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  1. NK Cell Exhaustion

    Science.gov (United States)

    Bi, Jiacheng; Tian, Zhigang

    2017-01-01

    Natural killer cells are important effector lymphocytes of the innate immune system, playing critical roles in antitumor and anti-infection host defense. Tumor progression or chronic infections, however, usually leads to exhaustion of NK cells, thus limiting the antitumor/infection potential of NK cells. In many tumors or chronic infections, multiple mechanisms might contribute to the exhaustion of NK cells, such as dysregulated NK cell receptors signaling, as well as suppressive effects by regulatory cells or soluble factors within the microenvironment. Better understanding of the characteristics, as well as the underlying mechanisms of NK cell exhaustion, not only should increase our understanding of the basic biology of NK cells but also could reveal novel NK cell-based antitumor/infection targets. Here, we provide an overview of our current knowledge on NK cell exhaustion in tumors, and in chronic infections. PMID:28702032

  2. Bioenergetic Insufficiencies Due to Metabolic Alterations Regulated by the Inhibitory Receptor PD-1 Are an Early Driver of CD8(+) T Cell Exhaustion.

    Science.gov (United States)

    Bengsch, Bertram; Johnson, Andy L; Kurachi, Makoto; Odorizzi, Pamela M; Pauken, Kristen E; Attanasio, John; Stelekati, Erietta; McLane, Laura M; Paley, Michael A; Delgoffe, Greg M; Wherry, E John

    2016-08-16

    Dynamic reprogramming of metabolism is essential for T cell effector function and memory formation. However, the regulation of metabolism in exhausted CD8(+) T (Tex) cells is poorly understood. We found that during the first week of chronic lymphocytic choriomeningitis virus (LCMV) infection, before severe dysfunction develops, virus-specific CD8(+) T cells were already unable to match the bioenergetics of effector T cells generated during acute infection. Suppression of T cell bioenergetics involved restricted glucose uptake and use, despite persisting mechanistic target of rapamycin (mTOR) signaling and upregulation of many anabolic pathways. PD-1 regulated early glycolytic and mitochondrial alterations and repressed transcriptional coactivator PGC-1α. Improving bioenergetics by overexpression of PGC-1α enhanced function in developing Tex cells. Therapeutic reinvigoration by anti-PD-L1 reprogrammed metabolism in a subset of Tex cells. These data highlight a key metabolic control event early in exhaustion and suggest that manipulating glycolytic and mitochondrial metabolism might enhance checkpoint blockade outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. T Cell Exhaustion During Persistent Viral Infections

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    Kahan, Shannon M.; Wherry, E. John; Zajac, Allan J.

    2015-01-01

    Although robust and highly effective anti-viral T cells contribute to the clearance of many acute infections, viral persistence is associated with the development of functionally inferior, exhausted, T cell responses. Exhaustion develops in a step-wise and progressive manner, ranges in severity, and can culminate in the deletion of the anti-viral T cells. This disarming of the response is consequential as it compromises viral control and potentially serves to dampen immune-mediated damage. Exhausted T cells are unable to elaborate typical anti-viral effector functions. They are characterized by the sustained upregulation of inhibitory receptors and display a gene expression profile that distinguishes them from prototypic effector and memory T cell populations. In this review we discuss the properties of exhausted T cells; the virological and immunological conditions that favor their development; the cellular and molecular signals that sustain the exhausted state; and strategies for preventing and reversing exhaustion to favor viral control. PMID:25620767

  4. T cell exhaustion and Interleukin 2 downregulation.

    Science.gov (United States)

    Balkhi, Mumtaz Y; Ma, Qiangzhong; Ahmad, Shazia; Junghans, Richard P

    2015-02-01

    T cells reactive to tumor antigens and viral antigens lose their reactivity when exposed to the antigen-rich environment of a larger tumor bed or viral load. Such non-responsive T cells are termed exhausted. T cell exhaustion affects both CD8+ and CD4+ T cells. T cell exhaustion is attributed to the functional impairment of T cells to produce cytokines, of which the most important may be Interleukin 2 (IL2). IL2 performs functions critical for the elimination of cancer cells and virus infected cells. In one such function, IL2 promotes CD8+ T cell and natural killer (NK) cell cytolytic activities. Other functions include regulating naïve T cell differentiation into Th1 and Th2 subsets upon exposure to antigens. Thus, the signaling pathways contributing to T cell exhaustion could be linked to the signaling pathways contributing to IL2 loss. This review will discuss the process of T cell exhaustion and the signaling pathways that could be contributing to T cell exhaustion. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. A Predictive Model for Life Assessment of Automotive Exhaust Mufflers Subject to Internal Corrosion Failure due to Exhaust Gases Condensation

    OpenAIRE

    Nazir, H.; Khan, Zulfiqar Ahmad; Stokes, K.

    2016-01-01

    A study has been presented of pitting corrosion on internal walls of automotive exhaust muffler due to exhaust gases condensation. The problem mainly exists in the rear section of exhaust system close to tail end pipe such as muffler, especially when the temperature of muffler does not go up during short distance run or winter. The water vapor condenses on the muffler's inner wall in the form of water droplets. The dissolution of corrosive gases which are coming from internal combustion of en...

  6. Malaria drives T cells to exhaustion

    Directory of Open Access Journals (Sweden)

    Michelle N Wykes

    2014-05-01

    Full Text Available Malaria is a significant global burden but after >30 years of effort there is no vaccine on the market. While the complex life cycle of the parasite presents several challenges, many years of research have also identified several mechanisms of immune evasion by Plasmodium spp.. Recent research on malaria, has investigated the Programmed cell death-1 (PD-1 pathway which mediates exhaustion of T cells, characterized by poor effector functions and recall responses and in some cases loss of the cells by apoptosis. Such studies have shown exhaustion of CD4+ T cells and an unappreciated role for CD8+ T cells in promoting sterile immunity against blood stage malaria. This is because PD-1 mediates up to a 95% reduction in numbers and functional capacity of parasite-specific CD8+ T cells, thus masking their role in protection. The role of T cell exhaustion during malaria provides an explanation for the absence of sterile immunity following the clearance of acute disease which will be relevant to future malaria-vaccine design and suggests the need for novel therapeutic solutions. This review will thus examine the role of PD-1-mediated T cell exhaustion in preventing lasting immunity against malaria.

  7. T cell exhaustion and immune-mediated disease-the potential for therapeutic exhaustion.

    Science.gov (United States)

    McKinney, Eoin F; Smith, Kenneth Gc

    2016-12-01

    T cell exhaustion represents a continuous spectrum of cellular dysfunction induced during chronic viral infection, facilitating viral persistence and associating with poor clinical outcome. Modulation of T cell exhaustion can restore function in exhausted CD8 T cells, promoting viral clearance. Exhaustion has also been implicated as playing an important role in anti-tumour responses, whereby exhausted tumour-infiltrating lymphocytes fail to control tumour progression. More recently exhaustion has been linked to long-term clinical outcome in multiple autoimmune diseases but, in contrast to cancer or infection, it is associated with a favourable clinical outcome characterised by fewer relapses. An increasing understanding of key inhibitory signals promoting exhaustion has led to advances in therapy for chronic infection and cancer. An increasing understanding of this biology may facilitate novel treatment approaches for autoimmunity through the therapeutic induction of exhaustion. Copyright © 2016. Published by Elsevier Ltd.

  8. B-cell exhaustion in HIV infection: the role of immune activation.

    Science.gov (United States)

    Moir, Susan; Fauci, Anthony S

    2014-09-01

    To discuss a component of the pathogenic mechanisms of HIV infection in the context of phenotypic and functional alterations in B cells that are due to persistent viral replication leading to aberrant immune activation and cellular exhaustion. We explore how B-cell exhaustion arises during persistent viremia and how it compares with T-cell exhaustion and similar B-cell alterations in other diseases. HIV-associated B-cell exhaustion was first described in 2008, soon after the demonstration of persistent virus-induced T-cell exhaustion, as well as the identification of a subset B cells in tonsil tissues with immunoregulatory features similar to those observed in T-cell exhaustion. Our understanding of B-cell exhaustion has since expanded in two important areas: the role of inhibitory receptors in the unresponsiveness of exhausted B cells and the increasing evidence that similar B cells are found in other diseases that are associated with aberrant immune activation and inflammation. The phenomenon of B-cell exhaustion is now well established in HIV infection and other diseases characterized by immune activation. Over the coming years, it will be important to understand how cellular exhaustion affects the capacity of the immune system to respond to persisting primary pathogens, as well as to other microbial antigens, whether encountered as secondary infections or following immunization.

  9. Molecular and cellular insights into T cell exhaustion

    Science.gov (United States)

    Wherry, E. John; Kurachi, Makoto

    2016-01-01

    In chronic infections and cancer, T cells are exposed to persistent antigen and/or inflammatory signals. This scenario is often associated with the deterioration of T cell function: a state called ‘exhaustion’. Exhausted T cells lose robust effector functions, express multiple inhibitory receptors and are defined by an altered transcriptional programme. T cell exhaustion is often associated with inefficient control of persisting infections and tumours, but revitalization of exhausted T cells can reinvigorate immunity. Here, we review recent advances that provide a clearer molecular understanding of T cell exhaustion and reveal new therapeutic targets for persisting infections and cancer. PMID:26205583

  10. T Cell exhaustion in protozoan disease

    Science.gov (United States)

    Gigley, Jason P.; Bhadra, Rajarshi; Moretto, Magali M.; Khan, Imtiaz A.

    2012-01-01

    Protozoan parasites cause severe morbidity and mortality in humans worldwide, especially in developing countries where access to chemotherapeutic agents is limited. Although parasites initially evoke a robust immune response, subsequent immunity fails to clear infection, ultimately leading to the chronic stage. This enigmatic situation was initially addressed in chronic viral models, where T cells lose their function, a phenomenon referred to as ’exhaustion‘. However, recent studies demonstrate that this paradigm can be extended to protozoan diseases as well, albeit with notable differences. These studies have revealed that T cell responses generated against Toxoplasma gondii, Plasmodium sp. and Leishmania sp. can become dysfunctional. This Review discusses T cell exhaustion in parasitic infection, mechanisms of development, and a possible role in disease outcome. PMID:22832368

  11. T-cell exhaustion in allograft rejection and tolerance.

    Science.gov (United States)

    Thorp, Edward B; Stehlik, Christian; Ansari, M Javeed

    2015-02-01

    The role of T-cell exhaustion in the failure of clearance of viral infections and tumors is well established. There are several ongoing trials to reverse T-cell exhaustion for treatment of chronic viral infections and tumors. The mechanisms leading to T-cell exhaustion and its role in transplantation, however, are only beginning to be appreciated and are the focus of the present review. Exhausted T cells exhibit a distinct molecular profile reflecting combinatorial mechanisms involving the interaction of multiple transcription factors important in control of cell metabolism, acquisition of effector function and memory capacity. Change of microenvironmental cues and limiting leukocyte recruitment can modulate T-cell exhaustion. Impaired leukocyte recruitment induces T-cell exhaustion and prevents allograft rejection. Preventing or reversing T-cell exhaustion may lead to prevention of transplant tolerance or triggering of rejection; therefore, caution should be exercised in the use of agents blocking inhibitory receptors for the treatment of chronic viral infections or tumors in transplant recipients. Further definition of the role of T-cell exhaustion in clinical transplantation and an understanding of the mechanisms of induction of T-cell exhaustion are needed to develop strategies for preventing allograft rejection and induction of tolerance.

  12. Biodiesel exhaust-induced cytotoxicity and proinflammatory mediator production in human airway epithelial cells.

    Science.gov (United States)

    Mullins, Benjamin J; Kicic, Anthony; Ling, Kak-Ming; Mead-Hunter, Ryan; Larcombe, Alexander N

    2016-01-01

    Increasing use of biodiesel has prompted research into the potential health effects of biodiesel exhaust exposure. Few studies directly compare the health consequences of mineral diesel, biodiesel, or blend exhaust exposures. Here, we exposed human epithelial cell cultures to diluted exhaust generated by the combustion of Australian ultralow-sulfur-diesel (ULSD), unprocessed canola oil, 100% canola biodiesel (B100), and a blend of 20% canola biodiesel mixed with 80% ULSD. The physicochemical characteristics of the exhaust were assessed and we compared cellular viability, apoptosis, and levels of interleukin (IL)-6, IL-8, and Regulated on Activation, Normal T cell Expressed and Secreted (RANTES) in exposed cultured cells. Different fuel types produced significantly different amounts of exhaust gases and different particle characteristics. All exposures resulted in significant apoptosis and loss of viability when compared with control, with an increasing proportion of biodiesel being correlated with a decrease in viability. In most cases, exposure to exhaust resulted in an increase in mediator production, with the greatest increases most often in response to B100. Exposure to pure canola oil (PCO) exhaust did not increase mediator production, but resulted in a significant decrease in IL-8 and RANTES in some cases. Our results show that canola biodiesel exhaust exposure elicits inflammation and reduces viability of human epithelial cell cultures in vitro when compared with ULSD exhaust exposure. This may be related to an increase in particle surface area and number in B100 exhaust when compared with ULSD exhaust. Exposure to PCO exhaust elicited the greatest loss of cellular viability, but virtually no inflammatory response, likely due to an overall increase in average particle size. © 2014 Wiley Periodicals, Inc.

  13. Biophysical Assessment of Single Cell Cytotoxicity: Diesel Exhaust Particle-Treated Human Aortic Endothelial Cells

    OpenAIRE

    Wu, Yangzhe; Yu, Tian; Gilbertson, Timothy A.; Zhou, Anhong; Xu, Hao; Nguyen, Kytai Truong

    2012-01-01

    Exposure to diesel exhaust particles (DEPs), a major source of traffic-related air pollution, has become a serious health concern due to its adverse influences on human health including cardiovascular and respiratory disorders. To elucidate the relationship between biophysical properties (cell topography, cytoskeleton organizations, and cell mechanics) and functions of endothelial cells exposed to DEPs, atomic force microscope (AFM) was applied to analyze the toxic effects of DEPs on a model ...

  14. T-cell exhaustion in tuberculosis: pitfalls and prospects.

    Science.gov (United States)

    Khan, Nargis; Vidyarthi, Aurobind; Amir, Mohammed; Mushtaq, Khurram; Agrewala, Javed Naim

    2017-03-01

    T-cells play an important role in immunity but when these cells are overexposed to specific antigens, their function may decline. This state is usually referred to as exhaustion and the T-cells show reduced proliferation and functions such as cytokine release. T-cell exhaustion has been observed in several cancers as well as in chronic infections such as tuberculosis (TB). In chronic Mycobacterium tuberculosis (Mtb) infection, T-cells may express the exhaustion phenotype and show a progressive loss of secretion of IL-2, IFN-γ and TNF-α. In some cancers and chronic infection models, blocking the exhaustion phenotype can be achieved with the so-called checkpoint inhibitors. This results in tumor control and more effective immunity. However, in the case of TB, the T-cell exhaustion results are quite ambiguous. Hence, there is a need to investigate and explain the contribution of checkpoint at a molecular level to the outcome of events in chronic TB. Such information could help to guide the success of new therapies against chronic TB. This review highlights the mechanism through which T-cells undergo exhaustion and the approaches that can avert such events. This will help to design immunotherapies that can reinvigorate T-cell potency to protect patients from TB.

  15. Overcoming T cell exhaustion in infection and cancer

    Science.gov (United States)

    Pauken, Kristen E.; Wherry, E. John

    2015-01-01

    Inhibitors of the PD-1:PD-L1 pathway, a central regulator of T cell exhaustion, have been recently shown to be effective for treatment of different cancers. However, clinical responses are mixed, highlighting the need to better understand the mechanisms of action of PD-1:PD-L1, the role of this pathway in immunity to different tumors, and the molecular and cellular effects of PD-1 blockade. Here we review the molecular regulation of T cell exhaustion, placing recent findings on PD-1 blockade therapies in cancer in the context of the broader understanding of the roles of the PD-1:PD-L1 pathway in T cell exhaustion during chronic infection. We discuss the current understanding of the mechanisms involved in reversal T cell exhaustion, and outline critical areas of focus for future research, both basic and clinical. PMID:25797516

  16. T cell exhaustion in cancer: mechanisms and clinical implications.

    Science.gov (United States)

    Wang, Jin-Cheng; Xu, Yong; Huang, Zheng-Ming; Lu, Xiao-Jie

    2017-12-23

    During chronic viral infection or cancer, the immune system usually induces a corresponding immune response against pathogens or cancer cells so as to prevent worsening disease. T cell exhaustion in which reduced and dysfunctional effector T cells lead to immune escape is one of the mechanisms that pathogens or cancer cells get rid of control from the immune system. In this review, we discuss some mechanisms associated with T cell exhaustion and enumerate current methods of reversing T cell exhaustion. We also summarize current targeted treatment strategies and put forward following aspects that required to research. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  17. Tolerance and Exhaustion: Defining Mechanisms of T cell Dysfunction

    Science.gov (United States)

    Schietinger, Andrea; Greenberg, Philip D.

    2013-01-01

    CD8 T cell activation and differentiation is tightly controlled, and dependent on the context in which naïve T cells encounter antigen, can either result in functional memory or T cell dysfunction, including exhaustion, tolerance, anergy, or senescence. With the identification of phenotypic and functional traits shared in different settings of T cell dysfunction, distinctions between such dysfunctional `states' have become blurred. Here, we discuss distinct states of CD8 T cell dysfunction, with emphasis on (i) T cell tolerance to self-antigens (self-tolerance), (ii) T cell exhaustion during chronic infections, and (iii) tumor-induced T cell dysfunction. We highlight recent findings on cellular and molecular characteristics defining these states, cell-intrinsic regulatory mechanisms that induce and maintain them, and strategies that can lead to their reversal. PMID:24210163

  18. Immunology: Exhausted T cells perk up

    Science.gov (United States)

    Williams, Matthew A.; Bevan, Michael J.

    2006-02-01

    During persistent infections, the immune cells responsible for killing infected cells and maintaining inflammation gradually stop functioning, allowing the pathogen to thrive. But can this process be reversed?

  19. Exhaustion-associated regulatory regions in CD8+tumor-infiltrating T cells.

    Science.gov (United States)

    Mognol, Giuliana P; Spreafico, Roberto; Wong, Victor; Scott-Browne, James P; Togher, Susan; Hoffmann, Alexander; Hogan, Patrick G; Rao, Anjana; Trifari, Sara

    2017-03-28

    T-cell exhaustion is a progressive loss of effector function and memory potential due to persistent antigen exposure, which occurs in chronic viral infections and cancer. Here we investigate the relation between gene expression and chromatin accessibility in CD8 + tumor-infiltrating lymphocytes (TILs) that recognize a model tumor antigen and have features of both activation and functional exhaustion. By filtering out accessible regions observed in bystander, nonexhausted TILs and in acutely restimulated CD8 + T cells, we define a pattern of chromatin accessibility specific for T-cell exhaustion, characterized by enrichment for consensus binding motifs for Nr4a and NFAT transcription factors. Anti-PD-L1 treatment of tumor-bearing mice results in cessation of tumor growth and partial rescue of cytokine production by the dysfunctional TILs, with only limited changes in gene expression and chromatin accessibility. Our studies provide a valuable resource for the molecular understanding of T-cell exhaustion in cancer and other inflammatory settings.

  20. Proinflammatory Effects of Diesel Exhaust Nanoparticles on Scleroderma Skin Cells

    Directory of Open Access Journals (Sweden)

    A. Mastrofrancesco

    2014-01-01

    Full Text Available Autoimmune diseases are complex disorders of unknown etiology thought to result from interactions between genetic and environmental factors. We aimed to verify whether environmental pollution from diesel engine exhaust nanoparticulate (DEP of actually operating vehicles could play a role in the development of a rare immune-mediated disease, systemic sclerosis (SSc, in which the pathogenetic role of environment has been highlighted. The effects of carbon-based nanoparticulate collected at the exhaust of newer (Euro 5 and older (Euro 4 diesel engines on SSc skin keratinocytes and fibroblasts were evaluated in vitro by assessing the mRNA expression of inflammatory cytokines (IL-1α, IL-6, IL-8, and TNF-α and fibroblast chemical mediators (metalloproteases 2, 3, 7, 9, and 12; collagen types I and III; VEGF. DEP was shown to stimulate cytokine gene expression at a higher extent in SSc keratinocytes versus normal cells. Moreover, the mRNA gene expression of all MMPs, collagen types, and VEGF genes was significantly higher in untreated SSc fibroblasts versus controls. Euro 5 particle exposure increased the mRNA expression of MMP-2, -7, and -9 in SSc fibroblasts in a dose dependent manner and only at the highest concentration in normal cells. We suggest that environmental DEP could trigger the development of SSc acting on genetically hyperreactive cell systems.

  1. The masculinization of the fetus during pregnancy due to inhalation of diesel exhaust.

    OpenAIRE

    Watanabe, N; Kurita, M

    2001-01-01

    This study was conducted to determine the impact of diesel exhaust inhalation on the fetus. Seventy-two pregnant rats and 18 nonpregnant rats were divided into three groups: a group exposed to total diesel engine exhaust containing 5.63 mg/m(3) particulate matter, 4.10 ppm nitrogen dioxide, and 8.10 ppm nitrogen oxide; a group exposed to filtered exhaust without particulate matter; and a group exposed to clean air. The exposure period was from day 7 until day 20 of pregnancy. In addition, 15 ...

  2. IRF9 Prevents CD8+T Cell Exhaustion in an Extrinsic Manner during Acute Lymphocytic Choriomeningitis Virus Infection.

    Science.gov (United States)

    Huber, Magdalena; Suprunenko, Tamara; Ashhurst, Thomas; Marbach, Felix; Raifer, Hartmann; Wolff, Svenja; Strecker, Thomas; Viengkhou, Barney; Jung, So Ri; Obermann, Hannah-Lena; Bauer, Stefan; Xu, Haifeng C; Lang, Philipp A; Tom, Adomati; Lang, Karl S; King, Nicholas J C; Campbell, Iain L; Hofer, Markus J

    2017-11-15

    limited early LCMV replication by regulating expression of interferon-stimulated genes and Irf7 , encoding a transcription factor crucial for type I interferon (IFN-I) production, as well as by controlling the levels of IFN-I. Infection of IRF9-deficient mice led to a chronic infection that was accompanied by CD8 + T cell exhaustion due to defects extrinsic to T cells. Our findings illustrate an essential role for IRF9, as a mediator downstream of IFNAR, in preventing overwhelming antigen exposure causing CD8 + T cell exhaustion and leading to chronic viral infection. Copyright © 2017 American Society for Microbiology.

  3. T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection.

    Science.gov (United States)

    McKinney, Eoin F; Lee, James C; Jayne, David R W; Lyons, Paul A; Smith, Kenneth G C

    2015-07-30

    The clinical course of autoimmune and infectious disease varies greatly, even between individuals with the same condition. An understanding of the molecular basis for this heterogeneity could lead to significant improvements in both monitoring and treatment. During chronic infection the process of T-cell exhaustion inhibits the immune response, facilitating viral persistence. Here we show that a transcriptional signature reflecting CD8 T-cell exhaustion is associated with poor clearance of chronic viral infection, but conversely predicts better prognosis in multiple autoimmune diseases. The development of CD8 T-cell exhaustion during chronic infection is driven both by persistence of antigen and by a lack of accessory 'help' signals. In autoimmunity, we find that where evidence of CD4 T-cell co-stimulation is pronounced, that of CD8 T-cell exhaustion is reduced. We can reproduce the exhaustion signature by modifying the balance of persistent stimulation of T-cell antigen receptors and specific CD2-induced co-stimulation provided to human CD8 T cells in vitro, suggesting that each process plays a role in dictating outcome in autoimmune disease. The 'non-exhausted' T-cell state driven by CD2-induced co-stimulation is reduced by signals through the exhaustion-associated inhibitory receptor PD-1, suggesting that induction of exhaustion may be a therapeutic strategy in autoimmune and inflammatory disease. Using expression of optimal surrogate markers of co-stimulation/exhaustion signatures in independent data sets, we confirm an association with good clinical outcome or response to therapy in infection (hepatitis C virus) and vaccination (yellow fever, malaria, influenza), but poor outcome in autoimmune and inflammatory disease (type 1 diabetes, anti-neutrophil cytoplasmic antibody-associated vasculitis, systemic lupus erythematosus, idiopathic pulmonary fibrosis and dengue haemorrhagic fever). Thus, T-cell exhaustion plays a central role in determining outcome in

  4. Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells

    Science.gov (United States)

    2017-10-01

    since, in the absence of such knowledge, the development of effective therapeutic interventions to target CSCs and prevent cancer progression and...yes) (2) Presentations: a. 2016 Keystone Symposia- Stem Cells & Cancer, Breckenridge, “Epigenetic regulation promotes obesity related breast

  5. Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells

    Science.gov (United States)

    2016-10-01

    stably express miR-200c (pCDH- miR200c) and MCF7 cells with knock- down of miR-200c (pZIP-miR200c) (Months 1-2) Completed! We have successfully...established BT549-pCDH-miR200c and MCF7 - pZIP-miR200c and examined the protein expression levels as described in subtask 2 (Fig. 1). Subtask 2...Determine expression levels of PKCζ and phospho-NUMB (p- NUMB), by re-expressing PKCζ in BT549-pCDH-miR200c cells and knocking-down PKCζ in MCF7

  6. T Cell Exhaustion Signatures Vary with Tumor Type and are Severe in Glioblastoma.

    Science.gov (United States)

    Woroniecka, Karolina; Chongsathidkiet, Pakawat; Rhodin, Kristen E; Kemeny, Hanna R; Dechant, Cosette A; Farber, Samuel H; Elsamadicy, Aladine A; Cui, Xiuyu; Koyama, Shohei; Jackson, Christina C; Hansen, Landon J; Johanns, Tanner M; Sanchez-Perez, Luis; Chandramohan, Vidyalakshmi; Yu, Yen-Rei A; Bigner, Darell D; Giles, Amber J; Healy, Patrick; Dranoff, Glenn; Weinhold, Kent J; Dunn, Gavin P; Fecci, Peter E

    2018-02-07

    T cell dysfunction is a hallmark of GBM. While anergy and tolerance have been well characterized, T cell exhaustion remains relatively unexplored. Exhaustion, characterized in part by the upregulation of multiple immune checkpoints, is a known contributor to failures amidst immune checkpoint blockade, a strategy that has lacked success thus far in GBM. This study is among the first to examine, and credential as bona fide, exhaustion among T cells infiltrating human and murine GBM. Tumor-infiltrating and peripheral blood lymphocytes (TIL, PBL) were isolated from patients with GBM. Levels of exhaustion-associated inhibitory receptors and post-stimulation levels of the cytokines IFN-g, TNF-a, and IL-2 were assessed by flow cytometry. T cell receptor (TCR) Vβ chain expansion was also assessed in TIL and PBL. Similar analysis was extended to TIL isolated from intracranial and subcutaneous immunocompetent murine models of glioma, breast, lung, and melanoma cancers. Our data reveal that GBM elicits a particularly severe T cell exhaustion signature among infiltrating T cells characterized by: 1) prominent upregulation of multiple immune checkpoints; 2) stereotyped T cell transcriptional programs matching classical virus-induced exhaustion; and 3) notable T cell hypo-responsiveness in tumor-specific T cells. Exhaustion signatures differ predictably with tumor identity, but remain stable across manipulated tumor locations. Distinct cancers possess similarly distinct mechanisms for exhausting T cells. The poor TIL function and severe exhaustion observed in GBM highlights the need to better understand this tumor-imposed mode of T cell dysfunction in order to formulate effective immunotherapeutic strategies targeting GBM. Copyright ©2018, American Association for Cancer Research.

  7. Functional exhaustion of CD4+T cells induced by co-stimulatory signals from myeloid leukaemia cells.

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    Ozkazanc, Didem; Yoyen-Ermis, Digdem; Tavukcuoglu, Ece; Buyukasik, Yahya; Esendagli, Gunes

    2016-12-01

    To cope with immune responses, tumour cells implement elaborate strategies such as adaptive resistance and induction of T-cell exhaustion. T-cell exhaustion has been identified as a state of hyporesponsiveness that arises under continuous antigenic stimulus. Nevertheless, contribution of co-stimulatory molecules to T-cell exhaustion in cancer remains to be better defined. This study explores the role of myeloid leukaemia-derived co-stimulatory signals on CD4 + T helper (Th) cell exhaustion, which may limit anti-tumour immunity. Here, CD86 and inducible T-cell co-stimulator ligand (ICOS-LG) co-stimulatory molecules that are found on myeloid leukaemia cells supported Th cell activation and proliferation. However, under continuous stimulation, T cells co-cultured with leukaemia cells, but not with peripheral blood monocytes, became functionally exhausted. These in vitro-generated exhausted Th cells were defined by up-regulation of programmed cell death 1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), lymphocyte activation gene 3 (LAG3) and T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) inhibitory receptors. They were reluctant to proliferate upon re-stimulation and produced reduced amounts of interleukin-2 (IL-2), tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Nonetheless, IL-2 supplementation restored the proliferation capacity of the exhausted Th cells. When the co-stimulation supplied by the myeloid leukaemia cells were blocked, the amount of exhausted Th cells was significantly decreased. Moreover, in the bone marrow aspirates from patients with acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS), a subpopulation of Th cells expressing PD-1, TIM-3 and/or LAG3 was identified together with CD86 + and/or ICOS-LG + myeloid blasts. Collectively, co-stimulatory signals derived from myeloid leukaemia cells possess the capacity to facilitate functional exhaustion in Th cells. © 2016 John Wiley & Sons Ltd.

  8. T-cell exhaustion: understanding the interface of chronic viral and autoinflammatory diseases.

    Science.gov (United States)

    McKinney, Eoin F; Smith, Kenneth Gc

    2016-11-01

    During acute viral infection CD8 T cells rapidly expand before contracting down to a persistent memory population that confers long-lasting immunity. However when the antigen persists, such as during chronic viral infection, a dysfunctional process termed 'exhaustion' limits the antiviral response, facilitating ongoing viraemia and poor clinical outcome. CD8 T-cell exhaustion was originally identified in lymphocytic choriomeningitis virus infection of mice; however, new evidence has shown that exhaustion is associated with the control of a wide range of human chronic inflammatory states, including chronic viral infection, autoimmunity and cancer. Consequently, an understanding of the mechanisms controlling exhaustion during chronic infection may also indicate new strategies for controlling other chronic inflammatory diseases. In particular, the success of immune checkpoint blockade as a form of cancer immunotherapy has prompted renewed efforts to understand how T-cell immunity to chronic antigenic stimulation might similarly be measured or modulated in autoimmune diseases. Here we summarise the mechanisms controlling T-cell exhaustion and how they relate to the control of autoimmune responses, providing a future perspective on measuring or manipulating exhaustion to personalise therapy.

  9. Local and Systemic CD4+ T Cell Exhaustion Reverses with Clinical Resolution of Pulmonary Sarcoidosis

    Directory of Open Access Journals (Sweden)

    Charlene Hawkins

    2017-01-01

    Full Text Available Investigation of the Th1 immune response in sarcoidosis CD4+ T cells has revealed reduced proliferative capacity and cytokine expression upon TCR stimulation. In other disease models, such cellular dysfunction has been associated with a step-wise, progressive loss of T cell function that results from chronic antigenic stimulation. T cell exhaustion is defined by decreased cytokine production upon TCR activation, decreased proliferation, increased expression of inhibitory cell surface receptors, and increased susceptibility to apoptosis. We characterized sarcoidosis CD4+ T cell immune function in systemic and local environments among subjects undergoing disease progression compared to those experiencing disease resolution. Spontaneous and TCR-stimulated Th1 cytokine expression and proliferation assays were performed in 53 sarcoidosis subjects and 30 healthy controls. PD-1 expression and apoptosis were assessed by flow cytometry. Compared to healthy controls, sarcoidosis CD4+ T cells demonstrated reductions in Th1 cytokine expression, proliferative capacity (p<0.05, enhanced apoptosis (p<0.01, and increased PD-1 expression (p<0.001. BAL-derived CD4+ T cells also demonstrated multiple facets of T cell exhaustion (p<0.05. Reversal of CD4+ T cell exhaustion was observed in subjects undergoing spontaneous resolution (p<0.05. Sarcoidosis CD4+ T cells exhibit loss of cellular function during progressive disease that follows the archetype of T cell exhaustion.

  10. Cellular response of mucociliary differentiated primary bronchial epithelial cells to diesel exhaust

    NARCIS (Netherlands)

    Zarcone, M.C.; Duistermaat, E.; Schadewijk, A. van; Jedynksa, A.D.; Hiemstra, P.S.; Kooter, I.M.

    2016-01-01

    Cellular response of mucociliary differentiated primary bronchial epithelial cells to diesel exhaust. Am J Physiol Lung Cell Mol Physiol 311: L111–L123, 2016. First published May 17, 2016; doi:10.1152/ajplung.00064.2016.—Diesel emissions are the main source of air pollution in urban areas, and

  11. Acquired transcriptional programming in functional and exhausted virus-specific CD8 T cells.

    Science.gov (United States)

    Youngblood, Ben; Wherry, E John; Ahmed, Rafi

    2012-01-01

    Failure to control viral infections such as HIV results in T-cell receptor (TCR) and inhibitory receptor driven exhaustion of antigen-specific T cells. Persistent signaling by these receptors during chronic viral infection sculpts the transcriptional regulatory programs of virus-specific T cells. The resulting gene expression profile is tailored to temper the potentially damaging effector functions of cytotoxic T cells and adapt them to an antigen-rich and inflammation-rich environment. Here we review recent studies investigating mechanisms of transcriptional regulation of effector, functional memory, and exhausted T-cell functions during acute versus chronic infections. Patterns of gene expression in virus-specific CD8 T cells are a result of a combination of pro and inhibitory signals from antigen presentation (TCR-mediated) and co-inhibitory receptor ligation (PD-1, 2B4). Further, memory-specific transcriptional regulation of 2B4 expression and signaling impose a self-limiting secondary effector response to a prolonged viral infection. Additionally, differentiation of functional memory CD8 T cells is coupled with acquisition of a repressive epigenetic program for PD-1 expression. However, chronic infection provides a signal that blocks the acquisition of these epigenetic modifications reinforcing the suppression of cytotoxic lymphocyte (CTL) functions in exhausted cells. Current findings suggest that the mechanism(s) that delineate functional memory versus exhaustion are coupled with acquisition of transcriptional programs at the effector stage of differentiation, reinforced by cessation or persistence of TCR signaling.

  12. Effects of diesel exhaust particles on human lung epithelial cells: an in vitro study.

    Science.gov (United States)

    Mazzarella, G; Ferraraccio, F; Prati, M V; Annunziata, S; Bianco, A; Mezzogiorno, A; Liguori, G; Angelillo, I F; Cazzola, M

    2007-06-01

    Atmospheric particulate matter (PM), an ingredient of urban pollution matter, is a mixture of solid and liquid particles differing in origin, dimension and composition. There is big concern about inhaled PM in urban areas, especially due to its adverse effects on the respiratory system. Diesel exhaust particulate (DEP), which constitutes the major part of PM, is characterized by a carbonic mixture composed of approximately 18,000 different high-molecular-weight organic compounds. Diesel engines release 10 times the amount of NO(2) aldehydes and breathable PM compared to unleaded gasoline engines and more than 100 times that produced by catalysed gasoline engines; these data gain great significance when taken into account the fact that diesel-powered vehicles are becoming more and more popular. DEP polyaromatic hydrocarbons (PAH), once deposited on airways mucous surfaces easily pass through epithelial cells (ECs) membranes, bind themselves to cytosolic receptors and then affect cell growth and differentiation. Human lung epithelial cells and macrophages engulf DEP, this resulting in increased proinflammatory cytokines release (IL-6, IL-8 and GM-CSF). We investigated the biological effects of DEP-PM on the human lung EC line A549. Light microscopy analysis suggested the presence of cell wall alterations, and provided evidence of PM internalization and cytoplasmic vacuolization. Following PM stimulation, nuclei also were seen undergo clear gross morphological modifications. Immunocytochemistry was used to detect intracytoplasmic IL-6 and IL-8 expression.

  13. T-cell exhaustion in chronic hepatitis B infection: current knowledge and clinical significance

    Science.gov (United States)

    Ye, B; Liu, X; Li, X; Kong, H; Tian, L; Chen, Y

    2015-01-01

    Hepatitis B virus (HBV) infection is the major cause of inflammatory liver disease, of which the clinical recovery and effective anti-viral therapy is associated with the sustained viral control of effector T cells. In humans, chronic HBV infection often shows weak or absent virus-specific T-cell reactivity, which is described as the ‘exhaustion' state characterized by poor effector cytotoxic activity, impaired cytokine production and sustained expression of multiple inhibitory receptors, such as programmed cell death-1 (PD-1), lymphocyte activation gene-3, cytotoxic T lymphocyte-associated antigen-4 and CD244. As both CD4+ and CD8+ T cells participate in the immune responses against chronic hepatitis virus through distinct manners, compelling evidences have been proposed, which restore the anti-viral function of these exhausted T cells by blocking those inhibitory receptors with its ligand and will pave the way for the development of more effective immunotherapeutic and prophylactic strategies for the treatment of chronic infectious diseases. A large number of studies have stated the essentiality of T-cell exhaustion in virus-infected diseases, such as LCMV, hepatitis C virus (HCV), human immunodeficiency virus infections and cancers. Besides, the functional restoration of HCV- and HIV-specific CD8+ T cells by PD-1 blockade has already been repeatedly verified, and also for the immunological control of tumors in humans, blocking the PD-1 pathway could be a major immunotherapeutic strategy. Although the specific molecular pathways of T-cell exhaustion remain ambiguous, several transcriptional pathways have been implicated in T-cell exhaustion recently; among them Blimp-1, T-bet and NFAT2 were able to regulate exhausted T cells during chronic viral infection, suggesting a distinct lineage fate for this sub-population of T cells. This paper summarizes the current literature relevant to T-cell exhaustion in patients with HBV-related chronic hepatitis, the options

  14. Optimization of a thermoelectric generator subsystem for high temperature PEM fuel cell exhaust heat recovery

    DEFF Research Database (Denmark)

    Gao, Xin; Andreasen, Søren Juhl; Kær, Søren Knudsen

    2014-01-01

    In previous work, a thermoelectric (TE) exhaust heat recovery subsystem for a high temperature polymer electrolyte membrane (HT-PEM) fuel cell stack was developed and modeled. Numerical simulations were conducted and have identified an optimized subsystem configuration and 4 types of compact heat...... exchangers with superior performance for further analysis. In this work, the on-design performances of the 4 heat exchangers are more thoroughly assessed on their corresponding optimized subsystem configurations. Afterward, their off-design performances are compared on the whole working range of the fuel...... modules are now connected into branches. The procedures of designing and optimizing this TE exhaust heat recovery subsystem are drawn out. The contribution of TE exhaust heat recovery to the HT-PEM fuel cell power system is preliminarily concluded. Its feasibility is also discussed....

  15. Transcription factor regulation of CD8+ T-cell memory and exhaustion.

    Science.gov (United States)

    Angelosanto, Jill M; Wherry, E John

    2010-07-01

    During an infection, antigen-specific CD8+ T cells undergo numerous cellular and transcriptional changes as they develop from naive T cells into effector and memory cells. However, when the antigen persists in a chronic infection, the cellular programs governing effector and memory development are influenced by chronic stimulation, and dysfunctional or exhausted CD8+ T cells are generated. Recently, exhausted CD8+ T cells were found to differ dramatically from naive and functional memory CD8+ T cells on a transcriptional level, demonstrating that exposure to chronic antigen can impact T cells at a fundamental level. While transcriptional changes in CD8+ T cells during memory development is currently a topic of particular interest, the transcriptional changes related to exhaustion and other forms of T-cell dysfunction have received less attention. New computational methods are not only uncovering important transcription factors in these developmental processes but are also going further to define and connect these transcription factors into transcriptional modules that work in parallel to control cell fate and state. Understanding the molecular processes behind the development of CD8+ T-cell memory and exhaustion should not only increase our understanding of the immune system but also could reveal therapeutic targets and treatments for infectious and immunological diseases. Here, we provide a basic overview of acute and chronic viral infections and the transcription factors known to influence the development of virus-specific T cells in both settings. We also discuss recent innovations in genomic and computational tools that could be used to enhance the way we understand the development of T-cell responses to infectious disease.

  16. Blimp-1–mediated CD4 T cell exhaustion causes CD8 T cell dysfunction during chronic toxoplasmosis

    Science.gov (United States)

    Cobb, Dustin A.; Bhadra, Rajarshi

    2016-01-01

    CD8, but not CD4, T cells are considered critical for control of chronic toxoplasmosis. Although CD8 exhaustion has been previously reported in Toxoplasma encephalitis (TE)–susceptible model, our current work demonstrates that CD4 not only become exhausted during chronic toxoplasmosis but this dysfunction is more pronounced than CD8 T cells. Exhausted CD4 population expressed elevated levels of multiple inhibitory receptors concomitant with the reduced functionality and up-regulation of Blimp-1, a transcription factor. Our data demonstrates for the first time that Blimp-1 is a critical regulator for CD4 T cell exhaustion especially in the CD4 central memory cell subset. Using a tamoxifen-dependent conditional Blimp-1 knockout mixed bone marrow chimera as well as an adoptive transfer approach, we show that CD4 T cell–intrinsic deletion of Blimp-1 reversed CD8 T cell dysfunction and resulted in improved pathogen control. To the best of our knowledge, this is a novel finding, which demonstrates the role of Blimp-1 as a critical regulator of CD4 dysfunction and links it to the CD8 T cell dysfunctionality observed in infected mice. The critical role of CD4-intrinsic Blimp-1 expression in mediating CD4 and CD8 T cell exhaustion may provide a rational basis for designing novel therapeutic approaches. PMID:27481131

  17. Glucagon-Like Peptide-1 Receptor Agonists: Beta-Cell Protection or Exhaustion?

    Science.gov (United States)

    van Raalte, Daniël H; Verchere, C Bruce

    2016-07-01

    Glucagon-like peptide (GLP)-1 receptor agonists enhance insulin secretion and may improve pancreatic islet cell function. However, GLP-1 receptor (GLP-1R) agonist treatment may have more complex, and sometimes deleterious, effects on beta cells. We discuss the concepts of beta cell protection versus exhaustion for different GLP-1R agonists based on recent data. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Integration of a molten carbonate fuel cell with a direct exhaust absorption chiller

    Science.gov (United States)

    Margalef, Pere; Samuelsen, Scott

    A high market value exists for an integrated high-temperature fuel cell-absorption chiller product throughout the world. While high-temperature, molten carbonate fuel cells are being commercially deployed with combined heat and power (CHP) and absorption chillers are being commercially deployed with heat engines, the energy efficiency and environmental attributes of an integrated high-temperature fuel cell-absorption chiller product are singularly attractive for the emerging distributed generation (DG) combined cooling, heating, and power (CCHP) market. This study addresses the potential of cooling production by recovering and porting the thermal energy from the exhaust gas of a high-temperature fuel cell (HTFC) to a thermally activated absorption chiller. To assess the practical opportunity of serving an early DG-CCHP market, a commercially available direct fired double-effect absorption chiller is selected that closely matches the exhaust flow and temperature of a commercially available HTFC. Both components are individually modeled, and the models are then coupled to evaluate the potential of a DG-CCHP system. Simulation results show that a commercial molten carbonate fuel cell generating 300 kW of electricity can be effectively coupled with a commercial 40 refrigeration ton (RT) absorption chiller. While the match between the two "off the shelf" units is close and the simulation results are encouraging, the match is not ideal. In particular, the fuel cell exhaust gas temperature is higher than the inlet temperature specified for the chiller and the exhaust flow rate is not sufficient to achieve the potential heat recovery within the chiller heat exchanger. To address these challenges, the study evaluates two strategies: (1) blending the fuel cell exhaust gas with ambient air, and (2) mixing the fuel cell exhaust gases with a fraction of the chiller exhaust gas. Both cases are shown to be viable and result in a temperature drop and flow rate increase of the

  19. Muscle satellite cells are activated after exercise to exhaustion in Thoroughbred horses.

    Science.gov (United States)

    Kawai, M; Aida, H; Hiraga, A; Miyata, H

    2013-07-01

    Although satellite cells are well known as muscle stem cells capable of adding myonuclei during muscle repair and hypertrophy, the response of satellite cells in horse muscles to a run to exhaustion is still unknown. To investigate the time course of satellite cell activation in Thoroughbred horse muscle after running to exhaustion. We hypothesised that this type of intense exercise would induce satellite cell activation in skeletal muscle similar to a resistance exercise. Nine de-trained Thoroughbred horses (6 geldings and 3 mares) aged 3-6 years were studied. Biopsy samples were taken from the gluteus medius muscle of the horses before and 1 min, 3 h, 1 day, 3 days, 1 week and 2 weeks after a treadmill run to exhaustion. The numbers of satellite cells for each fibre type were determined by using immunofluorescence staining. Total RNA was extracted from these samples, and the expressions of interleukin (IL)-6, paired box transcriptional factor (Pax) 7, myogenic differentiation 1 (MyoD), myogenin, proliferating cell nuclear antigen (PCNA), insulin-like growth factor (IGF)-I and hepatocyte growth factor (HGF) mRNA were analysed using real-time reverse transcription-PCR. The numbers of satellite cells were significantly increased in type I and IIa fibres at 1 week and in type IIa/x fibre at 2 weeks post exercise. The expression of IL-6 mRNA increased significantly by 3 h post exercise. The expression of PCNA mRNA also increased by 1 day after running, indicating that running can initiate satellite cell proliferation. The expression of Pax7, MyoD, myogenin, IGF-I and HGF mRNA peaked at 1 week post exercise. Satellite cell activation and proliferation could be enhanced after a run to exhaustion without detectable injury as assessed by the histochemical analysis. Understanding the response of satellite cell activation to running exercise provides fundamental information about the skeletal muscle adaptation in Thoroughbred horses. © 2012 EVJ Ltd.

  20. Strategies to overcome HBV-specific T cell exhaustion: checkpoint inhibitors and metabolic re-programming.

    Science.gov (United States)

    Fisicaro, Paola; Boni, Carolina; Barili, Valeria; Laccabue, Diletta; Ferrari, Carlo

    2018-01-29

    HBV-specific T cells play a key role in antiviral protection and failure to control HBV is associated with severely dysfunctional T cell responses. Therefore, functional T cell reconstitution represents a potential way to treat chronically infected patients. The growing understanding of the dysregulated transcriptional/epigenetic and metabolic programs underlying T cell exhaustion allows to envisage functional T cell reconstitution strategies based on the combined/sequential use of compounds able to induce decline of antigen load, checkpoint modulation, metabolic and epigenetic reprogramming with possible boosting of functionally restored responses by specific vaccines. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. CAPTURING EXHAUST CO2 GAS USING MOLTEN CARBONATE FUEL CELLS

    Directory of Open Access Journals (Sweden)

    Prateek Dhawan

    2016-03-01

    Full Text Available Carbon dioxide is considered as one of the major contenders when the question of greenhouse effect arises. So for any industry or power plant it is of utmost importance to follow certain increasingly stringent environment protection rules and laws. So it is significant to keep eye on any possible methods to reduce carbon dioxide emissions in an efficient way. This paper reviews the available literature so as to try to provide an insight of the possibility of using Molten Carbonate Fuel Cells (MCFCs as the carbon capturing and segregating devices and the various factors that affect the performance of MCFCs during the process of CO2 capture.

  2. HCV coinfection contributes to HIV pathogenesis by increasing immune exhaustion in CD8 T-cells.

    Science.gov (United States)

    Rallón, Norma; García, Marcial; García-Samaniego, Javier; Rodríguez, Noelia; Cabello, Alfonso; Restrepo, Clara; Álvarez, Beatriz; García, Rosa; Górgolas, Miguel; Benito, José M

    2017-01-01

    There are several contributors to HIV-pathogenesis or insufficient control of the infection. However, whether HIV/HCV-coinfected population exhibits worst evolution of HIV-pathogenesis remains unclear. Recently, some markers of immune exhaustion have been proposed as preferentially upregulated on T-cells during HIV-infection. Herein, we have analyzed T-cell exhaustion together with several other contributors to HIV-pathogenesis that could be affected by HCV-coinfection. Ninety-six patients with chronic HIV-infection (60 HIV-monoinfected and 36 HIV/HCV-coinfected), and 20 healthy controls were included in the study. All patients were untreated for both infections. Several CD4 and CD8 T-cell subsets involved in HIV-pathogenesis were investigated. Non-parametric tests were used to establish differences between groups and associations between variables. Multivariate linear regression was used to ascertain the variables independently associated with CD4 counts. HIV-patients presented significant differences compared to healthy controls in most of the parameters analyzed. Both HIV and HIV/HCV groups were comparable in terms of age, CD4 counts and HIV-viremia. Compared to HIV group, HIV/HCV group presented significantly higher levels of exhaustion (Tim3+PD1- subset) in total CD8+ T-cells (p = 0.003), and higher levels of exhaustion in CD8+HLADR+CD38+ (p = 0.04), CD8+HLADR-CD38+ (p = 0.009) and CD8+HLADR-CD38- (p = 0.006) subsets of CD8+ T-cells. Interestingly these differences were maintained after adjusting by CD4 counts and HIV-viremia. We show a significant impact of HCV-coinfection on CD8 T-cells exhaustion, an important parameter associated with CD8 T-cell dysfunction in the setting of chronic HIV-infection. The relevance of this phenomenon on immunological and/or clinical HIV progression prompts HCV treatment to improve management of coinfected patients.

  3. Diesel exhaust particulate extracts inhibit transcription of nuclear respiratory factor-1 and cell viability in human umbilical vein endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Mattingly, Kathleen A.; Klinge, Carolyn M. [University of Louisville School of Medicine, Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, Louisville, KY (United States)

    2012-04-15

    Endothelial dysfunction precedes cardiovascular disease and is accompanied by mitochondrial dysfunction. Here we tested the hypothesis that diesel exhaust particulate extracts (DEPEs), prepared from a truck run at different speeds and engine loads, would inhibit genomic estrogen receptor activation of nuclear respiratory factor-1 (NRF-1) transcription in human umbilical vein endothelial cells (HUVECs). Additionally, we examined how DEPEs affect NRF-1-regulated TFAM expression and, in turn, Tfam-regulated mtDNA-encoded cytochrome c oxidase subunit I (COI, MTCO1) and NADH dehydrogenase subunit I (NDI) expression as well as cell proliferation and viability. We report that 17{beta}-estradiol (E{sub 2}), 4-hydroxytamoxifen (4-OHT), and raloxifene increased NRF-1 transcription in HUVECs in an ER-dependent manner. DEPEs inhibited NRF-1 transcription, and this suppression was not ablated by concomitant treatment with E{sub 2}, 4-OHT, or raloxifene, indicating that the effect was not due to inhibition of ER activity. While E{sub 2} increased HUVEC proliferation and viability, DEPEs inhibited viability but not proliferation. Resveratrol increased NRF-1 transcription in an ER-dependent manner in HUVECs, and ablated DEPE inhibition of basal NRF-1 expression. Given that NRF-1 is a key nuclear transcription factor regulating genes involved in mitochondrial activity and biogenesis, these data suggest that DEPEs may adversely affect mitochondrial function leading to endothelial dysfunction and resveratrol may block these effects. (orig.)

  4. Complementary role of HCV and HIV in T-cell activation and exhaustion in HIV/HCV coinfection.

    Science.gov (United States)

    Feuth, Thijs; Arends, Joop E; Fransen, Justin H; Nanlohy, Nening M; van Erpecum, Karel J; Siersema, Peter D; Hoepelman, Andy I M; van Baarle, Debbie

    2013-01-01

    To investigate whether T-cell activation and exhaustion is linked to HCV- and HIV disease parameters in HIV/HCV infected individuals, we studied T-cell characteristics in HIV/HCV coinfected patients and controls. 14 HIV/HCV coinfected, 19 HCV monoinfected, 10 HIV monoinfected patients and 15 healthy controls were included in this cross-sectional study. Differences in expression of activation and exhaustion markers (HLA-DR, CD38, PD-1, Tim-3 and Fas) and phenotypic markers on CD4(+) and CD8(+) T-cells were analysed by flow cytometry and were related to HCV disease parameters (HCV-viremia, ALT and liver fibrosis). Frequencies of activated CD4(+) and CD8(+) T-cells were higher in HIV/HCV-coinfected compared to healthy controls and HCV or HIV mono-infected individuals. Coinfected patients also showed high expression of the exhaustion marker PD-1 and death receptor Fas. In contrast, the exhaustion marker Tim-3 was only elevated in HIV-monoinfected patients. T-cell activation and exhaustion were correlated with HCV-RNA, suggesting that viral antigen influences T-cell activation and exhaustion. Interestingly, increased percentages of effector CD8(+) T-cells were found in patients with severe (F3-F4) liver fibrosis compared to those with no to minimal fibrosis (F0-F2). HIV/HCV coinfected patients display a high level of T-cell activation and exhaustion in the peripheral blood. Our data suggest that T-cell activation and exhaustion are influenced by the level of HCV viremia. Furthermore, high percentages of cytotoxic/effector CD8(+) T-cells are associated with liver fibrosis in both HCV monoinfected and HIV/HCV coinfected patients.

  5. Inflammatory Cytokines and White Blood Cell Counts Response to Environmental Levels of Diesel Exhaust and Ozone Inhalation Exposures

    Science.gov (United States)

    Epidemiological observations of urban inhalation exposures to diesel exhaust (DE) and ozone (O3) have shown pre-clinical cardiopulmonary responses in humans. Identifying the key biological mechanisms that initiate these health bioindicators is difficult due to variability in envi...

  6. Early and Delayed Antiretroviral Therapy Results in Comparable Reductions in CD8+T Cell Exhaustion Marker Expression.

    Science.gov (United States)

    Rutishauser, Rachel Lena; Hartogensis, Wendy; Deguit, Christian Deo; Krone, Melissa; Hoh, Rebecca; Hecht, Frederick M; Pilcher, Christopher D; Bacchetti, Peter; Deeks, Steven G; Hunt, Peter W; McCune, Joseph M

    2017-07-01

    In untreated HIV infection, CD8 + T cell exhaustion (i.e., decreased proliferative and effector capacity) is associated with high levels of expression of coinhibitory receptors, including PD-1, T cell immunoreceptor with Ig and ITIM domains (TIGIT), CD160, and 2B4. This is evident for both HIV-specific and non-HIV-specific CD8 + T cells. Antiretroviral therapy (ART) initiated during chronic infection decreases but may not completely normalize the expression of such "exhaustion markers." Compared to initiation of ART later in the course of disease, initiation soon after infection reduces some parameters of chronic inflammation and adaptive immune dysfunction. However, it is not known if Early ART (e.g., initiated within the first 6 months after HIV infection) versus Delayed ART (e.g., initiated during chronic infection) preferentially reduces expression of exhaustion markers. We evaluated exhaustion marker expression on subsets of circulating effector and memory CD8 + T cells at longitudinal pre- and post-ART (2 and 5 years on ART) time points from n = 19 (Early ART) and n = 23 (Delayed ART) individuals. Before ART, TIGIT and CD160 were expressed on a statistically significantly higher proportion of effector and transitional memory cells from individuals in the Delayed ART group: the timing of ART initiation, however, did not consistently affect the expression of the exhaustion markers once viral suppression was achieved. Understanding which factors do and do not regulate aspects of CD8 + T cell exhaustion, including the expression of exhaustion markers, is critical to inform the rational design of CD8 + T cell-based therapies to treat HIV, for which CD8 + T cell exhaustion remains an important barrier to efficacy.

  7. The Transcription Factor NFAT1 Participates in the Induction of CD4+T Cell Functional Exhaustion during Plasmodium yoelii Infection.

    Science.gov (United States)

    Ames, Rachel Y; Ting, Li-Min; Gendlina, Inessa; Kim, Kami; Macian, Fernando

    2017-09-01

    Repeated stimulation of T cells that occurs in the context of chronic infection results in progressively reduced responsiveness of T cells to pathogen-derived antigens. This phenotype, known as T cell exhaustion, occurs during chronic infections caused by a variety of pathogens, from persistent viruses to parasites. Unlike the memory cells that typically form after successful pathogen clearance following an acute infection, exhausted T cells secrete lower levels of effector cytokines, proliferate less in response to cognate antigen, and upregulate cell surface inhibitory molecules such as PD-1 and LAG-3. The molecular events that lead to the induction of this phenotype have, however, not been fully characterized. In T cells, members of the NFAT family of transcription factors not only are responsible for the expression of many activation-induced genes but also are crucial for the induction of transcriptional programs that inhibit T cell activation and maintain tolerance. Here we show that NFAT1-deficient CD4 + T cells maintain higher proliferative capacity and expression of effector cytokines following Plasmodium yoelii infection and are therefore more resistant to P. yoelii -induced exhaustion than their wild-type counterparts. Consequently, gene expression microarray analysis of CD4 + T cells following P. yoelii -induced exhaustion shows upregulation of effector T cell-associated genes in the absence of NFAT1 compared with wild-type exhausted T cells. Furthermore, adoptive transfer of NFAT1-deficient CD4 + T cells into mice infected with P. yoelii results in increased production of antibodies to cognate antigen. Our results support the idea that NFAT1 is necessary to fully suppress effector responses during Plasmodium -induced CD4 + T cell exhaustion. Copyright © 2017 American Society for Microbiology.

  8. Comparison of the toxicity of diesel exhaust produced by bio- and fossil diesel combustion in human lung cells in vitro

    Science.gov (United States)

    Steiner, Sandro; Czerwinski, Jan; Comte, Pierre; Popovicheva, Olga; Kireeva, Elena; Müller, Loretta; Heeb, Norbert; Mayer, Andreas; Fink, Alke; Rothen-Rutishauser, Barbara

    2013-12-01

    Alternative fuels are increasingly combusted in diesel- and gasoline engines and the contribution of such exhausts to the overall air pollution is on the rise. Recent findings on the possible adverse effects of biodiesel exhaust are contradictive, at least partly resulting from the various fuel qualities, engine types and different operation conditions that were tested. However, most of the studies are biased by undesired interactions between the exhaust samples and biological culture media. We here report how complete, freshly produced exhausts from fossil diesel (B0), from a blend of 20% rapeseed-methyl ester (RME) and 80% fossil diesel (B20) and from pure rapeseed methyl ester (B100) affect a complex 3D cellular model of the human airway epithelium in vitro by exposing the cells at the air-liquid interface. The induction of pro-apoptotic and necrotic cell death, cellular morphology, oxidative stress, and pro-inflammatory responses were assessed. Compared to B0 exhaust, B20 exhaust decreased oxidative stress and pro-inflammatory responses, whereas B100 exhaust, depending on exposure duration, decreased oxidative stress but increased pro-inflammatory responses. The effects are only very weak and given the compared to fossil diesel higher ecological sustainability of biodiesel, it appears that - at least RME - can be considered a valuable alternative to pure fossil diesel.

  9. Exhaustion of the CD8+T Cell Compartment in Patients with Mutations in Phosphoinositide 3-Kinase Delta.

    Science.gov (United States)

    Wentink, Marjolein W J; Mueller, Yvonne M; Dalm, Virgil A S H; Driessen, Gertjan J; van Hagen, P Martin; van Montfrans, Joris M; van der Burg, Mirjam; Katsikis, Peter D

    2018-01-01

    Pathogenic gain-of-function mutations in the gene encoding phosphoinositide 3-kinase delta (PI3Kδ) cause activated PI3Kδ syndrome (APDS), a disease characterized by humoral immunodeficiency, lymphadenopathy, and an inability to control persistent viral infections including Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections. Understanding the mechanisms leading to impaired immune response is important to optimally treat APDS patients. Immunosenescence of CD8 + T cells was suggested to contribute to APDS pathogenesis. However, the constitutive activation of T cells in APDS may also result in T cell exhaustion. Therefore, we studied exhaustion of the CD8 + T cell compartment in APDS patients and compared them with healthy controls and HIV patients, as a control for exhaustion. The subset distribution of the T cell compartment of APDS patients was comparable with HIV patients with decreased naive CD4 + and CD8 + T cells and increased effector CD8 + T cells. Like in HIV + patients, expression of activation markers and inhibitory receptors CD160, CD244, and programmed death receptor (PD)-1 on CD8 + T cells was increased in APDS patients, indicating exhaustion. EBV-specific CD8 + T cells from APDS patients exhibited an exhausted phenotype that resembled HIV-specific CD8 + T cells in terms of inhibitory receptor expression. Inhibition of PD-1 on EBV-specific CD8 + T cells from APDS patients enhanced in vitro proliferation and effector cytokine production. Based on these results, we conclude that total and EBV-specific CD8 + T cells from APDS patients are characterized by T cell exhaustion. Furthermore, PD-1 checkpoint inhibition may provide a possible therapeutic approach to support the immune system of APDS patients to control EBV and CMV.

  10. Diesel exhaust particles are mutagenic in FE1-MutaMouse lung epithelial cells.

    Science.gov (United States)

    Jacobsen, Nicklas Raun; Møller, Peter; Cohn, Corey Alexander; Loft, Steffen; Vogel, Ulla; Wallin, Håkan

    2008-05-10

    The particulate phase of diesel engine exhaust is likely carcinogenic. However, the mechanisms of diesel exhaust particles (DEPs) induced mutagenicity/carcinogenicity are still largely unknown. We determined the mutant frequency following eight repeated 72 h incubations with 37.5 or 75 microg/ml DEP (NIST SRM 1650) in the FE1-MutaMouse lung epithelial cell line. We measured DEP-induced acellular and intracellular production of reactive oxygen species (ROS) and compared with ROS production induced by carbon black, which we have previously shown is mutagenic in this cell line [N.R. Jacobsen, A.T. Saber, P. White, P. Moller, G. Pojana, U. Vogel, S. Loft, J. Gingerich, L. Soper, G.R. Douglas, H. Wallin. Increased mutant frequency by carbon black, but not quartz, in the lacZ and cII transgenes of mutamouse lung epithelial cells, Environ. Mol. Mutagen. 48(6) (2007) 451-461]. The mutant frequency was marginally elevated in cells treated with 37.5 microg/ml DEP (1.29-fold [95% CI: 0.96-1.60], p=0.08) and significantly increased in cells treated with 75 microg/ml DEP (1.55-fold [95% CI: 1.23-1.87], p production from DEP was low both within cells and in acellular systems when compared to carbon black. These results show that DEP are mutagenic in a mammalian cell line in vitro and that additional pathways besides ROS production, such as those involving the presence of polycyclic aromatic hydrocarbons, likely are involved in the mutagenesis.

  11. Nitrophenols isolated from diesel exhaust particles promote the growth of MCF-7 breast adenocarcinoma cells

    International Nuclear Information System (INIS)

    Furuta, Chie; Suzuki, Akira K.; Watanabe, Gen; Li, ChunMei; Taneda, Shinji; Taya, Kazuyoshi

    2008-01-01

    Diesel exhaust particles (DEPs) cause many adverse health problems, and reports indicate increased risk of breast cancer in men and women through exposure to gasoline and vehicle exhaust. However, DEPs include vast numbers of compounds, and the specific compound(s) responsible for these actions are not clear. We recently isolated two nitrophenols from DEPs-3-methyl-4-nitrophenol (4-nitro-m-cresol; PNMC) and 4-nitro-3-phenylphenol (PNMPP)-and showed that they had estrogenic and anti-androgenic activities. Here, we tried to clarify the involvement of these two nitrophenols in promoting the growth of the MCF-7 breast cancer cell line. First, comet assay was used to detect the genotoxicity of PNMC and PNMPP in a CHO cell line. At all doses tested, PNMC and PNMPP showed negative genotoxicity, indicating that they had no tumor initiating activity. Next, the estrogen-responsive breast cancer cell line MCF-7 was used to assess cell proliferation. Proliferation of MCF-7 cells was stimulated by PNMC, PNMPP, and estradiol-17β and the anti-estrogens 4-hydroxytamoxifen and ICI 182,780 inhibited the proliferation. To further investigate transcriptional activity through the estrogen receptor, MCF-7 cells were transfected with a receptor gene that allowed expression of luciferase enzyme under the control of the estrogen regulatory element. PNMC and PNMPP induced luciferase activity in a dose-dependent manner at submicromolar concentrations. ICI 182,780 inhibited the luciferase activity induced by PNMC and PNMPP. These results clearly indicate that PNMC and PNMPP do not show genotoxicity but act as tumor promoters in an estrogen receptor α-predominant breast cancer cell line

  12. Cooperation of Pd-1 and LAG-3 contributes to T-cell exhaustion in anaplasma marginale-infected cattle

    Science.gov (United States)

    The CD4+ T-cell response is central for control of Anaplasma marginale infection in cattle. However, the infection induces a functional exhaustion of antigen-specific CD4+ T cells in cattle immunized with A. marginale outer membrane proteins or purified outer membranes (OM), which presumably facilit...

  13. Complementary role of HCV and HIV in T-cell activation and exhaustion in HIV/HCV coinfection

    NARCIS (Netherlands)

    Feuth, T.; Arends, J.E.; Fransen, J.H.; Nanlohy, N.M.; Erpecum, K.J. van; Siersema, P.D.; Hoepelman, A.I.; Baarle, D. van

    2013-01-01

    OBJECTIVES: To investigate whether T-cell activation and exhaustion is linked to HCV- and HIV disease parameters in HIV/HCV infected individuals, we studied T-cell characteristics in HIV/HCV coinfected patients and controls. METHODS: 14 HIV/HCV coinfected, 19 HCV monoinfected, 10 HIV monoinfected

  14. Sepsis Induces Hematopoietic Stem Cell Exhaustion and Myelosuppression through Distinct Contributions of TRIF and MYD88

    Directory of Open Access Journals (Sweden)

    Huajia Zhang

    2016-06-01

    Full Text Available Toll-like receptor 4 (TLR4 plays a central role in host responses to bacterial infection, but the precise mechanism(s by which its downstream signaling components coordinate the bone marrow response to sepsis is poorly understood. Using mice deficient in TLR4 downstream adapters MYD88 or TRIF, we demonstrate that both cell-autonomous and non-cell-autonomous MYD88 activation are major causes of myelosuppression during sepsis, while having a modest impact on hematopoietic stem cell (HSC functions. In contrast, cell-intrinsic TRIF activation severely compromises HSC self-renewal without directly affecting myeloid cells. Lipopolysaccharide-induced activation of MYD88 or TRIF contributes to cell-cycle activation of HSC and induces rapid and permanent changes in transcriptional programs, as indicated by persistent downregulation of Spi1 and CebpA expression after transplantation. Thus, distinct mechanisms downstream of TLR4 signaling mediate myelosuppression and HSC exhaustion during sepsis through unique effects of MyD88 and TRIF.

  15. The Chronic Stages of Bovine Fasciola hepatica Are Dominated by CD4 T-Cell Exhaustion

    Directory of Open Access Journals (Sweden)

    Divya Sachdev

    2017-08-01

    Full Text Available Fasciola hepatica infection of ruminants leads to non-resolving chronic infection, as patency develops, there is switching to a TGF-β and IL-10 led response. Here, we explore the responses of CD4 T-cells within the major draining lymph nodes. We found minimal expression of Foxp3 within CD4 cells but elevated levels within the γδ (WC1+ population. There is a strong T-cell-intrinsic exhaustion phenotype within the hepatic lymph node (HLN characterized by a lack of antigen-specific proliferation and cytokine secretion. CD4 T-cells recovered from the HLN had high levels of PD-1 expression and low levels of IL-2 secretion. Exogenous IL-2 partially rescued this defect; when combined with neutralization of IL-10 and TGF-β, full restoration of proliferation, and cytokine production was achieved. Moreover, there is a clear uncoupling of the mechanisms that facilitate this regulation with parasite-specific proliferation and cytokine secretion being governed by independent means. These data would suggest that there is a CD4 T-cell-intrinsic regulation in place early in chronic infection, potentially leading to failure in resistance to reinfection.

  16. The Chronic Stages of Bovine Fasciola hepatica Are Dominated by CD4 T-Cell Exhaustion

    Science.gov (United States)

    Sachdev, Divya; Gough, Kevin C.; Flynn, Robin J.

    2017-01-01

    Fasciola hepatica infection of ruminants leads to non-resolving chronic infection, as patency develops, there is switching to a TGF-β and IL-10 led response. Here, we explore the responses of CD4 T-cells within the major draining lymph nodes. We found minimal expression of Foxp3 within CD4 cells but elevated levels within the γδ (WC1+) population. There is a strong T-cell-intrinsic exhaustion phenotype within the hepatic lymph node (HLN) characterized by a lack of antigen-specific proliferation and cytokine secretion. CD4 T-cells recovered from the HLN had high levels of PD-1 expression and low levels of IL-2 secretion. Exogenous IL-2 partially rescued this defect; when combined with neutralization of IL-10 and TGF-β, full restoration of proliferation, and cytokine production was achieved. Moreover, there is a clear uncoupling of the mechanisms that facilitate this regulation with parasite-specific proliferation and cytokine secretion being governed by independent means. These data would suggest that there is a CD4 T-cell-intrinsic regulation in place early in chronic infection, potentially leading to failure in resistance to reinfection. PMID:28871261

  17. Nuclear magnetic resonance spectroscopic investigation of anode exhaust of direct methanol fuel cells without isotope enrichment

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Young Seok; Hwang, Reo Yun; Han, Ochee [Western Seoul Center, Korea Basic Science Institute, Seoul (Korea, Republic of)

    2016-12-15

    Fuel cells are devices that electrochemically convert the chemical energy of fuels such as natural gas, gasoline, and methanol, into electricity. Fuel cells more efficiently use energy than internal combustion engines and do not produce undesirable pollutants, such as NO{sub x} ,SO{sub x} and particulates. Fuel cells can be distinguished from one another by their electrolytes. Among the various direct alcohol fuel cells, direct methanol fuel cells (DMFCs) have been developed most. However, DMFCs have several practical problems such as methanol crossove r from an anode to a cathode and slow methanol oxidation reaction rates. Therefore, understanding the electrochemical reaction mechanisms of DMFCs may provide clues to solve these problems, and various analytical methods have been employed to examine these mechanisms. We demonstrated that {sup 1}H and {sup 13}C NMR spectroscopy can be used for analyzing anode exhausts of DMFCs operated with methanol without any isotope enrichment. However, the low sensitivity of NMR spectroscopy hindered our efforts to detect minor reaction intermediates. Therefore, sensitivity enhancement techniques such as dynamic nuclear polarization (DNP) NMR methods and/or presaturation methods to increase the dynamic range of the proton spectra by pre-saturating large water signals, are expected to be useful to detect low-concentration species.

  18. Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade.

