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Sample records for tumor evasion current

  1. Tumor immune evasion arises through loss of TNF sensitivity.

    Science.gov (United States)

    Kearney, Conor J; Vervoort, Stephin J; Hogg, Simon J; Ramsbottom, Kelly M; Freeman, Andrew J; Lalaoui, Najoua; Pijpers, Lizzy; Michie, Jessica; Brown, Kristin K; Knight, Deborah A; Sutton, Vivien; Beavis, Paul A; Voskoboinik, Ilia; Darcy, Phil K; Silke, John; Trapani, Joseph A; Johnstone, Ricky W; Oliaro, Jane

    2018-05-18

    Immunotherapy has revolutionized outcomes for cancer patients, but the mechanisms of resistance remain poorly defined. We used a series of whole-genome clustered regularly interspaced short palindromic repeat (CRISPR)-based screens performed in vitro and in vivo to identify mechanisms of tumor immune evasion from cytotoxic lymphocytes [CD8 + T cells and natural killer (NK) cells]. Deletion of key genes within the tumor necrosis factor (TNF) signaling, interferon-γ (IFN-γ) signaling, and antigen presentation pathways provided protection of tumor cells from CD8 + T cell-mediated killing and blunted antitumor immune responses in vivo. Deletion of a number of genes in the TNF pathway also emerged as the key mechanism of immune evasion from primary NK cells. Our screens also identified that the metabolic protein 2-aminoethanethiol dioxygenase (Ado) modulates sensitivity to TNF-mediated killing by cytotoxic lymphocytes and is required for optimal control of tumors in vivo. Remarkably, we found that tumors delete the same genes when exposed to perforin-deficient CD8 + T cells, demonstrating that the dominant immune evasion strategy used by tumor cells is acquired resistance to T cell-derived cytokine-mediated antitumor effects. We demonstrate that TNF-mediated bystander killing is a potent T cell effector mechanism capable of killing antigen-negative tumor cells. In addition to highlighting the importance of TNF in CD8 + T cell- and NK cell-mediated killing of tumor cells, our study also provides a comprehensive picture of the roles of the TNF, IFN, and antigen presentation pathways in immune-mediated tumor surveillance. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  2. Complement evasion by Bordetella pertussis: implications for improving current vaccines.

    Science.gov (United States)

    Jongerius, Ilse; Schuijt, Tim J; Mooi, Frits R; Pinelli, Elena

    2015-04-01

    Bordetella pertussis causes whooping cough or pertussis, a highly contagious disease of the respiratory tract. Despite high vaccination coverage, reported cases of pertussis are rising worldwide and it has become clear that the current vaccines must be improved. In addition to the well-known protective role of antibodies and T cells during B. pertussis infection, innate immune responses such as the complement system play an essential role in B. pertussis killing. In order to evade this complement activation and colonize the human host, B. pertussis expresses several molecules that inhibit complement activation. Interestingly, one of the known complement evasion proteins, autotransporter Vag8, is highly expressed in the recently emerged B. pertussis isolates. Here, we describe the current knowledge on how B. pertussis evades complement-mediated killing. In addition, we compare this to complement evasion strategies used by other bacterial species. Finally, we discuss the consequences of complement evasion by B. pertussis on adaptive immunity and how identification of the bacterial molecules and the mechanisms involved in complement evasion might help improve pertussis vaccines.

  3. Linking tumor glycolysis and immune evasion in cancer: Emerging concepts and therapeutic opportunities.

    Science.gov (United States)

    Ganapathy-Kanniappan, Shanmugasundaram

    2017-08-01

    Metabolic reprogramming and immune evasion are two hallmarks of cancer. Metabolic reprogramming is exemplified by cancer's propensity to utilize glucose at an exponential rate which in turn is linked with "aerobic glycolysis", popularly known as the "Warburg effect". Tumor glycolysis is pivotal for the efficient management of cellular bioenergetics and uninterrupted cancer growth. Mounting evidence suggests that tumor glycolysis also plays a key role in instigating immunosuppressive networks that are critical for cancer cells to escape immune surveillance ("immune evasion"). Recent data show that induction of cellular stress or metabolic dysregulation sensitize cancer cells to antitumor immune cells implying that metabolic reprogramming and immune evasion harmonize during cancer progression. However, the molecular link between these two hallmarks of cancer remains obscure. In this review the molecular intricacies of tumor glycolysis that facilitate immune evasion has been discussed in the light of recent research to explore immunotherapeutic potential of targeting cancer metabolism. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. International Tax Evasion in the Current Geopolitical Context

    OpenAIRE

    Constantin Sergiu-Bogdan

    2014-01-01

    Tax evasion means the avoidance of declaring and paying the tax obligations. Through the manifestation of this phenomenon, the state incomes are reduced, the governments not being capable of complying with their tasks. As the economic globalization progresses, tax evasion becomes international thanks to the tax havens which usually are small states that provide various tax facilities to those who want to carry out their activity through their agency, especially through offshore companies. It ...

  5. Tumor evasion from immune control: Strategies of a MISS to become a MASS

    Energy Technology Data Exchange (ETDEWEB)

    D' Onofrio, Alberto [Department of Epidemiology and Biostatistics, European Institute of Oncology, Via Ripamonti 435, I-20141 Milan (Italy)]. E-mail: alberto.d' onofrio@ieo.it

    2007-01-15

    We biologically describe the phenomenon of the evasion of tumors from immune surveillance where tumor cells, initially constrained to exist in a microscopic steady state (MISS) elaborate strategies to evade from the immune control and to reach a macroscopic steady state (MASS). We, then, describe 'evasion' as a long term loss of equilibrium in a framework of prey-predator-like models with adiabatic varying parameters, whose changes reflect the evolutionary adaptation of the tumor in a 'hostile' environment by means of the elaboration of new strategies of survival. Similarities and differences between the present work and the interesting seminal paper [Kuznetsov VA, Knott GD. Modeling tumor regrowth and immunotherapy. Math Comput Model 2001;33:1275-87] are discussed. We also propose and study a model of clonal resistance to the immune control with slowly varying adaptive mutation parameter.

  6. Tumor evasion from immune control: Strategies of a MISS to become a MASS

    International Nuclear Information System (INIS)

    D'Onofrio, Alberto

    2007-01-01

    We biologically describe the phenomenon of the evasion of tumors from immune surveillance where tumor cells, initially constrained to exist in a microscopic steady state (MISS) elaborate strategies to evade from the immune control and to reach a macroscopic steady state (MASS). We, then, describe 'evasion' as a long term loss of equilibrium in a framework of prey-predator-like models with adiabatic varying parameters, whose changes reflect the evolutionary adaptation of the tumor in a 'hostile' environment by means of the elaboration of new strategies of survival. Similarities and differences between the present work and the interesting seminal paper [Kuznetsov VA, Knott GD. Modeling tumor regrowth and immunotherapy. Math Comput Model 2001;33:1275-87] are discussed. We also propose and study a model of clonal resistance to the immune control with slowly varying adaptive mutation parameter

  7. Simple biophysical model of tumor evasion from immune system control

    Science.gov (United States)

    D'Onofrio, Alberto; Ciancio, Armando

    2011-09-01

    The competitive nonlinear interplay between a tumor and the host's immune system is not only very complex but is also time-changing. A fundamental aspect of this issue is the ability of the tumor to slowly carry out processes that gradually allow it to become less harmed and less susceptible to recognition by the immune system effectors. Here we propose a simple epigenetic escape mechanism that adaptively depends on the interactions per time unit between cells of the two systems. From a biological point of view, our model is based on the concept that a tumor cell that has survived an encounter with a cytotoxic T-lymphocyte (CTL) has an information gain that it transmits to the other cells of the neoplasm. The consequence of this information increase is a decrease in both the probabilities of being killed and of being recognized by a CTL. We show that the mathematical model of this mechanism is formally equal to an evolutionary imitation game dynamics. Numerical simulations of transitory phases complement the theoretical analysis. Implications of the interplay between the above mechanisms and the delivery of immunotherapies are also illustrated.

  8. DNA Tumor Virus Regulation of Host DNA Methylation and Its Implications for Immune Evasion and Oncogenesis.

    Science.gov (United States)

    Kuss-Duerkop, Sharon K; Westrich, Joseph A; Pyeon, Dohun

    2018-02-13

    Viruses have evolved various mechanisms to evade host immunity and ensure efficient viral replication and persistence. Several DNA tumor viruses modulate host DNA methyltransferases for epigenetic dysregulation of immune-related gene expression in host cells. The host immune responses suppressed by virus-induced aberrant DNA methylation are also frequently involved in antitumor immune responses. Here, we describe viral mechanisms and virus-host interactions by which DNA tumor viruses regulate host DNA methylation to evade antiviral immunity, which may contribute to the generation of an immunosuppressive microenvironment during cancer development. Recent trials of immunotherapies have shown promising results to treat multiple cancers; however, a significant number of non-responders necessitate identifying additional targets for cancer immunotherapies. Thus, understanding immune evasion mechanisms of cancer-causing viruses may provide great insights for reversing immune suppression to prevent and treat associated cancers.

  9. DNA Tumor Virus Regulation of Host DNA Methylation and Its Implications for Immune Evasion and Oncogenesis

    Directory of Open Access Journals (Sweden)

    Sharon K. Kuss-Duerkop

    2018-02-01

    Full Text Available Viruses have evolved various mechanisms to evade host immunity and ensure efficient viral replication and persistence. Several DNA tumor viruses modulate host DNA methyltransferases for epigenetic dysregulation of immune-related gene expression in host cells. The host immune responses suppressed by virus-induced aberrant DNA methylation are also frequently involved in antitumor immune responses. Here, we describe viral mechanisms and virus–host interactions by which DNA tumor viruses regulate host DNA methylation to evade antiviral immunity, which may contribute to the generation of an immunosuppressive microenvironment during cancer development. Recent trials of immunotherapies have shown promising results to treat multiple cancers; however, a significant number of non-responders necessitate identifying additional targets for cancer immunotherapies. Thus, understanding immune evasion mechanisms of cancer-causing viruses may provide great insights for reversing immune suppression to prevent and treat associated cancers.

  10. Tumor-secreted miR-214 induces regulatory T cells: a major link between immune evasion and tumor growth

    Science.gov (United States)

    Yin, Yuan; Cai, Xing; Chen, Xi; Liang, Hongwei; Zhang, Yujing; Li, Jing; Wang, Zuoyun; Chen, Xiulan; Zhang, Wen; Yokoyama, Seiji; Wang, Cheng; Li, Liang; Li, Limin; Hou, Dongxia; Dong, Lei; Xu, Tao; Hiroi, Takachika; Yang, Fuquan; Ji, Hongbin; Zhang, Junfeng; Zen, Ke; Zhang, Chen-Yu

    2014-01-01

    An increased population of CD4+CD25highFoxp3+ regulatory T cells (Tregs) in the tumor-associated microenvironment plays an important role in cancer immune evasion. However, the underlying mechanism remains unclear. Here we observed an increased secretion of miR-214 in various types of human cancers and mouse tumor models. Tumor-secreted miR-214 was sufficiently delivered into recipient T cells by microvesicles (MVs). In targeted mouse peripheral CD4+ T cells, tumor-derived miR-214 efficiently downregulated phosphatase and tensin homolog (PTEN) and promoted Treg expansion. The miR-214-induced Tregs secreted higher levels of IL-10 and promoted tumor growth in nude mice. Furthermore, in vivo studies indicated that Treg expansion mediated by cancer cell-secreted miR-214 resulted in enhanced immune suppression and tumor implantation/growth in mice. The MV delivery of anti-miR-214 antisense oligonucleotides (ASOs) into mice implanted with tumors blocked Treg expansion and tumor growth. Our study reveals a novel mechanism through which cancer cell actively manipulates immune response via promoting Treg expansion. PMID:25223704

  11. Mechanisms of immune evasion and current status of checkpoint inhibitors in non-small cell lung cancer.

    Science.gov (United States)

    Qin, Angel; Coffey, David G; Warren, Edus H; Ramnath, Nithya

    2016-09-01

    In the past several years, immunotherapy has emerged as a viable treatment option for patients with advanced non-small cell lung cancer (NSCLC) without actionable driver mutations that have progressed on standard chemotherapy. We are also beginning to understand the methods of immune evasion employed by NSCLC which likely contribute to the 20% response rate to immunotherapy. It is also yet unclear what tumor or patient factors predict response to immunotherapy. The objectives of this review are (1) review the immunogenicity of NSCLC (2) describe the mechanisms of immune evasion (3) summarize efforts to target the anti-program death-1 (PD-1) and anti-program death-ligand 1(PD-L1) pathway (4) outline determinants of response to PD-1/PD-L1 therapy and (5) discuss potential future areas for research. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  12. Lymphoma: Immune Evasion Strategies

    International Nuclear Information System (INIS)

    Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul; Brown, Brian; Merad, Miriam; Brody, Joshua D.

    2015-01-01

    While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care

  13. Lymphoma: Immune Evasion Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brown, Brian [Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Merad, Miriam [Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brody, Joshua D., E-mail: joshua.brody@mssm.edu [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States)

    2015-04-30

    While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care.

  14. Brainstem tumors: Current management and future directions

    Directory of Open Access Journals (Sweden)

    Pablo F Recinos

    2012-01-01

    Full Text Available Tumors arising in the brainstem comprise 10-20% of all pediatric central nervous system (CNS tumors and account for a small percentage in adults. The prognosis for these tumors was considered uniformly poor prior to the era of modern neuroimaging and the location was fraught with disaster being considered a ′no man′s land′ for neurosurgeons. Following the introduction of advanced imaging modalities and neurophysiological monitoring, striking progress has occurred in the management of these lesions. Brainstem tumors are presently classified based on their anatomic location, focality, and histopathology. This article reviews the current classification of brainstem tumors, current management options, and future directions in the treatment for these rare tumors.

  15. Prostate tumor-derived exosomes down-regulate NKG2D expression on natural killer cells and CD8+ T cells: mechanism of immune evasion.

    Directory of Open Access Journals (Sweden)

    Marie Lundholm

    Full Text Available Tumor-derived exosomes, which are nanometer-sized extracellular vesicles of endosomal origin, have emerged as promoters of tumor immune evasion but their role in prostate cancer (PC progression is poorly understood. In this study, we investigated the ability of prostate tumor-derived exosomes to downregulate NKG2D expression on natural killer (NK and CD8+ T cells. NKG2D is an activating cytotoxicity receptor whose aberrant loss in cancer plays an important role in immune suppression. Using flow cytometry, we found that exosomes produced by human PC cells express ligands for NKG2D on their surface. The NKG2D ligand-expressing prostate tumor-derived exosomes selectively induced downregulation of NKG2D on NK and CD8+ T cells in a dose-dependent manner, leading to impaired cytotoxic function in vitro. Consistent with these findings, patients with castration-resistant PC (CRPC showed a significant decrease in surface NKG2D expression on circulating NK and CD8+ T cells compared to healthy individuals. Tumor-derived exosomes are likely involved in this NKG2D downregulation, since incubation of healthy lymphocytes with exosomes isolated from serum or plasma of CRPC patients triggered downregulation of NKG2D expression in effector lymphocytes. These data suggest prostate tumor-derived exosomes as down-regulators of the NKG2D-mediated cytotoxic response in PC patients, thus promoting immune suppression and tumor escape.

  16. Timing Tax Evasion

    OpenAIRE

    Dirk Niepelt

    2004-01-01

    Standard models of tax evasion implicitly assume that evasion is either fully detected, or not detected at all. Empirically, this is not the case, casting into doubt the traditional rationales for interior evasion choices. I propose two alternative, dynamic explanations for interior tax evasion rates: Fines depending on the duration of an evasion spell, and different vintages of income sources subject to aggregate risk and fixed costs when switched between evasion states. The dynamic approach...

  17. The current status and future directions of myxoma virus, a master in immune evasion.

    Science.gov (United States)

    Spiesschaert, Bart; McFadden, Grant; Hermans, Katleen; Nauwynck, Hans; Van de Walle, Gerlinde R

    2011-06-09

    Myxoma virus (MYXV) gained importance throughout the twentieth century because of the use of the highly virulent Standard Laboratory Strain (SLS) by the Australian government in the attempt to control the feral Australian population of Oryctolagus cuniculus (European rabbit) and the subsequent illegal release of MYXV in Europe. In the European rabbit, MYXV causes a disease with an exceedingly high mortality rate, named myxomatosis, which is passively transmitted by biting arthropod vectors. MYXV still has a great impact on European rabbit populations around the world. In contrast, only a single cutaneous lesion, restricted to the point of inoculation, is seen in its natural long-term host, the South-American Sylvilagus brasiliensis and the North-American S. Bachmani. Apart from being detrimental for European rabbits, however, MYXV has also become of interest in human medicine in the last two decades for two reasons. Firstly, due to the strong immune suppressing effects of certain MYXV proteins, several secreted virus-encoded immunomodulators (e.g. Serp-1) are being developed to treat systemic inflammatory syndromes such as cardiovascular disease in humans. Secondly, due to the inherent ability of MYXV to infect a broad spectrum of human cancer cells, the live virus is also being developed as an oncolytic virotherapeutic to treat human cancer. In this review, an update will be given on the current status of MYXV in rabbits as well as its potential in human medicine in the twenty-first century.

  18. The current status and future directions of myxoma virus, a master in immune evasion

    Directory of Open Access Journals (Sweden)

    Spiesschaert Bart

    2011-06-01

    Full Text Available Abstract Myxoma virus (MYXV gained importance throughout the twentieth century because of the use of the highly virulent Standard Laboratory Strain (SLS by the Australian government in the attempt to control the feral Australian population of Oryctolagus cuniculus (European rabbit and the subsequent illegal release of MYXV in Europe. In the European rabbit, MYXV causes a disease with an exceedingly high mortality rate, named myxomatosis, which is passively transmitted by biting arthropod vectors. MYXV still has a great impact on European rabbit populations around the world. In contrast, only a single cutaneous lesion, restricted to the point of inoculation, is seen in its natural long-term host, the South-American Sylvilagus brasiliensis and the North-American S. Bachmani. Apart from being detrimental for European rabbits, however, MYXV has also become of interest in human medicine in the last two decades for two reasons. Firstly, due to the strong immune suppressing effects of certain MYXV proteins, several secreted virus-encoded immunomodulators (e.g. Serp-1 are being developed to treat systemic inflammatory syndromes such as cardiovascular disease in humans. Secondly, due to the inherent ability of MYXV to infect a broad spectrum of human cancer cells, the live virus is also being developed as an oncolytic virotherapeutic to treat human cancer. In this review, an update will be given on the current status of MYXV in rabbits as well as its potential in human medicine in the twenty-first century. Table of contents Abstract 1. The virus 2. History 3. Pathogenesis and disease symptoms 4. Immunomodulatory proteins of MYXV 4.1. MYXV proteins with anti-apoptotic functions 4.1.1. Inhibition of pro-apoptotic molecules 4.1.2. Inhibition by protein-protein interactions by ankyrin repeat viral proteins 4.1.3. Inhibition of apoptosis by enhancing the degradation of cellular proteins 4.1.4. Inhibition of apoptosis by blocking host Protein Kinase R (PKR 4

  19. Immunological Evasion in Glioblastoma

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    Roxana Magaña-Maldonado

    2016-01-01

    Full Text Available Glioblastoma is the most aggressive tumor in Central Nervous System in adults. Among its features, modulation of immune system stands out. Although immune system is capable of detecting and eliminating tumor cells mainly by cytotoxic T and NK cells, tumor microenvironment suppresses an effective response through recruitment of modulator cells such as regulatory T cells, monocyte-derived suppressor cells, M2 macrophages, and microglia as well as secretion of immunomodulators including IL-6, IL-10, CSF-1, TGF-β, and CCL2. Other mechanisms that induce immunosuppression include enzymes as indolamine 2,3-dioxygenase. For this reason it is important to develop new therapies that avoid this immune evasion to promote an effective response against glioblastoma.

  20. Cultural Norms, the Persistence of Tax Evasion, and Economic Growth

    OpenAIRE

    Dimitrios Varvarigos

    2015-01-01

    I study the effects of tax evasion on economic growth by focusing on the cultural aspects of tax compliance and their effect on the extensive margin of tax evasion. A cultural norm that determines the contemptibility of tax dodging practices links the past incidence of tax evasion with the tax payers’ current incentives to conceal sources of income. This dynamic complementarity may lead to multiple equilibria in the evolution of tax evasion. Due to the latter’s effect on capital accumulation,...

  1. Current Concepts on Gastric Carcinoid Tumors

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    George C. Nikou

    2012-01-01

    Full Text Available Gastric carcinoid tumors (GCs are rare lesions representing less than 10% of carcinoid tumors and less than 1% of all stomach neoplasms. There are three distinct types of gastric carcinoids; type I includes the vast majority (70–85% of these neoplasms that are closely linked to chronic atrophic gastritis. Type II which accounts for 5–10 %, is associated with Zollinger-Ellison syndrome and often occurs in the context of multiple endocrine neoplasia type 1. Type III, finally, represents 15–25% of gastric carcinoids and is characterized by a far more aggressive course. The optimal clinical approach to GCs remains to be elucidated, depending upon type, size, and number of carcinoids. While there is universal agreement about the surgical treatment of type III GCs, current options for type I and II include simple surveillance, endoscopic polypectomy, surgical excision associated with or without surgical antrectomy, or total gastrectomy. Moreover, the introduction of somatostatin analogues could represent another therapeutic option.

  2. Current concepts of salivary gland tumors

    Directory of Open Access Journals (Sweden)

    Raj Kumar Badam

    2015-01-01

    Full Text Available The embryonic development of salivary glands is a complex process that creates compact, highly organized secretory organs with functions essential for oral health. The development is an example of branching morphogenesis, recent research found to involve unexpectedly dynamic cell motility, and novel regulatory pathways. Numerous growth factors, extracellular matrix molecules, gene regulatory pathways, and mechanical forces contribute to salivary gland morphogenesis, but local gene regulation and morphological changes appear to play particularly notable roles. Salivary gland tumors are one of the most complex and relatively rare groups of lesions encountered in oral pathology practice. Their complexity is attributed to the heterogeneity of the cells of origin of these lesions. Frequent overlap of microscopic features among various neoplasms makes us sometimes even to differentiate benign and malignant lesions leading to a diagnostic dilemma. Here, we review and summarize the current concepts regarding the histogenetic and morphogenetic concepts of salivary gland tumors and their relevance to routine diagnosis and classification of these lesions.

  3. Current opinion on PET for gastrointestinal tumors

    International Nuclear Information System (INIS)

    Diederichs, C.G.; Schirrmeister, H.; Staib, L.

    2000-01-01

    The benefit of FDG-PET for restaging of colorectal carcinoma and for the differentiation of indeterminate hepatic lesions is well-documented. Accuracies of FDG-PET for recurrence, lymph node status and the detection of distant metastases are higher compared with computed tomography, for example. For other epithelial gastrointestinal tumors similar results have also been demonstrated in smaller trials or case presentations. The differentiation of recurrent rectal carcinoma from scar and PET for endocrine tumors are described elsewhere (Der Nuklearmediziner PET II, in preparation). Almost no data exist for rare tumors like anal carcinoma or tumors of the small intestines. For hepatocellular carcinoma, FDG-PET has a high positive predictive value, and the intensity of the uptake correlates well with grading. However, FDG-PET is not suitable for the exclusion of hepatocellular carcinoma due to insufficient sensitivity. The differentiation of benign and malignant pancreatic masses works well for selected patients. FDG-PET for lymph node staging is at least as accurate as conventional staging, and for the detection of distant metastases FDG-PET is superior compared with conventional staging. Few data exist on therapy control of gastrointestinal tumors. (orig.) [de

  4. Steering and evasion assist

    NARCIS (Netherlands)

    Dang, T.; Desens, J.; Franke, U.; Gavrila, D.; Schäfers, L.; Ziegler, W.; Eskandarian, A.

    2012-01-01

    Steering and evasion assistance defines a new and future class of driver assistance systems to avoid an impending collision with other traffic participants. Dynamic and kinematic considerations reveal that an evasive steering maneuver has high potential for collision avoidance in many driving

  5. Deciding on Tax Evasion

    DEFF Research Database (Denmark)

    Boll, Karen

    2015-01-01

    Purpose – The purpose of this paper is to analyse everyday reasoning in public administration. This is done by focusing on front line tax inspectors’ decisions about tax evasion. Design/methodology/approach – The paper presents ethnography of bureaucracy and field audits. The material stems from...... fieldwork conducted in the Central Customs and Tax Administration. Findings – The paper shows that the tax inspectors reason about tax evasion in a casuistic manner. They pay attention to similar cases and to particular circumstances of the individual cases. In deciding on tax evasion, the inspectors do...

  6. Complex Immune Evasion Strategies in Classical Hodgkin Lymphoma.

    Science.gov (United States)

    Wein, Frederik; Weniger, Marc A; Höing, Benedikt; Arnolds, Judith; Hüttmann, Andreas; Hansmann, Martin-Leo; Hartmann, Sylvia; Küppers, Ralf

    2017-12-01

    The cellular microenvironment in classical Hodgkin lymphoma (cHL) is dominated by a mixed infiltrate of inflammatory cells with typically only about 1% Hodgkin and Reed/Sternberg (HRS) tumor cells. T cells are usually the largest population of cells in the cHL microenvironment, encompassing T helper (Th) cells, regulatory T cells (Tregs), and cytotoxic T cells. Th cells and Tregs presumably provide essential survival signals for HRS cells. Tregs are also involved in rescuing HRS cells from antitumor immune responses. An understanding of the immune evasion strategies of HRS cells is not only relevant for a characterization of the pathophysiology of cHL but is also clinically relevant, given the current treatment approaches targeting checkpoint inhibitors. Here, we characterized the cHL-specific CD4 + T-cell infiltrate regarding its role in immune evasion. Global gene expression analysis of CD4 + Th cells and Tregs isolated from cHL lymph nodes and reactive tonsils revealed that Treg signatures were enriched in CD4 + Th cells of cHL. Hence, HRS cells may induce Treg differentiation in Th cells, a conclusion supported by in vitro studies with Th cells and cHL cell lines. We also found evidence for immune-suppressive purinergic signaling and a role of the inhibitory receptor-ligand pairs B- and T-cell lymphocyte attenuator-herpesvirus entry mediator and CD200R-CD200 in promoting immune evasion. Taken together, this study highlights the relevance of Treg induction and reveals new immune checkpoint-driven immune evasion strategies in cHL. Cancer Immunol Res; 5(12); 1122-32. ©2017 AACR . ©2017 American Association for Cancer Research.

  7. Tax Evasion and Inequality

    DEFF Research Database (Denmark)

    Alstadsæter, Annette; Johannesen, Niels; Zucman, Gabriel

    2017-01-01

    .01% of the wealth distribution, a group that includes households with more than $45 million in net wealth. A simple model of the supply of tax evasion services can explain why evasion rises steeply with wealth. Taking tax evasion into account increases the rise in inequality seen in tax data since the 1970s......This paper attempts to estimate the size and distribution of tax evasion in rich countries. We combine random audits—the key source used to study tax evasion so far—with new micro-data leaked from large offshore financial institutions—HSBC Switzerland (“Swiss leaks”) and Mossack Fonseca (“Panama...... Papers”)—matched to population-wide wealth records in Norway, Sweden, and Denmark. We find that tax evasion rises sharply with wealth, a phenomenon random audits fail to capture. On average about 3% of personal taxes are evaded in Scandinavia, but this figure rises to close to 30% in the top 0...

  8. An update: Epstein-Barr virus and immune evasion via microRNA regulation.

    Science.gov (United States)

    Zuo, Lielian; Yue, Wenxin; Du, Shujuan; Xin, Shuyu; Zhang, Jing; Liu, Lingzhi; Li, Guiyuan; Lu, Jianhong

    2017-06-01

    Epstein-Barr virus (EBV) is an oncogenic virus that ubiquitously establishes life-long persistence in humans. To ensure its survival and maintain its B cell transformation function, EBV has developed powerful strategies to evade host immune responses. Emerging evidence has shown that microRNAs (miRNAs) are powerful regulators of the maintenance of cellular homeostasis. In this review, we summarize current progress on how EBV utilizes miRNAs for immune evasion. EBV encodes miRNAs targeting both viral and host genes involved in the immune response. The miRNAs are found in two gene clusters, and recent studies have demonstrated that lack of these clusters increases the CD4 + and CD8 + T cell response of infected cells. These reports strongly indicate that EBV miRNAs are critical for immune evasion. In addition, EBV is able to dysregulate the expression of a variety of host miRNAs, which influence multiple immune-related molecules and signaling pathways. The transport via exosomes of EBV-regulated miRNAs and viral proteins contributes to the construction and modification of the inflammatory tumor microenvironment. During EBV immune evasion, viral proteins, immune cells, chemokines, pro-inflammatory cytokines, and pro-apoptosis molecules are involved. Our increasing knowledge of the role of miRNAs in immune evasion will improve the understanding of EBV persistence and help to develop new treatments for EBV-associated cancers and other diseases.

  9. Evasion of Apoptosis as a Cellular Stress Response in Cancer

    Directory of Open Access Journals (Sweden)

    Simone Fulda

    2010-01-01

    Full Text Available One of the hallmarks of human cancers is the intrinsic or acquired resistance to apoptosis. Evasion of apoptosis can be part of a cellular stress response to ensure the cell's survival upon exposure to stressful stimuli. Apoptosis resistance may contribute to carcinogenesis, tumor progression, and also treatment resistance, since most current anticancer therapies including chemotherapy as well as radio- and immunotherapies primarily act by activating cell death pathways including apoptosis in cancer cells. Hence, a better understanding of the molecular mechanisms regarding how cellular stress stimuli trigger antiapoptotic mechanisms and how this contributes to tumor resistance to apoptotic cell death is expected to provide the basis for a rational approach to overcome apoptosis resistance mechanisms in cancers.

  10. Mechanism of immune evasion in breast cancer

    Science.gov (United States)

    Wang, Mozhi; Zhang, Changwang; Song, Yongxi; Wang, Zhenning; Wang, Yaojia; Luo, Fang; Xu, Yujie; Zhao, Yi; Wu, Zhonghua; Xu, Yingying

    2017-01-01

    Breast cancer (BC) is the most common malignant tumor among women, with high morbidity and mortality. Its onset, development, metastasis, and prognosis vary among individuals due to the interactions between tumors and host immunity. Many diverse mechanisms have been associated with BC, with immune evasion being the most widely studied to date. Tumor cells can escape from the body’s immune response, which targets abnormal components and foreign bodies, using different approaches including modification of surface antigens and modulation of the surrounding environment. In this review, we summarize the mechanisms and factors that impact the immunoediting process and analyze their functions in detail. PMID:28352189

  11. Experimental study of anti-tumor activity of direct current

    International Nuclear Information System (INIS)

    Ito, Hisao; Hashimoto, Shozo

    1989-01-01

    The anti-tumor activity of direct current combined with radiation was studied. The experiments were performed with fibrosarcomas (FSA, NFSA) syngenetic to C3H mice. Direct current (0.6mA, 120min) alone was effective to reduce the tumor sizes, but could not cure the tumors. When the direct current therapy (DC therapy) was combined with radiation the DC therapy following radiation was more effective than that before radiation. Using TCD 50 assay, the DC therapy enhanced the effect of a single dose of radiation with the dose-modifying factor of 1.2. However, tumor control rates by the combination therapy were more improved at the smaller doses of radiation than at the larger ones. When the single DC therapy (0.6mA, 120min) was applied immediately after the first radiation of fractionated one the combination therapy still showed the enhanced effect. However, both DC therapy and the radiation therapy were divided in three fractions, and the DC therapy (0.6mA, 40min) was applied after each radiation. Tumor growth retardation by the combination therapy was no different from that by radiation alone. This result suggests that there might be a minimum required dose of coulombs to show the effect of the combination therapy. (author)

  12. Conic surveillance evasion

    NARCIS (Netherlands)

    Lewin, J.; Olsder, G.J.

    1979-01-01

    A surveillance-evasion differential game of degree with a detection zone in the shape of a two-dimensional cone is posed. The nature of the optimal strategies and the singular phenomena of the value function are described and correlated to subsets of the space of all possible parameter combinations,

  13. Current Perspectives on Desmoid Tumors: The Mayo Clinic Approach

    Directory of Open Access Journals (Sweden)

    Scott Okuno

    2011-08-01

    Full Text Available Desmoid tumors are a rare group of locally aggressive, non malignant tumors of fibroblastic origin that can lead to significant morbidity due to local invasion. Despite advances in the understanding of these tumors, their natural history is incompletely understood and the optimal treatment is still a matter of debate. Local control is the main goal of treatment and there has been a change in philosophy regarding the management of these tumors from aggressive surgical resection to function preservation. A multidisciplinary approach is essential to plan local control with acceptable morbidity. The current Mayo Clinic algorithm for the treatment of these tumors is based on institutional experience and the available evidence in the literature: asymptomatic/non progressive lesions away from vital structures are managed with observation and regular imaging; primary or recurrent desmoid tumors which are symptomatic or progressive or near vital structures are managed with wide surgical resection when wide surgical margins are possible with minimal functional and cosmetic loss. When positive or close surgical margins are likely, surgical resection with adjuvant radiotherapy or definitive radiotherapy is preferred. If likely functional or cosmetic deficit is unacceptable, radiotherapy is the treatment of choice. Unresectable lesions are considered for radiotherapy, chemotherapy or newer modalities however an unresectable lesion associated with a painful, functionless, infected extremity is managed with an amputation.

  14. Current Perspectives on Desmoid Tumors: The Mayo Clinic Approach

    International Nuclear Information System (INIS)

    Joglekar, Siddharth B.; Rose, Peter S.; Sim, Franklin; Okuno, Scott; Petersen, Ivy

    2011-01-01

    Desmoid tumors are a rare group of locally aggressive, non malignant tumors of fibroblastic origin that can lead to significant morbidity due to local invasion. Despite advances in the understanding of these tumors, their natural history is incompletely understood and the optimal treatment is still a matter of debate. Local control is the main goal of treatment and there has been a change in philosophy regarding the management of these tumors from aggressive surgical resection to function preservation. A multidisciplinary approach is essential to plan local control with acceptable morbidity. The current Mayo Clinic algorithm for the treatment of these tumors is based on institutional experience and the available evidence in the literature: asymptomatic/non progressive lesions away from vital structures are managed with observation and regular imaging; primary or recurrent desmoid tumors which are symptomatic or progressive or near vital structures are managed with wide surgical resection when wide surgical margins are possible with minimal functional and cosmetic loss. When positive or close surgical margins are likely, surgical resection with adjuvant radiotherapy or definitive radiotherapy is preferred. If likely functional or cosmetic deficit is unacceptable, radiotherapy is the treatment of choice. Unresectable lesions are considered for radiotherapy, chemotherapy or newer modalities however an unresectable lesion associated with a painful, functionless, infected extremity is managed with an amputation

  15. Evasion in the plane

    Science.gov (United States)

    Leitmann, G.; Liu, H. S.

    1977-01-01

    Dynamic systems were considered subject to control by two agents, one of whom desires that no trajectory of the system emanating from outside a given set, intersects that set no matter what the admissible actions of the other agent. Constructive conditions sufficient to yield a feedback control for the agent seeking avoidance were employed to deduce an evader control for the planar pursuit-evasion problem with bounded normal accelerations.

  16. Herpesvirus Evasion of Natural Killer Cells.

    Science.gov (United States)

    De Pelsmaeker, Steffi; Romero, Nicolas; Vitale, Massimo; Favoreel, Herman W

    2018-06-01

    Natural killer (NK) cells play an important role in the host response against viral infections and cancer development. They are able to kill virus-infected and tumor cells, and they produce different important cytokines that stimulate the antiviral and antitumor adaptive immune response, particularly interferon gamma. NK cells are of particular importance in herpesvirus infections, which is illustrated by systemic and life-threatening herpesvirus disease symptoms in patients with deficiencies in NK cell activity and by the myriad of reports describing herpesvirus NK cell evasion strategies. The latter is particularly obvious for cytomegaloviruses, but increasing evidence indicates that most, if not all, members of the herpesvirus family suppress NK cell activity to some extent. This review discusses the different NK cell evasion strategies described for herpesviruses and how this knowledge may translate to clinical applications. Copyright © 2018 American Society for Microbiology.

  17. The "Fas counterattack" is not an active mode of tumor immune evasion in colorectal cancer with high-level microsatellite instability.

    LENUS (Irish Health Repository)

    Houston, Aileen M

    2012-02-03

    Microsatellite instability (MSI) is an alternative pathway of colorectal carcinogenesis. It is found in 10% to 15% of sporadic colorectal neoplasms and is characterized by failure of the DNA mismatch-repair system. High-level MSI (MSI-H) is associated with tumor-infiltrating lymphocytes (TILs) and a favorable prognosis. Expression of Fas ligand (FasL\\/CD95L) by cancer cells may mediate tumor immune privilege by inducing apoptosis of antitumor immune cells. The aim of this study was to investigate the relationship between FasL expression and MSI status in primary colon tumors. Using immunohistochemistry, we detected FasL expression in 91 colorectal carcinoma specimens, previously classified according to the level of MSI as MSI-H (n = 26), MSI-low (MSI-L) (n = 29), and microsatellite stable (n = 36). Tumor-infiltrating lymphocyte density was quantified by immunohistochemical staining for CD3. MSI-H tumors were significantly associated with reduced frequency (P = .04) and intensity (P = .066) of FasL expression relative to non-MSI-H (ie, microsatellite stable and MSI-L) tumors. Higher FasL staining intensity correlated with reduced TIL density (P = .059). Together, these findings suggest that the abundance of TILs found in MSI-H tumors may be due to the failure of these tumor cells to up-regulate FasL and may explain, in part, the improved prognosis associated with these tumors.

  18. PHYLLOID TUMORS OF MAMMARY GLANDS. CURRENT STATE OF THE PROBLEM

    Directory of Open Access Journals (Sweden)

    A. D. Zikiryakhodzhaev

    2017-01-01

    Full Text Available Phylloid (leaf-shaped breast tumors are a rare disease and constitute 0.3–0.5% of all breast tumors. Due to the rare frequency of occurrence, as well as the small number of randomized studies that have been conducted on this pathology, there is currently no standardized approach to the diagnosis and treatment of phylloid tumors. The reports about these rare cases appearing in the literature are, as a rule, descriptive, which only emphasizes the difficulty of differential diagnosis, the development of the correct tactics for treating such patients. In connection with the rarity, it is very difficult to diagnose correctly this pathology, which requires a highly qualified doctor as a diagnostician in the initial contact with such a patient, and a pathologist doctor who establishes the final morphological diagnosis. Often, leaf-shaped tumors are mistaken for mammary fibroadenomas. Such difficulties in correct diagnosis in the preoperative period can lead to errors in the planning of treatment. Also, the recommendations for the treatment of patients with this diagnosis are not fully understood, since up to now there are no accepted treatment standards in both Russian and foreign recommendations. Due to the fact that this pathology of mammary glands is rare, the principles of treatment are based on small retrospective studies and clinical observations. In this review, we will discuss the results of major retrospective studies, including data on epidemiology, etiology, diagnostic approach, strategies and results of treatment of this complex group of breast pathologies.

  19. Treatment of giant cell tumor of bone: Current concepts.

    Science.gov (United States)

    Puri, Ajay; Agarwal, Manish

    2007-04-01

    Giant cell tumor (GCT) of bone though one of the commonest bone tumors encountered by an orthopedic surgeon continues to intrigue treating surgeons. Usually benign, they are locally aggressive and may occasionally undergo malignant transformation. The surgeon needs to strike a balance during treatment between reducing the incidence of local recurrence while preserving maximal function.Differing opinions pertaining to the use of adjuvants for extension of curettage, the relative role of bone graft or cement to pack the defect and the management of recurrent lesions are some of the issues that offer topics for eternal debate.Current literature suggests that intralesional curettage strikes the best balance between controlling disease and preserving optimum function in the majority of the cases though there may be occasions where the extent of the disease mandates resection to ensure adequate disease clearance.An accompanying treatment algorithm helps outline the management strategy in GCT.

  20. Treatment of giant cell tumor of bone: Current concepts

    Directory of Open Access Journals (Sweden)

    Puri Ajay

    2007-01-01

    Full Text Available Giant cell tumor (GCT of bone though one of the commonest bone tumors encountered by an orthopedic surgeon continues to intrigue treating surgeons. Usually benign, they are locally aggressive and may occasionally undergo malignant transformation. The surgeon needs to strike a balance during treatment between reducing the incidence of local recurrence while preserving maximal function. Differing opinions pertaining to the use of adjuvants for extension of curettage, the relative role of bone graft or cement to pack the defect and the management of recurrent lesions are some of the issues that offer topics for eternal debate. Current literature suggests that intralesional curettage strikes the best balance between controlling disease and preserving optimum function in the majority of the cases though there may be occasions where the extent of the disease mandates resection to ensure adequate disease clearance. An accompanying treatment algorithm helps outline the management strategy in GCT.

  1. Forms of Manifestation regarding Tax Evasion: New Approaches

    Directory of Open Access Journals (Sweden)

    Alia Gabriela DUŢĂ

    2015-09-01

    Full Text Available Tax evasion has existed, exists and will exist as long as the state and the tax will continue to exist, but the forms and ways of achievement are perfectly in time. In terms of how can be committed, the ratio that exists between this phenomenon and the current legislation, tax evasion, there are two manifestations: the lawful tax avoidance (performed at the shelter law; unlawful tax evasion (fraudulent or fraud. In terms of space can be identified: tax evasion and tax avoidance at national and international level. In recent years circumvention actions are transferred, increasingly more inside from national tax systems across state borders, action driven by trends economic globalization, political and social.

  2. Complex pattern of immune evasion in MSI colorectal cancer.

    Science.gov (United States)

    Ozcan, Mine; Janikovits, Jonas; von Knebel Doeberitz, Magnus; Kloor, Matthias

    2018-01-01

    Mismatch repair (MMR)-deficient cancers accumulate multiple insertion/deletion mutations at coding microsatellites (cMS), which give rise to frameshift peptide neoantigens. The high mutational neoantigen load of MMR-deficient cancers is reflected by pronounced anti-tumoral immune responses of the host and high responsiveness towards immune checkpoint blockade. However, immune evasion mechanisms can interfere with the immune response against MMR-deficient tumors. We here performed a comprehensive analysis of immune evasion in MMR-deficient colorectal cancers, focusing on HLA class I-mediated antigen presentation. 72% of MMR-deficient colorectal cancers of the DFCI database harbored alterations affecting genes involved in HLA class I-mediated antigen presentation, and 54% of these mutations were predicted to abrogate function. Mutations affecting the HLA class I transactivator NLRC5 were observed as a potential new immune evasion mechanism in 26% (6% abrogating) of the analyzed tumors. NLRC5 mutations in MMR-deficient cancers were associated with decreased levels of HLA class I antigen expression. In summary, the majority of MMR-deficient cancers display mutations interfering with HLA class I antigen presentation that reflect active immune surveillance and immunoselection during tumor development. Clinical studies focusing on immune checkpoint blockade in MSI cancer should account for the broad variety of immune evasion mechanisms as potential biomarkers of therapy success.

  3. Businessmen´s tax evasions

    OpenAIRE

    Karásková, Veronika

    2011-01-01

    The main goal of this bachelor thesis is categorize businessmen's tax evasions at personal income tax and find out their portion on total tax evasions. In the first chapter I focus on tax avoidance and tax evasion, causes of tax evasion and his measurement. Next parts of this thesis focus on businessmen's tax evasion at personal income tax. In the second part I describe some very frequented cases of tax evasions revealed by revenue authorities. In the last part I analyse these tax evasions, c...

  4. Current diagnostic approach of bone tumors in childhood

    International Nuclear Information System (INIS)

    Torre, Marcia Barbosa; Scatigno Neto, Andre

    1995-01-01

    The authors analyze the magnetic resonance imaging (MRI) as the imaging modality of choice for evaluation of patients with bone tumors or soft tissue tumors. The advent of such a sensitive imaging modality is fortuitous and coincides with a recent change in the therapeutic approach to primary bone tumors. MRI is extremely valuable in monitoring the tumor response to the initial chemotherapy and is accurate defining the margins of tumor, facilitating planning of limb salvage surgical procedures. (author). 5 refs., 8 figs

  5. Tax Evasion in Romania: New Approaches

    Directory of Open Access Journals (Sweden)

    Sebastian George Perpelea

    2016-11-01

    Full Text Available Tax evasion has existed and will exist, and moreover, it will always be "creative and active" and will represent a current problem for any state. With the emergence of taxes also the phenomenon of "escape" from their path emerged, since the taxes determine the individuals to adopt an avoidance behavior or, at the best, to mitigate them. This phenomenon occurs in all the countries, obviously to varying degrees, starting from the level of individuals, to the level of large companies, it being favored by the legislative hiatuses, sometimes it being even encouraged by legislation, which legislation is drafted and voted by very the people. Thus, in our approach we will try to emphasize the actual causes of tax evasion and the consequences of this phenomenon on the society and the economy.

  6. Evasion of Cell Senescence Leads to Medulloblastoma Progression

    Directory of Open Access Journals (Sweden)

    Lukas Tamayo-Orrego

    2016-03-01

    Full Text Available How brain tumors progress from precancerous lesions to advanced cancers is not well understood. Using Ptch1+/− mice to study medulloblastoma progression, we found that Ptch1 loss of heterozygosity (LOH is an early event that is associated with high levels of cell senescence in preneoplasia. In contrast, advanced tumors have evaded senescence. Remarkably, we discovered that the majority of advanced medulloblastomas display either spontaneous, somatic p53 mutations or Cdkn2a locus inactivation. Consistent with senescence evasion, these p53 mutations are always subsequent to Ptch1 LOH. Introduction of a p53 mutation prevents senescence, accelerates tumor formation, and increases medulloblastoma incidence. Altogether, our results show that evasion of senescence associated with Ptch1 LOH allows progression to advanced tumors.

  7. Childhood brain tumors: epidemiology, current management and future directions.

    Science.gov (United States)

    Pollack, Ian F; Jakacki, Regina I

    2011-07-26

    Brain tumors are the most common solid tumors in children. With the increasingly widespread availability of MRI, the incidence of childhood brain tumors seemed to rise in the 1980s, but has subsequently remained relatively stable. However, management of brain tumors in children has evolved substantially during this time, reflecting refinements in classification of tumors, delineation of risk groups within histological subsets of tumors, and incorporation of molecular techniques to further define tumor subgroups. Although considerable progress has been made in the outcomes of certain tumors, prognosis in other childhood brain tumor types is poor. Among the tumor groups with more-favorable outcomes, attention has been focused on reducing long-term morbidity without sacrificing survival rates. Studies for high-risk groups have examined the use of intensive therapy or novel, molecularly targeted approaches to improve disease control rates. In addition to reviewing the literature and providing an overview of the complexities in diagnosing childhood brain tumors, we will discuss advances in the treatment and categorization of several tumor types in which progress has been most apparent, as well as those in which improvements have been lacking. The latest insights from molecular correlative studies that hold potential for future refinements in therapy will also be discussed.

  8. Current status of indium-111 labeled bleomycin for tumor detection

    International Nuclear Information System (INIS)

    Taylor, R.D.; Blahd, W.H.

    1975-01-01

    The advantages and disadvantages of 111 In-labeled bleomycin for tumor detection are briefly mentioned. Indium-111 labeled bleomycin does localize in human tumors. However, its role in tumor detection and staging as compared with 67 Ga is still somewhat controversial

  9. Current diagnostic approach of bone tumors in childhood; Abordagem diagnostica atual dos tumores osseos na infancia

    Energy Technology Data Exchange (ETDEWEB)

    Torre, Marcia Barbosa; Scatigno Neto, Andre [Sao Paulo Univ., SP (Brazil). Faculdade de Medicina. Hospital das Clinicas

    1995-09-01

    The authors analyze the magnetic resonance imaging (MRI) as the imaging modality of choice for evaluation of patients with bone tumors or soft tissue tumors. The advent of such a sensitive imaging modality is fortuitous and coincides with a recent change in the therapeutic approach to primary bone tumors. MRI is extremely valuable in monitoring the tumor response to the initial chemotherapy and is accurate defining the margins of tumor, facilitating planning of limb salvage surgical procedures. (author). 5 refs., 8 figs.

  10. Tumor and target delineation: current research and future challenges

    International Nuclear Information System (INIS)

    Austin-Seymour, Mary; Chen, George T.Y.; Rosenman, Julian; Michalski, Jeff; Lindsley, Karen; Goitein, Michael

    1995-01-01

    In the past decade, significant progress has been made in the imaging of tumors, three dimensional (3D) treatment planning, and radiation treatment delivery. At this time one of the greatest challenges for conformal radiation therapy is the accurate delineation of tumor and target volumes. The physician encounters many uncertainties in the process of defining both tumor and target. The sources of these uncertainties are discussed, as well as the issues requiring study to reduce these uncertainties

  11. Current applications and future prospects of nanomaterials in tumor therapy

    Directory of Open Access Journals (Sweden)

    Huang Y

    2017-03-01

    Full Text Available Yu Huang,1 Chao-Qiang Fan,1 Hui Dong,1 Su-Min Wang,1 Xiao-Chao Yang,2 Shi-Ming Yang1 1Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, People’s Republic of China; 2Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, People’s Republic of China Abstract: Tumors are one of the most serious human diseases and cause numerous global deaths per year. In spite of many strategies applied in tumor therapy, such as radiation therapy, chemotherapy, surgery, and a combination of these treatments, tumors are still the foremost killer worldwide among human diseases, due to their specific limitations, such as multidrug resistance and side effects. Therefore, it is urgent and necessary to develop new strategies for tumor therapy. Recently, the fast development of nanoscience has paved the way for designing new strategies to treat tumors. Nanomaterials have shown great potential in tumor therapy, due to their unique properties, including passive targeting, hyperthermia effects, and tumor-specific inhibition. This review summarizes the recent progress using the innate antitumor properties of metallic and nonmetallic nanomaterials to treat tumors, and related challenges and prospects are discussed. Keywords: tumor, nanomaterials, nanoparticles, nanotechnology

  12. Immune evasion in cancer: Mechanistic basis and therapeutic strategies.

    Science.gov (United States)

    Vinay, Dass S; Ryan, Elizabeth P; Pawelec, Graham; Talib, Wamidh H; Stagg, John; Elkord, Eyad; Lichtor, Terry; Decker, William K; Whelan, Richard L; Kumara, H M C Shantha; Signori, Emanuela; Honoki, Kanya; Georgakilas, Alexandros G; Amin, Amr; Helferich, William G; Boosani, Chandra S; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I; Azmi, Asfar S; Keith, W Nicol; Bilsland, Alan; Bhakta, Dipita; Halicka, Dorota; Fujii, Hiromasa; Aquilano, Katia; Ashraf, S Salman; Nowsheen, Somaira; Yang, Xujuan; Choi, Beom K; Kwon, Byoung S

    2015-12-01

    Cancer immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Although considerable progress has been made in understanding how cancers evade destructive immunity, measures to counteract tumor escape have not kept pace. There are a number of factors that contribute to tumor persistence despite having a normal host immune system. Immune editing is one of the key aspects why tumors evade surveillance causing the tumors to lie dormant in patients for years through "equilibrium" and "senescence" before re-emerging. In addition, tumors exploit several immunological processes such as targeting the regulatory T cell function or their secretions, antigen presentation, modifying the production of immune suppressive mediators, tolerance and immune deviation. Besides these, tumor heterogeneity and metastasis also play a critical role in tumor growth. A number of potential targets like promoting Th1, NK cell, γδ T cell responses, inhibiting Treg functionality, induction of IL-12, use of drugs including phytochemicals have been designed to counter tumor progression with much success. Some natural agents and phytochemicals merit further study. For example, use of certain key polysaccharide components from mushrooms and plants have shown to possess therapeutic impact on tumor-imposed genetic instability, anti-growth signaling, replicative immortality, dysregulated metabolism etc. In this review, we will discuss the advances made toward understanding the basis of cancer immune evasion and summarize the efficacy of various therapeutic measures and targets that have been developed or are being investigated to enhance tumor rejection. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Current concepts in diagnosis of unusual salivary gland tumors

    Directory of Open Access Journals (Sweden)

    Ajay Kumar Bansal

    2012-01-01

    Full Text Available Salivary gland tumors are relatively uncommon and account for approximately 3-6% of all neoplasms of the head and neck. Tumors mostly involve the major salivary glands, 42.9-90% of which occur in the parotid glands and 8-19.5% in the sub-mandibular glands; tumors in the sub-lingual glands being uncommon. Despite the plethora of different malignant salivary gland tumor presented to pathologists for diagnosis, there is consensus on a limited number of pathologic observations that determine treatment and outcome. There are few absolutes in salivary gland tumor diagnosis given the marked spectrum and overlap of differentiated cell types that participate in the numerous benign and malignant tumors. Thus, there are enumerating antibodies that may be helpful in resolving difficult differential diagnoses when applied with astute morphologic correlation. In general, immunohistochemistry as an ancillary diagnostic tool should be used sparingly and wisely as a morphologic adjunct because of the lack of specificity of many markers for specific histologic tumor types. The aim of this review is to discuss the molecular profiling of salivary gland neoplasms and correlate this with histogenesis of salivary gland neoplasms. We have elected to discuss and illustrate some of the unusual salivary gland tumors that the practicing pathologist find difficult to diagnose. These have been selected because they readily simulate each other but have very different clinical therapies and, therefore, should be included routinely in differential diagnosis.

  14. Laser ablation of tumors: current concepts and recent developments

    International Nuclear Information System (INIS)

    Stroszczynski, C.; Gaffke, G.; Gnauck, M.; Ricke, J.; Felix, R.; Puls, R.; Speck, U.; Hosten, N.; Oettle, H.; Hohenberger, P.

    2004-01-01

    Purpose. The purpose of this paper is to present technical innovations and clinical results of percutaneous interventional laser ablation of tumors using new techniques. Methods. Laser ablation was performed in 182 patients (liver tumors: 131, non hepatic tumors - bone, lung, others: 51) after interdisciplinary consensus was obtained. The procedure was done using a combination of imaging modalities (CT/MRI, CT/US) or only closed high field MRI (1.5 T). All patients received an MRI-scan immediately after laser ablation. Results. In 90.9% of the patients with liver tumors, a complete ablation was achieved. Major events occurred in 5.4%. The technical success rate of laser ablation in non-hepatic tumors was high, clinical results differed depending on the treated organ. Conclusions. The treatment of tumors of the liver and other organs up to 5 cm by laser ablation was a safe procedure with a low rate of complications and side effects. Image guidance by MRI is advantageous for precise tumor visualization in all dimensions, therapy monitoring, and control of laser ablation results. (orig.) [de

  15. Current opinions on radiotherapy of pediatric central nervous system tumors

    International Nuclear Information System (INIS)

    Chojnacka, M.; Skowronska-Gardas, A.

    2006-01-01

    Primary central nervous system (CNS) neoplasms are the most frequent solid tumors in childhood accounting for 20% of all pediatric malignancies. Despite developments in neurosurgery, radiotherapy and chemotherapy, a significant proportion of these patients suffer progressive disease. A good treatment management strategy should consider not only survival but also the quality of life of the child. Irradiation is ann essential part of the management of the majority of CNS tumors. During then last decade, there significant advances in the technology of planning and delivery of radiation treatment. These new radiotherapy techniques such as conformal, intensity modulated photon beam and stereotactic methods allow a high homogenous dose to the tumor region with minimal doses to normal tissue. This is particularly important in children with localized low-grade tumors, whose prognosis of long-term survival is often excellent and should be accompanied by smallest risk of treatment toxicity. For small tumors fractionated radiotherapy stereotactic radiotherapy using multiple fixed non-coplanar beams is an appropriate treatment. Modification of craniospinal technique, lowering of the total craniospinal dose with adjuvant chemotherapy, new radiotherapy modalities to treat the posterior fossa may be employed to possibly decrease the late rectifies of radiation therapy. For malignant glioma and brain stem tumors we need new approaches, as chemo sensitization, angiogenesis inhibitors and gene therapies. These new methods in therapy of pediatric brain tumors and our experience in treatment of children with medulloblastoma, low-grade astrocytoma, craniopharyngioma and brain stem tumors are presented. We summarize therapeutic aspects of most childhood brain tumors. (author)

  16. Treatment of giant cell tumor of bone: Current concepts

    OpenAIRE

    Puri Ajay; Agarwal Manish

    2007-01-01

    Giant cell tumor (GCT) of bone though one of the commonest bone tumors encountered by an orthopedic surgeon continues to intrigue treating surgeons. Usually benign, they are locally aggressive and may occasionally undergo malignant transformation. The surgeon needs to strike a balance during treatment between reducing the incidence of local recurrence while preserving maximal function. Differing opinions pertaining to the use of adjuvants for extension of curettage, the relative role of bone ...

  17. 15 CFR 760.4 - Evasion.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Evasion. 760.4 Section 760.4 Commerce... BOYCOTTS § 760.4 Evasion. (a) No United States person may engage in any transaction or take any other... the coverage and intent of the exceptions set forth in this part do not constitute evasion regardless...

  18. Tax evasion: a game countermeasure

    Directory of Open Access Journals (Sweden)

    David Carfi'

    2015-08-01

    Full Text Available We propose a game-theoretic model analyzing the interaction between the State and any possible relative taxpayer, by using a realistic probability (frequency approach to the checking evasion strategy. Starting from Allingham and Sandmo's model (1972, we study a possible measure to prevent tax evasion and we also propose a ``honesty-award'' for Taxpayers declaring their entire income by using two Kalai-Smorodinsky solutions. This methodology leaves room for further development of the model, leading to a self-identification by tax evaders and honest citizens.

  19. Current management and prognostic features for gastrointestinal stromal tumor (GIST

    Directory of Open Access Journals (Sweden)

    Lamba Gurpreet

    2012-06-01

    Full Text Available Abstract Stromal or mesenchymal neoplasms affecting the gastrointestinal (GI tract have undergone a remarkable evolution in how they are perceived, classified, approached, diagnosed and managed over the last 30 years. Gastrointestinal stromal tumors (GIST account for approximately 1% to 3% of all malignant GI tumors. The clinical features can vary depending on the anatomic location, size and aggressiveness of the tumor. Metastatic GIST represents a successful example of molecular targeted therapy. In this comprehensive review, we discuss the epidemiology, clinical features and diagnostic modalities for GIST. We also describe treatment options for early stage, locally advanced and metastatic GIST. Indications for neoadjuvant and adjuvant therapy along with duration of therapy are also explained. A brief discussion of latest biomarkers and updates from recent meetings is also provided.

  20. Tax evasion under behavioral structures

    Directory of Open Access Journals (Sweden)

    Gabriela S. Pantoja

    2014-01-01

    Full Text Available We study the strategic interactions between the fiscal authority and the taxpayer regarding tax evasion and auditing. We fit this interaction into a Bayesian game and introduce the concept of behavioral consistency, which helps reducing the number of available strategies and models the stylized fact according to which the choice to evade is subject to behavioral patterns.

  1. Local anesthetics for brain tumor resection: Current perspectives

    NARCIS (Netherlands)

    J.W. Potters (Jan Willem); M. Klimek (Markus)

    2018-01-01

    textabstractThis review summarizes the added value of local anesthetics in patients undergoing craniotomy for brain tumor resection, which is a procedure that is carried out frequently in neurosurgical practice. The procedure can be carried out under general anesthesia, sedation with local

  2. Molecular Tumor Boards : Current Practice and Future Needs

    NARCIS (Netherlands)

    van der Velden, D. L.; van Herpen, C. M.L.; van Laarhoven, H. W.M.; Smit, E. F.; Groen, H. J.M.; Willems, S. M.; Nederlof, P. M.; Langenberg, M. H.G.; Cuppen, E.; Sleijfer, S.; Steeghs, N.; Voest, E. E.

    2017-01-01

    Background: Due to rapid technical advances, steeply declining sequencing costs, and the ever-increasing number of targeted therapies, it can be expected that extensive tumor sequencing such as whole-exome and whole-genome sequencing will soon be applied in standard care. Clinicians will thus be

  3. Molecular Tumor Boards : Current practice and future needs

    NARCIS (Netherlands)

    van der Velden, D. L.; van Herpen, C. M. L.; van Laarhoven, H. W. M.; Smit, E. F.; Groen, H. J. M.; Willems, S. M.; Nederlof, P. M.; Langenberg, M. H. G.; Cuppen, E.; Sleijfer, S.; Steeghs, N.; Voest, E. E.

    2017-01-01

    Background: Due to rapid technical advances, steeply declining sequencing costs, and the ever-increasing number of targeted therapies, it can be expected that extensive tumor sequencing such as whole-exome and whole-genome sequencing will soon be applied in standard care. Clinicians will thus be

  4. Molecular Tumor Boards: current practice and future needs

    NARCIS (Netherlands)

    van der Velden, D. L.; van Herpen, C. M. L.; van Laarhoven, H. W. M.; Smit, E. F.; Groen, H. J. M.; Willems, S. M.; Nederlof, P. M.; Langenberg, M. H. G.; Cuppen, E.; Sleijfer, S.; Steeghs, N.; Voest, E. E.

    2017-01-01

    Background: Due to rapid technical advances, steeply declining sequencing costs, and the ever-increasing number of targeted therapies, it can be expected that extensive tumor sequencing such as whole-exome and whole-genome sequencing will soon be applied in standard care. Clinicians will thus be

  5. Immune Evasion by Epstein-Barr Virus.

    Science.gov (United States)

    Ressing, Maaike E; van Gent, Michiel; Gram, Anna M; Hooykaas, Marjolein J G; Piersma, Sytse J; Wiertz, Emmanuel J H J

    2015-01-01

    Epstein-Bar virus (EBV) is widespread within the human population with over 90% of adults being infected. In response to primary EBV infection, the host mounts an antiviral immune response comprising both innate and adaptive effector functions. Although the immune system can control EBV infection to a large extent, the virus is not cleared. Instead, EBV establishes a latent infection in B lymphocytes characterized by limited viral gene expression. For the production of new viral progeny, EBV reactivates from these latently infected cells. During the productive phase of infection, a repertoire of over 80 EBV gene products is expressed, presenting a vast number of viral antigens to the primed immune system. In particular the EBV-specific CD4+ and CD8+ memory T lymphocytes can respond within hours, potentially destroying the virus-producing cells before viral replication is completed and viral particles have been released. Preceding the adaptive immune response, potent innate immune mechanisms provide a first line of defense during primary and recurrent infections. In spite of this broad range of antiviral immune effector mechanisms, EBV persists for life and continues to replicate. Studies performed over the past decades have revealed a wide array of viral gene products interfering with both innate and adaptive immunity. These include EBV-encoded proteins as well as small noncoding RNAs with immune-evasive properties. The current review presents an overview of the evasion strategies that are employed by EBV to facilitate immune escape during latency and productive infection. These evasion mechanisms may also compromise the elimination of EBV-transformed cells, and thus contribute to malignancies associated with EBV infection.

  6. Atypical Teratoid Rhabdoid Tumor: Current Therapy and Future Directions

    Energy Technology Data Exchange (ETDEWEB)

    Ginn, Kevin F.; Gajjar, Amar, E-mail: amar.gajjar@stjude.org [Division of Neuro-Oncology, St. Jude Children’s Research Hospital, Memphis, TN (United States)

    2012-09-12

    Atypical teratoid rhabdoid tumors (ATRTs) are rare central nervous system tumors that comprise approximately 1–2% of all pediatric brain tumors; however, in patients less than 3 years of age this tumor accounts for up to 20% of cases. ATRT is characterized by loss of the long arm of chromosome 22 which results in loss of the hSNF5/INI-1 gene. INI1, a member of the SWI/SNF chromatin remodeling complex, is important in maintenance of the mitotic spindle and cell cycle control. Overall survival in ATRT is poor with median survival around 17 months. Radiation is an effective component of therapy but is avoided in patients younger than 3 years of age due to long term neurocognitive sequelae. Most long term survivors undergo radiation therapy as a part of their upfront or salvage therapy, and there is a suggestion that sequencing the radiation earlier in therapy may improve outcome. There is no standard curative chemotherapeutic regimen, but anecdotal reports advocate the use of intensive therapy with alkylating agents, high-dose methotrexate, or therapy that includes high-dose chemotherapy with stem cell rescue. Due to the rarity of this tumor and the lack of randomized controlled trials it has been challenging to define optimal therapy and advance treatment. Recent laboratory investigations have identified aberrant function and/or regulation of cyclin D1, aurora kinase, and insulin-like growth factor pathways in ATRT. There has been significant interest in identifying and testing therapeutic agents that target these pathways.

