Current Drive

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

Faulconer, D.W

2004-03-15

Certain devices aimed at magnetic confinement of thermonuclear plasma rely on the steady flow of an electric current in the plasma. In view of the dominant place it occupies in both the world magnetic-confinement fusion effort and the author's own activity, the tokamak toroidal configuration is selected as prototype for discussing the question of how such a current can be maintained. Tokamaks require a stationary toroidal plasma current, this being traditionally provided by a pulsed magnetic induction which drives the plasma ring as the secondary of a transformer. Since this mechanism is essentially transient, and steady-state fusion reactor operation hasmore » manifold advantages, significant effort is now devoted to developing alternate steady-state means of generating toroidal current. These methods are classed under the global heading of 'noninductive current drive' or simply 'current drive', generally, though not exclusively, employing the injection of waves and/or toroidally directed particle beams. In what follows we highlight the physical mechanisms underlying surprisingly various approaches to driving current in a tokamak, downplaying a number of practical and technical issues. When a significant data base exists for a given method, its experimental current drive efficiency and future prospects are detailed.« less

Depletion of CD11c⁺ cells in the CD11c.DTR model drives expansion of unique CD64⁺ Ly6C⁺ monocytes that are poised to release TNF-α.

PubMed

Sivakumaran, Shivajanani; Henderson, Stephen; Ward, Sophie; Sousa, Pedro Santos E; Manzo, Teresa; Zhang, Lei; Conlan, Thomas; Means, Terry K; D'Aveni, Maud; Hermine, Olivier; Rubio, Marie-Thérèse; Chakraverty, Ronjon; Bennett, Clare L

2016-01-01

Dendritic cells (DCs) play a vital role in innate and adaptive immunities. Inducible depletion of CD11c(+) DCs engineered to express a high-affinity diphtheria toxin receptor has been a powerful tool to dissect DC function in vivo. However, despite reports showing that loss of DCs induces transient monocytosis, the monocyte population that emerges and the potential impact of monocytes on studies of DC function have not been investigated. We found that depletion of CD11c(+) cells from CD11c.DTR mice induced the expansion of a variant CD64(+) Ly6C(+) monocyte population in the spleen and blood that was distinct from conventional monocytes. Expansion of CD64(+) Ly6C(+) monocytes was independent of mobilization from the BM via CCR2 but required the cytokine, G-CSF. Indeed, this population was also expanded upon exposure to exogenous G-CSF in the absence of DC depletion. CD64(+) Ly6C(+) monocytes were characterized by upregulation of innate signaling apparatus despite the absence of inflammation, and an increased capacity to produce TNF-α following LPS stimulation. Thus, depletion of CD11c(+) cells induces expansion of a unique CD64(+) Ly6C(+) monocyte population poised to synthesize TNF-α. This finding will require consideration in experiments using depletion strategies to test the role of CD11c(+) DCs in immunity. © 2015 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stacked Device of Polymer Light-Emitting Diode Driven by Metal-Base Organic Transistor

NASA Astrophysics Data System (ADS)

Yoneda, Kazuhiro; Nakayama, Ken-ichi; Yokoyama, Masaaki

2008-02-01

We fabricated a new light-emitting device that combined a polymer light-emitting diode (PLED) and a vertical-type metal-base organic transistor (MBOT) through a floating electrode. By employing a layered floating electrode of Mg:Ag/Au, the MBOT on the PLED was operated successfully and a current amplification factor of approximately 20 was observed. The PLED luminescence exceeding 100 cd/m2 can be modulated using the MBOT with a low base voltage (2.8 V) and VCC (8 V). The emission contrast (on/off ratio) was improved with insertion of an insulating layer under the base, and the cut-off frequency was estimated to be 8 kHz. This device is expected to be a promising driving system of organic light-emitting diode (OLED), realizing low voltage and high numerical aperture.

Finite Element Analysis of Flexural Vibrations in Hard Disk Drive Spindle Systems

NASA Astrophysics Data System (ADS)

LIM, SEUNGCHUL

2000-06-01

This paper is concerned with the flexural vibration analysis of the hard disk drive (HDD) spindle system by means of the finite element method. In contrast to previous research, every system component is here analytically modelled taking into account its structural flexibility and also the centrifugal effect particularly on the disk. To prove the effectiveness and accuracy of the formulated models, commercial HDD systems with two and three identical disks are selected as examples. Then their major natural modes are computed with only a small number of element meshes as the shaft rotational speed is varied, and subsequently compared with the existing numerical results obtained using other methods and newly acquired experimental ones. Based on such a series of studies, the proposed method can be concluded as a very promising tool for the design of HDDs and various other high-performance computer disk drives such as floppy disk drives, CD ROM drives, and their variations having spindle mechanisms similar to those of HDDs.

Role of relative humidity and Cd/Zn stoichiometry in the photo-oxidation process of cadmium yellows (CdS/Cd1-xZnxS) in oil paintings.

PubMed

Monico, Letizia; Chieli, Annalisa; De Meyer, Steven; Cotte, Marine; de Nolf, Wout; Falkenberg, Gerald; Janssens, Koen; Romani, Aldo; Miliani, Costanza

2018-06-06

Cadmium yellows (CdYs) refer to a family of cadmium sulfide pigments which have been widely used by artists since the late 19th c. Despite being considered stable, they are suffering from discoloration in iconic paintings, such as Joy of Life by Matisse, Flowers in a blue vase by Van Gogh and the Scream by Munch, most likely due to the formation of CdSO₄·nH₂O. Questions about what the factors driving the CdYs degradation are and how they affect the overall process are still open. Here, we study a series of oil mock-up paints made of CdYs of different stoichiometry (CdS/Cd₀.₇₆Zn₀.₂₄S) and crystalline structure (hexagonal/cubic) before and after aging at variable relative humidity under exposure to light and in darkness. Synchrotron-based X-ray methods combined with UV-Visible and FTIR spectroscopies show that: (i) Cd₀.₇₆Zn₀.₂₄S is more susceptible to photo-oxidation than CdS; both compounds can act as photocatalysts for the oil oxidation. (ii) The photo-oxidation of CdS/Cd₀.₇₆Zn₀.₂₄S to CdSO₄·nH₂O is triggered by moisture. (iii) The nature of alteration products depends on the aging conditions and Cd/Zn stoichiometry. Based on our findings, we propose a scheme for the mechanism of the photocorrosion process and photocatalytic activity of CdY pigments in the oil binder. Overall, our results form a reliable basis for understanding the degradation of CdS-based paints of artworks and contribute towards developing better ways of preserving them for future generations. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Electrical motor/generator drive apparatus and method

DOEpatents

Su, Gui Jia

2013-02-12

The present disclosure includes electrical motor/generator drive systems and methods that significantly reduce inverter direct-current (DC) bus ripple currents and thus the volume and cost of a capacitor. The drive methodology is based on a segmented drive system that does not add switches or passive components but involves reconfiguring inverter switches and motor stator winding connections in a way that allows the formation of multiple, independent drive units and the use of simple alternated switching and optimized Pulse Width Modulation (PWM) schemes to eliminate or significantly reduce the capacitor ripple current.

G-CSF/anti-G-CSF antibody complexes drive the potent recovery and expansion of CD11b+Gr-1+ myeloid cells without compromising CD8+ T cell immune responses

PubMed Central

2013-01-01

Background Administration of recombinant G-CSF following cytoreductive therapy enhances the recovery of myeloid cells, minimizing the risk of opportunistic infection. Free G-CSF, however, is expensive, exhibits a short half-life, and has poor biological activity in vivo. Methods We evaluated whether the biological activity of G-CSF could be improved by pre-association with anti-G-CSF mAb prior to injection into mice. Results We find that the efficacy of G-CSF therapy can be enhanced more than 100-fold by pre-association of G-CSF with an anti-G-CSF monoclonal antibody (mAb). Compared with G-CSF alone, administration of G-CSF/anti-G-CSF mAb complexes induced the potent expansion of CD11b+Gr-1+ myeloid cells in mice with or without concomitant cytoreductive treatment including radiation or chemotherapy. Despite driving the dramatic expansion of myeloid cells, in vivo antigen-specific CD8+ T cell immune responses were not compromised. Furthermore, injection of G-CSF/anti-G-CSF mAb complexes heightened protective immunity to bacterial infection. As a measure of clinical value, we also found that antibody complexes improved G-CSF biological activity much more significantly than pegylation. Conclusions Our findings provide the first evidence that antibody cytokine complexes can effectively expand myeloid cells, and furthermore, that G-CSF/anti-G-CSF mAb complexes may provide an improved method for the administration of recombinant G-CSF. PMID:24279871

Decoupling activation and exhaustion of B cells in spontaneous controllers of HIV infection

PubMed Central

Sciaranghella, Gaia; Tong, Neath; Mahan, Alison E.; Suscovich, Todd J.; Alter, Galit

2013-01-01

Objective To define the impact of chronic viremia and associated immune activation on B-cell exhaustion in HIV infection. Design Progressive HIV infection is marked by B-cell anergy and exhaustion coupled with dramatic hypergammaglobulinemia. Although both upregulation of CD95 and loss of CD21 have been used as markers of infection-associated B-cell dysfunction, little is known regarding the specific profiles of dysfunctional B cells and whether persistent viral replication and its associated immune activation play a central role in driving B-cell dysfunction. Methods Multiparameter flow cytometry was used to define the profile of dysfunctional B cells. The changes in the expression of CD21 and CD95 were tracked on B-cell subpopulations in patients with differential control of viral replication. Results Although the emergence of exhausted, CD21low tissue-like memory B cells followed similar patterns in both progressors and controllers, the frequency of CD21low activated memory B cells was lower in spontaneous controllers. Conclusion Our results suggest that the loss of CD21 and the upregulation of CD95 occur as separate events during the development of B-cell dysfunction. The loss of CD21 is a marker of B-cell exhaustion induced in the absence of appreciable viral replication, whereas the upregulation of CD95 is tightly linked to persistent viral replication and its associated immune activation. Thus, these dysfunctional profiles potentially represent two functionally distinct states within the B-cell compartment. PMID:23135171

Clonal expansion of genome-intact HIV-1 in functionally polarized Th1 CD4+ T cells

PubMed Central

Orlova-Fink, Nina; Einkauf, Kevin; Chowdhury, Fatema Z.; Sun, Xiaoming; Harrington, Sean; Kuo, Hsiao-Hsuan; Hua, Stephane; Chen, Hsiao-Rong; Ouyang, Zhengyu; Reddy, Kavidha; Dong, Krista; Ndung’u, Thumbi; Walker, Bruce D.; Rosenberg, Eric S.; Yu, Xu G.

2017-01-01

HIV-1 causes a chronic, incurable disease due to its persistence in CD4+ T cells that contain replication-competent provirus, but exhibit little or no active viral gene expression and effectively resist combination antiretroviral therapy (cART). These latently infected T cells represent an extremely small proportion of all circulating CD4+ T cells but possess a remarkable long-term stability and typically persist throughout life, for reasons that are not fully understood. Here we performed massive single-genome, near-full-length next-generation sequencing of HIV-1 DNA derived from unfractionated peripheral blood mononuclear cells, ex vivo-isolated CD4+ T cells, and subsets of functionally polarized memory CD4+ T cells. This approach identified multiple sets of independent, near-full-length proviral sequences from cART-treated individuals that were completely identical, consistent with clonal expansion of CD4+ T cells harboring intact HIV-1. Intact, near-full-genome HIV-1 DNA sequences that were derived from such clonally expanded CD4+ T cells constituted 62% of all analyzed genome-intact sequences in memory CD4 T cells, were preferentially observed in Th1-polarized cells, were longitudinally detected over a duration of up to 5 years, and were fully replication- and infection-competent. Together, these data suggest that clonal proliferation of Th1-polarized CD4+ T cells encoding for intact HIV-1 represents a driving force for stabilizing the pool of latently infected CD4+ T cells. PMID:28628034

Clonal expansion of genome-intact HIV-1 in functionally polarized Th1 CD4+ T cells.

PubMed

Lee, Guinevere Q; Orlova-Fink, Nina; Einkauf, Kevin; Chowdhury, Fatema Z; Sun, Xiaoming; Harrington, Sean; Kuo, Hsiao-Hsuan; Hua, Stephane; Chen, Hsiao-Rong; Ouyang, Zhengyu; Reddy, Kavidha; Dong, Krista; Ndung'u, Thumbi; Walker, Bruce D; Rosenberg, Eric S; Yu, Xu G; Lichterfeld, Mathias

2017-06-30

HIV-1 causes a chronic, incurable disease due to its persistence in CD4+ T cells that contain replication-competent provirus, but exhibit little or no active viral gene expression and effectively resist combination antiretroviral therapy (cART). These latently infected T cells represent an extremely small proportion of all circulating CD4+ T cells but possess a remarkable long-term stability and typically persist throughout life, for reasons that are not fully understood. Here we performed massive single-genome, near-full-length next-generation sequencing of HIV-1 DNA derived from unfractionated peripheral blood mononuclear cells, ex vivo-isolated CD4+ T cells, and subsets of functionally polarized memory CD4+ T cells. This approach identified multiple sets of independent, near-full-length proviral sequences from cART-treated individuals that were completely identical, consistent with clonal expansion of CD4+ T cells harboring intact HIV-1. Intact, near-full-genome HIV-1 DNA sequences that were derived from such clonally expanded CD4+ T cells constituted 62% of all analyzed genome-intact sequences in memory CD4 T cells, were preferentially observed in Th1-polarized cells, were longitudinally detected over a duration of up to 5 years, and were fully replication- and infection-competent. Together, these data suggest that clonal proliferation of Th1-polarized CD4+ T cells encoding for intact HIV-1 represents a driving force for stabilizing the pool of latently infected CD4+ T cells.

Isotopic effect in experiments on lower hybrid current drive in the FT-2 tokamak

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

Lashkul, S. I., E-mail: Serguey.lashkul@mail.ioffe.ru; Altukhov, A. B.; Gurchenko, A. D., E-mail: aleksey.gurchenko@mail.ioffe.ru

To analyze factors influencing the limiting value of the plasma density at which lower hybrid (LH) current drive terminates, the isotopic factor (the difference in the LH resonance densities in hydrogen and deuterium plasmas) was used for the first time in experiments carried out at the FT-2 tokamak. It is experimentally found that the efficiency of LH current drive in deuterium plasma is appreciably higher than that in hydrogen plasma. The significant role of the parametric decay of the LH pumping wave, which hampers the use of the LH range of RF waves for current drive at high plasma densities,more » is confirmed. It is demonstrated that the parameters characterizing LH current drive agree well with the earlier results obtained at large tokamaks.« less

Universal power transistor base drive control unit

DOEpatents

Gale, Allan R.; Gritter, David J.

1988-01-01

A saturation condition regulator system for a power transistor which achieves the regulation objectives of a Baker clamp but without dumping excess base drive current into the transistor output circuit. The base drive current of the transistor is sensed and used through an active feedback circuit to produce an error signal which modulates the base drive current through a linearly operating FET. The collector base voltage of the power transistor is independently monitored to develop a second error signal which is also used to regulate base drive current. The current-sensitive circuit operates as a limiter. In addition, a fail-safe timing circuit is disclosed which automatically resets to a turn OFF condition in the event the transistor does not turn ON within a predetermined time after the input signal transition.

Universal power transistor base drive control unit

DOEpatents

Gale, A.R.; Gritter, D.J.

1988-06-07

A saturation condition regulator system for a power transistor is disclosed which achieves the regulation objectives of a Baker clamp but without dumping excess base drive current into the transistor output circuit. The base drive current of the transistor is sensed and used through an active feedback circuit to produce an error signal which modulates the base drive current through a linearly operating FET. The collector base voltage of the power transistor is independently monitored to develop a second error signal which is also used to regulate base drive current. The current-sensitive circuit operates as a limiter. In addition, a fail-safe timing circuit is disclosed which automatically resets to a turn OFF condition in the event the transistor does not turn ON within a predetermined time after the input signal transition. 2 figs.

Bootstrap and fast wave current drive for tokamak reactors

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

Ehst, D.A.

1991-09-01

Using the multi-species neoclassical treatment of Hirshman and Sigmar we study steady state bootstrap equilibria with seed currents provided by low frequency (ICRF) fast waves and with additional surface current density driven by lower hybrid waves. This study applies to reactor plasmas of arbitrary aspect ratio. IN one limit the bootstrap component can supply nearly the total equilibrium current with minimal driving power (< 20 MW). However, for larger total currents considerable driving power is required (for ITER: I{sub o} = 18 MA needs P{sub FW} = 15 MW, P{sub LH} = 75 MW). A computational survey of bootstrap fractionmore » and current drive efficiency is presented. 11 refs., 8 figs.« less

Using Newspapers on CD-ROM as a Resource.

ERIC Educational Resources Information Center

Seedhouse, Paul

1996-01-01

Presents the advantages of using newspapers stored on CD-ROM as a resource for teaching current topics in civilization/culture and current affairs in the foreign- language class. Articles on CD-ROM can be used for vocabulary exercises and comprehension tests, and on-screen text can be altered as desired to create classroom activities. (four…

CD95/Fas Increases Stemness in Cancer Cells by Inducing a STAT1-Dependent Type I Interferon Response.

PubMed

Qadir, Abdul S; Ceppi, Paolo; Brockway, Sonia; Law, Calvin; Mu, Liang; Khodarev, Nikolai N; Kim, Jung; Zhao, Jonathan C; Putzbach, William; Murmann, Andrea E; Chen, Zhuo; Chen, Wenjing; Liu, Xia; Salomon, Arthur R; Liu, Huiping; Weichselbaum, Ralph R; Yu, Jindan; Peter, Marcus E

2017-03-07

Stimulation of CD95/Fas drives and maintains cancer stem cells (CSCs). We now report that this involves activation of signal transducer and activator of transcription 1 (STAT1) and induction of STAT1-regulated genes and that this process is inhibited by active caspases. STAT1 is enriched in CSCs in cancer cell lines, patient-derived human breast cancer, and CD95 high -expressing glioblastoma neurospheres. CD95 stimulation of cancer cells induced secretion of type I interferons (IFNs) that bind to type I IFN receptors, resulting in activation of Janus-activated kinases, activation of STAT1, and induction of a number of STAT1-regulated genes that are part of a gene signature recently linked to therapy resistance in five primary human cancers. Consequently, we identified type I IFNs as drivers of cancer stemness. Knockdown or knockout of STAT1 resulted in a strongly reduced ability of CD95L or type I IFN to increase cancer stemness. This identifies STAT1 as a key regulator of the CSC-inducing activity of CD95. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Initial HIV-1 Antigen-Specific CD8+ T Cells in Acute HIV-1 Infection Inhibit Transmitted/Founder Virus Replication

PubMed Central

Freel, Stephanie A.; Picking, Ralph A.; Ferrari, Guido; Ding, Haitao; Ochsenbauer, Christina; Kappes, John C.; Kirchherr, Jennifer L.; Soderberg, Kelly A.; Weinhold, Kent J.; Cunningham, Coleen K.; Denny, Thomas N.; Crump, John A.; Cohen, Myron S.; McMichael, Andrew J.; Haynes, Barton F.

2012-01-01

CD8-mediated virus inhibition can be detected in HIV-1-positive subjects who naturally control virus replication. Characterizing the inhibitory function of CD8+ T cells during acute HIV-1 infection (AHI) can elucidate the nature of the CD8+ responses that can be rapidly elicited and that contribute to virus control. We examined the timing and HIV-1 antigen specificity of antiviral CD8+ T cells during AHI. Autologous and heterologous CD8+ T cell antiviral functions were assessed longitudinally during AHI in five donors from the CHAVI 001 cohort using a CD8+ T cell-mediated virus inhibition assay (CD8 VIA) and transmitted/founder (T/F) viruses. Potent CD8+ antiviral responses against heterologous T/F viruses appeared during AHI at the first time point sampled in each of the 5 donors (Fiebig stages 1/2 to 5). Inhibition of an autologous T/F virus was durable to 48 weeks; however, inhibition of heterologous responses declined concurrent with the resolution of viremia. HIV-1 viruses from 6 months postinfection were more resistant to CD8+-mediated virus inhibition than cognate T/F viruses, demonstrating that the virus escapes early from CD8+ T cell-mediated inhibition of virus replication. CD8+ T cell antigen-specific subsets mediated inhibition of T/F virus replication via soluble components, and these soluble responses were stimulated by peptide pools that include epitopes that were shown to drive HIV-1 escape during AHI. These data provide insights into the mechanisms of CD8-mediated virus inhibition and suggest that functional analyses will be important for determining whether similar antigen-specific virus inhibition can be induced by T cell-directed vaccine strategies. PMID:22514337

Caspase-3 Is Transiently Activated without Cell Death during Early Antigen Driven Expansion of CD8+ T Cells In Vivo

PubMed Central

McComb, Scott; Mulligan, Rebecca; Sad, Subash

2010-01-01

Background CD8+ T cell responses develop rapidly during infection and are swiftly reduced during contraction, wherein >90% of primed CD8+ T cells are eliminated. The role of apoptotic mechanisms in controlling this rapid proliferation and contraction of CD8+ T cells remains unclear. Surprisingly, evidence has shown non-apoptotic activation of caspase-3 to occur during in vitro T-cell proliferation, but the relevance of these mechanisms to in vivo CD8+ T cell responses has yet to be examined. Methods and Findings We have evaluated the activity of caspase-3, a key downstream inducer of apoptosis, throughout the entirety of a CD8+ T cell response. We utilized two infection models that differ in the intensity, onset and duration of antigen-presentation and inflammation. Expression of cleaved caspase-3 in antigen specific CD8+ T cells was coupled to the timing and strength of antigen presentation in lymphoid organs. We also observed coordinated activation of additional canonical apoptotic markers, including phosphatidylserine exposure. Limiting dilution analysis directly showed that in the presence of IL7, very little cell death occurred in both caspase-3hi and caspase-3low CD8+ T cells. The expression of active caspase-3 peaked before effector phenotype (CD62Llow) CD8+ T cells emerged, and was undetectable in effector-phenotype cells. In addition, OVA-specific CD8+ cells remained active caspase-3low throughout the contraction phase. Conclusions Our results specifically implicate antigen and not inflammation in driving activation of apoptotic mechanisms without cell death in proliferating CD8+ T cells. Furthermore, the contraction of CD8+ T cell response following expansion is likely not mediated by the key downstream apoptosis inducer, caspase-3. PMID:21203525

Multiple Inflammatory Cytokines Converge to Regulate CD8+ T cell Expansion and Function During Tuberculosis

PubMed Central

Booty, Matthew G.; Nunes-Alves, Cláudio; Carpenter, Stephen M.; Jayaraman, Pushpa; Behar, Samuel M.

2015-01-01

The differentiation of effector CD8+ T cells is a dynamically regulated process that varies during different infections and is influenced by the inflammatory milieu of the host. Here, we define three signals regulating CD8+ T cell responses during tuberculosis by focusing on cytokines known to affect disease outcome: IL-12, type I IFN, and IL-27. Using mixed bone marrow chimeras, we compared wild type and cytokine receptor knockout CD8+ T cells within the same mouse following aerosol infection with Mycobacterium tuberculosis. Four weeks post-infection, IL-12, type 1 IFN, and IL-27 were all required for efficient CD8+ T cell expansion in the lungs. We next determined if these cytokines directly promote CD8+ T cell priming or are required only for expansion in the lungs. Utilizing retrogenic CD8+ T cells specific for the Mtb antigen TB10.4 (EsxH), we observed that IL-12 is the dominant cytokine driving both CD8+ T cell priming in the lymph node and expansion in the lungs; however, type I IFN and IL-27 have non-redundant roles supporting pulmonary CD8+ T cell expansion. Thus, IL-12 is a major signal promoting priming in the lymph node, but a multitude of inflammatory signals converge in the lung to promote continued expansion. Furthermore, these cytokines regulate the differentiation and function of CD8+ T cells during tuberculosis. These data demonstrate distinct and overlapping roles for each of the cytokines examined and underscore the complexity of CD8+ T cell regulation during tuberculosis. PMID:26755819

Manipulating memory CD8 T cell numbers by timed enhancement of IL-2 signals1

PubMed Central

Kim, Marie T.; Kurup, Samarchith P.; Starbeck-Miller, Gabriel R.; Harty, John T.

2016-01-01

Due to the growing burden of tumors and chronic infections, manipulating CD8 T cell responses for clinical use has become an important goal for immunologists. Here, we show that dendritic cell (DC) immunization coupled with relatively early (days 1–3) or late (days 4–6) administration of enhanced IL-2-signals both increase peak effector CD8 T cell numbers, but only early IL-2 signals enhance memory numbers. IL-2 signals delivered at relatively late time points drive terminal differentiation, marked Bim mediated contraction and do not increase memory T cell numbers. In contrast, early IL-2 signals induce effector cell metabolic profiles more conducive to memory formation. Of note, down-regulation of CD80 and CD86 was observed on DCs in vivo following early IL-2 treatment. Mechanistically, early IL-2 treatment enhanced CTLA-4 expression on regulatory T (Treg) cells, and CTLA-4 blockade alongside IL-2 treatment in vivo prevented the decrease in CD80 and CD86, supporting a cell-extrinsic role of CTLA-4 in down-regulating B7-ligand expression on DCs. Finally, DC immunization followed by early IL-2 treatment and αCTLA-4 blockade resulted in lower memory CD8 T cell numbers compared to the DC + early IL-2 treatment group. These data suggest that curtailed signaling through the B7-CD28 co-stimulatory axis during CD8 T cell activation limits terminal differentiation and preserves memory CD8 T cell formation and thus, should be considered in future T cell vaccination strategies. PMID:27439516

Immunosurveillance and therapy of multiple myeloma are CD226 dependent

PubMed Central

Guillerey, Camille; Ferrari de Andrade, Lucas; Vuckovic, Slavica; Miles, Kim; Ngiow, Shin Foong; Yong, Michelle C.R.; Teng, Michele W.L.; Colonna, Marco; Ritchie, David S.; Chesi, Martha; Bergsagel, P. Leif; Hill, Geoffrey R.; Smyth, Mark J.; Martinet, Ludovic

2015-01-01

Multiple myeloma (MM) is an age-dependent hematological malignancy. Evaluation of immune interactions that drive MM relies on in vitro experiments that do not reflect the complex cellular stroma involved in MM pathogenesis. Here we used Vk*MYC transgenic mice, which spontaneously develop MM, and demonstrated that the immune system plays a critical role in the control of MM progression and the response to treatment. We monitored Vk*MYC mice that had been crossed with Cd226 mutant mice over a period of 3 years and found that CD226 limits spontaneous MM development. The CD226-dependent anti-myeloma immune response against transplanted Vk*MYC MM cells was mediated both by NK and CD8+ T cells through perforin and IFN-γ pathways. Moreover, CD226 expression was required for optimal antimyeloma efficacy of cyclophosphamide (CTX) and bortezomib (Btz), which are both standardly used to manage MM in patients. Activation of costimulatory receptor CD137 with mAb (4-1BB) exerted strong antimyeloma activity, while inhibition of coinhibitory receptors PD-1 and CTLA-4 had no effect. Taken together, the results of this study provide in vivo evidence that CD226 is important for MM immunosurveillance and indicate that specific immune components should be targeted for optimal MM treatment efficacy. As progressive immunosuppression associates with MM development, strategies aimed to increase immune functions may have important therapeutic implications in MM. PMID:25893601

Human CD68 promoter GFP transgenic mice allow analysis of monocyte to macrophage differentiation in vivo

PubMed Central

Iqbal, Asif J.; McNeill, Eileen; Kapellos, Theodore S.; Regan-Komito, Daniel; Norman, Sophie; Burd, Sarah; Smart, Nicola; Machemer, Daniel E. W.; Stylianou, Elena; McShane, Helen; Channon, Keith M.; Chawla, Ajay

2014-01-01

The recruitment of monocytes and their differentiation into macrophages at sites of inflammation are key events in determining the outcome of the inflammatory response and initiating the return to tissue homeostasis. To study monocyte trafficking and macrophage differentiation in vivo, we have generated a novel transgenic reporter mouse expressing a green fluorescent protein (GFP) under the control of the human CD68 promoter. CD68-GFP mice express high levels of GFP in both monocyte and embryo-derived tissue resident macrophages in adult animals. The human CD68 promoter drives GFP expression in all CD115+ monocytes of adult blood, spleen, and bone marrow; we took advantage of this to directly compare the trafficking of bone marrow–derived CD68-GFP monocytes to that of CX3CR1GFP monocytes in vivo using a sterile zymosan peritonitis model. Unlike CX3CR1GFP monocytes, which downregulate GFP expression on differentiation into macrophages in this model, CD68-GFP monocytes retain high-level GFP expression for 72 hours after differentiation into macrophages, allowing continued cell tracking during resolution of inflammation. In summary, this novel CD68-GFP transgenic reporter mouse line represents a powerful resource for analyzing monocyte mobilization and monocyte trafficking as well as studying the fate of recruited monocytes in models of acute and chronic inflammation. PMID:25030063

Human CD68 promoter GFP transgenic mice allow analysis of monocyte to macrophage differentiation in vivo.

PubMed

Iqbal, Asif J; McNeill, Eileen; Kapellos, Theodore S; Regan-Komito, Daniel; Norman, Sophie; Burd, Sarah; Smart, Nicola; Machemer, Daniel E W; Stylianou, Elena; McShane, Helen; Channon, Keith M; Chawla, Ajay; Greaves, David R

2014-10-09

The recruitment of monocytes and their differentiation into macrophages at sites of inflammation are key events in determining the outcome of the inflammatory response and initiating the return to tissue homeostasis. To study monocyte trafficking and macrophage differentiation in vivo, we have generated a novel transgenic reporter mouse expressing a green fluorescent protein (GFP) under the control of the human CD68 promoter. CD68-GFP mice express high levels of GFP in both monocyte and embryo-derived tissue resident macrophages in adult animals. The human CD68 promoter drives GFP expression in all CD115(+) monocytes of adult blood, spleen, and bone marrow; we took advantage of this to directly compare the trafficking of bone marrow-derived CD68-GFP monocytes to that of CX3CR1(GFP) monocytes in vivo using a sterile zymosan peritonitis model. Unlike CX3CR1(GFP) monocytes, which downregulate GFP expression on differentiation into macrophages in this model, CD68-GFP monocytes retain high-level GFP expression for 72 hours after differentiation into macrophages, allowing continued cell tracking during resolution of inflammation. In summary, this novel CD68-GFP transgenic reporter mouse line represents a powerful resource for analyzing monocyte mobilization and monocyte trafficking as well as studying the fate of recruited monocytes in models of acute and chronic inflammation. © 2014 by The American Society of Hematology.

Reproducible diagnosis of chronic lymphocytic leukemia by flow cytometry: An European Research Initiative on CLL (ERIC) & European Society for Clinical Cell Analysis (ESCCA) Harmonisation project

PubMed Central

Kreuzer, Karl‐Anton; Soosapilla, Asha; Spacek, Martin; Stehlikova, Olga; Gambell, Peter; McIver‐Brown, Neil; Villamor, Neus; Psarra, Katherina; Arroz, Maria; Milani, Raffaella; de la Serna, Javier; Cedena, M. Teresa; Jaksic, Ozren; Nomdedeu, Josep; Moreno, Carol; Rigolin, Gian Matteo; Cuneo, Antonio; Johansen, Preben; Johnsen, Hans E.; Rosenquist, Richard; Niemann, Carsten Utoft; Kern, Wolfgang; Westerman, David; Trneny, Marek; Mulligan, Stephen; Doubek, Michael; Pospisilova, Sarka; Hillmen, Peter; Oscier, David; Hallek, Michael; Ghia, Paolo; Montserrat, Emili

2018-01-01

The diagnostic criteria for CLL rely on morphology and immunophenotype. Current approaches have limitations affecting reproducibility and there is no consensus on the role of new markers. The aim of this project was to identify reproducible criteria and consensus on markers recommended for the diagnosis of CLL. ERIC/ESCCA members classified 14 of 35 potential markers as “required” or “recommended” for CLL diagnosis, consensus being defined as >75% and >50% agreement, respectively. An approach to validate “required” markers using normal peripheral blood was developed. Responses were received from 150 participants with a diagnostic workload >20 CLL cases per week in 23/150 (15%), 5–20 in 82/150 (55%), and <5 cases per week in 45/150 (30%). The consensus for “required” diagnostic markers included: CD19, CD5, CD20, CD23, Kappa, and Lambda. “Recommended” markers potentially useful for differential diagnosis were: CD43, CD79b, CD81, CD200, CD10, and ROR1. Reproducible criteria for component reagents were assessed retrospectively in 14,643 cases from 13 different centers and showed >97% concordance with current approaches. A pilot study to validate staining quality was completed in 11 centers. Markers considered as “required” for the diagnosis of CLL by the participants in this study (CD19, CD5, CD20, CD23, Kappa, and Lambda) are consistent with current diagnostic criteria and practice. Importantly, a reproducible approach to validate and apply these markers in individual laboratories has been identified. Finally, a consensus “recommended” panel of markers to refine diagnosis in borderline cases (CD43, CD79b, CD81, CD200, CD10, and ROR1) has been defined and will be prospectively evaluated. © 2017 International Clinical Cytometry Society PMID:29024461

Reproducible diagnosis of chronic lymphocytic leukemia by flow cytometry: An European Research Initiative on CLL (ERIC) & European Society for Clinical Cell Analysis (ESCCA) Harmonisation project.

PubMed

Rawstron, Andy C; Kreuzer, Karl-Anton; Soosapilla, Asha; Spacek, Martin; Stehlikova, Olga; Gambell, Peter; McIver-Brown, Neil; Villamor, Neus; Psarra, Katherina; Arroz, Maria; Milani, Raffaella; de la Serna, Javier; Cedena, M Teresa; Jaksic, Ozren; Nomdedeu, Josep; Moreno, Carol; Rigolin, Gian Matteo; Cuneo, Antonio; Johansen, Preben; Johnsen, Hans E; Rosenquist, Richard; Niemann, Carsten Utoft; Kern, Wolfgang; Westerman, David; Trneny, Marek; Mulligan, Stephen; Doubek, Michael; Pospisilova, Sarka; Hillmen, Peter; Oscier, David; Hallek, Michael; Ghia, Paolo; Montserrat, Emili

2018-01-01

The diagnostic criteria for CLL rely on morphology and immunophenotype. Current approaches have limitations affecting reproducibility and there is no consensus on the role of new markers. The aim of this project was to identify reproducible criteria and consensus on markers recommended for the diagnosis of CLL. ERIC/ESCCA members classified 14 of 35 potential markers as "required" or "recommended" for CLL diagnosis, consensus being defined as >75% and >50% agreement, respectively. An approach to validate "required" markers using normal peripheral blood was developed. Responses were received from 150 participants with a diagnostic workload >20 CLL cases per week in 23/150 (15%), 5-20 in 82/150 (55%), and <5 cases per week in 45/150 (30%). The consensus for "required" diagnostic markers included: CD19, CD5, CD20, CD23, Kappa, and Lambda. "Recommended" markers potentially useful for differential diagnosis were: CD43, CD79b, CD81, CD200, CD10, and ROR1. Reproducible criteria for component reagents were assessed retrospectively in 14,643 cases from 13 different centers and showed >97% concordance with current approaches. A pilot study to validate staining quality was completed in 11 centers. Markers considered as "required" for the diagnosis of CLL by the participants in this study (CD19, CD5, CD20, CD23, Kappa, and Lambda) are consistent with current diagnostic criteria and practice. Importantly, a reproducible approach to validate and apply these markers in individual laboratories has been identified. Finally, a consensus "recommended" panel of markers to refine diagnosis in borderline cases (CD43, CD79b, CD81, CD200, CD10, and ROR1) has been defined and will be prospectively evaluated. © 2017 International Clinical Cytometry Society. © 2017 The Authors. Cytometry Part B: Clinical Cytometry published by Wiley Periodicals, Inc. on behalf of International Clinical Cytometry Society.

Brief Report: Driving and Young Adults with ASD--Parents' Experiences

ERIC Educational Resources Information Center

Cox, Neill Broderick; Reeve, Ronald E.; Cox, Stephany M.; Cox, Daniel J.

2012-01-01

A paucity of research exists regarding driving skills and individuals with Autism Spectrum Disorders (ASD). The current study sought to gain a better understanding of driving and ASD by surveying parents/caregivers of adolescents/young adults with ASD who were currently attempting, or had previously attempted, to learn to drive. Respondents…

Real-time high-resolution PC-based system for measurement of errors on compact disks

NASA Astrophysics Data System (ADS)

Tehranchi, Babak; Howe, Dennis G.

1994-10-01

Hardware and software utilities are developed to directly monitor the Eight-to-Fourteen (EFM) demodulated data bytes at the input of a CD player's Cross-Interleaved Reed-Solomon Code (CIRC) block decoder. The hardware is capable of identifying erroneous data with single-byte resolution in the serial data stream read from a Compact Disc by a CDD 461 Philips CD-ROM drive. In addition, the system produces graphical maps that show the physical location of the measured errors on the entire disc, or via a zooming and planning feature, on user selectable local disc regions.

A Case Study: To Internet or Not To Internet.

ERIC Educational Resources Information Center

Carman, Jared; Boynton, Doug

1997-01-01

Interactive multimedia training can be delivered via CD-ROM, hard drive, local area networks (LAN), wide area networks (WAN), Intranet, Internet and hybrid systems. This article presents a case study of how two companies (Los Angeles Times and Allen Communication) evaluated alternative delivery systems, chose one, and implemented multimedia…

50 CFR 660.15 - Equipment requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... perceived weight of water, slime, mud, debris, or other materials. Scale printouts must show: (A) The vessel... with Pentium 75-MHz or higher. Random Access Memory (RAM) must have sufficient megabyte (MB) space to... space of 217 MB or greater. A CD-ROM drive with a Video Graphics Adapter (VGA) or higher resolution...

Storytelling: An Important Component of Successful Training.

ERIC Educational Resources Information Center

Siegel, Mark

1996-01-01

The director of production at Interactive Media Communications discusses its multimedia training models that address health and safety issues. Their purpose is to create entertaining instructional designs to guide the student in an interactive approach. The article describes two CD-ROM products (on hazardous chemicals and safe driving),…

The Reality, Direction, and Future of Computerized Publications.

ERIC Educational Resources Information Center

Levenstein, Nicholas

1994-01-01

Considers potential of personal computers, comparing development of computer today to that of cars in the 1920s. Examines recent changes in communications, university publications, and cultural habits. Explores technological issues, looking at modems and fiber optic cables, better screens, and CD-ROM and optical magnetic drives. (NB)

Plasma heating and current drive using intense, pulsed microwaves

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

Cohen, B.I.; Cohen, R.H.; Nevins, W.M.

1988-01-01

The use of powerful new microwave sources, e.g., free-electron lasers and relativistic gyrotrons, provide unique opportunities for novel heating and current-drive schemes in the electron-cyclotron and lower-hybrid ranges of frequencies. These high-power, pulsed sources have a number of technical advantages over conventional, low-intensity sources; and their use can lead to improved current-drive efficiencies and better penetration into a reactor-grade plasma in specific cases. The Microwave Tokamak Experiment at Lawrence Livermore National Laboratory will provide a test for some of these new heating and current-drive schemes. This paper reports theoretical progress both in modeling absorption and current drive for intense pulsesmore » and in analyzing some of the possible complications that may arise, e.g., parametric instabilities and nonlinear self-focusing. 22 refs., 9 figs., 1 tab.« less

Sensorless optimal sinusoidal brushless direct current for hard disk drives

NASA Astrophysics Data System (ADS)

Soh, C. S.; Bi, C.

2009-04-01

Initiated by the availability of digital signal processors and emergence of new applications, market demands for permanent magnet synchronous motors have been surging. As its back-emf is sinusoidal, the drive current should also be sinusoidal for reducing the torque ripple. However, in applications like hard disk drives, brushless direct current (BLDC) drive is adopted instead of sinusoidal drive for simplification. The adoption, however, comes at the expense of increased harmonics, losses, torque pulsations, and acoustics. In this paper, we propose a sensorless optimal sinusoidal BLDC drive. First and foremost, the derivation for an optimal sinusoidal drive is presented, and a power angle control scheme is proposed to achieve an optimal sinusoidal BLDC. The scheme maintains linear relationship between the motor speed and drive voltage. In an attempt to execute the sensorless drive, an innovative power angle measurement scheme is devised, which takes advantage of the freewheeling diodes and measures the power angle through the detection of diode voltage drops. The objectives as laid out will be presented and discussed in this paper, supported by derivations, simulations, and experimental results. The proposed scheme is straightforward, brings about the benefits of sensorless sinusoidal drive, negates the need for current sensors by utilizing the freewheeling diodes, and does not incur additional cost.

Modelling of minority ion cyclotron current drive during the activated phase of ITER

NASA Astrophysics Data System (ADS)

Laxåback, M.; Hellsten, T.

2005-12-01

Neoclassical tearing modes, triggered by the long-period sawteeth expected in tokamaks with large non-thermal α-particle populations, may impose a severe β limit on experiments with large fusion yields and on reactors. Sawtooth destabilization by localized current drive could relax the β limit and improve plasma performance. 3He minority ion cyclotron current drive around the sawtooth inversion radius has been planned for ITER. Several ion species, including beam injected D ions and fusion born α particles, are however also resonant in the plasma and may represent a parasitic absorption of RF power. Modelling of minority ion cyclotron current drive in an ITER-FEAT-like plasma is presented, including the effects of ion trapping, finite ion drift orbit widths, wave-induced radial transport and the coupled evolution of wave fields and resonant ion distributions. The parasitic absorption of RF power by the other resonant species is concluded to be relatively small, but the 3He minority current drive is nevertheless negligible due to the strong collisionality of the 3He ions and the drag current by toroidally counter-rotating background ions and co-rotating electrons. H minority current drive is found to be a significantly more effective alternative.

All Solution-processed Stable White Quantum Dot Light-emitting Diodes with Hybrid ZnO@TiO2 as Blue Emitters

PubMed Central

Chen, Jing; Zhao, Dewei; Li, Chi; Xu, Feng; Lei, Wei; Sun, Litao; Nathan, Arokia; Sun, Xiao Wei

2014-01-01

White quantum dot light-emitting diodes (QD-LEDs) have been a promising candidate for high-efficiency and color-saturated displays. However, it is challenging to integrate various QD emitters into one device and also to obtain efficient blue QDs. Here, we report a simply solution-processed white QD-LED using a hybrid ZnO@TiO2 as electron injection layer and ZnCdSeS QD emitters. The white emission is obtained by integrating the yellow emission from QD emitters and the blue emission generated from hybrid ZnO@TiO2 layer. We show that the performance of white QD-LEDs can be adjusted by controlling the driving force for hole transport and electroluminescence recombination region via varying the thickness of hole transport layer. The device is demonstrated with a maximum luminance of 730 cd/m2 and power efficiency of 1.7 lm/W, exhibiting the Commission Internationale de l'Enclairage (CIE) coordinates of (0.33, 0.33). The unencapsulated white QD-LED has a long lifetime of 96 h at its initial luminance of 730 cd/m2, primarily due to the fact that the device with hybrid ZnO@TiO2 has low leakage current and is insensitive to the oxygen and the moisture. These results indicate that hybrid ZnO@TiO2 provides an alternate and effective approach to achieve high-performance white QD-LEDs and also other optoelectronic devices. PMID:24522341

Avian Influenza Viruses, Inflammation, and CD8+ T Cell Immunity

PubMed Central

Wang, Zhongfang; Loh, Liyen; Kedzierski, Lukasz; Kedzierska, Katherine

2016-01-01

Avian influenza viruses (AIVs) circulate naturally in wild aquatic birds, infect domestic poultry, and are capable of causing sporadic bird-to-human transmissions. AIVs capable of infecting humans include a highly pathogenic AIV H5N1, first detected in humans in 1997, and a low pathogenic AIV H7N9, reported in humans in 2013. Both H5N1 and H7N9 cause severe influenza disease in humans, manifested by acute respiratory distress syndrome, multi-organ failure, and high mortality rates of 60% and 35%, respectively. Ongoing circulation of H5N1 and H7N9 viruses in wild birds and poultry, and their ability to infect humans emphasizes their epidemic and pandemic potential and poses a public health threat. It is, thus, imperative to understand the host immune responses to the AIVs so we can control severe influenza disease caused by H5N1 or H7N9 and rationally design new immunotherapies and vaccines. This review summarizes our current knowledge on AIV epidemiology, disease symptoms, inflammatory processes underlying the AIV infection in humans, and recent studies on universal pre-existing CD8+ T cell immunity to AIVs. Immune responses driving the host recovery from AIV infection in patients hospitalized with severe influenza disease are also discussed. PMID:26973644

Oscillating field current drive experiments in the Madison Symmetric Torus

NASA Astrophysics Data System (ADS)

Blair, Arthur P., Jr.

