adler, Adam J.

2010-01-01

Bone marrow-derived APC are critical for both priming effector/memory T cell responses to pathogens and inducing peripheral tolerance in self-reactive T cells. In particular, dendritic cells (DC) can acquire peripheral self-Ags under steady state conditions and are thought to present them to cognate T cells in a default tolerogenic manner, whereas exposure to pathogen-associated inflammatory mediators during the acquisition of pathogen-derived Ags appears to reprogram DCs to prime effector and memory T cell function. Recent studies have confirmed the critical role of DCs in priming CD8 cell effector responses to certain pathogens, although the necessity of steady state DCs in programming T cell tolerance to peripheral self-Ags has not been directly tested. In the current study, the role of steady state DCs in programming self-reactive CD4 cell peripheral tolerance was assessed by combining the CD11c-diphtheria toxin receptor transgenic system, in which DC can be depleted via treatment with diphtheria toxin, with a TCR-transgenic adoptive transfer system in which either naive or Th1 effector CD4 cells are induced to undergo tolerization after exposure to cognate parenchymally derived self-Ag. Although steady state DCs present parenchymal self-Ag and contribute to the tolerization of cognate naive and Th1 effector CD4 cells, they are not essential, indicating the involvement of a non-DC tolerogenic APC population(s). Tolerogenic APCs, however, do not require the cooperation of CD4+CD25+ regulatory T cells. Similarly, DC were required for maximal priming of naive CD4 cells to vaccinia viral-Ag, but priming could still occur in the absence of DC. PMID:17641018

Processing of Emotional Faces in Patients with Chronic Pain Disorder: An Eye-Tracking Study.

PubMed

Giel, Katrin Elisabeth; Paganini, Sarah; Schank, Irena; Enck, Paul; Zipfel, Stephan; Junne, Florian

2018-01-01

Problems in emotion processing potentially contribute to the development and maintenance of chronic pain. Theories focusing on attentional processing have suggested that dysfunctional attention deployment toward emotional information, i.e., attentional biases for negative emotions, might entail one potential developmental and/or maintenance factor of chronic pain. We assessed self-reported alexithymia, attentional orienting to and maintenance on emotional stimuli using eye tracking in 17 patients with chronic pain disorder (CP) and two age- and sex-matched control groups, 17 healthy individuals (HC) and 17 individuals who were matched to CP according to depressive symptoms (DC). In a choice viewing paradigm, a dot indicated the position of the emotional picture in the next trial to allow for strategic attention deployment. Picture pairs consisted of a happy or sad facial expression and a neutral facial expression of the same individual. Participants were asked to explore picture pairs freely. CP and DC groups reported higher alexithymia than the HC group. HC showed a previously reported emotionality bias by preferentially orienting to the emotional face and preferentially maintaining on the happy face. CP and DC participants showed no facilitated early attention to sad facial expressions, and DC participants showed no facilitated early attention to happy facial expressions, while CP and DC participants did. We found no group differences in attentional maintenance. Our findings are in line with the clinical large overlap between pain and depression. The blunted initial reaction to sadness could be interpreted as a failure of the attentional system to attend to evolutionary salient emotional stimuli or as an attempt to suppress negative emotions. These difficulties in emotion processing might contribute to etiology or maintenance of chronic pain and depression.

Helminth-conditioned dendritic cells prime CD4+ T cells to IL-4 production in vivo.

PubMed

Connor, Lisa M; Tang, Shiau-Choot; Camberis, Mali; Le Gros, Graham; Ronchese, Franca

2014-09-15

Dendritic cells (DC) are critical for the initiation of immune responses; however, their role in priming IL-4-producing Th2 cells in vivo is not fully understood. We used a model of intradermal injection with fluorescent-labeled, nonviable larvae from the helminth parasite nonviable Nippostrongylus brasiliensis L3 larvae (Nb), a strong inducer of Th2 responses, together with IL-4-GFP reporter mice that enable a sensitive detection of IL-4 production to examine the contribution of DC to the priming of IL-4-producing CD4(+) T cells in vivo. We found that parasite material is taken up by two distinct DC populations in draining lymph nodes: a mostly CD11c(int)MHC class II (MHCII)(hi)CD11b(+)Ly6C(-) dermal DC population and a CD11c(hi)MHCII(int)CD11b(+)Ly6C(+) monocyte-derived DC population. After Nb treatment, these two DC populations appeared in the draining lymph nodes in comparable numbers and with similar kinetics; however, treatment with pertussis toxin blocked the migration of dermal DC and the priming of IL-4-producing T cells, but only partially affected monocyte-derived DC numbers. In line with this observation, transfer of OVA-loaded CD11c(int)MHCII(hi) DC from Nb-treated mice into naive hosts could sensitize OVA-specific CD4(+) T cells to IL-4 production, whereas transfer of CD11c(int)MHCII(hi) DC from naive mice, or CD11c(hi)MHCII(int) DC from Nb-treated or naive mice, induced CD4(+) T cell expansion but no IL-4 production. Phenotypic analysis of Nb-loaded CD11c(int)MHCII(hi) DC revealed expression of programmed death ligand 2, CD301b, IFN regulatory factor 4, and moderate upregulation of OX40 ligand. However, thymic stromal lymphopoietin and OX40 ligand were not required for Th2 priming. Thus, our data suggest that appropriate stimuli can induce DC to express the unique signals sufficient to direct CD4(+) T cells to Th2 differentiation. Copyright © 2014 by The American Association of Immunologists, Inc.

JPL scientist Dr. David Imel and U.S. Air Force Colonel Gwen Linde lead Chilean students on a tour of the DC-8 aircraft in Punta Arenas, Chile

NASA Image and Video Library

2004-03-17

JPL scientist Dr. David Imel and U.S. Air Force Colonel Gwen Linde, the Defense Department Attache Officer assigned to the Chilean Embassy, lead Chilean students on a tour of the DC-8 aircraft at Carlos Ibanez del Campo International Airport in Punta Arenas, Chile. AirSAR 2004 is a three-week expedition by an international team of scientists that is using an all-weather imaging tool, called the Airborne Synthetic Aperture Radar (AirSAR) which is located onboard NASA's DC-8 airborne laboratory. Scientists from many parts of the world including NASA's Jet Propulsion Laboratory are combining ground research done in several areas in Central and South America with NASA's AirSAR technology to improve and expand on the quality of research they are able to conduct. In South America and Antarctica, AirSAR will collect imagery and data to help determine the contribution of Southern Hemisphere glaciers to sea level rise due to climate change. In Patagonia, researchers found this contribution had more than doubled from 1995 to 2000, compared to the previous 25 years. AirSAR data will make it possible to determine whether that trend is decreasing, continuing or accelerating. AirSAR will also provide reliable information on ice shelf thickness to measure the contribution of the glaciers to sea level.

Dendritic cells in transplantation and immune-based therapies.

PubMed

Young, James W; Merad, Miriam; Hart, Derek N J

2007-01-01

Dendritic cells (DCs) are specialized, bone marrow-derived leukocytes critical to the onset of both innate and adaptive immunity. The divisions of labor among distinct human DC subtypes achieve the most effective balance between steady-state tolerance and the induction of innate and adaptive immunity against pathogens, tumors, and other insults. Maintenance of tolerance in the steady state is an active process involving resting or semimature DCs. Breakdowns in this homeostasis can result in autoimmunity. Perturbation of the steady state should first lead to the onset of innate immunity mediated by rapid responders in the form of plasmacytoid and monocyte-derived DC stimulators and natural killer (NK) and NK T-cell responders. These innate effectors then provide additional inflammatory cytokines, including interferon-gamma, which support the activation and maturation of resident and circulating populations of DCs. These are critical to the onset and expansion of adaptive immunity, including Th1, Th2, and cytotoxic T-lymphocyte responses. Rodent models are now revealing important data about distinct DC precursors, homeostasis of tissue-resident DCs, and DC turnover in response to inflammation and pathological conditions like graft-versus-host disease. The use of defined DC subtypes to stimulate both innate and adaptive immunity, either in combination or in a prime-boost vaccine sequence, may prove most useful clinically by harnessing both effector cell compartments.

dc Resistivity of Quantum Critical, Charge Density Wave States from Gauge-Gravity Duality

NASA Astrophysics Data System (ADS)

Amoretti, Andrea; Areán, Daniel; Goutéraux, Blaise; Musso, Daniele

2018-04-01

In contrast to metals with weak disorder, the resistivity of weakly pinned charge density waves (CDWs) is not controlled by irrelevant processes relaxing momentum. Instead, the leading contribution is governed by incoherent, diffusive processes which do not drag momentum and can be evaluated in the clean limit. We compute analytically the dc resistivity for a family of holographic charge density wave quantum critical phases and discuss its temperature scaling. Depending on the critical exponents, the ground state can be conducting or insulating. We connect our results to dc electrical transport in underdoped cuprate high Tc superconductors. We conclude by speculating on the possible relevance of unstable, semilocally critical CDW states to the strange metallic region.

dc Resistivity of Quantum Critical, Charge Density Wave States from Gauge-Gravity Duality.

PubMed

Amoretti, Andrea; Areán, Daniel; Goutéraux, Blaise; Musso, Daniele

2018-04-27

In contrast to metals with weak disorder, the resistivity of weakly pinned charge density waves (CDWs) is not controlled by irrelevant processes relaxing momentum. Instead, the leading contribution is governed by incoherent, diffusive processes which do not drag momentum and can be evaluated in the clean limit. We compute analytically the dc resistivity for a family of holographic charge density wave quantum critical phases and discuss its temperature scaling. Depending on the critical exponents, the ground state can be conducting or insulating. We connect our results to dc electrical transport in underdoped cuprate high T_{c} superconductors. We conclude by speculating on the possible relevance of unstable, semilocally critical CDW states to the strange metallic region.

Bryn Bridges and mutagenesis: exploring the intellectual space.

PubMed

Walker, G C

2001-02-25

The products of the SOS-regulated umuDC genes are required for most UV and chemical mutagenesis in Escherichia coli. Recently it has been recognized that UmuC is the founding member of a superfamily of novel DNA polymerases found in all three kingdoms of life. Key findings leading to these insights are reviewed, placing a particular emphasis on contributions made by Bryn Bridges and on his interest in the importance of interactions between the umuDC gene products and the replicative DNA polymerase.

The McAndrews Leadership Lecture: February 2016, by Dr Greg Kawchuk. Putting the "Act" Back in Chiropractic.

PubMed

Kawchuk, Gregory Neil

2017-12-01

The McAndrews Leadership Lecture was developed by the American Chiropractic Association to honor the legacy of Jerome F. McAndrews, DC, and George P. McAndrews, JD, and their contributions to the chiropractic profession. This article is an edited and truncated version of the McAndrews Leadership Lecture given by Dr Greg Kawchuk on February 27, 2016, in Washington, DC, at the National Chiropractic Leadership Conference. This was the second McAndrews lecture in this annual series.

Fun D.C. Jobs for Physicists

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

Clark Cully

2009-09-30

Physicists make valuable contributions in a wide variety of careers, including those in Washington. Many national challenges, including energy, innovation, and security, create a demand for technically-competent individuals across government. Clark will discuss some of the many programs in D.C. designed to attract the best and brightest minds, from grad-students to professors, from short-term assignments to whole new careers. These are great opportunities to use your expertise and enrich your knowledge of the broader scientific enterprise, all while serving society.

Guidewire exchange vs new site placement for temporary dialysis catheter insertion in ICU patients: is there a greater risk of colonization or dysfunction?

PubMed

Coupez, Elisabeth; Timsit, Jean-François; Ruckly, Stéphane; Schwebel, Carole; Gruson, Didier; Canet, Emmanuel; Klouche, Kada; Argaud, Laurent; Bohe, Julien; Garrouste-Orgeas, Maïté; Mariat, Christophe; Vincent, François; Cayot, Sophie; Cointault, Olivier; Lepape, Alain; Darmon, Michael; Boyer, Alexandre; Azoulay, Elie; Bouadma, Lila; Lautrette, Alexandre; Souweine, Bertrand

2016-07-30

Intensive care unit (ICU) patients require dialysis catheters (DCs) for renal replacement therapy (RRT). They carry a high risk of developing end-stage renal disease, and therefore their vascular access must be preserved. Guidewire exchange (GWE) is often used to avoid venipuncture insertion (VPI) at a new site. However, the impact of GWE on infection and dysfunction of DCs in the ICU is unknown. Our aim was to compare the effect of GWE and VPI on DC colonization and dysfunction in ICU patients. Using data from the ELVIS randomized controlled trial (RCT) (1496 ICU adults requiring DC for RRT or plasma exchange) we performed a matched-cohort analysis. Cases were DCs inserted by GWE (n = 178). They were matched with DCs inserted by VPI. Matching criteria were participating centre, simplified acute physiology score (SAPS) II +/-10, insertion site (jugular or femoral), side for jugular site, and length of ICU stay before DC placement. We used a marginal Cox model to estimate the effect of DC insertion (GWE vs. VPI) on DC colonization and dysfunction. DC colonization rate was not different between GWE-DCs and VPI-DCs (10 (5.6 %) for both groups) but DC dysfunction was more frequent with GWE-DCs (67 (37.6 %) vs. 28 (15.7 %); hazard ratio (HR), 3.67 (2.07-6.49); p < 0.01). Results were similar if analysis was restricted to DCs changed for dysfunction. GWE for DCs in ICU patients, compared with VPI did not contribute to DC colonization or infection but was associated with more than twofold increase in DC dysfunction. This study is registered with ClinicalTrials.gov, number NCT00563342 . Registered 2 April 2009.

Identification of trans-acting factors regulating SamDC expression in Oryza sativa

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

Basu, Supratim, E-mail: supratim_genetics@yahoo.co.in; Division of Plant Biology, Bose Institute, Kolkata; Roychoudhury, Aryadeep

2014-03-07

Highlights: • Identification of cis elements responsible for SamDC expression by in silico analysis. • qPCR analysis of SamDC expression to abiotic and biotic stress treatments. • Detection of SamDC regulators using identified cis-elements as probe by EMSA. • Southwestern Blot analysis to predict the size of the trans-acting factors. - Abstract: Abiotic stress affects the growth and productivity of crop plants; to cope with the adverse environmental conditions, plants have developed efficient defense machinery comprising of antioxidants like phenolics and flavonoids, and osmolytes like polyamines. SamDC is a key enzyme in the polyamine biosynthesis pathway in plants. In ourmore » present communication we have done in silico analysis of the promoter region of SamDC to look for the presence of different cis-regulatory elements contributing to its expression. Based on the presence of different cis-regulatory elements we completed comparative analysis of SamDC gene expression in rice lamina of IR-29 and Nonabokra by qPCR in response to the abiotic stress treatments of salinity, drought, cold and the biotic stress treatments of ABA and light. Additionally, to explore the role of the cis-regulatory elements in regulating the expression of SamDC gene in plants we comparatively analyzed the binding of rice nuclear proteins prepared from IR-29 and Nonabokra undergoing various stress treatments. The intensity of the complex formed was low and inducible in IR-29 in contrast to Nonabokra. Southwestern blot analysis helped in predicting the size of the trans-acting factors binding to these cis-elements. To our knowledge this is the first report on the comprehensive analysis of SamDC gene expression in rice and identification of the trans-acting factors regulating its expression.« less

Dendritic cells issued in vitro from bone marrow produce PGE(2) that contributes to the immunomodulation induced by antigen-presenting cells.

PubMed

Harizi, H; Juzan, M; Grosset, C; Rashedi, M; Gualde, N

2001-04-10

Given that preliminary work has indicated that prostaglandins can play a role in modulating dendritic cell (DC) functions, we addressed the prostaglandin E(2) (PGE(2)) biosynthetic capacity of mouse DC produced in vitro from bone marrow cells. We observed production of significant amounts of PGE(2), which was reduced by at least 80% when cells were incubated in the presence of indomethacin, a COX-1 preferential inhibitor. Indeed, when tested by Western blot analysis with specific COX-1 and COX-2 antibodies, only COX-1 expression could be detected in the bone marrow (BM)-DC. For lipopolysaccharide (LPS)-treated BM-DC, inhibition of PGE(2) production by indomethacin or by NS-398 (a COX-2-selective inhibitor) used alone was less potent. After LPS treatment of BM-DC, COX-1 and COX-2 expression was potent, and inhibition of PGE(2) synthesis needed the presence of both indomethacin and NS-398. We also observed that exogenous PGE(2) diminished the expression of MHC class II molecules by BM-DC and that prostaglandin and indomethacin had antagonistic effects on cell proliferation during the mixed lymphocyte reaction using BM-DC as stimulatory cells. This assessment of PGE(2) suggests that endogenous PGE(2) produced by DC might play a role as an immunomodulating factor during the immune response. This hypothesis is sustained by the fact that IL-12 production by BM-DC is modulated by exogenous PGE(2) as well as endogenous prostaglandin, since either the addition of exogenous PGE(2) or the presence of LPS (which increases endogenous PGE(2) synthesis) decreases IL-12 production, while NS-398 (which decreases LPS-induced PGE(2) synthesis) increases IL-12 synthesis. Copyright 2001 Academic Press.

Plasmacytoid Dendritic Cell Infection and Sensing Capacity during Pathogenic and Nonpathogenic Simian Immunodeficiency Virus Infection

PubMed Central

Jochems, Simon P.; Jacquelin, Beatrice; Chauveau, Lise; Huot, Nicolas; Petitjean, Gaël; Lepelley, Alice; Liovat, Anne-Sophie; Ploquin, Mickaël J.; Cartwright, Emily K.; Bosinger, Steven E.; Silvestri, Guido; Barré-Sinoussi, Françoise; Lebon, Pierre; Schwartz, Olivier

2015-01-01

ABSTRACT Human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in macaques (MAC) lead to chronic inflammation and AIDS. Natural hosts, such as African green monkeys (AGM) and sooty mangabeys (SM), are protected against SIV-induced chronic inflammation and AIDS. Here, we report that AGM plasmacytoid dendritic cells (pDC) express extremely low levels of CD4, unlike MAC and human pDC. Despite this, AGM pDC efficiently sensed SIVagm, but not heterologous HIV/SIV isolates, indicating a virus-host adaptation. Moreover, both AGM and SM pDC were found to be, in contrast to MAC pDC, predominantly negative for CCR5. Despite such limited CD4 and CCR5 expression, lymphoid tissue pDC were infected to a degree similar to that seen with CD4+ T cells in both MAC and AGM. Altogether, our finding of efficient pDC infection by SIV in vivo identifies pDC as a potential viral reservoir in lymphoid tissues. We discovered low expression of CD4 on AGM pDC, which did not preclude efficient sensing of host-adapted viruses. Therefore, pDC infection and efficient sensing are not prerequisites for chronic inflammation. The high level of pDC infection by SIVagm suggests that if CCR5 paucity on immune cells is important for nonpathogenesis of natural hosts, it is possibly not due to its role as a coreceptor. IMPORTANCE The ability of certain key immune cell subsets to resist infection might contribute to the asymptomatic nature of simian immunodeficiency virus (SIV) infection in its natural hosts, such as African green monkeys (AGM) and sooty mangabeys (SM). This relative resistance to infection has been correlated with reduced expression of CD4 and/or CCR5. We show that plasmacytoid dendritic cells (pDC) of natural hosts display reduced CD4 and/or CCR5 expression, unlike macaque pDC. Surprisingly, this did not protect AGM pDC, as infection levels were similar to those found in MAC pDC. Furthermore, we show that AGM pDC did not consistently produce type I interferon (IFN-I) upon heterologous SIVmac/HIV type 1 (HIV-1) encounter, while they sensed autologous SIVagm isolates. Pseudotyping SIVmac/HIV-1 overcame this deficiency, suggesting that reduced uptake of heterologous viral strains underlays this lack of sensing. The distinct IFN-I responses depending on host species and HIV/SIV isolates reveal the host/virus species specificity of pDC sensing. PMID:25903334

Profiling MHC II immunopeptidome of blood-stage malaria reveals that cDC1 control the functionality of parasite-specific CD4 T cells.

PubMed

Draheim, Marion; Wlodarczyk, Myriam F; Crozat, Karine; Saliou, Jean-Michel; Alayi, Tchilabalo Dilezitoko; Tomavo, Stanislas; Hassan, Ali; Salvioni, Anna; Demarta-Gatsi, Claudia; Sidney, John; Sette, Alessandro; Dalod, Marc; Berry, Antoine; Silvie, Olivier; Blanchard, Nicolas

2017-11-01

In malaria, CD4 Th1 and T follicular helper (T FH ) cells are important for controlling parasite growth, but Th1 cells also contribute to immunopathology. Moreover, various regulatory CD4 T-cell subsets are critical to hamper pathology. Yet the antigen-presenting cells controlling Th functionality, as well as the antigens recognized by CD4 T cells, are largely unknown. Here, we characterize the MHC II immunopeptidome presented by DC during blood-stage malaria in mice. We establish the immunodominance hierarchy of 14 MHC II ligands derived from conserved parasite proteins. Immunodominance is shaped differently whether blood stage is preceded or not by liver stage, but the same ETRAMP-specific dominant response develops in both contexts. In naïve mice and at the onset of cerebral malaria, CD8α + dendritic cells (cDC1) are superior to other DC subsets for MHC II presentation of the ETRAMP epitope. Using in vivo depletion of cDC1, we show that cDC1 promote parasite-specific Th1 cells and inhibit the development of IL-10 + CD4 T cells. This work profiles the P. berghei blood-stage MHC II immunopeptidome, highlights the potency of cDC1 to present malaria antigens on MHC II, and reveals a major role for cDC1 in regulating malaria-specific CD4 T-cell responses. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Stable-carbon isotope ratios for sourcing the nerve-agent precursor methylphosphonic dichloride and its products

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

Moran, James J.; Fraga, Carlos G.; Nims, Megan K.

The ability to connect a chemical threat agent to a specific batch of a synthetic precursor can provide a fingerprint to contribute to effective forensic investigations. Stable isotope analysis can leverage intrinsic, natural isotopic variability within the molecules of a threat agent to unlock embedded chemical fingerprints in the material. Methylphosphonic dichloride (DC) is a chemical precursor to the nerve agent sarin. It is converted to methylphosphonic difluoride (DF) as part of the sarin synthesis process. We used a suite of commercially available DC stocks to both evaluate the potential for δ13C analysis to be used as a fingerprinting toolmore » in sarin-related investigations and to develop sample preparation techniques (using chemical hydrolysis) that can simplify isotopic analysis of DC and its synthetic products. We demonstrate that natural isotopic variability in DC results in at least three distinct, isotope-resolved clusters within the thirteen stocks we analyzed. Isotopic variability in the carbon feedstock (i.e., methanol) used for DC synthesis is likely inherited by the DC samples we measured. We demonstrate that the hydrolysis of DC and DF to methylphosphonic acid (MPA) can be used as a preparative step for isotopic analysis because the reaction does not impart a measureable isotopic fractionation. MPA is more chemically stable, less toxic, and easier to handle than DC or DF. Further, the hydrolysis method we demonstrated can be applied to a suite of other precursors or to sarin itself, thereby providing a potentially valuable forensic tool.« less

Nonmethane hydrocarbon measurements in the North Atlantic Flight Corridor during the Subsonic Assessment Ozone and Nitrogen Oxide Experiment

NASA Astrophysics Data System (ADS)

Simpson, I. J.; Sive, B. C.; Blake, D. R.; Blake, N. J.; Chen, T.-Y.; Lopez, J. P.; Anderson, B. E.; Sachse, G. W.; Vay, S. A.; Fuelberg, H. E.; Kondo, Y.; Thompson, A. M.; Rowland, F. S.

2000-02-01

Mixing ratios of nonmethane hydrocarbons (NMHCs) were not enhanced in whole air samples collected within the North Atlantic Flight Corridor (NAFC) during the fall of 1997. The investigation was conducted aboard NASA's DC-8 research aircraft, as part of the Subsonic Assessment (SASS) Ozone and Nitrogen Oxide Experiment (SONEX). NMHC enhancements were not detected within the general organized tracking system of the NAFC, nor during two tail chases of the DC-8's own exhaust. Because positive evidence of aircraft emissions was demonstrated by enhancements in both nitrogen oxides and condensation nuclei during SONEX, the NMHC results suggest that the commercial air traffic fleet operating in the North Atlantic region does not contribute at all or contributes negligibly to NMHCs in the NAFC.

Divide-and-conquer density functional theory on hierarchical real-space grids: Parallel implementation and applications

NASA Astrophysics Data System (ADS)

Shimojo, Fuyuki; Kalia, Rajiv K.; Nakano, Aiichiro; Vashishta, Priya

2008-02-01

A linear-scaling algorithm based on a divide-and-conquer (DC) scheme has been designed to perform large-scale molecular-dynamics (MD) simulations, in which interatomic forces are computed quantum mechanically in the framework of the density functional theory (DFT). Electronic wave functions are represented on a real-space grid, which is augmented with a coarse multigrid to accelerate the convergence of iterative solutions and with adaptive fine grids around atoms to accurately calculate ionic pseudopotentials. Spatial decomposition is employed to implement the hierarchical-grid DC-DFT algorithm on massively parallel computers. The largest benchmark tests include 11.8×106 -atom ( 1.04×1012 electronic degrees of freedom) calculation on 131 072 IBM BlueGene/L processors. The DC-DFT algorithm has well-defined parameters to control the data locality, with which the solutions converge rapidly. Also, the total energy is well conserved during the MD simulation. We perform first-principles MD simulations based on the DC-DFT algorithm, in which large system sizes bring in excellent agreement with x-ray scattering measurements for the pair-distribution function of liquid Rb and allow the description of low-frequency vibrational modes of graphene. The band gap of a CdSe nanorod calculated by the DC-DFT algorithm agrees well with the available conventional DFT results. With the DC-DFT algorithm, the band gap is calculated for larger system sizes until the result reaches the asymptotic value.

Autism and Mitochondrial Disease

ERIC Educational Resources Information Center

Haas, Richard H.

2010-01-01

Autism spectrum disorder (ASD) as defined by the revised Diagnostic and Statistical Manual of Mental Disorders: DSM IVTR criteria (American Psychiatric Association [2000] Washington, DC: American Psychiatric Publishing) as impairment before the age of 3 in language development and socialization with the development of repetitive behaviors, appears…

30 CFR 28.41 - Testing requirements; general.

Code of Federal Regulations, 2011 CFR

2011-07-01

...., or 600 volts d.c., depending on the voltage rating of the fuse being tested. (b) Time constant of the circuit (defined as T=L/R, where T is the time in seconds, L is the inductance in henries, and R is the...

30 CFR 28.41 - Testing requirements; general.

Code of Federal Regulations, 2012 CFR

2012-07-01

...., or 600 volts d.c., depending on the voltage rating of the fuse being tested. (b) Time constant of the circuit (defined as T=L/R, where T is the time in seconds, L is the inductance in henries, and R is the...

30 CFR 28.41 - Testing requirements; general.

Code of Federal Regulations, 2010 CFR

2010-07-01

...., or 600 volts d.c., depending on the voltage rating of the fuse being tested. (b) Time constant of the circuit (defined as T=L/R, where T is the time in seconds, L is the inductance in henries, and R is the...

30 CFR 28.41 - Testing requirements; general.

Code of Federal Regulations, 2013 CFR

2013-07-01

...., or 600 volts d.c., depending on the voltage rating of the fuse being tested. (b) Time constant of the circuit (defined as T=L/R, where T is the time in seconds, L is the inductance in henries, and R is the...

30 CFR 28.41 - Testing requirements; general.

Code of Federal Regulations, 2014 CFR

2014-07-01

...., or 600 volts d.c., depending on the voltage rating of the fuse being tested. (b) Time constant of the circuit (defined as T=L/R, where T is the time in seconds, L is the inductance in henries, and R is the...

Rapid RHD Zygosity Determination Using Digital PCR.

PubMed

Sillence, Kelly A; Halawani, Amr J; Tounsi, Wajnat A; Clarke, Kirsty A; Kiernan, Michele; Madgett, Tracey E; Avent, Neil D

2017-08-01

Paternal zygosity testing is used for determining homo- or hemizygosity of RHD in pregnancies that are at a risk of hemolytic disease of the fetus and newborn. At present, this is achieved by using real-time PCR or the Rhesus box PCR, which can be difficult to interpret and unreliable, particularly for black African populations. DNA samples extracted from 53 blood donors were analyzed using 2 multiplex reactions for RHD -specific targets against a reference ( AGO1 ) 2 to determine gene dosage by digital PCR. Results were compared with serological data, and the correct genotype for 2 discordant results was determined by long-range PCR (LR-PCR), next-generation sequencing, and conventional Sanger sequencing. The results showed clear and reliable determination of RHD zygosity using digital PCR and revealed that 4 samples did not match the serologically predicted genotype. Sanger sequencing and long-range PCR followed by next-generation sequencing revealed that the correct genotypes for samples 729M and 351D, which were serologically typed as R 1 R 2 (DCe/DcE), were R 2 r' (DcE/dCe) for 729M and R 1 r″ (DCe/dcE), R 0 r y (Dce/dCE), or R Z r (DCE/dce) for 351D, in concordance with the digital PCR data. Digital PCR provides a highly accurate method to rapidly define blood group zygosity and has clinical application in the analysis of Rh phenotyped or genotyped samples. The vast majority of current blood group genotyping platforms are not designed to define zygosity, and thus, this technique may be used to define paternal RH zygosity in pregnancies that are at a risk of hemolytic disease of the fetus and newborn and can distinguish between homo- and hemizygous RHD -positive individuals. © 2017 American Association for Clinical Chemistry.

Contributions of direct versus indirect mechanisms for regulatory dendritic cell suppression of asthmatic allergen-specific IgG1 antibody responses

PubMed Central

Ma, Yanna; Dawicki, Wojciech; Zhang, Xiaobei

2018-01-01

IL-10-differentiated dendritic cells (DC10) can reverse the asthma phenotype in mice, but how they suppress the asthmatic B cell response is unclear. Herein we assessed the mechanism(s) by which DC10 and DC10-induced Treg affect IgG1 production in asthma. We observed a rapid decline in lung-resident OVA-specific IgG1-secreting B cells on cessation of airway allergen challenge, and intraperitoneal DC10 therapy did not amplify that (p>0.05). It did however increase the loss of IgG1-B cells from the bone marrow (by 45+/-7.2%; p≤0.01) and spleen (by 65+/-17.8%; p≤0.05) over 2 wk. Delivery of OVA-loaded DC10 directly into the airways of asthmatic mice decreased the lung IgG1 B cell response assessed 2 dy later by 33+/-9.7% (p≤0.01), while their co-culture with asthmatic lung cell suspensions reduced the numbers of IgG1-secreting cells by 56.5+/-9.7% (p≤0.01). This effect was dependent on the DC10 carrying intact allergen on their cell surface; DC10 that had phagocytosed and fully processed their allergen were unable to suppress B cell responses, although they did suppress asthmatic Th2 cell responses. We had shown that therapeutic delivery of DC10-induced Treg can effectively suppress asthmatic T and B cell (IgE and IgG1) responses; herein CD4+ cells or Treg from the lungs of DC10-treated OVA-asthmatic mice suppressed in vitro B cell IgG1 production by 52.2+/-8.7% (p≤0.001) or 44.6+/-12.2% (p≤0.05), respectively, but delivery of DC10-induced Treg directly into the airways of asthmatic mice had no discernible impact over 2 dy on the numbers of lung IgG1-secreting cells (p≥0.05). In summary, DC10 treatment down-regulates OVA-specific B cell responses of asthmatic mice. While DC10 that carry intact allergen on their cell surface can dampen this response, DC10-induced Treg are critical for full realization of this outcome. This suggests that infectious tolerance is an essential element in regulatory DC control of the B cell response in allergic asthma. PMID:29293622

High static gain single-phase PFC based on a hybrid boost converter

NASA Astrophysics Data System (ADS)

Flores Cortez, Daniel; Maccarini, Marcello C.; Mussa, Samir A.; Barbi, Ivo

2017-05-01

In this paper, a single-phase unity power factor rectifier, based on a hybrid boost converter, resulting from the integration of a conventional dc-dc boost converter and a switched-capacitor voltage doubler is proposed, analysed, designed and tested. The high-power rectifier is controlled by two feedback loops with the same control strategy employed in the conventional boost-based rectifier. The main feature of the proposed rectifier is its ability to output a dc voltage larger than the double of the peak value of the input line voltage, while subjecting the power switches to half of the dc-link voltage, which contributes to reducing the cost and increasing the efficiency. Experimental data were obtained from a laboratory prototype with an input voltage of 220 Vrms, line frequency of 60 Hz, output voltage of 800 Vdc, load power of 1000 W and switching frequency of 50 kHz. The efficiency of the prototype, measured in the laboratory, was 96.5% for full load and 97% for half load.

Decontamination of Streptococci biofilms and Bacillus cereus spores on plastic surfaces with DC and pulsed corona discharges

NASA Astrophysics Data System (ADS)

Koval'ová, Zuzana; Tarabová, Kataŕna; Hensel, Karol; Machala, Zdenko

2013-02-01

Cold air plasmas of DC and pulsed corona discharges: positive streamers and negative Trichel pulses were used for bio-decontamination of Streptococci biofilm and Bacillus cereus spores on polypropylene plastic surfaces. The reduction of bacterial population (evaluated as log10) in the biofilm on plastic surfaces treated by DC corona reached 2.4 logs with 10 min treatment time and 3.3 logs with 2 min treatment time with water spraying. The enhancement of plasma biocidal effects on the biofilm by electro-spraying of water through a hollow needle high-voltage electrode was investigated. No significant polarity effect was found with DC corona. Pulsed corona was demonstrated slightly more bactericidal for spores, especially in the negative polarity where the bacterial population reduction reached up to 2.2 logs at 10 min exposure time. Contribution to the Topical Issue "13th International Symposium on High Pressure Low Temperature Plasma Chemistry (Hakone XIII)", Edited by Nicolas Gherardi, Henryca Danuta Stryczewska and Yvan Ségui.

Contemporary Population-Based Comparison of Localized Ductal Adenocarcinoma and High-Risk Acinar Adenocarcinoma of the Prostate.

PubMed

Packiam, Vignesh T; Patel, Sanjay G; Pariser, Joseph J; Richards, Kyle A; Weiner, Adam B; Paner, Gladell P; VanderWeele, David J; Zagaja, Gregory P; Eggener, Scott E

2015-10-01

To compare pathological characteristics, treatment patterns, and survival in patients with ductal adenocarcinoma (DC) compared to those with acinar adenocarcinoma (AC). Using the National Cancer Database, we identified patients diagnosed with clinically localized (cN0, cM0) pure DC (n = 1328) and AC (n = 751,635) between 1998 and 2011. High-risk AC was defined as Gleason 8-10. Demographic, treatment, pathological, and survival characteristics of patients were compared. Compared to patients with Gleason 8-10 AC, those with DC presented with lower mean prostate-specific antigen (10.3 vs 16.2 ng/mL, P <.001), had similar rates (11.7% vs 11.5%, P = .8) of clinical extra-capsular extension (stage ≥ cT3), and were more likely to undergo prostatectomy (54% vs 36%, P <.001). Compared to patients with Gleason 8-10 AC undergoing prostatectomy, those with DC had more favorable pathology: stage ≥ T3 (39% vs 52%, P <.001), fewer positive lymph nodes (4% vs 11%, P <.001), and fewer positive margins (25% vs 33%, P <.001). On Kaplan-Meier analysis, patients with DC had similar 5-year survival (75.0%, 95% confidence interval [CI] [71.7-78.9]) compared to those with Gleason 8-10 AC (77.1%, 95% CI [76.6%-77.6%], P = .2). On Cox multivariable analysis, patients with Gleason 8-10 AC had a similar risk of death compared to those with DC (hazards ratio = 0.92, 95% CI [0.69-1.23], P = 6). In this large contemporary population-based series, patients with DC of the prostate presented with lower prostate-specific antigen, had more favorable pathological features, and similar overall survival compared to men with Gleason 8-10 AC. Copyright © 2015 Elsevier Inc. All rights reserved.

Usefulness of Circulating Decoy Receptor 3 in Predicting Coronary Artery Disease Severity and Future Major Adverse Cardiovascular Events in Patients With Multivessel Coronary Artery Disease.

PubMed

Chang, Ting-Yung; Hsu, Chien-Yi; Huang, Po-Hsun; Chiang, Chia-Hung; Leu, Hsin-Bang; Huang, Chin-Chou; Chen, Jaw-Wen; Lin, Shing-Jong

2015-10-01

Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor superfamily, is an antiapoptotic soluble receptor considered to play an important role in immune modulation and has pro-inflammatory functions. This study was designed to test whether circulating DcR3 levels are associated with coronary artery disease (CAD) severity and predict future major adverse cardiovascular events (MACEs) in patients with CAD. Circulating DcR3 levels and the Syntax score (SXscore) were determined in patients with multivessel CAD. The primary end point was the MACE within 12 months. In total, 152 consecutive patients with angiographically confirmed multivessel CAD who had received percutaneous coronary intervention were enrolled and were divided into 3 groups according to CAD lesion severity. Group 1 was defined as low SXscore (≤13), group 2 as intermediate SXscore (>13 and ≤22), and group 3 as high SXscore (>22). DcR3 levels were significantly higher in the high SXscore group than the other 2 groups (13,602 ± 7,256 vs 8,025 ± 7,789 vs 4,637 ± 4,403 pg/ml, p <0.001). By multivariate analysis, circulating DcR3 levels were identified as an independent predictor for high SXscore (adjusted odds ratio 1.15, 95% confidence interval 1.09 to 1.21; p <0.001). The Kaplan-Meier analysis showed that increased circulating DcR3 levels are associated with enhanced 1-year MACE in patients with multivessel CAD (log-rank p <0.001). In conclusion, increased circulating DcR3 levels are associated with CAD severity and predict future MACE in patients with multivessel CAD. Copyright © 2015 Elsevier Inc. All rights reserved.

Pivotal role of PGE2 and IL-10 in the cross-regulation of dendritic cell-derived inflammatory mediators.

PubMed

Harizi, Hedi; Gualde, Norbert

2006-08-01

Exposure to pathogens induces antigen-presenting cells (APC) such as macrophages and dendritic cells (DC) to produce various endogenous mediators, including arachidonic acid (AA)-derived eicosanoids, cytokines, and nitric oxide (NO). Many secreted products of activated APC can act by themselves in an autocrine manner and modulate their function. Moreover, the cross-interaction between endogenous bioactive molecules regulates the function of professional APC with important consequences for their ability to activate and sustain immune and inflammatory responses, and to regulate immune homeostasis. Although neglected for many years when compared to their role in cardiovascular homeostasis, cancer and inflammation, the importance of eicosanoids in immunology is becoming more defined. The role of prostaglandin (PG) E2 (PGE2), one of the best known and most well studied eicosanoids, is of particular interest. It modulates the activities of professional DC by acting on their differentiation, maturation and their ability to secrete cytokines. Uniquely among haematopoietic cytokines, interleukin-10 (IL-10) is a pleiotropic molecule that displays both immunostimulatory and immunoregulatory activities. IL-10 has attached much attention because of its anti-inflammatory properties. It modulates expression of cytokines, soluble mediators and cell surface molecules by cells of myeloid origin, particularly macrophages and DC. We previously reported that PGE2 is a potent inducer of IL-10 in bone marrow-derived DC (BM-DC), and PGE2-induced IL-10 is a key regulator of the BM-DC pro-inflammatory phenotype. BM-DC may be considered as an important model to study complex interactions between endogenous mediators, and autocrine IL-10 plays a pivotal role in the crossregulation of AA-derived lipid mediators, cytokines, and NO, with critical effects on immune and inflammatory responses.

Toll-like receptors 2 and 4 contribute to sepsis-induced depletion of spleen dendritic cells.

PubMed

Pène, Frédéric; Courtine, Emilie; Ouaaz, Fatah; Zuber, Benjamin; Sauneuf, Bertrand; Sirgo, Gonzalo; Rousseau, Christophe; Toubiana, Julie; Balloy, Viviane; Chignard, Michel; Mira, Jean-Paul; Chiche, Jean-Daniel

2009-12-01

Depletion of dendritic cells (DC) in secondary lymphoid organs is a hallmark of sepsis-induced immune dysfunction. In this setting, we investigated if Toll-like receptor (TLR)-dependent signaling might modulate the maturation process and the survival of DC. Using a model of sublethal polymicrobial sepsis induced by cecal ligation and puncture, we investigated the quantitative and functional features of spleen DC in wild-type, TLR2(-/-), TLR4(-/-), and TLR2(-/-) TLR4(-/-) mice. By 24 h, a decrease in the relative percentage of CD11c(high) spleen DC occurred in wild-type mice but was prevented in TLR2(-/-), TLR4(-/-), and TLR2(-/-) TLR4(-/-) mice. In wild-type mice, sepsis dramatically affected both CD11c(+) CD8alpha(+) and CD11c(+) CD8alpha(-) subsets. In all three types of knockout mice studied, the CD11c(+) CD8alpha(+) subset followed a depletion pattern similar to that for wild-type mice. In contrast, the loss of CD11c(+) CD8alpha(-) cells was attenuated in TLR2(-/-) and TLR4(-/-) mice and completely prevented in TLR2(-/-) TLR4(-/-) mice. Accordingly, apoptosis of spleen DC was increased in septic wild-type mice and inhibited in knockout mice. In addition we characterized the functional features of spleen DC obtained from septic mice. As shown by increased expression of major histocompatibility complex class II and CD86, polymicrobial sepsis induced maturation of DC, with subsequent increased capacity to prime T lymphocytes, similarly in wild-type and knockout mice. In response to CpG DNA stimulation, production of interleukin-12 was equally impaired in DC obtained from wild-type and knockout septic mice. In conclusion, although dispensable for the DC maturation process, TLR2 and TLR4 are involved in the mechanisms leading to depletion of spleen DC following polymicrobial sepsis.

Liberal Arts: Carrier Pigeon or Albatross?

ERIC Educational Resources Information Center

Koch, Moses S.

1977-01-01

Liberal arts educators must direct their energies more toward defining the human condition than toward simply recreating its past glories. The liberal arts must prepare students for the future, as well as acquaint them with the past and must incorporate discussions of today's ethical concerns. (DC)

Infinity: The Twilight Zone of Mathematics.

ERIC Educational Resources Information Center

Love, William P.

1989-01-01

The theorems and proofs presented are designed to enhance student understanding of the theory of infinity as developed by Cantor and others. Three transfinite numbers are defined to express the cardinality of infinite algebraic sets, infinite sets of geometric points and infinite sets of functions. (DC)

Decidualization and angiogenesis in early pregnancy: unravelling the functions of DC and NK cells.

PubMed

Blois, Sandra M; Klapp, Burghard F; Barrientos, Gabriela

2011-03-01

Differentiation of endometrial stromal cells and formation of new maternal blood vessels at the time of embryo implantation are critical for the establishment and maintenance of gestation. The regulatory functions of decidual leukocytes during early pregnancy, particularly dendritic cells (DC) and NK cells, may be important not only for the generation of maternal immunological tolerance but also in the regulation of stromal cell differentiation and the vascular responses associated with the implantation process. However, the specific contributions of DC and NK cells during implantation are still difficult to dissect mainly due to reciprocal regulatory interactions established between them within the decidualizing microenvironment. The present review article discusses current evidence on the regulatory pathways driving decidualization in mice, suggesting that NK cells promote uterine vascular modifications that assist decidual growth but DC directly control stromal cell proliferation, angiogenesis and the homing and maturation of NK cell precursors in the pregnant uterus. Thus, successful implantation appears to result from an interplay between cellular components of the decidualizing endometrium involving immunoregulatory and pro-angiogenic functions of DC and NK cells. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

The MSPICE simulation of a saturating transformer

NASA Astrophysics Data System (ADS)

Maclean, David N.

A transformer is simulated using a nonlinear saturating magnetic model. Hysteresis and gradual smooth reduction of core permeability are achieved with standard SPICE networks and functions. The equations that define the nonlinear inductance and the MSPICE circuits used to simulate them are derived. A hierarchy of circuit complexity that is based on the structured logic design subcircuit method is used. An example of a push-pull buck regulator being operated in an unbalanced condition is given. Noise ripple on the input power cable generates a dc offset current in the transformer. The example demonstrates how avionics power equipment can be evaluated for large-signal ac, dc, and transient behavior.