  7. Genetic Mechanisms of Immune Evasion in Colorectal Cancer.

    Science.gov (United States)

    Grasso, Catherine S; Giannakis, Marios; Wells, Daniel K; Hamada, Tsuyoshi; Mu, Xinmeng Jasmine; Quist, Michael; Nowak, Jonathan A; Nishihara, Reiko; Qian, Zhi Rong; Inamura, Kentaro; Morikawa, Teppei; Nosho, Katsuhiko; Abril-Rodriguez, Gabriel; Connolly, Charles; Escuin-Ordinas, Helena; Geybels, Milan S; Grady, William M; Hsu, Li; Hu-Lieskovan, Siwen; Huyghe, Jeroen R; Kim, Yeon Joo; Krystofinski, Paige; Leiserson, Mark D M; Montoya, Dennis J; Nadel, Brian B; Pellegrini, Matteo; Pritchard, Colin C; Puig-Saus, Cristina; Quist, Elleanor H; Raphael, Ben J; Salipante, Stephen J; Shin, Daniel Sanghoon; Shinbrot, Eve; Shirts, Brian; Shukla, Sachet; Stanford, Janet L; Sun, Wei; Tsoi, Jennifer; Upfill-Brown, Alexander; Wheeler, David A; Wu, Catherine J; Yu, Ming; Zaidi, Syed H; Zaretsky, Jesse M; Gabriel, Stacey B; Lander, Eric S; Garraway, Levi A; Hudson, Thomas J; Fuchs, Charles S; Ribas, Antoni; Ogino, Shuji; Peters, Ulrike

    2018-06-01

    To understand the genetic drivers of immune recognition and evasion in colorectal cancer, we analyzed 1,211 colorectal cancer primary tumor samples, including 179 classified as microsatellite instability-high (MSI-high). This set includes The Cancer Genome Atlas colorectal cancer cohort of 592 samples, completed and analyzed here. MSI-high, a hypermutated, immunogenic subtype of colorectal cancer, had a high rate of significantly mutated genes in important immune-modulating pathways and in the antigen presentation machinery, including biallelic losses of B2M and HLA genes due to copy-number alterations and copy-neutral loss of heterozygosity. WNT/β-catenin signaling genes were significantly mutated in all colorectal cancer subtypes, and activated WNT/β-catenin signaling was correlated with the absence of T-cell infiltration. This large-scale genomic analysis of colorectal cancer demonstrates that MSI-high cases frequently undergo an immunoediting process that provides them with genetic events allowing immune escape despite high mutational load and frequent lymphocytic infiltration and, furthermore, that colorectal cancer tumors have genetic and methylation events associated with activated WNT signaling and T-cell exclusion. Significance: This multi-omic analysis of 1,211 colorectal cancer primary tumors reveals that it should be possible to better monitor resistance in the 15% of cases that respond to immune blockade therapy and also to use WNT signaling inhibitors to reverse immune exclusion in the 85% of cases that currently do not. Cancer Discov; 8(6); 730-49. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 663 . ©2018 American Association for Cancer Research.

  8. Local anesthetics for brain tumor resection: current perspectives

    Directory of Open Access Journals (Sweden)

    Potters JW

    2018-02-01

    Full Text Available Jan-Willem Potters, Markus Klimek Department of Anesthesiology, Erasmus MC, Rotterdam, The Netherlands Abstract: This review summarizes the added value of local anesthetics in patients undergoing craniotomy for brain tumor resection, which is a procedure that is carried out frequently in neurosurgical practice. The procedure can be carried out under general anesthesia, sedation with local anesthesia or under local anesthesia only. Literature shows a large variation in the postoperative pain intensity ranging from no postoperative analgesia requirement in two-thirds of the patients up to a rate of 96% of the patients suffering from severe postoperative pain. The only identified causative factor predicting higher postoperative pain scores is infratentorial surgery. Postoperative analgesia can be achieved with multimodal pain management where local anesthesia is associated with lower postoperative pain intensity, reduction in opioid requirement and prevention of development of chronic pain. In awake craniotomy patients, sufficient local anesthesia is a cornerstone of the procedure. An awake craniotomy and brain tumor resection can be carried out completely under local anesthesia only. However, the use of sedative drugs is common to improve patient comfort during craniotomy and closure. Local anesthesia for craniotomy can be performed by directly blocking the six different nerves that provide the sensory innervation of the scalp, or by local infiltration of the surgical site and the placement of the pins of the Mayfield clamp. Direct nerve block has potential complications and pitfalls and is technically more challenging, but mostly requires lower total doses of the local anesthetics than the doses required in surgical-site infiltration. Due to a lack of comparative studies, there is no evidence showing superiority of one technique versus the other. Besides the use of other local anesthetics for analgesia, intravenous lidocaine administration has

  9. Pursuit/evasion in orbit

    Science.gov (United States)

    Kelley, H. J.; Cliff, E. M.; Lutze, F. H.

    1981-01-01

    Maneuvers available to a spacecraft having sufficient propellant to escape an antisatellite satellite (ASAT) attack are examined. The ASAT and the evading spacecraft are regarded as being in circular orbits, and equations of motion are developed for the ASAT to commence a two-impulse maneuver sequence. The ASAT employs thrust impulses which yield a minimum-time-to-rendezvous, considering available fuel. Optimal evasion is shown to involve only in-plane maneuvers, and begins as soon as the ASAT launch information is gathered and thrust activation can be initiated. A closest approach, along with a maximum evasion by the target spacecraft, is calculated to be 14,400 ft. Further research to account for ASATs in parking orbit and for generalization of a continuous control-modeled differential game is indicated.

  10. CONTROVERSIAL ASPECTS REGARDING TAX EVASION

    Directory of Open Access Journals (Sweden)

    Mircea-Constantin SINESCU

    2018-05-01

    Full Text Available Throughout the paper, we have highlighted some controversial aspects regarding the crime of tax evasion, referring to some important decisions of the High Court of Cassation and Justice and also of the Bucharest Court of Appeal. Debating upon the impunity provision stated by art. 10 of Law no. 241/2005, the study also sheds light upon the issue of the perspective of the judicial organs regarding the juridical regime of the tax due for dividends. The main focus of the paper leads to the situations when there is legal ground for the tax due for dividends to be considered part of the damage caused by tax evasion crime. The study includes a short analysis of some relevant provisions of the Romanian Fiscal Code and also some aspects deriving from decisions issued by the Administrative and Tax Litigation Chamber of The High Court of Cassation and Justice concerning the legal regime of dividends. Consequently, the authors are presenting both perspectives of the interpretation of the issue regarding the tax due for dividends to be considered part of the damage caused by tax evasion crime, resulting from two decisions of the two Criminal Sections of The Bucharest Court of Appeal, also arguing in favour of the most solid interpretation among them

  11. Bureaucratic Corruption and Profit Tax Evasion

    OpenAIRE

    Laszlo Goerke

    2006-01-01

    Firms may evade taxes on profits and can also avoid fulfilling legal restrictions on production activities by bribing bureaucrats. It is shown that the existence of tax evasion does not affect corruption activities at the firm level, while the budgetary repercussions of tax evasion induce less corruption. Policy measures which alter the gains or losses from corruption have a non-systematic impact on tax evasion behaviour.

  12. Biomarkers of evasive resistance predict disease progression in cancer patients treated with antiangiogenic therapies

    Science.gov (United States)

    Pircher, Andreas; Jöhrer, Karin; Kocher, Florian; Steiner, Normann; Graziadei, Ivo; Heidegger, Isabel; Pichler, Renate; Leonhartsberger, Nicolai; Kremser, Christian; Kern, Johann; Untergasser, Gerold; Gunsilius, Eberhard; Hilbe, Wolfgang

    2016-01-01

    Numerous antiangiogenic agents are approved for the treatment of oncological diseases. However, almost all patients develop evasive resistance mechanisms against antiangiogenic therapies. Currently no predictive biomarker for therapy resistance or response has been established. Therefore, the aim of our study was to identify biomarkers predicting the development of therapy resistance in patients with hepatocellular cancer (n = 11), renal cell cancer (n = 7) and non-small cell lung cancer (n = 2). Thereby we measured levels of angiogenic growth factors, tumor perfusion, circulating endothelial cells (CEC), circulating endothelial progenitor cells (CEP) and tumor endothelial markers (TEM) in patients during the course of therapy with antiangiogenic agents, and correlated them with the time to antiangiogenic progression (aTTP). Importantly, at disease progression, we observed an increase of proangiogenic factors, upregulation of CEC/CEP levels and downregulation of TEMs, such as Robo4 and endothelial cell-specific chemotaxis regulator (ECSCR), reflecting the formation of torturous tumor vessels. Increased TEM expression levels tended to correlate with prolonged aTTP (ECSCR high = 275 days vs. ECSCR low = 92.5 days; p = 0.07 and for Robo4 high = 387 days vs. Robo4 low = 90.0 days; p = 0.08). This indicates that loss of vascular stabilization factors aggravates the development of antiangiogenic resistance. Thus, our observations confirm that CEP/CEC populations, proangiogenic cytokines and TEMs contribute to evasive resistance in antiangiogenic treated patients. Higher TEM expression during disease progression may have clinical and pathophysiological implications, however, validation of our results is warranted for further biomarker development. PMID:26956051

  13. Evasion of Neutrophil Extracellular Traps by Respiratory Pathogens.

    Science.gov (United States)

    Storisteanu, Daniel M L; Pocock, Joanna M; Cowburn, Andrew S; Juss, Jatinder K; Nadesalingam, Angalee; Nizet, Victor; Chilvers, Edwin R

    2017-04-01

    The release of neutrophil extracellular traps (NETs) is a major immune mechanism intended to capture pathogens. These histone- and protease-coated DNA structures are released by neutrophils in response to a variety of stimuli, including respiratory pathogens, and have been identified in the airways of patients with respiratory infection, cystic fibrosis, acute lung injury, primary graft dysfunction, and chronic obstructive pulmonary disease. NET production has been demonstrated in the lungs of mice infected with Staphylococcus aureus, Klebsiella pneumoniae, and Aspergillus fumigatus. Since the discovery of NETs over a decade ago, evidence that "NET evasion" might act as an immune protection strategy among respiratory pathogens, including group A Streptococcus, Bordetella pertussis, and Haemophilus influenzae, has been growing, with the majority of these studies being published in the past 2 years. Evasion strategies fall into three main categories: inhibition of NET release by down-regulating host inflammatory responses; degradation of NETs using pathogen-derived DNases; and resistance to the microbicidal components of NETs, which involves a variety of mechanisms, including encapsulation. Hence, the evasion of NETs appears to be a widespread strategy to allow pathogen proliferation and dissemination, and is currently a topic of intense research interest. This article outlines the evidence supporting the three main strategies of NET evasion-inhibition, degradation, and resistance-with particular reference to common respiratory pathogens.

  14. Tax Evasion in a Model of Endogenous Growth

    OpenAIRE

    Been-Lon Chen

    2003-01-01

    This paper integrates tax evasion into a standard AK growth model with public capital. In the model, the government optimizes the tax rate, while individuals optimize tax evasion. It studies tax rate, tax evasion and economic growth, and compares them with otherwise identical economies except those without tax evasion. It inquires into the effects of three government policies on tax rate, tax evasion, and economic growth. It finds that an increase in both unit cost of tax evasion and punishme...

  15. Immune evasion mechanisms and immune checkpoint inhibition in advanced merkel cell carcinoma.

    Science.gov (United States)

    Schadendorf, Dirk; Nghiem, Paul; Bhatia, Shailender; Hauschild, Axel; Saiag, Philippe; Mahnke, Lisa; Hariharan, Subramanian; Kaufman, Howard L

    2017-01-01

    Merkel cell carcinoma (MCC) is a rare skin cancer caused by Merkel cell polyomavirus (MCPyV) infection and/or ultraviolet radiation-induced somatic mutations. The presence of tumor-infiltrating lymphocytes is evidence that an active immune response to MCPyV and tumor-associated neoantigens occurs in some patients. However, inhibitory immune molecules, including programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1), within the MCC tumor microenvironment aid in tumor evasion of T-cell-mediated clearance. Unlike chemotherapy, treatment with anti-PD-L1 (avelumab) or anti-PD-1 (pembrolizumab) antibodies leads to durable responses in MCC, in both virus-positive and virus-negative tumors. As many tumors are established through the evasion of infiltrating immune-cell clearance, the lessons learned in MCC may be broadly relevant to many cancers.

  16. Brain tumor radiosurgery. Current status and strategies to enhance the effect of radiosurgery

    International Nuclear Information System (INIS)

    Niranjan, A.; Lunsford, L.D.; Gobbel, G.T.; Kondziolka, D.; Maitz, A.; Flickinger, J.C.

    2000-01-01

    First, the current status of brain tumor radiosurgery is reviewed, and radiosurgery for brain tumors, including benign tumors, malignant tumors, primary glial tumors, and metastatic tumors, is described. Rapid developments in neuroimaging, stereotactic techniques, and robotic technology in the last decade have contributed to improved results and wider applications of radiosurgery. Radiosurgery has become the preferred management modality for many intracranial tumors, including schwannomas, meningiomas, and metastatic tumors. Although radiosurgery provides survival benefits in patients with diffuse malignant brain tumors, cure is still not possible. Microscopic tumor infiltration into surrounding normal tissue is the main cause of recurrence. Additional strategies are needed to specifically target tumor cells. Next, strategies to enhance the effect of radiosurgery are reviewed. Whereas the long-term clinical results of radiosurgery have established its role in the treatment of benign tumors, additional strategies are needed to improve cell killing in malignant brain tumors and to protect normal surrounding brain. The first strategy included the use of various agents to protect normal brain while delivering a high dose to the tumor cells, but finding an effective radioprotective agent has been problematic. Pentobarbital and 21-aminosteroid (21-AS) are presented as examples. The second strategy for radiation protection aimed at the repair of radiation-induced damage to the normal brain. The cause of radiation-induced breakdown of normal tissue is unclear. The white matter and the cerebral vasculature appear to be particularly susceptible to radiation. Oligodendrocytes and endothelial cells may be critical targets of radiation. The authors hypothesize that radiation-induced damage to these cell types can be repaired by neural stem cells. They also describe the use of tumor necrosis factor alpha (TNF-alpha) and neural stem cells as a means of enhancing the effect of

  17. Bribes and Business Tax Evasion

    Directory of Open Access Journals (Sweden)

    Joulfaian, David

    2009-12-01

    Full Text Available This paper investigates the role of governance, in particular bribes to tax officials, in shaping business tax compliance behavior in transition economies. The empirical results show that business noncompliance rises with the frequency of tax related bribes. More specifically, the findings from 27 economies suggest that tax evasion thrives when bribes to tax officials are commonplace. These findings are robust to a number of specifications that control for firm and country attributes as well as address the potential endogeneity of bribes.

  18. Spirochetal Lipoproteins and Immune Evasion

    Science.gov (United States)

    Christodoulides, Alexei; Boyadjian, Ani; Kelesidis, Theodoros

    2017-01-01

    Spirochetes are a major threat to public health. However, the exact pathogenesis of spirochetal diseases remains unclear. Spirochetes express lipoproteins that often determine the cross talk between the host and spirochetes. Lipoproteins are pro-inflammatory, modulatory of immune responses, and enable the spirochetes to evade the immune system. In this article, we review the modulatory effects of spirochetal lipoproteins related to immune evasion. Understanding lipoprotein-induced immunomodulation will aid in elucidating innate pathogenesis processes and subsequent adaptive mechanisms potentially relevant to spirochetal disease vaccine development and treatment. PMID:28424696

  19. Pursuit-evasion differential games

    CERN Document Server

    Yavin, Y

    1987-01-01

    Twenty papers are devoted to the treatment of a wide spectrum of problems in the theory and applications of dynamic games with the emphasis on pursuit-evasion differential games. The problem of capturability is thoroughly investigated, also the problem of noise-corrupted (state) measurements. Attention is given to aerial combat problems and their attendant modelling issues, such as variable speed of the combatants, the three-dimensionality of physical space, and the combat problem, i.e. problems related to 'role determination'.

  20. Tax evasion and the law in Nigeria

    Directory of Open Access Journals (Sweden)

    Enya Matthew Nwocha

    2017-12-01

    Full Text Available This paper has dealt with the incidence of tax evasion and how the law in Nigeria has tackled the problem. It came against the background of massive tax evasion in the country which has resulted in the loss of needed revenue for development. Most individuals eligible to pay tax are not usually amenable to doing so willingly thereby resulting in tax evasion and tax avoidance. Neglect or refusal to pay tax invariably attracts various ranges of punishment. All of these issues have been discussed in this paper under introduction, conceptual framework, grounds for imposition of tax, statutory provisions on tax evasion, reasons for and implications of tax evasion, recommendations and conclusion. The paper in discussing the subject has focused on the principal tax legislations in the country, namely, the Personal Income Tax Act, Companies Income Tax Act, and the Federal Inland Revenue Service Act.

  1. Value added tax evasion and excise duty fraud on fuel market in the Czech Republic

    Directory of Open Access Journals (Sweden)

    Pavel Semerád

    2012-01-01

    Full Text Available This paper deals with analysis of current problems in the motor fuel market. It analyzes bottlenecks in setting the legislative changes in value added tax, excise tax and the legislation concerning fuels. The biggest problem is tax evasions that favor one group of business entities at the expense of another, and also cause that the state loses revenues mainly from indirect taxes. Therefore, attention is directed to quality control of fuels as a means of consumer protection and prevention of tax evasion and ways to combat tax evasion in import, distribution and storage of mineral oils. The examples are the most common errors found in fraudulent companies. Based on the data collected the possible ultimate evasion was estimated. Therefore, I propose that value added tax law should be amended and some other measures to improve supervision by public authorities like tax authorities and customs administration offices should be taken.

  2. Tax evasion – Notion and means to commit it

    Directory of Open Access Journals (Sweden)

    Diana G. IONAŞ

    2012-01-01

    Full Text Available Tax evasion is the circumvention, by any means, from the enforcement or payment of taxes, contributions or any amounts owed to the state budget, the local budget, the state social insurance budget and the budgets for special funds by Romanian or foreign natural persons or companies, commonly referred to as tax payers in the text of the law. It is currently present under various methods and represents a direct and dangerous threat for society’s stability.

  3. TAX EVASION BETWEEN FRAUD AND OPTIMIZATION

    Directory of Open Access Journals (Sweden)

    Emilia Cornelia STOICA

    2017-05-01

    Full Text Available Tax optimization, often called legal tax evasion is the use of methods and techniques that are within the law, in order to reduce or even cancel the tax liability. To achieve such an approach, the taxpayer or his advisers must know in depth the tax law - and by extension, the financial and administrative law - and, moreover, must be functional tax jurisdictions which allow the use of appropriate assemblies. The recent leasks, as WikiLeaks, LuxLeaks, SwissLeaks, Panama Papers etc. on financial flows to tax havens highlight the far-reaching unprecedented evasion and tax fraud, both in the amounts involved - trillions of dollars - and sophisticated assemblies used primarily by multinational companies to the detriment of the public finances of Member territory headquarters and branches which are located and, therefore, detrimental economic and social life of those countries. Tax evasion is based on legal mechanisms which, combined together in the montages of increasingly complex, allowing operators, mostly multinational legal entities to circumvent national tax law and not pay the taxes due. The border between tax optimization, tax evasion and fraud is very thin, optimization using various legal methods to reduce the tax owed, whereas tax evasion using illegal means, which covered crime. Tax evasion reveals either optimize or fraud. There is a significant international dimension of tax evasion because it is favored by multinational corporations operating conditions.

  4. Radiotherapy for pediatric brain tumors: Standard of care, current clinical trials, and new directions

    International Nuclear Information System (INIS)

    Kun, Larry E.

    1996-01-01

    Objectives: To review the clinical characteristics of childhood brain tumors, including neurologic signs, neuroimaging and neuropathology. To critically assess indications for therapy relevant to presenting characteristics, age, and disease status. To discuss current management strategies including neurosurgery, radiation therapy, and chemotherapy. To analyze current clinical trials and future directions of clinical research. Brain tumors account for 20% of neoplastic diseases in children. The most common tumors include astrocytoma and malignant gliomas, medulloblastoma and supratentorial PNET's, ependymoma, craniopharyngioma, and intracranial germ cell tumors. Tumor type and clinical course are often correlated with age at presentation and anatomic site. The clinical characteristics and disease extent largely determine the relative merits of available 'standard' and investigational therapeutic approaches. Treatment outcome, including disease control and functional integrity, is dependent upon age at presentation, tumor type, and disease extent. An understanding of the clinical, neuroimaging, and histologic characteristics as they relate to decisions regarding therapy is critical to the radiation oncologist. Appropriate radiation therapy is central to curative therapy for a majority of pediatric brain tumor presentations. Technical advances in neurosurgery provide greater safety for 'gross total resection' in a majority of hemispheric astrocytomas and medulloblastomas. The relative roles of 'standard' radiation therapy and evolving chemotherapy for centrally located astrocytomas (e.g., diencephalic, optic pathway) need to be analyzed in the context of initial and overall disease control, neurotoxicities, and potential modifications in the risk:benefit ratio apparent in the introduction of precision radiation techniques. Modifications in radiation delivery are fundamental to current investigations in medulloblastoma; the rationale for contemporary and projected

  5. Immune evasion mechanisms of human papillomavirus: An update.

    Science.gov (United States)

    Steinbach, Alina; Riemer, Angelika B

    2018-01-15

    Human papillomavirus (HPV) is the most frequently sexually transmitted agent in the world. It can cause cervical and other anogenital malignancies, and oropharyngeal cancer. HPV has the unique ability to persist in the host's epithelium for a long time-longer than most viruses do-which is necessary to complete its replication cycle. To this end, HPV has developed a variety of immune evasion mechanisms, which unfortunately also favor the progression of the disease from infection to chronic dysplasia and eventually to cancer. This article summarizes the current knowledge about HPV immune evasion strategies. A special emphasis lies in HPV-mediated changes of the antigen processing machinery, which is generating epitopes for T cells and contributes to the detectability of infected cells. © 2017 UICC.

  6. Viral evasion of DNA-stimulated innate immune responses

    Science.gov (United States)

    Christensen, Maria H; Paludan, Søren R

    2017-01-01

    Cellular sensing of virus-derived nucleic acids is essential for early defenses against virus infections. In recent years, the discovery of DNA sensing proteins, including cyclic GMP–AMP synthase (cGAS) and gamma-interferon-inducible protein (IFI16), has led to understanding of how cells evoke strong innate immune responses against incoming pathogens carrying DNA genomes. The signaling stimulated by DNA sensors depends on the adaptor protein STING (stimulator of interferon genes), to enable expression of antiviral proteins, including type I interferon. To facilitate efficient infections, viruses have evolved a wide range of evasion strategies, targeting host DNA sensors, adaptor proteins and transcription factors. In this review, the current literature on virus-induced activation of the STING pathway is presented and we discuss recently identified viral evasion mechanisms targeting different steps in this antiviral pathway. PMID:26972769

  7. Viral evasion of DNA-stimulated innate immune responses.

    Science.gov (United States)

    Christensen, Maria H; Paludan, Søren R

    2017-01-01

    Cellular sensing of virus-derived nucleic acids is essential for early defenses against virus infections. In recent years, the discovery of DNA sensing proteins, including cyclic GMP-AMP synthase (cGAS) and gamma-interferon-inducible protein (IFI16), has led to understanding of how cells evoke strong innate immune responses against incoming pathogens carrying DNA genomes. The signaling stimulated by DNA sensors depends on the adaptor protein STING (stimulator of interferon genes), to enable expression of antiviral proteins, including type I interferon. To facilitate efficient infections, viruses have evolved a wide range of evasion strategies, targeting host DNA sensors, adaptor proteins and transcription factors. In this review, the current literature on virus-induced activation of the STING pathway is presented and we discuss recently identified viral evasion mechanisms targeting different steps in this antiviral pathway.

  8. THE DETERMINANTS PERCEPTION OF TAX EVASION ETHICS

    Directory of Open Access Journals (Sweden)

    Ningsih D.N.C.

    2018-01-01

    Full Text Available This study aimed to examine the determinants perception of tax evasion ethics, and combined three models based on the research of McGee et al (2012, Lau et al (2013, Lemvora et al (2013. Data collection used survey method on 148 auditors who worked at Public Accountant Office (KAP Big Ten. The result of this study showed that the justice and taxation systems affect significantly negative toward the perception of tax evasion ethics. Religiosity strengthened the effect of justice, taxation systems, and discrimination on the perception of tax evasion ethics.

  9. THE POSSIBLY PREVENTION AND COMBATING TAX EVASION

    Directory of Open Access Journals (Sweden)

    Daniela P. POPA

    2014-11-01

    - A faulty legislation that allows them to circumvent the failure to pay taxes. Measures to combat tax evasion must act in the areas of legislative, administrative and educational. The legislative drafting tax legislation seeks appropriate, clear, concise, stable and consistent. It is also necessary to eliminate or withdrawal of exemptions, reductions and deductions that give rise to multiple interpretations. In terms of administrative measures aimed at creating a comprehensive and operational information system, ensuring adequate administrative structures and instruments effectively combating tax evasion and training specialists with morality and professionalism required of shapes and sizes evasion.

  10. Tax evasion, social norms and economic growth

    OpenAIRE

    Bethencourt, Carlos; Kunze, Lars

    2013-01-01

    This paper proposes a theoretical model to account for the most relevant micro- and macroeconomic empirical facts in the tax evasion literature. To do so, we integrate tax morale into a dynamic overlapping generations model of capital income tax evasion. Tax morale is modeled as a social norm for tax compliance. It is shown that accounting for such nonpecuniary costs of evasion may not only explain (i) why some taxpayers never evade even if the gamble is profitable, and (ii) how a higher tax ...

  11. TAX EVASION THROUGH FICTITIOUS ECONOMIC OPERATIONS, OBSTACLE TO SUSTAINABLE DEVELOPMENT

    OpenAIRE

    SERGIU-BOGDAN CONSTANTIN

    2016-01-01

    Tax evasion means the avoidance of declaring and paying taxes. The purpose of the research is to identify ways and mechanisms of tax evasion through fictitious economic operations and how this kind o tax evasion can influence sustainable development. The principal methods are researching tax evasion cases investigated by the Romanian authorities responsible for combating this phenomenon, court trials on tax evasion and using the bibliographic references in the field. The data used...

  12. Complement Evasion by Pathogenic Leptospira.

    Science.gov (United States)

    Fraga, Tatiana Rodrigues; Isaac, Lourdes; Barbosa, Angela Silva

    2016-01-01

    Leptospirosis is a neglected infectious disease caused by spirochetes from the genus Leptospira . Pathogenic microorganisms, notably those which reach the blood circulation such as Leptospira , have evolved multiple strategies to escape the host complement system, which is important for innate and acquired immunity. Leptospira avoid complement-mediated killing through: (i) recruitment of host complement regulators; (ii) acquisition of host proteases that cleave complement proteins on the bacterial surface; and, (iii) secretion of proteases that inactivate complement proteins in the Leptospira surroundings. The recruitment of host soluble complement regulatory proteins includes the acquisition of Factor H (FH) and FH-like-1 (alternative pathway), C4b-binding protein (C4BP) (classical and lectin pathways), and vitronectin (Vn) (terminal pathway). Once bound to the leptospiral surface, FH and C4BP retain cofactor activity of Factor I in the cleavage of C3b and C4b, respectively. Vn acquisition by leptospires may result in terminal pathway inhibition by blocking C9 polymerization. The second evasion mechanism lies in plasminogen (PLG) binding to the leptospiral surface. In the presence of host activators, PLG is converted to enzymatically active plasmin, which is able to degrade C3b, C4b, and C5 at the surface of the pathogen. A third strategy used by leptospires to escape from complement system is the active secretion of proteases. Pathogenic, but not saprophytic leptospires, are able to secrete metalloproteases that cleave C3 (central complement molecule), Factor B (alternative pathway), and C4 and C2 (classical and lectin pathways). The purpose of this review is to fully explore these complement evasion mechanisms, which act together to favor Leptospira survival and multiplication in the host.

  13. Radiotherapy for pediatric brain tumors: Standard of care, current clinical trials and new directions

    International Nuclear Information System (INIS)

    Kun, Larry E.

    1997-01-01

    Objectives: To review the clinical characteristics of childhood brain tumors, including neurologic signs, neuroimaging and neuropathology. To critically assess indications for therapy relevant to presenting characteristics, age, and disease status. To discuss current management strategies including neurosurgery, radiation therapy, and chemotherapy. To analyze current clinical trials and future directions of clinical research. Brain tumors account for 20% of neoplastic diseases in children. The most common tumors include astrocytoma and malignant gliomas, medulloblastoma and supratentorial PNET's, ependymoma, craniopharyngioma, and intracranial germ cell tumors. The clinical characteristics and disease extent largely determine the relative merits of available 'standard' and investigational therapeutic approaches. Treatment outcome, including disease control and functional integrity, is dependent upon tumor type and site, age at presentation, and disease extent. An understanding of the clinical, neuroimaging, and histologic characteristics as they relate to decisions regarding therapy is critical to the radiation oncologist. Appropriate radiation therapy is central to curative therapy for a majority of pediatric brain tumor presentations. Technical advances in neurosurgery provide greater safety for 'gross total resection' in a majority of hemispheric astrocytomas and medulloblastomas. The relative roles of radiation therapy and chemotherapy for centrally located astrocytomas (e.g., diencephalic, optic pathway) need to be analyzed in the context of initial and overall disease control, neurotoxicities, and potential modifications in the risk:benefit ratio apparent in the introduction of 3-dimensional radiation techniques. Modifications in radiation delivery are important components of current investigations in medulloblastoma; the rationale for contemporary cooperative group trials will be presented as well as the background data re surgical, radiotherapeutic, and

  14. VAT EVASION INLEBANON: CASES AND MAIN CAUSES

    Directory of Open Access Journals (Sweden)

    Rana Ismail

    2012-07-01

    Full Text Available The Value Added Tax (VAT is a very important source oftreasuryrevenuesinLebanon. It was initially introduced inLebanon in order to reduce the budgetdeficit and help contain the debt. However, VAT evasion growth inLebanon isleading to significant VAT revenue losses because of its size and frequency.In this paper, we will highlight the contribution of VAT to the treasury revenue. Inaddition, our research has led to figure out the most significant VAT evasion casesand the way tax payers evade paying their required VAT or try to have an illegalrefund. From these tax evasion cases, we will pinpoint the main causes of suchevasions and propose solutions to limit as much as possible VAT evasion inLebanon.

  15. SSAT State-of-the-Art Conference: Current Surgical Management of Gastric Tumors.

    Science.gov (United States)

    Norton, Jeffrey A; Kim, Teresa; Kim, Joseph; McCarter, Martin D; Kelly, Kaitlyn J; Wong, Joyce; Sicklick, Jason K

    2018-01-01

    The current era of gastric surgery is marked by low morbidity and mortality rates, innovative strategies to approach resections with a minimally invasive fashion or hyperthermic intraperitoneal chemotherapy (HIPEC), as well as improved understanding of the biology of sporadic and hereditary stromal, neuroendocrine, and epithelial malignancies. In 2017, the Society for Surgery of the Alimentary Tract convened a State-of-the-Art Conference on Current Surgical Management of Gastric Tumors with both international experts and emerging leaders in the field of gastric surgery. Martin D. McCarter, MD of the University of Colorado discussed the current management of gastric gastrointestinal stromal tumors (GIST). Kaitlyn J. Kelly, MD of the University of California, San Diego discussed the management of gastric carcinoid tumors. Jeffrey A. Norton of Stanford University discussed recent advances in the management of gastric adenocarcinoma including a focus on hereditary diffuse gastric cancer (HDGC). Joseph Kim, MD of Stony Brook University discussed a systematic approach to minimally invasive gastrectomy for cancer. Joyce Wong, MD of Pennsylvania State University discussed the role for cytoreductive surgery (CRS) and HIPEC for gastric adenocarcinoma. This review provides gastrointestinal surgeons with a concise update on the current surgical management of gastric tumors.

  16. Fiscal Policy under Indeterminacy and Tax Evasion

    DEFF Research Database (Denmark)

    Busato, Francesco; Chiarini, Bruno; Marchetti, Enrico

    This paper shows under indeterminacy and tax evasion, an increase in corporate,labor or income tax rates pushes the economy into an expansionary pattern.These effects are reversed when the steady state is saddle-path stable.......This paper shows under indeterminacy and tax evasion, an increase in corporate,labor or income tax rates pushes the economy into an expansionary pattern.These effects are reversed when the steady state is saddle-path stable....

  17. Tax evasion between fraud and legality

    Directory of Open Access Journals (Sweden)

    Opreţ Laura-Anca

    2017-12-01

    Full Text Available This paper focuses on detailing the general coordinates regarding tax evasion and the necessity of creating a common unitary European legal framework. Accounting information might mirror erroneously in a certain measure the micro to macroeconomic tendency of fraud by showing a gross image of available resources. It is of the utmost importance to become fully aware of causes for illicit practices, ways to fight any fraud attempts and to evaluate the accounting mechanism that both creates and identifies tax evasion.

  18. Tax Evasion and the Shadow Economy

    OpenAIRE

    Oliver Reimers

    2015-01-01

    Leading scholars examine recent evidence from theoretical and empirical research on tax compliance and tax evasion, and provide an in-depth analysis of underlying methods. Strategies to fight tax evasion are evaluated and the motivations behind it are explored, as are the impact and size of the shadow economy in Europe. As well as promoting a better understanding of the issues, this book intends to stimulate further debate and, in so doing, broaden the exchange of ideas and concepts.

  19. Signaling pathways and immune evasion mechanisms in classical Hodgkin lymphoma.

    Science.gov (United States)

    Liu, W Robert; Shipp, Margaret A

    2017-11-23

    Classical Hodgkin lymphoma (cHL) is an unusual B-cell-derived malignancy in which rare malignant Hodgkin and Reed-Sternberg (HRS) cells are surrounded by an extensive but ineffective inflammatory/immune cell infiltrate. This striking feature suggests that malignant HRS cells escape immunosurveillance and interact with immune cells in the cancer microenvironment for survival and growth. We previously found that cHLs have a genetic basis for immune evasion: near-uniform copy number alterations of chromosome 9p24.1 and the associated PD-1 ligand loci, CD274/PD-L1 and PDCD1LG2/PD-L2, and copy number-dependent increased expression of these ligands. HRS cells expressing PD-1 ligands are thought to engage PD-1 receptor-positive immune effectors in the tumor microenvironment and induce PD-1 signaling and associated immune evasion. The genetic bases of enhanced PD-1 signaling in cHL make these tumors uniquely sensitive to PD-1 blockade. © 2017 by The American Society of Hematology.

  20. Hypothalamic Circuits for Predation and Evasion.

    Science.gov (United States)

    Li, Yi; Zeng, Jiawei; Zhang, Juen; Yue, Chenyu; Zhong, Weixin; Liu, Zhixiang; Feng, Qiru; Luo, Minmin

    2018-02-21

    The interactions between predator and prey represent some of the most dramatic events in nature and constitute a matter of life and death for both sides. The hypothalamus has been implicated in driving predation and evasion; however, the exact hypothalamic neural circuits underlying these behaviors remain poorly defined. Here, we demonstrate that inhibitory and excitatory projections from the mouse lateral hypothalamus (LH) to the periaqueductal gray (PAG) in the midbrain drive, respectively, predation and evasion. LH GABA neurons were activated during predation. Optogenetically stimulating PAG-projecting LH GABA neurons drove strong predatory attack, and inhibiting these cells reversibly blocked predation. In contrast, LH glutamate neurons were activated during evasion. Stimulating PAG-projecting LH glutamate neurons drove evasion and inhibiting them impeded predictive evasion. Therefore, the seemingly opposite behaviors of predation and evasion are tightly regulated by two dissociable modular command systems within a single neural projection from the LH to the PAG. VIDEO ABSTRACT. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Inflammation promotes oral squamous carcinoma immune evasion via induced programmed death ligand-1 surface expression.

    Science.gov (United States)

    Lu, Wanlu; Lu, Libing; Feng, Yun; Chen, Jiao; Li, Yan; Kong, Xiangli; Chen, Sixiu; Li, Xiaoyu; Chen, Qianming; Zhang, Ping

    2013-05-01

    The association between inflammation and cancer provides a new target for tumor biotherapy. The inflammatory cells and molecules within the tumor microenvironment have decisive dual roles in antitumor immunity and immune evasion. In the present study, phytohemagglutinin (PHA) was used to stimulate peripheral blood mononuclear cells (PBMCs) to simulate the tumor inflammatory microenvironment. The effect of immune cells and inflammatory cytokines on the surface expression of programmed cell death-1 ligand 1 (PD-L1) and tumor immune evasion was investigated using flow cytometry (FCM) and an in vivo xenotransplantation model. Based on the data, PHA-activated, but not resting, immune cells were able to promote the surface expression of PD-L1 in Tca8113 oral squamous carcinoma cells via the secretion of inflammatory cytokines, but not by cell-cell contact. The majority of the inflammatory cytokines had no significant effect on the proliferation, cell cycle progression and apoptosis of the Tca8113 cells, although they each induced the expression of PD-L1 in a dose-dependent manner. In total, 99% of the Tca8113 cells expressed PD-L1 following treatment with the supernatant of PHA-stimulated PBMCs. The PHA-supernatant pretreated Tca8113 cells unusually induced Tca8113 antigen-specific CD8 + T cell apoptosis in vitro and the evasion of antigen-specific T cell attraction in a nude mouse tumor-bearing model. These results indicate a new mechanism for the promotion of tumor immune evasion by the tumor inflammatory microenvironment.

  2. Host evasion by Burkholderia cenocepacia

    Directory of Open Access Journals (Sweden)

    Shyamala eGanesan

    2012-01-01

    Full Text Available Burkholderia cenocepacia is an opportunistic respiratory pathogen of individuals with cystic fibrosis (CF. It is one of the highly transmissible species of Burkholderia cepacia complex and very resistant to almost all the antibiotics. Approximately 1/3rd of B. cenocepacia infected CF patients go on to develop fatal ‘cepacia syndrome’. During the last two decades, substantial progress has been made with regards to evasion of host innate defense mechanisms by B. cenocepacia. Almost all strains of B. cenocepacia has capacity to survive and replicate intracellularly in both airway epithelial cells and macrophages, which are primary centennials of the lung and play a pivotal role in clearance of infecting bacteria. Some strains of B. cenocepaica, which express cable pili and the associated 22kDa adhesin are also capable of transmigrating across airway epithelium and persist in mouse models of infection. In this review, we will discuss how this type of interaction between B. cenocepacia and host may lead to persistence of bacteria and contribute to lung inflammation in CF patients.

  3. General Considerations on fiscal evasion

    Directory of Open Access Journals (Sweden)

    Pripoaie Silviu

    2009-10-01

    Full Text Available Analysis of performance of any economy involves the measurement and correlation of three basic elements: the rate of economic growth,the rate of inflation and unemployment rate. When the rate of growth (rate of real GDP is high, the production of goods and services is growing andtherefore increasing the number of jobs, decrease unemployment and raise living standards. If the economy is in recession phase, increasing fiscalpressure to ensure the necessary budgetary funds triggers complex economic mechanisms. Rules more strictly is that those who are not able tooperate in the normal economy to slide towards the underground economy, and this not because he wants to tax evasion, but because they simplycannot cope with new regulations. It is widely accepted in economic theory and practice the idea that reliability scale macroeconomic indicators of acountry is affected by size of underground economy and the various tests made so far on this subject, focusing either on the social aspect or theeconomic or moral, or emphasizes the illegal or the edge of legality. This has led to various studies in this area do not provide comparable data orprovide data to the contrary. Worldwide were put in place, however, some calculation methods provided that applied the same country and sameperiod, the results are rarely consistent, sometimes even in fundamentally different.

  4. Current advances in mathematical modeling of anti-cancer drug penetration into tumor tissues.

    Science.gov (United States)

    Kim, Munju; Gillies, Robert J; Rejniak, Katarzyna A

    2013-11-18

    Delivery of anti-cancer drugs to tumor tissues, including their interstitial transport and cellular uptake, is a complex process involving various biochemical, mechanical, and biophysical factors. Mathematical modeling provides a means through which to understand this complexity better, as well as to examine interactions between contributing components in a systematic way via computational simulations and quantitative analyses. In this review, we present the current state of mathematical modeling approaches that address phenomena related to drug delivery. We describe how various types of models were used to predict spatio-temporal distributions of drugs within the tumor tissue, to simulate different ways to overcome barriers to drug transport, or to optimize treatment schedules. Finally, we discuss how integration of mathematical modeling with experimental or clinical data can provide better tools to understand the drug delivery process, in particular to examine the specific tissue- or compound-related factors that limit drug penetration through tumors. Such tools will be important in designing new chemotherapy targets and optimal treatment strategies, as well as in developing non-invasive diagnosis to monitor treatment response and detect tumor recurrence.

  5. Alternating current electrical stimulation enhanced chemotherapy: a novel strategy to bypass multidrug resistance in tumor cells

    International Nuclear Information System (INIS)

    Janigro, Damir; Perju, Catalin; Fazio, Vincent; Hallene, Kerri; Dini, Gabriele; Agarwal, Mukesh K; Cucullo, Luca

    2006-01-01

    Tumor burden can be pharmacologically controlled by inhibiting cell division and by direct, specific toxicity to the cancerous tissue. Unfortunately, tumors often develop intrinsic pharmacoresistance mediated by specialized drug extrusion mechanisms such as P-glycoprotein. As a consequence, malignant cells may become insensitive to various anti-cancer drugs. Recent studies have shown that low intensity very low frequency electrical stimulation by alternating current (AC) reduces the proliferation of different tumor cell lines by a mechanism affecting potassium channels while at intermediate frequencies interfere with cytoskeletal mechanisms of cell division. The aim of the present study is to test the hypothesis that permeability of several MDR1 over-expressing tumor cell lines to the chemotherapic agent doxorubicin is enhanced by low frequency, low intensity AC stimulation. We grew human and rodent cells (C6, HT-1080, H-1299, SKOV-3 and PC-3) which over-expressed MDR1 in 24-well Petri dishes equipped with an array of stainless steel electrodes connected to a computer via a programmable I/O board. We used a dedicated program to generate and monitor the electrical stimulation protocol. Parallel cultures were exposed for 3 hours to increasing concentrations (1, 2, 4, and 8 μM) of doxorubicin following stimulation to 50 Hz AC (7.5 μA) or MDR1 inhibitor XR9576. Cell viability was assessed by determination of adenylate kinase (AK) release. The relationship between MDR1 expression and the intracellular accumulation of doxorubicin as well as the cellular distribution of MDR1 was investigated by computerized image analysis immunohistochemistry and Western blot techniques. By the use of a variety of tumor cell lines, we show that low frequency, low intensity AC stimulation enhances chemotherapeutic efficacy. This effect was due to an altered expression of intrinsic cellular drug resistance mechanisms. Immunohistochemical, Western blot and fluorescence analysis revealed

  6. Profit Tax Evasion Under Oligopoly With Endogenous Market Structure

    OpenAIRE

    Goerke, Laszlo; Runkel, Marco

    2006-01-01

    This note investigates the impact of profit tax evasion on firms' output decisions in a Cournot oligopoly setting in which the market structure is determined endogenously. It is shown that tax evasion intensifies market entry and raises aggregate output, while production of each incumbent firm decreases. Therefore, tax evasion choices affect activity decisions and an evadable profit tax distorts the market outcome.

  7. Complement and innate immune evasion strategies of the human pathogenic fungus Candida albicans.

    Science.gov (United States)

    Luo, Shanshan; Skerka, Christine; Kurzai, Oliver; Zipfel, Peter F

    2013-12-15

    Candida albicans is a medically important fungus that can cause a wide range of diseases ranging from superficial infections to disseminated disease, which manifests primarily in immuno-compromised individuals. Despite the currently applied anti-fungal therapies, both mortality and morbidity caused by this human pathogenic fungus are still unacceptably high. Therefore new prophylactic and therapeutic strategies are urgently needed to prevent fungal infection. In order to define new targets for combating fungal disease, there is a need to understand the immune evasion strategies of C. albicans in detail. In this review, we summarize different sophisticated immune evasion strategies that are utilized by C. albicans. The description of the molecular mechanisms used for immune evasion does on one hand help to understand the infection process, and on the other hand provides valuable information to define new strategies and diagnostic approaches to fight and interfere with Candida infections. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Evasion Mechanisms Used by Pathogens to Escape the Lectin Complement Pathway

    DEFF Research Database (Denmark)

    Rosbjerg, Anne; Genster, Ninette; Pilely, Katrine

    2017-01-01

    the level of activity. The result is a pro-inflammatory response meant to combat foreign microbes. Microbial elimination is, however, not a straight forward procedure; pathogens have adapted to their environment by evolving a collection of evasion mechanisms that circumvent the human complement system....... Complement evasion strategies features different ways of exploiting human complement proteins and moreover features different pathogen-derived proteins that interfere with the normal processes. Accumulated, these mechanisms target all three complement activation pathways as well as the final common part...... of the cascade. This review will cover the currently known lectin pathway evasion mechanisms and give examples of pathogens that operate these to increase their chance of invasion, survival and dissemination....

  9. The Hidden Costs of Tax Evasion: Collaborative Tax Evasion in Markets for Expert Services

    OpenAIRE

    Balafoutas, Loukas; Beck, Adrian; Kerschbamer, Rudolf; Sutter, Matthias

    2015-01-01

    We experimentally examine the impact of tax evasion attempts on the performance of credence goods markets, where contractual incompleteness results from asymmetric information on the welfare maximizing quality of the good. Our results suggest that tax evasion attempts – independently of whether they are successful or not – lead to efficiency losses in the form of too low quality and less frequent trade. Thus, shadow economies may reduce welfare not only by inducing agents to incur costs to hi...

  10. Tax Evasion and Swiss Bank Deposits

    DEFF Research Database (Denmark)

    Johannesen, Niels

    Bank deposits in jurisdictions with banking secrecy constitute an effective tool to evade taxes on interest income. A recent EU reform reduces the scope for this type of tax evasion by introducing a source tax on interest income earned by EU residents in Switzerland and several other jurisdictions...

  11. Cytomegalovirus immune evasion of myeloid lineage cells.

    Science.gov (United States)

    Brinkmann, Melanie M; Dağ, Franziska; Hengel, Hartmut; Messerle, Martin; Kalinke, Ulrich; Čičin-Šain, Luka

    2015-06-01

    Cytomegalovirus (CMV) evades the immune system in many different ways, allowing the virus to grow and its progeny to spread in the face of an adverse environment. Mounting evidence about the antiviral role of myeloid immune cells has prompted the research of CMV immune evasion mechanisms targeting these cells. Several cells of the myeloid lineage, such as monocytes, dendritic cells and macrophages, play a role in viral control, but are also permissive for CMV and are naturally infected by it. Therefore, CMV evasion of myeloid cells involves mechanisms that qualitatively differ from the evasion of non-CMV-permissive immune cells of the lymphoid lineage. The evasion of myeloid cells includes effects in cis, where the virus modulates the immune signaling pathways within the infected myeloid cell, and those in trans, where the virus affects somatic cells targeted by cytokines released from myeloid cells. This review presents an overview of CMV strategies to modulate and evade the antiviral activity of myeloid cells in cis and in trans.

  12. Adversarial Feature Selection Against Evasion Attacks.

    Science.gov (United States)

    Zhang, Fei; Chan, Patrick P K; Biggio, Battista; Yeung, Daniel S; Roli, Fabio

    2016-03-01

    Pattern recognition and machine learning techniques have been increasingly adopted in adversarial settings such as spam, intrusion, and malware detection, although their security against well-crafted attacks that aim to evade detection by manipulating data at test time has not yet been thoroughly assessed. While previous work has been mainly focused on devising adversary-aware classification algorithms to counter evasion attempts, only few authors have considered the impact of using reduced feature sets on classifier security against the same attacks. An interesting, preliminary result is that classifier security to evasion may be even worsened by the application of feature selection. In this paper, we provide a more detailed investigation of this aspect, shedding some light on the security properties of feature selection against evasion attacks. Inspired by previous work on adversary-aware classifiers, we propose a novel adversary-aware feature selection model that can improve classifier security against evasion attacks, by incorporating specific assumptions on the adversary's data manipulation strategy. We focus on an efficient, wrapper-based implementation of our approach, and experimentally validate its soundness on different application examples, including spam and malware detection.

  13. Take-over performance in evasive manoeuvres

    NARCIS (Netherlands)

    Happee, R.; Gold, Christian; Radlmayr, Jonas; Hergeth, Sebastian; Bengler, Klaus

    2017-01-01

    We investigated after effects of automation in take-over scenarios in a high-end moving-base driving simulator. Drivers performed evasive manoeuvres encountering a blocked lane in highway driving. We compared the performance of drivers 1) during manual driving, 2) after automated driving with

  14. Tax evasion and growth: a banking approach

    Czech Academy of Sciences Publication Activity Database

    Gillman, M.; Kejak, Michal

    -, 2008/6 (2008), s. 1-32. ISBN 978-963-9796-21-8. ISSN 1785-377X Institutional research plan: CEZ:AV0Z70850503 Keywords : tax evasion * financial intermediation * endogenous growth Subject RIV: AH - Economics http://econ.core.hu/file/download/mtdp/MTDP0806.pdf

  15. Estimating Border Tax Evasion in Mozambique

    DEFF Research Database (Denmark)

    Arndt, Channing; Van Dunem, Joao Ernesto

    2009-01-01

    evasion. Results also strongly confirm the presence of fraudulent classification of merchandise into lower taxed product categories. Finally, analysis of the revenue implications of lower trade taxes finds that the revenue curve is quite flat but remains upward sloping with respect to the tax rate when...

  16. The current status of studies on mitochondrial DNA with tumor, radiation biological effects and aging

    International Nuclear Information System (INIS)

    Liu Qingjie; Sang Lu

    2004-01-01

    The mitochondrial plays a very important role in sustaining the normal physiological function, because it is the center of energy making and mitochondrial DNA (mtDNA) is the only genetic material outside the nuclear. The result of studies showed that many diseases have a close relationship with mtDNA mutation and deletion. This article reviewed the current status of research on mtDNA with tumor, radiation biological effects and aging, in order to initiate the application study of mtDNA in the circle of radiation medicine

  17. Does the Sole Description of a Tax Authority Affect Tax Evasion? - The Impact of Described Coercive and Legitimate Power

    Science.gov (United States)

    Hartl, Barbara; Hofmann, Eva; Gangl, Katharina; Hartner-Tiefenthaler, Martina; Kirchler, Erich

    2015-01-01

    Following the classic economic model of tax evasion, taxpayers base their tax decisions on economic determinants, like fine rate and audit probability. Empirical findings on the relationship between economic key determinants and tax evasion are inconsistent and suggest that taxpayers may rather rely on their beliefs about tax authority’s power. Descriptions of the tax authority’s power may affect taxpayers’ beliefs and as such tax evasion. Experiment 1 investigates the impact of fines and beliefs regarding tax authority’s power on tax evasion. Experiments 2-4 are conducted to examine the effect of varying descriptions about a tax authority’s power on participants’ beliefs and respective tax evasion. It is investigated whether tax evasion is influenced by the description of an authority wielding coercive power (Experiment 2), legitimate power (Experiment 3), and coercive and legitimate power combined (Experiment 4). Further, it is examined whether a contrast of the description of power (low to high power; high to low power) impacts tax evasion (Experiments 2-4). Results show that the amount of fine does not impact tax payments, whereas participants’ beliefs regarding tax authority’s power significantly shape compliance decisions. Descriptions of high coercive power as well as high legitimate power affect beliefs about tax authority’s power and positively impact tax honesty. This effect still holds if both qualities of power are applied simultaneously. The contrast of descriptions has little impact on tax evasion. The current study indicates that descriptions of the tax authority, e.g., in information brochures and media reports, have more influence on beliefs and tax payments than information on fine rates. Methodically, these considerations become particularly important when descriptions or vignettes are used besides objective information. PMID:25923770

  18. Does the sole description of a tax authority affect tax evasion?--the impact of described coercive and legitimate power.

    Science.gov (United States)

    Hartl, Barbara; Hofmann, Eva; Gangl, Katharina; Hartner-Tiefenthaler, Martina; Kirchler, Erich

    2015-01-01

    Following the classic economic model of tax evasion, taxpayers base their tax decisions on economic determinants, like fine rate and audit probability. Empirical findings on the relationship between economic key determinants and tax evasion are inconsistent and suggest that taxpayers may rather rely on their beliefs about tax authority's power. Descriptions of the tax authority's power may affect taxpayers' beliefs and as such tax evasion. Experiment 1 investigates the impact of fines and beliefs regarding tax authority's power on tax evasion. Experiments 2-4 are conducted to examine the effect of varying descriptions about a tax authority's power on participants' beliefs and respective tax evasion. It is investigated whether tax evasion is influenced by the description of an authority wielding coercive power (Experiment 2), legitimate power (Experiment 3), and coercive and legitimate power combined (Experiment 4). Further, it is examined whether a contrast of the description of power (low to high power; high to low power) impacts tax evasion (Experiments 2-4). Results show that the amount of fine does not impact tax payments, whereas participants' beliefs regarding tax authority's power significantly shape compliance decisions. Descriptions of high coercive power as well as high legitimate power affect beliefs about tax authority's power and positively impact tax honesty. This effect still holds if both qualities of power are applied simultaneously. The contrast of descriptions has little impact on tax evasion. The current study indicates that descriptions of the tax authority, e.g., in information brochures and media reports, have more influence on beliefs and tax payments than information on fine rates. Methodically, these considerations become particularly important when descriptions or vignettes are used besides objective information.

  19. Does the sole description of a tax authority affect tax evasion?--the impact of described coercive and legitimate power.

    Directory of Open Access Journals (Sweden)

    Barbara Hartl

    Full Text Available Following the classic economic model of tax evasion, taxpayers base their tax decisions on economic determinants, like fine rate and audit probability. Empirical findings on the relationship between economic key determinants and tax evasion are inconsistent and suggest that taxpayers may rather rely on their beliefs about tax authority's power. Descriptions of the tax authority's power may affect taxpayers' beliefs and as such tax evasion. Experiment 1 investigates the impact of fines and beliefs regarding tax authority's power on tax evasion. Experiments 2-4 are conducted to examine the effect of varying descriptions about a tax authority's power on participants' beliefs and respective tax evasion. It is investigated whether tax evasion is influenced by the description of an authority wielding coercive power (Experiment 2, legitimate power (Experiment 3, and coercive and legitimate power combined (Experiment 4. Further, it is examined whether a contrast of the description of power (low to high power; high to low power impacts tax evasion (Experiments 2-4. Results show that the amount of fine does not impact tax payments, whereas participants' beliefs regarding tax authority's power significantly shape compliance decisions. Descriptions of high coercive power as well as high legitimate power affect beliefs about tax authority's power and positively impact tax honesty. This effect still holds if both qualities of power are applied simultaneously. The contrast of descriptions has little impact on tax evasion. The current study indicates that descriptions of the tax authority, e.g., in information brochures and media reports, have more influence on beliefs and tax payments than information on fine rates. Methodically, these considerations become particularly important when descriptions or vignettes are used besides objective information.

  20. TAX EVASION THROUGH FICTITIOUS ECONOMIC OPERATIONS, OBSTACLE TO SUSTAINABLE DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    SERGIU-BOGDAN CONSTANTIN

    2016-06-01

    Full Text Available Tax evasion means the avoidance of declaring and paying taxes. The purpose of the research is to identify ways and mechanisms of tax evasion through fictitious economic operations and how this kind o tax evasion can influence sustainable development. The principal methods are researching tax evasion cases investigated by the Romanian authorities responsible for combating this phenomenon, court trials on tax evasion and using the bibliographic references in the field. The data used are obtained through open sources of the authorities specialized in combating tax evasion for the cases made public, the media and also from specialised literature. The principal results are that this type of tax evasion is manifested through transactions with “ghost companies”, with offshore companies and transactions between associated enterprises. The main causes of this problem are: high taxation, corruption, inefficient government and tax authorities, no fiscal education and very hard tax legislation. The consequences are that the state budget is affected, the companies that do business legally are affected and also the final consumers, so Romania will not have economic growth and the quality of life will not improve. The main conclusion is that in order to have sustainable development, tax evasion in general and this kind of tax evasion in particular must be eradicated. The measures that have to be taken are to prevent tax evasion and to tighten controls but without violating taxpayers rights and without making abuses

  1. Treatment of malignant brain tumor. Today and tomorrow. Image-guided neurosurgery for brain tumor. A current perspective

    International Nuclear Information System (INIS)

    Kajita, Yasukazu; Fujii, Masazumi; Yoshida, Jun; Maesawa, Satoshi

    2008-01-01

    Although usefulness of the image-guided neurosurgery is well documented, there are scarce facilities having the actually operating system in Japan. Since 2006, authors' Nagoya University Hospital has had an operating room named ''Brain THEATER'', where an open MRI system APERTO (Hitachi-Medical Co.) and a navigation system Vector Vision (BrainLAB) are connected to conduct the complete image-guided neurosurgery for brain tumor by using the intraoperative MRI for continuously updating the residual tumor tissue to be dissected out. The room is pre- and intra-operatively supported by Departments of image analysis and of radiation technology in the University, and as well, is connected by net-working with another image-guided surgical room ''Brain Suite'' (Siemens 1.5 T MRI system: BrainLAB) in the neighboring facility, Nagoya Central Hospital. This paper describes the circumstances of the introduction of these systems in the Hospital, details of the image-guided surgery in the operation rooms with illustration of actual photos of the rooms and of pre-, intra- and post-operative images, outcomes of image-guided neurosurgery for brain tumor reported hitherto, image-guided neurosurgery for brain tumor's future perspectives involving robotic surgery and operation on the virtual 3D image including the net-worked one. Efforts should be made to further spread the system for performing the more non-invasive and precise surgery, and for conducting the diagnosis united with treatment. (R.T.)

  2. Elements of Compared Law concerning Tax Evasion

    Directory of Open Access Journals (Sweden)

    Monica Pocora

    2015-08-01

    Full Text Available The resort to international tax evasion can be explained both through the game, often perverse, of the double taxation, due to the autonomy of the national fiscal regimes, as well as to the fiscal pressures deriving from these. In view of escaping to be subject to two different taxations, the taxpayer wishes actually to avoid them both. And in order to avoid being subject to either of them, he takes cover in the fiscally protected regions. The techniques are numerous and depend on the taxpayer’s imagination. They contain a series of subtle and agile combinations of using the disappearances between the fiscal systems by resorting sometimes to fraudulent mechanisms. This paper aims at analysing the European dimension of the evasion phenomenon, corresponding to some fiscal and social laws that are more favourable.

  3. THE LINK BETWEEN ACCOUNTING AND FISCAL EVASION

    Directory of Open Access Journals (Sweden)

    Silvia Lăzărescu (Marinescu

    2008-12-01

    Full Text Available In the literature, controversies have arisen concerning the link between accounting and fiscal evasion, which are the object of debates among specialists from different specialized organizations from many countries. Under the term of “creative accounting”, the American and European tax systems have made up an ensemble of accounting mechanisms and also of fiscal manipulation which increased the interest and involvement of the states in the mitigation of such fraud risks and fiscal subterfuges whose percentage in the countries’ GDP varies from 8 to 80%. Starting from the SWOT analysis of tax evasion in the real and underground economy, the specialists of the liberal trades are called to join the fight against fiscal fraud and share their professionalism in creating a real competitive environment characterized by fair play.

  4. Tax Havens: International Tax Avoidance and Evasion

    OpenAIRE

    Gravelle, Jane G.

    2009-01-01

    The federal government loses both individual and corporate income tax revenue from the shifting of profits and income into low-tax countries, often referred to as tax havens. Tax havens are located around the world with concentrations in the Caribbean and Europe. Corporate profit shifting may cost up to $60 billion in revenue and remedies are likely to involve tax law changes. Individual income tax losses more often arise from tax evasion, and are facilitated by the lack of information report...

  5. TAX EVASION IN CROSS BORDER TEXTILES OPERATIONS

    Directory of Open Access Journals (Sweden)

    ANDREESCU Nicoleta Alina

    2014-05-01

    Full Text Available We appreciated that the work can be divided into four chapters designed to enlighten, as far as possible the negative effects that evasion has, particularly the socio-economic phenomenon, faced by all countries. The negative effects generate an indisputable fraud phenomenon and tax evasion, which are felt directly on the level of tax revenue receipts, causing major distortions in the functioning of the mechanism of the market. Fiscal policy using the taxes generates psychological, financial, economic, social effects on a socio-economic environment. The public power that realizes the reality of the tax consequences of the action taken as solution changes of the tax system structure in order to modulate the effects according with the expected outcome. Therefore, the aimed pursued extent influences the technical characteristics of the taxes, and they influence the micro and macroeconomic effects. In this respect it has been proved that reducing tax evasion it allows the creation of budgetary resources necessary for allotting funds for economic growth. Developing and implementing a modern and predictable tax for a medium and long term, would be indispensable in the context of competition that occurs between the European states for attracting new investment and creating new jobs. The taxes do not have to shape the behavior of taxpayers, they must be the same regardless of the type of income, it should not include distortions. In order to be reasonable, the fiscal tax should be distributed as wide as possible.

  6. Tax Evasion and Economic Growth in an Endogenous Growth Model

    OpenAIRE

    加藤, 秀弥; KATO, Hideya

    2004-01-01

    This paper presents an endogenous growth model with tax evasion where government expenditures affect production. An individual evades a tax so as to maximize his or her utility, the tax authority controls the detection probability to maximize net tax revenue, and the government chooses the income tax rate to maximize individuals’ utility. The main conclusions are as follows. First, the optical income tax rate with tax evasion is higher than that without tax evasion. Second, the rise in a ...

  7. International capital tax evasion and the foreign tax credit puzzle

    OpenAIRE

    Kimberley A. Scharf

    2001-01-01

    This paper examines the role of international tax evasion for the choice of an optimal foreign tax credit by a capital exporting region. Since a foreign tax credit raises the opportunity cost of concealing foreign source income, it can be employed to discourage evasion activity. The existence of international tax evasion possibilities could thus help rationalize a choice of tax credit in excess of a deduction-equivalent credit level. Our analysis shows that, in general the optimal credit will...

  8. Tax Evasion Dynamics in Romania Reflected by Fiscal Inspection Activities

    Directory of Open Access Journals (Sweden)

    CORINA-MARIA ENE

    2010-06-01

    Full Text Available The paper aims to provide a panoramic view of the dynamics of tax evasion in Romania, reflected in terms of fiscal inspection activities. The author used the official data published by the institutions with attributions on the line of identification and fighting against tax evasion (National Agency of Fiscal Administration and Financial Guard with the view to reflect the real situation concerning the number of inspections, quantify and sanction tax evasion for 2003-2008 periods. Although the number of fiscal inspections and the number of tax payers who have violated the rules of fiscal discipline decreased compared with 2003, the frequency of tax evasion remained. At the same time, based on the data referring to the level and dynamics of the tax dodger phenomenon appreciations have been made regarding the fiscal discipline of the Romanian tax payer and to the attitude of the qualified institutions in discovering and sanctioning the fraudulent tax evasion. In this respect, the author observed that the level of willingness of tax legislation in relation to the Romanian tax payer has not changed considerably.The level of identified tax evasion reported to real GDP increased slightly. This situation can be interpreted as a success of institutions in charge of identification and fighting of tax evasion, a result of the increase of fiscal inspection number and detection probability, but also a result of GDP growth at a rate lower than the identified tax evasion. The author has also tried to find a causality relation between the option for tax evasion and corruption. The author found that a corrupt environment facilitates the decision to evade depending on detection probability, penalty system and bribery level as discouraging factors for tax evasion. The level of identified tax evasion is smaller than the real level of entire tax evasion, an important part being impossible to determine because of corruption.

  9. Study of seismological evasion. Part III. Evaluation of evasion possibilities using codas of large earthquakes

    International Nuclear Information System (INIS)

    Evernden, J.F.