Oscillating Field Current Drive (OFCD) is an inductive current drive method for toroidal pinches. To test OFCD, two 280 Hz 2 MVA oscillators were installed in the toroidal and poloidal magnetic field circuits of the Madison Symmetric Torus (MST) Reversed Field Pinch (RFP.) Partial sustainment experiments were conducted where the two voltage oscillations were superimposed on the standard MST power supplies. Supplementary current drive of about 10% has been demonstrated, comparable to theoretical predictions. However, maximum current drive does not coincide with maximum helicity injection rate - possibly due to an observed dependence of core and edge tearing modes on the relative phase of the oscillators. A dependence of wall interactions on phase was also observed, the largest interaction coinciding with negative current drive. Experiments were conducted at 280 and 530 Hz. 530 Hz proved to be too high and yielded little or no net current drive. Experiments at 280 Hz proved more fruitful. A 1D relaxed state model was used to predict the effects of voltage amplitudes, frequencies, and waveforms on performance and to optimize the design of OFCD hardware. Predicted current drive was comparable to experimental values, though the aforementioned phase dependence was not. Comparisons were also made with a more comprehensive 3D model which proved to be a more accurate predictor of current drive. Both 1D and 3D models predicted the feasability of full sustainment via OFCD. Experiments were also conducted with only the toroidal field oscillator applied. An entrainment of the natural sawtooth frequency to our applied oscillation was observed as well as a slow modulation of the edge tearing mode amplitudes. A large modulation (20 to 80 eV) of the ion temperature was also observed that can be partially accounted for by collisional heating via magnetic pumping. Work is in progress to increase the power of the existing OFCD hardware.

Method for Assessing Contrast Performance under Lighting Conditions such as Entering a Tunnel on Sunny Day.

PubMed

Huang, Y; Menozzi, M

2015-04-01

Clinical assessment of dark adaptation is time consuming and requires a specialised instrumentation such as a nyktometer. It is therefore not surprising that dark adaptation is rarely tested in practice. As for the case of testing fitness of a driver, demands on adaptation in daily driving tasks mostly depart from settings in a nyktometer. In daily driving, adaptation is stressed by high and fast transitions of light levels, and the period of time which is relevant to safe driving starts right after a transition and ends several seconds later. In the nyktometer dark adaptation is tested after completion of the adaptation process. RESULTS of a nyktometer test may therefore deliver little information about adaptation shortly after light transitions. In an attempt to develop a clinical test aiming to fulfill both a short measurement time and offering test conditions comparable to conditions in driving, we conducted a preliminary study in which contrast sensitivity thresholds were recorded for light transitions as found in daily driving tasks and for various times after transition onsets. Contrast sensitivity performance is compared to dark adaptation performance as assessed by a myktometer. Contrast sensitivity thresholds were recorded in 17 participants by means of a twin projection apparatus. The apparatus enabled the projection of an adapting field and of a Landolt ring both with a variable luminance. Five different stepwise transitions in levels of adapting luminance were tested. All transitions occurred from bright to dark. The Landolt ring was flashed 100 or 500 ms after the transition had occurred. Participants were instructed to report the orientation of the Landolt ring. A Rodenstock Nyktometer, Plate 501, was used to record dark adaptation threshold. Experimental data from the proposed test revealed a noticeably increasing contrast detection threshold measured in dark adaptation in the stronger transition from 14 000 to 8 cd/m2 than in the weaker transition from 2000 to 8 cd/m2. By raising the dark adaption luminance level from 8 to 60 cd/m2 in the stronger transition case, the contrast detection threshold was then improved by a factor of four. Another main finding showed that for the adaptation process from strong glare stimuli to the dark adaptation, a peak deterioration in contrast sensitivity occurred at the light adaptation level of 6000 cd/m2. Comparing the contrast performance assessed by the proposed test with that of the nyktometer test, there was no clear correlation between the two methods. Our suggested method to assess dark adaptation performance proved to be practical in use and, since the patient does not have to spend a long time to attain complete dark adaptation, the method required a short time for measurement. Our negative experience in the use of the myktometer was in agreement with reported experience in the literature. Georg Thieme Verlag KG Stuttgart · New York.

Photoemf in cadmium sulfide

NASA Technical Reports Server (NTRS)

Boeer, K. W.

1971-01-01

Theoretical and experimental investigations on CdS single crystals and CuxS:CdS photovoltaic cells prepared from CdS single crystals by a chemical-dip procedure are described. The studies are aimed at clarifying cell mechanisms which affect key cell properties (efficiency, reliability, and lifetime) by examining the properties of intrinsic and extrinsic defects in the junction and surface regions and their effects on carrier transport through these regions. The experimental research described includes studies of thermal, infrared, and field quenching of acceptor-doped CdS crystals; investigation of optical and electrical properties of CuxS:CdS photovoltaic cells (current-voltage characteristics, spectral distribution of photocurrent and photovoltage) and the dependence of these properties on temperature and light intensity; measurement of changes, as a result of heat treatment in ultrahigh vacuum, in the spectral distribution of photoconductivity at room temperature and liquid nitrogen temperature, the luminescence spectrum at liquid nitrogen temperature, and the thermally stimulated current curves of CdS crystals; determination of the effect of irradiation with 150 keV (maximum) X-rays on the spectral distribution of photoconductivity and thermally-stimulated current of CdS crystals; and studies of the effect of growth conditions on the photoconductive properties of CdS crystals.

Distributing the Wealth: Sliding CD-ROM into the Consumer Channel.

ERIC Educational Resources Information Center

Bowers, Richard A.

1994-01-01

Examines retail sales of CD-ROMs. Topics addressed include the current situation in CD-ROM retailing; channel distribution options; myths and realities of CD-ROM distribution; the distributor; affiliate labels; sales representatives; copublishers; distribution options; distributing resources; and recommendations for new CD-ROM publishers. (LRW)

Turbulent current drive mechanisms

NASA Astrophysics Data System (ADS)

McDevitt, Christopher J.; Tang, Xian-Zhu; Guo, Zehua

2017-08-01

Mechanisms through which plasma microturbulence can drive a mean electron plasma current are derived. The efficiency through which these turbulent contributions can drive deviations from neoclassical predictions of the electron current profile is computed by employing a linearized Coulomb collision operator. It is found that a non-diffusive contribution to the electron momentum flux as well as an anomalous electron-ion momentum exchange term provide the most efficient means through which turbulence can modify the mean electron current for the cases considered. Such turbulent contributions appear as an effective EMF within Ohm's law and hence provide an ideal means for driving deviations from neoclassical predictions.

Midkine inhibits inducible regulatory T cell differentiation by suppressing the development of tolerogenic dendritic cells.

PubMed

Sonobe, Yoshifumi; Li, Hua; Jin, Shijie; Kishida, Satoshi; Kadomatsu, Kenji; Takeuchi, Hideyuki; Mizuno, Tetsuya; Suzumura, Akio

2012-03-15

Midkine (MK), a heparin-binding growth factor, reportedly contributes to inflammatory diseases, including Crohn's disease and rheumatoid arthritis. We previously showed that MK aggravates experimental autoimmune encephalomyelitis (EAE) by decreasing regulatory CD4(+)CD25(+)Foxp3(+) T cells (Tregs), a population that regulates the development of autoimmune responses, although the precise mechanism remains uncertain. In this article, we show that MK produced in inflammatory conditions suppresses the development of tolerogenic dendritic cells (DCregs), which drive the development of inducible Treg. MK suppressed DCreg-mediated expansion of the CD4(+)CD25(+)Foxp3(+) Treg population. DCregs expressed significantly higher levels of CD45RB and produced significantly less IL-12 compared with conventional dendritic cells. However, MK downregulated CD45RB expression and induced IL-12 production by reducing phosphorylated STAT3 levels via src homology region 2 domain-containing phosphatase-2 in DCreg. Inhibiting MK activity with anti-MK RNA aptamers, which bind to the targeted protein to suppress the function of the protein, increased the numbers of CD11c(low)CD45RB(+) dendritic cells and Tregs in the draining lymph nodes and suppressed the severity of EAE, an animal model of multiple sclerosis. Our results also demonstrated that MK was produced by inflammatory cells, in particular, CD4(+) T cells under inflammatory conditions. Taken together, these results suggest that MK aggravates EAE by suppressing DCreg development, thereby impairing the Treg population. Thus, MK is a promising therapeutic target for various autoimmune diseases.

Contribution of herpesvirus specific CD8 T cells to anti-viral T cell response in humans.

PubMed

Sandalova, Elena; Laccabue, Diletta; Boni, Carolina; Tan, Anthony T; Fink, Katja; Ooi, Eng Eong; Chua, Robert; Shafaeddin Schreve, Bahar; Ferrari, Carlo; Bertoletti, Antonio

2010-08-19

Herpesviruses infect most humans. Their infections can be associated with pathological conditions and significant changes in T cell repertoire but evidences of symbiotic effects of herpesvirus latency have never been demonstrated. We tested the hypothesis that HCMV and EBV-specific CD8 T cells contribute to the heterologous anti-viral immune response. Volume of activated/proliferating virus-specific and total CD8 T cells was evaluated in 50 patients with acute viral infections: 20 with HBV, 12 with Dengue, 12 with Influenza, 3 with Adenovirus infection and 3 with fevers of unknown etiology. Virus-specific (EBV, HCMV, Influenza) pentamer+ and total CD8 T cells were analyzed for activation (CD38/HLA-DR), proliferation (Ki-67/Bcl-2(low)) and cytokine production. We observed that all acute viral infections trigger an expansion of activated/proliferating CD8 T cells, which differs in size depending on the infection but is invariably inflated by CD8 T cells specific for persistent herpesviruses (HCMV/EBV). CD8 T cells specific for other non-related non persistent viral infection (i.e. Influenza) were not activated. IL-15, which is produced during acute viral infections, is the likely contributing mechanism driving the selective activation of herpesvirus specific CD8 T cells. In addition we were able to show that herpesvirus specific CD8 T cells displayed an increased ability to produce the anti-viral cytokine interferon-gamma during the acute phase of heterologous viral infection. Taken together, these data demonstrated that activated herpesvirus specific CD8 T cells inflate the activated/proliferating CD8 T cells population present during acute viral infections in human and can contribute to the heterologous anti-viral T cell response.

Empirical, thermodynamic and quantum-chemical investigations of inclusion complexation between flavanones and (2-hydroxypropyl)-cyclodextrins.

PubMed

Liu, Benguo; Li, Wei; Nguyen, Tien An; Zhao, Jian

2012-09-15

The inclusion complexation of (2-hydroxypropyl)-cyclodextrins with flavanones was investigated by phase solubility measurements, as well as thermodynamic and quantum chemical methods. Inclusion complexes were formed between (2-hydroxypropyl)-α-cyclodextrin (HP-α-CD), (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD), (2-hydroxypropyl)-γ-cyclodextrin (HP-γ-CD) and β-cyclodextrin (β-CD) and four flavanones (naringenin, naringin, hesperetin and dihydromyricetin) in aqueous solutions and their phase solubility was determined. For all the flavanones, the stability constants of their complexes formed with different CDs followed the rank order: HP-β-CD (MW 1540)>HP-β-CD (MW 1460)>HP-β-CD (MW 1380)>β-CD>HP-γ-CD>HP-α-CD. Experimental results and quantum chemical calculations showed that the ability of flavanones to form inclusion complex with (2-hydroxypropyl)-cyclodextrins was determined by both the steric effect and hydrophobicity of the flavanones. For flavanones that have similar molecular volumes, the hydrophobicity of the molecule was the main determining factor of its ability to form inclusion complexes with HP-β-CD, and the hydrophobicity parameter Log P is highly correlated with the stability constant of the complexes. Results of thermodynamic study demonstrated that hydrophobic interaction is the main driving force for the formation process of the flavanone-CD inclusion complexes. Quantum chemical analysis of the most active hydroxyl groups and HOMO (the highest occupied molecular orbital) showed that the B ring of the flavanones was most likely involved in hydrogen bonding with the side groups in the cavity of the CDs, through which the inclusion complex was stabilised. Copyright © 2012 Elsevier Ltd. All rights reserved.

Thermal behavior of J-aggregates in a Langmuir-Blodgett film of pure merocyanine dye investigated by UV-visible and IR absorption spectroscopy.

PubMed

Hirano, Yoshiaki; Tateno, Shinsuke; Maio, Ari; Ozaki, Yukihiro

2009-03-05

We have characterized the structure of J-aggregate in a Langmuir-Blodgett film of pure merocyanine dye (MS18) fabricated under an aqueous subphase containing a cadmium ion (Cd2+) and have investigated its thermal behavior by UV-visible and IR absorption spectroscopy in the range from 25 to 250 degrees C with a continuous scan. The results of both UV-visible and IR absorption spectra indicate that temperature-dependent changes in the MS18 aggregation state in the pure MS18 system are closely and mildly linked with the MS18 intramolecular charge transfer and the behavior of the packing, orientation, conformation, and thermal mobility of MS18 hydrocarbon chain, respectively. The J-aggregate in the pure MS18 system dissociates from 25 to 150 degrees C, and the dissociation temperature at 150 degrees C is higher by 50 degrees C than that in the previous MS18- arachidic acid (C20) binary system. The lower dissociation temperature in the binary system originates from the fact that temperature-dependent structural disorder of cadmium arachidate (CdC20), being phase-separated from MS18, has an influence on the dissociation of J-aggregate. From 160 to 180 degrees C, thermally induced blue-shifted bands, caused by the oligomeric MS18 aggregation, appear at around 520 nm in the pure MS18 system by contraries, regardless of the lack of driving force by the melting phenomenon of CdC20. The temperature at which the 520 nm bands occur is in good agreement with the melting point (160 degrees C) of hydrocarbon chain in MS18 with Cd2+, whereas its chromophore part is clearly observed to melt near 205 degrees C by UV-visible spectra. Therefore, it is suggested that the driving force that induces the 520 nm band in the pure MS18 system arises from the partial melting of hydrocarbon chain in MS18 with Cd2+.

Prospects for Off-axis Current Drive via High Field Side Lower Hybrid Current Drive in DIII-D

NASA Astrophysics Data System (ADS)

Wukitch, S. J.; Shiraiwa, S.; Wallace, G. M.; Bonoli, P. T.; Holcomb, C.; Park, J. M.; Pinsker, R. I.

2017-10-01

An outstanding challenge for an economical, steady state tokamak is efficient off-axis current drive scalable to reactors. Previous studies have focused on high field side (HFS) launch of lower hybrid waves for current drive (LHCD) in double null configurations in reactor grade plasmas. The goal of this work is to find a HFS LHCD scenario for DIII-D that balances coupling, power penetration and damping. The higher magnetic field on the HFS improves wave accessibility, which allows for lower n||waves to be launched. These waves penetrate farther into the plasma core before damping at higher Te yielding a higher current drive efficiency. Utilizing advanced ray tracing and Fokker Planck simulation tools (GENRAY+CQL3D), wave penetration, absorption and drive current profiles in high performance DIII-D H-Mode plasmas were investigated. We found LH scenarios with single pass absorption, excellent wave penetration to r/a 0.6-0.8, FWHM r/a=0.2 and driven current up to 0.37 MA/MW coupled. These simulations indicate that HFS LHCD has potential to achieve efficient off-axis current drive in DIII-D and the latest results will be presented. Work supported by U.S. Dept. of Energy, Office of Science, Office of Fusion Energy Sciences, using User Facility DIII-D, under Award No. DE-FC02-04ER54698 and Contract No. DE-FC02-01ER54648 under Scientific Discovery through Advanced Computing Initiative.

Increasing Access to Modern Multidisciplinary Breast Cancer Care

DTIC Science & Technology

1998-08-01

S CD2 CD OS 0 cn CDCD r-. I-f fCf C- 0 00 ZZ CD ~ ~I II ADU ! t -l o 0 0 C CAD CD CD . j , - CD CD C >~ CD i -~ ~ ;~ CDCD C CD ~CD CD~ CDt~ CD- - -. CD... t -value Decisional Balance Barriers 6.9(2.9) 5.2(2.5) 4.36*** Promoters 12.7(1.9) 13.4(2.0) -1.97* Health Beliefs Fear 13.4(3.9) 13.2(4.2) NS Self...medical history, reproductive history, social desirability, aberrant eating patterns and depression , current behaviors and knowledge related to breast

Improving performance of Si/CdS micro-/nanoribbon p-n heterojunction light emitting diodes by trenched structure

NASA Astrophysics Data System (ADS)

Huang, Shiyuan; Wu, Yuanpeng; Ma, Xiangyang; Yang, Zongyin; Liu, Xu; Yang, Qing

2018-05-01

Realizing high performance silicon based light sources has been an unremitting pursuit for researchers. In this letter, we propose a simple structure to enhance electroluminescence emission and reduce the threshold of injected current of silicon/CdS micro-/nanoribbon p-n heterojunction visible light emitting diodes, by fabricating trenched structure on silicon substrate to mount CdS micro-/nanoribbon. A series of experiments and simulation analysis favors the rationality and validity of our mounting design. After mounting the CdS micro-/nanoribbon, the optical field confinement increases, and absorption and losses from high refractive silicon substrate are effectively reduced. Meanwhile the sharp change of silicon substrate near heterojunction also facilitates the balance between electron current and hole current, which substantially conduces to the stable amplification of electroluminescence emission in CdS micro-/nanoribbon.

Extrapolation of the DIII-D high poloidal beta scenario to ITER steady-state using transport modeling

NASA Astrophysics Data System (ADS)

McClenaghan, J.; Garofalo, A. M.; Meneghini, O.; Smith, S. P.

2016-10-01

Transport modeling of a proposed ITER steady-state scenario based on DIII-D high βP discharges finds that the core confinement may be improved with either sufficient rotation or a negative central shear q-profile. The high poloidal beta scenario is characterized by a large bootstrap current fraction( 80%) which reduces the demands on the external current drive, and a large radius internal transport barrier which is associated with improved normalized confinement. Typical temperature and density profiles from the non-inductive high poloidal beta scenario on DIII-D are scaled according to 0D modeling predictions of the requirements for achieving Q=5 steady state performance in ITER with ``day one'' H&CD capabilities. Then, TGLF turbulence modeling is carried out under systematic variations of the toroidal rotation and the core q-profile. Either strong negative central magnetic shear or rotation are found to successfully provide the turbulence suppression required to maintain the temperature and density profiles. This work supported by the US Department of Energy under DE-FC02-04ER54698.

Visual function and fitness to drive.

PubMed

Kotecha, Aachal; Spratt, Alexander; Viswanathan, Ananth

2008-01-01

Driving is recognized to be a visually intensive task and accordingly there is a legal minimum standard of vision required for all motorists. The purpose of this paper is to review the current United Kingdom (UK) visual requirements for driving and discuss the evidence base behind these legal rules. The role of newer, alternative tests of visual function that may be better indicators of driving safety will also be considered. Finally, the implications of ageing on driving ability are discussed. A search of Medline and PubMed databases was performed using the following keywords: driving, vision, visual function, fitness to drive and ageing. In addition, papers from the Department of Transport website and UK Royal College of Ophthalmologists guidelines were studied. Current UK visual standards for driving are based upon historical concepts, but recent advances in technology have brought about more sophisticated methods for assessing the status of the binocular visual field and examining visual attention. These tests appear to be better predictors of driving performance. Further work is required to establish whether these newer tests should be incorporated in the current UK visual standards when examining an individual's fitness to drive.

Atomically Resolved STM Characterization of the 3-D Dirac Semimetal Cd3As2

NASA Astrophysics Data System (ADS)

Butler, Christopher; Tseng, Yi; Hsing, Cheng-Rong; Wu, Yu-Mi; Sankar, Raman; Wang, Mei-Fang; Wei, Ching-Ming; Chou, Fang-Cheng; Lin, Minn-Tsong

Dirac semimetals such as Cd3As2 are a recently discovered class of materials which host three-dimensional linear dispersion around point-like band crossings in the bulk Brillouin zone, and hence represent three-dimensional analogues of graphene. This electronic phase is enabled by specific crystal symmetries: In the case of Cd3As2, a C4 rotational symmetry associated with its peculiar corkscrew arrangement of systematic Cd vacancies. Although this arrangement underpins the current crystallographic understanding of Cd3As2, and all its theoretical implications, it is strangely absent in surface microscopic investigations reported previously. Here we use a combined approach of scanning tunneling microscopy and ab initio calculations to show that the currently held crystallographic model of Cd3As2 is indeed predictive of a periodic zig-zag superstructure at the (112) surface, which we observe in scanning tunneling microscopy images. This helps to reconcile the current state of microscopic surface observations with the prevailing crystallographic and theoretical models.

Endogenous antigen processing drives the primary CD4+ T cell response to influenza

PubMed Central

Miller, Michael A.; Ganesan, Asha Purnima V.; Luckashenak, Nancy; Mendonca, Mark; Eisenlohr, Laurence C.

2015-01-01

By convention, CD4+ T lymphocytes recognize foreign and self peptides derived from internalized antigens in combination with MHC class II molecules. Alternative pathways of epitope production have been identified but their contributions to host defense have not been established. We show here in a mouse infection model that the CD4+ T cell response to influenza, critical for durable protection from the virus, is driven principally by unconventional processing of antigen synthesized within the infected antigen-presenting cell, not by classical processing of endocytosed virions or material from infected cells. Investigation of the cellular components involved, including the H2-M molecular chaperone, the proteasome, and gamma-interferon inducible lysosomal thiol reductase revealed considerable heterogeneity in the generation of individual epitopes, an arrangement that ensures peptide diversity and broad CD4+ T cell engagement. These results could fundamentally revise strategies for rational vaccine design and may lead to key insights into the induction of autoimmune and anti-tumor responses. PMID:26413780

CD206-positive myeloid cells bind galectin-9 and promote a tumor-supportive microenvironment.

PubMed

Enninga, Elizabeth Ann L; Chatzopoulos, Kyriakos; Butterfield, John T; Sutor, Shari L; Leontovich, Alexey A; Nevala, Wendy K; Flotte, Thomas J; Markovic, Svetomir N

2018-05-07

In patients with metastatic melanoma, high blood levels of galectin-9 are correlated with worse overall survival and a bias towards a Th2 inflammatory state supportive of tumor growth. Although galectin-9 signaling through TIM3 on T cells has been described, less is known about the interaction of galectin-9 with macrophages. We aimed to determine whether galectin-9 is a binding partner of CD206 on macrophages and whether the result of this interaction is tumor-supportive. It was determined that incubation of CD68+ macrophages with galectin-9 or anti-CD206 blocked target binding and that both CD206 and galectin-9 were detected by immunoprecipitation of cell lysates. CD206 and galectin-9 had a binding affinity of 2.8 × 10 -7 M. Galectin-9 causes CD206+ macrophages to make significantly more FGF2 and monocyte chemoattractant protein (MCP-1), but less macrophage-derived chemokine (MDC). Galectin-9 had no effect on classical monocyte subsets, but caused expansion of the non-classical populations. Lastly, there was a positive correlation between increasing numbers of CD206 macrophages and galectin-9 expression in tumors, and high levels of CD206 macrophages correlated negatively with melanoma survival. These results indicate that galectin-9 binds CD206 on M2 macrophages, which appear to drive angiogenesis and the production of chemokines that support tumor growth and poor patient prognoses. Targeting this interaction systemically through circulating monocytes may therefore be a novel way to improve local anti-tumor effects by macrophages. This article is protected by copyright. All rights reserved.

Elevated CD26 Expression by Skin Fibroblasts Distinguishes a Profibrotic Phenotype Involved in Scar Formation Compared to Gingival Fibroblasts.

PubMed

Mah, Wesley; Jiang, Guoqiao; Olver, Dylan; Gallant-Behm, Corrie; Wiebe, Colin; Hart, David A; Koivisto, Leeni; Larjava, Hannu; Häkkinen, Lari

2017-08-01

Compared to skin, wound healing in oral mucosa is faster and produces less scarring, but the mechanisms involved are incompletely understood. Studies in mice have linked high expression of CD26 to a profibrotic fibroblast phenotype, but this has not been tested in models more relevant for humans. We hypothesized that CD26 is highly expressed by human skin fibroblasts (SFBLs), and this associates with a profibrotic phenotype distinct from gingival fibroblasts (GFBLs). We compared CD26 expression in human gingiva and skin and in gingival and hypertrophic-like scar-forming skin wound healing in a pig model, and used three-dimensional cultures of human GFBLs and SFBLs. In both humans and pigs, nonwounded skin contained abundantly CD26-positive fibroblasts, whereas in gingiva they were rare. During skin wound healing, CD26-positive cells accumulated over time and persisted in forming hypertrophic-like scars, whereas few CD26-positive cells were present in the regenerated gingival wounds. Cultured human SFBLs displayed significantly higher levels of CD26 than GFBLs. This was associated with an increased expression of profibrotic genes and transforming growth factor-β signaling in SFBLs. The profibrotic phenotype of SFBLs partially depended on expression of CD26, but was independent of its catalytic activity. Thus, a CD26-positive fibroblast population that is abundant in human skin but not in gingiva may drive the profibrotic response leading to excessive scarring. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Discovering naturally processed antigenic determinants that confer protective T cell immunity

PubMed Central

Gilchuk, Pavlo; Spencer, Charles T.; Conant, Stephanie B.; Hill, Timothy; Gray, Jennifer J.; Niu, Xinnan; Zheng, Mu; Erickson, John J.; Boyd, Kelli L.; McAfee, K. Jill; Oseroff, Carla; Hadrup, Sine R.; Bennink, Jack R.; Hildebrand, William; Edwards, Kathryn M.; Crowe, James E.; Williams, John V.; Buus, Søren; Sette, Alessandro; Schumacher, Ton N.M.; Link, Andrew J.; Joyce, Sebastian

2013-01-01

CD8+ T cells (TCD8) confer protective immunity against many infectious diseases, suggesting that microbial TCD8 determinants are promising vaccine targets. Nevertheless, current T cell antigen identification approaches do not discern which epitopes drive protective immunity during active infection — information that is critical for the rational design of TCD8-targeted vaccines. We employed a proteomics-based approach for large-scale discovery of naturally processed determinants derived from a complex pathogen, vaccinia virus (VACV), that are presented by the most frequent representatives of four major HLA class I supertypes. Immunologic characterization revealed that many previously unidentified VACV determinants were recognized by smallpox-vaccinated human peripheral blood cells in a variegated manner. Many such determinants were recognized by HLA class I–transgenic mouse immune TCD8 too and elicited protective TCD8 immunity against lethal intranasal VACV infection. Notably, efficient processing and stable presentation of immune determinants as well as the availability of naive TCD8 precursors were sufficient to drive a multifunctional, protective TCD8 response. Our approach uses fundamental insights into T cell epitope processing and presentation to define targets of protective TCD8 immunity within human pathogens that have complex proteomes, suggesting that this approach has general applicability in vaccine sciences. PMID:23543059

Discovering naturally processed antigenic determinants that confer protective T cell immunity.

PubMed

Gilchuk, Pavlo; Spencer, Charles T; Conant, Stephanie B; Hill, Timothy; Gray, Jennifer J; Niu, Xinnan; Zheng, Mu; Erickson, John J; Boyd, Kelli L; McAfee, K Jill; Oseroff, Carla; Hadrup, Sine R; Bennink, Jack R; Hildebrand, William; Edwards, Kathryn M; Crowe, James E; Williams, John V; Buus, Søren; Sette, Alessandro; Schumacher, Ton N M; Link, Andrew J; Joyce, Sebastian

2013-05-01

CD8+ T cells (TCD8) confer protective immunity against many infectious diseases, suggesting that microbial TCD8 determinants are promising vaccine targets. Nevertheless, current T cell antigen identification approaches do not discern which epitopes drive protective immunity during active infection - information that is critical for the rational design of TCD8-targeted vaccines. We employed a proteomics-based approach for large-scale discovery of naturally processed determinants derived from a complex pathogen, vaccinia virus (VACV), that are presented by the most frequent representatives of four major HLA class I supertypes. Immunologic characterization revealed that many previously unidentified VACV determinants were recognized by smallpox-vaccinated human peripheral blood cells in a variegated manner. Many such determinants were recognized by HLA class I-transgenic mouse immune TCD8 too and elicited protective TCD8 immunity against lethal intranasal VACV infection. Notably, efficient processing and stable presentation of immune determinants as well as the availability of naive TCD8 precursors were sufficient to drive a multifunctional, protective TCD8 response. Our approach uses fundamental insights into T cell epitope processing and presentation to define targets of protective TCD8 immunity within human pathogens that have complex proteomes, suggesting that this approach has general applicability in vaccine sciences.

Persistent Simian Immunodeficiency Virus Infection Drives Differentiation, Aberrant Accumulation, and Latent Infection of Germinal Center Follicular T Helper Cells

PubMed Central

Xu, Huanbin; Wang, Xiaolei; Malam, Naomi; Aye, Pyone P.; Alvarez, Xavier; Lackner, Andrew A.

2015-01-01

ABSTRACT CD4+ follicular T helper (Tfh) cells play a prominent role in humoral immune responses, but the mechanisms of their accumulation and infection in AIDS remain unclear. Here we found that germinal center (GC) Tfh cells, defined here as CXCR5+ PD-1HIGH CD4+ T cells, do not express the HIV coreceptor CCR5 yet serve as a latent reservoir in GCs. With disease progression, an expansion of GC Tfh cells is accompanied by increases in dysfunctional CD8+ T cells. In contrast, Tfh precursor (CXCR5− CD4+ T) cells in lymph nodes do express CCR5 and differentiate into GC Tfh cells following interleukin-6 (IL-6) and IL-21 stimulation, and viral DNA is detectable in fully differentiated GC Tfh cells ex vivo. This suggests that SIV-infected GC Tfh cells may be derived from Tfh precursor cell subsets that become infected in marginal zones and then migrate into GCs as fully mature GC Tfh cells that serve as persistent virus reservoirs. These findings suggest that viral persistence in lymph nodes drives compensatory differentiation, aberrant accumulation, and latent infection of GC Tfh cells, resulting in marked impairment of humoral immune responses. IMPORTANCE Generation of antibodies that can effectively eliminate viruses requires interactions of B cells with highly specialized T cells in GCs of lymphoid tissues called follicular T helper cells. Here we show that in simian immunodeficiency virus infection, these cells are initially infected in a precursor stage that leads to alterations in their homing, accumulation, and function that may be responsible for the inability of human immunodeficiency virus-infected patients to generate effective antibody responses. PMID:26608323

Persistent Simian Immunodeficiency Virus Infection Drives Differentiation, Aberrant Accumulation, and Latent Infection of Germinal Center Follicular T Helper Cells.

PubMed

Xu, Huanbin; Wang, Xiaolei; Malam, Naomi; Aye, Pyone P; Alvarez, Xavier; Lackner, Andrew A; Veazey, Ronald S

2016-02-01

CD4(+) follicular T helper (Tfh) cells play a prominent role in humoral immune responses, but the mechanisms of their accumulation and infection in AIDS remain unclear. Here we found that germinal center (GC) Tfh cells, defined here as CXCR5(+) PD-1(HIGH) CD4(+) T cells, do not express the HIV coreceptor CCR5 yet serve as a latent reservoir in GCs. With disease progression, an expansion of GC Tfh cells is accompanied by increases in dysfunctional CD8(+) T cells. In contrast, Tfh precursor (CXCR5(-) CD4(+) T) cells in lymph nodes do express CCR5 and differentiate into GC Tfh cells following interleukin-6 (IL-6) and IL-21 stimulation, and viral DNA is detectable in fully differentiated GC Tfh cells ex vivo. This suggests that SIV-infected GC Tfh cells may be derived from Tfh precursor cell subsets that become infected in marginal zones and then migrate into GCs as fully mature GC Tfh cells that serve as persistent virus reservoirs. These findings suggest that viral persistence in lymph nodes drives compensatory differentiation, aberrant accumulation, and latent infection of GC Tfh cells, resulting in marked impairment of humoral immune responses. Generation of antibodies that can effectively eliminate viruses requires interactions of B cells with highly specialized T cells in GCs of lymphoid tissues called follicular T helper cells. Here we show that in simian immunodeficiency virus infection, these cells are initially infected in a precursor stage that leads to alterations in their homing, accumulation, and function that may be responsible for the inability of human immunodeficiency virus-infected patients to generate effective antibody responses. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Reduction of surface leakage current by surface passivation of CdZn Te and other materials using hyperthermal oxygen atoms

DOEpatents

Hoffbauer, Mark A.; Prettyman, Thomas H.

2001-01-01

Reduction of surface leakage current by surface passivation of Cd.sub.1-x Zn.sub.x Te and other materials using hyperthermal oxygen atoms. Surface effects are important in the performance of CdZnTe room-temperature radiation detectors used as spectrometers since the dark current is often dominated by surface leakage. A process using high-kinetic-energy, neutral oxygen atoms (.about.3 eV) to treat the surface of CdZnTe detectors at or near ambient temperatures is described. Improvements in detector performance include significantly reduced leakage current which results in lower detector noise and greater energy resolution for radiation measurements of gamma- and X-rays, thereby increasing the accuracy and sensitivity of measurements of radionuclides having complex gamma-ray spectra, including special nuclear materials.

Surface leakage current in 12.5  μm long-wavelength HgCdTe infrared photodiode arrays.

PubMed

Qiu, Weicheng; Hu, Weida; Lin, Chun; Chen, Xiaoshuang; Lu, Wei

2016-02-15

Long-wavelength (especially >12  μm) focal plane array (FPA) infrared detection is the cutting edge technique for third-generation infrared remote sensing. However, dark currents, which are very sensitive to the growth of small Cd composition HgCdTe, strongly limits the performance of long wavelength HgCdTe photodiode arrays in FPAs. In this Letter, 12.5 μm long-wavelength Hg_1-xCd_xTe (x≈0.219) infrared photodiode arrays are reported. The variable-area and variable-temperature electrical characteristics of the long-wavelength infrared photodiodes are measured. The characteristics of the extracted zero-bias resistance-area product (l/R₀A) varying with the perimeter-to-area (P/A) ratio clearly show that surface leakage current mechanisms severely limit the overall device performance. A sophisticated model has been developed for investigating the leakage current mechanism in the photodiodes. Modeling of temperature-dependent I-V characteristic indicates that the trap-assisted tunneling effect dominates the dark current at 50 K resulting in nonuniformities in the arrays. The extracted trap density, approximately 10¹³-10¹⁴  cm^-3, with an ionized energy of 30 meV is determined by simulation. The work described in this Letter provides the basic mechanisms for a better understanding of the leakage current mechanism for long-wavelength (>12  μm) HgCdTe infrared photodiode arrays.

Turbulent current drive mechanisms

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

McDevitt, Christopher J.; Tang, Xian-Zhu; Guo, Zehua

Mechanisms through which plasma microturbulence can drive a mean electron plasma current are derived. The efficiency through which these turbulent contributions can drive deviations from neoclassical predictions of the electron current profile is computed by employing a linearized Coulomb collision operator. It is found that a non-diffusive contribution to the electron momentum flux as well as an anomalous electron-ion momentum exchange term provide the most efficient means through which turbulence can modify the mean electron current for the cases considered. Such turbulent contributions appear as an effective EMF within Ohm’s law, and hence provide an ideal means for driving deviationsmore » from neoclassical predictions.« less

Turbulent current drive mechanisms

DOE PAGES

McDevitt, Christopher J.; Tang, Xian-Zhu; Guo, Zehua

2017-07-01

Mechanisms through which plasma microturbulence can drive a mean electron plasma current are derived. The efficiency through which these turbulent contributions can drive deviations from neoclassical predictions of the electron current profile is computed by employing a linearized Coulomb collision operator. It is found that a non-diffusive contribution to the electron momentum flux as well as an anomalous electron-ion momentum exchange term provide the most efficient means through which turbulence can modify the mean electron current for the cases considered. Such turbulent contributions appear as an effective EMF within Ohm’s law, and hence provide an ideal means for driving deviationsmore » from neoclassical predictions.« less

Coloring of the past via respondent's current psychological state, mediation, and the association between childhood disadvantage and morbidity in adulthood.

PubMed

Sheikh, Mashhood Ahmed

2018-05-31

Many researchers view retrospective reports with skepticism. Indeed, the observed association between retrospectively-reported childhood disadvantage (CD) and morbidity in adulthood has been criticized as an artefactual correlation driven by the psychological state of the respondent at the time of reporting (current psychological state). The aim of this study was to assess the role of current psychological state in the association between childhood disadvantage and morbidity in adulthood. The present analysis used cross-sectional data collected in 2007-2008 within the framework of the Tromsø Study (N = 10,765), a representative study of adult men and women in Norway. The association between CD and the physical health outcomes heart attack, angina pectoris, chronic bronchitis/emphysema/COPD, diabetes mellitus, hypothyroid/low metabolism, migraine, hypertension, and comorbidity (i.e., the sum of these physical health outcomes) was assessed with Poisson regression models. Relative risks (RR) and 95% confidence intervals (CI) were estimated. A wide range of indicators of respondents' current psychological state were included in the models to assess the % attenuation in estimates. CD was associated with an increased risk of heart attack, angina pectoris, chronic bronchitis/emphysema/COPD, diabetes mellitus, hypothyroid/low metabolism, migraine, hypertension, and comorbidity (p < 0.05), independent of respondents' current psychological state. A sizeable proportion (23-42%) of the association between CD and physical health outcomes was driven by recall bias or mediation via respondents' current psychological state. Controlling for indicators of current psychological state reduced the strength of associations between CD and physical health outcomes; however, the independent associations remained in the same direction. The association between retrospectively-reported CD and physical health outcomes in adulthood is not driven entirely by respondent's current psychological state. Copyright © 2018 Elsevier Ltd. All rights reserved.

Nationwide Survey of Soldier Perceptions of Reserve Component (RC) training

DTIC Science & Technology

1989-09-01

University Drive ELEMENT NO. NO. NO. ACCESSION NO. Boise_ TD 8A372 63007A 795 3308(516) X2 11. TITLE (Include Security Classification) Nationwide Survey...2.277) would not only be 22 0) N’ - w Cq If) ~ 4I CD IfO LC) Vf)r- V- co tf)- wc~)) u-, v ’ 0 0O tD 1-’- 4 C0 f 𔃾ICD Cy) C C -Il T-4 InOIoOD 0 - O...8217 wo LO) co C C -4 C’) -q w ) Co co) C’. i Cc.3 C2 C C) C’) C\\J C’) C’) C’) C’) C’) Co) t o C o CD co -4 C’) tD 1-4 C𔃽 S vi CD 0) lw El - 0) 14 co 0

birgHPC: creating instant computing clusters for bioinformatics and molecular dynamics.

PubMed

Chew, Teong Han; Joyce-Tan, Kwee Hong; Akma, Farizuwana; Shamsir, Mohd Shahir

2011-05-01

birgHPC, a bootable Linux Live CD has been developed to create high-performance clusters for bioinformatics and molecular dynamics studies using any Local Area Network (LAN)-networked computers. birgHPC features automated hardware and slots detection as well as provides a simple job submission interface. The latest versions of GROMACS, NAMD, mpiBLAST and ClustalW-MPI can be run in parallel by simply booting the birgHPC CD or flash drive from the head node, which immediately positions the rest of the PCs on the network as computing nodes. Thus, a temporary, affordable, scalable and high-performance computing environment can be built by non-computing-based researchers using low-cost commodity hardware. The birgHPC Live CD and relevant user guide are available for free at http://birg1.fbb.utm.my/birghpc.

Therapeutic PD-L1 and LAG-3 blockade rapidly clears established blood-stage Plasmodium infection

PubMed Central

Butler, Noah S.; Moebius, Jacqueline; Pewe, Lecia L.; Traore, Boubacar; Doumbo, Ogobara K.; Tygrett, Lorraine T.; Waldschmidt, Thomas J.; Crompton, Peter D.; Harty, John T.

2011-01-01

Plasmodium infection of erythrocytes induces clinical malaria. Parasite-specific CD4+ T cells correlate with reduced parasite burdens and severity of human malaria, and are required to control blood-stage infection in mice. However, the characteristics of CD4+ T cells that determine protection or parasite persistence remain unknown. Here we show that P. falciparum infection of humans increased expression of an inhibitory receptor (PD-1) associated with T cell dysfunction. In vivo blockade of PD-L1 and LAG-3 restored CD4+ T cell function, amplified T follicular helper cell and germinal center B cell and plasmablast numbers, enhanced protective antibodies and rapidly cleared blood-stage malaria in mice. Thus, chronic malaria drives specific T cell dysfunction, which can be rescued to enhance parasite control using inhibitory therapies. PMID:22157630

Multiple Inflammatory Cytokines Converge To Regulate CD8+ T Cell Expansion and Function during Tuberculosis.

PubMed

Booty, Matthew G; Nunes-Alves, Cláudio; Carpenter, Stephen M; Jayaraman, Pushpa; Behar, Samuel M

2016-02-15

The differentiation of effector CD8(+) T cells is a dynamically regulated process that varies during different infections and is influenced by the inflammatory milieu of the host. In this study, we define three signals regulating CD8(+) T cell responses during tuberculosis by focusing on cytokines known to affect disease outcome: IL-12, type I IFN, and IL-27. Using mixed bone marrow chimeras, we compared wild-type and cytokine receptor knockout CD8(+) T cells within the same mouse following aerosol infection with Mycobacterium tuberculosis. Four weeks postinfection, IL-12, type 1 IFN, and IL-27 were all required for efficient CD8(+) T cell expansion in the lungs. We next determined if these cytokines directly promote CD8(+) T cell priming or are required only for expansion in the lungs. Using retrogenic CD8(+) T cells specific for the M. tuberculosis Ag TB10.4 (EsxH), we observed that IL-12 is the dominant cytokine driving both CD8(+) T cell priming in the lymph node and expansion in the lungs; however, type I IFN and IL-27 have nonredundant roles supporting pulmonary CD8(+) T cell expansion. Thus, IL-12 is a major signal promoting priming in the lymph node, but a multitude of inflammatory signals converge in the lung to promote continued expansion. Furthermore, these cytokines regulate the differentiation and function of CD8(+) T cells during tuberculosis. These data demonstrate distinct and overlapping roles for each of the cytokines examined and underscore the complexity of CD8(+) T cell regulation during tuberculosis. Copyright © 2016 by The American Association of Immunologists, Inc.

Poliomyelitis in transgenic mice expressing CD155 under the control of the Tage4 promoter after oral and parenteral poliovirus inoculation

PubMed Central

Khan, Shaukat; Toyoda, Hidemi; Linehan, Melissa; Iwasaki, Akiko; Nomoto, Akio; Bernhardt, Günter; Wimmer, Eckard

2014-01-01

An important step in poliovirus (PV) infection by the oral route in humans is replication of the virus in lymphatic tissues of the gastrointestinal (GI) tract, thought to be mainly in the Peyer’s patches of the small intestine. No immunocompetent transgenic (tg) mice that express human PV receptor (CD155) under the control of different promoters can be infected orally. The mouse orthologue of human CD155 is Tage4, a protein expressed at the surface of enterocytes and in the Peyer’s patches. We describe here the generation of a tg mouse model in which the Tage4 promoter was used to drive expression of the human PV receptor-coding region (Tage4-CD155tg mice). In this model, CD155 expression was observed by immunostaining in different regions in the Peyer’s patches but not in their germinal centres. Although a similar pattern of staining was observed between 3- and 6-week-old Tage4-CD155tg mice, poliomyelitis was only seen in the younger mice after PV infection by the oral route. When compared with TgPVR21 mice that expressed CD155 driven by its human promoter, 3-week-old Tage4-CD155tg mice were more susceptible to gut infection and paralysis following feeding with PV. Also, Tage4-CD155tg mice exhibited higher susceptibility to poliomyelitis after parenteral inoculation of PV. Remarkably, the LD50 after intracerebral inoculation of PV was similar in both CD155 tg mouse strains. The CD155 tg mouse model reported here, although moderately susceptible to oral infection, may be suitable to study mechanisms of PV replication in the gastrointestinal tract and to dissect important aspects of PV neuroinvasiveness. PMID:24784416

Poliomyelitis in transgenic mice expressing CD155 under the control of the Tage4 promoter after oral and parenteral poliovirus inoculation.