Editorial [Special issue on software defined networks and infrastructures, network function virtualisation, autonomous systems and network management

DOE PAGES

Biswas, Amitava; Liu, Chen; Monga, Inder; ...

2016-01-01

For last few years, there has been a tremendous growth in data traffic due to high adoption rate of mobile devices and cloud computing. Internet of things (IoT) will stimulate even further growth. This is increasing scale and complexity of telecom/internet service provider (SP) and enterprise data centre (DC) compute and network infrastructures. As a result, managing these large network-compute converged infrastructures is becoming complex and cumbersome. To cope up, network and DC operators are trying to automate network and system operations, administrations and management (OAM) functions. OAM includes all non-functional mechanisms which keep the network running.

Molecular basis for ebolavirus VP35 suppression of human dendritic cell maturation.

PubMed

Yen, Benjamin; Mulder, Lubbertus C F; Martinez, Osvaldo; Basler, Christopher F

2014-11-01

Zaire ebolavirus (EBOV) VP35 is a double-stranded RNA (dsRNA)-binding protein that inhibits RIG-I signaling and alpha/beta interferon (IFN-α/β) responses by both dsRNA-binding-dependent and -independent mechanisms. VP35 also suppresses dendritic cell (DC) maturation. Here, we define the pathways and mechanisms through which VP35 impairs DC maturation. Wild-type VP35 (VP35-WT) and two well-characterized VP35 mutants (F239A and R322A) that independently ablate dsRNA binding and RIG-I inhibition were delivered to primary human monocyte-derived DCs (MDDCs) using a lentivirus-based expression system. VP35-WT suppressed not only IFN-α/β but also proinflammatory responses following stimulation of MDDCs with activators of RIG-I-like receptor (RLR) signaling, including RIG-I activators such as Sendai virus (SeV) or 5'-triphosphate RNA, or MDA5 activators such as encephalomyocarditis virus (EMCV) or poly(I · C). The F239A and R322A mutants exhibited greatly reduced suppression of IFN-α/β and proinflammatory cytokine production following treatment of DCs with RLR agonists. VP35-WT also blocked the upregulation of DC maturation markers and the stimulation of allogeneic T cell responses upon SeV infection, whereas the mutants did not. In contrast to the RLR activators, VP35-WT and the VP35 mutants impaired IFN-β production induced by Toll-like receptor 3 (TLR3) or TLR4 agonists but failed to inhibit proinflammatory cytokine production induced by TLR2, TLR3, or TLR4 agonists. Furthermore, VP35 did not prevent lipopolysaccharide (LPS)-induced upregulation of surface markers of MDDC maturation and did not prevent LPS-triggered allogeneic T cell stimulation. Therefore, VP35 is a general antagonist of DC responses to RLR activation. However, TLR agonists can circumvent many of the inhibitory effects of VP35. Therefore, it may be possible to counteract EBOV immune evasion by using treatments that bypass the VP35-imposed block to DC maturation. The VP35 protein, which is an inhibitor of RIG-I signaling and alpha/beta interferon (IFN-α/β) responses, has been implicated as an EBOV-encoded factor that contributes to suppression of dendritic cell (DC) function. We used wild-type VP35 and previously characterized VP35 mutants to clarify VP35-DC interactions. Our data demonstrate that VP35 is a general inhibitor of RIG-I-like receptor (RLR) signaling that blocks not only RIG-I- but also MDA5-mediated induction of IFN-α/β responses. Furthermore, in DCs, VP35 also impairs the RLR-mediated induction of proinflammatory cytokine production, upregulation of costimulatory markers, and activation of T cells. These inhibitory activities require VP35 dsRNA-binding activity, an activity previously correlated to VP35 RIG-I inhibitory function. In contrast, while VP35 can inhibit IFN-α/β production induced by TLR3 or TLR4 agonists, this occurs in a dsRNA-independent fashion, and VP35 does not inhibit TLR-mediated expression of proinflammatory cytokines. These data suggest strategies to overcome VP35 inhibition of DC function. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Plasmacytoid dendritic cell interferon-α production to R-848 stimulation is decreased in male infants.

PubMed

Wang, Jennifer P; Zhang, Lei; Madera, Rachel F; Woda, Marcia; Libraty, Daniel H

2012-07-06

Sex differences in response to microbial infections, especially viral ones, may be associated with Toll-like receptor (TLR)-mediated responses by plasmacytoid dendritic cells (pDCs). In this study, we identified sex differences in human infant pDC interferon-α production following challenge with the TLR7/8 agonist R-848. Male pDC responses were significantly lower than those of females during early infancy. This difference may be attributed to the androgen surge experienced by males during the early infancy period. Pretreatment of human pDCs with dihydrotestosterone produced a significant reduction in interferon-α production following R-848 challenge. Androgen-mediated regulation of pDC TLR7-driven innate immune responses may contribute to the observed sex differences in response to infections during early infancy.

Exogenous Thyropin from p41 Invariant Chain Diminishes Cysteine Protease Activity and Affects IL-12 Secretion during Maturation of Human Dendritic Cells

PubMed Central

Zavašnik-Bergant, Tina; Bergant Marušič, Martina

2016-01-01

Dendritic cells (DC) play a pivotal role as antigen presenting cells (APC) and their maturation is crucial for effectively eliciting an antigen-specific immune response. The p41 splice variant of MHC class II-associated chaperone, called invariant chain p41 Ii, contains an amino acid sequence, the p41 fragment, which is a thyropin-type inhibitor of proteolytic enzymes. The effects of exogenous p41 fragment and related thyropin inhibitors acting on human immune cells have not been reported yet. In this study we demonstrate that exogenous p41 fragment can enter the endocytic pathway of targeted human immature DC. Internalized p41 fragment has contributed to the total amount of the immunogold labelled p41 Ii-specific epitope, as quantified by transmission electron microscopy, in particular in late endocytic compartments with multivesicular morphology where antigen processing and binding to MHC II take place. In cell lysates of treated immature DC, diminished enzymatic activity of cysteine proteases has been confirmed. Internalized exogenous p41 fragment did not affect the perinuclear clustering of acidic cathepsin S-positive vesicles typical of mature DC. p41 fragment is shown to interfere with the nuclear translocation of NF-κB p65 subunit in LPS-stimulated DC. p41 fragment is also shown to reduce the secretion of interleukin-12 (IL-12/p70) during the subsequent maturation of treated DC. The inhibition of proteolytic activity of lysosomal cysteine proteases in immature DC and the diminished capability of DC to produce IL-12 upon their subsequent maturation support the immunomodulatory potential of the examined thyropin from p41 Ii. PMID:26960148

Effector and regulatory dendritic cells display distinct patterns of miRNA expression.

PubMed

Lombardi, Vincent; Luce, Sonia; Moussu, Hélène; Morizur, Lise; Gueguen, Claire; Neukirch, Catherine; Chollet-Martin, Sylvie; Mascarell, Laurent; Aubier, Michel; Baron-Bodo, Véronique; Moingeon, Philippe

2017-09-01

MicroRNAs (miRNAs) contribute to the regulation of dendritic cell (DC) polarization, thereby influencing the balance of adaptive immune responses. Herein, we studied the expression of miRNAs in polarized DCs and analyzed whether expression of these miRNAs could be associated with allergic rhinitis and allergen immunotherapy (AIT) outcome. Using specific culture conditions, we differentiated immature human monocyte-derived DCs into DC1, DC2, and DCreg subsets (supporting the differentiation of T H 1, T H 2 or regulatory T cells, respectively). Profiling of miRNA expression was performed in these DC subpopulations using microarrays. Levels of miRNAs specific for polarized DCs were then evaluated in a cohort of 58 patients with allergic rhinitis and 25 non-allergic controls, as well as in samples from 30 subjects treated with sublingual grass pollen tablets or placebo for four months. We successfully identified 16 miRNAs differentially regulated between immature DCs, DC1, DC2, and DCreg cells. In allergic rhinoconjunctivitis patients, the expression of two of those miRNAs (miR-132 and miR-155), was down-regulated compared to non-allergic individuals. However, the levels of these miRNAs were not significantly modified following four months of grass pollen immunotherapy. Studying polarized DCs and clinical samples from subjects with or without allergic rhinoconjunctivitis, we demonstrated that the expression of two miRNAs linked to effector DCs (i.e., DC1 and/or DC2 cells), was reduced in the blood of patients with allergic rhinoconjunctivitis. Nevertheless, these miRNAs did not represent relevant biomarkers to predict or follow-up AIT efficacy. © 2017 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

Effector and regulatory dendritic cells display distinct patterns of miRNA expression

PubMed Central

Luce, Sonia; Moussu, Hélène; Morizur, Lise; Gueguen, Claire; Neukirch, Catherine; Chollet‐Martin, Sylvie; Mascarell, Laurent; Aubier, Michel; Baron‐Bodo, Véronique; Moingeon, Philippe

2017-01-01

Abstract Introduction MicroRNAs (miRNAs) contribute to the regulation of dendritic cell (DC) polarization, thereby influencing the balance of adaptive immune responses. Herein, we studied the expression of miRNAs in polarized DCs and analyzed whether expression of these miRNAs could be associated with allergic rhinitis and allergen immunotherapy (AIT) outcome. Method Using specific culture conditions, we differentiated immature human monocyte‐derived DCs into DC1, DC2, and DCreg subsets (supporting the differentiation of TH1, TH2 or regulatory T cells, respectively). Profiling of miRNA expression was performed in these DC subpopulations using microarrays. Levels of miRNAs specific for polarized DCs were then evaluated in a cohort of 58 patients with allergic rhinitis and 25 non‐allergic controls, as well as in samples from 30 subjects treated with sublingual grass pollen tablets or placebo for four months. Results We successfully identified 16 miRNAs differentially regulated between immature DCs, DC1, DC2, and DCreg cells. In allergic rhinoconjunctivitis patients, the expression of two of those miRNAs (miR‐132 and miR‐155), was down‐regulated compared to non‐allergic individuals. However, the levels of these miRNAs were not significantly modified following four months of grass pollen immunotherapy. Conclusions Studying polarized DCs and clinical samples from subjects with or without allergic rhinoconjunctivitis, we demonstrated that the expression of two miRNAs linked to effector DCs (i.e., DC1 and/or DC2 cells), was reduced in the blood of patients with allergic rhinoconjunctivitis. Nevertheless, these miRNAs did not represent relevant biomarkers to predict or follow‐up AIT efficacy. PMID:28497578

DNA and protein co-administration induces tolerogenic dendritic cells through DC-SIGN mediated negative signals.

PubMed

Li, Jinyao; Geng, Shuang; Liu, Xiuping; Liu, Hu; Jin, Huali; Liu, Chang-Gong; Wang, Bin

2013-10-01

We previously demonstrated that DNA and protein co-administration induced differentiation of immature dendritic cells (iDCs) into CD11c(+)CD40(low)IL-10(+) regulatory DCs (DCregs) via the caveolin-1 (Cav-1) -mediated signal pathway. Here, we demonstrate that production of IL-10 and the low expression of CD40 play a critical role in the subsequent induction of regulatory T cells (Tregs) by the DCregs. We observed that DNA and protein were co-localized with DC-SIGN in caveolae and early lysosomes in the treated DCs, as indicated by co-localization with Cav-1 and EEA-1 compartment markers. DNA and protein also co-localized with LAMP-2. Gene-array analysis of gene expression showed that more than a thousand genes were significantly changed by the DC co-treatment with DNA + protein compared with controls. Notably, the level of DC-SIGN expression was dramatically upregulated in pOVA + OVA co-treated DCs. The expression levels of Rho and Rho GNEF, the down-stream molecules of DC-SIGN mediated signal pathway, were also greatly upregulated. Further, the level of TLR9, the traditional DNA receptor, was significantly downregulated. These results suggest that DC-SIGN as the potential receptor for DNA and protein might trigger the negative pathway to contribute the induction of DCreg combining with Cav-1 mediated negative signal pathway.

DNA and protein co-administration induces tolerogenic dendritic cells through DC-SIGN mediated negative signals

PubMed Central

Li, Jinyao; Geng, Shuang; Liu, Xiuping; Liu, Hu; Jin, Huali; Liu, Chang-Gong; Wang, Bin

2013-01-01

We previously demonstrated that DNA and protein co-administration induced differentiation of immature dendritic cells (iDCs) into CD11c+CD40lowIL-10+ regulatory DCs (DCregs) via the caveolin-1 (Cav-1) -mediated signal pathway. Here, we demonstrate that production of IL-10 and the low expression of CD40 play a critical role in the subsequent induction of regulatory T cells (Tregs) by the DCregs. We observed that DNA and protein were co-localized with DC-SIGN in caveolae and early lysosomes in the treated DCs, as indicated by co-localization with Cav-1 and EEA-1 compartment markers. DNA and protein also co-localized with LAMP-2. Gene-array analysis of gene expression showed that more than a thousand genes were significantly changed by the DC co-treatment with DNA + protein compared with controls. Notably, the level of DC-SIGN expression was dramatically upregulated in pOVA + OVA co-treated DCs. The expression levels of Rho and Rho GNEF, the down-stream molecules of DC-SIGN mediated signal pathway, were also greatly upregulated. Further, the level of TLR9, the traditional DNA receptor, was significantly downregulated. These results suggest that DC-SIGN as the potential receptor for DNA and protein might trigger the negative pathway to contribute the induction of DCreg combining with Cav-1 mediated negative signal pathway. PMID:24051433

Immature, Semi-Mature, and Fully Mature Dendritic Cells: Toward a DC-Cancer Cells Interface That Augments Anticancer Immunity

PubMed Central

Dudek, Aleksandra M.; Martin, Shaun; Garg, Abhishek D.; Agostinis, Patrizia

2013-01-01

Dendritic cells (DCs) are the sentinel antigen-presenting cells of the immune system; such that their productive interface with the dying cancer cells is crucial for proper communication of the “non-self” status of cancer cells to the adaptive immune system. Efficiency and the ultimate success of such a communication hinges upon the maturation status of the DCs, attained following their interaction with cancer cells. Immature DCs facilitate tolerance toward cancer cells (observed for many apoptotic inducers) while fully mature DCs can strongly promote anticancer immunity if they secrete the correct combinations of cytokines [observed when DCs interact with cancer cells undergoing immunogenic cell death (ICD)]. However, an intermediate population of DC maturation, called semi-mature DCs exists, which can potentiate either tolerogenicity or pro-tumorigenic responses (as happens in the case of certain chemotherapeutics and agents exerting ambivalent immune reactions). Specific combinations of DC phenotypic markers, DC-derived cytokines/chemokines, dying cancer cell-derived danger signals, and other less characterized entities (e.g., exosomes) can define the nature and evolution of the DC maturation state. In the present review, we discuss these different maturation states of DCs, how they might be attained and which anticancer agents or cell death modalities (e.g., tolerogenic cell death vs. ICD) may regulate these states. PMID:24376443

The First National Student Conference: NASA University Research Centers at Minority Institutions

NASA Technical Reports Server (NTRS)

Daso, Endwell O. (Editor); Mebane, Stacie (Editor)

1997-01-01

The conference includes contributions from 13 minority universities with NASA University Research Centers. Topics discussed include: leadership, survival strategies, life support systems, food systems, simulated hypergravity, chromium diffusion doping, radiation effects on dc-dc converters, metal oxide glasses, crystal growth of Bil3, science and communication on wheels, semiconductor thin films, numerical solution of random algebraic equations, fuzzy logic control, spatial resolution of satellite images, programming language development, nitric oxide in the thermosphere and mesosphere, high performance polyimides, crossover control in genetic algorithms, hyperthermal ion scattering, etc.

Does trans‐spinal and local DC polarization affect presynaptic inhibition and post‐activation depression?

PubMed Central

Kaczmarek, D.; Ristikankare, J.

2017-01-01

Key points Trans‐spinal polarization was recently introduced as a means to improve deficient spinal functions. However, only a few attempts have been made to examine the mechanisms underlying DC actions. We have now examined the effects of DC on two spinal modulatory systems, presynaptic inhibition and post‐activation depression, considering whether they might weaken exaggerated spinal reflexes and enhance excessively weakened ones.Direct current effects were evoked by using local intraspinal DC application (0.3–0.4 μA) in deeply anaesthetized rats and were compared with the effects of trans‐spinal polarization (0.8–1.0 mA).Effects of local intraspinal DC were found to be polarity dependent, as locally applied cathodal polarization enhanced presynaptic inhibition and post‐activation depression, whereas anodal polarization weakened them. In contrast, both cathodal and anodal trans‐spinal polarization facilitated them.The results suggest some common DC‐sensitive mechanisms of presynaptic inhibition and post‐activation depression, because both were facilitated or depressed by DC in parallel. Abstract Direct current (DC) polarization has been demonstrated to alleviate the effects of various deficits in the operation of the central nervous system. However, the effects of trans‐spinal DC stimulation (tsDCS) have been investigated less extensively than the effects of transcranial DC stimulation, and their cellular mechanisms have not been elucidated. The main objectives of this study were, therefore, to extend our previous analysis of DC effects on the excitability of primary afferents and synaptic transmission by examining the effects of DC on two spinal modulatory feedback systems, presynaptic inhibition and post‐activation depression, in an anaesthetized rat preparation. Other objectives were to compare the effects of locally and trans‐spinally applied DC (locDC and tsDCS). Local polarization at the sites of terminal branching of afferent fibres was found to induce polarity‐dependent actions on presynaptic inhibition and post‐activation depression, as cathodal locDC enhanced them and anodal locDC depressed them. In contrast, tsDCS modulated presynaptic inhibition and post‐activation depression in a polarity‐independent fashion because both cathodal and anodal tsDCS facilitated them. The results show that the local presynaptic actions of DC might counteract both excessively strong and excessively weak monosynaptic actions of group Ia and cutaneous afferents. However, they indicate that trans‐spinally applied DC might counteract the exaggerated spinal reflexes but have an adverse effect on pathologically weakened spinal activity by additional presynaptic weakening. The results are also relevant for the analysis of the basic properties of presynaptic inhibition and post‐activation depression because they indicate that some common DC‐sensitive mechanisms contribute to them. PMID:27891626

[The use of the sequential mathematical analysis for the determination of the driver's seat position inside the car passenger compartment from the injuries to the extremities in the case of a traffic accident].

PubMed

Habova, K; Smirenin, Eksp; Fetisov, D; Tamberg, Eksp

2015-01-01

The objective of the present study was to determine the diagnostic coefficients (DC) for the injuries to the upper and lower extremities of the vehicle drivers inflicted inside the passenger compartment in the case of a traffic accident. We have analysed the archival expert documents collected from 45 regional bureaus of forensic medical expertise during the period from 1995 to 2014 that contained the results of examination of 200 corpses and 300 survivors who had suffered injuries in the traffic accidents. The statistical and mathematical treatment of these materials with the use of sequential mathematical analysis based on the Bayes and Wald formulas yielded diagnostic coefficients that make it possible to elucidate the most informative features characterizing the driver of a vehicle. In case of a lethal outcome, the most significant injuries include bleeding from the posterior left elbow region (DC +7.6), skin scratches on the palm surface of the right wrist (DC +7.6), bleeding from the postrerior region of the left lower leg (DC +7.6), wounds on the dorsal surface of the left wrist (DC +6.3), bruises at the anterior surface of the left knee (DC +6.3), etc. The most informative features in the survivals of the traffic accidents are bone fractures (DC +7.0), tension of ligaments and dislocation of the right talocrural joint (DC +6.5), fractures of the left kneecap and left tibial epiphysis (DC +5.4), hemorrhage and bruises in the anterior right knee region (DC + 5.4 each), skin scratches in the right posterior carpal region (DC +5.1). It is concluded that the use of the diagnostic coefficients makes it possible to draw the attention of the experts to the above features and to objectively determine the driver's seat position inside the car passenger compartment in the case of a traffic accident. Moreover such an approach contributes to the improvement of the quality of expert conclusions and the results of forensic medical expertise of the circumstance of traffic accidents.

Dendritic Cell Response to HIV-1 Is Controlled by Differentiation Programs in the Cells and Strain-Specific Properties of the Virus.

PubMed

Nasi, Aikaterini; Amu, Sylvie; Göthlin, Mårten; Jansson, Marianne; Nagy, Noemi; Chiodi, Francesca; Réthi, Bence

2017-01-01

Dendritic cells (DCs) are potent antigen-presenting cells that might play contradictory roles during HIV-1 infection, contributing not only to antiviral immunity but also to viral dissemination and immune evasion. Although DCs are characterized by enormous functional diversity, it has not been analyzed how differentially programmed DCs interact with HIV-1. We have previously described the reprogramming of DC development by endogenously produced lactic acid that accumulated in a cell culture density-dependent manner and provided a long-lasting anti-inflammatory signal to the cells. By exploiting this mechanism, we generated immunostimulatory DCs characterized by the production of TH1 polarizing and inflammatory mediators or, alternatively, suppressed DCs that produce IL-10 upon activation, and we tested the interaction of these DC types with different HIV-1 strains. Cytokine patterns were monitored in HIV-1-exposed DC cultures. Our results showed that DCs receiving suppressive developmental program strongly upregulated their capacity to produce the TH1 polarizing cytokine IL-12 and the inflammatory chemokines CCL2 and CCL7 upon interaction with HIV-1 strains IIIB and SF162. On the contrary, HIV-1 abolished cytokine production in the more inflammatory DC types. Preincubation of the cells with the HIV-1 proteins gp120 and Nef could inhibit IL-12 production irrespectively of the tested DC types, whereas MyD88- and TRIF-dependent signals stimulated IL-12 production in the suppressed DC type only. Rewiring of DC cytokines did not require DC infections or ligation of the HIV-1 receptor CD209. A third HIV-1 strain, BaL, could not modulate DC cytokines in a similar manner indicating that individual HIV-1 strains can differ in their capacity to influence DCs. Our results demonstrated that HIV-1 could not induce definite and invariable modulatory programs in DCs. Instead, interaction with the virus triggered different responses in different DC types. Thus, the outcome of DC-HIV-1 interactions might be highly variable, shaped by endogenous features of the cells and diversity of the virus.

Dendritic Cell Response to HIV-1 Is Controlled by Differentiation Programs in the Cells and Strain-Specific Properties of the Virus

PubMed Central

Nasi, Aikaterini; Amu, Sylvie; Göthlin, Mårten; Jansson, Marianne; Nagy, Noemi; Chiodi, Francesca; Réthi, Bence

2017-01-01

Dendritic cells (DCs) are potent antigen-presenting cells that might play contradictory roles during HIV-1 infection, contributing not only to antiviral immunity but also to viral dissemination and immune evasion. Although DCs are characterized by enormous functional diversity, it has not been analyzed how differentially programmed DCs interact with HIV-1. We have previously described the reprogramming of DC development by endogenously produced lactic acid that accumulated in a cell culture density-dependent manner and provided a long-lasting anti-inflammatory signal to the cells. By exploiting this mechanism, we generated immunostimulatory DCs characterized by the production of TH1 polarizing and inflammatory mediators or, alternatively, suppressed DCs that produce IL-10 upon activation, and we tested the interaction of these DC types with different HIV-1 strains. Cytokine patterns were monitored in HIV-1-exposed DC cultures. Our results showed that DCs receiving suppressive developmental program strongly upregulated their capacity to produce the TH1 polarizing cytokine IL-12 and the inflammatory chemokines CCL2 and CCL7 upon interaction with HIV-1 strains IIIB and SF162. On the contrary, HIV-1 abolished cytokine production in the more inflammatory DC types. Preincubation of the cells with the HIV-1 proteins gp120 and Nef could inhibit IL-12 production irrespectively of the tested DC types, whereas MyD88- and TRIF-dependent signals stimulated IL-12 production in the suppressed DC type only. Rewiring of DC cytokines did not require DC infections or ligation of the HIV-1 receptor CD209. A third HIV-1 strain, BaL, could not modulate DC cytokines in a similar manner indicating that individual HIV-1 strains can differ in their capacity to influence DCs. Our results demonstrated that HIV-1 could not induce definite and invariable modulatory programs in DCs. Instead, interaction with the virus triggered different responses in different DC types. Thus, the outcome of DC-HIV-1 interactions might be highly variable, shaped by endogenous features of the cells and diversity of the virus. PMID:28348557

Runx1 and Cbfβ regulate the development of Flt3+ dendritic cell progenitors and restrict myeloproliferative disorder

PubMed Central

Satpathy, Ansuman T.; Briseño, Carlos G.; Cai, Xiongwei; Michael, Drew G.; Chou, Chun; Hsiung, Sunnie; Bhattacharya, Deepta; Speck, Nancy A.

2014-01-01

Runx1 and Cbfβ are critical for the establishment of definitive hematopoiesis and are implicated in leukemic transformation. Despite the absolute requirements for these factors in the development of hematopoietic stem cells and lymphocytes, their roles in the development of bone marrow progenitor subsets have not been defined. Here, we demonstrate that Cbfβ is essential for the development of Flt3+ macrophage-dendritic cell (DC) progenitors in the bone marrow and all DC subsets in the periphery. Besides the loss of DC progenitors, pan-hematopoietic Cbfb-deficient mice also lack CD105+ erythroid progenitors, leading to severe anemia at 3 to 4 months of age. Instead, Cbfb deficiency results in aberrant progenitor differentiation toward granulocyte-macrophage progenitors (GMPs), resulting in a myeloproliferative phenotype with accumulation of GMPs in the periphery and cellular infiltration of the liver. Expression of the transcription factor Irf8 is severely reduced in Cbfb-deficient progenitors, and overexpression of Irf8 restors DC differentiation. These results demonstrate that Runx proteins and Cbfβ restrict granulocyte lineage commitment to facilitate multilineage hematopoietic differentiation and thus identify their novel tumor suppressor function in myeloid leukemia. PMID:24677539

Assessment of Airborne Instrument Uncertainty via Measurement Comparisons Conducted During the DC3 and SEAC4RS Field Campaigns

NASA Astrophysics Data System (ADS)

Silverman, M. L.; Chen, G.; Shook, M.

2016-12-01

Airborne field campaigns have long understood the importance of well-defined measurement uncertainties and their impact on scientific research. Measurement comparisons are an effective way to assess the uncertainty of different techniques as well as gain insight into instrument performance. As part of the NASA DC3 (Deep Convective Clouds and Chemistry) airborne field campaign, there were several wing-tip-to-wing-tip formation flight segments designed for measurement comparison of the instruments onboard the NASA DC-8 and NSF/NCAR Gulfstream-V aircraft. This provides the opportunity to evaluate the consistency between multiple measurements of the same species/parameters on different platforms and based on different measurement techniques. The DC-8 aircraft was also instrumented with duplicate measurements of the same species, allowing for intraplatform comparisons. The NASA DC-8 was also used during the NASA SEAC4RS (Studies of Emission and Atmospheric Composition, Clouds, and Climate Coupling by Regional Surveys) airborne field campaign. While no wing-tip to wing-tip flights were flown, several instruments measuring the same species were aboard the DC-8 providing intraplatform comparisons. Time series and correlations are produced to show the relative agreement between the measurements both on a daily basis and over the course of the five inter-comparison days. We have also used a data-driven approach to analyze the instrument precisions as an important part of measurement uncertainty assessment. By conducting these analyses we provide insight to users on the quality of the measurements.

A domain-centric solution to functional genomics via dcGO Predictor

PubMed Central

2013-01-01

Background Computational/manual annotations of protein functions are one of the first routes to making sense of a newly sequenced genome. Protein domain predictions form an essential part of this annotation process. This is due to the natural modularity of proteins with domains as structural, evolutionary and functional units. Sometimes two, three, or more adjacent domains (called supra-domains) are the operational unit responsible for a function, e.g. via a binding site at the interface. These supra-domains have contributed to functional diversification in higher organisms. Traditionally functional ontologies have been applied to individual proteins, rather than families of related domains and supra-domains. We expect, however, to some extent functional signals can be carried by protein domains and supra-domains, and consequently used in function prediction and functional genomics. Results Here we present a domain-centric Gene Ontology (dcGO) perspective. We generalize a framework for automatically inferring ontological terms associated with domains and supra-domains from full-length sequence annotations. This general framework has been applied specifically to primary protein-level annotations from UniProtKB-GOA, generating GO term associations with SCOP domains and supra-domains. The resulting 'dcGO Predictor', can be used to provide functional annotation to protein sequences. The functional annotation of sequences in the Critical Assessment of Function Annotation (CAFA) has been used as a valuable opportunity to validate our method and to be assessed by the community. The functional annotation of all completely sequenced genomes has demonstrated the potential for domain-centric GO enrichment analysis to yield functional insights into newly sequenced or yet-to-be-annotated genomes. This generalized framework we have presented has also been applied to other domain classifications such as InterPro and Pfam, and other ontologies such as mammalian phenotype and disease ontology. The dcGO and its predictor are available at http://supfam.org/SUPERFAMILY/dcGO including an enrichment analysis tool. Conclusions As functional units, domains offer a unique perspective on function prediction regardless of whether proteins are multi-domain or single-domain. The 'dcGO Predictor' holds great promise for contributing to a domain-centric functional understanding of genomes in the next generation sequencing era. PMID:23514627

Interorganizational Collaborative Capacity: Development of a Database to Refine Instrumentation and Explore Patterns

DTIC Science & Technology

2009-08-24

of some defined population […].” ( Thorndike , 1971, p. 533). Norms in this context would allow an organization to understand its relative standing on...York: McGraw-Hill. Thorndike , R. L. (1971). Educational Measurement (2nd Ed.). Washington, DC: American Council on Education. Undersecretary for

7 CFR 1755.405 - Voiceband data transmission measurements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... inspection during normal business hours at RUS, room 2845, U.S. Department of Agriculture, STOP 1598..., room 2845, U.S. Department of Agriculture, STOP 1598, Washington, DC 20250-1598, or at the National... (RED). (3) EDD is specifically defined as the delay relative to the envelope delay at the reference...

7 CFR 1755.405 - Voiceband data transmission measurements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... inspection during normal business hours at RUS, room 2845, U.S. Department of Agriculture, STOP 1598..., room 2845, U.S. Department of Agriculture, STOP 1598, Washington, DC 20250-1598, or at the National... (RED). (3) EDD is specifically defined as the delay relative to the envelope delay at the reference...

7 CFR 1755.405 - Voiceband data transmission measurements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... inspection during normal business hours at RUS, room 2845, U.S. Department of Agriculture, STOP 1598..., room 2845, U.S. Department of Agriculture, STOP 1598, Washington, DC 20250-1598, or at the National... (RED). (3) EDD is specifically defined as the delay relative to the envelope delay at the reference...

7 CFR 1755.405 - Voiceband data transmission measurements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... inspection during normal business hours at RUS, room 2845, U.S. Department of Agriculture, STOP 1598..., room 2845, U.S. Department of Agriculture, STOP 1598, Washington, DC 20250-1598, or at the National... (RED). (3) EDD is specifically defined as the delay relative to the envelope delay at the reference...

An Examination of Effective Practice: Moving toward Elimination of Achievement Gaps in Science

ERIC Educational Resources Information Center

Johnson, Carla C.

2009-01-01

This longitudinal study of middle school science teachers explored the relationship between effective science instruction, as defined by the National Science Education Standards (NRC in National science education standards. National Academy Press, Washington, DC, 1996), and student achievement in science. Eleven teachers participated in a three…

10 CFR 810.10 - Grant of specific authorization.

Code of Federal Regulations, 2011 CFR

2011-01-01

... “sensitive nuclear technology” as defined in § 810.3, the requirements of sections 127 and 128 of the Atomic... is required may apply for the authorization to the U.S. Department of Energy, National Nuclear Security Administration, Washington, DC 20585, Attention: Director, Nuclear Transfer and Supplier Policy...

10 CFR 810.10 - Grant of specific authorization.

Code of Federal Regulations, 2010 CFR

2010-01-01

... “sensitive nuclear technology” as defined in § 810.3, the requirements of sections 127 and 128 of the Atomic... is required may apply for the authorization to the U.S. Department of Energy, National Nuclear Security Administration, Washington, DC 20585, Attention: Director, Nuclear Transfer and Supplier Policy...

14 CFR 1215.108 - Defining user service requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... to NASA Headquarters, Code OX, Space Network Division, Washington, DC 20546. Upon review and... submitted in writing to both NASA Headquarters, Code OX, Space Network Division, and GSFC, Code 501.... Request for services within priority groups shall be negotiated with non-NASA users on a first come, first...

Fifteen Reasons To Study Visual Literacy.

ERIC Educational Resources Information Center

Sutton, Ronald E.

This paper is a report on a decade of teaching visual literacy at the American University (Washington, D.C.). Visual literacy is defined as an awareness that comes with appropriate development of basic visual and aural competencies. The 15 reasons for studying visual literacy are perception, drawing, expression, brain awareness, design elements,…

Developing a Predictive Model for Facility Repair Costs on United States Air Force Installations

DTIC Science & Technology

2011-06-01

repair activities at different times ( Durango & Madanat, 2002). Christian and Pandeya (1997) define maintenance as “the effort to keep a device or...Washington DC: Secretary of the Air Force, Financial Management. Durango , P. L., & Madanat, S. M. (2002). Optimal maintenance and repair policies in

Ancestral Mutations Acquired in Refrex-1, a Restriction Factor against Feline Retroviruses, during its Cooption and Domestication

PubMed Central

Ito, Jumpei; Baba, Takuya; Kawasaki, Junna

2015-01-01

ABSTRACT Endogenous retroviruses (ERVs) are remnants of ancestral retroviral infections of germ cells. Retroviral endogenization is an adaptation process for the host genome, and ERVs are gradually attenuated or inactivated by mutation. However, some ERVs that have been “domesticated” by their hosts eventually gain physiological functions, such as placentation or viral resistance. We previously reported the discovery of Refrex-1, a soluble antiretroviral factor in domestic cats that specifically inhibits infection by feline leukemia virus subgroup D (FeLV-D), a chimeric virus of FeLV, and a feline ERV, ERV-DC. Refrex-1 is a truncated envelope protein (Env) encoded by both ERV-DC7 and ERV-DC16 proviral loci. Here, we reconstituted ancestral and functional Env from ERV-DC7 and ERV-DC16 envelope genes (env) by inducing reverse mutations. Unexpectedly, ERV-DC7 and ERV-DC16 full-length Env (ERV-DC7 fl and ERV-DC16 fl), reconstructed by removing stop codons, did not produce infectious viral particles. ERV-DC7 fl and ERV-DC16 fl were highly expressed in cells but were not cleaved into surface subunits (SU) and transmembrane subunits, nor were they incorporated into virions. G407R/N427I-A429T and Y431D substitutions within the SU C-terminal domain of ERV-DC7 fl and ERV-DC16 fl, respectively, caused these dysfunctions. The residues glycine 407 and tyrosine 431 are relatively conserved among infectious gammaretroviruses, and their substitution causes the same dysfunctions as the tested retroviruses. Our results reveal that specific mutations within the SU C-terminal domain suppressed Env cleavage and incorporation into virions and indicate that these mutations contributed to the domestication of Refrex-1 through multistep events that occurred in the postintegration period. IMPORTANCE Domestic cats are colonized with various exogenous retroviruses (exRVs), such as feline leukemia virus (FeLV), and their genomes contain numerous ERVs, some of which are replication-competent proviruses. The feline hosts, exRVs, and ERVs have complicated genetic interactions and provide an interesting field model for triangular relationships: recombination between FeLV and ERV-DC, which is a feline ERV, generated FeLV-D, a chimeric virus, and FeLV-D is restricted by Refrex-1, an antiretroviral factor corresponding to truncated Env of ERV-DC7 and ERV-DC16. Here, we reconstructed ancestral, functional Env from ERV-DC7 and ERV-DC16 env by inducing reverse mutations to elucidate how Refrex-1 was generated from its ancestor. Our results reveal that they were repeatedly inactivated by mutations preventing Env maturation. Our results provide insights into how ERVs were “domesticated” by their hosts and identify the mutations that mediated these evolutions. Notably, experiments that restore inactivated ERVs might uncover previously unrecognized features or properties of retroviruses. PMID:26581999

Codimension-Two Bifurcation Analysis in DC Microgrids Under Droop Control

NASA Astrophysics Data System (ADS)

Lenz, Eduardo; Pagano, Daniel J.; Tahim, André P. N.

This paper addresses local and global bifurcations that may appear in electrical power systems, such as DC microgrids, which recently has attracted interest from the electrical engineering society. Most sources in these networks are voltage-type and operate in parallel. In such configuration, the basic technique for stabilizing the bus voltage is the so-called droop control. The main contribution of this work is a codimension-two bifurcation analysis of a small DC microgrid considering the droop control gain and the power processed by the load as bifurcation parameters. The codimension-two bifurcation set leads to practical rules for achieving a robust droop control design. Moreover, the bifurcation analysis also offers a better understanding of the dynamics involved in the problem and how to avoid possible instabilities. Simulation results are presented in order to illustrate the bifurcation analysis.

Plasmacytoid dendritic cell interferon-α production to R-848 stimulation is decreased in male infants

PubMed Central

2012-01-01

Background Sex differences in response to microbial infections, especially viral ones, may be associated with Toll-like receptor (TLR)-mediated responses by plasmacytoid dendritic cells (pDCs). Results In this study, we identified sex differences in human infant pDC interferon-α production following challenge with the TLR7/8 agonist R-848. Male pDC responses were significantly lower than those of females during early infancy. This difference may be attributed to the androgen surge experienced by males during the early infancy period. Pretreatment of human pDCs with dihydrotestosterone produced a significant reduction in interferon-α production following R-848 challenge. Conclusions Androgen-mediated regulation of pDC TLR7-driven innate immune responses may contribute to the observed sex differences in response to infections during early infancy. PMID:22769054

Dielectric and AC conductivity studies on SrBi4Ti4O15

NASA Astrophysics Data System (ADS)

Jose, Roshan; Saravanan, K. Venkata

2018-05-01

The four layered SrBi4Ti4O15 ceramics which belong to the aurivillius family of oxide was prepared by conventional solid state reaction technique. Analysis of the dielectric data as a function of temperature and frequency revealed normal phase transition. The frequency dependent ac conductivity follows Jonscher's universal power law. Frequency exponent (n), pre-exponential factor (A), bulk dc conductivity (σdc), and hopping frequency (ωp) were determined from the fitting curves. The variation of frequency exponent with temperature indicates that large polaron hopping mechanism up to curie-temperature, then its changes to small polaron hopping. The activation energies were calculated from ac conductivity, bulk dc conductivity and hopping frequency. The activation energies revealed that conductivity had contributions from migrations of oxygen vacancies, bismuth ion vacancies and strontium ion vacancies.

Cause and Prevention of Explosions Involving DC Casting of Aluminum Sheet Ingot

NASA Astrophysics Data System (ADS)

Richter, Ray T.; Ekenes, J. Martin

The casting of aluminum alloy sheet ingot and T-bar presents the potential for some of the most volatile situations that can occur in DC (direct chill) and EMC (Electromagnetic) casting processes. Aluminum Association explosion incident data from over 300 explosions spanning a twenty-year period were reviewed and analyzed looking for common factors and repetitive reasons for explosions. Analysis of explosions occurring during the three stages of sheet ingot casting, `start of cast', `steady state' and `end of cast', were examined and prioritized. Case studies illustrate the need for understanding both technical and non-technical factors contributing to explosions involving molten metal. This paper identifies the major causes of explosions involving DC casting of aluminum alloy sheet ingot and makes recommendations for how to prevent the recurrence of such events and minimize the risk of injury.

Sensing of Immature Particles Produced by Dengue Virus Infected Cells Induces an Antiviral Response by Plasmacytoid Dendritic Cells

PubMed Central

Hillaire, Marine L. B.; Dejnirattisai, Wanwisa; Mongkolsapaya, Juthathip; Screaton, Gavin R.; Davidson, Andrew D.; Dreux, Marlène

2014-01-01

Dengue virus (DENV) is the leading cause of mosquito-borne viral illness and death in humans. Like many viruses, DENV has evolved potent mechanisms that abolish the antiviral response within infected cells. Nevertheless, several in vivo studies have demonstrated a key role of the innate immune response in controlling DENV infection and disease progression. Here, we report that sensing of DENV infected cells by plasmacytoid dendritic cells (pDCs) triggers a robust TLR7-dependent production of IFNα, concomitant with additional antiviral responses, including inflammatory cytokine secretion and pDC maturation. We demonstrate that unlike the efficient cell-free transmission of viral infectivity, pDC activation depends on cell-to-cell contact, a feature observed for various cell types and primary cells infected by DENV, as well as West Nile virus, another member of the Flavivirus genus. We show that the sensing of DENV infected cells by pDCs requires viral envelope protein-dependent secretion and transmission of viral RNA. Consistently with the cell-to-cell sensing-dependent pDC activation, we found that DENV structural components are clustered at the interface between pDCs and infected cells. The actin cytoskeleton is pivotal for both this clustering at the contacts and pDC activation, suggesting that this structural network likely contributes to the transmission of viral components to the pDCs. Due to an evolutionarily conserved suboptimal cleavage of the precursor membrane protein (prM), DENV infected cells release uncleaved prM containing-immature particles, which are deficient for membrane fusion function. We demonstrate that cells releasing immature particles trigger pDC IFN response more potently than cells producing fusion-competent mature virus. Altogether, our results imply that immature particles, as a carrier to endolysosome-localized TLR7 sensor, may contribute to regulate the progression of dengue disease by eliciting a strong innate response. PMID:25340500

Magnification of starting torques of dc motors by maximum power point trackers in photovoltaic systems

NASA Technical Reports Server (NTRS)

Appelbaum, J.; Singer, S.

1989-01-01

A calculation of the starting torque ratio of permanent magnet, series, and shunt-excited dc motors powered by solar cell arrays is presented for two cases, i.e., with and without a maximum-power-point tracker (MPPT). Defining motor torque magnification by the ratio of the motor torque with an MPPT to the motor torque without an MPPT, a magnification of 3 for the permanent magnet motor and a magnification of 7 for both the series and shunt motors are obtained. The study also shows that all motor types are less sensitive to solar insolation variation in systems including MPPTs as compared to systems without MPPTs.

DC-8 Airborne Laboratory arrival at NASA Dryden

NASA Image and Video Library

1997-12-29

NASA's DC-8 Airborne Science platform landed at Edwards Air Force Base, California, to join the fleet of aircraft at NASA's Dryden Flight Research Center. The white aircraft with a blue stripe running horizontally from the nose to the tail is shown with its main landing gear just above the runway. The former airliner is a "dash-72" model and has a range of 5,400 miles. The craft can stay airborne for 12 hours and has an operational speed range between 300 and 500 knots. The research flights are made at between 500 and 41,000 feet. The aircraft can carry up to 30,000 lbs of research/science payload equipment installed in 15 mission-definable spaces.

DC-8 Airborne Laboratory in flight

NASA Image and Video Library

1998-02-20

NASA's DC-8 Airborne Science platform shown against a background of a dark blue sky on February 20, 1998. The aircraft is shown from the right rear, slightly above its plane, with the right wing in the foreground and the left wing and horizontal tail in the background. The former airliner is a "dash-72" model and has a range of 5,400 miles. The craft can stay airborne for 12 hours and has an operational speed range between 300 and 500 knots. The research flights are made at between 500 and 41,000 feet. The aircraft can carry up to 30,000 lbs of research/science payload equipment installed in 15 mission-definable spaces.

Reduced bleed air extraction for DC-10 cabin air conditioning

NASA Technical Reports Server (NTRS)

Newman, W. H.; Viele, M. R.; Hrach, F. J.

1980-01-01

It is noted that a significant fuel savings can be achieved by reducing bleed air used for cabin air conditioning. Air in the cabin can be recirculated to maintain comfortable ventilation rates but the quality of the air tends to decrease due to entrainment of smoke and odors. Attention is given to a development system designed and fabricated under the NASA Engine Component Improvement Program to define the recirculation limit for the DC-10. It is shown that with the system, a wide range of bleed air reductions and recirculation rates is possible. A goal of 0.8% fuel savings has been achieved which results from a 50% reduction in bleed extraction from the engine.