    Science.gov (United States)

    Pauken, Kristen E; Sammons, Morgan A; Odorizzi, Pamela M; Manne, Sasikanth; Godec, Jernej; Khan, Omar; Drake, Adam M; Chen, Zeyu; Sen, Debattama R; Kurachi, Makoto; Barnitz, R Anthony; Bartman, Caroline; Bengsch, Bertram; Huang, Alexander C; Schenkel, Jason M; Vahedi, Golnaz; Haining, W Nicholas; Berger, Shelley L; Wherry, E John

    2016-12-02

    Blocking Programmed Death-1 (PD-1) can reinvigorate exhausted CD8 T cells (T EX ) and improve control of chronic infections and cancer. However, whether blocking PD-1 can reprogram T EX into durable memory T cells (T MEM ) is unclear. We found that reinvigoration of T EX in mice by PD-L1 blockade caused minimal memory development. After blockade, reinvigorated T EX became reexhausted if antigen concentration remained high and failed to become T MEM upon antigen clearance. T EX acquired an epigenetic profile distinct from that of effector T cells (T EFF ) and T MEM cells that was minimally remodeled after PD-L1 blockade. This finding suggests that T EX are a distinct lineage of CD8 T cells. Nevertheless, PD-1 pathway blockade resulted in transcriptional rewiring and reengagement of effector circuitry in the T EX epigenetic landscape. These data indicate that epigenetic fate inflexibility may limit current immunotherapies. Copyright © 2016, American Association for the Advancement of Science.

  19. High fat programming of beta cell compensation, exhaustion, death and dysfunction.

    Science.gov (United States)

    Cerf, Marlon E

    2015-03-01

    Programming refers to events during critical developmental windows that shape progeny health outcomes. Fetal programming refers to the effects of intrauterine (in utero) events. Lactational programming refers to the effects of events during suckling (weaning). Developmental programming refers to the effects of events during both fetal and lactational life. Postnatal programming refers to the effects of events either from birth (lactational life) to adolescence or from weaning (end of lactation) to adolescence. Islets are most plastic during the early life course; hence programming during fetal and lactational life is most potent. High fat (HF) programming is the maintenance on a HF diet (HFD) during critical developmental life stages that alters progeny metabolism and physiology. HF programming induces variable diabetogenic phenotypes dependent on the timing and duration of the dietary insult. Maternal obesity reinforces HF programming effects in progeny. HF programming, through acute hyperglycemia, initiates beta cell compensation. However, HF programming eventually leads to chronic hyperglycemia that triggers beta cell exhaustion, death and dysfunction. In HF programming, beta cell dysfunction often co-presents with insulin resistance. Balanced, healthy nutrition during developmental windows is critical for preserving beta cell structure and function. Thus early positive nutritional interventions that coincide with the development of beta cells may reduce the overwhelming burden of diabetes and metabolic disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Platform for a Hydrocarbon Exhaust Gas Sensor Utilizing a Pumping Cell and a Conductometric Sensor

    Directory of Open Access Journals (Sweden)

    Ralf Moos

    2009-09-01

    Full Text Available Very often, high-temperature operated gas sensors are cross-sensitive to oxygen and/or they cannot be operated in oxygen-deficient (rich atmospheres. For instance, some metal oxides like Ga2O3 or doped SrTiO3 are excellent materials for conductometric hydrocarbon detection in the rough atmosphere of automotive exhausts, but have to be operated preferably at a constant oxygen concentration. We propose a modular sensor platform that combines a conductometric two-sensor-setup with an electrochemical pumping cell made of YSZ to establish a constant oxygen concentration in the ambient of the conductometric sensor film. In this paper, the platform is introduced, the two-sensor-setup is integrated into this new design, and sensing performance is characterized. Such a platform can be used for other sensor principles as well.

  1. T cell exhaustion characterized by compromised MHC class I and II restricted cytotoxic activity associates with acute B lymphoblastic leukemia relapse after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Liu, Long; Chang, Ying-Jun; Xu, Lan-Ping; Zhang, Xiao-Hui; Wang, Yu; Liu, Kai-Yan; Huang, Xiao-Jun

    2018-02-22

    Acute B lymphoblastic leukemia (B-ALL) relapse contributes predominantly to the mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the mechanism of B-ALL relapse after allo-HSCT remains unknown. The eradication of leukemia after allo-HSCT largely relies on graft-versus-leukemia (GVL) effects mediated by donor T cells. T cell exhaustion, characterized by the increased expression of inhibitory receptors and impaired function, may suppress GVL effects. In this study, we evaluated whether T cell exhaustion was involved in B-ALL relapse after allo-HSCT. The results showed that CD4 + and CD8 + T cells exhibited increased coexpression of PD-1 and Tim-3, and compromised proliferative capacity, cytokine production and cytotoxic potentials in relapsed patients. Additionally, T cells at the tumor site were more easily exhausted than T cells in the peripheral blood. Moreover, the reversal of T cell exhaustion might correlate with effective anti-leukemic responses after reinduction. These results suggested that T cell exhaustion was associated with B-ALL relapse after allo-HSCT as well as its treatment outcome. Copyright © 2017. Published by Elsevier Inc.

  2. Immune Exhaustion and Transplantation.

    Science.gov (United States)

    Sanchez-Fueyo, A; Markmann, J F

    2016-07-01

    Exhaustion of lymphocyte function through chronic exposure to a high load of foreign antigen is well established for chronic viral infection and antitumor immunity and has been found to be associated with a distinct molecular program and characteristic cell surface phenotype. Although exhaustion has most commonly been studied in the context of CD8 viral responses, recent studies indicate that chronic antigen exposure may affect B cells, NK cells and CD4 T cells in a parallel manner. Limited information is available regarding the extent of lymphocyte exhaustion development in the transplant setting and its impact on anti-graft alloreactivity. By analogy to the persistence of a foreign virus, the large mass of alloantigen presented by an allograft in chronic residence could provide an ideal setting for exhausting donor-reactive T cells. The extent of T cell exhaustion occurring with various allografts, the kinetics of its development, whether exhaustion is influenced positively or negatively by different immunosuppressants, and the impact of exhaustion on graft survival and tolerance development remains a fertile area for investigation. Harnessing or encouraging the natural processes of exhaustion may provide a novel means to promote graft survival and transplantation tolerance. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  3. Inflammation-Related Effects of Diesel Engine Exhaust Particles: Studies on Lung Cells In Vitro

    Science.gov (United States)

    Schwarze, P. E.; Totlandsdal, A. I.; Låg, M.; Refsnes, M.; Holme, J. A.; Øvrevik, J.

    2013-01-01

    Diesel exhaust and its particles (DEP) have been under scrutiny for health effects in humans. In the development of these effects inflammation is regarded as a key process. Overall, in vitro studies report similar DEP-induced changes in markers of inflammation, including cytokines and chemokines, as studies in vivo. In vitro studies suggest that soluble extracts of DEP have the greatest impact on the expression and release of proinflammatory markers. Main DEP mediators of effects have still not been identified and are difficult to find, as fuel and engine technology developments lead to continuously altered characteristics of emissions. Involved mechanisms remain somewhat unclear. DEP extracts appear to comprise components that are able to activate various membrane and cytosolic receptors. Through interactions with receptors, ion channels, and phosphorylation enzymes, molecules in the particle extract will trigger various cell signaling pathways that may lead to the release of inflammatory markers directly or indirectly by causing cell death. In vitro studies represent a fast and convenient system which may have implications for technology development. Furthermore, knowledge regarding how particles elicit their effects may contribute to understanding of DEP-induced health effects in vivo, with possible implications for identifying susceptible groups of people and effect biomarkers. PMID:23509760

  4. Transcription Factor IRF4 Promotes CD8+T Cell Exhaustion and Limits the Development of Memory-like T Cells during Chronic Infection.

    Science.gov (United States)

    Man, Kevin; Gabriel, Sarah S; Liao, Yang; Gloury, Renee; Preston, Simon; Henstridge, Darren C; Pellegrini, Marc; Zehn, Dietmar; Berberich-Siebelt, Friederike; Febbraio, Mark A; Shi, Wei; Kallies, Axel

    2017-12-19

    During chronic stimulation, CD8 + T cells acquire an exhausted phenotype characterized by expression of inhibitory receptors, down-modulation of effector function, and metabolic impairments. T cell exhaustion protects from excessive immunopathology but limits clearance of virus-infected or tumor cells. We transcriptionally profiled antigen-specific T cells from mice infected with lymphocytic choriomeningitis virus strains that cause acute or chronic disease. T cell exhaustion during chronic infection was driven by high amounts of T cell receptor (TCR)-induced transcription factors IRF4, BATF, and NFATc1. These regulators promoted expression of inhibitory receptors, including PD-1, and mediated impaired cellular metabolism. Furthermore, they repressed the expression of TCF1, a transcription factor required for memory T cell differentiation. Reducing IRF4 expression restored the functional and metabolic properties of antigen-specific T cells and promoted memory-like T cell development. These findings indicate that IRF4 functions as a central node in a TCR-responsive transcriptional circuit that establishes and sustains T cell exhaustion during chronic infection. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  5. Task failure during exercise to exhaustion in normoxia and hypoxia is due to reduced muscle activation caused by central mechanisms while muscle metaboreflex does not limit performance

    Directory of Open Access Journals (Sweden)

    Rafael eTorres-Peralta

    2016-01-01

    Full Text Available To determine whether task failure during incremental exercise to exhaustion (IE is principally due to reduced neural drive and increased metaboreflex activation eleven men (22±2 years performed a 10s control isokinetic sprint (IS; 80 rpm after a short warm-up. This was immediately followed by an IE in normoxia (Nx, PIO2:143 mmHg and hypoxia (Hyp, PIO2:73 mmHg in random order, separated by a 120 min resting period. At exhaustion, the circulation of both legs was occluded instantaneously (300 mmHg during 10 or 60s to impede recovery and increase metaboreflex activation. This was immediately followed by an IS with open circulation. Electromyographic recordings were obtained from the vastus medialis and lateralis. Muscle biopsies and blood gases were obtained in separate experiments. During the last 10s of the IE, pulmonary ventilation, VO2, power output and muscle activation were lower in hypoxia than in normoxia, while pedaling rate was similar. Compared to the control sprint, performance (IS-Wpeak was reduced to a greater extent after the IE-Nx (11% lower P<0.05 than IE-Hyp. The root mean square (EMGRMS was reduced by 38 and 27% during IS performed after IE-Nx and IE-Hyp, respectively (Nx vs. Hyp: P<0.05. Post-ischemia IS-EMGRMS values were higher than during the last 10s of IE. Sprint exercise mean (IS-MPF and median (IS-MdPF power frequencies, and burst duration, were more reduced after IE-Nx than IE-Hyp (P<0.05. Despite increased muscle lactate accumulation, acidification, and metaboreflex activation from 10 to 60s of ischemia, IS-Wmean (+23% and burst duration (+10% increased, while IS-EMGRMS decreased (-24%, P<0.05, with IS-MPF and IS-MdPF remaining unchanged. In conclusion, close to task failure, muscle activation is lower in hypoxia than in normoxia. Task failure is predominantly caused by central mechanisms, which recover to great extent within one minute even when the legs remain ischemic. There is dissociation between the recovery of

  6. DIESEL EXHAUST PARTICULATE (DEP)-INDUCED ACTIV ATION OF STAT3 REQUIRES ACTIVITIES OF EGFR AND SRC IN AIRWAY EPITHELIAL CELLS

    Science.gov (United States)

    In vivo exposure to diesel exhaust particles (DEP) elicits acute inflammatory responses in the lung characterized by inflammatory cell influx and elevated expression of mediators such as cytokines, and chemokines. Signal transducers and activators of transcription (STAT) protein...

  7. Oxidative damage to DNA by diesel exhaust particle exposure in co-cultures of human lung epithelial cells and macrophages

    DEFF Research Database (Denmark)

    Jantzen, Kim; Roursgaard, Martin; Madsen, Claus Desler

    2012-01-01

    Studies in mono-culture of cells have shown that diesel exhaust particles (DEPs) increase the production of reactive oxygen species (ROS) and oxidative stress-related damage to DNA. However, the level of particle-generated genotoxicity may depend on interplay between different cell types, e.g. lung...... relationship between levels of respiration and ROS production. In conclusion, exposure of mono-cultured cells to DEPs generated oxidative stress to DNA, whereas co-cultures with macrophages had lower levels of oxidatively damaged DNA than A549 epithelial cells....... treatment with standard reference DEPs, SRM2975 and SRM1650b. The exposure to DEPs did not affect the colony-forming ability of A549 cells in co-culture with THP-1a cells. The DEPs generated DNA strand breaks and oxidatively damaged DNA, measured using the alkaline comet assay as formamidopyrimidine...

  8. Tim-3 co-stimulation promotes short-lived effector T cells, restricts memory precursors, and is dispensable for T cell exhaustion.

    Science.gov (United States)

    Avery, Lyndsay; Filderman, Jessica; Szymczak-Workman, Andrea L; Kane, Lawrence P

    2018-02-20

    Tim-3 is highly expressed on a subset of T cells during T cell exhaustion in settings of chronic viral infection and tumors. Using lymphocytic choriomeningitis virus (LCMV) Clone 13, a model for chronic infection, we found that Tim-3 was neither necessary nor sufficient for the development of T cell exhaustion. Nonetheless, expression of Tim-3 was sufficient to drive resistance to PD-L1 blockade therapy during chronic infection. Strikingly, expression of Tim-3 promoted the development of short-lived effector T cells, at the expense of memory precursor development, after acute LCMV infection. These effects were accompanied by increased Akt/mTOR signaling in T cells expressing endogenous or ectopic Tim-3. Conversely, Akt/mTOR signaling was reduced in effector T cells from Tim-3-deficient mice. Thus, Tim-3 is essential for optimal effector T cell responses, and may also contribute to exhaustion by restricting the development of long-lived memory T cells. Taken together, our results suggest that Tim-3 is actually more similar to costimulatory receptors that are up-regulated after T cell activation than to a dominant inhibitory protein like PD-1. These findings have significant implications for the development of anti-Tim-3 antibodies as therapeutic agents.

  9. Assessment of lung cell toxicity of various gasoline engine exhausts using a versatile in vitro exposure system.

    Science.gov (United States)

    Bisig, Christoph; Comte, Pierre; Güdel, Martin; Czerwinski, Jan; Mayer, Andreas; Müller, Loretta; Petri-Fink, Alke; Rothen-Rutishauser, Barbara

    2018-04-01

    Adverse effect studies of gasoline exhaust are scarce, even though gasoline direct injection (GDI) vehicles can emit a high number of particles. The aim of this study was to conduct an in vitro hazard assessment of different GDI exhausts using two different cell culture models mimicking the human airway. In addition to gasoline particle filters (GPF), the effects of two lubrication oils with low and high ash content were assessed, since it is known that oils are important contributors to exhaust emissions. Complete exhausts from two gasoline driven cars (GDI1 and GDI2) were applied for 6 h (acute exposure) to a multi-cellular human lung model (16HBE14o-cell line, macrophages, and dendritic cells) and a primary human airway model (MucilAir™). GDI1 vehicle was driven unfiltered and filtered with an uncoated and a coated GPF. GDI2 vehicle was driven under four settings with different fuels: normal unleaded gasoline, 2% high and low ash oil in gasoline, and 2% high ash oil in gasoline with a GPF. GDI1 unfiltered was also used for a repeated exposure (3 times 6 h) to assess possible adverse effects. After 6 h exposure, no genes or proteins for oxidative stress or pro-inflammation were upregulated compared to the filtered air control in both cell systems, neither in GDI1 with GPFs nor in GDI2 with the different fuels. However, the repeated exposure led to a significant increase in HMOX1 and TNFa gene expression in the multi-cellular model, showing the responsiveness of the system towards gasoline engine exhaust upon prolonged exposure. The reduction of particles by GPFs is significant and no adverse effects were observed in vitro during a short-term exposure. On the other hand, more data comparing different lubrication oils and their possible adverse effects are needed. Future experiments also should, as shown here, focus on repeated exposures. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. PRE-TREATMENT WITH DIESEL EXHAUST EXTRACT ALTERS INFLUENZA VIRUS REPLICATION IN LUNG EPITHELIAL CELLS

    Science.gov (United States)

    Diesel Exhaust (DE) has been demonstrated to generate inflammatory responses in the lung and modify immune responses to allergens. However, little is known about the effects of DE on common respiratory viral infections. We examined whether exposure to DE extracts (DEE) modifies i...

  11. Method and system for the purification of exhaust gas with an electrochemical cell

    DEFF Research Database (Denmark)

    2015-01-01

    The present invention relates to a method for electrochemical reduction of nitrogen oxides and concomitant oxidation of soot, as well as systems useful therefor. Such methods and systems in particular are useful in the context of exhaust gas purification, in particular for diesel engines....

  12. Hepatitis B Virus-Specific CD8+ T Cells Maintain Functional Exhaustion after Antigen Reexposure in an Acute Activation Immune Environment.

    Science.gov (United States)

    Wang, Qin; Pan, Wen; Liu, Yanan; Luo, Jinzhuo; Zhu, Dan; Lu, Yinping; Feng, Xuemei; Yang, Xuecheng; Dittmer, Ulf; Lu, Mengji; Yang, Dongliang; Liu, Jia

    2018-01-01

    Chronic hepatitis B virus (HBV) infection is characterized by the presence of functionally exhausted HBV-specific CD8+ T cells. To characterize the possible residual effector ability of these cells, we reexposed CD8+ T cells from chronically HBV replicating mice to HBV antigens in an acute activation immune environment. We found that after transfer into naive mice, exhausted CD8+ T cells reexpanded in a comparable magnitude as naive CD8+ T cells in response to acute HBV infection; however, their proliferation intensity was significantly lower than that of CD8+ T cells from acute-resolving HBV replicating mice (AR mice). The differentiation phenotypes driven by acute HBV replication of donor exhausted and naive CD8+ T cells were similar, but were different from those of their counterparts from AR mice. Nevertheless, exhausted CD8+ T cells maintained less activated phenotype, an absence of effector cytokine production and poor antiviral function after HBV reexposure in an acute activation immune environment. We thus conclude that exhausted CD8+ T cells undergo a stable form of dysfunctional differentiation during chronic HBV replication and switching immune environment alone is not sufficient for the antiviral functional reconstitution of these cells.

  13. Combining regulatory T cell depletion and inhibitory receptor blockade improves reactivation of exhausted virus-specific CD8+ T cells and efficiently reduces chronic retroviral loads.

    Directory of Open Access Journals (Sweden)

    Kirsten K Dietze

    Full Text Available Chronic infections with human viruses, such as HIV and HCV, or mouse viruses, such as LCMV or Friend Virus (FV, result in functional exhaustion of CD8(+ T cells. Two main mechanisms have been described that mediate this exhaustion: expression of inhibitory receptors on CD8(+ T cells and expansion of regulatory T cells (Tregs that suppress CD8(+ T cell activity. Several studies show that blockage of one of these pathways results in reactivation of CD8(+ T cells and partial reduction in chronic viral loads. Using blocking antibodies against PD-1 ligand and Tim-3 and transgenic mice in which Tregs can be selectively ablated, we compared these two treatment strategies and combined them for the first time in a model of chronic retrovirus infection. Blocking inhibitory receptors was more efficient than transient depletion of Tregs in reactivating exhausted CD8(+ T cells and reducing viral set points. However, a combination therapy was superior to any single treatment and further augmented CD8(+ T cell responses and resulted in a sustained reduction in chronic viral loads. These results demonstrate that Tregs and inhibitory receptors are non-overlapping factors in the maintenance of chronic viral infections and that immunotherapies targeting both pathways may be a promising strategy to treat chronic infectious diseases.

  14. Repeated bouts of exhaustive exercise increase circulating cell free nuclear and mitochondrial DNA without development of tolerance in healthy men.

    Science.gov (United States)

    Stawski, Robert; Walczak, Konrad; Kosielski, Piotr; Meissner, Pawel; Budlewski, Tomasz; Padula, Gianluca; Nowak, Dariusz

    2017-01-01

    Acute single strenuous exercise increases circulating cell free DNA (cf DNA). We tested whether three repeated bouts of exhaustive exercise induced the cf DNA response without development of tolerance in healthy men. Eleven average-trained men (age 34.0±5.2 years, body mass index 26.2±3.1 kg/m2, maximal oxygen consumption-VO2max 49.6±4.5 ml/kg*min) performed three treadmill exercise tests to exhaustion at speed corresponding to 70% VO2max separated by 72 hours of resting. Blood was collected before and after each bout of exercise for determination of cell free nuclear and mitochondrial DNA (cf n-DNA, cf mt-DNA) by real-time PCR, selected markers of muscle damage, and blood cell count. Each bout induced the increase (pexercise, respectively. In a congruent way, cf mt-DNA rose significantly after the second (from 229±216 to 450±228*103 GE/mL) and third bout of exercise (from 173±120 to 462±314*103 GE/mL). Pre-exercise cf mt-DNA decreased (pexercise induced percentage increment of cf n-DNA was always many times higher than corresponding increments of the afore-mentioned markers at any occasion. Repeated bouts of exhaustive exercise induced remarkable increase in circulating cf n-DNA without signs of tolerance development. Baseline cf mt-DNA decreased in response to series of strenuous exercise. Since percentage increments of cf n-DNA in response to exercise were many times higher than those observed for other markers, measurement of circulating cf n-DNA could be a sensitive tool for monitoring acute exercise effects in human body.

  15. 4-1BB Costimulation Ameliorates T Cell Exhaustion Induced by Tonic Signaling of Chimeric Antigen Receptors

    Science.gov (United States)

    Long, Adrienne H.; Haso, Waleed M.; Shern, Jack F.; Wanhainen, Kelsey M.; Murgai, Meera; Ingaramo, Maria; Smith, Jillian P.; Walker, Alec J.; Kohler, M. Eric; Venkateshwara, Vikas R.; Kaplan, Rosandra N.; Patterson, George H.; Fry, Terry J.; Orentas, Rimas J.; Mackall, Crystal L.

    2015-01-01

    Chimeric antigen receptors (CARs) targeting CD19 have mediated dramatic anti-tumor responses in hematologic malignancies, but tumor regression has rarely occurred using CARs targeting other antigens. It remains unknown whether the impressive effects of CD19 CARs relate to greater susceptibility of hematologic malignancies to CAR therapies, or superior functionality of the CD19 CAR itself. We discovered that tonic CAR CD3ζ phosphorylation, triggered by antigen-independent clustering of CAR scFvs, can induce early exhaustion of CAR T cells that limits anti-tumor efficacy. Such activation is present to varying degrees in all CARs studied, with the exception of the highly effective CD19 CAR. We further identify that CD28 costimulation augments, while 4-1BB costimulation ameliorates, exhaustion induced by persistent CAR signaling. Our results provide biological explanations for the dramatic anti-tumor effects of CD19 CARs and for the observations that CD19.BBz CAR T cells are more persistent than CD19.28z CAR T cells in clinical trials. PMID:25939063

  16. The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation.

    Science.gov (United States)

    Mendes, Fernando; Domingues, Cátia; Rodrigues-Santos, Paulo; Abrantes, Ana Margarida; Gonçalves, Ana Cristina; Estrela, Jéssica; Encarnação, João; Pires, Ana Salomé; Laranjo, Mafalda; Alves, Vera; Teixo, Ricardo; Sarmento, Ana Bela; Botelho, Maria Filomena; Rosa, Manuel Santos

    2016-04-01

    Immune surveillance seems to represent an effective tumor suppressor mechanism. However, some cancer cells survive and become variants, being poorly immunogenic and able to enter a steady-state phase. These cells become functionally dormant or remain hidden clinically throughout. Neoplastic cells seem to be able to instruct immune cells to undergo changes promoting malignancy. Radiotherapy may act as a trigger of the immune response. After radiotherapy a sequence of reactions occurs, starting in the damage of oncogenic cells by multiple mechanisms, leading to the immune system positive feedback against the tumor. The link between radiotherapy and the immune system is evident. T cells, macrophages, Natural Killer cells and other immune cells seem to have a key role in controlling the tumor. T cells may be dysfunctional and remain in a state of T cell exhaustion, nonetheless, they often retain a high potential for successful defense against cancer, being able to be mobilized to become highly functional. The lack of clinical trials on a large scale makes data a little robust, in spite of promising information, there are still many variables in the studies relating to radiation and immune system. The clarification of the mechanisms underlying immune response to radiation exposure may contribute to treatment improvement, gain of life quality and span of patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Upregulation of the Tim-3/galectin-9 pathway of T cell exhaustion in chronic hepatitis B virus infection.

    Directory of Open Access Journals (Sweden)

    Gaia Nebbia

    Full Text Available The S-type lectin galectin-9 binds to the negative regulatory molecule Tim-3 on T cells and induces their apoptotic deletion or functional inactivation. We investigated whether galectin-9/Tim-3 interactions contribute to the deletion and exhaustion of the antiviral T cell response in chronic hepatitis B virus infection (CHB. We found Tim-3 to be expressed on a higher percentage of CD4 and CD8 T cells from patients with CHB than healthy controls (p<0.0001 and to be enriched on activated T cells and those infiltrating the HBV-infected liver. Direct ex vivo examination of virus-specific CD8 T cells binding HLA-A2/peptide multimers revealed that Tim-3 was more highly upregulated on HBV-specific CD8 T cells than CMV-specific CD8 T cells or the global CD8 T cell population in patients with CHB (p<0.001 or than on HBV-specific CD8 after resolution of infection. T cells expressing Tim-3 had an impaired ability to produce IFN-γ and TNF-α upon recognition of HBV-peptides and were susceptible to galectin-9-triggered cell death in vitro. Galectin-9 was detectable at increased concentrations in the sera of patients with active CHB-related liver inflammation (p = 0.02 and was strongly expressed by Kupffer cells within the liver sinusoidal network. Tim-3 blockade resulted in enhanced expansion of HBV-specific CD8 T cells able to produce cytokines and mediate cytotoxicity in vitro. Blocking PD-1 in combination with Tim-3 enhanced the number of patients from whom functional antiviral responses could be recovered and/or the strength of responses, indicating that these co-inhibitory molecules play a non-redundant role in driving T cell exhaustion in CHB. Patients taking antivirals able to potently suppress HBV viraemia continued to express Tim-3 on their T cells and respond to Tim-3 blockade. In summary, both Tim-3 and galectin-9 are increased in CHB and may contribute to the inhibition and deletion of T cells as they infiltrate the HBV-infected liver.

  18. T-bet and Eomes Are Differentially Linked to the Exhausted Phenotype of CD8+T Cells in HIV Infection

    DEFF Research Database (Denmark)

    Buggert, Marcus; Tauriainen, Johanna; Yamamoto, Takuya

    2014-01-01

    . Here, we examined the relationship between these transcription factors and the expression of several inhibitory receptors (PD-1, CD160, and 2B4), functional characteristics and memory differentiation of CD8+ T cells in chronic and treated HIV infection. The expression of PD-1, CD160, and 2B4 on total...... displayed a balanced expression pattern of T-bet and Eomes. The T-betdimEomeshi virus-specific CD8+ T cells did not show features of terminal differentiation, but rather a transitional memory phenotype with poor polyfunctional (effector) characteristics. The transitional and exhausted phenotype of HIV...... to an inverse expression balance between T-bet and Eomes, which is not reversed despite long-term viral control through ART. These results aid to explain the inability of HIV-specific CD8+ T cells to control the viral replication post-ART cessation....

  19. Distinct Metabolic Requirements of Exhausted and Functional Virus-Specific CD8 T Cells in the Same Host

    Directory of Open Access Journals (Sweden)

    Anna Schurich

    2016-08-01

    Full Text Available T cells undergo profound metabolic changes to meet the increased energy demands of maintaining an antiviral response. We postulated that differences in metabolic reprogramming would shape the efficacy of CD8 T cells mounted against persistent viral infections. We found that the poorly functional PD-1hi T cell response against hepatitis B virus (HBV had upregulated the glucose transporter, Glut1, an effect recapitulated by oxygen deprivation to mimic the intrahepatic environment. Glut1hi HBV-specific T cells were dependent on glucose supplies, unlike the more functional cytomegalovirus (CMV-specific T cells that could utilize oxidative phosphorylation in the absence of glucose. The inability of HBV-specific T cells to switch to oxidative phosphorylation was accompanied by increased mitochondrial size and lower mitochondrial potential, indicative of mitochondrial dysfunction. Interleukin (IL-12, which recovers HBV-specific T cell effector function, increased their mitochondrial potential and reduced their dependence on glycolysis. Our findings suggest that mitochondrial defects limit the metabolic plasticity of exhausted HBV-specific T cells.

  20. Phenotypic T cell exhaustion in a murine model of bacterial infection in the setting of pre-existing malignancy.

    Directory of Open Access Journals (Sweden)

    Rohit Mittal

    Full Text Available While much of cancer immunology research has focused on anti-tumor immunity both systemically and within the tumor microenvironment, little is known about the impact of pre-existing malignancy on pathogen-specific immune responses. Here, we sought to characterize the antigen-specific CD8+ T cell response following a bacterial infection in the setting of pre-existing pancreatic adenocarcinoma. Mice with established subcutaneous pancreatic adenocarcinomas were infected with Listeria monocytogenes, and antigen-specific CD8+ T cell responses were compared to those in control mice without cancer. While the kinetics and magnitude of antigen-specific CD8+ T cell expansion and accumulation was comparable between the cancer and non-cancer groups, bacterial antigen-specific CD8+ T cells and total CD4+ and CD8+ T cells in cancer mice exhibited increased expression of the coinhibitory receptors BTLA, PD-1, and 2B4. Furthermore, increased inhibitory receptor expression was associated with reduced IFN-γ and increased IL-2 production by bacterial antigen-specific CD8+ T cells in the cancer group. Taken together, these data suggest that cancer's immune suppressive effects are not limited to the tumor microenvironment, but that pre-existing malignancy induces phenotypic exhaustion in T cells by increasing expression of coinhibitory receptors and may impair pathogen-specific CD8+ T cell functionality and differentiation.

  1. Precocious pseudopuberty due to juvenile granulosa cell tumor

    International Nuclear Information System (INIS)

    Saeed, G.A.; Farooq, N.

    2003-01-01

    A case of precocious puberty occurring in a young girl is presented. Vaginal bleeding and secondary sexual characteristics had occurred at 7 years of age associated with an abdominal mass. These findings were due to a functional juvenile granulosa cell tumor in the right ovary. Right adenectomy was performed. Histopathology was confirmatory. (author)

  2. CXCR4 blockade decreases CD4+ T cell exhaustion and improves survival in a murine model of polymicrobial sepsis.

    Science.gov (United States)

    Ramonell, Kimberly M; Zhang, Wenxiao; Hadley, Annette; Chen, Ching-Wen; Fay, Katherine T; Lyons, John D; Klingensmith, Nathan J; McConnell, Kevin W; Coopersmith, Craig M; Ford, Mandy L

    2017-01-01

    Sepsis is a dysregulated systemic response to infection involving many inflammatory pathways and the induction of counter-regulatory anti-inflammatory processes that results in a state of immune incompetence and can lead to multi-organ failure. CXCR4 is a chemokine receptor that, following ligation by CXCL12, directs cells to bone marrow niches and also plays an important role in T cell cosignaling and formation of the immunological synapse. Here, we investigated the expression and function of CXCR4 in a murine model of polymicrobial sepsis. Results indicate that CXCR4 is selectively upregulated on naïve CD4+ and CD8+ T cells and CD4+ central memory T cells following the induction of sepsis, and that CXCR4 antagonism resulted in a significant decrease in sepsis-induced mortality. We probed the mechanistic basis for these findings and found that CXCR4 antagonism significantly increased the number of peripheral CD4+ and CD8+ T cells following sepsis. Moreover, mice treated with the CXCR4 antagonist contained fewer PD-1+ LAG-3+ 2B4+ cells, suggesting that blockade of CXCR4 mitigates CD4+ T cell exhaustion during sepsis. Taken together, these results characterize CXCR4 as an important pathway that modulates immune dysfunction and mortality following sepsis, which may hold promise as a target for future therapeutic intervention in septic patients.

  3. CXCR4 blockade decreases CD4+ T cell exhaustion and improves survival in a murine model of polymicrobial sepsis.

    Directory of Open Access Journals (Sweden)

    Kimberly M Ramonell

    Full Text Available Sepsis is a dysregulated systemic response to infection involving many inflammatory pathways and the induction of counter-regulatory anti-inflammatory processes that results in a state of immune incompetence and can lead to multi-organ failure. CXCR4 is a chemokine receptor that, following ligation by CXCL12, directs cells to bone marrow niches and also plays an important role in T cell cosignaling and formation of the immunological synapse. Here, we investigated the expression and function of CXCR4 in a murine model of polymicrobial sepsis. Results indicate that CXCR4 is selectively upregulated on naïve CD4+ and CD8+ T cells and CD4+ central memory T cells following the induction of sepsis, and that CXCR4 antagonism resulted in a significant decrease in sepsis-induced mortality. We probed the mechanistic basis for these findings and found that CXCR4 antagonism significantly increased the number of peripheral CD4+ and CD8+ T cells following sepsis. Moreover, mice treated with the CXCR4 antagonist contained fewer PD-1+ LAG-3+ 2B4+ cells, suggesting that blockade of CXCR4 mitigates CD4+ T cell exhaustion during sepsis. Taken together, these results characterize CXCR4 as an important pathway that modulates immune dysfunction and mortality following sepsis, which may hold promise as a target for future therapeutic intervention in septic patients.

  4. Modeling the integration of thermoelectrics in anode exhaust combustors for waste heat recovery in fuel cell systems

    Science.gov (United States)

    Maghdouri Moghaddam, Anita

    Recently developed small-scale hydrocarbon-fueled fuel cell systems for portable power under 1 kW have overall system efficiencies typically no higher than 30-35%. This study explores the possibility of using of thermoelectric waste heat recovery in anode exhaust combustors to improve the fuel cell system efficiencies by as much as 4-5% points and further to reduce required battery power during system start-up. Two models were used to explore this. The first model simulated an integrated SOFC system with a simplified catalytic combustor model with TEs integrated between the combustor and air preheating channels for waste heat recovery. This model provided the basis for assessing how much additional power can achieve during SOFC operation as a function of fuel cell operating conditions. Results for the SOFC system indicate that while the TEs may recover as much as 4% of the total fuel energy into the system, their benefit is reduced in part because they reduce the waste heat transferred back to the incoming air stream and thereby lower the SOFC operating temperatures and operating efficiencies. A second model transient model of a TE-integrated catalytic combustor explored the performance of the TEs during transient start-up of the combustor. This model incorporated more detailed catalytic combustion chemistry and enhanced cooling air fin heat transfer to show the dynamic heating of the integrated combustor. This detailed model provided a basis for exploring combustor designs and showed the importance of adequate reactant preheating when burning exhaust from a reformer during start-up for the TEs to produce significant power to reduce the size of system batteries for start-up.

  5. The Role of LAT in Increased CD8+ T Cell Exhaustion in Trigeminal Ganglia of Mice Latently Infected with Herpes Simplex Virus 1▿

    Science.gov (United States)

    Allen, Sariah J.; Hamrah, Pedram; Gate, David; Mott, Kevin R.; Mantopoulos, Dimosthenis; Zheng, Lixin; Town, Terrence; Jones, Clinton; von Andrian, Ulrich H.; Freeman, Gordon J.; Sharpe, Arlene H.; BenMohamed, Lbachir; Ahmed, Rafi; Wechsler, Steven L.; Ghiasi, Homayon

    2011-01-01

    Herpes simplex virus (HSV) infection is a classic example of latent viral infection in humans and experimental animal models. The HSV-1 latency-associated transcript (LAT) plays a major role in the HSV-1 latency reactivation cycle and thus in recurrent disease. Whether the presence of LAT leads to generation of dysfunctional T cell responses in the trigeminal ganglia (TG) of latently infected mice is not known. To address this issue, we used LAT-positive [LAT(+)] and LAT-deficient [LAT(−)] viruses to evaluate the effect of LAT on CD8 T cell exhaustion in TG of latently infected mice. The amount of latency as determined by quantitative reverse transcription-PCR (qRT-PCR) of viral DNA in total TG extracts was 3-fold higher with LAT(+) than with LAT(−) virus. LAT expression and increased latency correlated with increased mRNA levels of CD8, PD-1, and Tim-3. PD-1 is both a marker for exhaustion and a primary factor leading to exhaustion, and Tim-3 can also contribute to exhaustion. These results suggested that LAT(+) TG contain both more CD8+ T cells and more CD8+ T cells expressing the exhaustion markers PD-1 and Tim-3. This was confirmed by flow cytometry analyses of expression of CD3/CD8/PD-1/Tim-3, HSV-1, CD8+ T cell pentamer (specific for a peptide derived from residues 498 to 505 of glycoprotein B [gB498–505]), interleukin-2 (IL-2), and tumor necrosis factor alpha (TNF-α). The functional significance of PD-1 and its ligands in HSV-1 latency was demonstrated by the significantly reduced amount of HSV-1 latency in PD-1- and PD-L1-deficient mice. Together, these results may suggest that both PD-1 and Tim-3 are mediators of CD8+ T cell exhaustion and latency in HSV-1 infection. PMID:21307196

  6. The Chronic Stages of BovineFasciola hepaticaAre Dominated by CD4 T-Cell Exhaustion.

    Science.gov (United States)

    Sachdev, Divya; Gough, Kevin C; Flynn, Robin J

    2017-01-01

    Fasciola hepatica infection of ruminants leads to non-resolving chronic infection, as patency develops, there is switching to a TGF-β and IL-10 led response. Here, we explore the responses of CD4 T-cells within the major draining lymph nodes. We found minimal expression of Foxp3 within CD4 cells but elevated levels within the γδ (WC1 + ) population. There is a strong T-cell-intrinsic exhaustion phenotype within the hepatic lymph node (HLN) characterized by a lack of antigen-specific proliferation and cytokine secretion. CD4 T-cells recovered from the HLN had high levels of PD-1 expression and low levels of IL-2 secretion. Exogenous IL-2 partially rescued this defect; when combined with neutralization of IL-10 and TGF-β, full restoration of proliferation, and cytokine production was achieved. Moreover, there is a clear uncoupling of the mechanisms that facilitate this regulation with parasite-specific proliferation and cytokine secretion being governed by independent means. These data would suggest that there is a CD4 T-cell-intrinsic regulation in place early in chronic infection, potentially leading to failure in resistance to reinfection.

  7. Chronic hepatitis C virus infection triggers spontaneous differential expression of biosignatures associated with T cell exhaustion and apoptosis signaling in peripheral blood mononucleocytes.

    Science.gov (United States)

    Barathan, Muttiah; Gopal, Kaliappan; Mohamed, Rosmawati; Ellegård, Rada; Saeidi, Alireza; Vadivelu, Jamuna; Ansari, Abdul W; Rothan, Hussin A; Ravishankar Ram, M; Zandi, Keivan; Chang, Li Y; Vignesh, Ramachandran; Che, Karlhans F; Kamarulzaman, Adeeba; Velu, Vijayakumar; Larsson, Marie; Kamarul, Tunku; Shankar, Esaki M

    2015-04-01

    Persistent hepatitis C virus (HCV) infection appears to trigger the onset of immune exhaustion to potentially assist viral persistence in the host, eventually leading to hepatocellular carcinoma. The role of HCV on the spontaneous expression of markers suggestive of immune exhaustion and spontaneous apoptosis in immune cells of chronic HCV (CHC) disease largely remain elusive. We investigated the peripheral blood mononuclear cells of CHC patients to determine the spontaneous recruitment of cellular reactive oxygen species (cROS), immunoregulatory and exhaustion markers relative to healthy controls. Using a commercial QuantiGenePlex(®) 2.0 assay, we determined the spontaneous expression profile of 80 different pro- and anti-apoptotic genes in persistent HCV disease. Onset of spontaneous apoptosis significantly correlated with the up-regulation of cROS, indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2/prostaglandin H synthase (COX-2/PGHS), Foxp3, Dtx1, Blimp1, Lag3 and Cd160. Besides, spontaneous differential surface protein expression suggestive of T cell inhibition viz., TRAIL, TIM-3, PD-1 and BTLA on CD4+ and CD8+ T cells, and CTLA-4 on CD4+ T cells was also evident. Increased up-regulation of Tnf, Tp73, Casp14, Tnfrsf11b, Bik and Birc8 was observed, whereas FasLG, Fas, Ripk2, Casp3, Dapk1, Tnfrsf21, and Cflar were moderately up-regulated in HCV-infected subjects. Our observation suggests the spontaneous onset of apoptosis signaling and T cell exhaustion in chronic HCV disease.

  8. Controlled exposure to diesel exhaust and traffic noise - Effects on oxidative stress and activation in mononuclear blood cells

    DEFF Research Database (Denmark)

    Hemmingsen, Jette Gjerke; Møller, Peter; Jantzen, Kim

    2015-01-01

    exhaust (DE) at 276μg/m(3) from a passenger car or filtered air, with co-exposure to traffic noise at 48 or 75dB(A). Gene expression markers of inflammation, (interleukin-8 and tumor necrosis factor), oxidative stress (heme oxygenase (decycling-1)) and DNA repair (8-oxoguanine DNA glycosylase (OGG1)) were...... unaltered in peripheral blood mononuclear cells (PBMCs). No significant differences in DNA damage levels, measured by the comet assay, were observed after DE exposure, whereas exposure to high noise levels was associated with significantly increased levels of hOGG1-sensitive sites in PBMCs. Urinary levels...... of 8-oxo-7,8-dihydro-2'-deoxyguanosine were unaltered. In auxiliary ex vivo experiments whole blood was incubated with particles from the exposure chamber for 3h without effects on DNA damage in PBMCs or intracellular reactive oxygen species production and expression of CD11b and CD62L adhesion...

  9. Estimation of current density distribution of PAFC by analysis of cell exhaust gas

    Energy Technology Data Exchange (ETDEWEB)

    Kato, S.; Seya, A. [Fuji Electric Co., Ltd., Ichihara-shi (Japan); Asano, A. [Fuji Electric Corporate, Ltd., Yokosuka-shi (Japan)

    1996-12-31

    To estimate distributions of Current densities, voltages, gas concentrations, etc., in phosphoric acid fuel cell (PAFC) stacks, is very important for getting fuel cells with higher quality. In this work, we leave developed a numerical simulation tool to map out the distribution in a PAFC stack. And especially to Study Current density distribution in the reaction area of the cell, we analyzed gas composition in several positions inside a gas outlet manifold of the PAFC stack. Comparing these measured data with calculated data, the current density distribution in a cell plane calculated by the simulation, was certified.

  10. High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort

    Directory of Open Access Journals (Sweden)

    Colebunders Robert

    2011-02-01

    Full Text Available Abstract Background Antiretroviral therapy (ART partially corrects immune dysfunction associated with HIV infection. The levels of T-cell immune activation and exhaustion after long-term, suppressive ART and their correlation with CD4 T-cell count reconstitution among ART-treated patients in African cohorts have not been extensively evaluated. Methods T-cell activation (CD38+HLA-DR+ and immune exhaustion (PD-1+ were measured in a prospective cohort of patients initiated on ART; 128 patient samples were evaluated and subcategorized by CD4 reconstitution after long-term suppressive treatment: Suboptimal [median CD4 count increase 129 (-43-199 cells/μl], N = 34 ], optimal [282 (200-415 cells/μl, N = 64] and super-optimal [528 (416-878 cells/μl, N = 30]. Results Both CD4+ and CD8 T-cell activation was significantly higher among suboptimal CD4 T-cell responders compared to super-optimal responders. In a multivariate model, CD4+CD38+HLADR+ T-cells were associated with suboptimal CD4 reconstitution [AOR, 5.7 (95% CI, 1.4-23, P = 0.014]. T-cell exhaustion (CD4+PD1+ and CD8+PD1+ was higher among suboptimal relative to optimal (P P = 0.022]. Conclusion T-cell activation and exhaustion persist among HIV-infected patients despite long-term, sustained HIV-RNA viral suppression. These immune abnormalities were associated with suboptimal CD4 reconstitution and their regulation may modify immune recovery among suboptimal responders to ART.

  11. Alveolar epithelial cells (A549) exposed at the air-liquid interface to diesel exhaust: First study in TNO's powertrain test center

    NARCIS (Netherlands)

    Kooter, I.M.; Alblas, M.J.; Jedynska, A.D.; Steenhof, M.; Houtzager, M.M.G.; Ras, M.G. van

    2013-01-01

    Air–liquid interface (ALI) exposures enable in vitro testing ofmixtures of gases and particles such as diesel exhaust (DE). The main objective of this study was to investigate the feasibility of exposing human lung epithelial cells at the ALI to complete DE generated by a heavy-duty truck in the

  12. Numerical model of a thermoelectric generator with compact plate-fin heat exchanger for high temperature PEM fuel cell exhaust heat recovery

    DEFF Research Database (Denmark)

    Xin, Gao; Andreasen, Søren Juhl; Chen, Min

    2012-01-01

    This paper presents a numerical model of an exhaust heat recovery system for a high temperature polymer electrolyte membrane fuel cell (HTPEMFC) stack. The system is designed as thermoelectric generators (TEGs) sandwiched in the walls of a compact plate-fin heat exchanger. Its model is based on a...

  13. Atorvastatin reduces T-cell activation and exhaustion among HIV-infected cART-treated suboptimal immune responders in Uganda: a randomised crossover placebo-controlled trial.

    Science.gov (United States)

    Nakanjako, Damalie; Ssinabulya, Isaac; Nabatanzi, Rose; Bayigga, Lois; Kiragga, Agnes; Joloba, Moses; Kaleebu, Pontiano; Kambugu, Andrew D; Kamya, Moses R; Sekaly, Rafick; Elliott, Alison; Mayanja-Kizza, Harriet

    2015-03-01

    T-cell activation independently predicts mortality, poor immune recovery and non-AIDS illnesses during combination antiretroviral therapy (cART). Atorvastatin showed anti-immune activation effects among HIV-infected cART-naïve individuals. We investigated whether adjunct atorvastatin therapy reduces T-cell activation among cART-treated adults with suboptimal immune recovery. A randomised double-blind placebo-controlled crossover trial, of atorvastatin 80 mg daily vs. placebo for 12 weeks, was conducted among individuals with CD4 increase <295 cells/μl after seven years of suppressive cART. Change in T-cell activation (CD3 + CD4 + /CD8 + CD38 + HLADR+) and in T-cell exhaustion (CD3 + CD4 + /CD8 + PD1 + ) was measured using flow cytometry. Thirty patients were randomised, 15 to each arm. Atorvastatin resulted in a 28% greater reduction in CD4 T-cell activation (60% reduction) than placebo (32% reduction); P = 0.001. Atorvastatin also resulted in a 35% greater reduction in CD8-T-cell activation than placebo (49% vs. 14%, P = 0.0009), CD4 T-cell exhaustion (27% vs. 17% in placebo), P = 0.001 and CD8 T-cell exhaustion (27% vs. 16%), P = 0.004. There was no carry-over/period effect. Expected adverse events were comparable in both groups, and no serious adverse events were reported. Atorvastatin reduced T-cell immune activation and exhaustion among cART-treated adults in a Ugandan cohort. Atorvastatin adjunct therapy should be explored as a strategy to improve HIV treatment outcomes among people living with HIV in sub-Saharan Africa. © 2014 John Wiley & Sons Ltd.

  14. Diesel exhaust particles are mutagenic in FE1-MutaMouse lung epithelial cells

    DEFF Research Database (Denmark)

    Jacobsen, Nicklas Raun; Møller, Peter; Cohn, Corey Alexander

    2008-01-01

    /ml DEP (NIST SRM 1650) in the FE1-MutaMouse lung epithelial cell line. We measured DEP-induced acellular and intracellular production of reactive oxygen species (ROS) and compared with ROS production induced by carbon black, which we have previously shown is mutagenic in this cell line [N.R. Jacobsen, A.......T. Saber, P. White, P. Moller, G. Pojana, U. Vogel, S. Loft, J. Gingerich, L. Soper, G.R. Douglas, H. Wallin. Increased mutant frequency by carbon black, but not quartz, in the lacZ and cII transgenes of mutamouse lung epithelial cells, Environ. Mol. Mutagen. 48(6) (2007) 451-461]. The mutant frequency...... to carbon black. These results show that DEP are mutagenic in a mammalian cell line in vitro and that additional pathways besides ROS production, such as those involving the presence of polycyclic aromatic hydrocarbons, likely are involved in the mutagenesis....

  15. Piwi Is Required to Limit Exhaustion of Aging Somatic Stem Cells

    Directory of Open Access Journals (Sweden)

    Pedro Sousa-Victor

    2017-09-01

    Full Text Available Sophisticated mechanisms that preserve genome integrity are critical to ensure the maintenance of regenerative capacity while preventing transformation of somatic stem cells (SCs, yet little is known about mechanisms regulating genome maintenance in these cells. Here, we show that intestinal stem cells (ISCs induce the Argonaute family protein Piwi in response to JAK/STAT signaling during acute proliferative episodes. Piwi function is critical to ensure heterochromatin maintenance, suppress retrotransposon activation, and prevent DNA damage in homeostasis and under regenerative pressure. Accordingly, loss of Piwi results in the loss of actively dividing ISCs and their progenies by apoptosis. We further show that Piwi expression is sufficient to allay age-related retrotransposon expression, DNA damage, apoptosis, and mis-differentiation phenotypes in the ISC lineage, improving epithelial homeostasis. Our data identify a role for Piwi in the regulation of somatic SC function, and they highlight the importance of retrotransposon control in somatic SC maintenance.

  16. PD-1 Dependent Exhaustion of CD8+ T Cells Drives Chronic Malaria

    Directory of Open Access Journals (Sweden)

    Joshua M. Horne-Debets

    2013-12-01

    Full Text Available Malaria is a highly prevalent disease caused by infection by Plasmodium spp., which infect hepatocytes and erythrocytes. Blood-stage infections cause devastating symptoms and can persist for years. Antibodies and CD4+ T cells are thought to protect against blood-stage infections. However, there has been considerable difficulty in developing an efficacious malaria vaccine, highlighting our incomplete understanding of immunity against this disease. Here, we used an experimental rodent malaria model to show that PD-1 mediates up to a 95% reduction in numbers and functional capacity of parasite-specific CD8+ T cells. Furthermore, in contrast to widely held views, parasite-specific CD8+ T cells are required to control both acute and chronic blood-stage disease even when parasite-specific antibodies and CD4+ T cells are present. Our findings provide a molecular explanation for chronic malaria that will be relevant to future malaria-vaccine design and may need consideration when vaccine development for other infections is problematic.

  17. Everolimus Alleviates Obstructive Hydrocephalus due to Subependymal Giant Cell Astrocytomas.

    Science.gov (United States)

    Moavero, Romina; Carai, Andrea; Mastronuzzi, Angela; Marciano, Sara; Graziola, Federica; Vigevano, Federico; Curatolo, Paolo

    2017-03-01

    Subependymal giant cell astrocytomas (SEGAs) are low-grade tumors affecting up to 20% of patients with tuberous sclerosis complex (TSC). Early neurosurgical resection has been the only standard treatment until few years ago when a better understanding of the molecular pathogenesis of TSC led to the use of mammalian target of rapamycin (mTOR) inhibitors. Surgical resection of SEGAs is still considered as the first line treatment in individuals with symptomatic hydrocephalus and intratumoral hemorrhage. We describe four patients with symptomatic or asymptomatic hydrocephalus who were successfully treated with the mTOR inhibitor everolimus. We collected the clinical data of four consecutive patients presenting with symptomatic or asymptomatic hydrocephalus due to a growth of subependymal giant cell atrocytomas and who could not undergo surgery for different reasons. All patients experienced a clinically significant response to everolimus and an early shrinkage of the SEGA with improvement in ventricular dilatation. Everolimus was well tolerated by all individuals. Our clinical series demonstrate a possible expanding indication for mTOR inhibition in TSC, which can be considered in patients with asymptomatic hydrocephalus or even when the symptoms already appeared. It offers a significant therapeutic alternative to individuals that once would have undergone immediate surgery. Everolimus might also allow postponement of a neurosurgical resection, making it elective with an overall lower risk. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Activation and exhaustion of antigen-specific CD8+T cells occur in different splenic compartments during infection with Plasmodium berghei.

    Science.gov (United States)

    Bayarsaikhan, Ganchimeg; Miyakoda, Mana; Yamamoto, Kazuo; Kimura, Daisuke; Akbari, Masoud; Yuda, Masao; Yui, Katsuyuki

    2017-06-01

    The spleen is the major organ in which T cells are primed during infection with malaria parasites. However, little is known regarding the dynamics of the immune responses and their localization within the splenic tissue during malaria infection. We examined murine CD8 + T cell responses during infection with Plasmodium berghei using recombinant parasites expressing a model antigen ovalbumin (OVA) protein and compared the responses with those elicited by Listeria monocytogenes expressing the same antigen. OVA-specific CD8 + T cells were mainly activated in the white pulp of the spleen during malaria infection, as similarly observed during Listeria infection. However, the fates of these activated CD8 + T cells were distinct. During infection with malaria parasites, activated CD8 + T cells preferentially accumulated in the red pulp and/or marginal zone, where cytokine production of OVA-specific CD8 + T cells decreased, and the expression of multiple inhibitory receptors increased. These cells preferentially underwent apoptosis, suggesting that T cell exhaustion mainly occurred in the red pulp and/or marginal zone. However, during Listeria infection, OVA-specific CD8 + T cells only transiently expressed inhibitory receptors in the white pulp and maintained their ability to produce cytokines and become memory cells. These results highlighted the distinct fates of CD8 + T cells during infection with Plasmodium parasites and Listeria, and suggested that activation and exhaustion of specific CD8 + T cells occurred in distinct spleen compartments during infection with malaria parasites. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Persistent inflammation and T cell exhaustion in severe sepsis in the elderly

    Science.gov (United States)

    2014-01-01

    Introduction Sepsis is known as a complex immunological response with hyperinflammation in the acute phase followed by immunosuppression. Although aging is crucial in sepsis, the impact of aging on inflammation and immunosuppression is still unclear. The purpose of this study was to investigate the relationship between inflammation and immunosuppression in aged patients and mice after sepsis. Methods Fifty-five patients with severe sepsis and 30 healthy donors were prospectively enrolled, and 90-day survival was compared between elderly (≥65 years) and adult (18–64 years) septic patients with serial measurement of serum interleukin (IL)-6. Within 24 h after diagnosis of severe sepsis, peripheral blood mononuclear cells were stimulated ex vivo to measure expression of the activation maker CD25 in T cells, IL-2 levels in the supernatant, and proliferation. In the mouse study, young (6–8 weeks) and aged (20–22 months) C57/B6 mice were subjected to cecal ligation and puncture (CLP), and survival was compared after 7 days with serial measurement of serum IL-6. Expression of the negative co-stimulatory molecules, CD25, and IL-2 in CD4+ T cells was measured. Results The survival rate in elderly sepsis patients and aged septic mice was significantly lower than that in adult patients and young septic mice (60% vs. 93% in septic patients, 0% vs. 63% in septic mice, P elderly sepsis patients and aged septic mice were persistently higher than those in adult patients and young septic mice. Expression of negative co-stimulatory molecules in CD4+ T cells in the spleen, lymph nodes, and peripheral blood was significantly higher in aged mice than in young mice (P elderly patients and aged septic mice than in those from adult patients and young septic mice. Elderly patients demonstrated increased detection of gram-negative bacteria at days 14–16 and 28–32 after sepsis (P elderly patients and mice after sepsis. PMID:24962182

  20. Controlled exposure to diesel exhaust and traffic noise--Effects on oxidative stress and activation in mononuclear blood cells.

    Science.gov (United States)

    Hemmingsen, Jette Gjerke; Møller, Peter; Jantzen, Kim; Jönsson, Bo A G; Albin, Maria; Wierzbicka, Aneta; Gudmundsson, Anders; Loft, Steffen; Rissler, Jenny

    2015-05-01

    Particulate air pollution increases risk of cancer and cardiopulmonary disease, partly through oxidative stress. Traffic-related noise increases risk of cardiovascular disease and may cause oxidative stress. In this controlled random sequence study, 18 healthy subjects were exposed for 3h to diesel exhaust (DE) at 276 μg/m(3) from a passenger car or filtered air, with co-exposure to traffic noise at 48 or 75 dB(A). Gene expression markers of inflammation, (interleukin-8 and tumor necrosis factor), oxidative stress (heme oxygenase (decycling-1)) and DNA repair (8-oxoguanine DNA glycosylase (OGG1)) were unaltered in peripheral blood mononuclear cells (PBMCs). No significant differences in DNA damage levels, measured by the comet assay, were observed after DE exposure, whereas exposure to high noise levels was associated with significantly increased levels of hOGG1-sensitive sites in PBMCs. Urinary levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine were unaltered. In auxiliary ex vivo experiments whole blood was incubated with particles from the exposure chamber for 3h without effects on DNA damage in PBMCs or intracellular reactive oxygen species production and expression of CD11b and CD62L adhesion molecules in leukocyte subtypes. 3-h exposure to DE caused no genotoxicity, oxidative stress or inflammation in PBMCs, whereas exposure to noise might cause oxidatively damaged DNA. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Age-specific bone tumour incidence rates are governed by stem cell exhaustion influencing the supply and demand of progenitor cells.

    Science.gov (United States)

    Richardson, Richard B

    2014-07-01

    Knudson's carcinogenic model, which simulates incidence rates for retinoblastoma, provides compelling evidence for a two-stage mutational process. However, for more complex cancers, existing multistage models are less convincing. To fill this gap, I hypothesize that neoplasms preferentially arise when stem cell exhaustion creates a short supply of progenitor cells at ages of high proliferative demand. To test this hypothesis, published datasets were employed to model the age distribution of osteochondroma, a benign lesion, and osteosarcoma, a malignant one. The supply of chondrogenic stem-like cells in femur growth plates of children and adolescents was evaluated and compared with the progenitor cell demand of longitudinal bone growth. Similarly, the supply of osteoprogenitor cells from birth to old age was compared with the demands of bone formation. Results show that progenitor cell demand-to-supply ratios are a good risk indicator, exhibiting similar trends to the unimodal and bimodal age distributions of osteochondroma and osteosarcoma, respectively. The hypothesis also helps explain Peto's paradox and the finding that taller individuals are more prone to cancers and have shorter lifespans. The hypothesis was tested, in the manner of Knudson, by its ability to convincingly explain and demonstrate, for the first time, a bone tumour's bimodal age-incidence curve. Crown Copyright © 2014. Published by Elsevier Ireland Ltd. All rights reserved.

  2. Exhaustion of T lymphocytes in the tumor microenvironment: Significance and effective mechanisms.

    Science.gov (United States)

    Davoodzadeh Gholami, Mohammad; Kardar, Gholam Ali; Saeedi, Yousef; Heydari, Sahel; Garssen, Johan; Falak, Reza

    2017-12-01

    T lymphocytes play crucial roles in adaptive immune responses to tumors. However, due to different tolerance mechanisms and inhibitory effects of the tumor microenvironment (TME) on T cells, responses to tumors are insufficient. In fact, cellular and molecular suppressive mechanisms repress T cell responses in the TME, resulting in senescent, anergic and exhausted lymphocytes. Exhaustion is a poor responsive status of T cells, with up-regulated expression of inhibitory receptors, decreased production of effective cytokines, and reduced cytotoxic activity. Low immunogenicity of tumor antigens and inadequate presentation of tumor-specific antigens results in inappropriate activation of naive T lymphocytes against tumor antigens. Moreover, when effector cytotoxic T cells enter TME, they encounter a complicated network of cells and cytokines that suppress their effectiveness and turn them into exhausted T cells. Thus, the mechanism of T cell exhaustion in cancer is different from that in chronic infections. In this review we will discuss the main components such as inhibitory receptors, inflammatory cells, stromal cells, cytokine milieu as well as environmental and metabolic conditions in TME which play role in development of exhaustion. Furthermore, recent therapeutic methods available to overcome exhaustion will be discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Implication of scavenger receptors in the interactions between diesel exhaust particles and immature or mature dendritic cells

    Directory of Open Access Journals (Sweden)

    Lassalle Philippe

    2009-03-01

    Full Text Available Abstract Background The exposure to pollutants such as diesel exhaust particles (DEP is associated with an increased incidence of respiratory diseases. However, the mechanisms by which DEP have an effect on human health are not completely understood. In addition to their action on macrophages and airway epithelial cells, DEP also modulate the functions of dendritic cells (DC. These professional antigen-presenting cells are able to discriminate unmodified self from non-self thanks to pattern recognition receptors such as the Toll like Receptors (TLR and Scavenger Receptors (SR. SR were originally identified by their ability to bind and internalize modified lipoproteins and microorganisms but also particles and TLR agonists. In this study, we assessed the implication of SR in the effects of DEP associated or not with TLR agonists on monocyte-derived DC (MDDC. For this, we studied the regulation of CD36, CXCL16, LOX-1, SR-A1 and SR-B1 expression on MDDC treated with DEP associated or not with TLR2, 3 and 4 ligands. Then, the capacity of SR ligands (dextran sulfate and maleylated-ovalbumin to block the effects of DEP on the function of lipopolysaccharide (LPS-activated DC has been evaluated. Results Our data demonstrate that TLR2 agonists mainly augmented CXCL16, LOX-1 and SR-B1 expression whereas DEP alone had only a weak effect. Interestingly, DEP modulated the action of TLR2 and TLR4 ligands on the expression of LOX-1 and SR-B1. Pretreatment with the SR ligand maleylated-ovalbumin but not dextran sulfate inhibited the endocytosis of DEP by MDDC. Moreover, this SR ligand blocked the effect by DEP at low dose (1 μg/ml on MDDC phenotype (a decrease of CD86 and HLA-DR expression and on the secretion of CXCL10, IL-12 and TNF-α. In contrast, the decrease of IL-12 and CXCL10 secretion and the generation of oxygen metabolite induced by DEP at 10 μg/ml was not affected by SR ligands Conclusion Our results show for the first time that the modulation of

  4. Coccydynia due to a benign notochordal cell tumor.

    Science.gov (United States)

    Haasper, Carl; Länger, Florian; Rosenthal, Herbert; Knobloch, Karsten; Mössinger, Eckart; Krettek, Christian; Bastian, Leonhard

    2007-06-15

    Case report. To present a rare case of a notochordal cell tumor. We report on a 27-year-old female patient with pain at the lower back and muscle cramps in the area of the right hip. Image studies demonstrated a cystic lesion of the coccyx. As clinical symptoms became chronic and were resistant to conservative treatment, a resection of the coccyx was performed. Histology revealed an intraosseous benign notochordal cell tumor. This tumor represents a recently described notochordal cell proliferation biologically distinct from chordomas. Overdiagnosis of these notochordal cell proliferations as chordomas may occur if clinicians and pathologists are unfamiliar with the spectrum of notochordal proliferations.

  5. Delayed menopause due to granulosa cell tumor of the ovary

    Directory of Open Access Journals (Sweden)

    Bhushan Murkey

    2011-01-01

    Full Text Available A 52-year-old patient presented with complaints of menorrhagia. Endometrial biopsy revealed simple hyperplasia of the endometrium. Total abdominal hysterectomy with bilateral oophorectomy was carried out. The ovaries looked grossly normal, but histopathology reported granulosa cell tumor of the right ovary. Granulosa cell tumors belong to the sexcord stromal category and account for approximately 2% of all ovarian tumors. We review the features and treatment of granulosa cell tumors and the importance of screening for ovarian tumors in a case of endometrial hyperplasia and delayed menopause.

  6. Orbital Infarction due to Sickle Cell Disease without Orbital Pain

    Directory of Open Access Journals (Sweden)

    Cameron L. McBride

    2016-01-01

    Full Text Available Sickle cell disease is a hemoglobinopathy that results in paroxysmal arteriolar occlusion and tissue infarction that can manifest in a plurality of tissues. Rarely, these infarcted crises manifest in the bony orbit. Orbital infarction usually presents with acute onset of periorbital tenderness, swelling, erythema, and pain. Soft tissue swelling can result in proptosis and attenuation of extraocular movements. Expedient diagnosis of sickle cell orbital infarction is crucial because this is a potentially sight-threatening entity. Diagnosis can be delayed since the presentation has physical and radiographic findings mimicking various infectious and traumatic processes. We describe a patient who presented with sickle cell orbital crisis without pain. This case highlights the importance of maintaining a high index of suspicion in patients with known sickle cell disease or of African descent born outside the United States in a region where screening for hemoglobinopathy is not routine, even when the presentation is not classic.

  7. Human peripheral late/exhausted memory B cells express a senescent-associated secretory phenotype and preferentially utilize metabolic signaling pathways.

    Science.gov (United States)

    Frasca, Daniela; Diaz, Alain; Romero, Maria; Blomberg, Bonnie B

    2017-01-01

    The percentage of late/exhausted memory (LM) B cells increases with age and we show here that this is associated with a lower influenza vaccine response. To identify novel contributors to the phenotypic and functional changes observed in aged B cells, we sorted the major peripheral B cell subsets [naïve, IgM memory, switched memory (swIg) and late/exhausted memory (LM)] and determined their percentages in the peripheral blood as well as their level of immune activation by measuring basal levels of expression of multiple senescence-associated secretory phenotype (SASP) markers, such as pro-inflammatory cytokines (TNF-α/IL-6/IL-8), inflammatory micro-RNAs (miRs, miR-155/16/93), cell cycle regulators (p16 INK4 ). We found that only memory B cells express SASP markers, and especially the LM B cell subset, which is also showing spontaneous activation of AMP-activated protein kinase (AMPK), the energy sensing enzyme which is ubiquitously expressed in mammalian cells. LM B cells, but not IgM memory B cells, activate a p38MAPK signaling pathway, downstream of AMPK, leading to the expression of SASP mediators, while class switch recombination is downregulated. These data show that some B cell subsets are more inflammatory than others, that they are pre-activated and that this signaling through metabolic pathways is associated with a senescence phenotype, demonstrating for the first time in human B lymphocytes the link between aging, cellular senescence, SASP and metabolism. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Impact of after-treatment devices and biofuels on diesel exhausts genotoxicity in A549 cells exposed at air-liquid interface.

    Science.gov (United States)

    Barraud, C; Corbière, C; Pottier, I; Estace, E; Blanchard, K; Logie, C; Lagadu, S; Kéravec, V; Pottier, D; Dionnet, F; Morin, J P; Préterre, D; André, V; Monteil, C; Sichel, F

    2017-12-01

    Using an air-liquid interface (ALI) device in dynamic conditions, we evaluated the efficiency of fuel after-treatment strategies (diesel oxidation catalysis, DOC, and diesel particulate filter, DPF, devices) and the impact of 7% and 30% rapeseed methyl esters (RME) blending on oxidative stress and genotoxicity induced in A549 lung cells after 3h exposure to whole Diesel exhausts. Oxidative stress was studied using assays of ROS production, glutathione level, catalase and superoxide-dismutase (SOD) activities. No oxidative stress and no clear differences on cytotoxicity patterns between biodiesel and standard Diesel exhausts were found. A weak but significant genotoxicity (8-oxodGuo adducts) and, for standard Diesel only, a DNA damage response (DDR) as evidenced by ƔH2AX foci, remained after DOC+DPF flowing. All together, these data could contribute to the improvement of the after treatment strategies and to health risk assessment of current diesel exhausts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Chylous ascites due to signet ring cell gastric adenocarcinoma

    African Journals Online (AJOL)

    2011-09-04

    Sep 4, 2011 ... He was underwent to medium chain triglycerides based diet, total parenteric diet and treatment with somatostatin ... esophageal, lung, colorectal, prostate or gastric cancer.[4,5]. Signet ring cell gastric adenocarcinoma is a .... pattern and performs subsequent analysis that disclosed high triglycerides levels.

  10. Bacterial Cell Surface Damage Due to Centrifugal Compaction

    NARCIS (Netherlands)

    Peterson, Brandon W.; Sharma, Prashant K.; van der Mei, Henny C.; Busscher, Henk J.

    Centrifugal damage has been known to alter bacterial cell surface properties and interior structures, including DNA. Very few studies exist on bacterial damage caused by centrifugation because of the difficulty in relating centrifugation speed and container geometry to the damage caused. Here, we

  11. Curve Fitting Solar Cell Degradation Due to Hard Particle Radiation

    Science.gov (United States)

    Gaddy, Edward M.; Cikoski, Rebecca; Mekadenaumporn, Danchai

    2003-01-01

    This paper investigates the suitability of the equation for accurately defining solar cell parameter degradation as a function of hard particle radiation. The paper also provides methods for determining the constants in the equation and compares results from this equation to those obtained by the more traditionally used.

  12. Recurrent Syncope due to Esophageal Squamous Cell Carcinoma

    OpenAIRE

    Casini, Alessandro; Tschanz, Elisabeth; Dietrich, Pierre-Yves; Nendaz, Mathieu

    2011-01-01

    Syncope is caused by a wide variety of disorders. Recurrent syncope as a complication of malignancy is uncommon and may be difficult to diagnose and to treat. Primary neck carcinoma or metastases spreading in parapharyngeal and carotid spaces can involve the internal carotid artery and cause neurally mediated syncope with a clinical presentation like carotid sinus syndrome. We report the case of a 76-year-old man who suffered from recurrent syncope due to invasion of the right carotid sinus b...

  13. Paediatric cyclical Cushing's disease due to corticotroph cell hyperplasia.

    LENUS (Irish Health Repository)

    Noctor, E

    2015-06-01

    Cushing\\'s disease is very rare in the paediatric population. Although uncommon, corticotroph hyperplasia causing Cushing\\'s syndrome has been described in the adult population, but appears to be extremely rare in children. Likewise, cyclical cortisol hypersecretion, while accounting for 15 % of adult cases of Cushing\\'s disease, has only rarely been described in the paediatric population. Here, we describe a very rare case of a 13-year old boy with cyclical cortisol hypersecretion secondary to corticotroph cell hyperplasia.

  14. Gonadal vein tumor thrombosis due to renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Hamidreza Haghighatkhah

    2015-01-01

    Full Text Available Renal cell carcinoma (RCC had a tendency to extend into the renal vein and inferior vena cava, while extension into the gonadal vein has been rarely reported. Gonadal vein tumor thrombosis appears as an enhancing filling defect within the dilated gonadal vein anterior to the psoas muscle and shows an enhancement pattern identical to that of the original tumor. The possibility of gonadal vein thrombosis should be kept in mind when looking at an imaging study of patients with RCC

  15. CD8 cells of patients with diffuse cutaneous leishmaniasis display functional exhaustion: the latter is reversed, in vitro, by TLR2 agonists.