PubMed

Khan, Shaukat; Toyoda, Hidemi; Linehan, Melissa; Iwasaki, Akiko; Nomoto, Akio; Bernhardt, Günter; Cello, Jeronimo; Wimmer, Eckard

2014-08-01

An important step in poliovirus (PV) infection by the oral route in humans is replication of the virus in lymphatic tissues of the gastrointestinal (GI) tract, thought to be mainly in the Peyer's patches of the small intestine. No immunocompetent transgenic (tg) mice that express human PV receptor (CD155) under the control of different promoters can be infected orally. The mouse orthologue of human CD155 is Tage4, a protein expressed at the surface of enterocytes and in the Peyer's patches. We describe here the generation of a tg mouse model in which the Tage4 promoter was used to drive expression of the human PV receptor-coding region (Tage4-CD155tg mice). In this model, CD155 expression was observed by immunostaining in different regions in the Peyer's patches but not in their germinal centres. Although a similar pattern of staining was observed between 3- and 6-week-old Tage4-CD155tg mice, poliomyelitis was only seen in the younger mice after PV infection by the oral route. When compared with TgPVR21 mice that expressed CD155 driven by its human promoter, 3-week-old Tage4-CD155tg mice were more susceptible to gut infection and paralysis following feeding with PV. Also, Tage4-CD155tg mice exhibited higher susceptibility to poliomyelitis after parenteral inoculation of PV. Remarkably, the LD50 after intracerebral inoculation of PV was similar in both CD155 tg mouse strains. The CD155 tg mouse model reported here, although moderately susceptible to oral infection, may be suitable to study mechanisms of PV replication in the gastrointestinal tract and to dissect important aspects of PV neuroinvasiveness. © 2014 The Authors.

Changes in membrane lipids drive increased endocytosis following Fas ligation.

PubMed

Degli Esposti, Mauro; Matarrese, Paola; Tinari, Antonella; Longo, Agostina; Recalchi, Serena; Khosravi-Far, Roya; Malorni, Walter; Misasi, Roberta; Garofalo, Tina; Sorice, Maurizio

2017-05-01

Once activated, some surface receptors promote membrane movements that open new portals of endocytosis, in part to facilitate the internalization of their activated complexes. The prototypic death receptor Fas (CD95/Apo1) promotes a wave of enhanced endocytosis that induces a transient intermixing of endosomes with mitochondria in cells that require mitochondria to amplify death signaling. This initiates a global alteration in membrane traffic that originates from changes in key membrane lipids occurring in the endoplasmic reticulum (ER). We have focused the current study on specific lipid changes occurring early after Fas ligation. We analyzed the interaction between endosomes and mitochondria in Jurkat T cells by nanospray-Time-of-flight (ToF) Mass Spectrometry. Immediately after Fas ligation, we found a transient wave of lipid changes that drives a subpopulation of early endosomes to merge with mitochondria. The earliest event appears to be a decrease of phosphatidylcholine (PC), linked to a metabolic switch enhancing phosphatidylinositol (PI) and phosphoinositides, which are crucial for the formation of vacuolar membranes and endocytosis. Lipid changes occur independently of caspase activation and appear to be exacerbated by caspase inhibition. Conversely, inhibition or compensation of PC deficiency attenuates endocytosis, endosome-mitochondria mixing and the induction of cell death. Deficiency of receptor interacting protein, RIP, also limits the specific changes in membrane lipids that are induced by Fas activation, with parallel reduction of endocytosis. Thus, Fas activation rapidly changes the interconversion of PC and PI, which then drives enhanced endocytosis, thus likely propagating death signaling from the cell surface to mitochondria and other organelles.

NLRP3 signaling drives macrophage-induced adaptive immune suppression in pancreatic carcinoma

PubMed Central

Daley, Donnele; Mani, Vishnu R.; Mohan, Navyatha; Akkad, Neha; Savadkar, Shivraj; Lee, Ki Buom; Torres-Hernandez, Alejandro; Aykut, Berk; Diskin, Brian; Wang, Wei; Farooq, Mohammad S.; Mahmud, Arif I.; Werba, Gregor; Morales, Eduardo J.; Lall, Sarah; Rubin, Amanda G.; Berman, Matthew E.; Hundeyin, Mautin

2017-01-01

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDA) is characterized by immune tolerance, which enables disease to progress unabated by adaptive immunity. However, the drivers of this tolerogenic program are incompletely defined. In this study, we found that NLRP3 promotes expansion of immune-suppressive macrophages in PDA. NLRP3 signaling in macrophages drives the differentiation of CD4+ T cells into tumor-promoting T helper type 2 cell (Th2 cell), Th17 cell, and regulatory T cell populations while suppressing Th1 cell polarization and cytotoxic CD8+ T cell activation. The suppressive effects of NLRP3 signaling were IL-10 dependent. Pharmacological inhibition or deletion of NLRP3, ASC (apoptosis-associated speck-like protein containing a CARD complex), or caspase-1 protected against PDA and was associated with immunogenic reprogramming of innate and adaptive immunity within the TME. Similarly, transfer of PDA-entrained macrophages or T cells from NLRP3−/− hosts was protective. These data suggest that targeting NLRP3 holds the promise for the immunotherapy of PDA. PMID:28442553

Microbial fuel cell driving electrokinetic remediation of toxic metal contaminated soils.

PubMed

Habibul, Nuzahat; Hu, Yi; Sheng, Guo-Ping

2016-11-15

An investigation of the feasibility of in-situ electrokinetic remediation for toxic metal contaminated soil driven by microbial fuel cell (MFC) is presented. Results revealed that the weak electricity generated from MFC could power the electrokinetic remediation effectively. The metal removal efficiency and its influence on soil physiological properties were also investigated. With the electricity generated through the oxidation of organics in soils by microorganisms, the metals in the soils would mitigate from the anode to the cathode. The concentrations of Cd and Pb in the soils increased gradually through the anode to the cathode regions after remediation. After about 143days and 108 days' operation, the removal efficiencies of 31.0% and 44.1% for Cd and Pb at the anode region could be achieved, respectively. Soil properties such as pH and soil conductivity were also significantly redistributed from the anode to the cathode regions. The study shows that the MFC driving electrokinetic remediation technology is cost-effective and environmental friendly, with a promising application in soil remediation. Copyright © 2016 Elsevier B.V. All rights reserved.

Higher Body Mass Index Is Associated With Greater Proportions of Effector CD8+ T Cells Expressing CD57 in Women Living With HIV.

PubMed

Reid, Michael J A; Baxi, Sanjiv M; Sheira, Lila A; Landay, Alan L; Frongillo, Edward A; Adedimeji, Adebola; Cohen, Mardge H; Wentz, Eryka; Gustafson, Deborah R; Merenstein, Daniel; Hunt, Peter W; Tien, Phyllis C; Weiser, Sheri D

2017-08-15

A low proportion of CD28CD8 T cells that express CD57 is associated with increased mortality in HIV infection. The effect of increasing body mass index (BMI) changes in the proportion of CD57CD28CD8 T cells among HIV-infected individuals on antiretroviral therapy is unknown. In a US cohort of HIV-infected women, we evaluated associations of BMI and waist circumference with 3 distinct CD8 T cell phenotypes: % CD28CD57CD8 T cells, % CD57 of CD28CD8 T cells, and % CD28 of all CD8 T cells. Multivariable linear regression analysis was used to estimate beta coefficients for each of 3 T-cell phenotypes. Covariates included HIV parameters (current and nadir CD4, current viral load), demographics (age, race, income, and study site), and lifestyle (tobacco and alcohol use) factors. Of 225 participants, the median age was 46 years and 50% were obese (BMI >30 m/kg). Greater BMI and waist circumference were both associated with higher % CD28CD57CD8 T cells and % CD57 of all CD28CD8 T cells in multivariable analysis, including adjustment for HIV viral load (all P < 0.05). The association between greater BMI and the overall proportion of CD28 CD8 cells in fully adjusted models (0.078, 95% confidence interval: -0.053 to 0.209) was not significant. In this analysis, greater BMI and waist circumference are associated with greater expression of CD57 on CD28CD8 T cells and a greater proportion of CD57CD28 CD8 T cells. These findings may indicate that increasing BMI is immunologically protective in HIV-infected women. Future research is needed to understand the prognostic importance of these associations on clinical outcomes.

CD Nomenclature 2015: Human Leukocyte Differentiation Antigen Workshops as a Driving Force in Immunology.

PubMed

Engel, Pablo; Boumsell, Laurence; Balderas, Robert; Bensussan, Armand; Gattei, Valter; Horejsi, Vaclav; Jin, Bo-Quan; Malavasi, Fabio; Mortari, Frank; Schwartz-Albiez, Reinhard; Stockinger, Hannes; van Zelm, Menno C; Zola, Heddy; Clark, Georgina

2015-11-15

CD (cluster of differentiation) Ags are cell surface molecules expressed on leukocytes and other cells relevant for the immune system. CD nomenclature has been universally adopted by the scientific community and is officially approved by the International Union of Immunological Societies and sanctioned by the World Health Organization. It provides a unified designation system for mAbs, as well as for the cell surface molecules that they recognize. This nomenclature was established by the Human Leukocyte Differentiation Antigens Workshops. In addition to defining the CD nomenclature, these workshops have been instrumental in identifying and determining the expression and function of cell surface molecules. Over the past 30 y, the data generated by the 10 Human Leukocyte Differentiation Antigens Workshops have led to the characterization and formal designation of more than 400 molecules. CD molecules are commonly used as cell markers, allowing the identification and isolation of leukocyte populations, subsets, and differentiation stages. mAbs against these molecules have proven to be essential for biomedical research and diagnosis, as well as in biotechnology. More recently, they have been recognized as invaluable tools for the treatment of several malignancies and autoimmune diseases. In this article, we describe how the CD nomenclature was established, present the official updated list of CD molecules, and provide a rationale for their usefulness in the 21st century. Copyright © 2015 by The American Association of Immunologists, Inc.

Regulation of a TGF-β1-CD147 self-sustaining network in the differentiation plasticity of hepatocellular carcinoma cells.

PubMed

Wu, J; Lu, M; Li, Y; Shang, Y-K; Wang, S-J; Meng, Y; Wang, Z; Li, Z-S; Chen, H; Chen, Z-N; Bian, H

2016-10-20

Cellular plasticity has an important role in the progression of hepatocellular carcinoma (HCC). In this study, the involvement of a TGF-β1-CD147 self-sustaining network in the regulation of the dedifferentiation progress was fully explored in HCC cell lines, hepatocyte-specific basigin/CD147-knockout mice and human HCC tissues. We demonstrated that TGF-β1 stimulation upregulated CD147 expression and mediated the dedifferentiation of HCC cells, whereas all-trans-retinoic acid induced the downregulation of CD147 and promoted differentiation in HCC cells. Overexpression of CD147 induced the dedifferentiation and enhanced the malignancy of HCC cells, and increased the transcriptional expression of TGF-β1 by activating β-catenin. CD147-induced matrix metalloproteinase (MMP) production activated pro-TGF-β1. The activated TGF-β1 signaling subsequently repressed the HNF4α expression via Smad-Snail1 signaling and enhanced the dedifferentiation progress. Hepatocyte-specific basigin/CD147-knockout mice decreased the susceptibility to N-nitrosodiethylamine-induced tumorigenesis by suppressing TGF-β1-CD147 signaling and inhibiting dedifferentiation in hepatocytes during tumor progression. CD147 was positively correlated with TGF-β1 and negatively correlated with HNF4α in human HCC tissues. Positive CD147 staining and lower HNF4α levels in tumor tissues were significantly associated with poor survival of patients with HCC. The overexpression of HNF4α and Smad7 and the deletion of CD147 by lentiviral vectors jointly reprogrammed the expression profile of hepatocyte markers and attenuated malignant properties including proliferation, cell survival and tumor growth of HCC cells. Our results highlight the important role of the TGF-β1-CD147 self-sustaining network in driving HCC development by regulating differentiation plasticity, which provides a strong basis for further investigations of the differentiation therapy of HCC targeting TGF-β1 and CD147.

TiO2 nanocrystals decorated Z-schemed core-shell CdS-CdO nanorod arrays as high efficiency anodes for photoelectrochemical hydrogen generation.

PubMed

Li, Chia-Hsun; Hsu, Chan-Wei; Lu, Shih-Yuan

2018-07-01

TiO 2 nanocrystals decorated core-shell CdS-CdO nanorod arrays, TiO 2 @CdO/CdS NR, were fabricated as high efficiency anodes for photoelctrochemical hydrogen generation. The novel sandwich heterostructure was constructed from first growth of CdS nanorod arrays on a fluorine doped tin oxide (FTO) substrate with a hydrothermal process, followed by in situ generation of CdO thin films of single digit nanometers from the CdS nanorod surfaces through thermal oxidation, and final decoration of TiO 2 nanocrystals of 10-20 nm via a successive ionic layer absorption and reaction process. The core-shell CdS-CdO heterostructure possesses a Z-scheme band structure to enhance interfacial charge transfer, facilitating effective charge separation to suppress electron-hole recombination within CdS for much improved current density generation. The final decoration of TiO 2 nanocrystals passivates surface defects and trap states of CdO, further suppressing surface charge recombination for even higher photovoltaic conversion efficiencies. The photoelectrochemical performances of the plain CdS nanorod array were significantly improved with the formation of the sandwich heterostructure, achieving a photo current density of 3.2 mA/cm 2 at 1.23 V (vs. RHE), a 141% improvement over the plain CdS nanorod array and a 32% improvement over the CdO/CdS nanorod array. Copyright © 2018 Elsevier Inc. All rights reserved.

Hepatocytes and IL-15: a favorable microenvironment for T cell survival and CD8+ T cell differentiation.

PubMed

Correia, Margareta P; Cardoso, Elsa M; Pereira, Carlos F; Neves, Rui; Uhrberg, Markus; Arosa, Fernando A

2009-05-15

Human intrahepatic lymphocytes are enriched in CD1d-unrestricted T cells coexpressing NKR. Although the origin of this population remains controversial, it is possible to speculate that the hepatic microenvironment, namely epithelial cells or the cytokine milieu, may play a role in its shaping. IL-15 is constitutively expressed in the liver and has a key role in activation and survival of innate and tissue-associated immune cells. In this in vitro study, we examined whether hepatocyte cell lines and/or IL-15 could play a role in the generation of NK-like T cells. The results show that both HepG2 cells and a human immortalized hepatocyte cell line increase survival and drive basal proliferation of T cells. In addition, IL-15 was capable of inducing Ag-independent up-regulation of NKR, including NKG2A, Ig-like receptors, and de novo expression of CD56 and NKp46 in CD8(+)CD56(-) T cells. In conclusion, our study suggests that hepatocytes and IL-15 create a favorable microenvironment for T cells to growth and survive. It can be proposed that the increased percentage of intrahepatic nonclassical NKT cells could be in part due to a local CD8(+) T cell differentiation.

CD59 signaling and membrane pores drive Syk-dependent erythrocyte necroptosis

PubMed Central

LaRocca, T J; Stivison, E A; Mal-Sarkar, T; Hooven, T A; Hod, E A; Spitalnik, S L; Ratner, A J

2015-01-01

Mature erythrocytes (red blood cells (RBCs)) undergo the programmed cell death (PCD) pathway of necroptosis in response to bacterial pore-forming toxins (PFTs) that target human CD59 (hCD59) but not hCD59-independent PFTs. Here, we investigate the biochemical mechanism of RBC necroptosis with a focus on the mechanism of induction and the minimal requirements for such RBC death. Binding or crosslinking of the hCD59 receptor led to Syk-dependent induction of vesiculated morphology (echinocytes) that was associated with phosphorylation of Band 3 and was required for Fas ligand (FasL) release. FasL-dependent phosphorylation of receptor-interacting protein kinase 1 (RIP1) in combination with plasma membrane pore formation was required for execution of RBC necroptosis. RIP1 phosphorylation led to the phosphorylation of RIP3, which was also critical for RBC necroptosis. Notably, RBC necroptosis was mediated by FasL and not by other candidate inducers, including tumor necrosis factor alpha (TNF-α) and TNF-related apoptosis-inducing ligand (TRAIL). Other types of RBC damage, such as eryptotic damage, failed to induce necroptosis when combined with hCD59 crosslinking. This work sheds light on the requirements for this recently discovered PCD in RBCs and provides a clear picture of the biochemical mechanism of induction of RBC necroptosis. PMID:26018734

CD59 signaling and membrane pores drive Syk-dependent erythrocyte necroptosis.

PubMed

LaRocca, T J; Stivison, E A; Mal-Sarkar, T; Hooven, T A; Hod, E A; Spitalnik, S L; Ratner, A J

2015-05-28

Mature erythrocytes (red blood cells (RBCs)) undergo the programmed cell death (PCD) pathway of necroptosis in response to bacterial pore-forming toxins (PFTs) that target human CD59 (hCD59) but not hCD59-independent PFTs. Here, we investigate the biochemical mechanism of RBC necroptosis with a focus on the mechanism of induction and the minimal requirements for such RBC death. Binding or crosslinking of the hCD59 receptor led to Syk-dependent induction of vesiculated morphology (echinocytes) that was associated with phosphorylation of Band 3 and was required for Fas ligand (FasL) release. FasL-dependent phosphorylation of receptor-interacting protein kinase 1 (RIP1) in combination with plasma membrane pore formation was required for execution of RBC necroptosis. RIP1 phosphorylation led to the phosphorylation of RIP3, which was also critical for RBC necroptosis. Notably, RBC necroptosis was mediated by FasL and not by other candidate inducers, including tumor necrosis factor alpha (TNF-α) and TNF-related apoptosis-inducing ligand (TRAIL). Other types of RBC damage, such as eryptotic damage, failed to induce necroptosis when combined with hCD59 crosslinking. This work sheds light on the requirements for this recently discovered PCD in RBCs and provides a clear picture of the biochemical mechanism of induction of RBC necroptosis.

Deletion of the membrane complement inhibitor CD59a drives age and gender-dependent alterations to bone phenotype in mice.

PubMed

Bloom, Anja C; Collins, Fraser L; Van't Hof, Rob J; Ryan, Elizabeth S; Jones, Emma; Hughes, Timothy R; Morgan, B Paul; Erlandsson, Malin; Bokarewa, Maria; Aeschlimann, Daniel; Evans, Bronwen A J; Williams, Anwen S

2016-03-01

Degenerative joint diseases such as osteoarthritis are characterised by aberrant region-specific bone formation and abnormal bone mineral content. A recent study suggested a role for the complement membrane attack complex in experimental models of osteoarthritis. Since CD59a is the principal regulator of the membrane attack complex in mice, we evaluated the impact of CD59a gene deletion upon maintenance of bone architecture. In vivo bone morphology analysis revealed that male CD59a-deficient mice have increased femur length and cortical bone volume, albeit with reduced bone mineral density. However, this phenomenon was not observed in female mice. Histomorphometric analysis of the trabecular bone showed increased rates of bone homeostasis, with both increased bone resorption and mineral apposition rate in CD59a-deficient male mice. When bone cells were studied in isolation, in vitro osteoclastogenesis was significantly increased in male CD59a-deficient mice, although osteoblast formation was not altered. Our data reveal, for the first time, that CD59a is a regulator of bone growth and homeostasis. CD59a ablation in male mice results in longer and wider bones, but with less density, which is likely a major contributing factor for their susceptibility to osteoarthritis. These findings increase our understanding of the role of complement regulation in degenerative arthritis. Copyright © 2016 Amgen Inc. Published by Elsevier Inc. All rights reserved.

CD73 Regulates Stemness and Epithelial-Mesenchymal Transition in Ovarian Cancer-Initiating Cells.

PubMed

Lupia, Michela; Angiolini, Francesca; Bertalot, Giovanni; Freddi, Stefano; Sachsenmeier, Kris F; Chisci, Elisa; Kutryb-Zajac, Barbara; Confalonieri, Stefano; Smolenski, Ryszard T; Giovannoni, Roberto; Colombo, Nicoletta; Bianchi, Fabrizio; Cavallaro, Ugo

2018-04-10

Cancer-initiating cells (CICs) have been implicated in tumor development and aggressiveness. In ovarian carcinoma (OC), CICs drive tumor formation, dissemination, and recurrence, as well as drug resistance, thus accounting for the high death-to-incidence ratio of this neoplasm. However, the molecular mechanisms that underlie such a pathogenic role of ovarian CICs (OCICs) remain elusive. Here, we have capitalized on primary cells either from OC or from its tissues of origin to obtain the transcriptomic profile associated with OCICs. Among the genes differentially expressed in OCICs, we focused on CD73, which encodes the membrane-associated 5'-ectonucleotidase. The genetic inactivation of CD73 in OC cells revealed that this molecule is causally involved in sphere formation and tumor initiation, thus emerging as a driver of OCIC function. Furthermore, functional inhibition of CD73 via either a chemical compound or a neutralizing antibody reduced sphere formation and tumorigenesis, highlighting the druggability of CD73 in the context of OCIC-directed therapies. The biological function of CD73 in OCICs required its enzymatic activity and involved adenosine signaling. Mechanistically, CD73 promotes the expression of stemness and epithelial-mesenchymal transition-associated genes, implying a regulation of OCIC function at the transcriptional level. CD73, therefore, is involved in OCIC biology and may represent a therapeutic target for innovative treatments aimed at OC eradication. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Numerical analysis on the synergy between electron cyclotron current drive and lower hybrid current drive in tokamak plasmas

NASA Astrophysics Data System (ADS)

Chen, S. Y.; Hong, B. B.; Liu, Y.; Lu, W.; Huang, J.; Tang, C. J.; Ding, X. T.; Zhang, X. J.; Hu, Y. J.

2012-11-01

The synergy between electron cyclotron current drive (ECCD) and lower hybrid current drive (LHCD) is investigated numerically with the parameters of the HL-2A tokamak. Based on the understanding of the synergy mechanisms, a high current driven efficiency or a desired radial current profile can be achieved through properly matching the parameters of ECCD and LHCD due to the flexibility of ECCD. Meanwhile, it is found that the total current driven by the electron cyclotron wave (ECW) and the lower hybrid wave (LHW) simultaneously can be smaller than the sum of the currents driven by the ECW and LHW separately, when the power of the ECW is much larger than the LHW power. One of the reasons leading to this phenomenon (referred to as negative synergy in this context) is that fast current-carrying electrons tend to be trapped, when the perpendicular velocity driven by the ECW is large and the parallel velocity decided by the LHW is correspondingly small.

Regulation of expression of the ligand for CD40 on T helper lymphocytes.

PubMed

Castle, B E; Kishimoto, K; Stearns, C; Brown, M L; Kehry, M R

1993-08-15

Activated Th cells deliver contact-dependent signals to resting B lymphocytes that initiate and drive B cell proliferation. Recently, a ligand for the B lymphocyte membrane protein, CD40, has been identified that delivers contact-dependent Th cell signals to B cells. A dimeric soluble form of CD40 was produced and used to further characterize the regulation of expression of the CD40 ligand. Expression of the CD40 ligand was rapidly induced after Th lymphocyte activation, and its stability depended upon whether Th cells were activated with soluble or plastic-bound stimuli. Th cells activated with soluble stimuli rapidly turned over cell-surface CD40 ligand whereas Th cells activated with plastic-bound stimuli exhibited more stable CD40 ligand expression for up to 48 h. Removal of activated Th cells from the plastic-bound stimulus resulted in a rapid turnover of CD40 ligand, suggesting that continuous stimulation could maintain CD40 ligand expression. Ligation by soluble CD40 could also stabilize expression of CD40 ligand on the Th cell surface. Both CD40 ligand and IL-2 were transiently synthesized from 1 to 12 h after Th cell activation and had similar kinetics of synthesis. In Con A-activated Th cells newly synthesized CD40 ligand exhibited an initial high turnover (1.5 h t1/2) and after 5 h of Th cell activation became more stable (10-h t1/2). In Th cells activated with plastic-bound anti-CD3, CD40 ligand exhibited a similar biphasic turnover except that the rapid turnover phase began significantly later. This delay could allow more time for newly synthesized CD40 ligand to assemble or associate with other molecules and thus become stabilized on the cell surface. Newly synthesized CD40 ligand in Con A-activated Th cells appeared to not be efficient in delivering Th cell-dependent contact signals to resting B cells, implying the need for assembly or accessory proteins. Regulation of CD40 ligand expression was consistent with all the characteristics of Th cell-delivered contact signals to B cells and may contribute to the high degree of specificity in B cell responses.

Lack of security of networked medical equipment in radiology.

PubMed

Moses, Vinu; Korah, Ipeson

2015-02-01

OBJECTIVE. There are few articles in the literature describing the security and safety aspects of networked medical equipment in radiology departments. Most radiologists are unaware of the security issues. We review the security of the networked medical equipment of a typical radiology department. MATERIALS AND METHODS. All networked medical equipment in a radiology department was scanned for vulnerabilities with a port scanner and a network vulnerability scanner, and the vulnerabilities were classified using the Common Vulnerability Scoring System. A network sniffer was used to capture and analyze traffic on the radiology network for exposure of confidential patient data. We reviewed the use of antivirus software and firewalls on the networked medical equipment. USB ports and CD and DVD drives in the networked medical equipment were tested to see whether they allowed unauthorized access. Implementation of the virtual private network (VPN) that vendors use to access the radiology network was reviewed. RESULTS. Most of the networked medical equipment in our radiology department used vulnerable software with open ports and services. Of the 144 items scanned, 64 (44%) had at least one critical vulnerability, and 119 (83%) had at least one high-risk vulnerability. Most equipment did not encrypt traffic and allowed capture of confidential patient data. Of the 144 items scanned, two (1%) used antivirus software and three (2%) had a firewall enabled. The USB ports were not secure on 49 of the 58 (84%) items with USB ports, and the CD or DVD drive was not secure on 17 of the 31 (55%) items with a CD or DVD drive. One of three vendors had an insecure implementation of VPN access. CONCLUSION. Radiologists and the medical industry need to urgently review and rectify the security issues in existing networked medical equipment. We hope that the results of our study and this article also raise awareness among radiologists about the security issues of networked medical equipment.

Effect of Intense Optical Excitation on Internal Electric Field Evolution in CdTe Gamma-Ray Detectors

NASA Astrophysics Data System (ADS)

Suzuki, K.; Ichinohe, Y.; Seto, S.

2018-03-01

The time-of-flight (TOF) transient currents in radiation detectors made of CdTe and Cd0.9Zn0.1Te (CZT) have been measured at several optical excitation intensities to investigate the effect of drifting carriers on the internal field. Both detectors show so-called space-charge-perturbed (SCP) current under intense optical excitation. A Monte Carlo (MC) simulation combined with an iterative solution of Poisson's equation is used to reproduce the observed currents under several bias voltages and excitation intensities. The SCP theory describes well the transient current in the CZT detector, whereas injection of holes from the anode and a corresponding reduction of the electron lifetime are further required to describe that in the CdTe detector. We visualize the temporal changes in the charge distribution and internal electric field profiles of both detectors.

Ex vivo identification and characterization of a population of CD13(high) CD105(+) CD45(-) mesenchymal stem cells in human bone marrow.

PubMed

Muñiz, Carmen; Teodosio, Cristina; Mayado, Andrea; Amaral, Ana Teresa; Matarraz, Sergio; Bárcena, Paloma; Sanchez, Maria Luz; Alvarez-Twose, Iván; Diez-Campelo, María; García-Montero, Andrés C; Blanco, Juan F; Del Cañizo, Maria Consuelo; del Pino Montes, Javier; Orfao, Alberto

2015-09-07

Mesenchymal stem cells (MSCs) are multipotent cells capable of self-renewal and multilineage differentiation. Their multipotential capacity and immunomodulatory properties have led to an increasing interest in their biological properties and therapeutic applications. Currently, the definition of MSCs relies on a combination of phenotypic, morphological and functional characteristics which are typically evaluated upon in vitro expansion, a process that may ultimately lead to modulation of the immunophenotypic, functional and/or genetic features of these cells. Therefore, at present there is great interest in providing markers and phenotypes for direct in vivo and ex vivo identification and isolation of MSCs. Multiparameter flow cytometry immunophenotypic studies were performed on 65 bone marrow (BM) samples for characterization of CD13(high) CD105(+) CD45(-) cells. Isolation and expansion of these cells was performed in a subset of samples in parallel to the expansion of MSCs from mononuclear cells following currently established procedures. The protein expression profile of these cells was further assessed on (paired) primary and in vitro expanded BM MSCs, and their adipogenic, chondrogenic and osteogenic differentiation potential was also determined. Our results show that the CD13(high) CD105(+) CD45(-) immunophenotype defines a minor subset of cells that are systematically present ex vivo in normal/reactive BM (n = 65) and that display immunophenotypic features, plastic adherence ability, and osteogenic, adipogenic and chondrogenic differentiation capacities fully compatible with those of MSCs. In addition, we also show that in vitro expansion of these cells modulates their immunophenotypic characteristics, including changes in the expression of markers currently used for the definition of MSCs, such as CD105, CD146 and HLA-DR. BM MSCs can be identified ex vivo in normal/reactive BM, based on a robust CD13(high) CD105(+) and CD45(-) immunophenotypic profile. Furthermore, in vitro expansion of these cells is associated with significant changes in the immunophenotypic profile of MSCs.

Opioid maintenance therapy restores CD4+ T cell function by normalizing CD4+CD25(high) regulatory T cell frequencies in heroin user.

PubMed

Riss, Gina-Lucia; Chang, Dae-In; Wevers, Carolin; Westendorf, Astrid M; Buer, Jan; Scherbaum, Norbert; Hansen, Wiebke

2012-08-01

There is an increasing body of evidence that heroin addiction is associated with severe alterations in immune function, which might contribute to an increased risk to contract infectious diseases like hepatitis B and C or HIV. However, the impact of heroin consumption on the CD4(+) T cell compartment is not well understood. Therefore, we analyzed the frequency and functional phenotype of CD4(+) T cells as well as immune-suppressive CD4(+)CD25(high) regulatory T cells (Tregs) isolated from the peripheral blood of opiate addicts currently abusing heroin (n=27) in comparison to healthy controls (n=25) and opiate addicts currently in opioid maintenance treatment (OMT; n=27). Interestingly, we detected a significant increase in the percentage of CD4(+)CD25(high) Tregs in the peripheral blood of heroin addicted patients in contrast to patients in OMT. The proliferative response of CD4(+) T cells upon stimulation with anti-CD3 and anti-CD28 antibodies was significantly decreased in heroin users, but could be restored by depletion of CD25(high) regulatory T cells from CD4(+) T cells to similar values as observed from healthy controls and patients in OMT. These results suggest that impaired immune responses observed in heroin users are related to the expansion of CD4(+)CD25(high) Tregs and more importantly, can be restored by OMT. Copyright © 2012 Elsevier Inc. All rights reserved.

Th1 differentiation drives the accumulation of intravascular, non-protective CD4 T cells during tuberculosis

PubMed Central

Sallin, Michelle A.; Sakai, Shunsuke; Kauffman, Keith D.; Young, Howard A.; Zhu, Jinfang; Barber, Daniel L.

2017-01-01

SUMMARY Recent data indicate that the differentiation state of Th1 cells determines their protective capacity against tuberculosis. Therefore, we examined the role of Th1 polarizing factors in the generation of protective and non-protective subsets of Mtb-specific Th1 cells. We find IL-12/23p40 promotes Th1 cell expansion and maturation beyond the CD73+CXCR3+T-betdim stage, and T-bet prevents deviation of Th1 cells into Th17 cells. Nevertheless, IL-12/23p40 and T-bet are also essential for the production of a prominent subset of intravascular CX3CR1+KLRG1+ Th1 cells that persists poorly and can neither migrate into the lung parenchyma nor control Mtb growth. Furthermore, T-bet suppresses development of CD69+CD103+ tissue resident phenotype effectors in lung. In contrast, Th1 cell-derived IFNγ inhibits the accumulation of intravascular CX3CR1+KLRG1+ Th1 cells. Thus, although IL-12 and T-bet are essential host survival factors, they simultaneously oppose lung CD4 T cell responses at several levels, demonstrating the dual nature of Th1 polarization in tuberculosis. PMID:28355562

Lab on a CD.

PubMed

Madou, Marc; Zoval, Jim; Jia, Guangyao; Kido, Horacio; Kim, Jitae; Kim, Nahui

2006-01-01

In this paper, centrifuge-based microfluidic platforms are reviewed and compared with other popular microfluidic propulsion methods. The underlying physical principles of centrifugal pumping in microfluidic systems are presented and the various centrifuge fluidic functions, such as valving, decanting, calibration, mixing, metering, heating, sample splitting, and separation, are introduced. Those fluidic functions have been combined with analytical measurement techniques, such as optical imaging, absorbance, and fluorescence spectroscopy and mass spectrometry, to make the centrifugal platform a powerful solution for medical and clinical diagnostics and high throughput screening (HTS) in drug discovery. Applications of a compact disc (CD)-based centrifuge platform analyzed in this review include two-point calibration of an optode-based ion sensor, an automated immunoassay platform, multiple parallel screening assays, and cellular-based assays. The use of modified commercial CD drives for high-resolution optical imaging is discussed as well. From a broader perspective, we compare technical barriers involved in applying microfluidics for sensing and diagnostic use and applying such techniques to HTS. The latter poses less challenges and explains why HTS products based on a CD fluidic platform are already commercially available, whereas we might have to wait longer to see commercial CD-based diagnostics.

Glycogen Synthase Kinase 3 Inactivation Drives T-bet-Mediated Downregulation of Co-receptor PD-1 to Enhance CD8+ Cytolytic T Cell Responses

PubMed Central

Taylor, Alison; Harker, James A.; Chanthong, Kittiphat; Stevenson, Philip G.; Zuniga, Elina I.; Rudd, Christopher E.

2016-01-01

Summary Despite the importance of the co-receptor PD-1 in T cell immunity, the upstream signaling pathway that regulates PD-1 expression has not been defined. Glycogen synthase kinase 3 (GSK-3, isoforms α and β) is a serine-threonine kinase implicated in cellular processes. Here, we identified GSK-3 as a key upstream kinase that regulated PD-1 expression in CD8+ T cells. GSK-3 siRNA downregulation, or inhibition by small molecules, blocked PD-1 expression, resulting in increased CD8+ cytotoxic T lymphocyte (CTL) function. Mechanistically, GSK-3 inactivation increased Tbx21 transcription, promoting enhanced T-bet expression and subsequent suppression of Pdcd1 (encodes PD-1) transcription in CD8+ CTLs. Injection of GSK-3 inhibitors in mice increased in vivo CD8+ OT-I CTL function and the clearance of murine gamma-herpesvirus 68 and lymphocytic choriomeningitis clone 13 and reversed T cell exhaustion. Our findings identify GSK-3 as a regulator of PD-1 expression and demonstrate the applicability of GSK-3 inhibitors in the modulation of PD-1 in immunotherapy. PMID:26885856

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

Harvey, R. W.

This DOE grant supported fusion energy research, a potential long-term solution to the world's energy needs. Magnetic fusion, exemplified by confinement of very hot ionized gases, i.e., plasmas, in donut-shaped tokamak vessels is a leading approach for this energy source. Thus far, a mixture of hydrogen isotopes has produced 10's of megawatts of fusion power for seconds in a tokamak reactor at Princeton Plasma Physics Laboratory in New Jersey. The research grant under consideration, ER54684, uses computer models to aid in understanding and projecting efficacy of heating and current drive sources in the National Spherical Torus Experiment, a tokamak variant,more » at PPPL. The NSTX experiment explores the physics of very tight aspect ratio, almost spherical tokamaks, aiming at producing steady-state fusion plasmas. The current drive is an integral part of the steady-state concept, maintaining the magnetic geometry in the steady-state tokamak. CompX further developed and applied models for radiofrequency (rf) heating and current drive for applications to NSTX. These models build on a 30 year development of rf ray tracing (the all-frequencies GENRAY code) and higher dimensional Fokker-Planck rf-collisional modeling (the 3D collisional-quasilinear CQL3D code) at CompX. Two mainline current-drive rf modes are proposed for injection into NSTX: (1) electron Bernstein wave (EBW), and (2) high harmonic fast wave (HHFW) modes. Both these current drive systems provide a means for the rf to access the especially high density plasma--termed high beta plasma--compared to the strength of the required magnetic fields. The CompX studies entailed detailed modeling of the EBW to calculate the efficiency of the current drive system, and to determine its range of flexibility for driving current at spatial locations in the plasma cross-section. The ray tracing showed penetration into NSTX bulk plasma, relatively efficient current drive, but a limited ability to produce current over the whole radial plasma cross-section. The actual EBW experiment will cost several million dollars, and remains in the proposal stage. The HHFW current drive system has been experimentally implemented on NSTX, and successfully drives substantial current. The understanding of the experiment is to be accomplished in terms of general concepts of rf current drive, and also detailed modeling of the experiment which can discern the various competing processes which necessarily occur simultaneously in the experiment. An early discovery of the CompX codes, GENRAY and CQL3D, was that there could be significant interference between the neutral beam injection fast ions in the machine (injected for plasma heating) and the HHFW energy. Under many NSTX experimental conditions, power which could go to the fast ions would then be unavailable for current drive by the desired HHFW interaction with electrons. This result has been born out by experiments; the modeling helps in understanding difficulties with HHFW current drive, and has enabled adjustment of the experiment to avoid interaction with neutral beam injected fast ions thereby achieving stronger HHFW current drive. The detailed physics modeling of the various competing processes is almost always required in fusion energy plasma physics, to ensure a reasonably accurate and certain interpretation of the experiment, enabling the confident design of future, more advanced experiments and ultimately a commercial fusion reactor. More recent work entails detailed investigation of the interaction of the HHFW radiation for fast ions, accounting for the particularly large radius orbits in NSTX, and correlations between multiple HHFW-ion interactions. The spherical aspect of the NSTX experiment emphasized particular physics such as the large orbits which are present to some degree in all tokamaks, but gives clearer clues on the resulting physics phenomena since competing physics effects are reduced.« less

Structural and compositional dependence of the CdTexSe1−x alloy layer photoactivity in CdTe-based solar cells

PubMed Central

Poplawsky, Jonathan D.; Guo, Wei; Paudel, Naba; Ng, Amy; More, Karren; Leonard, Donovan; Yan, Yanfa

2016-01-01

The published external quantum efficiency data of the world-record CdTe solar cell suggests that the device uses bandgap engineering, most likely with a CdTexSe1−x alloy layer to increase the short-circuit current and overall device efficiency. Here atom probe tomography, transmission electron microscopy and electron beam-induced current are used to clarify the dependence of Se content on the photoactive properties of CdTexSe1−x alloy layers in bandgap-graded CdTe solar cells. Four solar cells were prepared with 50, 100, 200 and 400 nm-thick CdSe layers to reveal the formation, growth, composition, structure and photoactivity of the CdTexSe1−x alloy with respect to the degree of Se diffusion. The results show that the CdTexSe1−x layer photoactivity is highly dependent on the crystalline structure of the alloy (zincblende versus wurtzite), which is also dependent on the Se and Te concentrations. PMID:27460872

Structural and compositional dependence of the CdTexSe 1-x alloy layer photoactivity in CdTe-based solar cells

DOE PAGES

Poplawsky, Jonathan D.; Guo, Wei; Paudel, Naba; ...

2016-07-27

The published external quantum efficiency data of the world-record CdTe solar cell suggests that the device uses bandgap engineering, most likely with a CdTe xSe 1₋x alloy layer to increase the short-circuit current and overall device efficiency. Here atom probe tomography, transmission electron microscopy and electron beam-induced current are used to clarify the dependence of Se content on the photoactive properties of CdTe xSe 1₋x alloy layers in bandgap-graded CdTe solar cells. Four solar cells were prepared with 50, 100, 200 and 400 nm-thick CdSe layers to reveal the formation, growth, composition, structure and photoactivity of the CdTe xSe 1₋xmore » alloy with respect to the degree of Se diffusion. Finally, the results show that the CdTe xSe 1₋x layer photoactivity is highly dependent on the crystalline structure of the alloy (zincblende versus wurtzite), which is also dependent on the Se and Te concentrations.« less

CD-ROM Growth: Unleashing the Potential.

ERIC Educational Resources Information Center

Nelson, Nancy Melin

1991-01-01

Discusses the use of CD-ROMs in library processing and public services units. Topics discussed include local area networks, workstations, network security, search software, disk operating systems (DOS), computer viruses, CD-ROM selection and acquisition, licensing, and standards. A sidebar lists current CD-ROM products appropriate for reference…

Imaging Technology in Libraries: Photo CD Offers New Possibilities.

ERIC Educational Resources Information Center

Beiser, Karl

1993-01-01

Describes Kodak's Photo CD technology, a format for the storage and retrieval of photographic images in electronic form. Highlights include current and future Photo CD formats; computer imaging technology; ownership issues; hardware for using Photo CD; software; library and information center applications, including image collections and…

Engagement of CD22 on B cells with the monoclonal antibody epratuzumab stimulates the phosphorylation of upstream inhibitory signals of the B cell receptor.

PubMed

Lumb, Simon; Fleischer, Sarah J; Wiedemann, Annika; Daridon, Capucine; Maloney, Alison; Shock, Anthony; Dörner, Thomas

2016-06-01

The binding of antigen to the B cell receptor (BCR) results in a cascade of signalling events that ultimately drive B cell activation. Uncontrolled B cell activation is regulated by negative feedback loops that involve inhibitory co-receptors such as CD22 and CD32B that exert their functions following phosphorylation of immunoreceptor tyrosine-based inhibition motifs (ITIMs). The CD22-targeted antibody epratuzumab has previously been shown to inhibit BCR-driven signalling events, but its effects on ITIM phosphorylation of CD22 and CD32B have not been properly evaluated. The present study therefore employed both immunoprecipitation and flow cytometry approaches to elucidate the effects of epratuzumab on direct phosphorylation of key tyrosine (Tyr) residues on both these proteins, using both transformed B cell lines and primary human B cells. Epratuzumab induced the phosphorylation of Tyr(822) on CD22 and enhanced its co-localisation with SHP-1. Additionally, in spite of high basal phosphorylation of other key ITIMs on CD22, in primary human B cells epratuzumab also enhanced phosphorylation of Tyr(807), a residue involved in the recruitment of Grb2. Such initiation events could explain the effects of epratuzumab on downstream signalling in B cells. Finally, we were able to demonstrate that epratuzumab stimulated the phosphorylation of Tyr(292) on the low affinity inhibitory Fc receptor CD32B which would further attenuate BCR-induced signalling. Together, these data demonstrate that engagement of CD22 with epratuzumab leads to the direct phosphorylation of key upstream inhibitory receptors of BCR signalling and may help to explain how this antibody modulates B cell function.

Physiological β-catenin signaling controls self-renewal networks and generation of stem-like cells from nasopharyngeal carcinoma.

PubMed

Cheng, Yue; Cheung, Arthur Kwok Leung; Ko, Josephine Mun Yee; Phoon, Yee Peng; Chiu, Pui Man; Lo, Paulisally Hau Yi; Waterman, Marian L; Lung, Maria Li

2013-09-27

A few reports suggested that low levels of Wnt signaling might drive cell reprogramming, but these studies could not establish a clear relationship between Wnt signaling and self-renewal networks. There are ongoing debates as to whether and how the Wnt/β-catenin signaling is involved in the control of pluripotency gene networks. Additionally, whether physiological β-catenin signaling generates stem-like cells through interactions with other pathways is as yet unclear. The nasopharyngeal carcinoma HONE1 cells have low expression of β-catenin and wild-type expression of p53, which provided a possibility to study regulatory mechanism of stemness networks induced by physiological levels of Wnt signaling in these cells. Introduction of increased β-catenin signaling, haploid expression of β-catenin under control by its natural regulators in transferred chromosome 3, resulted in activation of Wnt/β-catenin networks and dedifferentiation in HONE1 hybrid cell lines, but not in esophageal carcinoma SLMT1 hybrid cells that had high levels of endogenous β-catenin expression. HONE1 hybrid cells displayed stem cell-like properties, including enhancement of CD24(+) and CD44(+) populations and generation of spheres that were not observed in parental HONE1 cells. Signaling cascades were detected in HONE1 hybrid cells, including activation of p53- and RB1-mediated tumor suppressor pathways, up-regulation of Nanog-, Oct4-, Sox2-, and Klf4-mediated pluripotency networks, and altered E-cadherin expression in both in vitro and in vivo assays. qPCR array analyses further revealed interactions of physiological Wnt/β-catenin signaling with other pathways such as epithelial-mesenchymal transition, TGF-β, Activin, BMPR, FGFR2, and LIFR- and IL6ST-mediated cell self-renewal networks. Using β-catenin shRNA inhibitory assays, a dominant role for β-catenin in these cellular network activities was observed. The expression of cell surface markers such as CD9, CD24, CD44, CD90, and CD133 in generated spheres was progressively up-regulated compared to HONE1 hybrid cells. Thirty-four up-regulated components of the Wnt pathway were identified in these spheres. Wnt/β-catenin signaling regulates self-renewal networks and plays a central role in the control of pluripotency genes, tumor suppressive pathways and expression of cancer stem cell markers. This current study provides a novel platform to investigate the interaction of physiological Wnt/β-catenin signaling with stemness transition networks.