    1976-01-01

    The seismological aspects of various proposed means of obscuring or hiding the seismic signatures of explosions from a surveillance network are discussed. These so-called evasion schemes are discussed from the points of view of both the evader and the monitor. The analysis will be conducted in terms of the USSR solely because that country is so vast and the geological/geophysical complexities of the country are so great that the complete spectrum of hypothesized evasion schemes requires discussion. Techniques appropriate for use when the seismic noise problem is interference due to codas of P and surface waves from earthquakes are described, and the capabilities of several seismological networks to restrain use of such codas for effective evasion are analyzed

  10. Current diagnosis of tumors developed in the internal auditory canal and cerebellopontine angle

    International Nuclear Information System (INIS)

    Vignaud, J.; Doyon, D.

    1988-01-01

    The introduction of CT scan and, more recently, magnetic resonance imaging, has radically changed the diagnostic approach to tumors developed in the internal auditory canal and cerebellopontine angle. CT scan with intravenous injection visualizes tumors lying in the cerebellopontine angle. Magnetic resonance imaging, especially using gadolinium, is a very accurate means for diagnosing tumors of both the auditory canal and cerebellopontine angle [fr

  11. FORMS OF TAX EVASION IN ROMANIA. ANALYTICAL PERSPECTIVE

    Directory of Open Access Journals (Sweden)

    PETRE BREZEANU

    2011-01-01

    Full Text Available This study brings to the fore an analysis of the phenomenon of tax evasion in Romania. The perspective is broad, with a descriptive substrate, originally founded by highlighting the dimensions that define this phenomenon; later, the perspective is materialized by the presentation of tax evasion schemes that often takes the form of real complex fiscal and also financial engineering. The purpose of this work consists in the awareness of practitioners, academics and the public of the tax evasion forms useful in order to identify precise modalities to combat it. Since the volume of funds subject to the phenomenon of tax evasion is greater, the negative effects of macroeconomic environment.

  12. Tax Evasion and the Impact on Economic Growth Acta Universitatis Danubius. OEconomica

    Directory of Open Access Journals (Sweden)

    Shkendije Demalijaj Ukaj

    2014-12-01

    Full Text Available The level of taxation is very important for the development of current and future of a country and fiscal policy should always be considered as an important factor in the behavior of participants and their ability to tax evasion and informality. Government fiscal policies can trigger tax increase under pressure, especially in situations such as economic crisis, inflation, unemployment, instability, when the burden of this obligation grows, its effects are considered to take them to tax evasion and informality (Dragomir. et al. 2011. However, these reasons do not relate to all the great presence of this phenomenon in Kosovo, taking into account the recent economic crisis has not reflected in the economy of Kosovo and the Kosovo tax burden is among the lowest in the region, but leading cause of tax evasion and informality can be considered above the corruption of public administration officials including tax and customs officials, insufficient staff for his fighting, weak rule of law, as well as lower fiscal culture for paying taxes. For this reason the scope of this paper will be the theoretical treatment of the informal economy and tax evasion in view of tax avoidance, meaning, characteristics and their effects on the economy and possible recommendations on these viewpoints.

  13. Loss of function JAK1 mutations occur at high frequency in cancers with microsatellite instability and are suggestive of immune evasion.

    Science.gov (United States)

    Albacker, Lee A; Wu, Jeremy; Smith, Peter; Warmuth, Markus; Stephens, Philip J; Zhu, Ping; Yu, Lihua; Chmielecki, Juliann

    2017-01-01

    Immune evasion is a well-recognized hallmark of cancer and recent studies with immunotherapy agents have suggested that tumors with increased numbers of neoantigens elicit greater immune responses. We hypothesized that the immune system presents a common selective pressure on high mutation burden tumors and therefore immune evasion mutations would be enriched in high mutation burden tumors. The JAK family of kinases is required for the signaling of a host of immune modulators in tumor, stromal, and immune cells. Therefore, we analyzed alterations in this family for the hypothesized signature of an immune evasion mutation. Here, we searched a database of 61,704 unique solid tumors for alterations in the JAK family kinases (JAK1/2/3, TYK2). We used The Cancer Genome Atlas and Cancer Cell Line Encyclopedia data to confirm and extend our findings by analyzing gene expression patterns. Recurrent frameshift mutations in JAK1 were associated with high mutation burden and microsatellite instability. These mutations occurred in multiple tumor types including endometrial, colorectal, stomach, and prostate carcinomas. Analyzing gene expression signatures in endometrial and stomach adenocarcinomas revealed that tumors with a JAK1 frameshift exhibited reduced expression of interferon response signatures and multiple anti-tumor immune signatures. Importantly, endometrial cancer cell lines exhibited similar gene expression changes that were expected to be tumor cell intrinsic (e.g. interferon response) but not those expected to be tumor cell extrinsic (e.g. NK cells). From these data, we derive two primary conclusions: 1) JAK1 frameshifts are loss of function alterations that represent a potential pan-cancer adaptation to immune responses against tumors with microsatellite instability; 2) The mechanism by which JAK1 loss of function contributes to tumor immune evasion is likely associated with loss of the JAK1-mediated interferon response.

  14. ERAP1 overexpression in HPV-induced malignancies: A possible novel immune evasion mechanism.

    Science.gov (United States)

    Steinbach, Alina; Winter, Jan; Reuschenbach, Miriam; Blatnik, Renata; Klevenz, Alexandra; Bertrand, Miriam; Hoppe, Stephanie; von Knebel Doeberitz, Magnus; Grabowska, Agnieszka K; Riemer, Angelika B

    2017-01-01

    Immune evasion of tumors poses a major challenge for immunotherapy. For human papillomavirus (HPV)-induced malignancies, multiple immune evasion mechanisms have been described, including altered expression of antigen processing machinery (APM) components. These changes can directly influence epitope presentation and thus T-cell responses against tumor cells. To date, the APM had not been studied systematically in a large array of HPV + tumor samples. Therefore in this study, systematic expression analysis of the APM was performed on the mRNA and protein level in a comprehensive collection of HPV16 + cell lines. Subsequently, HPV + cervical tissue samples were examined by immunohistochemistry. ERAP1 (endoplasmic reticulum aminopeptidase 1) was the only APM component consistently altered - namely overexpressed - in HPV16 + tumor cell lines. ERAP1 was also found to be overexpressed in cervical intraepithelial neoplasia and cervical cancer samples; expression levels were increasing with disease stage. On the functional level, the influence of ERAP1 expression levels on HPV16 E7-derived epitope presentation was investigated by mass spectrometry and in cytotoxicity assays with HPV16-specific T-cell lines. ERAP1 overexpression did not cause a complete destruction of any of the HPV epitopes analyzed, however, an influence of ERAP1 overexpression on the presentation levels of certain HPV epitopes could be demonstrated by HPV16-specific CD8 + T-cells. These showed enhanced killing toward HPV16 + CaSki cells whose ERAP1 expression had been attenuated to normal levels. ERAP1 overexpression may thus represent a novel immune evasion mechanism in HPV-induced malignancies, in cases when presentation of clinically relevant epitopes is reduced by overactivity of this peptidase.

  15. Radiotherapy for pediatric brain tumors: Standards of care, current clinical trials, and new directions

    International Nuclear Information System (INIS)

    Goldwein, Joel W.

    1995-01-01

    The objectives of the course are to evaluate the role of radiation therapy in the treatment of pediatric brain tumors. Areas where the role is evolving will be identified, and the results of clinical trials which been mounted to clarify radiotherapy's role will be reviewed. Brain tumors are the second most common malignancy of childhood after leukemias and lymphomas. However, they remain the most common group of childhood tumors to require radiation therapy. Therefore, a thorough understanding of these tumors, and the appropriate role of surgery, radiation and chemotherapy is critical. Issues surrounding the management of sequelae are no less important. The role of radiotherapy for the treatment of these tumors is far different from that for adults. These differences relate to the profound potential for sequelae from therapy, the higher overall cure rates, and the utility of multimodality therapies. In addition, the rarity of childhood brain tumors compared with adults' makes them more difficult to study. In this session, the following issues will be reviewed; 1. Incidence of pediatric brain tumors, 2. General issues regarding symptoms, diagnosis, diagnostic tests and evaluation, 3. Importance of a team approach, 4. General issues regarding treatment sequelae, 5. Specific tumor types/entities; a. Cerebellar Astrocytomas b. Benign and malignant Gliomas including brainstem and chiasmatic lesions c. Primitive Neuroectodermal Tumors (PNET) and Medulloblastoma d. Ependymomas e. Craniopharyngiomas f. Germ cell tumors g. Miscellaneous and rare pediatric brain tumors 6. Management of sequelae 7. New and future directions a. Treatment of infants b. The expanding role of chemotherapy c. Advances in radiotherapy. The attendees will complete the course with a better understanding of the role that radiation therapy plays in the treatment of pediatric brain tumors. They will be knowledgeable in the foundation for that role, and the changes which are likely to take place in the

  16. Introduction to "Binding Maritime China: Control, Evasion, and Interloping"

    Directory of Open Access Journals (Sweden)

    Eugenio Menegon

    2017-12-01

    Full Text Available Maritime Asia is a confusing morass of contested sovereignties and geopolitical rivalries. Yet the seaways of Asia have, in their history, also fostered cultural exchange and economic integration. The liminal maritime zone surrounding China remains a paradox between seas and ports teeming with legal and illegal exchange and governmental policies attempting to monopolize and restrict that exchange. Vast and fluid, maritime China has long hindered state control and fostered connections determined as much by bottom-up economic and cultural logic as by top-down official impositions. This issue of Cross-Currents proposes to reexamine the rich history of maritime China and adjacent areas by tracing the interactions of the three initiatives of control, evasion, and interloping. This special issue stems from a conference the guest editors organized in Boston in 2015, with support from Boston University, Brandeis University, Northeastern University, and the Taiwan Ministry of Education. We invited a distinguished group of scholars to explore the many facets of maritime China’s history. Our key postulation was that state control, evasion from that control, and interloping within the interstices of China’s maritime world literally bound an array of actors and locales for distinct but interrelated goals, from the early modern era to the modern era. This concept is encapsulated in the title of the current issue, “Binding Maritime China.” What “creates” and gives coherence to the concept of maritime China as a social, economic, political, and geographic space is, to a large extent, how human actors (Chinese and Western merchants and businessmen, navy officers, bureaucrats, fishermen, pirates, missionaries, and so on productively interacted or experienced conflicts and resisted one another’s control. They did so across oceanic and coastal spaces, administrative boundaries, class lines, bureaucratic institutions, commercial organizations, and

  17. Multiagent pursuit-evasion games: Algorithms and experiments

    Science.gov (United States)

    Kim, Hyounjin

    Deployment of intelligent agents has been made possible through advances in control software, microprocessors, sensor/actuator technology, communication technology, and artificial intelligence. Intelligent agents now play important roles in many applications where human operation is too dangerous or inefficient. There is little doubt that the world of the future will be filled with intelligent robotic agents employed to autonomously perform tasks, or embedded in systems all around us, extending our capabilities to perceive, reason and act, and replacing human efforts. There are numerous real-world applications in which a single autonomous agent is not suitable and multiple agents are required. However, after years of active research in multi-agent systems, current technology is still far from achieving many of these real-world applications. Here, we consider the problem of deploying a team of unmanned ground vehicles (UGV) and unmanned aerial vehicles (UAV) to pursue a second team of UGV evaders while concurrently building a map in an unknown environment. This pursuit-evasion game encompasses many of the challenging issues that arise in operations using intelligent multi-agent systems. We cast the problem in a probabilistic game theoretic framework and consider two computationally feasible pursuit policies: greedy and global-max. We also formulate this probabilistic pursuit-evasion game as a partially observable Markov decision process and employ a policy search algorithm to obtain a good pursuit policy from a restricted class of policies. The estimated value of this policy is guaranteed to be uniformly close to the optimal value in the given policy class under mild conditions. To implement this scenario on real UAVs and UGVs, we propose a distributed hierarchical hybrid system architecture which emphasizes the autonomy of each agent yet allows for coordinated team efforts. We then describe our implementation on a fleet of UGVs and UAVs, detailing components such

  18. Aspects of random geometric graphs : Pursuit-evasion and treewidth

    NARCIS (Netherlands)

    Li, A.

    2015-01-01

    In this thesis, we studied two aspects of random geometric graphs: pursuit-evasion and treewidth. We first studied one pursuit-evasion game: Cops and Robbers. This game, which dates back to 1970s, are studied extensively in recent years. We investigate this game on random geometric graphs, and get

  19. Rank dependent expected utility models of tax evasion.

    OpenAIRE

    Erling Eide

    2001-01-01

    In this paper the rank-dependent expected utility theory is substituted for the expected utility theory in models of tax evasion. It is demonstrated that the comparative statics results of the expected utility, portfolio choice model of tax evasion carry over to the more general rank dependent expected utility model.

  20. Diagnosis and therapy of carcinoid tumors-current state of the art and future directions

    International Nuclear Information System (INIS)

    Khan, Mazhar U.; Coleman, R. Edward

    2008-01-01

    Carcinoid tumors account for less than 1% of all malignancies and the majority arise in the gastrointestinal system. These tumors are slow growing compared with adenocarcinomas and they differ from the other neuroendocrine malignancies by their protean clinical presentation. Carcinoid tumors were previously considered indolent, but they can manifest malignant characteristics with metastatic spread which often results in a poor prognosis. Although there have been advances in diagnostic and treatment modalities, carcinoid tumors are still often diagnosed late, often when the tumor has metastasized and patients develop carcinoid syndrome. Diagnosis, prognosis and treatment options are based on biochemical markers and imaging investigations. High concentration of urinary 5-HIAA, elevated plasma serotonin and chromogranin A levels help to establish the initial diagnosis of carcinoid tumors. In addition to the CT and MRI, molecular imaging modalities such as OctreoScan, MIBG imaging and more recently PET imaging are vital in detection of primary malignancy and metastatic involvement. Surgery is the mainstay of treatment of nonmetastatic carcinoid tumors. Cytotoxic chemotherapy is not beneficial due to the chemoresistant nature of these tumors. Because carcinoid tumors express somatostatin receptors, somatostatin analogues, which inhibit the release of serotonin and other neuroendocrine peptides, are often used, but their use is limited to symptom control. Treatment using high doses of radionuclides such as radiolabeled somatostatin analogues and MIBG is a more recent option which offers a definite advantage in management. In this article, we review typical features of the carcinoid tumors, examine contemporary methods of detecting and assessing carcinoid tumors and discuss the role of various diagnostic and therapeutic options

  1. Viral Evasion of Natural Killer Cell Activation.

    Science.gov (United States)

    Ma, Yi; Li, Xiaojuan; Kuang, Ersheng

    2016-04-12

    Natural killer (NK) cells play a key role in antiviral innate defenses because of their abilities to kill infected cells and secrete regulatory cytokines. Additionally, NK cells exhibit adaptive memory-like antigen-specific responses, which represent a novel antiviral NK cell defense mechanism. Viruses have evolved various strategies to evade the recognition and destruction by NK cells through the downregulation of the NK cell activating receptors. Here, we review the recent findings on viral evasion of NK cells via the impairment of NK cell-activating receptors and ligands, which provide new insights on the relationship between NK cells and viral actions during persistent viral infections.

  2. Viral Evasion of Natural Killer Cell Activation

    Directory of Open Access Journals (Sweden)

    Yi Ma

    2016-04-01

    Full Text Available Natural killer (NK cells play a key role in antiviral innate defenses because of their abilities to kill infected cells and secrete regulatory cytokines. Additionally, NK cells exhibit adaptive memory-like antigen-specific responses, which represent a novel antiviral NK cell defense mechanism. Viruses have evolved various strategies to evade the recognition and destruction by NK cells through the downregulation of the NK cell activating receptors. Here, we review the recent findings on viral evasion of NK cells via the impairment of NK cell-activating receptors and ligands, which provide new insights on the relationship between NK cells and viral actions during persistent viral infections.

  3. TAX EVASION BETWEEN FRAUD AND OPTIMIZATION

    OpenAIRE

    Emilia Cornelia STOICA

    2017-01-01

    Tax optimization, often called legal tax evasion is the use of methods and techniques that are within the law, in order to reduce or even cancel the tax liability. To achieve such an approach, the taxpayer or his advisers must know in depth the tax law - and by extension, the financial and administrative law - and, moreover, must be functional tax jurisdictions which allow the use of appropriate assemblies. The recent leasks, as WikiLeaks, LuxLeaks, SwissLeaks, Panama Papers etc. on financial...

  4. ACCOUNTING INFORMATION INDISPENSABLE SOURCE FOR THE DISCOVERY OF TAX EVASION IN THE FIELD OF PRODUCTS SUBJECT TO EXCISE

    Directory of Open Access Journals (Sweden)

    Dorel MATEȘ

    2015-12-01

    Full Text Available The present article aims to highlight the kinds of tax evasion methods in the field of products subject to excise duty and the role of the tax inspection in combating them. The research reveals which are the most common methods of tax evasion, but it tries to discern the probable developments of the process. The article has in view the inexorable reality, namely that the ingenuity method of tax fraud increases with the emergence of the new rules or barriers to the fraud. Following the research carried out we found that the tax evasion phenomenon in the field of products subject to excise duty has currently a significant impact in the economic and social Romanian reality. In order to reduce the tax evasion phenomenon in the field of products subject to excise duty, it must set up a mechanism for monitoring, oversight and fiscal control as well as the amendment of legislation, the tax evasion being mainly a consequence of the inaccuracies or imperfection of laws.

  5. Tax Evasion and the Impact on Economic Growth Acta Universitatis Danubius. OEconomica

    OpenAIRE

    Shkendije Demalijaj Ukaj

    2014-01-01

    The level of taxation is very important for the development of current and future of a country and fiscal policy should always be considered as an important factor in the behavior of participants and their ability to tax evasion and informality. Government fiscal policies can trigger tax increase under pressure, especially in situations such as economic crisis, inflation, unemployment, instability, when the burden of this obligation grows, its effects are considered to take them t...

  6. Bone marrow micrometastases and circulating tumor cells: current aspects and future perspectives

    International Nuclear Information System (INIS)

    Müller, Volkmar; Pantel, Klaus

    2004-01-01

    Early tumor cell dissemination at the single-cell level can be revealed in patients with breast cancer by using sensitive immunocytochemical and molecular assays. Recent clinical studies involving more than 4000 breast cancer patients demonstrated that the presence of disseminated tumor cells in bone marrow at primary diagnosis is an independent prognostic factor. In addition, various assays for the detection of circulating tumor cells in the peripheral blood have recently been developed and some studies also suggest a potential clinical relevance of this measure. These findings provide the basis for the potential use of disseminated tumor cells in bone marrow or blood as markers for the early assessment of therapeutic response in prospective clinical trials

  7. Evasion of immunosurveillance by genomic alterations of PPARγ/RXRα in bladder cancer.

    Science.gov (United States)

    Korpal, Manav; Puyang, Xiaoling; Jeremy Wu, Zhenhua; Seiler, Roland; Furman, Craig; Oo, Htoo Z; Seiler, Michael; Irwin, Sean; Subramanian, Vanitha; Julie Joshi, Jaya; Wang, Chris K; Rimkunas, Victoria; Tortora, Davide; Yang, Hua; Kumar, Namita; Kuznetsov, Galina; Matijevic, Mark; Chow, Jesse; Kumar, Pavan; Zou, Jian; Feala, Jacob; Corson, Laura; Henry, Ryan; Selvaraj, Anand; Davis, Allison; Bloudoff, Kristjan; Douglas, James; Kiss, Bernhard; Roberts, Morgan; Fazli, Ladan; Black, Peter C; Fekkes, Peter; Smith, Peter G; Warmuth, Markus; Yu, Lihua; Hao, Ming-Hong; Larsen, Nicholas; Daugaard, Mads; Zhu, Ping

    2017-07-24

    Muscle-invasive bladder cancer (MIBC) is an aggressive disease with limited therapeutic options. Although immunotherapies are approved for MIBC, the majority of patients fail to respond, suggesting existence of complementary immune evasion mechanisms. Here, we report that the PPARγ/RXRα pathway constitutes a tumor-intrinsic mechanism underlying immune evasion in MIBC. Recurrent mutations in RXRα at serine 427 (S427F/Y), through conformational activation of the PPARγ/RXRα heterodimer, and focal amplification/overexpression of PPARγ converge to modulate PPARγ/RXRα-dependent transcription programs. Immune cell-infiltration is controlled by activated PPARγ/RXRα that inhibits expression/secretion of inflammatory cytokines. Clinical data sets and an in vivo tumor model indicate that PPARγ High /RXRα S427F/Y impairs CD8 + T-cell infiltration and confers partial resistance to immunotherapies. Knockdown of PPARγ or RXRα and pharmacological inhibition of PPARγ significantly increase cytokine expression suggesting therapeutic approaches to reviving immunosurveillance and sensitivity to immunotherapies. Our study reveals a class of tumor cell-intrinsic "immuno-oncogenes" that modulate the immune microenvironment of cancer.Muscle-invasive bladder cancer (MIBC) is a potentially lethal disease. Here the authors characterize diverse genetic alterations in MIBC that convergently lead to constitutive activation of PPARgamma/RXRalpha and result in immunosurveillance escape by inhibiting CD8+ T-cell recruitment.

  8. [Regulatory Mechanisms of PD-L1 Expression and Its Role in Immune Evasion].

    Science.gov (United States)

    Kataoka, Keisuke

    2017-11-01

    Immune checkpoint blockade therapy using anti-PD-1 or anti-PD-L1 antibodies can unleash anti-tumor immunity and induce durable remission in a variety ofhuman cancers. However, the regulatory mechanisms of PD-L1 expression mediating immune evasion ofcancer cells have not been fully elucidated, including the genetic alterations causing PD-L1 overexpression. Recently, we have reported a novel genetic mechanism ofimmune evasion associated with structural variations(SVs)disrupting the 3'-untranslated region(UTR)ofthe PD-L1 gene in various malignancies, such as aggressive lymphomas and gastrointestinal cancers. Despite a heterogenous nature ofthese SVs, they are closely associated with a marked upregulation of PD-L1 expression, which augments tumor growth and escape from anti-tumor immunity. Here we present an overview of the regulatory mechanisms of PD-L1 expression in cancer cells, highlighting the genetic mechanisms of PD-L1 constitutive activation, with specific focus on PD-L1 3'-UTR disruption.

  9. Determination of mercury evasion in a contaminated headwater stream.

    Science.gov (United States)

    Maprani, Antu C; Al, Tom A; Macquarrie, Kerry T; Dalziel, John A; Shaw, Sean A; Yeats, Phillip A

    2005-03-15

    Evasion from first- and second-order streams in a watershed may be a significant factor in the atmospheric recycling of volatile pollutants such as mercury; however, methods developed for the determination of Hg evasion rates from larger water bodies are not expected to provide satisfactory results in highly turbulent and morphologically complex first- and second-order streams. A new method for determining the Hg evasion rates from these streams, involving laboratory gas-indexing experiments and field tracer tests, was developed in this study to estimate the evasion rate of Hg from Gossan Creek, a first-order stream in the Upsalquitch River watershed in northern New Brunswick, Canada. Gossan Creek receives Hg-contaminated groundwater discharge from a gold mine tailings pile. Laboratory gas-indexing experiments provided the ratio of gas-exchange coefficients for zero-valent Hg to propane (tracer gas) of 0.81+/-0.16, suggesting that the evasion mechanism in highly turbulent systems can be described by the surface renewal model with an additional component of enhanced gas evasion probably related to the formation of bubbles. Deliberate field tracer tests with propane and chloride tracers were found to be a reliable and practical method for the determination of gas-exchange coefficients for small streams. Estimation of Hg evasion from the first 1 km of Gossan Creek indicates that about 6.4 kg of Hg per year is entering the atmosphere, which is a significant fraction of the regional sources of Hg to the atmosphere.

  10. Current clinical practice: differential management of uveal melanoma in the era of molecular tumor analyses

    Directory of Open Access Journals (Sweden)

    Aaberg Jr TM

    2014-12-01

    Full Text Available Thomas M Aaberg Jr,1 Robert W Cook,2 Kristen Oelschlager,2 Derek Maetzold,2 P Kumar Rao,3 John O Mason III41Michigan State University Medical School and Retina Specialists of Michigan, Grand Rapids, MI, 2Castle Biosciences, Friendswood, TX, 3Washington University School of Medicine in St Louis, St Louis, MO, 4Retina Consultants of Alabama and University of Alabama Birmingham, Birmingham, AL, USA Objective: Assess current clinical practices for uveal melanoma (UM and the impact of molecular prognostic testing on treatment decisions.Design: Cross-sectional survey and sequential medical records review.Participants: Ophthalmologists who treat UM.Methods: (A Medical records review of all Medicare beneficiaries tested by UM gene expression profile in 2012, conducted under an institutional review board-approved protocol. (B 109 ophthalmologists specializing in the treatment of UM were invited to participate in 24-question survey in 2012; 72 were invited to participate in a 23-question survey in 2014.Main outcome measures: Responses analyzed by descriptive statistics, frequency analyses (percentages, Tukey, histograms, and Fisher’s exact test. Descriptive presentation of essay answers.Results: The review of Medicare medical records included 191 evaluable patients, 88 (46% with documented medical treatment actions or institutional policies related to surveillance plans. Of these 88, all gene expression profiling (GEP Class 1 UM patients were treated with low-intensity surveillance. All GEP Class 2 UM patients were treated with high-intensity surveillance (P<0.0001 versus Class 1. There were 36 (19% with information concerning referrals after initial diagnosis. Of these 36, all 23 Class 2 patients were referred to medical oncology; however, none of the 13 Class 1 patients were referred (P<0.0001 versus Class 1. Only Class 2 patients were recommended for adjunctive treatment regimens. 2012 survey: 50 respondents with an annual median of 35 new UM

  11. Contributions to Pursuit-Evasion Game Theory

    Science.gov (United States)

    Oyler, Dave Wilson

    This dissertation studies adversarial conflicts among a group of agents moving in the plane, possibly among obstacles, where some agents are pursuers and others are evaders. The goal of the pursuers is to capture the evaders, where capture requires a pursuer to be either co-located with an evader, or in close proximity. The goal of the evaders is to avoid capture. These scenarios, where different groups compete to accomplish conflicting goals, are referred to as pursuit-evasion games, and the agents are called players. Games featuring one pursuer and one evader are analyzed using dominance, where a point in the plane is said to be dominated by a player if that player is able to reach the point before the opposing players, regardless of the opposing players' actions. Two generalizations of the Apollonius circle are provided. One solves games with environments containing obstacles, and the other provides an alternative solution method for the Homicidal Chauffeur game. Optimal pursuit and evasion strategies based on dominance are provided. One benefit of dominance analysis is that it extends to games with many players. Two foundational games are studied; one features multiple pursuers against a single evader, and the other features a single pursuer against multiple evaders. Both are solved using dominance through a reduction to single pursuer, single evader games. Another game featuring competing teams of pursuers is introduced, where an evader cooperates with friendly pursuers to rendezvous before being captured by adversaries. Next, the assumption of complete and perfect information is relaxed, and uncertainties in player speeds, player positions, obstacle locations, and cost functions are studied. The sensitivity of the dominance boundary to perturbations in parameters is provided, and probabilistic dominance is introduced. The effect of information is studied by comparing solutions of games with perfect information to games with uncertainty. Finally, a pursuit law

  12. The consequences of different strategies for measuring tax evasion behavior

    Directory of Open Access Journals (Sweden)

    Ghavam Ahmadi

    2014-11-01

    Full Text Available This paper presents a study to investigate the effect of tax strategy on tax evasion in province of Zanjan, Iran. The study selects two randomly selected populations of 100 people from Tax organization and the people who file income tax with revenue agency. The study designs a questionnaire in Likert scale to study the effects of five variables namely; promote tax culture, lack of belief in tax payment consequences, filing false tax statement, tax exemption and general culture community as independent variables on tax evasion behavior. Using regression technique, the study has determined positive and meaningful relationships between tax evasion and independent variables.

  13. Identifying Bacterial Immune Evasion Proteins Using Phage Display.

    Science.gov (United States)

    Fevre, Cindy; Scheepmaker, Lisette; Haas, Pieter-Jan

    2017-01-01

    Methods aimed at identification of immune evasion proteins are mainly rely on in silico prediction of sequence, structural homology to known evasion proteins or use a proteomics driven approach. Although proven successful these methods are limited by a low efficiency and or lack of functional identification. Here we describe a high-throughput genomic strategy to functionally identify bacterial immune evasion proteins using phage display technology. Genomic bacterial DNA is randomly fragmented and ligated into a phage display vector that is used to create a phage display library expressing bacterial secreted and membrane bound proteins. This library is used to select displayed bacterial secretome proteins that interact with host immune components.

  14. Colisional Cloud Debris and Propelled Evasive Maneuvers

    Science.gov (United States)

    Ferreira, L. S.; Jesus, A. D. C.; Carvalho, T. C. F.; Sousa, R. R.

    2017-10-01

    Space debris clouds exist at various altitudes in the environment outside the Earth. Fragmentation of debris and/or collision between the debris of a cloud increases the amount of debris, producing smaller debris. This event also increases significantly the chances of collision with operational vehicles in orbit. In this work we study clouds of debris that are close to a spacecraft in relation to its distance from the center of the Earth. The results show several layers of colliding debris depending on their size over time of evasive maneuvers of the vehicle. In addition, we have tested such maneuvers for propulsion systems with a linear and exponential mass variation model. The results show that the linear propulsion system is more efficient.

  15. Tax evasion between fiscal and penalty

    Directory of Open Access Journals (Sweden)

    Andreea Mihaela Corîci

    2017-12-01

    Full Text Available Although in present times a big importance is given to combating and preventing tax evasion, as well as to all tax frauds, there are, however, people who are tax evaders from the point of view of the criminal body, who manage to ease of payment of tax liabilities to the state. By imposing more drastic or lighter penalties, it is attempted to determine the taxpayer in order not to escape the payment of taxes and to commit the crime.If for the financial controlling authority a fiscal crime has a direct impact on the budget of a certain area, the fiscal action is a criminal one for the criminal authority.

  16. Tax evasion and Swiss bank deposits

    DEFF Research Database (Denmark)

    Johannesen, Niels

    2014-01-01

    quarters immediately before and after the tax was introduced. We also present evidence suggesting that the drop in Swiss bank deposits was driven by behavioral responses aiming to escape the tax - such as the transfer of funds to bank accounts in other offshore centers and the transfer of formal ownership......Bank deposits in offshore financial centers may be used to evade taxes on interest income. A recent EU reform limits the scope for this type of tax evasion by introducing a withholding tax on interest income earned by EU households in Switzerland and several other offshore centers. This paper...... estimates the impact of the withholding tax on Swiss bank deposits held by EU residents while using non-EU residents who were not subject to the tax as a comparison group. We present evidence that Swiss bank deposits owned by EU residents declined by 30–40% relative to other Swiss bank deposits in two...

  17. Current concepts in non-gastrointestinal stromal tumor soft tissue sarcomas: A primer for radiologists

    Energy Technology Data Exchange (ETDEWEB)

    Baheti, Akahay D. [Dept. of Radiology, Tata Memorial Centre, Mumbai (India); Tirumani, Harika [Dept. of Radiology, University of Arkansas for Medical Sciences, Little Rock (United States); O' Neill, Alibhe; Jagannathan, Jyothi P. [Dept. of Imaging, Dana-Farber Cancer Institute, Boston (United States)

    2017-01-15

    Non-gastrointestinal stromal tumor (GIST) soft tissue sarcomas (STSs) are a heterogeneous group of neoplasms whose classification and management continues to evolve with better understanding of their biologic behavior. The 2013 World Health Organization (WHO) has revised their classification based on new immunohistochemical and cytogenetic data. In this article, we will provide a brief overview of the revised WHO classification of soft tissue tumors, discuss in detail the radiology and management of the two most common adult non-GIST STS, namely liposarcoma and leiomyosarcoma, and review some of the emerging histology-driven targeted therapies in non-GIST STS, focusing on the role of the radiologist.

  18. Current concepts in non-gastrointestinal stromal tumor soft tissue sarcomas: A primer for radiologists

    International Nuclear Information System (INIS)

    Baheti, Akahay D.; Tirumani, Harika; O'Neill, Alibhe; Jagannathan, Jyothi P.

    2017-01-01

    Non-gastrointestinal stromal tumor (GIST) soft tissue sarcomas (STSs) are a heterogeneous group of neoplasms whose classification and management continues to evolve with better understanding of their biologic behavior. The 2013 World Health Organization (WHO) has revised their classification based on new immunohistochemical and cytogenetic data. In this article, we will provide a brief overview of the revised WHO classification of soft tissue tumors, discuss in detail the radiology and management of the two most common adult non-GIST STS, namely liposarcoma and leiomyosarcoma, and review some of the emerging histology-driven targeted therapies in non-GIST STS, focusing on the role of the radiologist

  19. Equilibrium Implications of Fiscal Policy with Tax Evasion

    DEFF Research Database (Denmark)

    Busato, Francesco; Chiarini, Bruno; Rey, Guido M.

    This paper studies equilibrium effects of fiscal policy disturbances within a dynamic general equilibrium model where tax evasion and underground activities are explicitly incorporated. There are three mainresults. (i) The underground sector mitigates the distortionary impact of fiscal policies......, while lesseningthe drop (and the rise) of aggregate production after restrictive (expansionary) tax shocks. (ii) Taxevasion and underground economy can rationalize expansionary response to contractionary fiscal policies;(iii) A dynamic general equilibrium with tax evasion gives a rational justification...

  20. The Effect of Tax Rates on Fiscal Evasion and Avoidance

    OpenAIRE

    Mentor Gashi; Halil Kukaj

    2016-01-01

    Abstract:In order to findelements that destimulate fiscal evasion or avoidance, we have submitted six elements, through the questionnaire, to determine which elements are that destimulate the fiscal evasion and avoidance, and evaluate their impact.This paper is focused in customs duty avoidance.The elements that we have submitted to evaluate their power, are: Powerful control during customs clearance, more efficient post clearance control, probability of subject investigation, higher fines, l...

  1. TAX EVASION UNDER THE INFLUENCE OF FISCAL POLICY MEASURES

    Directory of Open Access Journals (Sweden)

    IONUŢ-GHEORGHE CĂRĂUŞ

    2016-08-01

    Full Text Available The collection efficiency of the budget revenues depends largely on the ability of the State, through tax authorities empowered, to apply firm measures to prevent and fight against fraud and tax evasion. However, the phenomenon of fraud and tax evasion is a complex process that extends quickly beyond national borders. That is why it is necessary to the existence of international cooperation against fraud and tax evasion as much as possible, in accordance with the principle of good governess in the field of taxation, thus eliminating negative fiscal measures. Therefore it requires a strict monitoring of collection activities arranged by fiscal legislation of each EU Member State, the automatic exchange of information to be made permanent through mutual information between countries regarding incomes or financial liquidity held by individuals resident in other EU countries, by creating an effective mechanism to fight against tax evasion regarding VAT, by sending alerts between EU Member States in case of suspicious economic activities. Also, it is necessary to correlate and intensify measures to prevent and fight against tax evasion, addressing various issues in a different manner, namely in terms of the taxpayers. Thus, it is necessary to identify factors that cause taxpayers to evade from payment of tax liabilities and declarations in conjunction with tax burden or with the existing tax easing measures. Only in this context we can understand and fight against the phenomenon of tax evasion in the business environment. In this context, the research carried out has had as its principal objective to analyze the phenomenon of tax evasion in Romania as well as the capacity of the State to recover tax arrears through the application of enforcement measures. Descriptive analysis revealed a dynamic of tax evasion , the highest levels recorded in VAT .

  2. Asymmetric Information, Tax Evasion and Alternative Instruments of Government Revenue

    OpenAIRE

    Rangan Gupta

    2005-01-01

    Using a pure-exchange overlapping generations model, characterized with tax evasion and information asymmetry between the government (the social planner) and the financial intermediaries, we try and seek for the optimal tax and seigniorage plans, derived from the welfare maximizing objective of the social planner. We show that irrespective of whether the economy is characterized by tax evasion, or asymmetric information, a benevolent social planner, maximizing welfare and simultaneously finan...

  3. Establishing the link between money laundering and tax evasion

    OpenAIRE

    Storm, Ansia

    2013-01-01

    No clear link has yet been made between tax evasion and money laundering although many (or all) of the professionals in this field may have already assumed the relation. The aim of the research that was conducted for the purposes of this article was to explore whether there is a clear link between tax evasion and money laundering. This was done by studying the relevant literature available on both subjects. The findings, that there is a clear link between these two offences, we...

  4. Interleukin-36 cytokines may overcome microbial immune evasion strategies that inhibit interleukin-1 family signaling.

    Science.gov (United States)

    Jensen, Liselotte E

    2017-08-15

    Pathogens deploy immune evasion strategies to successfully establish infections within their hosts. Naturally, the host responds by acquiring mechanisms to counter these strategies. There is increasing evidence that the three interleukin-36 (IL-36) cytokines, IL-36α, IL-36β and IL-36γ, play important roles in host immunity. With a focus on the skin as a target for microbial and viral invasion, the current knowledge of IL-36 functions is reviewed. Furthermore, the hypothesis that the IL-36s have evolved to counteract virulence factors is presented using viruses as an example. The IL-36s are related to IL-1α, IL-1β, IL-18, and IL-33. Numerous viruses affecting the skin have developed immune evasion strategies that neutralize IL-1α, IL-1β, or IL-18 signaling or combinations of these pathways. Through small differences in activation mechanisms and receptor utilization, it is possible that IL-36 signaling may proceed unhindered in the presence of these viral inhibitors. Thus, one physiological function of the IL-36s may be to counteract microbial immune evasion. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  5. Evasion Mechanisms Used by Pathogens to Escape the Lectin Complement Pathway.

    Science.gov (United States)

    Rosbjerg, Anne; Genster, Ninette; Pilely, Katrine; Garred, Peter

    2017-01-01

    The complement system is a crucial defensive network that protects the host against invading pathogens. It is part of the innate immune system and can be initiated via three pathways: the lectin, classical and alternative activation pathway. Overall the network compiles a group of recognition molecules that bind specific patterns on microbial surfaces, a group of associated proteases that initiates the complement cascade, and a group of proteins that interact in proteolytic complexes or the terminal pore-forming complex. In addition, various regulatory proteins are important for controlling the level of activity. The result is a pro-inflammatory response meant to combat foreign microbes. Microbial elimination is, however, not a straight forward procedure; pathogens have adapted to their environment by evolving a collection of evasion mechanisms that circumvent the human complement system. Complement evasion strategies features different ways of exploiting human complement proteins and moreover features different pathogen-derived proteins that interfere with the normal processes. Accumulated, these mechanisms target all three complement activation pathways as well as the final common part of the cascade. This review will cover the currently known lectin pathway evasion mechanisms and give examples of pathogens that operate these to increase their chance of invasion, survival and dissemination.

  6. The Tax Evasion in Ukraine: Causes and Methods of Countering

    Directory of Open Access Journals (Sweden)

    Parfentii Liudmyla A.

    2018-03-01

    Full Text Available The essence of the concept of tax evasion is researched; reasons of occurrence and development of this phenomenon are analyzed; proposals on the main directions of prevention and countering tax evasion have been developed. Analyzing, systematizing and generalizing the scientific works of many scholars, it was found that there is no unified approach to interpretation of the essence of this phenomenon in the context of legality and awareness of relevant actions in the scientific literature. As a result of the research the factors of tax evasion with the allocation of moral, political, economic, technical, and legal reasons have been systematized. The preconditions of tax evasion in Ukraine are analyzed, the most common schemes are indicated, resulting from which the budget of Ukraine suffers the greatest losses. Methods of countering tax offenses have been researched and necessity of development and implementation of measures on prevention and countering tax evasion at the State level has been substantiated. Prospects for further researches in this direction are studying of foreign experience of countering tax evasion and detailed analyzing of the tax minimization schemes prevalent in Ukraine with the purpose of identifying ways of elimination of possibility of their use.

  7. Current Research of the Roles of IL-35 in Tumor Progression

    Directory of Open Access Journals (Sweden)

    Chongbiao HUANG

    2016-04-01

    Full Text Available Interleukin(IL-35 is a new member of the interleukin-12 superfamily. Since its first report in 2007, IL-35 rapidly became a research highlight in the field of immunology. Like other IL-12 superfamily members, IL-35 was a heterodimer which was composed of an α chain P35 and a β chain Epstein-Barr virus induced gene 3 (EBI3. Recent research work revealed two distinct roles of IL-35. Firstly, IL-35 is highly expressed in some kinds of inflammatory diseases and autoimmune diseases and plays import roles in the pathogenesis. Secondly, IL-35 is positively expressed in some cancers and plays some roles in the process of tumor progression. Here we demonstrate the structure and the signalling of IL-35. We reviewed the the roles of IL-35 in promoting tumor progression.

  8. Acromegaly in a patient with a pulmonary neuroendocrine tumor: case report and review of current literature.

    Science.gov (United States)

    Krug, Sebastian; Boch, Michael; Rexin, Peter; Pfestroff, Andreas; Gress, Thomas; Michl, Patrick; Rinke, Anja

    2016-06-27

    Pulmonary neuroendocrine tumors (NET) form a heterogeneous group of rare diseases. In these tumors, paraneoplastic syndromes have been described to drive the course of the disease, among them acromegaly induced by paraneoplastic secretion of growth hormone-releasing hormone (GHRH). We report the case of a 43 years old patient initially diagnosed with acromegaly accompanied by weight gain and acral enlargement. Subsequently, further diagnostic work-up identified a solitary pulmonary neuroendocrine tumor (NET). Laboratory tests revealed markedly increased growth hormone (GH) and insulin-like growth factor 1 (IGF-1) without GHRH elevation in the absence of pituitary pathologies confirming the paraneoplastic origin of clinical presentation with acromegaly. Curative surgery was performed leading to normalization of the elevated hormone levels and improvement of the clinical symptoms. Immunohistochemically, a typical carcinoid (TC) was seen with low proliferation index and abundant IGF-1 expression. The association of acromegaly and pulmonary NET has only rarely been reported. We present an individual case of paraneoplastic GH- and IGF-1 secretion in a patient with pulmonary NET. Based on their rarity, the knowledge of paraneoplastic syndromes occurring in patients with pulmonary NET such as acromegaly due to paraneoplastic GH- and IGF-1 secretion is mandatory to adequately diagnose and treat these patients.

  9. Molecular basis of Trypanosoma cruzi and Leishmania interaction with their host(s): exploitation of immune and defense mechanisms by the parasite leading to persistence and chronicity, features reminiscent of immune system evasion strategies in cancer diseases.

    Science.gov (United States)

    Ouaissi, Ali; Ouaissi, Mehdi

    2005-01-01

    A number of features occurring during host-parasite interactions in Chagas disease caused by the protozoan parasite, Trypanosoma cruzi, and Leishmaniasis, caused by a group of kinetoplastid protozoan parasites are reminiscent of those observed in cancer diseases. In fact,although the cancer is not a single disease, and that T.cruzi and Leishmania are sophisticated eukaryotic parasites presenting a high level of genotypic variability the growth of the parasites in their host and that of cancer cells share at least one common feature, that is their mutual capacity for rapid cell division. Surprisingly, the parasitic diseases and cancers share some immune evasion strategies. Consideration of these immunological alterations must be added to the evaluation of the pathogenic processes. The molecular and functional characterization of virulence factors and the study of their effect on the arms of the immune system have greatly improved understanding of the regulation of immune effectors functions. The purpose of this review is to analyze some of the current data related to the regulatory components or processes originating from the parasite that control or interfere with host cell physiology. Attempts are also made to delineate some similarities between the immune evasion strategies that parasites and tumors employ. The elucidation of the mode of action of parasite virulence factors toward the host cell allow not only provide us with a more comprehensive view of the host-parasite relationships but may also represent a step forward in efforts aimed to identify new target molecules for therapeutic intervention.

  10. Mechanisms of virus immune evasion lead to development from chronic inflammation to cancer formation associated with human papillomavirus infection.

    Science.gov (United States)

    Senba, Masachika; Mori, Naoki

    2012-10-02

    Human papillomavirus (HPV) has developed strategies to escape eradication by innate and adaptive immunity. Immune response evasion has been considered an important aspect of HPV persistence, which is the main contributing factor leading to HPV-related cancers. HPV-induced cancers expressing viral oncogenes E6 and E7 are potentially recognized by the immune system. The major histocompatibility complex (MHC) class I molecules are patrolled by natural killer cells and CD8+ cytotoxic T lymphocytes, respectively. This system of recognition is a main target for the strategies of immune evasion deployed by viruses. The viral immune evasion proteins constitute useful tools to block defined stages of the MHC class I presentation pathway, and in this way HPV avoids the host immune response. The long latency period from initial infection to persistence signifies that HPV evolves mechanisms to escape the immune response. It has now been established that there are oncogenic mechanisms by which E7 binds to and degrades tumor suppressor Rb, while E6 binds to and inactivates tumor suppressor p53. Therefore, interaction of p53 and pRb proteins can give rise to an increased immortalization and genomic instability. Overexpression of NF-κB in cervical and penile cancers suggests that NF-κB activation is a key modulator in driving chronic inflammation to cancer. HPV oncogene-mediated suppression of NF-κB activity contributes to HPV escape from the immune system. This review focuses on the diverse mechanisms of the virus immune evasion with HPV that leads to chronic inflammation and cancer.

  11. Schistosomiasis with special references to the mechanisms of evasion

    Directory of Open Access Journals (Sweden)

    Nawras M. El-Saghier Mowafy

    2015-11-01

    Full Text Available Schistosomiasis is a disease caused by infection with Schistosoma spp. It affects 200 million people worldwide, especially in the developing countries. There are five known species of Schistosoma which currently infect humans in various geographical locations. Infection with Schistosoma spp. leads to two forms of the disease: acute and chronic. Chronic infection can affect various organs within the human body including the brain, lungs, gut and the reproductive organs, which leads to neuroschistosomiasis, pulmonary schistosomiasis, hepatointestinal schistosomiasis and urinary genital schistosomiasis, respectively. All Schistosoma spp. have a common denominator that they have the ability to infect, invade and evade the host’s immune mechanism. Schistosoma sp. is a very complex organism that requires two hosts, mollusk and mammalian, to survive, propagate and complete its life cycle. Hence, it has developed specific immune evasion mechanisms for each of them. Once Schistosoma sp. has infected and established itself within its mammalian host as an adult worm, it evades the immune mechanism of that host. However, the antigens released by the eggs can elicit an immune response with formation of granuloma around eggs. Granuloma formation is the main characteristic lesion in schistosomiasis, which in the liver can cause hepatomegaly in hepatointestinal schistosomiasis. This paper will summarize various immune responses against the parasite as well as varieties of strategies which developed by the Schistosoma spp. to persist within human hosts.

  12. Staphylococcal Immune Evasion Proteins: Structure, Function, and Host Adaptation.

    Science.gov (United States)

    Koymans, Kirsten J; Vrieling, Manouk; Gorham, Ronald D; van Strijp, Jos A G

    2017-01-01

    Staphylococcus aureus is a successful human and animal pathogen. Its pathogenicity is linked to its ability to secrete a large amount of virulence factors. These secreted proteins interfere with many critical components of the immune system, both innate and adaptive, and hamper proper immune functioning. In recent years, numerous studies have been conducted in order to understand the molecular mechanism underlying the interaction of evasion molecules with the host immune system. Structural studies have fundamentally contributed to our understanding of the mechanisms of action of the individual factors. Furthermore, such studies revealed one of the most striking characteristics of the secreted immune evasion molecules: their conserved structure. Despite high-sequence variability, most immune evasion molecules belong to a small number of structural categories. Another remarkable characteristic is that S. aureus carries most of these virulence factors on mobile genetic elements (MGE) or ex-MGE in its accessory genome. Coevolution of pathogen and host has resulted in immune evasion molecules with a highly host-specific function and prevalence. In this review, we explore how these shared structures and genomic locations relate to function and host specificity. This is discussed in the context of therapeutic options for these immune evasion molecules in infectious as well as in inflammatory diseases.

  13. A Stochastic Growth Model with Income Tax Evasion: Implications for Australia

    OpenAIRE

    Ratbek Dzhumashev; Emin Gahramanov

    2009-01-01

    In this paper we develop a stochastic endogenous growth model augmented with income tax evasion. Our model avoids some existing discrepancies between empirical evidence and theoretical predictions of traditional tax evasion models. Further, we show that: i) productive government expenditures play an important role in affecting economy's tax evasion rate; ii) the average marginal income tax rate in Australia come close to the optimal; and iii) the phenomenon of tax evasion is not an excuse for...

  14. NLRC5/MHC class I transactivator is a target for immune evasion in cancer.

    Science.gov (United States)

    Yoshihama, Sayuri; Roszik, Jason; Downs, Isaac; Meissner, Torsten B; Vijayan, Saptha; Chapuy, Bjoern; Sidiq, Tabasum; Shipp, Margaret A; Lizee, Gregory A; Kobayashi, Koichi S

    2016-05-24

    Cancer cells develop under immune surveillance, thus necessitating immune escape for successful growth. Loss of MHC class I expression provides a key immune evasion strategy in many cancers, although the molecular mechanisms remain elusive. MHC class I transactivator (CITA), known as "NLRC5" [NOD-like receptor (NLR) family, caspase recruitment (CARD) domain containing 5], has recently been identified as a critical transcriptional coactivator of MHC class I gene expression. Here we show that the MHC class I transactivation pathway mediated by CITA/NLRC5 constitutes a target for cancer immune evasion. In all the 21 tumor types we examined, NLRC5 expression was highly correlated with the expression of MHC class I, with cytotoxic T-cell markers, and with genes in the MHC class I antigen-presentation pathway, including LMP2/LMP7, TAP1, and β2-microglobulin. Epigenetic and genetic alterations in cancers, including promoter methylation, copy number loss, and somatic mutations, were most prevalent in NLRC5 among all MHC class I-related genes and were associated with the impaired expression of components of the MHC class I pathway. Strikingly, NLRC5 expression was significantly associated with the activation of CD8(+) cytotoxic T cells and patient survival in multiple cancer types. Thus, NLRC5 constitutes a novel prognostic biomarker and potential therapeutic target of cancers.

  15. An MHC class I immune evasion gene of Marek׳s disease virus.

    Science.gov (United States)

    Hearn, Cari; Preeyanon, Likit; Hunt, Henry D; York, Ian A

    2015-01-15

    Marek׳s disease virus (MDV) is a widespread α-herpesvirus of chickens that causes T cell tumors. Acute, but not latent, MDV infection has previously been shown to lead to downregulation of cell-surface MHC class I (Virology 282:198-205 (2001)), but the gene(s) involved have not been identified. Here we demonstrate that an MDV gene, MDV012, is capable of reducing surface expression of MHC class I on chicken cells. Co-expression of an MHC class I-binding peptide targeted to the endoplasmic reticulum (bypassing the requirement for the TAP peptide transporter) partially rescued MHC class I expression in the presence of MDV012, suggesting that MDV012 is a TAP-blocking MHC class I immune evasion protein. This is the first unique non-mammalian MHC class I immune evasion gene identified, and suggests that α-herpesviruses have conserved this function for at least 100 million years. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Novel Evasion Mechanisms of the Classical Complement Pathway.

    Science.gov (United States)

    Garcia, Brandon L; Zwarthoff, Seline A; Rooijakkers, Suzan H M; Geisbrecht, Brian V

    2016-09-15

    Complement is a network of soluble and cell surface-associated proteins that gives rise to a self-amplifying, yet tightly regulated system with fundamental roles in immune surveillance and clearance. Complement becomes activated on the surface of nonself cells by one of three initiating mechanisms known as the classical, lectin, and alternative pathways. Evasion of complement function is a hallmark of invasive pathogens and hematophagous organisms. Although many complement-inhibition strategies hinge on hijacking activities of endogenous complement regulatory proteins, an increasing number of uniquely evolved evasion molecules have been discovered over the past decade. In this review, we focus on several recent investigations that revealed mechanistically distinct inhibitors of the classical pathway. Because the classical pathway is an important and specific mediator of various autoimmune and inflammatory disorders, in-depth knowledge of novel evasion mechanisms could direct future development of therapeutic anti-inflammatory molecules. Copyright © 2016 by The American Association of Immunologists, Inc.

  17. A Tax Evasion - Bribery Game: Experimental Evidence from Ukraine

    Directory of Open Access Journals (Sweden)

    Volodymyr Bilotkach

    2006-06-01

    Full Text Available This paper examines the issue of tax evasion by enterprises through underreporting activity. We develop a view of this phenomenon as an equilibrium of the game between a businessman and an imperfectly monitored supervising official, in which a businessman can hide part of his profit and offer bribe to official. We determine conditions under which such tax evasion and bribery become wide-spread in the society, resulting in shadow economy. The game is put into an experimental setting in Kiev, Ukraine, with the emphasis of spreading of the tax evasion and bribery activity in the laboratory setting. We find that once it becomes known that substantial share of subjects playing the role of supervising officials agree to accept bribes from subjects playing the role of businessmen, the latter offer bribes more aggressively. Yet, this in turn does not affect the behavior of subjects playing the role of supervising officials.

  18. The role of auditing in detecting tax evasion

    Directory of Open Access Journals (Sweden)

    Vržina Stefan

    2016-01-01

    Full Text Available Forthcoming paper opens questions about new area of audit operations and a new practical challenge for audit profession - detecting tax frauds. A growing problem of tax evasion, expressed as an act of illegal reduction of tax liabilities, points out to the inability of state authorities to reduce or neutralize tax evasion volume. Created as a consequence of previous fact, forthcoming paper has an objective to examine whether, and in which way, auditing financial statements could contribute to initial signalizing of tax evasion through expressing opinion about veracity and objectivity of accounting statements. Special focus is put on related-party transactions with entities registered in offshore zones. As they progress more and more, these transaction become materially significant, thus becoming a subject of audit examination.

  19. Synergistic Inhibition of Delayed Rectifier K+ and Voltage-Gated Na+ Currents by Artemisinin in Pituitary Tumor (GH3) Cells.

    Science.gov (United States)

    So, Edmund Cheung; Wu, Sheng-Nan; Wu, Ping-Ching; Chen, Hui-Zhen; Yang, Chia-Jung

    2017-01-01

    Artemisinin (ART) is an anti-malarial agent reported to influence endocrine function. Effects of ART on ionic currents and action potentials (APs) in pituitary tumor (GH3) cells were evaluated by patch clamp techniques. ART inhibited the amplitude of delayed-rectifier K+ current (IK(DR)) in response to membrane depolarization and accelerated the process of current inactivation. It exerted an inhibitory effect on IK(DR) with an IC50 value of 11.2 µM and enhanced IK(DR) inactivation with a KD value of 14.7 µM. The steady-state inactivation curve of IK(DR) was shifted to hyperpolarization by 10 mV. Pretreatment of chlorotoxin (1 µM) or iloprost (100 nM) did not alter the magnitude of ART-induced inhibition of IK(DR) in GH3 cells. ART also decreased the peak amplitude of voltage-gated Na+ current (INa) with a concentration-dependent slowing in inactivation rate. Application of KMUP-1, an inhibitor of late INa, was effective at reversing ART-induced prolongation in inactivation time constant of INa. Under current-clamp recordings, ART alone reduced the amplitude of APs and prolonged the duration of APs. Under ART exposure, the inhibitory actions on both IK(DR) and INa could be a potential mechanisms through which this drug influences membrane excitability of endocrine or neuroendocrine cells appearing in vivo. © 2017 The Author(s). Published by S. Karger AG, Basel.

  20. Tax Rates and Tax Evasion: Evidence from "Missing Imports" in China.

    Science.gov (United States)

    Fisman, Raymond; Wei, Shang-Jin

    2004-01-01

    Tax evasion, by its very nature, is difficult to observe. We quantify the effects of tax rates on tax evasion by examining the relationship in China between the tariff schedule and the "evasion gap," which we define as the difference between Hong Kong's reported exports to China at the product level and China's reported imports from Hong…

  1. Integration of chemotherapy into current treatment strategies for brain metastases from solid tumors

    Directory of Open Access Journals (Sweden)

    Thamm Reinhard

    2006-06-01

    Full Text Available Abstract Patients with brain metastases represent a heterogeneous group where selection of the most appropriate treatment depends on many patient- and disease-related factors. Eventually, a considerable proportion of patients are treated with palliative approaches such as whole-brain radiotherapy. Whole-brain radiotherapy in combination with chemotherapy has recently gained increasing attention and is hoped to augment the palliative effect of whole-brain radiotherapy alone and to extend survival in certain subsets of patients with controlled extracranial disease and good performance status. The randomized trials of whole-brain radiotherapy vs. whole-brain radiotherapy plus chemotherapy suggest that this concept deserves further study, although they failed to improve survival. However, survival might not be the most relevant endpoint in a condition, where most patients die from extracranial progression. Sometimes, the question arises whether patients with newly detected brain metastases and the indication for systemic treatment of extracranial disease can undergo standard systemic chemotherapy with the option of deferred rather than immediate radiotherapy to the brain. The literature contains numerous small reports on this issue, mainly in malignant melanoma, breast cancer, lung cancer and ovarian cancer, but very few sufficiently powered randomized trials. With chemotherapy alone, response rates were mostly in the order of 20–40%. The choice of chemotherapy regimen is often complicated by previous systemic treatment and takes into account the activity of the drugs in extracranial metastatic disease. Because the blood-brain barrier is partially disrupted in most macroscopic metastases, systemically administered agents can gain access to such tumor sites. Our systematic literature review suggests that both chemotherapy and radiochemotherapy for newly diagnosed brain metastases need further critical evaluation before standard clinical

  2. Integration of chemotherapy into current treatment strategies for brain metastases from solid tumors

    International Nuclear Information System (INIS)

    Nieder, Carsten; Grosu, Anca L; Astner, Sabrina; Thamm, Reinhard; Molls, Michael

    2006-01-01

    Patients with brain metastases represent a heterogeneous group where selection of the most appropriate treatment depends on many patient- and disease-related factors. Eventually, a considerable proportion of patients are treated with palliative approaches such as whole-brain radiotherapy. Whole-brain radiotherapy in combination with chemotherapy has recently gained increasing attention and is hoped to augment the palliative effect of whole-brain radiotherapy alone and to extend survival in certain subsets of patients with controlled extracranial disease and good performance status. The randomized trials of whole-brain radiotherapy vs. whole-brain radiotherapy plus chemotherapy suggest that this concept deserves further study, although they failed to improve survival. However, survival might not be the most relevant endpoint in a condition, where most patients die from extracranial progression. Sometimes, the question arises whether patients with newly detected brain metastases and the indication for systemic treatment of extracranial disease can undergo standard systemic chemotherapy with the option of deferred rather than immediate radiotherapy to the brain. The literature contains numerous small reports on this issue, mainly in malignant melanoma, breast cancer, lung cancer and ovarian cancer, but very few sufficiently powered randomized trials. With chemotherapy alone, response rates were mostly in the order of 20–40%. The choice of chemotherapy regimen is often complicated by previous systemic treatment and takes into account the activity of the drugs in extracranial metastatic disease. Because the blood-brain barrier is partially disrupted in most macroscopic metastases, systemically administered agents can gain access to such tumor sites. Our systematic literature review suggests that both chemotherapy and radiochemotherapy for newly diagnosed brain metastases need further critical evaluation before standard clinical implementation. A potential chemotherapy

  3. The Pleiotropic Role of L1CAM in Tumor Vasculature

    Directory of Open Access Journals (Sweden)

    Francesca Angiolini

    2017-01-01

    Full Text Available Angiogenesis, the formation of new vessels, is a key step in the development, invasion, and dissemination of solid tumors and, therefore, represents a viable target in the context of antitumor therapy. Indeed, antiangiogenic approaches have given promising results in preclinical models and entered the clinical practice. However, in patients, the results obtained so far with antiangiogenic drugs have not completely fulfilled expectations, especially because their effect has been transient with tumors developing resistance and evasion mechanisms. A better understanding of the mechanisms that underlie tumor vascularization and the functional regulation of cancer vessels is a prerequisite for the development of novel and alternative antiangiogenic treatments. The L1 cell adhesion molecule (L1CAM, a cell surface glycoprotein previously implicated in the development and plasticity of the nervous system, is aberrantly expressed in the vasculature of various cancer types. L1CAM plays multiple pro-angiogenic roles in the endothelial cells of tumor-associated vessels, thus emerging as a potential therapeutic target. In addition, L1CAM prevents the maturation of cancer vasculature and its inhibition promotes vessel normalization, a process that is thought to improve the therapeutic response of tumors to cytotoxic drugs. We here provide an overview on tumor angiogenesis and antiangiogenic therapies and summarize the current knowledge on the biological role of L1CAM in cancer vasculature. Finally, we highlight the clinical implications of targeting L1CAM as a novel antiangiogenic and vessel-normalizing approach.

  4. General Consideration on Legal Tax Evasion vs. Tax Fraud

    Directory of Open Access Journals (Sweden)

    Octavia-Daniela Steriopol

    2010-12-01

    Full Text Available The article is a brief overview of tax evasion as a complex social and economicphenomenon, of utmost importance, that today’s states confront with; its consequences seek to limitas much as possible, by legal and fiscal means, the eradication, which, at this point, is virtuallyimpossible. Tax evasion can be analysed from two points of view, the legal and the illegal aspect ofthe phenomenon or the fiscal fraud. The “fiscal paradises” had a very important role in the last years’activity.

  5. Tax Evasion, Information Reporting, and the Regressive Bias Prediction

    DEFF Research Database (Denmark)

    Boserup, Simon Halphen; Pinje, Jori Veng

    2013-01-01

    evasion and audit probabilities once we account for information reporting in the tax compliance game. When conditioning on information reporting, we find that both reduced-form evidence and simulations exhibit the predicted regressive bias. However, in the overall economy, this bias is negated by the tax......Models of rational tax evasion and optimal enforcement invariably predict a regressive bias in the effective tax system, which reduces redistribution in the economy. Using Danish administrative data, we show that a calibrated structural model of this type replicates moments and correlations of tax...

  6. Ectopic expression of X-linked lymphocyte-regulated protein pM1 renders tumor cells resistant to antitumor immunity.

    Science.gov (United States)

    Kang, Tae Heung; Noh, Kyung Hee; Kim, Jin Hee; Bae, Hyun Cheol; Lin, Ken Y; Monie, Archana; Pai, Sara I; Hung, Chien-Fu; Wu, T-C; Kim, Tae Woo

    2010-04-15

    Tumor immune escape is a major obstacle in cancer immunotherapy, but the mechanisms involved remain poorly understood. We have previously developed an immune evasion tumor model using an in vivo immune selection strategy and revealed Akt-mediated immune resistance to antitumor immunity induced by various cancer immunotherapeutic agents. In the current study, we used microarray gene analysis to identify an Akt-activating candidate molecule overexpressed in immune-resistant tumors compared with parental tumors. X-linked lymphocyte-regulated protein pM1 (XLR) gene was the most upregulated in immune-resistant tumors compared with parental tumor cells. Furthermore, the retroviral transduction of XLR in parental tumor cells led to activation of Akt, resulting in upregulation of antiapoptotic proteins and the induction of immune resistance phenotype in parental tumor cells. In addition, we found that transduction of parental tumor cells with other homologous genes from the mouse XLR family, such as synaptonemal complex protein 3 (SCP3) and XLR-related, meiosis-regulated protein (XMR) and its human counterpart of SCP3 (hSCP3), also led to activation of Akt, resulting in the upregulation of antiapoptotic proteins and induction of immune resistance phenotype. Importantly, characterization of a panel of human cervical cancers revealed relatively higher expression levels of hSCP3 in human cervical cancer tissue compared with normal cervical tissue. Thus, our data indicate that ectopic expression of XLR and its homologues in tumor cells represents a potentially important mechanism for tumor immune evasion and serves as a promising molecular target for cancer immunotherapy. (c) 2010 AACR.