    Directory of Open Access Journals (Sweden)

    Joselín Hernández-Ruiz

    Full Text Available Leishmania mexicana (Lm causes localized (LCL and diffuse (DCL cutaneous leishmaniasis. DCL patients have a poor cellular immune response leading to chronicity. It has been proposed that CD8 T lymphocytes (CD8 play a crucial role in infection clearance, although the role of CD8 cytotoxicity in disease control has not been elucidated. Lesions of DCL patients have been shown to harbor low numbers of CD8, as compared to patients with LCL, and leishmanicidal treatment restores CD8 numbers. The marked response of CD8 towards Leishmania parasites led us to analyze possible functional differences between CD8 from patients with LCL and DCL. We compared IFNγ production, antigen-specific proliferation, and cytotoxicity of CD8 purified from PBMC against autologous macrophages (MO infected with Leishmania mexicana (MOi. Additionally, we analyzed tissue biopsies from both groups of patients for evidence of cytotoxicity associated with apoptotic cells in the lesions. We found that CD8 cell of DCL patients exhibited low cytotoxicity, low antigen-specific proliferation and low IFNγ production when stimulated with MOi, as compared to LCL patients. Additionally, DCL patients had significantly less TUNEL+ cells in their lesions. These characteristics are similar to cellular "exhaustion" described in chronic infections. We intended to restore the functional capacity of CD8 cells of DCL patients by preincubating them with TLR2 agonists: Lm lipophosphoglycan (LPG or Pam3Cys. Cytotoxicity against MOi, antigen-specific proliferation and IFNγ production were restored with both stimuli, whereas PD-1 (a molecule associated with cellular exhaustion expression, was reduced. Our work suggests that CD8 response is associated with control of Lm infection in LCL patients and that chronic infection in DCL patients leads to a state of CD8 functional exhaustion, which could facilitate disease spread. This is the first report that shows the presence of functionally exhausted CD8

  16. Exhaust Gas Scrubber Washwater Effluent

    Science.gov (United States)

    2011-11-01

    oceans . However, this effect is minor compared to ocean acidification due to Exhaust Gas Scrubber Washwater Effluent...Section 6 -Assessment of Pollutants Discharged in Scrubber Washwater and Protectiveness of IMO Guidelines 29 increased carbon dioxide ...June 11, 2010 (http://www.motorship.com/news101/breakthrough-order-for-krystallon-scrubbers). Orr, J.C. et al. 2005. Anthropogenic ocean acidification

  17. Recurrent Syncope due to Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    A. Casini

    2011-09-01

    Full Text Available Syncope is caused by a wide variety of disorders. Recurrent syncope as a complication of malignancy is uncommon and may be difficult to diagnose and to treat. Primary neck carcinoma or metastases spreading in parapharyngeal and carotid spaces can involve the internal carotid artery and cause neurally mediated syncope with a clinical presentation like carotid sinus syndrome. We report the case of a 76-year-old man who suffered from recurrent syncope due to invasion of the right carotid sinus by metastases of a carcinoma of the esophagus, successfully treated by radiotherapy. In such cases, surgery, chemotherapy or radiotherapy can be performed. Because syncope may be an early sign of neck or cervical cancer, the diagnostic approach of syncope in patients with a past history of cancer should include the possibility of neck tumor recurrence or metastasis and an oncologic workout should be considered.

  18. Expression of adhesion molecules, monocyte interactions and oxidative stress in human endothelial cells exposed to wood smoke and diesel exhaust particulate matter

    DEFF Research Database (Denmark)

    Forchhammer, Lykke; Loft, Steffen; Roursgaard, Martin

    2012-01-01

    Toxicological effects of wood smoke particles are less investigated than traffic-related combustion particles. We investigated the effect of wood smoke particles, generated by smouldering combustion conditions, on human umbilical endothelial cells (HUVECs) co-cultured with or without monocytic THP......-1 cells. Standard reference material (SRM) 2975 diesel exhaust particles were used as benchmark particles. Wood smoke particles at 50µg/ml or 100µg/ml caused adhesion of THP-1 monocytes onto HUVECs in co-cultures, whereas SRM2975 had no such effect. Both types of particles from 1µg/ml increased VCAM......-1 expression on HUVECs in mono-cultures. However, only the exposure to wood smoke particles was associated with increased expression of TNF and IL8 mRNA in THP-1 cells. We found no effect on the intracellular production of reactive oxygen species by the fluorescent probe DCFH-DA, whereas especially...

  19. Initiation of Antiretroviral Therapy (ART) at Different Stages of HIV-1 Disease Is Not Associated with the Proportion of Exhausted CD8+ T Cells.

    Science.gov (United States)

    Jensen, Sanne Skov; Fomsgaard, Anders; Larsen, Tine Kochendorf; Tingstedt, Jeanette Linnea; Gerstoft, Jan; Kronborg, Gitte; Pedersen, Court; Karlsson, Ingrid

    2015-01-01

    CD8+ T cell-restricted immunity is important in the control of HIV-1 infection, but continued immune activation results in CD8+ T cell dysfunction. Early initiation of antiretroviral treatment (ART) and the duration of ART have been associated with immune reconstitution. Here, we evaluated whether restoration of CD8+ T cell function in HIV-1-infected individuals was dependent on early initiation of ART. HIV-specific CD107a, IFNγ, IL-2, TNFα and MIP-1β expression by CD8+ T cells and the frequency of CD8+ T cells expressing PD-1, 2B4 and CD160 were measured by flow cytometry. The frequency of CD8+ T cells expressing the inhibitory markers PD-1, 2B4 and CD160 was lower in ART-treated individuals compared with ART-naïve individuals and similar to the frequency in HIV-uninfected controls. The expression of the three markers was similarly independent of when therapy was initiated. Individuals treated before seroconversion displayed an HIV-specific CD8+ T cell response that included all five functional markers; this was not observed in individuals treated after seroconversion or in ART-naïve individuals. In summary, ART appears to restore the total CD8+ T cell population to a less exhausted phenotype, independent of the time point of initiation. However, to preserve multifunctional, HIV-1-specific CD8+ T cells, ART might have to be initiated before seroconversion.

  20. Loss of aryl hydrocarbon receptor promotes gene changes associated with premature hematopoietic stem cell exhaustion and development of a myeloproliferative disorder in aging mice.

    Science.gov (United States)

    Singh, Kameshwar P; Bennett, John A; Casado, Fanny L; Walrath, Jason L; Welle, Stephen L; Gasiewicz, Thomas A

    2014-01-15

    Loss of immune function and increased hematopoietic disease are among the most clinically significant consequences of aging. Hematopoietic stem cells (HSCs) from mice lacking aryl hydrocarbon receptor (AhR) have high rates of cell division. Studies were designed to test the hypothesis that aging AhR-null allele (AhR-KO) mice develop premature HSC exhaustion, and changes leading to hematological disease. Compared to wild-type, aging AhR-KO mice showed a decreased survival rate, splenomegaly, increased circulating white blood cells, hematopoietic cell accumulation in tissues, and anemia. Analysis of bone marrow indicated increased numbers of stem/progenitor and lineage-committed cells, but decreased erythroid progenitors. There was also decreased self-renewal capacity of HSCs determined by competitive repopulation and serial transplantation. HSCs also showed increased levels of reactive oxygen species (ROS), Ki-67, and γ-H2A.X, but decreased p16(Ink4a). Splenic cells from aging KO mice had abnormal expression of genes, including Gata-1, Sh2d3c, Gfi-1, p21, and c-myc, involved in trafficking and associated with leukemia. HSCs from AhR-KO mice had gene changes related to HSC maintenance and consistent with phenotype observed. The most prominent gene changes (overexpression of Srpk2, Creb1, Hes1, mtor, pdp1) have been associated with HSC hyperproliferation, leukemia, and accelerated aging. Pathway analyses also indicated an enrichment of genes associated with oxidative stress, acute myelogenous leukemia, aging, and heat shock response, and the β-catenin/Wnt pathways. These data indicate that loss of AhR and associated changes in multiple signaling pathways promote premature HSC exhaustion and development of a myeloproliferative disorder. They also implicate a critical role of the AhR in the regulation of HSCs.

  1. Metabolic exhaustion in infection, cancer and autoimmunity.

    Science.gov (United States)

    McKinney, E F; Smith, K G C

    2018-03-01

    It has become increasingly clear that changes in metabolism are not just consequences of T cell activation but instead are also essential drivers of that process that shape the extent and nature of differentiation and function. The process of T cell exhaustion has been linked to the outcome of chronic immune responses in multiple contexts, including chronic infection, cancer and autoimmunity. Factors that regulate the development and maintenance of exhaustion are of increasing interest as targets of therapeutic modulation. Studies have shown T cell immunometabolism to be integral to the control and development of T cell exhaustion. Early metabolic changes are responsible for the later emergence of exhaustion, do not simply reflect changes secondary to chronic activation and are modifiable. Increased understanding of this metabolic control promises to improve the ability to modulate T cell immunity to chronic antigen stimulation in multiple contexts.

  2. Initiation of Antiretroviral Therapy (ART) at Different Stages of HIV-1 Disease Is Not Associated with the Proportion of Exhausted CD8+ T Cells

    DEFF Research Database (Denmark)

    Jensen, Sanne Skov; Fomsgaard, Anders; Larsen, Tine Kochendorf

    2015-01-01

    CD8+ T cell-restricted immunity is important in the control of HIV-1 infection, but continued immune activation results in CD8+ T cell dysfunction. Early initiation of antiretroviral treatment (ART) and the duration of ART have been associated with immune reconstitution. Here, we evaluated whether...... restoration of CD8+ T cell function in HIV-1-infected individuals was dependent on early initiation of ART. HIV-specific CD107a, IFNγ, IL-2, TNFα and MIP-1β expression by CD8+ T cells and the frequency of CD8+ T cells expressing PD-1, 2B4 and CD160 were measured by flow cytometry. The frequency of CD8+ T...... before seroconversion displayed an HIV-specific CD8+ T cell response that included all five functional markers; this was not observed in individuals treated after seroconversion or in ART-naïve individuals. In summary, ART appears to restore the total CD8+ T cell population to a less exhausted phenotype...

  3. Exhaustion from prolonged gambling

    Directory of Open Access Journals (Sweden)

    Fatimah Lateef

    2013-01-01

    Full Text Available Complaints of fatigue and physical exhaustion are frequently seen in the acute medical setting, especially amongst athletes, army recruits and persons involved in strenuous and exertional physical activities. Stress-induced exhaustion, on the other hand, is less often seen, but can present with very similar symptoms to physical exhaustion. Recently, three patients were seen at the Department of Emergency Medicine, presenting with exhaustion from prolonged involvement in gambling activities. The cases serve to highlight some of the physical consequences of prolonged gambling.

  4. Local Exhaust Ventilation

    DEFF Research Database (Denmark)

    Madsen, Ulla; Breum, N. O.; Nielsen, Peter V.

    Capture efficiency of a local exhaust system, e.g. a kitchen hood, should include only contaminants being direct captured. In this study basic concepts of local exhaust capture efficiency are given, based on the idea of a control box. A validated numerical model is used for estimation of the capt......Capture efficiency of a local exhaust system, e.g. a kitchen hood, should include only contaminants being direct captured. In this study basic concepts of local exhaust capture efficiency are given, based on the idea of a control box. A validated numerical model is used for estimation...

  5. Effect of diesel exhaust generated by a city bus engine on stress responses and innate immunity in primary bronchial epithelial cell cultures.

    Science.gov (United States)

    Zarcone, M C; Duistermaat, E; Alblas, M J; van Schadewijk, A; Ninaber, D K; Clarijs, V; Moerman, M M; Vaessen, D; Hiemstra, P S; Kooter, I M

    2018-04-01

    Harmful effects of diesel emissions can be investigated via exposures of human epithelial cells, but most of previous studies have largely focused on the use of diesel particles or emission sources that are poorly representative of engines used in current traffic. We studied the cellular response of primary bronchial epithelial cells (PBECs) at the air-liquid interface (ALI) to the exposure to whole diesel exhaust (DE) generated by a Euro V bus engine, followed by treatment with UV-inactivated non-typeable Haemophilus influenzae (NTHi) bacteria to mimic microbial exposure. The effect of prolonged exposures was investigated, as well as the difference in the responses of cells from COPD and control donors and the effect of emissions generated during a cold start. HMOX1 and NQO1 expression was transiently induced after DE exposure. DE inhibited the NTHi-induced expression of human beta-defensin-2 (DEFB4A) and of the chaperone HSPA5/BiP. In contrast, expression of the stress-induced PPP1R15A/GADD34 and the chemokine CXCL8 was increased in cells exposed to DE and NTHi. HMOX1 induction was significant in both COPD and controls, while inhibition of DEFB4A expression by DE was significant only in COPD cells. No significant differences were observed when comparing cellular responses to cold engine start and prewarmed engine emissions. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Hyperventilation and exhaustion syndrome.

    Science.gov (United States)

    Ristiniemi, Heli; Perski, Aleksander; Lyskov, Eugene; Emtner, Margareta

    2014-12-01

    Chronic stress is among the most common diagnoses in Sweden, most commonly in the form of exhaustion syndrome (ICD-10 classification - F43.8). The majority of patients with this syndrome also have disturbed breathing (hyperventilation). The aim of this study was to investigate the association between hyperventilation and exhaustion syndrome. Thirty patients with exhaustion syndrome and 14 healthy subjects were evaluated with the Nijmegen Symptom Questionnaire (NQ). The participants completed questionnaires about exhaustion, mental state, sleep disturbance, pain and quality of life. The evaluation was repeated 4 weeks later, after half of the patients and healthy subjects had engaged in a therapy method called 'Grounding', a physical exercise inspired by African dance. The patients reported significantly higher levels of hyperventilation as compared to the healthy subjects. All patients' average score on NQ was 26.57 ± 10.98, while that of the healthy subjects was 15.14 ± 7.89 (t = -3.48, df = 42, p exhaustion (Karolinska Exhaustion Scale KES r = 0.772, p exhaustion scores and scores of depression and anxiety. The conclusion is that hyperventilation is common in exhaustion syndrome patients and that it can be reduced by systematic physical therapy such as Grounding. © 2013 The Authors. Scandinavian Journal of Caring Sciences published by John Wiley & Sons Ltd on behalf of Nordic College of Caring Science.

  7. Unemployment Benefit Exhaustion

    DEFF Research Database (Denmark)

    Filges, Trine; Pico Geerdsen, Lars; Knudsen, Anne-Sofie Due

    2015-01-01

    This systematic review studied the impact of exhaustion of unemployment benefits on the exit rate out of unemployment and into employment prior to benefit exhaustion or shortly thereafter. Method: We followed Campbell Collaboration guidelines to prepare this review, and ultimately located 12...

  8. Towards optimisation of induced pluripotent cell culture: Extracellular acidification results in growth arrest of iPSC prior to nutrient exhaustion.

    Science.gov (United States)

    Wilmes, Anja; Rauch, Caroline; Carta, Giada; Kern, Georg; Meier, Florian; Posch, Wilfried; Wilflingseder, Doris; Armstrong, Lyle; Lako, Majlinda; Beilmann, Mario; Gstraunthaler, Gerhard; Jennings, Paul

    2017-12-01

    Human induced pluripotent stem cells (iPSC) have the potential to radically reduce the number of animals used in both toxicological science and disease elucidation. One initial obstacle culturing iPSC is that they require daily medium exchange. This study attempts to clarify why and propose some practical solutions. Two iPSC lineages were fed at different intervals in a full growth area (FGA) or a restricted growth area (RGA). The FGA consisted of a well coated with Matrigel™ and the RGA consisted of a coated coverslip placed in a well. Glucose, lactate, extracellular pH and cell cycle phases were quantified. Without daily feeding, FGA cultured iPSC had significantly reduced growth rates by day 2 and began to die by day 3. In contrast, RGA cultured cells grew to confluence over 3days. Surprisingly, glucose was not exhausted under any condition. However, extracellular pH reached 6.8 after 72h in FGA cultures. Artificially reducing medium pH to 6.8 also inhibited glycolysis and initiated an increase in G0/G1 phase of the cell cycle, while adding an additional 10mM bicarbonate to the medium increased glycolysis rates. This study demonstrates that iPSC are highly sensitive to extracellular acidification, a likely limiting factor in maintenance of proliferative and pluripotent status. Culturing iPSC in RGA prevents rapid extracellular acidification, while still maintaining pluripotency and allowing longer feeding cycles. Copyright © 2017. Published by Elsevier Ltd.

  9. T-cell dysfunction in HIV infection: anergy due to defective antigen-presenting cell function?

    NARCIS (Netherlands)

    Meyaard, L.; Schuitemaker, H.; Miedema, F.

    1993-01-01

    Before CD4+ T cells are depleted, T cells in asymptomatic HIV-infected individuals are functionally abnormal. These T cells are programmed for death, are non-responsive and fail to produce interleukin-2 after antigenic stimulation. Our view is that these different T-cell abnormalities are explained

  10. Telomeres and HIV-1 infection: in search of exhaustion

    NARCIS (Netherlands)

    Wolthers, K. C.; Miedema, F.

    1998-01-01

    Telomere length analysis could be helpful in determining if exhaustion and replicative senescence are involved in HIV-1 pathogenesis. Evidence that CD8+ T cells have shorter telomeres may point towards an increased turnover of CD8+ T cells and exhaustion of the CD8+ T-cell responses in HIV-1

  11. Aircraft exhaust sulfur emissions

    Energy Technology Data Exchange (ETDEWEB)

    Brown, R.C.; Anderson, M.R.; Miake-Lye, R.C.; Kolb, C.E. [Aerodyne Research, Inc., Billerica, MA (United States). Center for Chemical and Environmental Physics; Sorokin, A.A.; Buriko, Y.I. [Scientific Research Center `Ecolen`, Moscow (Russian Federation)

    1997-12-31

    The extent to which fuel sulfur is converted to SO{sub 3} during combustion and the subsequent turbine flow in supersonic and subsonic aircraft engines is estimated numerically. The analysis is based on: a flamelet model with non-equilibrium sulfur chemistry for the combustor, and a one-dimensional, two-stream model with finite rate chemical kinetics for the turbine. The results indicate that between 2% and 10% of the fuel sulfur is emitted as SO{sub 3}. It is also shown that, for a high fuel sulfur mass loading, conversion in the turbine is limited by the level of atomic oxygen at the combustor exit, leading to higher SO{sub 2} oxidation efficiency at lower fuel sulfur loadings. While SO{sub 2} and SO{sub 3} are the primary oxidation products, the model results further indicate H{sub 2}SO{sub 4} levels on the order of 0.1 ppm for supersonic expansions through a divergent nozzle. This source of fully oxidized S(6) (SO{sub 3} + H{sub 2}SO{sub 4}) exceeds previously calculated S(6) levels due to oxidation of SO{sub 2} by OH in the exhaust plume outside the engine nozzle. (author) 26 refs.

  12. Diesel exhaust particles increase IL-1β-induced human β-defensin expression via NF-κB-mediated pathway in human lung epithelial cells

    Directory of Open Access Journals (Sweden)

    Lee Chun

    2006-05-01

    Full Text Available Abstract Background Human β-defensin (hBD-2, antimicrobial peptide primarily induced in epithelial cells, is a key factor in the innate immune response of the respiratory tract. Several studies showed increased defensin levels in both inflammatory lung diseases, such as cystic fibrosis, diffuse panbronchiolitis, idiopathic pulmonary fibrosis and acute respiratory distress syndrome, and infectious diseases. Recently, epidemiologic studies have demonstrated acute and serious adverse effects of particulate air pollution on respiratory health, especially in people with pre-existing inflammatory lung disease. To elucidate the effect of diesel exhaust particles (DEP on pulmonary innate immune response, we investigated the hBD-2 and interleukin-8 (IL-8 expression to DEP exposure in interleukin-1 beta (IL-1β-stimulated A549 cells. Results IL-1β markedly up-regulated the hBD-2 promoter activity, and the subsequent DEP exposure increased dose-dependently the expression of hBD-2 and inflammatory cytokine IL-8 at the transcriptional level. In addition, DEP further induced the NF-κB activation in IL-1β-stimulated A549 cells more rapidly than in unstimulated control cells, which was showed by nuclear translocation of p65 NF-κB and degradation of IκB-α. The experiment using two NF-κB inhibitors, PDTC and MG132, confirmed that this increase of hBD-2 expression following DEP exposure was regulated through NF-κB-mediated pathway. Conclusion These results demonstrated that DEP exposure increases the expression of antimicrobial peptide and inflammatory cytokine at the transcriptional level in IL-1β-primed A549 epithelial cells and suggested that the increase is mediated at least partially through NF-κB activation. Therefore, DEP exposure may contribute to enhance the airway-responsiveness especially on the patients suffering from chronic respiratory disease.

  13. Obtaining the Wakefield Due to Cell-to-Cell Misalignments in a Linear Accelerator Structure

    OpenAIRE

    Bane, Karl L. F.; Li, Zenghai

    2001-01-01

    A linear accelerator structure, such as will be used in the linacs of the JLC/NLC collider, is composed of on the order of 100 cells. The cells are constructed as individual cups that are brazed together to form a structure. Fabrication error will result in slight cell-to-cell misalignments along the finished structure. In this report we derive an approximation to the transverse wakefield of a structure with cell-to-cell misalignments in terms of the eigenfunctions and eigenvalues of the erro...

  14. Tokamak fusion reactor exhaust

    International Nuclear Information System (INIS)

    Harrison, M.F.A.; Harbour, P.J.; Hotston, E.S.

    1981-08-01

    This report presents a compilation of papers dealing with reactor exhaust which were produced as part of the TIGER Tokamak Installation for Generating Electricity study at Culham. The papers are entitled: (1) Exhaust impurity control and refuelling. (2) Consideration of the physical problems of a self-consistent exhaust and divertor system for a long burn Tokamak. (3) Possible bundle divertors for INTOR and TIGER. (4) Consideration of various magnetic divertor configurations for INTOR and TIGER. (5) A appraisal of divertor experiments. (6) Hybrid divertors on INTOR. (7) Refuelling and the scrape-off layer of INTOR. (8) Simple modelling of the scrape-off layer. (9) Power flow in the scrape-off layer. (10) A model of particle transport within the scrape-off plasma and divertor. (11) Controlled recirculation of exhaust gas from the divertor into the scrape-off plasma. (U.K.)

  15. Exhaust gas circulation apparatus

    Energy Technology Data Exchange (ETDEWEB)

    Shibano, K.

    1975-01-10

    An exhaust gas recirculation apparatus is described. An exhaust gas recirculation tube is connected between the exhaust pipe and the intake tube and the opening of the tube; the amount of recirculated gas is regulated by a piston-type cycle control valve which is connected to the throttle valve of the carburetor through an arm. The arm is designed in a two-step linkage so that the cycle valve closes the recirculation tube when the throttle valve is at a fully opened angle and a small angle. Therefore, no exhaust gas recirculation occurs when the automobile is in full power, idling, or low running conditions. This prevents lowered engine power at these conditions.

  16. MEMS measurements of single cell stiffness decay due to cyclic mechanical loading.

    Science.gov (United States)

    Barazani, Bruno; Warnat, Stephan; MacIntosh, Andrew J; Hubbard, Ted

    2017-08-25

    The goal of this study was to measure the mechanical stiffness of individual cells and to observe changes due to the application of repeated cell mechanical loads. 28 single baker's yeast cells (Saccharomyces cerevisiae) were fatigue tested and had their stiffness measured during repetitive loading cycles performed by a MEMS squeezer in aqueous media. Electrothermal micro-actuators compressed individual cells against a reference back spring; cell and spring motions were measured using a FFT image analysis technique with ~10 nm resolution. Cell stiffness was calculated based on measurements of cell elongation vs. applied force which resulted in stiffness values in the 2-10 N/m range. The effect of increased force was studied for cells mechanically cycled 37 times. Cell stiffness decreased as the force and the cycle number increased. After 37 loading cycles (~4 min), forces of 0.24, 0.29, 0.31, and 0.33 μN caused stiffness drops of 5%, 13%, 31% and 41% respectively. Cells force was then set to 0.29 μN and cells were tested over longer runs of 118 and 268 cycles. After 118 cycles (~12 min) cells experienced an average stiffness drop of 68%. After 268 cycles (~25 min) cells had a stiffness drop of 77%, and appeared to reach a stiffness plateau of 20-25% of the initial stiffness after approximately 200 cycles.

  17. Analyses of extracted biodiesel and petroleum diesel exhaust particle and the effects on endothelial cell toxicity and antioxidant response.

    Science.gov (United States)

    Biodiesel (BD) is a renewable energy source and is readily substituted in diesel engines. Combustion of biodiesel is cleaner due to the efficiency of the fuel to completely combust. Biodiesel combustion emissions contain less CO, PAHs, aldehydes, and particulate matter (PM) mas...

  18. Contact-independent cell death of human microglial cells due to pathogenic Naegleria fowleri trophozoites.

    Science.gov (United States)

    Kim, Jong-Hyun; Kim, Daesik; Shin, Ho-Joon

    2008-12-01

    Free-living Naegleria fowleri leads to a fatal infection known as primary amebic meningoencephalitis in humans. Previously, the target cell death could be induced by phagocytic activity of N. fowleri as a contact-dependent mechanism. However, in this study we investigated the target cell death under a non-contact system using a tissue-culture insert. The human microglial cells, U87MG cells, co-cultured with N. fowleri trophozoites for 30 min in a non-contact system showed morphological changes such as the cell membrane destruction and a reduction in the number. By fluorescence-activated cell sorter (FACS) analysis, U87MG cells co-cultured with N. fowleri trophozoites in a non-contact system showed a significant increase of apoptotic cells (16%) in comparison with that of the control or N. fowleri lysate. When U87MG cells were co-cultured with N. fowleri trophozoites in a non-contact system for 30 min, 2 hr, and 4 hr, the cytotoxicity of amebae against target cells was 40.5, 44.2, and 45.6%, respectively. By contrast, the cytotoxicity of non-pathogenic N. gruberi trophozoites was 10.2, 12.4, and 13.2%, respectively. These results suggest that the molecules released from N. fowleri in a contact-independent manner as well as phagocytosis in a contact-dependent manner may induce the host cell death.

  19. Impaired germ cell development due to compromised cell cycle progression in Skp2-deficient mice

    Directory of Open Access Journals (Sweden)

    Nakayama Keiko

    2006-04-01

    Full Text Available Abstract Background The gonads are responsible for the production of germ cells through both mitosis and meiosis. Skp2 is the receptor subunit of an SCF-type ubiquitin ligase and is a major regulator of the progression of cells into S phase of the cell cycle, which it promotes by mediating the ubiquitin-dependent degradation of p27, an inhibitor of cell proliferation. However, the role of the Skp2-p27 pathway in germ cell development remains elusive. Results We now show that disruption of Skp2 in mice results in a marked impairment in the fertility of males, with the phenotypes resembling Sertoli cell-only syndrome in men. Testes of Skp2-/- mice manifested pronounced germ cell hypoplasia accompanied by massive apoptosis in spermatogenic cells. Flow cytometry revealed an increased prevalence of polyploidy in spermatozoa, suggesting that the aneuploidy of these cells is responsible for the induction of apoptosis. Disruption of the p27 gene of Skp2-/- mice restored germ cell development, indicating that the testicular hypoplasia of Skp2-/- animals is attributable to the antiproliferative effect of p27 accumulation. Conclusion Our results thus suggest that compromised cell cycle progression caused by the accumulation of p27 results in aneuploidy and the induction of apoptosis in gonadal cells of Skp2-/- mice. The consequent reduction in the number of mature gametes accounts for the decreased fertility of these animals. These findings reinforce the importance of the Skp2-p27 pathway in cell cycle regulation and in germ cell development.

  20. Diesel exhaust particles induced release of interleukin 6 and 8 by (primed) human bronchial epithelial cells (BEAS 2B) in vitro.

    Science.gov (United States)

    Steerenberg, P A; Zonnenberg, J A; Dormans, J A; Joon, P N; Wouters, I M; van Bree, L; Scheepers, P T; Van Loveren, H

    1998-01-01

    Several epidemiological studies have recently shown associations of increased premature mortality rates with ambient particulate air pollution. Diesel exhaust particles (DEP) may constitute an important part of (ultra)fine particulate air pollution in urban areas and may therefore contribute to its toxicity. Epithelial lining of the respiratory tract may be the first target of the toxic effects of DEP, that upon exposure may release pro-inflammatory mediators such as interleukin 6 and 8 (IL-6, IL-8), ultimately causing airway tissue damage and immune alterations. In this study the effects of in vitro DEP exposure (0.04-0.33 mg/mL) on IL-6, IL-8 production by a human bronchial epithelial cell line (BEAS-2B) were investigated. For comparison, the production of interleukins during exposure to silica and titanium oxide (TiO2) were also studied, representing relatively toxic and non-toxic particles, respectively. Scanning and transmission electron microscopy showed that the size of the DEP particles ranged between 25 to 35 nm and that DEP was phagocytized by BEAS-2B cells. An increase in IL-6 and IL-8 production (11- and 4-fold, respectively) was found after 24 or 48 h of exposure to DEP compared to the non-exposed cells. This increase was lower compared to silica (17- and 3.3-fold) and higher as compared to TiO2 which showed no increase for IL-6 and IL-8. To study the DEP effect on inflammation-primed cells, BEAS-2B cells were exposed to both tumor necrosis factor-alpha (TNF-alpha) and subsequently to DEP. Exposure to TNF-alpha caused a strong increase in IL-6 and IL-8 production. Additive effects on the IL-6 and IL-8 production by BEAS-2B cells were found after TNF-alpha priming and subsequently exposure to DEP, only at a low dose of DEP and TNF-alpha (0.05-0.2 ng/mL). In conclusion, BEAS-2B phagocytized DEP and produced an increased amount of IL-6 and IL-8. In TNF-alpha primed BEAS-2B cells, DEP increased interleukin production only at low concentrations of DEP and

  1. Glutathione-S-transferase M1 regulation of diesel exhaust particle-induced pro-inflammatory mediator expression in normal human bronchial epithelial cells

    Directory of Open Access Journals (Sweden)

    Wu Weidong

    2012-08-01

    Full Text Available Abstract Background Diesel exhaust particles (DEP contribute substantially to ambient particulate matter (PM air pollution in urban areas. Inhalation of PM has been associated with increased incidence of lung disease in susceptible populations. We have demonstrated that the glutathione S-transferase M1 (GSTM1 null genotype could aggravate DEP-induced airway inflammation in human subjects. Given the critical role airway epithelial cells play in the pathogenesis of airway inflammation, we established the GSTM1 deficiency condition in primary bronchial epithelial cells from human volunteers with GSTM1 sufficient genotype (GSTM1+ using GSTM1 shRNA to determine whether GSTM1 deficiency could exaggerate DEP-induced expression of interleukin-8 (IL-8 and IL-1β proteins. Furthermore, the mechanisms underlying GSTM1 regulation of DEP-induced IL-8 and IL-1β expression were also investigated. Methods IL-8 and IL-1β protein levels were measured using enzyme-linked immunosorbent assay. GSTM1 deficiency in primary human bronchial epithelial cells was achieved using lentiviral GSTM1 shRNA particles and verified using real-time polymerase chain reaction and immunoblotting. Intracellular reactive oxygen species (ROS production was evaluated using flow cytometry. Phosphorylation of protein kinases was detected using immunoblotting. Results Exposure of primary human bronchial epithelial cells (GSTM1+ to 25-100 μg/ml DEP for 24 h significantly increased IL-8 and IL-1β protein expression. Knockdown of GSTM1 in these cells further elevated DEP-induced IL-8 and IL-1β expression, implying that GSTM1 deficiency aggravated DEP-induced pro-inflammatory response. DEP stimulation induced the phosphorylation of extracellular signal-regulated kinase (ERK and Akt, the downstream kinase of phosphoinositide 3-kinase (PI3K, in GSTM1+ bronchial epithelial cells. Pharmacological inhibition of ERK kinase and PI3K activity blocked DEP-induced IL-8 and IL-1β expression. DEP

  2. Ileum perforation due to cytomegalovirus infection in a patient with adult T-cell leukemia.

    Science.gov (United States)

    Nishimura, Takeshi; Nakao, Atsunori; Okamoto, Ayana; Kihara, Takako; Hirota, Seiichi; Fujisaki, Noritomo; Kotani, Joji

    2016-04-01

    A 73-year-old woman was transferred to our department due to severe abdominal pain with peritonitis. Her laboratory data showed that her white blood cell count was elevated to more than 50,000/mm 3 . Antibodies to HTLV-I were positive and we made the diagnosis of adult T-cell leukemia (ATL). Emergency laparotomy was performed and revealed two separate small perforations of the ileum, requiring bowel resection. Immunohistochemistry for cytomegalovirus (CMV) antigen revealed positive staining in the intestinal stromal cells. Despite surgery and antiviral therapy with ganciclovir, she died after 28 days. Adult T-cell leukemia patients may present acute abdominal pain due to intestinal perforation caused by CMV infection. We should be aware of CMV infection as one of the pathogens causing acute abdominal crises such as massive hemorrhage or visceral perforation.

  3. The aryl hydrocarbon receptor-mediated and genotoxic effects of fractionated extract of standard reference diesel exhaust particle material in pulmonary, liver and prostate cells.

    Science.gov (United States)

    Pálková, Lenka; Vondráček, Jan; Trilecová, Lenka; Ciganek, Miroslav; Pěnčíková, Kateřina; Neča, Jiří; Milcová, Alena; Topinka, Jan; Machala, Miroslav

    2015-04-01

    Diesel exhaust particles (DEP) and the associated complex mixtures of organic pollutants, such as polycyclic aromatic hydrocarbons (PAHs), or their derivatives, have been suggested to exert deleterious effects on human health. We used a set of defined cellular models representing liver, lung and prostate tissues, in order to compare non-genotoxic and genotoxic effects of crude and fractionated extract of a standard reference DEP material - SRM 1650b. We focused on the aryl hydrocarbon receptor (AhR)-mediated activity, modulation of cell proliferation, formation of DNA adducts, oxidative DNA damage, and induction of DNA damage responses, including evaluation of apoptosis, and phosphorylation of p53 tumor suppressor and checkpoint kinases (Chk). Both PAHs and the polar aromatic compounds contributed to the AhR-mediated activity of DEP-associated organic pollutants. The principal identified AhR agonists included benzo[k]fluoranthene, indeno[1,2,3-c,d]pyrene, chrysene and several non-priority PAHs, including benzochrysenes and methylated PAHs. In contrast to PAHs, polar compounds contributed more significantly to overall formation of DNA adducts associated with phosphorylation of p53, Chk1 or Chk2, and partly with apoptosis. Therefore, more attention should be paid to identification of DEP-associated polar organic compounds, contributing to the AhR activation and cytotoxic/genotoxic effects of complex airborne mixtures of organic contaminants produced by diesel engines. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Toxic Effects of the Major Components of Diesel Exhaust in Human Alveolar Basal Epithelial Cells (A549

    Directory of Open Access Journals (Sweden)

    Pavel Rossner

    2016-08-01

    Full Text Available We investigated the toxicity of benzo[a]pyrene (B[a]P, 1-nitropyrene (1-NP and 3-nitrobenzanthrone (3-NBA in A549 cells. Cells were treated for 4 h and 24 h with: B[a]P (0.1 and 1 μM, 1-NP (1 and 10 μM and 3-NBA (0.5 and 5 μM. Bulky DNA adducts, lipid peroxidation, DNA and protein oxidation and mRNA expression of CYP1A1, CYP1B1, NQO1, POR, AKR1C2 and COX2 were analyzed. Bulky DNA adducts were induced after both treatment periods; the effect of 1-NP was weak. 3-NBA induced high levels of bulky DNA adducts even after 4-h treatment, suggesting rapid metabolic activation. Oxidative DNA damage was not affected. 1-NP caused protein oxidation and weak induction of lipid peroxidation after 4-h incubation. 3-NBA induced lipid peroxidation after 24-h treatment. Unlike B[a]P, induction of the aryl hydrocarbon receptor, measured as mRNA expression levels of CYP1A1 and CYP1B1, was low after treatment with polycyclic aromatic hydrocarbon (PAH nitro-derivatives. All test compounds induced mRNA expression of NQO1, POR, and AKR1C2 after 24-h treatment. AKR1C2 expression indicates involvement of processes associated with reactive oxygen species generation. This was supported further by COX2 expression induced by 24-h treatment with 1-NP. In summary, 3-NBA was the most potent genotoxicant, whereas 1-NP exhibited the strongest oxidative properties.

  5. Getting older can be exhausting.

    Science.gov (United States)

    Mittal, Rohit; Ford, Mandy L; Coopersmith, Craig M

    2014-07-29

    Sepsis is a disease that affects primarily the aged. Although mortality is higher in both older septic patients and aged septic mice, the mechanisms underlying decreased survival in older hosts are incompletely understood. New work by Inoue and colleagues demonstrates persistent inflammation and T-cell exhaustion in older septic patients and aged septic mice. The clinical significance of these findings is manifested not only in increased mortality but also in a marked difference in secondary infections in older patients as long as a month following ICU admission.

  6. Novel exosome-targeted T-cell-based vaccine counteracts T-cell anergy and converts CTL exhaustion in chronic infection via CD40L signaling through the mTORC1 pathway.

    Science.gov (United States)

    Wang, Rong; Xu, Aizhang; Zhang, Xueying; Wu, Jie; Freywald, Andrew; Xu, Jianqing; Xiang, Jim

    2017-06-01

    CD8 + cytotoxic T lymphocyte (CTL) exhaustion is a chief issue for ineffective virus elimination in chronic infectious diseases. We generated novel ovalbumin (OVA)-specific OVA-Texo and HIV-specific Gag-Texo vaccines inducing therapeutic immunity. To assess their therapeutic effect in chronic infection, we developed a new chronic infection model by i.v. infecting C57BL/6 mice with the OVA-expressing adenovirus AdVova. During chronic AdVova infection, mouse CTLs were found to express the inhibitory molecules programmed cell-death protein-1 (PD-1) and lymphocyte-activation gene-3 (LAG-3) and to be functionally exhausted, showing a significant deficiency in T-cell proliferation, IFN-γ production and cytolytic effects. Naive CD8 + T cells upregulated inhibitory PD-ligand 1 (PD-L1), B- and T-lymphocyte attenuator and T-cell anergy-associated molecules (Grail and Itch) while down-regulating the proliferative response upon stimulation in mice with chronic infection. Remarkably, the OVA-Texo vaccine counteracted T-cell anergy and converted CTL exhaustion. The latter was associated with (i) the upregulation of a marker for CTL functionality, diacetylated histone-H3 (diAcH3), (ii) a fourfold increase in CTLs, occurring independent of host DCs or CD4 + T cells, and (iii) the restoration of CTL IFN-γ production and cytotoxicity. In vivo OVA-Texo-stimulated CTLs upregulated the activities of the mTORC1 pathway-related molecules Akt, S6, eIF4E and T-bet, and treatment of the CTLs with an mTORC1 inhibitor, rapamycin, significantly reduced the OVA-Texo-induced increase in CTLs. Interestingly, OVA-Texo-mediated CD40L signaling played a critical role in the observed immunological effects. Importantly, the Gag-Texo vaccine induced Gag-specific therapeutic immunity in chronic infection. Therefore, this study should have a serious impact on the development of new therapeutic vaccines for human immunodeficiency virus (HIV-1) infection.

  7. cgCorrect: a method to correct for confounding cell-cell variation due to cell growth in single-cell transcriptomics

    Science.gov (United States)

    Blasi, Thomas; Buettner, Florian; Strasser, Michael K.; Marr, Carsten; Theis, Fabian J.

    2017-06-01

    Accessing gene expression at a single-cell level has unraveled often large heterogeneity among seemingly homogeneous cells, which remains obscured when using traditional population-based approaches. The computational analysis of single-cell transcriptomics data, however, still imposes unresolved challenges with respect to normalization, visualization and modeling the data. One such issue is differences in cell size, which introduce additional variability into the data and for which appropriate normalization techniques are needed. Otherwise, these differences in cell size may obscure genuine heterogeneities among cell populations and lead to overdispersed steady-state distributions of mRNA transcript numbers. We present cgCorrect, a statistical framework to correct for differences in cell size that are due to cell growth in single-cell transcriptomics data. We derive the probability for the cell-growth-corrected mRNA transcript number given the measured, cell size-dependent mRNA transcript number, based on the assumption that the average number of transcripts in a cell increases proportionally to the cell’s volume during the cell cycle. cgCorrect can be used for both data normalization and to analyze the steady-state distributions used to infer the gene expression mechanism. We demonstrate its applicability on both simulated data and single-cell quantitative real-time polymerase chain reaction (PCR) data from mouse blood stem and progenitor cells (and to quantitative single-cell RNA-sequencing data obtained from mouse embryonic stem cells). We show that correcting for differences in cell size affects the interpretation of the data obtained by typically performed computational analysis.

  8. Pulmonary tumor thrombotic microangiopathy with cor pulmonale due to desmoplastic small round cell tumor.

    Science.gov (United States)

    Sadimin, Evita T; Collier, Adrienne G; Gaffney, Joseph W; Fyfe, Billie

    2012-04-01

    A 12-year-old boy presented acutely after an episode of syncope with perioral cyanosis. He died 19 hours after admission due to cor pulmonale as a complication of metastatic desmoplastic small round cell tumor in the lungs with associated tumor thrombotic microangiopathy. Copyright © 2012 Mosby, Inc. All rights reserved.

  9. The Herpes Simplex Virus Latency-Associated Transcript Gene Is Associated with a Broader Repertoire of Virus-Specific Exhausted CD8+ T Cells Retained within the Trigeminal Ganglia of Latently Infected HLA Transgenic Rabbits

    Science.gov (United States)

    Srivastava, Ruchi; Dervillez, Xavier; Khan, Arif A.; Chentoufi, Aziz A.; Chilukuri, Sravya; Shukr, Nora; Fazli, Yasmin; Ong, Nicolas N.; Afifi, Rasha E.; Osorio, Nelson; Geertsema, Roger; Nesburn, Anthony B.

    2016-01-01

    ABSTRACT Persistent pathogens, such as herpes simplex virus 1 (HSV-1), have evolved a variety of immune evasion strategies to avoid being detected and destroyed by the host's immune system. A dynamic cross talk appears to occur between the HSV-1 latency-associated transcript (LAT), the only viral gene that is abundantly transcribed during latency, and the CD8+ T cells that reside in HSV-1 latently infected human and rabbit trigeminal ganglia (TG). The reactivation phenotype of TG that are latently infected with wild-type HSV-1 or with LAT-rescued mutant (i.e., LAT+ TG) is significantly higher than TG latently infected with LAT-null mutant (i.e., LAT− TG). Whether LAT promotes virus reactivation by selectively shaping a unique repertoire of HSV-specific CD8+ T cells in LAT+ TG is unknown. In the present study, we assessed the frequency, function, and exhaustion status of TG-resident CD8+ T cells specific to 40 epitopes derived from HSV-1 gB, gD, VP11/12, and VP13/14 proteins, in human leukocyte antigen (HLA-A*0201) transgenic rabbits infected ocularly with LAT+ versus LAT– virus. Compared to CD8+ T cells from LAT– TG, CD8+ T cells from LAT+ TG (i) recognized a broader selection of nonoverlapping HSV-1 epitopes, (ii) expressed higher levels of PD-1, TIM-3, and CTLA-4 markers of exhaustion, and (iii) produced less tumor necrosis factor alpha, gamma interferon, and granzyme B. These results suggest a novel immune evasion mechanism by which the HSV-1 LAT may contribute to the shaping of a broader repertoire of exhausted HSV-specific CD8+ T cells in latently infected TG, thus allowing for increased viral reactivation. IMPORTANCE A significantly larger repertoire of dysfunctional (exhausted) HSV-specific CD8+ T cells were found in the TG of HLA transgenic rabbits latently infected with wild-type HSV-1 or with LAT-rescued mutant (i.e., LAT+ TG) than in a more restricted repertoire of functional HSV-specific CD8+ T cells in the TG of HLA transgenic rabbits latently

  10. Forces due to surface water measured by force microscopy. Consequences for anchoring biological cells to surfaces

    International Nuclear Information System (INIS)

    Schilcher, K.

    1997-05-01

    Interaction forces in 'Scanning Force Microscopy' (SFM). Force curves revealed exponentially decaying, attractive forces between silicon tip and silicon sample in aqueous media. Replacing the silicon sample by a sheet of mica, the interaction forces had both, an attractive and a repulsive component. Addition of salts generally reduced the forces. At 500 mM salt concentration, the attractive force became quantized with a residual force value of 23 pN. The attractive force is attributed to the gain in energy of water molecules which are released from surface water into free water during tip-sample approach. This conclusion is supported by a statistical model. The repulsive force contribution in the case of mica, is caused by hydration forces due to the spatial organization of crystalline water on the mica surface. Anchoring of biological cells. Molecular resolution of cell surfaces by SFM requires cell anchoring without interference with cell physiology. For this a novel strategy, 'hydrophobic anchoring' was designed. It avoids strong attractive forces between cell and by using a flexible spacer molecule. It establishes anchoring by a lipid (bound to the spacer), which weakly interacts with the hydrophobic core of the cell membrane. The method was subjected to tests using RBL-2H3, CH0 αβ and HEK-293 cells. The strength of cell anchoring was assayed by shear forces. In all cases 'hydrophobic anchoring' via a spacer caused elective anchoring much beyond controls. Such cell anchoring was employed for the imaging of RBL-2H3 cells by SFM. Images showed considerable finer details than images of loosely adsorbed cells. With about 50 rim resolution, SFM succeeded in imaging microvilli, filopodia, single cytoskeletal fibers (microtubules, microfilaments) and vesicles. In addition, as a consequence of cell stimulation upon ionomycin treatment, lamellae formation and the appearance of secretory granules on top of them were observed which indicates the viability of anchored

  11. Histological and finite element analysis of cell death due to irreversible electroporation.

    Science.gov (United States)

    Long, G; Bakos, G; Shires, P K; Gritter, L; Crissman, J W; Harris, J L; Clymer, J W

    2014-12-01

    Irreversible electroporation (IRE) has been shown to be an effective method of killing cells locally. In contrast to radiofrequency ablation, the mechanism by which cells are thought to die via IRE is the creation of pores in cell membranes, without substantial increase in tissue temperature. To determine the degree to which cell death is non-thermal, we evaluated IRE in porcine hepatocytes in vivo. Using pulse widths of 10 µs, bursts of 3 kV square-wave pulses were applied through a custom probe to the liver of an anesthetized pig. Affected tissue was evaluated histologically via stainings of hematoxylin & eosin (H&E), nitroblue tetrazolium (NBT) to monitor cell respiration and TUNEL to gauge apoptosis. Temperature was measured during the application of electroporation, and heat transfer was modeled via finite element analysis. Cell death was calculated via Arrhenius kinetics. Four distinct zones were observed within the ring return electrode; heat-fixed tissue, coagulation, necrotic, and viable. The Arrhenius damage integral estimated complete cell death only in the first zone, where the temperature exceeded 70°C, and partial or no cell death in the other zones, where maximum temperature was approximately 45°C. Except for a limited area near the electrode tip, cell death in IRE is predominantly due to a non-thermal mechanism.

  12. Performance of multi-junction cells due to illumination distribution across the cell surface

    International Nuclear Information System (INIS)

    Schultz, R.D.; Vorster, F.J; Dyk, E.E van

    2012-01-01

    This paper addresses the influence of illumination distribution on the performance of a high concentration photovoltaic (HCPV) module. CPV systems comprise of optical elements as well as mechanical tracking to concentrate the solar flux onto the solar receiver as well as to keep the system on track with the sun. The performance of the subcells of the multi-junction concentrator cell depends on the optical alignment of the system. Raster scanning of the incident intensity in the optical plane of the receiver and corresponding I–V measurements were used to investigate the influence of illumination distribution on performance. The results show that the illumination distribution that differs between cells does affect the performance of the module. The performance of the subcells of the multi-junction concentrator cell also depends on the optical alignment of the system.

  13. Performance of multi-junction cells due to illumination distribution across the cell surface

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, R.D., E-mail: s206029578@live.nmmu.ac.za [Nelson Mandela University, Physics Department, P.O. Box 77000, 6031, Port Elizabeth (South Africa); Vorster, F.J; Dyk, E.E van [Nelson Mandela University, Physics Department, P.O. Box 77000, 6031, Port Elizabeth (South Africa)

    2012-05-15

    This paper addresses the influence of illumination distribution on the performance of a high concentration photovoltaic (HCPV) module. CPV systems comprise of optical elements as well as mechanical tracking to concentrate the solar flux onto the solar receiver as well as to keep the system on track with the sun. The performance of the subcells of the multi-junction concentrator cell depends on the optical alignment of the system. Raster scanning of the incident intensity in the optical plane of the receiver and corresponding I-V measurements were used to investigate the influence of illumination distribution on performance. The results show that the illumination distribution that differs between cells does affect the performance of the module. The performance of the subcells of the multi-junction concentrator cell also depends on the optical alignment of the system.

  14. Aerodynamic Control of Exhaust

    DEFF Research Database (Denmark)

    Hyldgård, Carl-Erik

    In the autumn of 1985 the Unive!Sity of Aalborg was approached by the manufacturer C. P. Aaberg, who had obtained aerodynilmic control of the exhaust by means of injection. The remaining investigations comprising optimizations of the system with regard to effect, consumption, requirements...

  15. Proinflammatory effects of diesel exhaust particles from moderate blend concentrations of 1st and 2nd generation biodiesel in BEAS-2B bronchial epithelial cells-The FuelHealth project.

    Science.gov (United States)

    Skuland, Tonje S; Refsnes, Magne; Magnusson, Pål; Oczkowski, Michał; Gromadzka-Ostrowska, Joanna; Kruszewski, Marcin; Mruk, Remigiusz; Myhre, Oddvar; Lankoff, Anna; Øvrevik, Johan

    2017-06-01

    Biodiesel fuel fuels are introduced at an increasing extent as a more carbon-neutral alternative to reduce CO 2 -emissions, compared to conventional diesel fuel. In the present study we have investigated the impact of increasing the use of 1st generation fatty acid methyl ester (FAME) biodiesel from current 7% blend (B7) to 20% blend (B20), or by increasing the biodiesel content by adding 2nd generation hydrotreated vegetable oil (HVO) based biodiesel (SHB; Synthetic Hydrocarbon Biofuel) on toxicity of diesel exhaust particles (DEP) in an in vitro system. Human bronchial epithelial BEAS-2B cells were exposed for 4 and 20h to DEP from B7, B20 and SHB at different concentrations, and examined for effects on gene expression of interleukin 6 (IL-6), CXCL8 (IL-8), CYP1A1 and heme oxygenase-1 (HO-1). The results show that both B20 and SHB were more potent inducers of IL-6 expression compared to B7. Only B20 induced statistically significant increases in CXCL8 expression. By comparison the rank order of potency to induce CYP1A1 was SHB>B7>B20. No statistically significant difference were observed form HO-1 expression, suggesting that the differences in cytokine responses were not due to oxidative stress. The results show that even moderate increases in biodiesel blends, from 7% to 20%, may increase the proinflammatory potential of emitted DEP in BEAS-2B cells. This effect was observed for both addition of 1st generation FAME and 2nd generation HVO biodiesel. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Unusual Cushing’s Syndrome and Hypercalcitoninaemia due to a Small Cell Prostate Carcinoma

    Directory of Open Access Journals (Sweden)

    Antonio Balestrieri

    2016-01-01

    Full Text Available A 75-year-old man was hospitalized because of severe hypokalaemia due to ACTH dependent Cushing’s syndrome. Total body computed tomography (TBCT and 68 Gallium DOTATATE PET/CT localized a voluminous prostate tumour. A subsequent transurethral prostate biopsy documented a small cell carcinoma positive for ACTH and calcitonin and negative for prostatic specific antigen (PSA at immunocytochemical study; serum prostatic specific antigen (PSA was normal. Despite medical treatments, Cushing’s syndrome was not controlled and the patient’s clinical condition progressively worsened. Surgical resection was excluded; the patient underwent a cycle of chemotherapy followed by febrile neutropenia and fatal intestinal perforation. This case report describes a rare case of Cushing’s syndrome and hypercalcitoninaemia due to a small cell carcinoma of the prostate, a rare tumour with very few therapeutic options and negative prognosis.

  17. Investigation of dental pulp stem cells isolated from discarded human teeth extracted due to aggressive periodontitis.

    Science.gov (United States)

    Sun, Hai-Hua; Chen, Bo; Zhu, Qing-Lin; Kong, Hui; Li, Qi-Hong; Gao, Li-Na; Xiao, Min; Chen, Fa-Ming; Yu, Qing

    2014-11-01

    Recently, human dental pulp stem cells (DPSCs) isolated from inflamed dental pulp tissue have been demonstrated to retain some of their pluripotency and regenerative potential. However, the effects of periodontal inflammation due to periodontitis and its progression on the properties of DPSCs within periodontally compromised teeth remain unknown. In this study, DPSCs were isolated from discarded human teeth that were extracted due to aggressive periodontitis (AgP) and divided into three experimental groups (Groups A, B and C) based on the degree of inflammation-induced bone resorption approaching the apex of the tooth root before tooth extraction. DPSCs derived from impacted or non-functional third molars of matched patients were used as a control. Mesenchymal stem cell (MSC)-like characteristics, including colony-forming ability, proliferation, cell cycle, cell surface antigens, multi-lineage differentiation capability and in vivo tissue regeneration potential, were all evaluated in a patient-matched comparison. It was found that STRO-1- and CD146-positive DPSCs can be isolated from human teeth, even in very severe cases of AgP. Periodontal inflammation and its progression had an obvious impact on the characteristics of DPSCs isolated from periodontally affected teeth. Although all the isolated DPSCs in Groups A, B and C showed decreased colony-forming ability and proliferation rate (P periodontitis. Furthermore, the cells did not necessarily show significantly diminished in vitro multi-differentiation potential. Only DPSCs from Group A and the Control group formed dentin-like matrix in vivo when cell-seeded biomaterials were transplanted directly into an ectopic transplantation model. However, when cell-seeded scaffolds were placed in the root fragments of human teeth, all the cells formed significant dentin- and pulp-like tissues. The ability of DPSCs to generate dental tissues decreased when the cells were isolated from periodontally compromised teeth (P

  18. Exhaust gas filter

    International Nuclear Information System (INIS)

    Wada, Tadamasa; Hiraki, Akimitsu.

    1993-01-01

    A filter material formed by joining glass clothes to both surfaces of a glass fiber non-woven fabric is used. The filter material is disposed at the inside of a square filter material support frame made of stainless steel. The filter material is attached in a zig-zag manner in the flowing direction of the exhaust gases so as to increase the filtration area. Separators, for example, made of stainless steel are inserted between the filter materials. The separator is corrugated so as to sandwich and support the filter materials from both sides by the ridged crests. The longitudinal bottom of the separator formed by corrugating it defines a flow channel of the exhaustion gases. The longitudinal bottom is also used as a channel for back blowing air. With such a constitution, combustion gases of radioactive miscellaneous solid wastes can be completely filtered. In addition, a back wash can be conducted under high temperature. (I.N.)

  19. Severe Dyspnea due to Pulmonary Metastasis of Renal Cell Carcinoma: Is Cytoreductive Surgery of Value

    Directory of Open Access Journals (Sweden)

    Mohammad Kazem Moslemi

    2010-09-01

    Full Text Available Here, we present a case in which cytoreductive surgery, like left radical nephrectomy, was effective in the treatment of pulmonary metastases and para-aortic metastases from renal cell carcinoma. A 28-year-old man underwent left radical nephrectomy with pulmonary metastasectomy for the diagnosis of metastatic left renal cell carcinoma. The histologic diagnosis was clear cell carcinoma G2, pT3N1M1. He subsequently underwent i.m. administration of IFN-α, 5 million units per day for 30 days. The nasal oxygen mask was weaned gradually, and the chest tube was removable due to cessation of the continuous production of pleural fluid. The patient was well until one year after operation.

  20. The herpes simplex virus 1 latency-associated transcript promotes functional exhaustion of virus-specific CD8+ T cells in latently infected trigeminal ganglia: a novel immune evasion mechanism.

    Science.gov (United States)

    Chentoufi, Aziz A; Kritzer, Elizabeth; Tran, Michael V; Dasgupta, Gargi; Lim, Chang Hyun; Yu, David C; Afifi, Rasha E; Jiang, Xianzhi; Carpenter, Dale; Osorio, Nelson; Hsiang, Chinhui; Nesburn, Anthony B; Wechsler, Steven L; BenMohamed, Lbachir

    2011-09-01

    Following ocular herpes simplex virus 1 (HSV-1) infection of C57BL/6 mice, HSV-specific (HSV-gB(498-505) tetramer(+)) CD8(+) T cells are induced, selectively retained in latently infected trigeminal ganglia (TG), and appear to decrease HSV-1 reactivation. The HSV-1 latency-associated transcript (LAT) gene, the only viral gene that is abundantly transcribed during latency, increases reactivation. Previously we found that during latency with HSV-1 strain McKrae-derived viruses, more of the total TG resident CD8 T cells expressed markers of exhaustion with LAT(+) virus compared to LAT(-) virus. Here we extend these findings to HSV-1 strain 17syn+-derived LAT(+) and LAT(-) viruses and to a virus expressing just the first 20% of LAT. Thus, the previous findings were not an artifact of HSV-1 strain McKrae, and the LAT function involved mapped to the first 1.5 kb of LAT. Importantly, to our knowledge, we show here for the first time that during LAT(+) virus latency, most of the HSV-1-specific TG resident CD8 T cells were functionally exhausted, as judged by low cytotoxic function and decreased gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) production. This resulted in LAT(-) TG having more functional HSV-gB(498-505) tetramer(+) CD8(+) T cells compared to LAT(+) TG. In addition, LAT expression, in the absence of other HSV-1 gene products, appeared to be able to directly or indirectly upregulate both PD-L1 and major histocompatibility complex class I (MHC-I) on mouse neuroblastoma cells (Neuro2A). These findings may constitute a novel immune evasion mechanism whereby the HSV-1 LAT directly or indirectly promotes functional exhaustion (i.e., dysfunction) of HSV-specific CD8(+) T cells in latently infected TG, resulting in increased virus reactivation.

  1. Unusual Upper Gastrointestinal Bleeding due to Late Metastasis from Renal Cell Carcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Wen-Tsan Chang

    2004-03-01

    Full Text Available A case of recurrent massive upper gastrointestinal bleeding originating from metastatic renal cell carcinoma is reported. A 63-year-old woman underwent right nephrectomy 9 years previously and experienced no recurrence during follow-up. A gradually enlarging ulcerative tumor over the bulb of the duodenum and four subsequent episodes of massive bleeding from this tumor occurred between June 2001 and March 2002. The patient underwent surgery in April 2002 for intractable bleeding from the tumor. Renal cell carcinoma metastasis to the duodenum was confirmed from the surgical specimen. Upper gastrointestinal bleeding due to malignancy is very rare and the duodenum is the least frequently involved site. Furthermore, a solitary late renal cell carcinoma metastasis 9 years after a nephrectomy is extremely uncommon. This case suggests that life-long follow-up of renal cell carcinoma patients is necessary, owing to unpredictable behavior and the possibility of long disease-free intervals. In nephrectomized patients suffering from gastrointestinal bleeding, complete evaluation, especially endoscopic examination, is indicated. The possibility of late recurrent renal cell carcinoma metastasis to the gastrointestinal tract should be kept in mind, although it is rare. If the patient is fit for surgery, metastatectomy is the first choice of treatment.

  2. Intrahepatic Vγ9Vδ2 T-cells from HCV-infected patients show an exhausted phenotype but can inhibit HCV replication.

    Science.gov (United States)

    Cimini, E; Bordoni, V; Sacchi, A; Visco-Comandini, U; Montalbano, M; Taibi, C; Casetti, R; Lalle, E; D'Offizi, G; Capobianchi, M R; Agrati, C

    2018-01-02

    Hepatitis C virus (HCV) persistence results from inefficiencies of both innate and adaptive immune responses to eradicate the infection. A functional impairment of circulating Vγ9Vδ2 T-cells was described but few data are available on Vγ9Vδ2 T-cells in the liver that, however, represents the battlefield in the HCV/host interaction. Aim of this work was to compare circulating and intrahepatic Vγ9Vδ2 T-cells in chronic HCV-infected patients (HCV pos ) and in HCV-negative (HCV neg ) subjects. Phenotypic and functional analysis was performed by flow cytometry. Anti-HCV activity was analyzed by using an in vitro autologous liver culture system. Independently from HCV infection, the liver was enriched of Vγ9Vδ2 T-cells expressing an effector/activated phenotype. In contrast, an enrichment of PD-1 expressing Vγ9Vδ2 T-cells was observed both in the peripheral blood and in the liver of HCV pos patients, probably due to a persistent antigenic stimulation. Moreover, a lower frequency of IFN-γ producing Vγ9Vδ2 T-cells was observed in the liver of HCV pos patients, suggesting a functional impairment in the cytokine production in HCV pos liver. Despite this hypo-responsiveness, intrahepatic Vγ9Vδ2 T-cells are able to exert an anti-HCV activity after specific stimulation. Altogether, our data show that HCV infection induced a dysregulation of intrahepatic Vγ9Vδ2 T cells that maintain their anti-HCV activity after specific stimulation. A study aimed to evaluate the mechanisms of the antiviral activity may be useful to identify new pathways able to improve Vγ9Vδ2 T-cells intrahepatic function during HCV infection. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Choice of Cell Source in Cell-Based Therapies for Retinal Damage due to Age-Related Macular Degeneration: A Review

    Directory of Open Access Journals (Sweden)

    Sudhakar John

    2013-01-01

    Full Text Available Background. Age-related macular degeneration (AMD is a complex disorder that affects primarily the macula involving the retinal pigment epithelium (RPE but also to a certain extent the photoreceptor layer and the retinal neurons. Cell transplantation is a promising option for AMD and clinical trials are underway using different cell types. Methods. We hypothesize that instead of focusing on a particular cell source for concurrent regeneration of all the retinal layers and also to prevent exhaustive research on an array of cell sources for regeneration of each layer, the choice should depend on, precisely, which layer is damaged. Results. Thus, for a damage limited to the retinal pigment epithelial (RPE layer, the choice we suggest would be RPE cells. When the damage extends to rods and cones, the choice would be bone marrow stem cells and when retinal neurons are involved, relatively immature stem cell populations with an inherent capacity to yield neuronal lineage such as hematopoietic stem cells, embryonic stem cells, or induced pluripotent stem cells can be tried. Conclusion. This short review will prove to be a valuable guideline for those working on cell therapy for AMD to plan their future directions of research and therapy for this condition.

  4. Acute cor pulmonale due to pulmonary tumour thrombotic microangiopathy from renal cell carcinoma.

    Science.gov (United States)

    Story, Maria; Kwon, Sook Kyung; Robinson, Robert; Fortis, Spyridon

    2017-06-28

    We report the case of a previously healthy man who presented with subacute dyspnoea after a long drive. He developed hypoxic respiratory failure, thought secondary to a massive pulmonary embolism and was treated with tissue plasminogen activator but died in the hospital despite aggressive medical measures. Autopsy revealed pulmonary tumour thrombotic microangiopathy (PTTM) from papillary renal cell carcinoma. PTTM is a rare clinicopathological syndrome that clinically results in symptoms of dyspnoea and right heart failure. Pathologically, a localised paraneoplastic process evolves from tumour microemboli in the pulmonary arterioles, resulting in fibrocellular proliferation and narrowing of the vessels, causing subacute right heart failure. To our knowledge, this is the first case of PTTM due to papillary renal cell carcinoma. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. Realizing 'integral control' in living cells: how to overcome leaky integration due to dilution?

    Science.gov (United States)

    Qian, Yili; Del Vecchio, Domitilla

    2018-02-01

    A major problem in the design of synthetic genetic circuits is robustness to perturbations and uncertainty. Because of this, there have been significant efforts in recent years in finding approaches to implement integral control in genetic circuits. Integral controllers have the unique ability to make the output of a process adapt perfectly to disturbances. However, implementing an integral controller is challenging in living cells. This is because a key aspect of any integral controller is a 'memory' element that stores the accumulation (integral) of the error between the output and its desired set-point. The ability to realize such a memory element in living cells is fundamentally challenged by the fact that all biomolecules dilute as cells grow, resulting in a 'leaky' memory that gradually fades away. As a consequence, the adaptation property is lost. Here, we propose a general principle for designing integral controllers such that the performance is practically unaffected by dilution. In particular, we mathematically prove that if the reactions implementing the integral controller are all much faster than dilution, then the adaptation error due to integration leakiness becomes negligible. We exemplify this design principle with two synthetic genetic circuits aimed at reaching adaptation of gene expression to fluctuations in cellular resources. Our results provide concrete guidance on the biomolecular processes that are most appropriate for implementing integral controllers in living cells. © 2018 The Author(s).

  6. DNA damage and cytotoxicity in type II lung epithelial (A549) cell cultures after exposure to diesel exhaust and urban street particles

    DEFF Research Database (Denmark)

    Danielsen, Pernille Høgh; Loft, Steffen; Møller, Peter

    2008-01-01

    can be reproduced independently, but exposure to such samples may not mimic the effects observed after exposure to authentic air pollution particles. This study was designed to compare the DNA oxidizing effects of authentic street particles with SRM1650 and SRM2975. The authentic street particles were...... be due to the much higher level of transition metals. CONCLUSION: Authentic street particles and SRMs differ in their ability to oxidize DNA in a cell-free environment, whereas cell culture experiments indicate that the particle preparations elicit a similar alteration of the level of DNA damage...... and small differences in cytotoxicity. Although it cannot be ruled out that SRMs and authentic street particles might elicit different effects in animal experimental models, this study indicates that on the cellular level, SRM1650 and SRM2975 are suitable surrogate samples for the study of authentic street...

  7. Population attributable fraction of Esophageal squamous cell carcinoma due to smoking and alcohol in Uganda

    International Nuclear Information System (INIS)

    Okello, Samson; Churchill, Cristina; Owori, Rogers; Nasasira, Benson; Tumuhimbise, Christine; Abonga, Charles Lagoro; Mutiibwa, David; Christiani, David C.; Corey, Kathleen E.

    2016-01-01

    Despite the high rates and regional variation of esophageal squamous cell carcinoma (ESCC) in East Africa, the contributions of smoking and alcohol to the ESCC burden in the general population are unknown. We conducted a case-control study of patients presenting for upper gastrointestinal endoscopic examination at Mbarara Regional Referral Hospital, Uganda. Sociodemographic data including smoking and alcohol intake were collected prior to endoscopy. Cases were those with histological diagnosis of ESCC and controls were participants with normal endoscopic examination and gastritis/duodentitis or normal histology. We used odds ratios associated with ESCC risk to determine the population attributable fractions for smoking, alcohol use, and a combination of smoking and alcohol use among adults aged 30 years or greater who underwent upper gastrointestinal endoscopy. Our study consisted of 67 cases and 142 controls. Median age was 51 years (IQR 40–64); and participants were predominantly male (59 %). Dysphagia and/or odynophagia as indications for endoscopy were significantly more in cases compared to controls (72 % vs 6 %, p < 0.0001). Male gender and increasing age were statistically associated with ESCC. In the unadjusted models, the population attributable fraction of ESCC due to male gender was 55 %, female gender - 49 %, smoking 20 %, alcohol 9 % and a combination of alcohol & smoking 15 %. After adjusting for gender and age, the population attributable fraction of ESCC due to smoking, alcohol intake and a combination of alcohol & smoking were 16, 10, and 13 % respectively. In this population, 13 % of esophageal squamous cell carcinoma cases would be avoided if smoking and alcohol use were discontinued. These results suggest that other important risk factors for ESCC in southwestern Uganda remain unknown

  8. Lifespan differences in hematopoietic stem cells are due to imperfect repair and unstable mean-reversion.

    Directory of Open Access Journals (Sweden)

    Hans B Sieburg

    2013-04-01

    Full Text Available The life-long supply of blood cells depends on the long-term function of hematopoietic stem cells (HSCs. HSCs are functionally defined by their multi-potency and self-renewal capacity. Because of their self-renewal capacity, HSCs were thought to have indefinite lifespans. However, there is increasing evidence that genetically identical HSCs differ in lifespan and that the lifespan of a HSC is predetermined and HSC-intrinsic. Lifespan is here defined as the time a HSC gives rise to all mature blood cells. This raises the intriguing question: what controls the lifespan of HSCs within the same animal, exposed to the same environment? We present here a new model based on reliability theory to account for the diversity of lifespans of HSCs. Using clonal repopulation experiments and computational-mathematical modeling, we tested how small-scale, molecular level, failures are dissipated at the HSC population level. We found that the best fit of the experimental data is provided by a model, where the repopulation failure kinetics of each HSC are largely anti-persistent, or mean-reverting, processes. Thus, failure rates repeatedly increase during population-wide division events and are counteracted and decreased by repair processes. In the long-run, a crossover from anti-persistent to persistent behavior occurs. The cross-over is due to a slow increase in the mean failure rate of self-renewal and leads to rapid clonal extinction. This suggests that the repair capacity of HSCs is self-limiting. Furthermore, we show that the lifespan of each HSC depends on the amplitudes and frequencies of fluctuations in the failure rate kinetics. Shorter and longer lived HSCs differ significantly in their pre-programmed ability to dissipate perturbations. A likely interpretation of these findings is that the lifespan of HSCs is determined by preprogrammed differences in repair capacity.

  9. Automotive Fuel and Exhaust Systems.

    Science.gov (United States)

    Irby, James F.; And Others

    Materials are provided for a 14-hour course designed to introduce the automotive mechanic to the basic operations of automotive fuel and exhaust systems incorporated on military vehicles. The four study units cover characteristics of fuels, gasoline fuel system, diesel fuel systems, and exhaust system. Each study unit begins with a general…

  10. Exhaustive Training Increases Uncoupling Protein 2 Expression and Decreases Bcl-2/Bax Ratio in Rat Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    W. Y. Liu

    2013-01-01

    Full Text Available This work investigates the effects of oxidative stress due to exhaustive training on uncoupling protein 2 (UCP2 and Bcl-2/Bax in rat skeletal muscles. A total of 18 Sprague-Dawley female rats were randomly divided into three groups: the control group (CON, the trained control group (TC, and the exhaustive trained group (ET. Malondialdehyde (MDA, superoxide dismutase (SOD, xanthine oxidase (XOD, ATPase, UCP2, and Bcl-2/Bax ratio in red gastrocnemius muscles were measured. Exhaustive training induced ROS increase in red gastrocnemius muscles, which led to a decrease in the cell antiapoptotic ability (Bcl-2/Bax ratio. An increase in UCP2 expression can reduce ROS production and affect mitochondrial energy production. Thus, oxidative stress plays a significant role in overtraining.

  11. Toxicity of aged gasoline exhaust particles to normal and diseased airway epithelia.

    Science.gov (United States)

    Künzi, Lisa; Krapf, Manuel; Daher, Nancy; Dommen, Josef; Jeannet, Natalie; Schneider, Sarah; Platt, Stephen; Slowik, Jay G; Baumlin, Nathalie; Salathe, Matthias; Prévôt, André S H; Kalberer, Markus; Strähl, Christof; Dümbgen, Lutz; Sioutas, Constantinos; Baltensperger, Urs; Geiser, Marianne

    2015-06-29

    Particulate matter (PM) pollution is a leading cause of premature death, particularly in those with pre-existing lung disease. A causative link between particle properties and adverse health effects remains unestablished mainly due to complex and variable physico-chemical PM parameters. Controlled laboratory experiments are required. Generating atmospherically realistic aerosols and performing cell-exposure studies at relevant particle-doses are challenging. Here we examine gasoline-exhaust particle toxicity from a Euro-5 passenger car in a uniquely realistic exposure scenario, combining a smog chamber simulating atmospheric ageing, an aerosol enrichment system varying particle number concentration independent of particle chemistry, and an aerosol deposition chamber physiologically delivering particles on air-liquid interface (ALI) cultures reproducing normal and susceptible health status. Gasoline-exhaust is an important PM source with largely unknown health effects. We investigated acute responses of fully-differentiated normal, distressed (antibiotics-treated) normal, and cystic fibrosis human bronchial epithelia (HBE), and a proliferating, single-cell type bronchial epithelial cell-line (BEAS-2B). We show that a single, short-term exposure to realistic doses of atmospherically-aged gasoline-exhaust particles impairs epithelial key-defence mechanisms, rendering it more vulnerable to subsequent hazards. We establish dose-response curves at realistic particle-concentration levels. Significant differences between cell models suggest the use of fully-differentiated HBE is most appropriate in future toxicity studies.