Th17 Cells and Activated Dendritic Cells Are Increased in Vitiligo Lesions

PubMed Central

Fuentes-Duculan, Judilyn; Moussai, Dariush; Gulati, Nicholas; Sullivan-Whalen, Mary; Gilleaudeau, Patricia; Cohen, Jules A.; Krueger, James G.

2011-01-01

Background Vitiligo is a common skin disorder, characterized by progressive skin de-pigmentation due to the loss of cutaneous melanocytes. The exact cause of melanocyte loss remains unclear, but a large number of observations have pointed to the important role of cellular immunity in vitiligo pathogenesis. Methodology/Principal Findings In this study, we characterized T cell and inflammation-related dermal dendritic cell (DC) subsets in pigmented non-lesional, leading edge and depigmented lesional vitiligo skin. By immunohistochemistry staining, we observed enhanced populations of CD11c+ myeloid dermal DCs and CD207+ Langerhans cells in leading edge vitiligo biopsies. DC-LAMP+ and CD1c+ sub-populations of dermal DCs expanded significantly in leading edge and lesional vitiligo skin. We also detected elevated tissue mRNA levels of IL-17A in leading edge skin biopsies of vitiligo patients, as well as IL-17A positive T cells by immunohistochemistry and immunofluorescence. Langerhans cells with activated inflammasomes were also noted in lesional vitiligo skin, along with increased IL-1ß mRNA, which suggest the potential of Langerhans cells to drive Th17 activation in vitiligo. Conclusions/Significance These studies provided direct tissue evidence that implicates active Th17 cells in vitiligo skin lesions. We characterized new cellular immune elements, in the active margins of vitiligo lesions (e.g. populations of epidermal and dermal dendritic cells subsets), which could potentially drive the inflammatory responses. PMID:21541348

Highly Simplified Reddish Orange Phosphorescent Organic Light-Emitting Diodes Incorporating a Novel Carrier- and Exciton-Confining Spiro-Exciplex-Forming Host for Reduced Efficiency Roll-off.

PubMed

Xu, Ting; Zhang, Ye-Xin; Wang, Bo; Huang, Chen-Chao; Murtaza, Imran; Meng, Hong; Liao, Liang-Sheng

2017-01-25

A novel exciplex-forming host is applied so as to design highly simplified reddish orange light-emitting diodes (OLEDs) with low driving voltage, high efficiency, and an extraordinarily low efficiency roll-off, by combining N,N-10-triphenyl-10H-spiro [acridine-9,9'-fluoren]-3'-amine (SAFDPA) with 4,7-diphenyl-1,10-phenanthroline (Bphen) doped with trivalent iridium complex bis(2-methyldibenzo[f,h]quinoxaline) (acetylacetonate)iridium(III) (Ir(MDQ) 2 (acac)). The reddish orange OLEDs achieve a strikingly high power efficiency (PE) of 31.80 lm/W with an ultralow threshold voltage of 2.24 V which is almost equal to the triplet energy level of the phosphorescent reddish orange emitting dopant. The power efficiency of the device with the exciplex-forming host is enhanced, achieving 36.2% mainly owing to the lower operating voltage by the novel exciplex forming cohost, compared with the reference device (23.54 lm/W). Moreover, the OLEDs show extraordinarily low current efficiency (CE) roll-off to 1.41% at the brightness from 500 to 5000 cd/m 2 with a maximal CE of 32.87 cd/A (EQE max = 11.01%). The devices display a good reddish orange color (CIE of (0.628, 0.372) at 500 cd/m 2 ) nearly without color shift with increasing brightness. Co-host architecture phosphorescent OLEDs show a simpler device structure, lower working voltage, and a better efficiency and stability than those of the reference devices without the cohost architecture, which helps to simplify the OLED structure, lower the cost, and popularize OLED technology.

Manipulation of a VEGF-Notch signaling circuit drives formation of functional vascular endothelial progenitors from human pluripotent stem cells

PubMed Central

Sahara, Makoto; Hansson, Emil M; Wernet, Oliver; Lui, Kathy O; Später, Daniela; Chien, Kenneth R

2014-01-01

Human pluripotent stem cell (hPSC)-derived endothelial lineage cells constitutes a promising source for therapeutic revascularization, but progress in this arena has been hampered by a lack of clinically-scalable differentiation protocols and inefficient formation of a functional vessel network integrating with the host circulation upon transplantation. Using a human embryonic stem cell reporter cell line, where green fluorescent protein expression is driven by an endothelial cell-specific VE-cadherin (VEC) promoter, we screened for > 60 bioactive small molecules that would promote endothelial differentiation, and found that administration of BMP4 and a GSK-3β inhibitor in an early phase and treatment with VEGF-A and inhibition of the Notch signaling pathway in a later phase led to efficient differentiation of hPSCs to the endothelial lineage within six days. This sequential approach generated > 50% conversion of hPSCs to endothelial cells (ECs), specifically VEC+CD31+CD34+CD14−KDRhigh endothelial progenitors (EPs) that exhibited higher angiogenic and clonogenic proliferation potential among endothelial lineage cells. Pharmaceutical inhibition or genetical knockdown of Notch signaling, in combination with VEGF-A treatment, resulted in efficient formation of EPs via KDR+ mesodermal precursors and blockade of the conversion of EPs to mature ECs. The generated EPs successfully formed functional capillary vessels in vivo with anastomosis to the host vessels when transplanted into immunocompromised mice. Manipulation of this VEGF-A-Notch signaling circuit in our protocol leads to rapid large-scale production of the hPSC-derived EPs by 12- to 20-fold vs current methods, which may serve as an attractive cell population for regenerative vascularization with superior vessel forming capability compared to mature ECs. PMID:24810299

Elevating the triplet energy levels of dibenzofuran-based ambipolar phosphine oxide hosts for ultralow-voltage-driven efficient blue electrophosphorescence: from D-A to D-π-A systems.

PubMed

Han, Chunmiao; Zhang, Zhensong; Xu, Hui; Li, Jing; Zhao, Yi; Yan, Pengfei; Liu, Shiyong

2013-01-21

A series of donor (D)-π-acceptor (A)-type phosphine-oxide hosts (DBF(x) POPhCz(n)), which were composed of phenylcarbazole, dibenzofuran (DBF), and diphenylphosphine-oxide (DPPO) moieties, were designed and synthesized. Phenyl π-spacer groups were inserted between the carbazolyl and DBF groups, which effectively weakened the charge transfer and triplet-excited-state extension. As the result, the first triplet energy levels (T(1)) of DBF(x)POPhCz(n) are elevated to about 3.0 eV, 0.1 eV higher than their D-A-type analogues. Nevertheless, the electrochemical analysis and DFT calculations demonstrated the ambipolar characteristics of DBF(x)POPhCz(n). The phenyl π spacers hardly influenced the frontier molecular orbital (FMO) energy levels and the carrier-transporting ability of the materials. Therefore, these D-π-A systems are endowed with higher T(1) states, as well as comparable electrical properties to D-A systems. Phosphorescent blue-light-emitting diodes (PHOLEDs) that were based on DBF(x)POPhCz(n) not only inherited the ultralow driving voltages (2.4 V for onset, about 2.8 V at 200 cd m(-2), and <3.4 V at 1000 cd m(-2)) but also had much-improved efficiencies, including about 26 cd A(-1) for current efficiency, 30 Lm W(-1) for power efficiency, and 13% for external quantum efficiency, which were more than twice the values of devices that are based on conventional unipolar host materials. This performance makes DBFDPOPhCz(n) among the best hosts for ultralow-voltage-driven blue PHOLEDs reported so far. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Computer-Aided Engineering for Electric-Drive Vehicle Batteries (CAEBAT)

Science.gov Websites

Laboratory Battery Design LLC CD-adapco EC Power ESim Ford General Motors (GM) Johnson Controls, Inc battery modeling" April 2013: R. Spotnitz, Design and Simulation of Spirally-Wound, Lithium-Ion Cells ;Effect of Tab Design on Large-Format Li-ion Cell Performance," Journal of Power Sources 257 70-79

Digital Holographic Memories

NASA Astrophysics Data System (ADS)

Hesselink, Lambertus; Orlov, Sergei S.

Optical data storage is a phenomenal success story. Since its introduction in the early 1980s, optical data storage devices have evolved from being focused primarily on music distribution, to becoming the prevailing data distribution and recording medium. Each year, billions of optical recordable and prerecorded disks are sold worldwide. Almost every computer today is shipped with a CD or DVD drive installed.

Assessing the role of peripheral CD8 T cells in neurocognitive impairment in HIV-infected men who have sex with men: data from the MSM Neurocog Study.

PubMed

Rawson, T M; Dubb, S; Pozniak, A; Kelleher, W P; Mandalia, S; Gazzard, B; Barber, T J

2015-02-01

Studies have suggested CD8 lymphocytes may be a possible marker for inflammation, which is believed to be a contributing factor to neurocognitive impairment. Individuals enrolled in the MSM Neurocog Study were analysed. Those with depression, anxiety or mood disorders were excluded. Individuals with neurocognitive impairment were identified using the Brief NeuroCognitive Screen and compared to those with normal scores. CD4 and CD8 T cell values and CD4:CD8 ratios were compared between groups. In all, 144 men, aged 18-50 years, were included in the analysis. Twenty were diagnosed with neurocognitive impairment. We were unable to identify any significant difference between current, nadir or peak CD4 and CD8 counts. CD4:CD8 ratios and CD4:CD8 ratio inversion (<1) were also found to be similar between both groups. However, neurocognitive impairment subjects were 8% more likely to have inversion of CD4:CD8 ratio and higher median peak CD8 cell counts reported compared to non-impaired subjects. Analysis of data from the MSM Neurocog Study, demonstrated trends in peripheral CD8 counts and CD4:CD8 ratios. However, we are unable to demonstrate any significant benefit. Plasma biomarkers of neurocognitive impairment in HIV-infected subjects would be of great benefit over current methods of invasive CSF analysis and technical neuroimaging used in the diagnosis of neurocognitive impairment. Future, prospective, longitudinal work with large numbers of neurocognitive impairment subjects is required to further investigate the role of peripheral CD8 T cells as markers of neurocognitive impairment. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Current-drive by lower hybrid waves in the presence of energetic alpha-particles

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

Fisch, N.J.; Rax, J.M.

1991-10-01

Many experiments have now proved the effectiveness of lower hybrid waves for driving toroidal current in tokamaks. The use of these waves, however, to provide all the current in a reactor is thought to be uncertain because the waves may not penetrate the center of the more energetic reactor plasma, and, if they did, the wave power may be absorbed by alpha particles rather than by electrons. This paper explores the conditions under which lower-hybrid waves might actually drive all the current. 26 refs.

Atypical Activin A and IL-10 Production Impairs Human CD16+ Monocyte Differentiation into Anti-Inflammatory Macrophages.

PubMed

González-Domínguez, Érika; Domínguez-Soto, Ángeles; Nieto, Concha; Flores-Sevilla, José Luis; Pacheco-Blanco, Mariana; Campos-Peña, Victoria; Meraz-Ríos, Marco A; Vega, Miguel A; Corbí, Ángel L; Sánchez-Torres, Carmen

2016-02-01

Human CD14(++)CD16(-) and CD14(+/lo)CD16(+) monocyte subsets comprise 85 and 15% of blood monocytes, respectively, and are thought to represent distinct stages in the monocyte differentiation pathway. However, the differentiation fates of both monocyte subsets along the macrophage (Mϕ) lineage have not yet been elucidated. We have now evaluated the potential of CD14(++) CD16(-) and CD16(+) monocytes to differentiate and to be primed toward pro- or anti-inflammatory Mϕs upon culture with GM-CSF or M-CSF, respectively (subsequently referred to as GM14, M14, GM16, or M16). Whereas GM16 and GM14 were phenotypic and functionally analogous, M16 displayed a more proinflammatory profile than did M14. Transcriptomic analyses evidenced that genes associated with M-CSF-driven Mϕ differentiation (including FOLR2, IL10, IGF1, and SERPINB2) are underrepresented in M16 with respect to M14. The preferential proinflammatory skewing of M16 relative to M14 was found to be mediated by the secretion of activin A and the low levels of IL-10 produced by M16. In fact, activin A receptor blockade during the M-CSF-driven differentiation of CD16(+) monocytes, or addition of IL-10-containing M14-conditioned medium, significantly enhanced their expression of anti-inflammatory-associated molecules while impairing their acquisition of proinflammatory-related markers. Thus, we propose that M-CSF drives CD14(++)CD16- monocyte differentiation into bona fide anti-inflammatory Mϕs in a self-autonomous manner, whereas M-CSF-treated CD16(+) monocytes generate Mϕs with a skewed proinflammatory profile by virtue of their high activin A expression unless additional anti-inflammatory stimuli such as IL-10 are provided. Copyright © 2016 by The American Association of Immunologists, Inc.

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

O-GlcNAc: a novel regulator of immunometabolism.

PubMed

Machacek, Miranda; Slawson, Chad; Fields, Patrick E

2018-06-01

The rapidly expanding field of immunometabolism focuses on how metabolism controls the function of immune cells. CD4 + T cells are essential for the adaptive immune response leading to the eradication of specific pathogens. However, when T cells are inappropriately over-active, they can drive autoimmunity, allergic disease, and chronic inflammation. The mechanisms by which metabolic changes influence function in CD4 + T cells are not fully understood. The post-translational protein modification, O-GlcNAc (O-linked β-N-acetylglucosamine), dynamically cycles on and off of intracellular proteins as cells respond to their environment and flux through metabolic pathways changes. As the rate of O-GlcNAc cycling fluctuates, protein function, stability, and/or localization can be affected. Thus, O-GlcNAc is critically poised at the nexus of cellular metabolism and function. This review highlights the intra- and extracellular metabolic factors that influence CD4 + T cell activation and differentiation and how O-GlcNAc regulates these processes. We also propose areas of future research that may illuminate O-GlcNAc's role in the plasticity and pathogenicity of CD4 + T cells and uncover new potential therapeutic targets.

Effect of Al doping on structural and mechanical properties of Ni-Cd ferrites

NASA Astrophysics Data System (ADS)

Shidaganal, Lata C.; Gandhad, Sheela S.; Hiremath, C. S.; Mathad, S. N.; Jeergal, P. R.; Pujar, R. B.

2018-05-01

Ferrites are ceramic magnetic materials which behave like a conventional ferromagnetic. Ni-Zn ferrites are commercially used as electromagnetic interfaces in hard disc drives, laptops and other electronic devices. Here we are going to report on the structural and mechanical properties of Al doped Ni-Cd ferrites synthesized by standard double sintering ceramic method by using AR grade Al oxide, Ni oxide, Cd oxide and ferric oxide in molar proportions with a general chemical formula Ni0.5 Cd0.5 Alx Fe2-x O4 where x=0.1 to 0.4.X-ray analysis confirms the formation of single phase FCC spinel structure. The decrease in lattice constant with Al concentration is attributed to Vegard's law. IR spectra indicate prominent absorption bands near 400cm-1and 600cm-1 which are assigned to fundamental vibrations of complexes in A and B sites respectively. SEM micrographs exhibit fine grains without segregation of impurities. The average grain diameter is found vary from 1.00µm to 0.9 µm which is in agreement with Vegard's law.

Influence of confinement layers in the emitting layer of the blue phosphorescent organic light-emitting diodes

NASA Astrophysics Data System (ADS)

Ji, Chang-Yan; Gu, Zheng-Tian; Kou, Zhi-Qi

2016-10-01

The electrical and optical properties of the blue phosphorescent organic light-emitting diodes (PHOLEDs) can be affected by the various structure of confinement layer in the emitting layer (EML). A series of devices with different electron or hole confinement layer (TCTA or Bphen) are fabricated, it is more effective to balance charge carriers injection for the device with the double electron confinement layers structure, the power efficiency and luminance can reach 17.7 lm/W (at 103 cd/m2) and 3536 cd/m2 (at 8 V). In case of the same double electron confinement layers, another series of devices with different profile of EML are fabricated by changing the confinement layers position, the power efficiency and luminance can be improved to 21.7 lm/W (at 103 cd/m2) and 7674 cd/m2 (at 8 V) when the thickness of EML separated by confinement layers increases gradually from the hole injection side to the electron injection side, the driving voltage can also be reduced.

Microstructural Evolution of Secondary Phases in the Cast Duplex Stainless Steels CD3MN and CD3MWCuN

NASA Astrophysics Data System (ADS)

Kim, Yoon-Jun; Ugurlu, Ozan; Jiang, Chao; Gleeson, Brian; Chumbley, L. Scott

2007-02-01

The isothermal formation behavior of secondary phases in two types of duplex stainless steels (DSS), CD3MN and CD3MWCuN, was characterized. Samples were heat treated from 1 minute to 30 days at temperatures from 700°C to 900°C. Small carbide (M23C6) and nitride (Cr2N) precipitates, together with the intermetallic phases sigma and chi, were observed using scanning electron microscopy (SEM) and confirmed by transmission electron microscopy (TEM) analyses. Based on SEM analysis, time-temperature-transformation (TTT) curves for the sigma and chi phases were determined by measuring their volume fractions from backscattered electron micrographs of heat-treated and quenched sample cross sections. Resulting TTT curves showed that the maximum formation temperature for chi is lower than that for sigma, while the time to reach 1 vol pct formation is much less for sigma than it is for chi. The thermodynamic driving forces associated with the sigma and chi formation were assessed using Thermo-Calc.

Maternal-Fetal rejection reactions are unconstrained in preeclamptic women.

PubMed

Nguyen, Tina A; Kahn, Daniel A; Loewendorf, Andrea I

2017-01-01

The risk factors for preeclampsia, extremes of maternal age, changing paternity, concomitant maternal autoimmunity, and/or birth intervals greater than 5 years, suggest an underlying immunopathology. We used peripheral blood and lymphocytes from the UteroPlacental Interface (UPI) of 3rd trimester healthy pregnant women in multicolor flow cytometry-and in vitro suppression assays. The major end-point was the characterization of activation markers, and potential effector functions of different CD4-and CD8 subsets as well as T regulatory cells (Treg). We observed a significant shift of peripheral CD4 -and CD8- T cells from naïve to memory phenotype in preeclamptic women compared to healthy pregnant women consistent with long-standing immune activation. While the proportions of the highly suppressive Cytokine and Activated Treg were increased in preeclampsia, Treg tolerance toward fetal antigens was dysfunctional. Thus, our observations indicate a long-standing inflammatory derangement driving immune activation in preeclampsia; in how far the Treg dysfunction is caused by/causes this immune activation in preeclampsia will be the object of future studies.

Immune regulation of systemic hypertension, pulmonary arterial hypertension, and preeclampsia: shared disease mechanisms and translational opportunities.

PubMed

Jafri, Salema; Ormiston, Mark L

2017-12-01

Systemic hypertension, preeclampsia, and pulmonary arterial hypertension (PAH) are diseases of high blood pressure in the systemic or pulmonary circulation. Beyond the well-defined contribution of more traditional pathophysiological mechanisms, such as changes in the renin-angiotensin-aldosterone system, to the development of these hypertensive disorders, there is substantial clinical evidence supporting an important role for inflammation and immunity in the pathogenesis of each of these three conditions. Over the last decade, work in small animal models, bearing targeted deficiencies in specific cytokines or immune cell subsets, has begun to clarify the immune-mediated mechanisms that drive changes in vascular structure and tone in hypertensive disease. By summarizing the clinical and experimental evidence supporting a contribution of the immune system to systemic hypertension, preeclampsia, and PAH, the current review highlights the cellular and molecular pathways that are common to all three hypertensive disorders. These mechanisms are centered on an imbalance in CD4 + helper T cell populations, defined by excessive Th17 responses and impaired T reg activity, as well as the excessive activation or impairment of additional immune cell types, including macrophages, dendritic cells, CD8 + T cells, B cells, and natural killer cells. The identification of common immune mechanisms in systemic hypertension, preeclampsia, and PAH raises the possibility of new therapeutic strategies that target the immune component of hypertension across multiple disorders. Copyright © 2017 the American Physiological Society.

Activation of human T cells in hypertension: Studies of Humanized Mice and Hypertensive Humans

PubMed Central

Itani, Hana A.; McMaster, William G.; Saleh, Mohamed A.; Nazarewicz, Rafal R.; Mikolajczyk, Tomasz P.; Kaszuba, Anna; Konior, Anna; Prejbisz, Aleksander; Januszewicz, Andrzej; Norlander, Allison E.; Chen, Wei; Bonami, Rachel H.; Marshall, Andrew F.; Poffenberger, Greg; Weyand, Cornelia M.; Madhur, Meena S.; Moore, Daniel J.; Harrison, David G.; Guzik, Tomasz J.

2016-01-01

Emerging evidence supports an important role for T cells in the genesis of hypertension. Because this work has predominantly been performed in experimental animals, we sought to determine whether human T cells are activated in hypertension. We employed a humanized mouse model in which the murine immune system is replaced by the human immune system. Angiotensin II increased systolic pressure to 162 mm Hg vs. 116 mm Hg for sham treated animals. Flow cytometry of thoracic lymph nodes, thoracic aorta and kidney revealed increased infiltration of human leukocytes (CD45+) and T lymphocytes (CD3+ and CD4+) in response to angiotensin II infusion. Interestingly, there was also an increase in the memory T cells (CD3+/CD45RO+) in the aortas and lymph nodes. Prevention of hypertension using hydralazine and hydrochlorothiazide prevented the accumulation of T cells in these tissues. Studies of isolated human T cells and monocytes indicated that angiotensin II had no direct effect on cytokine production by T cells or the ability of dendritic cells to drive T cell proliferation. We also observed an increase in circulating IL-17A producing CD4+ T cells and both CD4+ and CD8+ T cells that produce IFN-γ in hypertensive compared to normotensive humans. Thus, human T cells become activated and invade critical end-organ tissues in response to hypertension in a humanized mouse model. This response likely reflects the hypertensive milieu encountered in vivo and is not a direct effect of the hormone angiotensin II. PMID:27217403

Activation of Human T Cells in Hypertension: Studies of Humanized Mice and Hypertensive Humans.

PubMed

Itani, Hana A; McMaster, William G; Saleh, Mohamed A; Nazarewicz, Rafal R; Mikolajczyk, Tomasz P; Kaszuba, Anna M; Konior, Anna; Prejbisz, Aleksander; Januszewicz, Andrzej; Norlander, Allison E; Chen, Wei; Bonami, Rachel H; Marshall, Andrew F; Poffenberger, Greg; Weyand, Cornelia M; Madhur, Meena S; Moore, Daniel J; Harrison, David G; Guzik, Tomasz J

2016-07-01

Emerging evidence supports an important role for T cells in the genesis of hypertension. Because this work has predominantly been performed in experimental animals, we sought to determine whether human T cells are activated in hypertension. We used a humanized mouse model in which the murine immune system is replaced by the human immune system. Angiotensin II increased systolic pressure to 162 versus 116 mm Hg for sham-treated animals. Flow cytometry of thoracic lymph nodes, thoracic aorta, and kidney revealed increased infiltration of human leukocytes (CD45(+)) and T lymphocytes (CD3(+) and CD4(+)) in response to angiotensin II infusion. Interestingly, there was also an increase in the memory T cells (CD3(+)/CD45RO(+)) in the aortas and lymph nodes. Prevention of hypertension using hydralazine and hydrochlorothiazide prevented the accumulation of T cells in these tissues. Studies of isolated human T cells and monocytes indicated that angiotensin II had no direct effect on cytokine production by T cells or the ability of dendritic cells to drive T-cell proliferation. We also observed an increase in circulating interleukin-17A producing CD4(+) T cells and both CD4(+) and CD8(+) T cells that produce interferon-γ in hypertensive compared with normotensive humans. Thus, human T cells become activated and invade critical end-organ tissues in response to hypertension in a humanized mouse model. This response likely reflects the hypertensive milieu encountered in vivo and is not a direct effect of the hormone angiotensin II. © 2016 American Heart Association, Inc.

Is the gut the major source of virus in early simian immunodeficiency virus infection?

PubMed

Lay, Matthew D H; Petravic, Janka; Gordon, Shari N; Engram, Jessica; Silvestri, Guido; Davenport, Miles P

2009-08-01

The acute phases of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection are characterized by rapid and profound depletion of CD4+ T cells from the guts of infected individuals. The large number of CD4+ T cells in the gut (a large fraction of which are activated and express the HIV/SIV coreceptor CCR5), the high level of infection of these cells, and the temporal coincidence of this CD4+ T-cell depletion with the peak of virus in plasma in acute infection suggest that the intestinal mucosa may be the major source of virus driving the peak viral load. Here, we used data on CD4+ T-cell proportions in the lamina propria of the rectums of SIV-infected rhesus macaques (which progress to AIDS) and sooty mangabeys (which do not progress) to show that in both species, the depletion of CD4+ T cells from this mucosal site and its maximum loss rate are often observed several days before the peak in viral load, with few CD4+ T cells remaining in the rectum by the time of peak viral load. In contrast, the maximum loss rate of CD4+ T cells from bronchoalveolar lavage specimens and lymph nodes coincides with the peak in virus. Analysis of the kinetics of depletion suggests that, in both rhesus macaques and sooty mangabeys, CD4+ T cells in the intestinal mucosa are a highly susceptible population for infection but not a major source of plasma virus in acute SIV infection.

Is the Gut the Major Source of Virus in Early Simian Immunodeficiency Virus Infection? ▿

PubMed Central

Lay, Matthew D. H.; Petravic, Janka; Gordon, Shari N.; Engram, Jessica; Silvestri, Guido; Davenport, Miles P.

2009-01-01

The acute phases of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection are characterized by rapid and profound depletion of CD4+ T cells from the guts of infected individuals. The large number of CD4+ T cells in the gut (a large fraction of which are activated and express the HIV/SIV coreceptor CCR5), the high level of infection of these cells, and the temporal coincidence of this CD4+ T-cell depletion with the peak of virus in plasma in acute infection suggest that the intestinal mucosa may be the major source of virus driving the peak viral load. Here, we used data on CD4+ T-cell proportions in the lamina propria of the rectums of SIV-infected rhesus macaques (which progress to AIDS) and sooty mangabeys (which do not progress) to show that in both species, the depletion of CD4+ T cells from this mucosal site and its maximum loss rate are often observed several days before the peak in viral load, with few CD4+ T cells remaining in the rectum by the time of peak viral load. In contrast, the maximum loss rate of CD4+ T cells from bronchoalveolar lavage specimens and lymph nodes coincides with the peak in virus. Analysis of the kinetics of depletion suggests that, in both rhesus macaques and sooty mangabeys, CD4+ T cells in the intestinal mucosa are a highly susceptible population for infection but not a major source of plasma virus in acute SIV infection. PMID:19458001

A prospective study of appetite and food craving in 30 patients with Cushing's disease.

PubMed

Geer, Eliza B; Lalazar, Yelena; Couto, Lizette M; Cohen, Vanessa; Lipton, Lianna R; Shi, Wei; Bagiella, Emilia; Conwell, Irene; Bederson, Joshua; Kostadinov, Jane; Post, Kalmon D; Freda, Pamela U

2016-04-01

Glucocorticoid (GC) exposure increases food intake, but the mechanisms in humans are not known. Investigation of appetite and food craving has not been done in patients with chronic GC exposure due to Cushing's disease (CD), either before or after treatment, and could provide insight into mechanisms of food intake and obesity in these patients. To examine whether surgical remission of CD changes appetite (prospective consumption, hunger, satisfaction, and fullness) and food cravings (sweet, salty, fatty, and savory); and to identify predictors of appetite and craving in CD remission. 30 CD patients, mean age 40.0 years (range 17-70), mean BMI 32.3 ± 6.4, were prospectively studied before and at a mean of 17.4 mo. after remission. At each visit fasting and post-test meal (50% carbohydrate, 35% protein, 15% fat) appetite and craving scores were assessed. Remission decreased prospective consumption, sweet and savory craving (p < 0.05), but did not change hunger, satisfaction, fullness, or fat craving, despite decreases in BMI and fat mass. In CD remission, serum cortisol predicted lower satisfaction and fullness, and masses of abdominal fat depots predicted higher hunger and consumption (p < 0.05). Chronic GC exposure in CD patients may stimulate the drive to eat by enhancing craving, rather than regulating the sensation of hunger. Continued alterations in appetite regulation due to abdominal fat mass and circulating cortisol could play a role in the cardiovascular and metabolic risk that has been reported in CD patients despite remission.

Vitamin C treatment of mouse bone marrow-derived dendritic cells enhanced CD8(+) memory T cell production capacity of these cells in vivo.

PubMed

Jeong, Young-Joo; Kim, Jin-Hee; Hong, Jun-Man; Kang, Jae Seung; Kim, Hang-Rae; Lee, Wang Jae; Hwang, Young-il

2014-07-01

Vitamin C has been found to stimulate dendritic cells (DCs) to secrete more IL-12 and thereby drive naïve CD4(+) T cells to differentiate into Th1 cells. In the present study, we evaluated the effect of these vitamin C-treated DCs on CD8(+) T cell differentiation both in vitro and in vivo. Mouse bone marrow-derived DCs were prepared in the presence of GM-CSF and IL-15. With vitamin C treatment, these DCs, when LPS-stimulated, secreted more IL-12p70 and IL-15 than did untreated DCs. And when co-cultured with T cells, they yielded a higher frequency of IFN-γ(+) CD8(+) T cells. Moreover, we found that administering vitamin C-treated and tumor lysate-loaded DCs into mice yielded a higher frequency of CD44(high) CD62L(low) CD8(+) effector and effector memory T cells, which showed an increased ex vivo killing effect of the tumor cells. These DCs also elicited enhanced protective effects against inoculated tumor cells, most probably by way of the increased cytotoxic T cells, as was revealed by the decreased growth of the inoculated tumor cells in these mice. This ex vivo vitamin C treatment effect on DCs can be considered as a strategy for boosting DC vaccination potency against tumors. Copyright © 2014 Elsevier GmbH. All rights reserved.

Coeliac Disease – New Pathophysiological Findings and Their Implications for Therapy

PubMed Central

Stein, Jürgen; Schuppan, Detlef

2014-01-01

Summary Coeliac disease (CD) is one of the most common diseases worldwide, resulting from a combination of environmental (gluten) and genetic (human leucocyte antigen (HLA) and non-HLA genes) factors. Depending on the geographical location, the prevalence of CD has been estimated to approximate 0.5-1%. The only treatment currently available for CD is a gluten-free diet (GFD) excluding gluten-containing cereals such as wheat, rye, and barley, and other foodstuffs with natural or added gluten. However, adherence rates and patient acceptance are often poor. Moreover, even in fully adherent patients, the diet may fail to induce clinical or histological improvement. Hence, it is unsurprising that studies show CD patients to be highly interested in non-dietary alternatives. The following review focuses on current pathophysiological concepts of CD, spotlighting those pathways which may serve as new possible, non-dietary therapeutic targets in the treatment of CD. PMID:26288589

Base drive circuit for a four-terminal power Darlington

DOEpatents

Lee, Fred C.; Carter, Roy A.

1983-01-01

A high power switching circuit which utilizes a four-terminal Darlington transistor block to improve switching speed, particularly in rapid turn-off. Two independent reverse drive currents are utilized during turn off in order to expel the minority carriers of the Darlington pair at their own charge sweep-out rate. The reverse drive current may be provided by a current transformer, the secondary of which is tapped to the base terminal of the power stage of the Darlington block. In one application, the switching circuit is used in each power switching element in a chopper-inverter drive of an electric vehicle propulsion system.

Current Research Activities in Drive System Technology in Support of the NASA Rotorcraft Program

NASA Technical Reports Server (NTRS)

Handschuh, Robert F.; Zakrajsek, James J.

2006-01-01

Drive system technology is a key area for improving rotorcraft performance, noise/vibration reduction, and reducing operational and manufacturing costs. An overview of current research areas that support the NASA Rotorcraft Program will be provided. Work in drive system technology is mainly focused within three research areas: advanced components, thermal behavior/emergency lubrication system operation, and diagnostics/prognostics (also known as Health and Usage Monitoring Systems (HUMS)). Current research activities in each of these activities will be presented. Also, an overview of the conceptual drive system requirements and possible arrangements for the Heavy Lift Rotorcraft program will be reviewed.

A Yellow-Emitting Homoleptic Iridium(III) Complex Constructed from a Multifunctional Spiro Ligand for Highly Efficient Phosphorescent Organic Light-Emitting Diodes.

PubMed

Ren, Bao-Yi; Guo, Run-Da; Zhong, Dao-Kun; Ou, Chang-Jin; Xiong, Gang; Zhao, Xiang-Hua; Sun, Ya-Guang; Jurow, Matthew; Kang, Jun; Zhao, Yi; Li, Sheng-Biao; You, Li-Xin; Wang, Lin-Wang; Liu, Yi; Huang, Wei

2017-07-17

To suppress concentration quenching and to improve charge-carrier injection/transport in the emission layer (EML) of phosphorescent organic light-emitting diodes (PhOLEDs), a facial homoleptic iridium(III) complex emitter with amorphous characteristics was designed and prepared in one step from a multifunctional spiro ligand containing spiro[fluorene-9,9'-xanthene] (SFX) unit. Single-crystal X-ray analysis of the resulting fac-Ir(SFXpy) 3 complex revealed an enlarged Ir···Ir distance and negligible intermolecular π-π interactions between the spiro ligands. The emitter exhibits yellow emission and almost equal energy levels compared to the commercial phosphor iridium(III) bis(4-phenylthieno[3,2-c]pyridinato-N,C 2 ')acetylacetonate (PO-01). Dry-processed devices using a common host, 4,4'-bis(N-carbazolyl)-1,1'-biphenyl, and the fac-Ir(SFXpy) 3 emitter at a doping concentration of 15 wt % exhibited a peak performance of 46.2 cd A -1 , 36.3 lm W -1 , and 12.1% for the current efficiency (CE), power efficiency (PE), and external quantum efficiency (EQE), respectively. Compared to control devices using PO-01 as the dopant, the fac-Ir(SFXpy) 3 -based devices remained superior in the doping range between 8 and 15 wt %. The current densities went up with increasing doping concentration at the same driving voltage, while the roll-offs remain relatively low even at high doping levels. The superior performance of the new emitter-based devices was ascribed to key roles of the spiro ligand for suppressing aggregation and assisting charge-carrier injection/transport. Benefiting from the amorphous stability of the emitter, the wet-processed device also exhibited respectful CE, PE, and EQE of 32.2 cd A -1 , 22.1 lm W -1 , and 11.3%, respectively, while the EQE roll-off was as low as 1.7% at the luminance of 1000 cd m -2 . The three-dimensional geometry and binary-conjugation features render SFX the ideal multifunctional module for suppressing concentration quenching, facilitating charge-carrier injection/transport, and improving the amorphous stability of iridium(III)-based phosphorescent emitters.

Influence of driving frequency on discharge modes in a dielectric-barrier discharge with multiple current pulses

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

Jiang, Weiman; Tang, Jie; Wang, Yishan

2013-07-15

A one-dimensional self-consistent fluid model was employed to investigate the effect of the driving frequency on the discharge modes in atmospheric-pressure argon discharge with multiple current pulses. The discharge mode was discussed in detail not only at current peaks but also between two adjacent peaks. The simulation results show that different transitions between the Townsend and glow modes during the discharge take place with the driving frequency increased. A complicated transition from the Townsend mode, through glow, Townsend, and glow, and finally back to the Townsend one is found in the discharge with the driving frequency of 8 kHz. Theremore » is a tendency of transition from the Townsend to glow mode for the discharge both at the current peaks and troughs with the increasing frequency. The discharge in the half period can all along operate in the glow mode with the driving frequency high enough. This is resulted from the preservation of more electrons in the gas gap and acquisition of more electron energy from the swiftly varying electric field with the increase in driving frequency. Comparison of the spatial and temporal evolutions of the electron density at different driving frequencies indicates that the increment of the driving frequency allows the plasma chemistry to be enhanced. This electrical characteristic is important for the applications, such as surface treatment and biomedical sterilization.« less

Cutaneous T cell lymphoma: Current practices in blood assessment and the utility of T-cell receptor Vβ chain restriction

PubMed Central

Gibson, Juliet F; Huang, Jing; Liu, Kristina J; Carlson, Kacie R; Foss, Francine; Choi, Jaehyuk; Edelson, Richard; Hussong, Jerry W.; Mohl, Ramsey; Hill, Sally; Girardi, Sally

2016-01-01

Background Accurate quantification of malignant cells in the peripheral blood of patients with cutaneous T cell lymphoma (CTCL) is important for early detection, prognosis, and monitoring disease burden. Objective Determine the spectrum of current clinical practices; critically evaluate elements of current ISCL B1 and B2 staging criteria; and assess the potential role of TCR-Vβ analysis by flow cytometry. Methods We assessed current clinical practices by survey, and performed a retrospective analysis of 161 patients evaluated at Yale (2011-2014) to compare the sensitivity, specificity, PPV, and NPV of parameters for ISCL B2 staging. Results There was heterogeneity in clinical practices among institutions. ISCL B1 criteria did not capture five Yale cohort patients with immunophenotypic abnormalities who later progressed. TCR-Vβ testing was more specific than PCR and aided diagnosis in detecting clonality, but was of limited benefit in quantification of tumor burden. Limitations Because of limited follow-up involving a single center, further investigation will be necessary to conclude whether our proposed diagnostic algorithm is of general clinical benefit. Conclusion We propose further study of “modified B1 criteria”: CD4/CD8 ratio ≥5, %CD4+/CD26- ≥ 20%, %CD4+/CD7- ≥ 20%, with evidence of clonality. TCR-Vβ testing should be considered in future diagnostic and staging algorithms. PMID:26874819

Persistent viral infection in humans can drive high frequency low-affinity T-cell expansions

PubMed Central

Khan, Naeem; Cobbold, Mark; Cummerson, Joanne; Moss, Paul A H

2010-01-01

CD8 T cells that recognize cytomegalovirus (CMV) -encoded peptides can be readily detected by staining with human leucocyte antigen (HLA) –peptide tetramers. These cells are invariably highly differentiated effector memory cells with high avidity T-cell receptors (TCR). In this report we demonstrate an HLA-A*0201 restricted CMV-specific CD8 T-cell response (designated YVL) that represents several percent of the CD8 T-cell subset, yet fails to bind tetrameric major histocompatibility complex (MHC) ligands. However, these tetramer-negative cells are both phenotypically and functionally similar to other CMV-specific CD8 T cells. YVL peptide-specific CD8 T-cell clones were generated and found to be of high avidity in both cytotoxicity and interferon-γ (IFN-γ) assays, and comparable with other CMV peptide-specific CD8 T-cell clones. However, under conditions of CD8 blockade, the response was almost nullified even at very high ligand concentrations. This was also the case in IFN-γ experiments using peripheral blood mononuclear cells stimulated with peptide ex vivo. In contrast, all other CMV specificities (tetramer-positive) displayed minimal or only partial CD8 dependence. This suggests that YVL-specific responses depict a low-affinity TCR–MHC–peptide interaction, that is compensated by substantial CD8 involvement for functional purposes, yet cannot engage multivalent soluble ligands for ex vivo analysis. It is interesting that such a phenomenon is apparent in the face of a persistent virus infection such as CMV, where the responding cells represent an immunodominant response in that individual and may present a highly differentiated effector phenotype. PMID:20722762

Bach2 Controls Homeostasis of Eosinophils by Restricting the Type-2 Helper Function of T Cells.

PubMed

Sato, Yuki; Kato, Hiroki; Ebina-Shibuya, Risa; Itoh-Nakadai, Ari; Okuyama, Ryuhei; Igarashi, Kazuhiko

2017-03-01

Bach2 is a transcription factor which represses its target genes and plays important roles in the differentiation of B and T lymphoid cells. Bach2-deficient (KO) mice develop severe pulmonary alveolar proteinosis, which is associated with increased numbers of granulocytes and T cells. Bach2 is essential for the regulation of T cells, but its role in the regulation of granulocytes is not clear. Here, we observed increased numbers of eosinophils but not neutrophils in the bone marrow, spleen, peripheral blood, and bronchoalveolar lavage fluids of Bach2 KO mice compared with those of wild-type (WT) mice. Upon co-transplantation of the bone marrow cells from CD45.2 Bach2 KO and CD45.1/CD45.2 double-positive WT mice to irradiated WT CD45.1/CD45.2 mice, the reconstituted numbers of eosinophils were similar between Bach2 KO and WT cells. These results showed that the deficiency of Bach2 in eosinophils did not directly drive the differentiation of eosinophils. To investigate the effect of Bach2 KO CD4 + T cells upon eosinophils, we analyzed Rag2/Bach2-double deficient (dKO) mice which lack lymphocytes including CD4 + T cells. Rag2/Bach2 dKO mice did not show any increase in the numbers of eosinophils. Importantly, Bach2 KO mice showed an increase of interleukin-5 (Il-5) in the sera compared with WT mice. These results suggest that up-regulated functions of CD4 + T cells including secretion of Il-5 resulted in proliferation and/or migration to peripheral tissues of eosinophils in Bach2 KO mice. We propose that Bach2 controls homeostasis of eosinophils via restricting the production of Il-5 in CD4 + T cells.

Role of CD14 in responses to clinical isolates of Escherichia coli: effects of K1 capsule expression.

PubMed

Metkar, Shalaka; Awasthi, Shanjana; Denamur, Erick; Kim, Kwang Sik; Gangloff, Sophie C; Teichberg, Saul; Haziot, Alain; Silver, Jack; Goyert, Sanna M

2007-11-01

Severe bacterial infections leading to sepsis or septic shock can be induced by bacteria that utilize different factors to drive pathogenicity and/or virulence, leading to disease in the host. One major factor expressed by all clinical isolates of gram-negative bacteria is lipopolysaccharide (LPS); a second factor expressed by some Escherichia coli strains is a K1 polysaccharide capsule. To determine the role of the CD14 LPS receptor in the pathogenic effects of naturally occurring E. coli, the responses of CD14-/- and CD14+/+ mice to three different isolates of E. coli obtained from sepsis patients were compared; two isolates express both smooth LPS and the K1 antigen, while the third isolate expresses only LPS and is negative for K1. An additional K1-positive isolate obtained from a newborn with meningitis and a K1-negative isogenic mutant of this strain were also used for these studies. CD14-/- mice were resistant to the lethal effects of the K1-negative isolates. This resistance was accompanied by significantly lower levels of systemic tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) in these mice than in CD14+/+ mice, enhanced clearance of the bacteria, and significantly fewer additional gross symptoms. In contrast, CD14-/- mice were as sensitive as CD14+/+ mice to the lethal effects of the K1-positive isolates, even though they had significantly lower levels of TNF-alpha and IL-6 than CD14+/+ mice. These studies show that different bacterial isolates can use distinctly different mechanisms to cause disease and suggest that new, nonantibiotic therapeutics need to be directed against multiple targets.

Current status of EVA degradation in Si modules and interface stability in CdTe/CdS modules

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

Czanderna, A.W.

1994-06-30

The goals, objectives, background, technical approach, status, and accomplishments on the PV Module Reliability Research Task are summarized for FY 1993. The accomplishments are reported in two elements, ethylene vinyl acetate (EVA) degradation and stability in CdTe/CdS modules. The EVA results are presented under the headings modified EVA and potential EVA replacements, degradation mechanisms, efficiency losses from yellowed EVA, and equipment acquisitions. The results on CdTe/CdS modules are presented under subheadings of stability of the SnO[sub 2]/CdS interface and degradation at the CdTe/CdS interface.

A current drive by using the fast wave in frequency range higher than two timeslower hybrid resonance frequency on tokamaks

NASA Astrophysics Data System (ADS)

Kim, Sun Ho; Hwang, Yong Seok; Jeong, Seung Ho; Wang, Son Jong; Kwak, Jong Gu

2017-10-01

An efficient current drive scheme in central or off-axis region is required for the steady state operation of tokamak fusion reactors. The current drive by using the fast wave in frequency range higher than two times lower hybrid resonance (w>2wlh) could be such a scheme in high density, high temperature reactor-grade tokamak plasmas. First, it has relatively higher parallel electric field to the magnetic field favorable to the current generation, compared to fast waves in other frequency range. Second, it can deeply penetrate into high density plasmas compared to the slow wave in the same frequency range. Third, parasitic coupling to the slow wave can contribute also to the current drive avoiding parametric instability, thermal mode conversion and ion heating occured in the frequency range w<2wlh. In this study, the propagation boundary, accessibility, and the energy flow of the fast wave are given via cold dispersion relation and group velocity. The power absorption and current drive efficiency are discussed qualitatively through the hot dispersion relation and the polarization. Finally, those characteristics are confirmed with ray tracing code GENRAY for the KSTAR plasmas.