  7. Tranexamic acid for the management of uterine fibroid tumors: A systematic review of the current evidence

    Science.gov (United States)

    Peitsidis, Panagiotis; Koukoulomati, Anna

    2014-01-01

    AIM: To conduct a detailed systematic review of the current evidence on the administration and efficacy of tranexamic acid in patients with menorrhagia due to uterine fibroids. METHODS: We conducted an electronic search on the following databases PubMed and Medline (1950-2013); (1980-2013); Cochrane library (1993-2013). RESULTS: A total of 36 articles were retrieved after the initial electronic search. Careful assessment of the retrieved studies led to the final selection of 5 articles for inclusion in the review. CONCLUSION: Tranexamic acid may reduce blood loss perioperatively in myomectomies. It may reduce the menorrhagia in patients with fibroids, however a stratification of fibroids by size and location is required to define the responses. It is safe in general, with mild adverse effects observed in some cases. More studies with a double-blind randomized design and larger numbers of participants are necessary to reach more precise and safe conclusions. PMID:25516866

  8. Universal immunity to influenza must outwit immune evasion

    Directory of Open Access Journals (Sweden)

    Sergio Manuel Quinones-Parra

    2014-06-01

    Full Text Available Although an influenza vaccine has been available for 70 years, influenza virus still causes seasonal epidemics and worldwide pandemics. Currently available vaccines elicit strain-specific antibody responses to the surface haemagglutinin (HA and neuraminidase (NA proteins, but these can be ineffective against serologically-distinct viral variants and novel subtypes. Thus, there is a need for cross-protective or universal influenza vaccines to overcome the necessity for annual immunisation against seasonal influenza and to provide immunity to reduce the severity of infection with pandemic or outbreak viruses. It is well established that natural influenza infection can provide cross-reactive immunity that can reduce the impact of infection with distinct influenza type A strains and subtypes, including H1N1, H3N2, H2N2, H5N1 and H7N9. The key to generating universal influenza immunity via vaccination is to target functionally-conserved regions of the virus, which include epitopes on the internal proteins for cross-reactive T cell immunity or on the HA stem for broadly reactive antibody responses. In the wake of the 2009 H1N1 pandemic, broadly neutralizing antibodies have been characterized and isolated from convalescent and vaccinated individuals, inspiring development of new vaccination techniques to elicit such responses. Induction of influenza-specific T cell responses through vaccination has also been examined in clinical trials. Strong evidence is available from human and animal models of influenza to show that established influenza-specific T cell memory can reduce viral shedding and symptom severity. However, the published evidence also shows that CD8+ T cells can efficiently select immune escape mutants early after influenza virus infection. Here, we discuss universal immunity to influenza viruses mediated by both cross-reactive T cells and antibodies, the mechanisms of immune evasion in influenza, and how to counteract commonly occurring

  9. Tax evasion and income source: A comparative experimental study

    NARCIS (Netherlands)

    Gërxhani, K.; Schram, A.J.H.C.

    2006-01-01

    We compare tax evasive behavior in a country in transition from communism to that in a developed economy by running an experiment across distinct social groups in Albania and the Netherlands. Aside from the tax compliance decision, subjects choose a source of income, where one type enables

  10. Tax Evasion, Information Reporting, and the Regressive Bias Hypothesis

    DEFF Research Database (Denmark)

    Boserup, Simon Halphen; Pinje, Jori Veng

    A robust prediction from the tax evasion literature is that optimal auditing induces a regressive bias in effective tax rates compared to statutory rates. If correct, this will have important distributional consequences. Nevertheless, the regressive bias hypothesis has never been tested empirically...

  11. Immune evasion of Plasmodium falciparum by RIFIN via inhibitory receptors

    DEFF Research Database (Denmark)

    Saito, Fumiji; Hirayasu, Kouyuki; Satoh, Takeshi

    2017-01-01

    , but the immune regulatory mechanisms used by P. falciparum remain largely unknown. Here we show that P. falciparum uses immune inhibitory receptors to achieve immune evasion. RIFIN proteins are products of a polymorphic multigene family comprising approximately 150-200 genes per parasite genome...

  12. Avoiding evasion: medical ethics education and emotion theory.

    NARCIS (Netherlands)

    Leget, C.J.W.

    2004-01-01

    Beginning with an exemplary case study, this paper diagnoses and analyses some important strategies of evasion and factors of hindrance that are met in the teaching of medical ethics to undergraduate medical students. Some of these inhibitions are inherent to ethical theories; others are connected

  13. Android Rooting: An Arms Race between Evasion and Detection

    Directory of Open Access Journals (Sweden)

    Long Nguyen-Vu

    2017-01-01

    Full Text Available We present an arms race between rooting detection and rooting evasion. We investigate different methods to detect rooted device at both Java and native level and evaluate the counterattack from major hooking tools. To this end, an extensive study of Android rooting has been conducted, which includes the techniques to root the device and make it invisible to the detection of mobile antimalware product. We then analyze the evasion loopholes and in turn enhance our rooting detection tool. We also apply evasion techniques on rooted device and compare our work with 92 popular root checking applications and 18 banking and finance applications. Results show that most of them do not suffice and can be evaded through API hooking or static file renaming. Furthermore, over 28000 Android applications have been analyzed and evaluated in order to diagnose the characteristics of rooting in recent years. Our study shows that rooting has become more and more prevalent as an inevitable trend, and it raises big security concerns regarding detection and evasion. As a proof of concept, we have published our rooting detection application to Google Play Store to demonstrate the work presented in this paper.

  14. Evasion of T cell immunity by Epstein-Barr virus

    NARCIS (Netherlands)

    Horst, D.

    2011-01-01

    Immune evasion strategies are thought to contribute essentially to the life cycle of persistent viruses by delaying the elimination of the infected cell long enough to enable the virus to replicate. Exemplary in this context are the herpesviruses, large DNA viruses that are carried as a persistent

  15. Tax evasive behavior and gender in a transition count

    NARCIS (Netherlands)

    Gërxhani, K.; Kuiper, E.

    2004-01-01

    In this paper, we provide a structural explanation of gender difference with respect to tax evasion. A unique data set, collected from a field survey of households in Albania, allows us to test and explore the established fact, in a transition country. The results show that women tend to evade taxes

  16. Itemised Deductions : A Device to Reduce Tax Evasion

    NARCIS (Netherlands)

    Piolatto, A.

    2010-01-01

    Direct incentives and punishments are the most common instruments to fight tax evasion. The theoretical literature disregarded indirect schemes, such as itemised deductions, in which an agent has an interest in that other agents declare their revenue. Itemised deductions provide an incentive for

  17. Microparticles shed from multidrug resistant breast cancer cells provide a parallel survival pathway through immune evasion.

    Science.gov (United States)

    Jaiswal, Ritu; Johnson, Michael S; Pokharel, Deep; Krishnan, S Rajeev; Bebawy, Mary

    2017-02-06

    Breast cancer is the most frequently diagnosed cancer in women. Resident macrophages at distant sites provide a highly responsive and immunologically dynamic innate immune response against foreign infiltrates. Despite extensive characterization of the role of macrophages and other immune cells in malignant tissues, there is very little known about the mechanisms which facilitate metastatic breast cancer spread to distant sites of immunological integrity. The mechanisms by which a key healthy defense mechanism fails to protect distant sites from infiltration by metastatic cells in cancer patients remain undefined. Breast tumors, typical of many tumor types, shed membrane vesicles called microparticles (MPs), ranging in size from 0.1-1 μm in diameter. MPs serve as vectors in the intercellular transfer of functional proteins and nucleic acids and in drug sequestration. In addition, MPs are also emerging to be important players in the evasion of cancer cell immune surveillance. A comparative analysis of effects of MPs isolated from human breast cancer cells and non-malignant human brain endothelial cells were examined on THP-1 derived macrophages in vitro. MP-mediated effects on cell phenotype and functionality was assessed by cytokine analysis, cell chemotaxis and phagocytosis, immunolabelling, flow cytometry and confocal imaging. Student's t-test or a one-way analysis of variance (ANOVA) was used for comparison and statistical analysis. In this paper we report on the discovery of a new cellular basis for immune evasion, which is mediated by breast cancer derived MPs. MPs shed from multidrug resistant (MDR) cells were shown to selectively polarize macrophage cells to a functionally incapacitated state and facilitate their engulfment by foreign cells. We propose this mechanism may serve to physically disrupt the inherent immune response prior to cancer cell colonization whilst releasing mediators required for the recruitment of distant immune cells. These findings

  18. The MLL1-H3K4me3 Axis-Mediated PD-L1 Expression and Pancreatic Cancer Immune Evasion.

    Science.gov (United States)

    Lu, Chunwan; Paschall, Amy V; Shi, Huidong; Savage, Natasha; Waller, Jennifer L; Sabbatini, Maria E; Oberlies, Nicholas H; Pearce, Cedric; Liu, Kebin

    2017-01-01

    Pancreatic cancer is one of the cancers where anti-PD-L1/PD-1 immunotherapy has been unsuccessful. What confers pancreatic cancer resistance to checkpoint immunotherapy is unknown. The aim of this study is to elucidate the underlying mechanism of PD-L1 expression regulation in the context of pancreatic cancer immune evasion. Pancreatic cancer mouse models and human specimens were used to determine PD-L1 and PD-1 expression and cancer immune evasion. Histone methyltransferase inhibitors, RNAi, and overexpression were used to elucidate the underlying molecular mechanism of PD-L1 expression regulation. All statistical tests were two-sided. PD-L1 is expressed in 60% to 90% of tumor cells in human pancreatic carcinomas and in nine of 10 human pancreatic cancer cell lines. PD-1 is expressed in 51.2% to 52.1% of pancreatic tumor-infiltrating cytotoxic T lymphocytes (CTLs). Tumors grow statistically significantly faster in FasL-deficient mice than in wild-type mice (P = .03-.001) and when CTLs are neutralized (P = .03-evasion. Targeting the MLL1-H3K4me3 axis is an effective approach to enhance the efficacy of checkpoint immunotherapy against pancreatic cancer. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. The underground economy in the U.S.A.: preliminary new evidence on the impact of income tax rates (and other factors on aggregate tax evasion 1975-2008

    Directory of Open Access Journals (Sweden)

    Richard J. Cebula

    2014-12-01

    Full Text Available This empirical study seeks to identify determinants of the underground economy in the U.S. in the form of aggregate federal personal income tax evasion over the period 1975-2008, with a specific focus upon the impact of higher federal income tax rates on tax evasion. In this study, we use the most recent data available on aggregate personal income tax evasion, data that are derived from the General Currency Ratio Model and measured in the form of the ratio of unreported AGI to reported AGI. Most other studies of federal income tax evasion for the U.S. do not use data this current. It is found that the impact of increases in the federal income tax rate on aggregate personal income tax evasion may, on balance, be ambiguous, possibly suggesting that the income effect is negative and outweighs the positive substitution effect for the representative taxpayer. It is also found that the degree of aggregate personal income tax evasion may be an increasing function of the percentage of federal personal income tax returns characterized by itemized deductions and a decreasing function of the Tax Reform Act of 1986 (during the first two years of implementation, the ratio of the tax free interest rate yield on high grade municipals to the interest rate yield on ten year Treasury notes, and higher audit rates of filed federal income tax returns (as a measure of risk from tax evasion by IRS personnel. Finally, unpopular wars may provide a secondary benefit for and therefore act as an inducement for greater tax evasion.

  20. The Current Landscape of 3D In Vitro Tumor Models: What Cancer Hallmarks Are Accessible for Drug Discovery?

    Science.gov (United States)

    Rodenhizer, Darren; Dean, Teresa; D'Arcangelo, Elisa; McGuigan, Alison P

    2018-04-01

    Cancer prognosis remains a lottery dependent on cancer type, disease stage at diagnosis, and personal genetics. While investment in research is at an all-time high, new drugs are more likely to fail in clinical trials today than in the 1970s. In this review, a summary of current survival statistics in North America is provided, followed by an overview of the modern drug discovery process, classes of models used throughout different stages, and challenges associated with drug development efficiency are highlighted. Then, an overview of the cancer hallmarks that drive clinical progression is provided, and the range of available clinical therapies within the context of these hallmarks is categorized. Specifically, it is found that historically, the development of therapies is limited to a subset of possible targets. This provides evidence for the opportunities offered by novel disease-relevant in vitro models that enable identification of novel targets that facilitate interactions between the tumor cells and their surrounding microenvironment. Next, an overview of the models currently reported in literature is provided, and the cancer biology they have been used to explore is highlighted. Finally, four priority areas are suggested for the field to accelerate adoption of in vitro tumour models for cancer drug discovery. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Role of Tertiary Lymphoid Structures (TLS) in Anti-Tumor Immunity: Potential Tumor-Induced Cytokines/Chemokines that Regulate TLS Formation in Epithelial-Derived Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Pimenta, Erica M. [Rutgers Biomedical and Health Sciences, New Jersey Medical School-Cancer Center, Newark, NJ 07103 (United States); Barnes, Betsy J., E-mail: barnesbe@njms.rutgers.edu [Department of Biochemistry and Molecular Biology, Rutgers Biomedical and Health Sciences, New Jersey Medical School-Cancer Center, Newark, NJ 07103 (United States)

    2014-04-23

    Following the successes of monoclonal antibody immunotherapies (trastuzumab (Herceptin{sup ®}) and rituximab (Rituxan{sup ®})) and the first approved cancer vaccine, Provenge{sup ®} (sipuleucel-T), investigations into the immune system and how it can be modified by a tumor has become an exciting and promising new field of cancer research. Dozens of clinical trials for new antibodies, cancer and adjuvant vaccines, and autologous T and dendritic cell transfers are ongoing in hopes of identifying ways to re-awaken the immune system and force an anti-tumor response. To date, however, few consistent, reproducible, or clinically-relevant effects have been shown using vaccine or autologous cell transfers due in part to the fact that the immunosuppressive mechanisms of the tumor have not been overcome. Much of the research focus has been on re-activating or priming cytotoxic T cells to recognize tumor, in some cases completely disregarding the potential roles that B cells play in immune surveillance or how a solid tumor should be treated to maximize immunogenicity. Here, we will summarize what is currently known about the induction or evasion of humoral immunity via tumor-induced cytokine/chemokine expression and how formation of tertiary lymphoid structures (TLS) within the tumor microenvironment may be used to enhance immunotherapy response.

  2. Role of Tertiary Lymphoid Structures (TLS in Anti-Tumor Immunity: Potential Tumor-Induced Cytokines/Chemokines that Regulate TLS Formation in Epithelial-Derived Cancers

    Directory of Open Access Journals (Sweden)

    Erica M. Pimenta

    2014-04-01

    Full Text Available Following the successes of monoclonal antibody immunotherapies (trastuzumab (Herceptin® and rituximab (Rituxan® and the first approved cancer vaccine, Provenge® (sipuleucel-T, investigations into the immune system and how it can be modified by a tumor has become an exciting and promising new field of cancer research. Dozens of clinical trials for new antibodies, cancer and adjuvant vaccines, and autologous T and dendritic cell transfers are ongoing in hopes of identifying ways to re-awaken the immune system and force an anti-tumor response. To date, however, few consistent, reproducible, or clinically-relevant effects have been shown using vaccine or autologous cell transfers due in part to the fact that the immunosuppressive mechanisms of the tumor have not been overcome. Much of the research focus has been on re-activating or priming cytotoxic T cells to recognize tumor, in some cases completely disregarding the potential roles that B cells play in immune surveillance or how a solid tumor should be treated to maximize immunogenicity. Here, we will summarize what is currently known about the induction or evasion of humoral immunity via tumor-induced cytokine/chemokine expression and how formation of tertiary lymphoid structures (TLS within the tumor microenvironment may be used to enhance immunotherapy response.

  3. PREDICTORS OF OVERALL SURVIVAL IN PATIENTS WITH RECURRENT NON-SEMINOMATOUS GERMINAL TESTICULAR TUMORS ON CURRENT SECOND-LINE CHEMOTHERAPY

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2010-01-01

    Full Text Available Objective: to define predictors that influence longevity in patients with recurrent non-seminomatous germinal testicular tumors (NGTT on standard second-line chemotherapy (CT including cisplatin and iphosphamide. Statistical analysis was performed using the statistical packages Graph Pad Prism 4.00 for Windows and SPSS 15.0 for Windows. Subjects and methods. Case history data were analyzed in 693 patients with disseminated NGTT who had received current CT and followed up at the Department of Clinical Pharmacology and CT, N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences. The median follow-up was 32 (range 3-215 months. The disease progressed in 181 (26% patients. Detailed information was available on the nature of second-line CT in only 138 patients. Half (71 (51.7% of the 138 patients had second-line CT including iphosphamide. Uni- and multivariate analyses were made to identify predictors that influence longevity in patients with recurrent NGTT on standard secondline CT including cisplatin and iphosphamide. Results. Five-year overall survival (OS was 32% (95% confidence interval 25-41%. The multivariate analysis showed the morphological pattern of a primary tumor (a yolk sac tumor component, a pre-induction CT lactate dehydrogenase (LDH level of ?d1.5 units of the upper normal range, progression during induction CT, and a pre-second-line CT LDH level of ?d 1000 U/l to be negative predictors. According to the number of negative factors, the patients were classified into 3 groups: 1 good prognosis [n = 10 (14% of the 71 patients], 100% 3-year OS; 2 intermediate prognosis (one negative factor [n = 33 (46.5% of the 71 patients], 50.2% 3-year OS; 3 poor prognosis (?d 2 negative factors, 6.7% 3-year OS. Conclusion. Standard iphosphamide-containing therapy enables all patients to be treated in the good prognosis group of those with recurrent NGTT. That fails to achieve such striking results in the intermediate and

  4. Lewis Lung Cancer Cells Promote SIGNR1(CD209b)-Mediated Macrophages Polarization Induced by IL-4 to Facilitate Immune Evasion.

    Science.gov (United States)

    Yan, Xiaolong; Li, Wenhai; Pan, Lei; Fu, Enqing; Xie, Yonghong; Chen, Min; Mu, Deguang

    2016-05-01

    Tumor-associated macrophages are a prominent component of lung cancer and contribute to tumor progression by facilitating the immune evasion of cancer cells. DC-SIGN (CD209) assists in the immune evasion of a broad spectrum of pathogens and neoplasms by inhibiting the maturation of DCs and subsequent cytokines production. However, the expression of DC-SIGN in macrophages and its role in mediating immune evasion in lung cancer and the underlying mechanism remain unclear. Our study aimed to identify the immunosuppressive role of SIGNR1 in murine macrophage differentiation and lung cancer progression. We found that SIGNR1-positive RAW264.7 macrophages were enriched in mixed cultures with Lewis lung cancer cells (LLC) (ratio of RAW 264.7 to LLC being 1:1) after stimulation with IL-4. Moreover, LLC-educated macrophages exhibited significantly higher levels of IL-10 but lower IL-12 in response to IL-4 treatment as determined by RT-PCR and ELISA. However, inhibition of SIGNR1 markedly hampered the production of IL-10, indicating that SIGNR1 was indispensable for IL-4+LLC induced macrophage polarization towards the M2 subtype. Furthermore, polarized M2 cells immersed in a tumor microenvironment promoted the migration of LLCs, as measured by transwell assays, but migration was suppressed after blockade of SIGNR1 using CD209b antibody. In addition, IL-4+LLC-educated macrophages reduced the proliferation of the activated T cells and reduced IFN-γ-mediated Th1 response in T cells, while SIGNR1 inhibition rescued Th1 cell functions. In conclusion, murine SIGNR1 expressed in LLC-educated macrophages appears to mediate IL-4-induced RAW264.7 macrophage polarization and thus facilitate lung cancer evasion. © 2015 Wiley Periodicals, Inc.

  5. Chemical compounds from anthropogenic environment and immune evasion mechanisms: potential interactions

    Science.gov (United States)

    Kravchenko, Julia; Corsini, Emanuela; Williams, Marc A.; Decker, William; Manjili, Masoud H.; Otsuki, Takemi; Singh, Neetu; Al-Mulla, Faha; Al-Temaimi, Rabeah; Amedei, Amedeo; Colacci, Anna Maria; Vaccari, Monica; Mondello, Chiara; Scovassi, A. Ivana; Raju, Jayadev; Hamid, Roslida A.; Memeo, Lorenzo; Forte, Stefano; Roy, Rabindra; Woodrick, Jordan; Salem, Hosni K.; Ryan, Elizabeth P.; Brown, Dustin G.; Lowe, Leroy; Lyerly, H.Kim

    2015-01-01

    An increasing number of studies suggest an important role of host immunity as a barrier to tumor formation and progression. Complex mechanisms and multiple pathways are involved in evading innate and adaptive immune responses, with a broad spectrum of chemicals displaying the potential to adversely influence immunosurveillance. The evaluation of the cumulative effects of low-dose exposures from the occupational and natural environment, especially if multiple chemicals target the same gene(s) or pathway(s), is a challenge. We reviewed common environmental chemicals and discussed their potential effects on immunosurveillance. Our overarching objective was to review related signaling pathways influencing immune surveillance such as the pathways involving PI3K/Akt, chemokines, TGF-β, FAK, IGF-1, HIF-1α, IL-6, IL-1α, CTLA-4 and PD-1/PDL-1 could individually or collectively impact immunosurveillance. A number of chemicals that are common in the anthropogenic environment such as fungicides (maneb, fluoxastrobin and pyroclostrobin), herbicides (atrazine), insecticides (pyridaben and azamethiphos), the components of personal care products (triclosan and bisphenol A) and diethylhexylphthalate with pathways critical to tumor immunosurveillance. At this time, these chemicals are not recognized as human carcinogens; however, it is known that they these chemicalscan simultaneously persist in the environment and appear to have some potential interfere with the host immune response, therefore potentially contributing to promotion interacting with of immune evasion mechanisms, and promoting subsequent tumor growth and progression. PMID:26002081

  6. DEEPENING SOCIAL INEQUALITIES AND SLOWING DOWN ECONOMIC GROWTH DUE TO CORRUPTION, UNDERGROUND ECONOMY AND TAX EVASION

    Directory of Open Access Journals (Sweden)

    Adrian-Ducu, MATEI

    2014-11-01

    Full Text Available The article highlights some sources of inequalities in a globalized world which does not only generate positive impact. In the event it is mismanaged, globalization can give life to a mechanism facilitating tax evasion and, in the same time, ensuring for a small group of individuals, a power position not only when negotiating inside a company but also across the political life of a society. Moreover, the most important traits of corruption and underground economy are marked out in relation to the deepening of social inequality in Romania. These negative phenomena are also present due to the malfunctioning of the market, strengthened monopolies, hindered competition and excessive use of asymmetric information. In the current context of an economic and financial crisis, one much linked to trust, phenomena such as corruption, underground economy and tax evasion have become omnipresent, hot topics in both Romania and Europe. This is how the economy is taken over and significant resources of the public budget are missed by the state. The consequences are severe and can lead to incapacity to ensure a decent standard of living and ultimately social peace. A continuous attempt to curb these phenomena could and should be a priority and a method to settle the public financial equilibrium in Europe and in Romania in particular.

  7. Immunotherapy and Immune Evasion in Prostate Cancer

    International Nuclear Information System (INIS)

    Thakur, Archana; Vaishampayan, Ulka; Lum, Lawrence G.

    2013-01-01

    Metastatic prostate cancer remains to this day a terminal disease. Prostatectomy and radiotherapy are effective for organ-confined diseases, but treatment for locally advanced and metastatic cancer remains challenging. Although advanced prostate cancers treated with androgen deprivation therapy achieves debulking of disease, responses are transient with subsequent development of castration-resistant and metastatic disease. Since prostate cancer is typically a slowly progressing disease, use of immune-based therapies offers an advantage to target advanced tumors and to induce antitumor immunity. This review will discuss the clinical merits of various vaccines and immunotherapies in castrate resistant prostate cancer and challenges to this evolving field of immune-based therapies

  8. Immunotherapy and Immune Evasion in Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Thakur, Archana, E-mail: thakur@karmanos.org; Vaishampayan, Ulka [Department of Oncology, Wayne State University, Detroit, MI 48201 (United States); Lum, Lawrence G., E-mail: thakur@karmanos.org [Department of Oncology, Wayne State University, Detroit, MI 48201 (United States); Department of Medicine, Wayne State University, Detroit, MI 48201 (United States); Department of Immunology and Microbiology, Wayne State University, Detroit, MI 48201 (United States)

    2013-05-24

    Metastatic prostate cancer remains to this day a terminal disease. Prostatectomy and radiotherapy are effective for organ-confined diseases, but treatment for locally advanced and metastatic cancer remains challenging. Although advanced prostate cancers treated with androgen deprivation therapy achieves debulking of disease, responses are transient with subsequent development of castration-resistant and metastatic disease. Since prostate cancer is typically a slowly progressing disease, use of immune-based therapies offers an advantage to target advanced tumors and to induce antitumor immunity. This review will discuss the clinical merits of various vaccines and immunotherapies in castrate resistant prostate cancer and challenges to this evolving field of immune-based therapies.

  9. Crioterapia de tumores renales: estado actual y desarrollos contemporáneos [= Cryotherapy for renal tumors: Current status and contemporary developments

    NARCIS (Netherlands)

    Rioja, J.; Tzortzis, V.; Mamoulakis, C.; Laguna, M. P.

    2010-01-01

    The proportion of renal tumors found incidentally dramatically increased in the past decade. More than half of them were diagnosed in patients over 70 years of age, a population with high associated comorbidity. Nephron-sparing minimally invasive surgical procedures are aimed at treating patients

  10. Multiagent Cooperative Learning Strategies for Pursuit-Evasion Games

    Directory of Open Access Journals (Sweden)

    Jong Yih Kuo

    2015-01-01

    Full Text Available This study examines the pursuit-evasion problem for coordinating multiple robotic pursuers to locate and track a nonadversarial mobile evader in a dynamic environment. Two kinds of pursuit strategies are proposed, one for agents that cooperate with each other and the other for agents that operate independently. This work further employs the probabilistic theory to analyze the uncertain state information about the pursuers and the evaders and uses case-based reasoning to equip agents with memories and learning abilities. According to the concepts of assimilation and accommodation, both positive-angle and bevel-angle strategies are developed to assist agents in adapting to their environment effectively. The case study analysis uses the Recursive Porous Agent Simulation Toolkit (REPAST to implement a multiagent system and demonstrates superior performance of the proposed approaches to the pursuit-evasion game.

  11. Tax havens: Features, operations and solving tax evasion problems

    Directory of Open Access Journals (Sweden)

    Obradović-Ćuk Jelena

    2016-01-01

    Full Text Available Tax haven offers minimal or no tax liability to foreign individuals and enterprises in economically and politically stable environment, where little or no financial information is shared with foreign tax authorities. The aim of this research is to create a comprehensive overview of the characteristics and operations of tax havens, as well as to point out to the ways to overcome the problem of tax evasion. The methodology used in the work is characteristic of social science research: analysis, synthesis and discussion, comparative, inductive and historical analysis, together with the usage of relevant national and international sources. This paper describes the basic features of tax havens, as well as specific business models applied in them. A separate chapter deals with overcoming the problem of tax evasion, which is the main adverse effect of doing business through tax havens.

  12. Avoiding evasion: medical ethics education and emotion theory.

    Science.gov (United States)

    Leget, C

    2004-10-01

    Beginning with an exemplary case study, this paper diagnoses and analyses some important strategies of evasion and factors of hindrance that are met in the teaching of medical ethics to undergraduate medical students. Some of these inhibitions are inherent to ethical theories; others are connected with the nature of medicine or cultural trends. It is argued that in order to avoid an attitude of evasion in medical ethics teaching, a philosophical theory of emotions is needed that is able to clarify on a conceptual level the ethical importance of emotions. An approach is proposed with the help of the emotion theory Martha Nussbaum works out in her book Upheavals of thought. The paper ends with some practical recommendations.

  13. Tax Evasion and Auditing in a Federal Economy

    OpenAIRE

    Traxler, Christian (Prof. Dr.); Stöwhase, Sven

    2017-01-01

    This paper analyzes the relation between tax auditing and fiscal equalization in the context of fiscal competition. We incorporate a model of tax evasion by firms into a standard tax competition framework where regional governments use their audit rates as a strategic instrument to engage in fiscal competition. We compare the region's choice of audit policies for three different cases: A scenario of unconfined competition without interregional transfers, a scenario with a gross revenue equali...

  14. Evasion of added isotopic mercury from a northern temperate lake

    Science.gov (United States)

    Southworth, G.; Lindberg, S.; Hintelmann, H.; Amyot, M.; Poulain, A.; Bogle, M.; Peterson, M.; Rudd, J.; Harris, R.; Sandilands, K.; Krabbenhoft, D.; Olsen, M.

    2007-01-01

    Isotopically enriched Hg (90% 202Hg) was added to a small lake in Ontario, Canada, at a rate equivalent to approximately threefold the annual direct atmospheric deposition rate that is typical of the northeastern United States. The Hg spike was thoroughly mixed into the epilimnion in nine separate events at two-week intervals throughout the summer growing season for three consecutive years. We measured concentrations of spike and ambient dissolved gaseous Hg (DGM) concentrations in surface water and the rate of volatilization of Hg from the lake on four separate, week-long sampling periods using floating dynamic flux chambers. The relationship between empirically measured rates of spike-Hg evasion were evaluated as functions of DGM concentration, wind velocity, and solar illumination. No individual environmental variable proved to be a strong predictor of the evasion flux. The DGM-normalized flux (expressed as the mass transfer coefficient, k) varied with wind velocity in a manner consistent with existing models of evasion of volatile solutes from natural waters but was higher than model estimates at low wind velocity. The empirical data were used to construct a description of evasion flux as a function of total dissolved Hg, wind, and solar illumination. That model was then applied to data for three summers for the experiment to generate estimates of Hg re-emission from the lake surface to the atmosphere. Based on ratios of spike Hg to ambient Hg in DGM and dissolved total Hg pools, ratios of DGM to total Hg in spike and ambient Hg pools, and flux estimates of spike and ambient Hg, we concluded that the added Hg spike was chemically indistinguishable from the ambient Hg in its behavior. Approximately 45% of Hg added to the lake over the summer was lost via volatilization. ?? 2007 SETAC.

  15. Cheating, Emotions, and Rationality: An Experiment on Tax Evasion

    OpenAIRE

    Giorgio Coricelli; Mateus Joffily; Claude Montmarquette; Marie Claire Villeval

    2010-01-01

    International audience; The economics-of-crime approach usually ignores the emotional cost and benefit of cheating. In this paper, we investigate the relationships between emotions, deception, and rational decision-making by means of an experiment on tax evasion. Emotions are measured by skin conductance responses and self-reports. We show that the intensity of anticipated and anticipatory emotions before reporting positively correlates with both the decision to cheat and the proportion of ev...

  16. Legal Considerations of Tax Evasion and Tax Avoidance

    OpenAIRE

    Dániel Deák

    2004-01-01

    The study of fiscal non-compliance - in particular, that of tax evasion - is quite extensive in the literature of economics. Lawyers do not show much interest in fiscal anomalies. An exception for this is perhaps tax avoidance which is usually interpreted as the problem of the form and substance. Apart from the modest interest in irregularities in fiscal law, the legal theories of obedience, or disobedience, and coherence have grown significantly, thanks to the precept of William Ross on prim...

  17. Does Tax Evasion Affect Unemployment and Educational Choice ?

    DEFF Research Database (Denmark)

    Kolm, Ann-Sofie; Larsen, Birthe

    2003-01-01

    While examining the macroeconomic effects of government taxand punishment policies, this paper develops a three-sector generalequilibrium model featuring matching frictions and worker-firm wagebargaining. Workers are assumed to differ in ability, and the choiceof education is determined endogenou...... to choose punishment rates so to more than fully counteractthe distortion created by the government's inability to tax theinformal sector.JEL-codes: H26, I21, J64Keywords: Tax evasion, underground economy, education, matching,unemployment....

  18. COMPARATIVE ANALYSIS OF TAX EVASION BETWEEN MOLDOVA AND ROMANIA

    Directory of Open Access Journals (Sweden)

    OANA-CARMEN RĂVAŞ

    2015-12-01

    Full Text Available Tax evasion is actually failure by the taxpayer, tax liabilities. And the negative effects of this are felt directly on the level of tax revenue receipts, causing major distortions in the functioning of the market mechanism. It is believed that the first cause of fraud is itself impossible, fairer tax system in which develops based on the principle of declaring taxpayer benefiting from a presumption of honesty and that is a temptation to hide.

  19. Tax havens: Features, operations and solving tax evasion problems

    OpenAIRE

    Obradović-Ćuk, Jelena; Mitić, Petar; Dinić, Vladimir

    2016-01-01

    Tax haven offers minimal or no tax liability to foreign individuals and enterprises in economically and politically stable environment, where little or no financial information is shared with foreign tax authorities. The aim of this research is to create a comprehensive overview of the characteristics and operations of tax havens, as well as to point out to the ways to overcome the problem of tax evasion. The methodology used in the work is characteristic of social science research: analysis,...

  20. The economic approach to the problem of tax evasion and recommendations for Serbia

    Directory of Open Access Journals (Sweden)

    Milosavljević Valentina

    2016-01-01

    Full Text Available Tax evasion is a global problem and it has severe consequences for every country, regardless of differences in socio-economic and political structure. The basis for tax criminal offenses is embodied in different manifestations of tax evasion, especially when taking into account that tax evasion is also the most important form of informal economy. Since the taxation achieves not only fiscal, but also objectives in the field of economic and social policy, tax evasion has consequences on the economic and socio-political level. After introductory considerations, the paper shows the topicality of this issue, then the analysis of theoretical and practical features of tax evasion, as the basic fiscal criminal offense in the new Criminal Law of the Republic of Serbia, while the economic approach to the problem of tax evasion is based on an analysis of individual behavior of taxpayers.

  1. Plasticity in early immune evasion strategies of a bacterial pathogen.

    Science.gov (United States)

    Bernard, Quentin; Smith, Alexis A; Yang, Xiuli; Koci, Juraj; Foor, Shelby D; Cramer, Sarah D; Zhuang, Xuran; Dwyer, Jennifer E; Lin, Yi-Pin; Mongodin, Emmanuel F; Marques, Adriana; Leong, John M; Anguita, Juan; Pal, Utpal

    2018-04-17

    Borrelia burgdorferi is one of the few extracellular pathogens capable of establishing persistent infection in mammals. The mechanisms that sustain long-term survival of this bacterium are largely unknown. Here we report a unique innate immune evasion strategy of B. burgdorferi , orchestrated by a surface protein annotated as BBA57, through its modulation of multiple spirochete virulent determinants. BBA57 function is critical for early infection but largely redundant for later stages of spirochetal persistence, either in mammals or in ticks. The protein influences host IFN responses as well as suppresses multiple host microbicidal activities involving serum complement, neutrophils, and antimicrobial peptides. We also discovered a remarkable plasticity in BBA57-mediated spirochete immune evasion strategy because its loss, although resulting in near clearance of pathogens at the inoculum site, triggers nonheritable adaptive changes that exclude detectable nucleotide alterations in the genome but incorporate transcriptional reprograming events. Understanding the malleability in spirochetal immune evasion mechanisms that ensures their host persistence is critical for the development of novel therapeutic and preventive approaches to combat long-term infections like Lyme borreliosis.

  2. Predator evasion by white-tailed deer fawns

    Science.gov (United States)

    Grovenburg, Troy W.; Monteith, Kevin L.; Klaver, Robert W.; Jenks, Jonathan A.

    2012-01-01

    Despite their importance for understanding predator–prey interactions, factors that affect predator evasion behaviours of offspring of large ungulates are poorly understood. Our objective was to characterize the influence of selection and availability of escape cover and maternal presence on predator evasion by white-tailed deer, Odocoileus virginianus, fawns in the northern Great Plains, U.S.A. We observed 45 coyote, Canis latrans, chases of fawns, and we participated in 83 human chases of fawns during 2007–2009, of which, 19 and 42 chases, respectively, ended with capture of the fawn. Evasive techniques used by fawns were similar for human and coyote chases. Likelihood of a white-tailed deer fawn escaping capture, however, was influenced by deer group size and a number of antipredator behaviours, including aggressive defence by females, initial habitat and selection of escape cover, all of which were modified by the presence of parturient females. At the initiation of a chase, fawns in grasslands were more likely to escape, whereas fawns in forested cover, cultivated land or wheat were more likely to be captured by a coyote or human. Fawns fleeing to wetlands and grasslands also were less likely to be captured compared with those choosing forested cover, wheat and cultivated land. Increased probability of capture was associated with greater distance to wetland and grassland habitats and decreased distance to wheat. Use of wetland habitat as a successful antipredator strategy highlights the need for a greater understanding of the importance of habitat complexity in predator avoidance.

  3. CAUSES OF TAX EVASION AND HOW TO REDUCE IT

    Directory of Open Access Journals (Sweden)

    Marcel ȘUVELEA

    2014-12-01

    Full Text Available The level of taxation is influenced and determined by several factors such as: the performance of the economy at any given time, the effectiveness of financed from taxes public expenditure, property structure, public needs as determined by Government policy and approved by the Parliament, the degree of contributors’ understanding of budgetary needs and adherence to Government policy, the stage of democracy in one country or another, etc. These make that between tax level and its base, represented by the GDP, not to be a strict correlation On the State budget and public finance, the cases of tax evasion or avoidance may not have manifested but negative effects. In reality, even the potentiality of cases of tax evasion by taxpayers, adversely affect public funds through the necessary expenditure to be earmarked for the prevention and monitoring of the tax payers. The higher is the extent of the phenomenon of tax evasion, the more the public finances of a State will suffer. If this phenomenon is joined by a weak economy and a shaky fiscal system, the negative effects are augmented. It should also be pointed out another important aspect of feeble public finances: chances are that fiscal bodies to act in that tough situation under emergency and pressure status and to deceive this tension on the economy, making it more unfit to uphold degraded public finances.

  4. A note on the neutrality of profit taxes with tax evasion and tax avoidance

    OpenAIRE

    Che-chiang Huang; Horn-in Kuo

    2014-01-01

    Traditional literature exploring the relationship between production and tax evasion ignores the impact of other activities on these two decisions. This paper incorporates firms' tax avoidance activities into the model of tax evasion. In contrast to conventional results, we find that profit tax is not necessarily neutral. In addition, the independency or separability of tax evasion and production decisions may not hold either whenever tax avoidance is present.

  5. A stressful microenvironment: opposing effects of the endoplasmic reticulum stress response in the suppression and enhancement of adaptive tumor immunity.

    Science.gov (United States)

    Rausch, Matthew P; Sertil, Aparna Ranganathan

    2015-03-01

    The recent clinical success of immunotherapy in the treatment of certain types of cancer has demonstrated the powerful ability of the immune system to control tumor growth, leading to significantly improved patient survival. However, despite these promising results current immunotherapeutic strategies are still limited and have not yet achieved broad acceptance outside the context of metastatic melanoma. The limitations of current immunotherapeutic approaches can be attributed in part to suppressive mechanisms present in the tumor microenvironment that hamper the generation of robust antitumor immune responses thus allowing tumor cells to escape immune-mediated destruction. The endoplasmic reticulum (ER) stress response has recently emerged as a potent regulator of tumor immunity. The ER stress response is an adaptive mechanism that allows tumor cells to survive in the harsh growth conditions inherent to the tumor milieu such as low oxygen (hypoxia), low pH and low levels of glucose. Activation of ER stress can also alter the cancer cell response to therapies. In addition, the ER stress response promotes tumor immune evasion by inducing the production of protumorigenic inflammatory cytokines and impairing tumor antigen presentation. However, the ER stress response can boost antitumor immunity in some situations by enhancing the processing and presentation of tumor antigens and by inducing the release of immunogenic factors from stressed tumor cells. Here, we discuss the dualistic role of the ER stress response in the modulation of tumor immunity and highlight how strategies to either induce or block ER stress can be employed to improve the clinical efficacy of tumor immunotherapy.

  6. Identification and utility of innate immune system evasion mechanisms of ASFV.

    Science.gov (United States)

    Correia, Sílvia; Ventura, Sónia; Parkhouse, Robert Michael

    2013-04-01

    intracellular signaling intermediates. Their deletion from wild type virus may strengthen the host interferon response and so provide an attenuated form with more restricted virus spread after the initial infection, perhaps "buying" sufficient time to allow the development of a protective adaptive immune response. The demonstration of multiple ASFV genes for the evasion of IFN responses will demand technology to construct viruses with multiple gene deletions. An alternative would be a multigene DNA vaccine. Finally, our work clearly demonstrates that unassigned viral genes may be viewed as a repository of host evasion strategies, only identifiable through functional assays. These may be considered to be "ready-made tools" for the experimental manipulation of cell biology and immune responses in health and disease and, as proof of concept, we have constructed a T-cell restricted transgenic mouse expressing the ASFV gene A238L, a dual inhibitor of NF-κB and NFAT activation. The resulting T cell restricted A238L transgenic mice developed a lymphoma with a phenotype reminiscent of some acute lymphoblastic lymphomas. In contrast, transgenic mice similarly expressing a mutant A238L solely inhibiting transcription mediated by NF-κB were indistinguishable from wild type mice, suggesting a transgene-NFAT-dependent transformation. Elucidation of the molecular events associated with the development of this virus host evasion molecule induced tumor may clarify some mechanisms of tumorigenesis in general, and in the development of T cell acute lymphoblastic leukemia in particular. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. The tax havens between measures of economic stimulation and measures against tax evasion

    Directory of Open Access Journals (Sweden)

    Manea, A. C.

    2010-11-01

    Full Text Available In the literature but also in the legal language there are ever-increasingly met the current economic notions of tax havens, offshore companies, offshore law or double taxation. These concepts are encountered, however, in legislative efforts of combating domestic and international business and tax evasion, because such tax havens, although offering financial benefits to individuals or legal residents, make it virtually impossible to control, by the national tax services, the level of imposed income tax and the fees payable by the taxpayer, and all these through operations under the legislation of the States where there are these tax havens. The terminology of tax havens is replaced in recent years with the more discreet terms. of center of international finance or financial haven.

  8. QUANTITATIVE EVALUATION OF TAXPAYERS’ BEHAVIOUR OF FISCAL NON-COMPLIANCE MANIFESTED BY TAX EVASION

    Directory of Open Access Journals (Sweden)

    Elena PĂDUREAN, PhD

    2012-09-01

    Full Text Available The existence, operation and perspectives of economic-social development of a country are linked to its fiscal system, to its performance and to the fiscal culture of the taxpayers, which formed during the fiscal history of that state. The current state of a contemporary state depends on the history of its fiscal system, on the way in which it has been conceived, on the way it has been adapted to the progressive stages of state development and to the way in which it managed to induce, beyond the feeling of constraint, the fiscal education of the taxpayers supporting the feeling of an efficient utilisation of the levied contributions. In this paper we are trying to make a quantitative evaluation of the Romanian fiscal system in terms of taxpayer‟s behaviour of fiscal non-compliance manifested by tax evasion.

  9. The Reform and Design of Commodity Taxes in the Presence of Tax Evasion with Illustrative Evidence from India

    OpenAIRE

    Ray, R.

    1994-01-01

    The literature on tax evasion and its implication for optimal tax theory has concentrated on income tax evasion. The issue of commodity tax evasion has received relatively little attention even though it is important in many cases, especially in developing countries. This paper proposes a theory of marginal reform of indirect taxes that recognises the presence of commodity tax evasion. Illustrative evidence from Indian data confirm the sensitivity of the Pareto improving direction of marginal...

  10. Design, Synthesis, and Biological Evaluation of Small, High-Affinity Siglec-7 Ligands: Toward Novel Inhibitors of Cancer Immune Evasion.

    Science.gov (United States)

    Prescher, Horst; Frank, Martin; Gütgemann, Stephan; Kuhfeldt, Elena; Schweizer, Astrid; Nitschke, Lars; Watzl, Carsten; Brossmer, Reinhard

    2017-02-09

    Natural killer cells are able to directly lyse tumor cells, thereby participating in the immune surveillance against cancer. Unfortunately, many cancer cells use immune evasion strategies to avoid their eradication by the immune system. A prominent escape strategy of malignant cells is to camouflage themselves with Siglec-7 ligands, thereby recruiting the inhibitory receptor Siglec-7 expressed on the NK cell surface which subsequently inhibits NK-cell-mediated lysis. Here we describe the synthesis and evaluation of the first, high-affinity low molecular weight Siglec-7 ligands to interfere with cancer cell immune evasion. The compounds are Sialic acid derivatives and bind with low micromolar K d values to Siglec-7. They display up to a 5000-fold enhanced affinity over the unmodified sialic acid scaffold αMe Neu5Ac, the smallest known natural Siglec-7 ligand. Our results provide a novel immuno-oncology strategy employing natural immunity in the fight against cancers, in particular blocking Siglec-7 with low molecular weight compounds.

  11. 34 CFR 668.207 - Preventing evasion of the consequences of cohort default rates.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false Preventing evasion of the consequences of cohort default rates. 668.207 Section 668.207 Education Regulations of the Offices of the Department of Education... Cohort Default Rates § 668.207 Preventing evasion of the consequences of cohort default rates. (a...

  12. 34 CFR 668.188 - Preventing evasion of the consequences of cohort default rates.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false Preventing evasion of the consequences of cohort default rates. 668.188 Section 668.188 Education Regulations of the Offices of the Department of Education... Two Year Cohort Default Rates § 668.188 Preventing evasion of the consequences of cohort default rates...

  13. Seeing Themselves through Borrowed Eyes: Asian Americans in Ethnic Ambivalence/Evasion.

    Science.gov (United States)

    Tse, Lucy

    1998-01-01

    Focuses on the second stage of ethnic identity development, Ethnic Ambivalence/Evasion, experienced by Asian Americans through 39 personal narratives. Ethnic Ambivalence/Evasion, one of four identified stages that culminate with ethnic identity incorporation, typically occurs during the years of childhood and adolescence, and so is a stage…

  14. The Tax Compliance Demand Curve: A Diagrammatical Approach to Income Tax Evasion

    Science.gov (United States)

    Yaniv, Gideon

    2009-01-01

    One of the most interesting results in the tax evasion literature is that an increase in the income tax rate would increase tax compliance. Despite its peculiarity, this result has gained acceptance as a cornerstone for further developments of the rational tax evasion model. However, because of the mathematical format by which it is conveyed, this…

  15. A VAR Analysis Regarding Tax Evasion and Tax Pressure in Romania

    Directory of Open Access Journals (Sweden)

    Boștină Florin

    2017-01-01

    The main aim of the paper is to identify the relationship that exists between tax evasion and tax pressure in Romania, between 2000 and 2013, using an autoregressive vector type of analysis. The VAR model with 3 lags can be considered as representative in order to describe autoregressive links between tax evasion and fiscal pressure in Romania.

  16. Lapse of time effects on tax evasion in an agent-based econophysics model

    Science.gov (United States)

    Seibold, Götz; Pickhardt, Michael

    2013-05-01

    We investigate an inhomogeneous Ising model in the context of tax evasion dynamics where different types of agents are parameterized via local temperatures and magnetic fields. In particular, we analyze the impact of lapse of time effects (i.e. backauditing) and endogenously determined penalty rates on tax compliance. Both features contribute to a microfoundation of agent-based econophysics models of tax evasion.

  17. Fixed Duration Pursuit-Evasion Differential Game with Integral Constraints

    International Nuclear Information System (INIS)

    Ibragimov G I; Kuchkarov A Sh

    2013-01-01

    We investigate a pursuit-evasion differential game of countably many pursuers and one evader. Integral constraints are imposed on control functions of the players. Duration of the game is fixed and the payoff of the game is infimum of the distances between the evader and pursuers when the game is completed. Purpose of the pursuers is to minimize the payoff and that of the evader is to maximize it. Optimal strategies of the players are constructed, and the value of the game is found. It should be noted that energy resource of any pursuer may be less than that of the evader.

  18. COMPARATIVE ASPECTS OF TAX EVASION IN CONCEPTS AND PRACTICES

    Directory of Open Access Journals (Sweden)

    Georgeta Dragomir

    2008-05-01

    Full Text Available The paper analyze the forms of the tax evasion, în construct representation and comparativelaw, with exemplification on several European states and manifestations identified în international plain. Thereare elucidate the aspects of „tax evasion” and „tax avoidance”, through realities of contemporary world înprogress more and more the eludation actions are transferred from the interior of the national fiscal systems,beyond the state frontiers, being defined by the economic, politic and social globalization tendencies - and thesolutions have there changes în view.

  19. Malaria parasite evasion of classical complement pathway attack

    DEFF Research Database (Denmark)

    Larsen, Mads Delbo; Ditlev, Sisse; Olmos, Rafael Bayarri

    2017-01-01

    of the protective antibodies that are gradually acquired in response to P. falciparum-IEs. Although this response is dominated by IgG1 and IgG3, complement-mediated attack following activation of the classical pathway does not appear to be a major effector mechanism. We hypothesized that this is related to the knob...... is that the knob-restricted expression of PfEMP1 on the IE surface may serve as a hitherto unappreciated immune evasion mechanism employed by P. falciparum parasites....

  20. Simulating effectiveness of helicopter evasive manoeuvres to RPG attack

    Science.gov (United States)

    Anderson, D.; Thomson, D. G.

    2010-04-01

    The survivability of helicopters under attack by ground troops using rocket propelled grenades has been amply illustrated over the past decade. Given that an RPG is unguided and it is infeasible to cover helicopters in thick armour, existing optical countermeasures are ineffective - the solution is to compute an evasive manoeuvre. In this paper, an RPG/helicopter engagement model is presented. Manoeuvre profiles are defined in the missile approach warning sensor camera image plane using a local maximum acceleration vector. Required control inputs are then computed using inverse simulation techniques. Assessments of platform survivability to several engagement scenarios are presented.

  1. [Evasion of anti-infectious immunity by Brucella - A review].

    Science.gov (United States)

    Quan, Wurong; Yang, Yongjie

    2016-05-04

    Brucellosis, caused by Brucella species, is a worldwide zoonosis. As facultative intracellular pathogens, Brucella possess non-classical virulence factor, but its virulence is very powerful and can elicit chronic infections of both animals and humans. Evasion of host anti-infectious immunity is a prerequisite for chronic infections, this ability appears increasingly crucial for Brucella virulence. As successful pathogens, Brucella can escape or suppress innate immunity and modulate adaptive immunity to establish long lasting infections in host cells. In this review, we address the molecular mechanisms of Brucella to evade anti-infectious immunity. This will shed new insights on Brucella virulence and will, potentially, open new prophylactic avenues.

  2. 27 CFR 25.177 - Evasion of or failure to pay tax; failure to file a tax return.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Evasion of or failure to... Pay Tax § 25.177 Evasion of or failure to pay tax; failure to file a tax return. Sections 5671, 5673, 5684, 6651, and 6656 of Title 26 United States Code provide penalties for evasion or failure to pay tax...

  3. The Reform and Design of Commodity Taxes in the Presence of Tax Evasion with Illustrative Evidence from India

    NARCIS (Netherlands)

    Ray, R.

    1994-01-01

    The literature on tax evasion and its implication for optimal tax theory has concentrated on income tax evasion. The issue of commodity tax evasion has received relatively little attention even though it is important in many cases, especially in developing countries. This paper proposes a theory of

  4. IMPACT OF TAX EVASION ON THE ECONOMIC GROWTH IN THE EUROPEAN UNION

    Directory of Open Access Journals (Sweden)

    FLORIN BOȘTINĂ

    2017-12-01

    Full Text Available The relevance of the research topic emerges from the fact that an important part of the fiscal revenues is lost annually through activities of fiscal planning, fiscal circumvention and tax evasion, undertaken by the private sector. In this respect, the aim of the paper is to estimate, by using the econometric analysis, the impact of tax evasion on the economic growth in the European Union for the period 1997-2010 for which the data was available. For the tax evasion it have been used index as a proxy that optimizes by maximum. Thus the main hypothesis (that the index tax evasion positively influences the economic growth was not rejected, even after including some specific control variables in the regressive models. In other words, as tax evasion is increased the economic growth is likely to decrease.

  5. Tumor radiosensitizers-current status of development of various approaches: Report of an International Atomic Energy Agency meeting

    International Nuclear Information System (INIS)

    Horsman, Michael R.; Bohm, Lothar; Margison, Geoffrey P.; Milas, Luka; Rosier, Jean-Francois; Safrany, Geza; Selzer, Edgar; Verheij, Marcel; Hendry, Jolyon H.

    2006-01-01

    Purpose: The International Atomic Energy Agency (IAEA) held a Technical Meeting of Consultants to (1) discuss a selection of relatively new agents, not those well-established in clinical practice, that operated through a variety of mechanisms to sensitize tumors to radiation and (2) to compare and contrast their tumor efficacy, normal tissue toxicity, and status of development regarding clinical application. The aim was to advise the IAEA as to which developing agent or class of agents would be worth promoting further, by supporting additional laboratory research or clinical trials, with the eventual goal of improving cancer control rates using radiotherapy, in developing countries in particular. Results: The agents under discussion included a wide, but not complete, range of different types of drugs, and antibodies that interfered with molecules in cell signaling pathways. These were contrasted with new molecular antisense and gene therapy strategies. All the drugs discussed have previously been shown to act as tumor cell radiosensitizers or to kill hypoxic cells present in tumors. Conclusion: Specific recommendations were made for more preclinical studies with certain of the agents and for clinical trials that would be suitable for industrialized countries, as well as trials that were considered more appropriate for developing countries

  6. A synthesis of rates and controls on elemental mercury evasion in the Great Lakes Basin

    International Nuclear Information System (INIS)

    Denkenberger, Joseph S.; Driscoll, Charles T.; Branfireun, Brian A.; Eckley, Chris S.; Cohen, Mark; Selvendiran, Pranesh

    2012-01-01

    Rates of surface-air elemental mercury (Hg 0 ) fluxes in the literature were synthesized for the Great Lakes Basin (GLB). For the majority of surfaces, fluxes were net positive (evasion). Digital land-cover data were combined with representative evasion rates and used to estimate annual Hg 0 evasion for the GLB (7.7 Mg/yr). This value is less than our estimate of total Hg deposition to the area (15.9 Mg/yr), suggesting the GLB is a net sink for atmospheric Hg. The greatest contributors to annual evasion for the basin are agricultural (∼55%) and forest (∼25%) land cover types, and the open water of the Great Lakes (∼15%). Areal evasion rates were similar across most land cover types (range: 7.0–21.0 μg/m 2 -yr), with higher rates associated with urban (12.6 μg/m 2 -yr) and agricultural (21.0 μg/m 2 -yr) lands. Uncertainty in these estimates could be partially remedied through a unified methodological approach to estimating Hg 0 fluxes. - Highlights: ► Considerable variability exists across spatial/temporal scales in Hg 0 evasion rates. ► Methodological approaches vary for estimating and reporting gaseous Hg 0 fluxes. ► Hg 0 evasion from the Great Lakes Basin is estimated at 7.7 Mg/yr (10.2 μg/m 2 -yr). ► Hg flux estimates suggest region is a net sink for atmospheric Hg. ► 95% of Hg 0 evasion in the region is from agriculture, forest, and the Great Lakes. - A synthesis of Hg evasion was conducted and this information was used to develop an estimate of Hg evasion for the Great Lakes Basin.

  7. Small Business Tax Evasion, is There a Case of Internal Finance?

    Directory of Open Access Journals (Sweden)

    Ilirjan Lipi

    2017-04-01

    Full Text Available As long as there are taxes, the incentive for evasion will exist as well. Studies for tax evasion are of interest in different fields like that of economics, public finance, personal finance, business administration, business finance, financial accounting, in the banking system etc. However, there are only a few studies about the internal causes and financial incentives that oblige decision-makers of small firms towards tax evasion. When we refer to business tax evasion, always brings to mind sensational cases of large businesses that evade taxes, but business tax evasion is a widespread phenomenon even to small firms. To be more competitive, small business must have a consistently entrepreneurial orientation, but limited financing prevents this, therefore the business savings from tax evasion is believed to be an internally funding path. The restrictions on small firms financing often make them orientate more toward internal generation of funds, which also has few alternatives. As a way to internal saving, firms often find tax evasion, which is not only a deviant and unethical behavior, but also puts firms into many difficulties in the long run. Consequently, the study aims to discuss the phenomenon of tax evasion in the managerial practice of small business in an Albanian region, as well as its financial cause as is perceived by the small business. The study findings report that the deviant behavior of businesses from taxes considers the need for internal financing as an important reason. The study concluded that savings from tax evasion is an alternative of internal financing primarily for small and early-staged firms, and that if entrepreneurs are capable of a good business model and competitive strategy, they will not need to make evasion.

  8. Chemical compounds from anthropogenic environment and immune evasion mechanisms: potential interactions.

    Science.gov (United States)

    Kravchenko, Julia; Corsini, Emanuela; Williams, Marc A; Decker, William; Manjili, Masoud H; Otsuki, Takemi; Singh, Neetu; Al-Mulla, Faha; Al-Temaimi, Rabeah; Amedei, Amedeo; Colacci, Anna Maria; Vaccari, Monica; Mondello, Chiara; Scovassi, A Ivana; Raju, Jayadev; Hamid, Roslida A; Memeo, Lorenzo; Forte, Stefano; Roy, Rabindra; Woodrick, Jordan; Salem, Hosni K; Ryan, Elizabeth P; Brown, Dustin G; Bisson, William H; Lowe, Leroy; Lyerly, H Kim

    2015-06-01

    An increasing number of studies suggest an important role of host immunity as a barrier to tumor formation and progression. Complex mechanisms and multiple pathways are involved in evading innate and adaptive immune responses, with a broad spectrum of chemicals displaying the potential to adversely influence immunosurveillance. The evaluation of the cumulative effects of low-dose exposures from the occupational and natural environment, especially if multiple chemicals target the same gene(s) or pathway(s), is a challenge. We reviewed common environmental chemicals and discussed their potential effects on immunosurveillance. Our overarching objective was to review related signaling pathways influencing immune surveillance such as the pathways involving PI3K/Akt, chemokines, TGF-β, FAK, IGF-1, HIF-1α, IL-6, IL-1α, CTLA-4 and PD-1/PDL-1 could individually or collectively impact immunosurveillance. A number of chemicals that are common in the anthropogenic environment such as fungicides (maneb, fluoxastrobin and pyroclostrobin), herbicides (atrazine), insecticides (pyridaben and azamethiphos), the components of personal care products (triclosan and bisphenol A) and diethylhexylphthalate with pathways critical to tumor immunosurveillance. At this time, these chemicals are not recognized as human carcinogens; however, it is known that they these chemicalscan simultaneously persist in the environment and appear to have some potential interfere with the host immune response, therefore potentially contributing to promotion interacting with of immune evasion mechanisms, and promoting subsequent tumor growth and progression. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Immune evasion mechanisms of Entamoeba histolytica: progression to disease

    Directory of Open Access Journals (Sweden)

    Sharmin eBegum

    2015-12-01

    Full Text Available Entamoeba histolytica (Eh is a protozoan parasite that infects 10% of the world’s population and results in 100,000 deaths/year from amebic dysentery and/or liver abscess. In most cases, this extracellular parasite colonizes the colon by high affinity binding to MUC2 mucin without disease symptoms, whereas in some cases, Eh triggers an aggressive inflammatory response upon invasion of the colonic mucosa. The specific host-parasite factors critical for disease pathogenesis are still not well characterized. From the parasite, the signature events that lead to disease progression are cysteine protease cleavage of the C-terminus of MUC2 that dissolves the mucus layer followed by Eh binding and cytotoxicity of the mucosal epithelium. The host mounts an ineffective excessive host pro-inflammatory response following contact with host cells that causes tissue damage and participates in disease pathogenesis as Eh escapes host immune clearance by mechanisms that are not completely understood. Ameba can modulate or destroy effector immune cells by inducing neutrophil apoptosis and suppressing respiratory burst or nitric oxide (NO production from macrophages. Eh adherence to the host cells also induce multiple cytotoxic effects that can promote cell death through phagocytosis, apoptosis or by trogocytosis (ingestion of living cells that might play critical roles in immune evasion. This review focuses on the immune evasion mechanisms that Eh uses to survive and induce disease manifestation in the host.

  10. More than just immune evasion: Hijacking complement by Plasmodium falciparum.

    Science.gov (United States)

    Schmidt, Christoph Q; Kennedy, Alexander T; Tham, Wai-Hong

    2015-09-01

    Malaria remains one of the world's deadliest diseases. Plasmodium falciparum is responsible for the most severe and lethal form of human malaria. P. falciparum's life cycle involves two obligate hosts: human and mosquito. From initial entry into these hosts, malaria parasites face the onslaught of the first line of host defence, the complement system. In this review, we discuss the complex interaction between complement and malaria infection in terms of hosts immune responses, parasite survival and pathogenesis of severe forms of malaria. We will focus on the role of complement receptor 1 and its associated polymorphisms in malaria immune complex clearance, as a mediator of parasite rosetting and as an entry receptor for P. falciparum invasion. Complement evasion strategies of P. falciparum parasites will also be highlighted. The sexual forms of the malaria parasites recruit the soluble human complement regulator Factor H to evade complement-mediated killing within the mosquito host. A novel evasion strategy is the deployment of parasite organelles to divert complement attack from infective blood stage parasites. Finally we outline the future challenge to understand the implications of these exploitation mechanisms in the interplay between successful infection of the host and pathogenesis observed in severe malaria. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Immune Evasion Strategies and Persistence of Helicobacter pylori.

    Science.gov (United States)

    Mejías-Luque, Raquel; Gerhard, Markus

    Helicobacter pylori infection is commonly acquired during childhood, can persist lifelong if not treated, and can cause different gastric pathologies, including chronic gastritis, peptic ulcer disease, and eventually gastric cancer. H. pylori has developed a number of strategies in order to cope with the hostile conditions found in the human stomach as well as successful mechanisms to evade the strong innate and adaptive immune responses elicited upon infection. Thus, by manipulating innate immune receptors and related signaling pathways, inducing tolerogenic dendritic cells and inhibiting effector T cell responses, H. pylori ensures low recognition by the host immune system as well as its persistence in the gastric epithelium. Bacterial virulence factors such as cytotoxin-associated gene A, vacuolating cytotoxin A, or gamma-glutamyltranspeptidase have been extensively studied in the context of bacterial immune escape and persistence. Further, the bacterium possesses other factors that contribute to immune evasion. In this chapter, we discuss in detail the main evasion and persistence strategies evolved by the bacterium as well as the specific bacterial virulence factors involved.

  12. Hijacking Complement Regulatory Proteins for Bacterial Immune Evasion.

    Science.gov (United States)

    Hovingh, Elise S; van den Broek, Bryan; Jongerius, Ilse

    2016-01-01

    The human complement system plays an important role in the defense against invading pathogens, inflammation and homeostasis. Invading microbes, such as bacteria, directly activate the complement system resulting in the formation of chemoattractants and in effective labeling of the bacteria for phagocytosis. In addition, formation of the membrane attack complex is responsible for direct killing of Gram-negative bacteria. In turn, bacteria have evolved several ways to evade complement activation on their surface in order to be able to colonize and invade the human host. One important mechanism of bacterial escape is attraction of complement regulatory proteins to the microbial surface. These molecules are present in the human body for tight regulation of the complement system to prevent damage to host self-surfaces. Therefore, recruitment of complement regulatory proteins to the bacterial surface results in decreased complement activation on the microbial surface which favors bacterial survival. This review will discuss recent advances in understanding the binding of complement regulatory proteins to the bacterial surface at the molecular level. This includes, new insights that have become available concerning specific conserved motives on complement regulatory proteins that are favorable for microbial binding. Finally, complement evasion molecules are of high importance for vaccine development due to their dominant role in bacterial survival, high immunogenicity and homology as well as their presence on the bacterial surface. Here, the use of complement evasion molecules for vaccine development will be discussed.

  13. Supply Chain-based Solution to Prevent Fuel Tax Evasion

    Energy Technology Data Exchange (ETDEWEB)

    Franzese, Oscar [ORNL; Capps, Gary J [ORNL; Daugherty, Michael [United States Department of Transportation (USDOT), Federal Highway Administration (FHWA); Siekmann, Adam [ORNL; Lascurain, Mary Beth [ORNL; Barker, Alan M [ORNL

    2016-01-01

    The primary source of funding for the United States transportation system is derived from motor fuel and other highway use taxes. Loss of revenue attributed to fuel-tax evasion has been assessed to be somewhere between $1 billion per year, or approximately 25% of the total tax collected. Any solution that addresses this problem needs to include not only the tax-collection agencies and auditors, but also the carriers transporting oil products and the carriers customers. This paper presents a system developed by the Oak Ridge National Laboratory for the Federal Highway Administration which has the potential to reduce or eliminate many fuel-tax evasion schemes. The solution balances the needs of tax-auditors and those of the fuel-hauling companies and their customers. The technology was deployed and successfully tested during an eight-month period on a real-world fuel-hauling fleet. Day-to-day operations of the fleet were minimally affected by their interaction with this system. The results of that test are discussed in this paper.