  12. DNA damage and cytotoxicity in type II lung epithelial (A549 cell cultures after exposure to diesel exhaust and urban street particles

    Directory of Open Access Journals (Sweden)

    Møller Peter

    2008-04-01

    Full Text Available Abstract Background Exposure to air pollution particles has been acknowledged to be associated with excess generation of oxidative damage to DNA in experimental model systems and humans. The use of standard reference material (SRM, such as SRM1650 and SRM2975, is advantageous because experiments can be reproduced independently, but exposure to such samples may not mimic the effects observed after exposure to authentic air pollution particles. This study was designed to compare the DNA oxidizing effects of authentic street particles with SRM1650 and SRM2975. The authentic street particles were collected at a traffic intensive road in Copenhagen, Denmark. Results All of the particles generated strand breaks and oxidized purines in A549 lung epithelial cells in a dose-dependent manner and there were no overt differences in their potency. The exposures also yielded dose-dependent increase of cytotoxicity (as lactate dehydrogenase release and reduced colony forming ability with slightly stronger cytotoxicity of SRM1650 than of the other particles. In contrast, only the authentic street particles were able to generate 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG in calf thymus DNA, which might be due to the much higher level of transition metals. Conclusion Authentic street particles and SRMs differ in their ability to oxidize DNA in a cell-free environment, whereas cell culture experiments indicate that the particle preparations elicit a similar alteration of the level of DNA damage and small differences in cytotoxicity. Although it cannot be ruled out that SRMs and authentic street particles might elicit different effects in animal experimental models, this study indicates that on the cellular level, SRM1650 and SRM2975 are suitable surrogate samples for the study of authentic street particles.

  13. Phosphor-doping enhanced efficiency in bilayer organic solar cells due to longer exciton diffusion length

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Kang [Siyuan Laboratory, Department of Physics, Jinan University, Guangzhou 510632 (China); Hou, Lintao, E-mail: thlt@jnu.edu.cn [Siyuan Laboratory, Department of Physics, Jinan University, Guangzhou 510632 (China); Wang, Ping, E-mail: wangping996633@163.com [Siyuan Laboratory, Department of Physics, Jinan University, Guangzhou 510632 (China); Xia, Yuxin [Siyuan Laboratory, Department of Physics, Jinan University, Guangzhou 510632 (China); Chen, Dongcheng; Xiao, Biao [Institute of Polymer Optoelectronic Materials and Devices, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou 510640 (China)

    2014-07-01

    We fabricated bilayer organic solar cells (OSCs) in the structure glass/ITO/PEDOT:PSS/PtOEP:MEH-PPV/C{sub 70}/Al, where MEH-PPV was doped with platinum octaethylporphyrin (PtOEP). Enhanced exciton diffusion length (L{sub D}) is realized via converting generated singlet excitons to triplet excitons. Investigation based on transfer matrix simulations reveals that it is the extended exciton L{sub D} of the doping donor layer that leads to the short-circuit current density (J{sub sc}) and power conversion efficiency (PCE) improvement, when compared with those of the OSCs with a non-doping donor layer. As a result of the increased L{sub D}, J{sub sc} and PCE increase by 30% and 42% respectively for a device with 5 wt% PtOEP-doped 25 nm-thick donor layer. Meanwhile, by doping with phosphorescent bis(1-phenyl-isoquinoline)(acetylacetonato)iridium(III), the reduction in open-circuit voltage and the comparable J{sub sc} are shown due to its higher HOMO level and higher LUMO level, leading to the decrease of PCE. It demonstrates that doping a polymer with a suitable phosphorescent molecule is an important approach to be considered to increase the exciton L{sub D}. - Highlights: • Optical model based on transfer matrix method was used to study phosphor-doped organic planar hetero-junction solar cells. • The enhanced exciton diffusion length was experimentally investigated by absorption, PL, time-resolved transient PL, J–V and EQE curves. • Only suitable phosphor dyes can increase exciton diffusion length.

  14. Health effects of exhaust particles

    Energy Technology Data Exchange (ETDEWEB)

    Pihlava, T.; Uuppo, M.; Niemi, S.

    2013-11-01

    This report introduces general information about diesel particles and their health effects. The purpose of this report is to introduce particulate matter pollution and present some recent studies made regarding the health effects of particulate matter. The aim is not to go very deeply into the science, but instead to keep the text understandable for the average layman. Particulate matter is a complex mixture of extremely small particles and liquid droplets. These small particles are made up of a number of components that include for example acids, such as nitrates and sulphates, as well as organic chemicals, metals and dust particles from the soil. Particulate matter comes from several sources, such as transportation emissions, industrial emissions, forest fires, cigarette smoke, volcanic ash and climate variations. Particles are divided into coarse particles with diameters less than 10 ..m, fine particles with diameters smaller than 2.5 ..m and ultra-fine particles with diameters less than 0.1 ..m. The particulate matter in diesel exhaust gas is a highly complex mixture of organic, inorganic, solid, volatile and partly volatile compounds. Many of these particles do not form until they reach the air. Many carcinogenic compounds have been found in diesel exhaust gas and it is considered carcinogenic to humans. Particulate matter can cause several health effects, such as premature death in persons with heart or lung disease, cancer, nonfatal heart attacks, irregular heartbeat, aggravated asthma, decreased lung function and an increase in respiratory symptoms, such as irritation of the airways, coughing or difficulty breathing. It is estimated that in Finland about 1300 people die prematurely due to particles and the economic loss in the EU due to the health effects of particles can be calculated in the billions. Ultra-fine particles are considered to be the most harmful to human health. Ultrafine particles usually make the most of their quantity and surface area

  15. Alloimmunization due to red cell antibodies in Rhesus positive Omani Pregnant Women: Maternal and Perinatal outcome

    Directory of Open Access Journals (Sweden)

    Tamima Al-Dughaishi

    2015-01-01

    Full Text Available Objective: This study is aimed to determine the prevalence of alloimmunization due to antibodies to red blood cell (RBC antigens (other than rhesus [Rh] antigen and report the maternal, perinatal, and neonatal outcomes. Materials and Methods: A retrospective review of medical records of all patients with minor RBCs antibodies alloimmunization who were followed and delivered at Sultan Qaboos University Hospital, Oman from June 2011 to June 2013. Maternal characteristics, antibody type, antibody titer in addition to perinatal and neonatal outcomes were reviewed. Results: There were 1160 patients with Rh positive status in the study. The most common ABO blood group was O, followed by A, B, and AB. We found 33 out of 1160 Rh positive women alloimmunized with minor RBCs antibodies that gave a prevalence of minor RBCs alloimmunization of 2.7%. The most frequent antibody was anti-E 38%, followed by anti-c 17% and anti-kell 17%. 6 of these 33 patients were identified to have significant antibody titer, and two cases showed evidence of fetal anemia. Only one case required an intrauterine blood transfusion. The most common neonatal complication was jaundice in 53%, followed by respiratory distress syndrome in 28%. Two cases complicated by neonatal anemia required a postnatal blood transfusion. Conclusion: Alloimmunization with anti-E, anti-c, and anti-kell were the most common antibodies among the study group. Minor RBCs alloimmunization was an important cause of neonatal morbidity.

  16. Conjunctival Squamous Cell Carcinoma due to Long-term Placement of Ocular Prosthesis.

    Science.gov (United States)

    Hayashi, Ayato; Komoto, Masakazu; Matsumura, Takashi; Horiguchi, Masatoshi; Tanaka, Rica; Arakawa, Atsushi; Mizuno, Hiroshi

    2015-03-01

    Conjunctival squamous cell carcinoma (SCC) arising from an anophthalmic socket is quite rare, with few reports in the English literature. A 59-year-old man who had used an ocular prosthesis for 40 years had not removed the ocular prosthesis at all during the last 5 years. He had developed a mass on his entire right upper eyelid, and biopsy revealed a moderately differentiated SCC. Orbital exenteration including the upper and lower eyelid skin was performed. The defect was reconstructed with a free forearm flap followed by the placement of a facial epithesis. The pathology revealed an intraepithelial carcinoma on the upper palpebral conjunctiva, which seemed to infiltrate exclusively from that site to the upper eyelid and into the orbit. Other risk factors were not detected; therefore, chronic irritation or microtrauma of the upper conjunctiva from the prosthesis due to persistent prosthesis placement could have been the main trigger for the development of SCC. In cases where the ocular prosthesis is not fitted properly or removed appropriately, clinicians should be aware of this possible long-term consequence.

  17. Conjunctival Squamous Cell Carcinoma due to Long-term Placement of Ocular Prosthesis

    Directory of Open Access Journals (Sweden)

    Ayato Hayashi, MD

    2015-03-01

    Full Text Available Summary: Conjunctival squamous cell carcinoma (SCC arising from an anophthalmic socket is quite rare, with few reports in the English literature. A 59-year-old man who had used an ocular prosthesis for 40 years had not removed the ocular prosthesis at all during the last 5 years. He had developed a mass on his entire right upper eyelid, and biopsy revealed a moderately differentiated SCC. Orbital exenteration including the upper and lower eyelid skin was performed. The defect was reconstructed with a free forearm flap followed by the placement of a facial epithesis. The pathology revealed an intraepithelial carcinoma on the upper palpebral conjunctiva, which seemed to infiltrate exclusively from that site to the upper eyelid and into the orbit. Other risk factors were not detected; therefore, chronic irritation or microtrauma of the upper conjunctiva from the prosthesis due to persistent prosthesis placement could have been the main trigger for the development of SCC. In cases where the ocular prosthesis is not fitted properly or removed appropriately, clinicians should be aware of this possible long-term consequence.

  18. Secondary Involvement of the Mandible due to Basal Cell Carcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Pegah Mosannen Mozaffary

    2015-05-01

    Full Text Available Basal cell carcinoma (BCC is the most common cutaneous malignancy among Caucasians. Rare examples of aggressive and neglected BCC have been reported. Here we report a unique case of a neglected BCC with significant jaw involvement. A 50-year-old female, referred by an otorhinologist, presented with a large ulcer on her chin, which was extended to her mandibular vestibule. The ulcer was 9×5.5 cm in size, and tissue destruction, necrosis was observed in the central portion, and the mandibular bone was exposed. On intraoral examination, tooth mobility and severe bone loss were evident. Due to the primary cutaneous origin of the lesion, BCC was considered as preliminary diagnosis. Biopsy was performed and diagnosis of BCC was confirmed. The diseased mandibular bone was resected and reconstructed with a surgical plate. The soft tissue defect was reconstructed with deltopectoral flap. The patient refused secondary stage plastic surgery. Although BCC is not a lethal malignancy, if left untreated and neglected, it can result in severe destruction, disfigurement, and even mortality.

  19. Impedance Spectroscopic Investigation of the Degraded Dye-Sensitized Solar Cell due to Ageing

    Directory of Open Access Journals (Sweden)

    Parth Bhatt

    2016-01-01

    Full Text Available This paper investigates the effect of ageing on the performance of dye-sensitized solar cells (DSCs. The electrical characterization of fresh and degraded DSCs is done under AM1.5G spectrum and the current density-voltage (J-V characteristics are analyzed. Short circuit current density (JSC decreases significantly whereas a noticeable increase in open circuit voltage is observed. These results have been further investigated electroanalytically using electrochemical impedance spectroscopy (EIS. An increase in net resistance results in a lower JSC for the degraded DSC. This decrease in current is mainly due to degradation of TiO2-dye interface, which is observed from light and dark J-V characteristics and is further confirmed by EIS measurements. A reduction in the chemical capacitance of the degraded DSC is observed, which is responsible for the shifting of Fermi level with respect to conduction band edge that further results in an increase of open circuit voltage for the degraded DSC. It is also confirmed from EIS that the degradation leads to a better contact formation between the electrolyte and Pt electrode, which improves the fill factor of the DSC. But the recombination throughout the DSC is found to increase along with degradation. This study suggests that the DSC should be used under low illumination conditions and around room temperature for a longer life.

  20. A Cinnamon-Derived Procyanidin Compound Displays Anti-HIV-1 Activity by Blocking Heparan Sulfate- and Co-Receptor- Binding Sites on gp120 and Reverses T Cell Exhaustion via Impeding Tim-3 and PD-1 Upregulation.

    Directory of Open Access Journals (Sweden)

    Bridgette Janine Connell

    Full Text Available Amongst the many strategies aiming at inhibiting HIV-1 infection, blocking viral entry has been recently recognized as a very promising approach. Using diverse in vitro models and a broad range of HIV-1 primary patient isolates, we report here that IND02, a type A procyanidin polyphenol extracted from cinnamon, that features trimeric and pentameric forms displays an anti-HIV-1 activity against CXCR4 and CCR5 viruses with 1-7 μM ED50 for the trimer. Competition experiments, using a surface plasmon resonance-based binding assay, revealed that IND02 inhibited envelope binding to CD4 and heparan sulphate (HS as well as to an antibody (mAb 17b directed against the gp120 co-receptor binding site with an IC50 in the low μM range. IND02 has thus the remarkable property of simultaneously blocking gp120 binding to its major host cell surface counterparts. Additionally, the IND02-trimer impeded up-regulation of the inhibitory receptors Tim-3 and PD-1 on CD4+ and CD8+ cells, thereby demonstrating its beneficial effect by limiting T cell exhaustion. Among naturally derived products significantly inhibiting HIV-1, the IND02-trimer is the first component demonstrating an entry inhibition property through binding to the viral envelope glycoprotein. These data suggest that cinnamon, a widely consumed spice, could represent a novel and promising candidate for a cost-effective, natural entry inhibitor for HIV-1 which can also down-modulate T cell exhaustion markers Tim-3 and PD-1.

  1. Variations in insulin responsiveness in rat fat cells are due to metabolic differences rather than insulin binding

    DEFF Research Database (Denmark)

    Hansen, Finn Mølgård; Nilsson, Poul; Sonne, Ole

    1983-01-01

    -insulin to fat cells. Insulin binding was not correlated to the plasma insulin level which however was reflected in the lipoprotein lipase activity in the adipose tissue. In conclusion, these results indicate that variations in insulin responsiveness in fat cells are due to alterations in cellular metabolism...

  2. Highly selective NOx reduction for diesel engine exhaust via an electrochemical system

    DEFF Research Database (Denmark)

    Shao, Jing; Tao, Youkun; Kammer Hansen, Kent

    2016-01-01

    It is challenging to reduce the nitrogen oxides (NOx) in diesel engine exhaust due to the inhibiting effect of excess oxygen. In this study, a novel electrochemical deNOx system was developed, which eliminated the need for additional reducing materials or a sophisticated controlling system as used...... in current diesel after-treatment techniques. The electrochemical system consisted of an electrochemical cell modified with NOx adsorbents and a diesel oxidation catalyst placed upstream of the cell. The system offers highly selective NOx reduction and a strong resistance to oxygen interference with almost...

  3. Viral Immune Evasion Due to Persistence of Activated T Cells Without Effector Function

    OpenAIRE

    Zajac, Allan J.; Blattman, Joseph N.; Murali-Krishna, Kaja; Sourdive, David J.D.; Suresh, M.; Altman, John D.; Ahmed, Rafi

    1998-01-01

    We examined the regulation of virus-specific CD8 T cell responses during chronic lymphocytic choriomeningitis virus (LCMV) infection of mice. Our study shows that within the same persistently infected host, different mechanisms can operate to silence antiviral T cell responses; CD8 T cells specific to one dominant viral epitope were deleted, whereas CD8 T cells responding to another dominant epitope persisted indefinitely. These virus-specific CD8 T cells expressed activation markers (CD69hi,...

  4. Rapid proliferation of daughter cells lacking particular chromosomes due to multipolar mitosis promotes clonal evolution in colorectal cancer cells.

    Science.gov (United States)

    Yang, Chao; Shi, Xiaoyun; Huang, Yun; Zhang, Zhen; Cooke, Howard J; Wang, Mingrong; Shi, Qinghua

    2012-07-15

    Aneuploidy and chromosome instability (CIN) are hallmarks of the vast majority of solid tumors. However, the origins of aneuploid cells are unknown. The aim of this study is to improve our understanding of how aneuploidy and/or CIN arise and of karyotype evolution in cancer cells. By using fluorescence in situ hybridization (FISH) on cells after long-term live cell imaging, we demonstrated that most (> 90%) of the newly generated aneuploid cells resulted from multipolar divisions. Multipolar division occurred in mononucleated and binucleated parental cells, resulting in variation of chromosome compositions in daughter cells. These karyotypes can have the same chromosome number as their mother clone or lack a copy of certain chromosomes. Interestingly, daughter cells that lost a chromosome were observed to survive and form clones with shorter cell cycle duration. In our model of cancer cell evolution, the rapid proliferation of daughter cells from multipolar mitosis promotes colonal evolution in colorectal cancer cells.

  5. Exhaustion of CTL memory and recrudescence of viremia in lymphocytic choriomeningitis virus-infected MHC class II-deficient mice and B cell-deficient mice

    DEFF Research Database (Denmark)

    Thomsen, Allan Randrup; Johansen, J; Marker, O

    1996-01-01

    To study the contribution of CD4+ T cells and B cells to antiviral immunity and long term virus control, MHC class II-deficient and B cell-deficient mice were infected with lymphocytic choriomeningitis virus. In class II-deficient mice, which lack CD4+ T cells, the primary CTL response is virtually...

  6. Change in spectrum of Brownian fluctuations of optically trapped red blood cells due to malarial infection

    Science.gov (United States)

    Saraogi, Vishal; Padmapriya, P.; Paul, Apurba; Tatu, Utpal S.; Natarajan, Vasant

    2010-05-01

    We study the properties of single red blood cells (RBCs) held in an optical-tweezers trap. We observe a change in the spectrum of Brownian fluctuations between RBCs from normal and malaria-infected samples. The change, caused by infection-induced structural changes in the cell, appears as a statistical increase in the mean (by 25%) and standard deviation (by 200%) of the corner frequency measured over ~100 cells. The increase is observed even though the ensemble of cells being measured consists mostly of cells that do not actually host the parasite, but are from an infected pool. This bystander effect appears to vindicate other observations that infected cells can affect the biomechanical properties of uninfected cells. The change is also observed to be independent of the stage of infection and its duration, highlighting its potential for disease detection.

  7. Viral immune evasion due to persistence of activated T cells without effector function.

    Science.gov (United States)

    Zajac, A J; Blattman, J N; Murali-Krishna, K; Sourdive, D J; Suresh, M; Altman, J D; Ahmed, R

    1998-12-21

    We examined the regulation of virus-specific CD8 T cell responses during chronic lymphocytic choriomeningitis virus (LCMV) infection of mice. Our study shows that within the same persistently infected host, different mechanisms can operate to silence antiviral T cell responses; CD8 T cells specific to one dominant viral epitope were deleted, whereas CD8 T cells responding to another dominant epitope persisted indefinitely. These virus-specific CD8 T cells expressed activation markers (CD69(hi), CD44(hi), CD62Llo) and proliferated in vivo but were unable to elaborate any antiviral effector functions. This unresponsive phenotype was more pronounced under conditions of CD4 T cell deficiency, highlighting the importance of CD8- CD4 T cell collaboration in controlling persistent infections. Importantly, in the presence of CD4 T cell help, adequate CD8 effector activity was maintained and the chronic viral infection eventually resolved. The persistence of activated virus-specific CD8 T cells without effector function reveals a novel mechanism for silencing antiviral immune responses and also offers new possibilities for enhancing CD8 T cell immunity in chronically infected hosts.

  8. Concept of Heat Recovery from Exhaust Gases

    Science.gov (United States)

    Bukowska, Maria; Nowak, Krzysztof; Proszak-Miąsik, Danuta; Rabczak, Sławomir

    2017-10-01

    The theme of the article is to determine the possibility of waste heat recovery and use it to prepare hot water. The scope includes a description of the existing sample of coal-fired boiler plant, the analysis of working condition and heat recovery proposals. For this purpose, a series of calculations necessary to identify the energy effect of exhaust temperature decreasing and transferring recovery heat to hot water processing. Heat recover solutions from the exhaust gases channel between boiler and chimney section were proposed. Estimation for the cost-effectiveness of such a solution was made. All calculations and analysis were performed for typical Polish conditions, for coal-fired boiler plant. Typicality of this solution is manifested by the volatility of the load during the year, due to distribution of heat for heating and hot water, determining the load variation during the day. Analysed system of three boilers in case of load variation allows to operational flexibility and adaptation of the boilers load to the current heat demand. This adaptation requires changes in the operating conditions of boilers and in particular assurance of properly conditions for the combustion of fuel. These conditions have an impact on the existing thermal loss and the overall efficiency of the boiler plant. On the boiler plant efficiency affects particularly exhaust gas temperature and the excess air factor. Increasing the efficiency of boilers plant is possible to reach by following actions: limiting the excess air factor in coal combustion process in boilers and using an additional heat exchanger in the exhaust gas channel outside of boilers (economizer) intended to preheat the hot water.

  9. Variations in insulin responsiveness in rat fat cells are due to metabolic differences rather than insulin binding

    DEFF Research Database (Denmark)

    Hansen, Finn Mølgård; Nilsson, Poul; Sonne, Ole

    1983-01-01

    to fat cells. Insulin binding was not correlated to the plasma insulin level which however was reflected in the lipoprotein lipase activity in the adipose tissue. In conclusion, these results indicate that variations in insulin responsiveness in fat cells are due to alterations in cellular metabolism......Insulin resistance was studied by comparing insulin response and insulin binding in four groups of rats. Glucose metabolism in isolated fat cells from male Wistar rats weighing 340 g was less responsive to a supramaximal dose of insulin than glucose metabolism in fat cells from rats weighing 200 g....... Induction of streptozotocin-diabetes in rats weighing 200 g resulted in a marked decrease in the insulin responsiveness of fat cells. Ventromedial hypothalamic lesions of 340 g rats had the opposite effect and restored the insulin responsiveness of fat cells. The responsiveness in the four groups...

  10. Capture of Heat Energy from Diesel Engine Exhaust

    Energy Technology Data Exchange (ETDEWEB)

    Chuen-Sen Lin

    2008-12-31

    Diesel generators produce waste heat as well as electrical power. About one-third of the fuel energy is released from the exhaust manifolds of the diesel engines and normally is not captured for useful applications. This project studied different waste heat applications that may effectively use the heat released from exhaust of Alaskan village diesel generators, selected the most desirable application, designed and fabricated a prototype for performance measurements, and evaluated the feasibility and economic impact of the selected application. Exhaust flow rate, composition, and temperature may affect the heat recovery system design and the amount of heat that is recoverable. In comparison with the other two parameters, the effect of exhaust composition may be less important due to the large air/fuel ratio for diesel engines. This project also compared heat content and qualities (i.e., temperatures) of exhaust for three types of fuel: conventional diesel, a synthetic diesel, and conventional diesel with a small amount of hydrogen. Another task of this project was the development of a computer-aided design tool for the economic analysis of selected exhaust heat recovery applications to any Alaskan village diesel generator set. The exhaust heat recovery application selected from this study was for heating. An exhaust heat recovery system was fabricated, and 350 hours of testing was conducted. Based on testing data, the exhaust heat recovery heating system showed insignificant effects on engine performance and maintenance requirements. From measurements, it was determined that the amount of heat recovered from the system was about 50% of the heat energy contained in the exhaust (heat contained in exhaust was evaluated based on environment temperature). The estimated payback time for 100% use of recovered heat would be less than 3 years at a fuel price of $3.50 per gallon, an interest rate of 10%, and an engine operation of 8 hours per day. Based on experimental data

  11. Changes in adipose tissue stromal-vascular cells in primary culture due to porcine sera

    International Nuclear Information System (INIS)

    Jewell, D.E.; Hausman, G.J.

    1986-01-01

    This study was conducted to determine the response of rat stromal-vascular cells to pig sea. Sera were collected from unselected contemporary (lean) and high backfat thickness selected (obese) pigs. Sera from obese pigs were collected either by exsanguination or cannulation. sera from lean pigs during the growing phase (45 kg) and the fattening phase (100-110 kg) were collected. Stromal-vascular cells derived rom rat inguinal tissue were cultured on either 25 cm 2 flasks, collagen-coated coverslips or petri dishes. Cell proliferation was measured by [ 3 H]-thymidine incorporation during the fourth day of culture. Coverslip cultures were used for histochemical analysis. Petri dish cultures were used for analysis of Sn-glycerol-3-phosphate dehydrogenase (GPDH) activity. All cells were plated for 24 hours in media containing 10 fetal bovine sera. Test media contained 2.5, 5.0, 10.0% sera. Sera from obese pigs increased GPDH activity and fat cell production when compared to the lean controls. The increased concentration of sera increased esterase activity and lipid as measured with oil red O. The sera from obese pigs collected at slaughter stimulated more fat cell production than obese sera collected by cannulation. These studies show there are adipogenic factors in obese pigs sera which promote fat cell development in primary cell culture

  12. Antigen-presenting cells in human cutaneous leishmaniasis due to Leishmania major

    DEFF Research Database (Denmark)

    ElHassan, A M; Gaafar, A; Theander, T G

    1995-01-01

    keratinocytes and endothelial cells also showed these characteristics, they may also act as APC. By examining tissue samples from skin lesions and draining lymph nodes it was possible to follow the probable route of trafficking of various inflammatory cells between the skin lesion and lymph nodes. Leishmania...

  13. Cell phenotypic change due to Cryptosporidium parvum infection in immunocompetent mice.

    Science.gov (United States)

    Codices, Vera; Martins, Catarina; Novo, Carlos; Pinho, Mário; de Sousa, Bruno; Lopes, Angela; Borrego, Miguel; Matos, Olga

    2013-03-01

    Cryptosporidium parvum is an intracellular parasite causing enteritis which can become life-threatening in immunocompromised host. Immunoregulatory T cells play a central role in the regulatory network of the host. Here, we proposed to characterize the populations of immune cells during infection and reinfection with C. parvum. Four-week-old BALB/C mice were inoculated with oocysts of C. parvum at days 0 and 22. Fecal and blood samples, spleens, and small intestines were collected for analysis. Peripheral blood and spleen cell populations were characterized by flow cytometry. After infection (days 0 to 21), mice presented higher values of neutrophils, eosinophils, NK cells and CD4(+)CD25(high) T cells in peripheral blood. After reinfection, this upward trend continued in the following days for all four populations in infected mice. At day 35, infected mice presented similar values to the control group, except for CD4(+)CD25(high) T cells, which remained higher in infected mice. A possible correlation between alterations in blood and spleen cell populations was also studied, but no consistent association could be established. Small intestine sections were screened for intracellular stages of the parasite but no evidence of pathology was observed. Here, we report information which may be important for the understanding of the specific cell-mediated response in immunocompetent mice to C. parvum infection. Although some questions remain unanswered and complementary studies are needed, our results are expected to contribute to a better understanding of innate and Treg cells role in the clearance process of this parasite.

  14. Radioactive air emissions notice of construction use of a portable exhauster at 244-AR vault. Revision 2

    Energy Technology Data Exchange (ETDEWEB)

    Carrell, D.J.

    1997-12-17

    This document serves as a notice of construction (NOC), pursuant to the requirements of Washington Administrative Code (WAC) 246-247-060, and as a request for approval to construct, pursuant to 40 Code of Federal Regulations (CFR) 61.96, a portable exhauster at the 244-AR Vault. The exhauster would be used during air jetting of accumulated liquids from the cell sumps into the tanks and to make transfers among the tanks within the vault when needed. The 244-AR Vault is considered to be a double-contained receiver tank (OCRT) based on its functional characteristics, although it is not listed as one of the five designated DCRTs in the 200 Area Tank Farm systems. Process operations at the vault have been inactive since 1978 and the vault`s two stacks have not operated since 1993. Since cessation of vault operations an extremely large amount of rain water and snow melt have accumulated in the cell sumps. The water level in the sumps is substantially above their respective operating levels and there is concern for leakage to the environment through containment failure due to corrosion from backed-up sump liquid. Active ventilation is required to provide contamination control during air jetting operations within the vault. It has been determined that it would not be cost effective to repair the existing exhaust systems to an operational condition; thus, a portable exhauster will be used to support the intermittent operations.

  15. Case of Small Bowel Perforation due to Enteropathy-Type T-Cell Lymphoma

    Science.gov (United States)

    Kim, Yong Seok; Park, Jun Seok; Kim, Beom Gyu; Cha, Seong Jae; Chi, Kyong Choun; Park, Sung Jun; Chang, In Taik; Park, Sung Il

    2009-01-01

    Enteropathy-type T-cell lymphoma (ETTL) is a rare disease with a poor prognosis. According to the World Health Organization (WHO) classification, it is a subtype of the peripheral T-cell lymphomas. This disease is associated with gluten-sensitive enteropathy, has a high risk of intestinal perforation and obstruction, and is refractory to chemotherapeutic treatment. We report the case of a 73-year-old woman who was diagnosed with enteropathy-type T-cell lymphoma of the small intestine, which was positive for the markers of cytotoxic T cells, CD3, CD8, and CD56, on immunohistochemical staining after resection of the perforated terminal ileum. PMID:20046432

  16. Computed tomographic demonstration of a spontaneous subcapsular hematoma due to a small renal cell carcinoma

    International Nuclear Information System (INIS)

    Hilton, S.; Bosniak, M.A.; Megibow, A.J.; Ambos, M.A.

    1981-01-01

    Computed tomography (CT) was able to demonstrate a small renal cell carcinoma as the cause of a spontaneous subcapsular hematoma. Angiographic and pathologic correlation were obtained. A review of the causes for nontraumatic renal subcapsular hematoma is included

  17. Changes in circulatory white blood cells of mice and rats due to acute trichothecene intoxication.

    Science.gov (United States)

    Bergers, W W; van Dura, E A; van der Stap, J G

    1987-04-01

    In mice, administration of pure T-2 toxin caused a rapid decrease of lymphocyte counts, which was linear with respect to dose, whereas granulocyte counts showed a delayed decrease. The blood cell counts of both cell types attained normal values after 4-7 days. Similar results were obtained for crude A-, B- and macrocyclic type trichothecene. Intoxication of rats with T-2 toxin or crude A-type trichothecene caused changes in white blood cells, which differed quantitatively from those in the mouse: lymphocyte counts decreased less and a rapid transient increase of granulocytes was more obvious. Results of this study show that lymphocyte and granulocyte blood cell counts of small rodents respond sensitively to acute intoxication with various trichothecenes.

  18. β-cell dysfunction due to increased ER stress in a stem cell model of Wolfram syndrome.

    Science.gov (United States)

    Shang, Linshan; Hua, Haiqing; Foo, Kylie; Martinez, Hector; Watanabe, Kazuhisa; Zimmer, Matthew; Kahler, David J; Freeby, Matthew; Chung, Wendy; LeDuc, Charles; Goland, Robin; Leibel, Rudolph L; Egli, Dieter

    2014-03-01

    Wolfram syndrome is an autosomal recessive disorder caused by mutations in WFS1 and is characterized by insulin-dependent diabetes mellitus, optic atrophy, and deafness. To investigate the cause of β-cell failure, we used induced pluripotent stem cells to create insulin-producing cells from individuals with Wolfram syndrome. WFS1-deficient β-cells showed increased levels of endoplasmic reticulum (ER) stress molecules and decreased insulin content. Upon exposure to experimental ER stress, Wolfram β-cells showed impaired insulin processing and failed to increase insulin secretion in response to glucose and other secretagogues. Importantly, 4-phenyl butyric acid, a chemical protein folding and trafficking chaperone, restored normal insulin synthesis and the ability to upregulate insulin secretion. These studies show that ER stress plays a central role in β-cell failure in Wolfram syndrome and indicate that chemical chaperones might have therapeutic relevance under conditions of ER stress in Wolfram syndrome and other forms of diabetes.

  19. Spinal osteomyelitis due to Aspergillus flavus in a child: a rare complication after haematopoietic stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Beluffi, Giampiero [Fondazione IRCCS Policlinico ' S.Matteo' , Section of Paediatric Radiology, Department of Radiodiagnosis, Pavia PV (Italy); Bernardo, Maria E.; Locatelli, Franco [University of Pavia, Fondazione IRCCS Policlinico ' S.Matteo' , Department of Paediatric Haematology/Oncology, Pavia (Italy); Meloni, Giulia [University of Pavia, Fondazione IRCCS Policlinico ' S.Matteo' , Institute of Radiology, Pavia (Italy); Spinazzola, Angelo [Fondazione IRCCS Policlinico ' S.Matteo' , Section of Paediatric Radiology, Department of Radiodiagnosis, Pavia PV (Italy); Ospedale Maggiore, Crema CR (Italy)

    2008-06-15

    We report the case of a child affected by acute myeloid leukaemia who was treated with allogeneic haematopoietic stem cell transplantation and developed cervicothoracic spinal osteomyelitis due to Aspergillus flavus. The diagnosis was difficult on a clinical basis, but made possible by conventional radiography and MRI. (orig.)

  20. Chronic ulceration of the leg following extensive scarring due to a snake bite complicated by squamous cell carcinoma

    International Nuclear Information System (INIS)

    Mello, L.F.B.; Barcelos, M.G.; Nogueira Neto, N.C.; Meohas, W.; Pinto, L.W.; Melo, P.A.; Smith, J.

    2000-01-01

    Chronic ulcers of the leg are common in Brazil, perhaps more common than in the developed world. We report a case of a chronic ulcer of the leg following extensive scarring due to a bite by a venomous snake, which eventually led to a squamous cell carcinoma. (orig.)

  1. A new role for mast cells as scavengers for clearance of erythrocytes damaged due to oxidative stress.

    Science.gov (United States)

    Sharma, Priyanka; Puri, Niti

    2018-04-07

    Anemia, inflammation, and oxidative stress are interconnected. Erythrocytes are continuously exposed to oxidative stress, normally and during inflammatory diseases. Systemic mastocytosis and genetic depletion of mast cells affect anemia. In the present study, a direct role for mast cells in clearance of erythrocytes was explored. We show, for the first time, direct phagocytosis of opsonized as well as oxidatively damaged erythrocytes in vitro by mast cell lines, bone marrow derived mast cells (BMMCs) and in vivo by murine peritoneal mast cells. Also, activated mast cells, as may be present in inflammatory conditions, showed a significantly higher uptake of oxidatively damaged erythrocytes than resting mast cells. This suggests the involvement of mast cells in erythrocyte clearance during oxidative stress or inflammatory disorders. Partial inhibition of phagocytosis by various inhibitors indicated that this process may be controlled by several pathways. Our study provides important evidence for a scavenging role for mast cells in anemia due to inflammation and oxidative stress. Copyright © 2018. Published by Elsevier B.V.

  2. Plasma generated in culture medium induces damages of HeLa cells due to flow phenomena

    Science.gov (United States)

    Sato, Yusuke; Sato, Takehiko; Yoshino, Daisuke

    2018-03-01

    Plasma in a liquid has been anticipated as an effective tool for medical applications, however, few reports have described cellular responses to plasma generated in a liquid similar to biological fluids. Herein we report the effects of plasma generated in a culture medium on HeLa cells. The plasma in the culture medium produced not only heat, shock waves, and reactive chemical species but also a jet flow with sub millimeter-sized bubbles. Cells exposed to the plasma exhibited detachment, morphological changes, and changes in the actin cytoskeletal structure. The experimental results suggest that wall shear stress over 160 Pa was generated on the surface of the cells by the plasma. It is one of the main factors that cause those cellular responses. We believe that our findings would provide valuable insight into advancements in medical applications of plasma in a liquid.

  3. Pancreatic α-cell hyperplasia and hyperglucagonemia due to a mutation of the glucagon

    DEFF Research Database (Denmark)

    Larger, Etienne; Albrechtsen, Nicolai Jacob Wewer; Hansen, L.H.

    2016-01-01

    Glucagon stimulates hepatic glucose production by activating specific glucagon receptors in the liver, which in turn increase hepatic glycogenolysis as well as gluconeogenesis and ureagenesis from amino acids. Conversely, glucagon secretion is regulated by concentrations of glucose and amino acids...... to hyperglucagonemia and α-cell hyperplasia, as well as elevated plasma amino acid levels. Together with the glucagon-induced hypoaminoacidemia in glucagonoma patients, our case supports recent suggestions that amino acids may provide the feedback link between the liver and the pancreatic α-cells....

  4. MMP-19 deficiency causes aggravation of colitis due to defects in innate immune cell function

    Czech Academy of Sciences Publication Activity Database

    Brauer, Rena; Turečková, Jolana; Kanchev, Ivan; Khoylou, M.; Škarda, J.; Procházka, Jan; Špoutil, František; Beck, Inken; Žbodáková, Olga; Kašpárek, Petr; Kořínek, Vladimír; Chalupský, Karel; Karhu, T.; Herzig, K.H.; Hajduch, M.; Gregor, Martin; Sedláček, Radislav

    2016-01-01

    Roč. 9, č. 4 (2016), s. 974-985 ISSN 1933-0219 R&D Projects: GA ČR GAP302/11/2048; GA ČR GAP303/10/2044; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378050 Keywords : human matrix-metalloproteinase * inflammatory-bowel-disease * differential expression * chemokine fractalkine * epithelial-cells * myeloid cells * in-vivo * mice * tissue * identification Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.478, year: 2016

  5. Semiconductor industry wafer fab exhaust management

    CERN Document Server

    Sherer, Michael J

    2005-01-01

    Given the myriad exhaust compounds and the corresponding problems that they can pose in an exhaust management system, the proper choice of such systems is a complex task. Presenting the fundamentals, technical details, and general solutions to real-world problems, Semiconductor Industry: Wafer Fab Exhaust Management offers practical guidance on selecting an appropriate system for a given application. Using examples that provide a clear understanding of the concepts discussed, Sherer covers facility layout, support facilities operations, and semiconductor process equipment, followed by exhaust types and challenges. He reviews exhaust point-of-use devices and exhaust line requirements needed between process equipment and the centralized exhaust system. The book includes information on wet scrubbers for a centralized acid exhaust system and a centralized ammonia exhaust system and on centralized equipment to control volatile organic compounds. It concludes with a chapter devoted to emergency releases and a separ...

  6. Therapeutic immunization with a mixture of herpes simplex virus 1 glycoprotein D-derived “asymptomatic” human CD8+ T-cell epitopes decreases spontaneous ocular shedding in latently infected HLA transgenic rabbits: association with low frequency of local PD-1+ TIM-3+ CD8+ exhausted T cells.

    Science.gov (United States)

    Khan, Arif A; Srivastava, Ruchi; Chentoufi, Aziz A; Geertsema, Roger; Thai, Nhi Thi Uyen; Dasgupta, Gargi; Osorio, Nelson; Kalantari, Mina; Nesburn, Anthony B; Wechsler, Steven L; BenMohamed, Lbachir

    2015-07-01

    Most blinding ocular herpetic disease is due to reactivation of herpes simplex virus 1 (HSV-1) from latency rather than to primary acute infection. No herpes simplex vaccine is currently available for use in humans. In this study, we used the HLA-A*02:01 transgenic (HLA Tg) rabbit model of ocular herpes to assess the efficacy of a therapeutic vaccine based on HSV-1 gD epitopes that are recognized mainly by CD8(+) T cells from "naturally" protected HLA-A*02:01-positive, HSV-1-seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease). Three ASYMP CD8(+) T-cell epitopes (gD(53-61), gD(70-78), and gD(278-286)) were linked with a promiscuous CD4(+) T-cell epitope (gD(287-317)) to create 3 separate pairs of CD4-CD8 peptides, which were then each covalently coupled to an Nε-palmitoyl-lysine moiety, a Toll-like receptor 2 (TLR-2) ligand. This resulted in the construction of 3 CD4-CD8 lipopeptide vaccines. Latently infected HLA Tg rabbits were immunized with a mixture of these 3 ASYMP lipopeptide vaccines, delivered as eye drops in sterile phosphate-buffered saline (PBS). The ASYMP therapeutic vaccination (i) induced HSV-specific CD8(+) T cells that prevent HSV-1 reactivation ex vivo from latently infected explanted trigeminal ganglia (TG), (ii) significantly reduced HSV-1 shedding detected in tears, (iii) boosted the number and function of HSV-1 gD epitope-specific CD8(+) T cells in draining lymph nodes (DLN), conjunctiva, and TG, and (iv) was associated with fewer exhausted HSV-1 gD-specific PD-1(+) TIM-3+ CD8(+) T cells. The results underscore the potential of an ASYMP CD8(+) T-cell epitope-based therapeutic vaccine strategy against recurrent ocular herpes. Seventy percent to 90% of adults harbor herpes simplex virus 1 (HSV-1), which establishes lifelong latency in sensory neurons of the trigeminal ganglia. This latent state sporadically switches to spontaneous reactivation, resulting in viral shedding in tears. Most blinding

  7. Hydrodynamic forces on a wall-bound leukocyte due to interactions with flowing red cells

    Science.gov (United States)

    Isfahani, Amir H. G.; Freund, Jonathan B.

    2011-11-01

    As part of both healthy and pathologically physiological mechanisms sphere-like white blood cells (leukocytes) adhere to the walls of small blood vessels. We use quantitative numerical simulations to compare the forces from flowing red blood cells on a wall-adhered leukocyte to a homogenized model of blood at the same flow conditions. We model the highly flexible red blood cells using a fast O (N log N) boundary integral formulation. These elastic membranes deform substantially but strongly resist surface dilatation. They enclose a higher than plasma viscosity hemoglobin solution. The no-slip condition is enforced on the stationary leukocyte as well as the vessel walls. Vessel diameters of 10 to 20 microns are studied. Different hematocrits, leukocyte shapes, and flow conditions are examined. In vessels comparable to the size of the cells, we show that the particulate character of blood significantly affects the magnitude of the forces that the leukocyte experiences, transiently increasing it well above the homogenized-blood prediction: for example, for a tube hematocrit of 25 % and a spherical protrusion with a diameter 0.75 that of the tube, the average forces are increased by about 40 % and the local forces by more than 100 % relative to those expected for a blood model homogenized by its effective viscosity.

  8. CD133-positive cells are resistant to TRAIL due to up-regulation of FLIP

    Czech Academy of Sciences Publication Activity Database

    Zobalová, Renata; McDermott, L.; Stantic, M.; Prokopová, Kateřina; Dong, L.-F.; Neužil, Jiří

    2008-01-01

    Roč. 373, č. 4 (2008), s. 567-571 ISSN 0006-291X R&D Projects: GA AV ČR(CZ) IAA500520702 Institutional research plan: CEZ:AV0Z50520701 Keywords : Cancer stem cells * apoptosis * resistance to apoptosis induction Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.648, year: 2008

  9. Inhibition of pH fronts in corrosion cells due to the formation of cerium hydroxide

    NARCIS (Netherlands)

    Soestbergen, M. van; Erich, S.J.F.; Huinink, H.P.; Adan, O.C.G.

    2013-01-01

    The effect of cerium-based corrosion inhibitors on the pH front between the alkaline cathode and acidic anode in corrosion cells has been studied. The cerium component of these inhibitors can affect the pH front since it precipitates in an alkaline environment as cerium hydroxide, which is important

  10. Antigen-presenting cells in human cutaneous leishmaniasis due to Leishmania major

    DEFF Research Database (Denmark)

    ElHassan, A M; Gaafar, A; Theander, T G

    1995-01-01

    In this study biopsies from skin lesions and draining lymph nodes of patients suffering from cutaneous leishmaniasis caused by Leishmania major were examined by immunohistochemistry, and by light and electron microscopy to identify the types of antigen-presenting cells (APC) and their location. APC...

  11. Single-epitope DNA vaccination prevents exhaustion and facilitates a broad antiviral CD8+ T cell response during chronic viral infection

    DEFF Research Database (Denmark)

    Bartholdy, Christina; Stryhn, Anette; Christensen, Jan Pravsgaard

    2004-01-01

    a single dominant epitope may suppress the response to other viral epitopes, and this may lead to increased susceptibility to reinfection with escape variants circulating in the host population. To address these issues, we induced a memory response consisting solely of monospecific, CD8+ T cells by use...... of DNA vaccines encoding immunodominant epitopes of lymphocytic choriomeningitis virus (LCMV). We analyzed the spectrum of the CD8+ T cell response and the susceptibility to infection in H-2(b) and H-2(d) mice. Priming for a monospecific, CD8+ T cell response did not render mice susceptible to viral...... variants. Thus, vaccinated mice were protected against chronic infection with LCMV, and no evidence indicating biologically relevant viral escape was obtained. In parallel, a broad and sustained CD8+ T cell response was generated upon infection, and in H-2(d) mice epitope spreading was observed. Even after...

  12. Exhaustion of CTL memory and recrudescence of viremia in lymphocytic choriomeningitis virus-infected MHC class II-deficient mice and B cell-deficient mice

    DEFF Research Database (Denmark)

    Thomsen, Allan Randrup; Johansen, J; Marker, O

    1996-01-01

    intact, and the infection is initially controlled in most organ sites including the blood. However, approximately 2 mo postinfection, CTL memory cannot be detected, and recrudescence of viremia to titers as high as seen during the acute phase of the infection is observed. To investigate whether...... this phenomenon could reflect participation of B cells and/or Abs in long term virus control, similar experiments were performed with mice that do not have mature B cells because of a disrupted membrane exon of the mu chain gene. In these mice, the cell-mediated immune response was slightly delayed, but transient...... virus control was observed in most mice. However, approximately 3 mo postinfection, blood virus titers were as high as observed during the acute infection, and no CTL memory could be demonstrated. These results indicate that Abs and/or B cells are required for permanent virus control...

  13. Ship exhaust gas plume cooling

    NARCIS (Netherlands)

    Schleijpen, H.M.A.; Neele, P.P.

    2004-01-01

    The exhaust gas plume is an important and sometimes dominating contributor to the infrared signature of ships. Suppression of the infrared ship signatures has been studied by TNO for the Royal Netherlands Navy over considerable time. This study deals with the suppression effects, which can be

  14. Shunts due to laser scribing of solar cells evaluated by highly sensitive lock-in thermography

    Energy Technology Data Exchange (ETDEWEB)

    Breitenstein, O.; Langenkamp, M. [Max-Planck-Institut fuer Mikrostrukturphysik, Weinberg 2, D-06120 Halle (Germany); Lang, O. [SOLARC, Gustav-Meyer-Allee 25, Geb. 12, D-13355 Berlin (Germany); Schirrmacher, A. [LMTB, Rudower Chaussee 6, Geb. 19/2, D-12489 Berlin (Germany)

    2001-01-01

    Using a 217Hz focal plane array (FPA) thermocamera attached to two parallel-running DSP frame grabber boards in a PC, a highly sensitive lock-in thermography system has been built, enabling the detection of periodic surface temperature oscillations below 10{mu}K (r.m.s). This system has been used to investigate edge leakage currents in silicon solar cells after laser scribing and cleavage.

  15. Pancreatic α-cell hyperplasia and hyperglucagonemia due to a glucagon receptor splice mutation

    Directory of Open Access Journals (Sweden)

    Etienne Larger

    2016-11-01

    Full Text Available Glucagon stimulates hepatic glucose production by activating specific glucagon receptors in the liver, which in turn increase hepatic glycogenolysis as well as gluconeogenesis and ureagenesis from amino acids. Conversely, glucagon secretion is regulated by concentrations of glucose and amino acids. Disruption of glucagon signaling in rodents results in grossly elevated circulating glucagon levels but no hypoglycemia. Here, we describe a patient carrying a homozygous G to A substitution in the invariant AG dinucleotide found in a 3′ mRNA splice junction of the glucagon receptor gene. Loss of the splice site acceptor consensus sequence results in the deletion of 70 nucleotides encoded by exon 9, which introduces a frame shift and an early termination signal in the receptor mRNA sequence. The mutated receptor neither bound 125I-labeled glucagon nor induced cAMP production upon stimulation with up to 1 μM glucagon. Despite the mutation, the only obvious pathophysiological trait was hyperglucagonemia, hyperaminoacidemia and massive hyperplasia of the pancreatic α-cells assessed by histology. Our case supports the notion of a hepato–pancreatic feedback system, which upon disruption leads to hyperglucagonemia and α-cell hyperplasia, as well as elevated plasma amino acid levels. Together with the glucagon-induced hypoaminoacidemia in glucagonoma patients, our case supports recent suggestions that amino acids may provide the feedback link between the liver and the pancreatic α-cells.

  16. Single-epitope DNA vaccination prevents exhaustion and facilitates a broad antiviral CD8+ T cell response during chronic viral infection

    DEFF Research Database (Denmark)

    Bartholdy, Christina; Stryhn, Anette; Christensen, Jan Pravsgaard

    2004-01-01

    of DNA vaccines encoding immunodominant epitopes of lymphocytic choriomeningitis virus (LCMV). We analyzed the spectrum of the CD8+ T cell response and the susceptibility to infection in H-2(b) and H-2(d) mice. Priming for a monospecific, CD8+ T cell response did not render mice susceptible to viral...... acute LCMV infection, DNA vaccination did not significantly impair naturally induced immunity. Thus, the response to the other immunogenic epitopes was not dramatically suppressed in DNA-immunized mice undergoing normal immunizing infection, and the majority of mice were protected against rechallenge...... variants. Thus, vaccinated mice were protected against chronic infection with LCMV, and no evidence indicating biologically relevant viral escape was obtained. In parallel, a broad and sustained CD8+ T cell response was generated upon infection, and in H-2(d) mice epitope spreading was observed. Even after...

  17. An autopsy case of subacute cor pulmonale due to pulmonary tumor cell emboli in a patient with gastric cancer.

    Science.gov (United States)

    Iwakami, Shin-ichiro; Sato, Teruhiko; Takagi, Haruhi; Fujii, Mitsuhiro; Iwakami, Naoko; Yoshimi, Kaku; Koyama, Ryo; Ichikawa, Masako; Yoshioka, Masakata; Takahashi, Kazuhisa

    2009-01-01

    A 53-year-old woman was admitted to our hospital due to a severe respiratory condition and malnutrition. Radiological and electrophysiological findings suggested the existence of inexplicable cor pulmonale. Although we commenced to determine the causes of her severe condition, she suddenly died 3 days after admission. Postmortem autopsy revealed tumor cell microemboli in the small pulmonary arteries due to gastric cancer. Such a case of cor pulmonale as the first clinical manifestation is exceptionally rare. Occult malignancy should be considered as a differential diagnosis when one encounters a patient with subacutely aggravated respiratory condition and inexplicable cor pulmonale.

  18. Possible Explanation for Cancer in Rats due to Cell Phone Radio Frequency Radiation

    Science.gov (United States)

    Feldman, Bernard J.

    Very recently, the National Toxicology Program reported a correlation between exposure to whole body 900 MHz radio frequency radiation and cancer in the brains and hearts of Sprague Dawley male rats. Assuming that the National Toxicology Program is statistically significant, I propose the following explanation for these results. The neurons around the brain and heart form closed electrical circuits and, following Faraday's Law, 900 MHz radio frequency radiation induces 900 MHz electrical currents in these neural circuits. In turn, these 900 MHz currents in the neural circuits generate sufficient localized heat in the neural cells to shift the equilibrium concentration of carcinogenic radicals to higher levels and thus, to higher incidences of cancer.

  19. Male pseudohermaphroditism due to Leydig cell agenesia and absence of testicular LH receptors.

    Science.gov (United States)

    Martínez-Mora, J; Sáez, J M; Torán, N; Isnard, R; Pérez-Iribarne, M M; Egozcue, J; Audí, L

    1991-06-01

    The aim of our study was to establish the definitive diagnosis in an adult patient with male pseudohermaphroditism in whom testicular feminization syndrome had been suspected at the age of 8, based on genetic, clinical and pathological studies. Hypothalamo-hypophysio-testicular function was assessed in vivo. Androgen mechanism of action and testicular gonadotrophin binding were studied in vitro. At the age of 33 the phenotype was almost completely feminine except for slight clitoral enlargement and posterior labial fusion. Internal genital duct derivatives were masculine except for a short vagina. Both testes were cryptorchid. LH and FSH were determined pre- and post-gonadectomy. Progesterone, 17-OH-progesterone, androstenedione, dehydroepiandrosterone testosterone (T) and oestradiol were determined basally in peripheral and spermatic blood post-hCG stimulation, and in peripheral blood after orchidectomy. Dihydrotestosterone (DHT) receptors and 5 alpha-reductase activity were determined in genital skin fibroblasts. Receptors for LH and FSH were determined in membrane preparations from both testes. LH was high (31 IU/l) and FSH (8 IU/ml) normal. T or steroid precursors were detected basally or after hCG stimulation in peripheral blood showing absence of testicular production. Spermatic venous blood steroid concentrations were consistent with slight T production, in accordance with testis histology which showed few Leydig-like cells among fibroblasts in the interstitial space. DHT specific binding capacity and affinity and 5 alpha-reductase activity were normal in genital skin fibroblasts. Gonadotrophin binding studies in testicular membranes confirmed the absence of LH specific binding, whereas FSH binding was higher than normal when expressed per mg of protein (27.0 vs 9.4 +/- 0.6 fmol/mg protein in controls), and lower than normal in both testes since patient's testicular weights were abnormally low. The patient was considered to have an almost complete form of

  20. Rhabdomyolysis due to Trimethoprim-Sulfamethoxazole Administration following a Hematopoietic Stem Cell Transplant

    Directory of Open Access Journals (Sweden)

    Alexander Augustyn

    2015-01-01

    Full Text Available Rhabdomyolysis, a syndrome of muscle necrosis, is a life-threatening event. Here we describe the case of a patient with chronic myeloid leukemia who underwent a haploidentical stem cell transplant and subsequently developed rhabdomyolysis after beginning trimethoprim-sulfamethoxazole (TMP/SMX prophylaxis therapy. Rechallenge with TMP/SMX resulted in a repeat episode of rhabdomyolysis and confirmed the association. Withdrawal of TMP/SMX led to sustained normalization of creatine kinase levels in the patient. A high index of suspicion is necessary to identify TMP/SMX as the cause of rhabdomyolysis in immunocompromised patients.

  1. Effect of diesel exhaust generated by a city bus engine on stress responses and innate immunity in primary bronchial epithelial cell cultures

    NARCIS (Netherlands)

    Zarcone, M.C.; Duistermaat, E.; Alblas, M.J.; Schadewijk, A. van; Ninaber, D.K.; Clarijs, V.; Moerman, M.M.; Vaessen, D.; Hiemstra, P.S.; Kooter, I.M.

    2018-01-01

    Harmful effects of diesel emissions can be investigated via exposures of human epithelial cells, but most of previous studies have largely focused on the use of diesel particles or emission sources that are poorly representative of engines used in current traffic. We studied the cellular response of

  2. Estimation of the mechanical consequences due to the saturation of a radwaste storage cell

    Energy Technology Data Exchange (ETDEWEB)

    Robbe, M.F. [CEA Saclay, Dept. de Mecanique et de Technologie, 91 - Gif-sur-Yvette (France)

    2001-07-01

    Man y projects of underground repositories for high level rad wastes involve cells containing waste canisters surrounded by an engineered clay barrier. The cell is closed by a clay plug isolating the canisters from the gallery. By hydrating progressively, the barrier and the plug swell, seal the gaps and provide a good global mechanical stability of the waste - clay barrier - host rock system. From a physical point of view, the evolution of the clay behaviour is governed by thermal, hydraulic and mechanical processes, these three processes being coupled in the following way: the waste induces a thermal field; interstitial water infiltrates the clay material; temperature modifies the fluid density and viscosity and vaporizes the liquid water; steam diffuses towards the cold area and condensates; the capillary pressure induces mechanical stresses which in turn modify the porosity accessible to the interstitial water. In this paper, we take into consideration the hydro-mechanical aspect of the phenomenon. The hydraulic model is based on a mixed hybrid finite element formulation, on the Darcy's law and the resolution of the Richard's equation. This model only takes into account the water flows inside the ground: air flows, thermal exchanges and water vaporization are assumed to be negligible. (author)

  3. Altered host cell-bacteria interaction due to nanoparticle interaction with a bacterial biofilm.

    Science.gov (United States)

    Raftery, Tara D; Lindler, Heidi; McNealy, Tamara L

    2013-02-01

    Nanoparticle (NP) use in everyday applications creates the potential for NPs to enter the environment where, in aquatic systems, they are likely to settle on substrates and interact with microbial communities. Legionella pneumophila biofilms are found as part of microbial communities in both natural and man-made environments, especially in man-made cooling systems. The bacterium is the causative agent of Legionnaires' disease. Legionella requires a host cell for replication in the environment, and amoebae commonly serve as this host cell. Our previous work demonstrated significant changes in Legionella biofilm morphology after exposure to 0.7 μg/L gold NPs (AuNPs). Here, we investigate how these morphology changes alter host-bacteria interactions using Acanthamoeba polyphaga as a model. Host-bacteria-NP interactions are affected by NP characteristics. Biofilms exposed to 4- and 18-nm, citrate-capped, spherical AuNPs significantly altered the grazing ability of A. polyphaga, which was not observed in biofilms exposed to 24-nm polystyrene beads. Uptake and replication of NP-exposed planktonic L. pneumophila within A. polyphaga were not altered regardless of NP size or core chemistry. Nanomaterial effects on the interaction of benthic organisms and bacteria may be directly or, as shown here, indirectly dependent on bacterial morphology. NP contamination therefore may alter interactions in a normal ecosystem function.

  4. AFM study shows prominent physical changes in elasticity and pericellular layer in human acute leukemic cells due to inadequate cell-cell communication

    Science.gov (United States)

    Guz, Nataliia V.; Patel, Sapan J.; Dokukin, Maxim E.; Clarkson, Bayard; Sokolov, Igor

    2016-12-01

    Biomechanical properties of single cells in vitro or ex vivo and their pericellular interfaces have recently attracted a lot of attention as a potential biophysical (and possibly prognostic) marker of various diseases and cell abnormalities. At the same time, the influence of the cell environment on the biomechanical properties of cells is not well studied. Here we use atomic force microscopy to demonstrate that cell-cell communication can have a profound effect on both cell elasticity and its pericellular coat. A human pre-B p190BCR/ABL acute lymphoblastic leukemia cell line (ALL3) was used in this study. Assuming that cell-cell communication is inversely proportional to the distance between cells, we study ALL3 cells in vitro growing at different cell densities. ALL3 cells demonstrate a clear density dependent behavior. These cells grow very well if started at a relatively high cell density (HD, >2 × 105 cells ml-1) and are poised to grow at low cell density (LD, <1 × 104 cells ml-1). Here we observe ˜6× increase in the elastic (Young’s) modulus of the cell body and ˜3.6× decrease in the pericellular brush length of LD cells compared to HD ALL3 cells. The difference observed in the elastic modulus is much larger than typically reported for pathologically transformed cells. Thus, cell-cell communication must be taken into account when studying biomechanics of cells, in particular, correlating cell phenotype and its biophysical properties.

  5. Exhaustion measured by the SF-36 vitality scale is associated with a flattened diurnal cortisol profile

    DEFF Research Database (Denmark)

    Lindeberg, Sara I; Eek, Frida; Lindbladh, Eva

    2008-01-01

    cortisol profile. The study population included 78 working individuals. The study group was dichotomised into exhausted and non-exhausted groups by means of the SF-36 vitality scale. Salivary cortisol was measured at three times during 1 workday: at awakening, 30min after awakening, and in the evening....... The results showed that diurnal cortisol variation was significantly reduced in exhausted individuals. The difference in cortisol variation was mainly due to lowered morning cortisol in the exhausted group. Differences in cortisol levels at each sampling time or in mean diurnal output of cortisol were...... not statistically significant. The results would support the notion that exhaustion is associated with HPA axis hypoactivity as assessed by salivary cortisol. Furthermore, the SF-36 vitality provides a measure of exhaustion that may be useful in epidemiological studies in order to explore long-term health effects...

  6. Conditional Loss of Pten in Myogenic Progenitors Leads to Postnatal Skeletal Muscle Hypertrophy but Age-Dependent Exhaustion of Satellite Cells.

    Science.gov (United States)

    Yue, Feng; Bi, Pengpeng; Wang, Chao; Li, Jie; Liu, Xiaoqi; Kuang, Shihuan

    2016-11-22

    Skeletal muscle stem cells (satellite cells [SCs]) are normally maintained in a quiescent (G 0 ) state. Muscle injury not only activates SCs locally, but also alerts SCs in distant uninjured muscles via circulating factors. The resulting G Alert SCs are adapted to regenerative cues and regenerate injured muscles more efficiently, but whether they provide any long-term benefits to SCs is unknown. Here, we report that embryonic myogenic progenitors lacking the phosphatase and tensin homolog (Pten) exhibit enhanced proliferation and differentiation, resulting in muscle hypertrophy but fewer SCs in adult muscles. Interestingly, Pten null SCs are predominantly in the G Alert state, even in the absence of an injury. The G Alert SCs are deficient in self-renewal and subjected to accelerated depletion during regeneration and aging and fail to repair muscle injury in old mice. Our findings demonstrate a key requirement of Pten in G 0 entry of SCs and provide functional evidence that prolonged G Alert leads to stem cell depletion and regenerative failure. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Exhaust System Reinforced by Jet Flow

    DEFF Research Database (Denmark)

    Pedersen, Lars Germann; Nielsen, Peter V.

    Since 1985 the University of Aalborg and Nordfab A/S have been working on an exhaust principle which is quite different from traditional exhaust systems. The REEXS principle (Reinforced Exhaust System), which originally was designed for the agricultural sector, is particularly well-suited for ind...

  8. Petrol and diesel exhaust particles accelerate the horizontal transfer of plasmid-mediated antimicrobial resistance genes.

    Science.gov (United States)

    Zhang, Ye; Gu, April Z; Cen, Tianyu; Li, Xiangyang; Li, Dan; Chen, Jianmin

    2018-03-07

    Particles exhausted from petrol and diesel consumptions are major components of urban air pollution that can be exposed to human via direct inhalation or other routes due to atmospheric deposition into water and soil. Antimicrobial resistance is one of the most serious threats to modern health care. However, how the petrol and diesel exhaust particles affect the development and spread of antimicrobial resistance genes (ARGs) in various environments remain largely unknown. This study investigated the effects and potential mechanisms of four representative petrol and diesel exhaust particles, namely 97 octane petrol, 93 octane petrol, light diesel oil, and marine heavy diesel oil, on the horizontal transfer of ARGs between two opportunistic Escherichia coli (E. coli) strains, E. coli S17-1 (donor) and E. coli K12 (recipient). The results demonstrated that these four representative types of nano-scale particles induced concentration-dependent increases in conjugative transfer rates compared with the controls. The underlying mechanisms involved in the accelerated transfer of ARGs were also identified, including the generation of intracellular reactive oxygen species (ROS) and the consequent induction of oxidative stress, SOS response, changes in cell morphology, and the altered mRNA expression of membrane protein genes and those involved in the promotion of conjugative transfer. The findings provide new evidences and mechanistic insights into the antimicrobial resistance risks posed by petrol and diesel exhaust particles, and highlight the implications and need for stringent strategies on alternative fuels to mitigate air pollution and health risks. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Electrophysiologic Study of Exhaustive Exercise

    Directory of Open Access Journals (Sweden)

    MA Babaee Bigi

    2010-12-01

    Full Text Available Background: Exhaustive exercise is well known to pose a variety ofhealth hazards, such as sudden cardiac death reported in ultra-marathon runners.Depressed parasympathetic tone is associated with increased risk of suddencardiac death, thus parasympathetic withdrawal in post-exercise phase may be ahigh risk period for sudden death. To date, the effect on cardiacelectrophysiology after exhaustive strenuous exercise has not been described.The aim of this study was to evaluate the impact of severe exhaustive exerciseon cardiac electrophysiology.Methods: The subjects in ranger training were invited to participatein this prospective study. The parameters measured consisted of PR interval, QRSduration, and macro T wave alternans as well as corrected QT, QTc dispersion,Tpeak –Tend interval and Tpeak –Tend dispersion.Results: The study group consisted of 40 consecutive male rangers whocompleted training and the control group (22 healthy age and height matched malesubjects. In regard to electrocardiographic criteria, no differences were foundbetween rangers before and after training program. In respect of therepolarization markers, there were no significant differences between therangers before and after training program.

  10. Recent advances in investigations of toxicity of automotive exhaust

    Science.gov (United States)

    Stupfel, Maurice

    1976-01-01

    The influence of auto exhaust on man's health is difficult to gauge considering the intricacy of human environmental urban stresses and particularly of other air polluting (industrial, domestic) emissions. Epidemiological surveys made in road tunnel employees and in traffic officers have not demonstrated specific effects and have often been complicated by cigarette smoking as a factor. Long-term animal experiments run mostly on small rodents give evidence of little effect of the pathological actions of dilutions such as those encountered in high polluted cities. However the acute toxicity of gasoline exhaust emission is well known and mostly due to carbon monoxide. Considering the different types of cycles and operating conditions of vehicles (gasoline and diesel), auto exhaust gases constitute no more a chemical entity than they show, a definite toxicity. A great number of substances that they contain (nitrogen oxides, aldehydes, antiknock additives, heavy metals, possible catalysts are highly toxic as shown by in vivo and in vitro (mutagenic) tests. Interactions of the components are for the moment ignored or poorly understood. Besides, the evolution of the physicochemical properties and natures of the auto exhaust emission in the gaseous biotope of man under determined conditions of ultraviolet irradiation, temperature, and hygrometry provoke the formation of secondary products such as oxidants and ozone. Several experiments show clearly that irradiation increases the toxicity of auto exhaust significantly. For these reasons, geographical, meteorological, and chronological (circadian and seasonal) factors should be taken into consideration, especially with regard to emission standards. PMID:67944

  11. Productivity loss due to premature mortality caused by blood cancer: a study based on patients undergoing stem cell transplantation.

    Science.gov (United States)

    Ortega-Ortega, Marta; Oliva-Moreno, Juan; Jiménez-Aguilera, Juan de Dios; Romero-Aguilar, Antonio; Espigado-Tocino, Ildefonso

    2015-01-01

    Stem cell transplantation has been used for many years to treat haematological malignancies that could not be cured by other treatments. Despite this medical breakthrough, mortality rates remain high. Our purpose was to evaluate labour productivity losses associated with premature mortality due to blood cancer in recipients of stem cell transplantations. We collected primary data from the clinical histories of blood cancer patients who had undergone stem cell transplantation between 2006 and 2011 in two Spanish hospitals. We carried out a descriptive analysis and calculated the years of potential life lost and years of potential productive life lost. Labour productivity losses due to premature mortality were estimated using the Human Capital method. An alternative approach, the Friction Cost method, was used as part of the sensitivity analysis. Our findings suggest that, in a population of 179 transplanted and deceased patients, males and people who die between the ages of 30 and 49 years generate higher labour productivity losses. The estimated loss amounts to over €31.4 million using the Human Capital method (€480,152 using the Friction Cost method), which means an average of €185,855 per death. The highest labour productivity losses are produced by leukaemia. However, lymphoma generates the highest loss per death. Further efforts are needed to reduce premature mortality in blood cancer patients undergoing transplantations and reduce economic losses. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

  12. Treatment and prevention of pain due to vaso-occlusive crises in adults with sickle cell disease: an educational void.

    Science.gov (United States)

    Solomon, Lawrence R

    2008-02-01

    Pain due to vaso-occlusive crisis is the major cause of hospital use in sickle cell disease. Although available guidelines provide recommendations for opioid administration in this setting, only 4 (21%) of 19 medical textbooks present treatment regimens that are consistent with them. Moreover, only 7 texts (37%) note that addiction is infrequent in this population, while 11 (92%) of 12 texts provide such reassurance for cancer-related pain (P occlusive crises is completely defined only in 2 textbooks. Thus, most medical texts provide neither adequate information for the treatment or prevention of pain due to vaso-occlusive crisis in sickle cell disease nor reassurance of the unlikelihood of addiction in this population. In contrast, treatment recommendations for less common hematologic disorders are consistent with current standards in 53% to 84% of appropriate texts (P training on pain control in sickle cell disease are needed to parallel studies of environmental and genetic factors contributing to the known clinical heterogeneity of this disorder.

  13. Honey can repairing damage of liver tissue due to protein energy malnutrition through induction of endogenous stem cells.

    Science.gov (United States)

    Prasetyo, R Heru; Hestianah, Eka Pramyrtha

    2017-06-01

    This study was to evaluate effect of honey in repairing damage of liver tissue due to energy protein malnutrition and in mobilization of endogenous stem cells. Male mice model of degenerative liver was obtained through food fasting but still have drinking water for 5 days. It caused energy protein malnutrition and damage of liver tissue. The administration of 50% (v/v) honey was performed for 10 consecutive days, while the positive control group was fasted and not given honey and the negative control not fasted and without honey. Observations of regeneration the liver tissue based on histologically examination, observation of Hsp70 expression, and homing signal based on vascular endothelial growth factor-1 (VEGF-1) expression using immunohistochemistry technique. Observation on expression of CD34 and CD45 as the marker of auto mobilization of hematopoietic stem cells using flow cytometry technique. There is regeneration of the liver tissue due to protein energy malnutrition, decrease of Hsp70 expression, increase of VEGF-1 expression, and high expression of CD34 and CD45. Honey can improve the liver tissue based on: (1) Mobilization of endogenous stem cells (CD34 and CD45); (2) Hsp70 and VEGF-1 expressions as regeneration marker of improvement, and (3) regeneration histologically of liver tissue.

  14. 20 CFR 636.5 - Exhaustion of grantee level procedure.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Exhaustion of grantee level procedure. 636.5..., INVESTIGATIONS AND HEARINGS § 636.5 Exhaustion of grantee level procedure. (a) Exhaustion required. No... have been exhausted. (b) Exhaustion exceptions. Complainants who have not exhausted the procedures at...

  15. Hazard assessment of exhaust emissions - The next generation of fast and reliable tools for in vitro screening

    Science.gov (United States)

    Rothen-Rutishauser, B.

    2017-12-01

    Hazard assessment of exhaust emissions - The next generation of fast and reliable tools for in vitro screening Barbara Rothen-Rutishauser Adolphe Merkle Institute, University of Fribourg, Switzerland; barbara.rothen@unifr.ch Pollution by vehicles is a major problem for the environment due to the various components in the exhaust gasses that are emitted into the atmosphere. A large number of epidemiological studies demonstrate the profound impact of vehicle emissions upon human health [1-3]. Such studies however, are unable to attribute a given subset of emissions to a certain adverse effect, which renders decision making difficult. Standardized protocols for exhaust toxicity assessment are lacking and it relies in many aspects on epidemiological and in vivo studies (animals), which are very time and cost-intensive and suffer from considerable ethical issues. An overview about the current state of research and clinical aspects in the field, as well as about the development of sophisticated in vitro approaches mimicking the inhalation of airborne particles / exhaust for the toxicological testing of engine emissions will be provided. Data will be presented that show that the combination of an air-liquid exposure system and 3D lung-cell culture model offers an adequate tool for fast and reliable investigations of complete exhaust toxicity as well as the effects of particulate fraction [4,5]. This approach yields important results for novel and improved emission technologies in the early stages of product development. [1] Donaldson et al. Part Fibre Toxicol 2005, 2: 10. [2] Ghio et al. J Toxicol Environ Health B Crit Rev 2012, 15: 1-21. [3] Peters et al. Res Rep Health Eff Inst 2009, 5-77. [4] Bisig et al. Emiss Control Sci Technol 2015, 1: 237-246. [5] Steiner et al. Atmos Environ 2013, 81: 380-388.