New Technique of AC drive in Tokamak using Permanent Magnets

NASA Astrophysics Data System (ADS)

Matteucci, Jackson; Zolfaghari, Ali

2013-10-01

This study investigates a new technique of capturing the rotational energy of alternating permanent magnets in order to inductively drive an alternating current in tokamak devices. The use of rotational motion bypasses many of the pitfalls seen in typical inductive and non-inductive current drives. Three specific designs are presented and assessed in the following criteria: the profile of the current generated, the RMS loop voltage generated as compared to the RMS power required to maintain it, the system's feasibility from an engineering perspective. All of the analysis has been done under ideal E&M conditions using the Maxwell 3D program. Preliminary results indicate that it is possible to produce an over 99% purely toroidal current with a RMS d Φ/dt of over 150 Tm2/s, driven by 20 MW or less of rotational power. The proposed mechanism demonstrates several key advantages including an efficient mechanical drive system, the generation of pure toroidal currents, and the potential for a quasi-steady state fusion reactor. The following quantities are presented for various driving frequencies and magnet strengths: plasma current generated, loop voltage, torque and power required. This project has been supported by DOE Funding under the SULI program.

Quantum dot solar cells. Tuning photoresponse through size and shape control of CdSe-TiO2 architecture.

PubMed

Kongkanand, Anusorn; Tvrdy, Kevin; Takechi, Kensuke; Kuno, Masaru; Kamat, Prashant V

2008-03-26

Different-sized CdSe quantum dots have been assembled on TiO2 films composed of particle and nanotube morphologies using a bifunctional linker molecule. Upon band-gap excitation, CdSe quantum dots inject electrons into TiO2 nanoparticles and nanotubes, thus enabling the generation of photocurrent in a photoelectrochemical solar cell. The results presented in this study highlight two major findings: (i) ability to tune the photoelectrochemical response and photoconversion efficiency via size control of CdSe quantum dots and (ii) improvement in the photoconversion efficiency by facilitating the charge transport through TiO2 nanotube architecture. The maximum IPCE (photon-to-charge carrier generation efficiency) obtained with 3 nm diameter CdSe nanoparticles was 35% for particulate TiO2 and 45% for tubular TiO2 morphology. The maximum IPCE observed at the excitonic band increases with decreasing particle size, whereas the shift in the conduction band to more negative potentials increases the driving force and favors fast electron injection. The maximum power-conversion efficiency

Divergent Roles of Interferon-γ and Innate Lymphoid Cells in Innate and Adaptive Immune Cell-Mediated Intestinal Inflammation.

PubMed

Brasseit, Jennifer; Kwong Chung, Cheong K C; Noti, Mario; Zysset, Daniel; Hoheisel-Dickgreber, Nina; Genitsch, Vera; Corazza, Nadia; Mueller, Christoph

2018-01-01

Aberrant interferon gamma (IFNγ) expression is associated with the pathogenesis of numerous autoimmune- and inflammatory disorders, including inflammatory bowel diseases (IBD). However, the requirement of IFNγ for the pathogenesis of chronic intestinal inflammation remains controversial. The aim of this study was thus to investigate the role of IFNγ in experimental mouse models of innate and adaptive immune cell-mediated intestinal inflammation using genetically and microbiota-stabilized hosts. While we find that IFNγ drives acute intestinal inflammation in the anti-CD40 colitis model in an innate lymphoid cell (ILC)-dependent manner, IFNγ secreted by both transferred CD4 T cells and/or cells of the lymphopenic Rag1 -/- recipient mice was dispensable for CD4 T cell-mediated colitis. In the absence of IFNγ, intestinal inflammation in CD4 T cell recipient mice was associated with enhanced IL17 responses; consequently, targeting IL17 signaling in IFNγ-deficient mice reduced T cell-mediated colitis. Intriguingly, in contrast to the anti-CD40 model of colitis, depletion of ILC in the Rag1 -/- recipients of colitogenic CD4 T cells did not prevent induction of colonic inflammation. Together, our findings demonstrate that IFNγ represents an essential, or a redundant, pro-inflammatory cytokine for the induction of intestinal inflammation, depending on the experimental mouse model used and on the nature of the critical disease inducing immune cell populations involved.

Engineering antigens for in situ erythrocyte binding induces T-cell deletion.

PubMed

Kontos, Stephan; Kourtis, Iraklis C; Dane, Karen Y; Hubbell, Jeffrey A

2013-01-02

Antigens derived from apoptotic cell debris can drive clonal T-cell deletion or anergy, and antigens chemically coupled ex vivo to apoptotic cell surfaces have been shown correspondingly to induce tolerance on infusion. Reasoning that a large number of erythrocytes become apoptotic (eryptotic) and are cleared each day, we engineered two different antigen constructs to target the antigen to erythrocyte cell surfaces after i.v. injection, one using a conjugate with an erythrocyte-binding peptide and another using a fusion with an antibody fragment, both targeting the erythrocyte-specific cell surface marker glycophorin A. Here, we show that erythrocyte-binding antigen is collected much more efficiently than free antigen by splenic and hepatic immune cell populations and hepatocytes, and that it induces antigen-specific deletional responses in CD4(+) and CD8(+) T cells. We further validated T-cell deletion driven by erythrocyte-binding antigens using a transgenic islet β cell-reactive CD4(+) T-cell adoptive transfer model of autoimmune type 1 diabetes: Treatment with the peptide antigen fused to an erythrocyte-binding antibody fragment completely prevented diabetes onset induced by the activated, autoreactive CD4(+) T cells. Thus, we report a translatable modular biomolecular approach with which to engineer antigens for targeted binding to erythrocyte cell surfaces to induce antigen-specific CD4(+) and CD8(+) T-cell deletion toward exogenous antigens and autoantigens.

Minimum entropy principle-based solar cell operation without a pn-junction and a thin CdS layer to extract the holes from the emitter

NASA Astrophysics Data System (ADS)

Böer, Karl W.

2016-10-01

The solar cell does not use a pn-junction to separate electrons from holes, but uses an undoped CdS layer that is p-type inverted when attached to a p-type collector and collects the holes while rejecting the backflow of electrons and thereby prevents junction leakage. The operation of the solar cell is determined by the minimum entropy principle of the cell and its external circuit that determines the electrochemical potential, i.e., the Fermi-level of the base electrode to the operating (maximum power point) voltage. It leaves the Fermi level of the metal electrode of the CdS unchanged, since CdS does not participate in the photo-emf. All photoelectric actions are generated by the holes excited from the light that causes the shift of the quasi-Fermi levels in the generator and supports the diffusion current in operating conditions. It is responsible for the measured solar maximum power current. The open circuit voltage (Voc) can approach its theoretical limit of the band gap of the collector at 0 K and the cell increases the efficiency at AM1 to 21% for a thin-film CdS/CdTe that is given as an example here. However, a series resistance of the CdS forces a limitation of its thickness to preferably below 200 Å to avoid unnecessary reduction in efficiency or Voc. The operation of the CdS solar cell does not involve heated carriers. It is initiated by the field at the CdS/CdTe interface that exceeds 20 kV/cm that is sufficient to cause extraction of holes by the CdS that is inverted to become p-type. Here a strong doubly charged intrinsic donor can cause a negative differential conductivity that switches-on a high-field domain that is stabilized by the minimum entropy principle and permits an efficient transport of the holes from the CdTe to the base electrode. Experimental results of the band model of CdS/CdTe solar cells are given and show that the conduction bands are connected in the dark, where the electron current must be continuous, and the valence bands are connected with light where the hole currents are dominant and must be continuous through the junction. The major shifts of the bands in operating conditions are self-adjusting by a change in the junction dipole momentum.

Nationwide prevalence and drug treatment practices of inflammatory bowel diseases in Hungary: A population-based study based on the National Health Insurance Fund database.

PubMed

Kurti, Zsuzsanna; Vegh, Zsuzsanna; Golovics, Petra A; Fadgyas-Freyler, Petra; Gecse, Krisztina B; Gonczi, Lorant; Gimesi-Orszagh, Judit; Lovasz, Barbara D; Lakatos, Peter L

2016-11-01

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases associated with a substantial healthcare utilization. Our aim was to estimate the national prevalence of inflammatory bowel disease (IBD), CD and UC and to describe current drug treatment practices in CD and UC. Patients and drug dispensing events were identified according to international classification codes for UC and CD in in-patient care, non-primary out-patient care and drug prescription databases (2011-2013) of the National Health Insurance Fund. A total of 55,039 individuals (men: 44.6%) with physician-diagnosed IBD were alive in Hungary in 2013, corresponding to a prevalence of 0.55% (95% CI, 0.55-0.56). The prevalence of CD 0.20% (95% CI, 0.19-0.20), and UC was 0.34% (95% CI, 0.33-0.34). The prevalence both in men and women was the highest in the 20-39 year-olds in CD. Current use of immunosuppressives and biological therapy was highest in the pediatric CD population (44% and 15%) followed by adult CD (33% and 9%), while their use was lowest in elderly patients. Interestingly, current use of 5-ASA (5-aminosalicylates) was high in both UC and CD irrespective of the age group. The Hungarian IBD prevalence based on nationwide database of the National Health Insurance Fund was high. We identified significant differences in the drug prescription practices according to age-groups. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Social phobia in coeliac disease.

PubMed

Addolorato, Giovanni; Mirijello, Antonio; D'Angelo, Cristina; Leggio, Lorenzo; Ferrulli, Anna; Vonghia, Luisa; Cardone, Silvia; Leso, Veruscka; Miceli, Antonio; Gasbarrini, Giovanni

2008-01-01

A high prevalence of anxiety and depression has been reported in coeliac disease (CD). Although social phobia is included among the anxiety disorders, its presence in CD has never been investigated. The aim of the present study was to evaluate social phobia in CD patients. A total of 40 CD patients were consecutively enrolled in the study. Fifty healthy subjects were studied as controls. Social phobia was assessed by the Liebowitz Social Anxiety Scale (LSAS) and current depression by the modified version of the Zung Self-rating Depression Scale (M-SDS). The percentage of subjects with social phobia was significantly higher in CD patients than in controls (70% versus 16%; p<0.0001), and also when the more severe generalized form was considered (15.0% versus 0%; p=0.006). The percentage of subjects with social phobia was not statistically different between newly diagnosed subjects and patients on a gluten free diet (73.3% versus 68%; p: NS), nor considering its generalized form (7.0% versus 20%; p: NS). Current depression was present in a significantly higher percentage of CD patients in comparison with controls (52.5% versus 8%; p<0.0001). A direct correlation between social phobia and current depression was found in CD patients (r=0.582; p<0.0001). Despite the limited number of cases evaluated, the present study showed a significantly higher prevalence of social phobia in CD patients compared with in healthy subjects. Future studies are needed to clarify the possible social phobia-induced risks such as school and/or work failure in CD patients.

Pulse-Width-Modulating Driver for Brushless dc Motor

NASA Technical Reports Server (NTRS)

Salomon, Phil M.

1991-01-01

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

Pediatric Crohn Disease Clinical Outcome Assessments and Biomarkers: Current State and Path Forward for Global Collaboration.

PubMed

Sun, Haihao; Vesely, Richard; Lee, Kerry Jo; Klein, Agnes; Ikima, Mutsuhiro; Mulberg, Andrew E

2017-03-01

There is a pressing need for drug development in pediatric Crohn disease (CD). Our aim was to provide strategic approaches toward harmonization of current thinking about clinical outcome assessments (COAs) and biomarkers to facilitate drug development in pediatric CD. Scientists from the United States Food and Drug Administration, European Medicines Agency, Health Canada, and the Pharmaceuticals and Medical Devices Agency of Japan had monthly teleconferences from January 2014 through May 2015. A literature review was conducted to assess the measurement properties of all existing COA tools and to evaluate the current landscape of biomarkers used in pediatric CD. Based on the findings of literature review, we reached the consensus on the strategic approaches for evaluating outcomes in pediatric CD trials. The pediatric Crohn's Disease Activity Index, Crohn's Disease Activity Index, and Harvey-Bradshaw's index were used in pediatric CD clinical studies. But they lack adequate measurement properties (validity, reliability, and ability to detect change of the treatment) that are required to support approval of products intended to treat pediatric CD. Biomarkers (ie, fecal lactoferrin, osteoprotegerin, and calprotectin) have shown some promise for their potential as noninvasive surrogate endpoints in CD. Lack of well-defined and reliable COAs presents a hurdle for global drug development in pediatric CD. It is essential to develop well-defined and reliable COAs that can measure meaningful clinical benefit for patients in terms of how they feel, function, and survive. Development of noninvasive biomarkers as reliable surrogate endpoints needs to be further explored.

Nuclear Factor kappa B is central to Marek’s Disease herpesvirus induced neoplastic transformation of CD30 expressing lymphocytes in-vivo

PubMed Central

2012-01-01

Background Marek’s Disease (MD) is a hyperproliferative, lymphomatous, neoplastic disease of chickens caused by the oncogenic Gallid herpesvirus type 2 (GaHV-2; MDV). Like several human lymphomas the neoplastic MD lymphoma cells overexpress the CD30 antigen (CD30hi) and are in minority, while the non-neoplastic cells (CD30lo) form the majority of population. MD is a unique natural in-vivo model of human CD30hi lymphomas with both natural CD30hi lymphomagenesis and spontaneous regression. The exact mechanism of neoplastic transformation from CD30lo expressing phenotype to CD30hi expressing neoplastic phenotype is unknown. Here, using microarray, proteomics and Systems Biology modeling; we compare the global gene expression of CD30lo and CD30hi cells to identify key pathways of neoplastic transformation. We propose and test a specific mechanism of neoplastic transformation, and genetic resistance, involving the MDV oncogene Meq, host gene products of the Nuclear Factor Kappa B (NF-κB) family and CD30; we also identify a novel Meq protein interactome. Results Our results show that a) CD30lo lymphocytes are pre-neoplastic precursors and not merely reactive lymphocytes; b) multiple transformation mechanisms exist and are potentially controlled by Meq; c) Meq can drive a feed-forward cycle that induces CD30 transcription, increases CD30 signaling which activates NF-κB, and, in turn, increases Meq transcription; d) Meq transcriptional repression or activation of the CD30 promoter generally correlates with polymorphisms in the CD30 promoter distinguishing MD-lymphoma resistant and susceptible chicken genotypes e) MDV oncoprotein Meq interacts with proteins involved in physiological processes central to lymphomagenesis. Conclusions In the context of the MD lymphoma microenvironment (and potentially in other CD30hi lymphomas as well), our results show that the neoplastic transformation is a continuum and the non-neoplastic cells are actually pre-neoplastic precursor cells and not merely immune bystanders. We also show that NF-κB is a central player in MDV induced neoplastic transformation of CD30-expressing lymphocytes in vivo. Our results provide insights into molecular mechanisms of neoplastic transformation in MD specifically and also herpesvirus induced lymphoma in general. PMID:22979947

Power-control switch

NASA Technical Reports Server (NTRS)

Kessler, L. L.

1976-01-01

Constant-current source creates drive current independent of input-voltage variations, 50% reduction in power loss in base drive circuitry, maintains essentially constant charge rate, and improves rise-time consistency over input voltage range.

Using AORSA to simulate helicon waves in DIII-D

NASA Astrophysics Data System (ADS)

Lau, C.; Jaeger, E. F.; Bertelli, N.; Berry, L. A.; Blazevski, D.; Green, D. L.; Murakami, M.; Park, J. M.; Pinsker, R. I.; Prater, R.

2015-12-01

Recent efforts have shown that helicon waves (fast waves at > 20ωci) may be an attractive option for driving efficient off-axis current drive during non-inductive tokamak operation for DIII-D, ITER and DEMO. For DIII-D scenarios, the ray tracing code, GENRAY, has been extensively used to study helicon current drive efficiency and location as a function of many plasma parameters. The full wave code, AORSA, which is applicable to arbitrary Larmor radius and can resolve arbitrary ion cyclotron harmonic order, has been recently used to validate the ray tracing technique at these high cyclotron harmonics. If the SOL is ignored, it will be shown that the GENRAY and AORSA calculated current drive profiles are comparable for the envisioned high beta advanced scenarios for DIII-D, where there is high single pass absorption due to electron Landau damping and minimal ion damping. AORSA is also been used to estimate possible SOL effects on helicon current drive coupling and SOL absorption due to collisional and slow wave effects.

CD-I: From Boob Tube to Teacher's Assistant--The Birth of the Smart TV.

ERIC Educational Resources Information Center

Luskin, Bernard J.

1993-01-01

Explains compact disc interactive (CD-I) and discusses possible uses in education. Advances in technology are considered; the current status of CD-I and recent developments are described, including marketing and costs; and future possibilities of CD-I in education are suggested, including digital technology and electronic and optical publishing.…

Models of anxiety: responses of mice to novelty and open spaces in a 3D maze.

PubMed

Ennaceur, A; Michalikova, S; van Rensburg, R; Chazot, P L

2006-11-01

The present report describes the emotional responses of different strains of mice to exposure to a novel open space model of anxiety using a 3D spatial navigation task. The 3D maze is modification of the radial maze with flexible arms that can be raised above or lowered below the horizontal level of a central platform. To access the arms animals need to cross a bridge linking the arms to the central platform. In this model, mice are exposed to novelty in an unfamiliar open space setting with no safe alternative. Fear from novelty is compounded with the need to explore. The drive to escape and the drive to approach are intermingled making this open space model radically different from the current models of anxiety which provide animals with the choice between safe and anxiogenic spaces. In a series of experiments, we examined the behaviour of different groups of mice from C57, C3H, CD1 and Balb/c strains. In the first experiment, different groups of C57 mice were tested in one of the three arms configurations. In the second experiment, C57 mice were compared to C3H mice. In the third experiment, C57 mice were compared to CD1 and Balb/c mice in the raised arm configuration over three successive sessions. In the fourth experiment, we examined the behaviour of C57 mice in the lowered arm configuration with an open and an enclosed central. In the final experiment, we examined the difference between C57 and C3H mice of both genders. Using several spatio-temporal parameters of the transition responses between central platform, bridges and arms, we have been able to show consistent results demonstrating significant differences between C57 and C3H mice, and between Balb/c and both C57 and CD1 mice. C3H appear more anxious than C57 mice, and Balb/c mice seem more anxious than C57 and CD1 mice. We also observed significant differences between sexes in C3H mice but not in C57 mice. C3H male mice appear more anxious than C3H female mice and than both C57 male and female mice. In the lowered arm configuration with an enclosed central platform, C57 mice took longer time to make a first entry to an arm, made more visits to bridges before first entry to an arm and required longer time between re-entries to arms, spent longer time on the central platform and shorter time on arms compared to mice in the other arm configurations. They also made frequent entries to the centre and bridges compared to mice in the lowered arm with an open central platform. These results demonstrate not only the sensitivity of the parameters of the test but also the consistencies and concordances of the results which make this 3D maze a valuable new tool in the study of the underlying neural mechanisms of anxiety responses in addition to learning and memory, and in assessing the effects of potential anxiolytic drugs. In this report we examine methodological issues related to the design of animal behavioural paradigms and question the value and the construct validity of the current models of human anxiety.

CD151 supports VCAM-1-mediated lymphocyte adhesion to liver endothelium and is upregulated in chronic liver disease and hepatocellular carcinoma

PubMed Central

Wadkin, James C. R.; Patten, Daniel A.; Kamarajah, Sivesh K.; Shepherd, Emma L.; Novitskaya, Vera; Berditchevski, Fedor; Adams, David H.; Weston, Chris J.

2017-01-01

CD151, a member of the tetraspanin family of receptors, is a lateral organizer and modulator of activity of several families of transmembrane proteins. It has been implicated in the development and progression of several cancers, but its role in chronic inflammatory disease is less well understood. Here we show that CD151 is upregulated by distinct microenvironmental signals in a range of chronic inflammatory liver diseases and in primary liver cancer, in which it supports lymphocyte recruitment. CD151 was highly expressed in endothelial cells of the hepatic sinusoids and neovessels developing in fibrotic septa and tumor margins. Primary cultures of human hepatic sinusoidal endothelial cells (HSECs) expressed CD151 at the cell membrane and in intracellular vesicles. CD151 was upregulated by VEGF and HepG2 conditioned media but not by proinflammatory cytokines. Confocal microscopy confirmed that CD151 colocalized with the endothelial adhesion molecule/immunoglobulin superfamily member, VCAM-1. Functional flow-based adhesion assays with primary human lymphocytes and HSECs demonstrated a 40% reduction of lymphocyte adhesion with CD151 blockade. Inhibition of lymphocyte adhesion was similar between VCAM-1 blockade and a combination of CD151/VCAM-1 blockade, suggesting a collaborative role between the two receptors. These studies demonstrate that CD151 is upregulated within the liver during chronic inflammation, where it supports lymphocyte recruitment via liver endothelium. We propose that CD151 regulates the activity of VCAM-1 during lymphocyte recruitment to the human liver and could be a novel anti-inflammatory target in chronic liver disease and hepatocellular cancer prevention. NEW & NOTEWORTHY Chronic hepatitis is characterized by lymphocyte accumulation in liver tissue, which drives fibrosis and carcinogenesis. Here, we demonstrate for the first time that the tetraspanin CD151 supports lymphocyte adhesion to liver endothelium. We show that CD151 is upregulated in chronic liver disease and hepatocellular carcinoma (HCC) and is regulated on endothelium by tissue remodeling and procarcinogenic factors. These regulatory and functional studies identify CD151 as a potential therapeutic target to treat liver fibrosis and HCC. PMID:28473332

CD151 supports VCAM-1-mediated lymphocyte adhesion to liver endothelium and is upregulated in chronic liver disease and hepatocellular carcinoma.

PubMed

Wadkin, James C R; Patten, Daniel A; Kamarajah, Sivesh K; Shepherd, Emma L; Novitskaya, Vera; Berditchevski, Fedor; Adams, David H; Weston, Chris J; Shetty, Shishir

2017-08-01

CD151, a member of the tetraspanin family of receptors, is a lateral organizer and modulator of activity of several families of transmembrane proteins. It has been implicated in the development and progression of several cancers, but its role in chronic inflammatory disease is less well understood. Here we show that CD151 is upregulated by distinct microenvironmental signals in a range of chronic inflammatory liver diseases and in primary liver cancer, in which it supports lymphocyte recruitment. CD151 was highly expressed in endothelial cells of the hepatic sinusoids and neovessels developing in fibrotic septa and tumor margins. Primary cultures of human hepatic sinusoidal endothelial cells (HSECs) expressed CD151 at the cell membrane and in intracellular vesicles. CD151 was upregulated by VEGF and HepG2 conditioned media but not by proinflammatory cytokines. Confocal microscopy confirmed that CD151 colocalized with the endothelial adhesion molecule/immunoglobulin superfamily member, VCAM-1. Functional flow-based adhesion assays with primary human lymphocytes and HSECs demonstrated a 40% reduction of lymphocyte adhesion with CD151 blockade. Inhibition of lymphocyte adhesion was similar between VCAM-1 blockade and a combination of CD151/VCAM-1 blockade, suggesting a collaborative role between the two receptors. These studies demonstrate that CD151 is upregulated within the liver during chronic inflammation, where it supports lymphocyte recruitment via liver endothelium. We propose that CD151 regulates the activity of VCAM-1 during lymphocyte recruitment to the human liver and could be a novel anti-inflammatory target in chronic liver disease and hepatocellular cancer prevention. NEW & NOTEWORTHY Chronic hepatitis is characterized by lymphocyte accumulation in liver tissue, which drives fibrosis and carcinogenesis. Here, we demonstrate for the first time that the tetraspanin CD151 supports lymphocyte adhesion to liver endothelium. We show that CD151 is upregulated in chronic liver disease and hepatocellular carcinoma (HCC) and is regulated on endothelium by tissue remodeling and procarcinogenic factors. These regulatory and functional studies identify CD151 as a potential therapeutic target to treat liver fibrosis and HCC. Copyright © 2017 the American Physiological Society.

Design of epitaxial CdTe solar cells on InSb substrates

DOE PAGES

Song, Tao; Kanevce, Ana; Sites, James R.

2015-11-01

Epitaxial CdTe has been shown by others to have a radiative recombination rate approaching unity, high carrier concentration, and low defect density. It has, therefore, become an attractive candidate for high-efficiency solar cells, perhaps becoming competitive with GaAs. The choice of substrate is a key design feature for epitaxial CdTe solar cells, and several possibilities (CdTe, Si, GaAs, and InSb) have been investigated by others. All have challenges, and these have generally been addressed through the addition of intermediate layers between the substrate and CdTe absorber. InSb is an attractive substrate choice for CdTe devices, because it has a closemore » lattice match with CdTe, it has low resistivity, and it is easy to contact. However, the valence-band alignment between InSb and p-type CdTe, which can both impede hole current and enhance forward electron current, is not favorable. Three strategies to address the band-offset problem are investigated by numerical simulation: heavy doping of the back part of the CdTe layer, incorporation of an intermediate CdMgTe or CdZnTe layer, and the formation of an InSb tunnel junction. Lastly, wach of these strategies is predicted to be helpful for higher cell performance, but a combination of the first two should be most effective.« less

Self-consistent modeling of the dynamic evolution of magnetic island growth in the presence of stabilizing electron-cyclotron current drive

NASA Astrophysics Data System (ADS)

Chatziantonaki, Ioanna; Tsironis, Christos; Isliker, Heinz; Vlahos, Loukas

2013-11-01

The most promising technique for the control of neoclassical tearing modes in tokamak experiments is the compensation of the missing bootstrap current with an electron-cyclotron current drive (ECCD). In this frame, the dynamics of magnetic islands has been studied extensively in terms of the modified Rutherford equation (MRE), including the presence of a current drive, either analytically described or computed by numerical methods. In this article, a self-consistent model for the dynamic evolution of the magnetic island and the driven current is derived, which takes into account the island's magnetic topology and its effect on the current drive. The model combines the MRE with a ray-tracing approach to electron-cyclotron wave-propagation and absorption. Numerical results exhibit a decrease in the time required for complete stabilization with respect to the conventional computation (not taking into account the island geometry), which increases by increasing the initial island size and radial misalignment of the deposition.

Sensorless Sinusoidal Drives for Fan and Pump Motors by V/f Control

NASA Astrophysics Data System (ADS)

Kiuchi, Mitsuyuki; Ohnishi, Tokuo

This paper proposes sensorless sinusoidal driving methods of permanent magnet synchronous motors for fans and pumps by V/f control. The proposed methods are simple methods that control the motor peak current constant by voltage or frequency control, and are characterized by DC link current detection using a single shunt resistor at carrier wave signal bottom timing. As a result of the dumping factor from square torque load characteristics of fan and pump motors, it is possible to control stable starting and stable steady state by V/f control. In general, pressure losses as a result of the fluid pass of fan and pump systems are nearly constant; therefore, the flow rate and motor torque are determined by revolutions. Accordingly, high efficiency driving is possible by setting corresponding currents to q-axis currents (torque currents) at target revolutions. Because of the simple current detection and motor control methods, the proposed methods are optimum for fan and pump motor driving systems of home appliances.

Experimental demonstration of an efficient hybrid equalizer for short-reach optical SSB systems

NASA Astrophysics Data System (ADS)

Zhu, Mingyue; Ying, Hao; Zhang, Jing; Yi, Xingwen; Qiu, Kun

2018-02-01

We propose an efficient enhanced hybrid equalizer combining the feed forward equalization (FFE) with a modified Volterra filter to mitigate the linear and nonlinear interference for the short-reach optical single side-band (SSB) system. The optical SSB signal is generated by a relatively low-cost dual-drive Mach-Zehnder modulator (DDMZM). The two driving signals are a pair of Hilbert signals with Nyquist pulse-shaped four-level pulse amplitude modulation (NPAM-4). After the fiber transmission, the neighboring received symbols are strongly correlated due to the pulse spreading in time domain caused by the chromatic dispersion (CD). At the receiver equalization stage, the FFE followed by higher order terms of modified Volterra filter, which utilizes the forward and backward neighboring symbols to construct the kernels with strong correlation, are used as an enhanced hybrid equalizer to mitigate the inter symbol interference (ISI) and nonlinear distortion due to the interaction of the CD and the square-law detection. We experimentally demonstrate that the optical SSB NPAM-4 signal of 40 Gb/s transmitting over 80 km standard single mode fiber (SSMF) with a bit-error-rate (BER) of 7 . 59 × 10-4.

Thy1+IL-7+ lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation

PubMed Central

Shinoda, Kenta; Hirahara, Kiyoshi; Iinuma, Tomohisa; Ichikawa, Tomomi; Suzuki, Akane S.; Sugaya, Kaoru; Tumes, Damon J.; Yamamoto, Heizaburo; Hara, Takahiro; Tani-ichi, Shizue; Ikuta, Koichi; Okamoto, Yoshitaka; Nakayama, Toshinori

2016-01-01

Memory CD4+ T helper (Th) cells are central to long-term protection against pathogens, but they can also be pathogenic and drive chronic inflammatory disorders. How these pathogenic memory Th cells are maintained, particularly at sites of local inflammation, remains unclear. We found that ectopic lymphoid-like structures called inducible bronchus-associated lymphoid tissue (iBALT) are formed during chronic allergic inflammation in the lung, and that memory-type pathogenic Th2 (Tpath2) cells capable of driving allergic inflammation are maintained within the iBALT structures. The maintenance of memory Th2 cells within iBALT is supported by Thy1+IL-7–producing lymphatic endothelial cells (LECs). The Thy1+IL-7–producing LECs express IL-33 and T-cell–attracting chemokines CCL21 and CCL19. Moreover, ectopic lymphoid structures consisting of memory CD4+ T cells and IL-7+IL-33+ LECs were found in nasal polyps of patients with eosinophilic chronic rhinosinusitis. Thus, Thy1+IL-7–producing LECs control chronic allergic airway inflammation by providing a survival niche for memory-type Tpath2 cells. PMID:27140620

Chronic Inflammation-Related HPV: A Driving Force Speeds Oropharyngeal Carcinogenesis

PubMed Central

Liu, Xin; Ma, Xiangrui; Lei, Zhengge; Feng, Hao; Wang, Shasha; Cen, Xiao; Gao, Shiyu; Jiang, Yaping; Jiang, Jian; Chen, Qianming; Tang, Yajie; Tang, Yaling; Liang, Xinhua

2015-01-01

Oropharyngeal squamous cell carcinoma (OPSCC) has been known to be a highly aggressive disease associated with human papilloma virus (HPV) infection. To investigate the relationship between HPV and chronic inflammation in oropharyngeal carcinogenesis, we collected 140 oral mucous fresh specimens including 50 OPSCC patients, 50 cancer in situ, 30 precancerous lesions, and 10 normal oral mucous. Our data demonstrated that there was a significantly higher proportion of severe chronic inflammation in dysplastic epithelia in comparison with that in normal tissues (P<0.001). The positive rate of HPV 16 was parallel with the chronic inflammation degrees from mild to severe inflammation (P<0.05). The positive rate of HPV 16 was progressively improved with the malignant progression of oral mucous (P<0.05). In addition, CD11b+ LIN- HLA-DR-CD33+ MDSCs were a critical cell population that mediates inflammation response and immune suppression in HPV-positive OPSCC. These indicated that persistent chronic inflammation-related HPV infection might drive oropharyngeal carcinogenesis and MDSCs might pay an important role during this process. Thus, a combination of HPV infection and inflammation expression might become a helpful biomedical marker to predict oropharyngeal carcinogenesis. PMID:26193368

Chronic Inflammation-Related HPV: A Driving Force Speeds Oropharyngeal Carcinogenesis.

PubMed

Liu, Xin; Ma, Xiangrui; Lei, Zhengge; Feng, Hao; Wang, Shasha; Cen, Xiao; Gao, Shiyu; Jiang, Yaping; Jiang, Jian; Chen, Qianming; Tang, Yajie; Tang, Yaling; Liang, Xinhua

2015-01-01

Oropharyngeal squamous cell carcinoma (OPSCC) has been known to be a highly aggressive disease associated with human papilloma virus (HPV) infection. To investigate the relationship between HPV and chronic inflammation in oropharyngeal carcinogenesis, we collected 140 oral mucous fresh specimens including 50 OPSCC patients, 50 cancer in situ, 30 precancerous lesions, and 10 normal oral mucous. Our data demonstrated that there was a significantly higher proportion of severe chronic inflammation in dysplastic epithelia in comparison with that in normal tissues (P<0.001). The positive rate of HPV 16 was parallel with the chronic inflammation degrees from mild to severe inflammation (P<0.05). The positive rate of HPV 16 was progressively improved with the malignant progression of oral mucous (P<0.05). In addition, CD11b+ LIN- HLA-DR-CD33+ MDSCs were a critical cell population that mediates inflammation response and immune suppression in HPV-positive OPSCC. These indicated that persistent chronic inflammation-related HPV infection might drive oropharyngeal carcinogenesis and MDSCs might pay an important role during this process. Thus, a combination of HPV infection and inflammation expression might become a helpful biomedical marker to predict oropharyngeal carcinogenesis.

Lower hybrid current drive experiments in the HT-6M tokamak

NASA Astrophysics Data System (ADS)

Jiang, Tongwen; Liu, Yuexiu; Guo, Wenkang; Zhang, Xuelei; Luo, Jiarong

1987-07-01

Lower hybrid current drive (LHCD) experiments with a multijunction grill have been performed in the HT-6M tokamak. When the RF power pulse with 15ms risetime is injected into the plasma, the toroidal current amplitude is raised, but the temporal variation of the loop voltage does not have measurable change. The efficiency of current drive is Irf/Prf=0.57kA/kW at bar ne=3 × 1012cm-3 and Bt=8KG. It seems that the multijunction grill has the same efficiency as the ordinary grill on the LHCD experiments.

CD44 standard and CD44v10 isoform expression on leukemia cells distinctly influences niche embedding of hematopoietic stem cells.

PubMed

Erb, Ulrike; Megaptche, Amelie Pajip; Gu, Xiaoyu; Büchler, Markus W; Zöller, Margot

2014-03-31

A blockade of CD44 is considered a therapeutic option for the elimination of leukemia initiating cells. However, anti-panCD44 can interfere with hematopoiesis. Therefore we explored, whether a CD44 variant isoform (CD44v)-specific antibody can inhibit leukemia growth without attacking hematopoiesis. As a model we used CD44v10 transfected EL4 thymoma cells (EL4-v10). The therapeutic efficacy of anti-panCD44 and anti-CD44v10 was evaluated after intravenous application of EL4/EL4-v10. Ex vivo and in vitro studies evaluated the impact of anti-panCD44 and anti-CD44v10 as well as of EL4 and EL4-v10 on hematopoietic stem cells (HSC) in cocultures with bone marrow stroma cells with a focus on adhesion, migration, cell cycle progression and apoptosis resistance. Intravenously injected EL4-v10 grow in bone marrow and spleen. Anti-panCD44 and, more pronounced anti-CD44v10 prolong the survival time. The higher efficacy of anti-CD44v10 compared to anti-panCD44 does not rely on stronger antibody-dependent cellular cytotoxicity or on promoting EL4-v10 apoptosis. Instead, EL4 compete with HSC niche embedding. This has consequences on quiescence and apoptosis-protecting signals provided by the stroma. Anti-panCD44, too, more efficiently affected embedding of HSC than of EL4 in the bone marrow stroma. EL4-v10, by catching osteopontin, migrated on bone marrow stroma and did not or weakly interfere with HSC adhesion. Anti-CD44v10, too, did not affect the HSC--bone marrow stroma crosstalk. The therapeutic effect of anti-panCD44 and anti-CD44v10 is based on stimulation of antibody-dependent cellular cytotoxicity. The superiority of anti-CD44v10 is partly due to blocking CD44v10-stimulated osteopontin expression that could drive HSC out of the niche. However, the main reason for the superiority of anti-CD44v10 relies on neither EL4-v10 nor anti-CD44v10 severely interfering with HSC--stroma cell interactions that, on the other hand, are affected by EL4 and anti-panCD44. Anti-panCD44 disturbing HSC embedding in the osteogenic niche weakens its therapeutic effect towards EL4. Thus, as far as leukemic cells express CD44v isoforms, the therapeutic use of anti-panCD44 should be avoided in favor of CD44v-specific antibodies.

CD44 standard and CD44v10 isoform expression on leukemia cells distinctly influences niche embedding of hematopoietic stem cells

PubMed Central

2014-01-01

Background A blockade of CD44 is considered a therapeutic option for the elimination of leukemia initiating cells. However, anti-panCD44 can interfere with hematopoiesis. Therefore we explored, whether a CD44 variant isoform (CD44v)-specific antibody can inhibit leukemia growth without attacking hematopoiesis. As a model we used CD44v10 transfected EL4 thymoma cells (EL4-v10). Methods The therapeutic efficacy of anti-panCD44 and anti-CD44v10 was evaluated after intravenous application of EL4/EL4-v10. Ex vivo and in vitro studies evaluated the impact of anti-panCD44 and anti-CD44v10 as well as of EL4 and EL4-v10 on hematopoietic stem cells (HSC) in cocultures with bone marrow stroma cells with a focus on adhesion, migration, cell cycle progression and apoptosis resistance. Results Intravenously injected EL4-v10 grow in bone marrow and spleen. Anti-panCD44 and, more pronounced anti-CD44v10 prolong the survival time. The higher efficacy of anti-CD44v10 compared to anti-panCD44 does not rely on stronger antibody-dependent cellular cytotoxicity or on promoting EL4-v10 apoptosis. Instead, EL4 compete with HSC niche embedding. This has consequences on quiescence and apoptosis-protecting signals provided by the stroma. Anti-panCD44, too, more efficiently affected embedding of HSC than of EL4 in the bone marrow stroma. EL4-v10, by catching osteopontin, migrated on bone marrow stroma and did not or weakly interfere with HSC adhesion. Anti-CD44v10, too, did not affect the HSC – bone marrow stroma crosstalk. Conclusion The therapeutic effect of anti-panCD44 and anti-CD44v10 is based on stimulation of antibody-dependent cellular cytotoxicity. The superiority of anti-CD44v10 is partly due to blocking CD44v10-stimulated osteopontin expression that could drive HSC out of the niche. However, the main reason for the superiority of anti-CD44v10 relies on neither EL4-v10 nor anti-CD44v10 severely interfering with HSC – stroma cell interactions that, on the other hand, are affected by EL4 and anti-panCD44. Anti-panCD44 disturbing HSC embedding in the osteogenic niche weakens its therapeutic effect towards EL4. Thus, as far as leukemic cells express CD44v isoforms, the therapeutic use of anti-panCD44 should be avoided in favor of CD44v-specific antibodies. PMID:24684724

Analytical approaches to optimizing system "Semiconductor converter-electric drive complex"

NASA Astrophysics Data System (ADS)

Kormilicin, N. V.; Zhuravlev, A. M.; Khayatov, E. S.

2018-03-01

In the electric drives of the machine-building industry, the problem of optimizing the drive in terms of mass-size indicators is acute. The article offers analytical methods that ensure the minimization of the mass of a multiphase semiconductor converter. In multiphase electric drives, the form of the phase current at which the best possible use of the "semiconductor converter-electric drive complex" for active materials is different from the sinusoidal form. It is shown that under certain restrictions on the phase current form, it is possible to obtain an analytical solution. In particular, if one assumes the shape of the phase current to be rectangular, the optimal shape of the control actions will depend on the width of the interpolar gap. In the general case, the proposed algorithm can be used to solve the problem under consideration by numerical methods.

Tomorrow's Online in Today's CD-ROM: Interfaces and Images.

ERIC Educational Resources Information Center

Jacso, Peter

1994-01-01

Considers the appropriateness of using CD-ROM versus online systems. Topics discussed include cost effectiveness; how current the information is; full-text capabilities; a variety of interfaces; graphical user interfaces on CD-ROM; and possibilities for image representations. (LRW)

Leishmania amazonensis Engages CD36 to Drive Parasitophorous Vacuole Maturation

PubMed Central

Okuda, Kendi; Tong, Mei; Dempsey, Brian; Moore, Kathryn J.; Gazzinelli, Ricardo T.; Silverman, Neal

2016-01-01

Leishmania amastigotes manipulate the activity of macrophages to favor their own success. However, very little is known about the role of innate recognition and signaling triggered by amastigotes in this host-parasite interaction. In this work we developed a new infection model in adult Drosophila to take advantage of its superior genetic resources to identify novel host factors limiting Leishmania amazonensis infection. The model is based on the capacity of macrophage-like cells, plasmatocytes, to phagocytose and control the proliferation of parasites injected into adult flies. Using this model, we screened a collection of RNAi-expressing flies for anti-Leishmania defense factors. Notably, we found three CD36-like scavenger receptors that were important for defending against Leishmania infection. Mechanistic studies in mouse macrophages showed that CD36 accumulates specifically at sites where the parasite contacts the parasitophorous vacuole membrane. Furthermore, CD36-deficient macrophages were defective in the formation of the large parasitophorous vacuole typical of L. amazonensis infection, a phenotype caused by inefficient fusion with late endosomes and/or lysosomes. These data identify an unprecedented role for CD36 in the biogenesis of the parasitophorous vacuole and further highlight the utility of Drosophila as a model system for dissecting innate immune responses to infection. PMID:27280707

Immune-driven recombination and loss of control after HIV superinfection.

PubMed

Streeck, Hendrik; Li, Bin; Poon, Art F Y; Schneidewind, Arne; Gladden, Adrianne D; Power, Karen A; Daskalakis, Demetre; Bazner, Suzane; Zuniga, Rosario; Brander, Christian; Rosenberg, Eric S; Frost, Simon D W; Altfeld, Marcus; Allen, Todd M

2008-08-04

After acute HIV infection, CD8(+) T cells are able to control viral replication to a set point. This control is often lost after superinfection, although the mechanism behind this remains unclear. In this study, we illustrate in an HLA-B27(+) subject that loss of viral control after HIV superinfection coincides with rapid recombination events within two narrow regions of Gag and Env. Screening for CD8(+) T cell responses revealed that each of these recombination sites (approximately 50 aa) encompassed distinct regions containing two immunodominant CD8 epitopes (B27-KK10 in Gag and Cw1-CL9 in Env). Viral escape and the subsequent development of variant-specific de novo CD8(+) T cell responses against both epitopes were illustrative of the significant immune selection pressures exerted by both responses. Comprehensive analysis of the kinetics of CD8 responses and viral evolution indicated that the recombination events quickly facilitated viral escape from both dominant WT- and variant-specific responses. These data suggest that the ability of a superinfecting strain of HIV to overcome preexisting immune control may be related to its ability to rapidly recombine in critical regions under immune selection pressure. These data also support a role for cellular immune pressures in driving the selection of new recombinant forms of HIV.

Human T-lymphotropic virus type I-associated myelopathy and tax gene expression in CD4+ T lymphocytes.

PubMed

Moritoyo, T; Reinhart, T A; Moritoyo, H; Sato, E; Izumo, S; Osame, M; Haase, A T

1996-07-01

Infection by human T-lymphotropic virus type I (HTLV-I) is associated with adult T-cell leukemia and a slowly progressive disease of the central nervous system (CNS), HTLV-I-associated myelopathy/tropical spastic paraparesis, characterized pathologically by inflammation and white matter degeneration in the spinal cord. One of the explanations for the tissue destruction is that HTLV-I infects cells in the CNS, or HTLV-I-infected CD4+ T lymphocytes enter the CNS, and this drives local expansion of virus-specific CD8+ cytotoxic T lymphocytes, which along with cytokines cause the pathological changes. Because both in the circulation and in the cerebrospinal fluid, CD8+ cytotoxic T lymphocytes are primarily reactive to the product of the HTLV-I tax gene, we sought evidence of expression of this gene within cells in the inflammatory lesions. After using double-label in situ hybridization techniques, we now report definitive localization of HTLV-I tax gene expression in CD4+ T lymphocytes in areas of inflammation and white matter destruction. These findings lend support to a hypothetical scheme of neuropathogenesis in which HTLV-I tax gene expression provokes and sustains an immunopathological process that progressively destroys myelin and axons in the spinal cord.

Rapid activation of spleen dendritic cell subsets following lymphocytic choriomeningitis virus infection of mice: analysis of the involvement of type 1 IFN.