  14. Immune Evasion Mechanisms of Entamoeba histolytica: Progression to Disease.

    Science.gov (United States)

    Begum, Sharmin; Quach, Jeanie; Chadee, Kris

    2015-01-01

    Entamoeba histolytica (Eh) is a protozoan parasite that infects 10% of the world's population and results in 100,000 deaths/year from amebic dysentery and/or liver abscess. In most cases, this extracellular parasite colonizes the colon by high affinity binding to MUC2 mucin without disease symptoms, whereas in some cases, Eh triggers an aggressive inflammatory response upon invasion of the colonic mucosa. The specific host-parasite factors critical for disease pathogenesis are still not well characterized. From the parasite, the signature events that lead to disease progression are cysteine protease cleavage of the C-terminus of MUC2 that dissolves the mucus layer followed by Eh binding and cytotoxicity of the mucosal epithelium. The host mounts an ineffective excessive host pro-inflammatory response following contact with host cells that causes tissue damage and participates in disease pathogenesis as Eh escapes host immune clearance by mechanisms that are not completely understood. Ameba can modulate or destroy effector immune cells by inducing neutrophil apoptosis and suppressing respiratory burst or nitric oxide (NO) production from macrophages. Eh adherence to the host cells also induce multiple cytotoxic effects that can promote cell death through phagocytosis, apoptosis or by trogocytosis (ingestion of living cells) that might play critical roles in immune evasion. This review focuses on the immune evasion mechanisms that Eh uses to survive and induce disease manifestation in the host.

  15. Complement Attack against Aspergillus and Corresponding Evasion Mechanisms

    Directory of Open Access Journals (Sweden)

    Cornelia Speth

    2012-01-01

    Full Text Available Invasive aspergillosis shows a high mortality rate particularly in immunocompromised patients. Perpetually increasing numbers of affected patients highlight the importance of a clearer understanding of interactions between innate immunity and fungi. Innate immunity is considered to be the most significant host defence against invasive fungal infections. Complement represents a crucial part of this first line defence and comprises direct effects against invading pathogens as well as bridging functions to other parts of the immune network. However, despite the potency of complement to attack foreign pathogens, the prevalence of invasive fungal infections is increasing. Two possible reasons may explain that phenomenon: First, complement activation might be insufficient for an effective antifungal defence in risk patients (due to, e.g., low complement levels, poor recognition of fungal surface, or missing interplay with other immune elements in immunocompromised patients. On the other hand, fungi may have developed evasion strategies to avoid recognition and/or eradication by complement. In this review, we summarize the most important interactions between Aspergillus and the complement system. We describe the various ways of complement activation by Aspergillus and the antifungal effects of the system, and also show proven and probable mechanisms of Aspergillus for complement evasion.

  16. Tumor radiosensitizers - current status of development of various approaches: Report of an International Atomic Energy Agency meeting

    DEFF Research Database (Denmark)

    Horsman, Michael Robert; Bohm, Lothar; Margison, Geoffrey P.

    2006-01-01

    PURPOSE: The International Atomic Energy Agency (IAEA) held a Technical Meeting of Consultants to (1) discuss a selection of relatively new agents, not those well-established in clinical practice, that operated through a variety of mechanisms to sensitize tumors to radiation and (2) to compare...... and contrast their tumor efficacy, normal tissue toxicity, and status of development regarding clinical application. The aim was to advise the IAEA as to which developing agent or class of agents would be worth promoting further, by supporting additional laboratory research or clinical trials...... and for clinical trials that would be suitable for industrialized countries, as well as trials that were considered more appropriate for developing countries.PURPOSE: The International Atomic Energy Agency (IAEA) held a Technical Meeting of Consultants to (1) discuss a selection of relatively new agents, not those...

  17. Current status of submucosal tunneling endoscopic resection for gastrointestinal submucosal tumors originating from the muscularis propria layer.

    Science.gov (United States)

    Tan, Yuyong; Huo, Jirong; Liu, Deliang

    2017-11-01

    Gastrointestinal submucosal tumors (SMTs) have been increasingly identified via the use of endoscopic ultrasonography, and removal is often recommended for SMTs that are >2 cm in diameter or symptomatic. Submucosal tunneling endoscopic resection (STER), also known as submucosal endoscopic tumor resection, endoscopic submucosal tunnel dissection or tunneling endoscopic muscularis dissection, is a novel endoscopic technique for treating gastrointestinal SMTs originating from the muscularis propria layer, and has been demonstrated to be effective in the removal of SMTs with a decreased rate of recurrence by clinical studies. STER may be performed for patients with esophageal or cardia SMTs, and its application has expanded beyond these types of SMTs due to modifications to the technique. The present study reviewed the applications, procedure, efficacy and complications associated with STER.

  18. Spatially selective depleting tumor-associated negative regulatory T-(Treg) cells with near infrared photoimmunotherapy (NIR-PIT): A new cancer immunotherapy (Conference Presentation)

    Science.gov (United States)

    Kobayashi, Hisataka

    2017-02-01

    Near infrared photoimmunotherapy (NIR-PIT) is a new type of molecularly-targeted photo-therapy based on conjugating a near infrared silica-phthalocyanine dye, IR700, to a monoclonal antibody (MAb) targeting target-specific cell-surface molecules. When exposed to NIR light, the conjugate rapidly induces a highly-selective cell death only in receptor-positive, MAb-IR700-bound cells. Current immunotherapies for cancer seek to modulate the balance among different immune cell populations, thereby promoting anti-tumor immune responses. However, because these are systemic therapies, they often cause treatment-limiting autoimmune adverse effects. It would be ideal to manipulate the balance between suppressor and effector cells within the tumor without disturbing homeostasis elsewhere in the body. CD4+CD25+Foxp3+ regulatory T cells (Tregs) are well-known immune-suppressor cells that play a key role in tumor immuno-evasion and have been the target of systemic immunotherapies. We used CD25-targeted NIR-PIT to selectively deplete Tregs, thus activating CD8+ T and NK cells and restoring local anti-tumor immunity. This not only resulted in regression of the treated tumor but also induced responses in separate untreated tumors of the same cell-line derivation. We conclude that CD25-targeted NIR-PIT causes spatially selective depletion of Tregs, thereby providing an alternative approach to cancer immunotherapy that can treat not only local tumors but also distant metastatic tumors.

  19. Corruption and Tax Evasion = Yolsuzluk ve Vergi Kaçakçılığı

    Directory of Open Access Journals (Sweden)

    Sacit Hadi AKDEDE

    2006-06-01

    Full Text Available Corruption and tax evasion problems have been investigated separately before. Tax evasion is also considered to be a corrupt behavior itself. However, in this paper, corruption is taken to be a bribe taken by a government official and tax evasion is defined as an illegal act to avoid paying taxes by violating tax laws. An interesting research question would be to see whether corruption can induce tax evasion in individuals ? It is found in the paper that the size of bribe can negatively affect tax evasion. It is shown that when a bribe is sufficiently large, taxpayers prefer to pay their taxes voluntarily, not to evade taxes.

  20. [What future for circulating tumor DNA? Current data and prospects in colorectal, non-small cell lung and pancreatic cancers].

    Science.gov (United States)

    Pietrasz, Daniel; Pécuchet, Nicolas; Fabre, Elizabeth; Blons, Hélène; Chevalier, Line; Taly, Valérie; Laurent-Puig, Pierre; Bachet, Jean-Baptiste

    2016-01-01

    Ten years after the discovery of the predictive value of KRAS status for anti-EGFR antibodies, other genes involved in oncogenesis and therapeutic responses were identified and are now systematically sought. Molecular diagnosis often requires invasive procedures, sometimes iatrogenic, and is limited by feasibility problems, quantity and quality of samples. Identifying these mutations from blood biomarkers would reduce costs and diagnostic delay. The circulating tumor DNA (ctDNA) is one of the most promising blood biomarkers. In this review, we report and discuss the latest results obtained with ctDNA in colorectal cancer, non-small cell lung cancer, and adenocarcinoma of the pancreas. If the methods highlighting appear very heterogeneous, the correlation between mutations found in tumor and those identified in the blood exceeds 95 % specificity in numerous studies. The detection sensitivity is in turn strongly related to tumor stage patients. The presence of ctDNA appears as a prognostic factor for progression-free survival and overall survival. Finally, recent studies have shown that the changing rate ctDNA during systemic treatments had a predictive value for therapeutic efficacy. These results allow to consider the use of ctDNA in monitoring patients to identify early recurrence or progression. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  1. Issues, Challenges and Problems with Tax Evasion: The Institutional Factors Approach

    Directory of Open Access Journals (Sweden)

    Mohd Rizal Palil

    2016-08-01

    Full Text Available Tax evasion, particularly in developing countries is a debatable issue. Evasion is a disease and needs to be minimized so that the black economy or hidden economy can be mitigated. This paper attempts to reveal the determinants of tax evasion from the institutional perspectives. The objective of this study is to identify the determinants of tax evasion a decade after the introduction of a Self-Assessment System (SAS. Three institutional perspectives of the determinants of tax evasion were examined, namely the probability of being detected, the role of the tax authority and the complexity of the tax system. The results suggested that the complexity of the system, and the probability of being detected had a significant impact on tax evasion. The results of this study could possibly contribute to the body of knowledge in lieu of combating tax evasion, as well as being an input to tax administrators and policymakers into which ways the determinants can affect compliance. The findings also provide an indicator for tax administrators of the relative importance of the tax system in assisting with the design of tax education programs, simplifying tax systems and developing a wider understanding of taxpayers’ behavior.

  2. Cigarette tax avoidance and evasion: findings from the International Tobacco Control Policy Evaluation (ITC) Project.

    Science.gov (United States)

    Guindon, G Emmanuel; Driezen, Pete; Chaloupka, Frank J; Fong, Geoffrey T

    2014-03-01

    Decades of research have produced overwhelming evidence that tobacco taxes reduce tobacco use and increase government tax revenue. The magnitude and effectiveness of taxes in reducing tobacco use provide an incentive for tobacco users, manufacturers and others, most notably criminal networks, to devise ways to avoid or evade tobacco taxes. Consequently, tobacco tax avoidance and tax evasion can reduce the public health and fiscal benefit of tobacco taxes. First, this study aims to document, using data from the International Tobacco Control Policy Evaluation Project (ITC), levels and trends in cigarette users' tax avoidance and tax evasion behaviour in a sample of 16 low-, middle- and high-income countries. Second, this study explores factors associated with cigarette tax avoidance and evasion. We used data from ITC surveys conducted in 16 countries to estimate the extent and type of cigarette tax avoidance/evasion between countries and across time. We used self-reported information about the source of a smoker's last purchase of cigarettes or self-reported packaging information, or similar information gathered by the interviewers during face-to-face interviews to measure tax avoidance/evasion behaviours. We used generalised estimating equations to explore individual-level factors that may affect the likelihood of cigarette tax avoidance or evasion in Canada, the USA, the UK and France. We found prevalence estimates of cigarette tax avoidance/evasion vary substantially between countries and across time. In Canada, France and the UK, more than 10% of smokers reported last purchasing cigarettes from low or untaxed sources, while in Malaysia some prevalence estimates suggested substantial cigarette tax avoidance/evasion. We also found important associations between household income and education and the likelihood to engage in tax avoidance/evasion. These associations, however, varied both in direction and magnitude across countries.

  3. Cigarette tax avoidance and evasion: findings from the International Tobacco Control Policy Evaluation Project

    Science.gov (United States)

    Guindon, G. Emmanuel; Driezen, Pete; Chaloupka, Frank J.; Fong, Geoffrey T.

    2014-01-01

    Background Decades of research have produced overwhelming evidence that tobacco taxes reduce tobacco use and increase government tax revenue. The magnitude and effectiveness of taxes at reducing tobacco use provide an incentive for tobacco users, manufacturers and others, most notably criminal networks, to devise ways to avoid or evade tobacco taxes. Consequently, tobacco tax avoidance and tax evasion can reduce the public health and fiscal benefit of tobacco taxes. Objectives First, this study aims to document, using data from the International Tobacco Control Policy Evaluation Project (ITC), levels and trends in cigarette users’ tax avoidance and tax evasion behaviour in a sample of sixteen low-, middle- and high-income countries. Second, this study explores factors associated with cigarette tax avoidance and evasion. Methods We use data from ITC surveys conducted in 16 countries to estimate the extent and the type of cigarette tax avoidance/evasion between countries and across time. We use self-reported information about the source of a smoker’s last purchase of cigarettes or self-reported packaging information, or similar information gathered by the interviewers during face-to-face interviews to measure tax avoidance/evasion behaviours. We use generalized estimating equations (GEE) to explore individual-level factors that may affect the likelihood of cigarette tax avoidance or evasion in Canada, United States, United Kingdom and France. Findings We find prevalence estimates of cigarette tax avoidance/evasion vary substantially between countries and across time. In Canada, France and the United Kingdom, more than 10% of smokers report last purchasing cigarettes from low or untaxed sources while in Malaysia, some prevalence estimates suggest substantial cigarette tax avoidance/evasion. We also find important associations between household income and education and the likelihood to engage in tax avoidance/evasion. These associations, however, vary both in

  4. Tax evasion and corruption in the development of Romanian

    Directory of Open Access Journals (Sweden)

    Măndescu, I.

    2011-01-01

    Full Text Available Tax evasion is one of economic phenomena - social complex of most importance that states face today and unintended consequences which seeks to limit as much as possible, eradication is impossible. She has a direct effect on levels of tax revenues and immediately, which leads directly to imbalances in market mechanisms and the enrichment, unlawfully and practitioners of this method of fraud affecting the state and ultimately each of us, honest tax payers. Fraud produced at the expense of public budgets amid corruption, at the lower level to the higher level, where we already discuss government officials, politicians or even trust the media that influence important decisions based on interests, is a reality of which passed on the economy should not be neglected.

  5. Innate Immune Evasion Mediated by Flaviviridae Non-Structural Proteins.

    Science.gov (United States)

    Chen, Shun; Wu, Zhen; Wang, Mingshu; Cheng, Anchun

    2017-10-07

    Flaviviridae-caused diseases are a critical, emerging public health problem worldwide. Flaviviridae infections usually cause severe, acute or chronic diseases, such as liver damage and liver cancer resulting from a hepatitis C virus (HCV) infection and high fever and shock caused by yellow fever. Many researchers worldwide are investigating the mechanisms by which Flaviviridae cause severe diseases. Flaviviridae can interfere with the host's innate immunity to achieve their purpose of proliferation. For instance, dengue virus (DENV) NS2A, NS2B3, NS4A, NS4B and NS5; HCV NS2, NS3, NS3/4A, NS4B and NS5A; and West Nile virus (WNV) NS1 and NS4B proteins are involved in immune evasion. This review discusses the interplay between viral non-structural Flaviviridae proteins and relevant host proteins, which leads to the suppression of the host's innate antiviral immunity.

  6. Neutrophil evasion strategies by Streptococcus pneumoniae and Staphylococcus aureus.

    Science.gov (United States)

    Lewis, Megan L; Surewaard, Bas G J

    2018-03-01

    Humans are well equipped to defend themselves against bacteria. The innate immune system employs diverse mechanisms to recognize, control and initiate a response that can destroy millions of different microbes. Microbes that evade the sophisticated innate immune system are able to escape detection and could become pathogens. The pathogens Streptococcus pneumoniae and Staphylococcus aureus are particularly successful due to the development of a wide variety of virulence strategies for bacterial pathogenesis and they invest significant efforts towards mechanisms that allow for neutrophil evasion. Neutrophils are a primary cellular defense and can rapidly kill invading microbes, which is an indispensable function for maintaining host health. This review compares the key features of Streptococcus pneumoniae and Staphylococcus aureus in epidemiology, with a specific focus on virulence mechanisms utilized to evade neutrophils in bacterial pathogenesis. It is important to understand the complex interactions between pathogenic bacteria and neutrophils so that we can disrupt the ability of pathogens to cause disease.

  7. Evasive Maneuvers in Space Debris Environment and Technological Parameters

    Directory of Open Access Journals (Sweden)

    Antônio D. C. Jesus

    2012-01-01

    Full Text Available We present a study of collisional dynamics between space debris and an operational vehicle in LEO. We adopted an approach based on the relative dynamics between the objects on a collisional course and with a short warning time and established a semianalytical solution for the final trajectories of these objects. Our results show that there are angular ranges in 3D, in addition to the initial conditions, that favor the collisions. These results allowed the investigation of a range of technological parameters for the spacecraft (e.g., fuel reserve that allow a safe evasive maneuver (e.g., time available for the maneuver. The numerical model was tested for different values of the impact velocity and relative distance between the approaching objects.

  8. Dynamics of tax evasion through an epidemic-like model

    Science.gov (United States)

    Brum, Rafael M.; Crokidakis, Nuno

    In this work, we study a model of tax evasion. We considered a fixed population divided in three compartments, namely honest tax payers, tax evaders and a third class between the mentioned two, which we call susceptibles to become evaders. The transitions among those compartments are ruled by probabilities, similarly to a model of epidemic spreading. These probabilities model social interactions among the individuals, as well as the government’s fiscalization. We simulate the model on fully-connected graphs, as well as on scale-free and random complex networks. For the fully-connected and random graph cases, we observe that the emergence of tax evaders in the population is associated with an active-absorbing nonequilibrium phase transition, that is absent in scale-free networks.

  9. Religion, Culture, and Tax Evasion: Evidence from the Czech Republic

    Directory of Open Access Journals (Sweden)

    Wadim Strielkowski

    2015-06-01

    Full Text Available Our paper analyzes the impact of culture and religion on tax evasions in the Czech Republic, which represents one of the most atheistic countries in Europe, and a very interesting example of attitudes to the church and religion, as well as the influence of religion on the social and economic aspects of everyday life. Our results suggest that, in the Czech Republic, religion plays the role of tax compliance, but only through a positive effect of visiting the church. National pride supports tax morality while trust in government institutions and attitudes towards government are not associated with tax compliance. These results suggest that the Czech Republic is no different from other countries regarding the relationship between religion and tax compliance. Moreover, the role of government as the authority for improving tax compliance is different from what is observed in other countries.

  10. Large Lakes Dominate CO2 Evasion From Lakes in an Arctic Catchment

    Science.gov (United States)

    Rocher-Ros, Gerard; Giesler, Reiner; Lundin, Erik; Salimi, Shokoufeh; Jonsson, Anders; Karlsson, Jan

    2017-12-01

    CO2 evasion from freshwater lakes is an important component of the carbon cycle. However, the relative contribution from different lake sizes may vary, since several parameters underlying CO2 flux are size dependent. Here we estimated the annual lake CO2 evasion from a catchment in northern Sweden encompassing about 30,000 differently sized lakes. We show that areal CO2 fluxes decreased rapidly with lake size, but this was counteracted by the greater overall coverage of larger lakes. As a result, total efflux increased with lake size and the single largest lake in the catchment dominated the CO2 evasion (53% of all CO2 evaded). By contrast, the contribution from the smallest ponds (about 27,000) was minor (evasion at the landscape scale.

  11. Tax design-tax evasion relationship in Serbia: New empirical approach to standard theoretical model

    Directory of Open Access Journals (Sweden)

    Ranđelović Saša

    2015-01-01

    Full Text Available This paper provides evidence on the impact of the change in income tax rates and the degree of its progressivity on the scale of labour taxes evasion in Serbia, using the tax-benefit microsimulation model and econometric methods, on 2007 Living Standard Measurement Survey data. The empirical analysis is based on novel assumption that individual's tax evasion decision depends on a change in disposable income, which is captured by the variation in their Effective Marginal Tax Rates (EMTR, rather than on a change in after-tax income. The results suggest that the elasticity of tax evasion to EMTR equals -0.3, confirming the Yitzhaki's theory, while the propensity to evade is decreasing in the level of wages and increasing in the level of self-employment income. The results also show that introduction of revenue-neutral, progressive taxation of labour income would lead to increase in labour tax evasion by 1 percentage point.

  12. Contrasting distributions of dissolved gaseous mercury concentration and evasion in the North Pacific Subarctic Gyre and the Subarctic Front

    Science.gov (United States)

    Kim, Hyunji; Rhee, Tae Siek; Hahm, Doshik; Hwang, Chung Yeon; Yang, Jisook; Han, Seunghee

    2016-04-01

    The distribution of dissolved gaseous mercury (DGM) and the oxidation-reduction processes of mercury (Hg) in the surface and subsurface ocean are currently understudied despite their importance in ocean-atmosphere interactions. We investigated the Hg(0) evasion and the DGM distribution at water depths of 2-500 m in the Subarctic Front, Western Subarctic Gyre, and Bering Sea of the Northwestern Pacific. The mean DGM concentration in the surface mixed water (evasion flux were significantly higher in the Subarctic Front (125±5.0 fM and 15 pmol m-2 h-1, respectively), which typically has lower nutrient levels and higher primary production, than in the Western Subarctic Gyre and the Bering Sea (74±18 fM and 3.2±1.2 pmol m-2 h-1, respectively). The variation in the chlorophyll-a concentration and extracellular protease activity predicted 54% and 48% of the DGM variation, respectively, in the euphotic zone (2-50 m). The DGM concentration in aphotic intermediate water (415±286 fM) was positively correlated to the apparent oxygen utilization (AOU; r2=0.94 and pevasion is closely linked to primary production in euphotic water and organic remineralization in aphotic intermediate water. The oceanic alterations in these factors may induce significant modification in Hg redox speciation in the Northwestern Pacific.

  13. Conservation of a Unique Mechanism of Immune Evasion across the Lyssavirus Genus

    Science.gov (United States)

    Wiltzer, L.; Larrous, F.; Oksayan, S.; Ito, N.; Marsh, G. A.; Wang, L. F.; Blondel, D.; Bourhy, H.; Jans, D. A.

    2012-01-01

    The evasion of host innate immunity by Rabies virus, the prototype of the genus Lyssavirus, depends on a unique mechanism of selective targeting of interferon-activated STAT proteins by the viral phosphoprotein (P-protein). However, the immune evasion strategies of other lyssaviruses, including several lethal human pathogens, are unresolved. Here, we show that this mechanism is conserved between the most distantly related members of the genus, providing important insights into the pathogenesis and potential therapeutic targeting of lyssaviruses. PMID:22740405

  14. Tax avoidance, tax evasion, and tax flight: Do legal differences matter?

    OpenAIRE

    Schneider, Friedrich; Kirchler, Erich; Maciejovsky, Boris

    2001-01-01

    Although from an economic point of view, legal considerations apart, tax avoidance, tax evasion and tax flight have similar effects, namely a reduction of revenue yields, and are based on the same desire to reduce the tax burden, it is likely that individuals perceive them as different and as unequally fair. Overall, 252 fiscal officers, business students, business lawyers, and entrepreneurs produced spontaneous associations to a scenario either describing tax avoidance, tax evasion, or tax f...

  15. Conservation of a unique mechanism of immune evasion across the Lyssavirus genus.

    Science.gov (United States)

    Wiltzer, L; Larrous, F; Oksayan, S; Ito, N; Marsh, G A; Wang, L F; Blondel, D; Bourhy, H; Jans, D A; Moseley, G W

    2012-09-01

    The evasion of host innate immunity by Rabies virus, the prototype of the genus Lyssavirus, depends on a unique mechanism of selective targeting of interferon-activated STAT proteins by the viral phosphoprotein (P-protein). However, the immune evasion strategies of other lyssaviruses, including several lethal human pathogens, are unresolved. Here, we show that this mechanism is conserved between the most distantly related members of the genus, providing important insights into the pathogenesis and potential therapeutic targeting of lyssaviruses.

  16. Toward Simulating Realistic Pursuit-Evasion Using a Roadmap-Based Approach

    KAUST Repository

    Rodriguez, Samuel

    2010-01-01

    In this work, we describe an approach for modeling and simulating group behaviors for pursuit-evasion that uses a graph-based representation of the environment and integrates multi-agent simulation with roadmap-based path planning. We demonstrate the utility of this approach for a variety of scenarios including pursuit-evasion on terrains, in multi-level buildings, and in crowds. © 2010 Springer-Verlag Berlin Heidelberg.

  17. Estimation of tax evasion and the effectiveness of tax collection for Thailand

    OpenAIRE

    Janbunjong, Pichit

    2009-01-01

    ABSTRACT Low tax revenue is an acute problem for the Thai Government, one which causes a lack of funds for much needed economic and social development. The cause of the low tax revenue is ineffective tax administration. Thus the purpose of this research was to measure the tax effectiveness in Thailand. The review presents the popular Tanzi’s monetary approach for estimating the level of tax evasion and it has resulted in the hypothesis that tax evasion generally increases ...

  18. A comparative analysis of the factors of tax evasion in Ukraine and USA

    OpenAIRE

    N. Frolova

    2014-01-01

    The purpose of the article is to reveal effects on the individual's tax compliance, to examine weak points of tax legislation of Ukraine that may induce tax evasion, and to develop recommendations for the improvement of Ukraine's tax system in terms of minimization of tax evasion, in particular, by introducing comprehensive tax reporting. The article presents the findings of various theoretical and empiric investigations by leading domestic and foreign experts on the issues of estimation and ...

  19. International Tax Evasion, State Purchases of Confidential Bank Data and Voluntary Disclosures

    OpenAIRE

    Bethmann, Dirk; Kvasnicka, Michael

    2017-01-01

    State purchases of bank data on suspected tax evaders from international tax havens constitute a potential tool to combat international tax evasion. Using self-compiled data for North-Rhine Westphalia on the timing and content of such data acquisitions from whistleblowers and on monthly voluntary disclosures of international tax evasion involving Swiss banks, we show that purchases of data by tax authorities on potential tax evaders have a positive and sizeable effect on voluntary disclosures.

  20. Tänapäevased liikursuurtükid / Anna Kern

    Index Scriptorium Estoniae

    Kern, Anna

    2013-01-01

    Riigikaitse arengukavas (a. 2013-2022) on ette nähtud võimalused 1. jalaväebrigaadile hankida tänapäevased liikursuurtükid. Ülevaade liikursuurtükkide loomisest, kasutamisest sõdades ja tänapäevase liikursuurtüki iseloomustus. Näiteid erinevtest liikursuurtükkidest: Archer (Rootsi), Panzerhaubitze 2000 (Saksamaa), Caesar (Prantsusmaa), M777 (USA). Lisatud tabel tehniliste andmetega

  1. Evasion of CO2 and dissolved carbon in river waters of three small catchments in an area occupied by small family farms in the eastern Amazon

    Directory of Open Access Journals (Sweden)

    Maria Beatriz Silva da Rosa

    2017-08-01

    Full Text Available CO2 effluxes from streams and rivers have been hypothesized to be a critical pathway of carbon flow from the biosphere back to the atmosphere. This study was conducted in three small Amazonian catchments to evaluate carbon evasion and dynamics, where land-use change has occurred on small family-farms. Monthly field campaigns were conducted from June 2006 to May 2007 in the Cumaru (CM, Pachibá (PB and São João (SJ streams. Electrical conductivity, pH, temperature, and dissolved oxygen measurements were done in situ, while water samples were collected to determine dissolved organic carbon (DOC and dissolved inorganic carbon (DIC concentrations, as well as carbon dioxide partial pressures (pCO2 and CO2 evasion fluxes. Instantaneous discharge measured by a current meter was used to calculate DOC fluxes. Considering all the sites, DOC, DIC, pCO2, and CO2 flux measurements ranged as follows, respectively: 0.27 - 12.13 mg L-1; 3.5 - 38.9 mg L-1; 2,265 - 26,974 ppm; and 3.39 - 75.35 μmol m-2 s-1. DOC annual flux estimates for CM, SJ and PB were, respectively, 281, 245, and 169 kg C ha-1. CO2 evasion fluxes had an average of 22.70 ± 1.67 μmol m-2 s-1. These CO2 evasion fluxes per unit area were similar to those measured for major Amazonian rivers, thus confirming our hypothesis that small streams can evade substantial quantities of CO2. As secondary vegetation is abundant as a result of family farming management in the region, we conclude that this vegetation can be a major driver of an abundant carbon cycle.

  2. Object and subject of evasion of taxes and other compulsory payments

    Directory of Open Access Journals (Sweden)

    Koval L.

    2014-01-01

    Full Text Available The paper is devoted to such topical issue of Criminal Law as Object and Subject of Evasion of Taxes and Other Compulsory Payments. There are analyzed researched crime determination problems, which are connected with subject and object of tax and other compulsory payments evasion. In the course of the research, the author has made the conclusions that the object of the evasion of taxes and other compulsory payments group is the national economic interests. The direct object is the national economic interests in the sphere of state revenues or the national fiscal interests. While analyzing the law and regulations it is concluded that the subject of the evasion of taxes and other compulsory payments is the tax base (income, property, expenses and consumption, taxes, state and local government fees, as well as other payments determined by the State. The author has also concluded that the subject of the evasion of taxes and other compulsory payments does not include increase in the tax principal debt, fine and late charge, which are covered by the financial responsibility. The subject of the evasion of taxes and other compulsory payments may not include also income from illegal activity or proceeds resulting from criminal offences.

  3. Legalizing altruistic surrogacy in response to evasive travel? An Icelandic proposal

    Directory of Open Access Journals (Sweden)

    Sigurður Kristinsson

    2016-12-01

    Full Text Available Surrogate motherhood has been prohibited by Icelandic law since 1996, but in recent years, Icelandic couples have sought transnational surrogacy in India and the United States despite uncertainties about legal parental status as they return to Iceland with infants born to surrogate mothers. This reflects global trends of increased reproductive tourism, which forces restrictive regimes not only to make decisions concerning the citizenship and parentage of children born to surrogate mothers abroad, but also to confront difficult moral issues concerning surrogacy, global justice, human rights and exploitation. In March 2015, a legislative proposal permitting altruistic surrogacy, subject to strict regulation and oversight, and prohibiting the solicitation of commercial surrogacy abroad, was presented in the Icelandic Parliament. The proposal aims to protect the interest of the child first, respect the autonomy of the surrogate second, and accommodate the intended parents’ wishes third. After a brief overview of the development of the surrogacy issue in Iceland, this article describes the main features of this legislative proposal and evaluates it from an ethical and global justice perspective. It concludes that the proposed legislation is a response to problems generated by cross-border surrogacy in the context of evolving public attitudes toward the issue, and constitutes a valid attempt to reduce the moral hazards of surrogacy consistent with insights from current bioethical literature. Although the proposed legislation arguably represents an improvement over the current ban, however, difficult problems concerning evasive travel and global injustice are likely to persist until effective international coordination is achieved.

  4. Legalizing altruistic surrogacy in response to evasive travel? An Icelandic proposal.

    Science.gov (United States)

    Kristinsson, Sigurður

    2016-12-01

    Surrogate motherhood has been prohibited by Icelandic law since 1996, but in recent years, Icelandic couples have sought transnational surrogacy in India and the United States despite uncertainties about legal parental status as they return to Iceland with infants born to surrogate mothers. This reflects global trends of increased reproductive tourism, which forces restrictive regimes not only to make decisions concerning the citizenship and parentage of children born to surrogate mothers abroad, but also to confront difficult moral issues concerning surrogacy, global justice, human rights and exploitation. In March 2015, a legislative proposal permitting altruistic surrogacy, subject to strict regulation and oversight, and prohibiting the solicitation of commercial surrogacy abroad, was presented in the Icelandic Parliament. The proposal aims to protect the interest of the child first, respect the autonomy of the surrogate second, and accommodate the intended parents' wishes third. After a brief overview of the development of the surrogacy issue in Iceland, this article describes the main features of this legislative proposal and evaluates it from an ethical and global justice perspective. It concludes that the proposed legislation is a response to problems generated by cross-border surrogacy in the context of evolving public attitudes toward the issue, and constitutes a valid attempt to reduce the moral hazards of surrogacy consistent with insights from current bioethical literature. Although the proposed legislation arguably represents an improvement over the current ban, however, difficult problems concerning evasive travel and global injustice are likely to persist until effective international coordination is achieved.

  5. Analysis of Driver Evasive Maneuvering Prior to Intersection Crashes Using Event Data Recorders.

    Science.gov (United States)

    Scanlon, John M; Kusano, Kristofer D; Gabler, Hampton C

    2015-01-01

    Intersection crashes account for over 4,500 fatalities in the United States each year. Intersection Advanced Driver Assistance Systems (I-ADAS) are emerging vehicle-based active safety systems that have the potential to help drivers safely navigate across intersections and prevent intersection crashes and injuries. The performance of an I-ADAS is expected to be highly dependent upon driver evasive maneuvering prior to an intersection crash. Little has been published, however, on the detailed evasive kinematics followed by drivers prior to real-world intersection crashes. The objective of this study was to characterize the frequency, timing, and kinematics of driver evasive maneuvers prior to intersection crashes. Event data recorders (EDRs) downloaded from vehicles involved in intersection crashes were investigated as part of NASS-CDS years 2001 to 2013. A total of 135 EDRs with precrash vehicle speed and braking application were downloaded to investigate evasive braking. A smaller subset of 59 EDRs that collected vehicle yaw rate was additionally analyzed to investigate evasive steering. Each vehicle was assigned to one of 3 precrash movement classifiers (traveling through the intersection, completely stopped, or rolling stop) based on the vehicle's calculated acceleration and observed velocity profile. To ensure that any significant steering input observed was an attempted evasive maneuver, the analysis excluded vehicles at intersections that were turning, driving on a curved road, or performing a lane change. Braking application at the last EDR-recorded time point was assumed to indicate evasive braking. A vehicle yaw rate greater than 4° per second was assumed to indicate an evasive steering maneuver. Drivers executed crash avoidance maneuvers in four-fifths of intersection crashes. A more detailed analysis of evasive braking frequency by precrash maneuver revealed that drivers performing complete or rolling stops (61.3%) braked less often than drivers

  6. Exosomes as a tumor immune escape mechanism: possible therapeutic implications

    Directory of Open Access Journals (Sweden)

    Hanley Harold H

    2008-07-01

    Full Text Available Abstract Advances in cancer therapy have been substantial in terms of molecular understanding of disease mechanisms, however these advances have not translated into increased survival in the majority of cancer types. One unsolved problem in current cancer therapeutics is the substantial immune suppression seen in patients. Conventionally, investigations in this area have focused on antigen-nonspecific immune suppressive molecules such as cytokines and T cell apoptosis inducing molecules such as Fas ligand. More recently, studies have demonstrated nanovesicle particles termed exosomes are involved not only in stimulation but also inhibition of immunity in physiological conditions. Interestingly, exosomes secreted by cancer cells have been demonstrated to express tumor antigens, as well as immune suppressive molecules such as PD-1L and FasL. Concentrations of exosomes from plasma of cancer patients have been associated with spontaneous T cell apoptosis, which is associated in some situations with shortened survival. In this paper we place the "exosome-immune suppression" concept in perspective of other tumor immune evasion mechanisms. We conclude by discussing a novel therapeutic approach to cancer immune suppression by extracorporeal removal of exosomes using hollow fiber filtration technology

  7. Immunohistochemical expression of CD44s in human neuroblastic tumors: Moroccan experience and highlights on current data

    Science.gov (United States)

    2013-01-01

    Background Peripheral neuroblastic tumors (pNTs), including neuroblastoma (NB), ganglioneuroblastoma (GNB) and ganglioneuroma (GN), are extremely heterogeneous pediatric tumors responsible for 15 % of childhood cancer death. The aim of the study was to evaluate the expression of CD44s (‘s’: standard form) cell adhesion molecule by comparison with other specific prognostic markers. Methods An immunohistochemical profile of 32 formalin-fixed paraffin-embedded pNTs tissues, diagnosed between January 2007 and December 2010, was carried out. Results Our results have demonstrated the association of CD44s negative pNTs cells to lack of differentiation and tumour progression. A significant association between absence of CD44s expression and metastasis in human pNTs has been reported. We also found that expression of CD44s defines subgroups of patients without MYCN amplification as evidenced by its association with low INSS stages, absence of metastasis and favorable Shimada histology. Discussion These findings support the thesis of the role of CD44s glycoprotein in the invasive growth potential of neoplastic cells and suggest that its expression could be taken into consideration in the therapeutic approaches targeting metastases. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1034403150888863 Résumé Introduction les tumeurs neuroblastiques périphériques (TNPs), comprenant le neuroblastome (NB), le ganglioneuroblastome (GNB) et le ganglioneurome (GN), sont des tumeurs pédiatriques extrêmement hétérogènes responsables de 15% des décès par cancer chez les enfants. Le but de cette étude était d’évaluer l’expression de la molécule d’adhésion cellulaire CD44s (‘s’: pour standard) par rapport à d’autres facteurs pronostiques spécifiques. Méthodes Un profil immunohistochimique de 32 TNPs fixées au formol et incluses en paraffine, diagnostiquées entre Janvier 2007 et D

  8. Psl Produced by Mucoid Pseudomonas aeruginosa Contributes to the Establishment of Biofilms and Immune Evasion.

    Science.gov (United States)

    Jones, Christopher J; Wozniak, Daniel J

    2017-06-20

    Despite years of research and clinical advances, chronic pulmonary infections with mucoid Pseudomonas aeruginosa remain the primary concern for cystic fibrosis patients. Much of the research on these strains has focused on the contributions of the polysaccharide alginate; however, it is becoming evident that the neutral polysaccharide Psl also contributes to biofilm formation and the maintenance of chronic infections. Here, we demonstrate that Psl produced by mucoid strains has significant roles in biofilm structure and evasion of immune effectors. Though mucoid strains produce less Psl than nonmucoid strains, the Psl that is produced is functional, since it mediates adhesion to human airway cells and epithelial cell death. Additionally, Psl protects mucoid bacteria from opsonization and killing by complement components in human serum. Psl production by mucoid strains stimulates a proinflammatory response in the murine lung, leading to reduced colonization. To determine the relevance of these data to clinical infections, we tested Psl production and biofilm formation of a panel of mucoid clinical isolates. We demonstrated three classes of mucoid isolates, those that produce Psl and form robust biofilms, those that did not produce Psl and have a poor biofilm phenotype, and exopolysaccharide (EPS) redundant strains. Collectively, these experimental results demonstrate that Psl contributes to the biofilm formation and immune evasion of many mucoid strains. This is a novel role for Psl in the establishment and maintenance of chronic pulmonary infections by mucoid strains. IMPORTANCE Cystic fibrosis patients are engaged in an ongoing battle against chronic lung infections by the bacterium Pseudomonas aeruginosa One key factor contributing to the maintenance of chronic infections is the conversion to a mucoid phenotype, where the bacteria produce copious amounts of the polysaccharide alginate. Once the bacteria become mucoid, existing treatments are poorly effective. We

  9. The Evasion of the Text; Invasion of the Text; Again, Evasion of the Text; "The Eagle and the Mole": The Affective Fallacy Revisited.

    Science.gov (United States)

    Ducharme, Edward R.; And Others

    1970-01-01

    Three writers debate whether English teachers should depend on external or internal criteria when analyzing and teaching literature. Each writer discusses the meaning of Elinor Wylie's poem, "The Eagle and the Mole," according to his particular view of literary analysis. Edward Ducharme, in "The Evasion of the Text," submits…

  10. Immune evasion by a staphylococcal inhibitor of myeloperoxidase

    Science.gov (United States)

    de Jong, Nienke W. M.; Ramyar, Kasra X.; Guerra, Fermin E.; Fevre, Cindy; Voyich, Jovanka M.; McCarthy, Alex J.; Garcia, Brandon L.; van Kessel, Kok P. M.; van Strijp, Jos A. G.; Geisbrecht, Brian V.; Haas, Pieter-Jan A.

    2017-01-01

    Staphylococcus aureus is highly adapted to its host and has evolved many strategies to resist opsonization and phagocytosis. Even after uptake by neutrophils, S. aureus shows resistance to killing, which suggests the presence of phagosomal immune evasion molecules. With the aid of secretome phage display, we identified a highly conserved protein that specifically binds and inhibits human myeloperoxidase (MPO), a major player in the oxidative defense of neutrophils. We have named this protein “staphylococcal peroxidase inhibitor” (SPIN). To gain insight into inhibition of MPO by SPIN, we solved the cocrystal structure of SPIN bound to a recombinant form of human MPO at 2.4-Å resolution. This structure reveals that SPIN acts as a molecular plug that prevents H2O2 substrate access to the MPO active site. In subsequent experiments, we observed that SPIN expression increases inside the neutrophil phagosome, where MPO is located, compared with outside the neutrophil. Moreover, bacteria with a deleted gene encoding SPIN showed decreased survival compared with WT bacteria after phagocytosis by neutrophils. Taken together, our results demonstrate that S. aureus secretes a unique proteinaceous MPO inhibitor to enhance survival by interfering with MPO-mediated killing. PMID:28808028

  11. Evasion of host immune defenses by human papillomavirus.

    Science.gov (United States)

    Westrich, Joseph A; Warren, Cody J; Pyeon, Dohun

    2017-03-02

    A majority of human papillomavirus (HPV) infections are asymptomatic and self-resolving in the absence of medical interventions. Various innate and adaptive immune responses, as well as physical barriers, have been implicated in controlling early HPV infections. However, if HPV overcomes these host immune defenses and establishes persistence in basal keratinocytes, it becomes very difficult for the host to eliminate the infection. The HPV oncoproteins E5, E6, and E7 are important in regulating host immune responses. These oncoproteins dysregulate gene expression, protein-protein interactions, posttranslational modifications, and cellular trafficking of critical host immune modulators. In addition to the HPV oncoproteins, sequence variation and dinucleotide depletion in papillomavirus genomes has been suggested as an alternative strategy for evasion of host immune defenses. Since anti-HPV host immune responses are also considered to be important for antitumor immunity, immune dysregulation by HPV during virus persistence may contribute to immune suppression essential for HPV-associated cancer progression. Here, we discuss cellular pathways dysregulated by HPV that allow the virus to evade various host immune defenses. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Viral evasion of intracellular DNA and RNA sensing

    Science.gov (United States)

    Chan, Ying Kai; Gack, Michaela U.

    2016-01-01

    The co-evolution of viruses with their hosts has led to the emergence of viral pathogens that are adept at evading or actively suppressing host immunity. Pattern recognition receptors (PRRs) are key components of antiviral immunity that detect conserved molecular features of viral pathogens and initiate signalling that results in the expression of antiviral genes. In this Review, we discuss the strategies that viruses use to escape immune surveillance by key intracellular sensors of viral RNA or DNA, with a focus on RIG-I-like receptors (RLRs), cyclic GMP–AMP synthase (cGAS) and interferon-γ (IFNγ)-inducible protein 16 (IFI16). Such viral strategies include the sequestration or modification of viral nucleic acids, interference with specific post-translational modifications of PRRs or their adaptor proteins, the degradation or cleavage of PRRs or their adaptors, and the sequestration or relocalization of PRRs. An understanding of viral immune-evasion mechanisms at the molecular level may guide the development of vaccines and antivirals. PMID:27174148

  13. Plasmodium falciparum erythrocyte invasion: combining function with immune evasion.

    Directory of Open Access Journals (Sweden)

    Gavin J Wright

    2014-03-01

    Full Text Available All the symptoms and pathology of malaria are caused by the intraerythrocytic stages of the Plasmodium parasite life cycle. Because Plasmodium parasites cannot replicate outside a host cell, their ability to recognize and invade erythrocytes is an essential step for both parasite survival and malaria pathogenesis. This makes invasion a conceptually attractive vaccine target, especially because it is one of the few stages when the parasite is directly exposed to the host humoral immune system. This apparent vulnerability, however, has been countered by the parasite, which has evolved sophisticated molecular mechanisms to evade the host immune response so that parasites asymptomatically replicate within immune individuals. These mechanisms include the expansion of parasite invasion ligands, resulting in multiple and apparently redundant invasion "pathways", highly polymorphic parasite surface proteins that are immunologically distinct, and parasite proteins which are poorly immunogenic. These formidable defences have so far thwarted attempts to develop an effective blood-stage vaccine, leading many to question whether there really is an exploitable chink in the parasite's immune evasion defences. Here, we review recent advances in the molecular understanding of the P. falciparum erythrocyte invasion field, discuss some of the challenges that have so far prevented the development of blood-stage vaccines, and conclude that the parasite invasion ligand RH5 represents an essential pinch point that might be vulnerable to vaccination.

  14. Transfer Pricing – Between Optimization and International Tax Evasion

    Directory of Open Access Journals (Sweden)

    Valentin SAVA

    2017-04-01

    Full Text Available Each enterprise in the private sector aims to increase financial return, which is achieved by obtaining the higher net profit by increasing revenue and reducing expenditure. In this endeavor, compliance with tax obligations occupy a very important role because handling taxes may lead to an increase in revenue and / or a reduction of spending, and this action is called tax optimization. In the case of multinational companies, the main tool that can be used to lower the tax burden and increasing, sometimes in sizeable benefits in net, is the transfer prices or the prices they registered entities in the group transactions between them, along with another instrument with great impact, ie tax havens. Tax evasion, designating evading payment obligations of a company according to the national tax system, may be legal in the sense that tax optimization does not violate the rules, but exploiting loopholes that are in them. But when legal tax rules are violated, we deal with tax fraud, which will be subject to punitive measures by public authorities as it affects the whole population.

  15. Immune evasion by a staphylococcal inhibitor of myeloperoxidase

    Energy Technology Data Exchange (ETDEWEB)

    de Jong, Nienke W. M.; Ramyar, Kasra X.; Guerra, Fermin E.; Nijland, Reindert; Fevre, Cindy; Voyich, Jovanka M.; McCarthy, Alex J.; Garcia, Brandon L.; van Kessel, Kok P. M.; van Strijp, Jos A. G.; Geisbrecht, Brian V.; Haas, Pieter-Jan A.

    2017-08-14

    Staphylococcus aureus is highly adapted to its host and has evolved many strategies to resist opsonization and phagocytosis. Even after uptake by neutrophils, S. aureus shows resistance to killing, which suggests the presence of phagosomal immune evasion molecules. With the aid of secretome phage display, we identified a highly conserved protein that specifically binds and inhibits human myeloperoxidase (MPO), a major player in the oxidative defense of neutrophils. We have named this protein “staphylococcal peroxidase inhibitor” (SPIN). To gain insight into inhibition of MPO by SPIN, we solved the cocrystal structure of SPIN bound to a recombinant form of human MPO at 2.4-Å resolution. This structure reveals that SPIN acts as a molecular plug that prevents H2O2 substrate access to the MPO active site. In subsequent experiments, we observed that SPIN expression increases inside the neutrophil phagosome, where MPO is located, compared with outside the neutrophil. Moreover, bacteria with a deleted gene encoding SPIN showed decreased survival compared with WT bacteria after phagocytosis by neutrophils. Taken together, our results demonstrate that S. aureus secretes a unique proteinaceous MPO inhibitor to enhance survival by interfering with MPO-mediated killing.

  16. Transfer Pricing - between Optimization and International Tax Evasion

    Directory of Open Access Journals (Sweden)

    Valentin SAVA

    2017-06-01

    Full Text Available Each enterprise in the private sector aims to increase financial return, which is achieved by obtaining a the higher net profit by increasing revenue and reducing expenditure. In this endeavor, compliance with tax obligations occupy a very important role because handling taxes may lead to an increase in revenue and / or a reduction of spending, and this action is called tax optimization. In the case of multinational companies, the main tool that can be used to lower the tax burden and increasing, sometimes in sizeable benefits in net, is the transfer prices or the prices they registered entities in the group transactions between them, along with another instrument with great impact, ie tax havens. Tax evasion, designating evading payment obligations of a company according to the national tax system, may be legal in the sense that tax optimization does not violate the rules, but exploiting loopholes that are in them. But when legal tax rules are violated, we deal with tax fraud, which will be subject to punitive measures by public authorities as it affects the whole population.

  17. Pneumococcal lipoproteins involved in bacterial fitness, virulence, and immune evasion.

    Science.gov (United States)

    Kohler, Sylvia; Voß, Franziska; Gómez Mejia, Alejandro; Brown, Jeremy S; Hammerschmidt, Sven

    2016-11-01

    Streptococcus pneumoniae (pneumococcus) has evolved sophisticated strategies to survive in several niches within the human body either as a harmless commensal or as a serious pathogen causing a variety of diseases. The dynamic interaction between pneumococci and resident host cells during colonization of the upper respiratory tract and at the site of infection is critical for bacterial survival and the development of disease. Pneumococcal lipoproteins are peripherally anchored membrane proteins and have pivotal roles in bacterial fitness including envelope stability, cell division, nutrient acquisition, signal transduction, transport (as substrate-binding proteins of ABC transporter systems), resistance to oxidative stress and antibiotics, and protein folding. In addition, lipoproteins are directly involved in virulence-associated processes such as adhesion, colonization, and persistence through immune evasion. Conversely, lipoproteins are also targets for the host response both as ligands for toll-like receptors and as targets for acquired antibodies. This review summarizes the multifaceted roles of selected pneumococcal lipoproteins and how this knowledge can be exploited to combat pneumococcal infections. © 2016 Federation of European Biochemical Societies.

  18. Structure-guided evolution of antigenically distinct adeno-associated virus variants for immune evasion.

    Science.gov (United States)

    Tse, Longping Victor; Klinc, Kelli A; Madigan, Victoria J; Castellanos Rivera, Ruth M; Wells, Lindsey F; Havlik, L Patrick; Smith, J Kennon; Agbandje-McKenna, Mavis; Asokan, Aravind

    2017-06-13

    Preexisting neutralizing antibodies (NAbs) against adeno-associated viruses (AAVs) pose a major, unresolved challenge that restricts patient enrollment in gene therapy clinical trials using recombinant AAV vectors. Structural studies suggest that despite a high degree of sequence variability, antibody recognition sites or antigenic hotspots on AAVs and other related parvoviruses might be evolutionarily conserved. To test this hypothesis, we developed a structure-guided evolution approach that does not require selective pressure exerted by NAbs. This strategy yielded highly divergent antigenic footprints that do not exist in natural AAV isolates. Specifically, synthetic variants obtained by evolving murine antigenic epitopes on an AAV serotype 1 capsid template can evade NAbs without compromising titer, transduction efficiency, or tissue tropism. One lead AAV variant generated by combining multiple evolved antigenic sites effectively evades polyclonal anti-AAV1 neutralizing sera from immunized mice and rhesus macaques. Furthermore, this variant displays robust immune evasion in nonhuman primate and human serum samples at dilution factors as high as 1:5, currently mandated by several clinical trials. Our results provide evidence that antibody recognition of AAV capsids is conserved across species. This approach can be applied to any AAV strain to evade NAbs in prospective patients for human gene therapy.

  19. HIV reservoirs and immune surveillance evasion cause the failure of structured treatment interruptions: a computational study.

    Directory of Open Access Journals (Sweden)

    Emiliano Mancini

    Full Text Available Continuous antiretroviral therapy is currently the most effective way to treat HIV infection. Unstructured interruptions are quite common due to side effects and toxicity, among others, and cannot be prevented. Several attempts to structure these interruptions failed due to an increased morbidity compared to continuous treatment. The cause of this failure is poorly understood and often attributed to drug resistance. Here we show that structured treatment interruptions would fail regardless of the emergence of drug resistance. Our computational model of the HIV infection dynamics in lymphoid tissue inside lymph nodes, demonstrates that HIV reservoirs and evasion from immune surveillance themselves are sufficient to cause the failure of structured interruptions. We validate our model with data from a clinical trial and show that it is possible to optimize the schedule of interruptions to perform as well as the continuous treatment in the absence of drug resistance. Our methodology enables studying the problem of treatment optimization without having impact on human beings. We anticipate that it is feasible to steer new clinical trials using computational models.

  20. Metastatic castration-resistant prostate cancer: a current view on drug therapy and alternative tumor cell regulation

    Directory of Open Access Journals (Sweden)

    R. A. Gafanov

    2018-01-01

    Full Text Available Prostate cancer (PC is one of the most common causes of death from malignant neoplasms in men in many countries around the world. Transmission of the signal in the androgenic axis of regulation is crucial for the development and progression of PC. Despite the constant dependence on androgen receptor signals in castration resistance, the use of new anti-androgenic drugs invariably leads to the stability  of the ongoing treatment. The interaction of androgen receptor and alternative (phosphoinositide-3-kinases, PI3K pathways in the regulation of cells can be one of the mechanisms of resistance to treatment. In this article, we describe current treatments for metastatic castration-resistant PC and the possible role of the PI3K pathway in the pathogenesis and progression of PC.

  1. Amide proton transfer imaging in clinics: Basic concepts and current and future use in brain tumors and stoke

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ji Eun [Dept. of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Jahng, Geon Ho [Dept. of Radiology, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul (Korea, Republic of); Jeong, Ha Kyu [Philips Korea, Seoul (Korea, Republic of)

    2016-12-15

    Amide proton transfer (APT) imaging is gaining attention as a relatively new in vivo molecular imaging technique that has higher sensitivity and spatial resolution than magnetic resonance spectroscopy imaging. APT imaging is a subset of the chemical exchange saturation transfer mechanism, which can offer unique image contrast by selectively saturating protons in target molecules that get exchanged with protons in bulk water. In this review, we describe the basic concepts of APT imaging, particularly with regard to the benefit in clinics from the current literature. Clinical applications of APT imaging are described from two perspectives: in the diagnosis and monitoring of the treatment response in brain glioma by reflecting endogenous mobile proteins and peptides, and in the potential for stroke imaging with respect to tissue acidity.

  2. Combined Effects of Pericytes in the Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Aline Lopes Ribeiro

    2015-01-01

    Full Text Available Pericytes are multipotent perivascular cells whose involvement in vasculature development is well established. Evidences in the literature also suggest that pericytes display immune properties and that these cells may serve as an in vivo reservoir of stem cells, contributing to the regeneration of diverse tissues. Pericytes are also capable of tumor homing and are important cellular components of the tumor microenvironment (TME. In this review, we highlight the contribution of pericytes to some classical hallmarks of cancer, namely, tumor angiogenesis, growth, metastasis, and evasion of immune destruction, and discuss how collectively these hallmarks could be tackled by therapies targeting pericytes, providing a rationale for cancer drugs aiming at the TME.

  3. Predictive Virtual Infection Modeling of Fungal Immune Evasion in Human Whole Blood.

    Science.gov (United States)

    Prauße, Maria T E; Lehnert, Teresa; Timme, Sandra; Hünniger, Kerstin; Leonhardt, Ines; Kurzai, Oliver; Figge, Marc Thilo

    2018-01-01

    Bloodstream infections by the human-pathogenic fungi Candida albicans and Candida glabrata increasingly occur in hospitalized patients and are associated with high mortality rates. The early immune response against these fungi in human blood comprises a concerted action of humoral and cellular components of the innate immune system. Upon entering the blood, the majority of fungal cells will be eliminated by innate immune cells, i.e., neutrophils and monocytes. However, recent studies identified a population of fungal cells that can evade the immune response and thereby may disseminate and cause organ dissemination, which is frequently observed during candidemia. In this study, we investigate the so far unresolved mechanism of fungal immune evasion in human whole blood by testing hypotheses with the help of mathematical modeling. We use a previously established state-based virtual infection model for whole-blood infection with C. albicans to quantify the immune response and identified the fungal immune-evasion mechanism. While this process was assumed to be spontaneous in the previous model, we now hypothesize that the immune-evasion process is mediated by host factors and incorporate such a mechanism in the model. In particular, we propose, based on previous studies that the fungal immune-evasion mechanism could possibly arise through modification of the fungal surface by as of yet unknown proteins that are assumed to be secreted by activated neutrophils. To validate or reject any of the immune-evasion mechanisms, we compared the simulation of both immune-evasion models for different infection scenarios, i.e., infection of whole blood with either C. albicans or C. glabrata under non-neutropenic and neutropenic conditions. We found that under non-neutropenic conditions, both immune-evasion models fit the experimental data from whole-blood infection with C. albicans and C. glabrata . However, differences between the immune-evasion models could be observed for the

  4. Predictive Virtual Infection Modeling of Fungal Immune Evasion in Human Whole Blood

    Directory of Open Access Journals (Sweden)

    Maria T. E. Prauße

    2018-03-01

    Full Text Available Bloodstream infections by the human-pathogenic fungi Candida albicans and Candida glabrata increasingly occur in hospitalized patients and are associated with high mortality rates. The early immune response against these fungi in human blood comprises a concerted action of humoral and cellular components of the innate immune system. Upon entering the blood, the majority of fungal cells will be eliminated by innate immune cells, i.e., neutrophils and monocytes. However, recent studies identified a population of fungal cells that can evade the immune response and thereby may disseminate and cause organ dissemination, which is frequently observed during candidemia. In this study, we investigate the so far unresolved mechanism of fungal immune evasion in human whole blood by testing hypotheses with the help of mathematical modeling. We use a previously established state-based virtual infection model for whole-blood infection with C. albicans to quantify the immune response and identified the fungal immune-evasion mechanism. While this process was assumed to be spontaneous in the previous model, we now hypothesize that the immune-evasion process is mediated by host factors and incorporate such a mechanism in the model. In particular, we propose, based on previous studies that the fungal immune-evasion mechanism could possibly arise through modification of the fungal surface by as of yet unknown proteins that are assumed to be secreted by activated neutrophils. To validate or reject any of the immune-evasion mechanisms, we compared the simulation of both immune-evasion models for different infection scenarios, i.e., infection of whole blood with either C. albicans or C. glabrata under non-neutropenic and neutropenic conditions. We found that under non-neutropenic conditions, both immune-evasion models fit the experimental data from whole-blood infection with C. albicans and C. glabrata. However, differences between the immune-evasion models could be

  5. The effects of magnetite (Fe3O4 nanoparticles on electroporation-induced inward currents in pituitary tumor (GH3 cells and in RAW 264.7 macrophages

    Directory of Open Access Journals (Sweden)

    Liu YC

    2012-03-01

    Full Text Available Yen-Chin Liu1, Ping-Ching Wu2, Dar-Bin Shieh2–5, Sheng-Nan Wu3,6,71Department of Anesthesiology, 2Institute of Oral Medicine and Department of Stomatology, 3Department of Physiology, National Cheng Kung University Hospital, College of Medicine, 4Advanced Optoelectronic Technology Center, 5Center for Micro/Nano Science and Technology, National Cheng Kung University, 6Innovation Center for Advanced Medical Device Technology, National Cheng Kung University, 7Department of Anatomy and Cell Biology, National Cheng Kung University Medical College, Tainan, TaiwanAims: Fe3O4 nanoparticles (NPs have been known to provide a distinct image contrast effect for magnetic resonance imaging owing to their super paramagnetic properties on local magnetic fields. However, the possible effects of these NPs on membrane ion currents that concurrently induce local magnetic field perturbation remain unclear.Methods: We evaluated whether amine surface-modified Fe3O4 NPs have any effect on ion currents in pituitary tumor (GH3 cells via voltage clamp methods.Results: The addition of Fe3O4 NPs decreases the amplitude of membrane electroporation-induced currents (IMEP with a half-maximal inhibitory concentration at 45 µg/mL. Fe3O4 NPs at a concentration of 3 mg/mL produced a biphasic response in the amplitude of IMEP, ie, an initial decrease followed by a sustained increase. A similar effect was also noted in RAW 264.7 macrophages.Conclusion: The modulation of magnetic electroporation-induced currents by Fe3O4 NPs constitutes an important approach for cell tracking under various imaging modalities or facilitated drug delivery.Keywords: iron oxide, ion current, free radical

  6. Adoptive T cell Therapy Against Solid Tumors: Success Requires Safe TCRs and Countering Immune Evasion

    NARCIS (Netherlands)

    A. Kunert (Andre)

    2018-01-01

    textabstractImmune therapy has proven its feasibility in cancer treatment and in some cases even its preeminence over other treatment modalities such as chemotherapy. Despite promising results observed in clinical trials utilizing or targeting various components of the patient’s own immune system,

  7. A evasão no ensino superior brasileiro Higher education institutions' evasion

    Directory of Open Access Journals (Sweden)

    Roberto Leal Lobo e Silva Filho

    2007-12-01

    Full Text Available Neste trabalho a evasão nas instituições de educação superior no Brasil é estudada com base em dados oficiais, em que se incluem análises regionais dos índices da evasão anual média e da evasão por tipo de instituição. Verifica-se uma correlação negativa entre os índices de evasão e a demanda por curso. Com vistas a possibilitar comparações, são apresentados dados internacionais que indicam que a evasão no Brasil não difere muito das médias internacionais.In this work, evasion in institutions of higher education is studied, based on official data, including regional analyses of annual mean evasion rates and evasion rates by type of institution. It was verified that there is a negative correlation between evasion rates an demand for undergraduate courses. Comparisons with international data are presented, pointing out that the evasion rates in Brazil do not differ a lot from those of other countries.

  8. TAX EVASION, LEVEL OF INTERNET CORPORATE REPORTING AND FIRM VALUE: EVIDENCE FROM INDONESIAN MANUFACTURING FIRMS

    Directory of Open Access Journals (Sweden)

    Asmoro P.S.

    2018-03-01

    Full Text Available As a developing country that accumulates its source of revenue to taxes, Indonesia is not spared from tax compliance issues. The low level of tax compliance indicates a different point of view between the government and the Taxpayer. The low level of tax compliance indicates a different point of view between the government and the Taxpayer. Taxpayers still consider the obligation to pay taxes as an expense that can reduce their income or profits. Therefore, the rational Taxpayer will try to minimize the tax burden. One of them is by doing Tax Evasion. Taxation management is more often done by the Taxpayer Agency, especially the Manufacturing company. This is because the company has a very high business risk. Tax Evasion can increase organizational complexity which in turn can reduce financial transparency. Therefore, companies are required to disclose more information and provide flexible reporting systems that facilitate stakeholders. This encourages companies in the world to take advantage of the development of information technology and interconnection networking through internet corporate reporting. Utilization of internet corporate reporting is expected to increase the value of the company. This study aims to analyze the relationship between the concept of Tax Evasion, the level of internet corporate reporting disclosure, and the firm value. The results showed that the three hypotheses in this study were accepted. Tax Evasion affects the level of internet corporate reporting disclosure. In addition, Tax Evasion also directly or indirectly influence the firm value through the level disclosure of internet corporate reporting.

  9. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  10. Thermodynamic Mechanism for the Evasion of Antibody Neutralization in Flaviviruses

    Science.gov (United States)

    2015-01-01

    Mutations in the epitopes of antigenic proteins can confer viral resistance to antibody-mediated neutralization. However, the fundamental properties that characterize epitope residues and how mutations affect antibody binding to alter virus susceptibility to neutralization remain largely unknown. To address these questions, we used an ensemble-based algorithm to characterize the effects of mutations on the thermodynamics of protein conformational fluctuations. We applied this method to the envelope protein domain III (ED3) of two medically important flaviviruses: West Nile and dengue 2. We determined an intimate relationship between the susceptibility of a residue to thermodynamic perturbations and epitope location. This relationship allows the successful identification of the primary epitopes in each ED3, despite their high sequence and structural similarity. Mutations that allow the ED3 to evade detection by the antibody either increase or decrease conformational fluctuations of the epitopes through local effects or long-range interactions. Spatially distant interactions originate in the redistribution of conformations of the ED3 ensembles, not through a mechanically connected array of contiguous amino acids. These results reconcile previous observations of evasion of neutralization by mutations at a distance from the epitopes. Finally, we established a quantitative correlation between subtle changes in the conformational fluctuations of the epitope and large defects in antibody binding affinity. This correlation suggests that mutations that allow viral growth, while reducing neutralization, do not generate significant structural changes and underscores the importance of protein fluctuations and long-range interactions in the mechanism of antibody-mediated neutralization resistance. PMID:24950171

  11. Evasion of the Interferon-Mediated Antiviral Response by Filoviruses

    Directory of Open Access Journals (Sweden)

    Washington B. Cárdenas

    2010-01-01

    Full Text Available The members of the filoviruses are recognized as some of the most lethal viruses affecting human and non-human primates. The only two genera of the Filoviridae family, Marburg virus (MARV and Ebola virus (EBOV, comprise the main etiologic agents of severe hemorrhagic fever outbreaks in central Africa, with case fatality rates ranging from 25 to 90%. Fatal outcomes have been associated with a late and dysregulated immune response to infection, very likely due to the virus targeting key host immune cells, such as macrophages and dendritic cells (DCs that are necessary to mediate effective innate and adaptive immune responses. Despite major progress in the development of vaccine candidates for filovirus infections, a licensed vaccine or therapy for human use is still not available. During the last ten years, important progress has been made in understanding the molecular mechanisms of filovirus pathogenesis. Several lines of evidence implicate the impairment of the host interferon (IFN antiviral innate immune response by MARV or EBOV as an important determinant of virulence. In vitro and in vivo experimental infections with recombinant Zaire Ebola virus (ZEBOV, the best characterized filovirus, demonstrated that the viral protein VP35 plays a key role in inhibiting the production of IFN-α/β. Further, the action of VP35 is synergized by the inhibition of cellular responses to IFN-α/β by the minor matrix viral protein VP24. The dual action of these viral proteins may contribute to an efficient initial virus replication and dissemination in the host. Noticeably, the analogous function of these viral proteins in MARV has not been reported. Because the IFN response is a major component of the innate immune response to virus infection, this chapter reviews recent findings on the molecular mechanisms of IFN-mediated antiviral evasion by filovirus infection.