  16. Therapeutic Effect of Human Adipose Tissue-Derived Mesenchymal Stem Cells in Experimental Corneal Failure Due to Limbal Stem Cell Niche Damage.

    Science.gov (United States)

    Galindo, Sara; Herreras, José M; López-Paniagua, Marina; Rey, Esther; de la Mata, Ana; Plata-Cordero, María; Calonge, Margarita; Nieto-Miguel, Teresa

    2017-10-01

    Limbal stem cells are responsible for the continuous renewal of the corneal epithelium. The destruction or dysfunction of these stem cells or their niche induces limbal stem cell deficiency (LSCD) leading to visual loss, chronic pain, and inflammation of the ocular surface. To restore the ocular surface in cases of bilateral LSCD, an extraocular source of stem cells is needed to avoid dependence on allogeneic limbal stem cells that are difficult to obtain, isolate, and culture. The aim of this work was to test the tolerance and the efficacy of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) to regenerate the ocular surface in two experimental models of LSCD that closely resemble different severity grades of the human pathology. hAT-MSCs transplanted to the ocular surface of the partial and total LSCD models developed in rabbits were well tolerated, migrated to inflamed tissues, reduced inflammation, and restrained the evolution of corneal neovascularization and corneal opacity. The expression profile of the corneal epithelial cell markers CK3 and E-cadherin, and the limbal epithelial cell markers CK15 and p63 was lost in the LSCD models, but was partially recovered after hAT-MSC transplantation. For the first time, we demonstrated that hAT-MSCs improve corneal and limbal epithelial phenotypes in animal LSCD models. These results support the potential use of hAT-MSCs as a novel treatment of ocular surface failure due to LSCD. hAT-MSCs represent an available, non-immunogenic source of stem cells that may provide therapeutic benefits in addition to reduce health care expenses. Stem Cells 2017;35:2160-2174. © 2017 AlphaMed Press.

  17. Gas turbine exhaust system silencing design

    International Nuclear Information System (INIS)

    Ozgur, D.

    1991-01-01

    Gas turbines are the preferred prime mover in many applications because of their high efficiency, fuel flexibility, and low environmental impact. A typical mid-size machine might have a power rating of 80 MW, a flow of about 1000 kg/hr, and an exhaust temperature of over 500C. The most powerful single source of noise is generally the exhaust, which may generate over a kilowatt of acoustic energy. This paper reports that there are two important ways in which exhaust systems can radiate noise. The first is through the discharge of the exhaust duct, with the exhaust gas. Because of the large quantity of hot gas, the duct exit is always oriented vertically; it may be fairly high in the air in order to promote dispersion of the exhaust plume. This source is almost always attenuated by means of a silencer located somewhere in the ductwork. The second source of noise is often called breakout; it is the radiation of exhaust noise through the walls of the ducting. Breakout is most important for those sections of the exhaust duct which lie upstream of the silencer, where sound levels inside the ducting are highest. Both exhaust duct exit noise and breakout noise can be calculated from the sound power level of the gas turbine exhaust and the sound transmission loss (TL) of the silencer and ducting

  18. IC ENGINE SUPERCHARGING AND EXHAUST GAS RECIRCULATION USING JET COMPRESSOR

    Directory of Open Access Journals (Sweden)

    Adhimoulame Kalaisselvane

    2010-01-01

    Full Text Available Supercharging is a process which is used to improve the performance of an engine by increasing the specific power output whereas exhaust gas recirculation reduces the NOx produced by engine because of supercharging. In a conventional engine, supercharger functions as a compressor for the forced induction of the charge taking mechanical power from the engine crankshaft. In this study, supercharging is achieved using a jet compressor. In the jet compressor, the exhaust gas is used as the motive stream and the atmospheric air as the propelled stream. When high pressure motive stream from the engine exhaust is expanded in the nozzle, a low pressure is created at the nozzle exit. Due to this low pressure, atmospheric air is sucked into the expansion chamber of the compressor, where it is mixed and pressurized with the motive stream. The pressure of the mixed stream is further increased in the diverging section of the jet compressor. A percentage volume of the pressurized air mixture is then inducted back into the engine as supercharged air and the balance is let out as exhaust. This process not only saves the mechanical power required for supercharging but also dilutes the constituents of the engine exhaust gas thereby reducing the emission and the noise level generated from the engine exhaust. The geometrical design parameters of the jet compressor were obtained by solving the governing equations using the method of constant rate of momentum change. Using the theoretical design parameters of the jet compressor, a computational fluid dinamics analysis using FLUENT software was made to evaluate the performance of the jet compressor for the application of supercharging an IC engine. This evaluation turned out to be an efficient diagnostic tool for determining performance optimization and design of the jet compressor. A jet compressor was also fabricated for the application of supercharging and its performance was studied.

  19. Development of alternative ship propulsion in terms of exhaust emissions

    Directory of Open Access Journals (Sweden)

    Markowski Jarosław

    2016-01-01

    Full Text Available The introduction of new emission limits for exhaust emissions of ship engines contributes to the development of new powertrain solutions. New solutions in the simplest approach concern the reduction of the concentration of sulfur in motor fuels. Typically, the aforementioned fuels have a lower value of viscosity which causes a number of supply system problems. It is becoming more and more common to use fuel cells in engine rooms of various types of marine vessels. Unlike conventional systems that use internal combustion engines, these systems have zero exhaust emissions. Hydrogen, methanol, methane and other substances may be used as a fuel in fuel cells. However, so far the best operating parameters are manifested by cells powered by hydrogen, which is associated with difficulties in obtaining and storing this fuel. Therefore, the use of turbine engines allows the obtaining of large operating and environmental advantages. The paper presents a comparison of the ecological parameters of turbine and piston engines.

  20. Desulphurization of exhaust gases in chemical processes

    Energy Technology Data Exchange (ETDEWEB)

    Asperger, K.; Wischnewski, W.

    1981-01-01

    The sulfur content of exhaust gases can be reduced by: desulphurization of fuels; modification of processes; or treatment of resultant gases. In this paper a few selected examples from the chemical industry in the German Democratic Republic are presented. Using modified processes and treating the resultant gases, the sulphuric content of exhaust gases is effectively reduced. Methods to reduce the sulfur content of exhaust gases are described in the field of production of: sulphuric acid; viscose; fertilizers; and paraffin.

  1. Dicer1 depletion in male germ cells leads to infertility due to cumulative meiotic and spermiogenic defects.

    Directory of Open Access Journals (Sweden)

    Yannick Romero

    Full Text Available BACKGROUND: Spermatogenesis is a complex biological process that requires a highly specialized control of gene expression. In the past decade, small non-coding RNAs have emerged as critical regulators of gene expression both at the transcriptional and post-transcriptional level. DICER1, an RNAse III endonuclease, is essential for the biogenesis of several classes of small RNAs, including microRNAs (miRNAs and endogenous small interfering RNAs (endo-siRNAs, but is also critical for the degradation of toxic transposable elements. In this study, we investigated to which extent DICER1 is required for germ cell development and the progress of spermatogenesis in mice. PRINCIPAL FINDINGS: We show that the selective ablation of Dicer1 at the early onset of male germ cell development leads to infertility, due to multiple cumulative defects at the meiotic and post-meiotic stages culminating with the absence of functional spermatozoa. Alterations were observed in the first spermatogenic wave and include delayed progression of spermatocytes to prophase I and increased apoptosis, resulting in a reduced number of round spermatids. The transition from round to mature spermatozoa was also severely affected, since the few spermatozoa formed in mutant animals were immobile and misshapen, exhibiting morphological defects of the head and flagellum. We also found evidence that the expression of transposable elements of the SINE family is up-regulated in Dicer1-depleted spermatocytes. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that DICER1 is dispensable for spermatogonial stem cell renewal and mitotic proliferation, but is required for germ cell differentiation through the meiotic and haploid phases of spermatogenesis.

  2. Exhaustible-resource theory and the uranium market

    International Nuclear Information System (INIS)

    Hsieh, Y.L.

    1982-01-01

    Exhaustible-resource theory has been developed rapidly by economists since the OPEC shocks of 1973-1974 and the theory now provides a framework for analyzing the optimal production pattern for resource commodities. However, applications of the theory to particular markets, such as crude oil, have not provided accurate predictions due no doubt to theoretical problems in explaining exploration and discovery events, market organization changes, and uncertainty. This thesis investigated the uranium market in an effort to determine how well the exhaustible-resource theory explains the past price and quantity time paths of this energy resource, and what might be expected in the future. The exhaustible-resource theory was first developed in a form appropriate to an application to the uranium market. An econometric simulation model that combines the history of uranium price formation and the exhaustible-resource theory was developed to forecast future uranium prices. The model was designed not only to reflect the physical processes of drilling activities, changing reserves, production, and prices of uranium through individual equations, but also to account for the interaction of all these interrelationships at the same time

  3. The Role of Inspiratory Muscle Training in Sickle Cell Anemia Related Pulmonary Damage due to Recurrent Acute Chest Syndrome Attacks

    Directory of Open Access Journals (Sweden)

    Burcu Camcıoğlu

    2015-01-01

    Full Text Available Background. The sickling of red blood cells causes a constellation of musculoskeletal, cardiovascular, and pulmonary manifestations. A 32-year-old gentleman with sickle cell anemia (SCA had been suffering from recurrent acute chest syndrome (ACS. Aim. To examine the effects of inspiratory muscle training (IMT on pulmonary functions, respiratory and peripheral muscle strength, functional exercise capacity, and quality of life in this patient with SCA. Methods. Functional exercise capacity was evaluated using six-minute walk test, respiratory muscle strength using mouth pressure device, hand grip strength using hand-held dynamometer, pain using Visual Analogue Scale, fatigue using Fatigue Severity Scale, dyspnea using Modified Medical Research Council Scale, and health related quality of life using European Organization for Research and Treatment of Cancer QOL measurement. Results. A significant improvement has been demonstrated in respiratory muscle strength, functional exercise capacity, pain, fatigue, dyspnea, and quality of life. There was no admission to emergency department due to acute chest syndrome in the following 12 months after commencing regular erythrocytapheresis. Conclusion. This is the first report demonstrating the beneficial effects of inspiratory muscle training on functional exercise capacity, respiratory muscle strength, pain, fatigue, dyspnea, and quality of life in a patient with recurrent ACS.

  4. The Role of Inspiratory Muscle Training in Sickle Cell Anemia Related Pulmonary Damage due to Recurrent Acute Chest Syndrome Attacks.

    Science.gov (United States)

    Camcıoğlu, Burcu; Boşnak-Güçlü, Meral; Karadallı, Müşerrefe Nur; Akı, Şahika Zeynep; Türköz-Sucak, Gülsan

    2015-01-01

    Background. The sickling of red blood cells causes a constellation of musculoskeletal, cardiovascular, and pulmonary manifestations. A 32-year-old gentleman with sickle cell anemia (SCA) had been suffering from recurrent acute chest syndrome (ACS). Aim. To examine the effects of inspiratory muscle training (IMT) on pulmonary functions, respiratory and peripheral muscle strength, functional exercise capacity, and quality of life in this patient with SCA. Methods. Functional exercise capacity was evaluated using six-minute walk test, respiratory muscle strength using mouth pressure device, hand grip strength using hand-held dynamometer, pain using Visual Analogue Scale, fatigue using Fatigue Severity Scale, dyspnea using Modified Medical Research Council Scale, and health related quality of life using European Organization for Research and Treatment of Cancer QOL measurement. Results. A significant improvement has been demonstrated in respiratory muscle strength, functional exercise capacity, pain, fatigue, dyspnea, and quality of life. There was no admission to emergency department due to acute chest syndrome in the following 12 months after commencing regular erythrocytapheresis. Conclusion. This is the first report demonstrating the beneficial effects of inspiratory muscle training on functional exercise capacity, respiratory muscle strength, pain, fatigue, dyspnea, and quality of life in a patient with recurrent ACS.

  5. An acute hemolytic transfusion reaction due to anti-IH in a patient with sickle cell disease.

    Science.gov (United States)

    Campbell, S A; Shirey, R S; King, K E; Ness, P M

    2000-07-01

    A hemolytic transfusion reaction (HTR) due to anti-IH is reported in a patient with sickle cell disease (SCD). An 18-year-old woman with SCD and a complete phenotype on file had been identified as group B-positive with negative antibody-screening tests and had received 1 unit of packed RBCs. Ten days later, she was readmitted in painful crisis with a Hb of 4.2 g per dL. Antibody-screening tests and panel cells were positive at all test phases with a negative autocontrol, which suggested alloantibodies. Phenotypically matched group O RBCs were issued emergently. After the transfusion of 100 mL, the patient had an HTR with chills, fever, and tachycardia and laboratory findings of hemoglobinemia, hemoglobinuria, and negative DATs. A high-titer, IgM anti-IH with a high thermal amplitude (reactive with group O, but not group B RBCs at 37 degrees C) was identified. Autologous RBCs appeared to have normal I antigen expression, but less H antigen than pooled group B RBCs. She was given group B RBCs, uneventfully, by use of a blood warmer. This is a rare case of anti-IH as the cause of a HTR, as a serologic problem that may be seen in SCD, and as an autoantibody that may mimic an alloantibody. Ironically, this HTR resulted from the effort to provide phenotypically matched RBCs, which necessitated the selection of group O RBCs.

  6. Severe Cushing’s syndrome due to small cell prostate carcinoma: a case and review of literature

    Directory of Open Access Journals (Sweden)

    M S Elston

    2017-07-01

    Full Text Available Cushing’s syndrome (CS due to ectopic adrenocorticotrophic hormone (ACTH is associated with a variety of tumours most of which arise in the thorax or abdomen. Prostate carcinoma is a rare but important cause of rapidly progressive CS. To report a case of severe CS due to ACTH production from prostate neuroendocrine carcinoma and summarise previous published cases. A 71-year-old male presented with profound hypokalaemia, oedema and new onset hypertension. The patient reported two weeks of weight gain, muscle weakness, labile mood and insomnia. CS due to ectopic ACTH production was confirmed with failure to suppress cortisol levels following low- and high-dose dexamethasone suppression tests in the presence of a markedly elevated ACTH and a normal pituitary MRI. Computed tomography demonstrated an enlarged prostate with features of malignancy, confirmed by MRI. Subsequent prostatic biopsy confirmed neuroendocrine carcinoma of small cell type and conventional adenocarcinoma of the prostate. Adrenal steroidogenesis blockade was commenced using ketoconazole and metyrapone. Complete biochemical control of CS and evidence of disease regression on imaging occurred after four cycles of chemotherapy with carboplatin and etoposide. By the sixth cycle, the patient demonstrated radiological progression followed by recurrence of CS and died nine months after initial presentation. Prostate neuroendocrine carcinoma is a rare cause of CS that can be rapidly fatal, and early aggressive treatment of the CS is important. In CS where the cause of EAS is unable to be identified, a pelvic source should be considered and imaging of the pelvis carefully reviewed.

  7. Toxicity of Exhaust Gases and Particles from IC-Engines -- International Activities Survey (EngToxIn)

    Energy Technology Data Exchange (ETDEWEB)

    Czerwinski, J. [University for Applied Sciences, Biel-Bienne (Switzerland)

    2011-09-15

    Exhaust gases from engines, as well as from other combustion -- and industrial processes contain different gaseous, semi volatile and solid compounds which are toxic. Some of these compounds are not regarded by the respective legislations; some new substances may appear, due to the progressing technical developments and new systems of exhaust gas aftertreatment. The toxical effects of exhaust gases as whole aerosols (i.e. all gaseous components together with particle matter and nanoparticles) can be investigated in a global way, by exposing the living cells, or cell cultures to the aerosol, which means a simultaneous superposition of all toxic effects from all active components. On several places researchers showed, that this method offers more objective results of validation of toxicity, than other methods used up to date. It also enables a relatively quick insight in the toxic effects with consideration of all superimposed influences of the aerosol. This new methodology can be applied for all kinds of emission sources. It bears potentials of giving new contributions to the present state of knowledge in this domain and can in some cases lead to a change of paradigma. The present report gives short information about the activities concerning the research on toxicity of exhaust gases from IC-engines in different countries. It also gives some ideas about research of information sources. It can be stated that there are worldwide a lot of activities concerning health effects. They have different objectives, different approaches and methodologies and rarely the results can be directly compared to each other. Nevertheless there also are some common lines and with appropriate efforts there are possible ways to establish the harmonised biological test procedures.

  8. Vital exhaustion and risk for cancer

    DEFF Research Database (Denmark)

    Bergelt, Corinna; Christensen, Jane Hvarregaard; Prescott, Eva

    2005-01-01

    Vital exhaustion, defined as feelings of depression and fatigue, has previously been investigated mainly as a risk factor for cardiovascular disease. The authors investigated the association between depressive feelings and fatigue as covered by the concept of vital exhaustion and the risk...... for cancer....

  9. Local Exhaust Optimization and Worker Exposure

    DEFF Research Database (Denmark)

    Heiselberg, Per; Pedersen, Morten; Plath, Thomas

    This paper describes a process of optimisation of exhaust efficiency and of minimisation of worker exposure at a semiautomatic printing machine at a printing office.......This paper describes a process of optimisation of exhaust efficiency and of minimisation of worker exposure at a semiautomatic printing machine at a printing office....

  10. Vital exhaustion and risk for cancer

    DEFF Research Database (Denmark)

    Bergelt, Corinna; Christensen, Jane Hvarregaard; Prescott, Eva

    2005-01-01

    Vital exhaustion, defined as feelings of depression and fatigue, has previously been investigated mainly as a risk factor for cardiovascular disease. The authors investigated the association between depressive feelings and fatigue as covered by the concept of vital exhaustion and the risk...

  11. 46 CFR 119.430 - Engine exhaust pipe installation.

    Science.gov (United States)

    2010-10-01

    ... an exhaust pipe. (b) Exhaust gas must not leak from the piping or any connections. The piping must be... stresses resulting from the expansion of the exhaust piping. (g) A dry exhaust pipe must: (1) If it passes... discharge terminating in a transom must be located as far outboard as practicable so that exhaust gases...

  12. Method for removing soot from exhaust gases

    Science.gov (United States)

    Suib, Steven L.; Dharmarathna, D. A. Saminda; Pahalagedara, Lakshitha R.

    2018-01-16

    A method for oxidizing soot from diesel exhaust gas from a diesel engine. The method involves providing a diesel particulate filter for receiving the diesel exhaust gas; coating a catalyst composition on the diesel particulate filter; and contacting the soot from the diesel exhaust gas with the catalyst coated diesel particulate filter at a temperature sufficient to oxidize the soot to carbon dioxide. The catalyst composition is a doped or undoped manganese oxide octahedral molecular sieve (OMS-2) material. A diesel exhaust gas treatment system that includes a diesel particulate filter for receiving diesel exhaust gas from a diesel engine and collecting soot; and a catalyst composition coated on the diesel particulate filter. The catalyst composition is a doped or undoped manganese oxide octahedral molecular sieve (OMS-2).

  13. [Vital exhaustion is significantly linked to acute coronary events in Argentine population].

    Science.gov (United States)

    Bonet, José; Mautner, Branco; Kerbage, Soraya; Bonet, María F; Pérez Lloret, Santiago

    2009-01-01

    To determine the strength of the association between the Vital exhaustion syndrome (VES) and acute coronary ischemic events in hospitalized Argentinean sample. VES was measured in 180 patients of both sexes, 90 admitted due to an acute coronary ischemic syndrome (AMI or unstable angina) and a control group of 90 admitted due to an acute non-coronary cardiac event. VES was evaluated with the Maastricht questionnaire during the first week of hospitalization. Dividing the sample in two categories: exhausted and non-exhausted, 57 (63,33%) of the coronary were exhausted, while among the non coronary group, 33 were exhausted (36,66%)(OR=3.1 (1.7-5.8)). The exhaustion score was: control mean score: 17,1 (sd 8,96); case mean score: 21,1 (sd10,60) p: 0.006. Dislipemia was another factor with a significant difference: control 27 (30%) case 44 (62%) OR= 2.2 (1.2-4.1) p=0.01. Logistic regression was performed, including an interaction model between DLP and exhaustion, and it did not show a significant effect. Our results indicate that in Argentina, among other countries as reported in the literature, VES is a psychological condition that is strongly and independent associated to acute coronary events.

  14. Higher efficiency with cylinder-bank comprehensive exhaust manifold; Effizienzsteigerung durch Zylinderbank-uebergreifenden Kruemmer

    Energy Technology Data Exchange (ETDEWEB)

    Diez, Rainer; Kornherr, Heinz; Pirntke, Frank; Schmidt, Juergen [Friedrich Boysen GmbH und Co. KG, Altensteig (Germany)

    2010-05-15

    In close interdisciplinary cooperation with BMW Group, Boysen has developed an air-gap-insulated exhaust manifold that encompasses both banks of the 4.4 l V8 spark-ignition twin turbo engine of the BMW X5 M and BMW X6 M. The manifold merges the exhaust gas flow from the cylinders of the left-hand and right-hand cylinder banks in opposing pairs, thus optimising gas exchange. Due to improvements in response, torque and power characteristics of the engine, the cylinder-bank comprehensive exhaust manifold helps achieve high fuel efficiency. (orig.)

  15. Hemolytic disease of fetus and newborn due to maternal red blood cell alloantibodies in the Malay population

    Science.gov (United States)

    Hassan, Mohd Nazri; Mohd Noor, Noor Haslina; Johan Noor, Shah Reza; Sukri, Salamah Ahmad; Mustafa, Rapiaah; Luc Aster, Hans Van Rostenberghe

    2014-01-01

    Background: Maternal red blood cell (RBC) alloimmunization may lead to production of harmful antibodies that result in hemolytic disease of fetus and newborn (HDFN). There is insufficient data on the prevalence of HDFN due to RBC alloantibodies in the Malay neonatal population. Aim: The aim of this study was to determine the incidence of HDFN in the Malay neonatal population due to clinically significant RBC alloantibodies. Subjects and Methods: A cross sectional study was conducted in Transfusion Medicine Unit, Hospital Universitiy Sains Malaysia over one year period from January to December 2009. A total of 5163 Malay pregnant women who attended labor room for delivery were collected and analyzed prospectively. The blood samples were subjected to the standard immunohematological procedure for RBC antibody screening and identification using reagents of Diamed-ID Gel microtyping system. All the newborns with RBC alloantibody were investigated for the evidence of HDFN. Results: Thirty (0.58%) women were found to have clinically significant RBC alloantibodies. Most of the alloantibodies belonged to Rhesus (Rh) system (56.7%) where anti-E (33.3%) was the most common followed by anti-D (10.0%). Rh antibodies were the main cause of HDFN in fourteen (0.27%) neonates. Anti-D and anti-c were identified to cause moderate to very severe HDFN. Conclusions: With the low prevalence of clinically significant RBC alloantibodies and HDFN, routine antenatal antibody screening practice may not be advised as a routine practice at present, preferably reserved for those women of RhD negative or with history of HDFN, significantly of those attributed to anti-c. PMID:25161351

  16. Hemolytic disease of fetus and newborn due to maternal red blood cell alloantibodies in the Malay population

    Directory of Open Access Journals (Sweden)

    Mohd Nazri Hassan

    2014-01-01

    Full Text Available Background: Maternal red blood cell (RBC alloimmunization may lead to production of harmful antibodies that result in hemolytic disease of fetus and newborn (HDFN. There is insufficient data on the prevalence of HDFN due to RBC alloantibodies in the Malay neonatal population. Aim: The aim of this study was to determine the incidence of HDFN in the Malay neonatal population due to clinically significant RBC alloantibodies. Subjects and Methods: A cross sectional study was conducted in Transfusion Medicine Unit, Hospital Universitiy Sains Malaysia over one year period from January to December 2009. A total of 5163 Malay pregnant women who attended labor room for delivery were collected and analyzed prospectively. The blood samples were subjected to the standard immunohematological procedure for RBC antibody screening and identification using reagents of Diamed-ID Gel microtyping system. All the newborns with RBC alloantibody were investigated for the evidence of HDFN. Results: Thirty (0.58% women were found to have clinically significant RBC alloantibodies. Most of the alloantibodies belonged to Rhesus (Rh system (56.7% where anti-E (33.3% was the most common followed by anti-D (10.0%. Rh antibodies were the main cause of HDFN in fourteen (0.27% neonates. Anti-D and anti-c were identified to cause moderate to very severe HDFN . Conclusions: With the low prevalence of clinically significant RBC alloantibodies and HDFN, routine antenatal antibody screening practice may not be advised as a routine practice at present, preferably reserved for those women of RhD negative or with history of HDFN, significantly of those attributed to anti-c.

  17. Lack of role for mononuclear cell-derived histamine releasing factors in occupational asthma due to western red cedar.

    Science.gov (United States)

    Frew, A J; Chan, H; Chan-Yeung, M

    1993-10-01

    Occupational asthma due to Western Red Cedar (WRCA) is attributed to sensitization to plicatic acid (PA), but does not appear to be dependent on PA-specific IgE antibodies. Exposure to PA induces histamine release in vivo and in vitro, so if IgE is not important, other mechanisms of histamine release must presumably operate in WRCA. To explore the possible role of histamine-releasing factors in WRCA, peripheral blood mononuclear cells were obtained and cultured with PA, PA-albumin conjugate plicatic acid-human serum albumin (PA-HSA), grass pollen or Concanavalin A using a standard histamine releasing factor (HRF) generation protocol. Supernatants were dialysed to remove endogenous histamine and then assayed for histamine releasing activity using human basophils as targets and a Con A-induced bulk supernatant as an internal HRF standard. In contrast to some previous reports, spontaneous HRF release from the peripheral blood mononuclear cells (PBMC) of WRCA patients (n=9) and atopic asthmatic subjects (n=5) was not elevated compared with the non-asthmatic controls (n=11; five atopic and six non-atopic). Both PA and PA-HSA induced the production of small amounts of HRF by PBMC of WRCA patients, but a similar degree of HRF generation was also observed in PBMC from the atopic asthmatic, atopic nonasthmatic, and non-atopic subjects. In contrast, grass pollen induced the production of HRF by PBMC from the subjects with positive skin tests to grass pollen but not by PBMC of non-atopic subjects, confirming that our methods and assay were capable of detecting antigen-specific HRF production. Since neither PA nor PA-HSA induced significantly elevated HRF production from PBMC of WRCA patients, it seems unlikely that PA-induced HRFs play a substantial role in the pathogenesis of WRCA.

  18. Decreased CD8+ T cell response to Epstein-Barr virus infected B cells in multiple sclerosis is not due to decreased HLA class I expression on B cells or monocytes

    Directory of Open Access Journals (Sweden)

    Csurhes Peter A

    2011-08-01

    Full Text Available Abstract Background Patients with multiple sclerosis (MS have a decreased frequency of CD8+ T cells reactive to their own Epstein-Barr virus (EBV infected B cells. We have proposed that this might predispose to the development of MS by allowing EBV-infected autoreactive B cells to accumulate in the central nervous system. The decreased CD8+ T cell response to EBV results from a general CD8+ T cell deficiency and also a decreased proportion of EBV-specific T cells within the total CD8+ T cell population. Because decreased HLA class I expression on monocytes and B cells has been reported in MS and could influence the generation and effector function of EBV-specific CD8+ T cells, the present study was undertaken to measure the expression of HLA molecules on B cells and monocytes in patients with MS. Methods We used flow cytometry to determine the proportions of T cells, natural killer cells, B cells and monocytes in peripheral blood mononuclear cells (PBMC and to quantify the expression of HLA molecules on T cells, B cells and monocytes of 59 healthy subjects and 62 patients with MS who had not received corticosteroids or immunomodulatory therapy in the previous 3 months. Results The levels of HLA class I and class II molecules expressed on T cells, B cells and monocytes were normal in patients with MS, with the exception of two patients with secondary progressive MS with very low class II expression on B cells. In confirmation of previous studies we also found that the percentage of CD8+ T cells was significantly decreased whereas the percentage of CD4+ T cells and the CD4:CD8 ratio were significantly increased in patients with MS compared to healthy subjects. Conclusions The decreased CD8+ T cell response to EBV-infected B cells in MS patients is not due to decreased HLA class I expression on monocytes or B cells. In a small proportion of patients decreased HLA class II expression on B cells might impair the CD8+ T cell response to EBV by

  19. Emergency Pancreatoduodenectomy with Preservation of Gastroduodenal Artery for Massive Gastrointestinal Bleeding due to Duodenal Metastasis by Clear Cell Renal Cell Carcinoma in a Patient with Celiac Artery Stenosis

    Directory of Open Access Journals (Sweden)

    Kyriakos Neofytou

    2014-01-01

    Full Text Available Duodenal metastasis from renal cell carcinoma is rare, and even rarer is a massive gastrointestinal bleeding from such tumours. Coeliac occlusive disease, although rarely symptomatic, can lead to ischaemic changes with anastomotic dehiscence and leaks when a patient undergoes pancreatoduodenectomy. A 41-year-old man with known metastasis to the adrenal glands and the second part of the duodenum close to the ampulla of Vater from clear cell renal cell carcinoma was admitted to our department due to massive gastrointestinal bleeding from the duodenal metastasis. Endoscopic control of the bleed was not possible, while the bleeding vessel embolization was able to control the haemorrhage only temporarily. An angiography during the embolization demonstrated the presence of stenosis of the coeliac artery and also hypertrophic inferior pancreaticoduodenal arteries supplying the proper hepatic artery via the gastroduodenal artery (GDA. The patient underwent emergency pancreatoduodenectomy with preservation of the gastroduodenal artery. The patient had an uneventful recovery and did not experience further bleeding. Also the blood flow to the liver was compromised as shown by the normal liver function tests (LFTs postoperatively. To the best of our knowledge, this is the first report of a preservation of the GDA during an emergency pancreatoduodenectomy.

  20. Suppressing Energy Loss due to Triplet Exciton Formation in Organic Solar Cells: The Role of Chemical Structures and Molecular Packing

    KAUST Repository

    Chen, Xiankai

    2017-04-21

    In the most efficient solar cells based on blends of a conjugated polymer (electron donor) and a fullerene derivative (electron acceptor),ultrafast formation of charge-transfer (CT) electronic states at the donor-acceptor interfaces and efficient separation of these CT states into free charges, lead to internal quantum efficiencies near 100%. However, there occur substantial energy losses due to the non-radiative recombinations of the charges, mediated by the loweset-energy (singlet and triplet) CT states; for example, such recombinations can lead to the formation of triplet excited electronic states on the polymer chains, which do not generate free charges. This issue remains a major factor limiting the power conversion efficiencies (PCE) of these devices. The recombination rates are, however, difficult to quantify experimentally. To shed light on these issues, here, an integrated multi-scale theoretical approach that combines molecular dynamics simulations with quantum chemistry calculations is employed in order to establish the relationships among chemical structures, molecular packing, and non-radiative recombination losses mediated by the lowest-energy charge-transfer states.

  1. Exhaust gas recirculation system for an internal combustion engine

    Science.gov (United States)

    Wu, Ko-Jen

    2013-05-21

    An exhaust gas recirculation system for an internal combustion engine comprises an exhaust driven turbocharger having a low pressure turbine outlet in fluid communication with an exhaust gas conduit. The turbocharger also includes a low pressure compressor intake and a high pressure compressor outlet in communication with an intake air conduit. An exhaust gas recirculation conduit fluidly communicates with the exhaust gas conduit to divert a portion of exhaust gas to a low pressure exhaust gas recirculation branch extending between the exhaust gas recirculation conduit and an engine intake system for delivery of exhaust gas thereto. A high pressure exhaust gas recirculation branch extends between the exhaust gas recirculation conduit and the compressor intake and delivers exhaust gas to the compressor for mixing with a compressed intake charge for delivery to the intake system.

  2. A NEW EXHAUST VENTILATION SYSTEM DESIGN SOFTWARE

    Directory of Open Access Journals (Sweden)

    H. Asilian Mahabady

    2007-09-01

    Full Text Available A Microsoft Windows based ventilation software package is developed to reduce time-consuming and boring procedure of exhaust ventilation system design. This program Assure accurate and reliable air pollution control related calculations. Herein, package is tentatively named Exhaust Ventilation Design Software which is developed in VB6 programming environment. Most important features of Exhaust Ventilation Design Software that are ignored in formerly developed packages are Collector design and fan dimension data calculations. Automatic system balance is another feature of this package. Exhaust Ventilation Design Software algorithm for design is based on two methods: Balance by design (Static pressure balance and design by Blast gate. The most important section of software is a spreadsheet that is designed based on American Conference of Governmental Industrial Hygienists calculation sheets. Exhaust Ventilation Design Software is developed so that engineers familiar with American Conference of Governmental Industrial Hygienists datasheet can easily employ it for ventilation systems design. Other sections include Collector design section (settling chamber, cyclone, and packed tower, fan geometry and dimension data section, a unit converter section (that helps engineers to deal with units, a hood design section and a Persian HTML help. Psychometric correction is also considered in Exhaust Ventilation Design Software. In Exhaust Ventilation Design Software design process, efforts are focused on improving GUI (graphical user interface and use of programming standards in software design. Reliability of software has been evaluated and results show acceptable accuracy.

  3. [The carcinogenic and genotoxic action of the substances in the exhaust gases from internal combustion engines].

    Science.gov (United States)

    Makhover, M S; Khesina, A Ia

    1990-01-01

    The review presents physicochemical methods of the study of polycyclic aromatic hydrocarbons (PAH) and analysis of substances composing the exhausts of the internal combustion engines (ICE). High carcinogenic effect of the ICE exhausts due to the presence of nitro-PAHs was confirmed in the experiments with animals and the mutagenic effect was detected in the Ames test. A necessity to study carcinogenic and mutagenic effects of nitro-PAHs in a view to reveal their potential human health hazard is emphasized.

  4. Telomere Dynamics in Immune Senescence and Exhaustion Triggered by Chronic Viral Infection.

    Science.gov (United States)

    Bellon, Marcia; Nicot, Christophe

    2017-10-05

    The progressive loss of immunological memory during aging correlates with a reduced proliferative capacity and shortened telomeres of T cells. Growing evidence suggests that this phenotype is recapitulated during chronic viral infection. The antigenic volume imposed by persistent and latent viruses exposes the immune system to unique challenges that lead to host T-cell exhaustion, characterized by impaired T-cell functions. These dysfunctional memory T cells lack telomerase, the protein capable of extending and stabilizing chromosome ends, imposing constraints on telomere dynamics. A deleterious consequence of this excessive telomere shortening is the premature induction of replicative senescence of viral-specific CD8+ memory T cells. While senescent cells are unable to expand, they can survive for extended periods of time and are more resistant to apoptotic signals. This review takes a closer look at T-cell exhaustion in chronic viruses known to cause human disease: Epstein-Barr virus (EBV), Hepatitis B/C/D virus (HBV/HCV/HDV), human herpesvirus 8 (HHV-8), human immunodeficiency virus (HIV), human T-cell leukemia virus type I (HTLV-I), human papillomavirus (HPV), herpes simplex virus-1/2(HSV-1/2), and Varicella-Zoster virus (VZV). Current literature linking T-cell exhaustion with critical telomere lengths and immune senescence are discussed. The concept that enduring antigen stimulation leads to T-cell exhaustion that favors telomere attrition and a cell fate marked by enhanced T-cell senescence appears to be a common endpoint to chronic viral infections.

  5. Design and Optimisation of Electrostatic Precipitator for Diesel Exhaust

    Science.gov (United States)

    Srinivaas, A.; Sathian, Samanyu; Ramesh, Arjun

    2018-02-01

    The principle of an industrially used emission reduction technique is employed in automotive diesel exhaust to reduce the diesel particulate emission. As the Emission regulation are becoming more stringent legislations have been formulated, due to the hazardous increase in the air quality index in major cities. Initially electrostatic precipitation principle and working was investigated. The High voltage requirement in an Electrostatic precipitator is obtained by designing an appropriate circuit in MATLAB -SIMULINK. Mechanical structural design of the new model after treatment device for the specific diesel exhaust was done. Fluid flow analysis of the ESP model was carried out using ANSYS CFX for optimized fluid with a reduced back pressure. Design reconsideration was done in accordance with fluid flow analysis. Accordingly, a new design is developed by considering diesel particulate filter and catalytic converter design to ESP model.

  6. Modelling and Operation of Diesel Engine Exhaust Gas Cleaning Systems

    DEFF Research Database (Denmark)

    Åberg, Andreas

    importance due to their effect on urban air quality, and because of new legislation. In modern heavy-duty applications, the exhaust gases are typically treated with four different catalysts: a Diesel Oxidation Catalyst (DOC) which oxidises HC and CO into H2O and CO2, and NO into NO2, a Diesel Particulate......Diesel engine exhaust gases contain several harmful substances. The main pollutants are carbon monoxide (CO), hydrocarbons (HC), particulate matter (PM), and nitrous gases such as nitrogen oxide (NO) and nitrogen dioxide (NO2) (together NOx). Reducing the emission of these pollutants is of great...... Filter (DPF) which filters PM, a Selective Catalytic Reduction (SCR) catalyst which removes NO and NO2 through reaction with NH3, and an Ammonia Slip Catalyst (ASC) which removes excess ammonia (NH3) before the gases are released to the atmosphere. SCR is a widely used technology to reduce NOx to N2...

  7. Increased radiosensitivity of HPV-positive head and neck cancer cell lines due to cell cycle dysregulation and induction of apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Arenz, Andrea; Ziemann, Frank; Wittig, Andrea; Preising, Stefanie; Engenhart-Cabillic, Rita [Philipps-University, Department of Radiotherapy and Radiooncology, BMFZ - Biomedical Research Center, Marburg (Germany); Mayer, Christina; Wagner, Steffen; Klussmann, Jens-Peter; Wittekindt, Claus [Justus Liebig University, Department of Otorhinolaryngology and Head and Neck Surgery, Giessen (Germany); Dreffke, Kirstin [Philipps-University, Institute for Radiobiology and Molecular Radiooncology, Marburg (Germany)

    2014-09-15

    Human Papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) respond favourably to radiotherapy as compared to HPV-unrelated HNSCC. We investigated DNA damage response in HPV-positive and HPV-negative HNSCC cell lines aiming to identify mechanisms, which illustrate reasons for the increased sensitivity of HPV-positive cancers of the oropharynx. Radiation response including clonogenic survival, apoptosis, DNA double-strand break (DSB) repair, and cell cycle redistribution in four HPV-positive (UM-SCC-47, UM-SCC-104, 93-VU-147T, UPCI:SCC152) and four HPV-negative (UD-SCC-1, UM-SCC-6, UM-SCC-11b, UT-SCC-33) cell lines was evaluated. HPV-positive cells were more radiosensitive (mean SF2: 0.198 range: 0.22-0.18) than HPV-negative cells (mean SF2: 0.34, range: 0.45-0.27; p = 0.010). Irradiated HPV-positive cell lines progressed faster through S-phase showing a more distinct accumulation in G2/M. The abnormal cell cycle checkpoint activation was accompanied by a more pronounced increase of cell death after x-irradiation and a higher number of residual and unreleased DSBs. The enhanced responsiveness of HPV-related HNSCC to radiotherapy might be caused by a higher cellular radiosensitivity due to cell cycle dysregulation and impaired DNA DSB repair. (orig.) [German] Fuer Patienten mit HPV-assoziierten Kopf-Hals-Tumoren (HNSCC) ist im Vergleich zu Patienten mit nicht-HPV-assoziierten Tumoren ein besseres Ueberleben nach Radiotherapie gesichert. Ziel der Untersuchung war die Identifizierung von Unterschieden in der zellulaeren DNA-Schadensantwort von HPV-positiven und HPV-negativen Zelllinien, wodurch die bereits in Erprobung stehende Deeskalation einer Radiotherapie bei Patienten mit HPV-assoziierten HNSCC durch experimentelle Daten abgesichert werden koennte. Klonogenes Ueberleben, Induktion von Apoptose, DNA-Doppelstrang-Reparatur und Zellzyklusverhalten wurden in vier HPV-positiven (UM-SCC-47, UM-SCC-104, 93-VU-147T, UPCI:SCC152) und vier HPV

  8. Current sheets and pressure anisotropy in the reconnection exhaust

    International Nuclear Information System (INIS)

    Le, A.; Karimabadi, H.; Roytershteyn, V.; Egedal, J.; Ng, J.; Scudder, J.; Daughton, W.; Liu, Y.-H.

    2014-01-01

    A particle-in-cell simulation shows that the exhaust during anti-parallel reconnection in the collisionless regime contains a current sheet extending 100 inertial lengths from the X line. The current sheet is supported by electron pressure anisotropy near the X line and ion anisotropy farther downstream. Field-aligned electron currents flowing outside the magnetic separatrices feed the exhaust current sheet and generate the out-of-plane, or Hall, magnetic field. Existing models based on different mechanisms for each particle species provide good estimates for the levels of pressure anisotropy. The ion anisotropy, which is strong enough to reach the firehose instability threshold, is also important for overall force balance. It reduces the outflow speed of the plasma

  9. Gravimetric Measurements of Filtering Facepiece Respirators Challenged With Diesel Exhaust.

    Science.gov (United States)

    Satish, Swathi; Swanson, Jacob J; Xiao, Kai; Viner, Andrew S; Kittelson, David B; Pui, David Y H

    2017-07-01

    Elevated concentrations of diesel exhaust have been linked to adverse health effects. Filtering facepiece respirators (FFRs) are widely used as a form of respiratory protection against diesel particulate matter (DPM) in occupational settings. Previous results (Penconek A, Drążyk P, Moskal A. (2013) Penetration of diesel exhaust particles through commercially available dust half masks. Ann Occup Hyg; 57: 360-73.) have suggested that common FFRs are less efficient than would be expected for this purpose based on their certification approvals. The objective of this study was to measure the penetration of DPM through NIOSH-certified R95 and P95 electret respirators to verify this result. Gravimetric-based penetration measurements conducted using polytetrafluoroethylene (PTFE) and polypropylene (PP) filters were compared with penetration measurements made with a Scanning Mobility Particle Sizer (SMPS, TSI Inc.), which measures the particle size distribution. Gravimetric measurements using PP filters were variable compared to SMPS measurements and biased high due to adsorption of gas phase organic material. Relatively inert PTFE filters adsorbed less gas phase organic material resulting in measurements that were more accurate. To attempt to correct for artifacts associated with adsorption of gas phase organic material, primary and secondary filters were used in series upstream and downstream of the FFR. Correcting for adsorption by subtracting the secondary mass from the primary mass improved the result for both PTFE and PP filters but this correction is subject to 'equilibrium' conditions that depend on sampling time and the concentration of particles and gas phase hydrocarbons. Overall, the results demonstrate that the use of filters to determine filtration efficiency of FFRs challenged with diesel exhaust produces erroneous results due to the presence of gas phase hydrocarbons in diesel exhaust and the tendency of filters to adsorb organic material. Published by

  10. CD40 agonist converting CTL exhaustion via the activation of the mTORC1 pathway enhances PD-1 antagonist action in rescuing exhausted CTLs in chronic infection.

    Science.gov (United States)

    Xu, Aizhang; Wang, Rong; Freywald, Andrew; Stewart, Kristoffor; Tikoo, Suresh; Xu, Jianqing; Zheng, Changyu; Xiang, Jim

    2017-03-11

    Expansion of PD-1-expressing CD8 + cytotoxic T lymphocytes (CTLs) and associated CTL exhaustion are chief issues for ineffective virus-elimination in chronic infectious diseases. PD-1 blockade using antagonistic anti-PD-L1 antibodies results in a moderate conversion of CTL exhaustion. We previously demonstrated that CD40L signaling of ovalbumin (OVA)-specific vaccine, OVA-Texo, converts CTL exhaustion via the activation of the mTORC1 pathway in OVA-expressing adenovirus (AdVova)-infected B6 mice showing CTL inflation and exhaustion. Here, we developed AdVova-infected B6 and transgenic CD11c-DTR (termed AdVova-B6 and AdVova-CD11c-DTR) mice with chronic infection, and assessed a potential effect of CD40 agonist on the conversion of CTL exhaustion and on a potential enhancement of PD-1 antagonist action in rescuing exhausted CTLs in our chronic infection models. We demonstrate that a single dose of anti-CD40 alone can effectively convert CTL exhaustion by activating the mTORC1 pathway, leading to CTL proliferation, up-regulation of an effector-cytokine IFN-γ and the cytolytic effect in AdVova-B6 mice. Using anti-CD4 antibody and diphtheria toxin (DT) to deplete CD4 + T-cells and dendritic cells (DCs), we discovered that the CD40 agonist-induced conversion in AdVova-B6 and AdVova-CD11c-DTR mice is dependent upon host CD4 + T-cell and DC involvements. Moreover, CD40 agonist significantly enhances PD-1 antagonist effectiveness in rescuing exhausted CTLs in chronic infection. Taken together, our data demonstrate the importance of CD40 signaling in the conversion of CTL exhaustion and its ability to enhance PD-1 antagonist action in rescuing exhausted CTLs in chronic infection. Therefore, our findings may positively impact the design of new therapeutic strategies for chronic infectious diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Experimental Analysis of Exhaust Manifold with Ceramic Coating for Reduction of Heat Dissipation

    Science.gov (United States)

    Saravanan, J.; Valarmathi, T. N.; Nathc, Rajdeep; Kumar, Prasanth

    2017-05-01

    Exhaust manifold plays an important role in the exhaust system, the manifold delivers the waste toxic gases to a safe distance and it is used to reduce the sound pollution and air pollution. Exhaust manifold suffers with lot of thermal stress, due to this blow holes occurs in the surface of the exhaust manifold and also more noise is developed. The waste toxic gases from the multiple cylinders are collected into a single pipe by the exhaust manifold. The waste toxic gases can damage the material of the manifold. In this study, to prevent the damage zirconia powder has been coated in the inner surface and alumina (60%) combined with titania (40%) has been used for coating the outer surface of the exhaust manifold. After coating experiments have been performed using a multiple-cylinder four stroke stationary petrol engine. The test results of hardness, emission, corrosion and temperature of the coated and uncoated manifolds have been compared. The result shows that the performance is improved and also emission is reduced in the coated exhaust manifold.

  12. Reduced Mortality of Cytomegalovirus Pneumonia After Hematopoietic Cell Transplantation Due to Antiviral Therapy and Changes in Transplantation Practices.

    Science.gov (United States)

    Erard, Veronique; Guthrie, Katherine A; Seo, Sachiko; Smith, Jeremy; Huang, MeeiLi; Chien, Jason; Flowers, Mary E D; Corey, Lawrence; Boeckh, Michael

    2015-07-01

    Despite major advances in the prevention of cytomegalovirus (CMV) disease, the treatment of CMV pneumonia in recipients of hematopoietic cell transplant remains a significant challenge. We examined recipient, donor, transplant, viral, and treatment factors associated with overall and attributable mortality using Cox regression models. Four hundred twenty-one cases were identified between 1986 and 2011. Overall survival at 6 months was 30% (95% confidence interval [CI], 25%-34%). Outcome improved after the year 2000 (all-cause mortality: adjusted hazard ratio [aHR], 0.7 [95% CI, .5-1.0]; P = .06; attributable mortality: aHR, 0.6 [95% CI, .4-.9]; P = .01). Factors independently associated with an increased risk of all-cause and attributable mortality included female sex, elevated bilirubin, lymphopenia, and mechanical ventilation; grade 3/4 acute graft-vs-host disease was associated with all-cause mortality only. An analysis of patients who received transplants in the current preemptive therapy era (n = 233) showed only lymphopenia and mechanical ventilation as significant risk factors for overall and attributable mortality. Antiviral treatment with ganciclovir or foscarnet was associated with improved outcome compared with no antiviral treatment. However, the addition of intravenous pooled or CMV-specific immunoglobulin to antiviral treatment did not seem to improve overall or attributable mortality. Outcome of CMV pneumonia showed a modest improvement over the past 25 years. However, advances seem to be due to antiviral treatment and changes in transplant practices rather than immunoglobulin-based treatments. Novel treatment strategies for CMV pneumonia are needed. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Catalytic diesel particulate filters reduce the in vitro estrogenic activity of diesel exhaust

    Energy Technology Data Exchange (ETDEWEB)

    Wenger, Daniela; Gerecke, Andreas C.; Heeb, Norbert V. [Laboratory for Analytical Chemistry, Empa, Swiss Federal Laboratories for Materials Testing and Research, Duebendorf (Switzerland); Naegeli, Hanspeter [University of Zurich-Vetsuisse, Institute of Pharmacology and Toxicology, Zurich (Switzerland); Zenobi, Renato [ETH Zurich, Department of Chemistry and Applied Biosciences, Zurich (Switzerland)

    2008-04-15

    An in vitro reporter gene assay based on human breast cancer T47D cells (ER-CALUX {sup registered}) was applied to examine the ability of diesel exhaust to induce or inhibit estrogen receptor (ER)-mediated gene expression. Exhaust from a heavy-duty diesel engine was either treated by iron- or copper/iron-catalyzed diesel particulate filters (DPFs) or studied as unfiltered exhaust. Collected samples included particle-bound and semivolatile constituents of diesel exhaust. Our findings show that all of the samples contained compounds that were able to induce ER-mediated gene expression as well as compounds that suppressed the activity of the endogenous hormone 17{beta}-estradiol (E2). Estrogenic activity prevailed over antiestrogenic activity. We found an overall ER-mediated activity of 1.63 {+-} 0.31 ng E2 CALUX equivalents (E2-CEQs) per m{sup 3} of unfiltered exhaust. In filtered exhaust, we measured 0.74 {+-} 0.07 (iron-catalyzed DPF) and 0.55 {+-} 0.09 ng E2-CEQ m{sup -3} (copper/iron-catalyzed DPF), corresponding to reductions in estrogenic activity of 55 and 66%, respectively. Our study demonstrates that both catalytic DPFs lowered the ER-mediated endocrine-disrupting potential of diesel exhaust. (orig.)

  14. Two phase exhaust for internal combustion engine

    Science.gov (United States)

    Vuk, Carl T [Denver, IA

    2011-11-29

    An internal combustion engine having a reciprocating multi cylinder internal combustion engine with multiple valves. At least a pair of exhaust valves are provided and each supply a separate power extraction device. The first exhaust valves connect to a power turbine used to provide additional power to the engine either mechanically or electrically. The flow path from these exhaust valves is smaller in area and volume than a second flow path which is used to deliver products of combustion to a turbocharger turbine. The timing of the exhaust valve events is controlled to produce a higher grade of energy to the power turbine and enhance the ability to extract power from the combustion process.

  15. Power and particle exhaust in tokamaks

    International Nuclear Information System (INIS)

    Stambaugh, R.D.

    1998-01-01

    The status of power and particle exhaust research in tokamaks is reviewed in the light of ITER requirements. There is a sound basis for ITER's nominal design positions; important directions for further research are identified

  16. Muscle Weakness and Fibrosis Due to Cell Autonomous and Non-cell Autonomous Events in Collagen VI Deficient Congenital Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Satoru Noguchi

    2017-02-01

    Full Text Available Congenital muscular dystrophies with collagen VI deficiency are inherited muscle disorders with a broad spectrum of clinical presentation and are caused by mutations in one of COL6A1–3 genes. Muscle pathology is characterized by fiber size variation and increased interstitial fibrosis and adipogenesis. In this study, we define critical events that contribute to muscle weakness and fibrosis in a mouse model with collagen VI deficiency. The Col6a1GT/GT mice develop non-progressive weakness from younger age, accompanied by stunted muscle growth due to reduced IGF-1 signaling activity. In addition, the Col6a1GT/GT mice have high numbers of interstitial skeletal muscle mesenchymal progenitor cells, which dramatically increase with repeated myofiber necrosis/regeneration. Our results suggest that impaired neonatal muscle growth and the activation of the mesenchymal cells in skeletal muscles contribute to the pathology of collagen VI deficient muscular dystrophy, and more importantly, provide the insights on the therapeutic strategies for collagen VI deficiency.

  17. Fuel consumption and exhaust emissions of aircrafts

    Energy Technology Data Exchange (ETDEWEB)

    Buechler, R. [Institute of Flightmechanics, Braunschweig (Germany)

    1997-12-31

    The reduction of contamination of sensitive atmospheric layers by improved flight planning steps, is investigated. Calculated results have shown, that a further development of flight track planning allows considerable improvements on fuel consumption and exhaust emissions. Even if air traffic will further increase, optimistic investigations forecast a reduction of the environmental damage by aircraft exhausts, if the effects of improved flight track arrangement and engine innovations will be combined. (R.P.) 4 refs.

  18. Function of Treg Cells Decreased in Patients With Systemic Lupus Erythematosus Due To the Effect of Prolactin.

    Science.gov (United States)

    Legorreta-Haquet, María Victoria; Chávez-Rueda, Karina; Chávez-Sánchez, Luis; Cervera-Castillo, Hernando; Zenteno-Galindo, Edgar; Barile-Fabris, Leonor; Burgos-Vargas, Rubén; Álvarez-Hernández, Everardo; Blanco-Favela, Francisco

    2016-02-01

    Prolactin has different functions, including cytokine secretion and inhibition of the suppressor effect of regulatory T (Treg) cells in healthy individuals. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by defects in the functions of B, T, and Treg cells. Prolactin plays an important role in the physiopathology of SLE. Our objective was to establish the participation of prolactin in the regulation of the immune response mediated by Treg cells from patients with SLE. CD4CD25CD127 cells were purified using magnetic beads and the relative expression of prolactin receptor was measured. The functional activity was evaluated by proliferation assay and cytokine secretion in activated cells, in the presence and absence of prolactin. We found that both percentage and function of Treg cells decrease in SLE patients compared to healthy individuals with statistical significance. The prolactin receptor is constitutively expressed on Treg and effector T (Teff) cells in SLE patients, and this expression is higher than in healthy individuals. The expression of this receptor differs in inactive and active patients: in the former, the expression is higher in Treg cells than in Teff cells, similar to healthy individuals, whereas there is no difference in the expression between Treg and Teff cells from active patients. In Treg:Teff cell cocultures, addition of prolactin decreases the suppressor effect exerted by Treg cells and increases IFNγ secretion. Our results suggest that prolactin plays an important role in the activation of the disease in inactive patients by decreasing the suppressor function exerted by Treg cells over Teff cells, thereby favoring an inflammatory microenvironment.

  19. Workplace Bullying and Presenteeism: The Path Through Emotional Exhaustion and Psychological Wellbeing.

    Science.gov (United States)

    Neto, Mariana; Ferreira, Aristides I; Martinez, Luis F; Ferreira, Paula C

    2017-06-01

    Workplace bullying is an increasing phenomenon that concerns managers and employees. However, few studies have investigated how workplace bullying relates with work-related exhaustion and indicators of productivity loss due to presenteeism. Thus, the aim of the present study was to examine the intervening variables of emotional exhaustion and psychological wellbeing in the direct and indirect relationships between workplace bullying and indicators of productivity loss due to presenteeism. In a cross-sectional study, we tested a structural equation model using web survey data of 353 workers from a service company, with the variables: workplace bullying (Quine, 1999), emotional exhaustion (Maslach Burnout Inventory; MBI), psychological wellbeing (GHQ-28), and indicators of productivity loss due to presenteeism (SPS-6). All variables presented acceptable psychometric evidence. The final model revealed a reasonable fit. Workplace bullying was significantly and positively related to emotional exhaustion, which in turn, was significantly related to the loss of psychological wellbeing. Workplace bullying, emotional exhaustion, and the loss of psychological wellbeing were negatively related to concentration (avoiding distraction). Emotional exhaustion and psychological wellbeing mediated the studied structural relationships. Our study contributes to theory and practice, since occupational health professionals should be aware that burnout and the loss of wellbeing may be related to workplace bullying and that productivity loss due to presenteeism may be a warning sign. Leaders can understand the underlying mechanism that explains employees' productivity loss due to presenteeism by addressing workplace bullying and its negative relation with emotional exhaustion and wellbeing. © The Author 2017. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

  20. Reversible changes in cell morphology due to cytoskeletal rearrangements measured in real-time by QCM-D.

    Science.gov (United States)

    Tymchenko, Nina; Nilebäck, Erik; Voinova, Marina V; Gold, Julie; Kasemo, Bengt; Svedhem, Sofia

    2012-12-01

    The mechanical properties and responses of cells to external stimuli (including drugs) are closely connected to important phenomena such as cell spreading, motility, activity, and potentially even differentiation. Here, reversible changes in the viscoelastic properties of surface-attached fibroblasts were induced by the cytoskeleton-perturbing agent cytochalasin D, and studied in real-time by the quartz crystal microbalance with dissipation (QCM-D) technique. QCM-D is a surface sensitive technique that measures changes in (dynamically coupled) mass and viscoelastic properties close to the sensor surface, within a distance into the cell that is usually only a fraction of its size. In this work, QCM-D was combined with light microscopy to study in situ cell attachment and spreading. Overtone-dependent changes of the QCM-D responses (frequency and dissipation shifts) were first recorded, as fibroblast cells attached to protein-coated sensors in a window equipped flow module. Then, as the cell layer had stabilised, morphological changes were induced in the cells by injecting cytochalasin D. This caused changes in the QCM-D signals that were reversible in the sense that they disappeared upon removal of cytochalasin D. These results are compared to other cell QCM-D studies. Our results stress the combination of QCM-D and light microscopy to help interpret QCM-D results obtained in cell assays and thus suggests a direction to develop the QCM-D technique as an even more useful tool for real-time cell studies.

  1. Attenuation of radiation-induced DNA damage due to paracrine interactions between normal human epithelial and stromal cells

    International Nuclear Information System (INIS)

    Saenko, V.A.; Nakazawa, Yu.; Rogounovitch, T.I.; Suzuki, K.; Mitsutake, N.; Matsuse, M.; Yamashita, S.

    2007-01-01

    Complete text of publication follows. Objective: Developmentally, every tissue accommodates different types of cells, such as epitheliocytes and stromal cells in parenchymal organs. To better understand the complexity of radiation response, it is necessary to evaluate possible cross-talk between different tissue components. This work was set out to investigate reciprocal influence of normal human epithelial cells and fibroblasts on the extent of radiation-induced DNA damage. Methods: Model cultures of primary human thyrocytes (PT), normal diploid fibroblasts (BJ), PT/BJ cell co-culture and conditioned medium transfer were used to examine DNA damage in terms of γ-H2AX foci number per cell or by Comet assay after exposure to different doses of γ-rays. Results: In co-cultures, the kinetics of γ-H2AX foci number change was dose-dependent and similar to that in individual PT and BJ cultures. The number of γ-H2AX foci in co-cultures was significantly lower (∼25%) in both types of cells comparing to individual cultures. Reciprocal conditioned medium transfer to individual counterpart cells prior to irradiation resulted in approximately 35% reduction in the number γ-H2AX foci at 1 Gy and lower doses in both PT and BJ demonstrating the role of paracrine soluble factors. Comet assay corroborated the results of γ-H2AX foci counting in conditioned medium transfer experiments. In contrast to medium conditioned on PT cells, conditioned medium collected from several human thyroid cancer cell lines failed to establish DNA-protected state in BJ fibroblasts. In its turn, medium conditioned on BJ cells did not change the extent of radiation-induced DNA damage in cancer cell lines tested. Conclusion: The results imply the existence of a network of soluble factor-mediated paracrine interactions between normal epithelial and stromal cells that could be a part of natural mechanism by which cells protect DNA from genotoxic stress.

  2. Hydrogen cyanide exhaust emissions from in-use motor vehicles.

    Science.gov (United States)

    Baum, Marc M; Moss, John A; Pastel, Stephen H; Poskrebyshev, Gregory A

    2007-02-01

    Motor vehicle exhaust emissions are known to contain hydrogen cyanide (HCN), but emission rate data are scarce and, in the case of idling vehicles, date back over 20 years. For the first time, vehicular HCN exhaust emissions from a modern, in-use fleet at idle have been measured. The 14 tested light duty motor vehicles were operating at idle as these conditions are associated with the highest risk exposure scenarios (i.e., enclosed spaces). Vehicular HCN was detected in 89% of the sampled exhaust streams and did not correlate with instantaneous air-fuel-ratio or with any single, coemitted pollutant. However, a moderate correlation between HCN emissions and the product of carbon monoxide and nitric oxide emissions was observed under cold-start conditions. Fleet average, cold-start, undiluted HCN emissions were 105 +/- 97 ppbV (maximum: 278 ppbV), whereas corresponding emissions from vehicles operating under stabilized conditions were 79 +/- 71 ppbV (maximum: 245 ppbV); mean idle fleet HCN emission rates were 39 +/- 35 and 21 +/- 18 microg-min(-1) for cold-start and stabilized vehicles, respectively. The significance of these results is discussed in terms of HCN emissions inventories in the South Coast Air Basin of California and of health risks due to exposure to vehicular HCN.

  3. Dislocation Starvation and Exhaustion Hardening in Mo-alloy Nanofibers

    Energy Technology Data Exchange (ETDEWEB)

    Chisholm, Claire [University of California, Berkeley & LBNL; Bei, Hongbin [ORNL; Lowry, M. B. [University of California, Berkeley; Oh, Jason [Hysitron, Inc., MN; Asif, S.A. Syed [Hysitron, Inc., MN; Warren, O. [Hysitron, Inc., MN; Shan, Zhiwei [Xi' an Jiaotong University, China & Hysitron, Inc., MN; George, Easo P [ORNL; Minor, Andrew [University of California, Berkeley & LBNL

    2012-01-01

    The evolution of defects in Mo alloy nanofibers with initial dislocation densities ranging from 0 to 1.6 1014 m2 were studied using an in situ push-to-pull device in conjunction with a nanoindenter in a transmission electron microscope. Digital image correlation was used to determine stress and strain in local areas of deformation. When they had no initial dislocations the Mo alloy nanofibers suffered sudden catastrophic elongation following elastic deformation to ultrahigh stresses. At the other extreme fibers with a high dislocation density underwent sustained homogeneous deformation after yielding at much lower stresses. Between these two extremes nanofibers with intermediate dislocation densities demonstrated a clear exhaustion hardening behavior, where the progressive exhaustion of dislocations and dislocation sources increases the stress required to drive plasticity. This is consistent with the idea that mechanical size effects ( smaller is stronger ) are due to the fact that nanostructures usually have fewer defects that can operate at lower stresses. By monitoring the evolution of stress locally we find that exhaustion hardening causes the stress in the nanofibers to surpass the critical stress predicted for self-multiplication, supporting a plasticity mechanism that has been hypothesized to account for the rapid strain softening observed in nanoscale bcc materials at high stresses.

  4. Thermal analysis on x-ray tube for exhaust process

    Science.gov (United States)

    Kumar, Rakesh; Rao Ratnala, Srinivas; Veeresh Kumar, G. B.; Shivakumar Gouda, P. S.

    2018-02-01

    It is great importance in the use of X-rays for medical purposes that the dose given to both the patient and the operator is carefully controlled. There are many types of the X- ray tubes used for different applications based on their capacity and power supplied. In present thesis maxi ray 165 tube is analysed for thermal exhaust processes with ±5% accuracy. Exhaust process is usually done to remove all the air particles and to degasify the insert under high vacuum at 2e-05Torr. The tube glass is made up of Pyrex material, 95%Tungsten and 5%rhenium is used as target material for which the melting point temperature is 3350°C. Various materials are used for various parts; during the operation of X- ray tube these waste gases are released due to high temperature which in turn disturbs the flow of electrons. Thus, before using the X-ray tube for practical applications it has to undergo exhaust processes. Initially we build MX 165 model to carry out thermal analysis, and then we simulate the bearing temperature profiles with FE model to match with test results with ±5%accuracy. At last implement the critical protocols required for manufacturing processes like MF Heating, E-beam, Seasoning and FT.

  5. 14 CFR 29.1125 - Exhaust heat exchangers.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Exhaust heat exchangers. 29.1125 Section 29... exchangers. For reciprocating engine powered rotorcraft the following apply: (a) Each exhaust heat exchanger... is subject to contact with exhaust gases; and (4) No exhaust heat exchanger or muff may have stagnant...

  6. 14 CFR 25.1125 - Exhaust heat exchangers.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Exhaust heat exchangers. 25.1125 Section 25... exchangers. For reciprocating engine powered airplanes, the following apply: (a) Each exhaust heat exchanger... provisions wherever it is subject to contact with exhaust gases; and (4) No exhaust heat exchanger or muff...

  7. Changes in T cell populations due to local irradiation of a portion of the maxilla in mice

    International Nuclear Information System (INIS)

    Satoh, Daigo

    1997-01-01

    The aim of this study was to investigate the changes in the immune organs after head and neck irradiation. The numbers of lymphocytes in peripheral blood, the spleen and the thymus following local irradiation of a portion of the maxilla in mice were studied using three-color fluorometry and were compared with a non-irradiation group. In the peripheral blood, the absolute numbers of T cells, CD4 + SP cells and CD8 + SP cells decreased after irradiation, and the period of the decrease was longer than the decreases in number of leukocytes and lymphocytes. The ratio of CD4 + SP cells showed a significant decrease, and the ratio of CD8+ S P cells showed a significant increase 1 day after irradiation. In the spleen, the absolute number of T cells, the radio of CD4 + SP and CD8 + SP cell subsets showed a decrease, and the period of the decrease was longer than the decrease of the wet-weight of the spleen, and also longer than the decrease of the number of leukocytes. The number of CD4 + SP cells showed a signigicant increase, and CD8 + SP cells showed a significant decrease 21 days after irradiation. In the thymus, the absolute number of TCR αβ-thymocytes did not show a significant decrease. However, the number of DN thymocytes showed a marked decrease. These results indicate that the numbers of T cells in peripheral blood, the spleen and the thymus change immediately after irradiation, and the numbers of lymphocytes and the T cells in the spleen recover more slowly than that in the peripheral blood. As lymphoid tissues showed the suppression of immunological response for a long period, it was suggested that lymphoid tissues have to be observed carefully after irradiation to prevent cancer metastasis. (K.H.)

  8. Biosynthesis of Various Steroids in vitro by Isolated Adrenal Cells in Primary Aldosteronism, Cushing's Syndrome, and Adrenogenital Syndrome due to Adrenocortical Adenoma

    OpenAIRE

    MIZUNO, SHIGERU; FUNAHASHI, HIROOMI

    1981-01-01

    To a further understanding of the role of steroid hormones in adrenal disorders, we have prepared free cell system of adrenal cells, using adrenal tissues that had been removed by operation from (i) cases of Cushing's syndrome due to adrenocortical adenoma or adrenocortical hyperplasia, (ii) a case of primary aldosteronism, and (iii) a patient with virilizing adrenal tumor. Twelve important steroid hormones were measured, such as pregnenolone, cortisol and aldosterone, which were produced by ...

  9. Formaldehyde monitor for automobile exhausts

    Science.gov (United States)

    Easley, W. C.

    1973-01-01

    Device makes use of microwave spectral absorption in low-Q resonant Stark cell, and indications are that ultimate sensitivity of instrument is within 100 parts per billion of formaldehyde. Microwave source is very small and requires only six-volt dc bias for operation. Coarse tuning is accomplished mechanically and fine tuning by adjusting dc-bias voltage.

  10. Tracheal ulcer due to Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly.

    Science.gov (United States)

    Ito, Takeo; Fujisaki, Hideaki; Nishio, Suehiro; Hiroshige, Shigeo; Miyazaki, Eishi; Kadota, Jun-ichi

    2014-03-01

    A 74-year-old man was referred to our hospital because of a tracheal stenosis circumscribed with soft tissue density and a left pulmonary nodule. Open biopsy of a right submandibular lymph node revealed diffuse large B-cell lymphoma, and the malignant cells were positive for Epstein-Barr virus gene products. Bronchofiberscopy revealed a tracheal necrotizing ulcer. After chemotherapy, the tracheal ulcer resolved. To our knowledge, this is the first report of a case of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly with a tracheal ulcer. © 2013 Published by The Japanese Respiratory Society on behalf of The Japanese Respiratory Society.

  11. Exhaust purification with on-board ammonia production

    Science.gov (United States)

    Robel, Wade J [Peoria, IL; Driscoll, James Joshua [Dunlap, IL; Coleman, Gerald N [Peterborough, GB

    2008-05-13

    A system of ammonia production for a selective catalytic reduction system is provided. The system includes producing an exhaust gas stream within a cylinder group, wherein the first exhaust gas stream includes NOx. The exhaust gas stream may be supplied to an exhaust passage and cooled to a predetermined temperature range, and at least a portion of the NOx within the exhaust gas stream may be converted into ammonia.

  12. Performance of Installed Cooking Exhaust Devices

    Energy Technology Data Exchange (ETDEWEB)

    Singer, Brett C.; Delp, William W.; Apte, Michael G.; Price, Philip N.

    2011-11-01

    The performance metrics of airflow, sound, and combustion product capture efficiency (CE) were measured for a convenience sample of fifteen cooking exhaust devices, as installed in residences. Results were analyzed to quantify the impact of various device- and installation-dependent parameters on CE. Measured maximum airflows were 70% or lower than values noted on product literature for 10 of the devices. Above-the-cooktop devices with flat bottom surfaces (no capture hood) – including exhaust fan/microwave combination appliances – were found to have much lower CE at similar flow rates, compared to devices with capture hoods. For almost all exhaust devices and especially for rear-mounted downdraft exhaust and microwaves, CE was substantially higher for back compared with front burner use. Flow rate, and the extent to which the exhaust device extends over the burners that are in use, also had a large effect on CE. A flow rate of 95 liters per second (200 cubic feet per minute) was necessary, but not sufficient, to attain capture efficiency in excess of 75% for the front burners. A-weighted sound levels in kitchens exceeded 57 dB when operating at the highest fan setting for all 14 devices evaluated for sound performance.

  13. Engineering task plan for five portable exhausters

    International Nuclear Information System (INIS)

    Rensink, G.E.