PubMed

Montoya, Maria; Edwards, Matthew J; Reid, Delyth M; Borrow, Persephone

2005-02-15

In this study, we report the dynamic changes in activation and functions that occur in spleen dendritic cell (sDC) subsets following infection of mice with a natural murine pathogen, lymphocytic choriomeningitis virus (LCMV). Within 24 h postinfection (pi), sDCs acquired the ability to stimulate naive LCMV-specific CD8+ T cells ex vivo. Conventional (CD11chigh CD8+ and CD4+) sDC subsets rapidly up-regulated expression of costimulatory molecules and began to produce proinflammatory cytokines. Their tendency to undergo apoptosis ex vivo simultaneously increased, and in vivo the number of conventional DCs in the spleen decreased markedly, dropping approximately 2-fold by day 3 pi. Conversely, the number of plasmacytoid (CD11clowB220+) DCs in the spleen increased, so that they constituted almost 40% of sDCs by day 3 pi. Type 1 IFN production was up-regulated in plasmacytoid DCs by 24 h pi. Analysis of DC activation and maturation in mice unable to respond to type 1 IFNs implicated these cytokines in driving infection-associated phenotypic activation of conventional DCs and their enhanced tendency to undergo apoptosis, but also indicated the existence of type 1 IFN-independent pathways for the functional maturation of DCs during LCMV infection.

Insulin stimulation of rat ventricular K+ currents depends on the integrity of the cytoskeleton.

PubMed

Shimoni, Y; Ewart, H S; Severson, D

1999-02-01

1. The effect of insulin on K+ currents was studied with enzymatically dispersed ventricular myocytes from insulin-deficient (type I) diabetic rats. Diabetic conditions were induced by a single intravenous injection of streptozotocin (100 mg kg-1) given 8-13 days before the experiments. Measurements of plasma glucose and insulin levels confirmed the diabetic status of the animals. 2. A Ca2+-independent transient outward K+ current, It, and a slowly inactivating, quasi-steady-state current, Iss, which are depressed in diabetic myocytes, could be restored by exposure to 1, 10 or 100 nM insulin. This was only observed after a delay of 5-6 h, although an insulin exposure of only 1 h was sufficient to initiate its stimulatory action on It and Iss. The stimulatory effect of insulin on these K+ currents was prevented by 2 microM cycloheximide, which in itself had no direct effect on these currents. 3. Disruption of the actin microfilament network with 1 microM cytochalasin D (CD) also prevented the stimulatory effect of 100 nM insulin on both It and Iss. Since CD was added 1 h after insulin, inhibitory effects on insulin signalling were ruled out. Adding CD (1 microM) 5-9 h after insulin, when currents were already augmented, had no effect (up to 50 min exposure). Incubating control cells for 6-10 h with 1 microM CD had no effect on any of the currents measured. 4. Stabilization of the actin network by pre-exposure to 2.5 microM phalloidin restored the stimulatory effect of insulin, in the continued presence of CD, ruling out any effects of CD on components other than the cytoskeleton. 5. The stimulatory effect of insulin was also prevented by incubating cells with insulin in the presence of the microtubule-disrupting agent colchicine (5 microM). 6. These results suggest that the insulin-mediated augmentation of K+ currents in diabetic myocytes requires protein synthesis, possibly of K+ channels, as well as an intact cytoskeleton. The possibility that newly formed channels translocate to the plasma membrane in a process dependent on different elements of the cytoskeleton is discussed.

Numerical calculations of non-inductive current driven by microwaves in JET

NASA Astrophysics Data System (ADS)

Kirov, K. K.; Baranov, Yu; Mailloux, J.; Nave, M. F. F.; Contributors, JET

2016-12-01

Recent studies at JET focus on analysis of the lower hybrid (LH) wave power absorption and current drive (CD) calculations by means of a new ray tracing (RT)/Fokker-Planck (FP) package. The RT code works in real 2D geometry accounting for the plasma boundary and the launcher shape. LH waves with different parallel refractive index, {{N}\\parallel} , spectra in poloidal direction can be launched thus simulating authentic antenna spectrum with rows fed by different combinations of klystrons. Various FP solvers were tested most advanced of which is a relativistic bounce averaged FP code. LH wave power deposition profiles from the new RT/FP code were compared to the experimental results from electron cyclotron emission (ECE) analysis of pulses at 3.4 T low and high density. This kind of direct comparison between power deposition profiles from experimental ECE data and numerical model were carried out for the first time for waves in the LH range of frequencies. The results were in a reasonable agreement with experimental data at lower density, line averaged values of {{n}\\text{e}}≈ 2.4× {{10}19} {{\\text{m}}-3} . At higher density, {{n}\\text{e}}≈ 3× {{10}19} {{\\text{m}}-3} , the code predicted larger on-axis LH power deposition, which is inconsistent with the experimental observations. Both calculations were unable to produce LH wave absorption at the plasma periphery, which contradicts to the analysis of the ECE data and possible sources of these discrepancies have been briefly discussed in the paper. The code was also used to calculate the LH power deposition and CD profiles for the low-density preheat phase of JET’s advanced tokamak (AT) scenario. It was found that as the density evolves from hollow to flat and then to a more peaked profile the LH power and driven current move inward i.e. towards the plasma axis. A total driven current of about 70 kA for 1 MW of launched LH power was predicted in these conditions.

Probing matter at extreme Gbar pressures at the NIF

DOE PAGES

Kritcher, A. L.; Doeppner, T.; Swift, D.; ...

2013-12-04

Here we describe a platform to measure the material properties, specifically the equation of state and electron temperature, at pressures of 100 Mbar to a Gbar at the National Ignition Facility (NIF). In our experiments we launch spherically convergent shock waves into solid CH, CD, or diamond samples using a hohlraum radiation drive, in an indirect drive laser geometry. X-ray radiography is applied to measure the shock speed and infer the mass density profile, enabling determination of the material pressure and Hugoniot equation of state. X-ray scattering is applied to measure the electron temperature through probing of the electron velocitymore » distribution via Doppler broadening.« less

Modeling of LWIR HgCdTe Auger-Suppressed Infrared Photodiodes under Nonequilibrium Operation

NASA Astrophysics Data System (ADS)

Emelie, P. Y.; Velicu, S.; Grein, C. H.; Phillips, J. D.; Wijewarnasuriya, P. S.; Dhar, N. K.

2008-09-01

The general approach and effects of nonequilibrium operation of Auger-suppressed HgCdTe infrared photodiodes are well understood. However, the complex relationships of carrier generation and dependencies on nonuniform carrier profiles in the device prevent the development of simplistic analytical device models with acceptable accuracy. In this work, finite element methods are used to obtain self-consistent steady-state solutions of Poisson’s equation and the carrier continuity equations. Experimental current-voltage characteristics between 120 K and 300 K of HgCdTe Auger-suppressed photodiodes with cutoff wavelength of λ c = 10 μm at 120 K are fitted using our numerical model. Based on this fitting, we study the lifetime in the absorber region, extract the current mechanisms limiting the dark current in these photodiodes, and discuss design and fabrication considerations in order to optimize future HgCdTe Auger-suppressed photodiodes.

Driving reduction and cessation : transitioning to not driving.

DOT National Transportation Integrated Search

2009-09-01

This project examined the process of driving reduction and cessation from the perspective of older adults (current and former drivers) and adult children. The objectives were to identify common markers of the process of driving cessation and to gain ...

Three Trailblazing Technologies for Schools.

ERIC Educational Resources Information Center

McGinty, Tony

1987-01-01

Provides an overview of the capabilities and potential educational applications of CD-ROM (compact disk read-only memory), artificial intelligence, and speech technology. Highlights include reference materials on CD-ROM; current developments in CD-I (compact disk interactive); synthesized and digital speech for microcomputers, including specific…

Status of HgCdTe Barrier Infrared Detectors Grown by MOCVD in Military University of Technology

NASA Astrophysics Data System (ADS)

Kopytko, M.; Jóźwikowski, K.; Martyniuk, P.; Gawron, W.; Madejczyk, P.; Kowalewski, A.; Markowska, O.; Rogalski, A.; Rutkowski, J.

2016-09-01

In this paper we present the status of HgCdTe barrier detectors with an emphasis on technological progress in metalorganic chemical vapor deposition (MOCVD) growth achieved recently at the Institute of Applied Physics, Military University of Technology. It is shown that MOCVD technology is an excellent tool for HgCdTe barrier architecture growth with a wide range of composition, donor /acceptor doping, and without post-grown annealing. The device concept of a specific barrier bandgap architecture integrated with Auger-suppression is as a good solution for high-operating temperature infrared detectors. Analyzed devices show a high performance comparable with the state-of-the-art of HgCdTe photodiodes. Dark current densities are close to the values given by "Rule 07" and detectivities of non-immersed detectors are close to the value marked for HgCdTe photodiodes. Experimental data of long-wavelength infrared detector structures were confirmed by numerical simulations obtained by a commercially available software APSYS platform. A detailed analysis applied to explain dark current plots was made, taking into account Shockley-Read-Hall, Auger, and tunneling currents.

Analysis of electroluminescence images in small-area circular CdTe solar cells

NASA Astrophysics Data System (ADS)

Bokalič, Matevž; Raguse, John; Sites, James R.; Topič, Marko

2013-09-01

The electroluminescence (EL) imaging process of small area solar cells is investigated in detail to expose optical and electrical effects that influence image acquisition and corrupt the acquired image. An approach to correct the measured EL images and to extract the exact EL radiation as emitted from the photovoltaic device is presented. EL images of circular cadmium telluride (CdTe) solar cells are obtained under different conditions. The power-law relationship between forward injection current and EL emission and a negative temperature coefficient of EL radiation are observed. The distributed Simulation Program with Integrated Circuit Emphasis (SPICE®) model of the circular CdTe solar cell is used to simulate the dark J-V curve and current distribution under the conditions used during EL measurements. Simulation results are presented as circularly averaged EL intensity profiles, which clearly show that the ratio between resistive parameters determines the current distribution in thin-film solar cells. The exact resistance values for front and back contact layers and for CdTe bulk layer are determined at different temperatures, and a negative temperature coefficient for the CdTe bulk resistance is observed.

ZnS/Al2S3 Layer as a Blocking Layer in Quantum Dot Sensitized Solar Cells

NASA Astrophysics Data System (ADS)

Vafapoor, Borzoo; Fathi, Davood; Eskandari, Mehdi

2017-12-01

In this research, the effect of treatment of the CdS/CdSe sensitized ZnO photoanode by ZnS, Al2S3, and ZnS/Al2S3 nanoparticles as a barrier layer on the performance of quantum dot sensitized solar cell is investigated. Current density-voltage (J-V) characteristics show that cell efficiency is enhanced from 3.62% to 4.82% with treatment of a CdS/CdSe/ZnS sensitized ZnO photoanode by Al2S3 nanoparticles. In addition, short- circuit current density (J sc) is increased from 11.5 mA/cm2 to 14.8 mA/cm2. The results extracted from electrochemical impedance spectroscopy indicate that charge transfer resistance (R ct) in photoanode/electrolyte interfaces decreases with deposition of Al2S3 nanoparticles on CdS/CdSe/ZnS sensitized ZnO photoanodes, while the chemical capacitance of photoanode (C μ ) and electron lifetime (t n) increase. Also, results revealed that cell performance is considerably decreased with the treatment of the AL2S3 blocking layer incorporated between ZnO nanorods and CdS/CdSe QDs.

ZnS/Al2S3 Layer as a Blocking Layer in Quantum Dot Sensitized Solar Cells

NASA Astrophysics Data System (ADS)

Vafapoor, Borzoo; Fathi, Davood; Eskandari, Mehdi

2018-03-01

In this research, the effect of treatment of the CdS/CdSe sensitized ZnO photoanode by ZnS, Al2S3, and ZnS/Al2S3 nanoparticles as a barrier layer on the performance of quantum dot sensitized solar cell is investigated. Current density-voltage ( J- V) characteristics show that cell efficiency is enhanced from 3.62% to 4.82% with treatment of a CdS/CdSe/ZnS sensitized ZnO photoanode by Al2S3 nanoparticles. In addition, short- circuit current density ( J sc) is increased from 11.5 mA/cm2 to 14.8 mA/cm2. The results extracted from electrochemical impedance spectroscopy indicate that charge transfer resistance ( R ct) in photoanode/electrolyte interfaces decreases with deposition of Al2S3 nanoparticles on CdS/CdSe/ZnS sensitized ZnO photoanodes, while the chemical capacitance of photoanode ( C μ ) and electron lifetime ( t n) increase. Also, results revealed that cell performance is considerably decreased with the treatment of the AL2S3 blocking layer incorporated between ZnO nanorods and CdS/CdSe QDs.

Novel patterning of CdS / CdTe thin film with back contacts for photovoltaic application

NASA Astrophysics Data System (ADS)

Ilango, Murugaiya Sridar; Ramasesha, Sheela K.

2018-04-01

The heterostructure of patterned CdS / CdTe thin films with back contact have been devised with electron beam lithography and fabricated using sputter deposition technique. The metallic contacts for n-CdS and p-CdTe are patterned such that both are placed at the bottom of the cell. This avoids losses due to contact shading and increases absorption in the window layer. Patterning of the device surface helps in increasing the junction area which can modulate the absorption of more number of photons due to total internal reflection. Computing the surface area between a planar and a patterned device has revealed 133% increase in the junction area. The physical and optical properties of the sputter-deposited CdS / CdTe layers are also presented. J- V characteristics of the solar cell showed the fill factor to be 25.9%, open circuit voltage to be 17 mV and short-circuit current density to be 113.68 A/m2. The increase in surface area is directly related to the increase in the short circuit current of the photovoltaic cell, which is observed from the results of simulated model in Atlas / Silvaco.

Screening for celiac disease in the general population and in high-risk groups

PubMed Central

Card, Timothy R; Kaukinen, Katri; Bai, Julio; Zingone, Fabiana; Sanders, David S; Murray, Joseph A

2015-01-01

Background Celiac disease (CD) occurs in approximately 1% of the Western population. It is a lifelong disorder that is associated with impaired quality of life (QOL) and an excessive risk of comorbidity and death. Objectives To review the literature on screening for CD in relation to the current World Health Organization (WHO) criteria for mass screening. Methods We performed a PubMed search to identify indexed papers on CD screening with a publication date from 1900 until 1 June 2014. When we deemed an abstract relevant, we read the corresponding paper in detail. Results CD fulfills several WHO criteria for mass screening (high prevalence, available treatment and difficult clinical detection), but it has not yet been established that treatment of asymptomatic CD may reduce the excessive risk of severe complications, leading to higher QOL nor that it is cost-effective. Conclusions Current evidence is not sufficient to support mass screening for CD, but active case-finding may be appropriate, as we recognize that most patients with CD will still be missed by this strategy. Although proof of benefit is still lacking, screening for CD may be appropriate in high-risk groups. PMID:25922671

CD-SEM real time bias correction using reference metrology based modeling

NASA Astrophysics Data System (ADS)

Ukraintsev, V.; Banke, W.; Zagorodnev, G.; Archie, C.; Rana, N.; Pavlovsky, V.; Smirnov, V.; Briginas, I.; Katnani, A.; Vaid, A.

2018-03-01

Accuracy of patterning impacts yield, IC performance and technology time to market. Accuracy of patterning relies on optical proximity correction (OPC) models built using CD-SEM inputs and intra die critical dimension (CD) control based on CD-SEM. Sub-nanometer measurement uncertainty (MU) of CD-SEM is required for current technologies. Reported design and process related bias variation of CD-SEM is in the range of several nanometers. Reference metrology and numerical modeling are used to correct SEM. Both methods are slow to be used for real time bias correction. We report on real time CD-SEM bias correction using empirical models based on reference metrology (RM) data. Significant amount of currently untapped information (sidewall angle, corner rounding, etc.) is obtainable from SEM waveforms. Using additional RM information provided for specific technology (design rules, materials, processes) CD extraction algorithms can be pre-built and then used in real time for accurate CD extraction from regular CD-SEM images. The art and challenge of SEM modeling is in finding robust correlation between SEM waveform features and bias of CD-SEM as well as in minimizing RM inputs needed to create accurate (within the design and process space) model. The new approach was applied to improve CD-SEM accuracy of 45 nm GATE and 32 nm MET1 OPC 1D models. In both cases MU of the state of the art CD-SEM has been improved by 3x and reduced to a nanometer level. Similar approach can be applied to 2D (end of line, contours, etc.) and 3D (sidewall angle, corner rounding, etc.) cases.

Anomalous-viscosity current drive

DOEpatents

Stix, T.H.; Ono, M.

1986-04-25

The present invention relates to a method and apparatus for maintaining a steady-state current for magnetically confining the plasma in a toroidal magnetic confinement device using anomalous viscosity current drive. A second aspect of this invention relates to an apparatus and method for the start-up of a magnetically confined toroidal plasma.

Dose-Response Relationship of CD8+ Tumor Infiltrating Lymphocytes and Survival Time in High-Grade Serous Ovarian Cancer

PubMed Central

Goode, Ellen L; Block, Matthew S; Kalli, Kimberly R; Vierkant, Robert A; Chen, Wenqian; Fogarty, Zachary C; Gentry-Maharaj, Aleksandra; Tołoczko, Aleksandra; Hein, Alexander; Bouligny, Aliecia L; Jensen, Allan; Osorio, Ana; Hartkopf, Andreas D; Ryan, Andy; Chudecka-Głaz, Anita; Magliocco, Anthony M; Hartmann, Arndt; Jung, Audrey Y; Gao, Bo; Hernandez, Brenda Y; Fridley, Brooke L; McCauley, Bryan M; Kennedy, Catherine J; Wang, Chen; Karpinskyj, Chloe; de Sousa, Christiani B; Tiezzi, Daniel G; Wachter, David L; Herpel, Esther; Taran, Florin Andrei; Modugno, Francesmary; Nelson, Gregg; Lubiński, Jan; Menkiszak, Janusz; Alsop, Jennifer; Lester, Jenny; García-Donas, Jesús; Nation, Jill; Hung, Jillian; Palacios, José; Rothstein, Joseph H; Kelley, Joseph L; de Andrade, Jurandyr M; Robles-Díaz, Luis; Intermaggio, Maria P; Widschwendter, Martin; Beckmann, Matthias W; Ruebner, Matthias; Jimenez-Linan, Mercedes; Singh, Naveena; Oszurek, Oleg; Harnett, Paul R; Rambau, Peter F; Sinn, Peter; Wagner, Philipp; Ghatage, Prafull; Sharma, Raghwa; Edwards, Robert P; Ness, Roberta B; Orsulic, Sandra; Brucker, Sara Y; Johnatty, Sharon E; Longacre, Teri A; Eilber, Ursula; McGuire, Valerie; Sieh, Weiva; Natanzon, Yanina; Li, Zheng; Whittemore, Alice S; deFazio, Anna; Staebler, Annette; Karlan, Beth Y; Gilks, Blake; Bowtell, David D; Høgdall, Estrid; Candido dos Reis, Francisco J; Steed, Helen; Campbell, Ian G; Gronwald, Jacek; Benítez, Javier; Koziak, Jennifer M; Chang-Claude, Jenny; Moysich, Kirsten B; Kelemen, Linda E; Cook, Linda S; Goodman, Marc T; García, María José; Fasching, Peter A; Kommoss, Stefan; Deen, Suha; Kjaer, Susanne K; Menon, Usha; Brenton, James D; Pharoah, Paul DP; Chenevix-Trench, Georgia; Huntsman, David G; Winham, Stacey J; Köbel, Martin; Ramus, Susan J

2017-01-01

Importance Cytotoxic CD8+ T lymphocytes (TILs) participate in immune control of ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors. Objective To define the prognostic role of CD8+ TILs in epithelial ovarian cancer. Design Prospective survival cohort. Setting Multi-center observational. Participants Over 5,500 patients, including 3,196 high-grade serous ovarian carcinomas (HGSOCs), followed prospectively for over 24,650 person-years. Exposure(s) Following immunohistochemistry, CD8+ TILs were identified within the epithelial components of tumor islets. Patients were grouped based on the estimated number of CD8+ TILs per high-powered field: negative (none), low (1–2), moderate (3–19), and high (≥20). CD8+ TILs in a subset of patients were also assessed in a quantitative, uncategorized manner, and the functional form of associations with survival was assessed using penalized B-splines. Main Outcome Measure(s) Overall survival time. Results Among the five major invasive histotypes, HGSOCs showed the most infiltration. CD8+ TILs in HGSOCs were significantly associated with longer overall survival; median survival was 2.8 years for patients with no CD8+ TILs and 3.0 years, 3.8 years, and 5.1 years for patients with low, moderate, or high levels of CD8+ TILs, respectively (p-trend=4.2 × 10−16). A survival benefit was also observed among women with endometrioid and mucinous carcinomas, but not the other histotypes. Among HGSOCs, CD8+ TILs were favorable regardless of extent of residual disease following cytoreduction, known standard treatment, and germline BRCA1 pathogenic mutation, but were not prognostic for BRCA2 mutation carriers. Evaluation of uncategorized CD8+ TIL counts showed a near linear functional form. Conclusions and Relevance This study demonstrates the histotype-specific nature of immune infiltration and provides definitive evidence for a dose-response relationship between CD8+ TILs and HGSOC survival. That the extent of infiltration is prognostic, not merely its presence or absence, suggests that understanding factors which drive infiltration will be key to unravelling outcome heterogeneity in this cancer. PMID:29049607

Environmental factors associated with Crohn's disease in India.

PubMed

Pugazhendhi, Srinivasan; Sahu, Manoj Kumar; Subramanian, Venkataraman; Pulimood, Anna; Ramakrishna, Balakrishnan S

2011-12-01

The frequency of diagnosis of Crohn's disease (CD) in India is increasing. This case-control study was designed to detect associations of environmental and dietary factors with the diagnosis of CD. In 200 consecutive patients with CD and 200 control subjects without gastrointestinal disease, environmental hygiene exposures in childhood and in the past one year, and dietary preferences were recorded using a questionnaire. Univariate and multivariate analyses were done. In univariate analysis, CD showed positive association with urban residence (at birth and current), availability of protected drinking water (childhood and current), availability of piped water in the house (childhood and current), and strict vegetarian dietary habit, and negative association with regular fish consumption and presence of cattle in the house compound. Multivariate analysis showed that regular fish consumption (OR 0.52, 95% CI 0.33-0.80, p = 0.003), and presence of cattle in the house compound currently (OR 0.57, 95% CI 0.35-0.92, p = 0.023) were significant protective associations, whereas use of safe drinking water was positively associated (OR 1.59, 95% CI 1.02-2.47, p = 0.042) with the disease. Occurrence of CD was associated with dietary and environmental exposures, which indicate that diet and hygiene may influence the development of this disease.

A self-assembly aptasensor based on thick-shell quantum dots for sensing of ochratoxin A

NASA Astrophysics Data System (ADS)

Chu, Xianfeng; Dou, Xiaowen; Liang, Ruizheng; Li, Menghua; Kong, Weijun; Yang, Xihui; Luo, Jiaoyang; Yang, Meihua; Zhao, Ming

2016-02-01

A novel self-assembling aptasensor was fabricated by precisely attaching three phosphorothioate-modified capture aptamers onto a single thick-shell quantum dot in a controllable manner for monitoring of ochratoxin A (OTA), a poisonous contaminant widespread in foodstuffs. Herein, CdSe/CdS QDs coated in ten layer CdS shells were synthesized using a continual precursor injection method. Analysis of the prepared CdSe/CdS QDs showed a zinc-blende structure, high photoluminescence quantum yields (>80%), and a photoemission peak with a narrow full-width at half-maximum (about 29 nm), all qualities that render them as a superior choice for optical applications. By adjusting the number of phosphorothioate bases in the anchor domain, the tunable-valency aptasensor was able to self-assemble. In the sensing strategy, the thick-shell quantum dot was provided as an acceptor while OTA itself was used as a donor. In the presence of OTA, the capture aptamers drive the aptasensor function into a measurable signal through a fluorescence resonance energy transfer (FRET) system. The newly developed aptasensor had a detection limit as low as 0.5 ng mL-1, with a linear concentration in the range of 1 to 30 ng mL-1, and therefore meets the requirements for rapid, effective, and anti-interference sensors for real-world applications. Moreover, the high quality thick-shell QDs provide an ideal alternative for highly sensitive imaging and intensive illumination in the fields of biotechnology and bioengineering.A novel self-assembling aptasensor was fabricated by precisely attaching three phosphorothioate-modified capture aptamers onto a single thick-shell quantum dot in a controllable manner for monitoring of ochratoxin A (OTA), a poisonous contaminant widespread in foodstuffs. Herein, CdSe/CdS QDs coated in ten layer CdS shells were synthesized using a continual precursor injection method. Analysis of the prepared CdSe/CdS QDs showed a zinc-blende structure, high photoluminescence quantum yields (>80%), and a photoemission peak with a narrow full-width at half-maximum (about 29 nm), all qualities that render them as a superior choice for optical applications. By adjusting the number of phosphorothioate bases in the anchor domain, the tunable-valency aptasensor was able to self-assemble. In the sensing strategy, the thick-shell quantum dot was provided as an acceptor while OTA itself was used as a donor. In the presence of OTA, the capture aptamers drive the aptasensor function into a measurable signal through a fluorescence resonance energy transfer (FRET) system. The newly developed aptasensor had a detection limit as low as 0.5 ng mL-1, with a linear concentration in the range of 1 to 30 ng mL-1, and therefore meets the requirements for rapid, effective, and anti-interference sensors for real-world applications. Moreover, the high quality thick-shell QDs provide an ideal alternative for highly sensitive imaging and intensive illumination in the fields of biotechnology and bioengineering. Electronic supplementary information (ESI) available: Table S1. See DOI: 10.1039/c5nr08284f

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

Li, Chen; Paudel, Naba R.; Yan, Yanfa

Atom probe tomography (APT) data acquired from a CAMECA LEAP 4000 XHR for the CdS/CdTe interface for a non-CdCl 2 treated CdTe solar cell as well as the mass spectrum of an APT data set including a GB in a CdCl 2-treated CdTe solar cell are presented. Scanning electron microscopy (SEM) data showing the evolution of sample preparation for APT and scanning transmission electron microscopy (STEM) electron beam induced current (EBIC) are also presented. As a result, these data show mass spectrometry peak decomposition of Cu and Te within an APT dataset, the CdS/CdTe interface of an untreated CdTe solarmore » cell, preparation of APT needles from the CdS/CdTe interface in superstrate grown CdTe solar cells, and the preparation of a cross-sectional STEM EBIC sample.« less

Is current smoking still an important environmental factor in inflammatory bowel diseases? Results from a population-based incident cohort.

PubMed

Lakatos, Peter L; Vegh, Zsuzsanna; Lovasz, Barbara D; David, Gyula; Pandur, Tunde; Erdelyi, Zsuzsanna; Szita, Istvan; Mester, Gabor; Balogh, Mihaly; Szipocs, Istvan; Molnar, Csaba; Komaromi, Erzsebet; Golovics, Petra A; Mandel, Michael; Horvath, Agnes; Szathmari, Miklos; Kiss, Lajos S; Lakatos, Laszlo

2013-04-01

Previous studies suggest that smoking is an important environmental factor in inflammatory bowel diseases (IBDs), with dichotomous effects in ulcerative colitis (UC) and Crohn's disease (CD). The aim of this study was to analyze the relationship between smoking and IBD risk in a population-based database from Veszprem Province, which included incident cases diagnosed between January 1, 1977, and December 31, 2008. Data from 1420 incident patients were analyzed (UC: 914, age at diagnosis: 38.9 years; CD: 506, age at diagnosis: 31.5 years). Both inpatient and outpatient records were collected and comprehensively reviewed. Overall, smoking frequency in the adult general population was 36.1%. Of patients with CD, 47.2% were current smokers at diagnosis. Smoking was more frequent in male patients (P = 0.002) and was associated with an increased risk of CD (odds ratio, 1.96; 95% confidence interval, 1.63-2.37; P < 0.001). In contrast, current smoking was protective against UC (odds ratio, 0.33; 95% confidence interval, 0.27-0.41). The effect of smoking was linked to gender (in CD, more deleterious in male patients) and age at diagnosis and was most prominent in young adults, with a difference already being seen in 18- to 19-year-olds. In CD, a change in disease behavior (P = 0.02), location from ileal or colonic to ileocolonic (P = 0.003), arthritis/arthropathy (P = 0.002), need for steroids (P = 0.06), or AZA (P = 0.038) was more common in current smokers. Smoking in UC was associated with more extensive disease (P = 0.01) and a tendency for decreased need for colectomy (P = 0.06). Current smoking was associated with the risk of IBD. This effect was linked to gender and age at diagnosis and was most prominent in young adults. No association was observed in pediatric or elderly patients. The deleterious and protective effects of smoking on the course in CD and UC were partially confirmed.

Performance and Safety Characteristics of Sanyo NiCd Cells

NASA Technical Reports Server (NTRS)

Deng, Yi; Jeevarajan, Judith; Bragg, Bobby; Zhang, Wenlin

2002-01-01

NiCd batteries are widely used for high drain applications like power tools and also in other portable equipment like cameras, PCs, etc. NASA and Dreamtime Holdings, Inc. worked together to have the capability of a High Definition TV (HDTV) on the ISS and Space Shuttle. The Sanyo HD camcorder was used on the STS 105 fight in July, 2001 . The camcorder used two versions of a NiCd battery. One was a cOlnmercial off-the-shelf Sony BP90 battery pack that had Sanyo NiCd D cells. The other was a modified battery (FBP-90) made by Frezzi Energy, which also had the same Sanyo NiCd D cells. The battery has 10 NiCd D cells in series to form a 12 V pack with 5.0 Ah capacity. Our current study involved the perforn1ance and abuse tests on the Sanyo NiCd 5.0 Ah D cells. The best combination of charge/discharge current rate is 0.3C for charge and 1/2e for discharge within 200 cycles. No significant changes in capacity were observed in 200 cycles. The cell also showed capability of 5C (25.0A) high rate discharge. In overcharge and overdischarge tests, all tested cells passed the tests without venting. In imbalance tests, the battery pack could be charged and discharged only at relatively low current. At charge current of 1.0A or less, the imbalanced cells in the battery pack displayed relatively high temperatures during charge or discharge. The cells functioned normally during internal short and no mishap occurred during external short. Cells passed exposure tests at 80 C and no leakage till 150 C during heat-tovent tests.

Alcohol and Traffic Safety.

ERIC Educational Resources Information Center

Dickman, Frances Baker, Ed.

1988-01-01

Seven papers discuss current issues and applied social research concerning alcohol traffic safety. Prevention, policy input, methodology, planning strategies, anti-drinking/driving programs, social-programmatic orientations of Mothers Against Drunk Driving, Kansas Driving Under the Influence Law, New Jersey Driving While Impaired Programs,…

Immunosuppressive myeloid cells induced by chemotherapy attenuate antitumor CD4+ T-cell responses through the PD-1-PD-L1 axis.

PubMed

Ding, Zhi-Chun; Lu, Xiaoyun; Yu, Miao; Lemos, Henrique; Huang, Lei; Chandler, Phillip; Liu, Kebin; Walters, Matthew; Krasinski, Antoni; Mack, Matthias; Blazar, Bruce R; Mellor, Andrew L; Munn, David H; Zhou, Gang

2014-07-01

In recent years, immune-based therapies have become an increasingly attractive treatment option for patients with cancer. Cancer immunotherapy is often used in combination with conventional chemotherapy for synergistic effects. The alkylating agent cyclophosphamide (CTX) has been included in various chemoimmunotherapy regimens because of its well-known immunostimulatory effects. Paradoxically, cyclophosphamide can also induce suppressor cells that inhibit immune responses. However, the identity and biologic relevance of these suppressor cells are poorly defined. Here we report that cyclophosphamide treatment drives the expansion of inflammatory monocytic myeloid cells (CD11b(+)Ly6C(hi)CCR2(hi)) that possess immunosuppressive activities. In mice with advanced lymphoma, adoptive transfer (AT) of tumor-specific CD4(+) T cells following cyclophosphamide treatment (CTX+CD4 AT) provoked a robust initial antitumor immune response, but also resulted in enhanced expansion of monocytic myeloid cells. These therapy-induced monocytes inhibited long-term tumor control and allowed subsequent relapse by mediating functional tolerization of antitumor CD4(+) effector cells through the PD-1-PD-L1 axis. PD-1/PD-L1 blockade after CTX+CD4 AT therapy led to persistence of CD4(+) effector cells and durable antitumor effects. Depleting proliferative monocytes by administering low-dose gemcitabine effectively prevented tumor recurrence after CTX+CD4 AT therapy. Similarly, targeting inflammatory monocytes by disrupting the CCR2 signaling pathway markedly potentiated the efficacy of cyclophosphamide-based therapy. Besides cyclophosphamide, we found that melphalan and doxorubicin can also induce monocytic myeloid suppressor cells. These findings reveal a counter-regulation mechanism elicited by certain chemotherapeutic agents and highlight the importance of overcoming this barrier to prevent late tumor relapse after chemoimmunotherapy. ©2014 American Association for Cancer Research.

Deletion of BCG Hip1 protease enhances dendritic cell and CD4 T cell responses.

PubMed

Bizzell, Erica; Sia, Jonathan Kevin; Quezada, Melanie; Enriquez, Ana; Georgieva, Maria; Rengarajan, Jyothi

2018-04-01

Dendritic cells (DCs) play a key role in the generation of CD4 T cell responses to pathogens. Mycobacterium tuberculosis (Mtb) harbors immune evasion mechanisms that impair DC responses and prevent optimal CD4 T cell immunity. The vaccine strain Mycobacterium bovis Bacille Calmette-Guérin (BCG) shares many of the immune evasion proteins utilized by Mtb, but the role of these proteins in DC and T cell responses elicited by BCG is poorly understood. We previously reported that the Mtb serine protease, Hip1, promotes sub-optimal DC responses during infection. Here, we tested the hypothesis that BCG Hip1 modulates DC functions and prevents optimal antigen-specific CD4 T cell responses that limit the immunogenicity of BCG. We generated a strain of BCG lacking hip1 (BCGΔhip1) and show that it has superior capacity to induce DC maturation and cytokine production compared with the parental BCG. Furthermore, BCGΔhip1-infected DCs were more effective at driving the production of IFN-γ and IL-17 from antigen-specific CD4 T cells in vitro. Mucosal transfer of BCGΔhip1-infected DCs into mouse lungs induced robust CD4 T cell activation in vivo and generated antigen-specific polyfunctional CD4 T cell responses in the lungs. Importantly, BCGΔhip1-infected DCs enhanced control of pulmonary bacterial burden following Mtb aerosol challenge compared with the transfer of BCG-infected DCs. These results reveal that BCG employs Hip1 to impair DC activation, leading to attenuated lung CD4 T cell responses with limited capacity to control Mtb burden after challenge. ©2017 Society for Leukocyte Biology.

Tumor-Targeting Anti-CD20 Antibodies Mediate In Vitro Expansion of Memory Natural Killer Cells: Impact of CD16 Affinity Ligation Conditions and In Vivo Priming.

PubMed

Capuano, Cristina; Battella, Simone; Pighi, Chiara; Franchitti, Lavinia; Turriziani, Ombretta; Morrone, Stefania; Santoni, Angela; Galandrini, Ricciarda; Palmieri, Gabriella

2018-01-01

Natural killer (NK) cells represent a pivotal player of innate anti-tumor immune responses. The impact of environmental factors in shaping the representativity of different NK cell subsets is increasingly appreciated. Human cytomegalovirus (HCMV) infection profoundly affects NK cell compartment, as documented by the presence of a CD94/NKG2C + FcεRIγ - long-lived "memory" NK cell subset, endowed with enhanced CD16-dependent functional capabilities, in a fraction of HCMV-seropositive subjects. However, the requirements for memory NK cell pool establishment/maintenance and activation have not been fully characterized yet. Here, we describe the capability of anti-CD20 tumor-targeting therapeutic monoclonal antibodies (mAbs) to drive the selective in vitro expansion of memory NK cells and we show the impact of donor' HCMV serostatus and CD16 affinity ligation conditions on this event. In vitro expanded memory NK cells maintain the phenotypic and functional signature of their freshly isolated counterpart; furthermore, our data demonstrate that CD16 affinity ligation conditions differently affect memory NK cell proliferation and functional activation, as rituximab-mediated low-affinity ligation represents a superior proliferative stimulus, while high-affinity aggregation mediated by glycoengineered obinutuzumab results in improved multifunctional responses. Our work also expands the molecular and functional characterization of memory NK cells, and investigates the possible impact of CD16 functional allelic variants on their in vivo and in vitro expansions. These results reveal new insights in Ab-driven memory NK cell responses in a therapeutic setting and may ultimately inspire new NK cell-based intervention strategies against cancer, in which the enhanced responsiveness to mAb-bound target could significantly impact therapeutic efficacy.

DNA bases thymine and adenine in bio-organic light emitting diodes.

PubMed

Gomez, Eliot F; Venkatraman, Vishak; Grote, James G; Steckl, Andrew J

2014-11-24

We report on the use of nucleic acid bases (NBs) in organic light emitting diodes (OLEDs). NBs are small molecules that are the basic building blocks of the larger DNA polymer. NBs readily thermally evaporate and integrate well into the vacuum deposited OLED fabrication. Adenine (A) and thymine (T) were deposited as electron-blocking/hole-transport layers (EBL/HTL) that resulted in increases in performance over the reference OLED containing the standard EBL material NPB. A-based OLEDs reached a peak current efficiency and luminance performance of 48 cd/A and 93,000 cd/m(2), respectively, while T-based OLEDs had a maximum of 76 cd/A and 132,000 cd/m(2). By comparison, the reference OLED yielded 37 cd/A and 113,000 cd/m(2). The enhanced performance of T-based devices is attributed to a combination of energy levels and structured surface morphology that causes more efficient and controlled hole current transport to the emitting layer.

APT mass spectrometry and SEM data for CdTe solar cells

DOE PAGES

Li, Chen; Paudel, Naba R.; Yan, Yanfa; ...

2016-03-16

Atom probe tomography (APT) data acquired from a CAMECA LEAP 4000 XHR for the CdS/CdTe interface for a non-CdCl 2 treated CdTe solar cell as well as the mass spectrum of an APT data set including a GB in a CdCl 2-treated CdTe solar cell are presented. Scanning electron microscopy (SEM) data showing the evolution of sample preparation for APT and scanning transmission electron microscopy (STEM) electron beam induced current (EBIC) are also presented. As a result, these data show mass spectrometry peak decomposition of Cu and Te within an APT dataset, the CdS/CdTe interface of an untreated CdTe solarmore » cell, preparation of APT needles from the CdS/CdTe interface in superstrate grown CdTe solar cells, and the preparation of a cross-sectional STEM EBIC sample.« less

High speed, high current pulsed driver circuit

DOEpatents

Carlen, Christopher R.

2017-03-21

Various technologies presented herein relate to driving a LED such that the LED emits short duration pulses of light. This is accomplished by driving the LED with short duration, high amplitude current pulses. When the LED is driven by short duration, high amplitude current pulses, the LED emits light at a greater amplitude compared to when the LED is driven by continuous wave current.

Evaluation of a new photomask CD metrology tool

NASA Astrophysics Data System (ADS)

Dubuque, Leonard F.; Doe, Nicholas G.; St. Cin, Patrick

1996-12-01

In the integrated circuit (IC) photomask industry today, dense IC patterns, sub-micron critical dimensions (CD), and narrow tolerances for 64 M technologies and beyond are driving increased demands to minimize and characterize all components of photomask CD variation. This places strict requirements on photomask CD metrology in order to accurately characterize the mask CD error distribution. According to the gauge-maker's rule, measurement error must not exceed 30% of the tolerance on the product dimension measured or the gauge is not considered capable. The traditional single point repeatability tests are a poor measure of overall measurement system error in a dynamic, leading-edge technology environment. In such an environment, measurements may be taken at different points in the field- of-view due to stage in-accuracy, pattern recognition requirements, and throughput considerations. With this in mind, a set of experiments were designed to characterize thoroughly the metrology tool's repeatability and systematic error. Original experiments provided inconclusive results and had to be extended to obtain a full characterization of the system. Tests demonstrated a performance of better than 15 nm total CD error. Using this test as a tool for further development, the authors were able to determine the effects of various system components and measure the improvement with changes in optics, electronics, and software. Optimization of the optical path, electronics, and system software has yielded a new instrument with a total system error of better than 8 nm. Good collaboration between the photomask manufacturer and the equipment supplier has led to a realistic test of system performance and an improved CD measurement instrument.

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

Prototyping of MWIR MEMS-based optical filter combined with HgCdTe detector

NASA Astrophysics Data System (ADS)

Kozak, Dmitry A.; Fernandez, Bautista; Velicu, Silviu; Kubby, Joel

2010-02-01

In the past decades, there have been several attempts to create a tunable optical detector with operation in the infrared. The drive for creating such a filter is its wide range of applications, from passive night vision to biological and chemical sensors. Such a device would combine a tunable optical filter with a wide-range detector. In this work, we propose using a Fabry-Perot interferometer centered in the mid-wave infrared (MWIR) spectrum with an HgCdTe detector. Using a MEMS-based interferometer with an integrated Bragg stack will allow in-plane operation over a wide range. Because such devices have a tendency to warp, creating less-than-perfect optical surfaces, the Fabry-Perot interferometer is prototyped using the SOI-MUMPS process to ensure desirable operation. The mechanical design is aimed at optimal optical flatness of the moving membranes and a low operating voltage. The prototype is tested for these requirements. An HgCdTe detector provides greater performance than a pyroelectic detector used in some previous work, allowing for lower noise, greater detection speed and higher sensitivity. Both a custom HgCdTe detector and commercially available pyroelectric detector are tested with commercial optical filter. In previous work, monolithic integration of HgCdTe detectors with optical filters proved to be problematic. Part of this work investigates the best approach to combining these two components, either monolithically in HgCdTe or using a hybrid packaging approach where a silicon MEMS Fabry-Perot filter is bonded at low temperature to a HgCdTe detector.

A prospective study of appetite and food craving in 30 patients with Cushing’s disease

PubMed Central

Geer, Eliza B.; Lalazar, Yelena; Couto, Lizette M.; Cohen, Vanessa; Lipton, Lianna R.; Shi, Wei; Bagiella, Emilia; Conwell, Irene; Bederson, Joshua; Kostadinov, Jane; Post, Kalmon D.; Freda, Pamela U.

2015-01-01

Context Glucocorticoid (GC) exposure increases food intake, but the mechanisms in humans are not known. Investigation of appetite and food craving has not been done in patients with chronic GC exposure due to Cushing’s disease (CD), either before or after treatment, and could provide insight into mechanisms of food intake and obesity in these patients. Purpose To examine whether surgical remission of CD changes appetite (prospective consumption, hunger, satisfaction, and fullness) and food cravings (sweet, salty, fatty, and savory); and to identify predictors of appetite and craving in CD remission. Methods 30 CD patients, mean age 40.0 yr. (range 17–70), mean BMI 32.3 ± 6.4, were prospectively studied before and at a mean of 17.4 mo. after remission. At each visit fasting and post-test meal (50% carbohydrate, 35% protein, 15% fat) appetite and craving scores were assessed. Results Remission decreased prospective consumption, sweet and savory craving (p<0.05), but did not change hunger, satisfaction, fullness, or fat craving, despite decreases in BMI and fat mass. In CD remission, serum cortisol predicted lower satisfaction and fullness, and masses of abdominal fat depots predicted higher hunger and consumption (p<0.05). Conclusions Chronic GC exposure in CD patients may stimulate the drive to eat by enhancing craving, rather than regulating the sensation of hunger. Continued alterations in appetite regulation due to abdominal fat mass and circulating cortisol could play a role in the cardiovascular and metabolic risk that has been reported in CD patients despite remission. PMID:26496766

Myosin 1g Contributes to CD44 Adhesion Protein and Lipid Rafts Recycling and Controls CD44 Capping and Cell Migration in B Lymphocytes

PubMed Central

López-Ortega, Orestes; Santos-Argumedo, Leopoldo

2017-01-01

Cell migration and adhesion are critical for immune system function and involve many proteins, which must be continuously transported and recycled in the cell. Recycling of adhesion molecules requires the participation of several proteins, including actin, tubulin, and GTPases, and of membrane components such as sphingolipids and cholesterol. However, roles of actin motor proteins in adhesion molecule recycling are poorly understood. In this study, we identified myosin 1g as one of the important motor proteins that drives recycling of the adhesion protein CD44 in B lymphocytes. We demonstrate that the lack of Myo1g decreases the cell-surface levels of CD44 and of the lipid raft surrogate GM1. In cells depleted of Myo1g, the recycling of CD44 was delayed, the delay seems to be caused at the level of formation of recycling complex and entry into recycling endosomes. Moreover, a defective lipid raft recycling in Myo1g-deficient cells had an impact both on the capping of CD44 and on cell migration. Both processes required the transportation of lipid rafts to the cell surface to deliver signaling components. Furthermore, the extramembrane was essential for cell expansion and remodeling of the plasma membrane topology. Therefore, Myo1g is important during the recycling of lipid rafts to the membrane and to the accompanied proteins that regulate plasma membrane plasticity. Thus, Myosin 1g contributes to cell adhesion and cell migration through CD44 recycling in B lymphocytes. PMID:29321775

Impaired NK Cell Responses to Pertussis and H1N1 Influenza Vaccine Antigens in Human Cytomegalovirus-Infected Individuals

PubMed Central

Nielsen, Carolyn M.; White, Matthew J.; Bottomley, Christian; Lusa, Chiara; Rodríguez-Galán, Ana; Turner, Scarlett E. G.; Goodier, Martin R.