Decentralized DC Microgrid Monitoring and Optimization via Primary Control Perturbations

NASA Astrophysics Data System (ADS)

Angjelichinoski, Marko; Scaglione, Anna; Popovski, Petar; Stefanovic, Cedomir

2018-06-01

We treat the emerging power systems with direct current (DC) MicroGrids, characterized with high penetration of power electronic converters. We rely on the power electronics to propose a decentralized solution for autonomous learning of and adaptation to the operating conditions of the DC Mirogrids; the goal is to eliminate the need to rely on an external communication system for such purpose. The solution works within the primary droop control loops and uses only local bus voltage measurements. Each controller is able to estimate (i) the generation capacities of power sources, (ii) the load demands, and (iii) the conductances of the distribution lines. To define a well-conditioned estimation problem, we employ decentralized strategy where the primary droop controllers temporarily switch between operating points in a coordinated manner, following amplitude-modulated training sequences. We study the use of the estimator in a decentralized solution of the Optimal Economic Dispatch problem. The evaluations confirm the usefulness of the proposed solution for autonomous MicroGrid operation.

Application of the SeDeM Diagram and a new mathematical equation in the design of direct compression tablet formulation.

PubMed

Suñé-Negre, Josep M; Pérez-Lozano, Pilar; Miñarro, Montserrat; Roig, Manel; Fuster, Roser; Hernández, Carmen; Ruhí, Ramon; García-Montoya, Encarna; Ticó, Josep R

2008-08-01

Application of the new SeDeM Method is proposed for the study of the galenic properties of excipients in terms of the applicability of direct-compression technology. Through experimental studies of the parameters of the SeDeM Method and their subsequent mathematical treatment and graphical expression (SeDeM Diagram), six different DC diluents were analysed to determine whether they were suitable for direct compression (DC). Based on the properties of these diluents, a mathematical equation was established to identify the best DC diluent and the optimum amount to be used when defining a suitable formula for direct compression, depending on the SeDeM properties of the active pharmaceutical ingredient (API) to be used. The results obtained confirm that the SeDeM Method is an appropriate system, effective tool for determining a viable formulation for tablets prepared by direct compression, and can thus be used as the basis for the relevant pharmaceutical development.

Permanent magnet machine and method with reluctance poles and non-identical PM poles for high density operation

DOEpatents

Hsu, John S.

2010-05-18

A method and apparatus in which a stator (11) and a rotor (12) define a primary air gap (20) for receiving AC flux and at least one source (23, 40), and preferably two sources (23, 24, 40) of DC excitation are positioned for inducing DC flux at opposite ends of the rotor (12). Portions of PM material (17, 17a) are provided as boundaries separating PM rotor pole portions from each other and from reluctance poles. The PM poles (18) and the reluctance poles (19) can be formed with poles of one polarity having enlarged flux paths in relation to flux paths for pole portions of an opposite polarity, the enlarged flux paths communicating with a core of the rotor (12) so as to increase reluctance torque produced by the electric machine. Reluctance torque is increased by providing asymmetrical pole faces. The DC excitation can also use asymmetric poles and asymmetric excitation sources. Several embodiments are disclosed with additional variations.

Numerical Evaluation of the "Dual-Kernel Counter-flow" Matric Convolution Integral that Arises in Discrete/Continuous (D/C) Control Theory

NASA Technical Reports Server (NTRS)

Nixon, Douglas D.

2009-01-01

Discrete/Continuous (D/C) control theory is a new generalized theory of discrete-time control that expands the concept of conventional (exact) discrete-time control to create a framework for design and implementation of discretetime control systems that include a continuous-time command function generator so that actuator commands need not be constant between control decisions, but can be more generally defined and implemented as functions that vary with time across sample period. Because the plant/control system construct contains two linear subsystems arranged in tandem, a novel dual-kernel counter-flow convolution integral appears in the formulation. As part of the D/C system design and implementation process, numerical evaluation of that integral over the sample period is required. Three fundamentally different evaluation methods and associated algorithms are derived for the constant-coefficient case. Numerical results are matched against three available examples that have closed-form solutions.

Defined contribution: a part of our future.

PubMed Central

Baugh, Reginald F.

2003-01-01

Rising employer health care costs and consumer backlash against managed care are trends fostering the development of defined contribution plans. Defined contribution plans limit employer responsibility to a fixed financial contribution rather than a benefit program and dramatically increase consumer responsibility for health care decision making. Possible outcomes of widespread adoption of defined contribution plans are presented. PMID:12934869

Bias Voltage-Dependent Impedance Spectroscopy Analysis of Hydrothermally Synthesized ZnS Nanoparticles

NASA Astrophysics Data System (ADS)

Dey, Arka; Dhar, Joydeep; Sil, Sayantan; Jana, Rajkumar; Ray, Partha Pratim

2018-04-01

In this report, bias voltage-dependent dielectric and electron transport properties of ZnS nanoparticles were discussed. ZnS nanoparticles were synthesized by introducing a modified hydrothermal process. The powder XRD pattern indicates the phase purity, and field emission scanning electron microscope image demonstrates the morphology of the synthesized sample. The optical band gap energy (E g = 4.2 eV) from UV measurement explores semiconductor behavior of the synthesized material. The electrical properties were performed at room temperature using complex impedance spectroscopy (CIS) technique as a function of frequency (40 Hz-10 MHz) under different forward dc bias voltages (0-1 V). The CIS analysis demonstrates the contribution of bulk resistance in conduction mechanism and its dependency on forward dc bias voltages. The imaginary part of the impedance versus frequency curve exhibits the existence of relaxation peak which shifts with increasing dc forward bias voltages. The dc bias voltage-dependent ac and dc conductivity of the synthesized ZnS was studied on thin film structure. A possible hopping mechanism for electrical transport processes in the system was investigated. Finally, it is worth to mention that this analysis of bias voltage-dependent dielectric and transport properties of as-synthesized ZnS showed excellent properties for emerging energy applications.

The arithmetic of achieving universal primary education

NASA Astrophysics Data System (ADS)

Fredrisken, Birger

1983-06-01

In spite of an enrolment growth during the past two decades unparalleled in history, the battle to reach universal primary education (UPE) is still far from won for most developing countries (DC). High population growth and persistent high levels of repetition and drop-out contribute to the elusiveness of this target. About half the 142% primary school enrolment increase achieved between 1960 and 1980 was required just to keep pace with population growth. Repetition consumes about 15% of the DC's primary school capacity and about 40% of those starting Grade 1 drop out prior to Grade 4. Net of repetition, the DC had in 1980 an enrolment capacity corresponding to about 3/4 of their children of primary school age. While the capacity for new admission almost equalled the size of the population of admission age, because of high drop-out and repetition, the number of non-repeaters enrolled in the final grade of the cycle was only about half that of the corresponding population age-group. Maintaining present levels of repetition, the DC would have to more than double their 1980 enrolment to attain UPE by the year 2000. Therefore, in view of the present economic crisis, it is likely that many DC will enter the 21st century without having reached this target.

Infraslow Electroencephalographic and Dynamic Resting State Network Activity.

PubMed

Grooms, Joshua K; Thompson, Garth J; Pan, Wen-Ju; Billings, Jacob; Schumacher, Eric H; Epstein, Charles M; Keilholz, Shella D

2017-06-01

A number of studies have linked the blood oxygenation level dependent (BOLD) signal to electroencephalographic (EEG) signals in traditional frequency bands (δ, θ, α, β, and γ), but the relationship between BOLD and its direct frequency correlates in the infraslow band (<1 Hz) has been little studied. Previously, work in rodents showed that infraslow local field potentials play a role in functional connectivity, particularly in the dynamic organization of large-scale networks. To examine the relationship between infraslow activity and network dynamics in humans, direct current (DC) EEG and resting state magnetic resonance imaging data were acquired simultaneously. The DC EEG signals were correlated with the BOLD signal in patterns that resembled resting state networks. Subsequent dynamic analysis showed that the correlation between DC EEG and the BOLD signal varied substantially over time, even within individual subjects. The variation in DC EEG appears to reflect the time-varying contribution of different resting state networks. Furthermore, some of the patterns of DC EEG and BOLD correlation are consistent with previous work demonstrating quasiperiodic spatiotemporal patterns of large-scale network activity in resting state. These findings demonstrate that infraslow electrical activity is linked to BOLD fluctuations in humans and that it may provide a basis for large-scale organization comparable to that observed in animal studies.

Infraslow Electroencephalographic and Dynamic Resting State Network Activity

PubMed Central

Grooms, Joshua K.; Thompson, Garth J.; Pan, Wen-Ju; Billings, Jacob; Schumacher, Eric H.; Epstein, Charles M.

2017-01-01

Abstract A number of studies have linked the blood oxygenation level dependent (BOLD) signal to electroencephalographic (EEG) signals in traditional frequency bands (δ, θ, α, β, and γ), but the relationship between BOLD and its direct frequency correlates in the infraslow band (<1 Hz) has been little studied. Previously, work in rodents showed that infraslow local field potentials play a role in functional connectivity, particularly in the dynamic organization of large-scale networks. To examine the relationship between infraslow activity and network dynamics in humans, direct current (DC) EEG and resting state magnetic resonance imaging data were acquired simultaneously. The DC EEG signals were correlated with the BOLD signal in patterns that resembled resting state networks. Subsequent dynamic analysis showed that the correlation between DC EEG and the BOLD signal varied substantially over time, even within individual subjects. The variation in DC EEG appears to reflect the time-varying contribution of different resting state networks. Furthermore, some of the patterns of DC EEG and BOLD correlation are consistent with previous work demonstrating quasiperiodic spatiotemporal patterns of large-scale network activity in resting state. These findings demonstrate that infraslow electrical activity is linked to BOLD fluctuations in humans and that it may provide a basis for large-scale organization comparable to that observed in animal studies. PMID:28462586

An optimal ultrasonographic diagnostic test for early gout: A prospective controlled study

PubMed Central

Petraitis, Mykolas; Apanaviciene, Indre; Virviciute, Dalia; Baranauskaite, Asta

2017-01-01

Objective To identify the optimal sites for classification of early gout by ultrasonography. Methods Sixty patients with monosodium urate crystal-proven gout (25 with early gout [≤2-year symptom duration], 35 with late gout [>2-year symptom duration], and 36 normouricemic healthy controls) from one centre were prospectively evaluated. Standardized blinded ultrasound examination of 36 joints and the triceps and patellar tendons was performed to identify tophi and the double contour (DC) sign. Results Ultrasonographic sensitivity was lower in early than late gout. Binary logistic regression analysis showed that two ultrasonographic signs (tophi in the first metatarsophalangeal joint [odds ratio, 16.46] and the DC sign in the ankle [odds ratio, 25.18]) significantly contributed to the final model for early gout diagnosis (sensitivity and specificity of 84% and 81%, respectively). The inter-reader reliability kappa value for the DC sign and tophi was 0.712. Conclusions Four-joint investigation (both first metatarsophalangeal joints for tophi and both ankles for the DC sign) is feasible and reliable and could be proposed as a screening test for early ultrasonographic gout classification in daily practice. PMID:28617199

An optimal ultrasonographic diagnostic test for early gout: A prospective controlled study.

PubMed

Norkuviene, Eleonora; Petraitis, Mykolas; Apanaviciene, Indre; Virviciute, Dalia; Baranauskaite, Asta

2017-08-01

Objective To identify the optimal sites for classification of early gout by ultrasonography. Methods Sixty patients with monosodium urate crystal-proven gout (25 with early gout [≤2-year symptom duration], 35 with late gout [>2-year symptom duration], and 36 normouricemic healthy controls) from one centre were prospectively evaluated. Standardized blinded ultrasound examination of 36 joints and the triceps and patellar tendons was performed to identify tophi and the double contour (DC) sign. Results Ultrasonographic sensitivity was lower in early than late gout. Binary logistic regression analysis showed that two ultrasonographic signs (tophi in the first metatarsophalangeal joint [odds ratio, 16.46] and the DC sign in the ankle [odds ratio, 25.18]) significantly contributed to the final model for early gout diagnosis (sensitivity and specificity of 84% and 81%, respectively). The inter-reader reliability kappa value for the DC sign and tophi was 0.712. Conclusions Four-joint investigation (both first metatarsophalangeal joints for tophi and both ankles for the DC sign) is feasible and reliable and could be proposed as a screening test for early ultrasonographic gout classification in daily practice.

Modulation of dendritic cell and T cell cross-talk during aging: The potential role of checkpoint inhibitory molecules.

PubMed

Gardner, Joanne K; Mamotte, Cyril D S; Jackaman, Connie; Nelson, Delia J

2017-09-01

Dendritic cells (DCs) undergo continuous changes throughout life, and there is evidence that elderly DCs have a reduced capacity to stimulate T cells, which may contribute to impaired anti-tumour immune responses in elderly people with cancer. Changes in checkpoint inhibitory molecules/pathways during aging may be one mechanism that impairs the ability of elderly DCs to activate T cells. However, little is currently known regarding the combined effects of aging and cancer on DC and T cell inhibitory molecules/pathways. In this review, we discuss our current understanding of the influence of aging and cancer on key DC and T cell inhibitory molecules/pathways, the potential underlying cellular and molecular mechanisms contributing to their modulation, and the possibility of therapeutically targeting inhibitory molecules in elderly cancer patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Norm- and hypo-fractionated radiotherapy is capable of activating human dendritic cells.

PubMed

Kulzer, Lorenz; Rubner, Yvonne; Deloch, Lisa; Allgäuer, Andrea; Frey, Benjamin; Fietkau, Rainer; Dörrie, Jan; Schaft, Niels; Gaipl, Udo S

2014-10-01

Despite the transient immunosuppressive properties of local radiotherapy (RT), this classical treatment modality of solid tumors is capable of inducing immunostimulatory forms of tumor-cell death. The resulting 'immunotoxicity' in the tumor, but not in healthy tissues, may finally lead to immune-mediated destruction of the tumor. However, little is known about the best irradiation scheme in this setting. This study examines the immunological effects of differently irradiated human colorectal tumor cells on human monocyte-derived dendritic cells (DC). Human SW480 tumor cells were irradiated with a norm-fractionation scheme (5 × 2 Gy), a hypo-fractionated protocol (3 × 5 Gy), and with a high single irradiation dose (radiosurgery; 1 × 15 Gy). Subsequently, human immature DC (iDC) were co-incubated with supernatants (SN) of these differently treated tumor cells. Afterwards, DC were analyzed regarding the expression of maturation markers, the release of cytokines, and the potential to stimulate CD4(+) T-cells. The co-incubation of iDC with SN of tumor cells exposed to norm- or hypo-fractionated RT resulted in a significantly increased secretion of the immune activating cytokines IL-12p70, IL-8, IL-6, and TNFα, compared to iDC co-incubated with SN of tumor cells that received a high single irradiation dose or were not irradiated. In addition, DC-maturation markers CD80, CD83, and CD25 were also exclusively elevated after co-incubation with the SN of fractionated irradiated tumor cells. Furthermore, the SN of tumor cells that were irradiated with norm- or hypo-fractionated RT triggered iDC to stimulate CD4(+) T-cells not only in an allogenic, but also in an antigen-specific manner like mature DC. Collectively, these results demonstrate that norm- and hypo-fractionated RT induces a fast human colorectal tumor-cell death with immunogenic potential that can trigger DC maturation and activation in vitro. Such findings may contribute to the improvement of irradiation protocols for the most beneficial induction of anti-tumor immunity.

Fair Share or Freeride: Burden Sharing in Post-Cold War NATO

DTIC Science & Technology

2015-05-23

military facilities in Europe. 56 Carl Elk, NATO Common Funds Burdensharing: Background and Current Issues (Washington DC: Congressional Research...Defense Minister Franz Joseph Jung replied, “our contribution is excellent.”114 Germany was clearly proud of its contribution to NATO operations, but...Monsanto, Portugal: NATO Joint Analysis Lessons Learned Centre (JALLC), 2011. Elk, Carl . NATO Common Funds Burdensharing: Background and Current

Role of the Dc domain of the bacterial hook protein FlgE in hook assembly and function

PubMed Central

Moriya, Nao; Minamino, Tohru; Ferris, Hedda U.; Morimoto, Yusuke V.; Ashihara, Masamichi; Kato, Takayuki; Namba, Keiichi

2013-01-01

The bacterial flagellar hook acts as a universal joint to smoothly transmit torque produced by the motor to the filament. The hook protein FlgE assembles into a 55 nm tubular structure with the help of the hook cap (FlgD). FlgE consists of four domains, D0, Dc, D1 and D2, arranged from the inner to the outer part of the tubular structure of the hook. The Dc domain contributes to the structural stability of the hook, but it is unclear how this Dc domain is responsible for the universal joint mechanism. Here, we carried out a deletion analysis of the FlgE Dc domain. FlgEΔ4/5 with deletion of residues 30 to 49 was not secreted into the culture media. FlgEΔ5 and FlgEΔ6 with deletions of residues 40 to 49 and 50 to 59, respectively, still formed hooks, allowing the export apparatus to export the hook-filament junction proteins FlgK and FlgL and flagellin FliC. However, these deletions inhibited the replacement of the FlgD hook cap by FlgK at the hook tip, thereby abolishing filament formation. Deletion of residues 50 to 59 significantly affected hook morphology. These results suggest that the Dc domain is responsible not only for hook assembly but also for FlgE export, the interaction with FlgK, and the polymorphic supercoiling mechanism of the hook. PMID:27493542

Transcriptional reprogramming of gene expression in bovine somatic cell chromatin transfer embryos

PubMed Central

Rodriguez-Osorio, Nelida; Wang, Zhongde; Kasinathan, Poothappillai; Page, Grier P; Robl, James M; Memili, Erdogan

2009-01-01

Background Successful reprogramming of a somatic genome to produce a healthy clone by somatic cells nuclear transfer (SCNT) is a rare event and the mechanisms involved in this process are poorly defined. When serial or successive rounds of cloning are performed, blastocyst and full term development rates decline even further with the increasing rounds of cloning. Identifying the "cumulative errors" could reveal the epigenetic reprogramming blocks in animal cloning. Results Bovine clones from up to four generations of successive cloning were produced by chromatin transfer (CT). Using Affymetrix bovine microarrays we determined that the transcriptomes of blastocysts derived from the first and the fourth rounds of cloning (CT1 and CT4 respectively) have undergone an extensive reprogramming and were more similar to blastocysts derived from in vitro fertilization (IVF) than to the donor cells used for the first and the fourth rounds of chromatin transfer (DC1 and DC4 respectively). However a set of transcripts in the cloned embryos showed a misregulated pattern when compared to IVF embryos. Among the genes consistently upregulated in both CT groups compared to the IVF embryos were genes involved in regulation of cytoskeleton and cell shape. Among the genes consistently upregulated in IVF embryos compared to both CT groups were genes involved in chromatin remodelling and stress coping. Conclusion The present study provides a data set that could contribute in our understanding of epigenetic errors in somatic cell chromatin transfer. Identifying "cumulative errors" after serial cloning could reveal some of the epigenetic reprogramming blocks shedding light on the reprogramming process, important for both basic and applied research. PMID:19393066

SOA derived from isoprene epoxydiols: Insights into formation, aging and distribution over the continental US from the DC3 and SEAC4RS campaigns

NASA Astrophysics Data System (ADS)

Campuzano Jost, P.; Hu, W.; Palm, B. B.; Day, D. A.; Jimenez, J. L.; Rivera, J. C.; Keutsch, F. N.; Zhao, R.; Lee, A.; Abbatt, J.; Marais, E. A.; Liao, J.; Froyd, K. D.; Pollack, I. B.; Peischl, J.; Ryerson, T. B.; St Clair, J. M.; Crounse, J. D.; Wennberg, P. O.; Mikoviny, T.; Armin, W.; Scarino, A. J.; Hair, J. W.; Ferrare, R. A.

2017-12-01

Secondary Organic Aerosol (SOA) formed by uptake of isoprene epoxide (IEPOX), a key isoprene oxidation product under low-NO conditions (<100 pptv), has been recently shown to be a major contributor to the total aerosol burden in many regions of the world with high isoprene emissions, such as the SE US or Amazonia. In the present study, we have used Positive Matrix Factorization (PMF) to extract and identify IEPOX-SOA factors from data recorded by the CU High-Resolution Aerosol Mass Spectrometer (AMS) during the DC3 and SEAC4RS aircraft missions on the NASA DC-8. These campaigns sampled the continental US over the Spring of 2012 and the Summer of 2013, respectively. The contribution of IEPOX-SOA to total OA mass in the SE US was substantial for both DC3 (28% on average) and SEAC4RS flights (26%). IEPOX-SOA was observed in isoprene-rich areas in the W US, albeit with smaller contributions (up to 10% of OA). Highest concentrations of IEPOX-SOA were mostly found downwind and/or aloft of source regions, where IEPOX was already depleted but both inorganic sulfate and particle water/relative humidity were higher. IEPOX sulfate, a specific product of IEPOX uptake, correlates reasonably well with total IEPOX-SOA close to sources at low RH, with an observed contribution between 1-10% to total IEPOX-SOA in the SEUS. While the IEPOX-SOA mass spectrum near the ground was very similar to other ground studies in the SEUS, at higher altitudes differences were observed, likely reflecting aging chemistry aloft. In particular we identify, near the top of the boundary layer/cloud deck, a new OA factor likely resulting from aqueous oxidation of IEPOX-SOA. This factor closely matches the spectrum obtained in recent laboratory experiments simulating aqueous IEPOX-SOA aging, and contributed about 25% to total IEPOX-SOA during SEAC4RS; modeling of this new factor in GEOS-Chem will be presented. Measured IEPOX-SOA concentrations and their overall contribution to the total OA burden were substantially higher for SEAC4RS than those measured at the SOAS ground site the same summer (both total and site overflights). Average daily ground temperatures were substantially higher during the SEAC4RS period, with the overall dependence of concentrations of IEPOX-SOA closely following the isoprene source temperature dependence used in the MEGAN inventory.

Threshold-linear analysis of measures of fertility in artificial insemination data and days to calving in beef cattle.

PubMed

Donoghue, K A; Rekaya, R; Bertrand, J K; Misztal, I

2004-04-01

Mating and calving records for 47,533 first-calf heifers in Australian Angus herds were used to examine the relationship between days to calving (DC) and two measures of fertility in AI data: 1) calving to first insemination (CFI) and 2) calving success (CS). Calving to first insemination and calving success were defined as binary traits. A threshold-linear Bayesian model was employed for both analyses: 1) DC and CFI and 2) DC and CS. Posterior means (SD) of additive covariance and corresponding genetic correlation between the DC and CFI were -0.62 d (0.19 d) and -0.66 (0.12), respectively. The corresponding point estimates between the DC and CS were -0.70 d (0.14 d) and -0.73 (0.06), respectively. These genetic correlations indicate a strong, negative relationship between DC and both measures of fertility in AI data. Selecting for animals with shorter DC intervals genetically will lead to correlated increases in both CS and CFI. Posterior means (SD) for additive and residual variance and heritability for DC for the DC-CFI analysis were 23.5 d2 (4.1 d2), 363.2 d2 (4.8 d2), and 0.06 (0.01), respectively. The corresponding parameter estimates for the DC-CS analysis were very similar. Posterior means (SD) for additive, herd-year and service sire variance and heritability for CFI were 0.04 (0.01), 0.06 (0.06), 0.14 (0.16), and 0.03 (0.01), respectively. Posterior means (SD) for additive, herd-year, and service sire variance and heritability for CS were 0.04 (0.01), 0.07 (0.07), 0.14 (0.16), and 0.03 (0.01), respectively. The similarity of the parameter estimates for CFI and CS suggest that either trait could be used as a measure of fertility in AI data. However, the definition of CFI allows the identification of animals that not only record a calving event, but calve to their first insemination, and the value of this trait would be even greater in a more complete dataset than that used in this study. The magnitude of the correlations between DC and CS-CFI suggest that it may be possible to use a multitrait approach in the evaluation of AI and natural service data, and to report one genetic value that could be used for selection purposes.

Dual Active Bridge based DC Transformer LabVIEW FPGA Control Code

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

In the area of power electronics control, Field Programmable Gate Arrays (FPGAs) have the capability to outperform their Digital Signal Processor (DSP) counterparts due to the FPGA’s ability to implement true parallel processing and therefore facilitate higher switching frequencies, higher control bandwidth, and/or enhanced functionality. National Instruments (NI) has developed two platforms, Compact RIO (cRIO) and Single Board RIO (sbRIO), which combine a real-time processor with an FPGA. The FPGA can be programmed with a subset of the well-known LabVIEW graphical programming language. The candidate software implements complete control algorithms in LabVIEW FPGA for a DC Transformer (DCX) based onmore » a dual active bridge (DAB). A DCX is an isolated bi-directional DC-DC converter designed to operate at unity conversion ratio, M, defined by where Vin is the primary-side DC bus voltage, Vout is the secondary-side DC bus voltage, and n is the turns ratio of the embedded high frequency transformer (HFX). The DCX based on a DAB incorporates two H-bridges, a resonant inductor, and an HFX to provide this functionality. The candidate software employs phase-shift modulation of the two H-bridges and a feedback loop to regulate the conversion ratio at unity. The software also includes alarm-handling capabilities as well as debugging and tuning tools. The software fits on the Xilinx Virtex V LX110 FPGA embedded in the NI cRIO-9118 FPGA chassis, and with a 40 MHz base clock, supports a modulation update rate of 40 MHz, and user-settable switching frequencies and synchronized control loop update rates of tens of kHz.« less

The Incidence of Complex Regional Pain Syndrome in Simultaneous Surgical Treatment of Carpal Tunnel Syndrome and Dupuytren Contracture.

PubMed

Buller, Mitchell; Schulz, Steven; Kasdan, Morton; Wilhelmi, Bradon J

2017-07-01

To determine the incidence of complex regional pain syndrome (CRPS) in the concurrent surgical treatment of Dupuytren contracture (DC) and carpal tunnel syndrome (CTS) through a thorough review of evidence available in the literature. The indices of 260 hand surgery books and PubMed were searched for concomitant references to DC and CTS. Studies were eligible for inclusion if they evaluated the outcome of patients treated with simultaneous fasciectomy or fasciotomy for DC and carpal tunnel release using CRPS as a complication of treatment. Of the literature reviewed, only 4 studies met the defined criteria for use in the study. Data from the 4 studies were pooled, and the incidence of recurrence and complications, specifically CRPS, was noted. The rate of CRPS was found to be 10.4% in the simultaneous treatment group versus 4.1% in the fasciectomy-only group. This rate is nearly half the 8.3% rate of CRPS found in a randomized trial of patients undergoing carpal tunnel release. Our analysis demonstrates a marginal increase in the occurrence of CRPS by adding the carpal tunnel release to patients in need of fasciectomy, contradicting the original reports demonstrating a much higher rate of CRPS. This indicates that no clear clinical risk is associated with simultaneous surgical treatment of DC and CTS. In some patients, simultaneous surgical management of DC and CTS can be accomplished safely with minimal increased risk of CRPS type 1.

The Theory and Measurement of Interorganizational Collaborative Capacity in the Acquisition and Contracting Context

DTIC Science & Technology

2009-04-22

members) of some defined population” ( Thorndike , 1971, p. 533). Norms in this context would allow an organization to understand its relative standing on...theory. New York: McGraw-Hill. Thorndike , R.L. (1971). Educational measurement (2nd Ed.). Washington, DC: American Council on Education. USD (AT&L

21 CFR 184.1095 - Sulfuric acid.

Code of Federal Regulations, 2012 CFR

2012-04-01

... from the National Academy Press, 2101 Constitution Ave. NW., Washington, DC 20418, or may be examined... this material at NARA, call 202-741-6030, or go to: http://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html. (c) The ingredient is used as a pH control agent as defined in...

76 FR 40605 - Exemptions for Security-Based Swaps

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-11

...., Washington, DC 20549, on official business days between the hours of 10 a.m. and 3 p.m. All comments received... Settlements, Triennial and Semiannual Surveys--Positions in Global Over-the-Counter (OTC) Derivatives Markets... transactions with persons who are eligible contract participants as that term is defined today and relating to...

Straight A's: Public Education Policy and Progress. Volume 5, Number 8

ERIC Educational Resources Information Center

Amos, Jason, Ed.

2005-01-01

"Straight A's: Public Education Policy and Progress" is a biweekly newsletter that focuses on education news and events both in Washington, DC and around the country. The following articles are included in this issue: (1) New Report Offers Recommendations for Defining and Improving Graduation Rates: Calls for New Federal Funding Stream…

5 CFR 353.110 - OPM placement assistance.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., NW., Washington, DC 20415.) (i) Executive branch employees (other than an employee of an intelligence... control; and (iv) Employees of the intelligence agencies (defined in 5 U.S.C. 2302(a)(2)(C)(ii)) when... competitive status or is eligible to acquire it under 5 U.S.C. 3304(C). If the employee's agency is abolished...

76 FR 79110 - Service Rules and Policies for the Broadcasting Satellite Service (BSS)

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-21

... defined parallel to a line passing through the center of the Earth, with the positive direction pointing... and Policies for the Broadcasting Satellite Service (BSS) AGENCY: Federal Communications Commission... Communications Commission, Room 1-C823, 445 12th Street SW., Washington, DC 20554. Please include the OMB Control...

Cardiovascular disease among Black Americans: comparisons between the U.S. Virgin Islands and the 50 U.S. states.

PubMed

Lee, Hedwig; Kershaw, Kiarri N; Hicken, Margaret T; Abdou, Cleopatra M; Williams, Eric S; Rivera-O'Reilly, Nereida; Jackson, James S

2013-01-01

Consistent findings show that black Americans have high rates of cardiovascular disease (CVD) and related behavioral risk factors. Despite this body of work, studies on black Americans are generally limited to the 50 U.S. states. We examined variation in CVD and related risk factors among black Americans by comparing those residing within the U.S. Virgin Islands (USVI) with those residing in the 50 U.S. states and Washington, D.C. (US 50/DC) and residing in different regions of the US 50/DC (Northeast, Midwest, South, and West). Using data from the 2007 and 2009 Behavioral Risk Factor Surveillance System, we compared CVD and CVD risk factor prevalence in non-Hispanic black people (≥20 years of age) in the USVI and US 50/DC, examining the relative contributions of health behaviors, health insurance, and socioeconomic status (SES). Accounting for age, sex, education, health insurance, and health behaviors, US 50/DC black Americans were significantly more likely than USVI black people to report ever having a stroke and coronary heart disease, and to be hypertensive, diabetic, or obese. While there was heterogeneity by region, similar patterns emerged when comparing the USVI with different regions of the US 50/DC. USVI black people have lower CVD and risk factor prevalence than US 50/DC black people. These lower rates are not explained by differences in health behaviors or SES. Understanding health in this population may provide important information on the etiology of racial/ethnic variation in health in the U.S. and elsewhere, and highlight relevant public health policies to reduce racial/ethnic group disparities.

Purified Dendritic Cell-Tumor Fusion Hybrids Supplemented with Non-Adherent Dendritic Cells Fraction Are Superior Activators of Antitumor Immunity

PubMed Central

Wang, Yucai; Liu, Yunyan; Zheng, Lianhe

2014-01-01

Background Strong evidence supports the DC-tumor fusion hybrid vaccination strategy, but the best fusion product components to use remains controversial. Fusion products contain DC-tumor fusion hybrids, unfused DCs and unfused tumor cells. Various fractions have been used in previous studies, including purified hybrids, the adherent cell fraction or the whole fusion mixture. The extent to which the hybrids themselves or other components are responsible for antitumor immunity or which components should be used to maximize the antitumor immunity remains unknown. Methods Patient-derived breast tumor cells and DCs were electro-fused and purified. The antitumor immune responses induced by the purified hybrids and the other components were compared. Results Except for DC-tumor hybrids, the non-adherent cell fraction containing mainly unfused DCs also contributed a lot in antitumor immunity. Purified hybrids supplemented with the non-adherent cell population elicited the most powerful antitumor immune response. After irradiation and electro-fusion, tumor cells underwent necrosis, and the unfused DCs phagocytosed the necrotic tumor cells or tumor debris, which resulted in significant DC maturation. This may be the immunogenicity mechanism of the non-adherent unfused DCs fraction. Conclusions The non-adherent cell fraction (containing mainly unfused DCs) from total DC/tumor fusion products had enhanced immunogenicity that resulted from apoptotic/necrotic tumor cell phagocytosis and increased DC maturation. Purified fusion hybrids supplemented with the non-adherent cell population enhanced the antitumor immune responses, avoiding unnecessary use of the tumor cell fraction, which has many drawbacks. Purified hybrids supplemented with the non-adherent cell fraction may represent a better approach to the DC-tumor fusion hybrid vaccination strategy. PMID:24466232

Mesenteric Lymph Nodes Confine Dendritic Cell-Mediated Dissemination of Salmonella enterica Serovar Typhimurium and Limit Systemic Disease in Mice▿

PubMed Central

Voedisch, Sabrina; Koenecke, Christian; David, Sascha; Herbrand, Heike; Förster, Reinhold; Rhen, Mikael; Pabst, Oliver

2009-01-01

In humans with typhoid fever or in mouse strains susceptible to Salmonella enterica serovar Typhimurium (S. Typhimurium) infection, bacteria gain access to extraintestinal tissues, causing severe systemic disease. Here we show that in the gut-draining mesenteric lymph nodes (MLN), the majority of S. Typhimurium-carrying cells show dendritic-cell (DC) morphology and express the DC marker CD11c, indicating that S. Typhimurium bacteria are transported to the MLN by migratory DCs. In vivo FLT-3L-induced expansion of DCs, as well as stimulation of DC migration by Toll-like receptor agonists, results in increased numbers of S. Typhimurium bacteria reaching the MLN. Conversely, genetically impaired DC migration in chemokine receptor CCR7-deficient mice reduces the number of S. Typhimurium bacteria reaching the MLN. This indicates that transport of S. Typhimurium from the intestine into the MLN is limited by the number of migratory DCs carrying S. Typhimurium bacteria. In contrast, modulation of DC migration does not affect the number of S. Typhimurium bacteria reaching systemic tissues, indicating that DC-bound transport of S. Typhimurium does not substantially contribute to systemic S. Typhimurium infection. Surgical removal of the MLN results in increased numbers of S. Typhimurium bacteria reaching systemic sites early after infection, thereby rendering otherwise resistant mice susceptible to fatal systemic disease development. This suggests that the MLN provide a vital barrier shielding systemic compartments from DC-mediated dissemination of S. Typhimurium. Thus, confinement of S. Typhimurium in gut-associated lymphoid tissue and MLN delays massive extraintestinal dissemination and at the same time allows for the establishment of protective adaptive immune responses. PMID:19506012

Cyclooxygenase-2-issued prostaglandin e(2) enhances the production of endogenous IL-10, which down-regulates dendritic cell functions.

PubMed

Harizi, Hedi; Juzan, Monique; Pitard, Vincent; Moreau, Jean-François; Gualde, Norbert

2002-03-01

PGE(2) is a well-known immunomodulator produced in the immune response by APCs, such as dendritic cells (DCs), the most potent APC of the immune system. We investigated the PGE(2) biosynthetic capacity of bone marrow-derived DC (BM-DC) and the effects of PG on the APC. We observed that BM-DC produce PGE(2) and other proinflammatory mediators, such as leukotriene B(4) and NO, after LPS exposure. Constitutively present in BM-DC, cyclooxygenase (COX)-1 did not contribute significantly to the total pool of PGE(2) compared with the LPS-induced COX-2-produced PGE(2). Treatment of BM-DC with exogenous PGE(2) induced the production of large amounts of IL-10 and less IL-12p70. In addition, selective inhibition of COX-2, but not COX-1, was followed by significant decrements in PGE(2) and IL-10, a concomitant restoration of IL-12 production, and an enhancement of DC stimulatory potential. In contrast, we found no demonstrable role for leukotriene B(4) or NO. In view of the potential of PGE(2) to stimulate IL-10, we examined the possibility that the suppressive effect of PGE(2) is mediated via IL-10. We found that exogenous IL-10 inhibits IL-12p70 production in the presence of NS-398, a COX-2 selective inhibitor, while the inhibitory effects of PGE(2) were totally reversed by anti-IL-10. We conclude that COX-2-mediated PGE(2) up-regulates IL-10, which down-regulates IL-12 production and the APC function of BM-DC.

Sex differences in predictors of longitudinal changes in carotid artery stiffness: the Multi-Ethnic Study of Atherosclerosis.

PubMed

Stern, Rebecca; Tattersall, Matthew C; Gepner, Adam D; Korcarz, Claudia E; Kaufman, Joel; Colangelo, Laura A; Liu, Kiang; Stein, James H

2015-02-01

To identify sex differences in predictors of longitudinal changes in carotid arterial stiffness in a multiethnic cohort. Carotid artery distensibility coefficient (DC) and Young's elastic modulus (YEM) were measured in 2650 Multi-Ethnic Study of Atherosclerosis participants (45-84 years old and free of cardiovascular disease) at baseline and after a mean of 9.4 years. Predictors of changes in DC and YEM for each sex were evaluated using multivariable linear regression models. The 1236 men (46.6%) were 60.0 (SD, 9.3) years: 40% were white, 22% black, 16% Chinese, and 22% Hispanic. The 1414 (53.4%) women were 59.8 (9.4) years old with a similar race distribution. Despite similar rates of change in DC and YEM, predictors of changes in distensibility markers differed by sex. In men, Chinese (P=0.002) and black (P=0.003) race/ethnicity, systolic blood pressure (P=0.012), and diabetes mellitus (P=0.05) were associated with more rapidly decreasing DC (accelerated stiffening). Starting antihypertensive medication was associated with improved DC (P=0.03); stopping antihypertensives was associated with more rapid stiffening (increased YEM, P=0.05). In women, higher education was associated with slower stiffening (DC, P=0.041; YEM, P<0.001) as was use of lipid-lowering medication (P=0.03), whereas baseline use of antihypertensive medications (YEM, P=0.01) and systolic blood pressure (DC, P=0.02; P=0.04) predicted increasing stiffening in women. Longitudinal changes in carotid artery stiffness are associated with systolic blood pressure and antihypertensive therapy in both sexes; however, race/ethnicity (in men) and level of education (in women) may have different contributions between the sexes. © 2014 American Heart Association, Inc.

Atmospheric pollution and the prevalence of asthma: study among schoolchildren of 2 areas in Rio de Janeiro, Brazil.

PubMed

Rios, José Luiz Magalhães; Boechat, José Laerte; Sant'Anna, Clemax Couto; França, Alfeu Tavares

2004-06-01

Air pollutants have been associated with the exacerbation of respiratory diseases. They may intensify the inflammatory allergic response and airways reactivity to inhaled allergens. However, it is still not clear if air pollution contributes to the increased prevalence of asthma. To investigate if different levels of air pollution exposure can be related to differences in the prevalence of asthma. The International Study of Asthma and Allergies in Childhood (ISAAC) protocol was used to determine and compare the prevalence of asthma among schoolchildren in 2 cities of the metropolitan region of Rio de Janeiro, Brazil, Duque de Caxias (DC) and Seropédica (SR), which have different levels of atmospheric pollution. The research involved 4,064 students aged 13 to 14 years from 49 schools in DC and 1,129 from 17 schools in SR. Air pollution was evaluated by the concentration of inhalable particulate matter (PM10). ISAAC's written questionnaire was answered by 4,040 students aged 13 to 14 years in DC and 1,080 in SR. Between 1998 and 2000, the PM10 annual arithmetic mean was 124 microg/m3 in DC and 35 microg/m3 in SR (acceptable level is up to 50 microg/m3). The prevalence of wheezing ever was 35.1% in DC and 29.9% in SR (P = .001), and the prevalence of wheezing in the last 12 months was 19.0% in DC and 15.0% in SR (P = .002). In DC, 14.5% of the adolescents presented 1 to 3 crises of wheezing in the last year, whereas in SR only 11.0% presented 1 to 3 crises (P = .003). In this study, the prevalence of asthma in adolescents was directly related to atmospheric pollution.

D.C. Municipal Separate Storm Sewer System (MS4)

EPA Pesticide Factsheets

This permit covers all areas within the jurisdictional boundary of the District of Columbia served by, or otherwise contributing to discharges from, the Municipal Separate Storm Sewer System (MS4) owned or operated by the District of Columbia.

Investigating Evolutionary Conservation of Dendritic Cell Subset Identity and Functions

PubMed Central

Vu Manh, Thien-Phong; Bertho, Nicolas; Hosmalin, Anne; Schwartz-Cornil, Isabelle; Dalod, Marc

2015-01-01

Dendritic cells (DCs) were initially defined as mononuclear phagocytes with a dendritic morphology and an exquisite efficiency for naïve T-cell activation. DC encompass several subsets initially identified by their expression of specific cell surface molecules and later shown to excel in distinct functions and to develop under the instruction of different transcription factors or cytokines. Very few cell surface molecules are expressed in a specific manner on any immune cell type. Hence, to identify cell types, the sole use of a small number of cell surface markers in classical flow cytometry can be deceiving. Moreover, the markers currently used to define mononuclear phagocyte subsets vary depending on the tissue and animal species studied and even between laboratories. This has led to confusion in the definition of DC subset identity and in their attribution of specific functions. There is a strong need to identify a rigorous and consensus way to define mononuclear phagocyte subsets, with precise guidelines potentially applicable throughout tissues and species. We will discuss the advantages, drawbacks, and complementarities of different methodologies: cell surface phenotyping, ontogeny, functional characterization, and molecular profiling. We will advocate that gene expression profiling is a very rigorous, largely unbiased and accessible method to define the identity of mononuclear phagocyte subsets, which strengthens and refines surface phenotyping. It is uniquely powerful to yield new, experimentally testable, hypotheses on the ontogeny or functions of mononuclear phagocyte subsets, their molecular regulation, and their evolutionary conservation. We propose defining cell populations based on a combination of cell surface phenotyping, expression analysis of hallmark genes, and robust functional assays, in order to reach a consensus and integrate faster the huge but scattered knowledge accumulated by different laboratories on different cell types, organs, and species. PMID:26082777

Negative Capacitance in BaTiO3/BiFeO3 Bilayer Capacitors.

PubMed

Hou, Ya-Fei; Li, Wei-Li; Zhang, Tian-Dong; Yu, Yang; Han, Ren-Lu; Fei, Wei-Dong

2016-08-31

Negative capacitances provide an approach to reduce heat generations in field-effect transistors during the switch processes, which contributes to further miniaturization of the conventional integrated circuits. Although there are many studies about negative capacitances using ferroelectric materials, the direct observation of stable ferroelectric negative capacitances has rarely been reported. Here, we put forward a dc bias assistant model in bilayer capacitors, where one ferroelectric layer with large dielectric constant and the other ferroelectric layer with small dielectric constant are needed. Negative capacitances can be obtained when external dc bias electric fields are larger than a critical value. Based on the model, BaTiO3/BiFeO3 bilayer capacitors are chosen as study objects, and negative capacitances are observed directly. Additionally, the upward self-polarization effect in the ferroelectric layer reduces the critical electric field, which may provide a method for realizing zero and/or small dc bias assistant negative capacitances.

A study of the parallel algorithm for large-scale DC simulation of nonlinear systems

NASA Astrophysics Data System (ADS)

Cortés Udave, Diego Ernesto; Ogrodzki, Jan; Gutiérrez de Anda, Miguel Angel

Newton-Raphson DC analysis of large-scale nonlinear circuits may be an extremely time consuming process even if sparse matrix techniques and bypassing of nonlinear models calculation are used. A slight decrease in the time required for this task may be enabled on multi-core, multithread computers if the calculation of the mathematical models for the nonlinear elements as well as the stamp management of the sparse matrix entries are managed through concurrent processes. This numerical complexity can be further reduced via the circuit decomposition and parallel solution of blocks taking as a departure point the BBD matrix structure. This block-parallel approach may give a considerable profit though it is strongly dependent on the system topology and, of course, on the processor type. This contribution presents the easy-parallelizable decomposition-based algorithm for DC simulation and provides a detailed study of its effectiveness.