    1997-01-01

    Exhausters will be employed to ventilate certain single-shell tanks (SSTs) during salt well pumping campaigns. Active ventilation is necessary to reduce the potential flammable gas inventory (LANL 1996a) in the dome space that may accumulate during steady-state conditions or during/after postulated episodic gas release events. The tanks described in this plan support the activities required to fabricate and test three 500 cfm portable exhausters in the 200 W area shops, and to procure, design, fabricate and test two 1000 cfm units. Appropriate Notice of Construction (NOC) radiological and toxic air pollutant permits will be obtained for the portable exhausters. The portable exhauster design media to be employed to support this task was previously developed for the 241-A-101 exhauster. The same design as A101 will be fabricated with only minor improvements to the design based upon operator input/lessons learned. The safety authorization basis for this program effort will follow SAD 36 (LANL 1996b), and each tank will be reviewed against this SAD for changes or updates. The 1000 cfm units will be designed by the selected offsite contractor according to the specification requirements in KHC-S-O490. The offsite units have been specified to utilize as many of the same components as the 500 cfm units to ensure a more cost effective operation and maintenance through the reduction of spare parts and additional procedures

  14. Lightweight Exhaust Manifold and Exhaust Pipe Ducting for Internal Combustion Engines

    Science.gov (United States)

    Northam, G. Burton (Inventor); Ransone, Philip O. (Inventor); Rivers, H. Kevin (Inventor)

    1999-01-01

    An improved exhaust system for an internal combustion gasoline-and/or diesel-fueled engine includes an engine exhaust manifold which has been fabricated from carbon- carbon composite materials in operative association with an exhaust pipe ducting which has been fabricated from carbon-carbon composite materials. When compared to conventional steel. cast iron. or ceramic-lined iron paris. the use of carbon-carbon composite exhaust-gas manifolds and exhaust pipe ducting reduces the overall weight of the engine. which allows for improved acceleration and fuel efficiency: permits operation at higher temperatures without a loss of strength: reduces the "through-the wall" heat loss, which increases engine cycle and turbocharger efficiency and ensures faster "light-off" of catalytic converters: and, with an optional thermal reactor, reduces emission of major pollutants, i.e. hydrocarbons and carbon monoxide.

  15. Payload dose rate from direct beam radiation and exhaust gas fission products. [for nuclear engine for rocket vehicles

    Science.gov (United States)

    Capo, M. A.; Mickle, R.

    1975-01-01

    A study was made to determine the dose rate at the payload position in the NERVA System (1) due to direct beam radiation and (2) due to the possible effect of fission products contained in the exhaust gases for various amounts of hydrogen propellant in the tank. Results indicate that the gamma radiation is more significant than the neutron flux. Under different assumptions the gamma contribution from the exhaust gases was 10 to 25 percent of total gamma flux.

  16. Telomeres in ICF syndrome cells are vulnerable to DNA damage due to elevated DNA:RNA hybrids

    Science.gov (United States)

    Sagie, Shira; Toubiana, Shir; Hartono, Stella R.; Katzir, Hagar; Tzur-Gilat, Aya; Havazelet, Shany; Francastel, Claire; Velasco, Guillaume; Chédin, Frédéric; Selig, Sara

    2017-01-01

    DNA:RNA hybrids, nucleic acid structures with diverse physiological functions, can disrupt genome integrity when dysregulated. Human telomeres were shown to form hybrids with the lncRNA TERRA, yet the formation and distribution of these hybrids among telomeres, their regulation and their cellular effects remain elusive. Here we predict and confirm in several human cell types that DNA:RNA hybrids form at many subtelomeric and telomeric regions. We demonstrate that ICF syndrome cells, which exhibit short telomeres and elevated TERRA levels, are enriched for hybrids at telomeric regions throughout the cell cycle. Telomeric hybrids are associated with high levels of DNA damage at chromosome ends in ICF cells, which are significantly reduced with overexpression of RNase H1. Our findings suggest that abnormally high TERRA levels in ICF syndrome lead to accumulation of telomeric hybrids that, in turn, can result in telomeric dysfunction. PMID:28117327

  17. Due diligence

    International Nuclear Information System (INIS)

    Sanghera, G.S.

    1999-01-01

    The Occupational Health and Safety (OHS) Act requires that every employer shall ensure the health and safety of workers in the workplace. Issues regarding the practices at workplaces and how they should reflect the standards of due diligence were discussed. Due diligence was described as being the need for employers to identify hazards in the workplace and to take active steps to prevent workers from potentially dangerous incidents. The paper discussed various aspects of due diligence including policy, training, procedures, measurement and enforcement. The consequences of contravening the OHS Act were also described

  18. The Role of Inspiratory Muscle Training in Sickle Cell Anemia Related Pulmonary Damage due to Recurrent Acute Chest Syndrome Attacks

    OpenAIRE

    Camc?o?lu, Burcu; Bo?nak-G??l?, Meral; Karadall?, M??errefe Nur; Ak?, ?ahika Zeynep; T?rk?z-Sucak, G?lsan

    2015-01-01

    Background. The sickling of red blood cells causes a constellation of musculoskeletal, cardiovascular, and pulmonary manifestations. A 32-year-old gentleman with sickle cell anemia (SCA) had been suffering from recurrent acute chest syndrome (ACS). Aim. To examine the effects of inspiratory muscle training (IMT) on pulmonary functions, respiratory and peripheral muscle strength, functional exercise capacity, and quality of life in this patient with SCA. Methods. Functional exercise capacity w...

  19. Quantification of vehicle fleet PM10 particulate matter emission factors from exhaust and non-exhaust sources using tunnel measurement techniques.

    Science.gov (United States)

    Lawrence, Samantha; Sokhi, Ranjeet; Ravindra, Khaiwal

    2016-03-01

    Road tunnels act like large laboratories; they provide an excellent environment to quantify atmospheric particles emission factors from exhaust and non-exhaust sources due to their known boundary conditions. Current work compares the High Volume, Dichotomous Stacked Filter Unit and Partisol Air Sampler for coarse, PM10 and PM2.5 particle concentration measurement and found that they do not differ significantly (p = 95%). PM2.5 fraction contributes 66% of PM10 proportions and significantly influenced by traffic (turbulence) and meteorological conditions. Mass emission factors for PM10 varies from 21.3 ± 1.9 to 28.8 ± 3.4 mg/vkm and composed of Motorcycle (0.0003-0.001 mg/vkm), Cars (26.1-33.4 mg/vkm), LDVs (2.4-3.0 mg/vkm), HDVs (2.2-2.8 mg/vkm) and Buses (0.1 mg/vkm). Based on Lawrence et al. (2013), source apportionment modelling, the PM10 emission of brake wear (3.8-4.4 mg/vkm), petrol exhaust (3.9-4.5 mg/vkm), diesel exhaust (7.2-8.3 mg/vkm), re-suspension (9-10.4 mg/vkm), road surface wear (3.9-4.5 mg/vkm), and unexplained (7.2 mg/vkm) were also calculated. The current study determined that the combined non-exhaust fleet PM10 emission factor (16.7-19.3 mg/vkm) are higher than the combined exhaust emission factor (11.1-12.8 mg/vkm). Thus, highlight the significance of non-exhaust emissions and the need for legislation and abatement strategies to reduce their contributions to ambient PM concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Therapy with Bone Marrow-Derived Autologous Adult Stem Cells in Quadriparesis due to Motor Neuron Disease.

    Science.gov (United States)

    Bansal, Himanshu; Singh, Lipi; Agrawal, Anupama; Leon, Jerry; Sundell, I Birgitta; Koka, Prasad S

    To report the safety and therapeutic effectiveness of application of concentrated bone marrow aspirate in three bedridden patients with weakness in both legs, and monitor potential improvement in neurological outcomes. Case report. Intervention: Five infusions of 3x10 8 mononuclear cells were administrated with 12 week intervals. Bone marrow (240ML) were obtained from the posterior superior iliac spine and Bone marrow mononuclear cells were enriched by standard manual close method under aseptic condition. During the follow-up study of one year after stem cell implantation, the conditions of all three patients were improved and were confirmed by physical assessment, muscle charting and Electromyography (EMG). One year after stem cell implantation patients who were bedridden before treatment could sit without support and walk with support up to 200 feet at a stretch. The local application of a cocktail of regenerative cell population found in an MNC fraction of bone marrow was safe and effective in improving quality of life and muscle strength in ALS patients. This case opens the need for further investigations on Autogenic stem cell transplant therapies for MND disease.

  1. Dose response relationship of disturbed migration of Purkinje cells in the cerebellum due to X-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Darmanto, W.; Inouye, Minoru; Hayasaka, Shizu; Takagishi, Yoshiko; Aolad, H.; Murata, Yoshiharu [Nagoya Univ. (Japan). Research Inst. of Environmental Medicine

    1998-10-01

    Pregnant rats were exposed to 2.0, 2.25 or 2.5 Gy X-irradiation on gestation day 21. Pups were sacrificed 12 hr after exposure, and on postnatal day 5 (P5), P7 and P9. Their cerebella were observed immunohistochemically using anti-inositol 1,4,5 triphosphate (IP3) receptor antibody to identify Purkinje cells. These cells were disturbed to migrate and remained in the internal granular layer and white matter of the cerebellum. They had short dendrites, and some showed an abnormal direction of dendrites in rats exposed to 2.25 or 2.5 Gy. Alignment of Purkinje cells was also disturbed when examined either on P5, P7 or P9 especially by doses of 2.25 and 2.5 Gy. There was a relationship between X-ray doses and the number of cells piling up in the Purkinje cell layer of the cerebellum. The dose-response relationship with the number of ectopic Purkinje cells was noted in the anterior lobes of the cerebellum. (author)

  2. Dose response relationship of disturbed migration of Purkinje cells in the cerebellum due to X-irradiation

    International Nuclear Information System (INIS)

    Darmanto, W.; Inouye, Minoru; Hayasaka, Shizu; Takagishi, Yoshiko; Aolad, H.; Murata, Yoshiharu

    1998-01-01

    Pregnant rats were exposed to 2.0, 2.25 or 2.5 Gy X-irradiation on gestation day 21. Pups were sacrificed 12 hr after exposure, and on postnatal day 5 (P5), P7 and P9. Their cerebella were observed immunohistochemically using anti-inositol 1,4,5 triphosphate (IP3) receptor antibody to identify Purkinje cells. These cells were disturbed to migrate and remained in the internal granular layer and white matter of the cerebellum. They had short dendrites, and some showed an abnormal direction of dendrites in rats exposed to 2.25 or 2.5 Gy. Alignment of Purkinje cells was also disturbed when examined either on P5, P7 or P9 especially by doses of 2.25 and 2.5 Gy. There was a relationship between X-ray doses and the number of cells piling up in the Purkinje cell layer of the cerebellum. The dose-response relationship with the number of ectopic Purkinje cells was noted in the anterior lobes of the cerebellum. (author)

  3. ATR Prohibits Replication Catastrophe by Preventing Global Exhaustion of RPA

    DEFF Research Database (Denmark)

    Toledo Lazaro, Luis Ignacio; Altmeyer, Matthias; Rask, Maj-Britt

    2013-01-01

    ATR, activated by replication stress, protects replication forks locally and suppresses origin firing globally. Here, we show that these functions of ATR are mechanistically coupled. Although initially stable, stalled forks in ATR-deficient cells undergo nucleus-wide breakage after unscheduled...... origin firing generates an excess of single-stranded DNA that exhausts the nuclear pool of RPA. Partial reduction of RPA accelerated fork breakage, and forced elevation of RPA was sufficient to delay such "replication catastrophe" even in the absence of ATR activity. Conversely, unscheduled origin firing...... commonly feature intrinsically high replication stress, this study also provides a molecular rationale for their hypersensitivity to ATR inhibitors....

  4. Monitoring Engine Vibrations And Spectrum Of Exhaust

    Science.gov (United States)

    Martinez, Carol L.; Randall, Michael R.; Reinert, John W.

    1991-01-01

    Real-time computation of intensities of peaks in visible-light emission spectrum of exhaust combined with real-time spectrum analysis of vibrations into developmental monitoring technique providing up-to-the-second information on conditions of critical bearings in engine. Conceived to monitor conditions of bearings in turbopump suppling oxygen to Space Shuttle main engine, based on observations that both vibrations in bearings and intensities of visible light emitted at specific wavelengths by exhaust plume of engine indicate wear and incipient failure of bearings. Applicable to monitoring "health" of other machinery via spectra of vibrations and electromagnetic emissions from exhausts. Concept related to one described in "Monitoring Bearing Vibrations For Signs Of Damage", (MFS-29734).

  5. Combined cytotoxic effects of tumor necrosis factor-alpha with various cytotoxic agents in tumor cell lines that are drug resistant due to mutated p53

    NARCIS (Netherlands)

    Sleijfer, S; Le, T. K. P.; de Jong, S.; Timmer-Bosscha, H; Withoff, S; Mulder, NH

    Several studies suggest that tumor necrosis factor-alpha (TNF) is able to overcome drug resistance in tumors. Whether TNF is able to do so in tumor cell lines that are drug resistant due to a mutation in the tumor suppressor gene p53 is unclear. Therefore, we studied the in vitro cytotoxic effects

  6. Cycling before and after Exhaustion Differently Affects Cardiac Autonomic Control during Heart Rate Matched Exercise.

    Science.gov (United States)

    Weippert, Matthias; Behrens, Martin; Mau-Moeller, Anett; Bruhn, Sven; Behrens, Kristin

    2017-01-01

    During cycling before (PRE) and after exhaustion (POST) different modes of autonomic cardiac control might occur due to different interoceptive input and altered influences from higher brain centers. We hypothesized that heart rate variability (HRV) is significantly affected by an interaction of the experimental period (PRE vs. POST) and exercise intensity (HIGH vs. LOW; HIGH = HR > HR at the lactate threshold (HR LT ), LOW = HR ≤ HR LT ) despite identical average HR. Methods: Fifty healthy volunteers completed an incremental cycling test until exhaustion. Workload started with 30 W at a constant pedaling rate (60 revolutions · min -1 ) and was gradually increased by 30 W · 5 min -1 . Five adjacent 60 s inter-beat (R-R) interval segments from the immediate recovery period (POST 1-5 at 30 W and 60 rpm) were each matched with their HR-corresponding 60 s-segments during the cycle test (PRE 1-5). An analysis of covariance was carried out with one repeated-measures factor (PRE vs. POST exhaustion), one between-subject factor (HIGH vs. LOW intensity) and respiration rate as covariate to test for significant effects ( p exhaustion at HIGH intensity. On the opposite, at LOW intensity cycling, a stronger coactivational cardiac autonomic modulation pattern occurs during PRE-exhaustion if compared to POST-exhaustion cycling. The different autonomic modes during these phases might be the result of different afferent and/or central inputs to the cardiovascular control centers in the brainstem.

  7. Multiple Lymphomatous Polyposis of the Intestine with Ileocecal Intussusception Due to Mantle Cell Lymphoma: A Case Report of a 34-Year-Old Man.

    Science.gov (United States)

    Xie, Chuan-Gao; Xu, Xiao-Ming; Wei, Shu-Mei

    2018-03-08

    BACKGROUND Multiple lymphomatous polyposis of the gastrointestinal tract can be associated with the B-cell lymphoma variant, mantle cell lymphoma, with most cases having been described in patients who are more than 50 years-of-age. A rare case of multiple lymphomatous polyposis due to mantle cell lymphoma is reported in a 34-year-old man. CASE REPORT A 34-year-old man presented with paroxysmal abdominal pain followed by spontaneous remission, which had been previously diagnosed as gastritis. An episode of ileocecal intussusception occurred, which was confirmed on imaging studies. The diagnosis of multiple lymphomatous polyposis due to mantle cell lymphoma was confirmed following ileocecal resection and histopathology. The patient refused to receive chemotherapy following surgery. Currently, at two-year follow-up, no further abnormality has been found. A review of the literature has shown the importance of endoscopic evaluation in the diagnosis of lymphomatous polyposis. CONCLUSIONS Multiple lymphomatous polyposis due to mantle cell lymphoma has rarely been described in young patients under the age of 50 years. Gastrointestinal endoscopic examination is important for the early diagnosis of multiple lymphomatous polyposis.

  8. GADTs and Exhaustiveness: Looking for the Impossible

    Directory of Open Access Journals (Sweden)

    Jacques Garrigue

    2017-02-01

    Full Text Available Sound exhaustiveness checking of pattern-matching is an essential feature of functional programming languages, and OCaml supports it for GADTs. However this check is incomplete, in that it may fail to detect that a pattern can match no concrete value. In this paper we show that this problem is actually undecidable, but that we can strengthen the exhaustiveness and redundancy checks so that they cover more practical cases. The new algorithm relies on a clever modification of type inference for patterns.

  9. PUREX exhaust ventilation system installation test report

    International Nuclear Information System (INIS)

    Blackaby, W.B.

    1997-01-01

    This Acceptance Test Report validates the testing performed, the exceptions logged and resolved and certifies this portion of the SAMCONS has met all design and test criteria to perform as an operational system. The proper installation of the PUREX exhaust ventilation system components and wiring was systematically evaluated by performance of this procedure. Proper operation of PUREX exhaust fan inlet, outlet, and vortex damper actuators and limit switches were verified, using special test equipment, to be correct and installed wiring connections were verified by operation of this equipment

  10. Kupffer Cell-Derived Tnf Triggers Cholangiocellular Tumorigenesis through JNK due to Chronic Mitochondrial Dysfunction and ROS.

    Science.gov (United States)

    Yuan, Detian; Huang, Shan; Berger, Emanuel; Liu, Lei; Gross, Nina; Heinzmann, Florian; Ringelhan, Marc; Connor, Tracy O; Stadler, Mira; Meister, Michael; Weber, Julia; Öllinger, Rupert; Simonavicius, Nicole; Reisinger, Florian; Hartmann, Daniel; Meyer, Rüdiger; Reich, Maria; Seehawer, Marco; Leone, Valentina; Höchst, Bastian; Wohlleber, Dirk; Jörs, Simone; Prinz, Marco; Spalding, Duncan; Protzer, Ulrike; Luedde, Tom; Terracciano, Luigi; Matter, Matthias; Longerich, Thomas; Knolle, Percy; Ried, Thomas; Keitel, Verena; Geisler, Fabian; Unger, Kristian; Cinnamon, Einat; Pikarsky, Eli; Hüser, Norbert; Davis, Roger J; Tschaharganeh, Darjus F; Rad, Roland; Weber, Achim; Zender, Lars; Haller, Dirk; Heikenwalder, Mathias

    2017-06-12

    Intrahepatic cholangiocarcinoma (ICC) is a highly malignant, heterogeneous cancer with poor treatment options. We found that mitochondrial dysfunction and oxidative stress trigger a niche favoring cholangiocellular overgrowth and tumorigenesis. Liver damage, reactive oxygen species (ROS) and paracrine tumor necrosis factor (Tnf) from Kupffer cells caused JNK-mediated cholangiocellular proliferation and oncogenic transformation. Anti-oxidant treatment, Kupffer cell depletion, Tnfr1 deletion, or JNK inhibition reduced cholangiocellular pre-neoplastic lesions. Liver-specific JNK1/2 deletion led to tumor reduction and enhanced survival in Akt/Notch- or p53/Kras-induced ICC models. In human ICC, high Tnf expression near ICC lesions, cholangiocellular JNK-phosphorylation, and ROS accumulation in surrounding hepatocytes are present. Thus, Kupffer cell-derived Tnf favors cholangiocellular proliferation/differentiation and carcinogenesis. Targeting the ROS/Tnf/JNK axis may provide opportunities for ICC therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Diesel exhaust particle exposure in vitro alters monocyte differentiation and function.

    Directory of Open Access Journals (Sweden)

    Nazia Chaudhuri

    Full Text Available Air pollution by diesel exhaust particles is associated with elevated mortality and increased hospital admissions in individuals with respiratory diseases such as asthma and chronic obstructive pulmonary disease. During active inflammation monocytes are recruited to the airways and can replace resident alveolar macrophages. We therefore investigated whether chronic fourteen day exposure to low concentrations of diesel exhaust particles can alter the phenotype and function of monocytes from healthy individuals and those with chronic obstructive pulmonary disease. Monocytes were purified from the blood of healthy individuals and people with a diagnosis of chronic obstructive pulmonary disease. Monocyte-derived macrophages were generated in the presence or absence of diesel exhaust particles and their phenotypes studied through investigation of their lifespan, cytokine generation in response to Toll like receptor agonists and heat killed bacteria, and expression of surface markers. Chronic fourteen day exposure of monocyte-derived macrophages to concentrations of diesel exhaust particles >10 µg/ml caused mitochondrial and lysosomal dysfunction, and a gradual loss of cells over time both in healthy and chronic obstructive pulmonary disease individuals. Chronic exposure to lower concentrations of diesel exhaust particles impaired CXCL8 cytokine responses to lipopolysaccharide and heat killed E. coli, and this phenotype was associated with a reduction in CD14 and CD11b expression. Chronic diesel exhaust particle exposure may therefore alter both numbers and function of lung macrophages differentiating from locally recruited monocytes in the lungs of healthy people and patients with chronic obstructive pulmonary disease.

  12. Work-related exhaustion and telomere length: a population-based study.

    Directory of Open Access Journals (Sweden)

    Kirsi Ahola

    Full Text Available Psychological stress is suggested to accelerate the rate of biological aging. We investigated whether work-related exhaustion, an indicator of prolonged work stress, is associated with accelerated biological aging, as indicated by shorter leukocyte telomeres, that is, the DNA-protein complexes that cap chromosomal ends in cells.We used data from a representative sample of the Finnish working-age population, the Health 2000 Study. Our sample consisted of 2911 men and women aged 30-64. Work-related exhaustion was assessed using the Maslach Burnout Inventory--General Survey. We determined relative leukocyte telomere length using a quantitative real-time polymerase chain reaction (PCR -based method.After adjustment for age and sex, individuals with severe exhaustion had leukocyte telomeres on average 0.043 relative units shorter (standard error of the mean 0.016 than those with no exhaustion (p = 0.009. The association between exhaustion and relative telomere length remained significant after additional adjustment for marital and socioeconomic status, smoking, body mass index, and morbidities (adjusted difference 0.044 relative units, standard error of the mean 0.017, p = 0.008.These data suggest that work-related exhaustion is related to the acceleration of the rate of biological aging. This hypothesis awaits confirmation in a prospective study measuring changes in relative telomere length over time.

  13. Work-related exhaustion and telomere length: a population-based study.

    Science.gov (United States)

    Ahola, Kirsi; Sirén, Ilari; Kivimäki, Mika; Ripatti, Samuli; Aromaa, Arpo; Lönnqvist, Jouko; Hovatta, Iiris

    2012-01-01

    Psychological stress is suggested to accelerate the rate of biological aging. We investigated whether work-related exhaustion, an indicator of prolonged work stress, is associated with accelerated biological aging, as indicated by shorter leukocyte telomeres, that is, the DNA-protein complexes that cap chromosomal ends in cells. We used data from a representative sample of the Finnish working-age population, the Health 2000 Study. Our sample consisted of 2911 men and women aged 30-64. Work-related exhaustion was assessed using the Maslach Burnout Inventory--General Survey. We determined relative leukocyte telomere length using a quantitative real-time polymerase chain reaction (PCR) -based method. After adjustment for age and sex, individuals with severe exhaustion had leukocyte telomeres on average 0.043 relative units shorter (standard error of the mean 0.016) than those with no exhaustion (p = 0.009). The association between exhaustion and relative telomere length remained significant after additional adjustment for marital and socioeconomic status, smoking, body mass index, and morbidities (adjusted difference 0.044 relative units, standard error of the mean 0.017, p = 0.008). These data suggest that work-related exhaustion is related to the acceleration of the rate of biological aging. This hypothesis awaits confirmation in a prospective study measuring changes in relative telomere length over time.

  14. Ganoderma tsugae Hepatoprotection against Exhaustive Exercise-Induced Liver Injury in Rats

    Directory of Open Access Journals (Sweden)

    Wan-Teng Lin

    2013-01-01

    Full Text Available Several studies have been shown that accelerated apoptosis is involved in post-exercise lymphocytopenia and tissue damage after high-intensity exercise. Ganoderma tsugae (GT is one of the well-known medicinal mushrooms that possess various pharmacological functions. This mushroom has traditionally been used for health promotion purposes. This study investigates the hepatoprotective effects of GT on exhaustive exercise-induced liver damage. Twenty-four male Sprague-Dawley rats were randomly divided into four groups and designated as exhaustive exercise only (E, exhaustive exercise with low dosage (EL, medium dosage (EM and high dosage (EH GT at 0, 0.1875, 0.9375 and 1.875 g/kg/day, respectively. After 30 days all rats were euthanized immediately after an exhaustive running challenge on a motorized treadmill. The rat livers were immediately harvested. Evidence of apoptotic liver cell death was revealed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assay and caspases mediated cascade events. DNA fragmentation, an apoptosis process, can be examined using TUNEL assay. A few TUNEL-positive hepatocytes, compared to the exercise only group, were observed in the livers from exhaustive animals supplemented with GT. Immunoblot analysis also showed that caspase-6-mediated specific cleavage of lamin A/C was increased significantly in the livers of group E, but was significantly decreased in the EM and EH groups. Our observations demonstrate that GT possesses anti-apoptotic and hepatoprotective potential after exhaustive exercise.

  15. Ganoderma tsugae hepatoprotection against exhaustive exercise-induced liver injury in rats.

    Science.gov (United States)

    Huang, Chi-Chang; Huang, Wen-Ching; Yang, Suh-Ching; Chan, Chih-Chi; Lin, Wan-Teng

    2013-01-29

    Several studies have been shown that accelerated apoptosis is involved in post-exercise lymphocytopenia and tissue damage after high-intensity exercise. Ganoderma tsugae (GT) is one of the well-known medicinal mushrooms that possess various pharmacological functions. This mushroom has traditionally been used for health promotion purposes. This study investigates the hepatoprotective effects of GT on exhaustive exercise-induced liver damage. Twenty-four male Sprague-Dawley rats were randomly divided into four groups and designated as exhaustive exercise only (E), exhaustive exercise with low dosage (EL), medium dosage (EM) and high dosage (EH) GT at 0, 0.1875, 0.9375 and 1.875 g/kg/day, respectively. After 30 days all rats were euthanized immediately after an exhaustive running challenge on a motorized treadmill. The rat livers were immediately harvested. Evidence of apoptotic liver cell death was revealed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and caspases mediated cascade events. DNA fragmentation, an apoptosis process, can be examined using TUNEL assay. A few TUNEL-positive hepatocytes, compared to the exercise only group, were observed in the livers from exhaustive animals supplemented with GT. Immunoblot analysis also showed that caspase-6-mediated specific cleavage of lamin A/C was increased significantly in the livers of group E, but was significantly decreased in the EM and EH groups. Our observations demonstrate that GT possesses anti-apoptotic and hepatoprotective potential after exhaustive exercise.

  16. Th1 Cell Development Induced by Cysteine Proteinases A and B in Localized Cutaneous Leishmaniasis Due to Leishmania guyanensis

    Science.gov (United States)

    Pascalis, Hervé; Lavergne, Anne; Bourreau, Eliane; Prévot-Linguet, Ghislaine; Kariminia, Amina; Pradinaud, Roger; Rafati, Sima; Launois, Pascal

    2003-01-01

    The cysteine proteinases CPA and CPB from Leishmania major induced Th1 responses in patients with leishmaniasis due to Leishmania guyanensis. Furthermore, cysteine proteinases induced neither interleukin 4 (IL-4) nor IL-13 and low levels of IL-10 in controls and patients. The results suggest that CPs would be quite good candidates for a vaccine against different Leishmania species. PMID:12704171

  17. Photon absorption and photocurrent in solar cells below semiconductor bandgap due to electron photoemission from plasmonic nanoantennas

    DEFF Research Database (Denmark)

    Novitsky, Andrey; Uskov, Alexander; Gritti, Claudia

    2014-01-01

    We model the electron photoemission frommetal nanoparticles into a semiconductor in a Schottky diode with a conductive oxide electrode hosting the nanoparticles. We show that plasmonic effects in the nanoparticles lead to a substantial enhancement in photoemission compared with devices with conti....... Such structure can form the dais of the development of plasmonic photoemission enhanced solar cells....

  18. Anticarcinogenic Effect of Spices Due to Phenolic and Flavonoid Compounds—In Vitro Evaluation on Prostate Cells

    Directory of Open Access Journals (Sweden)

    Zuzana Lackova

    2017-09-01

    Full Text Available This study shows the effects of spices, and their phenolic and flavonoid compounds, on prostate cell lines (PNT1A, 22RV1 and PC3. The results of an MTT assay on extracts from eight spices revealed the strongest inhibitory effects were from black pepper and caraway seed extracts. The strongest inhibitory effect on prostatic cells was observed after the application of extracts of spices in concentration of 12.5 mg·mL−1. An LC/MS analysis identified that the most abundant phenolic and flavonoid compounds in black pepper are 3,4-dihydroxybenzaldehyde and naringenin chalcone, while the most abundant phenolic and flavonoid compounds in caraway seeds are neochlorogenic acid and apigenin. Using an MTT assay for the phenolic and flavonoid compounds from spices, we identified the IC50 value of ~1 mmol·L−1 PNT1A. The scratch test demonstrated that the most potent inhibitory effect on PNT1A, 22RV1 and PC3 cells is from the naringenin chalcone contained in black pepper. From the spectrum of compounds assessed, the naringenin chalcone contained in black pepper was identified as the most potent inhibitor of the growth of prostate cells.

  19. Air pollution of hydrocarbons exhausted from vehicle in tunnels, bridges of Istanbul and detection of 3-nitrophthalic in seawater near the side of boat

    OpenAIRE

    Güven, Selin Cumalı and Kasım Cemal

    2007-01-01

    Abstract The air pollution due to exhausted gas from vehicles was studied in tunnels, bridges in Istanbul city and the contribution of exhausted gas from boat to the seawater in Golden Horn. The component of hydrocarbons of fuels and exhausted gas from vehicles was also compared. The gas samples were collected in tubes containing Tenax GR or activated charcoal adsorbent. They were extracted with dichloro-methane and analysis performed by UVF, GC/MS and HPLC. The petroleum hydrocarbon amounts ...

  20. Toxicity of Exhaust Gases and Particles from IC-Engines – International Activities Survey (EngToxIn). 2nd Information Report for IEA Implementing Agreement AMF

    Energy Technology Data Exchange (ETDEWEB)

    Czerwinski, J. [University for Applied Sciences, Biel-Bienne (Switzerland)

    2012-10-15

    Exhaust gases from engines, as well as from other technical combustion processes contain gaseous, semi volatile and solid compounds which are toxic. Some of these compounds are not yet limited by the respective legislations; but may need to be based on ongoing health research findings and some new substances did appear recently, due to the progressing technical developments providing new systems of exhaust gas aftertreatment. A new approach described here is that the toxic effects of exhaust gases as an aerosol containing gaseous components as well as particulate matter and nanoparticles can be investigated in a global way, by exposing the living cells, or cell cultures to the aerosol, which means a simultaneous superposition of all toxic effects from all active components. At several research sites it has been showed, that this method offers more objective results of validation of toxicity, than other methods used until now. It also enables a relatively quick insight in the toxic effects with consideration of all superimposed influences of the aerosol. This new methodology can be applied for all kinds of emission sources. It also bears the potential of giving new contributions to the present state of knowledge in this domain and can in some cases lead to a change of paradigma. The present report gives information about activities concerning the research on toxicity of exhaust gases from IC-engines in different countries. It also gives some ideas about the available information sources. The general situation and the basic information have not changed much so the chapters 1 and 2 are repeated from the last year report, [1] with only a few modifications. We observe fast increasing research activities concerning health effects worldwide. They have different objectives, different approaches and methodologies and sometimes the results can be directly compared to each other. There are mostly common lines and with appropriate efforts there might be possible ways to

  1. Rarity of human T helper 17 cells is due to retinoic acid orphan receptor-dependent mechanisms that limit their expansion.

    Science.gov (United States)

    Santarlasci, Veronica; Maggi, Laura; Capone, Manuela; Querci, Valentina; Beltrame, Luca; Cavalieri, Duccio; D'Aiuto, Elena; Cimaz, Rolando; Nebbioso, Angela; Liotta, Francesco; De Palma, Raffaele; Maggi, Enrico; Cosmi, Lorenzo; Romagnani, Sergio; Annunziato, Francesco

    2012-02-24

    The reason why CD4(+) T helper 17 (Th17) cells, despite their well-known pathogenic role in chronic inflammatory disorders, are very rare in the inflammatory sites remains unclear. We demonstrate that human Th17 cells exhibit low ability to proliferate and to produce the T cell growth factor interleukin-2 (IL-2), in response to combined CD3 and CD28 stimulation. This was due to the upregulated expression of IL-4-induced gene 1 (IL4I1) mRNA, a secreted L-phenylalanine oxidase, which associated with a decrease in CD3ζ chain expression and consequent abnormalities in the molecular pathway that allows IL-2 production and cell proliferation. High IL4I1 mRNA expression was detectable in Th17 cell precursors and was strictly dependent on Th17 cell master gene, the retinoid acid related orphan receptor (RORC). Th17 cells also exhibited RORC-dependent CD28 hyperexpression and the ability to produce IL-17A after CD28 stimulation without CD3 triggering. Our findings suggest that the rarity of human Th17 cells in inflamed tissues results from RORC-dependent mechanisms limiting their expansion. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Altered cell adhesion activity by pervanadate due to the dissociation of alpha-catenin from the E-cadherin.catenin complex.

    Science.gov (United States)

    Ozawa, M; Kemler, R

    1998-03-13

    Leukemia cells (K562) that grow as non-adhesive single cells and have no endogenous cadherin were transfected with an E-cadherin expression vector, and cell clones stably expressing E-cadherin on their surface were established. The expression of E-cadherin induced the up-regulation of catenins, and E-cadherin became associated with catenins. The transfected cells grew as floating aggregates. Cell aggregation was Ca2+-dependent and was inhibited by E-cadherin antibodies. The aggregates dissociated into single cells on the addition of pervanadate. Pervanadate caused a dramatic augmentation of the phosphorylation of E-cadherin, beta-catenin, and gamma-catenin (plakoglobin), but alpha-catenin was not detectably phosphorylated. After pervanadate treatment, beta-catenin and gamma-catenin migrated more slowly on gel electrophoresis, suggesting changes in their conformations due to eventual changes in their phosphorylation levels. In the treated cells, a significant amount of alpha-catenin was dissociated from the E-cadherin.catenin complex. Aggregates of cells expressing an E-cadherin chimeric molecule covalently linked with alpha-catenin were not dissociated on pervanadate treatment, supporting the idea that the dissociation of alpha-catenin from the complex underlies the observed E-cadherin dysfunction.

  3. The Lund University Checklist for Incipient Exhaustion: a prospective validation of the onset of sustained stress and exhaustion warnings

    Directory of Open Access Journals (Sweden)

    Kai Österberg

    2016-09-01

    Full Text Available Abstract Background The need for instruments that can assist in detecting the prodromal stages of stress-related exhaustion has been acknowledged. The aim of the present study was to evaluate whether the Lund University Checklist for Incipient Exhaustion (LUCIE could accurately and prospectively detect the onset of incipient exhaustion and to what extent work stressor exposure and private burdens were associated with increasing LUCIE scores. Methods Using surveys, 1355 employees were followed for 11 quarters. Participants with prospectively elevated LUCIE scores were targeted by three algorithms entailing 4 quarters: (1 abrupt onset to a sustained Stress Warning (n = 18, (2 gradual onset to a sustained Stress Warning (n = 42, and (3 sustained Exhaustion Warning (n = 36. The targeted participants’ survey reports on changes in work situation and private life during the fulfillment of any algorithm criteria were analyzed, together with the interview data. Participants untargeted by the algorithms constituted a control group (n = 745. Results Eighty-seven percent of participants fulfilling any LUCIE algorithm criteria (LUCIE indication cases rated a negative change in their work situation during the 4 quarters, compared to 48 % of controls. Ratings of negative changes in private life were also more common in the LUCIE indication groups than among controls (58 % vs. 29 %, but free-text commentaries revealed that almost half of the ratings in the LUCIE indication groups were due to work-to-family conflicts and health problems caused by excessive workload, assigned more properly to work-related negative changes. When excluding the themes related to work-stress-related private life compromises, negative private life changes in the LUCIE indication groups dropped from 58 to 32 %, while only a negligible drop from 29 to 26 % was observed among controls. In retrospective interviews, 79 % of the LUCIE indication participants

  4. The Lund University Checklist for Incipient Exhaustion: a prospective validation of the onset of sustained stress and exhaustion warnings.

    Science.gov (United States)

    Österberg, Kai; Persson, Roger; Viborg, Njördur; Jönsson, Peter; Tenenbaum, Artur

    2016-09-29

    The need for instruments that can assist in detecting the prodromal stages of stress-related exhaustion has been acknowledged. The aim of the present study was to evaluate whether the Lund University Checklist for Incipient Exhaustion (LUCIE) could accurately and prospectively detect the onset of incipient exhaustion and to what extent work stressor exposure and private burdens were associated with increasing LUCIE scores. Using surveys, 1355 employees were followed for 11 quarters. Participants with prospectively elevated LUCIE scores were targeted by three algorithms entailing 4 quarters: (1) abrupt onset to a sustained Stress Warning (n = 18), (2) gradual onset to a sustained Stress Warning (n = 42), and (3) sustained Exhaustion Warning (n = 36). The targeted participants' survey reports on changes in work situation and private life during the fulfillment of any algorithm criteria were analyzed, together with the interview data. Participants untargeted by the algorithms constituted a control group (n = 745). Eighty-seven percent of participants fulfilling any LUCIE algorithm criteria (LUCIE indication cases) rated a negative change in their work situation during the 4 quarters, compared to 48 % of controls. Ratings of negative changes in private life were also more common in the LUCIE indication groups than among controls (58 % vs. 29 %), but free-text commentaries revealed that almost half of the ratings in the LUCIE indication groups were due to work-to-family conflicts and health problems caused by excessive workload, assigned more properly to work-related negative changes. When excluding the themes related to work-stress-related private life compromises, negative private life changes in the LUCIE indication groups dropped from 58 to 32 %, while only a negligible drop from 29 to 26 % was observed among controls. In retrospective interviews, 79 % of the LUCIE indication participants confirmed exclusively/predominantly work stressors

  5. Subacute Cerebellar Degeneration due to a Paraneoplastic Phenomenon Associated with Metastatic Merkel Cell Carcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Angelos Sharobeam

    2017-08-01

    Full Text Available Purpose: The aim of this article is to illustrate the diagnostic challenges and management of paraneoplastic neurological syndromes in Merkel cell carcinoma. Materials and Methods: We describe a previously functionally independent 85-year-old woman who presented with subacute onset of dizziness and gait ataxia in the setting of metastatic Merkel cell carcinoma. Results: Diagnosis was made on biopsy after positron emission tomography imaging revealed increased metabolic activity in 2 left inguinofemoral lymph nodes. Cerebrospinal fluid analysis was positive for anti-Hu on subsequent admission. Her functional status improved with methylprednisolone treatment and radiotherapy. Conclusion: The case highlights the challenge of the evaluation of patients who present with progressive cerebellar signs and the need to consider a paraneoplastic syndrome, especially in the setting of previous malignancy.

  6. Experimental Observation of Convective Cell Formation due to a Fast Wave Antenna in the Large Plasma Device.

    Science.gov (United States)

    Martin, M J; Gekelman, W; Van Compernolle, B; Pribyl, P; Carter, T

    2017-11-17

    An experiment in a linear device, the Large Plasma Device, is used to study sheaths caused by an actively powered radio frequency (rf) antenna. The rf antenna used in the experiment consists of a single current strap recessed inside a copper box enclosure without a Faraday screen. A large increase in the plasma potential was observed along magnetic field lines that connect to the antenna limiter. The electric field from the spatial variation of the rectified plasma potential generated E[over →]×B[over →]_{0} flows, often referred to as convective cells. The presence of the flows generated by these potentials is confirmed by Mach probes. The observed convective cell flows are seen to cause the plasma in front of the antenna to flow away and cause a density modification near the antenna edge. These can cause hot spots and damage to the antenna and can result in a decrease in the ion cyclotron range of frequencies antenna coupling.

  7. PHYSICO-CHEMICAL ASSESSMENT OF POMACE EXHAUSTED ...

    African Journals Online (AJOL)

    M’Sadak Y, Makhlouf M and El Amrouni S

    2016-05-01

    May 1, 2016 ... 2851. 6093. 3.1.2. Physico-chemical characterization. The physicochemical characteristics vary across different pomace oil extraction systems. (classic, press and continuous). Classical system. Table 2. Qualitative Characterization of pomace exhausted by the classical system. Parameters. Abbreviation.

  8. 40 CFR 1065.130 - Engine exhaust.

    Science.gov (United States)

    2010-07-01

    ... generators, such as orifice plates or fins, to achieve good mixing. We recommend a minimum Reynolds number... specify speed and torque points, measure pressure while the engine produces maximum power. Use an exhaust... separately using a method that we approve in advance, or route open crankcase emissions directly into the...

  9. Application of plasma techniques for exhaust aftertreatment

    Czech Academy of Sciences Publication Activity Database

    Pospíšil, M.; Viden, I.; Šimek, Milan; Pekárek, S.

    2001-01-01

    Roč. 27, 1-4 (2001), s. 306-314 ISSN 0143-3369 R&D Projects: GA ČR GA202/99/1298 Institutional research plan: CEZ:AV0Z2043910 Keywords : Non-thermal plasma, elctrical discharge, exhaust aftertreatment Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 0.190, year: 2001

  10. Assessing population exposures to motor vehicle exhaust.

    Science.gov (United States)

    Van Atten, Chris; Brauer, Michael; Funk, Tami; Gilbert, Nicolas L; Graham, Lisa; Kaden, Debra; Miller, Paul J; Bracho, Leonora Rojas; Wheeler, Amanda; White, Ronald H

    2005-01-01

    The need is growing for a better assessment of population exposures to motor vehicle exhaust in proximity to major roads and highways. This need is driven in part by emerging scientific evidence of adverse health effects from such exposures and policy requirements for a more targeted assessment of localized public health impacts related to road expansions and increasing commercial transportation. The momentum for improved methods in measuring local exposures is also growing in the scientific community, as well as for discerning which constituents of the vehicle exhaust mixture may exert greater public health risks for those who are exposed to a disproportionate share of roadway pollution. To help elucidate the current state-of-the-science in exposure assessments along major roadways and to help inform decision makers of research needs and trends, we provide an overview of the emerging policy requirements, along with a conceptual framework for assessing exposure to motor-vehicle exhaust that can help inform policy decisions. The framework includes the pathway from the emission of a single vehicle, traffic emissions from multiple vehicles, atmospheric transformation of emissions and interaction with topographic and meteorologic features, and contact with humans resulting in exposure that can result in adverse health impacts. We describe the individual elements within the conceptual framework for exposure assessment and discuss the strengths and weaknesses of various approaches that have been used to assess public exposures to motor vehicle exhaust.

  11. Exhaust gas treatment by electron beam irradiation

    International Nuclear Information System (INIS)

    Shibamura, Yokichi; Suda, Shoichi; Kobayashi, Toshiki

    1991-01-01

    Among global environmental problems, atmospheric pollution has been discussed since relatively old days, and various countermeasures have been taken, but recently in connection with acid rain, the efficient and economical treatment technology is demanded. As the denitration and desulfurization technology for the exhaust gas from the combustion of fossil fuel, the incineration of city trash and internal combustion engines, three is the treatment method by electron beam irradiation. By irradiating electron beam to exhaust gas, nitrogen oxides and sulfur oxides are oxidized to nitric acid and sulfuric acid, and by promoting the neutralization of these acids with injected alkali, harmless salts are recovered. This method has the merit that nitrogen oxides and surfur oxides can be removed efficiently with a single system. In this report, as for the exhaust gas treatment by electron beam irradiation, its principle, features, and the present status of research and development are described, and in particular, the research on the recent exhaust gas treatment in city trash incineration is introduced. This treatment method is a dry process, accordingly, waste water disposal is unnecessary. The reaction products are utilized as fertilizer, and waste is not produced. (K.I.)

  12. The Effect of Unemployment Insurance Exhaustion

    DEFF Research Database (Denmark)

    Lyk-Jensen, Stéphanie; Weatherall, Cecilie Dohlmann

    . To identify the effect of UI exhaustion, we exploit the 1999 legislative change in the duration of benefit that progressively reduced regular UI entitlement from five to four years. According to time of entry into the UI system, all UI recipients had their potential UI period shortened. We use a competing...

  13. Propagation of light through ship exhaust plumes

    Science.gov (United States)

    van Iersel, M.; Mack, A.; van Eijk, A. M. J.; Schleijpen, H. M. A.

    2014-10-01

    Looking through the atmosphere, it is sometimes difficult to see the details of an object. Effects like scintillation and blur are the cause of these difficulties. Exhaust plumes of e.g. a ship can cause extreme scintillation and blur, making it even harder to see the details of what lies behind the plume. Exhaust plumes come in different shapes, sizes, and opaqueness and depending on atmospheric parameters like wind speed and direction, as well as engine settings (power, gas or diesel, etc.). A CFD model is used to determine the plume's flow field outside the stack on the basis of exhaust flow properties, the interaction with the superstructure of the ship, the meteorological conditions and the interaction of ship's motion and atmospheric wind fields. A modified version of the NIRATAM code performs the gas radiation calculations and provides the radiant intensity of the (hot) exhaust gases and the transmission of the atmosphere around the plume is modeled with MODTRAN. This allows assessing the irradiance of a sensor positioned at some distance from the ship and its plume, as function of the conditions that influence the spatial distribution and thermal properties of the plume. Furthermore, an assessment can be made of the probability of detecting objects behind the plume. This plume module will be incorporated in the TNO EOSTAR-model, which provides estimates of detection range and image quality of EO-sensors under varying meteorological conditions.

  14. Propagation of light through ship exhaust plumes

    NARCIS (Netherlands)

    Iersel, M. van; Mack, A.; Eijk, A.M.J. van; Schleijpen, H.M.A.

    2014-01-01

    Looking through the atmosphere, it is sometimes difficult to see the details of an object. Effects like scintillation and blur are the cause of these difficulties. Exhaust plumes of e.g. a ship can cause extreme scintillation and blur, making it even harder to see the details of what lies behind the

  15. Emotional labour, emotional exhaustion, job satisfaction and ...

    African Journals Online (AJOL)

    This study investigated the relationship between emotional labour strategies, emotional exhaustion, job satisfaction and organisational citizenship behaviour among Korean fitness employees. Three hundred and sixty-six (n=366) fitness employees participated in a self-administered survey aimed at measuring the impact of ...

  16. Biophysical alteration of the secretory track in β-cells due to molecular overcrowding: the relevance for diabetes.

    Science.gov (United States)

    Ionescu-Tirgoviste, Constantin; Despa, Florin

    2011-03-01

    Recent data demonstrate that accumulation of misfolded proteins within the early part of the secretory track of β-cells causes impaired insulin synthesis and development of diabetes. The molecular mechanism of this cellular dysfunction remains largely unknown. Using basic molecular principles and computer simulations, we suggested recently that hyperglycemic conditions can generate substantial molecular crowding effects in the secretory track of β-cells leading to significant alterations of the insulin biosynthesis capabilities. Here, we review the major molecular mechanisms that may be implicated in the alteration of insulin synthesis in susceptible β-cells. Steric repulsions and volume exclusion in the endoplasmic reticulum (ER) increase the propensity of misfolding of proinsulin (the precursor molecule of insulin). In addition, similar forces might act in the next secretory compartments (Golgi and vesicles) leading to (i) altered packaging of proinsulin in vesicles (ii) entrapment of proinsulin convertases and/or restricted accessibility for these convertases to the cleavage sites on the surface of the proinsulin and (iii) depressed kinetic rate of the transformation of the native proinsulin in active insulin and C-peptide. These concepts are expressed in simple mathematical terms relating the kinetic coefficient of proinsulin to insulin conversion to the levels of proinsulin misfolding and hyperglycemic stress. The present approach is useful for understanding molecular phenomena associated with the pathogenesis of diabetes. It also offers practical means for predicting the state of pancreatic β-cells from measurements of the insulin to proinsulin ratio in the blood. This is of immediate clinical relevance and may improve the diagnosis of diabetes.

  17. Alterations in the properties of the cell membrane due to glycosphingolipid accumulation in a model of Gaucher disease

    OpenAIRE

    Batta, Gyula; Soltész, Lilla; Kovács, Tamás; Bozó, Tamás; Mészár, Zoltán; Kellermayer, Miklós; Szöllősi, János; Nagy, Peter

    2018-01-01

    Gaucher disease is a lysosomal storage disease characterized by the malfunction of glucocerebrosidase resulting in the accumulation of glucosylceramide and other sphingolipids in certain cells. Although the disease symptoms are usually attributed to the storage of undigested substrate in lysosomes, here we show that glycosphingolipids accumulating in the plasma membrane cause profound changes in the properties of the membrane. The fluidity of the sphingolipid-enriched membrane decreased accom...

  18. Diversity of T cell epitopes in Plasmodium falciparum circumsporozoite protein likely due to protein-protein interactions.

    Directory of Open Access Journals (Sweden)

    Nagesh R Aragam

    Full Text Available Circumsporozoite protein (CS is a leading vaccine antigen for falciparum malaria, but is highly polymorphic in natural parasite populations. The factors driving this diversity are unclear, but non-random assortment of the T cell epitopes TH2 and TH3 has been observed in a Kenyan parasite population. The recent publication of the crystal structure of the variable C terminal region of the protein allows the assessment of the impact of diversity on protein structure and T cell epitope assortment. Using data from the Gambia (55 isolates and Malawi (235 isolates, we evaluated the patterns of diversity within and between epitopes in these two distantly-separated populations. Only non-synonymous mutations were observed with the vast majority in both populations at similar frequencies suggesting strong selection on this region. A non-random pattern of T cell epitope assortment was seen in Malawi and in the Gambia, but structural analysis indicates no intramolecular spatial interactions. Using the information from these parasite populations, structural analysis reveals that polymorphic amino acids within TH2 and TH3 colocalize to one side of the protein, surround, but do not involve, the hydrophobic pocket in CS, and predominately involve charge switches. In addition, free energy analysis suggests residues forming and behind the novel pocket within CS are tightly constrained and well conserved in all alleles. In addition, free energy analysis shows polymorphic residues tend to be populated by energetically unfavorable amino acids. In combination, these findings suggest the diversity of T cell epitopes in CS may be primarily an evolutionary response to intermolecular interactions at the surface of the protein potentially counteracting antibody-mediated immune recognition or evolving host receptor diversity.

  19. Diversity of T cell epitopes in Plasmodium falciparum circumsporozoite protein likely due to protein-protein interactions.

    Science.gov (United States)

    Aragam, Nagesh R; Thayer, Kelly M; Nge, Nabi; Hoffman, Irving; Martinson, Francis; Kamwendo, Debbie; Lin, Feng-Chang; Sutherland, Colin; Bailey, Jeffrey A; Juliano, Jonathan J

    2013-01-01

    Circumsporozoite protein (CS) is a leading vaccine antigen for falciparum malaria, but is highly polymorphic in natural parasite populations. The factors driving this diversity are unclear, but non-random assortment of the T cell epitopes TH2 and TH3 has been observed in a Kenyan parasite population. The recent publication of the crystal structure of the variable C terminal region of the protein allows the assessment of the impact of diversity on protein structure and T cell epitope assortment. Using data from the Gambia (55 isolates) and Malawi (235 isolates), we evaluated the patterns of diversity within and between epitopes in these two distantly-separated populations. Only non-synonymous mutations were observed with the vast majority in both populations at similar frequencies suggesting strong selection on this region. A non-random pattern of T cell epitope assortment was seen in Malawi and in the Gambia, but structural analysis indicates no intramolecular spatial interactions. Using the information from these parasite populations, structural analysis reveals that polymorphic amino acids within TH2 and TH3 colocalize to one side of the protein, surround, but do not involve, the hydrophobic pocket in CS, and predominately involve charge switches. In addition, free energy analysis suggests residues forming and behind the novel pocket within CS are tightly constrained and well conserved in all alleles. In addition, free energy analysis shows polymorphic residues tend to be populated by energetically unfavorable amino acids. In combination, these findings suggest the diversity of T cell epitopes in CS may be primarily an evolutionary response to intermolecular interactions at the surface of the protein potentially counteracting antibody-mediated immune recognition or evolving host receptor diversity.

  20. Copper induces hepatocyte injury due to the endoplasmic reticulum stress in cultured cells and patients with Wilson disease

    Energy Technology Data Exchange (ETDEWEB)

    Oe, Shinji, E-mail: ooes@med.uoeh-u.ac.jp; Miyagawa, Koichiro, E-mail: koichiro@med.uoeh-u.ac.jp; Honma, Yuichi, E-mail: y-homma@med.uoeh-u.ac.jp; Harada, Masaru, E-mail: msrharada@med.uoeh-u.ac.jp

    2016-09-10

    Copper is an essential trace element, however, excess copper is harmful to human health. Excess copper-derived oxidants contribute to the progression of Wilson disease, and oxidative stress induces accumulation of abnormal proteins. It is known that the endoplasmic reticulum (ER) plays an important role in proper protein folding, and that accumulation of misfolded proteins disturbs ER homeostasis resulting in ER stress. However, copper-induced ER homeostasis disturbance has not been fully clarified. We treated human hepatoma cell line (Huh7) and immortalized-human hepatocyte cell line (OUMS29) with copper and chemical chaperones, including 4-phenylbutyrate and ursodeoxycholic acid. We examined copper-induced oxidative stress, ER stress and apoptosis by immunofluorescence microscopy and immunoblot analyses. Furthermore, we examined the effects of copper on carcinogenesis. Excess copper induced not only oxidative stress but also ER stress. Furthermore, excess copper induced DNA damage and reduced cell proliferation. Chemical chaperones reduced this copper-induced hepatotoxicity. Excess copper induced hepatotoxicity via ER stress. We also confirmed the abnormality of ultra-structure of the ER of hepatocytes in patients with Wilson disease. These findings show that ER stress plays a pivotal role in Wilson disease, and suggests that chemical chaperones may have beneficial effects in the treatment of Wilson disease.

  1. Copper induces hepatocyte injury due to the endoplasmic reticulum stress in cultured cells and patients with Wilson disease

    International Nuclear Information System (INIS)

    Oe, Shinji; Miyagawa, Koichiro; Honma, Yuichi; Harada, Masaru

    2016-01-01

    Copper is an essential trace element, however, excess copper is harmful to human health. Excess copper-derived oxidants contribute to the progression of Wilson disease, and oxidative stress induces accumulation of abnormal proteins. It is known that the endoplasmic reticulum (ER) plays an important role in proper protein folding, and that accumulation of misfolded proteins disturbs ER homeostasis resulting in ER stress. However, copper-induced ER homeostasis disturbance has not been fully clarified. We treated human hepatoma cell line (Huh7) and immortalized-human hepatocyte cell line (OUMS29) with copper and chemical chaperones, including 4-phenylbutyrate and ursodeoxycholic acid. We examined copper-induced oxidative stress, ER stress and apoptosis by immunofluorescence microscopy and immunoblot analyses. Furthermore, we examined the effects of copper on carcinogenesis. Excess copper induced not only oxidative stress but also ER stress. Furthermore, excess copper induced DNA damage and reduced cell proliferation. Chemical chaperones reduced this copper-induced hepatotoxicity. Excess copper induced hepatotoxicity via ER stress. We also confirmed the abnormality of ultra-structure of the ER of hepatocytes in patients with Wilson disease. These findings show that ER stress plays a pivotal role in Wilson disease, and suggests that chemical chaperones may have beneficial effects in the treatment of Wilson disease.

  2. Changes in cell migration due to the combined effects of sonodynamic therapy and photodynamic therapy on MDA-MB-231 cells

    Science.gov (United States)

    Wang, Haiping; Wang, Pan; Zhang, Kun; Wang, Xiaobing; Liu, Quanhong

    2015-03-01

    Sono-photodynamic therapy is an emerging method with an increasing amount of research having demonstrated its anti-cancer efficacy. However, the impacts of cell migration ability after sono-photodynamic therapy have seldom been reported. In this study, we identified cell migration by wound healing and transwell assays. Significant inability of cell migration was observed in combined groups accompanied by the decline of cell adhesion. Cells in combined treatment groups showed serious microfilament network collapse as well as decreased expression of matrix metalloproteinases-9. These results suggested that sono-photodynamic therapy could inhibit MDA-MB-231 cell migration and that the microfilament and matrix metalloproteinases-9 disorder might be involved.

  3. Efeitos da suplementação de fibras solúveis sobre as células do sistema imune após exercício exaustivo em ratos treinados Effects of soluble fibers supplementation on immune system cells after exhausting exercise in trained rats

    Directory of Open Access Journals (Sweden)

    Felipe F. Donatto

    2008-12-01

    Full Text Available A intensidade, volume, modalidade de exercício, assim como o nível de aptidão e fatores nutricionais podem alterar a reposta imunológica. O objetivo deste estudo foi avaliar o efeito da suplementação crônica de farelo de aveia (fonte de fibras solúveis sobre as células do sistema imunológico em ratos treinados, frente a um teste de exaustão. Foram utilizados ratos Wistar, ± dois meses, peso ± 200g, divididos em três grupos (n = 9, cada um: 1 controle sedentário (C; 2 treinado oito semanas submetido ao teste de exaustão (EX; e 3 treinado oito semanas submetido ao teste de exaustão com suplementação de 30% de farelo de aveia (EXA. O treinamento consistiu de 60 minutos de natação diários, cinco dias por semana durante oito semanas. As análises realizadas foram: contagem total de leucócitos, linfócitos dos linfonodos mesentéricos, macrófagos peritoneais e capacidade fagocitária de macrófagos peritoneais. Aplicou-se o teste estatístico ANOVA two way, seguido do post hoc de Tukey com p Exercise modality, volume, intensity, as well as physical fitness and nutritional factors may modulate the immune response. The purpose of this investigation was to verify the effects of chronic oat bran supplementation on immune cells in trained rats submitted to an extenuating test. Wistar rats (two months old, +200g weight, divided into three groups (n = 9, per group were used: 1 a sedentary control (C 2 trained for eight weeks submitted to an exhaustion test (EX, and 3 trained for eight weeks submitted to an exhaustion test with 30% oat bran supplementation (EXA. Training consisted of 60 daily minutes of swimming, five days a week, during eight weeks. The analyses conducted were: total leukocytes, lymphocytes from lymph nodes, peritoneal macrophages and peritoneal macrophages phagocytic capacity. Statistical analyses were done by the two-way ANOVA test, followed by Tukey's post hoc test (p < 0.05. EX group presented leukocytosis when

  4. Unique Preservation of Neural Cells in Hutchinson- Gilford Progeria Syndrome Is Due to the Expression of the Neural-Specific miR-9 MicroRNA

    Directory of Open Access Journals (Sweden)

    Xavier Nissan

    2012-07-01

    Full Text Available One puzzling observation in patients affected with Hutchinson-Gilford progeria syndrome (HGPS, who overall exhibit systemic and dramatic premature aging, is the absence of any conspicuous cognitive impairment. Recent studies based on induced pluripotent stem cells derived from HGPS patient cells have revealed a lack of expression in neural derivatives of lamin A, a major isoform of LMNA that is initially produced as a precursor called prelamin A. In HGPS, defective maturation of a mutated prelamin A induces the accumulation of toxic progerin in patient cells. Here, we show that a microRNA, miR-9, negatively controls lamin A and progerin expression in neural cells. This may bear major functional correlates, as alleviation of nuclear blebbing is observed in nonneural cells after miR-9 overexpression. Our results support the hypothesis, recently proposed from analyses in mice, that protection of neural cells from progerin accumulation in HGPS is due to the physiologically restricted expression of miR-9 to that cell lineage.

  5. Activation of Natural Killer Cells in Patients with Chronic Bone and Joint Infection due to Staphylococci Expressing or Not the Small Colony Variant Phenotype

    Directory of Open Access Journals (Sweden)

    Sébastien Viel

    2014-01-01

    Full Text Available Chronic bone and joint infections (BJI are devastating diseases. Relapses are frequently observed, as some pathogens, especially staphylococci, can persist intracellularly by expressing a particular phenotype called small colony variant (SCV. As natural killer (NK cells are lymphocytes specialized in the killing of host cells infected by intracellular pathogens, we studied NK cells of patients with chronic BJI due to staphylococci expressing or not SCVs (10 patients in both groups. Controls were patients infected with other bacteria without detectable expression of SCVs, and healthy volunteers. NK cell phenotype was evaluated from PBMCs by flow cytometry. Degranulation capacity was evaluated after stimulation with K562 cells in vitro. We found that NK cells were activated in terms of CD69 expression, loss of CD16 and perforin, in all infected patients in comparison with healthy volunteers, independently of the SCV phenotype. Peripheral NK cells in patients with chronic BJI display signs of recent activation and degranulation in vivo in response to CD16-mediated signals, regardless of the type of bacteria involved. This could involve a universal capacity of isolates responsible for chronic BJI to produce undetectable SCVs in vivo, which might be a target of future intervention.

  6. Quantification of vehicle fleet PM10 particulate matter emission factors from exhaust and non-exhaust sources using tunnel measurement techniques

    International Nuclear Information System (INIS)

    Lawrence, Samantha; Sokhi, Ranjeet; Ravindra, Khaiwal

    2016-01-01

    Road tunnels act like large laboratories; they provide an excellent environment to quantify atmospheric particles emission factors from exhaust and non-exhaust sources due to their known boundary conditions. Current work compares the High Volume, Dichotomous Stacked Filter Unit and Partisol Air Sampler for coarse, PM 10 and PM 2.5 particle concentration measurement and found that they do not differ significantly (p = 95%). PM 2.5 fraction contributes 66% of PM 10 proportions and significantly influenced by traffic (turbulence) and meteorological conditions. Mass emission factors for PM 10 varies from 21.3 ± 1.9 to 28.8 ± 3.4 mg/vkm and composed of Motorcycle (0.0003–0.001 mg/vkm), Cars (26.1–33.4 mg/vkm), LDVs (2.4–3.0 mg/vkm), HDVs (2.2–2.8 mg/vkm) and Buses (0.1 mg/vkm). Based on Lawrence et al. (2013), source apportionment modelling, the PM 10 emission of brake wear (3.8–4.4 mg/vkm), petrol exhaust (3.9–4.5 mg/vkm), diesel exhaust (7.2–8.3 mg/vkm), re-suspension (9–10.4 mg/vkm), road surface wear (3.9–4.5 mg/vkm), and unexplained (7.2 mg/vkm) were also calculated. The current study determined that the combined non-exhaust fleet PM 10 emission factor (16.7–19.3 mg/vkm) are higher than the combined exhaust emission factor (11.1–12.8 mg/vkm). Thus, highlight the significance of non-exhaust emissions and the need for legislation and abatement strategies to reduce their contributions to ambient PM concentrations. - Highlights: • Calculations of exhaust/non-exhaust particulate emission factors using tunnel sampling and source apportionment techniques. • Non-exhaust emission dominates in the fine particle fraction, considered responsible for adverse human health impacts. • Emission factors for non-exhaust sources (e.g. tyre and brake) were calculated. • Fleet source PM 10 emission factor were also calculated, which can be used in dispersion modelling and health risk assessment. • Tukey mean-difference plot shows

  7. Tumorigenesis of diesel exhaust, gasoline exhaust, and related emission extracts on SENCAR mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Nesnow, S; Triplett, L L; Slaga, T J

    1980-01-01

    The tumorigenicity of diesel exhaust particulate emissions was examined using a sensitive mouse skin tumorigenesis model (SENCAR). The tumorigenic potency of particulate emissions from diesel, gasoline, and related emission sources was compared.

  8. IPEX due to an exon 7 skipping FOXP3 mutation with autoimmune diabetes mellitus cured by selective TReg cell engraftment.

    Science.gov (United States)

    Magg, Thomas; Wiebking, Volker; Conca, Raffaele; Krebs, Stefan; Arens, Stefan; Schmid, Irene; Klein, Christoph; Albert, Michael H; Hauck, Fabian

    2018-03-19

    Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare inherited disorder leading to severe organ-specific autoimmunity. IPEX is caused by hemizygous mutations in FOXP3, which codes for a master transcription factor of regulatory T (T Reg ) cell development and function. We describe a four-year-old boy with typical but slightly delayed-onset of IPEX with autoimmune diabetes mellitus, enteropathy, hepatitis and skin disease. We found the unreported FOXP3 splice site mutation c.816+2T>A that leads to the loss of leucine-zipper coding exon 7. RNA-Seq revealed that FOXP3Δ7 leads to differential expression of FOXP3 regulated genes. After myeloablative conditioning the patient underwent allogeneic HSCT from a matched unrelated donor. HSCT led to the resolution of all IPEX symptoms including insulin requirement despite persisting autoantibody levels. After initial full donor engraftment nearly complete autologous reconstitution was documented, but donor-derived T Reg cells persisted with a lineage-specific chimerism of >70% and the patient remained in clinical remission. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Dendritic cell-mediated HIV-1 transmission to T cells of LAD-1 patients is impaired due to the defect in LFA-1

    NARCIS (Netherlands)

    Groot, Fedde; Kuijpers, Taco W.; Berkhout, Ben; de Jong, Esther C.

    2006-01-01

    BACKGROUND: Dendritic cells (DC) have been proposed to mediate sexual HIV-1 transmission by capturing the virus in the mucosa and subsequently presenting it to CD4+ T cells. We have demonstrated before that DC subsets expressing higher levels of intercellular adhesion molecule-1 (ICAM-1) are better

  10. Hemolytic disease of the fetus and newborn due to anti-Ge3: combined antibody-dependent hemolysis and erythroid precursor cell growth inhibition.

    Science.gov (United States)

    Blackall, Douglas P; Pesek, Gina D; Montgomery, Matthew M; Oza, Krishna K; Arndt, Patricia A; Garratty, George; Shahcheraghi, Ali; Denomme, Gregory A

    2008-10-01

    The Gerbich (Ge) antigens are a collection of high-incidence antigens carried on the red blood cell membrane glycoproteins, glycophorins C and D. Antibodies against these antigens are uncommon, and there have been only rare case reports of hemolytic disease of the fetus and newborn due to anti-Ge. In this case report, we present a neonate with severe anemia and hyperbilirubinemia due to anti-Ge3. Routine and special laboratory studies undertaken in this case suggested two mechanisms for the patient's hemolysis and persistent anemia. Antibody-dependent hemolysis was associated with early-onset hyperbilirubinemia, anemia, and a mild reticulocytosis, and inhibition of erythroid progenitor cell growth was associated with late anemia and normal bilirubin and reticulocyte values. Though rare, anti-Ge3 can be a dangerous antibody in pregnancy. Affected neonates may require intensive initial therapy and close follow-up for at least several weeks after delivery.

  11. Hypotension due to Chemotherapy in a Patient with Small Cell Lung Cancer and Lambert-Eaton Myasthenic Syndrome Undergoing Hemodialysis: A First Case Report

    Directory of Open Access Journals (Sweden)

    Taiji Kuwata

    2012-01-01

    Full Text Available We present the first case of small cell lung cancer with Lambert-Eaton myasthenic syndrome during hemodialysis (HD. A 72-year-old male patient receiving HD experienced progressive muscle weakness. He was diagnosed with small cell lung cancer with Lambert-Eaton myasthenic syndrome due to an increased serum level of anti-voltage-gated calcium channel antibody and aspiration cytology on endobronchial ultrasonography for the swelling of a subcarinal lymph node. He received chemotherapy consisting of carboplatin (300 mg/m2 and etoposide (50 mg/m2, to which he had a partial response. However, the second therapy course could not be administered because of the unexpected development of severe hematological adverse events, which also prevented him from undergoing further HD. This case indicates that caution should be taken when using chemotherapy for such patients because of hypotension due to chemotherapy, with which it is impossible to undergo HD.

  12. CMV latent infection improves CD8+ T response to SEB due to expansion of polyfunctional CD57+ cells in young individuals.

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    Alejandra Pera

    Full Text Available Cytomegalovirus (CMV latent infection has a deleterious effect on the efficacy of influenza vaccination in the elderly, suggesting that CMV restricts immunological diversity impairing the immune system functionality in old age. Polyfunctional T cells produce multiple cytokines and higher amounts than mono-functional T cells. High number of polyfunctional T cells correlates with better prognosis during infection. Thus, the efficiency of T cell response associates with quality (polyfunctionality rather than with quantity (percentage of T cells. We analyze the effect of CMV infection on CD8+ T cells polyfunctionality --degranulation (CD107a, IFN-gamma and TNF-alpha production--, from young CMV-seropositive and CMV-seronegative individuals and in middle age CMV-seropositive donors, in response to Staphylococcal Enterotoxin B (SEB. Our results show a higher percentage of polyfunctional CD8+ T cells in young CMV-seropositive individuals compared to CMV-seronegative. Also, we find an expansion of CD8+CD57+ T cells in CMV-seropositive individuals, which are more polyfunctional than CD8+CD57- cells. In middle age individuals there is a higher frequency of SEB-responding CD8+ T cells, mainly TNF-alpha or TNF-alpha/IFN-gamma producers, whereas the percentage of polyfunctional cells (IFN-gamma/TNF-alpha/CD107a is similar to the percentages found in young CMV-seropositive. Therefore, whereas it has been shown that CMV latent infection can be detrimental for immune response in old individuals, our results indicate that CMV-seropositivity is associated to higher levels of polyfunctional CD8+ T cells in young and middle age donors. This increase in polyfunctionality, which can provide an immunological advantage in the response to other pathogens, is due to a CD8+CD57+ T cell expansion in CMV-seropositive individuals and it is independent of age. Conversely, age could contribute to the inflammation found in old individuals by increasing the percentage of cells

  13. Circulating tumour cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition

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    Gorges Tobias M

    2012-05-01

    Full Text Available Abstract Background Circulating tumour cells (CTCs have shown prognostic relevance in metastatic breast, prostate, colon and pancreatic cancer. For further development of CTCs as a biomarker, we compared the performance of different protocols for CTC detection in murine breast cancer xenograft models (MDA-MB-231, MDA-MB-468 and KPL-4. Blood samples were taken from tumour bearing animals (20 to 200 mm2 and analysed for CTCs using 1. an epithelial marker based enrichment method (AdnaTest, 2. an antibody independent technique, targeting human gene transcripts (qualitative PCR, and 3. an antibody-independent approach, targeting human DNA-sequences (quantitative PCR. Further, gene expression changes associated with epithelial-to-mesenchymal transition (EMT were determined with an EMT-specific PCR assay. Methods We used the commercially available Adna Test, RT-PCR on human housekeeping genes and a PCR on AluJ sequences to detect CTCs in xenografts models. Phenotypic changes in CTCs were tested with the commercially available “Human Epithelial to Mesenchymal Transition RT-Profiler PCR Array”. Results Although the AdnaTest detects as few as 1 tumour cell in 1 ml of mouse blood spiking experiments, no CTCs were detectable with this approach in vivo despite visible metastasis formation. The presence of CTCs could, however, be demonstrated by PCR targeting human transcripts or DNA-sequences - without epithelial pre-enrichment. The failure of CTC detection by the AdnaTest resulted from downregulation of EpCAM, whereas mesenchymal markers like Twist and EGFR were upregulated on CTCs. Such a change in the expression profile during metastatic spread of tumour cells has already been reported and was linked to a biological program termed epithelial-mesenchymal transition (EMT. Conclusions The use of EpCAM-based enrichment techniques leads to the failure to detect CTC populations that have undergone EMT. Our findings may explain clinical results where low

  14. Circulating tumour cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition

    International Nuclear Information System (INIS)

    Gorges, Tobias M; Tinhofer, Ingeborg; Drosch, Michael; Röse, Lars; Zollner, Thomas M; Krahn, Thomas

    2012-01-01

    Circulating tumour cells (CTCs) have shown prognostic relevance in metastatic breast, prostate, colon and pancreatic cancer. For further development of CTCs as a biomarker, we compared the performance of different protocols for CTC detection in murine breast cancer xenograft models (MDA-MB-231, MDA-MB-468 and KPL-4). Blood samples were taken from tumour bearing animals (20 to 200 mm 2 ) and analysed for CTCs using 1. an epithelial marker based enrichment method (AdnaTest), 2. an antibody independent technique, targeting human gene transcripts (qualitative PCR), and 3. an antibody-independent approach, targeting human DNA-sequences (quantitative PCR). Further, gene expression changes associated with epithelial-to-mesenchymal transition (EMT) were determined with an EMT-specific PCR assay. We used the commercially available Adna Test, RT-PCR on human housekeeping genes and a PCR on AluJ sequences to detect CTCs in xenografts models. Phenotypic changes in CTCs were tested with the commercially available “Human Epithelial to Mesenchymal Transition RT-Profiler PCR Array”. Although the AdnaTest detects as few as 1 tumour cell in 1 ml of mouse blood spiking experiments, no CTCs were detectable with this approach in vivo despite visible metastasis formation. The presence of CTCs could, however, be demonstrated by PCR targeting human transcripts or DNA-sequences - without epithelial pre-enrichment. The failure of CTC detection by the AdnaTest resulted from downregulation of EpCAM, whereas mesenchymal markers like Twist and EGFR were upregulated on CTCs. Such a change in the expression profile during metastatic spread of tumour cells has already been reported and was linked to a biological program termed epithelial-mesenchymal transition (EMT). The use of EpCAM-based enrichment techniques leads to the failure to detect CTC populations that have undergone EMT. Our findings may explain clinical results where low CTC numbers have been reported even in patients with late

  15. Telomere Dynamics in Immune Senescence and Exhaustion Triggered by Chronic Viral Infection

    Directory of Open Access Journals (Sweden)

    Marcia Bellon

    2017-10-01

    Full Text Available The progressive loss of immunological memory during aging correlates with a reduced proliferative capacity and shortened telomeres of T cells. Growing evidence suggests that this phenotype is recapitulated during chronic viral infection. The antigenic volume imposed by persistent and latent viruses exposes the immune system to unique challenges that lead to host T-cell exhaustion, characterized by impaired T-cell functions. These dysfunctional memory T cells lack telomerase, the protein capable of extending and stabilizing chromosome ends, imposing constraints on telomere dynamics. A deleterious consequence of this excessive telomere shortening is the premature induction of replicative senescence of viral-specific CD8+ memory T cells. While senescent cells are unable to expand, they can survive for extended periods of time and are more resistant to apoptotic signals. This review takes a closer look at T-cell exhaustion in chronic viruses known to cause human disease: Epstein–Barr virus (EBV, Hepatitis B/C/D virus (HBV/HCV/HDV, human herpesvirus 8 (HHV-8, human immunodeficiency virus (HIV, human T-cell leukemia virus type I (HTLV-I, human papillomavirus (HPV, herpes simplex virus-1/2(HSV-1/2, and Varicella–Zoster virus (VZV. Current literature linking T-cell exhaustion with critical telomere lengths and immune senescence are discussed. The concept that enduring antigen stimulation leads to T-cell exhaustion that favors telomere attrition and a cell fate marked by enhanced T-cell senescence appears to be a common endpoint to chronic viral infections.