  12. Advances in Brain Tumor Surgery for Glioblastoma in Adults

    Directory of Open Access Journals (Sweden)

    Montserrat Lara-Velazquez

    2017-12-01

    Full Text Available Glioblastoma (GBM is the most common primary intracranial neoplasia, and is characterized by its extremely poor prognosis. Despite maximum surgery, chemotherapy, and radiation, the histological heterogeneity of GBM makes total eradication impossible, due to residual cancer cells invading the parenchyma, which is not otherwise seen in radiographic images. Even with gross total resection, the heterogeneity and the dormant nature of brain tumor initiating cells allow for therapeutic evasion, contributing to its recurrence and malignant progression, and severely impacting survival. Visual delimitation of the tumor’s margins with common surgical techniques is a challenge faced by many surgeons. In an attempt to achieve optimal safe resection, advances in approaches allowing intraoperative analysis of cancer and non-cancer tissue have been developed and applied in humans resulting in improved outcomes. In addition, functional paradigms based on stimulation techniques to map the brain’s electrical activity have optimized glioma resection in eloquent areas such as the Broca’s, Wernike’s and perirolandic areas. In this review, we will elaborate on the current standard therapy for newly diagnosed and recurrent glioblastoma with a focus on surgical approaches. We will describe current technologies used for glioma resection, such as awake craniotomy, fluorescence guided surgery, laser interstitial thermal therapy and intraoperative mass spectrometry. Additionally, we will describe a newly developed tool that has shown promising results in preclinical experiments for brain cancer: optical coherence tomography.

  13. Attitudes towards Tax Evasion in Turkey and Australia: A Comparative Study

    Directory of Open Access Journals (Sweden)

    Robert W. McGee

    2016-03-01

    Full Text Available The authors conducted a survey of 502 Turkish and Australian undergraduate and graduate business and economic students to determine their views regarding the ethics of tax evasion. These two groups were selected on the premise that their views represented the perceptions of two very different cultures, which has not been investigated in previous studies. The survey instrument required students to indicate their level of agreeableness to 18 general statements representing various scenarios in the socio-economic environment. The statements in the survey reflected the three main viewpoints regarding the ethics of tax evasion which have emerged from the literature to date. The results of the study show that although Turkish scores are significantly different from the Australian scores, both Turkish and Australian respondents believe that tax evasion can be ethically justifiable in certain situations, although some arguments are stronger than others.

  14. THE HARMONISATION OF LEGISLATION ON COMBATTING TAX EVASION IN THE EUROPEAN UNION

    Directory of Open Access Journals (Sweden)

    DANIELA IANCU

    2011-04-01

    Full Text Available Combating tax evasion is part of the Lisbon Strategy. Tax fraud created a significant distortion in the functioning of the internal market and prevented fair competition.In its resolution of 2th of September 2008 on a coordinated strategy to improve the fight against fiscal fraud (2008/2033 (INI the European Parliament stressed that the Member States cannot combat cross-border fraud in isolation and called on the Commission to propose mechanisms to promote cooperation between Member States.This paper aims to analyse the main mechanisms to combat the tax evasion at the European level and, also, the changes that our country had to make in the field of legislation in order to achieve the EU standard on the fight against tax evasion.

  15. Tumor immunology.

    Science.gov (United States)

    Mocellin, Simone; Lise, Mario; Nitti, Donato

    2007-01-01

    Advances in tumor immunology are supporting the clinical implementation of several immunological approaches to cancer in the clinical setting. However, the alternate success of current immunotherapeutic regimens underscores the fact that the molecular mechanisms underlying immune-mediated tumor rejection are still poorly understood. Given the complexity of the immune system network and the multidimensionality of tumor/host interactions, the comprehension of tumor immunology might greatly benefit from high-throughput microarray analysis, which can portrait the molecular kinetics of immune response on a genome-wide scale, thus accelerating the discovery pace and ultimately catalyzing the development of new hypotheses in cell biology. Although in its infancy, the implementation of microarray technology in tumor immunology studies has already provided investigators with novel data and intriguing new hypotheses on the molecular cascade leading to an effective immune response against cancer. Although the general principles of microarray-based gene profiling have rapidly spread in the scientific community, the need for mastering this technique to produce meaningful data and correctly interpret the enormous output of information generated by this technology is critical and represents a tremendous challenge for investigators, as outlined in the first section of this book. In the present Chapter, we report on some of the most significant results obtained with the application of DNA microarray in this oncology field.

  16. Evasion of adaptive and innate immune response mechanisms by γ-herpesviruses

    Science.gov (United States)

    Feng, Pinghui; Moses, Ashlee; Früh, Klaus

    2015-01-01

    γ-Herpesviral immune evasion mechanisms are optimized to support the acute, lytic and the longterm, latent phase of infection. During acute infection, specific immune modulatory proteins limit, but also exploit, the antiviral activities of cell intrinsic innate immune responses as well as those of innate and adaptive immune cells. During latent infection, a restricted gene expression program limits immune targeting and cis-acting mechanisms to reduce the antigen presentation as well as antigenicity of latency-associated proteins. Here, we will review recent progress in our understanding of γ-herpesviral immune evasion strategies. PMID:23735334

  17. TAX EVASION AND MONEY LAUNDERING – WAYS OF EVADING THE PAYMENT OF THE STATE BUDGET LIABILITIES

    Directory of Open Access Journals (Sweden)

    Constantin AFANASE

    2005-01-01

    Full Text Available Tax evasion is an antisocial phenomenon to be fight against with all forces. By reducing collection oftaxes, this phenomenon abridges society of significant public resources which could be used forachieving some social and economic goals used by the whole society. It is known that since the oldtimes tax payers were looking for means of reducing tax liabilities through various and ingeniousmethods. Basis of tax evasion phenomenon are in the deep structures of human cerebration, in theselfish spirit of human being, which always tend to bring specific interest before overall interest.

  18. The Underground Economy and Tax Evasion in Pakistan. A Fresh Assessment

    OpenAIRE

    Zafar Iqbal; Sarfraz Khan Qureshi; Riaz Mahmood

    1998-01-01

    This paper assesses the size of the underground ~conomy and tax evasion in Pakistan for the period 1973-96. Using monetary approach, the results confirm the existence of large underground economy and higher tax evasion over the period under analysis. The overall underground economy has remarkably increased from 20 percent of GDP in 1973 to 51 percent of GDP in 1996. The evidence also suggests that the rate of growth in th~ underground economy has been higher than the rate of growth of the for...

  19. Tax Evasion Causes and Prevenience or Rebutment Way of Tax Dodger Phenomenon

    Directory of Open Access Journals (Sweden)

    Corina Nichitcin

    2010-12-01

    Full Text Available Tax evasion phenomenon, having negative impact on many levels, must be constantly pursued in order to minimize tax circumvention and control section in the issue of tax fraud. From international theory and experience it is known that normal functioning of market economy is conditioned by promotion of certain efficient policies and adequate legislation implementation. So, as Republic of Moldova is no exception among countries where tax evasion is, the study of this subject is up-to-date and it is required for presenting these problems at national and international levels.

  20. A simultaneous navigation and radiation evasion algorithm (SNARE)

    Energy Technology Data Exchange (ETDEWEB)

    Khasawneh, Mohammed A., E-mail: mkha@ieee.org [Department of Electrical Engineering, Jordan University of Science and Technology, Irbid 221 10 (Jordan); Jaradat, Mohammad A., E-mail: majaradat@just.edu.jo [Department of Mechanical Engineering, Jordan University of Science and Technology, Irbid 221 10 (Jordan); Al-Shboul, Zeina Aman M., E-mail: xeinaaman@gmail.com [Department of Electrical Engineering, Jordan University of Science and Technology, Irbid 221 10 (Jordan)

    2013-12-15

    Highlights: • A new navigation algorithm for radiation evasion around nuclear facilities. • An optimization criteria minimized under algorithm operation. • A man-borne device guiding the occupational worker towards paths that warrant least radiation × time products. • Benefits of using localized navigation as opposed to global navigation schemas. • A path discrimination function for finding the navigational paths exhibiting the least amounts of radiation. - Abstract: In this paper, we address the issue of localization as pertains to indoor navigation under radiation contaminated environments. In this context, navigation, in the absence of any GPS signals, is guided by the location of the sensors that make up the entire wireless sensor network in a given locality within a nuclear facility. It, also, draws on the radiation levels as measured by the sensors around a given locale. Here, localization is inherently embedded into the algorithm presented in (Khasawneh et al., 2011a, 2011b) which was designed to provide navigational guidance to optimize any of two criteria: “Radiation Evasion” and “Nearest Exit”. As such, the algorithm can either be applied to setting a navigational “lowest” radiation exposure path from an initial point A to some other point B; a case typical of occupational workers performing maintenance operations around the facility; or providing a radiation-safe passage from point A to the nearest exit. Algorithm's navigational performance is tested under statistical reference, wherein for a given number of runs (trials) algorithm performance is evaluated as a function of the number of steps of look-ahead it uses to acquire navigational information, and is compared against the performance of the renowned Dijkstra global navigation algorithm. This is done with reference to the amount of (radiation × time) product and that of the time needed to reach an exit point, under the two optimization criteria. To evaluate algorithm

  1. A simultaneous navigation and radiation evasion algorithm (SNARE)

    International Nuclear Information System (INIS)

    Khasawneh, Mohammed A.; Jaradat, Mohammad A.; Al-Shboul, Zeina Aman M.

    2013-01-01

    Highlights: • A new navigation algorithm for radiation evasion around nuclear facilities. • An optimization criteria minimized under algorithm operation. • A man-borne device guiding the occupational worker towards paths that warrant least radiation × time products. • Benefits of using localized navigation as opposed to global navigation schemas. • A path discrimination function for finding the navigational paths exhibiting the least amounts of radiation. - Abstract: In this paper, we address the issue of localization as pertains to indoor navigation under radiation contaminated environments. In this context, navigation, in the absence of any GPS signals, is guided by the location of the sensors that make up the entire wireless sensor network in a given locality within a nuclear facility. It, also, draws on the radiation levels as measured by the sensors around a given locale. Here, localization is inherently embedded into the algorithm presented in (Khasawneh et al., 2011a, 2011b) which was designed to provide navigational guidance to optimize any of two criteria: “Radiation Evasion” and “Nearest Exit”. As such, the algorithm can either be applied to setting a navigational “lowest” radiation exposure path from an initial point A to some other point B; a case typical of occupational workers performing maintenance operations around the facility; or providing a radiation-safe passage from point A to the nearest exit. Algorithm's navigational performance is tested under statistical reference, wherein for a given number of runs (trials) algorithm performance is evaluated as a function of the number of steps of look-ahead it uses to acquire navigational information, and is compared against the performance of the renowned Dijkstra global navigation algorithm. This is done with reference to the amount of (radiation × time) product and that of the time needed to reach an exit point, under the two optimization criteria. To evaluate algorithm

  2. Retiform Sertoli-Leydig Cell Tumor in a 38-Year-Old Woman: A Case Report, Retrospective Review, and Review of Current Literature

    Directory of Open Access Journals (Sweden)

    Laura C. Nwogu

    2017-01-01

    Full Text Available Ovarian sex cord-stromal tumors arise from the stromal cells that surround and support the oocytes. Sertoli-Leydig cell tumors belong to this category of ovarian neoplasms. We present the case of a 38-year-old woman who was found to have a right ovarian mass. The mass was resected and diagnosed as Stage I Sertoli-Leydig cell tumor, retiform variant, following histopathologic and immunohistochemical examination. This case is unusual given the rarity of the retiform variant of Sertoli-Leydig cell tumor and the atypically older age of 38 years at presentation.

  3. Bone tumors

    International Nuclear Information System (INIS)

    Unni, K.K.

    1988-01-01

    This book contains the proceedings on bone tumors. Topics covered include: Bone tumor imaging: Contribution of CT and MRI, staging of bone tumors, perind cell tumors of bone, and metastatic bone disease

  4. The informal sector in transition: Tax evasion in an institutional vacuum

    NARCIS (Netherlands)

    Gërxhani, K.

    2002-01-01

    This thesis discusses the informal sector mainly focusing on the study of tax evasion. Individuals' decision whether or not to evade taxes is the core of the studies presented here. The role of institutions in this individual decision is considered to be of crucial importance. As a natural

  5. Functional motifs responsible for human metapneumovirus M2-2-mediated innate immune evasion.

    Science.gov (United States)

    Chen, Yu; Deng, Xiaoling; Deng, Junfang; Zhou, Jiehua; Ren, Yuping; Liu, Shengxuan; Prusak, Deborah J; Wood, Thomas G; Bao, Xiaoyong

    2016-12-01

    Human metapneumovirus (hMPV) is a major cause of lower respiratory infection in young children. Repeated infections occur throughout life, but its immune evasion mechanisms are largely unknown. We recently found that hMPV M2-2 protein elicits immune evasion by targeting mitochondrial antiviral-signaling protein (MAVS), an antiviral signaling molecule. However, the molecular mechanisms underlying such inhibition are not known. Our mutagenesis studies revealed that PDZ-binding motifs, 29-DEMI-32 and 39-KEALSDGI-46, located in an immune inhibitory region of M2-2, are responsible for M2-2-mediated immune evasion. We also found both motifs prevent TRAF5 and TRAF6, the MAVS downstream adaptors, to be recruited to MAVS, while the motif 39-KEALSDGI-46 also blocks TRAF3 migrating to MAVS. In parallel, these TRAFs are important in activating transcription factors NF-kB and/or IRF-3 by hMPV. Our findings collectively demonstrate that M2-2 uses its PDZ motifs to launch the hMPV immune evasion through blocking the interaction of MAVS and its downstream TRAFs. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Tax evasion and the source of income: An experimental study in Albania and the Netherlands

    NARCIS (Netherlands)

    Gërxhani, K.; Schram, A.

    2003-01-01

    A series of experiments among different social groups in both Albania and the Netherlands give the opportunity to compare behavioral patterns related to tax evasion. Aside from the decision whether or not to evade taxes, subjects have to choose a source of income, where one type enables subsequent

  7. Tax evasion in transition: Outcome of an institutional clash? - Testing Feige's conjecture

    NARCIS (Netherlands)

    Gërxhani, K.

    2003-01-01

    A field survey of households was conducted in Tirana, Albania in 2000. A response rate of 89.3% yielded 1.340 valid questionnaires, allowing us to test Feige’s (1997) conjecture that more tax evasion will be observed, when formal and informal institutions clash. Respondents’ attitudes towards formal

  8. Immune evasion strategies of ranaviruses and innate immune responses to these emerging pathogens.

    Science.gov (United States)

    Grayfer, Leon; Andino, Francisco De Jesús; Chen, Guangchun; Chinchar, Gregory V; Robert, Jacques

    2012-07-01

    Ranaviruses (RV, Iridoviridae) are large double-stranded DNA viruses that infect fish, amphibians and reptiles. For ecological and commercial reasons, considerable attention has been drawn to the increasing prevalence of ranaviral infections of wild populations and in aquacultural settings. Importantly, RVs appear to be capable of crossing species barriers of numerous poikilotherms, suggesting that these pathogens possess a broad host range and potent immune evasion mechanisms. Indeed, while some of the 95-100 predicted ranavirus genes encode putative evasion proteins (e.g., vIFα, vCARD), roughly two-thirds of them do not share significant sequence identity with known viral or eukaryotic genes. Accordingly, the investigation of ranaviral virulence and immune evasion strategies is promising for elucidating potential antiviral targets. In this regard, recombination-based technologies are being employed to knock out gene candidates in the best-characterized RV member, Frog Virus (FV3). Concurrently, by using animal infection models with extensively characterized immune systems, such as the African clawed frog, Xenopus laevis, it is becoming evident that components of innate immunity are at the forefront of virus-host interactions. For example, cells of the macrophage lineage represent important combatants of RV infections while themselves serving as targets for viral infection, maintenance and possibly dissemination. This review focuses on the recent advances in the understanding of the RV immune evasion strategies with emphasis on the roles of the innate immune system in ranaviral infections.

  9. Simple Motion Pursuit and Evasion Differential Games with Many Pursuers on Manifolds with Euclidean Metric

    Directory of Open Access Journals (Sweden)

    Atamurat Kuchkarov

    2016-01-01

    Full Text Available We consider pursuit and evasion differential games of a group of m pursuers and one evader on manifolds with Euclidean metric. The motions of all players are simple, and maximal speeds of all players are equal. If the state of a pursuer coincides with that of the evader at some time, we say that pursuit is completed. We establish that each of the differential games (pursuit or evasion is equivalent to a differential game of m groups of countably many pursuers and one group of countably many evaders in Euclidean space. All the players in any of these groups are controlled by one controlled parameter. We find a condition under which pursuit can be completed, and if this condition is not satisfied, then evasion is possible. We construct strategies for the pursuers in pursuit game which ensure completion the game for a finite time and give a formula for this time. In the case of evasion game, we construct a strategy for the evader.

  10. Stereoscopic filming for investigating evasive side-stepping and anterior cruciate ligament injury risk

    Science.gov (United States)

    Lee, Marcus J. C.; Bourke, Paul; Alderson, Jacqueline A.; Lloyd, David G.; Lay, Brendan

    2010-02-01

    Non-contact anterior cruciate ligament (ACL) injuries are serious and debilitating, often resulting from the performance of evasive sides-stepping (Ssg) by team sport athletes. Previous laboratory based investigations of evasive Ssg have used generic visual stimuli to simulate realistic time and space constraints that athletes experience in the preparation and execution of the manoeuvre. However, the use of unrealistic visual stimuli to impose these constraints may not be accurately identifying the relationship between the perceptual demands and ACL loading during Ssg in actual game environments. We propose that stereoscopically filmed footage featuring sport specific opposing defender/s simulating a tackle on the viewer, when used as visual stimuli, could improve the ecological validity of laboratory based investigations of evasive Ssg. Due to the need for precision and not just the experience of viewing depth in these scenarios, a rigorous filming process built on key geometric considerations and equipment development to enable a separation of 6.5 cm between two commodity cameras had to be undertaken. Within safety limits, this could be an invaluable tool in enabling more accurate investigations of the associations between evasive Ssg and ACL injury risk.

  11. Tax evasion dynamics in the Czech Republic: first evidence of an evasional Kuznets curve

    Czech Academy of Sciences Publication Activity Database

    Hanousek, Jan; Palda, F.

    -, č. 360 (2008), s. 1-38 ISSN 1211-3298 R&D Projects: GA ČR GA402/04/0166; GA MŠk LC542 Institutional research plan: CEZ:AV0Z70850503 Keywords : underground economy * tax evasion * evasional Kuznets curve Subject RIV: AH - Economics http://www.cerge-ei.cz/pdf/wp/Wp360.pdf

  12. Tariff evasion in sub-Saharan Africa: the influence of corruption in importing and exporting countries

    NARCIS (Netherlands)

    Worku, T.; Mendoza Rodriguez, J.P.; Wielhouwer, J.L.

    2016-01-01

    Multilateral organizations recommend sub-Saharan African (SSA) countries to increase international trade in order to attain sustainable economic growth. The benefits of trade can be hampered, however, by tariff evasion. Using trade data from 2008–2014 of 31 SSA countries, we examine how the

  13. Toward Simulating Realistic Pursuit-Evasion Using a Roadmap-Based Approach

    KAUST Repository

    Rodriguez, Samuel; Denny, Jory; Zourntos, Takis; Amato, Nancy M.

    2010-01-01

    In this work, we describe an approach for modeling and simulating group behaviors for pursuit-evasion that uses a graph-based representation of the environment and integrates multi-agent simulation with roadmap-based path planning. We demonstrate

  14. Tax evasion, human capital, and productivity-induced tax rate reduction

    Czech Academy of Sciences Publication Activity Database

    Gillman, Max; Kejak, Michal

    2014-01-01

    Roč. 8, č. 1 (2014), s. 42-79 ISSN 1932-8575 R&D Projects: GA ČR GA13-34096S Institutional support: RVO:67985998 Keywords : tax evasion * human capital * tax rates and tables Subject RIV: AH - Economics Impact factor: 0.600, year: 2014

  15. Tax evasion, human capital, and productivity-induced tax rate reduction

    Czech Academy of Sciences Publication Activity Database

    Gillman, M.; Kejak, Michal

    2014-01-01

    Roč. 8, č. 1 (2014), s. 42-79 ISSN 1932-8575 Grant - others:UK(CZ) UNCE 204005/2012 Institutional support: PRVOUK-P23 Keywords : tax evasion * human capital * tax rates and tables Subject RIV: AH - Economics Impact factor: 0.600, year: 2014

  16. CAR-T cells: the long and winding road to solid tumors.

    Science.gov (United States)

    D'Aloia, Maria Michela; Zizzari, Ilaria Grazia; Sacchetti, Benedetto; Pierelli, Luca; Alimandi, Maurizio

    2018-02-15

    Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host's defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles.

  17. The genomic features of parasitism, Polyembryony and immune evasion in the endoparasitic wasp Macrocentrus cingulum.

    Science.gov (United States)

    Yin, Chuanlin; Li, Meizhen; Hu, Jian; Lang, Kun; Chen, Qiming; Liu, Jinding; Guo, Dianhao; He, Kang; Dong, Yipei; Luo, Jiapeng; Song, Zhenkun; Walters, James R; Zhang, Wenqing; Li, Fei; Chen, Xuexin

    2018-05-30

    Parasitoid wasps are well-known natural enemies of major agricultural pests and arthropod borne diseases. The parasitoid wasp Macrocentrus cingulum (Hymenoptera: Braconidae) has been widely used to control the notorious insect pests Ostrinia furnacalis (Asian Corn Borer) and O. nubilalis (European corn borer). One striking phenomenon exhibited by M. cingulum is polyembryony, the formation of multiple genetically identical offspring from a single zygote. Moreover, M. cingulum employs a passive parasitic strategy by preventing the host's immune system from recognizing the embryo as a foreign body. Thus, the embryos evade the host's immune system and are not encapsulated by host hemocytes. Unfortunately, the mechanism of both polyembryony and immune evasion remains largely unknown. We report the genome of the parasitoid wasp M. cingulum. Comparative genomics analysis of M. cingulum and other 11 insects were conducted, finding some gene families with apparent expansion or contraction which might be linked to the parasitic behaviors or polyembryony of M. cingulum. Moreover, we present the evidence that the microRNA miR-14b regulates the polyembryonic development of M. cingulum by targeting the c-Myc Promoter-binding Protein 1 (MBP-1), histone-lysine N-methyltransferase 2E (KMT2E) and segmentation protein Runt. In addition, Hemomucin, an O-glycosylated transmembrane protein, protects the endoparasitoid wasp larvae from being encapsulated by host hemocytes. Motif and domain analysis showed that only the hemomucin in two endoparasitoids, M. cingulum and Venturia canescens, possessing the ability of passive immune evasion has intact mucin domain and similar O-glycosylation patterns, indicating that the hemomucin is a key factor modulating the immune evasion. The microRNA miR-14b participates in the regulation of polyembryonic development, and the O-glycosylation of the mucin domain in the hemomucin confers the passive immune evasion in this wasp. These key findings provide

  18. Staphylococcus aureus innate immune evasion is lineage-specific: a bioinfomatics study.

    Science.gov (United States)

    McCarthy, Alex J; Lindsay, Jodi A

    2013-10-01

    Staphylococcus aureus is a major human pathogen, and is targeted by the host innate immune system. In response, S. aureus genomes encode dozens of secreted proteins that inhibit complement, chemotaxis and neutrophil activation resulting in successful evasion of innate immune responses. These proteins include immune evasion cluster proteins (IEC; Chp, Sak, Scn), staphylococcal superantigen-like proteins (SSLs), phenol soluble modulins (PSMs) and several leukocidins. Biochemical studies have indicated that genetic variants of these proteins can have unique functions. To ascertain the scale of genetic variation in secreted immune evasion proteins, whole genome sequences of 88 S. aureus isolates, representing 25 clonal complex (CC) lineages, in the public domain were analysed across 43 genes encoding 38 secreted innate immune evasion protein complexes. Twenty-three genes were variable, with between 2 and 15 variants, and the variants had lineage-specific distributions. They include genes encoding Eap, Ecb, Efb, Flipr/Flipr-like, Hla, Hld, Hlg, Sbi, Scin-B/C and 13 SSLs. Most of these protein complexes inhibit complement, chemotaxis and neutrophil activation suggesting that isolates from each S. aureus lineage respond to the innate immune system differently. In contrast, protein complexes that lyse neutrophils (LukSF-PVL, LukMF, LukED and PSMs) were highly conserved, but can be carried on mobile genetic elements (MGEs). MGEs also encode proteins with narrow host-specificities arguing that their acquisition has important roles in host/environmental adaptation. In conclusion, this data suggests that each lineage of S. aureus evades host immune responses differently, and that isolates can adapt to new host environments by acquiring MGEs and the immune evasion protein complexes that they encode. Cocktail therapeutics that targets multiple variant proteins may be the most appropriate strategy for controlling S. aureus infections. Copyright © 2013 Elsevier B.V. All rights

  19. Cancer Stem Cell-Secreted Macrophage Migration Inhibitory Factor Stimulates Myeloid Derived Suppressor Cell Function and Facilitates Glioblastoma Immune Evasion

    DEFF Research Database (Denmark)

    Otvos, Balint; Silver, Daniel J; Mulkearns-Hubert, Erin E

    2016-01-01

    Shifting the balance away from tumor-mediated immune suppression toward tumor immune rejection is the conceptual foundation for a variety of immunotherapy efforts currently being tested. These efforts largely focus on activating antitumor immune responses but are confounded by multiple immune cel...

  20. Perception of pathogenic or beneficial bacteria and their evasion of host immunity: pattern recognition receptors in the frontline

    Czech Academy of Sciences Publication Activity Database

    Trdá, Lucie; Boutrot, F.; Claverie, J.; Brule, D.; Dorey, S.; Poinssot, B.

    2015-01-01

    Roč. 6, APR 8 (2015) ISSN 1664-462X Institutional support: RVO:61389030 Keywords : plant-microbe interactions * innate immunity * evasion Subject RIV: ED - Physiology Impact factor: 4.495, year: 2015

  1. On Some Pursuit and Evasion Differential Game Problems for an Infinite Number of First-Order Differential Equations

    Directory of Open Access Journals (Sweden)

    Abbas Badakaya Ja'afaru

    2012-01-01

    Full Text Available We study pursuit and evasion differential game problems described by infinite number of first-order differential equations with function coefficients in Hilbert space l2. Problems involving integral, geometric, and mix constraints to the control functions of the players are considered. In each case, we give sufficient conditions for completion of pursuit and for which evasion is possible. Consequently, strategy of the pursuer and control function of the evader are constructed in an explicit form for every problem considered.

  2. Testis tumors

    International Nuclear Information System (INIS)

    White, R.L.; Maier, J.G.

    1987-01-01

    Clinical trials are evaluating new combinations of drugs with the goal of diminishing the toxicity associated with the current regimens while not compromising the chance for cure. The evolution of information and staging studies such as tumor markers, CT scanning and MR scanning has made possible the detection of residual metastatic disease while obviating the need for surgical staging procedures. This has made less treatment possible for a large number of patients. The regularity of follow-up studies has made early detection of recurrences a possibility, so that effective and curative treatment is generally possible

  3. Trypanosoma brucei metabolite indolepyruvate decreases HIF-1α and glycolysis in macrophages as a mechanism of innate immune evasion.

    Science.gov (United States)

    McGettrick, Anne F; Corcoran, Sarah E; Barry, Paul J G; McFarland, Jennifer; Crès, Cécile; Curtis, Anne M; Franklin, Edward; Corr, Sinéad C; Mok, K Hun; Cummins, Eoin P; Taylor, Cormac T; O'Neill, Luke A J; Nolan, Derek P

    2016-11-29

    The parasite Trypanasoma brucei causes African trypanosomiasis, known as sleeping sickness in humans and nagana in domestic animals. These diseases are a major burden in the 36 sub-Saharan African countries where the tsetse fly vector is endemic. Untreated trypanosomiasis is fatal and the current treatments are stage-dependent and can be problematic during the meningoencephalitic stage, where no new therapies have been developed in recent years and the current drugs have a low therapeutic index. There is a need for more effective treatments and a better understanding of how these parasites evade the host immune response will help in this regard. The bloodstream form of T. brucei excretes significant amounts of aromatic ketoacids, including indolepyruvate, a transamination product of tryptophan. This study demonstrates that this process is essential in bloodstream forms, is mediated by a specialized isoform of cytoplasmic aminotransferase and, importantly, reveals an immunomodulatory role for indolepyruvate. Indolepyruvate prevents the LPS-induced glycolytic shift in macrophages. This effect is the result of an increase in the hydroxylation and degradation of the transcription factor hypoxia-inducible factor-1α (HIF-1α). The reduction in HIF-1α levels by indolepyruvate, following LPS or trypanosome activation, results in a decrease in production of the proinflammatory cytokine IL-1β. These data demonstrate an important role for indolepyruvate in immune evasion by T. brucei.

  4. Analysing and controlling the tax evasion dynamics via majority-vote model

    Energy Technology Data Exchange (ETDEWEB)

    Lima, F W S, E-mail: fwslima@gmail.co, E-mail: wel@ufpi.edu.b [Departamento de Fisica, Universidade Federal do PiauI, 64049-550, Teresina - PI (Brazil)

    2010-09-01

    Within the context of agent-based Monte-Carlo simulations, we study the well-known majority-vote model (MVM) with noise applied to tax evasion on simple square lattices, Voronoi-Delaunay random lattices, Barabasi-Albert networks, and Erdoes-Renyi random graphs. In the order to analyse and to control the fluctuations for tax evasion in the economics model proposed by Zaklan, MVM is applied in the neighborhood of the noise critical q{sub c} to evolve the Zaklan model. The Zaklan model had been studied recently using the equilibrium Ising model. Here we show that the Zaklan model is robust because this can be studied using equilibrium dynamics of Ising model also through the nonequilibrium MVM and on various topologies cited above giving the same behavior regardless of dynamic or topology used here.

  5. Analysing and controlling the tax evasion dynamics via majority-vote model

    International Nuclear Information System (INIS)

    Lima, F W S

    2010-01-01

    Within the context of agent-based Monte-Carlo simulations, we study the well-known majority-vote model (MVM) with noise applied to tax evasion on simple square lattices, Voronoi-Delaunay random lattices, Barabasi-Albert networks, and Erdoes-Renyi random graphs. In the order to analyse and to control the fluctuations for tax evasion in the economics model proposed by Zaklan, MVM is applied in the neighborhood of the noise critical q c to evolve the Zaklan model. The Zaklan model had been studied recently using the equilibrium Ising model. Here we show that the Zaklan model is robust because this can be studied using equilibrium dynamics of Ising model also through the nonequilibrium MVM and on various topologies cited above giving the same behavior regardless of dynamic or topology used here.

  6. Toward realistic pursuit-evasion using a roadmap-based approach

    KAUST Repository

    Rodriguez, Samuel

    2011-05-01

    In this work, we describe an approach for modeling and simulating group behaviors for pursuit-evasion that uses a graph-based representation of the environment and integrates multi-agent simulation with roadmap-based path planning. Our approach can be applied to more realistic scenarios than are typically studied in most previous work, including agents moving in 3D environments such as terrains, multi-story buildings, and dynamic environments. We also support more realistic three-dimensional visibility computations that allow evading agents to hide in crowds or behind hills. We demonstrate the utility of this approach on mobile robots and in simulation for a variety of scenarios including pursuit-evasion and tag on terrains, in multi-level buildings, and in crowds. © 2011 IEEE.

  7. Morphology of seahorse head hydrodynamically aids in capture of evasive prey.

    Science.gov (United States)

    Gemmell, Brad J; Sheng, Jian; Buskey, Edward J

    2013-01-01

    Syngnathid fish (seahorses, pipefish and sea dragons) are slow swimmers yet capture evasive prey (copepods) using a technique known as the 'pivot' feeding, which involves rapid movement to overcome prey escape capabilities. However, this feeding mode functions only at short range and requires approaching very closely to hydrodynamically sensitive prey without triggering an escape. Here we investigate the role of head morphology on prey capture using holographic and particle image velocimetry (PIV). We show that head morphology functions to create a reduced fluid deformation zone, minimizing hydrodynamic disturbance where feeding strikes occur (above the end of the snout), and permits syngnathid fish to approach highly sensitive copepod prey (Acartia tonsa) undetected. The results explain how these animals can successfully employ short range 'pivot' feeding effectively on evasive prey. The need to approach prey with stealth may have selected for a head shape that produces lower deformation rates than other fish.

  8. Evasion Mechanisms Used by Pathogens to Escape the Lectin Complement Pathway

    DEFF Research Database (Denmark)

    Rosbjerg, Anne; Genster, Ninette; Pilely, Katrine

    2017-01-01

    The complement system is a crucial defensive network that protects the host against invading pathogens. It is part of the innate immune system and can be initiated via three pathways: the lectin, classical and alternative activation pathway. Overall the network compiles a group of recognition...... the level of activity. The result is a pro-inflammatory response meant to combat foreign microbes. Microbial elimination is, however, not a straight forward procedure; pathogens have adapted to their environment by evolving a collection of evasion mechanisms that circumvent the human complement system....... Complement evasion strategies features different ways of exploiting human complement proteins and moreover features different pathogen-derived proteins that interfere with the normal processes. Accumulated, these mechanisms target all three complement activation pathways as well as the final common part...

  9. Social Dimensions of Tax Evasion: Trust and Tax Morale in Contemporary Spain

    Directory of Open Access Journals (Sweden)

    Sandro Giachi

    2014-01-01

    Full Text Available This article tackles the problem of tax evasion from a sociological view. The rational action approach is integrated here with the concepts of trust and tax morale. The aim is to discover why people justify fi scal fraud or have lax tax morale. The main hypothesis maintained here is that tax system social factors ?such as trust? have an effect on the justifi cation of fraud. Using two survey datasets referred to the past ten years, we observe that tax morale seems to be mainly composed by trust in tax system, trust in other taxpayers as well as diverse contextual factors. Finally, I present an interpretive framework that takes into consideration individual factors as well as social and geographic dimensions of tax evasion in Spain.

  10. PREVENTION AND CONTROL OF THE TAX EVASION IMPACT ON ROMANIAN ECONOMY

    Directory of Open Access Journals (Sweden)

    Raluca Andreea TRANDAFIR

    2015-04-01

    Full Text Available Time of occurrence of tax evasion is closely linked even to social developments, this social phenomenon has emerged and evolved at the same time with the company. Since tax evasion is a phenomenon particularly harmful and despicable paradoxically, it has unfortunately been a negative and unintended consequence, with directions of development and different incidents in any country, regardless of size, level of development or form power organization. In Romania, the underground economy is strong because it is determined by the size of the phenomenon of crime in the economic and financial (dirty money, a phenomenon characterized by a very high level of "financial engineering" made in the privatization, investment, financial institutions - banks and the use of public funds. Thus, effective tools are triggered by conversion and diversion of capital flows in order to remove it from licit financial circuit.

  11. CMV immune evasion and manipulation of the immune system with aging.

    Science.gov (United States)

    Jackson, Sarah E; Redeker, Anke; Arens, Ramon; van Baarle, Debbie; van den Berg, Sara P H; Benedict, Chris A; Čičin-Šain, Luka; Hill, Ann B; Wills, Mark R

    2017-06-01

    Human cytomegalovirus (HCMV) encodes numerous proteins and microRNAs that function to evade the immune response and allow the virus to replicate and disseminate in the face of a competent innate and acquired immune system. The establishment of a latent infection by CMV, which if completely quiescent at the level of viral gene expression would represent an ultimate in immune evasion strategies, is not sufficient for lifelong persistence and dissemination of the virus. CMV needs to reactivate and replicate in a lytic cycle of infection in order to disseminate further, which occurs in the face of a fully primed secondary immune response. Without reactivation, latency itself would be redundant for the virus. It is also becoming clear that latency is not a totally quiescent state, but is characterized by limited viral gene expression. Therefore, the virus also needs immune evasion strategies during latency. An effective immune response to CMV is required or viral replication will cause morbidity and ultimately mortality in the host. There is clearly a complex balance between virus immune evasion and host immune recognition over a lifetime. This poses the important question of whether long-term evasion or manipulation of the immune response driven by CMV is detrimental to health. In this meeting report, three groups used the murine model of CMV (MCMV) to examine if the contribution of the virus to immune senescence is set by the (i) initial viral inoculum, (ii) inflation of T cell responses, (iii) or the balance between functionally distinct effector CD4+ T cells. The work of other groups studying the CMV response in humans is discussed. Their work asks whether the ability to make immune responses to new antigens is compromised by (i) age and HCMV carriage, (ii) long-term exposure to HCMV giving rise to an overall immunosuppressive environment and increased levels of latent virus, or (iii) adapted virus mutants (used as potential vaccines) that have the capacity to

  12. Pursit-evasion game analysis in a line of sight coordinate system

    Science.gov (United States)

    Shinar, J.; Davidovitz, A.

    1985-01-01

    The paper proposes to use line of sight coordinates for the analysis of pursuit-evasion games. The advantage of this method for two-target games is shown to be evident. As a demonstrative example the game of two identical cars is formulated and solved in such coordinate systems. A new type of singular surface, overlooked in a previous study of the same problem, is discovered as a consequence of the simplicity of the solution.

  13. Interferon Response and Viral Evasion by Members of the Family Rhabdoviridae

    OpenAIRE

    Matthias J. Schnell; Elizabeth J. Faul; Douglas S. Lyles

    2009-01-01

    Like many animal viruses, those of the Rhabdoviridae family, are able to antagonize the type I interferon response and cause disease in mammalian hosts. Though these negative-stranded RNA viruses are very simple and code for as few as five proteins, they have been seen to completely abrogate the type I interferon response early in infection. In this review, we will discuss the viral organization and type I interferon evasion of rhabdoviruses, focusing on vesicular stomatitis virus (VSV) and r...

  14. Decomposing Revenue Effects of Tax Evasion, Base Broadening and Tax Rate Reduction

    OpenAIRE

    Ira N. Gang; Arindam Das-Gupta

    1998-01-01

    This paper proposes a method for evaluating the impact of tax reform on tax revenues and the distribution of the tax burden. The technique consists of decomposing actual revenue relative to potential revenue into components attributable to (i) changes in the tax rate structure (ii) deductions and (iii) tax evasion. If the standard reform package is successful, revenue loss from deductions should be curtailed by base broadening. Furthermore, revenues lost by lowering tax rates should be more t...

  15. Would Tax Evasion and Tax Avoidance Undermine a National Retail Sales Tax?

    OpenAIRE

    Murray, Matthew N.

    1997-01-01

    Argues that shifting to an indirect tax system (a national sales tax) will not necessarily reduce tax avoidance and tax evasion behavior by businesses and individuals, particularly if the tax rate is set high to maintain revenue neutrality. Lack of experience in administering a high-rate, indirect tax system precludes definitive statements regarding the likely extent of tax base erosion under a national sales tax.

  16. Illustratsioon eesti tänapäevases täiskasvanute ilukirjanduses / Martin Tõnts

    Index Scriptorium Estoniae

    Tõnts, Martin

    2010-01-01

    Uuritakse illustratsiooni funktsioone tänapäevases eesti ilukirjanduses, kas ja kuidas on need seotud tekstiga, on sellest inspireeritud või ei, kuivõrd annavad edasi tekstis peituvat või iseseisvat informatsiooni või on pelgalt kaunistavad, nagu peamiselt luulekogudes esinevad illustratsioonid. Praktilise tööna on Birk Rohelennu "Alexander ja Belle" raamatu kujundus, küljendus ja illustratsioonid

  17. Everyday Representations of Tax Avoidance, Tax Evasion, and Tax Flight: Do Legal Differences Matter?

    OpenAIRE

    Kirchler, Erich; Maciejovsky, Boris; Schneider, Friedrich

    2001-01-01

    From an economic point of view, legal considerations apart, tax avoidance, tax evasion and tax flight have similar effects, namely a reduction of revenue yields, and are based on the same desire to reduce the tax burden. Due to legal differences and moral concerns it is, however, likely that individuals perceive them as different and as unequally fair. Overall, 252 fiscal officers, business students, business lawyers, and entrepreneurs produced spontaneous associations to a scenario either de...

  18. Tax Evasion and Tax Avoidance in Developing Countries: The Role of International Profit Shifting

    OpenAIRE

    Clemens Fuest; Nadine Riedel

    2010-01-01

    In the debate on the impact of illicit capital flows on developing countries, the view is widespread that profit shifting to low tax jurisdictions undermines the ability of developing countries to raise tax revenue. While the shifting of income out of developed countries is a widely debated issue, empirical evidence on the magnitude of the problem and on the factors driving income shifting is scarce. This paper reviews the literature on tax avoidance and evasion through border crossing income...

  19. Automatic Exchange of Information as the new global standard: the end of (offshore tax evasion) history?

    OpenAIRE

    Meinzer, Markus

    2017-01-01

    Automatic exchange of information (AEoI) for tax purposes has become the global standard for international tax cooperation in 2013. As a tool for containing offshore tax evasion, it has encountered opposition in the past and continues to be fraught with challenges. This paper recapitulates the rationale for AEoI, including estimates on the magnitudes of assets held offshore, with a specific focus on Turkish assets held in Germany (chapter 1). Subsequently, chapter 2 summarises the recent hist...

  20. Tax Evasion in Switzerland: The Roles of Deterrence and Tax Morale

    OpenAIRE

    Feld, Lars P; Frey, Bruno S

    2006-01-01

    The traditional economic approach to tax evasion does not appear to be particularly successful in explaining the extent of tax compliance. We argue instead that a psychological tax contract which establishes a fiscal exchange between the state and the citizens shapes tax compliance to a large extent. In that respect, a case study of Switzerland is useful because the small size of the cantons and their direct democratic political systems procedurally establish a close exchange relationship bet...

  1. L'evasione in Italia e nei paesi OCSE: evidenze empiriche, determinanti ed effetti economici (Evasion in Italy and in OECD countries: empirical evidence, determinants and economic effects

    Directory of Open Access Journals (Sweden)

    M. MARÈ

    2013-10-01

    Full Text Available The paper analyses evasion in terms of size and its main determinants, and discusses some of the measures to reduce its extension. Instead of attempting a new estimate of evasion, the author uses the many existing estimates and compares them, highlighting their strengths and weaknesses. The available data on the underground economy and fiscal evasion in Italy and in major OECD countries is shown. Then, after recalling its effects on public budgets, the other economic effects of evasion are discussed. Some determinants of tax evasion, in particular those that appear most significant for our country, are then analysed. Finally, major issues of economic policy and measures to reduce tax evasion are discussed.JEL: H26

  2. Immune Evasion Strategies of Pathogens in Macrophages: the Potential for Limiting Pathogen Transmission.

    Science.gov (United States)

    Ren, Yuwei; Khan, Faheem Ahmed; Pandupuspitasari, Nuruliarizki Shinta; Zhang, Shujun

    2017-01-01

    Preventing pathogen transmission to a new host is of major interest to the immunologist and could benefit from a detailed investigation of pathogen immune evasion strategies. The first line of defense against pathogen invasion is provided by macrophages. When they sense pathogens, macrophages initiate signals to inflammatory and pro-inflammatory cytokines through pattern recognition receptors (PRRs) subsequently mediating phagocytosis and inflammation. The macrophage immune machinery classically includes two subsets: the activated M1 and the activated M2 that respond accordingly in diverse immune challenges. The lipid and glycogen metabolic pathways work together with the lysosome to help the mature phagosome to degrade and eliminate intracellular pathogens in macrophages. The viral evasion strategies are even more complex due to the interplay between autophagy and apoptosis. However, pathogens evolve several strategies to camouflage themselves against immune responses in order to ensure their survival, replication and transmission. These strategies include the muting of PRRs initiated inflammatory responses, attenuation of M1 and/or induction of M2 macrophages, suppression of autophago-lysosomal formation, interference with lipid and glycogen metabolism, and viral mediation of autophagy and apoptosis cross-talk to enhance viral replication. This review focuses on pathogen immune evasion methods and on the strategies used by the host against camouflaged pathogens.

  3. Unpredictability of escape trajectory explains predator evasion ability and microhabitat preference of desert rodents.

    Science.gov (United States)

    Moore, Talia Y; Cooper, Kimberly L; Biewener, Andrew A; Vasudevan, Ramanarayan

    2017-09-05

    Mechanistically linking movement behaviors and ecology is key to understanding the adaptive evolution of locomotion. Predator evasion, a behavior that enhances fitness, may depend upon short bursts or complex patterns of locomotion. However, such movements are poorly characterized by existing biomechanical metrics. We present methods based on the entropy measure of randomness from Information Theory to quantitatively characterize the unpredictability of non-steady-state locomotion. We then apply the method by examining sympatric rodent species whose escape trajectories differ in dimensionality. Unlike the speed-regulated gait use of cursorial animals to enhance locomotor economy, bipedal jerboa (family Dipodidae) gait transitions likely enhance maneuverability. In field-based observations, jerboa trajectories are significantly less predictable than those of quadrupedal rodents, likely increasing predator evasion ability. Consistent with this hypothesis, jerboas exhibit lower anxiety in open fields than quadrupedal rodents, a behavior that varies inversely with predator evasion ability. Our unpredictability metric expands the scope of quantitative biomechanical studies to include non-steady-state locomotion in a variety of evolutionary and ecologically significant contexts.Biomechanical understanding of animal gait and maneuverability has primarily been limited to species with more predictable, steady-state movement patterns. Here, the authors develop a method to quantify movement predictability, and apply the method to study escape-related movement in several species of desert rodents.

  4. Evasion of CO2 injected into the ocean in the context of CO2 stabilization

    International Nuclear Information System (INIS)

    Kheshgi, Haroon S.

    2004-01-01

    The eventual evasion of injected CO 2 to the atmosphere is one consideration when assessing deep-sea disposal of CO 2 as a potential response option to climate change concerns. Evasion estimated using an ocean carbon cycle model is compared to long-term trajectories for future CO 2 emissions, including illustrative cases leading to stabilization of CO 2 concentration at various levels. Modeled residence time for CO 2 injected into the deep ocean exceeds the 100-year time-scale usually considered in scenarios for future emissions, and the potential impacts of climate change. Illustrative cases leading monotonically to constant CO 2 concentration have been highlighted by the Intergovernmental Panel on Climate Change to give guidance on possible timing of emission reductions that may be required to stabilize greenhouse gas concentrations at various levels. For stabilization cases considered, significant modeled evasion does not occur until long after CO 2 emissions have reached a maximum and begun to decline. Illustrative cases can also lead to a maximum in CO 2 concentration followed by a decline to slowly decreasing concentrations. In such cases, future injection of emissions into the deep ocean leads to lower maximum CO 2 concentration, with less effect on concentration later on in time

  5. Regional-scale lateral carbon transport and CO2 evasion in temperate stream catchments

    Science.gov (United States)

    Magin, Katrin; Somlai-Haase, Celia; Schäfer, Ralf B.; Lorke, Andreas

    2017-11-01

    Inland waters play an important role in regional to global-scale carbon cycling by transporting, processing and emitting substantial amounts of carbon, which originate mainly from their catchments. In this study, we analyzed the relationship between terrestrial net primary production (NPP) and the rate at which carbon is exported from the catchments in a temperate stream network. The analysis included more than 200 catchment areas in southwest Germany, ranging in size from 0.8 to 889 km2 for which CO2 evasion from stream surfaces and downstream transport with stream discharge were estimated from water quality monitoring data, while NPP in the catchments was obtained from a global data set based on remote sensing. We found that on average 13.9 g C m-2 yr-1 (corresponding to 2.7 % of terrestrial NPP) are exported from the catchments by streams and rivers, in which both CO2 evasion and downstream transport contributed about equally to this flux. The average carbon fluxes in the catchments of the study area resembled global and large-scale zonal mean values in many respects, including NPP, stream evasion and the carbon export per catchment area in the fluvial network. A review of existing studies on aquatic-terrestrial coupling in the carbon cycle suggests that the carbon export per catchment area varies in a relatively narrow range, despite a broad range of different spatial scales and hydrological characteristics of the study regions.

  6. THE VAT SPLIT-PAYMENT MECHANISM, MEASURE FOR COMBATING TAX EVASION IN ROMANIA

    Directory of Open Access Journals (Sweden)

    IONUT - GHEORGHE CARAUS

    2017-12-01

    Full Text Available The need to improve the methods of collecting and detecting value-added tax amounts is an increasingly difficult process for tax authorities. In this respect, a rigorous analysis of the ways in which the state manages to prevent or combat VAT evasion, in the context in which VAT fraud accounts for about 60% of Romania's total tax evasion, is required. Therefore, the new provisions concerning the VAT split payments, applicable from January 1, 2018 for all categories of taxpayers, can contribute significantly to the efficiency of collection, of the amounts derived from the VAT, as well as to reduce tax evasion in the field of value added tax and providing a fair competitive environment, by eliminating benefits for economic operators with incorrect tax behavior who do not pay VAT to the State budget. Also, through these measures taken by the state, the main motivation for the introduction of the value added tax splitpayments mechanism, contributes to the increase of the voluntary compliance degree by providing the financial resources for the payment of VAT due to the State budget.

  7. Carbon Dioxide Evasion from Boreal Lakes: Drivers, Variability and Revised Global Estimate

    Science.gov (United States)

    Hastie, A. T.; Lauerwald, R.; Weyhenmeyer, G. A.; Sobek, S.; Verpoorter, C.; Regnier, P. A. G.

    2016-12-01

    Carbon dioxide evasion (FCO2) from lakes and reservoirs is established as an important component of the global carbon (C) cycle, a fact reflected by the inclusion of these waterbodies in the most recent IPCC assessment report. In this study we developed a statistical model driven by environmental geodata, to predict CO2 partial pressure (pCO2) in boreal lakes, and to create the first high resolution map (0.5°) of boreal (50°- 70°) lake pCO2. The resulting map of pCO2 was combined with lake area (lakes >0.01km2) from the recently developed GLOWABO database (Verpoorter et al., 2014) and estimates of gas transfer velocity k, to produce the first high resolution map of boreal lake FCO2. Before training our model, the geodata as well as approximately 27,000 samples of `open water' (excluding periods of ice cover) pCO2 from the boreal region, were gridded at 0.5° resolution and log transformed where necessary. A multilinear regression was used to derive a prediction equation for log10 pCO2 as a function of log10 lake area, net primary productivity (NPP), precipitation, wind speed and soil pH (r2= 0.66), and then applied in ArcGIS to build the map of pCO2. After validation, the map of boreal lake pCO2 was used to derive a map of boreal lake FCO2. For the boreal region we estimate an average, lake area weighted, pCO2 of 930 μatm and FCO2 of 170 (121-243) Tg C yr-1. Our estimate of FCO2 will soon be updated with the incorporation of the smallest lakes (<0.01km2). Despite the current exclusion of the smallest lakes, our estimate is higher than the highest previous estimate of approximately 110 Tg C yr-1 (Aufdenkampe et al, 2011). Moreover, our empirical approach driven by environmental geodata can be used as the basis for estimating future FCO2 from boreal lakes, and their sensitivity to climate change.

  8. Tumor-Induced CD8+ T-Cell Dysfunction in Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Heriberto Prado-Garcia

    2012-01-01

    Full Text Available Lung cancer is the leading cause of cancer deaths worldwide and one of the most common types of cancers. The limited success of chemotherapy and radiotherapy regimes have highlighted the need to develop new therapies like antitumor immunotherapy. CD8+ T-cells represent a major arm of the cell-mediated anti-tumor response and a promising target for developing T-cell-based immunotherapies against lung cancer. Lung tumors, however, have been considered to possess poor immunogenicity; even so, lung tumor-specific CD8+ T-cell clones can be established that possess cytotoxicity against autologous tumor cells. This paper will focus on the alterations induced in CD8+ T-cells by lung cancer. Although memory CD8+ T-cells infiltrate lung tumors, in both tumor-infiltrating lymphocytes (TILs and malignant pleural effusions, these cells are dysfunctional and the effector subset is reduced. We propose that chronic presence of lung tumors induces dysfunctions in CD8+ T-cells and sensitizes them to activation-induced cell death, which may be associated with the poor clinical responses observed in immunotherapeutic trials. Getting a deeper knowledge of the evasion mechanisms lung cancer induce in CD8+ T-cells should lead to further understanding of lung cancer biology, overcome tumor evasion mechanisms, and design improved immunotherapeutic treatments for lung cancer.

  9. Renal tumors in infancy

    International Nuclear Information System (INIS)

    Lucaya, J.; Garcia, P.

    1997-01-01

    The classification of childhood renal masses in updated, including the clinical signs and imaging techniques currently employed to confirm their presence and type them. Several bening and malignant childhood tumors are described in substantial detail. (Author) 24 refs

  10. Management of CNS tumors

    International Nuclear Information System (INIS)

    Griem, M.L.

    1987-01-01

    The treatment of tumors of the CNS has undergone a number of changes based on the impact of CT. The use of intraoperative US for the establishment of tumor location and tumor histology is demonstrated. MR imaging also is beginning to make an impact on the diagnosis and treatment of tumors of the CNS. Examples of MR images are shown. The authors then discuss the important aspects of tumor histology as it affects management and newer concepts in surgery, radiation, and chemotherapy on tumor treatment. The role of intraoperative placement of radioactive sources, the utilization of heavy particle radiation therapy, and the potential role of other experimental radiation therapy techniques are discussed. The role of hyperfractionated radiation and of neutrons and x-ray in a mixed-beam treatment are discussed in perspective with standard radiation therapy. Current chemotherapy techniques, including intraarterial chemotherapy, are discussed. The complications of radiation therapy alone and in combination with chemotherapy in the management of primary brain tumors, brain metastases, and leukemia are reviewed. A summary of the current management of pituitary tumors, including secreting pituitary adenomas and chromophobe adenomas, are discussed. The treatment with heavy particle radiation, transsphenoidal microsurgical removal, and combined radiotherapeutic and surgical management are considered. Tumor metastasis management of lesions of the brain and spinal cord are considered

  11. "The Impact of Mycobacterium tuberculosis Immune Evasion on Protective Immunity: Implications for TB Vaccine Design" - Meeting report.

    Science.gov (United States)

    Boggiano, Cesar; Eichelberg, Katrin; Ramachandra, Lakshmi; Shea, Jaqueline; Ramakrishnan, Lalita; Behar, Samuel; Ernst, Joel D; Porcelli, Steven A; Maeurer, Markus; Kornfeld, Hardy

    2017-06-14

    Tuberculosis (TB) is the major cause of death from infectious diseases around the world, particularly in HIV infected individuals. TB vaccine design and development have been focused on improving Bacille Calmette-Guérin (BCG) and evaluating recombinant and viral vector expressed Mycobacterium tuberculosis (Mtb) proteins, for boosting BCG-primed immunity, but these approaches have not yet yielded significant improvements over the modest effects of BCG in protecting against infection or disease. On March 7-8, 2016, the National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop on "The Impact of Mtb Immune Evasion on Protective Immunity: Implications for TB Vaccine Design" with the goal of defining immune mechanisms that could be targeted through novel research approaches, to inform vaccine design and immune therapeutic interventions for prevention of TB. The workshop addressed early infection events, the impact of Mtb evolution on the development and maintenance of an adaptive immune response, and the factors that influence protection against and progression to active disease. Scientific gaps and areas of study to revitalize and accelerate TB vaccine design were discussed and prioritized. These included a comprehensive evaluation of innate and Mtb-specific adaptive immune responses in the lung at different stages of disease; determining the role of B cells and antibodies (Abs) during Mtb infection; development of better assays to measure Mtb burden following exposure, infection, during latency and after treatment, and approaches to improving current animal models to study Mtb immunogenicity, TB disease and transmission. Copyright © 2017.

  12. Remodeling of Tumor Stroma and Response to Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Johansson, Anna; Ganss, Ruth, E-mail: ganss@waimr.uwa.edu.au [Western Australian Institute for Medical Research, Centre for Medical Research, University of Western Australia, Perth 6000 (Australia)

    2012-03-27

    Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy.

  13. Remodeling of Tumor Stroma and Response to Therapy

    International Nuclear Information System (INIS)

    Johansson, Anna; Ganss, Ruth

    2012-01-01

    Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy

  14. Targeting the PD-1/PD-L1 Immune Evasion Axis With DNA Aptamers as a Novel Therapeutic Strategy for the Treatment of Disseminated Cancers.

    Science.gov (United States)

    Prodeus, Aaron; Abdul-Wahid, Aws; Fischer, Nicholas W; Huang, Eric H-B; Cydzik, Marzena; Gariépy, Jean

    2015-04-28

    Blocking the immunoinhibitory PD-1:PD-L1 pathway using monoclonal antibodies has led to dramatic clinical responses by reversing tumor immune evasion and provoking robust and durable antitumor responses. Anti-PD-1 antibodies have now been approved for the treatment of melanoma, and are being clinically tested in a number of other tumor types as both a monotherapy and as part of combination regimens. Here, we report the development of DNA aptamers as synthetic, nonimmunogenic antibody mimics, which bind specifically to the murine extracellular domain of PD-1 and block the PD-1:PD-L1 interaction. One such aptamer, MP7, functionally inhibits the PD-L1-mediated suppression of IL-2 secretion in primary T-cells. A PEGylated form of MP7 retains the ability to block the PD-1:PD-L1 interaction, and significantly suppresses the growth of PD-L1+ colon carcinoma cells in vivo with a potency equivalent to an antagonistic anti-PD-1 antibody. Importantly, the anti-PD-1 DNA aptamer treatment was not associated with off-target TLR-9-related immune responses. Due to the inherent advantages of aptamers including their lack of immunogenicity, low cost, long shelf life, and ease of synthesis, PD-1 antagonistic aptamers may represent an attractive alternative over antibody-based anti PD-1 therapeutics.

  15. Targeting the PD-1/PD-L1 Immune Evasion Axis With DNA Aptamers as a Novel Therapeutic Strategy for the Treatment of Disseminated Cancers

    Directory of Open Access Journals (Sweden)

    Aaron Prodeus

    2015-01-01

    Full Text Available Blocking the immunoinhibitory PD-1:PD-L1 pathway using monoclonal antibodies has led to dramatic clinical responses by reversing tumor immune evasion and provoking robust and durable antitumor responses. Anti-PD-1 antibodies have now been approved for the treatment of melanoma, and are being clinically tested in a number of other tumor types as both a monotherapy and as part of combination regimens. Here, we report the development of DNA aptamers as synthetic, nonimmunogenic antibody mimics, which bind specifically to the murine extracellular domain of PD-1 and block the PD-1:PD-L1 interaction. One such aptamer, MP7, functionally inhibits the PD-L1-mediated suppression of IL-2 secretion in primary T-cells. A PEGylated form of MP7 retains the ability to block the PD-1:PD-L1 interaction, and significantly suppresses the growth of PD-L1+ colon carcinoma cells in vivo with a potency equivalent to an antagonistic anti-PD-1 antibody. Importantly, the anti-PD-1 DNA aptamer treatment was not associated with off-target TLR-9-related immune responses. Due to the inherent advantages of aptamers including their lack of immunogenicity, low cost, long shelf life, and ease of synthesis, PD-1 antagonistic aptamers may represent an attractive alternative over antibody-based anti PD-1 therapeutics.

  16. Trichinella spiralis Calreticulin Binds Human Complement C1q As an Immune Evasion Strategy.

    Science.gov (United States)

    Zhao, Limei; Shao, Shuai; Chen, Yi; Sun, Ximeng; Sun, Ran; Huang, Jingjing; Zhan, Bin; Zhu, Xinping

    2017-01-01

    As a multicellular parasitic nematode, Trichinella spiralis regulates host immune responses by producing a variety of immunomodulatory molecules to escape from host immune attack, but the mechanisms underlying the immune evasion are not well understood. Here, we identified that T. spiralis calreticulin ( Ts -CRT), a Ca 2+ -binding protein, facilitated T. spiralis immune evasion by interacting with the first component of human classical complement pathway, C1q. In the present study, Ts -CRT was found to be expressed on the surface of different developmental stages of T. spiralis as well as in the secreted products of adult and muscle larval worms. Functional analysis identified that Ts -CRT was able to bind to human C1q, resulting in the inhibition of C1q-initiated complement classical activation pathway reflected by reduced C4/C3 generation and C1q-dependent lysis of antibody-sensitized sheep erythrocytes. Moreover, recombinant Ts -CRT (r Ts -CRT) binding to C1q suppressed C1q-induced THP-1-derived macrophages chemotaxis and reduced monocyte-macrophages release of reactive oxygen intermediates (ROIs). Blocking Ts -CRT on the surface of newborn larvae (NBL) of T. spiralis with anti- Ts -CRT antibody increased the C1q-mediated adherence of monocyte-macrophages to larvae and impaired larval infectivity. All of these results suggest that T. spiralis -expressed Ts -CRT plays crucial roles in T. spiralis immune evasion and survival in host mostly by directly binding to host complement C1q, which not only reduces C1q-mediated activation of classical complement pathway but also inhibits the C1q-induced non-complement activation of macrophages.

  17. The Surface-Exposed Protein SntA Contributes to Complement Evasion in Zoonotic Streptococcus suis.

    Science.gov (United States)

    Deng, Simin; Xu, Tong; Fang, Qiong; Yu, Lei; Zhu, Jiaqi; Chen, Long; Liu, Jiahui; Zhou, Rui

    2018-01-01

    Streptococcus suis is an emerging zoonotic pathogen causing streptococcal toxic shock like syndrome (STSLS), meningitis, septicemia, and even sudden death in human and pigs. Serious septicemia indicates this bacterium can evade the host complement surveillance. In our previous study, a functionally unknown protein SntA of S. suis has been identified as a heme-binding protein, and contributes to virulence in pigs. SntA can interact with the host antioxidant protein AOP2 and consequently inhibit its antioxidant activity. In the present study, SntA is identified as a cell wall anchored protein that functions as an important player in S. suis complement evasion. The C3 deposition and membrane attack complex (MAC) formation on the surface of sntA -deleted mutant strain Δ sntA are demonstrated to be significantly higher than the parental strain SC-19 and the complementary strain CΔ sntA . The abilities of anti-phagocytosis, survival in blood, and in vivo colonization of Δ sntA are obviously reduced. SntA can interact with C1q and inhibit hemolytic activity via the classical pathway. Complement activation assays reveal that SntA can also directly activate classical and lectin pathways, resulting in complement consumption. These two complement evasion strategies may be crucial for the pathogenesis of this zoonotic pathogen. Concerning that SntA is a bifunctional 2',3'-cyclic nucleotide 2'-phosphodiesterase/3'-nucleotidase in many species of Gram-positive bacteria, these complement evasion strategies may have common biological significance.

  18. Energetics and evasion dynamics of large predators and prey: pumas vs. hounds.

    Science.gov (United States)

    Bryce, Caleb M; Wilmers, Christopher C; Williams, Terrie M

    2017-01-01

    Quantification of fine-scale movement, performance, and energetics of hunting by large carnivores is critical for understanding the physiological underpinnings of trophic interactions. This is particularly challenging for wide-ranging terrestrial canid and felid predators, which can each affect ecosystem structure through distinct hunting modes. To compare free-ranging pursuit and escape performance from group-hunting and solitary predators in unprecedented detail, we calibrated and deployed accelerometer-GPS collars during predator-prey chase sequences using packs of hound dogs ( Canis lupus familiaris , 26 kg, n  = 4-5 per chase) pursuing simultaneously instrumented solitary pumas ( Puma concolor , 60 kg, n  = 2). We then reconstructed chase paths, speed and turning angle profiles, and energy demands for hounds and pumas to examine performance and physiological constraints associated with cursorial and cryptic hunting modes, respectively. Interaction dynamics revealed how pumas successfully utilized terrain (e.g., fleeing up steep, wooded hillsides) as well as evasive maneuvers (e.g., jumping into trees, running in figure-8 patterns) to increase their escape distance from the overall faster hounds (avg. 2.3× faster). These adaptive strategies were essential to evasion in light of the mean 1.6× higher mass-specific energetic costs of the chase for pumas compared to hounds (mean: 0.76 vs. 1.29 kJ kg -1  min -1 , respectively). On an instantaneous basis, escapes were more costly for pumas, requiring exercise at ≥90% of predicted [Formula: see text] and consuming as much energy per minute as approximately 5 min of active hunting. Our results demonstrate the marked investment of energy for evasion by a large, solitary carnivore and the advantage of dynamic maneuvers to postpone being overtaken by group-hunting canids.