The UT 19-channel DC SQUID based neuromagnetometer.

PubMed

ter Brake, H J; Flokstra, J; Jaszczuk, W; Stammis, R; van Ancum, G K; Martinez, A; Rogalla, H

1991-01-01

A 19-channel DC SQUID based neuromagnetometer is under construction at the University of Twente (UT). Except for the cryostat all elements of the system are developed at the UT. It comprises 19 wire-wound first-order gradiometers in a hexagonal configuration. The gradiometers are connected to planar DC SQUIDs fabricated with a Nb/Al, AlO kappa/Nb technology. For this connection we developed a method to bond a Nb wire to a Nb thin-film. The SQUIDs are placed in compartmentalised Nb modules. Further, external feedback is incorporated in order to eliminate cross talk between the gradiometers. The electronics basically consist of a phase-locked loop operating with a modulation frequency of 100 kHz. Between SQUID and preamplifier a small transformer is used to limit the noise contribution of the preamplifier. In the paper the overall system is described, and special attention is paid to the SQUID module (bonding, compartments, external-feedback setup, output transformer).

Knowledge sharing and collaboration in translational research, and the DC-THERA Directory

PubMed Central

Gündel, Michaela; Austyn, Jonathan M.; Cavalieri, Duccio; Scognamiglio, Ciro; Brandizi, Marco

2011-01-01

Biomedical research relies increasingly on large collections of data sets and knowledge whose generation, representation and analysis often require large collaborative and interdisciplinary efforts. This dimension of ‘big data’ research calls for the development of computational tools to manage such a vast amount of data, as well as tools that can improve communication and access to information from collaborating researchers and from the wider community. Whenever research projects have a defined temporal scope, an additional issue of data management arises, namely how the knowledge generated within the project can be made available beyond its boundaries and life-time. DC-THERA is a European ‘Network of Excellence’ (NoE) that spawned a very large collaborative and interdisciplinary research community, focusing on the development of novel immunotherapies derived from fundamental research in dendritic cell immunobiology. In this article we introduce the DC-THERA Directory, which is an information system designed to support knowledge management for this research community and beyond. We present how the use of metadata and Semantic Web technologies can effectively help to organize the knowledge generated by modern collaborative research, how these technologies can enable effective data management solutions during and beyond the project lifecycle, and how resources such as the DC-THERA Directory fit into the larger context of e-science. PMID:21969471

Technical Advance: Live-imaging analysis of human dendritic cell migrating behavior under the influence of immune-stimulating reagents in an organotypic model of lung

PubMed Central

Nguyen Hoang, Anh Thu; Chen, Puran; Björnfot, Sofia; Högstrand, Kari; Lock, John G.; Grandien, Alf; Coles, Mark; Svensson, Mattias

2014-01-01

This manuscript describes technical advances allowing manipulation and quantitative analyses of human DC migratory behavior in lung epithelial tissue. DCs are hematopoietic cells essential for the maintenance of tissue homeostasis and the induction of tissue-specific immune responses. Important functions include cytokine production and migration in response to infection for the induction of proper immune responses. To design appropriate strategies to exploit human DC functional properties in lung tissue for the purpose of clinical evaluation, e.g., candidate vaccination and immunotherapy strategies, we have developed a live-imaging assay based on our previously described organotypic model of the human lung. This assay allows provocations and subsequent quantitative investigations of DC functional properties under conditions mimicking morphological and functional features of the in vivo parental tissue. We present protocols to set up and prepare tissue models for 4D (x, y, z, time) fluorescence-imaging analysis that allow spatial and temporal studies of human DCs in live epithelial tissue, followed by flow cytometry analysis of DCs retrieved from digested tissue models. This model system can be useful for elucidating incompletely defined pathways controlling DC functional responses to infection and inflammation in lung epithelial tissue, as well as the efficacy of locally administered candidate interventions. PMID:24899587

Preparation of antibodies and development of an enzyme-linked immunosorbent assay (ELISA) for the determination of doxycycline antibiotic in milk samples.

PubMed

Adrian, Javier; Fernández, Fátima; Sánchez-Baeza, Francisco; Marco, M-Pilar

2012-04-18

This paper reports the development of an immunoassay for the specific analysis of doxycycline (DC), a congener of the tetracycline antibiotic family (TCs), in milk samples. This is the first time that DC antibody production is reported, based on a rationally designed and well-characterized immunizing hapten. The chemical structure of the immunizing hapten (13-[(2-carboxyethyl)thiol]-5-hydroxy-6-α-deoxytetracycline, TC1) was designed to maximize recognition of the tetracycline characteristic moiety defined as lower periphery of the TCs plus the region of the upper periphery composed by the hydroxyl group at position C(5) (B ring) and the dimethylamino group in ring A. Polyclonal antibodies raised against TC1 coupled to horseshoe crab hemocianyn (HCH) were used to develop a homologous indirect competitive enzyme-linked immunosorbent assay (ELISA). The microplate ELISA can detect DC in buffer down to 0.1 μg L(-1). The ELISA has been proven to tolerate a wide range of ionic strengths and pH values. The assay is very selective for DC with a minor recognition of methacycline (32% of cross-reactivity). Experiments performed with whole milk samples demonstrate that samples can be directly analyzed after a simple treatment method, reaching detectability values below 5 μg L(-1).

Plasmacytoid Dendritic Cells Suppress HIV-1 Replication but Contribute to HIV-1 Induced Immunopathogenesis in Humanized Mice

PubMed Central

Li, Guangming; Cheng, Menglan; Nunoya, Jun-ichi; Cheng, Liang; Guo, Haitao; Yu, Haisheng; Liu, Yong-jun; Su, Lishan; Zhang, Liguo

2014-01-01

The role of plasmacytoid dendritic cells (pDC) in human immunodeficiency virus type 1 (HIV-1) infection and pathogenesis remains unclear. HIV-1 infection in the humanized mouse model leads to persistent HIV-1 infection and immunopathogenesis, including type I interferons (IFN-I) induction, immune-activation and depletion of human leukocytes, including CD4 T cells. We developed a monoclonal antibody that specifically depletes human pDC in all lymphoid organs in humanized mice. When pDC were depleted prior to HIV-1 infection, the induction of IFN-I and interferon-stimulated genes (ISGs) were abolished during acute HIV-1 infection with either a highly pathogenic CCR5/CXCR4-dual tropic HIV-1 or a standard CCR5-tropic HIV-1 isolate. Consistent with the anti-viral role of IFN-I, HIV-1 replication was significantly up-regulated in pDC-depleted mice. Interestingly, the cell death induced by the highly pathogenic HIV-1 isolate was severely reduced in pDC-depleted mice. During chronic HIV-1 infection, depletion of pDC also severely reduced the induction of IFN-I and ISGs, associated with elevated HIV-1 replication. Surprisingly, HIV-1 induced depletion of human immune cells including T cells in lymphoid organs, but not the blood, was reduced in spite of the increased viral replication. The increased cell number in lymphoid organs was associated with a reduced level of HIV-induced cell death in human leukocytes including CD4 T cells. We conclude that pDC play opposing roles in suppressing HIV-1 replication and in promoting HIV-1 induced immunopathogenesis. These findings suggest that pDC-depletion and IFN-I blockade will provide novel strategies for treating those HIV-1 immune non-responsive patients with persistent immune activation despite effective anti-retrovirus treatment. PMID:25077616

Influence of organophosphate poisoning on human dendritic cells.

PubMed

Schäfer, Marina; Koppe, Franziska; Stenger, Bernhard; Brochhausen, Christoph; Schmidt, Annette; Steinritz, Dirk; Thiermann, Horst; Kirkpatrick, Charles James; Pohl, Christine

2013-12-05

Organophosphourus compounds (OPC, including nerve agents and pesticides) exhibit acute toxicity by inhibition of acetylcholinesterase. Lung affections are frequent complications and a risk factor for death. In addition, epidemiological studies reported immunological alterations after OPC exposure. In our experiments we investigated the effects of organophosphourus pesticides dimethoate and chlorpyrifos on dendritic cells (DC) that are essential for the initial immune response, especially in the pulmonary system. DC, differentiated from the monocyte cell line THP-1 by using various cytokines (IL-4, GM-CSF, TNF-α, Ionomycin), were exposed to organophosphourus compounds at different concentrations for a 24h time period. DC were characterized by flow cytometry and immunofluorescence using typical dendritic cell markers (e.g., CD11c, CD209 and CD83). After OPC exposure we investigated cell death, the secretion profile of inflammatory mediators, changes of DC morphology, and the effect on protein kinase signalling pathways. Our results revealed a successful differentiation of THP-1 into DC. OPC exposure caused a significant concentration-dependent influence on DC: Dendrites of the DC were shortened and damaged, DC-specific cell surface markers (i.e., CD83and CD209) decreased dramatically after chlorpyrifos exposure. Interestingly, the effects caused by dimethoate were in general less pronounced. The organophosphourus compounds affected the release of inflammatory cytokines, such as IL-1ß and IL-8. The anti-inflammatory cytokine IL-10 was significantly down regulated. Protein kinases like the Akt family or ERK, which are essential for cell survival and proliferation, were inhibited by both OPC. These findings indicate that the tested organophosphourus compounds induced significant changes in cell morphology, inhibited anti-inflammatory cytokines and influenced important protein signalling pathways which are involved in regulation of apoptosis. Thus our results highlight novel aspects -apparently independent of AChE inhibition- of OPC poisoning with regard to lung toxicity. Our findings contribute to the basic understanding of pulmonary complications caused by OPC poisoning. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Maintaining Stability During a Conducted-Ripple EMC Test

NASA Technical Reports Server (NTRS)

Vorperian, Vatche

2007-01-01

An improved technique, and electronic circuitry to implement the technique, have been developed for a military-standard electromagnetic-compatibility (EMC) test in which one analyzes susceptibility to low-frequency ripple conducted into the equipment under test via a DC power line. In the traditional technique for performing the particular test, the ripple is coupled onto the DC power line via a transformer. Depending upon some design details of the equipment under test, the inductance of the transformer can contribute a degree of instability that results in an oscillation of amplitude large enough to destroy the equipment. It is usually possible to suppress the oscillation by connecting a damping resistor to the primary terminals of the ripple-injection transformer. However, it is important to emphasize the usually in the preceding sentence: sometimes, the resistive damping becomes insufficient to suppress destructive oscillation. In addition, undesirably, the resistor contributes to power dissipation and power demand, and thereby also necessitates the use of a larger ripple voltage amplifier. Yet another disadvantage of the transformer-coupling technique is that the transformer introduces low-frequency distortion of the injected ripple voltage. The improved technique makes it possible to inject ripple with very low distortion at low frequency, without inducing oscillation. In this technique, a transformer is not used: Instead, power is fed to the equipment under test via series power field-effect transistors (FETs) controlled by a summing operational amplifier. One of the inputs to the amplifier controls the DC component of the power-line voltage; the other input, generated by an external oscillator, controls the ripple component. The circuitry for implementing this technique includes panel displays, an internal power supply for the operational amplifier and panel displays, and amplitude controls for the DC and ripple powerline voltage components.

Acetylcholine contributes to control the physiological inflammatory response during the peri-implantation period.

PubMed

Paparini, D; Gori, S; Grasso, E; Scordo, W; Calo, G; Pérez Leirós, C; Ramhorst, R; Salamone, G

2015-06-01

Maternal antigen-presenting cells attracted to the pregnant uterus interact with trophoblast cells and modulate their functional profile to favour immunosuppressant responses. Non-neuronal cholinergic system is expressed in human cytotrophoblast cells and in immune cells with homeostatic regulatory functions. The aim of this work was to evaluate whether non-neuronal acetylcholine conditions maternal monocyte and DC migration and activation profiles. We used an in vitro model resembling maternal-placental interface represented by the co-culture of human trophoblast cells (Swan-71 cell line) and monocytes or DC. When cytotrophoblast cells were treated with neostigmine (Neo) to concentrate endogenous acetylcholine levels, monocyte migration was increased. In parallel, high levels of IL-10 and decreased levels of TNF-α were observed upon interaction of maternal monocytes with trophoblast cells. This effect was synergized by Neo and was prevented by atropine, a muscarinic acetylcholine receptor antagonist. Similarly, trophoblast cells increased the migration of DC independently of Neo treatment; however, enhanced IL-10 and MCP-1 synthesis in trophoblast-DC co-cultures with no changes in TNF-α and IL-6 was observed. In fact, there were no changes in HLA-DR, CD86 or CD83 expression. Finally, trophoblast cells treated with Neo increased the expression of two antigen-presenting cells attracting chemokines, MCP-1, MIP-1α and RANTES through muscarinic receptors, and it was prevented by atropine. Our present results support a novel role of acetylcholine synthesized by trophoblast cells to modulate antigen-presenting cell migration and activation favouring an immunosuppressant profile that contributes to immune homeostasis maintenance at the maternal-foetal interface. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Complex phenotype of dyskeratosis congenita and mood dysregulation with novel homozygous RTEL1 and TPH1 variants.

PubMed

Ungar, Rachel A; Giri, Neelam; Pao, Maryland; Khincha, Payal P; Zhou, Weiyin; Alter, Blanche P; Savage, Sharon A

2018-06-01

Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome caused by germline mutations in telomere biology genes. Patients have extremely short telomeres for their age and a complex phenotype including oral leukoplakia, abnormal skin pigmentation, and dysplastic nails in addition to bone marrow failure, pulmonary fibrosis, stenosis of the esophagus, lacrimal ducts and urethra, developmental anomalies, and high risk of cancer. We evaluated a patient with features of DC, mood dysregulation, diabetes, and lack of pubertal development. Family history was not available but genome-wide genotyping was consistent with consanguinity. Whole exome sequencing identified 82 variants of interest in 80 genes based on the following criteria: homozygous, <0.1% minor allele frequency in public and in-house databases, nonsynonymous, and predicted deleterious by multiple in silico prediction programs. Six genes were identified likely contributory to the clinical presentation. The cause of DC is likely due to homozygous splice site variants in regulator of telomere elongation helicase 1, a known DC and telomere biology gene. A homozygous, missense variant in tryptophan hydroxylase 1 may be clinically important as this gene encodes the rate limiting step in serotonin biosynthesis, a biologic pathway connected with mood disorders. Four additional genes (SCN4A, LRP4, GDAP1L1, and SPTBN5) had rare, missense homozygous variants that we speculate may contribute to portions of the clinical phenotype. This case illustrates the value of conducting detailed clinical and genomic evaluations on rare patients in order to identify new areas of research into the functional consequences of rare variants and their contribution to human disease. © 2018 Wiley Periodicals, Inc.

2011 John M. Eisenberg Patient Safety and Quality Awards.

PubMed

2012-07-01

The 2011 John M. Eisenberg Patient Safety and Quality Awards were presented on April 5, 2012, in Washington, D.C. Individual award recipients were interviewed for this issue, and organization or group award recipients contributed articles describing their work.

KIR and HLA-C Interactions Promote Differential Dendritic Cell Maturation and Is a Major Determinant of Graft Failure following Kidney Transplantation

PubMed Central

Hanvesakul, Raj; Kubal, Chandrashekhar; Moore, Jason; Neil, Desley; Cook, Mark; Ball, Simon; Briggs, David; Moss, Paul; Cockwell, Paul

2011-01-01

Background HLA-C is an important ligand for killer immunoglobulin like receptors (KIR) that regulate natural killer (NK) cell function. Based on KIR specificity HLA-C molecules are allocated into two groups, HLA-C1 or HLA-C2; HLA-C2 is more inhibiting to NK cell function than HLA-C1. We studied the clinical importance of HLA-C genotypes on the long-term graft survival of 760 kidney transplants performed at our centre utilising a population based genetic study and cell culture model to define putative mechanisms. Methods and Findings Genotyping was performed using conventional DNA PCR techniques and correlations made to clinical outcomes. We found that transplant recipients with HLA-C2 had significantly better long-term graft survival than transplant recipients with HLA-C1 (66% versus 44% at 10 years, log-rank p = 0.002, HR = 1.51, 95%CI = 1.16–1.97). In in-vitro NK and dendritic cell (DC) co-culture model we made several key observations that correlated with the population based genetic study. We observed that donor derived NK cells, on activation with IL-15, promoted differential HLA-C genotype dependent DC maturation. In NK-DC co-culture, the possession of HLA-C2 by DC was associated with anti-inflammatory cytokine production (IL-1RA/IL-6), diminished DC maturation (CD86, HLA-DR), and absent CCR7 expression. Conversely, possession of HLA-C1 by DC was associated with pro-inflammatory cytokine synthesis (TNF-α, IL-12p40/p70), enhanced DC maturation and up-regulation of CCR7 expression. By immunohistochemistry the presence of donor NK cells was confirmed in pre-transplant kidneys. Conclusions We propose that after kidney transplantation IL-15 activated donor derived NK cells interact with recipient DC with less activation of indirect allo-reactivity in HLA-C2 positive recipients than HLA-C1 positive recipients; this has implications for long-term graft survival. Early events following kidney transplantation involving NK-DC interaction via KIR and HLA-C immune synapse may have a central role in long-term kidney transplant outcomes. PMID:21912600

Design, fabrication and calibration of alpha particle densitometers for measuring planetary atmospheric density

NASA Technical Reports Server (NTRS)

Sellers, B.; Hunerwadel, J. L.; Hanser, F. A.

1972-01-01

An alpha particle densitometer was developed for possible application to measurement of the atmospheric density-altitude profile on Martian entry. The device uses an Am-241 radioactive-foil source, which emits a distributed energy spectrum, located about 25 to 75 cm from a semiconductor detector. System response - defined as the number of alphas per second reaching the detector with energy above a fixed threshold - is given for Ar and CO2. The altitude profile of density measurement accuracy is given for a pure CO2 atmosphere with 5 mb surface pressure. The entire unit, including dc-dc converters, requires less than 350 milliwatts of power from +28 volts, weighs about 0.85 lb and occupies less than 15 cubic inches volume.

Development of a standardized control module for dc-to-dc converters

NASA Technical Reports Server (NTRS)

Yu, Y.; Iwens, R. I.; Lee, F. C.; Inouye, L. Y.

1977-01-01

The electrical performance of a power processor depends on the quality of its control system. Most of the existing control circuits suffer one or more of the following imperfections that tend to restrict their respective utility: (1) inability to perform different modes of duty cycle control; (2) lack of immunity to output filter parameter changes, and (3) lack of capability to provide power component stress limiting on an instantaneous basis. The three lagging aspects of existing control circuits have been used to define the major objectives of the current Standardized Control Module (SCM) Program. Detailed information on the SCM functional block diagram, its universality, and performance features, circuit description, test results, and modeling and analysis efforts are presented.

Decoy receptor 3 polymorphisms are not associated with the risk of esophageal cancer in a Chinese population.

PubMed

Ren, Zhengbing; Zhu, Jingfeng; Gu, Haiyong; Liu, Ruiping; Chen, Suocheng; Rong, Guoxiang; Sun, Bin

2014-06-01

Esophageal cancer (EC) is the sixth most common cancer worldwide, and esophageal squamous-cell carcinoma (ESCC) accounts for more than 90% of ECs. We hypothesized that genetic factors might play an important role in ESCC carcinogenesis. We conducted a hospital-based case-control study to evaluate the association between two single nucleotide polymorphisms of decoy receptor 3 (DcR3), namely, rs2297441 G > A and rs2257440 T > C, on the ESCC risk. In all, 629 ESCC cases and 686 controls were included. Genotypes were determined using the ligation detection reaction method. When the DcR3 rs2297441 GG homozygote genotype was used as the reference group, the GA genotype showed no association with the ESCC risk (GA versus GG: adjusted OR = 1.11, 95% CI = 0.88-1.40, p = 0.396); similarly, even the TT genotype showed no association with the ESCC risk (AA versus GG: adjusted OR = 0.80, 95% CI = 0.55-1.18, p = 0.268). Logistic regression analyses revealed that the DcR3 rs2257440 T > C polymorphism was not associated with the ESCC risk. DcR3 rs2297441 G > A and DcR3 rs2257440 T > C polymorphisms may not contribute to the ESCC risk, and additional, larger studies are required to confirm our results.

Index - DC Open Government

Science.gov Websites

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Children, nature, and the urban environment: proceedings of a symposium-fair

Treesearch

Northeastern Forest Experiment Station

1977-01-01

A report on the symposium-fair held 19-23 May, 1975 at the C. H. Marvin Center, the George Washington University, Washington, D.C., containing 33 papers. Sections are devoted to defining the role of natural environments and human development, research on urban children and the natural environment, and community and institutional response to fostering desirable...

Treatment of Mestastatic Breast Cancer by Photodynamic Therapy Induced Anti-Tumor Immunity in a Murine Model

DTIC Science & Technology

2005-12-01

dinucleotide and were more common in the genomes of bacteria compared to humans. Immunostimulatory sequences in bacterial ( bDNA ) that are structurally defined...stimulates B cells, natural killer (NK) cells, dendritic cells (DC), and macrophages, regardless of whether the DNA is in the form of genomic bDNA or

Straight A's: Public Education Policy and Progress. Volume 7, Number 8

ERIC Educational Resources Information Center

Amos, Jason, Ed.

2007-01-01

"Straight A's: Public Education Policy and Progress" is a biweekly newsletter that focuses on education news and events both in Washington, DC and around the country. The following articles are included in this issue: (1) "The Gap Defined": ACT Report Cites Poor State Standards and Assessments as Possible Reason for Gap Between Postsecondary…

78 FR 52497 - Notice of a Request for Extension of a Currently Approved Information Collection

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-23

... DEPARTMENT OF AGRICULTURE Foreign Agricultural Service Notice of a Request for Extension of a... Service, U.S. Department of Agriculture, 1400 Independence Avenue SW., Washington, DC 20250-1025; or by... reportable commodities except soybean oil are defined as 100,000 metric tons or more of one commodity in 1...

Proceedings of the Aircraft Wake Vortices Conference. Volume 2 : papers 30-55

DOT National Transportation Integrated Search

1992-06-01

This volume contains the proceedings of the international conference of Aircraft Wake Vortices held at the Quality Hotel Capitol Hill, Washington, DC. on October 29-31. 1991. The contributed papers discuss technological advances in the knowledge of t...

Proceedings of the Aircraft Wake Vortices Conference. Volume 1 : papers 1-29

DOT National Transportation Integrated Search

1992-06-01

This volume contains the proceedings of the international conference of Aircraft Wake Vortices held at the Quality Hotel Capitol Hill, Washington, DC. on October 29-31. 1991. The contributed papers discuss technological advances in the knowledge of t...

Energy Neutral Wireless Bolt for Safety Critical Fastening

PubMed Central

Seyoum, Biruk B.

2017-01-01

Thermoelectric generators (TEGs) are now capable of powering the abundant low power electronics from very small (just a few degrees Celsius) temperature gradients. This factor along with the continuously lowering cost and size of TEGs, has contributed to the growing number of miniaturized battery-free sensor modules powered by TEGs. In this article, we present the design of an ambient-powered wireless bolt for high-end electro-mechanical systems. The bolt is equipped with a temperature sensor and a low power RF chip powered from a TEG. A DC-DC converter interfacing the TEG with the RF chip is used to step-up the low TEG voltage. The work includes the characterizations of different TEGs and DC-DC converters to determine the optimal design based on the amount of power that can be generated from a TEG under different loads and at temperature gradients typical of industrial environments. A prototype system was implemented and the power consumption of this system under different conditions was also measured. Results demonstrate that the power generated by the TEG at very low temperature gradients is sufficient to guarantee continuous wireless monitoring of the critical fasteners in critical systems such as avionics, motorsport and aerospace. PMID:28954432

Energy Neutral Wireless Bolt for Safety Critical Fastening.

PubMed

Seyoum, Biruk B; Rossi, Maurizio; Brunelli, Davide

2017-09-26

Thermoelectric generators (TEGs) are now capable of powering the abundant low power electronics from very small (just a few degrees Celsius) temperature gradients. This factor along with the continuously lowering cost and size of TEGs, has contributed to the growing number of miniaturized battery-free sensor modules powered by TEGs. In this article, we present the design of an ambient-powered wireless bolt for high-end electro-mechanical systems. The bolt is equipped with a temperature sensor and a low power RF chip powered from a TEG. A DC-DC converter interfacing the TEG with the RF chip is used to step-up the low TEG voltage. The work includes the characterizations of different TEGs and DC-DC converters to determine the optimal design based on the amount of power that can be generated from a TEG under different loads and at temperature gradients typical of industrial environments. A prototype system was implemented and the power consumption of this system under different conditions was also measured. Results demonstrate that the power generated by the TEG at very low temperature gradients is sufficient to guarantee continuous wireless monitoring of the critical fasteners in critical systems such as avionics, motorsport and aerospace.

Comprehensive Evaluation of Power Supplies at Cryogenic Temperatures for Deep Space Applications

NASA Technical Reports Server (NTRS)

Patterson, Richard L.; Gerber, Scott; Hammoud, Ahmad; Elbuluk, Malik E.; Lyons, Valerie (Technical Monitor)

2002-01-01

The operation of power electronic systems at cryogenic temperatures is anticipated in many future space missions such as planetary exploration and deep space probes. In addition to surviving the space hostile environments, electronics capable of low temperature operation would contribute to improving circuit performance, increasing system efficiency, and reducing development and launch costs. DC/DC converters are widely used in space power systems in the areas of power management, conditioning, and control. As part of the on-going Low Temperature Electronics Program at NASA, several commercial-off-the-shelf (COTS) DC/DC converters, with specifications that might fit the requirements of specific future space missions have been selected for investigation at cryogenic temperatures. The converters have been characterized in terms of their performance as a function of temperature in the range of 20 C to - 180 C. These converters ranged in electrical power from 8 W to 13 W, input voltage from 9 V to 72 V and an output voltage of 3.3 V. The experimental set-up and procedures along with the results obtained on the converters' steady state and dynamic characteristics are presented and discussed.

An assessment of solar hot water heating in the Washington, D.C. area - Implications for local utilities

NASA Astrophysics Data System (ADS)

Stuart, M. W.

1980-04-01

A survey of residential solar hot water heating in the Washington, D.C. area is presented with estimates of the total solar energy contribution per year. These estimates are examined in relation to a local utility's peak-load curves to determine the impact of a substantial increase in solar domestic hot water use over the next 20 yr in the area of utility management. The results indicate that a 10% market penetration of solar water heaters would have no detrimental effect on the utility's peak-load profile and could save several million dollars in new plant construction costs.

Structural and mutational analyses of the receptor binding domain of botulinum D/C mosaic neurotoxin: Insight into the ganglioside binding mechanism

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

Nuemket, Nipawan; Tanaka, Yoshikazu; Faculty of Advanced Life Science, Hokkaido University, Sapporo 060-0810

2011-07-29

Highlights: {yields} We determined the crystal structure of the receptor binding domain of BoNT in complex with 3'-sialyllactose. {yields} An electron density derived from the 3'-sialyllactose was confirmed at the cleft in the C-terminal subdomain. {yields} Alanine site-directed mutagenesis showed that GBS and GBL are important for ganglioside binding. {yields} A cell binding mechanism, which involves cooperative contribution of two sites, was proposed. -- Abstract: Clostridium botulinum type D strain OFD05, which produces the D/C mosaic neurotoxin, was isolated from cattle killed by the recent botulism outbreak in Japan. The D/C mosaic neurotoxin is the most toxic of the botulinummore » neurotoxins (BoNT) characterized to date. Here, we determined the crystal structure of the receptor binding domain of BoNT from strain OFD05 in complex with 3'-sialyllactose at a resolution of 3.0 A. In the structure, an electron density derived from the 3'-sialyllactose was confirmed at the cleft in the C-terminal subdomain. Alanine site-directed mutagenesis showed the significant contribution of the residues surrounding the cleft to ganglioside recognition. In addition, a loop adjoining the cleft also plays an important role in ganglioside recognition. In contrast, little effect was observed when the residues located around the surface previously identified as the protein receptor binding site in other BoNTs were substituted. The results of cell binding analysis of the mutants were significantly correlated with the ganglioside binding properties. Based on these observations, a cell binding mechanism of BoNT from strain OFD05 is proposed, which involves cooperative contribution of two ganglioside binding sites.« less

Temporal variability of Polycyclic Aromatic Hydrocarbons (PAHs) in a receptor site of the Puebla-Tlaxcala Valley

NASA Astrophysics Data System (ADS)

Padilla, Z. V.; Torres, R.; Ruiz Suarez, L.; Molina, L. T.

2013-05-01

This contribution documents the presence and possible origin of PAHs, their temporal concentration patterns and correlations with other air pollutants in the so-called Puebla-Tlaxcala valley. This valley is located to the east of the Mexico City Metropolitan Area and is a very populated region which suffers of air pollution problems. Emission sources of PAHs include open burning, industrial boilers, automobiles and trucks, but vehicle emissions vary significantly depending on the use of: fuel, engine type and catalytic converter. An important emission source in the Puebla-Tlaxcala region is wood burning for cooking. Therefore, it is expected to have contributions of PAHS from this type of sources. PAHs measurements were performed in an air pollution semi-rural receptor site (Chipilo) southwest the City of Puebla, using an aerosol photoelectric sensor (PAS 2000 CE) to measure the concentration of PAHs and a diffuser charger (DC 2000 CE) to evaluate the active surface (DC) of the particles. The measuring period included March and April of 2012 during the ozne season in central Mexico. The use of these two sensors in parallel has been identified as a fingerprint technique to identify different types of particles from several combustion processes and is a useful tool to identify quantitatively the major source of emissions, as well as to describe thephysical and chemical characteristics of the particles. Correlations between PAHs and DC, with NOx and CO, together with an analysis of atmospheric transport may approximate the possible origin of these particles. The coefficient PAHs / DC associated with backward trajectory analysis represents a tool to identify potential areas of emission. The correlation between PAHs and NOx emissions reflects association with diesel combustion, while the correlation between PAHs and CO, the combustion of gasoline. The results show that vehicle emissions are the major source of PAHs with an associated increase in the concentration of PAHs in the morning, when there is more vehicular traffic. The time series of PAHs also exhibit synchronized peaks of PAHs and DC that correspond to hours of traffic which shows the relationship of PAHs with DC. However, correlations of PAHs with DC show a relatively strong scattering suggesting that aerosols are a mixture of particles of different sources and different ages. Throughout the day is observed the aging of primary combustion particles due to the secondary aerosols coating. This coating may prolong the life time of the PAHs in the atmosphere. Also occurs a decrease in the ratio PAHs / DC during the day. Low ratios indicate the abundance of large particles, whereas high ratios indicate abundance dominated by small particle emissions from diesel engines. The resulting correlations show a significant linear trend evolution of PAHs with NOx, indicating that the PAHs are associated with the combustion of diesel, and a linear trend of PAHs with DC for each type of aerosol combustion, while the correlation of PAHs with CO results in an exponential trend which implies that PAHs are related to the combustion of diesel.

Abnormal brain functional connectivity leads to impaired mood and cognition in hyperthyroidism: a resting-state functional MRI study

PubMed Central

Li, Ling; Zhi, Mengmeng; Hou, Zhenghua; Zhang, Yuqun; Yue, Yingying; Yuan, Yonggui

2017-01-01

Patients with hyperthyroidism frequently have neuropsychiatric complaints such as lack of concentration, poor memory, depression, anxiety, nervousness, and irritability, suggesting brain dysfunction. However, the underlying process of these symptoms remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI), we depicted the altered graph theoretical metric degree centrality (DC) and seed-based resting-state functional connectivity (FC) in 33 hyperthyroid patients relative to 33 healthy controls. The peak points of significantly altered DC between the two groups were defined as the seed regions to calculate FC to the whole brain. Then, partial correlation analyses were performed between abnormal DC, FC and neuropsychological performances, as well as some clinical indexes. The decreased intrinsic functional connectivity in the posterior lobe of cerebellum (PLC) and medial frontal gyrus (MeFG), as well as the abnormal seed-based FC anchored in default mode network (DMN), attention network, visual network and cognitive network in this study, possibly constitutes the latent mechanism for emotional and cognitive changes in hyperthyroidism, including anxiety and impaired processing speed. PMID:28009983

Dendritic cell MST1 inhibits Th17 differentiation

PubMed Central

Li, Chunxiao; Bi, Yujing; Li, Yan; Yang, Hui; Yu, Qing; Wang, Jian; Wang, Yu; Su, Huilin; Jia, Anna; Hu, Ying; Han, Linian; Zhang, Jiangyuan; Li, Simin; Tao, Wufan; Liu, Guangwei

2017-01-01

Although the differentiation of CD4+T cells is widely studied, the mechanisms of antigen-presenting cell-dependent T-cell modulation are unclear. Here, we investigate the role of dendritic cell (DC)-dependent T-cell differentiation in autoimmune and antifungal inflammation and find that mammalian sterile 20-like kinase 1 (MST1) signalling from DCs negatively regulates IL-17 producing-CD4+T helper cell (Th17) differentiation. MST1 deficiency in DCs increases IL-17 production by CD4+T cells, whereas ectopic MST1 expression in DCs inhibits it. Notably, MST1-mediated DC-dependent Th17 differentiation regulates experimental autoimmune encephalomyelitis and antifungal immunity. Mechanistically, MST1-deficient DCs promote IL-6 secretion and regulate the activation of IL-6 receptor α/β and STAT3 in CD4+T cells in the course of inducing Th17 differentiation. Activation of the p38 MAPK signal is responsible for IL-6 production in MST1-deficient DCs. Thus, our results define the DC MST1–p38MAPK signalling pathway in directing Th17 differentiation. PMID:28145433

Abnormal brain functional connectivity leads to impaired mood and cognition in hyperthyroidism: a resting-state functional MRI study.

PubMed

Li, Ling; Zhi, Mengmeng; Hou, Zhenghua; Zhang, Yuqun; Yue, Yingying; Yuan, Yonggui

2017-01-24

Patients with hyperthyroidism frequently have neuropsychiatric complaints such as lack of concentration, poor memory, depression, anxiety, nervousness, and irritability, suggesting brain dysfunction. However, the underlying process of these symptoms remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI), we depicted the altered graph theoretical metric degree centrality (DC) and seed-based resting-state functional connectivity (FC) in 33 hyperthyroid patients relative to 33 healthy controls. The peak points of significantly altered DC between the two groups were defined as the seed regions to calculate FC to the whole brain. Then, partial correlation analyses were performed between abnormal DC, FC and neuropsychological performances, as well as some clinical indexes. The decreased intrinsic functional connectivity in the posterior lobe of cerebellum (PLC) and medial frontal gyrus (MeFG), as well as the abnormal seed-based FC anchored in default mode network (DMN), attention network, visual network and cognitive network in this study, possibly constitutes the latent mechanism for emotional and cognitive changes in hyperthyroidism, including anxiety and impaired processing speed.

Performance of an X-ray single pixel TES microcalorimeter under DC and AC biasing

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

Gottardi, L.; Kuur, J. van der; Korte, P. A. J. de

2009-12-16

We are developing Frequency Domain Multiplexing (FDM) for the read-out of TES imaging microcalorimeter arrays for future X-ray missions like IXO. In the FDM configuration the TES is AC voltage biased at a well defined frequencies (between 0.3 to 10 MHz) and acts as an AM modulating element. In this paper we will present a full comparison of the performance of a TES microcalorimeter under DC bias and AC bias at a frequency of 370 kHz. In both cases we measured the current-to-voltage characteristics, the complex impedance, the noise, the X-ray responsivity, and energy resolution. The behaviour is very similarmore » in both cases, but deviations in performances are observed for detector working points low in the superconducting transition (R/R{sub N}<0.5). The measured energy resolution at 5.89 keV is 2.7 eV for DC bias and 3.7 eV for AC bias, while the baseline resolution is 2.8 eV and 3.3 eV, respectively.« less

Effect of fluorescent particle size on the modulation efficiency of ultrasound-modulated fluorescence.

PubMed

Liu, Yuan; Yuan, Baohong; Vignola, Joseph

2012-01-01

To investigate whether the size of fluorescent particles affects the modulation efficiency of ultrasound-modulated fluorescence (UMF), we measured UMF and DC (direct current) signals of the fluorescence emission from four different sized fluorescent particles: (1) three carboxylate-modified fluorescent microspheres (FM) with diameters of 20 nm, 200 nm, and 1.0 µm and (2) streptavidin-conjugated Alexa Fluor 647 with a diameter of approximately 5 nm. The UMF and DC signals were simultaneously measured using a broadband lock-in amplifier and a narrowband amplifier, respectively. The ratio of the UMF strength to the DC signal strength is defined as the modulation efficiency. This modulation efficiency was then used to evaluate the effects of fluorophore size and concentration. Results show that the modulation efficiency was improved by approximately a factor of two when the size of the fluorescent particles is increased from 5 nm to 1 µm. In addition, the linear relationship between the UMF strength and ultrasound pressure (observed in our previous study) were maintained regardless of the fluorescent particle sizes.

Effect of fluorescent particle size on the modulation efficiency of ultrasound-modulated fluorescence

PubMed Central

Liu, Yuan; Yuan, Baohong; Vignola, Joseph

2013-01-01

To investigate whether the size of fluorescent particles affects the modulation efficiency of ultrasound-modulated fluorescence (UMF), we measured UMF and DC (direct current) signals of the fluorescence emission from four different sized fluorescent particles: (1) three carboxylate-modified fluorescent microspheres (FM) with diameters of 20 nm, 200 nm, and 1.0 µm and (2) streptavidin-conjugated Alexa Fluor 647 with a diameter of approximately 5 nm. The UMF and DC signals were simultaneously measured using a broadband lock-in amplifier and a narrowband amplifier, respectively. The ratio of the UMF strength to the DC signal strength is defined as the modulation efficiency. This modulation efficiency was then used to evaluate the effects of fluorophore size and concentration. Results show that the modulation efficiency was improved by approximately a factor of two when the size of the fluorescent particles is increased from 5 nm to 1 µm. In addition, the linear relationship between the UMF strength and ultrasound pressure (observed in our previous study) were maintained regardless of the fluorescent particle sizes. PMID:24179476

42. INTERIOR, FIRST FLOOR, NORTHWEST CORNER OF GRAND STAIRCASE (STAIRS ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

42. INTERIOR, FIRST FLOOR, NORTHWEST CORNER OF GRAND STAIRCASE (STAIRS G), SIDE AISLE, WEST WALL, THE NEGRO'S CONTRIBUTION IN THE SOCIAL AND CULTURAL DEVELOPMENT OF AMERICA: SCIENCE MURAL - U.S. Department of the Interior, Eighteenth & C Streets Northwest, Washington, District of Columbia, DC

45. INTERIOR, FIRST FLOOR, SOUTHEAST CORNER OF GRAND STAIRCASE (STAIRS ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

45. INTERIOR, FIRST FLOOR, SOUTHEAST CORNER OF GRAND STAIRCASE (STAIRS G), SIDE AISLE, EAST WALL, THE NEGRO'S CONTRIBUTION IN THE SOCIAL AND CULTURAL DEVELOPMENT OF AMERICA: EDUCATION MURAL - U.S. Department of the Interior, Eighteenth & C Streets Northwest, Washington, District of Columbia, DC

Salicylic acid biosynthesis is enhanced and contributes to increased biotrophic pathogen resistance in Arabidopsis hybrids

PubMed Central

Yang, Li; Li, Bosheng; Zheng, Xiao-yu; Li, Jigang; Yang, Mei; Dong, Xinnian; He, Guangming; An, Chengcai; Deng, Xing Wang

2015-01-01

Heterosis, the phenotypic superiority of a hybrid over its parents, has been demonstrated for many traits in Arabidopsis thaliana, but its effect on defence remains largely unexplored. Here, we show that hybrids between some A. thaliana accessions show increased resistance to the biotrophic bacterial pathogen Pseudomonas syringae pv. tomato (Pst) DC3000. Comparisons of transcriptomes between these hybrids and their parents after inoculation reveal that several key salicylic acid (SA) biosynthesis genes are significantly upregulated in hybrids. Moreover, SA levels are higher in hybrids than in either parent. Increased resistance to Pst DC3000 is significantly compromised in hybrids of pad4 mutants in which the SA biosynthesis pathway is blocked. Finally, increased histone H3 acetylation of key SA biosynthesis genes correlates with their upregulation in infected hybrids. Our data demonstrate that enhanced activation of SA biosynthesis in A. thaliana hybrids may contribute to their increased resistance to a biotrophic bacterial pathogen. PMID:26065719

RAD hard PROM design study

NASA Technical Reports Server (NTRS)

1981-01-01

The results of a preliminary study on the design of a radiation hardened fusible link programmable read-only memory (PROM) are presented. Various fuse technologies and the effects of radiation on MOS integrated circuits are surveyed. A set of design rules allowing the fabrication of a radiation hardened PROM using a Si-gate CMOS process is defined. A preliminary cell layout was completed and the programming concept defined. A block diagram is used to describe the circuit components required for a 4 K design. A design goal data sheet giving target values for the AC, DC, and radiation parameters of the circuit is presented.

Formation of manganese nanoclusters in a sputtering/aggregation source and the roles of individual operating parameters

NASA Astrophysics Data System (ADS)

Khojasteh, Malak; Kresin, Vitaly V.

2016-12-01

We describe the production of size selected manganese nanoclusters using a dc magnetron sputtering/aggregation source. Since nanoparticle production is sensitive to a range of overlapping operating parameters (in particular, the sputtering discharge power, the inert gas flow rates, and the aggregation length) we focus on a detailed map of the influence of each parameter on the average nanocluster size. In this way it is possible to identify the main contribution of each parameter to the physical processes taking place within the source. The discharge power and argon flow supply the atomic vapor, and argon also plays the crucial role in the formation of condensation nuclei via three-body collisions. However, neither the argon flow nor the discharge power have a strong effect on the average nanocluster size in the exiting beam. Here the defining role is played by the source residence time, which is governed by the helium supply and the aggregation path length. The size of mass selected nanoclusters was verified by atomic force microscopy of deposited particles.

Characteristics of individuals with integrated pensions.

PubMed

Bender, K A

1999-01-01

Employer pensions that integrate benefits with Social Security have been the focus of relatively little research. Since changes in Social Security benefit levels and other program characteristics can affect the benefit levels and other features of integrated pension plans, it is important to know who is covered by these plans. This article examines the characteristics of workers covered by integrated pension plans, compared to those with nonintegrated plans and those with no pension coverage. Integrated pension plans are those that explicitly adjust their benefit structure to help compensate for the employer's contributions to the Social Security program. There are two basic integration methods used by defined benefit (DB) plans. The offset method causes a reduction in employer pension benefits by up to half of the Social Security retirement benefit; the excess rate method is characterized by an accrual rate that is lower for earnings below the Social Security taxable maximum than above it. Defined contribution (DC) pension plans can be integrated along the lines of the excess rate method. To date, research on integrated pensions has focused on plan characteristics, as reported to the Bureau of Labor Statistics (BLS) through its Employee Benefits Survey (EBS). This research has examined the prevalence of integration among full-time, private sector workers by industry, firm size, and broad occupational categories. However, because the EBS provides virtually no data on worker characteristics, analyses of the effects of pension integration on retirement benefits have used hypothetical workers, varying according to assumed levels of earnings and job tenure. This kind of analysis is not particularly helpful in examining the potential effects of changes in the Social Security program on workers' pension benefits. However, data on pension integration at the individual level are available, most recently from the Health and Retirement Study (HRS), a nationally representative survey of individuals aged 51-61 in 1992. This dataset provides the basis for the analysis presented here. The following are some of the major findings from this analysis. The incidence of pension integration in the HRS sample is 32 percent of all workers with a pension (14 percent of all workers). The HRS can also identify integrated DC plans, a statistic that is not available from BLS data. The rate of integration for workers with only DC plans is 8 percent. After controlling for other variables, several socio-demographic characteristics are significantly related to the incidence of integration. The probability of having an integrated pension is 4.6 percentage points less for men compared to women. Non-Hispanic blacks are 6.4 percentage points less likely than non-Hispanic whites to have integrated pensions. Union members are 14 percentage points less likely to have integrated pensions, while workers with less than a graduate level education are at least 15 percentage points more likely to have a pension that is integrated. Some earnings and pension characteristics are also significantly correlated with pension integration. Earnings are positively related, with the probability of having an integrated pension increasing by 2 percentage points for an increase of $1,000 in annual pay. An even larger effect comes from earning at or above the Social Security taxable maximum. Workers at or above this income level are 10 percentage points more likely to have an integrated plan, but for those with more than one plan the probability of pension integration goes up by 13 percentage points.