  16. 46 CFR 111.33-9 - Ventilation exhaust.

    Science.gov (United States)

    2010-10-01

    ... REQUIREMENTS Power Semiconductor Rectifier Systems § 111.33-9 Ventilation exhaust. The exhaust of each forced-air semiconductor rectifier system must: (a) Terminate in a location other than a hazardous location...

  17. Flow instabilities due to the interfacial formation of surfactant-fatty acid material in a Hele-Shaw cell.

    Science.gov (United States)

    Niroobakhsh, Zahra; Litman, Matthew; Belmonte, Andrew

    2017-11-01

    We present an experimental study of pattern formation during the penetration of an aqueous surfactant solution into a liquid fatty acid in a Hele-Shaw cell. When a solution of the cationic surfactant cetylpyridinium chloride is injected into oleic acid, a wide variety of fingering patterns are observed as a function of surfactant concentration and flow rate, which are strikingly different than the classic Saffman-Taylor (ST) instability. We observe evidence of interfacial material forming between the two liquids, causing these instabilities. Moreover, the number of fingers decreases with increasing flow rate Q, while the average finger width increases with Q, both trends opposite to the ST case. Bulk rheology on related mixtures indicates a gel-like state. Comparison of experiments using other oils indicates the importance of pH and the carboxylic head group in the formation of the surfactant-fatty acid material.

  18. On-chip automation of cell-free protein synthesis: new opportunities due to a novel reaction mode.

    Science.gov (United States)

    Georgi, V; Georgi, L; Blechert, M; Bergmeister, M; Zwanzig, M; Wüstenhagen, D A; Bier, F F; Jung, E; Kubick, S

    2016-01-21

    Many pharmaceuticals are proteins or their development is based on proteins. Cell-free protein synthesis (CFPS) is an innovative alternative to conventional cell based systems which enables the production of proteins with complex and even new characteristics. However, the short lifetime, low protein production and expensive reagent costs are still limitations of CFPS. Novel automated microfluidic systems might allow continuous, controllable and resource conserving CFPS. The presented microfluidic TRITT platform (TRITT for Transcription - RNA Immobilization & Transfer - Translation) addresses the individual biochemical requirements of the transcription and the translation step of CFPS in separate compartments, and combines the reaction steps by quasi-continuous transfer of RNA templates to enable automated CFPS. In detail, specific RNA templates with 5' and 3' hairpin structures for stabilization against nucleases were immobilized during in vitro transcription by newly designed and optimized hybridization oligonucleotides coupled to magnetizable particles. Transcription compatibility and reusability for immobilization of these functionalized particles was successfully proven. mRNA transfer was realized on-chip by magnetic actuated particle transfer, RNA elution and fluid flow to the in vitro translation compartment. The applicability of the microfluidic TRITT platform for the production of the cytotoxic protein Pierisin with simultaneous incorporation of a non-canonical amino acid for fluorescence labeling was demonstrated. The new reaction mode (TRITT mode) is a modified linked mode that fulfills the precondition for an automated modular reactor system. By continual transfer of new mRNA, the novel procedure overcomes problems caused by nuclease digestion and hydrolysis of mRNA during TL in standard CFPS reactions.

  19. Exhaustive search of linear information encoding protein-peptide recognition.

    Science.gov (United States)

    Kelil, Abdellali; Dubreuil, Benjamin; Levy, Emmanuel D; Michnick, Stephen W

    2017-04-01

    High-throughput in vitro methods have been extensively applied to identify linear information that encodes peptide recognition. However, these methods are limited in number of peptides, sequence variation, and length of peptides that can be explored, and often produce solutions that are not found in the cell. Despite the large number of methods developed to attempt addressing these issues, the exhaustive search of linear information encoding protein-peptide recognition has been so far physically unfeasible. Here, we describe a strategy, called DALEL, for the exhaustive search of linear sequence information encoded in proteins that bind to a common partner. We applied DALEL to explore binding specificity of SH3 domains in the budding yeast Saccharomyces cerevisiae. Using only the polypeptide sequences of SH3 domain binding proteins, we succeeded in identifying the majority of known SH3 binding sites previously discovered either in vitro or in vivo. Moreover, we discovered a number of sites with both non-canonical sequences and distinct properties that may serve ancillary roles in peptide recognition. We compared DALEL to a variety of state-of-the-art algorithms in the blind identification of known binding sites of the human Grb2 SH3 domain. We also benchmarked DALEL on curated biological motifs derived from the ELM database to evaluate the effect of increasing/decreasing the enrichment of the motifs. Our strategy can be applied in conjunction with experimental data of proteins interacting with a common partner to identify binding sites among them. Yet, our strategy can also be applied to any group of proteins of interest to identify enriched linear motifs or to exhaustively explore the space of linear information encoded in a polypeptide sequence. Finally, we have developed a webserver located at http://michnick.bcm.umontreal.ca/dalel, offering user-friendly interface and providing different scenarios utilizing DALEL.

  20. Energy Efficient Waste Heat Recovery from an Engine Exhaust System

    Science.gov (United States)

    2016-12-01

    AND DATES COVERED Master’s thesis 4. TITLE AND SUBTITLE ENERGY EFFICIENT WASTE HEAT RECOVERY FROM AN ENGINE EXHAUST SYSTEM 5. FUNDING NUMBERS 6...release. Distribution is unlimited. ENERGY EFFICIENT WASTE HEAT RECOVERY FROM AN ENGINE EXHAUST SYSTEM Aaron R. VanDenBerg Lieutenant, United...HEAT RECOVERY DEVICES Ships mainly extract heat and energy from exhaust gases by using a waste heat boiler located in the actual exhaust duct. The

  1. The role of psychological flexibility in the demands-exhaustion-performance relationship

    NARCIS (Netherlands)

    Onwezen, M.C.; Veldhoven, van M.J.P.M.; Biron, M.

    2014-01-01

    Employees in the service sector deal with a variety of emotional job demands due to interactions with clients. Emotional job demands often result in heightened levels of emotional exhaustion and decreased levels of performance. The current study aims to explore whether the adaptive behavioural

  2. Hyper-Expression of PD-1 Is Associated with the Levels of Exhausted and Dysfunctional Phenotypes of Circulating CD161++TCR iVα7.2+ Mucosal-Associated Invariant T Cells in Chronic Hepatitis B Virus Infection

    Directory of Open Access Journals (Sweden)

    Yean K. Yong

    2018-03-01

    Full Text Available Mucosal-associated invariant T (MAIT cells, defined as CD161++TCR iVα7.2+ T cells, play an important role in the innate defense against bacterial infections, and their functionality is impaired in chronic viral infections. Here, we investigated the frequency and functional role of MAIT cells in chronic hepatitis B virus (HBV infection. The peripheral CD3+CD161++TCR iVα7.2+ MAIT cells in chronic HBV-infected patients and healthy controls were phenotypically characterized based on CD57, PD-1, TIM-3, and CTLA-4, as well as HLA-DR and CD38 expression. The frequency of MAIT cells was significantly decreased among chronic HBV-infected individuals as compared to controls. Expression of CD57, PD-1, CTLA-4, as well as HLA-DR and CD38 on MAIT cells was significantly elevated in chronic HBV-infected individuals relative to controls. The percentage of T cell receptor (TCR iVα7.2+ CD161+ MAIT cells did not correlate with HBV viral load but inversely with HLA-DR on CD4+ T cells and MAIT cells and with CD57 on CD8+ T cells suggesting that decrease of MAIT cells may not be attributed to direct infection by HBV but driven by HBV-induced chronic immune activation. The percentage and expression levels of PD-1 as well as CTLA-4 on MAIT cells inversely correlated with plasma HBV-DNA levels, which may suggest either a role for MAIT cells in the control of HBV infection or the effect of HBV replication in the liver on MAIT cell phenotype. We report that decrease of TCR iVα7.2+ MAIT cells in the peripheral blood and their functions were seemingly impaired in chronic HBV-infected patients likely because of the increased expression of PD-1.

  3. Cold Autoimmune Hemolytic Anemia due to High-grade non Hodgkin's B cell Lymphoma with Weak Response to Rituximab and Chemotherapy Regimens.

    Science.gov (United States)

    Nazel Khosroshahi, Behzad; Jafari, Mohammad; Vazini, Hossein; Ahmadi, Alireza; Shams, Keivan; Kholoujini, Mahdi

    2015-07-01

    Autoimmune hemolytic anemia (AIHA) is characterized by shortening of red blood cell (RBC) survival and the presence of autoantibodies directed against autologous RBCs. Approximately 20% of autoimmune hemolytic anemia cases are associated with cold-reactive antibody. About half of patients with AIHA have no underlying associated disease; these cases are termed primary or idiopathic. Secondary cases are associated with underlying diseases or with certain drugs. We report herein a rare case of cold autoimmiune hemolytic anemia due to high-grade non-Hodgkin's lymphoma of B-cell type with weak response to rituximab and chemotherapy regimens. For treatment B cell lymphoma, Due to lack of treatment response, we used chemotherapy regimens including R- CHOP for the first time, and then Hyper CVAD, R- ICE and ESHAP were administered, respectively. For treatment of autoimmune hemolytic anemia, we have used the corticosteroid, rituximab, plasmapheresis and blood transfusion and splenectomy. In spite of all attempts, the patient died of anemia and aggressive lymphoma nine months after diagnosis. To our knowledge, this is a rare report from cold autoimmune hemolytic anemia in combination with high-grade non-Hodgkin's lymphoma of B-cell type that is refractory to conventional therapies.

  4. 14 CFR 23.1125 - Exhaust heat exchangers.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Exhaust heat exchangers. 23.1125 Section 23... § 23.1125 Exhaust heat exchangers. For reciprocating engine powered airplanes the following apply: (a) Each exhaust heat exchanger must be constructed and installed to withstand the vibration, inertia, and...

  5. 46 CFR 52.25-20 - Exhaust gas boilers.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Exhaust gas boilers. 52.25-20 Section 52.25-20 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING POWER BOILERS Other Boiler Types § 52.25-20 Exhaust gas boilers. Exhaust gas boilers with a maximum allowable working pressure...

  6. 34 CFR 110.39 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Exhaustion of administrative remedies. 110.39 Section... FINANCIAL ASSISTANCE Investigation, Conciliation, and Enforcement Procedures § 110.39 Exhaustion of administrative remedies. (a) A complainant may file a civil action following the exhaustion of administrative...

  7. 38 CFR 18.550 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Exhaustion of..., Conciliation, and Enforcement Procedures § 18.550 Exhaustion of administrative remedies. (a) A complainant may file a civil action following the exhaustion of administrative remedies under the Act. Administrative...

  8. 45 CFR 91.50 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Exhaustion of administrative remedies. 91.50... Investigation, Conciliation, and Enforcement Procedures § 91.50 Exhaustion of administrative remedies. (a) A complainant may file a civil action following the exhaustion of administrative remedies under the Act...

  9. 45 CFR 90.50 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Exhaustion of administrative remedies. 90.50..., Conciliation and Enforcement Procedures § 90.50 Exhaustion of administrative remedies. (a) The agency shall provide in its regulations that a complainant may file a civil action following the exhaustion of...

  10. 12 CFR 1780.56 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Exhaustion of administrative remedies. 1780.56 Section 1780.56 Banks and Banking OFFICE OF FEDERAL HOUSING ENTERPRISE OVERSIGHT, DEPARTMENT OF HOUSING... Posthearing Proceedings § 1780.56 Exhaustion of administrative remedies. To exhaust administrative remedies as...

  11. 14 CFR 1252.410 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Exhaustion of administrative remedies. 1252..., Conciliation, and Enforcement Procedures § 1252.410 Exhaustion of administrative remedies. (a) A complainant may file a civil action following the exhaustion of administrative remedies under the Act...

  12. 12 CFR 1777.27 - Exhaustion and review.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Exhaustion and review. 1777.27 Section 1777.27... 1366 of the 1992 Act § 1777.27 Exhaustion and review. (a) Judicial review—(1) Review of certain actions... in section 1369D of the 1992 Act (12 U.S.C. 4623). (b) Exhaustion of administrative remedies. In...

  13. 10 CFR 4.340 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Exhaustion of administrative remedies. 4.340 Section 4.340... Act of 1975, as Amended Investigation, Conciliation, and Enforcement Procedures § 4.340 Exhaustion of administrative remedies. (a) A complainant may file a civil action following the exhaustion of administrative...

  14. 12 CFR 908.66 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Exhaustion of administrative remedies. 908.66 Section 908.66 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOUSING FINANCE BOARD ORGANIZATION... Proceedings § 908.66 Exhaustion of administrative remedies. To exhaust administrative remedies as to any issue...

  15. 45 CFR 1156.21 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Exhaustion of administrative remedies. 1156.21... Investigation, Conciliation, and Enforcement Procedures § 1156.21 Exhaustion of administrative remedies. (a) A complainant may file a civil action following the exhaustion of administrative remedies under the Act...

  16. 41 CFR 101-8.724 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Exhaustion of administrative remedies. 101-8.724 Section 101-8.724 Public Contracts and Property Management Federal Property... Exhaustion of administrative remedies. (a) A complainant may file a civil action following the exhaustion of...

  17. 43 CFR 17.339 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Exhaustion of administrative remedies. 17... Investigation, Conciliation, and Enforcement Procedures § 17.339 Exhaustion of administrative remedies. (a) A complainant may file a civil action following the exhaustion of administrative remedies under the Act...

  18. 44 CFR 7.949 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Exhaustion of administrative... Investigation, Conciliation, and Enforcement Procedures § 7.949 Exhaustion of administrative remedies. (a) A complainant may file a civil action following the exhaustion of administrative remedies under the Act...

  19. 24 CFR 26.53 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Exhaustion of administrative remedies. 26.53 Section 26.53 Housing and Urban Development Office of the Secretary, Department of Housing... Hearings § 26.53 Exhaustion of administrative remedies. In order to fulfill the requirement of exhausting...

  20. 10 CFR 1040.89-13 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Exhaustion of administrative remedies. 1040.89-13 Section... Investigation, Conciliation and Enforcement Procedures § 1040.89-13 Exhaustion of administrative remedies. (a) A complainant may file a civil action following the exhaustion of administrative remedies under the Act...

  1. 24 CFR 146.45 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Exhaustion of administrative remedies. 146.45 Section 146.45 Housing and Urban Development Regulations Relating to Housing and Urban... Exhaustion of administrative remedies. (a) A complainant may file a civil action following the exhaustion of...

  2. 29 CFR 35.40 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Exhaustion of administrative remedies. 35.40 Section 35.40... Enforcement Procedures § 35.40 Exhaustion of administrative remedies. (a) A complainant may file a civil action under the Act following the exhaustion of administrative remedies. Administrative remedies are...

  3. 14 CFR 25.941 - Inlet, engine, and exhaust compatibility.

    Science.gov (United States)

    2010-01-01

    ... malfunctions) upon the aerodynamic control of the airplane may not result in any condition that would require..., engine, and exhaust compatibility. For airplanes using variable inlet or exhaust system geometry, or both...), and exhaust must be shown to function properly under all operating conditions for which approval is...

  4. Exhaust air cleaning of PWR nuclear power plants

    International Nuclear Information System (INIS)

    Wang Rufan.

    1987-01-01

    This paper describes requirements, design criteria and major equipments of exhaust air cleaning for PWR nuclear power plants. The particularity of exhaust air cleaning for NPP is stressed in this paper. Finally, the exhaust air cleaning systems of Qinshan NPP are briefly introduced

  5. 40 CFR 89.416 - Raw exhaust gas flow.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Raw exhaust gas flow. 89.416 Section... Procedures § 89.416 Raw exhaust gas flow. The exhaust gas flow shall be determined by one of the methods...) Measurement of the air flow and the fuel flow by suitable metering systems (for details see SAE J244. This...

  6. Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain metastases due to non-small-cell lung cancer.

    Science.gov (United States)

    Yang, R F; Yu, B; Zhang, R Q; Wang, X H; Li, C; Wang, P; Zhang, Y; Han, B; Gao, X X; Zhang, L; Jiang, Z M

    2017-11-17

    Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. This retrospective study proposed to assess whether bevacizumab or gefitinib can be used to improve the effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain metastases. A total of 218 NSCLC patients with multiple brain metastases were retrospectively included in this study and were randomly allocated to bevacizumab-gefitinib-WBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75). Then, tumor responses were evaluated every 2 months based on Response Evaluation Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic examination were documented every 6 months after the treatment. Compared to the standard WBRT, bevacizumab and gefitinib could significantly enhance response rate (RR) and disease control rate (DCR) of WBRT (Pbevacizumab-gefitinib-WBRT were higher than those who received gefitinib-WBRT. The overall survival (OS) rates and progression-free survival (PFS) rates also differed significantly among the bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and WBRT (9.8 and 14.6%) groups (Pbevacizumab-gefitinib-WBRT was slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested by prolonged PFS and OS status, bevacizumab substantially improved the overall efficacy of WBRT in the management of patients with NSCLC.

  7. DECREASED PRODUCTION OF SURFACTANT PROTEINS AFTER DIESEL EXHAUST EXPOSURE INCREASES SUSCEPTIBILITY TO INFLUENZA INFECTION

    Science.gov (United States)

    Pulmonary surfactant proteins A and D (SP-A and SP-D), termed collectins, enhance the opsonization of foreign particles and pathogens by phagocytic cells. Inhaled pollutants such as diesel exhaust (DE) have a possible role in suppressing the production of surfactant proteins whic...

  8. Automobile diesel exhaust particles induce lipid droplet formation in macrophages in vitro

    DEFF Research Database (Denmark)

    Cao, Yi; Jantzen, Kim; Gouveia, Ana Cecilia Damiao

    2015-01-01

    Exposure to diesel exhaust particles (DEP) has been associated with adverse cardiopulmonary health effects, which may be related to dysregulation of lipid metabolism and formation of macrophage foam cells. In this study, THP-1 derived macrophages were exposed to an automobile generated DEP (A...

  9. EFFECT OF SHORT TERM DIESEL EXHAUST EXPOSURE ON NASAL RESPONSES TO INFLUENZA IN ALLERGIC RHINITICS.

    Science.gov (United States)

    Introduction: Recently published data suggest that diesel exhaust (DE) has special impact on allergic inflammation, suppressing Th1 and augmenting Th2 responses to allergen via oxidant stress effects on airway cells. Exposures to particulate air pollutants including DE are also a...

  10. Contextualizing Emotional Exhaustion and Positive Emotional Display : The Signaling Effects of Supervisors' Emotional Exhaustion and Service Climate

    NARCIS (Netherlands)

    Lam, Catherine K.; Huang, Xu; Janssen, Onne; Lam, K.C.

    In this study, we investigated how supervisors' emotional exhaustion and service climate jointly influence the relationship between subordinates' emotional exhaustion and their display of positive emotions at work. Using data from frontline sales employees and their immediate supervisors in a

  11. Vital Exhaustion and Coronary Heart Disease Risk

    DEFF Research Database (Denmark)

    Frestad, Daria; Prescott, Eva

    2017-01-01

    OBJECTIVES: The construct of vital exhaustion has been identified as a potential independent psychological risk factor for incident and recurrent coronary heart disease (CHD). Despite several decades of research, no systematic review or meta-analysis has previously attempted to collate the empiri......OBJECTIVES: The construct of vital exhaustion has been identified as a potential independent psychological risk factor for incident and recurrent coronary heart disease (CHD). Despite several decades of research, no systematic review or meta-analysis has previously attempted to collate.......22-1.85) for prospective studies, and 2.61 (95% CI = 1.66-4.10) for case-control studies using hospital controls. Risk of recurrent events in patients with CHD was 2.03 (95% CI = 1.54-2.68). The pooled adjusted risk of chronic heart failure in healthy populations was 1.37 (95% CI = 1.21-1.56), but this was based...

  12. Noise study in laboratories with exhaust fans

    International Nuclear Information System (INIS)

    Shaikh, G.H.; Hashmi, R.; Shareef, A.

    2005-01-01

    Noise study has been carried out in 25 laboratories fitted with exhaust fans. We have studied A- Weighted equivalent sound pressure levels (dB(A) LAeJ and equivalent octave band sound pressure levels (dB L/sub eq/ in each of the laboratories surveyed. The data collected has been analyzed for Preferred Speech Interference Levels (PSIL). The results show that the interior noise levels in these laboratories vary from 59.6 to 72.2 dB(A) L/sub Aeq/, which are very high and much beyond the interior noise limits recommended for laboratories. Some ways and means to limit emission of high-level noise from exhaust fans are also discussed. (author)

  13. Neural activation in stress-related exhaustion

    DEFF Research Database (Denmark)

    Gavelin, Hanna Malmberg; Neely, Anna Stigsdotter; Andersson, Micael

    2017-01-01

    The primary purpose of this study was to investigate the association between burnout and neural activation during working memory processing in patients with stress-related exhaustion. Additionally, we investigated the neural effects of cognitive training as part of stress rehabilitation. Fifty......-five patients with clinical diagnosis of exhaustion disorder were administered the n-back task during fMRI scanning at baseline. Ten patients completed a 12-week cognitive training intervention, as an addition to stress rehabilitation. Eleven patients served as a treatment-as-usual control group. At baseline......, burnout level was positively associated with neural activation in the rostral prefrontal cortex, the posterior parietal cortex and the striatum, primarily in the 2-back condition. Following stress rehabilitation, the striatal activity decreased as a function of improved levels of burnout. No significant...

  14. Cell-free DNA fragmentation patterns in amniotic fluid identify genetic abnormalities and changes due to storage.

    Science.gov (United States)

    Peter, Inga; Tighiouart, Hocine; Lapaire, Olav; Johnson, Kirby L; Bianchi, Diana W; Terrin, Norma

    2008-09-01

    Circulating cell-free DNA (cfDNA) has become a promising biomarker in prenatal diagnosis. However, despite extensive studies in different body fluids, cfDNA predictive value is uncertain owing to the confounding factors that can affect its levels, such as gestational age, maternal weight, smoking status, and medications. Residual fresh and archived amniotic fluid (AF) supernatants were obtained from gravid women (mean gestational age 17 wk) carrying euploid (N=36) and aneuploid (N=29) fetuses, to characterize cfDNA-fragmentation patterns with regard to aneuploidy and storage time (-80 degrees C). AF cfDNA was characterized by the real-time quantitative polymerase chain reaction amplification of glyceraldehyde-3-phosphate dehydrogenase, gel electrophoresis, and pattern recognition of the DNA fragmentation. The distributions of cfDNA fragment lengths were compared using 6 measures that defined the locations and slopes for the first and last peaks, after elimination of the confounding variables. This method allowed for the unique classification of euploid and aneuploid cfDNA samples in AF, which had been matched for storage time. In addition, we showed that archived euploid AF samples gradually lose long cfDNA fragments: this loss accurately distinguishes them from the fresh samples. We present preliminary data using cfDNA-fragmentation patterns, to uniquely distinguish between AF samples of pregnant women with regard to aneuploidy and storage time, independent of gestational age and initial DNA amount. In addition to potential applications in prenatal diagnosis, these data suggest that archived AF samples consist of large amounts of short cfDNA fragments, which are undetectable using standard real-time polymerase chain reaction amplification.

  15. Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain metastases due to non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yang, R.F.; Yu, B.; Zhang, R.Q.; Wang, X.H.; Li, C.; Wang, P.; Zhang, Y.; Han, B.; Gao, X.X.; Zhang, L. [Taian City Central Hospital, Taian, Shandong (China); Jiang, Z.M., E-mail: dmyh2436@126.com [Qianfoshan Hospital of Shandong Province, Shandong University, Ji’nan, Shandong (China)

    2018-02-01

    Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. This retrospective study proposed to assess whether bevacizumab or gefitinib can be used to improve the effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain metastases. A total of 218 NSCLC patients with multiple brain metastases were retrospectively included in this study and were randomly allocated to bevacizumab-gefitinibWBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75). Then, tumor responses were evaluated every 2 months based on Response Evaluation Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic examination were documented every 6 months after the treatment. Compared to the standard WBRT, bevacizumab and gefitinib could significantly enhance response rate (RR) and disease control rate (DCR) of WBRT (Po0.001). At the same time, RR and DCR of patients who received bevacizumab-gefitinib-WBRT were higher than those who received gefitinib-WBRT. The overall survival (OS) rates and progression-free survival (PFS) rates also differed significantly among the bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and WBRT (9.8 and 14.6%) groups (Po0.05). Although bevacizumabgefitinib-WBRT was slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested by prolonged PFS and OS status, bevacizumab substantially improved the overall efficacy of WBRT in the management of patients with NSCLC. (author)

  16. Rare earth metals for automotive exhaust catalysts

    International Nuclear Information System (INIS)

    Shinjoh, Hirohumi

    2006-01-01

    The usage of rare earth metals for automotive exhaust catalysts is demonstrated in this paper. Rare earth metals have been widely used in automotive catalysts. In particular, three-way catalysts require the use of ceria compounds as oxygen storage materials, and lanthana as both a stabilizer of alumina and a promoter. The application for diesel catalysts is also illustrated. Effects of inclusion of rare earth metals in automotive catalysts are discussed

  17. Fronting and exhaustive exclusion in Biblical Hebrew

    African Journals Online (AJOL)

    Kate H

    48, 2017, 219-222 doi: 10.5774/48-0-292. Fronting and exhaustive exclusion in Biblical Hebrew. Christo H. J. van der Merwe. Department of Ancient Studies, University of Stellenbosch, South ... Merwe, Naudé and Kroeze 2017: 491-493). .... “And I will give him to the Lord all the days of his life, and no razor shall touch his.

  18. Exhaust Gas Emissions from a Rotating Detonation-wave Engine

    Science.gov (United States)

    Kailasanath, Kazhikathra; Schwer, Douglas

    2015-11-01

    Rotating detonation-wave engines (RDE) are a form of continuous detonation-wave engines. They potentially provide further gains in performance than an intermittent or pulsed detonation-wave engine (PDE). The overall flow field in an idealized RDE, primarily consisting of two concentric cylinders, has been discussed in previous meetings. Because of the high pressures involved and the lack of adequate reaction mechanisms for this regime, previous simulations have typically used simplified chemistry models. However, understanding the exhaust species concentrations in propulsion devices is important for both performance considerations as well as estimating pollutant emissions. Progress towards addressing this need will be discussed in this talk. In this approach, an induction parameter model is used for simulating the detonation but a more detailed finite-chemistry model including NOx chemistry is used in the expansion flow region, where the pressures are lower and the uncertainties in the chemistry model are greatly reduced. Results show that overall radical concentrations in the exhaust flow are substantially lower than from earlier predictions with simplified models. The performance of a baseline hydrogen/air RDE increased from 4940 s to 5000 s with the expansion flow chemistry, due to recombination of radicals and more production of H2O, resulting in additional heat release. Work sponsored by the Office of Naval Research.

  19. Validation of Karolinska Exhaustion Scale: psychometric properties of a measure of exhaustion syndrome.

    Science.gov (United States)

    Saboonchi, Fredrik; Perski, Aleksander; Grossi, Giorgio

    2013-12-01

    The syndrome of exhaustion is currently a medical diagnosis in Sweden. The description of the syndrome largely corresponds to the suggested core component of burnout, that is exhaustion. Karolinska Exhaustion Scale (KES) has been constructed to provide specific assessment of exhaustion in clinical and research settings. The purpose of the present study was to examine the psychometric properties of this scale in its original and revised versions by examining the factorial structure and measures of convergent and discriminant validity. Data gathered from two independent samples (n1 = 358 & n2 = 403) consisting of patients diagnosed with 'reaction to severe stress, and adjustment disorder' were subjected to confirmatory factor analysis. The study's instruments were Karolinska Exhaustion Scale and Shirom Melam Burnout Measure. Correlation analyses were employed to follow up the established factorial structure of the scale. The study was ethically approved by Karolinska Institute regional ethic committee. The findings demonstrated adequate fit of the data to the measurement model provided by the revised version of KES Limitations: The main limitation of the present study is the lack of a gold standard of exhaustion for direct comparison with KES. (KES-26) and partially supported convergent validity and discriminant validity of the scale. The demonstrated psychometric properties of KES-26 indicate sound construct validity for this scale encouraging use of this scale in assessment of exhaustion. The factorial structure of KES-26 may also be used to provide information concerning possible different clinical profiles. © 2012 The Authors Scandinavian Journal of Caring Sciences © 2012 Nordic College of Caring Science.

  20. Low temperature caused modifications in the arrangement of cell wall pectins due to changes of osmotic potential of cells of maize leaves (Zea mays L.).

    Science.gov (United States)

    Bilska-Kos, Anna; Solecka, Danuta; Dziewulska, Aleksandra; Ochodzki, Piotr; Jończyk, Maciej; Bilski, Henryk; Sowiński, Paweł

    2017-03-01

    The cell wall emerged as one of the important structures in plant stress responses. To investigate the effect of cold on the cell wall properties, the content and localization of pectins and pectin methylesterase (PME) activity, were studied in two maize inbred lines characterized by different sensitivity to cold. Low temperature (14/12 °C) caused a reduction of pectin content and PME activity in leaves of chilling-sensitive maize line, especially after prolonged treatment (28 h and 7 days). Furthermore, immunocytohistological studies, using JIM5 and JIM7 antibodies, revealed a decrease of labeling of both low- and high-methylesterified pectins in this maize line. The osmotic potential, quantified by means of incipient plasmolysis was lower in several types of cells of chilling-sensitive maize line which was correlated with the accumulation of sucrose. These studies present new finding on the effect of cold stress on the cell wall properties in conjunction with changes in the osmotic potential of maize leaf cells.

  1. Changes in thymocytes due to local irradiation of a portion of the maxilla in mice. A study of NKT cells and γδT cells

    International Nuclear Information System (INIS)

    Satho, Taigo; Tamasawa, Ken; Yosue, Takashi; Arai, Thiaki

    2000-01-01

    We have been investigating the changes of lymphocyte subsets in immune organs after head and neck irradiation. The aim of the present study was to determine the influence of local irradiation (10 Gy) of a portion of the maxilla on the thymocyte subsets, specifically NKT cells and γδT cells in mice. The thymocyte subsets were analyzed following irradiation using a fluorometer (anti-CD4, CD8, TCRαβ, TCRγδ and NK1.1 monoclonal antibodies) and the outcome compared with that obtained from no-irradiation groups. The following results were obtained: The total number of thymocytes showed a significant decrease one day and three days after irradiation. The absolute number of DN (double negative; CD4 - CD8 - ), CD4 + SP (CD4 + single positive; CD4 + CD8 - ) and CD8 + SP (CD8 + single positive; CD4 - CD8 + ) thymocytes showed a significant decrease one day after irradiation. The absolute number of DP (double positive; CD4 + CD8 + ) thymocytes showed a significant decrease one day and three days after irradiation. The absolute number of NKT and γδT cells showed a significant decrease one day after irradiation. In conclusion, the results suggest that NKT cells and γδT cells exhibit behavior which is the same as main stream thymocytes, except DP thymocytes. (author)

  2. Changes in thymocytes due to local irradiation of a portion of the maxilla in mice. A study of NKT cells and {gamma}{delta}T cells

    Energy Technology Data Exchange (ETDEWEB)

    Satho, Taigo; Tamasawa, Ken; Yosue, Takashi [Nippon Dental Univ., Tokyo (Japan); Arai, Thiaki

    2000-07-01

    We have been investigating the changes of lymphocyte subsets in immune organs after head and neck irradiation. The aim of the present study was to determine the influence of local irradiation (10 Gy) of a portion of the maxilla on the thymocyte subsets, specifically NKT cells and {gamma}{delta}T cells in mice. The thymocyte subsets were analyzed following irradiation using a fluorometer (anti-CD4, CD8, TCR{alpha}{beta}, TCR{gamma}{delta} and NK1.1 monoclonal antibodies) and the outcome compared with that obtained from no-irradiation groups. The following results were obtained: The total number of thymocytes showed a significant decrease one day and three days after irradiation. The absolute number of DN (double negative; CD4{sup -} CD8{sup -}), CD4{sup +} SP (CD4{sup +} single positive; CD4{sup +} CD8{sup -}) and CD8{sup +} SP (CD8{sup +} single positive; CD4{sup -} CD8{sup +}) thymocytes showed a significant decrease one day after irradiation. The absolute number of DP (double positive; CD4{sup +} CD8{sup +}) thymocytes showed a significant decrease one day and three days after irradiation. The absolute number of NKT and {gamma}{delta}T cells showed a significant decrease one day after irradiation. In conclusion, the results suggest that NKT cells and {gamma}{delta}T cells exhibit behavior which is the same as main stream thymocytes, except DP thymocytes. (author)

  3. Measurement of VOCs in vehicle exhaust by extractive FTIR spectroscopy

    Science.gov (United States)

    Lechner, Bernhard; Paar, H.; Sturm, Peter J.

    2001-02-01

    12 The detection of benzene and other organic compounds in vehicle exhaust by FT-IR-spectroscopy is seriously limited by the strong interference of carbon dioxide and the rather weak absorption coefficient of the gases. Therefore, a measurement device was developed which separates the components of interest (mostly VOCs) from carbon dioxide, water and nitric oxide. In addition the VOCs have to be pre- concentrated. To avoid condensation of VOCs the measurements have to take place at higher temperatures. The vehicle exhaust was led through an activated charcoal tube where the organic compounds were adsorbed. Afterwards, the charcoal tube was heated in a furnace, the VOCs were desorbed thermically and were carried by (heated) nitrogen into a gas cell with a path-length of 10 m where the concentration of the different species was measured. With the help of this measurement device a lot of VOC- components like benzene, toluene, and xylene were detected successfully. Measurements were performed on an engine test bed and a chassis dynamometer for heavy duty vehicles. The detection limit of most of the VOCs was about 2 to 3 ppb for a sampling time of 20 min. Calibration measurements showed an accuracy of 15%.

  4. Mutagenicity of diesel exhaust soot dispersed in phospholipid surfactants

    Energy Technology Data Exchange (ETDEWEB)

    Wallace, W.; Keane, M.; Xing, S.; Harrison, J.; Gautam, M.; Ong, T.

    1994-06-01

    Organics extractable from respirable diesel exhaust soot particles by organic solvents have been known for some time to be direct acting frameshift mutagens in the Ames Salmonella typhimurium histidine reversion assay. Upon deposition in a pulmonary alveolus or respiratory bronchiole, respirable diesel soot particles will contact first the hypophase which is coated by and laden with surfactants. To model interactions of soot and pulmonary surfactant, the authors dispersed soots in vitro in the primary phospholipid pulmonary surfactant dipalmitoyl glycerophosphorylcholine (lecithin) (DPL) in physiological saline. They have shown that diesel soots dispersed in lecithin surfactant can express mutagenic activity, in the Ames assay system using S. typhimurium TA98, comparable to that expressed by equal amounts of soot extracted by dichloromethane/dimethylsulfoxide (DCM/DMSO). Here the authors report additional data on the same system using additional exhaust soots and also using two other phospholipids, dipalmitoyl glycerophosphoryl ethanolamine (DPPE), and dipalmitoyl phosphatidic acid (DPPA), with different ionic character hydrophilic moieties. A preliminary study of the surfactant dispersed soot in an eucaryotic cell test system also is reported.

  5. Anesthesiologists work-related exhaustion: A comparison study with other hospital employees

    Directory of Open Access Journals (Sweden)

    Waleed Riad

    2011-01-01

    Full Text Available Background: Anesthesia is a demanding occupation due to long working hours, sustained vigilance, unpredictability of stressful situation, fear of litigation, competence, and production pressure. Work-related exhaustion can lead to several physical and psychological symptoms and delay decision making. The aim of this study was to evaluate how different work conditions affect personnel exhaustion by studying a sample of anesthesiologists comparing them with ophthalmologists and ancillary hospital staff Methods: One hundred fifty persons divided into three equal groups (50 each were invited to participate in this study. Subjects were asked to answer two self report questionnaires: The Multidimensional Fatigue Inventory (MFI-20 and General Health Questionnaire (GHQ-12 which used to assess work related exhaustion and mental health, respectively. Results: Multidimensional Fatigue Inventory scale (MFI 20 and General Health Questionnaire (GHQ 12 were significantly higher in anesthesiologists than in other groups ( P = 0.001. Different aspects of work-related exhaustion showed that general, physical and mental fatigue were significantly higher in anesthesiologists ( P = 0.002 and 0.001, respectively. Reduced activity and reduced motivation were also higher in anesthesiologists compare to the other groups ( P = 0.005 and 0.001, respectively. Conclusion: Work-related exhaustion under the current study is more obvious among anesthesiologists. Ophthalmologist and ancillary hospital employees felt that they had less stress at their work.

  6. A pathway to eliminate the gas flow dependency of a hydrocarbon sensor for automotive exhaust applications

    Directory of Open Access Journals (Sweden)

    G. Hagen

    2018-02-01

    Full Text Available Gas sensors will play an essential role in future combustion-based mobility to effectively reduce emissions and monitor the exhausts reliably. In particular, an application in automotive exhausts is challenging due to the high gas temperatures that come along with highly dynamic flow rates. Recently, a thermoelectric hydrocarbon sensor was developed by using materials which are well known in the exhausts and therefore provide the required stability. As a sensing mechanism, the temperature difference that is generated between a catalytically activated area during the exothermic oxidation of said hydrocarbons and an inert area of the sensor is measured by a special screen-printed thermopile structure. As a matter of principle, this thermovoltage significantly depends on the mass flow rate of the exhausts under certain conditions. The present contribution helps to understand this cross effect and proposes a possible setup for its avoidance. By installing the sensor in the correct position of a bypass solution, the gas flow around the sensor is almost free of turbulence. Now, the signal depends only on the hydrocarbon concentration and not on the gas flow. Such a setup may open up new possibilities of applying novel sensors in automotive exhausts for on-board-measurement (OBM purposes.

  7. High-Efficiency Nanowire Solar Cells with Omnidirectionally Enhanced Absorption Due to Self-Aligned Indium-Tin-Oxide Mie Scatterers.

    Science.gov (United States)

    van Dam, Dick; van Hoof, Niels J J; Cui, Yingchao; van Veldhoven, Peter J; Bakkers, Erik P A M; Gómez Rivas, Jaime; Haverkort, Jos E M

    2016-12-27

    Photovoltaic cells based on arrays of semiconductor nanowires promise efficiencies comparable or even better than their planar counterparts with much less material. One reason for the high efficiencies is their large absorption cross section, but until recently the photocurrent has been limited to less than 70% of the theoretical maximum. Here we enhance the absorption in indium phosphide (InP) nanowire solar cells by employing broadband forward scattering of self-aligned nanoparticles on top of the transparent top contact layer. This results in a nanowire solar cell with a photovoltaic conversion efficiency of 17.8% and a short-circuit current of 29.3 mA/cm 2 under 1 sun illumination, which is the highest reported so far for nanowire solar cells and among the highest reported for III-V solar cells. We also measure the angle-dependent photocurrent, using time-reversed Fourier microscopy, and demonstrate a broadband and omnidirectional absorption enhancement for unpolarized light up to 60° with a wavelength average of 12% due to Mie scattering. These results unambiguously demonstrate the potential of semiconductor nanowires as nanostructures for the next generation of photovoltaic devices.

  8. Cytotoxicity of trans-chalcone and licochalcone A against breast cancer cells is due to apoptosis induction and cell cycle arrest.

    Science.gov (United States)

    Bortolotto, Luis Felipe Buso; Barbosa, Flávia Regina; Silva, Gabriel; Bitencourt, Tamires Aparecida; Beleboni, Rene Oliveira; Baek, Seung Joon; Marins, Mozart; Fachin, Ana Lúcia

    2017-01-01

    Chalcones are precursors of flavonoids that exhibit structural heterogeneity and potential antitumor activity. The objective of this study was to characterize the cytotoxicity of trans-chalcone and licochalcone A (LicoA 1 ) against a breast cancer cell line (MCF-7) and normal murine fibroblasts (3T3). Also the mechanisms of the anti-cancer activity of these two compounds were studied. The alkaline comet assay revealed dose-dependent genotoxicity, which was more responsive against the tumor cell line, compared to the 3T3 mouse fibroblast cell line. Flow cytometry showed that the two chalcones caused the cell cycle arrest in the G1 phase and induced apoptosis in MCF-7 cells. Using PCR Array, we found that trans-chalcone and LicoA trigger apoptosis mediated by the intrinsic pathway as demonstrated by the inhibition of Bcl-2 and induction of Bax. In western blot assay, the two chalcones reduced the expression of cell death-related proteins such as Bcl-2 and cyclin D1 and promoted the cleavage of PARP. However, only trans-chalcone induced the expression of the CIDEA gene and protein in these two experiments. Furthermore, transient transfections of MCF-7 using a construction of a promoter-luciferase vector showed that trans-chalcone induced the expression of the CIDEA promoter activity in 24 and 48h. In conclusion, the results showed that trans-chalcone promoted high induction of the CIDEA promoter gene and protein, which is related to DNA fragmentation during apoptosis. Copyright © 2016. Published by Elsevier Masson SAS.

  9. Numerical investigation of a novel burner to combust anode exhaust gases of SOFC stacks

    Directory of Open Access Journals (Sweden)

    Pianko-Oprych Paulina

    2017-09-01

    Full Text Available The aim of the present study was a numerical investigation of the efficiency of the combustion process of a novel concept burner under different operating conditions. The design of the burner was a part of the development process of a complete SOFC based system and a challenging combination of technical requirements to be fulfilled. A Computational Fluid Dynamics model of a non-premixed burner was used to simulate combustion of exhaust gases from the anode region of Solid Oxide Fuel Cell stacks. The species concentrations of the exhaust gases were compared with experimental data and a satisfactory agreement of the conversion of hydrocarbons was obtained. This validates the numerical methodology and also proves applicability of the developed approach that quantitatively characterized the interaction between the exhaust gases and burner geometry for proper combustion modelling. Thus, the proposed CFD approach can be safely used for further numerical optimisation of the burner design.

  10. Narcolepsy: Autoimmunity, Effector T Cell Activation Due to Infection, or T Cell Independent, Major Histocompatibility Complex Class II Induced Neuronal Loss?

    Science.gov (United States)

    Fontana, Adriano; Gast, Heidemarie; Reith, Walter; Recher, Mike; Birchler, Thomas; Bassetti, Claudio L.

    2010-01-01

    Human narcolepsy with cataplexy is a neurological disorder, which develops due to a deficiency in hypocretin producing neurons in the hypothalamus. There is a strong association with human leucocyte antigens HLA-DR2 and HLA-DQB1*0602. The disease typically starts in adolescence. Recent developments in narcolepsy research support the hypothesis of…

  11. Engine with exhaust gas recirculation system and variable geometry turbocharger

    Science.gov (United States)

    Keating, Edward J.

    2015-11-03

    An engine assembly includes an intake assembly, an internal combustion engine defining a plurality of cylinders and configured to combust a fuel and produce exhaust gas, and an exhaust assembly in fluid communication with a first subset of the plurality of cylinders. Each of the plurality of cylinders are provided in fluid communication with the intake assembly. The exhaust assembly is provided in fluid communication with a first subset of the plurality of cylinders, and a dedicated exhaust gas recirculation system in fluid communication with both a second subset of the plurality of cylinders and with the intake assembly. The dedicated exhaust gas recirculation system is configured to route all of the exhaust gas from the second subset of the plurality of cylinders to the intake assembly. Finally, the engine assembly includes a turbocharger having a variable geometry turbine in fluid communication with the exhaust assembly.

  12. Peribronchiolar fibrosis in lungs of cats chronically exposed to diesel exhaust

    International Nuclear Information System (INIS)

    Hyde, D.M.; Plopper, C.G.; Weir, A.J.; Murnane, R.D.; Warren, D.L.; Last, J.A.; Pepelko, W.E.

    1985-01-01

    This study reports the quantitative changes in the pulmonary proximal acinar region following chronic exposure to diesel exhaust and following an additional 6 months in clean air. Cats (13 months of age) from a minimum disease colony were exposed to clean air (eight cats for 27 months and nine cats for 33 months), diesel exhaust for 8 hours/day, 7 days/week (nine cats for 27 months), or diesel exhaust for 27 months followed by 6 months in clean air (10 cats). Morphologic and morphometric evaluation using light microscopy and scanning and transmission electron microscopy revealed two major exposure-related lesions in proximal acinar regions of lungs of cats: peribronchiolar fibrosis associated with significant increases in lymphocytes, fibroblasts, and interstitial macrophages containing diesel particulate-like inclusions and bronchiolar epithelial metaplasia associated with the presence of ciliated and basal cells and alveolar macrophages containing diesel particulate-like inclusions. Peribronchiolar fibrosis was greater at the end of the 6 months in clean air following exposure, whereas the bronchiolar epithelial metaplasia was most severe at the end of exposure. Following an additional 6 months in clean air the epithelium more closely resembled the control epithelial cell population. The labeling index of terminal bronchiolar epithelium was significantly increased at the end of exposure but was not significantly different from controls or exposed cats following an additional 6 months in clean air. The ultrastructural appearance of epithelial cells remained relatively unchanged following diesel exhaust exposure with the exception of diesel particulate-like inclusions

  13. Diesel exhaust exposure, its multi-system effects, and the effect of new technology diesel exhaust.

    Science.gov (United States)

    Reis, Haley; Reis, Cesar; Sharip, Akbar; Reis, Wenes; Zhao, Yong; Sinclair, Ryan; Beeson, Lawrence

    2018-05-01

    Exposure to diesel exhaust (DE) from vehicles and industry is hazardous and affects proper function of organ systems. DE can interfere with normal physiology after acute and chronic exposure to particulate matter (PM). Exposure leads to potential systemic disease processes in the central nervous, visual, hematopoietic, respiratory, cardiovascular, and renal systems. In this review, we give an overview of the epidemiological evidence supporting the harmful effects of diesel exhaust, and the numerous animal studies conducted to investigate the specific pathophysiological mechanisms behind DE exposure. Additionally, this review includes a summary of studies that used biomarkers as an indication of biological plausibility, and also studies evaluating new technology diesel exhaust (NTDE) and its systemic effects. Lastly, this review includes new approaches to improving DE emissions, and emphasizes the importance of ongoing study in this field of environmental health. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Leydig Cell Tumor Associated with Testicular Adrenal Rest Tumors in a Patient with Congenital Adrenal Hyperplasia due to 11β-Hydroxylase Deficiency

    Directory of Open Access Journals (Sweden)

    Nadia Charfi

    2012-01-01

    Full Text Available Congenital adrenal hyperplasia (CAH describes a group of inherited autosomal recessive disorders characterized by enzyme defects in the steroidogenic pathways that lead to the biosynthesis of cortisol, aldosterone, and androgens. Chronic excessive adrenocorticotropic hormone (ACTH stimulation may result in hyperplasia of ACTH-sensitive tissues in adrenal glands and other sites such as the testes, causing testicular masses known as testicular adrenal rest tumors (TARTs. Leydig cell tumors (LCTs are make up a very small number of all testicular tumors and can be difficult to distinguish from TARTs. This distinction is interesting because LCTs and TARTs require different therapeutic approaches. Hereby, we present an unusual case of a 19-year-old patient with CAH due to 11β-hydroxylase deficiency, who presented with TARTs and an epididymal Leydig cell tumor.

  15. Detection of mutagenic activity in automobile exhaust.

    Science.gov (United States)

    Ohnishi, Y; Kachi, K; Sato, K; Tahara, I; Takeyoshi, H; Tokiwa, H

    1980-03-01

    Using the Ames Salmonella-microsome system, we detected mutagenic activity in the exhaust from two kinds of 4-cycle gasoline engines of unregulated and regulated cars, and from diesel engines, as well as in the particulates from air collected in tunnels. The mutagenicity of particulates from a car equipped with a catalyst (regulated car), as compared with that from an unregulated car, was reduced very much (down to 500 from 4500 revertants/plate/m3 in tester strain TA98). However, the mutagenicity of the ether-soluble acid and neutral fractions from the condensed water of emissions from a regulated car was still high (down to 2880 from 10 900 revertants/plate/m3 in tester strain TA100). The mutagenic activity of emission exhaust from old diesel car engines was very high; the particulates showed 9140 and 19 600 revertants/plate/m3 from strain TA98 incubated with an activating rat-liver S9 fraction. A small diesel engine of the type used for the generation of electric power or in farm machinery also produced exhaust with highly mutagenic particulates. The mutagenic activity of a methanol extract of particulate air pollutants collected in a highway tunnel showed 39 revertants/plate/m3 toward strain TA98 and 87 toward strain TA100. The ether-soluble neutral fraction yielded 86 revertants/plate/m3 from strain TA98 and 100 from strain TA100. This fraction also contained carcinogenic compounds, including benzo[a]pyrene, benzo[e]pyrene, benz[a]anthracene, benzo[ghi]perylene and chrysene. Very high mutagenic activity was detected, especially in the particulate air pollutants collected at night, in another tunnel on a superhighway: 60-88 revertants/plate/m3 from strain TA100 for the sample collected by day, but 121-238, by night. Night traffic includes many more diesel-powered vehicles compared with gasoline-powered automobiles.

  16. EGNAS: an exhaustive DNA sequence design algorithm

    Directory of Open Access Journals (Sweden)

    Kick Alfred

    2012-06-01

    Full Text Available Abstract Background The molecular recognition based on the complementary base pairing of deoxyribonucleic acid (DNA is the fundamental principle in the fields of genetics, DNA nanotechnology and DNA computing. We present an exhaustive DNA sequence design algorithm that allows to generate sets containing a maximum number of sequences with defined properties. EGNAS (Exhaustive Generation of Nucleic Acid Sequences offers the possibility of controlling both interstrand and intrastrand properties. The guanine-cytosine content can be adjusted. Sequences can be forced to start and end with guanine or cytosine. This option reduces the risk of “fraying” of DNA strands. It is possible to limit cross hybridizations of a defined length, and to adjust the uniqueness of sequences. Self-complementarity and hairpin structures of certain length can be avoided. Sequences and subsequences can optionally be forbidden. Furthermore, sequences can be designed to have minimum interactions with predefined strands and neighboring sequences. Results The algorithm is realized in a C++ program. TAG sequences can be generated and combined with primers for single-base extension reactions, which were described for multiplexed genotyping of single nucleotide polymorphisms. Thereby, possible foldback through intrastrand interaction of TAG-primer pairs can be limited. The design of sequences for specific attachment of molecular constructs to DNA origami is presented. Conclusions We developed a new software tool called EGNAS for the design of unique nucleic acid sequences. The presented exhaustive algorithm allows to generate greater sets of sequences than with previous software and equal constraints. EGNAS is freely available for noncommercial use at http://www.chm.tu-dresden.de/pc6/EGNAS.

  17. Infrared measurements of launch vehicle exhaust plumes

    Science.gov (United States)

    Schweitzer, Caroline; Ohmer, Phillip; Wendelstein, Norbert; Stein, Karin

    2017-10-01

    In the fields of early warning, one is depending on reliable analytical models for the prediction of the infrared threat signature: By having this as a basis, the warning sensors can be specified as suitable as possible to give timely threat approach alerts. In this paper, we will present preliminary results of measurement trials that have been carried out in 2015, where the exhaust plume of launch vehicles has been measured under various atmospheric conditions. The gathered data will be used to validate analytical models for the prediction of the plume signature.

  18. Stem Cell Therapy and Breast Cancer Treatment: review of stem cell research and potential therapeutic impact against cardiotoxicities due to breast cancer treatment

    Directory of Open Access Journals (Sweden)

    Thomas E. Sharp

    2014-11-01

    Full Text Available A new problem has emerged with the ever-increasing number of breast cancer survivors. While early screening and advances in treatment have allowed these patients to overcome their cancer, these treatments often have adverse cardiovascular side effects that can produce abnormal cardiovascular function. Chemotherapeutic and radiation therapy have both been linked to cardiotoxicity; these therapeutics can cause a loss of cardiac muscle and deterioration of vascular structure that can eventually lead to heart failure (HF. This cardiomyocyte toxicity can leave the breast cancer survivor with a probable diagnosis of dilated or restrictive cardiomyopathy (DCM or RCM. While current HF standard of care can alleviate symptoms, other than heart transplantation, there is no therapy that replaces cardiac myocytes that are killed during cancer therapies. There is a need to develop novel therapeutics that can either prevent or reverse the cardiac injury caused by cancer therapeutics. These new therapeutics should promote the regeneration of lost or deteriorating myocardium. Over the last several decades the therapeutic potential of cell-based therapy has been investigated for HF patients. In this review we discuss the progress of preclinical and clinical stem cell research for the diseased heart and discuss the possibility of utilizing these novel therapies to combat cardiotoxicity observed in breast cancer survivors.

  19. Differential Susceptibility of Bighorn Sheep (Ovis canadensis) and Domestic Sheep (Ovis aries) Neutrophils to Mannheimia haemolytica Leukotoxin is not due to Differential Expression of Cell Surface CD18.

    Science.gov (United States)

    Dassanayake, Rohana P; Shanthalingam, Sudarvili; Liu, Weiguo; Casas, Eduardo; Srikumaran, Subramaniam

    2017-07-01

    Bighornsheep ( Ovis canadensis ) are more susceptible to pneumonia caused by Mannheimia haemolytica than are domestic sheep ( Ovis aries ). Leukotoxin produced by M. haemolytica is the principal virulence factor involved in pneumonia pathogenesis. Although leukotoxin is cytolytic to all subsets of ruminant leukocytes, neutrophils are the most susceptible subset. Bighorn sheep neutrophils are four- to eightfold more susceptible to leukotoxin-induced cytolysis than are domestic sheep neutrophils. We hypothesized that the higher susceptibility of bighorn sheep neutrophils, in comparison to domestic sheep neutrophils, is due to higher expression of CD18, the receptor for leukotoxin on leukocytes. Our objective was to quantify CD18 expression on neutrophils of bighorn sheep and domestic sheep. Cell-surface CD18 expression on bighorn sheep and domestic sheep neutrophils was measured as antibody binding capacity of cells by flow cytometric analysis with two fluorochrome-conjugated anti-CD18 monoclonal antibodies (BAQ30A and HUH82A) and microspheres. Contrary to our expectations, CD18 expression was higher (Psheep neutrophils in comparison to bighorn sheep neutrophils. These findings suggest that the higher in vitro susceptibility to leukotoxin of bighorn sheep neutrophils compared to domestic sheep neutrophils is not due to higher expression of the leukotoxin receptor CD18 on bighorn sheep neutrophils.

  20. Protein Poly(ADP-ribosyl)ation System: Changes in Development and Aging as well as due to Restriction of Cell Proliferation.

    Science.gov (United States)

    Shilovsky, G A; Shram, S I; Morgunova, G V; Khokhlov, A N

    2017-11-01

    It is well known that the number of dividing cells in an organism decreases with age. The average rate of cell division in tissues and organs of a mature organism sharply decreases, which is probably a trigger for accumulation of damage leading to disturbance of genome integrity. This can be a cause for the development of many age-related diseases and appearance of phenotypic and physiological signs of aging. In this connection, the protein poly(ADP-ribosyl)ation system, which is activated in response to appearance of various DNA damage, attracts great interest. This review summarizes and analyzes data on changes in the poly(ADP-ribosyl)ation system during development and aging in vivo and in vitro, and due to restriction of cell proliferation. Special attention is given to methodological aspects of determination of activity of poly(ADP-ribose) polymerases (PARPs). Analysis of relevant publications and our own data has led us to the conclusion that PARP activity upon the addition of free DNA ends (in this review referred to as stimulated PARP activity) is steadily decreasing with age. However, the dynamics of PARP activity measured without additional activation of the enzyme (in this review referred to as unstimulated activity) does not have such a clear trend: in many studies, the presented differences are statistically non-significant, although it is well known that the number of unrepaired DNA lesions steadily increases with aging. Apparently, the cell has additional regulatory systems that limit its own capability of reacting to DNA damage. Special attention is given to the influence of the cell proliferative status on PARP activity. We have systematized and analyzed data on changes in PARP activity during development and aging of an organism, as well as data on differences in the dynamics of this activity in the presence/absence of additional stimulation and on cellular processes that are associated with activation of these enzymes. Moreover, data obtained in

  1. Cardiosphere Derived Cells from Pediatric End-Stage Heart Failure Patients Have Enhanced Functional Activity due to the Heat Shock Response Regulating the Secretome

    Science.gov (United States)

    Sharma, Sudhish; Mishra, Rachana; Simpson, David; Wehman, Brody; Colletti, Evan J.; Deshmukh, Savitha; Datla, Srinivasa Raju; Balachandran, Keerti; Guo, Yin; Chen, Ling; Siddiqui, Osama T.; Kaushal, Shalesh; Kaushal, Sunjay

    2016-01-01

    We have demonstrated that human neonatal cardiosphere derived cells (CDCs) derived from the young are more regenerative due to their robust secretome. However, it is unclear how the decompensated pediatric heart impacts the functional activity of their CDCs. Our aim was to characterize the potency of pediatric CDCs derived from normal functioning myocardium of control heart disease (CHD) patients to those generated from age matched end stage heart failure (ESHF) patients and determine the mechanisms involved. ESHF derived CDCs contained a higher number of c-kit+, Islet-1+, and Sca-1+ cells. When transplanted into an infarcted rodent model, ESHF derived CDCs significantly demonstrated higher restoration of ventricular function, prevented adverse remodeling, and enhanced angiogenesis when compared to CHD patients. The superior functional recovery of the ESHF derived CDCs was mediated in part by increased SDF-1α and VEGF-A secretion resulting in augmented recruitment of endogenous stem cells and proliferation of cardiomyocytes. We determined the mechanism is due to the secretome directed by the heat shock response (HSR), which is supported by three lines of evidence. Firstly, gain of function studies demonstrated that increased HSR induced the lower functioning CHD derived CDCs to significantly restore myocardial function. Secondly, loss-of function studies targeting the HSR impaired the ability of the ESHF derived CDCs to functionally recover the injured myocardium. Finally, the native ESHF myocardium had an increased number of c-kit+ CSCs. These findings suggest that the HSR enhances the functional activity of ESHF derived CDCs by increasing their secretome activity, notably SDF-1α and VEGF-A. PMID:25752510

  2. Transient hemolysis due to anti-D and anti-A1 produced by engrafted donor's lymphocytes after allogeneic unmanipulated haploidentical hematopoietic stem cell transplantation.

    Science.gov (United States)

    Bailén, Rebeca; Kwon, Mi; Pérez-Corral, Ana María; Pascual, Cristina; Buño, Ismael; Balsalobre, Pascual; Serrano, David; Gayoso, Jorge; Díez-Martín, José Luis; Anguita, Javier

    2017-10-01

    Development of de novo alloantibodies against recipient's red blood cell (RBC) antigens by engrafted donor's lymphocytes is a known phenomenon in the setting of allogeneic hematopoietic stem cell transplantation (HSCT). This situation is usually clinically insignificant. We report a case of early clinically relevant hemolytic anemia in a blood group A 1 D+ patient, due to a limited production of anti-D and anti-A 1 produced by nonpreviously sensitized newly engrafted donor's immune system. A 31-year-old Caucasian woman, blood group A 1 , D+, with Hodgkin's lymphoma, received an unmanipulated haploidentical allogeneic peripheral blood HSCT after a nonmyeloablative conditioning regimen. Donor blood group was A 2 B, D-. The patient had an uneventful course until Day +34, when she developed clinically significant hemolytic anemia with a positive direct antiglobulin test. Anti-D and anti-A 1 produced by the donor-engrafted lymphocytes were detected both in serum and in eluate. The hemolysis produced an accelerated group change, turning the patient's ABO group into A 2 B 2 weeks after the detection of the alloantibodies. As the residual patient's RBCs progressively disappeared, anti-D and anti-A 1 production decreased and were not detected in serum by Day +41. This case illustrates that de novo alloantibody production against ABO and D antigens by the newly engrafted donor's lymphocytes can occasionally cause clinically significant anemia. To our knowledge, this is the first case reported of clinically significant hemolytic anemia due to a transient anti-D anti-A 1 alloimmunization after T-cell-repleted haploidentical HSCT. © 2017 AABB.

  3. Up-regulation of serum periostin and squamous cell carcinoma antigen levels in infants with acute bronchitis due to respiratory syncytial virus

    Directory of Open Access Journals (Sweden)

    Hiroaki Nakamura

    2018-04-01

    Full Text Available Background: Periostin and squamous cell carcinoma antigen (SCCA are involved in the pathogenesis of asthma. Acute bronchitis due to respiratory syncytial virus (RSV infection during infancy exhibits an asthma-like pathogenesis, suggesting that it may be associated with the subsequent development of asthma. However, the mechanism by which RSV infection leads to development of asthma has not yet been fully elucidated. Methods: Infants younger than 36 months were enrolled and classified into three groups. Group I included patients hospitalized with RSV-induced bronchitis. These patients were further stratified into two sub-groups according to whether the criteria for the modified Asthma Predictive Index (mAPI had been met: Group I consisted of mAPI (+ and mAPI (− patients; Group II included patients with food allergy as a positive control group; and Group III included children with no allergy as a negative control group. Serum periostin and SCCA levels were measured in the groups. This study was registered as a clinical trial (UMIN000012339. Results: We enrolled 14 subjects in Group I mAPI (+, 22 in Group I mAPI (−, 18 in Group II, and 18 in Group III. In Group I, the serum periostin and SCCA levels were significantly higher during the acute phase compared with the recovery phase. However, no significant differences were found between Group I mAPI (+ and mAPI (−. Conclusions: The serum periostin and SCCA levels increased during acute RSV bronchitis. Both periostin and SCCA may play a role in the pathogenesis of acute bronchitis due to RSV. Keywords: Infants, Periostin, Respiratory syncytial virus, Squamous cell carcinoma antigen, T-helper 2 cell cytokines

  4. Effect of EGR on the exhaust gas temperature and exhaust opacity ...

    Indian Academy of Sciences (India)

    R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

    Abstract. In diesel engines, NOx formation is a highly temperature-dependent phenomenon and takes place when the temperature in the combustion chamber exceeds 2000 K. Therefore, in order to reduce NOx emissions in the exhaust, it is necessary to keep peak combustion temperatures under control. One simple way of ...

  5. On the exhaust of electromagnetic drive

    Directory of Open Access Journals (Sweden)

    Patrick Grahn

    2016-06-01

    Full Text Available Recent reports about propulsion without reaction mass have been met on one hand with enthusiasm and on the other hand with some doubts. Namely, closed metal cavities, when fueled with microwaves, have delivered thrust that could eventually maintain satellites on orbits using solar power. However, the measured thrust appears to be without any apparent exhaust. Thus the Law of Action-Reaction seems to have been violated. We consider the possibility that the exhaust is in a form that has so far escaped both experimental detection and theoretical attention. In the thruster’s cavity microwaves interfere with each other and invariably some photons will also end up co-propagating with opposite phases. At the destructive interference electromagnetic fields cancel. However, the photons themselves do not vanish for nothing but continue in propagation. These photon pairs without net electromagnetic field do not reflect back from the metal walls but escape from the resonator. By this action momentum is lost from the cavity which, according to the conservation of momentum, gives rise to an equal and opposite reaction. We examine theoretical corollaries and practical concerns that follow from the paired-photon conclusion.

  6. On the exhaust of electromagnetic drive

    Energy Technology Data Exchange (ETDEWEB)

    Grahn, Patrick, E-mail: patrick.grahn@comsol.fi [COMSOL, FI-00560 Helsinki (Finland); Annila, Arto, E-mail: arto.annila@helsinki.fi [Department of Physics, FI-00014 University of Helsinki, Helsinki (Finland); Department of Biosciences, FI-00014 University of Helsinki, Helsinki (Finland); Kolehmainen, Erkki, E-mail: erkki.t.kolehmainen@jyu.fi [Department of Chemistry, FI-40014 University of Jyväskylä, Jyväskylä (Finland)

    2016-06-15

    Recent reports about propulsion without reaction mass have been met on one hand with enthusiasm and on the other hand with some doubts. Namely, closed metal cavities, when fueled with microwaves, have delivered thrust that could eventually maintain satellites on orbits using solar power. However, the measured thrust appears to be without any apparent exhaust. Thus the Law of Action-Reaction seems to have been violated. We consider the possibility that the exhaust is in a form that has so far escaped both experimental detection and theoretical attention. In the thruster’s cavity microwaves interfere with each other and invariably some photons will also end up co-propagating with opposite phases. At the destructive interference electromagnetic fields cancel. However, the photons themselves do not vanish for nothing but continue in propagation. These photon pairs without net electromagnetic field do not reflect back from the metal walls but escape from the resonator. By this action momentum is lost from the cavity which, according to the conservation of momentum, gives rise to an equal and opposite reaction. We examine theoretical corollaries and practical concerns that follow from the paired-photon conclusion.

  7. Local Pain Dynamics during Constant Exhaustive Exercise.

    Directory of Open Access Journals (Sweden)

    Agne Slapsinskaite

    Full Text Available The purpose of this study was to delineate the topological dynamics of pain and discomfort during constant exercise performed until volitional exhaustion. Eleven physical education students were tested while cycling and running at a "hard" intensity level (e.g., corresponding to Borg's RPE (6-20 = 15. During the tests, participants reported their discomfort and pain on a body map every 15s. "Time on task" for each participant was divided into five equal non-overlapping temporal windows within which their ratings were considered for analysis. The analyses revealed that the number of body locations with perceived pain and discomfort increased throughout the five temporal windows until reaching the mean (± SE values of 4.2 ± 0.7 and 4.1 ± 0.6 in cycling and running, respectively. The dominant locations included the quadriceps and hamstrings during cycling and quadriceps and chest during running. In conclusion, pain seemed to spread throughout the body during constant cycling and running performed up to volitional exhaustion with differences between cycling and running in the upper body but not in the lower body dynamics.

  8. Aircraft exhaust aerosol formation and growth

    Energy Technology Data Exchange (ETDEWEB)

    Brown, R.C.; Miake-Lye, R.C.; Anderson, M.R.; Kolb, C.E. [Aerodyne Research, Inc., Billerica, MA (United States). Center for Chemical and Environmental Physics

    1997-12-31

    Aerosol formation and growth in the exhaust plume of the ATTAS aircraft at an altitude of approximately 9 km, burning fuels with 2 ppmm sulfur (`low`) and 266 ppmm (`high`) sulfur has been modeled using an aerosol dynamics model for nucleation, vapor condensation and coagulation, coupled to a 2-dimensional, axisymmetric flow code to treat plume dilution and turbulent mixing. For both the `low` and `high` sulfur fuels, approximately 60% of the available water had condensed within the first 200 m downstream of the exhaust exit. The contrail particle diameters ranged between 0.4 to 1.6 {mu}m. However, the size distributions as a function of radial position for the `low` sulfur plume were broader than the corresponding distributions for the `high` sulfur plume. The model results indicate for a fuel sulfur mass loading of 2 ppmm, sulfuric acid remains a viable activating agent and that the differences in the contrail particle size distributions for sulfur mass loadings between 2 ppmm and 260 ppmm would be difficult to detect. (author) 12 refs.