  19. Energetics and evasion dynamics of large predators and prey: pumas vs. hounds

    Directory of Open Access Journals (Sweden)

    Caleb M. Bryce

    2017-08-01

    Full Text Available Quantification of fine-scale movement, performance, and energetics of hunting by large carnivores is critical for understanding the physiological underpinnings of trophic interactions. This is particularly challenging for wide-ranging terrestrial canid and felid predators, which can each affect ecosystem structure through distinct hunting modes. To compare free-ranging pursuit and escape performance from group-hunting and solitary predators in unprecedented detail, we calibrated and deployed accelerometer-GPS collars during predator-prey chase sequences using packs of hound dogs (Canis lupus familiaris, 26 kg, n = 4–5 per chase pursuing simultaneously instrumented solitary pumas (Puma concolor, 60 kg, n = 2. We then reconstructed chase paths, speed and turning angle profiles, and energy demands for hounds and pumas to examine performance and physiological constraints associated with cursorial and cryptic hunting modes, respectively. Interaction dynamics revealed how pumas successfully utilized terrain (e.g., fleeing up steep, wooded hillsides as well as evasive maneuvers (e.g., jumping into trees, running in figure-8 patterns to increase their escape distance from the overall faster hounds (avg. 2.3× faster. These adaptive strategies were essential to evasion in light of the mean 1.6× higher mass-specific energetic costs of the chase for pumas compared to hounds (mean: 0.76 vs. 1.29 kJ kg−1 min−1, respectively. On an instantaneous basis, escapes were more costly for pumas, requiring exercise at ≥90% of predicted $\\dot {\\mathrm{V }}{\\mathrm{O}}_{2\\mathrm{MAX}}$ V ̇ O 2 MAX and consuming as much energy per minute as approximately 5 min of active hunting. Our results demonstrate the marked investment of energy for evasion by a large, solitary carnivore and the advantage of dynamic maneuvers to postpone being overtaken by group-hunting canids.

  20. Sinus Tumors

    Science.gov (United States)

    ... RESOURCES Medical Societies Patient Education About this Website Font Size + - Home > CONDITIONS > Sinus Tumors Adult Sinusitis Pediatric ... and they vary greatly in location, size and type. Care for these tumors is individualized to each ...

  1. Tumors markers

    International Nuclear Information System (INIS)

    Yamaguchi-Mizumoto, N.H.

    1989-01-01

    In order to study blood and cell components alterations (named tumor markers) that may indicate the presence of a tumor, several methods are presented. Aspects as diagnostic, prognostic, therapeutic value and clinical evaluation are discussed. (M.A.C.)

  2. Wilms tumor

    Science.gov (United States)

    ... suggested. Alternative Names Nephroblastoma; Kidney tumor - Wilms Images Kidney anatomy Wilms tumor References Babaian KN, Delacroix SE, Wood CG, Jonasch E. Kidney cancer. In: Skorecki K, Chertow GM, Marsden PA, ...

  3. Crackdown on tax evasion – improving ways of coordination between the tax authorities and automatic exchange of information developments in Romania

    Directory of Open Access Journals (Sweden)

    Ioniță Claudiu

    2017-07-01

    Full Text Available In an effort to reduce the tax transparency and banking secrecy, the Organisation for Economic Co-operation and Development (“OECD” has been taking the lead on the battle against cross-border tax evasion, seconded by the Internal Revenue Services (“IRS” of the United States of America (“USA”, the G20 and the European Commission. Understanding the power that is brought by information and knowledge, the international community proposed adapting the exchange of information tools that were available to them and extending them to a worldwide level. As a result, the Common Reporting Standard (“CRS” and the Foreign Account Tax Compliance Act (“FATCA” reporting standards were born. This paper aims at analyzing the improvements in automatic exchange of information brought by the CRS and FATCA standards, together with its limitations. An important section of this paper shall be dedicated to the role that Romania plays in the international efforts of fighting tax evasion, together with the tools and procedures developed in order to sustain the reporting standards. In order to analyze the effects of the CRS and FATCA, it is essential to understand the pros and the cons of the international cooperation on tax matters and its available tools before the CRS and FATCA were created. As there is limited previous literature on the subject, the methodology of the research will consist mainly of analyzing the guidelines issued by the international public body representatives and of the current legislative framework. The main finding of the paper can be considered the fact that the new developments in the automatic exchange of information field can represent a huge step forward towards limiting the tax evasion activity, however, one should be reserved due to aspects such as compliance costs, protection of private information, data gathering and processing techniques and tax residency uncertainty. Further analysis is required when the automatic

  4. Multivariate Analysis for the Choice and Evasion of the Student in a Higher Educational Institution from Southern of Santa Catarina, in Brazil

    Science.gov (United States)

    Queiroz, Fernanda Cristina Barbosa Pereira; Samohyl, Robert Wayne; Queiroz, Jamerson Viegas; Lima, Nilton Cesar; de Souza, Gustavo Henrique Silva

    2014-01-01

    This paper aims to develop and implement a method to identify the causes of the choice of a course and the reasons for evasion in higher education. This way, we sought to identify the factors that influence student choice to opt for Higher Education Institution parsed, as well as the factors influencing its evasion. The methodology employed was…

  5. Conserved hypothetical protein Rv1977 in Mycobacterium tuberculosis strains contains sequence polymorphisms and might be involved in ongoing immune evasion.

    Science.gov (United States)

    Jiang, Yi; Liu, Haican; Wang, Xuezhi; Li, Guilian; Qiu, Yan; Dou, Xiangfeng; Wan, Kanglin

    2015-01-01

    Host immune pressure and associated parasite immune evasion are key features of host-pathogen co-evolution. A previous study showed that human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved and thus it was deduced that M. tuberculosis lacks antigenic variation and immune evasion. Here, we selected 151 clinical Mycobacterium tuberculosis isolates from China, amplified gene encoding Rv1977 and compared the sequences. The results showed that Rv1977, a conserved hypothetical protein, is not conserved in M. tuberculosis strains and there are polymorphisms existed in the protein. Some mutations, especially one frameshift mutation, occurred in the antigen Rv1977, which is uncommon in M.tb strains and may lead to the protein function altering. Mutations and deletion in the gene all affect one of three T cell epitopes and the changed T cell epitope contained more than one variable position, which may suggest ongoing immune evasion.

  6. Rotorcraft pursuit-evasion in nap-of-the-earth flight

    Science.gov (United States)

    Menon, P. K. A.; Cheng, V. H. L.; Kim, E.

    1990-01-01

    Two approaches for studying the pursuit-evasion problem between rotorcraft executing nap-of-the-earth flight are presented. The first of these employs a constant speed kinematic helicopter model, while the second approach uses a three degree of freedom point-mass model. The candidate solutions to the first differential game are generated by integrating the state-costate equations backward in time. The second problem employs feedback linearization to obtain guidance laws in nonlinear feedback form. Both approaches explicitly use the terrain profile data. Sample extremals are presented.

  7. Evasion of HSR in S-wave charmonium decaying to P-wave light hadrons

    Energy Technology Data Exchange (ETDEWEB)

    Li, Gang [Qufu Normal University, Department of Physics, Qufu (China); Liu, Xiao-Hai [Peking University, Department of Physics and State Key Laboratory of Nuclear Physics and Technology, Beijing (China); Zhao, Qiang [Chinese Academy of Sciences, Institute of High Energy Physics, Beijing (China); CAS, Theoretical Physics Center for Science Facilities, Beijing (China)

    2013-09-15

    The S-wave charmonium decaying to a P-wave and S-wave light hadron pairs are supposed to be suppressed by the helicity selection rule in the perturbative QCD framework. With an effective Lagrangian method, we show that the intermediate charmed meson loops can provide a possible mechanism for the evasion of the helicity selection rule, and result in sizeable decay branching ratios in some of those channels. The theoretical predictions can be examined by the forthcoming BES-III data in the near future. (orig.)

  8. THE UNDERGROUND ECONOMY,THE CORRUPTION . A WAY OF MANIFESTING THE FISCAL EVASION

    OpenAIRE

    Din Alina Valentina

    2012-01-01

    Fiscal evasion is mainly found within the underground economy, came to the specialists’ attention within the 1960s, moment in which it took a great extent. The main cause which leads to activities within the underground economy is represented by the increase of direct taxes, which has the largest influence, followed by the intensity of the regulations and the complexity of the fiscal system. The imposed taxes determine more and more countries to act within the underground economy, as long a...

  9. Square and bow-tie configurations in the cyclic evasion problem

    Science.gov (United States)

    Arnold, M. D.; Golich, M.; Grim, A.; Vargas, L.; Zharnitsky, V.

    2017-05-01

    Cyclic evasion of four agents on the plane is considered. There are two stationary shapes of configurations: square and degenerate bow-tie. The bow-tie is asymptotically attracting while the square is of focus-center type. Normal form analysis shows that square is nonlinearly unstable. The stable manifold consists of parallelograms that all converge to the square configuration. Based on these observations and numerical simulations, it is conjectured that any non-parallelogram non-degenerate configuration converges to the bow-tie.

  10. THE VALUE ADDED TAX AND THE EVASION CHAIN OF INTRA-COMMUNITARIAN VAT

    Directory of Open Access Journals (Sweden)

    Deliman Eugen

    2011-12-01

    Full Text Available The relationship IRS taxpayer runs the risk of turning into a psychological war in which, however, given the positions held, the IRS is by far on a favorable footing. Between the apparently excessively formal position held by the IRS, which seems to conceal behind the laws, and the sometimes forced interpretation of the laws, by the taxpayer, there are the courts of law, also disturbed by the legislative changes which appear to have entered a perpetual motion. The objective of the fiscal administration regarding the value added tax is to combat tax evasion and fraud. It is very important to combat evasion in the VAT field because it represents the indirect tax of the largest share in the consolidated general budget. VAT evasion represents the intention of not paying the tax, withholding or not declaring it, or requesting its refund which would not be fit, due to the exaggeration of the deductible amount of the VAT. The essential aim of the IRS inspector is to verify the correctness of the declared amount of the value added tax. It should also be observed whether the incorrectness is deliberate or whether it was due to misunderstanding, carelessness or the ignorance of the payer. In all cases judgment is necessary, as for the cases of negligence the amount to be paid must be corrected and accompanied by applying fines and / or penalties, and in the cases of intended fraud legal actions are to be applied in order to obtain a conviction. Deceitful deductions represent other methods for tax evasion and are undertaken based on fake invoices, invoices often used several times for deduction, or invoices related to purchases that have never been made. Thus there are examples of economic agents who have practiced the right to deduct the VAT due to the acquisition of goods which consisted in the property of other economic agents. In other cases noticed was the deduction of VAT on goods or services that were not included in the activities of the economic

  11. On the Relation between Tax Rates and Evasion in a Multi-period Economy

    OpenAIRE

    Jordi Caball?Author-Email:; Judith Panad?

    2001-01-01

    We extend the basic tax evasion model to a multi-period economy exhibiting sustained growth. When individuals conceal part of their true income from the tax authority, they face the risk of being audited and hence of paying the corresponding fine. Both taxes and fines determine individual saving and the rate of capital accumulation. In this context we show that the sign of the relation between the level of the tax rate and the amount of evaded income is the same as that obtained in static set...

  12. Tax Rates, Tax Evasion, and Growth in a Multi-period Economy

    OpenAIRE

    Jordi Caballé; Judith Panadés

    2007-01-01

    We extend the basic tax evasion model to a multi-period economy exhibiting sustained growth. When individuals conceal part of their true income from the tax authority, they face the risk of being audited and hence of paying the corresponding fine. Both taxes and fines determine individual saving and the rate of capital accumulation. We show that, if the penalty imposed on tax evaders is proportional to the amount of evaded taxes, then the growth rate is decreasing in the tax rate. However, th...

  13. On the relation between tax rates and evasion in a multi-period economy

    OpenAIRE

    Caballé, Jordi

    2006-01-01

    We extend the basic tax evasion model to a multi-period economy exhibiting sustained growth. When individuals conceal part of their true income from the tax authority, they face the risk of being audited and hence of paying the corresponding fine. Both taxes and fines determine individual saving and the rate of capital accumulation. In this context we show that the sign of the relation between the level of the tax rate and the amount of evaded income is the same as that obtained in static set...

  14. TAX OPTIMIZATION, TAX AVOIDANCE OR TAX EVASION? CONTRIBUTIONS TO THE OFFSHORE COMPANIES’ LEGAL BACKGROUND

    OpenAIRE

    Eva ERDÕS

    2010-01-01

    Is it a legal or illegal activity to give money to establish offshore firms? What is the offshore practice is it a method of tax optimization, tax minimization or is it a harmful activity, which means tax avoidance or tax evasion. This question is very important in the European Union’s tax law system, because the EU tax law is against the harmful tax competition. Some member states’ legal system is permitted to use offshore companies’ rules, but in the European Union it is prohibited to estab...

  15. Filovirus pathogenesis and immune evasion: insights from Ebola virus and Marburg virus

    Energy Technology Data Exchange (ETDEWEB)

    Messaoudi, Ilhem; Amarasinghe, Gaya K.; Basler, Christopher F.

    2015-10-06

    Ebola viruses and Marburg viruses, members of the filovirus family, are zoonotic pathogens that cause severe disease in people, as highlighted by the latest Ebola virus epidemic in West Africa. Filovirus disease is characterized by uncontrolled virus replication and the activation of host responses that contribute to pathogenesis. Underlying these phenomena is the potent suppression of host innate antiviral responses, particularly the type I interferon response, by viral proteins, which allows high levels of viral replication. In this Review, we describe the mechanisms used by filoviruses to block host innate immunity and discuss the links between immune evasion and filovirus pathogenesis.

  16. Supply Chain Based Solution to Prevent Fuel Tax Evasion: Proof of Concept Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Capps, Gary J [ORNL; Lascurain, Mary Beth [ORNL; Franzese, Oscar [ORNL; Earl, Dennis Duncan [ORNL; West, David L [ORNL; McIntyre, Timothy J [ORNL; Chin, Shih-Miao [ORNL; Hwang, Ho-Ling [ORNL; Connatser, Raynella M [ORNL; Lewis Sr, Samuel Arthur [ORNL; Moore, Sheila A [ORNL

    2011-12-01

    The goal of this research was to provide a proof-of-concept (POC) system for preventing non-taxable (non-highway diesel use) or low-taxable (jet fuel) petrochemical products from being blended with taxable fuel products and preventing taxable fuel products from cross-jurisdiction evasion. The research worked to fill the need to validate the legitimacy of individual loads, offloads, and movements by integrating and validating, on a near-real-time basis, information from global positioning system (GPS), valve sensors, level sensors, and fuel-marker sensors.

  17. Spinal tumors

    International Nuclear Information System (INIS)

    Goethem, J.W.M. van; Hauwe, L. van den; Oezsarlak, Oe.; Schepper, A.M.A. de; Parizel, P.M.

    2004-01-01

    Spinal tumors are uncommon lesions but may cause significant morbidity in terms of limb dysfunction. In establishing the differential diagnosis for a spinal lesion, location is the most important feature, but the clinical presentation and the patient's age and gender are also important. Magnetic resonance (MR) imaging plays a central role in the imaging of spinal tumors, easily allowing tumors to be classified as extradural, intradural-extramedullary or intramedullary, which is very useful in tumor characterization. In the evaluation of lesions of the osseous spine both computed tomography (CT) and MR are important. We describe the most common spinal tumors in detail. In general, extradural lesions are the most common with metastasis being the most frequent. Intradural tumors are rare, and the majority is extramedullary, with meningiomas and nerve sheath tumors being the most frequent. Intramedullary tumors are uncommon spinal tumors. Astrocytomas and ependymomas comprise the majority of the intramedullary tumors. The most important tumors are documented with appropriate high quality CT or MR images and the characteristics of these tumors are also summarized in a comprehensive table. Finally we illustrate the use of the new World Health Organization (WHO) classification of neoplasms affecting the central nervous system

  18. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  19. Urogenital tumors

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1994-03-01

    An overview is provided for veterinary care of urogenital tumors in companion animals, especially the dog. Neoplasms discussed include tumors of the kidney, urinary bladder, prostate, testis, ovary, vagina, vulva and the canine transmissible venereal tumor. Topics addressed include description, diagnosis and treatment.

  20. Tumors of peripheral nerves

    International Nuclear Information System (INIS)

    Ho, Michael; Lutz, Amelie M.

    2017-01-01

    Differentiation between malignant and benign tumors of peripheral nerves in the early stages is challenging; however, due to the unfavorable prognosis of malignant tumors early identification is required. To show the possibilities for detection, differential diagnosis and clinical management of peripheral nerve tumors by imaging appearance in magnetic resonance (MR) neurography. Review of current literature available in PubMed and MEDLINE, supplemented by the authors' own observations in clinical practice. Although not pathognomonic, several imaging features have been reported for a differentiation between distinct peripheral nerve tumors. The use of MR neurography enables detection and initial differential diagnosis in tumors of peripheral nerves. Furthermore, it plays an important role in clinical follow-up, targeted biopsy and surgical planning. (orig.) [de

  1. America’s Underground Economy: Measuring the Size, Growth and Determinants of Income Tax Evasion in the U.S

    OpenAIRE

    Feige, Edgar L.; Cebula, Richard

    2011-01-01

    Abstract This study empirically investigates the extent of non compliance with the tax code and the determinants of federal income tax evasion in the U.S. Employing the most recent data we find that 18-19% of total reportable income is not properly reported to the IRS, giving rise to a “tax gap” approaching $500 billion dollars. Three time periods are studied, 1960-2008, 1970-2008, and 1980-2008. It is found across study periods that income tax evasion is an increasing function of the av...

  2. Evasion of Human Neutrophil-Mediated Host Defense during Toxoplasma gondii Infection.

    Science.gov (United States)

    Lima, Tatiane S; Gov, Lanny; Lodoen, Melissa B

    2018-02-13

    Neutrophils are a major player in host immunity to infection; however, the mechanisms by which human neutrophils respond to the intracellular protozoan parasite Toxoplasma gondii are still poorly understood. In the current study, we found that, whereas primary human monocytes produced interleukin-1beta (IL-1β) in response to T. gondii infection, human neutrophils from the same blood donors did not. Moreover, T. gondii inhibited lipopolysaccharide (LPS)-induced IL-1β synthesis in human peripheral blood neutrophils. IL-1β suppression required active parasite invasion, since heat-killed or mycalolide B-treated parasites did not inhibit IL-1β release. By investigating the mechanisms involved in this process, we found that T. gondii infection of neutrophils treated with LPS resulted in reduced transcript levels of IL-1β and NLRP3 and reduced protein levels of pro-IL-1β, mature IL-1β, and the inflammasome sensor NLRP3. In T. gondii -infected neutrophils stimulated with LPS, the levels of MyD88, TRAF6, IKKα, IKKβ, and phosphorylated IKKα/β were not affected. However, LPS-induced IκBα degradation and p65 phosphorylation were reduced in T. gondii- infected neutrophils, and degradation of IκBα was reversed by treatment with the proteasome inhibitor MG-132. Finally, we observed that T. gondii inhibited the cleavage and activity of caspase-1 in human neutrophils. These results indicate that T. gondii suppression of IL-1β involves a two-pronged strategy whereby T. gondii inhibits both NF-κB signaling and activation of the NLRP3 inflammasome. These findings represent a novel mechanism of T. gondii evasion of human neutrophil-mediated host defense by targeting the production of IL-1β. IMPORTANCE Toxoplasma gondii is an obligate intracellular parasite that infects approximately one-third of humans worldwide and can invade virtually any nucleated cell in the human body. Although it is well documented that neutrophils infiltrate the site of acute T

  3. Tumor immunology

    International Nuclear Information System (INIS)

    Otter, W. den

    1987-01-01

    Tumor immunology, the use of immunological techniques for tumor diagnosis and approaches to immunotherapy of cancer are topics covered in this multi-author volume. Part A, 'Tumor Immunology', deals with present views on tumor-associated antigens, the initiation of immune reactions of tumor cells, effector cell killing, tumor cells and suppression of antitumor immunity, and one chapter dealing with the application of mathematical models in tumor immunology. Part B, 'Tumor Diagnosis and Imaging', concerns the use of markers to locate the tumor in vivo, for the histological diagnosis, and for the monitoring of tumor growth. In Part C, 'Immunotherapy', various experimental approaches to immunotherapy are described, such as the use of monoclonal antibodies to target drugs, the use of interleukin-2 and the use of drugs inhibiting suppression. In the final section, the evaluation, a pathologist and a clinician evaluate the possibilities and limitations of tumor immunology and the extent to which it is useful for diagnosis and therapy. refs.; figs.; tabs

  4. Pituitary gland tumors

    International Nuclear Information System (INIS)

    Jesser, J.; Schlamp, K.; Bendszus, M.

    2014-01-01

    This article gives an overview of the most common tumors of the pituitary gland and the differential diagnostics with special emphasis on radiological diagnostic criteria. A selective search of the literature in PubMed was carried out. Pituitary adenomas constitute 10-15 % of all intracranial tumors and are the most common tumors of the sellar region. Tumors smaller than 1 cm in diameter are called microadenomas while those larger than 1 cm in diameter are called macroadenomas. Approximately 65 % of pituitary gland adenomas secrete hormones whereby approximately 50 % secrete prolactin, 10 % secrete growth hormone (somatotropin) and 6 % secrete corticotropin. Other tumors located in the sella turcica can also cause endocrinological symptoms, such as an oversecretion of pituitary hormone or pituitary insufficiency by impinging on the pituitary gland or its stalk. When tumors spread into the space cranial to the sella turcica, they can impinge on the optic chiasm and cause visual disorders. A common differential diagnosis of a sellar tumor is a craniopharyngeoma. In children up to 10 % of all intracranial tumors are craniopharyngeomas. Other differential diagnoses for sellar tumors are metastases, meningiomas, epidermoids and in rare cases astrocytomas, germinomas or Rathke cleft cysts As these tumors are located in an anatomically complex region of the skull base and are often very small, a highly focused imaging protocol is required. The currently favored modality is magnetic resonance imaging (MRI) with the administration of a contrast agent. The sellar region should be mapped in thin slices. In cases of suspected microadenoma the imaging protocol should also contain a sequence with dynamic contrast administration in order to assess the specific enhancement characteristics of the tumor and the pituitary gland. (orig.) [de

  5. [Pituitary gland tumors].

    Science.gov (United States)

    Jesser, J; Schlamp, K; Bendszus, M

    2014-10-01

    This article gives an overview of the most common tumors of the pituitary gland and the differential diagnostics with special emphasis on radiological diagnostic criteria. A selective search of the literature in PubMed was carried out. Pituitary adenomas constitute 10-15% of all intracranial tumors and are the most common tumors of the sellar region. Tumors smaller than 1 cm in diameter are called microadenomas while those larger than 1 cm in diameter are called macroadenomas. Approximately 65% of pituitary gland adenomas secrete hormones whereby approximately 50% secrete prolactin, 10% secrete growth hormone (somatotropin) and 6% secrete corticotropin. Other tumors located in the sella turcica can also cause endocrinological symptoms, such as an oversecretion of pituitary hormone or pituitary insufficiency by impinging on the pituitary gland or its stalk. When tumors spread into the space cranial to the sella turcica, they can impinge on the optic chiasm and cause visual disorders. A common differential diagnosis of a sellar tumor is a craniopharyngeoma. In children up to 10% of all intracranial tumors are craniopharyngeomas. Other differential diagnoses for sellar tumors are metastases, meningiomas, epidermoids and in rare cases astrocytomas, germinomas or Rathke cleft cysts As these tumors are located in an anatomically complex region of the skull base and are often very small, a highly focused imaging protocol is required. The currently favored modality is magnetic resonance imaging (MRI) with the administration of a contrast agent. The sellar region should be mapped in thin slices. In cases of suspected microadenoma the imaging protocol should also contain a sequence with dynamic contrast administration in order to assess the specific enhancement characteristics of the tumor and the pituitary gland.

  6. Plasmodium evasion of mosquito immunity and global malaria transmission: The lock-and-key theory.

    Science.gov (United States)

    Molina-Cruz, Alvaro; Canepa, Gaspar E; Kamath, Nitin; Pavlovic, Noelle V; Mu, Jianbing; Ramphul, Urvashi N; Ramirez, Jose Luis; Barillas-Mury, Carolina

    2015-12-08

    Plasmodium falciparum malaria originated in Africa and became global as humans migrated to other continents. During this journey, parasites encountered new mosquito species, some of them evolutionarily distant from African vectors. We have previously shown that the Pfs47 protein allows the parasite to evade the mosquito immune system of Anopheles gambiae mosquitoes. Here, we investigated the role of Pfs47-mediated immune evasion in the adaptation of P. falciparum to evolutionarily distant mosquito species. We found that P. falciparum isolates from Africa, Asia, or the Americas have low compatibility to malaria vectors from a different continent, an effect that is mediated by the mosquito immune system. We identified 42 different haplotypes of Pfs47 that have a strong geographic population structure and much lower haplotype diversity outside Africa. Replacement of the Pfs47 haplotypes in a P. falciparum isolate is sufficient to make it compatible to a different mosquito species. Those parasites that express a Pfs47 haplotype compatible with a given vector evade antiplasmodial immunity and survive. We propose that Pfs47-mediated immune evasion has been critical for the globalization of P. falciparum malaria as parasites adapted to new vector species. Our findings predict that this ongoing selective force by the mosquito immune system could influence the dispersal of Plasmodium genetic traits and point to Pfs47 as a potential target to block malaria transmission. A new model, the "lock-and-key theory" of P. falciparum globalization, is proposed, and its implications are discussed.

  7. Herpes simplex virus-1 evasion of CD8+ T cell accumulation contributes to viral encephalitis.

    Science.gov (United States)

    Koyanagi, Naoto; Imai, Takahiko; Shindo, Keiko; Sato, Ayuko; Fujii, Wataru; Ichinohe, Takeshi; Takemura, Naoki; Kakuta, Shigeru; Uematsu, Satoshi; Kiyono, Hiroshi; Maruzuru, Yuhei; Arii, Jun; Kato, Akihisa; Kawaguchi, Yasushi

    2017-10-02

    Herpes simplex virus-1 (HSV-1) is the most common cause of sporadic viral encephalitis, which can be lethal or result in severe neurological defects even with antiviral therapy. While HSV-1 causes encephalitis in spite of HSV-1-specific humoral and cellular immunity, the mechanism by which HSV-1 evades the immune system in the central nervous system (CNS) remains unknown. Here we describe a strategy by which HSV-1 avoids immune targeting in the CNS. The HSV-1 UL13 kinase promotes evasion of HSV-1-specific CD8+ T cell accumulation in infection sites by downregulating expression of the CD8+ T cell attractant chemokine CXCL9 in the CNS of infected mice, leading to increased HSV-1 mortality due to encephalitis. Direct injection of CXCL9 into the CNS infection site enhanced HSV-1-specific CD8+ T cell accumulation, leading to marked improvements in the survival of infected mice. This previously uncharacterized strategy for HSV-1 evasion of CD8+ T cell accumulation in the CNS has important implications for understanding the pathogenesis and clinical treatment of HSV-1 encephalitis.

  8. Diagnostic Evasion of Highly-Resistant Microorganisms: A Critical Factor in Nosocomial Outbreaks.

    Science.gov (United States)

    Zhou, Xuewei; Friedrich, Alexander W; Bathoorn, Erik

    2017-01-01

    Highly resistant microorganisms (HRMOs) may evade screening strategies used in routine diagnostics. Bacteria that have evolved to evade diagnostic tests may have a selective advantage in the nosocomial environment. Evasion of resistance detection can result from the following mechanisms: low-level expression of resistance genes not resulting in detectable resistance, slow growing variants, mimicry of wild-type-resistance, and resistance mechanisms that are only detected if induced by antibiotic pressure. We reviewed reports on hospital outbreaks in the Netherlands over the past 5 years. Remarkably, many outbreaks including major nation-wide outbreaks were caused by microorganisms able to evade resistance detection by diagnostic screening tests. We describe various examples of diagnostic evasion by several HRMOs and discuss this in a broad and international perspective. The epidemiology of hospital-associated bacteria may strongly be affected by diagnostic screening strategies. This may result in an increasing reservoir of resistance genes in hospital populations that is unnoticed. The resistance elements may horizontally transfer to hosts with systems for high-level expression, resulting in a clinically significant resistance problem. We advise to communicate the identification of HRMOs that evade diagnostics within national and regional networks. Such signaling networks may prevent inter-hospital outbreaks, and allow collaborative development of adapted diagnostic tests.

  9. Herpesvirus microRNAs for use in gene therapy immune-evasion strategies.

    Science.gov (United States)

    Bots, S T F; Hoeben, R C

    2017-07-01

    Transplantation of allogeneic cells as well as of genetically corrected autologous cells are potent approaches to restore cellular functions in patients suffering from genetic diseases. The recipient's immune responses against non-self-antigens may compromise the survival of the grafted cells. Recipients of the graft may therefore require lifelong treatment with immunosuppressive drugs. An alternative approach to reduce graft rejection could involve the use of immune-evasion molecules. Expression of such molecules in cells of the graft may subvert recognition by the host's immune system. Viruses in particular are masters of exploitation and modulation of their hosts immune response. The Herpesviridae family provides a proof of concept for this as these viruses are capable to establish latency and a lifelong persistence in the infected hosts. While several viral proteins involved in immune evasion have been characterized, the Herpesviridae also encode a multitude of viral microRNA (miRNAs). Several of these miRNAs have been demonstrated to reduce the sensitivity of the infected cells to the destructive action of the host's immune cells. In this review, the miRNAs of some common herpesviruses that are associated with immune modulation will be discussed with a focus on their potential use in strategies aiming at generating non-immunogenic cells for transplantation.

  10. A CRISPR-Cas system enhances envelope integrity mediating antibiotic resistance and inflammasome evasion.

    Science.gov (United States)

    Sampson, Timothy R; Napier, Brooke A; Schroeder, Max R; Louwen, Rogier; Zhao, Jinshi; Chin, Chui-Yoke; Ratner, Hannah K; Llewellyn, Anna C; Jones, Crystal L; Laroui, Hamed; Merlin, Didier; Zhou, Pei; Endtz, Hubert P; Weiss, David S

    2014-07-29

    Clustered, regularly interspaced, short palindromic repeats-CRISPR associated (CRISPR-Cas) systems defend bacteria against foreign nucleic acids, such as during bacteriophage infection and transformation, processes which cause envelope stress. It is unclear if these machineries enhance membrane integrity to combat this stress. Here, we show that the Cas9-dependent CRISPR-Cas system of the intracellular bacterial pathogen Francisella novicida is involved in enhancing envelope integrity through the regulation of a bacterial lipoprotein. This action ultimately provides increased resistance to numerous membrane stressors, including antibiotics. We further find that this previously unappreciated function of Cas9 is critical during infection, as it promotes evasion of the host innate immune absent in melanoma 2/apoptosis associated speck-like protein containing a CARD (AIM2/ASC) inflammasome. Interestingly, the attenuation of the cas9 mutant is complemented only in mice lacking both the AIM2/ASC inflammasome and the bacterial lipoprotein sensor Toll-like receptor 2, but not in single knockout mice, demonstrating that Cas9 is essential for evasion of both pathways. These data represent a paradigm shift in our understanding of the function of CRISPR-Cas systems as regulators of bacterial physiology and provide a framework with which to investigate the roles of these systems in myriad bacteria, including pathogens and commensals.

  11. Virion Glycoprotein-Mediated Immune Evasion by Human Cytomegalovirus: a Sticky Virus Makes a Slick Getaway

    Science.gov (United States)

    Gardner, Thomas J.

    2016-01-01

    SUMMARY The prototypic herpesvirus human cytomegalovirus (CMV) exhibits the extraordinary ability to establish latency and maintain a chronic infection throughout the life of its human host. This is even more remarkable considering the robust adaptive immune response elicited by infection and reactivation from latency. In addition to the ability of CMV to exist in a quiescent latent state, its persistence is enabled by a large repertoire of viral proteins that subvert immune defense mechanisms, such as NK cell activation and major histocompatibility complex antigen presentation, within the cell. However, dissemination outside the cell presents a unique existential challenge to the CMV virion, which is studded with antigenic glycoprotein complexes targeted by a potent neutralizing antibody response. The CMV virion envelope proteins, which are critical mediators of cell attachment and entry, possess various characteristics that can mitigate the humoral immune response and prevent viral clearance. Here we review the CMV glycoprotein complexes crucial for cell attachment and entry and propose inherent properties of these proteins involved in evading the CMV humoral immune response. These include viral glycoprotein polymorphism, epitope competition, Fc receptor-mediated endocytosis, glycan shielding, and cell-to-cell spread. The consequences of CMV virion glycoprotein-mediated immune evasion have a major impact on persistence of the virus in the population, and a comprehensive understanding of these evasion strategies will assist in designing effective CMV biologics and vaccines to limit CMV-associated disease. PMID:27307580

  12. Population genomics of the immune evasion (var genes of Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Alyssa E Barry

    2007-03-01

    Full Text Available Var genes encode the major surface antigen (PfEMP1 of the blood stages of the human malaria parasite Plasmodium falciparum. Differential expression of up to 60 diverse var genes in each parasite genome underlies immune evasion. We compared the diversity of the DBLalpha domain of var genes sampled from 30 parasite isolates from a malaria endemic area of Papua New Guinea (PNG and 59 from widespread geographic origins (global. Overall, we obtained over 8,000 quality-controlled DBLalpha sequences. Within our sampling frame, the global population had a total of 895 distinct DBLalpha "types" and negligible overlap among repertoires. This indicated that var gene diversity on a global scale is so immense that many genomes would need to be sequenced to capture its true extent. In contrast, we found a much lower diversity in PNG of 185 DBLalpha types, with an average of approximately 7% overlap among repertoires. While we identify marked geographic structuring, nearly 40% of types identified in PNG were also found in samples from different countries showing a cosmopolitan distribution for much of the diversity. We also present evidence to suggest that recombination plays a key role in maintaining the unprecedented levels of polymorphism found in these immune evasion genes. This population genomic framework provides a cost effective molecular epidemiological tool to rapidly explore the geographic diversity of var genes.

  13. Air-water CO2 evasion from US East Coast estuaries

    Science.gov (United States)

    Gildas Laruelle, Goulven; Goossens, Nicolas; Arndt, Sandra; Cai, Wei-Jun; Regnier, Pierre

    2017-05-01

    This study presents the first regional-scale assessment of estuarine CO2 evasion along the US East Coast (25-45° N). The focus is on 42 tidal estuaries, which together drain a catchment of 697 000 km2 or 76 % of the total area within this latitudinal band. The approach is based on the Carbon-Generic Estuary Model (C-GEM) that allows the simulation of hydrodynamics, transport, and biogeochemistry for a wide range of estuarine systems using readily available geometric parameters and global databases of seasonal climatic, hydraulic, and riverine biogeochemical information. Our simulations, performed using conditions representative of the year 2000, suggest that, together, US East Coast estuaries emit 1.9 Tg C yr-1 in the form of CO2, which corresponds to about 40 % of the carbon inputs from rivers, marshes, and mangroves. Carbon removal within estuaries results from a combination of physical (outgassing of supersaturated riverine waters) and biogeochemical processes (net heterotrophy and nitrification). The CO2 evasion and its underlying drivers show important variations across individual systems, but reveal a clear latitudinal pattern characterized by a decrease in the relative importance of physical over biogeochemical processes along a north-south gradient. Finally, the results reveal that the ratio of estuarine surface area to the river discharge, S/Q (which has a scale of per meter discharged water per year), could be used as a predictor of the estuarine carbon processing in future regional- and global-scale assessments.

  14. Mercury evasion from a boreal peatland shortens the timeline for recovery from legacy pollution.

    Science.gov (United States)

    Osterwalder, Stefan; Bishop, Kevin; Alewell, Christine; Fritsche, Johannes; Laudon, Hjalmar; Åkerblom, Staffan; Nilsson, Mats B

    2017-11-22

    Peatlands are a major source of methylmercury that contaminates downstream aquatic food webs. The large store of mercury (Hg) in peatlands could be a source of Hg for over a century even if deposition is dramatically reduced. However, the reliability of Hg mass balances can be questioned due to missing long-term land-atmosphere flux measurements. We used a novel micrometeorological system for continuous measurement of Hg peatland-atmosphere exchange to derive the first annual Hg budget for a peatland. The evasion of Hg (9.4 µg m -2 yr -1 ) over the course of a year was seven times greater than stream Hg export, and over two times greater than wet bulk deposition to the boreal peatland. Measurements of dissolved gaseous Hg in the peat pore water also indicate Hg evasion. The net efflux may result from recent declines in atmospheric Hg concentrations that have turned the peatland from a net sink into a source of atmospheric Hg. This net Hg loss suggests that open boreal peatlands and downstream ecosystems can recover more rapidly from past atmospheric Hg deposition than previously assumed. This has important implications for future levels of methylmercury in boreal freshwater fish and the estimation of historical Hg accumulation rates from peat profiles.

  15. Lateral line analogue aids vision in successful predator evasion for the brief squid, Lolliguncula brevis.

    Science.gov (United States)

    York, Carly A; Bartol, Ian K

    2014-07-15

    Cephalopods have visual and mechanoreception systems that may be employed to sense and respond to an approaching predator. While vision presumably plays the dominant role, the importance of the lateral line analogue for predator evasion has not been examined in cephalopods. To test the respective roles of vision and the lateral line analogue, brief squid, Lolliguncula brevis, were observed in the presence of summer flounder, Paralichthys dentatus, under light and dark conditions with their lateral line analogue intact and ablated. Hair cell ablation was achieved through a pharmacological technique used for the first time on a cephalopod. The proportion of predator-prey interactions survived was significantly higher in the light non-ablated and light ablated groups compared with the dark ablated group. The mean number of interactions survived varied across treatment groups with the light non-ablated group having significantly more success than the light ablated, dark non-ablated and dark ablated groups. These findings demonstrate that although vision is the primary sense, the lateral line analogue also contributes to predator evasion in squid. © 2014. Published by The Company of Biologists Ltd.

  16. Xenopus-FV3 host-pathogen interactions and immune evasion.

    Science.gov (United States)

    Jacques, Robert; Edholm, Eva-Stina; Jazz, Sanchez; Odalys, Torres-Luquis; Francisco, De Jesús Andino

    2017-11-01

    We first review fundamental insights into anti-ranavirus immunity learned with the Xenopus laevis/ranavirus FV3 model that are generally applicable to ectothermic vertebrates. We then further investigate FV3 genes involved in immune evasion. Focusing on FV3 knockout (KO) mutants defective for a putative viral caspase activation and recruitment domain-containing (CARD)-like protein (Δ64R-FV3), a β-hydroxysteroid dehydrogenase homolog (Δ52L-FV3), and an immediate-early18kDa protein (FV3-Δ18K), we assessed the involvement of these viral genes in replication, dissemination and interaction with peritoneal macrophages in tadpole and adult frogs. Our results substantiate the role of 64R and 52L as critical immune evasion genes, promoting persistence and dissemination in the host by counteracting type III IFN in tadpoles and type I IFN in adult frogs. Comparably, the substantial accumulation of genome copy numbers and exacerbation of type I and III IFN gene expression responses but deficient release of infectious virus suggests that 18K is a viral regulatory gene. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. A three-state kinetic agent-based model to analyze tax evasion dynamics

    Science.gov (United States)

    Crokidakis, Nuno

    2014-11-01

    In this work we study the problem of tax evasion on a fully-connected population. For this purpose, we consider that the agents may be in three different states, namely honest tax payers, tax evaders and undecided, that are individuals in an intermediate class among honests and evaders. Every individual can change his/her state following a kinetic exchange opinion dynamics, where the agents interact by pairs with competitive negative (with probability q) and positive (with probability 1-q) couplings, representing agreement/disagreement between pairs of agents. In addition, we consider the punishment rules of the Zaklan econophysics model, for which there is a probability pa of an audit each agent is subject to in every period and a length of time k detected tax evaders remain honest. Our results suggest that below the critical point qc=1/4 of the opinion dynamics the compliance is high, and the punishment rules have a small effect in the population. On the other hand, for q>qc the tax evasion can be considerably reduced by the enforcement mechanism. We also discuss the impact of the presence of the undecided agents in the evolution of the system.

  18. Transcriptional control of drug resistance, virulence and immune system evasion in pathogenic fungi: a cross-species comparison.

    Directory of Open Access Journals (Sweden)

    Pedro Pais

    2016-10-01

    Full Text Available Transcription factors are key players in the control of the activation or repression of gene expression programs in response to environmental stimuli. The study of regulatory networks taking place in fungal pathogens is a promising research topic that can help in the fight against these pathogens by targeting specific fungal pathways as a whole, instead of targeting more specific effectors of virulence or drug resistance. This review is focused on the analysis of regulatory networks playing a central role in the referred mechanisms in the human fungal pathogens Aspergillus fumigatus, Cryptococcus neoformans, Candida albicans, Candida glabrata, Candida parapsilosis and Candida tropicalis. Current knowledge on the activity of the transcription factors characterized in each of these pathogenic fungal species will be addressed. Particular focus is given to their mechanisms of activation, regulatory targets and phenotypic outcome. The review further provides an evaluation on the conservation of transcriptional circuits among different fungal pathogens, highlighting the pathways that translate common or divergent traits among these species in what concerns their drug resistance, virulence and host immune evasion features. It becomes evident that the regulation of transcriptional networks is complex and presents significant variations among different fungal pathogens. Only the oxidative stress regulators Yap1 and Skn7 are conserved among all studied species; while some transcription factors, involved in nutrient homeostasis, pH adaptation, drug resistance and morphological switching are present in several, though not all species. Interestingly, in some cases not very homologous transcription factors display orthologous functions, whereas some homologous proteins have diverged in terms of their function in different species. A few cases of species specific transcription factors are also observed.

  19. Transcriptional Control of Drug Resistance, Virulence and Immune System Evasion in Pathogenic Fungi: A Cross-Species Comparison.

    Science.gov (United States)

    Pais, Pedro; Costa, Catarina; Cavalheiro, Mafalda; Romão, Daniela; Teixeira, Miguel C

    2016-01-01

    Transcription factors are key players in the control of the activation or repression of gene expression programs in response to environmental stimuli. The study of regulatory networks taking place in fungal pathogens is a promising research topic that can help in the fight against these pathogens by targeting specific fungal pathways as a whole, instead of targeting more specific effectors of virulence or drug resistance. This review is focused on the analysis of regulatory networks playing a central role in the referred mechanisms in the human fungal pathogens Aspergillus fumigatus, Cryptococcus neoformans, Candida albicans, Candida glabrata, Candida parapsilosis , and Candida tropicalis . Current knowledge on the activity of the transcription factors characterized in each of these pathogenic fungal species will be addressed. Particular focus is given to their mechanisms of activation, regulatory targets and phenotypic outcome. The review further provides an evaluation on the conservation of transcriptional circuits among different fungal pathogens, highlighting the pathways that translate common or divergent traits among these species in what concerns their drug resistance, virulence and host immune evasion features. It becomes evident that the regulation of transcriptional networks is complex and presents significant variations among different fungal pathogens. Only the oxidative stress regulators Yap1 and Skn7 are conserved among all studied species; while some transcription factors, involved in nutrient homeostasis, pH adaptation, drug resistance and morphological switching are present in several, though not all species. Interestingly, in some cases not very homologous transcription factors display orthologous functions, whereas some homologous proteins have diverged in terms of their function in different species. A few cases of species specific transcription factors are also observed.

  20. Impact of bacteriophage Saint3 carriage on the immune evasion capacity and hemolytic potential of Staphylococcus aureus CC398.

    Science.gov (United States)

    Jung, Philipp; Abdelbary, Mohamed M H; Kraushaar, Britta; Fetsch, Alexandra; Geisel, Jürgen; Herrmann, Mathias; Witte, Wolfgang; Cuny, Christiane; Bischoff, Markus

    2017-02-01

    Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) isolates of clonal complex 398 (CC398) are frequently found in Europe, and recent studies highlighted the importance of mobile genetic element (MGE) exchange for host adaptation of this lineage. Of note, one of the MGEs commonly found in human S. aureus isolates, the immune evasion cluster (IEC) harboring bacteriophage Saint3, is very rarely found in LA-MRSA CC398 isolates obtained from farm animals, but more frequently found in LA-MRSA CC398 that were retransmitted to humans. Here, we analyzed with a set of S. aureus CC398 isolates harboring/lacking φSaint3 how this MGE affects (i) phagocytosis of CC398 isolates by polymorphonuclear neutrophils (PMNs), and (ii) hemolysis of human and livestock-derived erythrocytes. Isolates lacking φSaint3 were more efficiently phagocytosed by human PMNs in whole blood phagocytosis assays than isolates harboring this bacteriophage, irrespective of their origin. Notably, a similar effect was observed when equine blood was utilized, but not detected with porcine blood. Integration of φSaint3 into LA-MRSA CC398 strains lacking this MGE confirmed these findings, as φSaint3-harboring recipients were again less efficiently ingested by PMNs in equine and human blood than their parental strains. Integration of φSaint3 strongly reduced the hemolytic potential of the culture supernatants against human-derived erythrocytes, and to a smaller extent also against porcine-derived erythrocytes, while φSaint3 integration only slightly affected the hemolytic capacities against equine-derived red blood cells. The significant protective effect of φSaint3 against phagocytosis by equine PMNs suggests that the host specificity of the IEC components might be broader than currently assumed. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. RNA-seq analysis of early enteromyxosis in turbot (Scophthalmus maximus): new insights into parasite invasion and immune evasion strategies.

    Science.gov (United States)

    Ronza, Paolo; Robledo, Diego; Bermúdez, Roberto; Losada, Ana Paula; Pardo, Belén G; Sitjà-Bobadilla, Ariadna; Quiroga, María Isabel; Martínez, Paulino

    2016-07-01

    Enteromyxum scophthalmi, an intestinal myxozoan parasite, is the causative agent of a threatening disease for turbot (Scophthalmus maximus, L.) aquaculture. The colonisation of the digestive tract by this parasite leads to a cachectic syndrome associated with high morbidity and mortality rates. This myxosporidiosis has a long pre-patent period and the first detectable clinical and histopathological changes are subtle. The pathogenic mechanisms acting in the early stages of infection are still far from being fully understood. Further information on the host-parasite interaction is needed to assist in finding efficient preventive and therapeutic measures. Here, a RNA-seq-based transcriptome analysis of head kidney, spleen and pyloric caeca from experimentally-infected and control turbot was performed. Only infected fish with early signs of infection, determined by histopathology and immunohistochemical detection of E. scophthalmi, were selected. The RNA-seq analysis revealed, as expected, less intense transcriptomic changes than those previously found during later stages of the disease. Several genes involved in IFN-related pathways were up-regulated in the three organs, suggesting that the IFN-mediated immune response plays a main role in this phase of the disease. Interestingly, an opposite expression pattern had been found in a previous study on severely infected turbot. In addition, possible strategies for immune system evasion were suggested by the down-regulation of different genes encoding complement components and acute phase proteins. At the site of infection (pyloric caeca), modulation of genes related to different structural proteins was detected and the expression profile indicated the inhibition of cell proliferation and differentiation. These transcriptomic changes provide indications regarding the mechanisms of parasite attachment to and invasion of the host. The current results contribute to a better knowledge of the events that characterise the early

  2. Current evidence of anti-tumor necrosis factor α treatment efficacy in childhood chronic uveitis: a systematic review and meta-analysis approach of individual drugs.

    Science.gov (United States)

    Simonini, Gabriele; Druce, Katie; Cimaz, Rolando; Macfarlane, Gary J; Jones, Gareth T

    2014-07-01

    To summarize evidence regarding the effectiveness of anti-tumor necrosis factor α (anti-TNFα) treatments in childhood autoimmune chronic uveitis (ACU), refractory to previous disease-modifying antirheumatic drugs (DMARDs). A systematic search between January 2000 and October 2012 was conducted using EMBase, Ovid Medline, Evidence-Based Medicine (EBM) Reviews: American College of Physicians Journal Club, Cochrane libraries, and EBM Reviews. Studies investigating the efficacy of anti-TNFα therapy, in children ages ≤16 years, as the first treatment with a biologic agent for ACU, refractory to topical and/or systemic steroid therapy and at least 1 DMARD, were eligible for inclusion. The primary outcome measure was the improvement of intraocular inflammation, as defined by the Standardization of Uveitis Nomenclature Working Group criteria. We determined a combined estimate of the proportion of children responding to anti-TNFα treatment, including etanercept (ETA), infliximab (INF), or adalimumab (ADA). We initially identified 989 articles, of which 148 were potentially eligible. In total, 22 retrospective chart reviews and 1 randomized clinical trial were deemed eligible, thus including 229 children (ADA: n = 31, ETA: n = 54, and INF: n = 144). On pooled analysis of observational studies, the proportion of responding children was 87% (95% confidence interval [95% CI] 75-98%) for ADA, 72% (95% CI 64-79%) for INF, and 33% (95% CI 19-47%) for ETA. There was no difference in the proportion of responders between ADA and INF (χ(2) = 3.06, P = 0.08), although both showed superior efficacy compared with ETA (ADA versus ETA: χ(2) = 20.9, P < 0.001 and INF versus ETA: χ(2) = 20.9, P < 0.001). Although randomized controlled trials are needed, the available evidence suggests that INF and ADA provide proven similar benefits in the treatment of childhood ACU, and they are both superior to ETA. Copyright © 2014 by the American College of Rheumatology.

  3. Tax Evasion, Tax Avoidance and The Influence of Special Interest Groups: Taxation in Iceland from 1930 to the Present

    Directory of Open Access Journals (Sweden)

    Karlsson Johannes

    2015-12-01

    Full Text Available This paper focuses on tax evasion and tax avoidance in Iceland, and on how special interest groups have shaped the taxation system to serve their own ends. The period covered is from 1930, when the present Icelandic system of power was established, to the present.

  4. Is there a displacement deadweight loss from tax evasion? Estimates using firm surveys from the Czech Republic

    Czech Academy of Sciences Publication Activity Database

    Hanousek, Jan; Palda, F.

    2009-01-01

    Roč. 42, č. 3 (2009), s. 139-158 ISSN 1573-9414 R&D Projects: GA ČR GA402/09/1595; GA MŠk LC542 Institutional research plan: CEZ:MSM0021620846 Keywords : underground economy * social cost of public funds * taxation * tax evasion Subject RIV: AH - Economics

  5. ‘Do You Want a Receipt?’ Combating VAT and RST Evasion with Lottery Tickets

    NARCIS (Netherlands)

    S.J.C. Hemels (Sigrid); M. Fabbri (Marco)

    2013-01-01

    textabstractGovernments both in developed and developing countries are facing the problem of value added tax (VAT) and retail sales tax (RST) evasion. This explains a growing interest in policies alternative to the traditional methods of deterrence. This paper describes the achievements resulting

  6. T Cell-Tumor Interaction Directs the Development of Immunotherapies in Head and Neck Cancer

    Directory of Open Access Journals (Sweden)

    A. E. Albers

    2010-01-01

    Full Text Available The competent immune system controls disease effectively due to induction, function, and regulation of effector lymphocytes. Immunosurveillance is exerted mostly by cytotoxic T-lymphocytes (CTLs while specific immune suppression is associated with tumor malignancy and progression. In squamous cell carcinoma of the head and neck, the presence, activity, but also suppression of tumor-specific CTL have been demonstrated. Functional CTL may exert a selection pressure on the tumor cells that consecutively escape by a combination of molecular and cellular evasion mechanisms. Certain of these mechanisms target antitumor effector cells directly or indirectly by affecting cells that regulate CTL function. This results in the dysfunction or apoptosis of lymphocytes and dysregulated lymphocyte homeostasis. Another important tumor-escape mechanism is to avoid recognition by dysregulation of antigen processing and presentation. Thus, both induction of functional CTL and susceptibility of the tumor and its microenvironment to become T cell targets should be considered in CTL-based immunotherapy.

  7. [Current status of thoracoscopic surgery for thoracic and lumbar spine. Part 2: treatment of the thoracic disc hernia, spinal deformities, spinal tumors, infections and miscellaneous].

    Science.gov (United States)

    Verdú-López, Francisco; Beisse, Rudolf

    2014-01-01

    Thoracoscopic surgery or video-assisted thoracic surgery (VATS) of the thoracic and lumbar spine has evolved greatly since it appeared less than 20 years ago. It is currently used in a large number of processes and injuries. The aim of this article, in its two parts, is to review the current status of VATS of the thoracic and lumbar spine in its entire spectrum. After reviewing the current literature, we developed each of the large groups of indications where VATS takes place, one by one. This second part reviews and discusses the management, treatment and specific thoracoscopic technique in thoracic disc herniation, spinal deformities, tumour pathology, infections of the spine and other possible indications for VATS. Thoracoscopic surgery is in many cases an alternative to conventional open surgery. The transdiaphragmatic approach has made endoscopic treatment of many thoracolumbar junction processes possible, thus widening the spectrum of therapeutic indications. These include the treatment of spinal deformities, spinal tumours, infections and other pathological processes, as well as the reconstruction of injured spinal segments and decompression of the spinal canal if lesion placement is favourable to antero-lateral approach. Good clinical results of thoracoscopic surgery are supported by growing experience reflected in a large number of articles. The degree of complications in thoracoscopic surgery is comparable to open surgery, with benefits in regard to morbidity of the approach and subsequent patient recovery. Copyright © 2012 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

  8. Evasive Duality

    International Nuclear Information System (INIS)

    Zakharov, V.I.

    2009-01-01

    A mini-review concerning the duality between higher orders in perturbative expansions and the quadratic power corrections to the parton model. The note contains no new results and is prompted by a continuing controversy in the literature. Sometimes one considers the two ways of describing QCD observables - in terms of a long perturbative series and in terms of the leading quadratic power correction - as contradicting to each other. While they are in fact dual to each other

  9. Methane evasion and oxidation in the Big Cypress National Preserve—a low relief carbonate wetland

    Science.gov (United States)

    Ward, N. D.; Bianchi, T. S.; Cohen, M. J.; Martin, J. B.; Quintero, C.; Brown, A.; Osborne, T.; Sawakuchi, H. O.

    2016-12-01

    The Big Cypress National Preserve is a low relief carbonate wetland characterized by unique basin patterning known as "cypress domes." Here we examine the concentration and stable isotopic composition of methane in pore waters, surface waters, and bubbles from the sediment across horizontal gradients in four domes during three sampling campaigns. The proportion of methane oxidized in surface waters was estimated based on isotopic differences between surface water and pore waters/bubbles. Rates of methane evasion from surface waters, soils, and cypress knees to the atmosphere were also measured. Surface water CH4 concentrations ranged from 170 to 4,533 ppm with the highest levels generally being observed during wet periods. Pore water CH4 concentrations ranged from 748 to 75,213 ppm. The concentration of methane in bubbles ranged from 6.5 to 71%. The stable isotopic composition of CH4 ranged from -69.2 to -43.8‰ for all samples and was generally more enriched in surface waters compared to bubbles and porewaters, particularly in the two domes that were persistently inundated throughout the year. Based on these isotopic values, the average percentage of surface water CH4 that was oxidized was 37 ± 16% (maximum of 67%) and 19 ± 4% (maximum of 47%) in the two domes that are persistently inundated versus the two domes that are not inundated during the dry season, respectively. The average rate of CH4 evasion was 3.6 ± 1.6 mmol m-2 d-1 via diffusion, 7.6 ± 4.7 mmol m-2 d-1 via ebullition, 10.9 ± 11.4 mmol m-2 d-1­ from soil surfaces, and 34.3 ± 27.4 mmol m-2 d-1 from cypress knees. These results indicate that CH4 is produced in great quantities in inundated sediments, particularly in the center of the cypress domes. Diffusive fluxes from surface waters are suppressed by microbial oxidation in the water column, whereas ebullition from sediments and evasion through cypress knees, and likely other vascular vegetation, are the primary pathways for CH4 outgassing.

  10. ONCOLYTIC VIRUS-MEDIATED REVERSAL OF IMPAIRED TUMOR ANTIGEN PRESENTATION

    Directory of Open Access Journals (Sweden)

    Shashi Ashok Gujar

    2014-04-01

    Full Text Available Anti-tumor immunity can eliminate existing cancer cells and also maintain a constant surveillance against possible relapse. Such an antigen-specific adaptive response begins when tumor-specific T cells become activated. T cell activation requires two signals on antigen presenting cells (APCs: antigen presentation through MHC molecules and co-stimulation. In the absence of one or both of these signals, T cells remain inactivated or can even become tolerized. Cancer cells and their associated microenvironment strategically hinder the processing and presentation of tumor antigens and consequently prevent the development of anti-tumor immunity. Many studies, however, demonstrate that interventions that overturn tumor-associated immune evasion mechanisms can establish anti-tumor immune responses of therapeutic potential. One such intervention is oncolytic virus (OV-based anti-cancer therapy. Here we discuss how OV-induced immunological events override tumor-associated antigen presentation impairment and promote appropriate T cell:APC interaction. Detailed understanding of this phenomenon is pivotal for devising the strategies that will enhance the efficacy of OV-based anti-cancer therapy by complementing its inherent oncolytic

  11. Tumoral tracers

    International Nuclear Information System (INIS)

    Camargo, E.E.

    1979-01-01

    Direct tumor tracers are subdivided in the following categories:metabolite tracers, antitumoral tracers, radioactive proteins and cations. Use of 67 Ga-citrate as a clinically important tumoral tracer is emphasized and gallium-67 whole-body scintigraphy is discussed in detail. (M.A.) [pt

  12. Animal tumors

    International Nuclear Information System (INIS)

    Gillette, E.L.

    1983-01-01

    There are few trained veterinary radiation oncologists and the expense of facilities has limited the extent to which this modality is used. In recent years, a few cobalt teletherapy units and megavoltage x-ray units have been employed in larger veterinary institutions. In addition, some radiation oncologists of human medical institutions are interested and willing to cooperate with veterinarians in the treatment of animal tumors. Carefully designed studies of the response of animal tumors to new modalities serve two valuable purposes. First, these studies may lead to improved tumor control in companion animals. Second, these studies may have important implications to the improvement of therapy of human tumors. Much remains to be learned of animal tumor biology so that appropriate model systems can be described for such studies. Many of the latter studies can be sponsored by agencies interested in the improvement of cancer management

  13. Viral Inhibition of PRR-Mediated Innate Immune Response: Learning from KSHV Evasion Strategies.

    Science.gov (United States)

    Lee, Hye-Ra; Choi, Un Yung; Hwang, Sung-Woo; Kim, Stephanie; Jung, Jae U

    2016-11-30

    The innate immune system has evolved to detect and destroy invading pathogens before they can establish systemic infection. To successfully eradicate pathogens, including viruses, host innate immunity is activated through diverse pattern recognition receptors (PRRs) which detect conserved viral signatures and trigger the production of type I interferon (IFN) and pro-inflammatory cytokines to mediate viral clearance. Viral persistence requires that viruses co-opt cellular pathways and activities for their benefit. In particular, due to the potent antiviral activities of IFN and cytokines, viruses have developed various strategies to meticulously modulate intracellular innate immune sensing mechanisms to facilitate efficient viral replication and persistence. In this review, we highlight recent advances in the study of viral immune evasion strategies with a specific focus on how Kaposi's sarcoma-associated herpesvirus (KSHV) effectively targets host PRR signaling pathways.

  14. Polymorphism in liver-stage malaria vaccine candidate proteins: immune evasion and implications for vaccine design.

    Science.gov (United States)

    Flanagan, Katie L; Wilson, Kirsty L; Plebanski, Magdalena

    2016-01-01

    The pre-erythrocytic stage of infection by malaria parasites represents a key target for vaccines that aim to eradicate malaria. Two important broad immune evasion strategies that can interfere with vaccine efficacy include the induction of dendritic cell (DC) dysfunction and regulatory T cells (Tregs) by blood-stage malaria parasites, leading to inefficient priming of T cells targeting liver-stage infections. The parasite also uses 'surgical strike' strategies, whereby polymorphism in pre-erythrocytic antigens can interfere with host immunity. Specifically, we review how even single amino acid changes in T cell epitopes can lead to loss of binding to major histocompatibility complex (MHC), lack of cross-reactivity, or antagonism and immune interference, where simultaneous or sequential stimulation with related variants of the same T cell epitope can cause T cell anergy or the conversion of effector to immunosuppressive T cell phenotypes.

  15. Antimicrobial Mechanisms of Macrophages and the Immune Evasion Strategies of Staphylococcus aureus

    Science.gov (United States)

    Flannagan, Ronald S.; Heit, Bryan; Heinrichs, David E.

    2015-01-01

    Habitually professional phagocytes, including macrophages, eradicate microbial invaders from the human body without overt signs of infection. Despite this, there exist select bacteria that are professional pathogens, causing significant morbidity and mortality across the globe and Staphylococcus aureus is no exception. S. aureus is a highly successful pathogen that can infect virtually every tissue that comprises the human body causing a broad spectrum of diseases. The profound pathogenic capacity of S. aureus can be attributed, in part, to its ability to elaborate a profusion of bacterial effectors that circumvent host immunity. Macrophages are important professional phagocytes that contribute to both the innate and adaptive immune response, however from in vitro and in vivo studies, it is evident that they fail to eradicate S. aureus. This review provides an overview of the antimicrobial mechanisms employed by macrophages to combat bacteria and describes the immune evasion strategies and some representative effectors that enable S. aureus to evade macrophage-mediated killing. PMID:26633519

  16. hrHPV E5 oncoprotein: immune evasion and related immunotherapies.

    Science.gov (United States)

    de Freitas, Antonio Carlos; de Oliveira, Talita Helena Araújo; Barros, Marconi Rego; Venuti, Aldo

    2017-05-25

    The immune response is a key factor in the fight against HPV infection and related cancers, and thus, HPV is able to promote immune evasion through the expression of oncogenes. In particular, the E5 oncogene is responsible for modulation of several immune mechanisms, including antigen presentation and inflammatory pathways. Moreover, E5 was suggested as a promising therapeutic target, since there is still no effective medical therapy for the treatment of HPV-related pre-neoplasia and cancer. Indeed, several studies have shown good prospective for E5 immunotherapy, suggesting that it could be applied for the treatment of pre-cancerous lesions. Thus, insofar as the majority of cervical, oropharyngeal and anal cancers are caused by high-risk HPV (hrHPV), mainly by HPV16, the aim of this review is to discuss the immune pathways interfered by E5 oncoprotein of hrHPV highlighting the various aspects of the potential immunotherapeutic approaches.

  17. THE IMPORTANCE OF TAX AMNESTY POLICY IN EFFORTS TO OVERCOME TAX EVASION IN INDONESIA

    Directory of Open Access Journals (Sweden)

    Imas Sholihah

    2017-02-01

    Full Text Available Fundamental problems of taxation in Indonesia is a low tax ratio and management of the tax systemhas not been well ordered, especially the handling of the tax evaders. Tax amnesty policy is presentas one of the solutions of the problems of taxation and is part of the tax reform. There are pros andcons to this policy as it pertains to the settings in the Tax Forgiveness Act is considered less sense offairness and legal certainty and are vulnerable to abuse of authority. This policy became importantalthough it is less sense of fairness if the review facilities subject to tax amnesty even though thestate would get the revenue the state in large numbers in a short period of short-term benefits, butif managed by the management and human resources professionals, socialization, and optimizedcontrol, a long-term positive impact to minimize state income tax evasion. Keywords: tax amnesty, policy, tax evation (avoidance

  18. Surface modification of nanoparticles enables selective evasion of phagocytic clearance by distinct macrophage phenotypes

    Science.gov (United States)

    Qie, Yaqing; Yuan, Hengfeng; von Roemeling, Christina A.; Chen, Yuanxin; Liu, Xiujie; Shih, Kevin D.; Knight, Joshua A.; Tun, Han W.; Wharen, Robert E.; Jiang, Wen; Kim, Betty Y. S.