Technical advance: live-imaging analysis of human dendritic cell migrating behavior under the influence of immune-stimulating reagents in an organotypic model of lung.

PubMed

Nguyen Hoang, Anh Thu; Chen, Puran; Björnfot, Sofia; Högstrand, Kari; Lock, John G; Grandien, Alf; Coles, Mark; Svensson, Mattias

2014-09-01

This manuscript describes technical advances allowing manipulation and quantitative analyses of human DC migratory behavior in lung epithelial tissue. DCs are hematopoietic cells essential for the maintenance of tissue homeostasis and the induction of tissue-specific immune responses. Important functions include cytokine production and migration in response to infection for the induction of proper immune responses. To design appropriate strategies to exploit human DC functional properties in lung tissue for the purpose of clinical evaluation, e.g., candidate vaccination and immunotherapy strategies, we have developed a live-imaging assay based on our previously described organotypic model of the human lung. This assay allows provocations and subsequent quantitative investigations of DC functional properties under conditions mimicking morphological and functional features of the in vivo parental tissue. We present protocols to set up and prepare tissue models for 4D (x, y, z, time) fluorescence-imaging analysis that allow spatial and temporal studies of human DCs in live epithelial tissue, followed by flow cytometry analysis of DCs retrieved from digested tissue models. This model system can be useful for elucidating incompletely defined pathways controlling DC functional responses to infection and inflammation in lung epithelial tissue, as well as the efficacy of locally administered candidate interventions. © 2014 Society for Leukocyte Biology.

In-Situ Microphysics from the MPACE IOP

DOE Data Explorer

McFarquhar, Greg

2008-01-15

Best estimates of the size distributions of supercooled water droplets and ice crystals for mixed-phase clouds measured during M-PACE for spiral ascents/descents over Barrow and Oliktok Point, and for ramped ascents/descents between Barrow and Oliktok Point. Our best estimates of the bulk microphysical properties such as ice water content (IWC), liquid water content (LWC), effective radius of ice crystals defined following Fu (1996) (rei), effective radius of supercooled water droplets (rew), total ice crystal number concentration (Ni), total water droplet number concentration (Nw) and total condensed water content (CWC), are also provided. The quantities were derived from the FSSP, 1DC, 2DC, HVPS and the CVI. Note HVPS data are only available after 10 Oct 2004 and some procedures have been developed to account for the missing data.

Best Merge Region Growing with Integrated Probabilistic Classification for Hyperspectral Imagery

NASA Technical Reports Server (NTRS)

Tarabalka, Yuliya; Tilton, James C.

2011-01-01

A new method for spectral-spatial classification of hyperspectral images is proposed. The method is based on the integration of probabilistic classification within the hierarchical best merge region growing algorithm. For this purpose, preliminary probabilistic support vector machines classification is performed. Then, hierarchical step-wise optimization algorithm is applied, by iteratively merging regions with the smallest Dissimilarity Criterion (DC). The main novelty of this method consists in defining a DC between regions as a function of region statistical and geometrical features along with classification probabilities. Experimental results are presented on a 200-band AVIRIS image of the Northwestern Indiana s vegetation area and compared with those obtained by recently proposed spectral-spatial classification techniques. The proposed method improves classification accuracies when compared to other classification approaches.

76 FR 41828 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-15

..., DC 20549-0213. Extension: Form N-54A; SEC File No. 270-182; OMB Control No. 3235-0237. Notice is...(a)), any company defined in Section 2(a)(48)(A) and (B) may elect to be subject to the provisions of.... The Commission has adopted Form N-54A (17 CFR 274.53) as the form for notification of election to be...

Low-Dose Radiation Promotes Dendritic Cell Migration and IL-12 Production via the ATM/NF-KappaB Pathway.

PubMed

Yu, Nan; Wang, Sinian; Song, Xiujun; Gao, Ling; Li, Wei; Yu, Huijie; Zhou, Chuanchuan; Wang, Zhenxia; Li, Fengsheng; Jiang, Qisheng

2018-04-01

For dendritic cells (DCs) to initiate an immune response, their ability to migrate and to produce interleukin-12 (IL-12) is crucial. It has been previously shown that low-dose radiation (LDR) promoted IL-12 production by DCs, resulting in increased DC activity that contributed to LDR hormesis in the immune system. However, the molecular mechanism of LDR-induced IL-12 production, as well as the effect of LDR on DC migration capacity require further elucidation. Using the JAWSII immortalized mouse dendritic cell line, we showed that in vitro X-ray irradiation (0.2 Gy) of DCs significantly increased DC migration and IL-12 production, and upregulated CCR7. The neutralizing antibody against CCR7 has been shown to abolish LDR-enhanced DC migration, demonstrating that CCR7 mediates LDR-promoting DC migration. We identified nuclear factor kappaB (NF-κB) as the central signaling pathway that mediated LDR-enhanced expression of IL-12 and CCR7 based on findings that 0.2 Gy X-ray irradiation activated NF-κB, showing increased nuclear p65 translocation and NF-κB DNA-binding activity, while an NF-κB inhibitor blocked LDR-enhanced expression of IL-12 and CCR7, as well as DC migration. Finally, we demonstrated that 0.2 Gy X-ray irradiation promoted ATM phosphorylation and reactive oxygen species generation; however, only the ATM inhibitor abolished the LDR-induced NF-κB-mediated expression of IL-12 and CCR7. Altogether, our data show that exposure to LDR resulted in a hormetic effect on DCs regarding CCR7-mediated migration and IL-12 production by activating the ATM/NF-κB pathway.

Topoisomerase I peptide-loaded dendritic cells induce autoantibody response as well as skin and lung fibrosis.

PubMed

Mehta, Heena; Goulet, Philippe-Olivier; Nguyen, Vinh; Pérez, Gemma; Koenig, Martial; Senécal, Jean-Luc; Sarfati, Marika

2016-12-01

DNA Topoisomerase I (TopoI) is a candidate autoantigen for diffuse cutaneous systemic sclerosis (dcSSc) associated with fatal lung disease. Dendritic cells (DCs) contribute to bleomycin-induced lung fibrosis. However, the possibility that TopoI-loaded DCs are involved in the initiation and/or perpetuation of dcSSc has not been explored. Here, we show that immunization with TopoI peptide-loaded DCs induces anti-TopoI autoantibody response and long-term fibrosis. Mice were repeatedly immunized with unpulsed DCs or DCs loaded with either TOPOIA or TOPOIB peptides, selected from different regions of TopoI. At week 12 after initial DC immunization, TOPOIA DCs but not TOPOIB DCs immunization induced mixed inflammation and fibrosis in lungs and skin. At a late time point (week 18), both TOPOIA DCs and TOPOIB DCs groups displayed increased alpha-smooth muscle actin expression in lungs and dermis along with skin fibrosis distal from the site of injection when compared with unpulsed DCs. Both TopoI peptide-DC-immunized groups developed IgG2a anti-TopoI autoantibody response. At week 10, signs of perivascular, peribronchial, and parenchymal pulmonary inflammation were already observed in the TOPOIA DCs group, together with transient elevation in bronchoalveolar lavage cell counts, IL-17A expression, and CXCL4 production, a biomarker of early human dcSSc. Collectively, TopoI peptide DCs induce progressive autoantibody response as well as development of protracted skin and lung dcSSc-like disease. Pronounced lung inflammation, transient IL-17A, and CXCL4 expression precede fibrosis development. Our immunization strategy, that uses self immune system and autoantigen, will help to further investigate the pathogenesis of this complex autoimmune disorder with unmet medical needs.

Activated dendritic cells delivered in tissue compatible biomatrices induce in-situ anti-tumor CTL responses leading to tumor regression

PubMed Central

Verma, Vivek; Kim, Young; Lee, Min-Cheol; Lee, Jae-Tae; Cho, Sunghoon; Park, In-Kyu; Min, Jung Joon; Lee, Je Jung; Lee, Shee Eun; Rhee, Joon Haeng

2016-01-01

Dendritic cell (DC) based anti-cancer immunotherapy is well tolerated in patients with advanced cancers. However, the clinical responses seen after adoptive DC therapy have been suboptimal. Several factors including scarce DC numbers in tumors and immunosuppressive tumor microenvironments contribute to the inefficacy of DCs as cellular vaccines. Hence DC based vaccines can benefit from novel methods of cell delivery that would prevent the direct exposure of immune cells to suppressive tumor microenvironments. Here we evaluated the ability of DCs harbored in biocompatible scaffolds (referred to as biomatrix entrapped DCs; beDCs) in activating specific anti-tumor immune responses against primary and post-surgery secondary tumors. Using a preclinical cervical cancer and a melanoma model in mice, we show that single treatment of primary and post-surgery secondary tumors using beDCs resulted in significant tumor growth retardation while multiple inoculations were required to achieve a significant anti-tumor effect when DCs were given in free form. Additionally, we found that, compared to the tumor specific E6/E7 peptide vaccine, total tumor lysate induced higher expression of CD80 and CD40 on DCs that induced increased levels of IFNγ production upon interaction with host lymphocytes. Remarkably, a strong immunocyte infiltration into the host-implanted DC-scaffold was observed. Importantly, the host-implanted beDCs induced the anti-tumor immune responses in the absence of any stromal cell support, and the biomatrix structure was eventually absorbed into the surrounding host tissue. Collectively, these data indicate that the scaffold-based DC delivery may provide an efficient and safe way of delivering cell-based vaccines for treatment of primary and post-surgery secondary tumors. PMID:27223090

Research in Teacher Education: International Perspectives.

ERIC Educational Resources Information Center

Tisher, Richard P., Ed.; Wideen, Marvin F., Ed.

This book was developed in response to audience interest in a symposium sponsored by the American Educational Research Association (annual meeting, Washington, D.C., 1987). The book addresses international perspectives on research in teacher education and offers the following contributions from scholars from 12 countries: "The Role Played by…

43. INTERIOR, FIRST FLOOR, SOUTHWEST CORNER OF GRAND STAIRCASE (STAIRS ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

43. INTERIOR, FIRST FLOOR, SOUTHWEST CORNER OF GRAND STAIRCASE (STAIRS G), SIDE AISLE, WEST WALL, THE NEGRO'S CONTRIBUTION IN THE SOCIAL AND CULTURAL DEVELOPMENT OF AMERICA: THE ARTS MURAL - U.S. Department of the Interior, Eighteenth & C Streets Northwest, Washington, District of Columbia, DC

Combined cytotoxic activity of an infectious, but non-replicative herpes simplex virus type 1 and plasmacytoid dendritic cells against tumour cells

PubMed Central

Thomann, Sabrina; Boscheinen, Jan B; Vogel, Karin; Knipe, David M; DeLuca, Neal; Gross, Stefanie; Schuler-Thurner, Beatrice; Schuster, Philipp; Schmidt, Barbara

2015-01-01

Malignant melanoma is an aggressive tumour of the skin with increasing incidence, frequent metastasis and poor prognosis. At the same time, it is an immunogenic type of cancer with spontaneous regressions. Most recently, the tumoricidal effect of plasmacytoid dendritic cells (pDC) and their capacity to overcome the immunosuppressive tumour microenvironment are being investigated. In this respect, we studied the effect of the infectious, but replication-deficient, herpes simplex virus 1 (HSV-1) d106S vaccine strain, which lacks essential immediate early genes, in pDC co-cultures with 11 melanoma cell lines. We observed a strong cytotoxic activity, inducing apoptotic and necrotic cell death in most melanoma cell lines. The cytotoxic activity of HSV-1 d106S plus pDC was comparable to the levels of cytotoxicity induced by natural killer cells, but required only a fraction of cells with effector : target ratios of 1 : 20 (P < 0·05). The suppressive activity of cell-free supernatants derived from virus-stimulated pDC was significantly neutralized using antibodies against the interferon-α receptor (P < 0·05). In addition to type I interferons, TRAIL and granzyme B contributed to the inhibitory effect of HSV-1 d106S plus pDC to a minor extent. UV-irradiated viral stocks were significantly less active than infectious particles, both in the absence and presence of pDC (P < 0·05), indicating that residual activity of HSV-1 d106S is a major component and sensitizes the tumour cells to interferon-producing pDC. Three leukaemic cell lines were also susceptible to this treatment, suggesting a general anti-tumour effect. In conclusion, the potential of HSV-1 d106S for therapeutic vaccination should be further evaluated in patients suffering from different malignancies. PMID:26194553

Cetuximab-activated natural killer (NK) and dendritic cells (DC) collaborate to trigger tumor antigen-specific T cell immunity in head and neck cancer patients

PubMed Central

Srivastava, Raghvendra M.; Lee, Steve C.; Filho, Pedro A. Andrade; Lord, Christopher A.; Jie, Hyun-bae; Davidson, H. Carter; López-Albaitero, Andrés; Gibson, Sandra P.; Gooding, William E.; Ferrone, Soldano; Ferris, Robert L.

2013-01-01

Purpose Tumor antigen (TA)-specific monoclonal antibodies (mAb) block oncogenic signaling and induce Fcγ receptor (FcγR)-mediated cytotoxicity. However, the role of CD8+ cytotoxic T lymphocyte (CTL) and FcγR in initiating innate and adaptive immune responses in mAb-treated human cancer patients is still emerging. Experimental Design FcγRIIIa codon 158 polymorphism was correlated with survival in 107 cetuximab-treated head and neck cancer (HNC) patients. Flow cytometry was performed to quantify EGFR-specific T cells in cetuximab-treated HNC patients. The effect of cetuximab on NK cell, dendritic cell (DC), and T cell activation was measured using IFN-γ release assays and flow cytometry. Results FcγR IIIa polymorphism did not predict clinical outcome in cetuximab-treated HNC patients, however elevated circulating EGFR -specific CD8+ 853-861 T cells were found in cetuximab-treated HNC patients (p<0.005). Cetuximab promoted EGFR-specific cellular immunity through the interaction of EGFR+ tumor cells and FcγRIIIa on NK cells, but not on the polymorphism per se. Cetuximab-activated NK cells induced IFN-γ dependent expression of DC maturation markers, antigen presentation machinery (APM) components such as TAP-1/2, and Th1 chemokines through NKG2D/MICA binding. Cetuximab initiated adaptive immune responses via NK-cell induced DC maturation, which enhanced cross-presentation to CTL specific for EGFR as well as another TA, MAGE-3. Conclusion Cetuximab-activated NK cells promote DC maturation and CD8+ T cell priming, leading to TA spreading and Th1 cytokine release through ‘NK-DC cross-talk.’ FcγRIIIa polymorphism did not predict clinical response to cetuximab, but was necessary for NK-DC interaction and mAb induced cross-presentation. EGFR-specific T cells in cetuximab treated HNC patients may contribute to clinical response. PMID:23444227

Comments, with reply, on 'Parallel resonant converter with LLC-type commutation' by C. Q. Lee et al.

NASA Astrophysics Data System (ADS)

Hamill, David C.

1991-05-01

In a recent paper by Lee et al. (1989), the authors analyzed a DC-DC converter that they termed the LLC-type PRC (parallel resonant converter). Its resonant network contains three active components-two inductances and a parallel capacitance -and as a consequence the the converter might be expected to have third-order dynamics. But Lee et al. employed a matrix transformation to show that the behavior of the circuit may be represented as a state-plane trajectory, as for a second-order circuit. The purpose of this contribution is to show that the converter has a zero-frequency eigenvalue, associated with undesirable circulating DC. The second-order dynamics exhibited by the third-order converter are explained by an application of Thevenin's theorem. Some aerospace applications of the LLC-type parallel resonant converter (PRC) are discussed. In their reply, the authors show that the circulating direct current does not exist in the practical converter circuit.

Effect of Aging on Periodontal Inflammation, Microbial Colonization, and Disease Susceptibility

PubMed Central

Wu, Y.; Dong, G.; Xiao, W.; Xiao, E.; Miao, F.; Syverson, A.; Missaghian, N.; Vafa, R.; Cabrera-Ortega, A.A.; Rossa, C.; Graves, D.T.

2016-01-01

Periodontitis is a chronic inflammatory disease induced by a biofilm that forms on the tooth surface. Increased periodontal disease is associated with aging. We investigated the effect of aging on challenge by oral pathogens, examining the host response, colonization, and osteoclast numbers in aged versus young mice. We also compared the results with mice with lineage-specific deletion of the transcription factor FOXO1, which reduces dendritic cell (DC) function. Periodontitis was induced by oral inoculation of Porphyromonas gingivalis and Fusobacterium nucleatum in young (4 to 5 mo) and aged (14 to 15 mo) mice. Aged mice as well as mice with reduced DC function had decreased numbers of DCs in lymph nodes, indicative of a diminished host response. In vitro studies suggest that reduced DC numbers in lymph nodes of aged mice may involve the effect of advanced glycation end products on DC migration. Surprisingly, aged mice but not mice with genetically altered DC function had greater production of antibody to P. gingivalis, greater IL-12 expression, and more plasma cells in lymph nodes following oral inoculation as compared with young mice. The greater adaptive immune response in aged versus young mice was linked to enhanced levels of P. gingivalis and reduced bacterial diversity. Thus, reduced bacterial diversity in aged mice may contribute to increased P. gingivalis colonization following inoculation and increased periodontal disease susceptibility, reflected by higher TNF levels and osteoclast numbers in the periodontium of aged versus young mice. PMID:26762510

Effect of Aging on Periodontal Inflammation, Microbial Colonization, and Disease Susceptibility.

PubMed

Wu, Y; Dong, G; Xiao, W; Xiao, E; Miao, F; Syverson, A; Missaghian, N; Vafa, R; Cabrera-Ortega, A A; Rossa, C; Graves, D T

2016-04-01

Periodontitis is a chronic inflammatory disease induced by a biofilm that forms on the tooth surface. Increased periodontal disease is associated with aging. We investigated the effect of aging on challenge by oral pathogens, examining the host response, colonization, and osteoclast numbers in aged versus young mice. We also compared the results with mice with lineage-specific deletion of the transcription factor FOXO1, which reduces dendritic cell (DC) function. Periodontitis was induced by oral inoculation of Porphyromonas gingivalis and Fusobacterium nucleatum in young (4 to 5 mo) and aged (14 to 15 mo) mice. Aged mice as well as mice with reduced DC function had decreased numbers of DCs in lymph nodes, indicative of a diminished host response. In vitro studies suggest that reduced DC numbers in lymph nodes of aged mice may involve the effect of advanced glycation end products on DC migration. Surprisingly, aged mice but not mice with genetically altered DC function had greater production of antibody to P. gingivalis, greater IL-12 expression, and more plasma cells in lymph nodes following oral inoculation as compared with young mice. The greater adaptive immune response in aged versus young mice was linked to enhanced levels of P. gingivalis and reduced bacterial diversity. Thus, reduced bacterial diversity in aged mice may contribute to increased P. gingivalis colonization following inoculation and increased periodontal disease susceptibility, reflected by higher TNF levels and osteoclast numbers in the periodontium of aged versus young mice. © International & American Associations for Dental Research 2016.

Reduction in liver transplant wait-listing in the era of direct-acting antiviral therapy.

PubMed

Flemming, Jennifer A; Kim, W Ray; Brosgart, Carol L; Terrault, Norah A

2017-03-01

Direct-acting antiviral (DAA) therapy, recently approved for patients with decompensated cirrhosis (DC) secondary to hepatitis C virus (HCV), is associated with improved hepatic function. We analyzed trends in liver transplant (LT) wait-listing (WL) to explore potential impact of effective medical therapy on WL registration. This is a cohort study using the Scientific Registry of Transplant Recipients database from 2003 to 2015. A total of 47,591 adults wait-listed for LT from HCV, hepatitis B virus (HBV), and nonalcoholic steatohepatitis (NASH) were identified. LT indication was defined as DC if the Model for End-Stage Liver Disease (MELD) at WL was ≥15 or hepatocellular carcinoma (HCC). Era of listing was divided into interferon (IFN; 2003-2010), protease inhibitor (PI; 2011-2013), and direct-acting antiviral (DAA; 2014-2015). Annual standardized incidence rates of WL were analyzed using Poisson regression. Adjusted incidences of LT WL for DC in HCV patients decreased by 5% in the PI era (P = 0.004) and 32% in the DAA era (P < 0.001) compared to the IFN era. Listing for DC in HBV also decreased in the PI (-17%; P = 0.002) and DAA eras (-24%; P < 0.001). Conversely, WL for DC in NASH increased by 41% in the PI era (P < 0.001) and 81% in the DAA era (P < 0.001). WL for HCC in both the HCV and NASH populations increased in both the PI and DAA eras (P < 0.001 for all) whereas HCC WL in HBV remained stable (P > 0.05 for all). The rate of LT WL for HCV complicated by DC has decreased by over 30% in the era of DAA therapy. Further reductions in WL are anticipated with increased testing, linkage to care, and access to DAA therapy. (Hepatology 2017;65:804-812). © 2016 by the American Association for the Study of Liver Diseases.

The United States Antarctic Program Data Center (USAP-DC): Recent Developments

NASA Astrophysics Data System (ADS)

Nitsche, F. O.; Bauer, R.; Arko, R. A.; Shane, N.; Carbotte, S. M.; Scambos, T.

2017-12-01

Antarctic earth and environmental science data are highly valuable, often unique research assets. They are acquired with substantial and expensive logistical effort, frequently in areas that will not be re-visited for many years. The data acquired in support of Antarctic research span a wide range of disciplines. Historically, data management for the US Antarctic Program (USAP) has made use of existing disciplinary data centers, and the international Antarctic Master Directory (AMD) has served as a central metadata catalog linking to data files hosted in these external repositories. However, disciplinary repositories do not exist for all USAP-generated data types and often it is unclear what repositories are appropriate, leading to many datasets being served locally from scientist's websites or not available at all. The USAP Data Center (USAP-DC; www.usap-dc.org), operated as part of the Interdisciplinary Earth Data Alliance (IEDA), contributes to the broader preservation of research data acquired with funding from NSF's Office of Polar Programs by providing a repository for diverse data from the Antarctic region. USAP-DC hosts data that spans the range of Antarctic research from snow radar to volcano observatory imagery to penguin counts to meteorological model outputs. Data services include data documentation, long-term preservation, and web publication, as well as scientist support for registration of data descriptions into the AMD in fulfillment of US obligations under the International Antarctic Treaty. In Spring 2016, USAP-DC and the NSIDC began a new collaboration to consolidate data services for Antarctic investigators and to integrate the NSF-funded glaciology collection at NSIDC with the collection hosted by USAP-DC. Investigator submissions for NSF's Glaciology program now make use of USAP-DC's web submission tools, providing a uniform interface for Antarctic investigators. The tools have been redesigned to collect a broader range of metadata. Each data submission is reviewed and verified by a specialist from the USAP-DC/NSIDC team depending on disciplinary focus of the submission. A recently updated web search interface is available to search data by title, NSF program, award, dataset contributor, large scale project (e.g. WAIS Divide Ice Core) or by specifying an area in map view.

78 FR 40828 - Proposed Collection; Comment Request for Notice 2006-107

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-08

... Notice 2006-107, Diversification Requirements for Qualified Defined Contribution Plans Holding Publicly...: Title: Diversification Requirements for Qualified Defined Contribution Plans Holding Publicly Traded... diversification rights with respect to publicly traded employer securities held by a defined contribution plan...

Cigarette price variation around high schools: evidence from Washington DC.

PubMed

Cantrell, Jennifer; Ganz, Ollie; Anesetti-Rothermel, Andrew; Harrell, Paul; Kreslake, Jennifer M; Xiao, Haijun; Pearson, Jennifer L; Vallone, Donna; Kirchner, Thomas R

2015-01-01

This study examines lowest cigarette prices in all tobacco retail outlets in Washington D.C. (n=750) in relation to the type and number of high schools nearby, controlling for confounders. The lowest overall and Newport menthol prices were significantly lower at outlets near public non-charter and charter schools compared with outlets near private schools. Given higher smoking prevalence and more price-sensitive youth subgroups in U.S. public schools, exposure to low prices may contribute to tobacco-related health disparities in minority and low-income populations. Tobacco taxes combined with policies to minimize the increasing use of price as a marketing tool are critical. Copyright © 2014 Elsevier Ltd. All rights reserved.

The dynamic resistance of YBCO coated conductor wire: effect of DC current magnitude and applied field orientation

NASA Astrophysics Data System (ADS)

Jiang, Zhenan; Zhou, Wei; Li, Quan; Yao, Min; Fang, Jin; Amemiya, Naoyuki; Bumby, Chris W.

2018-07-01

Dynamic resistance, which occurs when a HTS coated conductor carries a DC current under an AC magnetic field, can have critical implications for the design of HTS machines. Here, we report measurements of dynamic resistance in a commercially available SuperPower 4 mm-wide YBCO coated conductor, carrying a DC current under an applied AC magnetic field of arbitrary orientation. The reduced DC current, I t/I c0, ranged from 0.01 to 0.9, where I t is the DC current level and I c0 is the self-field critical current of the conductor. The field angle (the angle between the magnetic field and the normal vector of the conductor wide-face) was varied between 0° and 90° at intervals of 10°. We show that the effective width of the conductor under study is ˜12% less than the physical wire width, and we attribute this difference to edge damage of the wire during or after manufacture. We then examine the measured dynamic resistance of this wire under perpendicular applied fields at very low DC current levels. In this regime we find that the threshold field, B th, of the conductor is well described by the nonlinear equation of Mikitik and Brandt. However, this model consistently underestimates the threshold field at higher current levels. As such, the dynamic resistance in a coated conductor under perpendicular magnetic fields is best described using two different equations for each of the low and high DC current regimes, respectively. At low DC currents where I t/I c0 ≤ 0.1, the nonlinear relationship of Mikitik and Brandt provides the closest agreement with experimental data. However, in the higher current regime where I t/I c0 ≥ 0.2, closer agreement is obtained using a simple linear expression which assumes a current-independent penetration field. We further show that for the conductor studied here, the measured dynamic resistance at different field angles is dominated by the perpendicular magnetic field component, with negligible contribution from the parallel component. Our findings now enable the dynamic resistance of a single conductor to be analytically determined for a very wide range of DC currents and at all applied field angles.

Magnification of starting torques of dc motors by maximum power point trackers in photovoltaic systems

NASA Technical Reports Server (NTRS)

Appelbaum, Joseph; Singer, S.

1989-01-01

Direct current (dc) motors are used in terrestrial photovoltaic (PV) systems such as in water-pumping systems for irrigation and water supply. Direct current motors may also be used for space applications. Simple and low weight systems including dc motors may be of special interest in space where the motors are directly coupled to the solar cell array (with no storage). The system will operate only during times when sufficient insolation is available. An important performance characteristic of electric motors is the starting to rated torque ratio. Different types of dc motors have different starting torque ratios. These ratios are dictated by the size of solar cell array, and the developed motor torque may not be sufficient to overcome the load starting torque. By including a maximum power point tracker (MPPT) in the PV system, the starting to rated torque ratio will increase, the amount of which depends on the motor type. The starting torque ratio is calculated for the permanent magnet, series and shunt excited dc motors when powered by solar cell arrays for two cases: with and without MPPT's. Defining a motor torque magnification by the ratio of the motor torque with an MPPT to the motor torque without an MPPT, a magnification of 3 was obtained for the permanent magnet motor and a magnification of 7 for both the series and shunt motors. The effect of the variation of solar insolation on the motor starting torque was covered. All motor types are less sensitive to insolation variation in systems including MPPT's as compared to systems with MPPT's. The analysis of this paper will assist the PV system designed to determine whether or not to include an MPPT in the system for a specific motor type.

Intracellular bacteria interfere with dendritic cell functions: role of the type I interferon pathway.

PubMed

Gorvel, Laurent; Textoris, Julien; Banchereau, Romain; Ben Amara, Amira; Tantibhedhyangkul, Wiwit; von Bargen, Kristin; Ka, Mignane B; Capo, Christian; Ghigo, Eric; Gorvel, Jean-Pierre; Mege, Jean-Louis

2014-01-01

Dendritic cells (DCs) orchestrate host defenses against microorganisms. In infectious diseases due to intracellular bacteria, the inefficiency of the immune system to eradicate microorganisms has been attributed to the hijacking of DC functions. In this study, we selected intracellular bacterial pathogens with distinct lifestyles and explored the responses of monocyte-derived DCs (moDCs). Using lipopolysaccharide as a control, we found that Orientia tsutsugamushi, the causative agent of scrub typhus that survives in the cytosol of target cells, induced moDC maturation, as assessed by decreased endocytosis activity, the ability to induce lymphocyte proliferation and the membrane expression of phenotypic markers. In contrast, Coxiella burnetii, the agent of Q fever, and Brucella abortus, the agent of brucellosis, both of which reside in vacuolar compartments, only partly induced the maturation of moDCs, as demonstrated by a phenotypic analysis. To analyze the mechanisms used by C. burnetii and B. abortus to alter moDC activation, we performed microarray and found that C. burnetii and B. abortus induced a specific signature consisting of TLR4, TLR3, STAT1 and interferon response genes. These genes were down-modulated in response to C. burnetii and B. abortus but up-modulated in moDCs activated by lipopolysaccharide and O. tsutsugamushi. This transcriptional alteration was associated with the defective interferon-β production. This study demonstrates that intracellular bacteria specifically affect moDC responses and emphasizes how C. burnetii and B. abortus interfere with moDC activation and the antimicrobial immune response. We believe that comparing infection by several bacterial species may be useful for defining new pathways and biomarkers and for developing new treatment strategies.

Kinetic studies of the folding of heterodimeric monellin: evidence for switching between alternative parallel pathways.

PubMed

Aghera, Nilesh; Udgaonkar, Jayant B

2012-07-13

Determining whether or not a protein uses multiple pathways to fold is an important goal in protein folding studies. When multiple pathways are present, defined by transition states that differ in their compactness and structure but not significantly in energy, they may manifest themselves by causing the dependence on denaturant concentration of the logarithm of the observed rate constant of folding to have an upward curvature. In this study, the folding mechanism of heterodimeric monellin [double-chain monellin (dcMN)] has been studied over a range of protein and guanidine hydrochloride (GdnHCl) concentrations, using the intrinsic tryptophan fluorescence of the protein as the probe for the folding reaction. Refolding is shown to occur in multiple kinetic phases. In the first stage of refolding, which is silent to any change in intrinsic fluorescence, the two chains of monellin bind to one another to form an encounter complex. Interrupted folding experiments show that the initial encounter complex folds to native dcMN via two folding routes. A productive folding intermediate population is identified on one route but not on both of these routes. Two intermediate subpopulations appear to form in a fast kinetic phase, and native dcMN forms in a slow kinetic phase. The chevron arms for both the fast and slow phases of refolding are shown to have upward curvatures, suggesting that at least two pathways each defined by a different intermediate are operational during these kinetic phases of structure formation. Refolding switches from one pathway to the other as the GdnHCl concentration is increased. Copyright © 2012 Elsevier Ltd. All rights reserved.

75 FR 34704 - Joint CFTC-SEC Advisory Committee on Emerging Regulatory Issues

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-18

... the Committee. The agenda for the meeting includes: (i) Committee organizational matters; (ii... make recommendations related to market structure issues that may have contributed to the volatility, as...'s Public Reference Room, 100 F St., NE., Washington, DC 20549, on official business days between the...

Symposium on Manpower and the War on Hunger (Washington, D.C., May 3-5, 1967).

ERIC Educational Resources Information Center

1967

Approximately 75 specialists from government, universities, foundations, international organizations, trade unions, cooperatives, and business organizations participated in a 3-day symposium to contribute to efforts of the United States Government and international organizations to decrease the gap between world food production and population…

Impaired Telomere Maintenance and Decreased Canonical WNT Signaling but Normal Ribosome Biogenesis in Induced Pluripotent Stem Cells from X-Linked Dyskeratosis Congenita Patients.

PubMed

Gu, Bai-Wei; Apicella, Marisa; Mills, Jason; Fan, Jian-Meng; Reeves, Dara A; French, Deborah; Podsakoff, Gregory M; Bessler, Monica; Mason, Philip J

2015-01-01

Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome characterized by the presence of short telomeres at presentation. Mutations in ten different genes, whose products are involved in the telomere maintenance pathway, have been shown to cause DC. The X-linked form is the most common form of the disease and is caused by mutations in the gene DKC1, encoding the protein dyskerin. Dyskerin is required for the assembly and stability of telomerase and is also involved in ribosomal RNA (rRNA) processing where it converts specific uridines to pseudouridine. DC is thought to result from failure to maintain tissues, like blood, that are renewed by stem cell activity, but research into pathogenic mechanisms has been hampered by the difficulty of obtaining stem cells from patients. We reasoned that induced pluripotent stem (iPS) cells from X-linked DC patients may provide information about the mechanisms involved. Here we describe the production of iPS cells from DC patients with DKC1 mutations Q31E, A353V and ΔL37. In addition we constructed "corrected" lines with a copy of the wild type dyskerin cDNA expressed from the AAVS1 safe harbor locus. We show that in iPS cells with DKC1 mutations telomere maintenance is compromised with short telomere lengths and decreased telomerase activity. The degree to which telomere lengths are affected by expression of telomerase during reprograming, or with ectopic expression of wild type dyskerin, is variable. The recurrent mutation A353V shows the most severe effect on telomere maintenance. A353V cells but not Q31E or ΔL37 cells, are refractory to correction by expression of wild type DKC1 cDNA. Because dyskerin is involved in both telomere maintenance and ribosome biogenesis it has been postulated that defective ribosome biogenesis and translation may contribute to the disease phenotype. Evidence from mouse and zebra fish models has supported the involvement of ribosome biogenesis but primary cells from human patients have so far not shown defects in pseudouridylation or ribosomal RNA processing. None of the mutant iPS cells presented here show decreased pseudouridine levels in rRNA or defective rRNA processing suggesting telomere maintenance defects account for most of the phenotype of X-linked DC. Finally gene expression analysis of the iPS cells shows that WNT signaling is significantly decreased in all mutant cells, raising the possibility that defective WNT signaling may contribute to disease pathogenesis.

Impaired Telomere Maintenance and Decreased Canonical WNT Signaling but Normal Ribosome Biogenesis in Induced Pluripotent Stem Cells from X-Linked Dyskeratosis Congenita Patients

PubMed Central

Gu, Bai-Wei; Apicella, Marisa; Mills, Jason; Fan, Jian-Meng; Reeves, Dara A.; French, Deborah; Podsakoff, Gregory M.; Bessler, Monica; Mason, Philip J.

2015-01-01

Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome characterized by the presence of short telomeres at presentation. Mutations in ten different genes, whose products are involved in the telomere maintenance pathway, have been shown to cause DC. The X-linked form is the most common form of the disease and is caused by mutations in the gene DKC1, encoding the protein dyskerin. Dyskerin is required for the assembly and stability of telomerase and is also involved in ribosomal RNA (rRNA) processing where it converts specific uridines to pseudouridine. DC is thought to result from failure to maintain tissues, like blood, that are renewed by stem cell activity, but research into pathogenic mechanisms has been hampered by the difficulty of obtaining stem cells from patients. We reasoned that induced pluripotent stem (iPS) cells from X-linked DC patients may provide information about the mechanisms involved. Here we describe the production of iPS cells from DC patients with DKC1 mutations Q31E, A353V and ΔL37. In addition we constructed “corrected” lines with a copy of the wild type dyskerin cDNA expressed from the AAVS1 safe harbor locus. We show that in iPS cells with DKC1 mutations telomere maintenance is compromised with short telomere lengths and decreased telomerase activity. The degree to which telomere lengths are affected by expression of telomerase during reprograming, or with ectopic expression of wild type dyskerin, is variable. The recurrent mutation A353V shows the most severe effect on telomere maintenance. A353V cells but not Q31E or ΔL37 cells, are refractory to correction by expression of wild type DKC1 cDNA. Because dyskerin is involved in both telomere maintenance and ribosome biogenesis it has been postulated that defective ribosome biogenesis and translation may contribute to the disease phenotype. Evidence from mouse and zebra fish models has supported the involvement of ribosome biogenesis but primary cells from human patients have so far not shown defects in pseudouridylation or ribosomal RNA processing. None of the mutant iPS cells presented here show decreased pseudouridine levels in rRNA or defective rRNA processing suggesting telomere maintenance defects account for most of the phenotype of X-linked DC. Finally gene expression analysis of the iPS cells shows that WNT signaling is significantly decreased in all mutant cells, raising the possibility that defective WNT signaling may contribute to disease pathogenesis. PMID:25992652

Tetraspanin CD37 contributes to the initiation of cellular immunity by promoting dendritic cell migration.

PubMed

Gartlan, Kate H; Wee, Janet L; Demaria, Maria C; Nastovska, Roza; Chang, Tsz Man; Jones, Eleanor L; Apostolopoulos, Vasso; Pietersz, Geoffrey A; Hickey, Michael J; van Spriel, Annemiek B; Wright, Mark D

2013-05-01

Previous studies on the role of the tetraspanin CD37 in cellular immunity appear contradictory. In vitro approaches indicate a negative regulatory role, whereas in vivo studies suggest that CD37 is necessary for optimal cellular responses. To resolve this discrepancy, we studied the adaptive cellular immune responses of CD37(-/-) mice to intradermal challenge with either tumors or model antigens and found that CD37 is essential for optimal cell-mediated immunity. We provide evidence that an increased susceptibility to tumors observed in CD37(-/-) mice coincides with a striking failure to induce antigen-specific IFN-γ-secreting T cells. We also show that CD37 ablation impairs several aspects of DC function including: in vivo migration from skin to draining lymph nodes; chemo-tactic migration; integrin-mediated adhesion under flow; the ability to spread and form actin protrusions and in vivo priming of adoptively transferred naïve T cells. In addition, multiphoton microscopy-based assessment of dermal DC migration demonstrated a reduced rate of migration and increased randomness of DC migration in CD37(-/-) mice. Together, these studies are consistent with a model in which the cellular defect that underlies poor cellular immune induction in CD37(-/-) mice is impaired DC migration. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Celecoxib-Induced Self-Assembly of Smart Albumin-Doxorubicin Conjugate for Enhanced Cancer Therapy.

PubMed

Shi, Leilei; Xu, Li; Wu, Chenwei; Xue, Bai; Jin, Xin; Yang, Jiapei; Zhu, Xinyuan

2018-03-14

Recent years have witnessed the great contributions that drug combination therapy has made for enhanced cancer therapy. However, because of the complicated pharmacokinetics of combined drug formulations, the majority of combination strategies show severe adverse effects at high dosage and poor biodistribution in vivo. To overcome these deficiencies and achieve enhanced cancer therapy, we put forward a method to construct a smart albumin-based nanoplatform, denoted as K237-HSA-DC, for codelivery of cyclooxygenase-2 (COX-2) inhibitor (celecoxib) and chemotherapeutic agent (doxorubicin, DOX). Both in vitro and in vivo studies indicate that K237-HSA-DC exhibits the best therapeutic efficacy on tumor cells compared with all the other formulations. Moreover, K237-HSA-DC shows fewer side effects on normal organs in contrast to other formulations. To understand the reasons behind the improved drug efficacy in depth, we performed a cell metabonomics-based mechanism study and found that celecoxib could enhance the inhibitory effect of DOX on the transport of glucose into cells and then lead to subsequent significant energy metabolism inhibition. Considering the above-mentioned advantages of K237-HSA-DC, we believe the smart albumin-based nanoplatform can serve as a promising drug delivery system for enhanced cancer therapy.

The power of power: electrokinetic control of PAH interactions with exfoliated graphite.

PubMed

Qin, Jinyi; Moustafa, Ahmed; Harms, Hauke; El-Din, Mohamed Gamal; Wick, Lukas Y

2015-05-15

Exfoliated graphite (EG) exhibits exceptional sorption capacity for petroleum and dissolved hydrocarbons owing to its highly hydrophobic surface and wide pore size distribution. The high price of preparing EG, however, restricts its application. Methods which increase the rate or extent of sorption to EG even further are thus longed for. Here, we assess the effects of weak direct current (DC) fields on the sorption of the polycyclic aromatic hydrocarbon phenanthrene (PHE) to EG. DC applied to an ionic solution in a solid matrix invokes electroosmotic flow (EOF), i.e., the surface charge-induced movement of the solution. EG was exposed to weak DC fields in the presence of dissolved PHE to test if EOF increases transport of PHE to poorly accessible sorption sites. DC fields increased PHE sorption rates in EG sevenfold and reduced the desorption rate of sorbed PHE by >99%. EOF thus appeared to be highly effective in translocating PHE into pores, which contribute most of the sorption sites, but are difficult to access in the absence of EOF by molecular diffusion only. The observed 'power of power' may be used to kinetically regulate the interaction of sorbates with EG or other porous sorbents in environmental (bio-) technology. Copyright © 2015 Elsevier B.V. All rights reserved.

Activation of nucleotide-binding domain-like receptor containing protein 3 inflammasome in dendritic cells and macrophages by Streptococcus sanguinis.

PubMed

Saeki, Ayumi; Suzuki, Toshihiko; Hasebe, Akira; Kamezaki, Ryousuke; Fujita, Mari; Nakazawa, Futoshi; Shibata, Ken-Ichiro

2017-03-01

Streptococcus sanguinis is frequently isolated from the blood of patients with infective endocarditis and contributes to the pathology of this disease through induction of interleukin (IL)-1β responsible for the development of the disease. However, the mechanism of IL-1β induction remains unknown. In this study, S. sanguinis activated a murine dendritic cell (DC) to induce IL-1β and this activity was attenuated by silencing the mRNAs of nucleotide-binding domain-like receptor containing protein 3 (NLRP3) and caspase-1. S. sanguinis induced IL-1β production in murine bone marrow-derived macrophage, but this activity was significantly reduced in bone marrow-derived macrophages from NLRP3-, apoptosis-associated speck-like protein containing a caspase-recruitment domain-, and caspase-1-deficient mice. DC phagocytosed S. sanguinis cells, followed by the release of adenosine triphosphate (ATP). The ATP-degradating enzyme attenuated the release of ATP and IL-1β. The inhibitors for ATP receptor reduced IL-1β release in DC. These results strongly suggest that S. sanguinis has the activity to induce IL-1β through the NLRP3 inflammasome in macrophage and DC and interaction of purinergic receptors with ATP released is involved in expression of the activity. © 2016 John Wiley & Sons Ltd.

Defining the Future; Planning with and for Technology in Higher Education. Proceedings of the EDUCOM Spring Conference (Washington, D.C., April 3-4, 1975).

ERIC Educational Resources Information Center

Interuniversity Communications Council (EDUCOM), Princeton, NJ.

Following the keynote address on the importance of planning and the changing style of management in colleges and universities, various prepared papers developed the meeting theme of using technology in college and university planning. William Massey described the development and use of a computer model for strategic planning at Stanford. Edmund…

Family Literacy: Directions in Research and Implications for Practice. Summary and Papers of a National Symposium (Washington, DC, September 7-8, 1995).

ERIC Educational Resources Information Center

Benjamin, L. Ann, Ed.; Lord, Jerome, Ed.

This document contains 10 commissioned papers presented at a research design symposium on family literacy. It also contains a summary of the symposium, which was structured around five themes: assumptions and perceptions about family literacy; what we know from research and practice and how we know it; defining the characteristics of family…

Spatial Geometry of the Human Pelvis

DTIC Science & Technology

1982-03-01

ADA118238 Spatial Geometry of the Human Pelvis , FEDERAL AVIATION ADMINISTRATION WASHINGTON DC MAR 1982 Distribution Statement A: Approved for public...OF THE HUMAN PELVIS March 1982 6. Performing Orgaenizatin Cede S. Perlorming Organizetion Report No. 7. Autitrs) Herbert M. Reynolds, Clyde C. Snow...Tdd skeletal collection. Ibrk done on this study, initiated to define and describe the spatial geomtry of the adult pelvis , was sponsored by the

76 FR 54818 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-02

..., DC 20549-0213. Extension: Form N-54C, SEC File No. 270-184, OMB Control No. 3235-0236. Notice is.... 80a-53(a)), any company defined in Section 2(a)(48)(A) and (B) of the Investment Company Act (15 U.S.C... with the Commission a notification of election on Form N-54A (17 CFR 274.53). Under Section 54(c) of...