  9. Exhaust constituent emission factors of printed circuit board pyrolysis processes and its exhaust control

    Energy Technology Data Exchange (ETDEWEB)

    Chiang, Hung-Lung, E-mail: hlchiang@mail.cmu.edu.tw [Department of Health Risk Management, China Medical University, Taichung, Taiwan (China); Lin, Kuo-Hsiung [Department of Environmental Engineering and Science, Fooyin University, Kaohsiung, Taiwan (China)

    2014-01-15

    Highlights: • Recycling of waste printed circuit boards is an important issue. • Pyrolysis is an emerging technology for PCB treatment. • Emission factors of VOCs are determined for PCB pyrolysis exhaust. • Iron-Al{sub 2}O{sub 3} catalyst was employed for the exhaust control. -- Abstract: The printed circuit board (PCB) is an important part of electrical and electronic equipment, and its disposal and the recovery of useful materials from waste PCBs (WPCBs) are key issues for waste electrical and electronic equipment. Waste PCB compositions and their pyrolysis characteristics were analyzed in this study. In addition, the volatile organic compound (VOC) exhaust was controlled by an iron-impregnated alumina oxide catalyst. Results indicated that carbon and oxygen were the dominant components (hundreds mg/g) of the raw materials, and other elements such as nitrogen, bromine, and copper were several decades mg/g. Exhaust constituents of CO, H{sub 2}, CH{sub 4}, CO{sub 2}, and NOx, were 60–115, 0.4–4.0, 1.1–10, 30–95, and 0–0.7 mg/g, corresponding to temperatures ranging from 200 to 500 °C. When the pyrolysis temperature was lower than 300 °C, aromatics and paraffins were the major species, contributing 90% of ozone precursor VOCs, and an increase in the pyrolysis temperature corresponded to a decrease in the fraction of aromatic emission factors. Methanol, ethylacetate, acetone, dichloromethane, tetrachloromethane and acrylonitrile were the main species of oxygenated and chlorinated VOCs. The emission factors of some brominated compounds, i.e., bromoform, bromophenol, and dibromophenol, were higher at temperatures over 400 °C. When VOC exhaust was flowed through the bed of Fe-impregnated Al{sub 2}O{sub 3}, the emission of ozone precursor VOCs could be reduced by 70–80%.

  10. Cisplatin sensitivity of testis tumour cells is due to deficiency in interstrand-crosslink repair and low ERCC1-XPF expression

    Directory of Open Access Journals (Sweden)

    Kaina Bernd

    2010-09-01

    Full Text Available Abstract Background Cisplatin based chemotherapy cures over 80% of metastatic testicular germ cell tumours (TGCT. In contrast, almost all other solid cancers in adults are incurable once they have spread beyond the primary site. Cell lines derived from TGCTs are hypersensitive to cisplatin reflecting the clinical response. Earlier findings suggested that a reduced repair capacity might contribute to the cisplatin hypersensitivity of testis tumour cells (TTC, but the critical DNA damage has not been defined. This study was aimed at investigating the formation and repair of intrastrand and interstrand crosslinks (ICLs induced by cisplatin in TTC and their contribution to TTC hypersensitivity. Results We observed that repair of intrastrand crosslinks is similar in cisplatin sensitive TTC and resistant bladder cancer cells, whereas repair of ICLs was significantly reduced in TTC. γH2AX formation, which serves as a marker of DNA breaks formed in response to ICLs, persisted in cisplatin-treated TTC and correlated with sustained phosphorylation of Chk2 and enhanced PARP-1 cleavage. Expression of the nucleotide excision repair factor ERCC1-XPF, which is implicated in the processing of ICLs, is reduced in TTC. To analyse the causal role of ERCC1-XPF for ICL repair and cisplatin sensitivity, we over-expressed ERCC1-XPF in TTC by transient transfection. Over-expression increased ICL repair and rendered TTC more resistant to cisplatin, which suggests that ERCC1-XPF is rate-limiting for repair of ICLs resulting in the observed cisplatin hypersensitivity of TTC. Conclusion Our data indicate for the first time that the exceptional sensitivity of TTC and, therefore, very likely the curability of TGCT rests on their limited ICL repair due to low level of expression of ERCC1-XPF.

  11. Effects of exhaust temperature on helicopter infrared signature

    International Nuclear Information System (INIS)

    Cheng-xiong, Pan; Jing-zhou, Zhang; Yong, Shan

    2013-01-01

    The effects of exhaust temperature on infrared signature (in 3–5 μm band) for a helicopter equipped with integrative infrared suppressor were numerically investigated. The internal flow of exhaust gas and the external downwash flow, as well as the mixing between exhaust gas and downwash were simulated by CFD software to determine the temperature distributions on the helicopter skin and in the exhaust plume. Based on the skin and plume temperature distributions, a forward–backward ray-tracing method was used to calculate the infrared radiation intensity from the helicopter with a narrow-band model. The results show that for a helicopter with its integrative infrared suppressor embedded inside its rear airframe, the exhaust temperature has significant influence on the plume radiation characteristics, while the helicopter skin radiation intensity has little impact. When the exhaust temperature is raised from 900 K to 1200 K, the plume radiation intensity in 3–5 μm band is increased by about 100%, while the skin radiation intensity is increased by only about 5%. In general, the effects of exhaust temperature on helicopter infrared radiation intensity are mainly concentrated on plume, especially obvious for a lower skin emissivity case. -- Highlights: ► The effect of exhaust temperature on infrared signature for a helicopter is numerically investigated. ► The impact of exhaust temperature on helicopter skin temperature is revealed. ► The impact of exhaust temperature on plume radiation characteristics is revealed. ► The impact of exhaust temperature on helicopter skin radiation is revealed. ► The impact of exhaust temperature on helicopter's total infrared radiation intensity is revealed

  12. Three-dimensional approach to exhaust gas energy analysis

    Science.gov (United States)

    Sekavčnik, M.; Ogorevc, T.; Katrašnik, T.; Rodman-Oprešnik, S.

    2012-06-01

    Presented work is based on an extensive CFD simulation of the exhaust stroke of a single-cylinder four-stroke internal combustion engine with the exhaust manifold attached. Since the dynamics of the exhaust flow are extremely 3D, an innovative approach to calculate the local entropy generation is developed and implemented in the discussed 3D numerical model. It allows temporal and spatial determination of critical regions and periods of entropy generation in the process with objective to reduce it.

  13. Personalized Stem Cell Therapy to Correct Corneal Defects Due to a Unique Homozygous-Heterozygous Mosaicism of Ectrodactyly-Ectodermal Dysplasia-Clefting Syndrome.

    Science.gov (United States)

    Barbaro, Vanessa; Nasti, Annamaria Assunta; Raffa, Paolo; Migliorati, Angelo; Nespeca, Patrizia; Ferrari, Stefano; Palumbo, Elisa; Bertolin, Marina; Breda, Claudia; Miceli, Francesco; Russo, Antonella; Caenazzo, Luciana; Ponzin, Diego; Palù, Giorgio; Parolin, Cristina; Di Iorio, Enzo

    2016-08-01

    : Ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome is a rare autosomal dominant disease caused by mutations in the p63 gene. To date, approximately 40 different p63 mutations have been identified, all heterozygous. No definitive treatments are available to counteract and resolve the progressive corneal degeneration due to a premature aging of limbal epithelial stem cells. Here, we describe a unique case of a young female patient, aged 18 years, with EEC and corneal dysfunction, who was, surprisingly, homozygous for a novel and de novo R311K missense mutation in the p63 gene. A detailed analysis of the degree of somatic mosaicism in leukocytes from peripheral blood and oral mucosal epithelial stem cells (OMESCs) from biopsies of buccal mucosa showed that approximately 80% were homozygous mutant cells and 20% were heterozygous. Cytogenetic and molecular analyses excluded genomic alterations, thus suggesting a de novo mutation followed by an allelic gene conversion of the wild-type allele by de novo mutant allele as a possible mechanism to explain the homozygous condition. R311K-p63 OMESCs were expanded in vitro and heterozygous holoclones selected following clonal analysis. These R311K-p63 OMESCs were able to generate well-organized and stratified epithelia in vitro, resembling the features of healthy tissues. This study supports the rationale for the development of cultured autologous oral mucosal epithelial stem cell sheets obtained by selected heterozygous R311K-p63 stem cells, as an effective and personalized therapy for reconstructing the ocular surface of this unique case of EEC syndrome, thus bypassing gene therapy approaches. This case demonstrates that in a somatic mosaicism context, a novel homozygous mutation in the p63 gene can arise as a consequence of an allelic gene conversion event, subsequent to a de novo mutation. The heterozygous mutant R311K-p63 stem cells can be isolated by means of clonal analysis and given their good regenerative

  14. Exhaust catalysis studies using in-situ positron emission

    International Nuclear Information System (INIS)

    Vonkeman, K.A.

    1990-01-01

    In this thesis the kinetics of noble metal catalysts with a formulation related to that of commercial automotive exhaust catalysts, have been examined. The application of a new radioisotope tracer technique in studies of catalyst kinetics is described. Reactant and product molecules were pulsed over a catalyst under conditions such, that the reaction rates were kinetically controlled. Labelling of the reacting molecules enables the in-situ measurement of transient phenomena in a reactor as a function of time and position, if a tomograph is used as detection system. Integral reactor profiles are measured, by which concentration gradients occurring in the reactor can be studied. The large amount of data obtained during each experiment were used to quantify the kinetics. To this end, a refined mathematical model of the kinetics based on the elementary steps of adsorption, desorption and surface reaction was used to simulate the experiments. The experimental conditions in this study were representative for the cold start of a car, when the catalyst is heating up. By applying small catalyst particles and high linear velocities the influence of transport phenomena was excluded so that the experiments were carried out in the kinetically controlled regime. Reaction kinetics of carbon monoxide oxidation by oxygen and nitrogen oxide were studied. Experimental data obtained with surface science techniques were very useful in constructing the kinetic model. By simulating the experiments, the relevant kinetic parameters could be quantified and information on the elementary reaction steps was obtained. Since carbon dioxide adsorbs strongly to the catalyst carrier; 10% carbon dioxide was added to the gas phase (in actual automotive exhaust gas the concentration of carbon dioxide is 10 - 15%). This enabled the determination of the transients due to the interaction of gas components with the catalytically active compounds of the catalyst. (author). 446 refs.; 57 figs.; 21 tabs

  15. Diesel exhaust augments allergen-induced lower airway inflammation in allergic individuals: a controlled human exposure study.

    Science.gov (United States)

    Carlsten, Chris; Blomberg, Anders; Pui, Mandy; Sandstrom, Thomas; Wong, Sze Wing; Alexis, Neil; Hirota, Jeremy

    2016-01-01

    Traffic-related air pollution has been shown to augment allergy and airway disease. However, the enhancement of allergenic effects by diesel exhaust in particular is unproven in vivo in the human lung, and underlying details of this apparent synergy are poorly understood. To test the hypothesis that a 2 h inhalation of diesel exhaust augments lower airway inflammation and immune cell activation following segmental allergen challenge in atopic subjects. 18 blinded atopic volunteers were exposed to filtered air or 300 µg PM(2.5)/m(3) of diesel exhaust in random fashion. 1 h post-exposure, diluent-controlled segmental allergen challenge was performed; 2 days later, samples from the challenged segments were obtained by bronchoscopic lavage. Samples were analysed for markers and modifiers of allergic inflammation (eosinophils, Th2 cytokines) and adaptive immune cell activation. Mixed effects models with ordinal contrasts compared effects of single and combined exposures on these end points. Diesel exhaust augmented the allergen-induced increase in airway eosinophils, interleukin 5 (IL-5) and eosinophil cationic protein (ECP) and the GSTT1 null genotype was significantly associated with the augmented IL-5 response. Diesel exhaust alone also augmented markers of non-allergic inflammation and monocyte chemotactic protein (MCP)-1 and suppressed activity of macrophages and myeloid dendritic cells. Inhalation of diesel exhaust at environmentally relevant concentrations augments allergen-induced allergic inflammation in the lower airways of atopic individuals and the GSTT1 genotype enhances this response. Allergic individuals are a susceptible population to the deleterious airway effects of diesel exhaust. NCT01792232. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  16. GASOLINE VEHICLE EXHAUST PARTICLE SAMPLING STUDY

    Energy Technology Data Exchange (ETDEWEB)

    Kittelson, D; Watts, W; Johnson, J; Zarling, D Schauer,J Kasper, K; Baltensperger, U; Burtscher, H

    2003-08-24

    The University of Minnesota collaborated with the Paul Scherrer Institute, the University of Wisconsin (UWI) and Ricardo, Inc to physically and chemically characterize the exhaust plume from recruited gasoline spark ignition (SI) vehicles. The project objectives were: (1) Measure representative particle size distributions from a set of on-road SI vehicles and compare these data to similar data collected on a small subset of light-duty gasoline vehicles tested on a chassis dynamometer with a dilution tunnel using the Unified Drive Cycle, at both room temperature (cold start) and 0 C (cold-cold start). (2) Compare data collected from SI vehicles to similar data collected from Diesel engines during the Coordinating Research Council E-43 project. (3) Characterize on-road aerosol during mixed midweek traffic and Sunday midday periods and determine fleet-specific emission rates. (4) Characterize bulk- and size-segregated chemical composition of the particulate matter (PM) emitted in the exhaust from the gasoline vehicles. Particle number concentrations and size distributions are strongly influenced by dilution and sampling conditions. Laboratory methods were evaluated to dilute SI exhaust in a way that would produce size distributions that were similar to those measured during laboratory experiments. Size fractionated samples were collected for chemical analysis using a nano-microorifice uniform deposit impactor (nano-MOUDI). In addition, bulk samples were collected and analyzed. A mixture of low, mid and high mileage vehicles were recruited for testing during the study. Under steady highway cruise conditions a significant particle signature above background was not measured, but during hard accelerations number size distributions for the test fleet were similar to modern heavy-duty Diesel vehicles. Number emissions were much higher at high speed and during cold-cold starts. Fuel specific number emissions range from 1012 to 3 x 1016 particles/kg fuel. A simple

  17. Improvement of the thermal and mechanical flow characteristics in the exhaust system of piston engine through the use of ejection effect

    Science.gov (United States)

    Plotnikov, L. V.; Zhilkin, B. P.; Brodov, Yu M.

    2017-11-01

    The results of experimental research of gas dynamics and heat transfer in the exhaust process in piston internal combustion engines are presented. Studies were conducted on full-scale models of piston engine in the conditions of unsteady gas-dynamic (pulsating flows). Dependences of the instantaneous flow speed and the local heat transfer coefficient from the crankshaft rotation angle in the exhaust pipe are presented in the article. Also, the flow characteristics of the exhaust gases through the exhaust systems of various configurations are analyzed. It is shown that installation of the ejector in the exhaust system lead to a stabilization of the flow and allows to improve cleaning of the cylinder from exhaust gases and to optimize the thermal state of the exhaust pipes. Experimental studies were complemented by numerical simulation of the working process of the DM-21 diesel engine (production of “Ural diesel-motor plant”). The object of modeling was the eight-cylinder diesel with turbocharger. The simulation was performed taking into account the processes nonstationarity in the intake and exhaust pipes for the various configurations of exhaust systems (with and without ejector). Numerical simulation of the working process of diesel was performed in ACTUS software (ABB Turbo Systems). The simulation results confirmed the stabilization of the flow due to the use of the ejection effect in the exhaust system of a diesel engine. The use of ejection in the exhaust system of the DM-21 diesel leads to improvement of cleaning cylinders up to 10 %, reduces the specific fuel consumption on average by 1 %.

  18. Study of SI engine fueled with methanol vapor and dissociation gas based on exhaust heat dissociating methanol

    International Nuclear Information System (INIS)

    Fu, Jianqin; Deng, Banglin; Liu, Jingping; Wang, Linjun; Xu, Zhengxin; Yang, Jing; Shu, Gequn

    2014-01-01

    Highlights: • The full load power decreases successively from gasoline engine, methanol vapor engine to dissociated methanol engine. • Both power and thermal efficiency of dissociated methanol engine can be improved by boosting pressure. • The conversion efficiency of recovered exhaust gas energy is largely influenced by the BMEP. • At the same BMEP, dissociated methanol engine has higher thermal efficiency than methanol vapor engine and gasoline engine. - Abstract: To improve the fuel efficiency of internal combustion (IC) engine and also achieve the goal of direct usage of methanol fuel on IC engine, an approach of exhaust heat dissociating methanol was investigated, which is a kind of method for IC engine exhaust heat recovery (EHR). A bottom cycle system is coupled with the IC engine exhaust system, which uses the exhaust heat to evaporate and dissociate methanol in its catalytic cracker. The methanol dissociation gas (including methanol vapor) is used as the fuel for IC engine. This approach was applied to both naturally aspirated (NA) engine and turbocharged engine, and the engine performance parameters were predicted by the software GT-power under various kinds of operating conditions. The improvement to IC engine performance and the conversion efficiency of recovered exhaust gas energy can be evaluated by comparing the performances of IC engine fueled with various kinds of fuels (or their compositions). Results show that, from gasoline engine, methanol vapor engine to dissociated methanol engine, the full load power decreases successively in the entire speed area due to the declining of volumetric efficiency, while it is contrary in the thermal efficiency at the same brake mean effective pressure (BMEP) level because of the improving of fuel heating value. With the increase of BMEP, the conversion efficiency of recovered exhaust gas energy is promoted. All those results indicate that the approach of exhaust heat dissociating methanol has large

  19. Ozone Enhances Diesel Exhaust Particles (DEP-Induced Interleukin-8 (IL-8 Gene Expression in Human Airway Epithelial Cells through Activation of Nuclear Factors- κB (NF-κB and IL-6 (NF-IL6

    Directory of Open Access Journals (Sweden)

    James Kelley

    2005-12-01

    Full Text Available Ozone, a highly reactive oxidant gas is a major component of photochemical smog. As an inhaled toxicant, ozone induces its adverse effects mainly on the lung. Inhalation of particulate matter has been reported to cause airway inflammation in humans and animals. Furthermore, epidemiological evidence has indicated that exposure to particulate matter (PM2.5-10, including diesel exhaust particles (DEP has been correlated with increased acute and chronic respiratory morbidity and exacerbation of asthma. Previously, exposure to ozone or particulate matter and their effect on the lung have been addressed as separate environmental problems. Ozone and particulate matter may be chemically coupled in the ambient air. In the present study we determined whether ozone exposure enhances DEP effect on interleukin-8 (IL-8 gene expression in human airway epithelial cells. We report that ozone exposure (0.5 ppm x 1 hr significantly increased DEP-induced IL-8 gene expression in A549 cells (117 ± 19 pg/ml, n = 6, p < 0.05 as compared to cultures treated with DEP (100 μg/ml x 4 hr alone (31 ± 3 pg/ml, n = 6, or cultures exposed to purified air (24 ± 6 pg/ml, n = 6. The increased DEP-induced IL-8 gene expression following ozone exposure was attributed to ozone-induced increase in the activity of the transcription factors NF-κB and NF-IL6. The results of the present study indicate that ozone exposure enhances the toxicity of DEP in human airway epithelial cells by augmenting IL-8 gene expression, a potent chemoattractant of neutrophils in the lung.

  20. Dexamethasone stimulated gene expression in peripheral blood indicates glucocorticoid-receptor hypersensitivity in job-related exhaustion.

    Science.gov (United States)

    Menke, Andreas; Arloth, Janine; Gerber, Markus; Rex-Haffner, Monika; Uhr, Manfred; Holsboer, Florian; Binder, Elisabeth B; Holsboer-Trachsler, Edith; Beck, Johannes

    2014-06-01

    Work-related stress can lead to various health problems ranging from job-related exhaustion to psychiatric and somatic diseases. Biomarkers of job-related exhaustion could help to improve our understanding of the biological mechanisms and might be useful to guide prevention and treatment strategies. The present study included 12 male cases suffering from job-related exhaustion and 12 matched healthy controls. Severity of exhaustion was assessed with the Maslach Burnout Inventory (MBI) and the Shirom-Melamed Burnout Measure (SMBM). Whole genome expression profiles derived from whole blood cells (baseline and following glucocorticoid-receptor (GR) stimulation with 1.5mg dexamethasone p.o.) and corresponding plasma cortisol levels were analyzed. All cases participated in regular aerobic exercise for 12 consecutive weeks and were then re-assessed at follow-up for exhaustion symptoms as well as for cortisol levels and gene expression profiles. At baseline, we found increased basal cortisol levels and an enhanced suppression of plasma cortisol concentrations following dexamethasone in cases suffering from job-related exhaustion. Gene expression analysis revealed that 1.6-fold more transcripts were significantly regulated by dexamethasone in cases as compared to controls. At follow-up after 12 weeks of regular exercise training which was accompanied by significantly improved exhaustion severity scores, cortisol levels and gene expression profiles of cases normalized to the levels observed in controls. In conclusion, we detected GR-induced neuroendocrine and gene expression changes in cases suffering from job-related exhaustion which are in line with an increased sensitivity of GR function. This GR dysregulation normalized with symptom recovery. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Diffusion of lead in automobile exhaust gas

    Energy Technology Data Exchange (ETDEWEB)

    Yamaga, S.; Ohmori, K.; Saito, H.; Tanizaki, A.

    1970-01-01

    The pattern of diffusion of lead from automobile exhaust gas was investigated by studying the amount of lead adhering to or contained in leaves of ginkgo trees growing along less-travelled roads that cross a busy highway. Samples were dried at 100 C, then pulverized, and a definite portion wet-digested. After extraction by dithizone, lead was determined by atomic absorption spectrophotometry. The same routine was followed for surface soil at the root of the trees. Leaves at heights of 3 and 6 m were examined. At one of the two sampling sites, the lead content in surface soil tended to decrease with distance from the trunk highway. At both sites, the amount of lead in leaves was found in larger amounts in the leaves at the lower level. Also, those leaves collected in October contained more lead than those assembled earlier in the year.

  2. Optimal Population and Exhaustible Resource Constraints.

    Science.gov (United States)

    Lawson, Nicholas; Spears, Dean

    2018-01-01

    A large literature considers the optimal size and growth rate of the human population, trading off the utility value of additional people with the costs of a larger population. In this literature, an important parameter is the social weight placed on population size; a standard result is that a planner with a larger weight on population chooses larger population levels and growth rates. We demonstrate that this result is conditionally overturned when an exhaustible resource constraint is introduced: if the discount rate is small enough, the optimal population today decreases with the welfare weight on population size. That is, a more total-utilitarian social planner could prefer a smaller population today than a more average-utilitarian social planner. We also present a numerical illustration applied to the case of climate change, where we show that under plausible real-world parameter values, our result matters for the direction and magnitude of optimal population policy.

  3. Exhaustive extraction of peptides by electromembrane extraction

    DEFF Research Database (Denmark)

    Huang, Chuixiu; Gjelstad, Astrid; Pedersen-Bjergaard, Stig

    2015-01-01

    trifluoroacetate, and leu-enkephalin were extracted from 600 μL of 25 mM phosphate buffer (pH 3.5), through a supported liquid membrane (SLM) containing di-(2-ethylhexyl)-phosphate (DEHP) dissolved in an organic solvent, and into 600 μL of an acidified aqueous acceptor solution using a thin flat membrane-based EME......This fundamental work illustrates for the first time the possibility of exhaustive extraction of peptides using electromembrane extraction (EME) under low system-current conditions (... device. Mass transfer of peptides across the SLM was enhanced by complex formation with the negatively charged DEHP. The composition of the SLM and the extraction voltage were important factors influencing recoveries and current with the EME system. 1-nonanol diluted with 2-decanone (1:1 v/v) containing...

  4. Jet engine exhaust noise due to rough combustion and nonsteady aerodynamic sources

    Science.gov (United States)

    Plett, E. G.; Summerfield, M.

    1972-01-01

    Internal sources are accounted for in terms of fluctuations of mass and momentum at the nozzle exit plane. At low Mach numbers, mass flow fluctuations generated at the exit plane by acoustic resonant type fluctuations inside the engine are found to be dominant. In the subsonic Mach number range between 0.3 and 0.5, exit plane mass flow fluctuations at frequencies characteristic of turbulence become most dominant. Above Mach 0.5, the turbulent momentum fluctuations at the exit plane become dominant, and the jet contribution is not found significant at subsonic speeds.

  5. Prognostic factors for death due to invasive aspergillosis after hematopoietic stem cell transplantation: a 1-year retrospective study of consecutive patients at French transplantation centers.

    Science.gov (United States)

    Cordonnier, Catherine; Ribaud, Patricia; Herbrecht, Raoul; Milpied, Noël; Valteau-Couanet, Dominique; Morgan, Caroline; Wade, Amath

    2006-04-01

    Invasive aspergillosis (IA) is a major cause of death after hematopoietic stem cell transplantation (HSCT). The goal of this retrospective and consecutive survey was to assess prognostic factors of death due to IA after HSCT at the time of diagnosis of IA. All 64 health care centers affiliated with the Société Française de Greffe de Moelle et de Thérapie Cellulaire were contacted to participate in this study of all proven or probable cases of IA that occurred among HSCT recipients in 2002. Data for 51 cases (41 involving allogeneic HSCT and 10 involving autologous HSCT) were collected from patient records and included diagnostic and therapeutic features of IA, outcome, presence of hematological disease, and transplantation data. Cox models were applied to risk factors for death attributed to IA that were initially identified using the usual tests. The proportion of deaths attributed to IA within 4 months after diagnosis was 0.62 (95% confidence interval, 0.47-0.76). Seven factors assessed at diagnosis were determined to be strongly related to death due to IA: age of 12-35 years, dissemination of IA, presence of a pleural effusion, monocyte count of or =2 mg/kg at the time of diagnosis, and uncontrolled graft-versus-host disease.Conclusions. Our study explored potential risk factors for death due to IA among HSCT recipients as a reference for investigation in larger future studies. These factors should help to identify HSCT recipients who would benefit from more-aggressive antifungal therapies.

  6. Comparative Study of Different Methods for Soot Sensing and Filter Monitoring in Diesel Exhausts

    Directory of Open Access Journals (Sweden)

    Markus Feulner

    2017-02-01

    Full Text Available Due to increasingly tighter emission limits for diesel and gasoline engines, especially concerning particulate matter emissions, particulate filters are becoming indispensable devices for exhaust gas after treatment. Thereby, for an efficient engine and filter control strategy and a cost-efficient filter design, reliable technologies to determine the soot load of the filters and to measure particulate matter concentrations in the exhaust gas during vehicle operation are highly needed. In this study, different approaches for soot sensing are compared. Measurements were conducted on a dynamometer diesel engine test bench with a diesel particulate filter (DPF. The DPF was monitored by a relatively new microwave-based approach. Simultaneously, a resistive type soot sensor and a Pegasor soot sensing device as a reference system measured the soot concentration exhaust upstream of the DPF. By changing engine parameters, different engine out soot emission rates were set. It was found that the microwave-based signal may not only indicate directly the filter loading, but by a time derivative, the engine out soot emission rate can be deduced. Furthermore, by integrating the measured particulate mass in the exhaust, the soot load of the filter can be determined. In summary, all systems coincide well within certain boundaries and the filter itself can act as a soot sensor.

  7. Diesel Exhaust Exposure, Wheezing and Sneezing

    Science.gov (United States)

    2012-01-01

    The rising incidence of allergic disorders in developed countries is unexplained. Exposure to traffic related air pollutants may be an important cause of wheezing and asthma in childhood. Experimental evidence from human studies suggests that diesel exhaust particles, constituents of fine particulate matter less than 2.5 microns (PM2.5), may act to enhance IgE mediated aeroallergen sensitization and Th2 directed cytokine responses. To date, epidemiologic investigations indicate that children living in close proximity to heavily travelled roads are more likely to be atopic and wheeze. The Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort study was initiated to test the hypothesis that early high exposure to traffic related air pollutants is associated with early aeroallergen sensitization and allergic respiratory phenotypes. Using an exposure cohort design, more than 700 infants born to atopic parents were recruited at age 1 living either less than 400 meters (high traffic pollutant exposure) or greater than 1,500 meters (low exposure) from a major road. Children were medically evaluated and underwent skin prick testing with aeroallergen at screening, and re-evaluated sequentially at ages 1, 2, 3, 4, and 7. In this study, both proximity and land use regression (LUR) models of traffic air pollutant exposure have been assessed. Proximity to stop and go traffic with large concentrations of bus and truck traffic predicted persistent wheezing during infancy. The LUR model estimated elemental carbon attributable to traffic (ECAT) as a proxy for diesel exhaust particulate exposure. High ECAT was significantly associated with wheezing at age 1 as well as persistent wheezing at age 3. High mold exposure predicted a well defined asthma phenotype at age 7. PMID:22754710

  8. Exposure to submicron particles (PM1.0) from diesel exhaust and pollen allergens of human lung epithelial cells induces morphological changes of mitochondria tonifilaments and rough endoplasmic reticulum.

    Science.gov (United States)

    Mazzarella, Gennaro; Lucariello, Angela; Bianco, Andrea; Calabrese, Cecilia; Thanassoulas, Theodoros; Savarese, Leonilde; Fiumarella, Angelamaria; Esposito, Vincenzo; DE Luca, Antonio

    2014-01-01

    In recent literature, little has been said regarding the morphological changes that occur in lung cells after treatment with particles and nanoparticles. Using an in vitro model of type-II lung epithelium (A549), we studied the effects of submicron particles (PM1.0), Parietaria officinalis (ALL), and PM1.0 + ALL together. To date several biochemical effects have been described, instead few data exist in literature regarding morphological events following these treatments, in particular we focused on the morphological changes and distribution of mitochondria, tonifilaments and rough endoplasmic reticulum, using a transmission electron microscopic (TEM) approach. After exposure to PM1.0 particles (PM1.0), Parietaria officinalis as allergen, and PM1.0 with P. officinalis, changes in the cytoplasmic area were observed, such as damage to mitochondria and morphological alterations of the tonifilaments and rough endoplasmic reticulum. The data obtained strongly support the hypothesis that cells in contact with submicron particles (PM1.0), or P. officinalis, undergo alteration of their metabolism. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  9. Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1

    Directory of Open Access Journals (Sweden)

    Zhao MZ

    2017-03-01

    Full Text Available Minzhi Zhao,* Haiyun Li,* Yan Ma, He Gong, Shu Yang, Qiaojun Fang, Zhiyuan Hu Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Abraxane (Abr, a US Food and Drug Administration-approved albumin-bound nanoparticle applied for the treatment of non-small-cell lung cancer, has been reported to be more effective than paclitaxel (PTX. To further understand the molecular mechanisms that produce this superior drug efficacy of Abr, a quantitative proteomic approach has been applied to investigate the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX. Only one protein, namely, glucosamine 6-phosphate N-acetyltransferase 1 (GNA1, showed significant differential expression (P<0.05 in the cutoff of 2.0 fold, suggesting that Abr can be used safely as a substitute for PTX. GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. Albumin plays a major role in the regulation of this protein. In summary, this study first shows that the superior drug effect of Abr is mainly due to the downregulation of GNA1, which causes proliferative delay and cell adhesion defect. It is also noteworthy that the deficiency of GNA1 might reduce insulin secretion which correlates with type 2 diabetes. Keywords: quantitative proteomics, nano-drug, drug efficacy, lung cancer, molecular mechanisms, abraxane

  10. Role of snow and cold environment in the fate and effects of nanoparticles and select organic pollutants from gasoline engine exhaust.

    Science.gov (United States)

    Nazarenko, Yevgen; Kurien, Uday; Nepotchatykh, Oleg; Rangel-Alvarado, Rodrigo B; Ariya, Parisa A

    2016-02-01

    Exposure to vehicle exhaust can drive up to 70 % of excess lifetime cancer incidences due to air pollution in urban environments. Little is known about how exhaust-derived particles and organic pollutants, implicated in adverse health effects, are affected by freezing ambient temperatures and the presence of snow. Airborne particles and (semi)volatile organic constituents in dilute exhaust were studied in a novel low-temperature environmental chamber system containing natural urban snow under controlled cold environmental conditions. The presence of snow altered the aerosol size distributions of dilute exhaust in the 10 nm to 10 μm range and decreased the number density of the nanoparticulate (snow from 0.218 ± 0.014 to 0.539 ± 0.009 mg L(-1), and over 40 additional (semi)volatile organic compounds and a large number of exhaust-derived carbonaceous and likely organic particles were identified. The concentrations of benzene, toluene, ethylbenzene, and xylenes (BTEX) increased from near the detection limit to 52.48, 379.5, 242.7, and 238.1 μg kg(-1) (± 10 %), respectively, indicating the absorption of exhaust-derived toxic organic compounds by snow. The alteration of exhaust aerosol size distributions at freezing temperatures and in the presence of snow, accompanied by changes of the organic pollutant content in snow, has potential to alter health effects of human exposure to vehicle exhaust.

  11. Potentially lethal damage versus sublethal damage: independent repair processes in actively growing Chinese hamster cells. [Effects of osmotic pressure differences due to NaCl concentrations in buffer solutions on sensitivity of cells to x rays

    Energy Technology Data Exchange (ETDEWEB)

    Utsumi, H.; Elkind, M.M.

    1979-02-01

    Actively growing V79 Chinese hamster cells, treated with anisotonic phosphate-buffered saline (PBS) after x irradiation, are more sensitive than cells treated with isotonic PBS or cells promptly incubated with complete medium immediately after irradiation. The sensitization of irradiated cells results from hypotonic as well as hypertonic NaCl concentrations in PBS, is strongly dependent on both temperature and time, and is mainly due to an increase in the final slope of the single-dose survival curve. After two x-ray dose fractions, the net response of cells sensitized after each fraction by anisotonic post-treatment is similar to that obtained for isotonically treated cells and indicates that sublethal damage repair is not influenced by the enhanced expression of lethal damage. Independence of the repair of damage which is potentially lethal from the repair of damage which is sublethal is further suggested by the more rapid rate of the former compared to that of the latter. The proposal is advanced that the enhanced expression of damage which, after x irradiation, can be shown to be potentially lethal results from a destabilization of the structural relationship between DNA and the nuclear envelope, and/or DNA and the nuclear protein matrix, as a consequence of osmotic changes produced by anisotonic treatment.

  12. Exhaustive comparison and classification of ligand-binding surfaces in proteins

    OpenAIRE

    Murakami, Yoichi; Kinoshita, Kengo; Kinjo, Akira R; Nakamura, Haruki

    2013-01-01

    Many proteins function by interacting with other small molecules (ligands). Identification of ligand-binding sites (LBS) in proteins can therefore help to infer their molecular functions. A comprehensive comparison among local structures of LBSs was previously performed, in order to understand their relationships and to classify their structural motifs. However, similar exhaustive comparison among local surfaces of LBSs (patches) has never been performed, due to computational complexity. To e...

  13. [Negligent homicide caused by exhaust gas escaping from a manipulated chimney].

    Science.gov (United States)

    Wirth, Ingo; Varchmin-schultheiss, Karin; Schmeling, Andreas

    2011-01-01

    A chimney built and operated according to the instructions is supposed to ensure that the combustion gases coming from the fireplace can escape safely. If the operational reliability is impaired, this presents a risk of acute poisoning. The report deals with a negligently caused carbon monoxide poisoning of a married couple as a consequence of improper installation of a cover of the chimney opening. Various causes of fatal poisoning due to defective exhaust systems are discussed in connection with the presented case report.

  14. 49 CFR 229.43 - Exhaust and battery gases.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Exhaust and battery gases. 229.43 Section 229.43... § 229.43 Exhaust and battery gases. (a) Products of combustion shall be released entirely outside the... conditions. (b) Battery containers shall be vented and batteries kept from gassing excessively. ...

  15. Diesel Exhaust in Miners Study: Q&A

    Science.gov (United States)

    The Diesel Exhaust in Miners Study was designed to evaluate the risk of death associated with diesel exhaust exposure, particularly as it may relate to lung cancer. The researchers observed increased risk for lung cancer death with increasing levels of ex

  16. Diesel Engine Exhaust: Basis for Occupational Exposure Limit Value.

    Science.gov (United States)

    Taxell, Piia; Santonen, Tiina

    2017-08-01

    Diesel engines are widely used in transport and power supply, making occupational exposure to diesel exhaust common. Both human and animal studies associate exposure to diesel exhaust with inflammatory lung effects, cardiovascular effects, and an increased risk of lung cancer. The International Agency for Research on Cancer has evaluated diesel exhaust as carcinogenic to humans. Yet national or regional limit values for controlling occupational exposure to diesel exhaust are rare. In recent decades, stricter emission regulations have led to diesel technologies evolving significantly, resulting in changes in exhaust emissions and composition. These changes are also expected to influence the health effects of diesel exhaust. This review provides an overview of the current knowledge on the health effects of diesel exhaust and the influence of new diesel technologies on the health risk. It discusses the relevant exposure indicators and perspectives for setting occupational exposure limit values for diesel exhaust, and outlines directions for future research. The review is based on a collaborative evaluation report by the Nordic Expert Group for Criteria Documentation of Health Risks from Chemicals and the Dutch Expert Committee on Occupational Safety. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Experimental studies of impact of exhaust gas recirculation on the ...

    African Journals Online (AJOL)

    This paper considers the problem of reducing the nitrogen oxides emissions in exhaust gases (EG) of diesel engine by exhaust gas recirculation (EGR). Based on the carried out study the influence of EGR on technical-and-economic and environmental performance of a diesel engine was found as well as main directions of ...

  18. 40 CFR 86.144-94 - Calculations; exhaust emissions.

    Science.gov (United States)

    2010-07-01

    ... light duty trucks: ER06OC93.051 Where: (1) YWM = Weighted mass emissions of each pollutant, i.e., THC... the dilute exhaust sample as calculated from the integrated THC traces, in ppm carbon equivalent. (B... dilute exhaust, ft3. (x) VDM=Volume of methanol sample withdrawn from dilution air, ft3. (xi) CS=GC...

  19. 46 CFR 63.25-7 - Exhaust gas boilers.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Exhaust gas boilers. 63.25-7 Section 63.25-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING AUTOMATIC AUXILIARY BOILERS Requirements for Specific Types of Automatic Auxiliary Boilers § 63.25-7 Exhaust gas boilers. (a) Construction...

  20. 44 CFR 5.58 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Exhaustion of administrative remedies. 5.58 Section 5.58 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY... Exhaustion of administrative remedies. Any person making a request to FEMA for records under this part shall...

  1. A Numerical and Experimental Study of Local Exhaust Capture Efficiency

    DEFF Research Database (Denmark)

    Madsen, U.; Breum, N. O.; Nielsen, Peter Vilhelm

    1993-01-01

    Direct capture efficiency of a local exhaust system is defined by introducing an imaginary control box surrounding the contaminant source and the exhaust opening. The imaginary box makes it possible to distinguish between contaminants directly captured and those that escape. Two methods...

  2. 33 CFR 331.12 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Exhaustion of administrative remedies. 331.12 Section 331.12 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE ADMINISTRATIVE APPEAL PROCESS § 331.12 Exhaustion of administrative remedies. No...

  3. 25 CFR 67.12 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Exhaustion of administrative remedies. 67.12 Section 67.12 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR TRIBAL GOVERNMENT PREPARATION OF A ROLL OF INDEPENDENT SEMINOLE INDIANS OF FLORIDA § 67.12 Exhaustion of administrative remedies. The...

  4. 29 CFR 4003.7 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Exhaustion of administrative remedies. 4003.7 Section 4003.7 Labor Regulations Relating to Labor (Continued) PENSION BENEFIT GUARANTY CORPORATION GENERAL RULES FOR ADMINISTRATIVE REVIEW OF AGENCY DECISIONS General Provisions § 4003.7 Exhaustion of administrative...

  5. 43 CFR 4.314 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Exhaustion of administrative remedies. 4.314 Section 4.314 Public Lands: Interior Office of the Secretary of the Interior DEPARTMENT HEARINGS... Applicable to Proceedings on Appeal Before the Interior Board of Indian Appeals § 4.314 Exhaustion of...

  6. Emotional exhaustion may trigger cut in working hours

    NARCIS (Netherlands)

    Koppes, L.

    2012-01-01

    Researchers in the Netherlands have been examining to what extent workers are modifying their hours to cope with high levels of work-related emotional exhaustion. Findings reveal that most full-time employees would prefer a cut in their hours, with those reporting emotional exhaustion wanting a

  7. 5 CFR 1208.21 - VEOA exhaustion requirement.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false VEOA exhaustion requirement. 1208.21 Section 1208.21 Administrative Personnel MERIT SYSTEMS PROTECTION BOARD ORGANIZATION AND PROCEDURES... THE VETERANS EMPLOYMENT OPPORTUNITIES ACT VEOA Appeals § 1208.21 VEOA exhaustion requirement. Before...

  8. 29 CFR 4901.17 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Exhaustion of administrative remedies. 4901.17 Section 4901.17 Labor Regulations Relating to Labor (Continued) PENSION BENEFIT GUARANTY CORPORATION INTERNAL AND... Procedure for Formal Requests § 4901.17 Exhaustion of administrative remedies. If the disclosure officer...

  9. 45 CFR 617.15 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Exhaustion of administrative remedies. 617.15 Section 617.15 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE... ASSISTANCE FROM NSF § 617.15 Exhaustion of administrative remedies. (a) A complainant may file a civil action...

  10. Exhaustion in University Students and the Effect of Coursework Involvement

    Science.gov (United States)

    Law, Daniel W.

    2007-01-01

    Although researchers have examined exhaustion extensively in occupational studies, this work-specific variable--despite its widespread acceptance and negative outcomes--has received little attention in regard to university students and their coursework. Objective: The author examined the severity of exhaustion in students and the relationship…

  11. 7 CFR 400.56 - Administrative appeal exhaustion.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Administrative appeal exhaustion. 400.56 Section 400.56 Agriculture Regulations of the Department of Agriculture (Continued) FEDERAL CROP INSURANCE... Administrative appeal exhaustion. The insured may appeal the approved APH yield in accordance with the procedures...

  12. 7 CFR 400.453 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Exhaustion of administrative remedies. 400.453 Section 400.453 Agriculture Regulations of the Department of Agriculture (Continued) FEDERAL CROP INSURANCE...-Compliance § 400.453 Exhaustion of administrative remedies. All administrative remedies contained herein or...

  13. 28 CFR 32.8 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Exhaustion of administrative remedies. 32.8 Section 32.8 Judicial Administration DEPARTMENT OF JUSTICE PUBLIC SAFETY OFFICERS' DEATH, DISABILITY, AND EDUCATIONAL ASSISTANCE BENEFIT CLAIMS General Provisions § 32.8 Exhaustion of administrative...

  14. Relations between Teachers' Emotional Exhaustion and Students' Educational Outcomes

    Science.gov (United States)

    Arens, A. Katrin; Morin, Alexandre J. S.

    2016-01-01

    Studies investigating the effects of emotional exhaustion among teachers have primarily focused on its relations with teacher-related outcome variables but little research has been done for examining its relations with student outcomes. Therefore, this study examines the relations between teachers' emotional exhaustion and educational outcomes…

  15. 26 CFR 301.7430-1 - Exhaustion of administrative remedies.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Exhaustion of administrative remedies. 301.7430-1 Section 301.7430-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... the United States § 301.7430-1 Exhaustion of administrative remedies. (a) In general. Section 7430(b...

  16. Unemployment Benefit Exhaustion: Incentive Effects on Job-Finding Rates

    Science.gov (United States)

    Filges, Trine; Geerdsen, Lars Pico; Knudsen, Anne-Sofie Due; Jørgensen, Anne-Marie Klint

    2015-01-01

    Purpose: This systematic review studied the impact of exhaustion of unemployment benefits on the exit rate out of unemployment and into employment prior to benefit exhaustion or shortly thereafter. Method: We followed Campbell Collaboration guidelines to prepare this review, and ultimately located 12 studies for final analysis and interpretation.…

  17. 40 CFR 7.175 - Exhaustion of administrative remedy.

    Science.gov (United States)

    2010-07-01

    ... Discrimination Prohibited on the Basis of Age § 7.175 Exhaustion of administrative remedy. (a) A complainant may file a civil action following the exhaustion of administrative remedies under the Age Discrimination... district in which the recipient is found or transacts business; (ii) A complainant prevailing in a civil...

  18. 30 CFR 36.26 - Composition of exhaust gas.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Composition of exhaust gas. 36.26 Section 36.26 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND... EQUIPMENT Construction and Design Requirements § 36.26 Composition of exhaust gas. (a) Preliminary engine...

  19. Effect of diesel generator exhaust pollutants on growth of Vinca ...

    African Journals Online (AJOL)

    The effects of exhaust pollutants of generator on root and shoot length, root and shoot weight, number of leaflets and leaf area, leaf and total plant dry weight of Vinca rosea and Ruellia tuberosa were studied. The treatment of exhaust pollutants produced significant effects on root, shoot growth, number of leaflet and leaf ...

  20. 30 CFR 70.1900 - Exhaust Gas Monitoring.

    Science.gov (United States)

    2010-07-01

    ... Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY HEALTH STANDARDS-UNDERGROUND COAL MINES DIESEL EXHAUST GAS MONITORING § 70.1900 Exhaust Gas... equipment on the longwall or shortwall face when mining equipment is being installed or removed; and (4) In...

  1. 40 CFR 86.211-94 - Exhaust gas analytical system.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 18 2010-07-01 2010-07-01 false Exhaust gas analytical system. 86.211-94 Section 86.211-94 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... New Medium-Duty Passenger Vehicles; Cold Temperature Test Procedures § 86.211-94 Exhaust gas...

  2. Solid State Electrochemical Sensors for Nitrogen Oxide (NOx) Detection in Lean Exhaust Gases

    OpenAIRE

    Rheaume, Jonathan Michael

    2010-01-01

    Solid state electrochemical sensors that measure nitrogen oxides (NOx) in lean exhaust have been investigated in order to help meet future on-board diagnostic (OBD) regulations for diesel vehicles. This impedancemetric detection technology consists of a planar, single cell sensor design with various sensing electrode materials and yttria-stabilized zirconia (YSZ) as the electrolyte. No reference to ambient air is required. An impedance analysis method yields a signal that is proportional to t...

  3. Occupational exposure to diesel engine exhaust and serum cytokine levels.

    Science.gov (United States)

    Dai, Yufei; Ren, Dianzhi; Bassig, Bryan A; Vermeulen, Roel; Hu, Wei; Niu, Yong; Duan, Huawei; Ye, Meng; Meng, Tao; Xu, Jun; Bin, Ping; Shen, Meili; Yang, Jufang; Fu, Wei; Meliefste, Kees; Silverman, Debra; Rothman, Nathaniel; Lan, Qing; Zheng, Yuxin

    2018-03-01

    The International Agency for Research on Cancer has classified diesel engine exhaust (DEE) as a human lung carcinogen. Given that inflammation is suspected to be an important underlying mechanism of lung carcinogenesis, we evaluated the relationship between DEE exposure and the inflammatory response using data from a cross-sectional molecular epidemiology study of 41 diesel engine testing workers and 46 unexposed controls. Repeated personal exposure measurements of PM 2.5 and other DEE constituents were taken for the diesel engine testing workers before blood collection. Serum levels of six inflammatory biomarkers including interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor (TNF)-α, macrophage inflammatory protein (MIP)-1β, and monocyte chemotactic protein (MCP)-1 were analyzed in all subjects. Compared to unexposed controls, concentrations of MIP-1β were significantly reduced by ∼37% in DEE exposed workers (P 397 µg/m 3 ) compared to unexposed controls. Further, significant inverse exposure-response relationships for IL-8 and MCP-1 were also found in relation to increasing PM 2.5 levels among the DEE exposed workers. Given that IL-8, MIP-1β, and MCP-1 are chemokines that play important roles in recruitment of immunocompetent cells for immune defense and tumor cell clearance, the observed lower levels of these markers with increasing PM 2.5 exposure may provide insight into the mechanism by which DEE promotes lung cancer. Environ. Mol. Mutagen. 59:144-150, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  4. Immunophenotyping of Newly Diagnosed and Recurrent Glioblastoma Defines Distinct Immune Exhaustion Profiles in Peripheral and Tumor-infiltrating Lymphocytes.

    Science.gov (United States)

    Mohme, Malte; Schliffke, Simon; Maire, Cecile L; Rünger, Alessandra; Glau, Laura; Mende, Klaus C; Matschke, Jakob; Gehbauer, Christina; Akyüz, Nuray; Zapf, Svenja; Holz, Mareike; Schaper, Miriam; Martens, Tobias; Schmidt, Nils O; Peine, Sven; Westphal, Manfred; Binder, Mascha; Tolosa, Eva; Lamszus, Katrin

    2018-02-14

    Immunotherapeutic treatment strategies for glioblastoma (GBM) are under investigation in clinical trials. However, our understanding of the immune phenotype of GBM-infiltrating T-cells (TILs) and changes during disease progression is limited. Deeper insight is urgently needed to therapeutically overcome tumor-induced immune exhaustion. We used flow-cytometry and cytokine assays to profile TILs and blood lymphocytes (PBL) from GBM patients, comparing newly diagnosed or recurrent GBM to long-term survivors (LTS) and healthy donors. TCR sequencing was performed on paired samples of newly diagnosed and recurrent GBM. We identified a clear immune signature of exhaustion and clonal restriction in the TIL of patients with GBM. Exhaustion of CD8+ TILs was defined by an increased prevalence of PD-1+, CD39+, Tim-3+, CD45RO+, HLA-DR+ marker expression and exhibition of an effector-/transitional memory differentiation phenotype, whereas KLRG1 and CD57 were underrepresented. Immune signatures were similar in primary and recurrent tumors, however, restricted TCR repertoire clonality and a more activated memory phenotype were observed in TIL from recurrent tumors. Moreover, a reduced cytokine response to PHA stimulation in the blood compartment indicates a dysfunctional peripheral T-cell response in GBM patients. LTS displayed a distinct profile, with abundant naïve and less exhausted CD8+ T-cells. TILs and PBLs exhibit contrasting immune profiles, with a distinct exhaustion signature present in TILs. While the exhaustion profiles of primary and recurrent GBM are comparable, TCR sequencing demonstrated a contracted repertoire in recurrent GBM, concomitant with an increased frequency of activated memory T-cells in recurrent tumors. Copyright ©2018, American Association for Cancer Research.

  5. Comparative study of diesel and biodiesel exhausts on lung oxidative stress and genotoxicity in rats.

    Science.gov (United States)

    Douki, Thierry; Corbière, Cécile; Preterre, David; Martin, Perrine J; Lecureur, Valérie; André, Véronique; Landkocz, Yann; Pottier, Ivannah; Keravec, Veronika; Fardel, Olivier; Moreira-Rebelo, Silvestre; Pottier, Didier; Vendeville, Cathy; Dionnet, Frédéric; Gosset, Pierre; Billet, Sylvain; Monteil, Christelle; Sichel, François

    2018-04-01

    The contribution of diesel exhaust to atmospheric pollution is a major concern for public health, especially in terms of occurrence of lung cancers. The present study aimed at addressing the toxic effects of a repeated exposure to these emissions in an animal study performed under strictly controlled conditions. Rats were repeatedly exposed to the exhaust of diesel engine. Parameters such as the presence of a particle filter or the use of gasoil containing rapeseed methyl ester were investigated. Various biological parameters were monitored in the lungs to assess the toxic and genotoxic effects of the exposure. First, a transcriptomic analysis showed that some pathways related to DNA repair and cell cycle were affected to a limited extent by diesel but even less by biodiesel. In agreement with occurrence of a limited genotoxic stress in the lungs of diesel-exposed animals, small induction of γ-H2AX and acrolein adducts was observed but not of bulky adducts and 8-oxodGuo. Unexpected results were obtained in the study of the effect of the particle filter. Indeed, exhausts collected downstream of the particle filter led to a slightly higher induction of a series of genes than those collected upstream. This result was in agreement with the formation of acrolein adducts and γH2AX. On the contrary, induction of oxidative stress remained very limited since only SOD was found to be induced and only when rats were exposed to biodiesel exhaust collected upstream of the particle filter. Parameters related to telomeres were identical in all groups. In summary, our results point to a limited accumulation of damage in lungs following repeated exposure to diesel exhausts when modern engines and relevant fuels are used. Yet, a few significant effects are still observed, mostly after the particle filter, suggesting a remaining toxicity associated with the gaseous or nano-particular phases. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Successful treatment of sepsis due to Pantoea agglomerans by polymyxin B-immobilized fiber column direct hemoperfusion therapy in a small cell lung carcinoma patient.

    Science.gov (United States)

    Tsubouchi, Hironobu; Matsumoto, Nobuhiro; Yanagi, Shigehisa; Arimura, Yasuji; Nakazato, Masamitsu

    2016-01-01

    Sepsis is a life-threatening condition caused by the inflammatory response to invading organisms. Polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) is used to reduce blood endotoxin levels and modulate circulating inflammatory cytokine levels in sepsis patients. Here we report that severe sepsis caused by an infection of the gram-negative bacterium Pantoea agglomerans in a patient with small cell lung carcinoma was treated successfully with antibiotics and PMX-DHP. The patient, a 49-year-old Japanese male smoker whose condition was complicated with hyponatremia due to SIADH (syndrome of inappropriate secretion of antidiuretic hormone), rapidly developed sepsis and disseminated intravascular coagulation (DIC) after the administration of cisplatin and irinotecan. Despite initial antibiotics therapy, severe host responses including hypotension, high body temperature and tachycardia were noted. We initiated PMX-DHP, and the patient's Sequential Organ Failure Assessment score was greatly reduced and his DIC improved immediately. To our knowledge, this is the first reported case of PMX-DHP therapy for severe sepsis caused by P. agglomerans infection. Although the efficacy of PMX-DHP in sepsis is not well defined, PMX-DHP therapy should be considered in cases of sepsis from gram-negative infections.

  7. Leishmaniosis due to Leishmania infantum in a FIV and FeIV positive cat with a squamous cell carcinoma diagnosed with histological, serological and isoenzymatic methods

    Directory of Open Access Journals (Sweden)

    Grevot A.

    2005-09-01

    Full Text Available Leishmaniosis caused by Leishmania infantum is an endemic zoonosis present in the Mediterranean area. Canidae (dog and fox constitute the main reservoir hosts for the parasite, whilst wild rodents or the cat can be carriers of the protozoan and are considered as secondary potential reservoirs. This paper describes a case of disseminated feline leishmaniosis with cutaneous (ulcerative, visceral (spleen and lymph nodes and blood involvement in a FIV-FelV positive cat. The microscopic identification of the Leishmania infection was initially made on a skin biopsy of the temporal area, where a squamous cell carcinoma was diagnosed. The diagnosis of the disease was achieved by several serological techniques (ELISA, IFAT and Western-blot. The strain was obtained by blood culture, characterized by electrophoresis of isoenzymes and identified as Leishmania infantum zymodeme MON-1. Since the infection due to L. infantum is a zoonosis, the potential feline reservoir should be more investigated. Serological analysis by Western blot on domestic cats provides a useful tool. In veterinary practice, feline leishmaniosis should be systematically included in the differential diagnosis when compatible cutaneous lesions are present, especially in the endemic areas of canine leishmaniosis.

  8. New catalysts for exhaust gas cleaning

    Energy Technology Data Exchange (ETDEWEB)

    Haerkoenen, M. [Kemira Metalkat Oy, Oulu (Finland)

    1996-12-31

    Major challenge for future catalyst systems was to develop thermally more stable washcoats for close coupled operating conditions and for engines operating under high speed and load conditions. To design these future emission systems extensive research and development was undertaken to develop methods to disperse and stabilize the key catalytic materials for operation at much higher temperatures. Second priority was to design catalysts that are more effective under low temperature exhaust conditions and have improved oxygen storage properties in the washcoats. Incorporating new materials and modified preparation technology a new generation of metallic catalyst formulations emerged, those being trimetallic K6 (Pt:Pd:Rh and bimetallic K7) (Pd+Pd:Rh). The target was to combine the best property of Pt:Rh (good NO{sub x} reduction) with that of the good HC oxidation activity of Pd and to ensure that precious metal/support interactions were positively maintained. Both K6 and K7 concepts contain special catalyst structures with optimized washcoat performance which can be brick converter configuration. Improvement in light-off, thermal stability and transient performance with these new catalyst formulations have clearly been shown in both laboratory and vehicle testing. (author) (20 refs.)

  9. Steam atmosphere drying exhaust steam recompression system

    Science.gov (United States)

    Becker, F.E.; Smolensky, L.A.; Doyle, E.F.; DiBella, F.A.

    1994-03-08

    This invention relates to a heated steam atmosphere drying system comprising dryer in combination with an exhaust recompression system which is extremely energy efficient and eliminates dangers known to air dryers. The system uses superheated steam as the drying medium, which recirculates through the system where its heat of evaporation and heat of compression is recovered, thereby providing a constant source of heat to the drying chamber. The dryer has inlets whereby feedstock and superheated steam are fed therein. High heat transfer and drying rates are achieved by intimate contact of the superheated steam with the particles being dried. The dryer comprises a vessel which enables the feedstock and steam to enter and recirculate together. When the feedstock becomes dry it will exit the dryer with the steam and become separated from the steam through the use of a curvilinear louver separator (CLS). The CLS enables removal of fine and ultrafine particles from the dryer. Water vapor separated from the particles in the CLS as superheated steam, may then be recovered and recirculated as steam through the use of a compressor to either directly or indirectly heat the dryer, and a heat exchanger or a heater to directly provide heat to the dryer. This system not only provides a very efficient heat transfer system but results in a minimum carry-over of ultrafine particles thereby eliminating any explosive hazard. 17 figures.

  10. Formation, function, and exhaustion of notochordal cytoplasmic vacuoles within intervertebral disc: current understanding and speculation.

    Science.gov (United States)

    Wang, Feng; Gao, Zeng-Xin; Cai, Feng; Sinkemani, Arjun; Xie, Zhi-Yang; Shi, Rui; Wei, Ji-Nan; Wu, Xiao-Tao

    2017-08-22

    Notochord nucleus pulposus cells are characteristic of containing abundant and giant cytoplasmic vacuoles. This review explores the embryonic formation, biological function, and postnatal exhaustion of notochord vacuoles, aiming to characterize the signal network transforming the vacuolated nucleus pulposus cells into the vacuole-less chondrocytic cells. Embryonically, the cytoplasmic vacuoles within vertebrate notochord originate from an evolutionarily conserved vacuolation process during neurulation, which may continue to provide mechanical and signal support in constructing a mammalian intervertebral disc. For full vacuolation, a vacuolating specification from dorsal organizer cells, synchronized convergent extension, well-structured notochord sheath, and sufficient post-Golgi trafficking in notochord cells are required. Postnatally, age-related and species-specific exhaustion of vacuolated nucleus pulposus cells could be potentiated by Fas- and Fas ligand-induced apoptosis, intolerance to mechanical stress and nutrient deficiency, vacuole-mediated proliferation check, and gradual de-vacuolation within the avascular and compression-loaded intervertebral disc. These results suggest that the notochord vacuoles are active and versatile organelles for both embryonic notochord and postnatal nucleus pulposus, and may provide novel information on intervertebral disc degeneration to guide cell-based regeneration.

  11. Electromagnetic Exhaust Valve Event Optimization for Enhancing Gasoline Engine Performance

    Directory of Open Access Journals (Sweden)

    Fan Xinyu

    2017-01-01

    Full Text Available Variable exhaust valve events have the potential to further improve the engine power output, fuel economy and decrease the NOX emissions. Based on the moving coil electromagnetic valve train applied to engine exhaust system, effects of variable exhaust valve events are analyzed in detail and the optimization approaches are carried out. Also with the fully variable intake and exhaust valve train, different internal EGR strategies can be achieved and the contrastive analyses are carried out between combustion chamber recirculation and exhaust port recirculation strategies at same operational condition. Results show that, the optimal exhaust valve opening motion can strengthen both power performance and fuel economy at engine part loads. And two principal EGR strategies are applied in a good combination under variable engine loads. At the engine speed of 2000 r/min, BMEP is about 0.3 MPa and with 30%~35% exhaust port recirculation rate, the BSFC and NOX emissions have decrease over 10% and 85% respectively compare with initial condition.

  12. Use of electromyography to detect muscle exhaustion in finishing barrows fed ractopamine HCl.

    Science.gov (United States)

    Noel, J A; Broxterman, R M; McCoy, G M; Craig, J C; Phelps, K J; Burnett, D D; Vaughn, M A; Barstow, T J; O'Quinn, T G; Woodworth, J C; DeRouchey, J M; Rozell, T G; Gonzalez, J M

    2016-06-01

    The objectives of this study were to determine the effects of dietary ractopamine HCl (RAC) on muscle fiber characteristics and electromyography (EMG) measures of finishing barrow exhaustion when barrows were subjected to increased levels of activity. Barrows ( = 34; 92 ± 2 kg initial BW) were assigned to 1 of 2 treatments: a conventional swine finishing diet containing 0 mg/kg ractopamine HCl (CON) or a diet formulated to meet the requirements of finishing barrows fed 10 mg/kg RAC (RAC+). After 32 d on feed, barrows were individually moved around a track at 0.79 m/s until subjectively exhausted. Wireless EMG sensors were affixed to the deltoideus (DT), triceps brachii lateral head (TLH), tensor fasciae latae (TFL), and semitendinosus (ST) muscles to measure median power frequency (MdPF) and root mean square (RMS) as indicators of action potential conduction velocity and muscle fiber recruitment, respectively. After harvest, samples of each muscle were collected for fiber type, succinate dehydrogenase (SDH), and capillary density analysis. Speed was not different ( = 0.82) between treatments, but RAC+ barrows reached subjective exhaustion earlier and covered less distance than CON barrows ( 0.29). There was a treatment × muscle interaction ( = 0.04) for end-point RMS values. The RAC diet did not change end-point RMS values in the DT or TLH ( > 0.37); however, the diet tended to decrease and increase end-point RMS in the ST and TFL, respectively ( 0.10). Muscles of RAC+ barrows tended to have less type I fibers and more capillaries per fiber ( < 0.07). Type I and IIA fibers of RAC+ barrows were larger ( < 0.07). Compared with all other muscles, the ST had more ( < 0.01) type IIB fibers and larger type I, IIA, and IIX fibers ( < 0.01). Type I, IIA, and IIX fibers of the ST also contained less SDH compared with the other muscles ( < 0.01). Barrows fed a RAC diet had increased time to subjective exhaustion due to loss of active muscle fibers in the ST, possibly due

  13. FTIR Determination of Pollutants in Automobile Exhaust: An Environmental Chemistry Experiment Comparing Cold-Start and Warm-Engine Conditions

    Science.gov (United States)

    Medhurst, Laura L.

    2005-01-01

    An experiment developed from the Advanced Integrated Environmental Laboratory illustrates the differences in automobile exhaust before and after the engine is warmed, using gas-phase Fourier transform infrared spectroscopy (FTIR). The apparatus consists of an Avatar 360 FTIR spectrometer from Nicolet fitted with a variable path length gas cell,…

  14. BREATHING 100% O2 HAS NO EFFECT ON BLOOD LACTATE CONCENTRATION DURING A SHORT PASSIVE RECOVERY FROM EXHAUSTIVE EXERCISE

    Directory of Open Access Journals (Sweden)

    Bartholomew Kay

    2005-06-01

    . Nonetheless, past research has focussed on methods by which the clearance of LA- from the blood could be expedited. As the clearance of LA- from the blood occurs primarily due to import and oxidation by other cells (Mengual et al., 2003, methods trialled include breathing hyperoxic gas mixtures during recovery (Maeda and Yasukouchi, 1997; Murphy, 1986; Shell et al., 1986. It has been argued, however, that due to the near horizontal nature of the oxyhaemoglobin dissociation curve (i.e. 95%+ O2 saturated at normal alveolar PO2 (~95 mmHg; it appears unlikely that the large increase in alveolar PO2 caused by breathing 100% O2 (667% % increase over ambient air would be effective in raising actual oxygen delivery to the mitochondria by a useful margin. However, Haseler et al. (1999 have shown that increasing the inspired O2 percentage to 100% during a passive recovery from exercise significantly reduced the time constant for phosphocreatine (PCr repletion (20-s vs. 25-s, p < 0.05. Given that PCr repletion is dependent on ATP, these findings provide surety that O2 delivery to, and uptake by the mitochondria is indeed usefully increased during passive recovery by breathing 100% O2 as compared with ~21% O2 (Haseler et al., 1999. We therefore undertook this investigation because previous methodologies and results regarding hyperoxic breathing and blood LA- concentration (Maeda and Yasukouchi, 1997; Murphy, 1986; Shell et al., 1986 are somewhat conflicting. Specifically; acute muscular exhaustion was not universally imposed, hyperoxia was often imposed during the exercise also, and subjects of differing aerobic or cardiovascular fitness showed differential responses. Given the above arguments, we intended to clarify the effect of breathing 100% O2 on blood LA- concentration during a brief period of passive recovery from incremental exercise to exhaustion under controlled conditions. We hypothesised that breathing 100% O2 during a 5-minute passive recovery from exhaustive incremental

  15. Non-Exhaust PM10 and Road Dust

    OpenAIRE

    Lundberg, Joacim

    2018-01-01

    Non-exhaust PM10 is an issue in the urban environment linked to health issues. Emissions of non-exhaust PM10 is relatable to pavement properties. Also of importance is resuspension of road dust stored from surfaces. This depends on the traffic and metrological conditions. Given this, the purpose of the thesis was to give an overview limited to Sweden and the Nordic countries regarding non-exhaust PM10 emissions and road dust. The overview includes how particles are related to human health. Al...

  16. Decontamination and size reduction of plutonium contaminated process exhaust ductwork and glove boxes

    International Nuclear Information System (INIS)

    LaFrate, P.; Elliott, J.; Valasquez, M.

    1996-01-01

    The Los Alamos National Laboratory (LANL) Decommissioning Program has decontaminated and demolished two filter plenum buildings at Technical Area 21 (TA-21). During the project a former hot cell was retrofitted to perform decontamination and size reduction of highly Pu contaminated process exhaust (1,100 ft) and gloveboxes. Pu-238/239 concentrations were as high a 1 Ci per linear foot and averaged approximately 1 mCi/ft. The Project decontamination objective was to reduce the plutonium contamination on surfaces below transuranic levels. If possible, metal surfaces were decontaminated further to meet Science and Ecology Group (SEG) waste classification guidelines to enable the metal to be recycled at their facility in oak Ridge, Tennessee. Project surface contamination acceptance criteria for low-level radioactive waste (LLRW), transuranic waste, and SEG waste acceptance criteria will be presented. Ninety percent of all radioactive waste for the project was characterized as LLRW. Twenty percent of this material was shipped to SEG. Process exhaust and glove boxes were brought to the project decontamination area, an old hot cell in Building 4 North. This paper focuses on process exhaust and glovebox decontamination methodology, size reduction techniques, waste characterization, airborne contamination monitoring, engineering controls, worker protection, lessons learned, and waste minimization. Decontamination objectives are discussed in detail

  17. Improved methane removal in exhaust gas from biogas upgrading process using immobilized methane-oxidizing bacteria.

    Science.gov (United States)

    Sun, Meng-Ting; Yang, Zhi-Man; Fu, Shan-Fei; Fan, Xiao-Lei; Guo, Rong-Bo

    2018-05-01

    Methane in exhaust gas from biogas upgrading process, which is a greenhouse gas, could cause global warming. The biofilter with immobilized methane-oxidizing bacteria (MOB) is a promising approach for methane removal, and the selections of inoculated MOB culture and support material are vital for the biofilter. In this work, five MOB consortia were enriched at different methane concentrations. The MOB-20 consortium enriched at the methane concentration of 20.0% (v/v) was then immobilized on sponge and two particle sizes of volcanic rock in biofilters to remove methane in exhaust gas from biogas upgrading process. Results showed that the immobilized MOB performed more admirable methane removal capacity than suspended cells. The immobilized MOB on sponge reached the highest methane removal efficiency (RE) of 35%. The rough surface, preferable hydroscopicity, appropriate pore size and particle size of support material might favor the MOB immobilization and accordingly methane removal. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Nitride precipitation during high temperature corrosion of ductile cast irons in synthetic exhaust gases

    Science.gov (United States)

    Tholence, F.; Norell, M.

    2005-02-01

    Internal nitrides form in two ductile cast irons (SiMo and Ni-Resist) intended for exhaust systems in vehicles. Samples oxidised at 650 1050 °C for 50 h in modified synthetic exhaust gases were analysed by using AES and FEG-SEM. No nitrides formed in absence of NOx. In dry petrol gas coarse nitrides (resistance of the alloy. In diesel and in normal petrol gases μ-sized MgSiN2 form in SiMo in cell boundaries where Mg segregates. This also occurs in Ni-Resist in both dry and normal petrol whereas no nitrides were observed in Ni-Resist exposed to diesel gases.

  19. Attempts to predict the long-term decrease in lung function due to radiotherapy of non-small cell lung cancer

    International Nuclear Information System (INIS)

    Nielsen, Morten; Hansen, Olfred; Vach, Werner

    2006-01-01

    Purpose: To obtain a model which can predict long-term decrease in lung function due to radiation damage from dose-volume data for patients with non-small cell lung cancer. Patients and methods: 27 patients were included, all long-term survivors after radical radiation therapy. For each patient a regression analysis was performed on a post-RT succession of measurements of FEV1 in order to estimate the decrease after 2 years and a standard error (SE) on this regression estimate. The modelling was based on dose-volume histograms (DVH) exported from the treatment planning system, and involved fits of threshold models, a mean lung dose model as well as more complex models based on the relative damaged volume (rdV). Results: Decreases after 2 years of up to 28% in FEV1 was measured (median 10%), with significant day-to-day variation in FEV1 for the individual patient. The threshold models predicted the long-term decrease in FEV1 well when the SE was interpreted as the uncertainty of the measured decrease. The best threshold value, marginally, was 30 Gy with an R 2 of 0.46. The mean lung dose model did not perform so well. A complex model based on rdV performed better than any of the other models (R 2 =0.52). Conclusion: The long-term decrease in FEV1 could be predicted from a simple dose-volume model when the SE was interpreted as the uncertainty of the measured decrease

  20. SBDS-Deficient Cells Have an Altered Homeostatic Equilibrium due to Translational Inefficiency Which Explains their Reduced Fitness and Provides a Logical Framework for Intervention

    Science.gov (United States)

    Miluzio, Annarita; Russo, Arianna; Ricciardi, Sara; Khanim, Farhat; Cheroni, Cristina; Alfieri, Roberta; Mancino, Marilena; Gorrini, Chiara; Peluso, Ivana; Pagani, Massimiliano; Medina, Diego L.

    2017-01-01

    Ribosomopathies are a family of inherited disorders caused by mutations in genes necessary for ribosomal function. Shwachman-Diamond Bodian Syndrome (SDS) is an autosomal recessive disease caused, in most patients, by mutations of the SBDS gene. SBDS is a protein required for the maturation of 60S ribosomes. SDS patients present exocrine pancreatic insufficiency, neutropenia, chronic infections, and skeletal abnormalities. Later in life, patients are prone to myelodisplastic syndrome and acute myeloid leukemia (AML). It is unknown why patients develop AML and which cellular alterations are directly due to the loss of the SBDS protein. Here we derived mouse embryonic fibroblast lines from an SbdsR126T/R126T mouse model. After their immortalization, we reconstituted them by adding wild type Sbds. We then performed a comprehensive analysis of cellular functions including colony formation, translational and transcriptional RNA-seq, stress and drug sensitivity. We show that: 1. Mutant Sbds causes a reduction in cellular clonogenic capability and oncogene-induced transformation. 2. Mutant Sbds causes a marked increase in immature 60S subunits, limited impact on mRNA specific initiation of translation, but reduced global protein synthesis capability. 3. Chronic loss of SBDS activity leads to a rewiring of gene expression with reduced ribosomal capability, but increased lysosomal and catabolic activity. 4. Consistently with the gene signature, we found that SBDS loss causes a reduction in ATP and lactate levels, and increased susceptibility to DNA damage. Combining our data, we conclude that a cell-specific fragile phenotype occurs when SBDS protein drops below a threshold level, and propose a new interpretation of the disease. PMID:28056084