2015-01-01

NK cells contribute to postvaccination immune responses after activation by IL-2 from Ag-specific memory T cells or by cross-linking of the low-affinity IgG receptor, CD16, by Ag–Ab immune complexes. Sensitivity of NK cells to these signals from the adaptive immune system is heterogeneous and influenced by their stage of differentiation. CD56dimCD57+ NK cells are less responsive to IL-2 and produce less IFN-γ in response to T cell–mediated activation than do CD56bright or CD56dimCD57− NK cells. Conversely, NK cell cytotoxicity, as measured by degranulation, is maintained across the CD56dim subsets. Human CMV (HCMV), a highly prevalent herpes virus causing lifelong, usually latent, infections, drives the expansion of the CD56dimCD57+NKG2C+ NK cell population, skewing the NK cell repertoire in favor of cytotoxic responses at the expense of cytokine-driven responses. We hypothesized, therefore, that HCMV seropositivity would be associated with altered NK cell responses to vaccine Ags. In a cross-sectional study of 152 U.K. adults, with HCMV seroprevalence rate of 36%, we find that HCMV seropositivity is associated with lower NK cell IFN-γ production and degranulation after in vitro restimulation with pertussis or H1N1 influenza vaccine Ags. Higher expression of CD57/NKG2C and lower expression of IL-18Rα on NK cells from HCMV seropositive subjects do not fully explain these impaired responses, which are likely the result of multiple receptor–ligand interactions. This study demonstrates for the first time, to our knowledge, that HCMV serostatus influences NK cell contributions to adaptive immunity and raises important questions regarding the impact of HCMV infection on vaccine efficacy. PMID:25855356

Challenging the roles of CD44 and lipolysis stimulated lipoprotein receptor in conveying Clostridium perfringens iota toxin cytotoxicity in breast cancer

PubMed Central

2014-01-01

Background Translational exploration of bacterial toxins has come to the forefront of research given their potential as a chemotherapeutic tool. Studies in select tissues have demonstrated that Clostridium perfringens iota toxin binds to CD44 and lipolysis stimulated lipoprotein receptor (LSR) cell-surface proteins. We recently demonstrated that LSR expression correlates with estrogen receptor positive breast cancers and that LSR signaling directs aggressive, tumor-initiating cell behaviors. Herein, we identify the mechanisms of iota toxin cytotoxicity in a tissue-specific, breast cancer model with the ultimate goal of laying the foundation for using iota toxin as a targeted breast cancer therapy. Methods In vitro model systems were used to determine the cytotoxic effect of iota toxin on breast cancer intrinsic subtypes. The use of overexpression and knockdown technologies confirmed the roles of LSR and CD44 in regulating iota toxin endocytosis and induction of cell death. Lastly, cytotoxicity assays were used to demonstrate the effect of iota toxin on a validated set of tamoxifen resistant breast cancer cell lines. Results Treatment of 14 breast cancer cell lines revealed that LSR+/CD44- lines were highly sensitive, LSR+/CD44+ lines were slightly sensitive, and LSR-/CD44+ lines were resistant to iota cytotoxicity. Reduction in LSR expression resulted in a significant decrease in toxin sensitivity; however, overexpression of CD44 conveyed toxin resistance. CD44 overexpression was correlated with decreased toxin-stimulated lysosome formation and decreased cytosolic levels of iota toxin. These findings indicated that expression of CD44 drives iota toxin resistance through inhibition of endocytosis in breast cancer cells, a role not previously defined for CD44. Moreover, tamoxifen-resistant breast cancer cells exhibited robust expression of LSR and were highly sensitive to iota-induced cytotoxicity. Conclusions Collectively, these data are the first to show that iota toxin has the potential to be an effective, targeted therapy for breast cancer. PMID:24990559

Challenging the roles of CD44 and lipolysis stimulated lipoprotein receptor in conveying Clostridium perfringens iota toxin cytotoxicity in breast cancer.

PubMed

Fagan-Solis, Katerina D; Reaves, Denise K; Rangel, M Cristina; Popoff, Michel R; Stiles, Bradley G; Fleming, Jodie M

2014-07-02

Translational exploration of bacterial toxins has come to the forefront of research given their potential as a chemotherapeutic tool. Studies in select tissues have demonstrated that Clostridium perfringens iota toxin binds to CD44 and lipolysis stimulated lipoprotein receptor (LSR) cell-surface proteins. We recently demonstrated that LSR expression correlates with estrogen receptor positive breast cancers and that LSR signaling directs aggressive, tumor-initiating cell behaviors. Herein, we identify the mechanisms of iota toxin cytotoxicity in a tissue-specific, breast cancer model with the ultimate goal of laying the foundation for using iota toxin as a targeted breast cancer therapy. In vitro model systems were used to determine the cytotoxic effect of iota toxin on breast cancer intrinsic subtypes. The use of overexpression and knockdown technologies confirmed the roles of LSR and CD44 in regulating iota toxin endocytosis and induction of cell death. Lastly, cytotoxicity assays were used to demonstrate the effect of iota toxin on a validated set of tamoxifen resistant breast cancer cell lines. Treatment of 14 breast cancer cell lines revealed that LSR+/CD44- lines were highly sensitive, LSR+/CD44+ lines were slightly sensitive, and LSR-/CD44+ lines were resistant to iota cytotoxicity. Reduction in LSR expression resulted in a significant decrease in toxin sensitivity; however, overexpression of CD44 conveyed toxin resistance. CD44 overexpression was correlated with decreased toxin-stimulated lysosome formation and decreased cytosolic levels of iota toxin. These findings indicated that expression of CD44 drives iota toxin resistance through inhibition of endocytosis in breast cancer cells, a role not previously defined for CD44. Moreover, tamoxifen-resistant breast cancer cells exhibited robust expression of LSR and were highly sensitive to iota-induced cytotoxicity. Collectively, these data are the first to show that iota toxin has the potential to be an effective, targeted therapy for breast cancer.

Carrier Transport, Recombination, and the Effects of Grain Boundaries in Polycrystalline Cadmium Telluride Thin Films for Photovoltaics

NASA Astrophysics Data System (ADS)

Tuteja, Mohit

Cadmium Telluride (CdTe), a chalcogenide semiconductor, is currently used as the absorber layer in one of the highest efficiency thin film solar cell technologies. Current efficiency records are over 22%. In 2011, CdTe solar cells accounted for 8% of all solar cells installed. This is because, in part, CdTe has a low degradation rate, high optical absorption coefficient, and high tolerance to intrinsic defects. Solar cells based on polycrystalline CdTe exhibit a higher short-circuit current, fill factor, and power conversion efficiency than their single crystal counterparts. This is despite the fact that polycrystalline CdTe devices exhibit lower open-circuit voltages. This is contrary to the observation for silicon and III-V semiconductors, where material defects cause a dramatic drop in device performance. For example, grain boundaries in covalently-bonded semiconductors (a) act as carrier recombination centers, and (b) lead to localized energy states, causing carrier trapping. Despite significant research to date, the mechanism responsible for the superior current collection properties of polycrystalline CdTe solar cells has not been conclusively answered. This dissertation focuses on the macro-scale electronic band structure, and micro scale electronic properties of grains and grain boundaries in device-grade CdTe thin films to answer this open question. My research utilized a variety of experimental techniques. Samples were obtained from leading groups fabricating the material and devices. A CdCl 2 anneal is commonly performed as part of this fabrication and its effects were also investigated. Photoluminescence (PL) spectroscopy was employed to study the band structure and defect states in CdTe polycrystals. Cadmium vacancy- and chlorine-related states lead to carrier recombination, as in CdTe films grown by other methods. Comparing polycrystalline and single crystal CdTe, showed that the key to explaining the improved performance of polycrystalline CdTe does not lie in macroscopic analysis. The nanoscale majority carrier concentration was studied using scanning microwave impedance microscopy, which revealed an existence of majority carrier depletion along the grain boundaries, independent of the growth process used, which was absent in films that were not subjected to CdCl2 annealing. This effect promotes carrier separation and collection. Conductive atomic force microscopy showed enhanced conduction of electrons along the grain boundaries in samples subjected to the CdCl2 anneal treatment while holes were shown to move through the grain bulk. The separation of conduction channels minimizes recombination while simultaneously reducing series resistance and hence enhancing fill factor. Several technical capabilities demonstrated in this work can be easily extended to other semiconductor materials.

Design and Development of Amplitude and phase measurement of RF signal with Digital I-Q Demodulator

NASA Astrophysics Data System (ADS)

Soni, Dipal; Rajnish, Kumar; Verma, Sriprakash; Patel, Hriday; Trivedi, Rajesh; Mukherjee, Aparajita

2017-04-01

ITER-India, working as a nodal agency from India for ITER project [1], is responsible to deliver one of the packages, called Ion Cyclotron Heating & Current Drive (ICH&CD) - Radio Frequency Power Sources (RFPS). RFPS is having two cascaded amplifier chains (10 kW, 130 kW & 1.5 MW) combined to get 2.5 MW RF power output. Directional couplers are inserted at the output of each stage to extract forward power and reflected power as samples for measurement of amplitude and phase. Using passive mixer, forward power and reflected power are down converted to 1MHz Intermediate frequency (IF). This IF signal is used as an input to the Digital IQ Demodulator (DIQDM). DIQDM is realized using National Instruments make PXI hardware & LabVIEW software tool. In this paper, Amplitude and Phase measurement of RF signal with DIQDM technique is described. Also test results with dummy signals and signal generated from low power RF systems is discussed here.

Reduced ion bootstrap current drive on NTM instability

NASA Astrophysics Data System (ADS)

Qu, Hongpeng; Wang, Feng; Wang, Aike; Peng, Xiaodong; Li, Jiquan

2018-05-01

The loss of bootstrap current inside magnetic island plays a dominant role in driving the neoclassical tearing mode (NTM) instability in tokamak plasmas. In this work, we investigate the finite-banana-width (FBW) effect on the profile of ion bootstrap current in the island vicinity via an analytical approach. The results show that even if the pressure gradient vanishes inside the island, the ion bootstrap current can partly survive due to the FBW effect. The efficiency of the FBW effect is higher when the island width becomes smaller. Nevertheless, even when the island width is comparable to the ion FBW, the unperturbed ion bootstrap current inside the island cannot be largely recovered by the FBW effect, and thus the current loss still exists. This suggests that FBW effect alone cannot dramatically reduce the ion bootstrap current drive on NTMs.

Synthesis and photoelectric properties of cadmium hydroxide and cadmium hydroxide/cadmium sulphide ultrafine nanowires

NASA Astrophysics Data System (ADS)

Dou, Baoli; Jiang, Xiaohong; Wang, Xiaohong; Tang, Liping; Du, Zuliang

2017-07-01

Cd(OH)2 ultrafine nanowires with a high aspect ratio were fabricated by the hydrothermal method and were subsequently used as a sacrificial template to generate Cd(OH)2/CdS nanowires. The transmission electron microscopy results show that the length of the nanowires reached several micrometres, and the diameter of the nanowires was approximately 10-20.0 nm. The charge transport properties of the Cd(OH)2 and Cd(OH)2/CdS nanowires assembled on comb Au electrodes was also investigated. The I-V results showed that the current intensity of the Cd(OH)2/CdS nanowires was increased by four orders of magnitude compared with the Cd(OH)2 nanowires, achieving 10-10A.

Shunt resistance and saturation current determination in CdTe and CIGS solar cells. Part 1: a new theoretical procedure and comparison with other methodologies

NASA Astrophysics Data System (ADS)

Rangel-Kuoppa, Victor-Tapio; Albor-Aguilera, María-de-Lourdes; Hérnandez-Vásquez, César; Flores-Márquez, José-Manuel; González-Trujillo, Miguel-Ángel; Contreras-Puente, Gerardo-Silverio

2018-04-01

A new proposal for the extraction of the shunt resistance (R sh ) and saturation current (I sat ) of a current-voltage (I-V) measurement of a solar cell, within the one-diode model, is given. First, the Cheung method is extended to obtain the series resistance (R s ), the ideality factor (n) and an upper limit for I sat . In this article which is Part 1 of two parts, two procedures are proposed to obtain fitting values for R sh and I sat within some voltage range. These two procedures are used in two simulated I-V curves (one in darkness and the other one under illumination) to recover the known solar cell parameters R sh , R s , n, I sat and the light current I lig and test its accuracy. The method is compared with two different common parameter extraction methods. These three procedures are used and compared in Part 2 in the I-V curves of CdS-CdTe and CIGS-CdS solar cells.

Fuel magnetization without external field coils (AutoMag)

NASA Astrophysics Data System (ADS)

Slutz, Stephen; Jennings, Christopher; Awe, Thomas; Shipley, Gabe; Lamppa, Derek; McBride, Ryan

2016-10-01

Magnetized Liner Inertial Fusion (MagLIF) has produced fusion-relevant plasma conditions on the Z accelerator where the fuel was magnetized using external field coils. We present a novel concept that does not need external field coils. This concept (AutoMag) magnetizes the fuel during the early part of the drive current by using a composite liner with helical conduction paths separated by insulating material. The drive is designed so the current rises slowly enough to avoid electrical breakdown of the insulators until a sufficiently strong magnetic field is established. Then the current rises more quickly, which causes the insulators to break down allowing the drive current to follow an axial path and implode the liner. Low inductance magnetically insulated power feeds can be used with AutoMag to increase the drive current without interfering with diagnostic access. Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the United States Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Radially Focused Eddy Current Sensor for Detection of Longitudinal Flaws in Metallic Tubes

NASA Technical Reports Server (NTRS)

Wincheski, Russell A. (Inventor); Simpson, John W. (Inventor); Fulton, James P. (Inventor); Nath, Shridhar C. (Inventor); Todhunter, Ronald G. (Inventor); Namkung, Min (Inventor)

1999-01-01

A radially focused eddy current sensor detects longitudinal flaws in a metal tube. A drive coil induces eddy currents within the wall of the metal tube. A pick-up cod is spaced apart from the drive coil along the length of the metal tube. The pick@up coil is positioned with one end thereof lying adjacent the wall of the metal tube such that the pick-up coil's longitudinal axis is perpendicular to the wall of the metal tube. To isolate the pick-up coil from the magnetic flux of the drive coil and the flux from the induced eddy currents. except the eddy currents diverted by a longitudinal flaw. an electrically conducting material high in magnetic permeability surrounds all of the pick-up coil except its one end that is adjacent the walls of the metal tube. The electrically conducting material can extend into and through the drive coil in a coaxial relationship therewith.

CD4 and CD8 T-Cell Responses to Mycobacterial Antigens in African Children

PubMed Central

Tena-Coki, Nontobeko G.; Scriba, Thomas J.; Peteni, Nomathemba; Eley, Brian; Wilkinson, Robert J.; Andersen, Peter; Hanekom, Willem A.; Kampmann, Beate

2010-01-01

Rationale: The current tuberculosis (TB) vaccine, bacille Calmette-Guérin (BCG), does not provide adequate protection against TB disease in children. Furthermore, more efficacious TB vaccines are needed for children with immunodeficiencies such as HIV infection, who are at highest risk of disease. Objectives: To characterize mycobacteria-specific T cells in children who might benefit from vaccination against TB, focusing on responses to antigens contained in novel TB vaccines. Methods: Whole blood was collected from three groups of BCG-vaccinated children: HIV-seronegative children receiving TB treatment (n = 30), HIV-infected children (n = 30), and HIV-unexposed healthy children (n = 30). Blood was stimulated with Ag85B and TB10.4, or purified protein derivative, and T-cell cytokine production by CD4 and CD8 was determined by flow cytometry. The memory phenotype of antigen-specific CD4 and CD8 T cells was also determined. Measurements and Main Results: Mycobacteria-specific CD4 and CD8 T-cell responses were detectable in all three groups of children. Children receiving TB treatment had significantly higher frequencies of antigen-specific CD4 T cells compared with HIV-infected children (P = 0.0176). No significant differences in magnitude, function, or phenotype of specific T cells were observed in HIV-infected children compared with healthy control subjects. CD4 T cells expressing IFN-γ, IL-2, or both expressed a CD45RA−CCR7−CD27+/− effector memory phenotype. Mycobacteria-specific CD8 T cells expressed mostly IFN-γ in all groups of children; these cells expressed CD45RA−CCR7−CD27+/− or CD45RA+CCR7−CD27+/− effector memory phenotypes. Conclusions: Mycobacteria-specific T-cell responses could be demonstrated in all groups of children, suggesting that the responses could be boosted by new TB vaccines currently in clinical trials. PMID:20224065

Radiation Induced Vaccination to Breast Cancer

DTIC Science & Technology

2016-12-01

in supporting a memory CD8 T cell response and decreased MDSCs but in reality the small patient numbers and the relatively short survival times...ABSTRACT Inhibiting TGFβ in the context of focal irradiation seems to create a favorable systemic immune landscape that drives T cell memory ...differentiation while limiting myeloid suppression. 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES

Driving Solar Innovations from Laboratory to Marketplace - Continuum

Science.gov Websites

. military-funded core technologies would someday lead to the internet. Or that a solar photovoltaics (PV more than a dozen start-up thin-film PV companies. This ultimately led to the creation of First Solar build a large-scale solar PV module plant in Colorado. As it has matured, CdTe technology has achieved

The 1996 IDA Cost Research Symposium.

DTIC Science & Technology

1996-08-01

5160 Christopher Deegan (703)602-6575 Performer: Naval Surface Warfare Center (211) Carderock Division, NSWC/CD Bethesda, Maryland 20084-5000...Moore (703) 602-0330, ext 208 Cost Engineering Research, Inc. 2011 Crystal Drive Arlington, VA 22202-3717 Bill Hugo Bob Craig Classification...Director, Force and Infrastructure Cost Analysis Division OD (PA&E) Room 2D278, The Pentagon Washington, DC 20301 Dr. Craig College LMI John Wallace

Sensor-less pseudo-sinusoidal drive for a permanent-magnet brushless ac motor

NASA Astrophysics Data System (ADS)

Liu, Li-Hsiang; Chern, Tzuen-Lih; Pan, Ping-Lung; Huang, Tsung-Mou; Tsay, Der-Min; Kuang, Jao-Hwa

2012-04-01

The precise rotor-position information is required for a permanent-magnet brushless ac motor (BLACM) drive. In the conventional sinusoidal drive method, either an encoder or a resolver is usually employed. For position sensor-less vector control schemes, the rotor flux estimation and torque components are obtained by complicated coordinate transformations. These computational intensive methods are susceptible to current distortions and parameter variations. To simplify the method complexity, this work presents a sensor-less pseudo-sinusoidal drive scheme with speed control for a three-phase BLACM. Based on the sinusoidal drive scheme, a floating period of each phase current is inserted for back electromotive force detection. The zero-crossing point is determined directly by the proposed scheme, and the rotor magnetic position and rotor speed can be estimated simultaneously. Several experiments for various active angle periods are undertaken. Furthermore, a current feedback control is included to minimize and compensate the torque fluctuation. The experimental results show that the proposed method has a competitive performance compared with the conventional drive manners for BLACM. The proposed scheme is straightforward, bringing the benefits of sensor-less drive and negating the need for coordinate transformations in the operating process.

Urinary tract infections in pregnant women with coeliac disease.

PubMed

Olén, Ola; Montgomery, Scott M; Ekbom, Anders; Bollgren, Ingela; Ludvigsson, Jonas F

2007-02-01

Previous research has indicated a link between coeliac disease (CD) and urinary tract infection (UTI). The objective of this study was to assess the risk of UTI and repeated episodes of UTI before the current pregnancy in women with diagnosed or undiagnosed CD. A national registry-based cohort study restricted to pregnant women was used in this investigation, with linkage between the Swedish National Medical Birth Registry and the National Inpatient Registry. We analysed the risk of UTI during pregnancy from 1973 to 1989 in 212 pregnancies to women who had received a diagnosis of CD prior to giving birth and in 786 pregnancies to women diagnosed after giving birth. We also assessed the risk of repeated episodes of UTI before the current pregnancy according to data in the national birth records of 1990-2001 in 617 women with CD diagnosed prior to giving birth and 109 women diagnosed after giving birth. UTI during pregnancy: UTI occurred during 19,139/1,678,304 pregnancies to women who had never had a diagnosis of CD, compared with in 12/786 pregnancies to women with undiagnosed CD (adjusted odds ratio (AOR)=1.37; 95% CI=0.78-2.43; p=0.276) and in 0/212 pregnancies to women with diagnosed CD (AOR=0.06; 95% CI=0.00-8.94; p=0.277) (ORs adjusted for maternal age, parity, nationality and calendar period). Repeated episodes of UTI before the current pregnancy: among 692,991 women who had never had a diagnosis of CD, 74,776 reported repeated episodes of UTI, compared with 14/101 women with undiagnosed CD (AOR=1.39; 95% CI=0.79-2.45; p=0.255) and 69/566 women with diagnosed CD (AOR=1.02; 95% CI=0.79-1.32; p=0.864) (ORs adjusted for maternal age, parity, nationality, calendar period and civil status). Adjustment for smoking in a subset of patients with available data did not change the risk estimates. It cannot be ruled out that undiagnosed CD in pregnant women is associated with a small, increased risk of UTI. In pregnant women with diagnosed CD, there seems to be no increased risk of UTI.

Nanotechniques Inactivate Cancer Stem Cells

NASA Astrophysics Data System (ADS)

Goltsev, Anatoliy N.; Babenko, Natalya N.; Gaevskaya, Yulia A.; Bondarovich, Nikolay A.; Dubrava, Tatiana G.; Ostankov, Maksim V.; Chelombitko, Olga V.; Malyukin, Yuriy V.; Klochkov, Vladimir K.; Kavok, Nataliya S.

2017-06-01

One of the tasks of current oncology is identification of cancer stem cells and search of therapeutic means capable of their specific inhibition. The paper presents the data on phenotype characteristics of Ehrlich carcinoma cells as convenient and easy-to-follow model of tumor growth. The evidence of cancer stem cells as a part of Ehrlich carcinoma and significance of CD44+ and CD44- subpopulations in maintaining the growth of this type of tumor were demonstrated. A high (tenfold) tumorigenic activity of the Ehrlich carcinoma CD44+ cells if compared to CD44- cells was proven. In this pair of comparison, the CD44+ cells had a higher potential of generating in peritoneal cavity of CD44high, CD44+CD24-, CD44+CD24+ cell subpopulations, highlighting the presence of cancer stem cells in a pool of CD44+ cells.

Using AORSA to simulate helicon waves in DIII-D

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

Lau, C., E-mail: lauch@ornl.gov; Blazevski, D.; Green, D. L.

2015-12-10

Recent efforts have shown that helicon waves (fast waves at > 20ω{sub ci}) may be an attractive option for driving efficient off-axis current drive during non-inductive tokamak operation for DIII-D, ITER and DEMO. For DIII-D scenarios, the ray tracing code, GENRAY, has been extensively used to study helicon current drive efficiency and location as a function of many plasma parameters. The full wave code, AORSA, which is applicable to arbitrary Larmor radius and can resolve arbitrary ion cyclotron harmonic order, has been recently used to validate the ray tracing technique at these high cyclotron harmonics. If the SOL is ignored,more » it will be shown that the GENRAY and AORSA calculated current drive profiles are comparable for the envisioned high beta advanced scenarios for DIII-D, where there is high single pass absorption due to electron Landau damping and minimal ion damping. AORSA is also been used to estimate possible SOL effects on helicon current drive coupling and SOL absorption due to collisional and slow wave effects.« less

Using AORSA to simulate helicon waves in DIII-D

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

Lau, Cornwall H; Jaeger, E. F.; Bertelli, Nicola

2015-01-01

Recent efforts have shown that helicon waves (fast waves at >20 omega(ci)) may be an attractive option for driving efficient off-axis current drive during non-inductive tokamak operation for DIII-D, ITER and DEMO. For DIII-D scenarios, the ray tracing code, GENRAY, has been extensively used to study helicon current drive efficiency and location as a function of many plasma parameters. The full wave code, AORSA, which is applicable to arbitrary Larmor radius and can resolve arbitrary ion cyclotron harmonic order, has been recently used to validate the ray tracing technique at these high cyclotron harmonics. If the SOL is ignored, itmore » will be shown that the GENRAY and AORSA calculated current drive profiles are comparable for the envisioned high beta advanced scenarios for DIII-D, where there is high single pass absorption due to electron Landau damping and minimal ion damping. AORSA is also been used to estimate possible SOL effects on helicon current drive coupling and SOL absorption due to collisional and slow wave effects.« less

LETTER: Investigation of the effect of Alfven resonance mode conversion on fast wave current drive in ITER

NASA Astrophysics Data System (ADS)

Alava, M. J.; Heikkinen, J. A.; Hellsten, T.

1995-07-01

In order to reduce or to avoid ion cyclotron damping, the use of frequencies below the ion cyclotron frequency of minority ion species or the second harmonic of majority ion species has been proposed for fast wave current drive based on direct electron absorption. For these scenarios, the Alfven or ion-ion hybrid resonance can appear on the high field side of a tokamak. The presence of these resonances causes parasitic absorption, competing with the electron Landau damping and transit time magnetic pumping responsible for the fast wave current drive. In the present study, neglecting effects from toroidicity, the mode conversion at the Alfven resonance is shown to be of the order of 5 to 10% in the current drive scenarios for the planned ITER experiment. If the single pass absorption in the centre can be made sufficiently high, the conversion at the Alfven resonance becomes negligible

Investigation of the effect of Alfven resonance absorption on fast wave current drive in ITER

NASA Astrophysics Data System (ADS)

Alava, M. J.; Heikkinen, J. A.; Hellsten, T.

The use of frequencies below the ion cyclotron frequency of minority ion species or second harmonic of majority species has been proposed for fast wave current drive in order to reduce or to avoid ion cyclotron damping. For these scenarios, the Alfven resonance can appear on the high field side of a tokamak. The presence of this resonance causes parasitic absorption competing with the electron Landau damping and transit time magnetic pumping responsible for the fast wave current drive. In the present study, the mode conversion at the Alfven resonance is shown to be of the order of 5 to 10 percent in the current drive scenarios for the planned International Thermonuclear Experimental Reactor (ITER) experiment. However, if the single pass absorption in the center can be made sufficiently high, the conversion at the Alfven resonance becomes negligible.

An Inverter Packaging Scheme for an Integrated Segmented Traction Drive System

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

Su, Gui-Jia; Tang, Lixin; Ayers, Curtis William

The standard voltage source inverter (VSI), widely used in electric vehicle/hybrid electric vehicle (EV/HEV) traction drives, requires a bulky dc bus capacitor to absorb the large switching ripple currents and prevent them from shortening the battery s life. The dc bus capacitor presents a significant barrier to meeting inverter cost, volume, and weight requirements for mass production of affordable EVs/HEVs. The large ripple currents become even more problematic for the film capacitors (the capacitor technology of choice for EVs/HEVs) in high temperature environments as their ripple current handling capability decreases rapidly with rising temperatures. It is shown in previous workmore » that segmenting the VSI based traction drive system can significantly decrease the ripple currents and thus the size of the dc bus capacitor. This paper presents an integrated packaging scheme to reduce the system cost of a segmented traction drive.« less

CD44v6 expression in patients with stage II or stage III sporadic colorectal cancer is superior to CD44 expression for predicting progression

PubMed Central

Zhao, LH; Lin, QL; Wei, J; Huai, YL; Wang, KJ; Yan, HY

2015-01-01

Background: Currently, it is difficult to predict the prognosis of patients exhibiting stage II or stage III colorectal cancer (CRC) and to identify those patients most likely to benefit from aggressive treatment. The current study was performed to examine the clinicopathological significance of CD44 and CD44v6 protein expression in these patients. Study design: We retrospectively investigated 187 consecutive patients who underwent surgery with curative intent for stage II to III CRC from 2007 to 2013 in the Beijing Civil Aviation Hospital. CD44 and CD44v6 protein expression levels were determined using immunohistochemistry and compared to the clinicopathological data. Results: Using immunohistochemical detection, CD44 expression was observed in 108 (57.75%) of the CRC patients; and its detection was significantly associated with greater invasion depth, lymph node metastasis, angiolymphatic invasion, and a more advanced pathological tumor-lymph node-metastasis (TNM) stage. CD44v6 expression was observed in 135 (72.19%) of the CRC patients; and its expression was significantly associated with a poorly differentiated histology, greater invasion depth, lymph node metastasis, angiolymphatic invasion, and a more advanced pathological TNM stage. Expression of CD44v6 was higher than that of CD44 in stage II and stage III sporadic CRC. Conclusion: CD44v6 is a more useful marker for predicting a poor prognosis in stage II and stage III sporadic CRC as compared to CD44. PMID:25755763

Outer membrane protein A of Acinetobacter baumannii induces differentiation of CD4+ T cells toward a Th1 polarizing phenotype through the activation of dendritic cells.

PubMed

Lee, Jun Sik; Lee, Je Chul; Lee, Chang-Min; Jung, In Duk; Jeong, Young-Il; Seong, Eun-Young; Chung, Hae-Young; Park, Yeong-Min

2007-06-30

Acinetobacter baumannii is an increasing hospital-acquired pathogen that causes a various type of infections, but little is known about the protective immune response to this microorganism. Outer membrane protein A of A. baumannii (AbOmpA) is a major porin protein and plays an important role in pathogenesis. We analyzed interaction between AbOmpA and dendritic cells (DCs) to characterize the role of this protein in promoting innate and adaptive immune responses. AbOmpA functionally activates bone marrow-derived DCs by augmenting expression of the surface markers, CD40, CD54, B7 family (CD80 and CD86) and major histocompatibility complex class I and II. AbOmpA induces production of Th1-promoting interleukin-12 from DCs and augments the syngeneic and allogeneic immunostimulatory capacity of DCs. AbOmpA stimulates production of interferon-gamma from T cells in mixed lymphocyte reactions, which suggesting Th1-polarizing capacity. CD4(+) T cells stimulated by AbOmpA-stimulated DCs show a Th1-polarizing cytokine profile. The expression of surface markers on DCs is mediated by both mitogen-activated protein kinases and NF-kappaB pathways. Our findings suggest that AbOmpA induces maturation of DCs and drives Th1 polarization, which are important properties for determining the nature of immune response against A. baumannii.

The RUNX1 +24 enhancer and P1 promoter identify a unique subpopulation of hematopoietic progenitor cells derived from human pluripotent stem cells

PubMed Central

Ferrell, Patrick I; Xi, Jiafei; Ma, Chao; Adlakha, Mitali; Kaufman, Dan S.

2016-01-01

Derivation of hematopoietic stem cells from human pluripotent stem cells remains a key goal for the fields of developmental biology and regenerative medicine. Here, we use a novel genetic reporter system to prospectively identify and isolate early hematopoietic cells derived from human embryonic stem cells (hESCs) and human induced pluripotent cells (iPSCs). Cloning the human RUNX1c P1 promoter and +24 enhancer to drive expression of tdTomato (tdTom) in hESCs and iPSCs, we demonstrate that tdTom expression faithfully enriches for RUNX1c-expressing hematopoietic progenitor cells. Time-lapse microscopy demonstrated the tdTom+ hematopoietic cells to emerge from adherent cells. Furthermore, inhibition of primitive hematopoiesis by blocking Activin/Nodal signaling promoted the expansion and/or survival of tdTom+ population. Notably, RUNX1c/tdTom+ cells represent only a limited subpopuation of CD34+CD45+ and CD34+CD43+ cells with a unique genetic signature. Using gene array analysis, we find significantly lower expression of Let-7 and mir181a microRNAs in the RUNX1c/tdTom+ cell population. These phenotypic and genetic analyses comparing the RUNX1c/tdTom+ population to CD34+CD45+ umbilical cord blood and fetal liver demonstrate several key differences that likely impact the development of HSCs capable of long-term multilineage engraftment from hESCs and iPSCs. PMID:25546363

Light-driven dinitrogen reduction catalyzed by a CdS:nitrogenase MoFe protein biohybrid.

PubMed

Brown, Katherine A; Harris, Derek F; Wilker, Molly B; Rasmussen, Andrew; Khadka, Nimesh; Hamby, Hayden; Keable, Stephen; Dukovic, Gordana; Peters, John W; Seefeldt, Lance C; King, Paul W

2016-04-22

The splitting of dinitrogen (N2) and reduction to ammonia (NH3) is a kinetically complex and energetically challenging multistep reaction. In the Haber-Bosch process, N2 reduction is accomplished at high temperature and pressure, whereas N2 fixation by the enzyme nitrogenase occurs under ambient conditions using chemical energy from adenosine 5'-triphosphate (ATP) hydrolysis. We show that cadmium sulfide (CdS) nanocrystals can be used to photosensitize the nitrogenase molybdenum-iron (MoFe) protein, where light harvesting replaces ATP hydrolysis to drive the enzymatic reduction of N2 into NH3 The turnover rate was 75 per minute, 63% of the ATP-coupled reaction rate for the nitrogenase complex under optimal conditions. Inhibitors of nitrogenase (i.e., acetylene, carbon monoxide, and dihydrogen) suppressed N2 reduction. The CdS:MoFe protein biohybrids provide a photochemical model for achieving light-driven N2 reduction to NH3. Copyright © 2016, American Association for the Advancement of Science.

Light-driven dinitrogen reduction catalyzed by a CdS:nitrogenase MoFe protein biohybrid

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

Brown, K. A.; Harris, D. F.; Wilker, M. B.

The splitting of dinitrogen (N2) and reduction to ammonia (NH3) is a kinetically complex and energetically challenging multistep reaction. In the Haber-Bosch process, N2 reduction is accomplished at high temperature and pressure, whereas N2 fixation by the enzyme nitrogenase occurs under ambient conditions using chemical energy from adenosine 5'-triphosphate (ATP) hydrolysis. We show that cadmium sulfide (CdS) nanocrystals can be used to photosensitize the nitrogenase molybdenum-iron (MoFe) protein, where light harvesting replaces ATP hydrolysis to drive the enzymatic reduction of N2 into NH3. The turnover rate was 75 per minute, 63% of the ATP-coupled reaction rate for the nitrogenase complexmore » under optimal conditions. Inhibitors of nitrogenase (i.e., acetylene, carbon monoxide, and dihydrogen) suppressed N2 reduction. The CdS:MoFe protein biohybrids provide a photochemical model for achieving light-driven N2 reduction to NH3.« less

Vpr Promotes Macrophage-Dependent HIV-1 Infection of CD4+ T Lymphocytes

PubMed Central

Collins, David R.; Lubow, Jay; Lukic, Zana; Mashiba, Michael; Collins, Kathleen L.

2015-01-01

Vpr is a conserved primate lentiviral protein that promotes infection of T lymphocytes in vivo by an unknown mechanism. Here we demonstrate that Vpr and its cellular co-factor, DCAF1, are necessary for efficient cell-to-cell spread of HIV-1 from macrophages to CD4+ T lymphocytes when there is inadequate cell-free virus to support direct T lymphocyte infection. Remarkably, Vpr functioned to counteract a macrophage-specific intrinsic antiviral pathway that targeted Env-containing virions to LAMP1+ lysosomal compartments. This restriction of Env also impaired virological synapses formed through interactions between HIV-1 Env on infected macrophages and CD4 on T lymphocytes. Treatment of infected macrophages with exogenous interferon-alpha induced virion degradation and blocked synapse formation, overcoming the effects of Vpr. These results provide a mechanism that helps explain the in vivo requirement for Vpr and suggests that a macrophage-dependent stage of HIV-1 infection drives the evolutionary conservation of Vpr. PMID:26186441

Tumor-propagating cells and Yap/Taz activity contribute to lung tumor progression and metastasis

PubMed Central

Lau, Allison N; Curtis, Stephen J; Fillmore, Christine M; Rowbotham, Samuel P; Mohseni, Morvarid; Wagner, Darcy E; Beede, Alexander M; Montoro, Daniel T; Sinkevicius, Kerstin W; Walton, Zandra E; Barrios, Juliana; Weiss, Daniel J; Camargo, Fernando D; Wong, Kwok-Kin; Kim, Carla F

2014-01-01

Metastasis is the leading cause of morbidity for lung cancer patients. Here we demonstrate that murine tumor propagating cells (TPCs) with the markers Sca1 and CD24 are enriched for metastatic potential in orthotopic transplantation assays. CD24 knockdown decreased the metastatic potential of lung cancer cell lines resembling TPCs. In lung cancer patient data sets, metastatic spread and patient survival could be stratified with a murine lung TPC gene signature. The TPC signature was enriched for genes in the Hippo signaling pathway. Knockdown of the Hippo mediators Yap1 or Taz decreased in vitro cellular migration and transplantation of metastatic disease. Furthermore, constitutively active Yap was sufficient to drive lung tumor progression in vivo. These results demonstrate functional roles for two different pathways, CD24-dependent and Yap/Taz-dependent pathways, in lung tumor propagation and metastasis. This study demonstrates the utility of TPCs for identifying molecules contributing to metastatic lung cancer, potentially enabling the therapeutic targeting of this devastating disease. PMID:24497554

Aurora A drives early signalling and vesicle dynamics during T-cell activation

PubMed Central

Blas-Rus, Noelia; Bustos-Morán, Eugenio; Pérez de Castro, Ignacio; de Cárcer, Guillermo; Borroto, Aldo; Camafeita, Emilio; Jorge, Inmaculada; Vázquez, Jesús; Alarcón, Balbino; Malumbres, Marcos; Martín-Cófreces, Noa B.; Sánchez-Madrid, Francisco

2016-01-01

Aurora A is a serine/threonine kinase that contributes to the progression of mitosis by inducing microtubule nucleation. Here we have identified an unexpected role for Aurora A kinase in antigen-driven T-cell activation. We find that Aurora A is phosphorylated at the immunological synapse (IS) during TCR-driven cell contact. Inhibition of Aurora A with pharmacological agents or genetic deletion in human or mouse T cells severely disrupts the dynamics of microtubules and CD3ζ-bearing vesicles at the IS. The absence of Aurora A activity also impairs the activation of early signalling molecules downstream of the TCR and the expression of IL-2, CD25 and CD69. Aurora A inhibition causes delocalized clustering of Lck at the IS and decreases phosphorylation levels of tyrosine kinase Lck, thus indicating Aurora A is required for maintaining Lck active. These findings implicate Aurora A in the propagation of the TCR activation signal. PMID:27091106

Hybrid Metrology and 3D-AFM Enhancement for CD Metrology Dedicated to 28 nm Node and Below Requirements

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

Foucher, J.; Faurie, P.; Dourthe, L.

2011-11-10

The measurement accuracy is becoming one of the major components that have to be controlled in order to guarantee sufficient production yield. Already at the R and D level, we have to come up with the accurate measurements of sub-40 nm dense trenches and contact holes coming from 193 immersion lithography or E-Beam lithography. Current production CD (Critical Dimension) metrology techniques such as CD-SEM (CD-Scanning Electron Microscope) and OCD (Optical Critical Dimension) are limited in relative accuracy for various reasons (i.e electron proximity effect, outputs parameters correlation, stack influence, electron interaction with materials...). Therefore, time for R and D ismore » increasing, process windows degrade and finally production yield can decrease because you cannot manufactured correctly if you are unable to measure correctly. A new high volume manufacturing (HVM) CD metrology solution has to be found in order to improve the relative accuracy of production environment otherwise current CD Metrology solution will very soon get out of steam.In this paper, we will present a potential Hybrid CD metrology solution that smartly tuned 3D-AFM (3D-Atomic Force Microscope) and CD-SEM data in order to add accuracy both in R and D and production. The final goal for 'chip makers' is to improve yield and save R and D and production costs through real-time feedback loop implement on CD metrology routines. Such solution can be implemented and extended to any kind of CD metrology solution. In a 2{sup nd} part we will discuss and present results regarding a new AFM3D probes breakthrough with the introduction of full carbon tips made will E-Beam Deposition process. The goal is to overcome the current limitations of conventional flared silicon tips which are definitely not suitable for sub-32 nm nodes production.« less

Temperature-sensitive junction transformations for mid-wavelength HgCdTe photovoltaic infrared detector arrays by laser beam induced current microscope

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

Qiu, Weicheng; National Laboratory for Infrared Physics, Shanghai Institute of Technical Physics, Chinese Academy of Sciences, Shanghai 200083; Hu, Weida, E-mail: wdhu@mail.sitp.ac.cn

2014-11-10

In this paper, we report on the disappearance of the photosensitive area extension effect and the unusual temperature dependence of junction transformation for mid-wavelength, n-on-p HgCdTe photovoltaic infrared detector arrays. The n-type region is formed by B{sup +} ion implantation on Hg-vacancy-doped p-type HgCdTe. Junction transformations under different temperatures are visually captured by a laser beam induced current microscope. A physical model of temperature dependence on junction transformation is proposed and demonstrated by using numerical simulations. It is shown that Hg-interstitial diffusion and temperature activated defects jointly lead to the p-n junction transformation dependence on temperature, and the weaker mixedmore » conduction compared with long-wavelength HgCdTe photodiode contributes to the disappearance of the photosensitive area extension effect in mid-wavelength HgCdTe infrared detector arrays.« less

Investigation of hyper-NA scanner emulation for photomask CDU performance

NASA Astrophysics Data System (ADS)

Poortinga, Eric; Scheruebl, Thomas; Conley, Will; Sundermann, Frank

2007-02-01

As the semiconductor industry moves toward immersion lithography using numerical apertures above 1.0 the quality of the photomask becomes even more crucial. Photomask specifications are driven by the critical dimension (CD) metrology within the wafer fab. Knowledge of the CD values at resist level provides a reliable mechanism for the prediction of device performance. Ultimately, tolerances of device electrical properties drive the wafer linewidth specifications of the lithography group. Staying within this budget is influenced mainly by the scanner settings, resist process, and photomask quality. Tightening of photomask specifications is one mechanism for meeting the wafer CD targets. The challenge lies in determining how photomask level metrology results influence wafer level imaging performance. Can it be inferred that photomask level CD performance is the direct contributor to wafer level CD performance? With respect to phase shift masks, criteria such as phase and transmission control are generally tightened with each technology node. Are there other photomask relevant influences that effect wafer CD performance? A comprehensive study is presented supporting the use of scanner emulation based photomask CD metrology to predict wafer level within chip CD uniformity (CDU). Using scanner emulation with the photomask can provide more accurate wafer level prediction because it inherently includes all contributors to image formation related to the 3D topography such as the physical CD, phase, transmission, sidewall angle, surface roughness, and other material properties. Emulated images from different photomask types were captured to provide CD values across chip. Emulated scanner image measurements were completed using an AIMS TM45-193i with its hyper-NA, through-pellicle data acquisition capability including the Global CDU Map TM software option for AIMS TM tools. The through-pellicle data acquisition capability is an essential prerequisite for capturing final CDU data (after final clean and pellicle mounting) before the photomask ships or for re-qualification at the wafer fab. Data was also collected on these photomasks using a conventional CD-SEM metrology system with the pellicles removed. A comparison was then made to wafer prints demonstrating the benefit of using scanner emulation based photomask CD metrology.

Genetics in arterial calcification: pieces of a puzzle and cogs in a wheel.