76 FR 56823 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-14

..., Washington, DC 20549-0213. Extension: Form N-54A, SEC File No. 270-182, OMB Control No. 3235-0237. Notice is.... 80a-53(a)), any company defined in Section 2(a)(48)(A) and (B) may elect to be subject to the... class of equity securities. The Commission has adopted Form N-54A (17 CFR 274.53) as the form for...

Competence development of registered nurses in municipal elderly care in Sweden: a questionnaire survey.

PubMed

Josefsson, Karin; Sonde, Lars; Wahlin, Tarja-Brita Robins

2008-03-01

Skilled and specialist registered nurses (RNs) are central to evolving elderly care. The past decades' organisational and structural changes have altered RNs' roles and work situations in municipal elderly care in Sweden. This calls for appropriate educational preparation. However, a substantial proportion of RNs in municipal elderly care lack adequate specialist competence. The focus of this study was to describe RNs' perceptions of needs and possibilities for competence development in municipal elderly care and compare the perceptions of RNs' who work solely in dementia care (DC) with those who work in general elder care (GC) where older persons have diverse diagnoses. A non-experimental, descriptive and comparative design was used. Sixty special housing with subunits in a large city in the middle of Sweden. Participating RNs were a total of 213, with a response rate of 62.3%. Of the 213 RNs, 95 (44.6%) worked in DC and 118 (55.4%) in GC. A structured questionnaire that was specifically designed for this study and focused on needs and possibilities for competence development in nursing. The RNs were on average not lacking or were hardly lacking knowledge in examined domains. However, RNs in GC lacked knowledge of dementia, falls, and fall injures to a greater extent than RNs in DC. RNs in DC perceived greater possibilities for competence development at work. Most RNs requested a better organisation for competence development, especially in GC. The majority of RNs had no supervision. The use of RNs' competence was high, although they used their highest competence about half of the working hours. The employers' financial contribution to RNs' continuing education was poor. A better organisation and greater possibilities for RNs' competence development is needed. The employers need to make a greater contribution financially to RNs' continuing education. It is essential to provide RNs with supervision.

Space processing applications payload equipment study. Volume 2D: SPA supplemental power and heat rejection kit

NASA Technical Reports Server (NTRS)

Hammel, R. L. (Editor); Smith, A. G. (Editor)

1974-01-01

The design and application of a supplementary power and heat rejection kit for the Spacelab are discussed. Two subsystems of electric power and thermal control were analyzed to define the requirements for the power and heat rejection kit (PHRK). Twelve exemplary experiments were defined and power timelines were developed. From these timeline, the experiment requirements for sustained power, peak power, and energy were determined. The electrical power subsystem of the PHRK will consist of two fuel cells, oxygen and hydrogen reactant tank assemblies, water storage tanks, plumbing, cabling, and inverters to convert the nominal 28 volt dc fuel cell output to ac power.

Dynamical properties of epitaxial ferroelectric superlattices

NASA Astrophysics Data System (ADS)

Kim, Y.; Gerhardt, R. A.; Erbil, A.

1997-04-01

The dynamical properties of epitaxial ferroelectric heterostructures have been investigated by studying the dielectric behavior under external electric field. A phenomenon with a giant permittivity was observed. At low frequencies, real permittivities as high as 420 000 have been measured. Real and imaginary parts of the dielectric constant show large dispersion at high frequencies. In dc measurements, a nonlinear resistance is observed with a well-defined threshold field, correlating with the dc bias-field dependence of ac permittivities. We model these observations as a result of the motion of pinned domain-wall lattices, having sliding-mode motion at high electric fields. The good agreement between the experimental and theoretical results suggests that the deposited interdigitated electrode pattern plays a crucial role in controlling domain-wall dynamics. The pinning of the domain wall comes from a nucleation barrier to the creation of new domain walls.

Microwave switching power divider. [antenna feeds

NASA Technical Reports Server (NTRS)

Stockton, R. J.; Johnson, R. W. (Inventor)

1981-01-01

A pair of parallel, spaced-apart circular ground planes define a microwave cavity with multi-port microwave power distributing switching circuitry formed on opposite sides of a thin circular dielectric substrate disposed between the ground planes. The power distributing circuitry includes a conductive disk located at the center of the substrate and connected to a source of microwave energy. A high speed, low insertion loss switching diode and a dc blocking capacitor are connected in series between the outer end of a transmission line and an output port. A high impedance, microwave blocking dc bias choke is connected between each switching diode and a source of switching current. The switching source forward biases the diodes to couple microwave energy from the conductive disk to selected output ports and, to associated antenna elements connected to the output ports to form a synthesized antenna pattern.

Fatigue and fail-safe design features of the DC-10 airplane

NASA Technical Reports Server (NTRS)

Stone, M. E.

1972-01-01

The philosophy and methods used in the design of the DC-10 aircraft to assure structural reliability against cracks under repeated service loads are described in detail. The approach consists of three complementary parts: (1) the structure is designed to be fatigue resistant for a crack-free life of 60,000 flight hours; (2) inasmuch as small undetected cracks could develop from other sources, such as material flaws and manufacturing preloads, the structure also is designed to arrest and control cracks within a reasonable service-inspection interval; and (3) a meaningful service-inspection program has been defined on the basis of analysis and test experience from the design development program. This service-inspection program closes the loop to assure the structural integrity of the DC-10 airframe. Selected materials, fasteners, and structural arrangements are used to achieve these design features with minimum structural weight and with economy in manufacturing and maintenance. Extensive analyses and testing were performed to develop and verify the design. The basic design considerations for fatigue-resistant structure are illustrated in terms of material selection, design loads spectra, methods for accurate stress and fatigue damage analysis, and proven concepts for efficient detail design.

Arcjet load characteristics

NASA Technical Reports Server (NTRS)

Hamley, John A.

1990-01-01

Experiments were conducted to define the interface characteristics and constraints of 1 kW class arcjets run on simulated decomposition products of hydrazine and power processors. The impacts of power supply output current ripple on arcjet performance were assessed by variation of the ripple frequency from 100 Hz to 100 kHz with 10 percent peak-to-peak ripple amplitude at 1.2 kW. Ripple had no significant effects on thrust, specific impulse or efficiency. The impact of output ripple on thruster lifetime was not assessed. The static and dynamic impedances of the arcjet were quantified with two thrusters of nearly identical configuration. Superposition of an AC component on the DC arc current was used to characterize the dynamic impedance as a function of flow rate and DC current level. A mathematical model was formulated from these data. Both the static and dynamic impedance magnitude were found to be dependent on mass flow rate. The amplitude of the AC component was found to have little effect on the dynamic impedance. Reducing the DC level from 10 to 8 amps led to a large change in the magnitude of the dynamic impedance with no observable phase change. The impedance data compared favorably between the two thrusters.

Factors influencing early referral, early diagnosis and management in patients with diffuse cutaneous systemic sclerosis.

PubMed

Distler, Oliver; Allanore, Yannick; Denton, Christopher P; Matucci-Cerinic, Marco; Pope, Janet E; Hinzmann, Barbara; Davies, Siobhan; de Oliveira Pena, Janethe; Khanna, Dinesh

2018-05-01

To gain insight into clinical practice regarding referral, early diagnosis and other aspects of the management of patients with dcSSc in Europe and the USA. Semi-structured interviews were conducted with 84 rheumatologists (or internal medicine physicians) and 40 dermatologists in different countries (the UK, France, Germany, Italy, Spain and the USA). Physicians were asked to identify key steps in the patient pathway relating to patient presentation, diagnosis and referral, in addition to other treatment and follow-up processes. The interviewed physicians reported that late presentation with dcSSc was common, with some patients presenting to primary care physicians after symptoms had persisted for up to 1 year. Awareness of dcSSc is reported to vary widely among primary care physicians. Final diagnosis, generally following guideline-based recommendations, was by rheumatologists in most cases (or internal medicine physicians in France) and they remained responsible for global patient management, with lesser involvement in diagnosis and management by dermatologists. Specialist centres were not well defined and did not exist in all countries. Patients and primary healthcare providers can be unaware of the symptoms of dcSSc, therefore presentation and referral to specialist care are often late. Thus, improved awareness among patients and primary care physicians is necessary to facilitate earlier referral and diagnosis. Once referred, more consistent use of the modified Rodnan skin score at diagnosis and follow-up may help to monitor disease progression. Furthermore, establishing specialist centres may help to promote such changes and improve patient care.

NASA JPL scientists Yunling Lou and Dr. Eric Rignot work on line selection while flying AirSAR missions over the Antarctic Peninsula

NASA Image and Video Library

2004-03-16

NASA JPL scientists Yunling Lou and Dr. Eric Rignot work on line selection while flying AirSAR missions over the Antarctic Peninsula. AirSAR 2004 is a three-week expedition in Central and South America by an international team of scientists that is using an all-weather imaging tool, called the Airborne Synthetic Aperture Radar (AirSAR), located onboard NASA's DC-8 airborne laboratory. Scientists from many parts of the world are combining ground research with NASA's AirSAR technology to improve and expand on the quality of research they are able to conduct. These photos are from the DC-8 aircraft while flying an AirSAR mission over Antarctica. The Antarctic Peninsula is more similar to Alaska and Patagonia than to the rest of the Antarctic continent. It is drained by fast glaciers, receives abundant precipitation, and melts significantly in the summer months. In recent decades, the Peninsula has experienced significant atmospheric warming (about 2 degrees C since 1950), which has triggered a vast and spectacular retreat of its floating ice shelves, glacier reduction, a decrease in permanent snow cover and a lengthening of the melt season. As a result, the contribution to sea level from this region could be rapid and substantial. With an area of 120,000 km, or ten times the Patagonia ice fields, the Peninsula could contribute as much as 0.4mm/yr sea level rise, which would be the largest single contribution to sea level from anywhere in the world. This region is being studied by NASA using a DC-8 equipped with the Airborne Synthetic Aperture Radar developed by scientists from NASA’s Jet Propulsion Laboratory. AirSAR will provide a baseline model and unprecedented mapping of the region. This data will make it possible to determine whether the warming trend is slowing, continuing or accelerating. AirSAR will also provide reliable information on ice shelf thickness to measure the contribution of the glaciers to sea level.

Effects of direct current electric fields on lung cancer cell electrotaxis in a PMMA-based microfluidic device.

PubMed

Li, Yaping; Xu, Tao; Chen, Xiaomei; Lin, Shin; Cho, Michael; Sun, Dong; Yang, Mengsu

2017-03-01

Tumor metastasis is the primary cause of cancer death. Numerous studies have demonstrated the electrotactic responses of various cancer cell types, and suggested its potential implications in metastasis. In this study, we used a microfluidic device to emulate endogenous direct current electric field (dcEF) environment, and studied the electrotactic migration of non-small cell lung cancer cell lines (H460, HCC827, H1299, and H1975) and the underlying mechanisms. These cell lines exhibited greatly different response in applied dcEFs (2-6 V/cm). While H460 cells (large cell carcinoma) showed slight migration toward cathode, H1299 cells (large cell carcinoma) showed increased motility and dcEF-dependent anodal migration with cell reorientation. H1975 cells (adenocarcinoma) showed dcEF-dependent cathodal migration with increased motility, and HCC827 cells (adenocarcinoma) responded positively in migration speed and reorientation but minimally in migrating directions to dcEF. Activation of MAPK and PI3K signaling pathways was found to be associated with the realignment and directed migration of lung cancer cells. In addition, both Ca 2+ influx through activated stretch-activated calcium channels (SACCs) (but not voltage-gated calcium channels, VGCCs) and Ca 2+ release from intracellular storage were involved in lung cancer cell electrotactic responses. The results demonstrated that the microfluidic device provided a stable and controllable microenvironment for cell electrotaxis study, and revealed that the electrotactic responses of lung cancer cells were heterogeneous and cell-type dependent, and multiple signals contributed to lung cancer cells electrotaxis.

Factors Associated with Interest in Science of West African Students in Washington, D.C.

ERIC Educational Resources Information Center

Onwere, Godfrey O.

1980-01-01

Describes a study designed to identify factors which students from Gambia, Ghana, Liberia, Nigeria, and Sierra Leone associated with precollege interest in science and factors which influenced or contributed to the choice of a science major or dissuaded students from entering a scientific field. (Author/GC)

Museum Education and Art Therapy: Promoting Wellness in Older Adults

ERIC Educational Resources Information Center

Rosenblatt, Brooke

2014-01-01

By combining museum education with art therapy, museums can make significant contributions to healthcare. The Creative Aging program at The Phillips Collection in Washington, D.C., unites these fields, using artworks and art-making as catalysts to explore feelings, invite self-exploration, and build community. The program fosters an interest in…

Delivering Electronic Information in a Knowledge-Based Democracy. Summary of Proceedings (Washington, DC, July 14, 1993).

ERIC Educational Resources Information Center

Library of Congress, Washington, DC.

The Library of Congress hosted a 1-day conference, "Delivering Electronic Information in a Knowledge-Based Democracy" to explore the public policy framework essential to creating electronic information resources and making them broadly available. Participants from a variety of sectors contributed to wide-ranging discussions on issues…

Southeast Asia Report

DTIC Science & Technology

1985-10-01

significant contributions to eliminating obstacles in production and business , stimulating the development of production, intensifying procurements in...views or attitudes of the U.S. Government. PROCUREMENT OF PUBLICATIONS JPRS publications may be ordered from the National Technical Information...Washington, D.C. 20402. Correspondence pertaining to matters other than procurement may be addressed to Joint Publications Research Service, 1000

43 CFR 19.7 - Private contributions and gifts.

Code of Federal Regulations, 2011 CFR

2011-10-01

... section 6(b), may accept on behalf of the United States any sums of money, marketable securities or other... Secretary of the Interior, Washington, DC 20240, stating the amount of money or describing the securities or... set forth that the offeror is the owner of the property free and clear of all encumbrances and adverse...

43 CFR 19.7 - Private contributions and gifts.

Code of Federal Regulations, 2014 CFR

2014-10-01

... section 6(b), may accept on behalf of the United States any sums of money, marketable securities or other... Secretary of the Interior, Washington, DC 20240, stating the amount of money or describing the securities or... set forth that the offeror is the owner of the property free and clear of all encumbrances and adverse...

43 CFR 19.7 - Private contributions and gifts.

Code of Federal Regulations, 2013 CFR

2013-10-01

... section 6(b), may accept on behalf of the United States any sums of money, marketable securities or other... Secretary of the Interior, Washington, DC 20240, stating the amount of money or describing the securities or... set forth that the offeror is the owner of the property free and clear of all encumbrances and adverse...

43 CFR 19.7 - Private contributions and gifts.

Code of Federal Regulations, 2010 CFR

2010-10-01

... section 6(b), may accept on behalf of the United States any sums of money, marketable securities or other... Secretary of the Interior, Washington, DC 20240, stating the amount of money or describing the securities or... set forth that the offeror is the owner of the property free and clear of all encumbrances and adverse...

43 CFR 19.7 - Private contributions and gifts.

Code of Federal Regulations, 2012 CFR

2012-10-01

... section 6(b), may accept on behalf of the United States any sums of money, marketable securities or other... Secretary of the Interior, Washington, DC 20240, stating the amount of money or describing the securities or... set forth that the offeror is the owner of the property free and clear of all encumbrances and adverse...

Jencks Comment on Downey and Condron

ERIC Educational Resources Information Center

Jencks, Christopher

2016-01-01

Christopher Jencks is the Malcolm Wiener Professor of Social Policy at the Harvard Kennedy School. Here he comments that Downey and Condron (2016) (DC) argue that the sociology of education suffers from a one-sided view of schools' contribution to inequality. He agrees that most sociologists who study what goes on inside schools tend to portray…

44. INTERIOR, FIRST FLOOR, NORTHEAST CORNER OF GRAND STAIRCASE (STAIRS ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

44. INTERIOR, FIRST FLOOR, NORTHEAST CORNER OF GRAND STAIRCASE (STAIRS G), SIDE AISLE, EAST WALL, THE NEGRO'S CONTRIBUTION IN THE SOCIAL AND CULTURAL DEVELOPMENT OF AMERICA: RELIGION MURAL (4' x 5' negative; 8' x 10' print) - U.S. Department of the Interior, Eighteenth & C Streets Northwest, Washington, District of Columbia, DC

Authoring Effective Demonstrations

DTIC Science & Technology

2007-06-22

Battle Focused Training. Washington, DC: Department of the Army. Fu, D., Jensen, R., & Hinkelman, E . (2007). “Evaluating Game Technologies for...Stottler Henke Associates, Inc. Univ. of Central Florida Elizabeth Hinkelman Don Lampton Galactic Village Games , LLC. Army Research Institute...training, and distributed game -based architectures contribute an added benefit of wide accessibility. Reusable and distributable virtual training

Ribavirin Contributes to Hepatitis C Virus Suppression by Augmenting pDC Activation and Type 1 IFN Production.

PubMed

Wang, Yang; McGivern, David R; Cheng, Liang; Li, Guangming; Lemon, Stanley M; Niu, Junqi; Su, Lishan; Reszka-Blanco, Natalia J

2015-01-01

Ribavirin is used as a component of combination therapies for the treatment of chronic hepatitis C virus (HCV) infection together with pegylated interferon and/or direct-acting antiviral drugs. Its mechanism of action, however, is not clear. Direct antiviral activity and immunomodulatory functions have been implicated. Plasmacytoid dendritic cells (pDCs) are the principal source of type 1 interferon during viral infection. The interaction of pDCs with HCV-infected hepatocytes is the subject of intense recent investigation, but the effect of ribavirin on pDC activation has not been evaluated. In this study we showed that ribavirin augments toll-like receptors 7 and 9-mediated IFNα/β expression from pDCs and up-regulated numerous interferon-stimulated genes. Using the H77S.3 HCV infection and replication system, we showed that ribavirin enhanced the ability of activated pDCs to inhibit HCV replication, correlated with elevated induction of IFNα. Our findings provide novel evidence that ribavirin contributes to HCV inhibition by augmenting pDCs-derived type 1 IFN production.

Ribavirin Contributes to Hepatitis C Virus Suppression by Augmenting pDC Activation and Type 1 IFN Production

PubMed Central

Wang, Yang; McGivern, David R; Cheng, Liang; Li, Guangming; Lemon, Stanley M; Niu, Junqi; Su, Lishan; Reszka-Blanco, Natalia J

2015-01-01

Ribavirin is used as a component of combination therapies for the treatment of chronic hepatitis C virus (HCV) infection together with pegylated interferon and/or direct-acting antiviral drugs. Its mechanism of action, however, is not clear. Direct antiviral activity and immunomodulatory functions have been implicated. Plasmacytoid dendritic cells (pDCs) are the principal source of type 1 interferon during viral infection. The interaction of pDCs with HCV-infected hepatocytes is the subject of intense recent investigation, but the effect of ribavirin on pDC activation has not been evaluated. In this study we showed that ribavirin augments toll-like receptors 7 and 9-mediated IFNα/β expression from pDCs and up-regulated numerous interferon-stimulated genes. Using the H77S.3 HCV infection and replication system, we showed that ribavirin enhanced the ability of activated pDCs to inhibit HCV replication, correlated with elevated induction of IFNα. Our findings provide novel evidence that ribavirin contributes to HCV inhibition by augmenting pDCs-derived type 1 IFN production. PMID:26274905

Improved Hierarchical Optimization-Based Classification of Hyperspectral Images Using Shape Analysis

NASA Technical Reports Server (NTRS)

Tarabalka, Yuliya; Tilton, James C.

2012-01-01

A new spectral-spatial method for classification of hyperspectral images is proposed. The HSegClas method is based on the integration of probabilistic classification and shape analysis within the hierarchical step-wise optimization algorithm. First, probabilistic support vector machines classification is applied. Then, at each iteration two neighboring regions with the smallest Dissimilarity Criterion (DC) are merged, and classification probabilities are recomputed. The important contribution of this work consists in estimating a DC between regions as a function of statistical, classification and geometrical (area and rectangularity) features. Experimental results are presented on a 102-band ROSIS image of the Center of Pavia, Italy. The developed approach yields more accurate classification results when compared to previously proposed methods.

Nonmethane Hydrocarbon Measurements on the North Atlantic Flight Corridor During SONEX

NASA Technical Reports Server (NTRS)

Simpson, I. J.; Sive, B. C.; Blake, D. R.; Blake, N. J.; Chen, T.-Y.; Lopez, J. P.; Sachse, G. W.; Vay, S. A.; Fuelberg, H. E.; Kondo, Y.

1999-01-01

Mixing ratios of nonmethane hydrocarbons (NMHCS) were not enhanced in whole air samples collected within the North Atlantic Flight Corridor (NAFC) during the fall of 1997. The investigation was conducted aboard NASA's DC-8 research aircraft, as part of the Subsonic Assessment-Ozone and Nitrogen Experiment (SONEX). NMHC enhancements were not detected within the general Organized Tracking System (OTS) of the NAFC, nor during two tail-chases of the DC-8's own exhaust. Because positive evidence of aircraft emissions was demonstrated by enhancements in both nitrogen oxides and condensation nuclei during SONEX, the NMHC results suggest that the commercial air traffic fleet operating in the North Atlantic region does not contribute significantly to NMHCs in the NAFC.

Giant self-biased magnetoelectric coupling in co-fired textured layered composites

NASA Astrophysics Data System (ADS)

Yan, Yongke; Zhou, Yuan; Priya, Shashank

2013-02-01

Co-fired magnetostrictive/piezoelectric/magnetostrictive laminate structure with silver inner electrode was synthesized and characterized. We demonstrate integration of textured piezoelectric microstructure with the cost-effective low-temperature co-fired layered structure to achieve strong magnetoelectric coupling. Using the co-fired composite, a strategy was developed based upon the hysteretic response of nickel-copper-zinc ferrite magnetostrictive materials to achieve peak magnetoelectric response at zero DC bias, referred as self-biased magnetoelectric response. Fundamental understanding of self-bias phenomenon in composites with single phase magnetic material was investigated by quantifying the magnetization and piezomagnetic changes with applied DC field. We delineate the contribution arising from the interfacial strain and inherent magnetic hysteretic behavior of copper modified nickel-zinc ferrite towards self-bias response.

Defining a Progress Metric for CERT RMM Improvement

DTIC Science & Technology

2017-09-14

Table 1) should be used along with clear guidance on what is to be measured, to avoid subjective interpretations by different project managers . In some...products for each CERT-RMM practice. Project managers should be trained to help the organization improve the accuracy and consistency of its reporting...and to the Office of Management and Budget, Paperwork Reduction Project (0704-0188), Washington, DC 20503. 1. AGENCY USE ONLY (Leave Blank) 2

The Educational Effectiveness of Historically Black Colleges and Universities: A Briefing before the United States Commission on Civil Rights Held in Washington, D.C. Briefing Report

ERIC Educational Resources Information Center

US Commission on Civil Rights, 2010

2010-01-01

The Black College and University Act defined an historically black college and university (HBCU) as one that existed before 1964 with a historic and contemporary mission of educating blacks while being open to all. An HBCU must either have earned accreditation from a nationally recognized accrediting agency or association or be making reasonable…

Ready for the Future: Assessing the Collaborative Capacity of State Emergency Management Agencies

DTIC Science & Technology

2013-03-01

Management and Budget, Paperwork Reduction Project (0704-0188) Washington DC 20503. 1. AGENCY USE ONLY (Leave blank) 2. REPORT DATE March 2013...Preparedness) SEOC State Emergency Operations Center xiv SFI Strategic Foresight Initiative SPSS Statistical Package for the Social Sciences UASI... management discipline and to define the core capabilities to meet those needs. The Strategic Foresight Initiative (SFI) resulted in a vision document

76 FR 69302 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-08

..., Washington, DC 20549-0213. Extension: Form N-54C; SEC File No. 270-184; OMB Control No. 3235-0236. Notice is... Investment Company Act (15 U.S.C. 80a-53(a)), any company defined in Section 2(a)(48)(A) and (B) of the Investment Company Act (15 U.S.C. 80a-2(a)(48)(A) and (B)), may, if it meets certain enumerated eligibility...

General analytical solutions for DC/AC circuit-network analysis

NASA Astrophysics Data System (ADS)

Rubido, Nicolás; Grebogi, Celso; Baptista, Murilo S.

2017-06-01

In this work, we present novel general analytical solutions for the currents that are developed in the edges of network-like circuits when some nodes of the network act as sources/sinks of DC or AC current. We assume that Ohm's law is valid at every edge and that charge at every node is conserved (with the exception of the source/sink nodes). The resistive, capacitive, and/or inductive properties of the lines in the circuit define a complex network structure with given impedances for each edge. Our solution for the currents at each edge is derived in terms of the eigenvalues and eigenvectors of the Laplacian matrix of the network defined from the impedances. This derivation also allows us to compute the equivalent impedance between any two nodes of the circuit and relate it to currents in a closed circuit which has a single voltage generator instead of many input/output source/sink nodes. This simplifies the treatment that could be done via Thévenin's theorem. Contrary to solving Kirchhoff's equations, our derivation allows to easily calculate the redistribution of currents that occurs when the location of sources and sinks changes within the network. Finally, we show that our solutions are identical to the ones found from Circuit Theory nodal analysis.

MDC-Analyzer: a novel degenerate primer design tool for the construction of intelligent mutagenesis libraries with contiguous sites.

PubMed

Tang, Lixia; Wang, Xiong; Ru, Beibei; Sun, Hengfei; Huang, Jian; Gao, Hui

2014-06-01

Recent computational and bioinformatics advances have enabled the efficient creation of novel biocatalysts by reducing amino acid variability at hot spot regions. To further expand the utility of this strategy, we present here a tool called Multi-site Degenerate Codon Analyzer (MDC-Analyzer) for the automated design of intelligent mutagenesis libraries that can completely cover user-defined randomized sequences, especially when multiple contiguous and/or adjacent sites are targeted. By initially defining an objective function, the possible optimal degenerate PCR primer profiles could be automatically explored using the heuristic approach of Greedy Best-First-Search. Compared to the previously developed DC-Analyzer, MDC-Analyzer allows for the existence of a small amount of undesired sequences as a tradeoff between the number of degenerate primers and the encoded library size while still providing all the benefits of DC-Analyzer with the ability to randomize multiple contiguous sites. MDC-Analyzer was validated using a series of randomly generated mutation schemes and experimental case studies on the evolution of halohydrin dehalogenase, which proved that the MDC methodology is more efficient than other methods and is particularly well-suited to exploring the sequence space of proteins using data-driven protein engineering strategies.

A 500 A device characterizer utilizing a pulsed-linear amplifier

NASA Astrophysics Data System (ADS)

Lacouture, Shelby; Bayne, Stephen

2016-02-01

With the advent of modern power semiconductor switching elements, the envelope defining "high power" is an ever increasing quantity. Characterization of these semiconductor power devices generally falls into two categories: switching, or transient characteristics, and static, or DC characteristics. With the increasing native voltage and current levels that modern power devices are capable of handling, characterization equipment meant to extract quasi-static IV curves has not kept pace, often leaving researchers with no other option than to construct ad hoc curve tracers from disparate pieces of equipment. In this paper, a dedicated 10 V, 500 A curve tracer was designed and constructed for use with state of the art high power semiconductor switching and control elements. The characterizer is a physically small, pulsed power system at the heart of which is a relatively high power linear amplifier operating in a switched manner in order to deliver well defined square voltage pulses. These actively shaped pulses are used to obtain device's quasi-static DC characteristics accurately without causing any damage to the device tested. Voltage and current waveforms from each pulse are recorded simultaneously by two separate high-speed analog to digital converters and averaged over a specified interval to obtain points in the reconstructed IV graph.

Dendritic cells: In vitro culture in two- and three-dimensional collagen systems and expression of collagen receptors in tumors and atherosclerotic microenvironments.

PubMed

Sprague, Leslee; Muccioli, Maria; Pate, Michelle; Singh, Manindra; Xiong, Chengkai; Ostermann, Alexander; Niese, Brandon; Li, Yihan; Li, Yandi; Courreges, Maria Cecilia; Benencia, Fabian

2014-04-15

Dendritic cells (DCs) are immune cells found in the peripheral tissues where they sample the organism for infections or malignancies. There they take up antigens and migrate towards immunological organs to contact and activate T lymphocytes that specifically recognize the antigen presented by these antigen presenting cells. In the steady state there are several types of resident DCs present in various different organs. For example, in the mouse, splenic DC populations characterized by the co-expression of CD11c and CD8 surface markers are specialized in cross-presentation to CD8 T cells, while CD11c/SIRP-1α DCs seem to be dedicated to activating CD4 T cells. On the other hand, DCs have also been associated with the development of various diseases such as cancer, atherosclerosis, or inflammatory conditions. In such disease, DCs can participate by inducing angiogenesis or immunosuppression (tumors), promoting autoimmune responses, or exacerbating inflammation (atherosclerosis). This change in DC biology can be prompted by signals in the microenvironment. We have previously shown that the interaction of DCs with various extracellular matrix components modifies the immune properties and angiogenic potential of these cells. Building on those studies, herewith we analyzed the angiogenic profile of murine myeloid DCs upon interaction with 2D and 3D type-I collagen environments. As determined by PCR array technology and quantitative PCR analysis we observed that interaction with these collagen environments induced the expression of particular angiogenic molecules. In addition, DCs cultured on collagen environments specifically upregulated the expression of CXCL-1 and -2 chemokines. We were also able to establish DC cultures on type-IV collagen environments, a collagen type expressed in pathological conditions such as atherosclerosis. When we examined DC populations in atherosclerotic veins of Apolipoprotein E deficient mice we observed that they expressed adhesion molecules capable of interacting with collagen. Finally, to further investigate the interaction of DCs with collagen in other pathological conditions, we determined that both murine ovarian and breast cancer cells express several collagen molecules that can contribute to shape their particular tumor microenvironment. Consistently, tumor-associated DCs were shown to express adhesion molecules capable of interacting with collagen molecules as determined by flow cytometry analysis. Of particular relevance, tumor-associated DCs expressed high levels of CD305/LAIR-1, an immunosuppressive receptor. This suggests that signaling through this molecule upon interaction with collagen produced by tumor cells might help define the poorly immunogenic status of these cells in the tumor microenvironment. Overall, these studies demonstrate that through interaction with collagen proteins, DCs can be capable of modifying the microenvironments of inflammatory disease such as cancer or atherosclerosis. Copyright © 2014. Published by Elsevier Inc.

Design and Implementation of an Innovative Residential PV System

NASA Astrophysics Data System (ADS)

Najm, Elie Michel

This work focuses on the design and implementation of an innovative residential PV system. In chapter one, after an introduction related to the rapid growth of solar systems' installations, the most commonly used state of the art solar power electronics' configurations are discussed, which leads to introducing the proposed DC/DC parallel configuration. The advantages and disadvantages of each of the power electronics' configurations are deliberated. The scope of work in the power electronics is defined in this chapter to be related to the panel side DC/DC converter. System integration and mechanical proposals are also within the scope of work and are discussed in later chapters. Operation principle of a novel low cost PV converter is proposed in chapter 2. The proposal is based on an innovative, simplified analog implementation of a master/slave methodology resulting in an efficient, soft-switched interleaved variable frequency flybacks, operating in the boundary conduction mode (BCM). The scheme concept and circuit configuration, operation principle and theoretical waveforms, design equations, and design considerations are presented. Furthermore, design examples are also given, illustrating the significance of the newly derived frequency equation for flybacks operating in BCM. In chapters 3, 4, and 5, the design implementation and optimization of the novel DC/DC converter illustrated in chapter 2 are discussed. In chapter 3, a detailed variable frequency BCM flyback design model leading to optimizing the component selections and transformer design, detailed in chapter 4, is presented. Furthermore, in chapter 4, the method enabling the use of lower voltage rating switching devices is also discussed. In chapter 5, circuitry related to Start-UP, drive for the main switching devices, zero-voltage-switching (ZVS) as well as turn OFF soft switching and interleaving control are fully detailed. The experimental results of the proposed DC/DC converter are presented in chapter 6. In chapter 7, a novel integration method is proposed for the residential PV solar system. The proposal presents solutions to challenges experimented in the implementation of today's approaches. Faster installation time, easier system grounding, and integration of the power electronics in order to reduce the number of connectors' and system cost are detailed. Installers with special skills as well as special tools are not required for implementing the proposed system integration. Photos of the experimental results related to the installation of a 3kW system, which was fully completed in less than an hour and a half, are also presented.

Slc15a4, a gene required for pDC sensing of TLR ligands, is required to control persistent viral infection.

PubMed

Blasius, Amanda L; Krebs, Philippe; Sullivan, Brian M; Oldstone, Michael B; Popkin, Daniel L

2012-09-01

Plasmacytoid dendritic cells (pDCs) are the major producers of type I IFN in response to viral infection and have been shown to direct both innate and adaptive immune responses in vitro. However, in vivo evidence for their role in viral infection is lacking. We evaluated the contribution of pDCs to acute and chronic virus infection using the feeble mouse model of pDC functional deficiency. We have previously demonstrated that feeble mice have a defect in TLR ligand sensing. Although pDCs were found to influence early cytokine secretion, they were not required for control of viremia in the acute phase of the infection. However, T cell priming was deficient in the absence of functional pDCs and the virus-specific immune response was hampered. Ultimately, infection persisted in feeble mice. We conclude that pDCs are likely required for efficient T cell priming and subsequent viral clearance. Our data suggest that reduced pDC functionality may lead to chronic infection.

Enhanced Passive RF-DC Converter Circuit Efficiency for Low RF Energy Harvesting

PubMed Central

Chaour, Issam; Fakhfakh, Ahmed; Kanoun, Olfa

2017-01-01

For radio frequency energy transmission, the conversion efficiency of the receiver is decisive not only for reducing sending power, but also for enabling energy transmission over long and variable distances. In this contribution, we present a passive RF-DC converter for energy harvesting at ultra-low input power at 868 MHz. The novel converter consists of a reactive matching circuit and a combined voltage multiplier and rectifier. The stored energy in the input inductor and capacitance, during the negative wave, is conveyed to the output capacitance during the positive one. Although Dickson and Villard topologies have principally comparable efficiency for multi-stage voltage multipliers, the Dickson topology reaches a better efficiency within the novel ultra-low input power converter concept. At the output stage, a low-pass filter is introduced to reduce ripple at high frequencies in order to realize a stable DC signal. The proposed rectifier enables harvesting energy at even a low input power from −40 dBm for a resistive load of 50 kΩ. It realizes a significant improvement in comparison with state of the art solutions. PMID:28282910

Antigen-specific IL-23/17 pathway activation by murine semi-mature DC-like cells

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

Nagasaka, Shinya; Iwasaki, Takumi; Okano, Tomoko

We analyzed the phenotype and function of bone marrow-derived dendritic cells (DCs) induced in vitro without using any serum during the late stage of cultivation. These 'serum-free' DCs (SF-DCs) possessed the ability to induce T cell proliferation as well as antibody responses, indicating that they were functional DCs. Surprisingly, the SF-DCs akin to semi-mature DCs in terms of both phenotypic and functional characteristics. The SF-DCs did not produce IL-12 but produced large amounts of IL-23 following lipopolysaccharide stimulation. The antigen-specific production of IL-17 by CD4{sup +} T cells co-cultured with OVA-loaded SF-DCs was significantly higher than that with OVA-loaded conventionalmore » DCs. These results suggest that SF-DCs tend to produce IL-23 and can consequently induce the IL-17 producing CD4{sup +} T cells. The semi-mature DC-like cells reported here will be useful vehicles for DC immunization and might contribute to studies on the possible involvement of semi-mature DCs in Th17 cell differentiation.« less

DC conductivity of twisted bilayer graphene: Angle-dependent transport properties and effects of disorder

NASA Astrophysics Data System (ADS)

Andelković, M.; Covaci, L.; Peeters, F. M.

2018-03-01

The in-plane dc conductivity of twisted bilayer graphene is calculated using an expansion of the real-space Kubo-Bastin conductivity in terms of Chebyshev polynomials. We investigate within a tight-binding approach the transport properties as a function of rotation angle, applied perpendicular electric field, and vacancy disorder. We find that for high-angle twists, the two layers are effectively decoupled, and the minimum conductivity at the Dirac point corresponds to double the value observed in monolayer graphene. This remains valid even in the presence of vacancies, hinting that chiral symmetry is still preserved. On the contrary, for low twist angles, the conductivity at the Dirac point depends on the twist angle and is not protected in the presence of disorder. Furthermore, for low angles and in the presence of an applied electric field, we find that the chiral boundary states emerging between AB and BA regions contribute to the dc conductivity, despite the appearance of localized states in the AA regions. The results agree qualitatively with recent transport experiments in low-angle twisted bilayer graphene.

Glass transition and relaxation processes of nanocomposite polymer electrolytes.

PubMed

Money, Benson K; Hariharan, K; Swenson, Jan

2012-07-05

This study focus on the effect of δ-Al(2)O(3) nanofillers on the dc-conductivity, glass transition, and dielectric relaxations in the polymer electrolyte (PEO)(4):LiClO(4). The results show that there are three dielectric relaxation processes, α, β, and γ, in the systems, although the structural α-relaxation is hidden in the strong conductivity contribution and could therefore not be directly observed. However, by comparing an enhanced dc-conductivity, by approximately 2 orders of magnitude with 4 wt % δ-Al(2)O(3) added, with a decrease in calorimetric glass transition temperature, we are able to conclude that the dc-conductivity is directly coupled to the hidden α-relaxation, even in the presence of nanofillers (at least in the case of δ-Al(2)O(3) nanofillers at concentrations up to 4 wt %). This filler induced speeding up of the segmental polymer dynamics, i.e., the α-relaxation, can be explained by the nonattractive nature of the polymer-filler interactions, which enhance the "free volume" and mobility of polymer segments in the vicinity of filler surfaces.

Enhanced Passive RF-DC Converter Circuit Efficiency for Low RF Energy Harvesting.

PubMed

Chaour, Issam; Fakhfakh, Ahmed; Kanoun, Olfa

2017-03-09

For radio frequency energy transmission, the conversion efficiency of the receiver is decisive not only for reducing sending power, but also for enabling energy transmission over long and variable distances. In this contribution, we present a passive RF-DC converter for energy harvesting at ultra-low input power at 868 MHz. The novel converter consists of a reactive matching circuit and a combined voltage multiplier and rectifier. The stored energy in the input inductor and capacitance, during the negative wave, is conveyed to the output capacitance during the positive one. Although Dickson and Villard topologies have principally comparable efficiency for multi-stage voltage multipliers, the Dickson topology reaches a better efficiency within the novel ultra-low input power converter concept. At the output stage, a low-pass filter is introduced to reduce ripple at high frequencies in order to realize a stable DC signal. The proposed rectifier enables harvesting energy at even a low input power from -40 dBm for a resistive load of 50 kΩ. It realizes a significant improvement in comparison with state of the art solutions.

11 CFR 114.2 - Prohibitions on contributions, expenditures and electioneering communications.

Code of Federal Regulations, 2010 CFR

2010-01-01

... are prohibited from making a contribution, as defined in 11 CFR 114.1(a), in connection with any... law of Congress are prohibited from making expenditures as defined in 11 CFR 114.1(a) for... organization is prohibited from making a contribution as defined in 11 CFR part 100, subpart B. Any corporation...

11 CFR 114.2 - Prohibitions on contributions, expenditures and electioneering communications.

Code of Federal Regulations, 2013 CFR

2013-01-01

... are prohibited from making a contribution, as defined in 11 CFR 114.1(a), in connection with any... law of Congress are prohibited from making expenditures as defined in 11 CFR 114.1(a) for... organization is prohibited from making a contribution as defined in 11 CFR part 100, subpart B. Any corporation...

Advances in fuel cell vehicle design

NASA Astrophysics Data System (ADS)

Bauman, Jennifer

Factors such as global warming, dwindling fossil fuel reserves, and energy security concerns combine to indicate that a replacement for the internal combustion engine (ICE) vehicle is needed. Fuel cell vehicles have the potential to address the problems surrounding the ICE vehicle without imposing any significant restrictions on vehicle performance, driving range, or refuelling time. Though there are currently some obstacles to overcome before attaining the widespread commercialization of fuel cell vehicles, such as improvements in fuel cell and battery durability, development of a hydrogen infrastructure, and reduction of high costs, the fundamental concept of the fuel cell vehicle is strong: it is efficient, emits zero harmful emissions, and the hydrogen fuel can be produced from various renewable sources. Therefore, research on fuel cell vehicle design is imperative in order to improve vehicle performance and durability, increase efficiency, and reduce costs. This thesis makes a number of key contributions to the advancement of fuel cell vehicle design within two main research areas: powertrain design and DC/DC converters. With regards to powertrain design, this research first analyzes various powertrain topologies and energy storage system types. Then, a novel fuel cell-battery-ultracapacitor topology is presented which shows reduced mass and cost, and increased efficiency, over other promising topologies found in the literature. A detailed vehicle simulator is created in MATLAB/Simulink in order to simulate and compare the novel topology with other fuel cell vehicle powertrain options. A parametric study is performed to optimize each powertrain and general conclusions for optimal topologies, as well as component types and sizes, for fuel cell vehicles are presented. Next, an analytical method to optimize the novel battery-ultracapacitor energy storage system based on maximizing efficiency, and minimizing cost and mass, is developed. This method can be applied to any system utilizing the novel battery-ultracapacitor energy storage system and is not limited in application to only fuel cell vehicles. With regards to DC/DC converters, it is important to design efficient and light-weight converters for use in fuel cell and other electric vehicles to improve overall vehicle fuel economy. Thus, this research presents a novel soft-switching method, the capacitor-switched regenerative snubber, for the high-power DC/DC boost converters commonly used in fuel cell vehicles. This circuit is shown to increase the efficiency and reduce the overall mass of the DC/DC boost converter.

Changes in markers associated with dendritic cells driving the differentiation of either TH2 cells or regulatory T cells correlate with clinical benefit during allergen immunotherapy.

PubMed

Gueguen, Claire; Bouley, Julien; Moussu, Hélène; Luce, Sonia; Duchateau, Magalie; Chamot-Rooke, Julia; Pallardy, Marc; Lombardi, Vincent; Nony, Emmanuel; Baron-Bodo, Véronique; Mascarell, Laurent; Moingeon, Philippe

2016-02-01

Regulatory dendritic cell (DC) markers, such as C1Q, are upregulated in PBMCs of patients with grass pollen allergy exhibiting clinical benefit during allergen immunotherapy (AIT). We sought to define markers differentially expressed in human monocyte-derived DCs differentiated toward a proallergic (DCs driving the differentiation of TH2 cells [DC2s]) phenotype and investigate whether changes in such markers in the blood correlate with AIT efficacy. Transcriptomes and proteomes of monocyte-derived DCs polarized toward DCs driving the differentiation of TH1 cells (DC1s), DC2s, or DCs driving the differentiation of regulatory T cells (DCreg cells) profiles were compared by using genome-wide cDNA microarrays and label-free quantitative proteomics, respectively. Markers differentially regulated in DC2s and DCreg cells were assessed by means of quantitative PCR in PBMCs from 80 patients with grass pollen allergy before and after 2 or 4 months of sublingual AIT in parallel with rhinoconjunctivitis symptom scores. We identified 20 and 26 new genes/proteins overexpressed in DC2s and DCreg cells, respectively. At an individual patient level, DC2-associated markers, such as CD141, GATA3, OX40 ligand, and receptor-interacting serine/threonine-protein kinase 4 (RIPK4), were downregulated after a 4-month sublingual AIT course concomitantly with an upregulation of DCreg cell-associated markers, including complement C1q subcomponent subunit A (C1QA), FcγRIIIA, ferritin light chain (FTL), and solute carrier organic anion transporter family member 2B1 (SLCO2B1), in the blood of clinical responders as opposed to nonresponders. Changes in such markers were better correlated with clinical benefit than alterations of allergen-specific CD4(+) T-cell or IgG responses. A combination of 5 markers predominantly expressed by blood DCs (ie, C1Q and CD141) or shared with lymphoid cells (ie, FcγRIIIA, GATA3, and RIPK4) reflecting changes in the balance of regulatory/proallergic responses in peripheral blood can be used as early as after 2 months to monitor the early onset of AIT efficacy. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Recognition of Aspergillus fumigatus hyphae by human plasmacytoid dendritic cells is mediated by dectin-2 and results in formation of extracellular traps.

PubMed

Loures, Flávio V; Röhm, Marc; Lee, Chrono K; Santos, Evelyn; Wang, Jennifer P; Specht, Charles A; Calich, Vera L G; Urban, Constantin F; Levitz, Stuart M

2015-02-01

Plasmacytoid dendritic cells (pDCs) were initially considered as critical for innate immunity to viruses. However, our group has shown that pDCs bind to and inhibit the growth of Aspergillus fumigatus hyphae and that depletion of pDCs renders mice hypersusceptible to experimental aspergillosis. In this study, we examined pDC receptors contributing to hyphal recognition and downstream events in pDCs stimulated by A. fumigatus hyphae. Our data show that Dectin-2, but not Dectin-1, participates in A. fumigatus hyphal recognition, TNF-α and IFN-α release, and antifungal activity. Moreover, Dectin-2 acts in cooperation with the FcRγ chain to trigger signaling responses. In addition, using confocal and electron microscopy we demonstrated that the interaction between pDCs and A. fumigatus induced the formation of pDC extracellular traps (pETs) containing DNA and citrullinated histone H3. These structures closely resembled those of neutrophil extracellular traps (NETs). The microarray analysis of the pDC transcriptome upon A. fumigatus infection also demonstrated up-regulated expression of genes associated with apoptosis as well as type I interferon-induced genes. Thus, human pDCs directly recognize A. fumigatus hyphae via Dectin-2; this interaction results in cytokine release and antifungal activity. Moreover, hyphal stimulation of pDCs triggers a distinct pattern of pDC gene expression and leads to pET formation.

CpG-island methylation study of liver fluke-related cholangiocarcinoma

PubMed Central

Sriraksa, R; Zeller, C; El-Bahrawy, M A; Dai, W; Daduang, J; Jearanaikoon, P; Chau-in, S; Brown, R; Limpaiboon, T

2011-01-01

Background: Genetic changes have been widely reported in association with cholangiocarcinoma (CCA), while epigenetic changes are poorly characterised. We aimed to further evaluate CpG-island hypermethylation in CCA at candidate loci, which may have potential as diagnostic or prognostic biomarkers. Methods: We analysed methylation of 26 CpG-islands in 102 liver fluke related-CCA and 29 adjacent normal samples using methylation-specific PCR (MSP). Methylation of interest loci was confirmed using pyrosequencing and/or combined bisulfite restriction analysis, and protein expression by immunohistochemistry. Results: A number of CpG-islands (OPCML, SFRP1, HIC1, PTEN and DcR1) showed frequency of hypermethylation in >28% of CCA, but not adjacent normal tissues. The results showed that 91% of CCA were methylated in at least one CpG-island. The OPCML was the most frequently methylated locus (72.5%) and was more frequently methylated in less differentiated CCA. Patients with methylated DcR1 had significantly longer overall survival (Median; 41.7 vs 21.7 weeks, P=0.027). Low-protein expression was found in >70% of CCA with methylation of OPCML or DcR1. Conclusion: Aberrant hypermethylation of certain loci is a common event in liver fluke-related CCA and may potentially contribute to cholangiocarcinogenesis. The OPCML and DcR1 might serve as methylation biomarkers in CCA that can be readily examined by MSP. PMID:21448164

In situ analysis of lung antigen-presenting cells during murine pulmonary infection with virulent Mycobacterium tuberculosis

PubMed Central

Pedroza-González, Alexander; García-Romo, Gina S; Aguilar-León, Diana; Calderon-Amador, Juana; Hurtado-Ortiz, Raquel; Orozco-Estevez, Hector; Lambrecht, Bart N; Estrada-García, Iris; Hernández-Pando, Rogelio; Flores-Romo, Leopoldo

2004-01-01

Scarce information exists about the role of lung antigen-presenting cells (APCs) in vivo during pulmonary tuberculosis. As APCs activate cellular immunity, following intratracheal inoculation with virulent Mycobacterium tuberculosis, we assessed in situ lung APC recruitment, distribution, granuloma involvement, morphology and mycobacterial burden by using MHC-CII, CD14, scavenger receptor class A (SRA), the murine dendritic cell (DC)-restricted marker CD11c and Ziehl–Neelsen staining. CD11c+ DC and CD14+ cell recruitment into lungs appeared by day 14, continuing until day 60. MHC-CII+ cells increased since day 7, persisting until day 60. Thus, virulent mycobacteria delays (14–21 days) lung APC recruitment compared to model antigens and nonvirulent bacilli (24–48 h). Regarding granuloma constitution, highly bacillary CD14+ and SRA+ cells were centrally located. MHC-CII+ cells were more peripheral, with less mycobacteria. CD11c+ cells were heterogeneously distributed within granulomas, with scarce bacilli. When labelling lung suspensions for MHC-CII and classifying cells as macrophages or DC, then staining for Ziehl–Neelsen, a remarkable segregation was found regarding bacillary burden. Most macrophage-like cells contained numerous bacilli, while DC had no or scarce mycobacteria. This implies differential APC contributions in situ during pulmonary tuberculosis regarding mycobacterial uptake, granuloma involvement and perhaps bacillary growth. PMID:15255967

Expression of Vitis amurensis VaERF20 in Arabidopsis thaliana Improves Resistance to Botrytis cinerea and Pseudomonas syringae pv. Tomato DC3000.

PubMed

Wang, Mengnan; Zhu, Yanxun; Han, Rui; Yin, Wuchen; Guo, Chunlei; Li, Zhi; Wang, Xiping

2018-03-01

Ethylene response factor (ERF) transcription factors play important roles in regulating immune responses in plants. In our study, we characterized a member of the ERF transcription factor family, VaERF20 , from the Chinese wild Vitis genotype, V. amurensis Rupr "Shuangyou". Phylogenetic analysis indicated that VaERF20 belongs to group IXc of the ERF family, in which many members are known to contribute to fighting pathogen infection. Consistent with this, expression of VaERF20 was induced by treatment with the necrotrophic fungal pathogen Botrytis cinerea (B. cinerea ) in "Shuangyou" and V. vinifera "Red Globe". Arabidopsis thaliana plants over-expressing VaERF20 displayed enhanced resistance to B. cinerea and the bacterium Pseudomonas syringae pv. tomato ( Pst ) DC3000. Patterns of pathogen-induced reactive oxygen species (ROS) accumulation were entirely distinct in B. cinerea and Pst DC3000 inoculated plants. Examples of both salicylic acid (SA) and jasmonic acid/ethylene (JA/ET) responsive defense genes were up-regulated after B. cinerea and Pst DC3000 inoculation of the VaERF20 -overexpressing transgenic A. thaliana plants. Evidence of pattern-triggered immunity (PTI), callose accumulation and stomatal defense, together with increased expression of PTI genes, was also greater in the transgenic lines. These data indicate that VaERF20 participates in various signal transduction pathways and acts as an inducer of immune responses.

Multielectronic conduction in La1-xSrxGa1/2Mn1/2O3-δ as solid oxide fuel cell cathode

NASA Astrophysics Data System (ADS)

Iguchi, E.; Hashimoto, Y.; Kurumada, M.; Munakata, F.

2003-08-01

Four-probe dc conductivities, capacitances, and thermopower have been measured in the temperature range of 80-1123 K for La1-xSrxGa1/2Mn1/2O3-δ, which is a desirable cathode material for lanthanum-gallate electrolytes of solid oxide fuel cells. The dc conductivities in the specimens (0.1⩽x⩽0.3) are insensitive to x but the thermopower is very sensitive to x, although the x=0 specimen exhibits a somewhat different conduction behavior. At T<300 K, a relaxation process has shown in dielectric loss factor with the activation energy higher than that for dc conduction in every specimen. These results at T<300 K have been numerically analyzed within the framework of the multielectronic conduction consisting of the polaronic conduction of Mn 3d eg holes created by Sr doping, the band conduction of O 2p holes and the hopping conduction of Mn 3d eg electrons, where the O 2p holes and Mn 3d eg electrons are created by thermal excitation of electrons from O 2p bands to Mn 3d eg narrow bands. At T>500 K, the band conduction dominates the electronic transports. The ionic conduction due to O2- migration seems difficult to contribute directly to the dc conduction even at high temperature.

Identification of candidates for interacting partners of the tail domain of DcNMCP1, a major component of the Daucus carota nuclear lamina-like structure.

PubMed

Mochizuki, Ryota; Tsugama, Daisuke; Yamazaki, Michihiro; Fujino, Kaien; Masuda, Kiyoshi

2017-05-04

NMCP/CRWN (NUCLEAR MATRIX CONSTITUENT PROTEIN/CROWDED NUCLEI) is a major component of a protein fibrous meshwork (lamina-like structure) on the plant inner nuclear membrane. NMCP/CRWN contributes to regulating nuclear shape and nuclear functions. An NMCP/CRWN protein in Daucus carota (DcNMCP1) is localized to the nuclear periphery in interphase cells, and surrounds chromosomes in cells in metaphase and anaphase. The N-terminal region and the C-terminal region of DcNMCP1 are both necessary for localizing DcNMCP1 to the nuclear periphery. Here candidate interacting partners of the amino acid position 975-1053 of DcNMCP1 (T975-1053), which is present in the C-terminal region and contains a conserved sequence that plays a role in localizing DcNMCP1 to the nuclear periphery, are screened for. Arabidopsis thaliana nuclear proteins were subjected to far-Western blotting with GST-fused T975-1053 as a probe, and signals were detected at the positions corresponding to ∼70, ∼40, and ∼18 kDa. These ∼70, ∼40, and ∼18 kDa nuclear proteins were identified by mass spectrometry, and subjected to a yeast 2-hybrid (Y2H) analysis with T975-1053 as bait. In this analysis, the ∼40 kDa protein ARP7, which is a nuclear actin-related protein possibly involved in regulating chromatin structures, was confirmed to interact with T975-1053. Independently of the far-Western blotting, a Y2H screen was performed using T975-1053 as bait. Targeted Y2H assays confirmed that 3 proteins identified in the screen, MYB3, SINAT1, and BIM1, interact with T975-1053. These proteins might have roles in NMCP/CRWN protein-mediated biologic processes.

Development of a Novel CD4+ TCR Transgenic Line That Reveals a Dominant Role for CD8+ Dendritic Cells and CD40 Signaling in the Generation of Helper and CTL Responses to Blood-Stage Malaria.

PubMed

Fernandez-Ruiz, Daniel; Lau, Lei Shong; Ghazanfari, Nazanin; Jones, Claerwen M; Ng, Wei Yi; Davey, Gayle M; Berthold, Dorothee; Holz, Lauren; Kato, Yu; Enders, Matthias H; Bayarsaikhan, Ganchimeg; Hendriks, Sanne H; Lansink, Lianne I M; Engel, Jessica A; Soon, Megan S F; James, Kylie R; Cozijnsen, Anton; Mollard, Vanessa; Uboldi, Alessandro D; Tonkin, Christopher J; de Koning-Ward, Tania F; Gilson, Paul R; Kaisho, Tsuneyasu; Haque, Ashraful; Crabb, Brendan S; Carbone, Francis R; McFadden, Geoffrey I; Heath, William R

2017-12-15

We describe an MHC class II (I-A b )-restricted TCR transgenic mouse line that produces CD4 + T cells specific for Plasmodium species. This line, termed PbT-II, was derived from a CD4 + T cell hybridoma generated to blood-stage Plasmodium berghei ANKA (PbA). PbT-II cells responded to all Plasmodium species and stages tested so far, including rodent (PbA, P. berghei NK65, Plasmodium chabaudi AS, and Plasmodium yoelii 17XNL) and human ( Plasmodium falciparum ) blood-stage parasites as well as irradiated PbA sporozoites. PbT-II cells can provide help for generation of Ab to P. chabaudi infection and can control this otherwise lethal infection in CD40L-deficient mice. PbT-II cells can also provide help for development of CD8 + T cell-mediated experimental cerebral malaria (ECM) during PbA infection. Using PbT-II CD4 + T cells and the previously described PbT-I CD8 + T cells, we determined the dendritic cell (DC) subsets responsible for immunity to PbA blood-stage infection. CD8 + DC (a subset of XCR1 + DC) were the major APC responsible for activation of both T cell subsets, although other DC also contributed to CD4 + T cell responses. Depletion of CD8 + DC at the beginning of infection prevented ECM development and impaired both Th1 and follicular Th cell responses; in contrast, late depletion did not affect ECM. This study describes a novel and versatile tool for examining CD4 + T cell immunity during malaria and provides evidence that CD4 + T cell help, acting via CD40L signaling, can promote immunity or pathology to blood-stage malaria largely through Ag presentation by CD8 + DC. Copyright © 2017 by The American Association of Immunologists, Inc.

Evaluation of Three Field-Based Methods for Quantifying Soil Carbon

PubMed Central

Izaurralde, Roberto C.; Rice, Charles W.; Wielopolski, Lucian; Ebinger, Michael H.; Reeves, James B.; Thomson, Allison M.; Francis, Barry; Mitra, Sudeep; Rappaport, Aaron G.; Etchevers, Jorge D.; Sayre, Kenneth D.; Govaerts, Bram; McCarty, Gregory W.

2013-01-01

Three advanced technologies to measure soil carbon (C) density (g C m−2) are deployed in the field and the results compared against those obtained by the dry combustion (DC) method. The advanced methods are: a) Laser Induced Breakdown Spectroscopy (LIBS), b) Diffuse Reflectance Fourier Transform Infrared Spectroscopy (DRIFTS), and c) Inelastic Neutron Scattering (INS). The measurements and soil samples were acquired at Beltsville, MD, USA and at Centro International para el Mejoramiento del Maíz y el Trigo (CIMMYT) at El Batán, Mexico. At Beltsville, soil samples were extracted at three depth intervals (0–5, 5–15, and 15–30 cm) and processed for analysis in the field with the LIBS and DRIFTS instruments. The INS instrument determined soil C density to a depth of 30 cm via scanning and stationary measurements. Subsequently, soil core samples were analyzed in the laboratory for soil bulk density (kg m−3), C concentration (g kg−1) by DC, and results reported as soil C density (kg m−2). Results from each technique were derived independently and contributed to a blind test against results from the reference (DC) method. A similar procedure was employed at CIMMYT in Mexico employing but only with the LIBS and DRIFTS instruments. Following conversion to common units, we found that the LIBS, DRIFTS, and INS results can be compared directly with those obtained by the DC method. The first two methods and the standard DC require soil sampling and need soil bulk density information to convert soil C concentrations to soil C densities while the INS method does not require soil sampling. We conclude that, in comparison with the DC method, the three instruments (a) showed acceptable performances although further work is needed to improve calibration techniques and (b) demonstrated their portability and their capacity to perform under field conditions. PMID:23383225

Method and apparatus for electromagnetically braking a motor

NASA Technical Reports Server (NTRS)

Davis, Donald R. (Inventor); Radford, Nicolaus A (Inventor); Permenter, Frank Noble (Inventor); Parsons, Adam H (Inventor); Mehling, Joshua S (Inventor)

2011-01-01

An electromagnetic braking system and method is provided for selectively braking a motor using an electromagnetic brake having an electromagnet, a permanent magnet, a rotor assembly, and a brake pad. The brake assembly applies when the electromagnet is de-energized and releases when the electromagnet is energized. When applied the permanent magnet moves the brake pad into frictional engagement with a housing, and when released the electromagnet cancels the flux of the permanent magnet to allow a leaf spring to move the brake pad away from the housing. A controller has a DC/DC converter for converting a main bus voltage to a lower braking voltage based on certain parameters. The converter utilizes pulse-width modulation (PWM) to regulate the braking voltage. A calibrated gap is defined between the brake pad and permanent magnet when the brake assembly is released, and may be dynamically modified via the controller.

Dynamic mesh for TCAD modeling with ECORCE

NASA Astrophysics Data System (ADS)

Michez, A.; Boch, J.; Touboul, A.; Saigné, F.

2016-08-01

Mesh generation for TCAD modeling is challenging. Because densities of carriers can change by several orders of magnitude in thin areas, a significant change of the solution can be observed for two very similar meshes. The mesh must be defined at best to minimize this change. To address this issue, a criterion based on polynomial interpolation on adjacent nodes is proposed that adjusts accurately the mesh to the gradients of Degrees of Freedom. Furthermore, a dynamic mesh that follows changes of DF in DC and transient mode is a powerful tool for TCAD users. But, in transient modeling, adding nodes to a mesh induces oscillations in the solution that appears as spikes at the current collected at the contacts. This paper proposes two schemes that solve this problem. Examples show that using these techniques, the dynamic mesh generator of the TCAD tool ECORCE handle semiconductors devices in DC and transient mode.

ARC length control for plasma welding

NASA Technical Reports Server (NTRS)

Iceland, William F. (Inventor)

1988-01-01

A control system to be used with a plasma arc welding apparatus is disclosed. The plasma arc welding apparatus includes a plasma arc power supply, a contactor, and an electrode assembly for moving the electrode relative to a work piece. The electrode assembly is raised or lowered by a drive motor. The present apparatus includes a plasma arc adapter connected across the power supply to measure the voltage across the plasma arc. The plasma arc adapter forms a dc output signal input to a differential amplifier. A second input is defined by an adjustable resistor connected to a dc voltage supply to permit operator control. The differential amplifier forms an output difference signal provided to an adder circuit. The adder circuit then connects with a power amplifier which forms the driving signal for the motor. In addition, the motor connects to a tachometor which forms a feedback signal delivered to the adder to provide damping, therby avoiding servo loop overshoot.

Reconnaissance electrical surveys in the Coso Range, California

NASA Astrophysics Data System (ADS)

Jackson, Dallas B.; O'Donnell, James E.

1980-05-01

Telluric current, audiomagnetotelluric (AMT), and direct current (dc) methods were used to study the electrical structure of the Coso Range and Coso geothermal area. Telluric current mapping outlined major resistivity lows associated with conductive valley fill of the Rose Valley basin, the Coso Basin, and the northern extension of the Coso Basin east of Coso Hot Springs. A secondary resistivity low with a north-south trend runs through the Coso Hot Springs-Devil's Kitchen geothermal area. The secondary low in the geothermal area, best defined by the 7.5-Hz AMT map and dc soundings, is caused by a shallow conductive zone (5-30 ohm m) interpreted to be hydrothermally altered Sierra Nevada basement rocks containing saline water of a hot water geothermal system. This zone of lowest apparent resistivities over the basement rocks lies within a closed contour of a heat flow anomaly where all values are greater than 10 heat flow units.

A study to define the research and technology requirements for advanced turbo/propfan transport aircraft

NASA Technical Reports Server (NTRS)

Goldsmith, I. M.

1981-01-01

The feasibility of the propfan relative to the turbofan is summarized, using the Douglas DC-9 Super 80 (DS-8000) as the actual operational base aircraft. The 155 passenger economy class aircraft (31,775 lb 14,413 kg payload), cruise Mach at 0.80 at 31,000 ft (8,450 m) initial altitude, and an operational capability in 1985 was considered. Three propfan arrangements, wing mounted, conventional horizontal tail aft mounted, and aft fuselage pylon mounted are selected for comparison with the DC-9 Super 80 P&WA JT8D-209 turbofan powered aircraft. The configuration feasibility, aerodynamics, propulsion, structural loads, structural dynamics, sonic fatigue, acoustics, weight maintainability, performance, rough order of magnitude economics, and airline coordination are examined. The effects of alternate cruise Mach number, mission stage lengths, and propfan design characteristics are considered. Recommendations for further study, ground testing, and flight testing are included.

Fuselage shell and cavity response measurements on a DC-9 test section

NASA Technical Reports Server (NTRS)

Simpson, M. A.; Mathur, G. P.; Cannon, M. R.; Tran, B. N.; Burge, P. L.

1991-01-01

A series of fuselage shell and cavity response measurements conducted on a DC-9 aircraft test section are described. The objectives of these measurements were to define the shell and cavity model characteristics of the fuselage, understand the structural-acoustic coupling characteristics of the fuselage, and measure the response of the fuselage to different types of acoustic and vibration excitation. The fuselage was excited with several combinations of acoustic and mechanical sources using interior and exterior loudspeakers and shakers, and the response to these inputs was measured with arrays of microphones and accelerometers. The data were analyzed to generate spatial plots of the shell acceleration and cabin acoustic pressure field, and corresponding acceleration and pressure wavenumber maps. Analysis and interpretation of the spatial plots and wavenumber maps provided the required information on modal characteristics, structural-acoustic coupling, and fuselage response.

Control method for peak power delivery with limited DC-bus voltage

DOEpatents

Edwards, John; Xu, Longya; Bhargava, Brij B.

2006-09-05

A method for driving a neutral point-clamped multi-level voltage source inverter supplying a synchronous motor is provided. A DC current is received at a neutral point-clamped multi-level voltage source inverter. The inverter has first, second, and third output nodes. The inverter also has a plurality of switches. A desired speed of a synchronous motor connected to the inverter by the first second and third nodes is received by the inverter. The synchronous motor has a rotor and the speed of the motor is defined by the rotational rate of the rotor. A position of the rotor is sensed, current flowing to the motor out of at least two of the first, second, and third output nodes is sensed, and predetermined switches are automatically activated by the inverter responsive to the sensed rotor position, the sensed current, and the desired speed.

Development and validation of the INCREMENT-ESBL predictive score for mortality in patients with bloodstream infections due to extended-spectrum-β-lactamase-producing Enterobacteriaceae

PubMed Central

Palacios-Baena, Zaira Raquel; Gutiérrez-Gutiérrez, Belén; De Cueto, Marina; Viale, Pierluigi; Venditti, Mario; Hernández-Torres, Alicia; Oliver, Antonio; Martínez-Martínez, Luis; Calbo, Esther; Pintado, Vicente; Gasch, Oriol; Almirante, Benito; Antonio Lepe, José; Pitout, Johann; Akova, Murat; Peña-Miralles, Carmen; Schwaber, Mitchell J.; Tumbarello, Mario; Tacconelli, Evelina; Origüen, Julia; Prim, Nuria; Bou, German; Giamarellou, Helen; Bermejo, Joaquín; Hamprecht, Axel; Pérez, Federico; Almela, Manuel; Lowman, Warren; Hsueh, Po-Ren; Navarro-San Francisco, Carolina; Torre-Cisneros, Julián; Carmeli, Yehuda; Bonomo, Robert A.; Paterson, David L.; Pascual, Álvaro; Rodríguez-Baño, Jesús

2017-01-01

Background. Bloodstream infections (BSIs) due to ESBL-producing Enterobacteriaceae (ESBL-E) are frequent yet outcome prediction rules for clinical use have not been developed. The objective was to define and validate a predictive risk score for 30 day mortality. Methods. A multinational retrospective cohort study including consecutive episodes of BSI due to ESBL-E was performed; cases were randomly assigned to a derivation cohort (DC) or a validation cohort (VC). The main outcome variable was all-cause 30 day mortality. A predictive score was developed using logistic regression coefficients for the DC, then tested in the VC. Results. The DC and VC included 622 and 328 episodes, respectively. The final multivariate logistic regression model for mortality in the DC included age >50 years (OR = 2.63; 95% CI: 1.18–5.85; 3 points), infection due to Klebsiella spp. (OR = 2.08; 95% CI: 1.21–3.58; 2 points), source other than urinary tract (OR = 3.6; 95% CI: 2.02–6.44; 3 points), fatal underlying disease (OR = 3.91; 95% CI: 2.24–6.80; 4 points), Pitt score >3 (OR = 3.04; 95 CI: 1.69–5.47; 3 points), severe sepsis or septic shock at presentation (OR = 4.8; 95% CI: 2.72–8.46; 4 points) and inappropriate early targeted therapy (OR = 2.47; 95% CI: 1.58–4.63; 2 points). The score showed an area under the receiver operating curve (AUROC) of 0.85 in the DC and 0.82 in the VC. Mortality rates for patients with scores of < 11 and ≥11 were 5.6% and 45.9%, respectively, in the DC, and 5.4% and 34.8% in the VC. Conclusions. We developed and validated an easy-to-collect predictive scoring model for all-cause 30 day mortality useful for identifying patients at high and low risk of mortality. PMID:28062685

Application of 1H and 23Na magic angle spinning NMR spectroscopy to define the HRBC up-taking of MRI contrast agents

NASA Astrophysics Data System (ADS)

Calabi, Luisella; Paleari, Lino; Biondi, Luca; Linati, Laura; De Miranda, Mario; Ghelli, Stefano

2003-09-01

The up-take of Gd(III) complexes of BOPTA, DTPA, DOTA, EDTP, HPDO3A, and DOTP in HRBC has been evaluated by measuring the lanthanide induced shift (LIS) produced by the corresponding dysprosium complexes (DC) on the MAS-NMR resonances of water protons and free sodium ions. These complexes are important in their use as MRI contrast agents (MRI-CA) in diagnostics. 1H and 23Na MAS-NMR spectra of HRBC suspension, collected at 9.395 T, show only one signal due to extra- and intra-cellular water (or sodium). In MAS spectra, the presence of DC in a cellular compartment produces the LIS of only the nuclei (water proton or sodium) in that cellular compartment and this LIS can be related to the DC concentrations (by the experimental curves of LIS vs. DC concentrations) collected in the physiological solution. To obtain correct results about LIS, the use of MAS technique is mandatory, because it guarantees the only the nuclei staying in the same cellular compartment where the LC is present show the LIS. In all the cases considered, the addition of the DC to HRBC (100% hematocrit) produced a shift of only the extra-cellular water (or sodium) signal and the gradient of concentration ( GC) between extra- and intra-cellular compartments resulted greater than 100:1, when calculated by means of sodium signals. These high values of GC are direct proofs that none of the tested dysprosium complexes crosses the HRBC membrane. Since the DC are iso-structural to the gadolinium complexes the corresponding gadolinium ones (MRI-CA) do not cross the HRBC membrane and, consequently, they are not up-taken in HRBC. The GC values calculated by means of water proton signals resulted much lower than those obtained by sodium signals. This proves that the choice of the isotope is a crucial step in order to use this method in the best way. In fact, GC value depends on the lowest detectable LIS which, in turn, depends on the nature of the LC (lanthanide complex) and the observed isotopes.

A Study to Determine Factors Contributing to the Medical Evaluation Board Processing Time at the Joint Military Medical Command - Booke Army Medical Center

DTIC Science & Technology

1990-07-16

achieving improved motivation and perfcrmance ( Szilagyi & Wallace , 1987). However, these goals need to be periodically reviewed and adjusted. Goals must...Washington, D.C.: Headquarters, Dept. of the Army. Szilagy, A.D. & M. J. Wallace . (1987). Organizational Behavior and Performance. Glenview, IL: Scott

Summit of the Research Coordination Networks for Undergraduate Biology Education

ERIC Educational Resources Information Center

Eaton, Carrie Diaz; Allen, Deborah; Anderson, Laurel J.; Bowser, Gillian; Pauley, Mark A.; Williams, Kathy S.; Uno, Gordon E.

2016-01-01

The first summit of projects funded by the National Science Foundation's Research Coordination Networks for Undergraduate Biology Education (RCN-UBE) program was held January 14-16, 2016, in Washington, DC. Sixty-five scientists and science educators from 38 of the 41 Incubator and Full RCN-UBE awards discussed the value and contributions of RCNs…

Basic Guidelines to Introduce Electric Circuit Simulation Software in a General Physics Course

ERIC Educational Resources Information Center

Moya, A. A.

2018-01-01

The introduction of electric circuit simulation software for undergraduate students in a general physics course is proposed in order to contribute to the constructive learning of electric circuit theory. This work focuses on the lab exercises based on dc, transient and ac analysis in electric circuits found in introductory physics courses, and…

Investigators Retreat: A Forum to Bridge Frederick and Bethesda Cancer Research | Poster

Cancer.gov

By Andrea Frydl, Contributing Writer Nearly 700 researchers, scientists, and laboratory technicians convened in the Ronald Reagan Building and International Trade Center in Washington, DC, for the 2014 NCI Intramural Scientific Investigators Retreat on Jan. 14. The event featured presentations and posters exploring topics in cancer research from KRAS signaling to animal care.

The Oral History of Evaluation: The Professional Development of Thomas D. Cook

ERIC Educational Resources Information Center

Mark, Melvin M.; Caracelli, Valerie; McNall, Miles A.; Miller, Robin Lin

2018-01-01

Since 2003, the Oral History Project Team has conducted interviews with individuals who have made particularly noteworthy contributions to the theory and practice of evaluation. In 2013, Mel Mark, Valerie Caracelli, and Miles McNall sat with Thomas Cook in Washington, D.C., during the American Evaluation Association (AEA) annual conference. The…

Mixed Methods in Education Research. IES Technical Working Group Meeting. Meeting Summary (Washington, DC, May 29, 2015)

ERIC Educational Resources Information Center

Institute of Education Sciences, 2015

2015-01-01

This meeting summary is organized into two major sections. The first section captures the individual contribution of meeting participants, including both Institute of Education Sciences (IES) staff and the invited technical working group members. The second section captures themes that arose during the group discussions, which were organized…

Transport and outflow to the North Atlantic in the lower marine troposphere during ICARTT 2004

NASA Astrophysics Data System (ADS)

Davis, S. R.; Talbot, R.; Mao, H.

2012-01-01

An analysis of pollution plumes emitted from sources in the Northeastern US was based on observations from the International Consortium for Atmospheric Research on Transport and Transformation (ICARTT) 2004 field campaign. Particular attention was given to the relation of these plumes to coastal transport patterns in lower tropospheric layers throughout the Gulf of Maine (GOM) and their contribution to large-scale pollution outflow from the North American continent. Using measurements obtained during a series of flights of the NOAA WP-3D and the NASA DC-8, a unique quasi-lagrangian case study was conducted for a freshly emitted plume emanating from the New York City source region in late July 2004. The initial development of this plume stemmed from the accumulation of boundary layer pollutants within a coastal residual layer where weak synoptic forcing triggered its advection by mean southwesterly flow. As the plume tracked into the GOM, analysis showed that the plume layer vertical structure evolved into an internal boundary layer form, with signatures of steep vertical gradients in temperature, moisture and wind speed often resulting in periodic turbulence. This structure remained well-defined during the plume study, allowing for the detachment of the plume layer from the surface and thus minimal deposition and plume-sea surface exchange. In contrast, lateral mixing with other low-level plumes was significant during its transit and facilitated in part by persistent shear driven turbulence which further contributed to the high spatial variability in trace gas mixing ratios. The impact of the plume inland was assessed using observations from the AIRMAP air quality network. This impact was noticeably detected as a contribution to poor surface ozone conditions and significant elevations of other major pollutants to levels equaling the highest observed that summer. Further contributions to larger-scale outflow across the North Atlantic was also observed and analyzed.

Compact, High Energy 2-micron Coherent Doppler Wind Lidar Development for NASA's Future 3-D Winds Measurement from Space

NASA Technical Reports Server (NTRS)

Singh, Upendra N.; Koch, Grady; Yu, Jirong; Petros, Mulugeta; Beyon, Jeffrey; Kavaya, Michael J.; Trieu, Bo; Chen, Songsheng; Bai, Yingxin; Petzar, paul;

DC-SIGN–expressing macrophages trigger activation of mannosylated IgM B-cell receptor in follicular lymphoma

PubMed Central

Amin, Rada; Mourcin, Frédéric; Uhel, Fabrice; Pangault, Céline; Ruminy, Philippe; Dupré, Loic; Guirriec, Marion; Marchand, Tony; Fest, Thierry; Lamy, Thierry

2015-01-01

Follicular lymphoma (FL) results from the accumulation of malignant germinal center (GC) B cells leading to the development of an indolent and largely incurable disease. FL cells remain highly dependent on B-cell receptor (BCR) signaling and on a specific cell microenvironment, including T cells, macrophages, and stromal cells. Importantly, FL BCR is characterized by a selective pressure to retain surface immunoglobulin M (IgM) BCR despite an active class-switch recombination process, and by the introduction, in BCR variable regions, of N-glycosylation acceptor sites harboring unusual high-mannose oligosaccharides. However, the relevance of these 2 FL BCR features for lymphomagenesis remains unclear. In this study, we demonstrated that IgM+ FL B cells activated a stronger BCR signaling network than IgG+ FL B cells and normal GC B cells. BCR expression level and phosphatase activity could both contribute to such heterogeneity. Moreover, we underlined that a subset of IgM+ FL samples, displaying highly mannosylated BCR, efficiently bound dendritic cell–specific intercellular adhesion molecule-3–grabbing nonintegrin (DC-SIGN), which could in turn trigger delayed but long-lasting BCR aggregation and activation. Interestingly, DC-SIGN was found within the FL cell niche in situ. Finally, M2 macrophages induced a DC-SIGN–dependent adhesion of highly mannosylated IgM+ FL B cells and triggered BCR-associated kinase activation. Interestingly, pharmacologic BCR inhibitors abolished such crosstalk between macrophages and FL B cells. Altogether, our data support an important role for DC-SIGN–expressing infiltrating cells in the biology of FL and suggest that they could represent interesting therapeutic targets. PMID:26272216

Shapiro steps for skyrmion motion on a washboard potential with longitudinal and transverse ac drives

DOE PAGES

Reichhardt, Charles; Reichhardt, Cynthia Jane

2015-12-28

In this work, we numerically study the behavior of two-dimensional skyrmions in the presence of a quasi-one-dimensional sinusoidal substrate under the influence of externally applied dc and ac drives. In the overdamped limit, when both dc and ac drives are aligned in the longitudinal direction parallel to the direction of the substrate modulation, the velocity-force curves exhibit classic Shapiro step features when the frequency of the ac drive matches the washboard frequency that is dynamically generated by the motion of the skyrmions over the substrate, similar to previous observations in superconducting vortex systems. In the case of skyrmions, the additionalmore » contribution to the skyrmion motion from a nondissipative Magnus force shifts the location of the locking steps to higher dc drives, and we find that the skyrmions move at an angle with respect to the direction of the dc drive. For a longitudinal dc drive and a perpendicular or transverse ac drive, the overdamped system exhibits no Shapiro steps; however, when a finite Magnus force is present, we find pronounced transverse Shapiro steps along with complex two-dimensional periodic orbits of the skyrmions in the phase-locked regimes. Both the longitudinal and transverse ac drives produce locking steps whose widths oscillate with increasing ac drive amplitude. We examine the role of collective skyrmion interactions and find that additional fractional locking steps occur for both longitudinal and transverse ac drives. Finally, at higher skyrmion densities, the system undergoes a series of dynamical order-disorder transitions, with the skyrmions forming a moving solid on the phase locking steps and a fluctuating dynamical liquid in regimes between the steps.« less

Modulation of human Th17 cell responses through complement receptor 3 (CD11 b/CD18) ligation on monocyte-derived dendritic cells.

PubMed

Nowatzky, Johannes; Manches, Olivier; Khan, Shaukat Ali; Godefroy, Emmanuelle; Bhardwaj, Nina

2018-06-13

Apoptotic cell receptors contribute to the induction of tolerance by modulating dendritic cell function following the uptake of apoptotic cells or microparticles. Dendritic cells that have bound or ingested apoptotic cells produce only low amounts of pro-inflammatory cytokines and fail to prime effector T cell responses. Specifically, ligation of the apoptotic cell receptor CR3 (CD11 b/CD18) on human monocyte-derived dendritic cells (moDC) down-modates proinflammatory cytokine secretion, but the consequences for human Th17 cell homeostasis and effector responses remain unknown. Here, we aimed to establish whether CD11b-ligated moDC modulate Th17 cell effector reponses to assess their potential for future use in moDC-based suppressive immunotherapy. We generated a bead-based surrogate system to target CD11b on monocyte-derived human dendritic cells and examined the effects of CD11b ligation on Th17-skewing cytokine secretion, priming, expansion and functional plasticity in DC/T cell co-culture systems at the poly- and monoclonal level. We show that Th17 cell expansion within the human memory CD4 + T cell compartment was efficiently constricted by targeting the CD11b receptor on moDC. This tolerogenic capacity was primarily dependent on cytokine skewing. Furthermore, ligation of CD11b on healthy homozygous carriers of the rs11143679 (ITGAM) variant - a strong genetic susceptibility marker for human systemic lupus erythematosus - also down-modulated the secretion of Th17-skewing cytokines. Overall, our findings underline the potential of targeted CD11b ligation on human dendritic cells for the engineering of suppressive immunotherapy for Th17-related autoimmune disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

ToF-SIMS and principal component analysis of lipids and amino acids from inflamed and dysplastic human colonic mucosa.

PubMed

Urbini, Marco; Petito, Valentina; de Notaristefani, Francesco; Scaldaferri, Franco; Gasbarrini, Antonio; Tortora, Luca

2017-10-01

Here, time of flight secondary ion mass spectrometry (ToF-SIMS) and multivariate analysis were combined to study the role of ulcerative colitis (UC), a type of inflammatory bowel disease (IBD), in the colon cancer progression. ToF-SIMS was used to obtain mass spectra and chemical maps from the mucosal surface of human normal (NC), inflamed (IC), and dysplastic (DC) colon tissues. Chemical mapping with a lateral resolution of ≈ 1 μm allowed to evaluate zonation of fatty acids and amino acids as well as the morphological condition of the intestinal glands. High mass resolution ToF-SIMS spectra showed chemical differences in lipid and amino acid composition as a function of pathological state. In positive ion mode, mono- (MAG), di- (DAG), and triacylglycerol (TAG) signals were detected in NC tissues, while in IC and DC tissues, the only cholesterol was present as lipid class representative. Signals from fatty acids, collected in negative ion mode, were subjected to principal component analysis (PCA). PCA showed a strict correlation between IC and DC samples, due to an increase of stearic, arachidonic, and linoleic acid. In the same way, differences in the amino acid composition were highlighted through multivariate analysis. PCA revealed that glutamic acid, leucine/isoleucine, and valine fragments are related to IC tissues. On the other hand, tyrosine, methionine, and tryptophan peaks contributed highly to the separation of DC tissues. Finally, a classification of NC, IC, and DC patients was also achieved through hierarchical cluster analysis of amino acid fragments. In this case, human colonic inflammation showed a stronger relationship with normal than dysplastic condition. Graphical Abstract ᅟ.

Neuronal nitric oxide synthase immunopositive neurons in cat claustrum--a light and electron microscopic study.

PubMed

Hinova-Palova, Dimka; Edelstein, Lawrence; Paloff, Adrian; Hristov, Stanislav; Papantchev, Vassil; Ovtscharoff, Wladimir

2008-08-01

Nitric oxide is a unique neurotransmitter, which participates in many physiological and pathological processes in the organism. Nevertheless there are little data about the neuronal Nitric Oxide Synthase immunoreactive (nNOS-ir) neurons and fibers in the dorsal claustrum (DC) of a cat. In this respect the aims of this study were: (1) to demonstrate nNOS-ir in the neurons and fibers of the DC; (2) to describe their light microscopic morphology and distribution; (3) to investigate and analyze the ultrastructure of the nNOS-ir neurons, fibers and synaptic terminals; (4) to verify whether the nNOS-ir neurons consist a specific subpopulation of claustral neurons; (5) to verify whether the nNOS-ir neurons have a specific pattern of organization throughout the DC. For demonstration of the nNOS-ir the Avidin-Biotin-Peroxidase Complex method was applied. Immunopositive for nNOS neurons and fibers were present in all parts of DC. On the light microscope level nNOS-ir neurons were different in shape and size. According to the latter they were divided into three groups-small (with diameter under 15 microm), medium-sized (with diameter from 16 to 20 microm) and large (with diameter over 21 microm). Some of nNOS-ir neurons were lightly-stained while others were darkly-stained. On the electron microscope level the immunoproduct was observed in neurons, dendrites and terminal boutons. Different types of nNOS-ir neurons differ according to their ultrastructural features. Three types of nNOS-ir synaptic boutons were found. As a conclusion we hope that the present study will contribute to a better understanding of the functioning of the DC in cat and that some of the data presented could be extrapolated to other mammals, including human.

A human dendritic cell-based in vitro model to assess Mycobacterium tuberculosis SO2 vaccine immunogenicity.

PubMed

Etna, Marilena P; Giacomini, Elena; Severa, Martina; Pardini, Manuela; Aguilo, Nacho; Martin, Carlos; Coccia, Eliana M

2014-01-01

Among the tuberculosis (TB) vaccine candidates, SO2 is the prototype of the first live-attenuated vaccine that recently entered into clinical trials. To investigate the capacity of SO2 to stimulate an appropriate immune response in vitro within a human immunological context, a comparative analysis of the effects promoted by SO2, the current Bacille Calmette-Guerin (BCG) vaccine and Mycobacterium tuberculosis (Mtb) was conducted in human primary dendritic cells (DC), which are critical modulators of vaccine-induced immunity. In particular, we found that SO2 promotes the expression of maturation markers similarly to BCG but at a lower extent than Mtb. Moreover, SO2-infected DC released higher levels of interleukin (IL)-23 than BCG-infected cells, which account for the expansion of interferon (IFN)-γ-producing T cells in an IL-12-independent manner. In the autologous mixed leukocyte reaction setting, the expansion of IL-17-producing T cells was also observed in response to SO2 infection. Interestingly, apoptosis and autophagic flux, events required for the antigen presentation within MHC class II complex, were not affected in DC infected with SO2, conversely to what observed upon Mtb stimulation. Collectively, our results indicate that SO2 represents a promising TB vaccine candidate, which displays an attenuated phenotype and promotes in DC a stronger capacity to stimulate the Th response than BCG vaccine. Interestingly, the data obtained by using the human DC-based experimental setting mirrored the results derived from studies in animal models, suggesting that this system could be used for an efficient and rapid down-selection of new TB vaccine candidates, contributing to achieve the "3Rs" objective.

Immunohistochemical evaluation of myofibroblasts in odontogenic cysts and tumors: A comparative study.

PubMed

Syamala, Deepa; Suresh, Rakesh; Janardhanan, Mahija; Savithri, Vindhya; Anand, Prem P; Jose, Amrutha

2016-01-01

Myofibroblasts are fibroblasts with smooth muscle-like features characterized by the presence of a contractile apparatus and found in the connective tissue stroma of normal tissues such as blood vessels and lymph nodes. They are now thought to play a role in the synthesis and reorganization of extracellular matrix, which could contribute to the aggressive biologic behavior of the lesions. To compare the mean number of stromal myofibroblasts in dentigerous cysts (DCs), keratocystic odontogenic tumor (KCOT) and ameloblastoma; and to derive a correlation between the stromal myofibroblasts and the known biologic behavior of the lesions. A cross-sectional immunohistochemical analysis of cases of DC, KCOT and ameloblastoma. Twenty paraffin-embedded tissue blocks each of DC, KCOT and multicystic ameloblastoma were selected for the study and diagnosis confirmed through hematoxylin and eosin staining. Tissue sections were analyzed for the number of myofibroblasts using alpha smooth muscle actin (α-SMA) immunostaining. Differences in the mean number of α-SMA positive cells in each group were analyzed using one-way ANOVA test. Intergroup comparisons of mean values of α-SMA positive cells were performed using Mann-Whitney U-test. Ameloblastoma showed the highest number of myofibroblasts, whereas DC showed the lowest. Among the groups, there were significant differences between the myofibroblast counts among DC and KCOT and between DC and ameloblastoma, whereas the difference in counts was not statistically significant between KCOT and ameloblastoma. A positive correlation was observed between the myofibroblast count and the known biologic behavior of the lesions. Myofibroblasts may act in close association with the epithelial cells to bring about changes in stromal microenvironment, favorable to the growth and progression of the lesion. They may be of great value in predicting the biologic behavior and growth potential of such lesions.

Plasmacytoid dendritic cell and functional HIV Gag p55-specific T cells before treatment interruption can inform set-point plasma HIV viral load after treatment interruption in chronically suppressed HIV-1(+) patients.