PubMed

Rutsch, Frank; Nitschke, Yvonne; Terkeltaub, Robert

2011-08-19

Artery calcification reflects an admixture of factors such as ectopic osteochondral differentiation with primary host pathological conditions. We review how genetic factors, as identified by human genome-wide association studies, and incomplete correlations with various mouse studies, including knockout and strain analyses, fit into "pieces of the puzzle" in intimal calcification in human atherosclerosis, and artery tunica media calcification in aging, diabetes mellitus, and chronic kidney disease. We also describe in sharp contrast how ENPP1, CD73, and ABCC6 serve as "cogs in a wheel" of arterial calcification. Specifically, each is a minor component in the function of a much larger network of factors that exert balanced effects to promote and suppress arterial calcification. For the network to normally suppress spontaneous arterial calcification, the "cogs" ENPP1, CD73, and ABCC6 must be present and in working order. Monogenic ENPP1, CD73, and ABCC6 deficiencies each drive a molecular pathophysiology of closely related but phenotypically different diseases (generalized arterial calcification of infancy (GACI), pseudoxanthoma elasticum (PXE) and arterial calcification caused by CD73 deficiency (ACDC)), in which premature onset arterial calcification is a prominent but not the sole feature.

Genetics in Arterial Calcification

PubMed Central

Rutsch, Frank; Nitschke, Yvonne; Terkeltaub, Robert

2011-01-01

Artery calcification reflects an admixture of factors such as ectopic osteochondral differentiation with primary host pathological conditions. We review how genetic factors, as identified by human genome-wide association studies, and incomplete correlations with various mouse studies, including knockout and strain analyses, fit into “pieces of the puzzle” in intimal calcification in human atherosclerosis, and artery tunica media calcification in aging, diabetes mellitus, and chronic kidney disease. We also describe in sharp contrast how ENPP1, CD73, and ABCC6 serve as “cogs in a wheel” of arterial calcification. Specifically, each is a minor component in the function of a much larger network of factors that exert balanced effects to promote and suppress arterial calcification. For the network to normally suppress spontaneous arterial calcification, the “cogs” ENPP1, CD73, and ABCC6 must be present and in working order. Monogenic ENPP1, CD73, and ABCC6 deficiencies each drive a molecular pathophysiology of closely related but phenotypically different diseases (generalized arterial calcification of infancy (GACI), pseudoxan-thoma elasticum (PXE) and arterial calcification caused by CD73 deficiency (ACDC)), in which premature onset arterial calcification is a prominent but not the sole feature. PMID:21852556

AHR Activation Is Protective against Colitis Driven by T Cells in Humanized Mice.

PubMed

Goettel, Jeremy A; Gandhi, Roopali; Kenison, Jessica E; Yeste, Ada; Murugaiyan, Gopal; Sambanthamoorthy, Sharmila; Griffith, Alexandra E; Patel, Bonny; Shouval, Dror S; Weiner, Howard L; Snapper, Scott B; Quintana, Francisco J

2016-10-25

Existing therapies for inflammatory bowel disease that are based on broad suppression of inflammation result in variable clinical benefit and unwanted side effects. A potential therapeutic approach for promoting immune tolerance is the in vivo induction of regulatory T cells (Tregs). Here we report that activation of the aryl hydrocarbon receptor using the non-toxic agonist 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) induces human Tregs in vitro that suppress effector T cells through a mechanism mediated by CD39 and Granzyme B. We then developed a humanized murine system whereby human CD4 + T cells drive colitis upon exposure to 2,4,6-trinitrobenzenesulfonic acid and assessed ITE as a potential therapeutic. ITE administration ameliorated colitis in humanized mice with increased CD39, Granzyme B, and IL10-secreting human Tregs. These results develop an experimental model to investigate human CD4 + T responses in vivo and identify the non-toxic AHR agonist ITE as a potential therapy for promoting immune tolerance in the intestine. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Site-Specific Gene Editing of Human Hematopoietic Stem Cells for X-Linked Hyper-IgM Syndrome.

PubMed

Kuo, Caroline Y; Long, Joseph D; Campo-Fernandez, Beatriz; de Oliveira, Satiro; Cooper, Aaron R; Romero, Zulema; Hoban, Megan D; Joglekar, Alok V; Lill, Georgia R; Kaufman, Michael L; Fitz-Gibbon, Sorel; Wang, Xiaoyan; Hollis, Roger P; Kohn, Donald B

2018-05-29

X-linked hyper-immunoglobulin M (hyper-IgM) syndrome (XHIM) is a primary immunodeficiency due to mutations in CD40 ligand that affect immunoglobulin class-switch recombination and somatic hypermutation. The disease is amenable to gene therapy using retroviral vectors, but dysregulated gene expression results in abnormal lymphoproliferation in mouse models, highlighting the need for alternative strategies. Here, we demonstrate the ability of both the transcription activator-like effector nuclease (TALEN) and clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) platforms to efficiently drive integration of a normal copy of the CD40L cDNA delivered by Adeno-Associated Virus. Site-specific insertion of the donor sequence downstream of the endogenous CD40L promoter maintained physiologic expression of CD40L while overriding all reported downstream mutations. High levels of gene modification were achieved in primary human hematopoietic stem cells (HSCs), as well as in cell lines and XHIM-patient-derived T cells. Notably, gene-corrected HSCs engrafted in immunodeficient mice at clinically relevant frequencies. These studies provide the foundation for a permanent curative therapy in XHIM. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Recent Progress on ECH Technology for ITER

NASA Astrophysics Data System (ADS)

Sirigiri, Jagadishwar

2005-10-01

The Electron Cyclotron Heating and Current Drive (ECH&CD) system for ITER is a critical ITER system that must be available for use on Day 1 of the ITER experimental program. The applications of the system include plasma start-up, plasma heating and suppression of Neoclassical Tearing Modes (NTMs). These applications are accomplished using 27 one megawatt continuous wave gyrotrons: 24 at a frequency of 170 GHz and 3 at a frequency of 120 GHz. There are DC power supplies for the gyrotrons, a transmission line system, one launcher at the equatorial plane and three upper port launchers. The US will play a major role in delivering parts of the ECH&CD system to ITER. The present state-of-the-art includes major advances in all areas of ECH technology. In the US, a major effort is underway to supply gyrotrons of up to 1.5 MW power level at 110 GHz to General Atomics for use in heating the DIII-D tokamak. This presentation will include a brief review of the state-of-the-art, worldwide, in ECH technology. The requirements for the ITER ECH&CD system will then be reviewed. ITER calls for gyrotrons capable of operating from a 50 kV power supply, after potential depression, with a minimum of 50% overall efficiency. This is a very significant challenge and some approaches to meeting this goal will be presented. Recent experimental results at MIT showing improved efficiency of high frequency, 1.5 MW gyrotrons will be described. These results will be incorporated into the planned development of gyrotrons for ITER. The ITER ECH&CD system will also be a challenge to the transmission lines, which must operate at high average power at up to 1000 seconds and with high efficiency. The technology challenges and efforts in the US and other ITER parties to solve these problems will be reviewed. *In collaboration with E. Choi, C. Marchewka, I. Mastovosky, M. A. Shapiro and R. J. Temkin. This work is supported by the Office of Fusion Energy Sciences of the U. S. Department of Energy.

Atypical memory B cells in human chronic infectious diseases: An interim report.

PubMed

Portugal, Silvia; Obeng-Adjei, Nyamekye; Moir, Susan; Crompton, Peter D; Pierce, Susan K

2017-11-01

Immunological memory is a remarkable phenomenon in which survival of an initial infection by a pathogen leads to life-long protection from disease upon subsequent exposure to that same pathogen. For many infectious diseases, long-lived protective humoral immunity is induced after only a single infection in a process that depends on the generation of memory B cells (MBCs) and long-lived plasma cells. However, over the past decade it has become increasingly evident that many chronic human infectious diseases to which immunity is not readily established, including HIV-AIDS, malaria and TB, are associated with fundamental alterations in the composition and functionality of MBC compartments. A common feature of these diseases appears to be a large expansion of what have been termed exhausted B cells, tissue-like memory B cells or atypical memory B cells (aMBCs) that, for simplicity's sake, we refer to here as aMBCs. It has been suggested that chronic immune activation and inflammation drive the expansion of aMBCs and that in some way aMBCs contribute to deficiencies in the acquisition of immunity in chronic infectious diseases. Although aMBCs are heterogeneous both within individuals and between diseases, they have several features in common including low expression of the cell surface markers that define classical MBCs in humans including CD21 and CD27 and high expression of genes not usually expressed by classical MBCs including T-bet, CD11c and a variety of inhibitory receptors, notably members of the FcRL family. Another distinguishing feature is their greatly diminished ability to be stimulated through their B cell receptors to proliferate, secrete cytokines or produce antibodies. In this review, we describe our current understanding of the phenotypic markers of aMBCs, their specificity in relation to the disease-causing pathogen, their functionality, the drivers of their expansion in chronic infections and their life span. We briefly summarize the features of aMBCs in healthy individuals and in autoimmune disease. We also comment on the possible relationship of human aMBCs and T-bet + , CD11c + age/autoimmune-associated B cells, also a topic of this review volume. Published by Elsevier Inc.

Integration of Stable Droplet Formation on a CD Microfluidic Device for Extreme Point of Care Applications

NASA Astrophysics Data System (ADS)

Ganesh, Shruthi Vatsyayani

With the advent of microfluidic technologies for molecular diagnostics, a lot of emphasis has been placed on developing diagnostic tools for resource poor regions in the form of Extreme Point of Care devices. To ensure commercial viability of such a device there is a need to develop an accurate sample to answer system, which is robust, portable, isolated yet highly sensitive and cost effective. This need has been a driving force for research involving integration of different microsystems like droplet microfluidics, Compact-disc (CD)microfluidics along with sample preparation and detection modules on a single platform. This work attempts to develop a proof of concept prototype of one such device using existing CD microfluidics tools to generate stable droplets used in point of care diagnostics (POC diagnostics). Apart from using a fairly newer technique for droplet generation and stabilization, the work aims to develop this method focused towards diagnostics for rural healthcare. The motivation for this work is first described with an emphasis on the current need for diagnostic testing in rural health-care and the general guidelines prescribed by WHO for such a sample to answer system. Furthermore, a background on CD and droplet microfluidics is presented to understand the merits and de-merits of each system and the need for integrating the two. This phase of the thesis also includes different methods employed/demonstrated to generate droplets on a spinning platform. An overview on the detection platforms is also presented to understand the challenges involved in building an extreme point of care device. In the third phase of the thesis, general manufacturing techniques and materials used to accomplish this work is presented. Lastly, design trials for droplet generation is presented. The shortcomings of these trials are solved by investigating mechanisms pertaining to design modification and use of agarose based droplet generation to ensure a more robust sample processing method. This method is further characterized and compared with non-agarose based system and the results are analyzed. In conclusion, future prospects of this work are discussed in relation to extreme POC applications.

Future trends in soil cadmium concentration under current cadmium fluxes to European agricultural soils.

PubMed

Six, L; Smolders, E

2014-07-01

The gradual increase of soil cadmium concentrations in European soils during the 20th century has prompted environmental legislation to limit soil cadmium (Cd) accumulation. Mass balances (input-output) reflecting the period 1980-1995 predicted larger Cd inputs via phosphate (P) fertilizers and atmospheric deposition than outputs via crop uptake and leaching. This study updates the Cd mass balance for the agricultural top soils of EU-27+Norway (EU-27+1). Over the past 15 years, the use of P fertilizers in the EU-27+1 has decreased by 40%. The current mean atmospheric deposition of Cd in EU is 0.35 g Cd ha(-1) yr(-1), this is strikingly smaller than values used in the previous EU mass balances (~3 g Cd ha(-1) yr(-1)). Leaching of Cd was estimated with most recent data of soil solution Cd concentrations in 151 soils, which cover the range of European soil properties. No significant time trends were found in the data of net applications of Cd via manure, compost, sludge and lime, all being small sources of Cd at a large scale. Modelling of the future long-term changes in soil Cd concentrations in agricultural top soils under cereal or potato culture predicts soil Cd concentrations to decrease by 15% over the next 100 years in an average scenario, with decreasing trends in some scenarios being more prevalent than increasing trends in other scenarios. These Cd balances have reverted from the general positive balances estimated 10 or more years ago. Uncertainty analysis suggests that leaching is the most uncertain relative to other fluxes. Copyright © 2014 Elsevier B.V. All rights reserved.

CD133+CD54+CD44+ circulating tumor cells as a biomarker of treatment selection and liver metastasis in patients with colorectal cancer

PubMed Central

Wang, Cun; Huang, Qiaorong; Meng, Wentong; Yu, Yongyang; Yang, Lie; Peng, Zhihai; Hu, Jiankun; Li, Yuan; Mo, Xianming; Zhou, Zongguang

2016-01-01

Introduction Liver is the most common site of distant metastasis in colorectal cancer (CRC). Early diagnosis and appropriate treatment selection decides overall prognosis of patients. However, current diagnostic measures were basically imaging but not functional. Circulating tumor cells (CTCs) known as hold the key to understand the biology of metastatic mechanism provide a novel and auxiliary diagnostic strategy for CRC with liver metastasis (CRC-LM). Results The expression of CD133+ and CD133+CD54+CD44+ cellular subpopulations were higher in the peripheral blood of CRC-LM patients when compared with those without metastasis (P<0.001). Multivariate analysis proved the association between the expression of CD133+CD44+CD54+ cellular subpopulation and the existence of CRC-LM (P<0.001). The combination of abdominal CT/MRI, CEA and the CD133+CD44+CD54+ cellular subpopulation showed increased detection and discrimination rate for liver metastasis, with a sensitivity of 88.2% and a specificity of 92.4%. Meanwhile, it also show accurate predictive value for liver metastasis (OR=2.898, 95% C.I.1.374–6.110). Materials and Method Flow cytometry and multivariate analysis was performed to detect the expression of cancer initiating cells the correlation between cellular subpopulations and liver metastasis in patients with CRC. The receiver operating characteristic curves combined with the area under the curve were generated to compare the predictive ability of the cellular subpopulation for liver metastasis with current CT and MRI images. Conclusions The identification, expression and application of CTC subpopulations will provide an ideal cellular predictive marker for CRC liver metastasis and a potential marker for further investigation. PMID:27764803

Combined magnetic and kinetic control of advanced tokamak steady state scenarios based on semi-empirical modelling

NASA Astrophysics Data System (ADS)

Moreau, D.; Artaud, J. F.; Ferron, J. R.; Holcomb, C. T.; Humphreys, D. A.; Liu, F.; Luce, T. C.; Park, J. M.; Prater, R.; Turco, F.; Walker, M. L.

2015-06-01

This paper shows that semi-empirical data-driven models based on a two-time-scale approximation for the magnetic and kinetic control of advanced tokamak (AT) scenarios can be advantageously identified from simulated rather than real data, and used for control design. The method is applied to the combined control of the safety factor profile, q(x), and normalized pressure parameter, βN, using DIII-D parameters and actuators (on-axis co-current neutral beam injection (NBI) power, off-axis co-current NBI power, electron cyclotron current drive power, and ohmic coil). The approximate plasma response model was identified from simulated open-loop data obtained using a rapidly converging plasma transport code, METIS, which includes an MHD equilibrium and current diffusion solver, and combines plasma transport nonlinearity with 0D scaling laws and 1.5D ordinary differential equations. The paper discusses the results of closed-loop METIS simulations, using the near-optimal ARTAEMIS control algorithm (Moreau D et al 2013 Nucl. Fusion 53 063020) for steady state AT operation. With feedforward plus feedback control, the steady state target q-profile and βN are satisfactorily tracked with a time scale of about 10 s, despite large disturbances applied to the feedforward powers and plasma parameters. The robustness of the control algorithm with respect to disturbances of the H&CD actuators and of plasma parameters such as the H-factor, plasma density and effective charge, is also shown.

My Favorite Things Electronically Speaking, 1997 Edition.

ERIC Educational Resources Information Center

Glantz, Shelley

1997-01-01

Responding to an informal survey, 96 media specialists named favorite software, CD-ROMs, and online sites. This article lists automation packages, electronic encyclopedias, CD-ROMs, electronic magazine indexes, CD-ROM and online database services, electronic sources of current events, laser disks for grades 6-12, word processing programs for…

Investigation of Cool and Hot Executive Function in ODD/CD Independently of ADHD

ERIC Educational Resources Information Center

Hobson, Christopher W.; Scott, Stephen; Rubia, Katya

2011-01-01

Background: Children with oppositional defiant disorder/conduct disorder (ODD/CD) have shown deficits in "cool" abstract-cognitive, and "hot" reward-related executive function (EF) tasks. However, it is currently unclear to what extent ODD/CD is associated with neuropsychological deficits, independently of attention deficit hyperactivity disorder…

CD-ROM and Libraries.

ERIC Educational Resources Information Center

Murphy, Brower

1985-01-01

The Compact Disc-Read Only Memory (CD-ROM) data format is explained and illustrated, noting current and potential applications. The "5-inch" compact laserdisc is described and photographs of an IBM PC/Hitachi CD-ROM system adopted by Library Corporation to support its MARC database--BiblioFile--are presented. Screen displays for…

Investigation of Processing, Microstructures and Efficiencies of Polycrystalline CdTe Photovoltaic Films and Devices

NASA Astrophysics Data System (ADS)

Munshi, Amit Harenkumar

CdTe based photovoltaics have been commercialized at multiple GWs/year level. The performance of CdTe thin film photovoltaic devices is sensitive to process conditions. Variations in deposition temperatures as well as other treatment parameters have a significant impact on film microstructure and device performance. In this work, extensive investigations are carried out using advanced microstructural characterization techniques in an attempt to relate microstructural changes due to varying deposition parameters and their effects on device performance for cadmium telluride based photovoltaic cells deposited using close space sublimation (CSS). The goal of this investigation is to apply advanced material characterization techniques to aid process development for higher efficiency CdTe based photovoltaic devices. Several techniques have been used to observe the morphological changes to the microstructure along with materials and crystallographic changes as a function of deposition temperature and treatment times. Traditional device structures as well as advanced structures with electron reflector and films deposited on Mg1-xZnxO instead of conventional CdS window layer are investigated. These techniques include Scanning Electron Microscopy (SEM) with Electron Back Scattered Diffraction (EBSD) and Energy dispersive X-ray spectroscopy (EDS) to study grain structure and High Resolution Transmission Electron Microscopy (TEM) with electron diffraction and EDS. These investigations have provided insights into the mechanisms that lead to change in film structure and device performance with change in deposition conditions. Energy dispersive X-ray spectroscopy (EDS) is used for chemical mapping of the films as well as to understand interlayer material diffusion between subsequent layers. Electrical performance of these devices has been studied using current density vs voltage plots. Devices with efficiency over 18% have been fabricated on low cost commercial glass substrates with processes suitable for mass production. These are the highest efficiencies reported by any university or national laboratory for polycrystalline thin-film CdTe photovoltaics bettered only by researchers at First Solar Inc. Processing experiments are traditionally designed based on simulation results however in these study microscopic materials characterization has been used as the primary driving force to understand the effects of processing conditions. Every structure and efficiency reported in this study has been extensively studied using microscopic imaging and materials characterization and processing conditions accordingly altered to achieve higher efficiencies. Understanding CdCl2 passivation treatment out of this has been critical to this process. Several observations with regard to effect of CdCl 2 passivation have allowed the use to this treatment to achieve optimum performance. The effects of deposition temperature are also studied in rigorous details. All of these studies have played an important role in optimization of process that lead to high efficiency thin-film CdTe photovoltaic devices. An effort is made in this study to better understand and establish a 3-way relationship between processing conditions, film microstructure and device efficiency for sublimated thin-film CdTe photovoltaics. Some crucial findings include impact of grain size on efficiency of photovoltaic devices and improvement in fill-factor resulting from use of thicker CdTe absorber with larger grain size. An attempt is also made to understand the microstructure as the device efficiency improves from 1% efficiency to over 18% efficiency.

Enhanced Photoelectrochemical Activity by Autologous Cd/CdO/CdS Heterojunction Photoanodes with High Conductivity and Separation Efficiency.

PubMed

Xie, Shilei; Zhang, Peng; Zhang, Min; Liu, Peng; Li, Wei; Lu, Xihong; Cheng, Faliang; Tong, Yexiang

2017-07-18

The development for hydrogen from solar energy has attracted great attention due to the global demand for clean, environmentally friendly energy. Herein, autologous Cd/CdO/CdS heterojunctions were prepared in a carefully controlled process with metallic Cd as the inner layer and CdO as the interlayer. Further research revealed that the transportation and separation of photogenerated pairs were enhanced due to low resistance of the Cd inner layer and the type II CdO/CdS heterojunction. As a result, the optimized Cd/CdO/CdS heterojunction photoanode showed outstanding and long-term photoelectrochemical activity for water splitting, with a current density of 3.52 mA cm -2 , or a benchmark specific hydrogen production rate of 1.65 μmol cm -2  min -1 at -0.3 V versus Ag/AgCl, by using the environmental pollutants of sulfide and sulfite as sacrificial agents. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

High-Throughput Screening based Identification of Small Molecule Antagonists of Integrin CD11b/CD18 Ligand Binding

PubMed Central

Faridi, Mohd Hafeez; Maiguel, Dony; Brown, Brock T.; Suyama, Eigo; Barth, Constantinos J.; Hedrick, Michael; Vasile, Stefan; Sergienko, Eduard; Schürer, Stephan; Gupta, Vineet

2010-01-01

Binding of leukocyte specific integrin CD11b/CD18 to its physiologic ligands is important for the development of normal immune response in vivo. Integrin CD11b/CD18 is also a key cellular effector of various inflammatory and autoimmune diseases. However, small molecules selectively inhibiting the function of integrin CD11b/CD18 are currently lacking. We used a newly described cell-based high throughput screening assay to identify a number of highly potent antagonists of integrin CD11b/CD18 from chemical libraries containing >100,000 unique compounds. Computational analyses suggest that the identified compounds cluster into several different chemical classes. A number of the newly identified compounds blocked adhesion of wild-type mouse neutrophils to CD11b/CD18 ligand fibrinogen. Mapping the most active compounds against chemical fingerprints of known antagonists of related integrin CD11a/CD18 shows little structural similarity, suggesting that the newly identified compounds are novel and unique. PMID:20188705

Simulation of MeV electron energy deposition in CdS quantum dots absorbed in silicate glass for radiation dosimetry

NASA Astrophysics Data System (ADS)

Baharin, R.; Hobson, P. R.; Smith, D. R.

2010-09-01

We are currently developing 2D dosimeters with optical readout based on CdS or CdS/CdSe core-shell quantum-dots using commercially available materials. In order to understand the limitations on the measurement of a 2D radiation profile the 3D deposited energy profile of MeV energy electrons in CdS quantum-dot-doped silica glass have been studied by Monte Carlo simulation using the CASINO and PENELOPE codes. Profiles for silica glass and CdS quantum-dot-doped silica glass were then compared.

Cutaneous T-cell lymphoma (CTCL): Current practices in blood assessment and the utility of T-cell receptor (TCR)-Vβ chain restriction.

PubMed

Gibson, Juliet F; Huang, Jing; Liu, Kristina J; Carlson, Kacie R; Foss, Francine; Choi, Jaehyuk; Edelson, Richard; Hussong, Jerry W; Mohl, Ramsey; Hill, Sally; Girardi, Michael

2016-05-01

Accurate quantification of malignant cells in the peripheral blood of patients with cutaneous T-cell lymphoma is important for early detection, prognosis, and monitoring disease burden. We sought to determine the spectrum of current clinical practices; critically evaluate elements of current International Society for Cutaneous Lymphomas (ISCL) B1 and B2 staging criteria; and assess the potential role of T-cell receptor-Vβ analysis by flow cytometry. We assessed current clinical practices by survey, and performed a retrospective analysis of 161 patients evaluated at Yale (2011-2014) to compare the sensitivity, specificity, positive predictive value, and negative predictive value of parameters for ISCL B2 staging. There was heterogeneity in clinical practices among institutions. ISCL B1 criteria did not capture 5 Yale cohort cases with immunophenotypic abnormalities that later progressed. T-cell receptor-Vβ testing was more specific than polymerase chain reaction and aided diagnosis in detecting clonality, but was of limited benefit in quantification of tumor burden. Because of limited follow-up involving a single center, further investigation will be necessary to conclude whether our proposed diagnostic algorithm is of general clinical benefit. We propose further study of modified B1 criteria: CD4/CD8 ratio 5 or greater, %CD4(+) CD26(-) 20% or greater, or %CD4(+) CD7(-) 20% or greater, with evidence of clonality. T-cell receptor-Vβ testing should be considered in future diagnostic and staging algorithms. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Active lamp pulse driver circuit. [optical pumping of laser media

NASA Technical Reports Server (NTRS)

Logan, K. E. (Inventor)

1983-01-01

A flashlamp drive circuit is described which uses an unsaturated transistor as a current mode switch to periodically subject a partially ionized gaseous laser excitation flashlamp to a stable, rectangular pulse of current from an incomplete discharge of an energy storage capacitor. A monostable multivibrator sets the pulse interval, initiating the pulse in response to a flash command by providing a reference voltage to a non-inverting terminal of a base drive amplifier; a tap on an emitter resistor provides a feedback signal sensitive to the current amplitude to an inverting terminal of amplifier, thereby controlling the pulse amplitude. The circuit drives the flashlamp to provide a squarewave current flashlamp discharge.

Surface Passivation of CdZnTe Detector by Hydrogen Peroxide Solution Etching

NASA Technical Reports Server (NTRS)

Hayes, M.; Chen, H.; Chattopadhyay, K.; Burger, A.; James, R. B.

1998-01-01

The spectral resolution of room temperature nuclear radiation detectors such as CdZnTe is usually limited by the presence of conducting surface species that increase the surface leakage current. Studies have shown that the leakage current can be reduced by proper surface preparation. In this study, we try to optimize the performance of CdZnTe detector by etching the detector with hydrogen peroxide solution as function of concentration and etching time. The passivation effect that hydrogen peroxide introduces have been investigated by current-voltage (I-V) measurement on both parallel strips and metal-semiconductor-metal configurations. The improvements on the spectral response of Fe-55 and 241Am due to hydrogen peroxide treatment are presented and discussed.

Rapid and efficient nonviral gene delivery of CD154 to primary chronic lymphocytic leukemia cells.

PubMed

Li, L H; Biagi, E; Allen, C; Shivakumar, R; Weiss, J M; Feller, S; Yvon, E; Fratantoni, J C; Liu, L N

2006-02-01

Interactions between CD40 and CD40 ligand (CD154) are essential in the regulation of both humoral and cellular immune responses. Forced expression of human CD154 in B chronic lymphocytic leukemia (B-CLL) cells can upregulate costimulatory and adhesion molecules and restore antigen-presenting capacity. Unfortunately, B-CLL cells are resistant to direct gene manipulation with most currently available gene transfer systems. In this report, we describe the use of a nonviral, clinical-grade, electroporation-based gene delivery system and a standard plasmid carrying CD154 cDNA, which achieved efficient (64+/-15%) and rapid (within 3 h) transfection of primary B-CLL cells. Consistent results were obtained from multiple human donors. Transfection of CD154 was functional in that it led to upregulated expression of CD80, CD86, ICAM-I and MHC class II (HLA-DR) on the B-CLL cells and induction of allogeneic immune responses in MLR assays. Furthermore, sustained transgene expression was demonstrated in long-term cryopreserved transfected cells. This simple and rapid gene delivery technology has been validated under the current Good Manufacturing Practice conditions, and multiple doses of CD154-expressing cells were prepared for CLL patients from one DNA transfection. Vaccination strategies using autologous tumor cells manipulated ex vivo for patients with B-CLL and perhaps with other hematopoietic malignancies could be practically implemented using this rapid and efficient nonviral gene delivery system.

White-light-emitting organic electroluminescent devices based on interlayer sequential energy transfer

NASA Astrophysics Data System (ADS)

Deshpande, R. S.; Bulović, V.; Forrest, S. R.

1999-08-01

We demonstrate efficient, molecular organic white-light-emitting devices using vacuum-deposited thin films of red luminescent [2-methyl-6-[2-(2,3,6,7-tetrahydro-1H, 5H-benzo [ij] quinolizin-9-yl) ethenyl]-4H-pyran-4-ylidene] propane-dinitrile (DCM2), doped into blue-emitting 4, 4' bis [N-1-napthyl-N-phenyl-amino]biphenyl (α-NPD), and green-emitting tris-(8-hydroxyquinolinato) aluminum(III) (AlQ3). The luminescent layers are separated by a hole-blocking layer of 2,9-dimethyl, 4,7-diphenyl, 1,10-phenanthroline (BCP), whose thickness is on the order of a typical Förster transfer radius of 30-40 Å. Excitons formed on α-NPD sequentially transfer their energy via a Förster mechanism to AlQ3 across the BCP layer, and from AlQ3 to DCM2. This interlayer sequential energy transfer results in partial excitation of all three molecular species, thereby producing white light emission. The thickness of the blocking layer and the concentration of DCM2 in α-NPD permit the tuning of the device spectrum to achieve a balanced white emission with Commission Internationale d'Eclairage chromaticity coordinates of (0.33, 0.33). The spectrum is largely insensitive to the drive current, and the devices have a maximum luminance of 13 500 cd/m2. At a luminance of 100 cd/m2, the quantum and power efficiencies are 0.5% and 0.35 lm/W, respectively.

Notch3 signaling-mediated melanoma-endothelial crosstalk regulates melanoma stem-like cell homeostasis and niche morphogenesis.

PubMed

Hsu, Mei-Yu; Yang, Moon Hee; Schnegg, Caroline I; Hwang, Soonyean; Ryu, Byungwoo; Alani, Rhoda M

2017-06-01

Melanoma is among the most virulent cancers, owing to its propensity to metastasize and its resistance to current therapies. The treatment failure is largely attributed to tumor heterogeneity, particularly subpopulations possessing stem cell-like properties, ie, melanoma stem-like cells (MSLCs). Evidence indicates that the MSLC phenotype is malleable and may be acquired by non-MSLCs through phenotypic switching upon appropriate stimuli, the so-called 'dynamic stemness'. Since the phenotypic characteristics and functional integrity of MSLCs depend on their vascular niche, using a two-dimensional (2D) melanoma-endothelium co-culture model, where the MSLC niche is recapitulated in vitro, we identified Notch3 signaling pathway as a micro-environmental cue governing MSLC phenotypic plasticity via pathway-specific gene expression arrays. Accordingly, lentiviral shRNA-mediated Notch3 knockdown (KD) in melanoma cell lines exhibiting high levels of endogenous Notch3 led to retarded/abolished tumorigenicity in vivo through both depleting MSLC fractions, evinced by MSLC marker downregulation (eg, CD133 and CD271); and impeding the MSLC niche, corroborated by the attenuated tumor angiogenesis as well as vasculogenic mimicry. In contrast, Notch3 KD affected neither tumor growth nor MSLC subsets in a melanoma cell line with relatively low endogenous Notch3 expression. Thus, Notch3 signaling may facilitate MSLC plasticity and niche morphogenesis in a cell context-dependent manner. Our findings illustrate Notch3 as a molecular switch driving melanoma heterogeneity, and provide the biological rationale for Notch inhibition as a promising therapeutic option.

Vertically aligned CdSe nanowire arrays for energy harvesting and piezotronic devices.

PubMed

Zhou, Yu Sheng; Wang, Kai; Han, Weihua; Rai, Satish Chandra; Zhang, Yan; Ding, Yong; Pan, Caofeng; Zhang, Fang; Zhou, Weilie; Wang, Zhong Lin

2012-07-24

We demonstrated the energy harvesting potential and piezotronic effect in vertically aligned CdSe nanowire (NW) arrays for the first time. The CdSe NW arrays were grown on a mica substrate by the vapor-liquid-solid process using a CdSe thin film as seed layer and platinum as catalyst. High-resolution transmission electron microscopy image and selected area electron diffraction pattern indicate that the CdSe NWs have a wurtzite structure and growth direction along (0001). Using conductive atomic force microscopy (AFM), an average output voltage of 30.7 mV and maximum of 137 mV were obtained. To investigate the effect of strain on electron transport, the current-voltage characteristics of the NWs were studied by positioning an AFM tip on top of an individual NW. By applying normal force/stress on the NW, the Schottky barrier between the Pt and CdSe was found to be elevated due to the piezotronic effect. With the change of strain of 0.12%, a current decreased from 84 to 17 pA at 2 V bias. This paper shows that the vertical CdSe NW array is a potential candidate for future piezo-phototronic devices.

Impact of New Regulations On Assessing Driving Status (INROADS): a South Australian seizure clinic cohort.

PubMed

Hafner, Jessica; Horn, Sharon; Robinson, Martin; Purdie, Grant; Jannes, Jim

2014-11-01

The ability to drive is important to patients and driving restriction often leads to restriction of employment and social opportunities. In March 2012, Austroads released revised Assessing Fitness to Drive Guidelines (AFTDG) with significant changes for drivers with seizures and epilepsy. Our study aimed to assess the impact of the 2012 AFTDG on a Seizure Clinic cohort compared to the previous 2003 AFTDG and an individual's current driving status. We also aimed to quantify the difference in AFTDG interpretation between expert and non-expert doctors. We performed a retrospective observational audit of case notes for all patients managed in a public hospital outpatient Seizure Clinic between 1 March 2010 and 1 March 2012. A total of 142 patients were included in the analysis. Comparison between the 2003 and 2012 AFTDG resulted in reduced eligibility to drive a private vehicle by 2.1% (52.5% versus 50.4%) and commercial vehicle by 2.2% (4.5% versus 2.3%). The proportion of those currently driving against guideline recommendations increased (private 8.8% versus 19%; commercial 50% versus 100%) and the non-expert assessor was more likely to agree with the experts with the 2012 AFTDG. In summary, the 2012 AFTDG has had a measurable impact on driving eligibility in individuals with seizure although it is easier to interpret for non-expert doctors. Greater awareness of the 2012 AFTDG is required to reduce the proportion of patients driving against current recommendations. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Single HIV-1 Cluster and a Skewed Immune Homeostasis Drive the Early Spread of HIV among Resting CD4+ Cell Subsets within One Month Post-Infection

PubMed Central

Avettand-Fenoël, Véronique; Nembot, Georges; Mélard, Adeline; Blanc, Catherine; Lascoux-Combe, Caroline; Slama, Laurence; Allegre, Thierry; Allavena, Clotilde; Yazdanpanah, Yazdan; Duvivier, Claudine; Katlama, Christine; Goujard, Cécile; Seksik, Bao Chau Phung; Leplatois, Anne; Molina, Jean-Michel; Meyer, Laurence; Autran, Brigitte; Rouzioux, Christine

2013-01-01

Optimizing therapeutic strategies for an HIV cure requires better understanding the characteristics of early HIV-1 spread among resting CD4+ cells within the first month of primary HIV-1 infection (PHI). We studied the immune distribution, diversity, and inducibility of total HIV-DNA among the following cell subsets: monocytes, peripheral blood activated and resting CD4 T cells, long-lived (naive [TN] and central-memory [TCM]) and short-lived (transitional-memory [TTM] and effector-memory cells [TEM]) resting CD4+T cells from 12 acutely-infected individuals recruited at a median 36 days from infection. Cells were sorted for total HIV-DNA quantification, phylogenetic analysis and inducibility, all studied in relation to activation status and cell signaling. One month post-infection, a single CCR5-restricted viral cluster was massively distributed in all resting CD4+ subsets from 88% subjects, while one subject showed a slight diversity. High levels of total HIV-DNA were measured among TN (median 3.4 log copies/million cells), although 10-fold less (p = 0.0005) than in equally infected TCM (4.5), TTM (4.7) and TEM (4.6) cells. CD3−CD4+ monocytes harbored a low viral burden (median 2.3 log copies/million cells), unlike equally infected resting and activated CD4+ T cells (4.5 log copies/million cells). The skewed repartition of resting CD4 subsets influenced their contribution to the pool of resting infected CD4+T cells, two thirds of which consisted of short-lived TTM and TEM subsets, whereas long-lived TN and TCM subsets contributed the balance. Each resting CD4 subset produced HIV in vitro after stimulation with anti-CD3/anti-CD28+IL-2 with kinetics and magnitude varying according to subset differentiation, while IL-7 preferentially induced virus production from long-lived resting TN cells. In conclusion, within a month of infection, a clonal HIV-1 cluster is massively distributed among resting CD4 T-cell subsets with a flexible inducibility, suggesting that subset activation and skewed immune homeostasis determine the conditions of viral dissemination and early establishment of the HIV reservoir. PMID:23691172

A standardized blood test for the routine clinical diagnosis of impaired GM-CSF signaling using flow cytometry.

PubMed

Kusakabe, Yoshiomi; Uchida, Kanji; Hiruma, Takahiro; Suzuki, Yoko; Totsu, Tokie; Suzuki, Takuji; Carey, Brenna C; Yamada, Yoshitsugu; Trapnell, Bruce C

2014-11-01

Impaired signaling by granulocyte/macrophage-colony stimulating factor (GM-CSF) drives the pathogenesis of two diseases (autoimmune and hereditary pulmonary alveolar proteinosis (PAP)) representing over ninety percent of patients who develop PAP syndrome but not a broad spectrum of diseases that cause PAP by other mechanisms. We previously exploited the ability of GM-CSF to rapidly increase cell-surface CD11b levels on neutrophils (CD11bSurface) to establish the CD11b stimulation index (CD11b-SI), a test enabling the clinical research diagnosis of impaired GM-CSF signaling based on measuring CD11bSurface by flow cytometry using fresh, heparinized blood. (CD11b-SI is defined as GM-CSF-stimulated- CD11bSurface minus unstimulated CD11bSurface divided by un-stimulated CD11bSurface multiplied by 100.) Notwithstanding important and unique diagnostic utility, the test is sensitive to experimental conditions that can affect test performance. The present study was undertaken to optimize and standardize CD11b-SI test for detecting impaired GM-CSF signaling in heparinized human blood specimens from PAP patients. Results demonstrated the test was sensitive to choice of anticoagulant, pretesting incubation on ice, a delay between phlebotomy and test performance of more than one hour, and the concentration GM-CSF used to stimulate blood. The standardized CD11b-SI test reliably distinguished blood specimens from autoimmune PAP patients with impaired GM-CSF signaling from those of health people with normal signaling. Intra-subject differences were smaller than inter-subject differences in repeated measures. Receiver operating characteristic curve analysis identified a CD11b-SI test result of 112 as the optimal cut off threshold for diagnosis of impaired GM-CSF signaling in autoimmune PAP for which the sensitivity and specificity were both 100%. These results support the use of this standardized CD11b-SI for routine clinical identification of impaired GM-CSF signaling in patients with autoimmune PAP. The CD11b-SI may also have utility in clinical trials of novel therapeutic strategies targeting reduction in GM-CSF bioactivity now under evaluation for multiple common autoimmune and inflammatory disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

Neoclassical Current Drive by Waves with a Symmetric Spectrum

NASA Astrophysics Data System (ADS)

Helander, Per

2000-10-01

It is well known that plasma waves can produce electric currents if the waves have an asymmetric spectrum, so that they either interact preferentially with electrons travelling in one direction along the magnetic field or impart net parallel momentum to the electrons [1]. This directionality creates an asymmetry in the electron distribution function and thereby produces a current parallel to the field. We demonstrate, somewhat surprisingly, that in a plasma confined by a curved magnetic field no such spectral asymmetry is necessary for current drive if the effect of collisions is properly taken into account. For instance, in a toroidal plasma a current can be produced by a spectrally symmetric wave field if this field is instead up-down asymmetric, which is frequently the case for electron cyclotron current drive (ECCD) in tokamaks. We have calculated the resulting current drive efficiency and found it to be smaller than that of the conventional current drive mechanism in the banana regime, but not insignificant in the plateau regime. The results will be compared with experiments in DIII-D, where the measured efficiency exceeds the classical prediction [2]. Our calculations are focused on this case of ECCD in tokamaks, but the basic physical mechanism is much more general. It is of a universal neoclassical nature and applies to all wave-particle interaction in curved magnetic fields. [1] N.J. Fisch, Rev. Mod. Phys. 59, 175 (1987). [2] Y. R. Lin-Liu et al., 26th EPS Conf. on Contr. Fusion and Plasma Phys.(European Phys. Soc. Paris, 1999) Vol. 23J, p 1245.

Sequential Dependencies in Driving

ERIC Educational Resources Information Center

Doshi, Anup; Tran, Cuong; Wilder, Matthew H.; Mozer, Michael C.; Trivedi, Mohan M.

2012-01-01

The effect of recent experience on current behavior has been studied extensively in simple laboratory tasks. We explore the nature of sequential effects in the more naturalistic setting of automobile driving. Driving is a safety-critical task in which delayed response times may have severe consequences. Using a realistic driving simulator, we find…

Direct imaging of Cl- and Cu-induced short-circuit efficiency changes in CdTe solar cells

DOE PAGES

Poplawsky, Jonathan D.; Parish, Chad M.; Leonard, Donovan N.; ...

2014-05-30

To achieve high-efficiency polycrystalline CdTe-based thin-film solar cells, the CdTe absorbers must go through a post-deposition CdCl 2 heat treatment followed by a Cu diffusion step. To better understand the roles of each treatment with regard to improving grains, grain boundaries, and interfaces, CdTe solar cells with and without Cu diffusion and CdCl 2 heat treatments are investigated using cross-sectional electron beam induced current, electron backscatter diffraction, and scanning transmission electron microscope techniques. The evolution of the cross-sectional carrier collection profile due to these treatments that cause an increase in short-circuit current and higher open-circuit voltage are identified. Additionally, anmore » increased carrier collection in grain boundaries after either/both of these treatments is revealed. The increased current at the grain boundaries is shown to be due to the presence of a space charge region with an intrinsic carrier collection profile width of ≈350 nm. Scanning transmission electron microscope electron-energy loss spectroscopy shows a decreased Te and increased Cl concentration in grain boundaries after treatment, which causes the inversion. Furthermore, each treatment improves the overall carrier collection efficiency of the cell separately, and, therefore, the benefits realized by each treatment are shown to be independent of each other.« less

Influence of anisotropic conductivity in the skull and white matter on transcranial direct current stimulation via an anatomically realistic finite element head model

NASA Astrophysics Data System (ADS)

Suh, Hyun Sang; Lee, Won Hee; Kim, Tae-Seong

2012-11-01

To establish safe and efficient transcranial direct current stimulation (tDCS), it is of particular importance to understand the electrical effects of tDCS in the brain. Since the current density (CD) and electric field (EF) in the brain generated by tDCS depend on various factors including complex head geometries and electrical tissue properties, in this work, we investigated the influence of anisotropic conductivity in the skull and white matter (WM) on tDCS via a 3D anatomically realistic finite element head model. We systematically incorporated various anisotropic conductivity ratios into the skull and WM. The effects of anisotropic tissue conductivity on the CD and EF were subsequently assessed through comparisons to the conventional isotropic solutions. Our results show that the anisotropic skull conductivity significantly affects the CD and EF distribution: there is a significant reduction in the ratio of the target versus non-target total CD and EF on the order of 12-14%. In contrast, the WM anisotropy does not significantly influence the CD and EF on the targeted cortical surface, only on the order of 1-3%. However, the WM anisotropy highly alters the spatial distribution of both the CD and EF inside the brain. This study shows that it is critical to incorporate anisotropic conductivities in planning of tDCS for improved efficacy and safety.

Construction and Characterization of a Chitosan-Immobilized-Enzyme and β-Cyclodextrin-Included-Ferrocene-Based Electrochemical Biosensor for H₂O₂ Detection.

PubMed

Dong, Wenbo; Wang, Kaiyin; Chen, Yu; Li, Weiping; Ye, Yanchun; Jin, Shaohua

2017-07-28

An electrochemical detection biosensor was prepared with the chitosan-immobilized-enzyme (CTS-CAT) and β-cyclodextrin-included-ferrocene (β-CD-FE) complex for the determination of H₂O₂. Ferrocene (FE) was included in β-cyclodextrin (β-CD) to increase its stability. The structure of the β-CD-FE was characterized. The inclusion amount, inclusion rate, and electrochemical properties of inclusion complexes were determined to optimize the reaction conditions for the inclusion. CTS-CAT was prepared by a step-by-step immobilization method, which overcame the disadvantages of the conventional preparation methods. The immobilization conditions were optimized to obtain the desired enzyme activity. CTS-CAT/β-CD-FE composite electrodes were prepared by compositing the CTS-CAT with the β-CD-FE complex on a glassy carbon electrode and used for the electrochemical detection of H₂O₂. It was found that the CTS-CAT could produce a strong reduction peak current in response to H₂O₂ and the β-CD-FE could amplify the current signal. The peak current exhibited a linear relationship with the H₂O₂ concentration in the range of 1.0 × 10 -7 -6.0 × 10 -3 mol/L. Our work provided a novel method for the construction of electrochemical biosensors with a fast response, good stability, high sensitivity, and a wide linear response range based on the composite of chitosan and cyclodextrin.