PubMed

Papasavvas, Emmanouil; Foulkes, Andrea; Yin, Xiangfan; Joseph, Jocelin; Ross, Brian; Azzoni, Livio; Kostman, Jay R; Mounzer, Karam; Shull, Jane; Montaner, Luis J

2015-07-01

The identification of immune correlates of HIV control is important for the design of immunotherapies that could support cure or antiretroviral therapy (ART) intensification-related strategies. ART interruptions may facilitate this task through exposure of an ART partially reconstituted immune system to endogenous virus. We investigated the relationship between set-point plasma HIV viral load (VL) during an ART interruption and innate/adaptive parameters before or after interruption. Dendritic cell (DC), natural killer (NK) cell and HIV Gag p55-specific T-cell functional responses were measured in paired cryopreserved peripheral blood mononuclear cells obtained at the beginning (on ART) and at set-point of an open-ended interruption from 31 ART-suppressed chronically HIV-1(+) patients. Spearman correlation and linear regression modeling were used. Frequencies of plasmacytoid DC (pDC), and HIV Gag p55-specific CD3(+)  CD4(-)  perforin(+)  IFN-γ(+) cells at the beginning of interruption associated negatively with set-point plasma VL. Inclusion of both variables with interaction into a model resulted in the best fit (adjusted R(2)  = 0·6874). Frequencies of pDC or HIV Gag p55-specific CD3(+)  CD4(-)  CSFE(lo)  CD107a(+) cells at set-point associated negatively with set-point plasma VL. The dual contribution of pDC and anti-HIV T-cell responses to viral control, supported by our models, suggests that these variables may serve as immune correlates of viral control and could be integrated in cure or ART-intensification strategies. © 2015 John Wiley & Sons Ltd.

PROSPECT: Profiling of Resistance Patterns Oncogenic Signaling Pathways in Evaluation of Cancers of the Thorax and Therapeutic Target Identification

DTIC Science & Technology

2011-06-01

8w DC in patients treated with erlotinib, but not sorafenib, indicating that it is not merely a prognostic signature; D) Both the 5-gene signature...disease-free, progression-free, and overall survival will vary across prognostically distinct groups. 3. Specific molecular signatures in primary tumors...therapeutic strategies at relapse. Specific Aims: Aim 1: To define characteristic TTF/gene expression profiles of prognostically distinct

Transactions of the Army Conference on Applied Mathematics and Computing (1st) Held at Washington, DC on 9-11 May 1983

DTIC Science & Technology

1984-02-01

I . . . . . . An Introduction to Geometric Programming Patrick D. Allen and David W. Baker . . . . . . , . . . . . . . Space and Time...Zarwyn, US-Army Electronics R & D Comhiand GEOMETRIC PROGRAMING SPACE AND TIFFE ANALYSIS IN DYNAMIC PROGRAMING ALGORITHMS Renne..tf Stizti, AkeanXa...physical and parameter space can be connected by asymptotic matching. The purpose of the asymptotic analysis is to define the simplest problems

CF6-6D engine short-term performance deterioration

NASA Technical Reports Server (NTRS)

Kramer, W. H.; Paas, J. E.; Smith, J. J.; Wulf, R. H.

1980-01-01

Studies conducted as part of the NASA-Lewis CF6 jet engine diagnostics program are summarized. An 82-engine sample of DC-10-10 aircraft engine checkout data that were gathered to define the extent and magnitude of CF6-6D short term performance deterioration were analyzed. These data are substantiated by the performance testing and analytical teardown of CF6-6D short term deterioration engine serial number (ESN) 451507.

Improving depiction of temporal bone anatomy with low-radiation dose CT by an integrated circuit detector in pediatric patients: a preliminary study.

PubMed

He, Jingzhen; Zu, Yuliang; Wang, Qing; Ma, Xiangxing

2014-12-01

The purpose of this study was to determine the performance of low-dose computed tomography (CT) scanning with integrated circuit (IC) detector in defining fine structures of temporal bone in children by comparing with the conventional detector. The study was performed with the approval of our institutional review board and the patients' anonymity was maintained. A total of 86 children<3 years of age underwent imaging of temporal bone with low-dose CT (80 kV/150 mAs) equipped with either IC detector or conventional discrete circuit (DC) detector. The image noise was measured for quantitative analysis. Thirty-five structures of temporal bone were further assessed and rated by 2 radiologists for qualitative analysis. κ Statistics were performed to determine the agreement reached between the 2 radiologists on each image. Mann-Whitney U test was used to determine the difference in image quality between the 2 detector systems. Objective analysis showed that the image noise was significantly lower (P<0.001) with the IC detector than with the DC detector. The κ values for qualitative assessment of the 35 fine anatomical structures revealed high interobserver agreement. The delineation for 30 of the 35 landmarks (86%) with the IC detector was superior to that with the conventional DC detector (P<0.05) although there were no differences in the delineation of the remaining 5 structures (P>0.05). The low-dose CT images acquired with the IC detector provide better depiction of fine osseous structures of temporal bone than that with the conventional DC detector.

The interplay between surfaces and soluble factors define the immunologic and angiogenic properties of myeloid dendritic cells

PubMed Central

2011-01-01

Background Dendritic cells (DCs) are antigen presenting cells capable of inducing specific immune responses against microbial infections, transplant antigens, or tumors. Interestingly, microenvironment conditions such as those present in tumor settings might induce a DC phenotype that is poorly immunogenic and with the capability of promoting angiogenesis. We hypothesize that this plasticity may be caused not only by the action of specific cytokines or growth factors but also by the properties of the surfaces with which they interact, such as extracellular matrix (ECM) components. Results Herewith we studied the effect of different surfaces and soluble factors on the biology of DCs. To accomplish this, we cultured murine myeloid(m) DCs on surfaces coated with fibronectin, collagen I, gelatin, and Matrigel using poly-D-lysine and polystyrene as non-biological surfaces. Further, we cultured these cells in the presence of regular DC medium (RPMI 10% FBS) or commercially available endothelial medium (EGM-2). We determined that mDCs could be kept in culture up to 3 weeks in these conditions, but only in the presence of GM-CSF. We were able to determine that long-term DC cultures produce an array of angiogenic factors, and that some of these cultures still retain the capability to induce T cell responses. Conclusions Altogether these data indicate that in order to design DC-based vaccines or treatments focused on changing the phenotype of DCs associated with diseases such as cancer or atherosclerosis, it becomes necessary to fully investigate the microenvironment in which these cells are present or will be delivered. PMID:21645356

The interplay between surfaces and soluble factors define the immunologic and angiogenic properties of myeloid dendritic cells.

PubMed

Sprague, Leslee; Muccioli, Maria; Pate, Michelle; Meles, Evan; McGinty, John; Nandigam, Harika; Venkatesh, Amritha K; Gu, Ming-Yu; Mansfield, Kristen; Rutowski, Andrew; Omosebi, Omowaleola; Courreges, Maria C; Benencia, Fabian

2011-06-06

Dendritic cells (DCs) are antigen presenting cells capable of inducing specific immune responses against microbial infections, transplant antigens, or tumors. Interestingly, microenvironment conditions such as those present in tumor settings might induce a DC phenotype that is poorly immunogenic and with the capability of promoting angiogenesis. We hypothesize that this plasticity may be caused not only by the action of specific cytokines or growth factors but also by the properties of the surfaces with which they interact, such as extracellular matrix (ECM) components. Herewith we studied the effect of different surfaces and soluble factors on the biology of DCs. To accomplish this, we cultured murine myeloid(m) DCs on surfaces coated with fibronectin, collagen I, gelatin, and Matrigel using poly-D-lysine and polystyrene as non-biological surfaces. Further, we cultured these cells in the presence of regular DC medium (RPMI 10% FBS) or commercially available endothelial medium (EGM-2). We determined that mDCs could be kept in culture up to 3 weeks in these conditions, but only in the presence of GM-CSF. We were able to determine that long-term DC cultures produce an array of angiogenic factors, and that some of these cultures still retain the capability to induce T cell responses. Altogether these data indicate that in order to design DC-based vaccines or treatments focused on changing the phenotype of DCs associated with diseases such as cancer or atherosclerosis, it becomes necessary to fully investigate the microenvironment in which these cells are present or will be delivered.

Licensed human natural killer cells aid dendritic cell maturation via TNFSF14/LIGHT

PubMed Central

Holmes, Tim D.; Wilson, Erica B.; Black, Emma V. I.; Benest, Andrew V.; Vaz, Candida; Tan, Betty; Tanavde, Vivek M.; Cook, Graham P.

2014-01-01

Interactions between natural killer (NK) cells and dendritic cells (DCs) aid DC maturation and promote T-cell responses. Here, we have analyzed the response of human NK cells to tumor cells, and we identify a pathway by which NK–DC interactions occur. Gene expression profiling of tumor-responsive NK cells identified the very rapid induction of TNF superfamily member 14 [TNFSF14; also known as homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes (LIGHT)], a cytokine implicated in the enhancement of antitumor responses. TNFSF14 protein expression was induced by three primary mechanisms of NK cell activation, namely, via the engagement of CD16, by the synergistic activity of multiple target cell-sensing NK-cell activation receptors, and by the cytokines IL-2 and IL-15. For antitumor responses, TNFSF14 was preferentially produced by the licensed NK-cell population, defined by the expression of inhibitory receptors specific for self-MHC class I molecules. In contrast, IL-2 and IL-15 treatment induced TNFSF14 production by both licensed and unlicensed NK cells, reflecting the ability of proinflammatory conditions to override the licensing mechanism. Importantly, both tumor- and cytokine-activated NK cells induced DC maturation in a TNFSF14-dependent manner. The coupling of TNFSF14 production to tumor-sensing NK-cell activation receptors links the tumor immune surveillance function of NK cells to DC maturation and adaptive immunity. Furthermore, regulation by NK cell licensing helps to safeguard against TNFSF14 production in response to healthy tissues. PMID:25512551

NASA's DC-8 Desert Shadow

NASA Image and Video Library

2017-12-08

The DC-8 research aircraft casting its shadow on the ground in California's Mojave Desert during an IceBridge instrument check flight. Prior to field campaigns, IceBridge instrument and aircraft teams run the aircraft through a series of tests to ensure that everything is operating at peak condition. Credit: NASA / Jim Yungel NASA's Operation IceBridge is an airborne science mission to study Earth's polar ice. For more information about IceBridge, visit: www.nasa.gov/icebridge NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

Effects of the Peptide Pheromone Plantaricin A and Cocultivation with Lactobacillus sanfranciscensis DPPMA174 on the Exoproteome and the Adhesion Capacity of Lactobacillus plantarum DC400

PubMed Central

Calasso, Maria; Di Cagno, Raffaella; Campanella, Daniela; Minervini, Fabio; Gobbetti, Marco

2013-01-01

This study aimed at investigating the extracellular and cell wall-associated proteins (exoproteome) of Lactobacillus plantarum DC400 when cultivated on modified chemically defined medium (CDM) supplemented with the chemically synthesized pheromone plantaricin A (PlnA) or cocultured with L. plantarum DPPMA20 or Lactobacillus sanfranciscensis DPPMA174. Compared to monoculture, two-dimensional gel electrophoresis (2-DE) analysis showed that the exoproteome of L. plantarum DC400 was affected by PlnA and cocultivation with strains DPPMA20 and, especially, DPPMA174. The highest similarity of the 2-DE maps was found between DC400 cells cultivated in monoculture and in coculture with strain DPPMA20. Almost all extracellular proteins (22 spots) and cell wall-associated proteins (40 spots) which showed decreased or increased levels of synthesis during growth in CDM supplemented with PlnA and/or in coculture with strain DPPMA20 or DPPMA174 were identified. On the basis of the sequences in the Kyoto Encyclopedia of Genes and Genomes database, changes to the exoproteome concerned proteins involved in quorum sensing (QS), the transport system, stress response, carbohydrate metabolism and glycolysis, oxidation/reduction processes, the proteolytic system, amino acid metabolism, cell wall and catabolic processes, and cell shape, growth, and division. Cultivation with PlnA and cocultivation with strains DPPMA20 and, especially, DPMMA174 markedly increased the capacity of L. plantarum DC400 to form biofilms, to adhere to human Caco-2 cells, and to prevent the adhesion of potential intestinal pathogens. These phenotypic traits were in part related to oversynthesized moonlighting proteins (e.g., DnaK and GroEL, pyruvate kinase, enolase, and glyceraldehyde-3-phosphate dehydrogenase) in response to QS mechanisms and interaction with L. plantarum DPPMA20 and, especially, L. sanfranciscensis DPPMA174. PMID:23396346

Profile of refractive errors in European Caucasian children with Autistic Spectrum Disorder; increased prevalence and magnitude of astigmatism.

PubMed

Anketell, Pamela M; Saunders, Kathryn J; Gallagher, Stephen; Bailey, Clare; Little, Julie-Anne

2016-07-01

Autistic Spectrum Disorder (ASD) is a common neurodevelopmental disorder characterised by impairment of communication, social interaction and repetitive behaviours. Only a small number of studies have investigated fundamental clinical measures of vision including refractive error. The aim of this study was to describe the refractive profile of a population of children with ASD compared to typically developing (TD) children. Refractive error was assessed using the Shin-Nippon NVision-K 5001 open-field autorefractor following the instillation of cyclopentolate hydrochloride 1% eye drops. A total of 128 participants with ASD (mean age 10.9 ± 3.3 years) and 206 typically developing participants (11.5 ± 3.1 years) were recruited. There was no significant difference in median refractive error, either by spherical equivalent or most ametropic meridian between the ASD and TD groups (Spherical equivalent, Mann-Whitney U307 = 1.15, p = 0.25; Most Ametropic Meridian, U305 = 0.52, p = 0.60). Median refractive astigmatism was -0.50DC (range 0.00 to -3.50DC) for the ASD group and -0.50DC (Range 0.00 to -2.25DC) for the TD group. Magnitude and prevalence of refractive astigmatism (defined as astigmatism ≥1.00DC) was significantly greater in the ASD group compared to the typically developing group (ASD 26%, TD 8%, magnitude U305 = 3.86, p = 0.0001; prevalence (χ12=17.71 , p < 0.0001). This is the first study to describe the refractive profile of a population of European Caucasian children with ASD compared to a TD population of children. Unlike other neurodevelopmental conditions, there was no increased prevalence of spherical refractive errors in ASD but astigmatic errors were significantly greater in magnitude and prevalence. This highlights the need to examine refractive errors in this population. © 2016 The Authors Ophthalmic & Physiological Optics © 2016 The College of Optometrists.

Autologous aldrithiol-2-inactivated HIV-1 combined with polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose as a vaccine platform for therapeutic dendritic cell immunotherapy.

PubMed

Miller, Elizabeth; Spadaccia, Meredith; Sabado, Rachel; Chertova, Elena; Bess, Julian; Trubey, Charles Mac; Holman, Rose Marie; Salazar, Andres; Lifson, Jeffrey; Bhardwaj, Nina

2015-01-03

Therapeutic interventions for HIV-1 that successfully augment adaptive immunity to promote killing of infected cells may be a requisite component of strategies to reduce latent cellular reservoirs. Adoptive immunotherapies utilizing autologous monocyte-derived dendritic cells (DCs) that have been activated and antigen loaded ex vivo may serve to circumvent defects in DC function that are present during HIV infection in order to enhance adaptive immune responses. Here we detail the clinical preparation of DCs loaded with autologous aldrithiol-2 (AT-2)-inactivated HIV that have been potently activated with the viral mimic, Polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose (Poly-ICLC). HIV is first propagated from CD4+ T cells from HIV-infected donors and then rendered non-replicative by chemical inactivation with aldrithiol-2 (AT-2), purified, and quantified. Viral inactivation is confirmed through measurement of Tat-regulated β-galactosidase reporter gene expression following infection of TZM-bl cells. In-process testing for sterility, mycoplasma, LPS, adventitious agents, and removal of AT-2 is performed on viral preparations. Autologous DCs are generated and pulsed with autologous AT-2-inactivated virus and simultaneously stimulated with Poly-ICLC to constitute the final DC vaccine product. Phenotypic identity, maturation, and induction of HIV-specific adaptive immune responses are confirmed via flow cytometric analysis of DCs and cocultured autologous CD4+ and CD8+ T cells. Lot release criteria for the DC vaccine have been defined in accordance with Good Manufacturing Practice (GMP) guidelines. The demonstrated feasibility of this approach has resulted in approval by the FDA for investigational use in antiretroviral (ART) suppressed individuals. We discuss how this optimized DC formulation may enhance the quality of anti-HIV adaptive responses beyond what has been previously observed during DC immunotherapy trials for HIV infection. Copyright © 2014 Elsevier Ltd. All rights reserved.

75 FR 21149 - Proposed Collection; Comment Request for Notice 2006-107

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-22

... Notice 2006-107, Diversification Requirements for Qualified Defined Contribution Plans Holding Publicly... INFORMATION: Title: Diversification Requirements for Qualified Defined Contribution Plans Holding Publicly... provides diversification rights with respect to publicly traded employer securities held by a defined...

A Crystal-Physical Model of Electrotransfer in the Superionic Conductor Pb1 - x Sc x F2 + x ( x = 0.1)

NASA Astrophysics Data System (ADS)

Sorokin, N. I.

2018-04-01

The frequency (ν = 10-1-107 Hz) dependences of electrical conductivity σ(ν) of single crystals of superionic conductor Pb0.9Sc0.1F2.1 (10 mol % ScF3) with fluorite type structure (CaF2) in the temperature range 153-410 K have been investigated. The static bulk conductivity σ dc =1.5 × 10-4 S/cm and average hopping frequency ν h = 1.5 × 107 Hz of charge carriers (mobile ions F-) at room temperature (293 K) have been defined from the σ dc (ν) experimental curves. Enthalpies of thermoactivated processes of ionic conductivity σ dc ( T) (Δ H σ = 0.393 ± 0.005 eV) and dielectric relaxation ν h ( T) (Δ H h = 0.37 ± 0.03 eV) coincide within their errors. A crystal-physical model of fluorine-ion transport in a Pb0.9Sc0.1F2.1 crystal lattice has been proposed. The characteristic parameters of charge carriers have been calculated: concentration n mob = 2.0 × 1021 cm-3, the distance of the hopping d ≈ 0.5 nm and mobility μmob = 4.5 × 10-7 cm2/s V (293 K).

Orchestration of transplantation tolerance by regulatory dendritic cell therapy or in situ targeting of dendritic cells

PubMed Central

Morelli, Adrian E.; Thomson, Angus W.

2014-01-01

Purpose of review Extensive research in murine transplant models over the past two decades has convincingly demonstrated the ability of regulatory dendritic cells (DCreg) to promote long-term allograft survival. We review important considerations regarding the source of therapeutic DCreg (donor or recipient) and their mode of action, in situ targeting of DCreg, and optimal therapeutic regimens to promote DCreg function. Recent findings Recent studies have defined protocols and mechanisms whereby ex vivo-generated DCreg of donor or recipient origin subvert allogeneic T cell responses and promote long-term organ transplant survival. Particular interest has focused on how donor antigen (Ag) is acquired, processed and presented by autologous DCs, on the stability of DCreg, and on in situ targeting of DC to promote their tolerogenic function. New evidence of the therapeutic efficacy of DCreg in a clinically-relevant non-human primate organ transplant model and production of clinical grade DCreg support early evaluation of DCreg therapy in human graft recipients. Summary We discuss strategies currently used to promote DC tolerogenicity, including DCreg therapy and in situ targeting of DC, with a view to improved understanding of underlying mechanisms and identification of the most promising strategies for therapeutic application. PMID:24926700

Defined contribution health care: future direction or fantasy?

PubMed

Ostuw, R

2000-01-01

Will payers embrace defined contribution plans as an alternative to traditional health insurance or is this new approach a pipe dream? Are consumers truly ready to make informed decisions on purchasing their own health care? This article explores barriers to defined contribution health plans, including consumer reluctance to take ownership of buying insurance and a preference for the cost predictability of liberal coverage in employer-sponsored programs versus MSAs or higher co-payment arrangements. For the ultimate form of defined contribution health care to work, several tax and insurance barriers must be overcome. As a practical matter, the author argues that the current employer-sponsored approach is the most efficient system for large employers.

Preliminary design for a Zero Gravity Test Facility (ZGTF). Volume 1: Technical

NASA Technical Reports Server (NTRS)

Germain, A.

1981-01-01

The functional requirements and best conceptual design of a test facility that simulates weightless operating conditions for a high gain antenna systems (HGAS), that will broadcast to the Tracking Data Relay Satellites were defined. The typical HGAS defined is mounted on a low Earth orbiting satellite, and consists of an antenna with a double gimbal pointing system mounted on a 13 foot long mast. Typically, the gimbals are driven by pulse modulated dc motors or stepper motors. These drivers produce torques on the mast, with jitter that excites the satellite and may cause disturbances to sensitive experiments. The dynamic properties of the antenna support structure (mast), including flexible mode characteristics were defined. The torque profile induced on the spacecraft by motion of the high gain antenna was estimated. Gain and phase margins of the servo control loop of the gimbal drive electronics was also verified.

Life cycles and biomass allocation in seed- and ramet-derived plants of Cryptotaenia canadensis (Apicea), a monocarpic species of eastern North America

Treesearch

Tracy S. Hawkins; Jerry M. Baskin; Carol C. Baskin

2005-01-01

Life cycles, survivorship, and biomass allocation for seed- and ramet-derived plants of Cryptotaenia canadensis (L.) DC. were studied to determine if variation existed between plant derivations, and how these attributes contribute to persistence of the species within a temperate forest habitat. Seed-derived plants behaved as biennials, reproducing...

Proceedings of the Annual Meeting of the Association for Education in Journalism and Mass Communication (84th, Washington, DC, August 5-8, 2001). Newspaper Division.

ERIC Educational Resources Information Center

Association for Education in Journalism and Mass Communication.

The Newspaper section, Part 1 of the proceedings contains the following selected papers: "Gatekeeping and the Editorial Cartoon: A Case Study of the 2000 Presidential Campaign Cartoons" (Jennifer M. Proffitt); "Campaign Contributions: Online Newspapers Go Beyond Shovelware in Covering Election 2000" (Jane B. Singer); "At…

Remarks by Drew S. Days III Before the Urban Mass Transportation Administration (Washington, D.C., June 30, 1979).

ERIC Educational Resources Information Center

Days, Drew S., III

Title VI was designed to put an end to Federal support of discrimination and to assure blacks the right of access to Federally assisted programs. However, the Federal government has not established sufficiently rigorous compliance and enforcement mechanisms to ensure that its programs do not contribute to racial discrimination. In order to enforce…

The Role of Sensory Modulation Deficits and Behavioral Symptoms in a Diagnosis for Early Childhood

ERIC Educational Resources Information Center

Perez-Robles, Ruth; Doval, Eduardo; Jane, Ma Claustre; da Silva, Pedro Caldeira; Papoila, Ana Luisa; Virella, Daniel

2013-01-01

To contribute to the validation of the sensory and behavioral criteria for Regulation Disorders of Sensory Processing (RDSP) (DC:0-3R, 2005), this study examined a sample of toddlers in a clinical setting to analyze: (1) the severity of sensory modulation deficits and the behavioral symptoms of RDSP; (2) the associations between sensory and…

Lyman C. Johnston, DC, FICC, FCCS(C): Canadian chiropractic's postural research pioneer and inventive entrepreneur

PubMed Central

Brown, Douglas M.

2001-01-01

This paper profiles Dr. Lyman Johnston and his contributions in the field of chiropractic research. Postural concepts, diagnostic instruments, therapeutic devices and treatment protocols are reviewed. Set out and briefly discussed are the Posturometer, Pyramidal Man, anterior-posterior gravity line, Postural Spinal Index, tension master, Spine Power Belt and the Mini-Gym. ImagesFigure 1

A STUDY OF PROCESS CONTRIBUTIONS TO OZONE FORMATION DURING THE 2004 ICARTT PERIOD USING THE ETA-CMAQ FORECAST MODEL OVER THE NORTHEASTERN U.S.

EPA Science Inventory

First, this study evaluates the Eta-CMAQ forecast model performances for O₃, and related chemical species with the observational data from the aircraft (NOAA P-3 and NASA DC-8) flights, Lidar and ozonesonde during the 2004 International Consortium for Atmospheric Resea...

A STUDY OF PROCESS CONTRIBUTIONS TO OZONE FORMATION DURING THE 2004 ICARTT PERIOD USING THE ETA- CMAQ FORECAST MODEL OVER THE NORTHEASTERN U.S.

EPA Science Inventory

First, this study evaluates the Eta-CMAQ forecast model performances for O₃, and related chemical species with the observational data from the aircraft (NOAA P-3 and NASA DC-8) flights, Lidar and ozonesonde during the 2004 International Consortium for Atmospheric Resea...

Porphyromonas gingivalis-dendritic cell interactions: consequences for coronary artery disease.

PubMed

Zeituni, Amir E; Carrion, Julio; Cutler, Christopher W

2010-12-21

An estimated 80 million US adults have one or more types of cardiovascular diseases. Atherosclerosis is the single most important contributor to cardiovascular diseases; however, only 50% of atherosclerosis patients have currently identified risk factors. Chronic periodontitis, a common inflammatory disease, is linked to an increased cardiovascular risk. Dendritic cells (DCs) are potent antigen presenting cells that infiltrate arterial walls and may destabilize atherosclerotic plaques in cardiovascular disease. While the source of these DCs in atherosclerotic plaques is presently unclear, we propose that dermal DCs from peripheral inflamed sites such as CP tissues are a potential source. This review will examine the role of the opportunistic oral pathogen Porphyromonas gingivalis in invading DCs and stimulating their mobilization and misdirection through the bloodstream. Based on our published observations, combined with some new data, as well as a focused review of the literature we will propose a model for how P. gingivalis may exploit DCs to gain access to systemic circulation and contribute to coronary artery disease. Our published evidence supports a significant role for P. gingivalis in subverting normal DC function, promoting a semimature, highly migratory, and immunosuppressive DC phenotype that contributes to the inflammatory development of atherosclerosis and, eventually, plaque rupture.

Human RTEL1 stabilizes long G-overhangs allowing telomerase-dependent over-extension.

PubMed

Porreca, Rosa M; Glousker, Galina; Awad, Aya; Matilla Fernandez, Maria I; Gibaud, Anne; Naucke, Christian; Cohen, Scott B; Bryan, Tracy M; Tzfati, Yehuda; Draskovic, Irena; Londoño-Vallejo, Arturo

2018-05-18

Telomere maintenance protects the cell against genome instability and senescence. Accelerated telomere attrition is a characteristic of premature aging syndromes including Dyskeratosis congenita (DC). Mutations in hRTEL1 are associated with a severe form of DC called Hoyeraal-Hreidarsson syndrome (HHS). HHS patients carry short telomeres and HHS cells display telomere damage. Here we investigated how hRTEL1 contributes to telomere maintenance in human primary as well as tumor cells. Transient depletion of hRTEL1 resulted in rapid telomere shortening only in the context of telomerase-positive cells with very long telomeres and high levels of telomerase. The effect of hRTEL1 on telomere length is telomerase dependent without impacting telomerase biogenesis or targeting of the enzyme to telomeres. Instead, RTEL1 depletion led to a decrease in both G-overhang content and POT1 association with telomeres with limited telomere uncapping. Strikingly, overexpression of POT1 restored telomere length but not the overhang, demonstrating that G-overhang loss is the primary defect caused by RTEL1 depletion. We propose that hRTEL1 contributes to the maintenance of long telomeres by preserving long G-overhangs, thereby facilitating POT1 binding and elongation by telomerase.

Human RTEL1 stabilizes long G-overhangs allowing telomerase-dependent over-extension

PubMed Central

Porreca, Rosa M; Glousker, Galina; Awad, Aya; Matilla Fernandez, Maria I; Gibaud, Anne; Naucke, Christian; Cohen, Scott B; Bryan, Tracy M; Tzfati, Yehuda; Draskovic, Irena; Londoño-Vallejo, Arturo

2018-01-01

Abstract Telomere maintenance protects the cell against genome instability and senescence. Accelerated telomere attrition is a characteristic of premature aging syndromes including Dyskeratosis congenita (DC). Mutations in hRTEL1 are associated with a severe form of DC called Hoyeraal-Hreidarsson syndrome (HHS). HHS patients carry short telomeres and HHS cells display telomere damage. Here we investigated how hRTEL1 contributes to telomere maintenance in human primary as well as tumor cells. Transient depletion of hRTEL1 resulted in rapid telomere shortening only in the context of telomerase-positive cells with very long telomeres and high levels of telomerase. The effect of hRTEL1 on telomere length is telomerase dependent without impacting telomerase biogenesis or targeting of the enzyme to telomeres. Instead, RTEL1 depletion led to a decrease in both G-overhang content and POT1 association with telomeres with limited telomere uncapping. Strikingly, overexpression of POT1 restored telomere length but not the overhang, demonstrating that G-overhang loss is the primary defect caused by RTEL1 depletion. We propose that hRTEL1 contributes to the maintenance of long telomeres by preserving long G-overhangs, thereby facilitating POT1 binding and elongation by telomerase. PMID:29522136

Index Theory-Based Algorithm for the Gradiometer Inverse Problem

DTIC Science & Technology

2015-03-28

greatest distance from the center of mass to an equipotential surface occurs when the generating mass of the admissible potential is from two equal point...point on an equipotential surface to the center of mass occurs when the generating mass is contained in an equatorial great circle with the closest...false, it still has practical utility for our purposes. One can also define DC in any Tangent Plane (TP) to the equipotential surface normal to the

No Nation Is Home Alone: Understanding The International Dimension Of Homeland Security Through Global Transportation Security Programs

DTIC Science & Technology

2016-03-01

organizational development” or “institutional building ”) helps define a country’s objectives in order to drive donor aid and projects . Lusthaus et al. argue...1204, Arlington, VA 22202-4302, and to the Office of Management and Budget, Paperwork Reduction Project (0704-0188) Washington, DC 20503. 1. AGENCY...Dominique Tarpey 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Naval Postgraduate School Monterey, CA 93943-5000 8. PERFORMING ORGANIZATION REPORT

TDF-1, The French Broadcasting Satellite (TDF-1, Satellite Francais de Radiodiffusion),

DTIC Science & Technology

1982-04-22

defines the general directions of the program and gives the necessary directives to a joint project directorate in Munich, Germany ( French projects ...AD-A117 961 NAVAL ZNTELIGENC SUPPORT CENTER WASHINGTON DC TRAN-(ITC F/0 17/2 TOF-Il, THE FRENCH BROADCASTING SATELLITE (TDP-I. SATELLITE PRAN-ETC(U...8201/80A UNCLASSIFIED TITLE: TDF-1, The French Broadcasting Satellite TDF 1, satellite francais de radiodiffusion AUTHOR(S) AND/OR EDITOR(S): C

Air Force Journal of Logsitics. Volume 31, Number 3, Fall 2007

DTIC Science & Technology

2007-01-01

of thc i ted .Sta’s (of should be worked in concert with the Air Force Global Logistics America, Washington, DC: Giovernment Printing Office, 2004, 7...operations. With airbase support being operational development FFG. in nature , it should not be confused with support as defined under 0 CSG is the...Australia. FCS Article Acronyms is a fundamental enabler for ADF and RAAF air operations, similar ACS - Agile Combat Support in nature to the way ACS

System of Systems Engineering and Integration Process for Network Transport Assessment

DTIC Science & Technology

2016-09-01

SOSE&I CONCEPTS The DOD-sourced “Systems Engineering Guide for Systems of Systems” provides an overview of the SoS environment and SE considerations...usage as a guide in application of systems engineering processes. They are listed verbatim below as defined in the DOD SE guide (ODUSD[A&T]SSE 2008...Technology (A&T), Systems and Software Engineering (SSE). 2008. Systems Engineering Guide for Systems of Systems. Washington, DC: ODUSD(A&T)SSE

The Noise Level Optimization for Induction Magnetometer of SEP System

NASA Astrophysics Data System (ADS)

Zhu, W.; Fang, G.

2011-12-01

The Surface Electromagnetic Penetration (SEP) System, subsidized by the SinoProbe Plan in China, is designed for 3D conductivity imaging in geophysical mineral exploration, underground water distribution exploration, oil and gas reservoir exploration. Both the Controlled Source Audio Magnetotellurics (CSAMT) method and Magnetotellurics (MT) method can be surveyed by SEP system. In this article, an optimization design is introduced, which can minimize the noise level of the induction magnetometer for SEP system magnetic field's acquisition. The induction magnetometer transfers the rate of the magnetic field's change to voltage signal by induction coil, and amplified it by Low Noise Amplifier The noise parts contributed to the magnetometer are: the coil's thermal noise, the equivalent input voltage and current noise of the pre-amplifier. The coil's thermal noise is decided by coil's DC resistance. The equivalent input voltage and current noise of the pre-amplifier depend on the amplifier's type and DC operation condition. The design here optimized the DC operation point of pre-amplifier, adjusted the DC current source, and realized the minimum of total noise level of magnetometer. The calculation and test results show that: the total noise is about 1pT/√Hz, the thermal noise of coils is 1.7nV/√Hz, the preamplifier equivalent input voltage and current noise is 3nV/ √Hz and 0.1pA/√Hz, the weight of the magnetometer is 4.5kg and meet the requirement of SEP system.

Expression of Vitis amurensis VaERF20 in Arabidopsis thaliana Improves Resistance to Botrytis cinerea and Pseudomonas syringae pv. Tomato DC3000

PubMed Central

Wang, Mengnan; Zhu, Yanxun; Han, Rui; Yin, Wuchen; Guo, Chunlei; Li, Zhi; Wang, Xiping

2018-01-01

Ethylene response factor (ERF) transcription factors play important roles in regulating immune responses in plants. In our study, we characterized a member of the ERF transcription factor family, VaERF20, from the Chinese wild Vitis genotype, V. amurensis Rupr “Shuangyou”. Phylogenetic analysis indicated that VaERF20 belongs to group IXc of the ERF family, in which many members are known to contribute to fighting pathogen infection. Consistent with this, expression of VaERF20 was induced by treatment with the necrotrophic fungal pathogen Botrytis cinerea (B. cinerea) in “Shuangyou” and V. vinifera “Red Globe”. Arabidopsis thaliana plants over-expressing VaERF20 displayed enhanced resistance to B. cinerea and the bacterium Pseudomonas syringae pv. tomato (Pst) DC3000. Patterns of pathogen-induced reactive oxygen species (ROS) accumulation were entirely distinct in B. cinerea and PstDC3000 inoculated plants. Examples of both salicylic acid (SA) and jasmonic acid/ethylene (JA/ET) responsive defense genes were up-regulated after B. cinerea and PstDC3000 inoculation of the VaERF20-overexpressing transgenic A. thaliana plants. Evidence of pattern-triggered immunity (PTI), callose accumulation and stomatal defense, together with increased expression of PTI genes, was also greater in the transgenic lines. These data indicate that VaERF20 participates in various signal transduction pathways and acts as an inducer of immune responses. PMID:29494485

Modeling radiation loads in the ILC main linac and a novel approach to treat dark current

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

Mokhov, Nilolai V.; Rakhno, Igor L.; Tropin, Igor S.

Electromagnetic and hadron showers generated by electrons of dark current (DC) can represent a significant radiation threat to the ILC linac equipment and personnel. In this study, a commissioning scenario is analysed which is considered as the worst-case scenario for the main linac regarding the DC contribution to the radiation environment in the tunnel. A normal operation scenario is analysed as well. An emphasis is made on radiation load to sensitive electronic equipment—cryogenic thermometers inside the cryomodules. Prompt and residual dose rates in the ILC main linac tunnels were also calculated in these new high-statistics runs. A novel approach wasmore » developed—as a part of general purpose Monte Carlo code MARS15—to model generation, acceleration and transport of DC electrons in electromagnetic fields inside SRF cavities. Comparisons were made with a standard approach when a set of pre-calculated DC electron trajectories is used, with a proper normalization, as a source for Monte Carlo modelling. Results of MARS15 Monte Carlo calculations, performed for the current main linac tunnel design, reveal that the peak absorbed dose in the cryogenic thermometers in the main tunnel for 20 years of operation is about 0.8 MGy. The calculated contact residual dose on cryomodules and tunnel walls in the main tunnel for typical irradiation and cooling conditions is 0.1 and 0.01 mSv/hr, respectively.« less

Recognition of Aspergillus fumigatus Hyphae by Human Plasmacytoid Dendritic Cells Is Mediated by Dectin-2 and Results in Formation of Extracellular Traps

PubMed Central

Loures, Flávio V.; Röhm, Marc; Lee, Chrono K.; Santos, Evelyn; Wang, Jennifer P.; Specht, Charles A.; Calich, Vera L. G.; Urban, Constantin F.; Levitz, Stuart M.

2015-01-01

Plasmacytoid dendritic cells (pDCs) were initially considered as critical for innate immunity to viruses. However, our group has shown that pDCs bind to and inhibit the growth of Aspergillus fumigatus hyphae and that depletion of pDCs renders mice hypersusceptible to experimental aspergillosis. In this study, we examined pDC receptors contributing to hyphal recognition and downstream events in pDCs stimulated by A. fumigatus hyphae. Our data show that Dectin-2, but not Dectin-1, participates in A. fumigatus hyphal recognition, TNF-α and IFN-α release, and antifungal activity. Moreover, Dectin-2 acts in cooperation with the FcRγ chain to trigger signaling responses. In addition, using confocal and electron microscopy we demonstrated that the interaction between pDCs and A. fumigatus induced the formation of pDC extracellular traps (pETs) containing DNA and citrullinated histone H3. These structures closely resembled those of neutrophil extracellular traps (NETs). The microarray analysis of the pDC transcriptome upon A. fumigatus infection also demonstrated up-regulated expression of genes associated with apoptosis as well as type I interferon-induced genes. Thus, human pDCs directly recognize A. fumigatus hyphae via Dectin-2; this interaction results in cytokine release and antifungal activity. Moreover, hyphal stimulation of pDCs triggers a distinct pattern of pDC gene expression and leads to pET formation. PMID:25659141

The defined-contribution plan: the next generation of healthcare financing.

PubMed

Emery, J D

2001-01-01

In response to rising health insurance premiums, many purchasers of coverage are evaluating the possibility of implementing defined-contribution health insurance plans. Under a defined-contribution plan, employers or the government pay a specified portion of the premium, and the consumer chooses a plan from a menu of options, paying the balance of the premium based on their plan selection. A shift to a defined-contribution model will have far-reaching implications for consumers, employer and government purchasers, payers, and providers. Providers will face changes in consumption patterns and the need to develop a brand image, market their strengths directly to consumers, educate consumers about their services and pricing, and reconfigure infrastructures to be able to respond efficiently to consumer demands.

Radiocarbon Analysis of Individual Amino Acids: Carbon Blank Quantification for a Small-Sample High-Pressure Liquid Chromatography Purification Method.

PubMed

Bour, Amy L; Walker, Brett D; Broek, Taylor A B; McCarthy, Matthew D

2016-04-05

Compound-specific radiocarbon analysis (CSRA) of amino acids (AAs) is of great interest as a proxy for organic nitrogen (N) cycling rates, dating archeological bone collagen, and investigating processes shaping the biogeochemistry of global N reservoirs. However, recoverable quantities of individual compounds from natural samples are often insufficient for radiocarbon ((14)C) analyses (<50 μg C). Constraining procedural carbon (C) blanks and their isotopic contributions is critical for reporting of accurate CSRA measurements. Here, we report the first detailed quantification of C blanks (including sources, magnitudes, and variability) for a high-pressure liquid chromatography (HPLC) method designed to purify individual AAs from natural samples. We used pairs of AA standards with either modern (M) or dead (D) fraction modern (Fm) values to quantify MC and DC blanks within several chromatographic regions. Blanks were determined for both individual and mixed AA standard injections with peak loadings ranging from 10 to 85 μg C. We found 0.8 ± 0.4 μg of MC and 1.0 ± 0.5 μg of DC were introduced by downstream sample preparation (drying, combustion, and graphitization), which accounted for essentially the entire procedural blank for early eluting AAs. For late-eluting AAs, higher eluent organic content and fraction collected volumes contributed to total blanks of 1.5 ± 0.75 μg of MC and 3.0 ± 1.5 μg of DC. Our final measurement uncertainty for 20 μg of C of most AAs was ±0.02 Fm, although sample size requirements are larger for similar uncertainty in late-eluting AAs. These results demonstrate the first CSRA protocol for many protein AAs with uncertainties comparable to the lowest achieved in prior studies.

Development of a pepper pot emittance probe and its application for ECR ion beam studies.

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

Kondrashev, S.; Barcikowski, A.; Mustapha, B.

2009-07-21

A pepper pot-scintillator screen system has been developed and used to measure the emittance of DC ion beams extracted from a high-intensity permanent magnet ECR ion source. The system includes a fast beam shutter with a minimum dwell time of 18 ms to reduce the degradation of the CsI(Tl) scintillator by DC ion beam irradiation and a CCD camera with a variable shutter speed in the range of 1 {micro}s-65 s. On-line emittance measurements are performed by an application code developed on a LabVIEW platform. The sensitivity of the device is sufficient to measure the emittance of DC ion beamsmore » with current densities down to about 100 nA/cm{sup 2}. The emittance of all ion species extracted from the ECR ion source and post-accelerated to an energy of 75-90 keV/charge have been measured downstream of the LEBT. As the mass-to-charge ratio of ion species increases, the normalized RMS emittances in both transverse phase planes decrease from 0.5-1.0 {pi} mm mrad for light ions to 0.05-0.09 {pi} mm mrad for highly charged {sup 209}Bi ions. The dependence of the emittance on ion's mass-to-charge ratio follows very well the dependence expected from beam rotation induced by decreasing ECR axial magnetic field. The measured emittance values cannot be explained by only ion beam rotation for all ion species and the contribution to emittance of ion temperature in plasma, non-linear electric fields and non-linear space charge is comparable or even higher than the contribution of ion beam rotation.« less

CCL19 with CCL21-tail displays enhanced glycosaminoglycan binding with retained chemotactic potency in dendritic cells.

PubMed

Jørgensen, Astrid S; Adogamhe, Pontian E; Laufer, Julia M; Legler, Daniel F; Veldkamp, Christopher T; Rosenkilde, Mette M; Hjortø, Gertrud M

2018-05-16

CCL19 is more potent than CCL21 in inducing chemotaxis of human dendritic cells (DC). This difference is attributed to 1) a stronger interaction of the basic C-terminal tail of CCL21 with acidic glycosaminoglycans (GAGs) in the environment and 2) an autoinhibitory function of this C-terminal tail. Moreover, different receptor docking modes and tissue expression patterns of CCL19 and CCL21 contribute to fine-tuned control of CCR7 signaling. Here, we investigate the effect of the tail of CCL21 on chemokine binding to GAGs and on CCR7 activation. We show that transfer of CCL21-tail to CCL19 (CCL19 CCL21-tail ) markedly increases binding of CCL19 to human dendritic cell surfaces, without impairing CCL19-induced intracellular calcium release or DC chemotaxis, although it causes reduced CCR7 internalization. The more potent chemotaxis induced by CCL19 and CCL19 CCL21-tail compared to CCL21 is not transferred to CCL21 by replacing its N-terminus with that of CCL19 (CCL21 CCL19-N-term ). Measurements of cAMP production in CHO cells uncover that CCL21-tail transfer (CCL19 CCL21-tail ) negatively affects CCL19 potency, whereas removal of CCL21-tail (CCL21 tailless ) increases signaling compared to full-length CCL21, indicating that the tail negatively affects signaling via cAMP. Similar to chemokine-driven calcium mobilization and chemotaxis, the potency of CCL21 in cAMP is not improved by transfer of the CCL19 N-terminus to CCL21 (CCL21 CCL19-N-term ). Together these results indicate that ligands containing CCL21 core and C-terminal tail (CCL21 and CCL21 CCL19-N-term ) are most restricted in their cAMP signaling; a phenotype attributed to a stronger GAG binding of CCL21 and defined structural differences between CCL19 and CCL21. ©2018 Society for Leukocyte Biology.