    2016-05-01

    Nanomedicine is a burgeoning industry but an understanding of the interaction of nanomaterials with the immune system is critical for clinical translation. Macrophages play a fundamental role in the immune system by engulfing foreign particulates such as nanoparticles. When activated, macrophages form distinct phenotypic populations with unique immune functions, however the mechanism by which these polarized macrophages react to nanoparticles is unclear. Furthermore, strategies to selectively evade activated macrophage subpopulations are lacking. Here we demonstrate that stimulated macrophages possess higher phagocytic activities and that classically activated (M1) macrophages exhibit greater phagocytic capacity than alternatively activated (M2) macrophages. We show that modification of nanoparticles with polyethylene-glycol results in decreased clearance by all macrophage phenotypes, but importantly, coating nanoparticles with CD47 preferentially lowers phagocytic activity by the M1 phenotype. These results suggest that bio-inspired nanoparticle surface design may enable evasion of specific components of the immune system and provide a rational approach for developing immune tolerant nanomedicines.

  19. Mechanisms of innate immune evasion in re-emerging RNA viruses.

    Science.gov (United States)

    Ma, Daphne Y; Suthar, Mehul S

    2015-06-01

    Recent outbreaks of Ebola, West Nile, Chikungunya, Middle Eastern Respiratory and other emerging/re-emerging RNA viruses continue to highlight the need to further understand the virus-host interactions that govern disease severity and infection outcome. As part of the early host antiviral defense, the innate immune system mediates pathogen recognition and initiation of potent antiviral programs that serve to limit virus replication, limit virus spread and activate adaptive immune responses. Concordantly, viral pathogens have evolved several strategies to counteract pathogen recognition and cell-intrinsic antiviral responses. In this review, we highlight the major mechanisms of innate immune evasion by emerging and re-emerging RNA viruses, focusing on pathogens that pose significant risk to public health. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Exploitation of herpesvirus immune evasion strategies to modify the immunogenicity of human mesenchymal stem cell transplants.

    Directory of Open Access Journals (Sweden)

    Anabel S de la Garza-Rodea

    Full Text Available BACKGROUND: Mesenchymal stem cells (MSCs are multipotent cells residing in the connective tissue of many organs and holding great potential for tissue repair. In culture, human MSCs (hMSCs are capable of extensive proliferation without showing chromosomal aberrations. Large numbers of hMSCs can thus be acquired from small samples of easily obtainable tissues like fat and bone marrow. MSCs can contribute to regeneration indirectly by secretion of cytokines or directly by differentiation into specialized cell types. The latter mechanism requires their long-term acceptance by the recipient. Although MSCs do not elicit immune responses in vitro, animal studies have revealed that allogeneic and xenogeneic MSCs are rejected. METHODOLOGY/PRINCIPAL FINDINGS: We aim to overcome MSC immune rejection through permanent down-regulation of major histocompatibility complex (MHC class I proteins on the surface of these MHC class II-negative cells through the use of viral immune evasion proteins. Transduction of hMSCs with a retroviral vector encoding the human cytomegalovirus US11 protein resulted in strong inhibition of MHC class I surface expression. When transplanted into immunocompetent mice, persistence of the US11-expressing and HLA-ABC-negative hMSCs at levels resembling those found in immunodeficient (i.e., NOD/SCID mice could be attained provided that recipients' natural killer (NK cells were depleted prior to cell transplantation. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate the potential utility of herpesviral immunoevasins to prevent rejection of xenogeneic MSCs. The observation that down-regulation of MHC class I surface expression renders hMSCs vulnerable to NK cell recognition and cytolysis implies that multiple viral immune evasion proteins are likely required to make hMSCs non-immunogenic and thereby universally transplantable.

  1. Hair analysis for the detection of drug use-is there potential for evasion?

    Science.gov (United States)

    Marrinan, Shanna; Roman-Urrestarazu, Andres; Naughton, Declan; Levari, Emerlinda; Collins, John; Chilcott, Robert; Bersani, Giuseppe; Corazza, Ornella

    2017-05-01

    Hair analysis for illicit substances is widely used to detect chronic drug consumption or abstention from drugs. Testees are increasingly seeking ways to avoid detection by using a variety of untested adulterant products (e.g., shampoos, cleansers) widely sold online. This study aims to investigate adulteration of hair samples and to assess effectiveness of such methods. The literature on hair test evasion was searched for on PubMed or MEDLINE, Psycinfo, and Google Scholar. Given the sparse nature of peer-reviewed data on this subject, results were integrated with a qualitative assessment of online sources, including user-orientated information or commercial websites, drug fora and "chat rooms". Over four million web sources were identified in a Google search by using "beat hair drug test" and the first 86 were monitored on regular basis and considered for further analysis. Attempts to influence hair test results are widespread. Various "shampoos," and "cleansers" among other products, were found for sale, which claim to remove analytes. Often advertised with aggressive marketing strategies, which include discounts, testimonials, and unsupported claims of efficacy. However, these products may pose serious health hazards and are also potentially toxic. In addition, many anecdotal reports suggest that Novel Psychoactive Substances are also consumed as an evasion technique, as these are not easily detectable via standard drug test. Recent changes on Novel Psychoactive Substances legislations such as New Psychoactive Bill in the UK might further challenge the testing process. Further research is needed by way of chemical analysis and trial of the adulterant products sold online and their effects as well as the development of more sophisticated hair testing techniques. Copyright © 2017 John Wiley & Sons, Ltd.

  2. When hawks attack: animal-borne video studies of goshawk pursuit and prey-evasion strategies

    Science.gov (United States)

    Kane, Suzanne Amador; Fulton, Andrew H.; Rosenthal, Lee J.

    2015-01-01

    Video filmed by a camera mounted on the head of a Northern Goshawk (Accipiter gentilis) was used to study how the raptor used visual guidance to pursue prey and land on perches. A combination of novel image analysis methods and numerical simulations of mathematical pursuit models was used to determine the goshawk's pursuit strategy. The goshawk flew to intercept targets by fixing the prey at a constant visual angle, using classical pursuit for stationary prey, lures or perches, and usually using constant absolute target direction (CATD) for moving prey. Visual fixation was better maintained along the horizontal than vertical direction. In some cases, we observed oscillations in the visual fix on the prey, suggesting that the goshawk used finite-feedback steering. Video filmed from the ground gave similar results. In most cases, it showed goshawks intercepting prey using a trajectory consistent with CATD, then turning rapidly to attack by classical pursuit; in a few cases, it showed them using curving non-CATD trajectories. Analysis of the prey's evasive tactics indicated that only sharp sideways turns caused the goshawk to lose visual fixation on the prey, supporting a sensory basis for the surprising frequency and effectiveness of this tactic found by previous studies. The dynamics of the prey's looming image also suggested that the goshawk used a tau-based interception strategy. We interpret these results in the context of a concise review of pursuit–evasion in biology, and conjecture that some prey deimatic ‘startle’ displays may exploit tau-based interception. PMID:25609783

  3. Hepatitis B virus evasion from cGAS sensing in human hepatocytes.

    Science.gov (United States)

    Verrier, Eloi R; Yim, Seung-Ae; Heydmann, Laura; El Saghire, Houssein; Bach, Charlotte; Turon-Lagot, Vincent; Mailly, Laurent; Durand, Sarah C; Lucifora, Julie; Durantel, David; Pessaux, Patrick; Manel, Nicolas; Hirsch, Ivan; Zeisel, Mirjam B; Pochet, Nathalie; Schuster, Catherine; Baumert, Thomas F

    2018-04-20

    Chronic hepatitis B virus (HBV) infection is a major cause of chronic liver disease and cancer worldwide. The mechanisms of viral genome sensing and the evasion of innate immune responses by HBV infection are still poorly understood. Recently, the cyclic GMP-AMP synthase (cGAS) was identified as a DNA sensor. In this study, we aimed to investigate the functional role of cGAS in sensing of HBV infection and elucidate the mechanisms of viral evasion. We performed functional studies including loss- and gain-of-function experiments combined with cGAS effector gene expression profiling in an infectious cell culture model, primary human hepatocytes and HBV-infected human liver chimeric mice. Here we show that cGAS is expressed in the human liver, primary human hepatocytes and human liver chimeric mice. While naked relaxed-circular HBV DNA is sensed in a cGAS-dependent manner in hepatoma cell lines and primary human hepatocytes, host cell recognition of viral nucleic acids is abolished during HBV infection, suggesting escape from sensing, likely during packaging of the genome into the viral capsid. While the hepatocyte cGAS pathway is functionally active, as shown by reduction of viral cccDNA levels in gain-of-function studies, HBV infection suppressed cGAS expression and function in cell culture models and humanized mice. HBV exploits multiple strategies to evade sensing and antiviral activity of cGAS and its effector pathways. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

  4. Central nervous system tumors

    International Nuclear Information System (INIS)

    Gavin, P.R.; Fike, J.R.; Hoopes, P.J.

    1995-01-01

    Central nervous system (CNS) tumors are relatively common in veterinary medicine, with most diagnoses occurring in the canine and feline species. Numerous tumor types from various cells or origins have been identified with the most common tumors being meningiomas and glial cell tumors. Radiation therapy is often used as an aid to control the clinical signs associated with these neoplasms. In general, these tumors have a very low metastatic potential, such that local control offers substantial benefit. Experience in veterinary radiation oncology would indicate that many patients benefit from radiation treatment. Current practice indicates the need for computed tomography or magnetic resonance imaging studies. These highly beneficial studies are used for diagnosis, treatment planning, and to monitor treatment response. Improvements in treatment planning and radiation delivered to the tumor, while sparing the normal tissues, should improve local control and decrease potential radiation related problems to the CNS. When possible, multiple fractions of 3 Gy or less should be used. The tolerance dose to the normal tissue with this fractionation schedule is 50 to 55 Gy. The most common and serious complications of radiation for CNS tumors is delayed radiation myelopathy and necrosis. Medical management of the patient during radiation therapy requires careful attention to anesthetic protocols, and medications to reduce intracranial pressure that is often elevated in these patients. Canine brain tumors have served as an experimental model to test numerous new treatments. Increased availability of advanced imaging modalities has spawned increased detection of these neoplasms. Early detection of these tumors with appropriate aggressive therapy should prove beneficial to many patients

  5. Patient-Derived Antibody Targets Tumor Cells

    Science.gov (United States)

    An NCI Cancer Currents blog on an antibody derived from patients that killed tumor cells in cell lines of several cancer types and slowed tumor growth in mouse models of brain and lung cancer without evidence of side effects.

  6. Pituitary Tumors

    Science.gov (United States)

    ... Association (ABTA) International RadioSurgery Association National Brain Tumor Society National Institute of Child Health and Human Development ... Definition The pituitary is a small, bean-sized gland ...

  7. Hypothalamic tumor

    Science.gov (United States)

    ... in the brain to reduce spinal fluid pressure. Risks of radiation therapy include damage to healthy brain cells when tumor cells are destroyed. Common side effects from chemotherapy include loss of appetite, nausea and vomiting, and fatigue.

  8. Which Is More Efficient in Fighting Tax Evasion: The Carrot or the Stick? A Cross-Country Comparison around the World

    OpenAIRE

    Bãtrâncea Larissa-Magareta; Bãtrâncea Ioan; Nichita Ramona-Anca

    2012-01-01

    Regardless of the economic development status, type of government or citizens’ trust level in tax authorities, tax evasion is a ubiquitous phenomenon across societies and a proof that people tend to display the same behavior all around the world. As tax evasion hinders economic growth and affects the provision of high quality public goods, tax authorities try to mitigate taxpayers’ tendency of dodging taxes by implementing either deterrence-based or reward-based strategies. The present paper ...

  9. Tumor Types: Understanding Brain Tumors

    Science.gov (United States)

    ... May cause excessive secretion of hormones Common among men and women in their 50s-80s Accounts for about 13 percent of all brain tumors Symptoms Headache Depression Vision loss Nausea or vomiting Behavioral and cognitive ...

  10. Tax Compliance Inventory: TAX-I Voluntary tax compliance, enforced tax compliance, tax avoidance, and tax evasion.

    Science.gov (United States)

    Kirchler, Erich; Wahl, Ingrid

    2010-06-01

    Surveys on tax compliance and non-compliance often rely on ad hoc formulated items which lack standardization and empirical validation. We present an inventory to assess tax compliance and distinguish between different forms of compliance and non-compliance: voluntary versus enforced compliance, tax avoidance, and tax evasion. First, items to measure voluntary and enforced compliance, avoidance, and evasion were drawn up (collected from past research and newly developed), and tested empirically with the aim of producing four validated scales with a clear factorial structure. Second, findings from the first analyses were replicated and extended to validation on the basis of motivational postures. A standardized inventory is provided which can be used in surveys in order to collect data which are comparable across research focusing on self-reports. The inventory can be used in either of two ways: either in its entirety, or by applying the single scales independently, allowing an economical and fast assessment of different facets of tax compliance.

  11. Host-pathogen interactions between the human innate immune system and Candida albicans - Understanding and modeling defense and evasion strategies

    Directory of Open Access Journals (Sweden)

    Sybille eDühring

    2015-06-01

    Full Text Available The diploid, polymorphic yeast Candida albicans is one of the most important humanpathogenic fungi. C. albicans can grow, proliferate and coexist as a commensal on or within thehuman host for a long time. Alterations in the host environment, however, can render C. albicansvirulent. In this review, we describe the immunological cross-talk between C. albicans and thehuman innate immune system. We give an overview in form of pairs of human defense strategiesincluding immunological mechanisms as well as general stressors such as nutrient limitation,pH, fever etc. and the corresponding fungal response and evasion mechanisms. FurthermoreComputational Systems Biology approaches to model and investigate these complex interactionare highlighted with a special focus on game-theoretical methods and agent-based models. Anoutlook on interesting questions to be tackled by Systems Biology regarding entangled defenseand evasion mechanisms is given.

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

    Science.gov (United States)

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

    2015-02-01

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

  13. Dynamics of riverine CO2 in the Yangtze River fluvial network and their implications for carbon evasion

    Science.gov (United States)

    Ran, Lishan; Lu, Xi Xi; Liu, Shaoda

    2017-04-01

    Understanding riverine carbon dynamics is critical for not only better estimates of various carbon fluxes but also evaluating their significance in the global carbon budget. As an important pathway of global land-ocean carbon exchange, the Yangtze River has received less attention regarding its vertical carbon evasion compared with lateral transport. Using long-term water chemistry data, we calculated CO2 partial pressure (pCO2) from pH and alkalinity and examined its spatial and temporal dynamics and the impacts of environmental settings. With alkalinity ranging from 415 to > 3400 µeq L-1, the river waters were supersaturated with dissolved CO2, generally 2-20-fold the atmospheric equilibrium (i.e., 390 µatm). Changes in pCO2 were collectively controlled by carbon inputs from terrestrial ecosystems, hydrological regime, and rock weathering. High pCO2 values were observed spatially in catchments with abundant carbonate presence and seasonally in the wet season when recently fixed organic matter was exported into the river network. In-stream processing of organic matter facilitated CO2 production and sustained the high pCO2, although the alkalinity presented an apparent dilution effect with water discharge. The decreasing pCO2 from the smallest headwater streams through tributaries to the mainstem channel illustrates the significance of direct terrestrial carbon inputs in controlling riverine CO2. With a basin-wide mean pCO2 of 2662 ± 1240 µatm, substantial CO2 evasion from the Yangtze River fluvial network is expected. Future research efforts are needed to quantify the amount of CO2 evasion and assess its biogeochemical implications for watershed-scale carbon cycle. In view of the Yangtze River's relative importance in global carbon export, its CO2 evasion would be significant for global carbon budget.

  14. Gravel bar thermal variability and its potential consequences for CO2 evasion from Alpine coldwater streams

    Science.gov (United States)

    Boodoo, Kyle; Battin, Tom; Schelker, Jakob

    2017-04-01

    Gravel bars (GB) are ubiquitous in-stream structures with relatively large exposed surfaces, capable of absorbing heat and possibly acting as a heat source to the underlying hyporheic zone (HZ). The distinctive mixing of groundwater and surface water within their HZ largely determines its characteristic physical and biogeochemical properties, including temperature distribution. To study thermal variability within GBs and its possible consequences for CO2 evasion fluxes we analysed high frequency spatio-temporal data for a range of stream and atmospheric physical parameters including the vertical GB temperature, in an Alpine cold water stream (Oberer Seebach, Austria) over the course of a year. We found the vertical temperature profiles within the GB to vary seasonally and with discharge. We extended our study to 13 other gravel bars of varying physical characteristics within the surrounding Ybbs and Erlauf catchments, conducting diurnal spot samplings in summer 2016. Temperatures within the observed permanently wetted hyporheic zone (-56 to -100cm depth below GB surface) of the OSB, were warmer than both end members, surface water and groundwater >18% of the year, particularly during summer. There was a general increase in exceedance within the periodically wetted gravel bar sediment toward the gravel bar surface, further evidencing downward heat transfer to the wetted HZ. Average CO2 flux from the GB was significantly higher than that of streamwater during summer and winter, with significantly higher temperatures and CO2 outgassing rates occurring at the GB tail as compared to streamwater and the head and mid of the GB throughout the year. Higher cumulative (over 6 h) GB seasonal temperatures were associated with increased CO2 evasion fluxes within the OSB, particularly during summer. This enhanced CO2 flux may result from the input of warmer CO2-rich groundwater into the HZ in autumn, while downward heat transfer in summer may enhance GB metabolism and therefore

  15. Pancreatic islet cell tumor

    Science.gov (United States)

    ... cell tumors; Islet of Langerhans tumor; Neuroendocrine tumors; Peptic ulcer - islet cell tumor; Hypoglycemia - islet cell tumor ... stomach acid. Symptoms may include: Abdominal pain Diarrhea ... and small bowel Vomiting blood (occasionally) Glucagonomas make ...

  16. Characterization of tumor vasculature in mouse brain by USPIO contrast-enhanced MRI.

    NARCIS (Netherlands)

    Gambarota, G.; Leenders, W.P.J.

    2011-01-01

    Detailed characterization of the tumor vasculature provides a better understanding of the complex mechanisms associated with tumor development and is especially important to evaluate responses to current therapies which target the tumor vasculature. Magnetic resonance imaging (MRI) studies of tumors

  17. Let's Tie the Knot: Marriage of Complement and Adaptive Immunity in Pathogen Evasion, for Better or Worse.

    Science.gov (United States)

    Bennett, Kaila M; Rooijakkers, Suzan H M; Gorham, Ronald D

    2017-01-01

    The complement system is typically regarded as an effector arm of innate immunity, leading to recognition and killing of microbial invaders in body fluids. Consequently, pathogens have engaged in an arms race, evolving molecules that can interfere with proper complement responses. However, complement is no longer viewed as an isolated system, and links with other immune mechanisms are continually being discovered. Complement forms an important bridge between innate and adaptive immunity. While its roles in innate immunity are well-documented, its function in adaptive immunity is less characterized. Therefore, it is no surprise that the field of pathogenic complement evasion has focused on blockade of innate effector functions, while potential inhibition of adaptive immune responses (via complement) has been overlooked to a certain extent. In this review, we highlight past and recent developments on the involvement of complement in the adaptive immune response. We discuss the mechanisms by which complement aids in lymphocyte stimulation and regulation, as well as in antigen presentation. In addition, we discuss microbial complement evasion strategies, and highlight specific examples in the context of adaptive immune responses. These emerging ties between complement and adaptive immunity provide a catalyst for future discovery in not only the field of adaptive immune evasion but in elucidating new roles of complement.

  18. Evasion of CO{sub 2} injected into the ocean in the content of CO{sub 2} stabilization

    Energy Technology Data Exchange (ETDEWEB)

    Kheshgi, H.S. [ExxonMobil Research and Engineering Co., Annandale, NJ (United States)

    2004-08-01

    The eventual evasion of injected CO{sub 2} to the atmosphere is one consideration when assessing deep-sea disposal of CO{sub 2} as a potential response option to climate change concerns. Evasion estimated using an ocean carbon cycle model is compared to long-term trajectories for future CO{sub 2} emissions, including illustrative cases leading to stabilization of CO{sub 2} concentration at various levels. Modeled residence time for CO{sub 2} injected into the deep ocean exceeds the 100-year time-scale usually considered in scenarios for future emissions, and the potential impacts of climate change. Illustrative cases leading monotonically to constant CO{sub 2} concentration have been highlighted by the Intergovernmental Panel on Climate Change to give guidance on possible timing of emission reductions that may be required to stabilize greenhouse gas concentrations at various levels. For stabilization cases considered, significant modeled evasion does not occur until long after CO{sub 2} emissions have reached a maximum and begun to decline. Illustrative cases can also lead to a maximum in CO{sub 2} concentration followed by a decline to slowly decreasing concentrations. In such cases, future injection of emissions into the deep ocean leads to lower maximum CO{sub 2} concentration, with less effect on concentration later on in time. (author)

  19. Evasion of CO{sub 2} injected into the ocean in the context of CO{sub 2} stabilization

    Energy Technology Data Exchange (ETDEWEB)

    Haroon S. Kheshgi [ExxonMobil Research and Engineering Company, Annandale, NJ (United States)

    2003-07-01

    The eventual evasion of injected CO{sub 2} to the atmosphere is one consideration when assessing deep sea disposal of CO{sub 2} as a potential response option to climate change concerns. Evasion estimated using an ocean carbon cycle model is compared to long-term trajectories for future CO{sub 2} emissions, including illustrative cases leading to stabilization of CO{sub 2} concentration at various levels. Modeled residence time for CO{sub 2} injected into the deep ocean exceeds the 100-year time scale usually considered in scenarios for future emissions, and the potential impacts of climate change. Illustrative cases leading monotonically to constant CO{sub 2} concentration have been highlighted by the Intergovernmental Panel on Climate Change to give guidance on possible timing of emission reductions that may be required to stabilize greenhouse gas concentrations at various levels. For stabilization cases considered, significant modeled evasion does not occur until long after CO{sub 2} emissions have reached a maximum and begun to decline. Illustrative cases can also lead to a maximum in CO{sub 2} concentration followed by a decline to slowly decreasing concentrations. In such cases, future injection of emissions into the deep ocean leads to lower maximum CO{sub 2} concentration, with less effect on concentration later on in time. 20 refs., 4 figs.

  20. Evasion of CO{sub 2} injected into the ocean in the context of CO{sub 2} stabilization

    Energy Technology Data Exchange (ETDEWEB)

    Kheshgi, Haroon S

    2004-08-01

    The eventual evasion of injected CO{sub 2} to the atmosphere is one consideration when assessing deep-sea disposal of CO{sub 2} as a potential response option to climate change concerns. Evasion estimated using an ocean carbon cycle model is compared to long-term trajectories for future CO{sub 2} emissions, including illustrative cases leading to stabilization of CO{sub 2} concentration at various levels. Modeled residence time for CO{sub 2} injected into the deep ocean exceeds the 100-year time-scale usually considered in scenarios for future emissions, and the potential impacts of climate change. Illustrative cases leading monotonically to constant CO{sub 2} concentration have been highlighted by the Intergovernmental Panel on Climate Change to give guidance on possible timing of emission reductions that may be required to stabilize greenhouse gas concentrations at various levels. For stabilization cases considered, significant modeled evasion does not occur until long after CO{sub 2} emissions have reached a maximum and begun to decline. Illustrative cases can also lead to a maximum in CO{sub 2} concentration followed by a decline to slowly decreasing concentrations. In such cases, future injection of emissions into the deep ocean leads to lower maximum CO{sub 2} concentration, with less effect on concentration later on in time.

  1. Let’s Tie the Knot: Marriage of Complement and Adaptive Immunity in Pathogen Evasion, for Better or Worse

    Science.gov (United States)

    Bennett, Kaila M.; Rooijakkers, Suzan H. M.; Gorham, Ronald D.

    2017-01-01

    The complement system is typically regarded as an effector arm of innate immunity, leading to recognition and killing of microbial invaders in body fluids. Consequently, pathogens have engaged in an arms race, evolving molecules that can interfere with proper complement responses. However, complement is no longer viewed as an isolated system, and links with other immune mechanisms are continually being discovered. Complement forms an important bridge between innate and adaptive immunity. While its roles in innate immunity are well-documented, its function in adaptive immunity is less characterized. Therefore, it is no surprise that the field of pathogenic complement evasion has focused on blockade of innate effector functions, while potential inhibition of adaptive immune responses (via complement) has been overlooked to a certain extent. In this review, we highlight past and recent developments on the involvement of complement in the adaptive immune response. We discuss the mechanisms by which complement aids in lymphocyte stimulation and regulation, as well as in antigen presentation. In addition, we discuss microbial complement evasion strategies, and highlight specific examples in the context of adaptive immune responses. These emerging ties between complement and adaptive immunity provide a catalyst for future discovery in not only the field of adaptive immune evasion but in elucidating new roles of complement. PMID:28197139

  2. Streptococcus pneumoniae PspC Subgroup Prevalence in Invasive Disease and Differences in Contribution to Complement Evasion.

    Science.gov (United States)

    van der Maten, Erika; van den Broek, Bryan; de Jonge, Marien I; Rensen, Kim J W; Eleveld, Marc J; Zomer, Aldert L; Cremers, Amelieke J H; Ferwerda, Gerben; de Groot, Ronald; Langereis, Jeroen D; van der Flier, Michiel

    2018-04-01

    The pneumococcal capsular serotype is an important determinant of complement resistance and invasive disease potential, but other virulence factors have also been found to contribute. Pneumococcal surface protein C (PspC), a highly variable virulence protein that binds complement factor H to evade C3 opsonization, is divided into two subgroups: choline-bound subgroup I and LPxTG-anchored subgroup II. The prevalence of different PspC subgroups in invasive pneumococcal disease (IPD) and functional differences in complement evasion are unknown. The prevalence of PspC subgroups in IPD isolates was determined in a collection of 349 sequenced strains of Streptococcus pneumoniae isolated from adult patients. pspC deletion mutants and isogenic pspC switch mutants were constructed to study differences in factor H binding and complement evasion in relation to capsule thickness. Subgroup I pspC was far more prevalent in IPD isolates than subgroup II pspC The presence of capsule was associated with a greater ability of bound factor H to reduce complement opsonization. Pneumococcal subgroup I PspC bound significantly more factor H and showed more effective complement evasion than subgroup II PspC in isogenic encapsulated pneumococci. We conclude that variation in the PspC subgroups, independent of capsule serotypes, affects pneumococcal factor H binding and its ability to evade complement deposition. Copyright © 2018 American Society for Microbiology.

  3. Quality control method to measure predator evasion in wild and mass-reared Mediterranean fruit flies (Diptera: Tephritidae)

    International Nuclear Information System (INIS)

    Hendrichs, M.; Wornoayporn, V.; Hendrichs, J.; Katsoyannos, B.

    2007-01-01

    Sterile male insects, mass-reared and released as part of sterile insect technique (SIT) programs, must survive long enough in the field to mature sexually and compete effectively with wild males for wild females. An often reported problem in Mediterranean fruit fly (medfly) Ceratitis capitata (Wiedemann) SIT programs is that numbers of released sterile males decrease rapidly in the field for various reasons, including losses to different types of predators. This is a serious issue in view that most operational programs release sterile flies at an age when they are still immature. Previous field and field-cage tests have confirmed that flies of laboratory strains are less able to evade predators than wild flies. Such tests involve, however, considerable manipulation and observation of predators and are therefore not suitable for routine measurements of predator evasion. Here we describe a simple quality control method with aspirators to measure agility in medflies and show that this parameter is related to the capacity of flies to evade predators. Although further standardization of the test is necessary to allow more accurate inter-strain comparisons, results confirm the relevance of measuring predator evasion in mass-reared medfly strains. Besides being a measure of this sterile male quality parameter, the described method could be used for the systematic selection of strains with a higher capacity for predator evasion. (author) [es

  4. Was there significant tax evasion after the 1999 50 cent per pack cigarette tax increase in California?

    Science.gov (United States)

    Emery, S; White, M; Gilpin, E; Pierce, J

    2002-01-01

    Objectives: Several states, including California, have implemented large cigarette excise tax increases, which may encourage smokers to purchase their cigarettes in other lower taxed states, or from other lower or non-taxed sources. Such tax evasion thwarts tobacco control objectives and may cost the state substantial tax revenues. Thus, this study investigates the extent of tax evasion in the 6–12 months after the implementation of California's $0.50/pack excise tax increase. Design and setting: Retrospective data analysis from the 1999 California Tobacco Surveys (CTS), a random digit dialled telephone survey of California households. Main outcome measures: Sources of cigarettes, average daily cigarette consumption, and reported price paid. Results: Very few (5.1 (0.7)% (±95% confidence limits)) of California smokers avoided the excise tax by usually purchasing cigarettes from non- or lower taxed sources, such as out-of-state outlets, military commissaries, or the internet. The vast majority of smokers purchased their cigarettes from the most convenient and expensive sources: convenience stores/gas (petrol) stations (45.0 (1.9)%), liquor/drug stores (16.4 (1.6)%), and supermarkets (8.8 (1.2)%). Conclusions: Despite the potential savings, tax evasion by individual smokers does not appear to pose a serious threat to California's excise tax revenues or its tobacco control objectives. PMID:12035006

  5. Conformational Occlusion of Blockade Antibody Epitopes, a Novel Mechanism of GII.4 Human Norovirus Immune Evasion.

    Science.gov (United States)

    Lindesmith, Lisa C; Mallory, Michael L; Debbink, Kari; Donaldson, Eric F; Brewer-Jensen, Paul D; Swann, Excel W; Sheahan, Timothy P; Graham, Rachel L; Beltramello, Martina; Corti, Davide; Lanzavecchia, Antonio; Baric, Ralph S

    2018-01-01

    Extensive antigenic diversity within the GII.4 genotype of human norovirus is a major driver of pandemic emergence and a significant obstacle to development of cross-protective immunity after natural infection and vaccination. However, human and mouse monoclonal antibody studies indicate that, although rare, antibodies to conserved GII.4 blockade epitopes are generated. The mechanisms by which these epitopes evade immune surveillance are uncertain. Here, we developed a new approach for identifying conserved GII.4 norovirus epitopes. Utilizing a unique set of virus-like particles (VLPs) representing the in vivo -evolved sequence diversity within an immunocompromised person, we identify key residues within epitope F, a conserved GII.4 blockade antibody epitope. The residues critical for antibody binding are proximal to evolving blockade epitope E. Like epitope F, antibody blockade of epitope E was temperature sensitive, indicating that particle conformation regulates antibody access not only to the conserved GII.4 blockade epitope F but also to the evolving epitope E. These data highlight novel GII.4 mechanisms to protect blockade antibody epitopes, map essential residues of a GII.4 conserved epitope, and expand our understanding of how viral particle dynamics may drive antigenicity and antibody-mediated protection by effectively shielding blockade epitopes. Our data support the notion that GII.4 particle breathing may well represent a major mechanism of humoral immune evasion supporting cyclic pandemic virus persistence and spread in human populations. IMPORTANCE In this study, we use norovirus virus-like particles to identify key residues of a conserved GII.4 blockade antibody epitope. Further, we identify an additional GII.4 blockade antibody epitope to be occluded, with antibody access governed by temperature and particle dynamics. These findings provide additional support for particle conformation-based presentation of binding residues mediated by a particle

  6. Imaging of brain tumors

    International Nuclear Information System (INIS)

    Gaensler, E.H.L.

    1995-01-01

    The contents are diagnostic approaches, general features of tumors -hydrocephalus, edema, attenuation and/or intensity value, hemorrhage, fat, contrast enhancement, intra-axial supratentorial tumors - tumors of glial origin, oligodendrogliomas, ependymomas, subependymomas, subependymal giant cell astrocytomas, choroid plexus papilloma; midline tumors - colloid cysts, craniopharyngiomas; pineal region tumors and miscellaneous tumors i.e. primary intracerebral lymphoma, primitive neuroectodermal tumors, hemangioblastomas; extraaxial tumors - meningiomas; nerve sheath tumors -schwannomas, epidermoids, dermoids, lipomas, arachnoid cysts; metastatic tumors (8 refs.)

  7. Imaging of brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Gaensler, E H.L. [California Univ., San Francisco, CA (United States). Dept. of Radiology

    1996-12-31

    The contents are diagnostic approaches, general features of tumors -hydrocephalus, edema, attenuation and/or intensity value, hemorrhage, fat, contrast enhancement, intra-axial supratentorial tumors - tumors of glial origin, oligodendrogliomas, ependymomas, subependymomas, subependymal giant cell astrocytomas, choroid plexus papilloma; midline tumors - colloid cysts, craniopharyngiomas; pineal region tumors and miscellaneous tumors i.e. primary intracerebral lymphoma, primitive neuroectodermal tumors, hemangioblastomas; extraaxial tumors - meningiomas; nerve sheath tumors -schwannomas, epidermoids, dermoids, lipomas, arachnoid cysts; metastatic tumors (8 refs.).

  8. Periostin Limits Tumor Response to VEGFA Inhibition.

    Science.gov (United States)

    Keklikoglou, Ioanna; Kadioglu, Ece; Bissinger, Stefan; Langlois, Benoît; Bellotti, Axel; Orend, Gertraud; Ries, Carola H; De Palma, Michele

    2018-03-06

    Resistance to antiangiogenic drugs limits their applicability in cancer therapy. Here, we show that revascularization and progression of pancreatic neuroendocrine tumors (PNETs) under extended vascular-endothelial growth factor A (VEGFA) blockade are dependent on periostin (POSTN), a matricellular protein expressed by stromal cells. Genetic deletion of Postn in RIP1-Tag2 mice blunted tumor rebounds of M2-like macrophages and αSMA + stromal cells in response to prolonged VEGFA inhibition and suppressed PNET revascularization and progression on therapy. POSTN deficiency also impeded the upregulation of basic fibroblast growth factor (FGF2), an adaptive mechanism previously implicated in PNET evasion from antiangiogenic therapy. Higher POSTN expression correlated with markers of M2-like macrophages in human PNETs, and depleting macrophages with a colony-stimulating factor 1 receptor (CSF1R) antibody inhibited PNET revascularization and progression under VEGFA blockade despite continued POSTN production. These findings suggest a role for POSTN in orchestrating resistance to anti-VEGFA therapy in PNETs. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. Periostin Limits Tumor Response to VEGFA Inhibition

    Directory of Open Access Journals (Sweden)

    Ioanna Keklikoglou

    2018-03-01

    Full Text Available Resistance to antiangiogenic drugs limits their applicability in cancer therapy. Here, we show that revascularization and progression of pancreatic neuroendocrine tumors (PNETs under extended vascular-endothelial growth factor A (VEGFA blockade are dependent on periostin (POSTN, a matricellular protein expressed by stromal cells. Genetic deletion of Postn in RIP1-Tag2 mice blunted tumor rebounds of M2-like macrophages and αSMA+ stromal cells in response to prolonged VEGFA inhibition and suppressed PNET revascularization and progression on therapy. POSTN deficiency also impeded the upregulation of basic fibroblast growth factor (FGF2, an adaptive mechanism previously implicated in PNET evasion from antiangiogenic therapy. Higher POSTN expression correlated with markers of M2-like macrophages in human PNETs, and depleting macrophages with a colony-stimulating factor 1 receptor (CSF1R antibody inhibited PNET revascularization and progression under VEGFA blockade despite continued POSTN production. These findings suggest a role for POSTN in orchestrating resistance to anti-VEGFA therapy in PNETs.

  10. Long non-coding RNA cox-2 prevents immune evasion and metastasis of hepatocellular carcinoma by altering M1/M2 macrophage polarization.

    Science.gov (United States)

    Ye, Yibiao; Xu, Yunxiuxiu; Lai, Yu; He, Wenguang; Li, Yanshan; Wang, Ruomei; Luo, Xinxi; Chen, Rufu; Chen, Tao

    2018-03-01

    Macrophages have been shown to demonstrate a high level of plasticity, with the ability to undergo dynamic transition between M1 and M2 polarized phenotypes. We investigate long non-coding RNA (lncRNA) cox-2 in macrophage polarization and the regulatory mechanism functions in hepatocellular carcinoma (HCC). Lipopolysaccharide (LPS) was used to induce RAW264.7 macrophages into M1 type, and IL-4 was to induce RAW264.7 macrophages into M2 type. We selected mouse hepatic cell line Hepal-6 and hepatoma cell line HepG2 for co-incubation with M1 or M2 macrophages. Quantitative real-time PCR was used to detect the expressions of lncRNA cox-2 and mRNAs. ELISA was conducted for testing IL-12 and IL-10 expressions; Western blotting for epithelial mesenchymal transition related factors (E-cadherin and Vimentin). An MTT, colony formation assay, flow cytometry, transwell assay, and stretch test were conducted to test cell abilities. The M1 macrophages had higher lncRNA cox-2 expression than that in the non-polarized macrophages and M2 macrophages. The lncRNA cox-2 siRNA decreased the expression levels of IL-12, iNOS, and TNF-α in M1 macrophages, increased the expression levels of IL-10, Arg-1, and Fizz-1 in M2 macrophages (all P evasion and tumor growth by inhibiting the polarization of M2 macrophages. © 2017 Wiley Periodicals, Inc.

  11. Similarities and differences between helminth parasites and cancer cell lines in shaping human monocytes: Insights into parallel mechanisms of immune evasion.

    Directory of Open Access Journals (Sweden)

    Prakash Babu Narasimhan

    2018-04-01

    Full Text Available A number of features at the host-parasite interface are reminiscent of those that are also observed at the host-tumor interface. Both cancer cells and parasites establish a tissue microenvironment that allows for immune evasion and may reflect functional alterations of various innate cells. Here, we investigated how the phenotype and function of human monocytes is altered by exposure to cancer cell lines and if these functional and phenotypic alterations parallel those induced by exposure to helminth parasites. Thus, human monocytes were exposed to three different cancer cell lines (breast, ovarian, or glioblastoma or to live microfilariae (mf of Brugia malayi-a causative agent of lymphatic filariasis. After 2 days of co-culture, monocytes exposed to cancer cell lines showed markedly upregulated expression of M1-associated (TNF-α, IL-1β, M2-associated (CCL13, CD206, Mreg-associated (IL-10, TGF-β, and angiogenesis associated (MMP9, VEGF genes. Similar to cancer cell lines, but less dramatically, mf altered the mRNA expression of IL-1β, CCL13, TGM2 and MMP9. When surface expression of the inhibitory ligands PDL1 and PDL2 was assessed, monocytes exposed to both cancer cell lines and to live mf significantly upregulated PDL1 and PDL2 expression. In contrast to exposure to mf, exposure to cancer cell lines increased the phagocytic ability of monocytes and reduced their ability to induce T cell proliferation and to expand Granzyme A+ CD8+ T cells. Our data suggest that despite the fact that helminth parasites and cancer cell lines are extraordinarily disparate, they share the ability to alter the phenotype of human monocytes.

  12. Similarities and differences between helminth parasites and cancer cell lines in shaping human monocytes: Insights into parallel mechanisms of immune evasion.

    Science.gov (United States)

    Narasimhan, Prakash Babu; Akabas, Leor; Tariq, Sameha; Huda, Naureen; Bennuru, Sasisekhar; Sabzevari, Helen; Hofmeister, Robert; Nutman, Thomas B; Tolouei Semnani, Roshanak

    2018-04-01

    A number of features at the host-parasite interface are reminiscent of those that are also observed at the host-tumor interface. Both cancer cells and parasites establish a tissue microenvironment that allows for immune evasion and may reflect functional alterations of various innate cells. Here, we investigated how the phenotype and function of human monocytes is altered by exposure to cancer cell lines and if these functional and phenotypic alterations parallel those induced by exposure to helminth parasites. Thus, human monocytes were exposed to three different cancer cell lines (breast, ovarian, or glioblastoma) or to live microfilariae (mf) of Brugia malayi-a causative agent of lymphatic filariasis. After 2 days of co-culture, monocytes exposed to cancer cell lines showed markedly upregulated expression of M1-associated (TNF-α, IL-1β), M2-associated (CCL13, CD206), Mreg-associated (IL-10, TGF-β), and angiogenesis associated (MMP9, VEGF) genes. Similar to cancer cell lines, but less dramatically, mf altered the mRNA expression of IL-1β, CCL13, TGM2 and MMP9. When surface expression of the inhibitory ligands PDL1 and PDL2 was assessed, monocytes exposed to both cancer cell lines and to live mf significantly upregulated PDL1 and PDL2 expression. In contrast to exposure to mf, exposure to cancer cell lines increased the phagocytic ability of monocytes and reduced their ability to induce T cell proliferation and to expand Granzyme A+ CD8+ T cells. Our data suggest that despite the fact that helminth parasites and cancer cell lines are extraordinarily disparate, they share the ability to alter the phenotype of human monocytes.

  13. Amplification of tumor inducing putative cancer stem cells (CSCs) by vitamin A/retinol from mammary tumors

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Rohit B. [Department of Microbiology and Molecular Genetics, University of Pittsburgh, PA 15261 (United States); Wang, Qingde [Department of Surgery, University of Pittsburgh, PA 15261 (United States); Khillan, Jaspal S., E-mail: khillan@pitt.edu [Department of Microbiology and Molecular Genetics, University of Pittsburgh, PA 15261 (United States)

    2013-07-12

    Highlights: •Vitamin A supports self renewal of putative CSCs from mammary tumors. •These cells exhibit impaired retinol metabolism into retinoic acid. •CSCs from mammary tumors differentiate into mammary specific cell lineages. •The cells express mammary stem cell specific CD29 and CD49f markers. •Putative CSCs form highly metastatic tumors in NOD SCID mouse. -- Abstract: Solid tumors contain a rare population of cancer stem cells (CSCs) that are responsible for relapse and metastasis. The existence of CSC however, remains highly controversial issue. Here we present the evidence for putative CSCs from mammary tumors amplified by vitamin A/retinol signaling. The cells exhibit mammary stem cell specific CD29{sup hi}/CD49f{sup hi}/CD24{sup hi} markers, resistance to radiation and chemo therapeutic agents and form highly metastatic tumors in NOD/SCID mice. The cells exhibit indefinite self renewal as cell lines. Furthermore, the cells exhibit impaired retinol metabolism and do not express enzymes that metabolize retinol into retinoic acid. Vitamin A/retinol also amplified putative CSCs from breast cancer cell lines that form highly aggressive tumors in NOD SCID mice. The studies suggest that high purity putative CSCs can be isolated from solid tumors to establish patient specific cell lines for personalized therapeutics for pre-clinical translational applications. Characterization of CSCs will allow understanding of basic cellular and molecular pathways that are deregulated, mechanisms of tumor metastasis and evasion of therapies that has direct clinical relevance.

  14. Bone tumors

    International Nuclear Information System (INIS)

    Moylan, D.J.; Yelovich, R.M.

    1991-01-01

    Primary bone malignancies are relatively rare with less than 4,000 new cases per year. Multiple myeloma (more correctly a hematologic malignancy) accounts for 40%; osteosarcomas, 28%; chondrosarcomas, 13%; fibrosarcomas arising in bone, 4%; and Ewing's sarcoma, 7%. The authors discuss various treatments for bone tumors, including radiotherapy, chemotherapy and surgery

  15. Wilms Tumor

    Science.gov (United States)

    ... a child's general health and to detect any adverse side effects (such as low red or white blood cell ... medicine needed, which helps reduce long-term side effects. The most common ... can be completely removed by surgery. About 41% of all Wilms tumors are stage ...

  16. Nephrogenic tumors

    International Nuclear Information System (INIS)

    Wiesbauer, P.

    2008-01-01

    Nephroblastomas are the most common malignant renal tumors in childhood. According to the guidelines of the SIOP (Societe Internationale d'Oncologie Pediatrique) and GPOH (Gesellschaft fuer Paediatrische Onkologie und Haematologie) pre-operative chemotherapy can be started without histological confirmation and thus initial imaging studies, in particular ultrasound, play an outstanding role for diagnostic purposes

  17. Structural basis of evasion of cellular adaptive immunity by HIV-1 Nef

    Energy Technology Data Exchange (ETDEWEB)

    Jia, Xiaofei; Singh, Rajendra; Homann, Stefanie; Yang, Haitao; Guatelli, John; Xiong, Yong (Yale); (VA); (UCSD)

    2012-10-24

    The HIV-1 protein Nef inhibits antigen presentation by class I major histocompatibility complex (MHC-I). We determined the mechanism of this activity by solving the crystal structure of a protein complex comprising Nef, the MHC-I cytoplasmic domain (MHC-I CD) and the {mu}1 subunit of the clathrin adaptor protein complex 1. A ternary, cooperative interaction clamps the MHC-I CD into a narrow binding groove at the Nef-{mu}1 interface, which encompasses the cargo-recognition site of {mu}1 and the proline-rich strand of Nef. The Nef C terminus induces a previously unobserved conformational change in {mu}1, whereas the N terminus binds the Nef core to position it optimally for complex formation. Positively charged patches on {mu}1 recognize acidic clusters in Nef and MHC-I. The structure shows how Nef functions as a clathrin-associated sorting protein to alter the specificity of host membrane trafficking and enable viral evasion of adaptive immunity.

  18. Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication.

    Directory of Open Access Journals (Sweden)

    Eveline Kindler

    2017-02-01

    Full Text Available Coronaviruses are of veterinary and medical importance and include highly pathogenic zoonotic viruses, such as SARS-CoV and MERS-CoV. They are known to efficiently evade early innate immune responses, manifesting in almost negligible expression of type-I interferons (IFN-I. This evasion strategy suggests an evolutionary conserved viral function that has evolved to prevent RNA-based sensing of infection in vertebrate hosts. Here we show that the coronavirus endonuclease (EndoU activity is key to prevent early induction of double-stranded RNA (dsRNA host cell responses. Replication of EndoU-deficient coronaviruses is greatly attenuated in vivo and severely restricted in primary cells even during the early phase of the infection. In macrophages we found immediate induction of IFN-I expression and RNase L-mediated breakdown of ribosomal RNA. Accordingly, EndoU-deficient viruses can retain replication only in cells that are deficient in IFN-I expression or sensing, and in cells lacking both RNase L and PKR. Collectively our results demonstrate that the coronavirus EndoU efficiently prevents simultaneous activation of host cell dsRNA sensors, such as Mda5, OAS and PKR. The localization of the EndoU activity at the site of viral RNA synthesis-within the replicase complex-suggests that coronaviruses have evolved a viral RNA decay pathway to evade early innate and intrinsic antiviral host cell responses.

  19. Host Innate Immunity against Hepatitis E Virus and Viral Evasion Mechanisms.

    Science.gov (United States)

    Kang, Sangmin; Myoung, Jinjong

    2017-10-28

    Hepatitis E virus (HEV) infections cause epidemic or sporadic acute hepatitis, which are mostly self-limiting. However, viral infection in immunocompromised patients and pregnant women may result in serious consequences, such as chronic hepatitis and liver damage, mortality of the latter of which reaches up to 20-30%. Type I interferon (IFN)-induced antiviral immunity is known to be the first-line defense against virus infection. Upon HEV infection in the cell, the virus genome is recognized by pathogen recognition receptors, leading to rapid activation of intracellular signaling cascades. Expression of type I IFN triggers induction of a barrage of IFN-stimulated genes, helping the cells cope with viral infection. Interestingly, some of the HEV-encoded genes seem to be involved in disrupting signaling cascades for antiviral immune responses, and thus crippling cytokine/chemokine production. Antagonistic mechanisms of type I IFN responses by HEV have only recently begun to emerge, and in this review, we summarize known HEV evasion strategies and compare them with those of other hepatitis viruses.

  20. Hiding in plain sight: immune evasion by the staphylococcal protein SdrE.

    Science.gov (United States)

    Herr, Andrew B; Thorman, Alexander W

    2017-05-10

    The human immune system is responsible for identification and destruction of invader cells, such as the bacterial pathogen Staphylococcus aureus In response, S. aureus brings to the fight a large number of virulence factors, including several that allow it to evade the host immune response. The staphylococcal surface protein SdrE was recently reported to bind to complement Factor H, an important regulator of complement activation. Factor H attaches to the surface of host cells to inhibit complement activation and amplification, preventing the destruction of the host cell. SdrE binding to Factor H allows S. aureus to mimic a host cell and reduces bacterial killing by granulocytes. In a new study published in Biochemical Journal , Zhang et al. describe crystal structures of SdrE and its complex with the C-terminal portion of Factor H. The structure of SdrE and its interaction with the Factor H peptide closely resemble a family of surface proteins that recognize extracellular matrix components such as fibrinogen. However, unbound SdrE forms a novel 'Closed' conformation with an occluded peptide-binding groove. These structures reveal a fascinating mechanism for immune evasion and provide a potential avenue for the development of novel antimicrobial agents to target SdrE. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  1. Immune evasion of porcine enteric coronaviruses and viral modulation of antiviral innate signaling.

    Science.gov (United States)

    Zhang, Qingzhan; Yoo, Dongwan

    2016-12-02

    Porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) are emerged and reemerging viruses in pigs, and together with transmissible gastroenteritis virus (TGEV), pose significant economic concerns to the swine industry. These viruses infect epithelial cells of the small intestine and cause watery diarrhea, dehydration, and a high mortality in neonatal piglets. Type I interferons (IFN-α/β) are major antiviral cytokines forming host innate immunity, and in turn, these enteric coronaviruses have evolved to modulate the host innate immune signaling during infection. Accumulating evidence however suggests that IFN induction and signaling in the intestinal epithelial cells differ from other epithelial cells, largely due to distinct features of the gut epithelial mucosal surface and commensal microflora, and it appears that type III interferon (IFN-λ) plays a key role to maintain the antiviral state in the gut. This review describes the recent understanding on the immune evasion strategies of porcine enteric coronaviruses and the role of different types of IFNs for intestinal antiviral innate immunity. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Immune Evasion Strategies during Chronic Hepatitis B and C Virus Infection

    Science.gov (United States)

    Ortega-Prieto, Ana Maria; Dorner, Marcus

    2017-01-01

    Both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are a major global healthcare problem with more than 240 million and 70 million infected, respectively. Both viruses persist within the liver and result in progressive liver disease, resulting in liver fibrosis, cirrhosis and hepatocellular carcinoma. Strikingly, this pathogenesis is largely driven by immune responses, unable to clear an established infection, rather than by the viral pathogens themselves. Even though disease progression is very similar in both infections, HBV and HCV have evolved distinct mechanisms, by which they ensure persistence within the host. Whereas HCV utilizes a cloak-and-dagger approach, disguising itself as a lipid-like particle and immediately crippling essential pattern-recognition pathways, HBV has long been considered a “stealth” virus, due to the complete absence of innate immune responses during infection. Recent developments and access to improved model systems, however, revealed that even though it is among the smallest human-tropic viruses, HBV may, in addition to evading host responses, employ subtle immune evasion mechanisms directed at ensuring viral persistence in the absence of host responses. In this review, we compare the different strategies of both viruses to ensure viral persistence by actively interfering with viral recognition and innate immune responses. PMID:28862649

  3. S-matrix equivalence theorem evasion and dimensional regularisation with the canonical MHV lagrangian

    International Nuclear Information System (INIS)

    Ettle, James H.; Fu, C.-H.; Fudger, Jonathan P.; Mansfield, Paul R.W.; Morris, Tim R.

    2007-01-01

    We demonstrate that the canonical change of variables that yields the MHV lagrangian, also provides contributions to scattering amplitudes that evade the equivalence theorem. This 'ET evasion' in particular provides the tree-level (-++) amplitude, which is non-vanishing off shell, or on shell with complex momenta or in (2,2) signature, and is missing from the MHV (/aka CSW) rules. At one loop there are ET-evading diagrammatic contributions to the amplitudes with all positive helicities. We supply the necessary regularisation in order to define these contributions (and quantum MHV methods in general) by starting from the light-cone Yang-Mills lagrangian in D dimensions and making a canonical change of variables for all D-2 transverse degrees of freedom of the gauge field. In this way, we obtain dimensionally regularised three- and four-point MHV amplitudes. Returning to the one-loop (++++) amplitude, we demonstrate that its quadruple cut coincides with the known result, and show how the original light-cone Yang-Mills contributions can in fact be algebraically recovered from the ET-evading contributions. We conclude that the canonical MHV lagrangian, supplemented with the extra terms brought to correlation functions by the non-linear field transformation, provide contributions which are just a rearrangement of those from light-cone Yang-Mills and thus coincide with them both on and off shell

  4. Immunoglobulin superfamily members encoded by viruses and their multiple roles in immune evasion.

    Science.gov (United States)

    Farré, Domènec; Martínez-Vicente, Pablo; Engel, Pablo; Angulo, Ana

    2017-05-01

    Pathogens have developed a plethora of strategies to undermine host immune defenses in order to guarantee their survival. For large DNA viruses, these immune evasion mechanisms frequently rely on the expression of genes acquired from host genomes. Horizontally transferred genes include members of the immunoglobulin superfamily, whose products constitute the most diverse group of proteins of vertebrate genomes. Their promiscuous immunoglobulin domains, which comprise the building blocks of these molecules, are involved in a large variety of functions mediated by ligand-binding interactions. The flexible structural nature of the immunoglobulin domains makes them appealing targets for viral capture due to their capacity to generate high functional diversity. Here, we present an up-to-date review of immunoglobulin superfamily gene homologs encoded by herpesviruses, poxviruses, and adenoviruses, that include CD200, CD47, Fc receptors, interleukin-1 receptor 2, interleukin-18 binding protein, CD80, carcinoembryonic antigen-related cell adhesion molecules, and signaling lymphocyte activation molecules. We discuss their distinct structural attributes, binding properties, and functions, shaped by evolutionary pressures to disarm specific immune pathways. We include several novel genes identified from extensive genome database surveys. An understanding of the properties and modes of action of these viral proteins may guide the development of novel immune-modulatory therapeutic tools. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Toxoplasma gondii exposes phosphatidylserine inducing a TGF-β1 autocrine effect orchestrating macrophage evasion

    International Nuclear Information System (INIS)

    Seabra, Sergio H.; Souza, Wanderley de; Matta, Renato A. da

    2004-01-01

    Toxoplasmosis is a worldwide disease caused by Toxoplasma gondii. Activated macrophages control T. gondii growth by nitric oxide (NO) production. However, T. gondii active invasion inhibits NO production, allowing parasite persistence. Here we show that the mechanism used by T. gondii to inhibit NO production persisting in activated macrophages depends on phosphatidylserine (PS) exposure. Masking PS with annexin-V on parasites or activated macrophages abolished NO production inhibition and parasite persistence. NO production inhibition depended on a transforming growth factor-β 1 (TGF-β 1 ) autocrine effect confirmed by the expression of Smad 2 and 3 in infected macrophages. TGF-β 1 led to inducible nitric oxide synthase (iNOS) degradation, actin filament (F-actin) depolymerization, and lack of nuclear factor-κB (NF-κB) in the nucleus. All these features were reverted by TGF-β 1 neutralizing antibody treatment. Thus, T. gondii mimics the evasion mechanism used by Leishmania amazonensis and also the anti-inflammatory response evoked by apoptotic cells

  6. Interferon Response and Viral Evasion by Members of the Family Rhabdoviridae

    Directory of Open Access Journals (Sweden)

    Matthias J. Schnell

    2009-11-01

    Full Text Available Like many animal viruses, those of the Rhabdoviridae family, are able to antagonize the type I interferon response and cause disease in mammalian hosts. Though these negative-stranded RNA viruses are very simple and code for as few as five proteins, they have been seen to completely abrogate the type I interferon response early in infection. In this review, we will discuss the viral organization and type I interferon evasion of rhabdoviruses, focusing on vesicular stomatitis virus (VSV and rabies virus (RABV. Despite their structural similarities, VSV and RABV have completely different mechanisms by which they avert the host immune response. VSV relies on the matrix protein to interfere with host gene transcription and nuclear export of anti-viral mRNAs. Alternatively, RABV uses its phosphoprotein to interfere with IRF-3 phosphorylation and STAT1 signaling. Understanding the virus-cell interactions and viral proteins necessary to evade the immune response is important in developing effective vaccines and therapeutics for this viral family.

  7. Anthropogenically enhanced chemical weathering and carbon evasion in the Yangtze Basin

    Science.gov (United States)

    Guo, Jingheng; Wang, Fushun; Vogt, Rolf David; Zhang, Yuhang; Liu, Cong-Qiang

    2015-01-01

    Chemical weathering is a fundamental geochemical process regulating the atmosphere-land-ocean fluxes and earth’s climate. It is under natural conditions driven primarily by weak carbonic acid that originates from atmosphere CO2 or soil respiration. Chemical weathering is therefore assumed as positively coupled with its CO2 consumption in contemporary geochemistry. Strong acids (i.e. sulfuric- and nitric acid) from anthropogenic sources have been found to influence the weathering rate and CO2 consumption, but their integrated effects remain absent in the world largest river basins. By interpreting the water chemistry and overall proton budget in the Yangtze Basin, we found that anthropogenic acidification had enhanced the chemical weathering by 40% during the past three decades, leading to an increase of 30% in solute discharged to the ocean. Moreover, substitution of carbonic acid by strong acids increased inorganic carbon evasion, offsetting 30% of the CO2 consumption by carbonic weathering. Our assessments show that anthropogenic loadings of sulfuric and nitrogen compounds accelerate chemical weathering but lower its CO2 sequestration. These findings have significant relevance to improving our contemporary global biogeochemical budgets. PMID:26150000

  8. Structural Conservation and Functional Diversity of the Poxvirus Immune Evasion (PIE) Domain Superfamily.

    Science.gov (United States)

    Nelson, Christopher A; Epperson, Megan L; Singh, Sukrit; Elliott, Jabari I; Fremont, Daved H

    2015-08-28

    Poxviruses encode a broad array of proteins that serve to undermine host immune defenses. Structural analysis of four of these seemingly unrelated proteins revealed the recurrent use of a conserved beta-sandwich fold that has not been observed in any eukaryotic or prokaryotic protein. Herein we propose to call this unique structural scaffolding the PIE (Poxvirus Immune Evasion) domain. PIE domain containing proteins are abundant in chordopoxvirinae, with our analysis identifying 20 likely PIE subfamilies among 33 representative genomes spanning 7 genera. For example, cowpox strain Brighton Red appears to encode 10 different PIEs: vCCI, A41, C8, M2, T4 (CPVX203), and the SECRET proteins CrmB, CrmD, SCP-1, SCP-2, and SCP-3. Characterized PIE proteins all appear to be nonessential for virus replication, and all contain signal peptides for targeting to the secretory pathway. The PIE subfamilies differ primarily in the number, size, and location of structural embellishments to the beta-sandwich core that confer unique functional specificities. Reported ligands include chemokines, GM-CSF, IL-2, MHC class I, and glycosaminoglycans. We expect that the list of ligands and receptors engaged by the PIE domain will grow as we come to better understand how this versatile structural architecture can be tailored to manipulate host responses to infection.

  9. Integration of Tax Administration to Curb Import and Domestic Tax Evasions in Ghana

    Directory of Open Access Journals (Sweden)

    John Adu Kwame

    2013-12-01

    Full Text Available As part of the Government of Ghana’s plans to maximize tax mobilization, it recently integrated its Regional Collection Agencies (RCA namely; the Internal Revenue Service (IRS, Customs Excise and Preventive service (CEPS and the Value Added Tax (VAT Services into the Ghana Revenue Authority (GRA. This research aims to find out whether Ghana’s tax administration reform of integrating the RCA into GRA has dealt with the inefficiencies in tax administration with respect to personal income tax, company tax, value added tax (VAT, import duties and self employed tax collection. To that end, questionnaires, interviews, observation and the Ministry of Finance and Economic Planning’s (MoFEP data on tax revenues were analyzed to establish whether there has been some level of efficiency in the mobilization of these taxes. From the field observation, it was discovered that many taxpayers in Ghana are not being issued receipts which could ensure proper accounting. Surprisingly, tax collectors from the RCAs were aware of this but refuse to act. Even though most of the taxes were not being collected, analysis of data from MoFEP showed an increase in revenue collection in the last four years and this has been attributed to the tax administration integration. The effect of tax evasion on the Ghanaian economy has also been thoroughly discussed

  10. An orbital emulator for pursuit-evasion game theoretic sensor management

    Science.gov (United States)

    Shen, Dan; Wang, Tao; Wang, Gang; Jia, Bin; Wang, Zhonghai; Chen, Genshe; Blasch, Erik; Pham, Khanh

    2017-05-01

    This paper develops and evaluates an orbital emulator (OE) for space situational awareness (SSA). The OE can produce 3D satellite movements using capabilities generated from omni-wheeled robot and robotic arm motion methods. The 3D motion of a satellite is partitioned into the movements in the equatorial plane and the up-down motions in the vertical plane. The 3D actions are emulated by omni-wheeled robot models while the up-down motions are performed by a stepped-motor-controlled-ball along a rod (robotic arm), which is attached to the robot. For multiple satellites, a fast map-merging algorithm is integrated into the robot operating system (ROS) and simultaneous localization and mapping (SLAM) routines to locate the multiple robots in the scene. The OE is used to demonstrate a pursuit-evasion (PE) game theoretic sensor management algorithm, which models conflicts between a space-based-visible (SBV) satellite (as pursuer) and a geosynchronous (GEO) satellite (as evader). The cost function of the PE game is based on the informational entropy of the SBV-tracking-GEO scenario. GEO can maneuver using a continuous and low thruster. The hard-in-loop space emulator visually illustrates the SSA problem solution based PE game.

  11. Implementation of a mobile base with evasion of obstacles using ROS navigation

    International Nuclear Information System (INIS)

    Arauz Villegas, Carolina

    2013-01-01

    A mobile base is implemented with evasion of obstacles using ROS Navigation. The simulation of that mobile base is performed with the 2D Stage simulator, firstly; and once understanded the operation of Navigation has proceeded to build the mobile base. The mobile base has had two DC motors, an Asus Xtion sensor, a netbook and a stm32f4-discovery microcontroller. ROS in the netbook was installed and then serial communication over USB was achieved between the netbook and the microcontroller. The microcontroller has received the velocity data sent by move_base of navigation through that communication and sends the odometry data back. A PWM control is implemented for the driving and for the speed of the motors having a control PI for the cycle of work of the same. The encoder interface of the microcontroller was used for the data acquisition of odometry. The communication between ROS and the mobile base was integrated to the navigation, which has allowed to generate mapping, location and move safely from a starting point to a point of arrival sending speed messages. (author) [es

  12. The genome of obligately intracellular Ehrlichia canis revealsthemes of complex membrane structure and immune evasion strategies

    Energy Technology Data Exchange (ETDEWEB)

    Mavromatis, K.; Kuyler Doyle, C.; Lykidis, A.; Ivanova, N.; Francino, P.; Chain, P.; Shin, M.; Malfatti, S.; Larimer, F.; Copeland,A.; Detter, J.C.; Land, M.; Richardson, P.M.; Yu, X.J.; Walker, D.H.; McBride, J.W.; Kyrpides, N.C.

    2005-09-01

    Ehrlichia canis, a small obligately intracellular, tick-transmitted, gram-negative, a-proteobacterium is the primary etiologic agent of globally distributed canine monocytic ehrlichiosis. Complete genome sequencing revealed that the E. canis genome consists of a single circular chromosome of 1,315,030 bp predicted to encode 925 proteins, 40 stable RNA species, and 17 putative pseudogenes, and a substantial proportion of non-coding sequence (27 percent). Interesting genome features include a large set of proteins with transmembrane helices and/or signal sequences, and a unique serine-threonine bias associated with the potential for O-glycosylation that was prominent in proteins associated with pathogen-host interactions. Furthermore, two paralogous protein families associated with immune evasion were identified, one of which contains poly G:C tracts, suggesting that they may play a role in phase variation and facilitation of persistent infections. Proteins associated with pathogen-host interactions were identified including a small group of proteins (12) with tandem repeats and another with eukaryotic-like ankyrin domains (7).

  13. Tumor markers in clinical oncology

    International Nuclear Information System (INIS)

    Novakovic, S.

    2004-01-01

    The subtle differences between normal and tumor cells are exploited in the detection and treatment of cancer. These differences are designated as tumor markers and can be either qualitative or quantitative in their nature. That means that both the structures that are produced by tumor cells as well as the structures that are produced in excessive amounts by host tissues under the influence of tumor cells can function as tumor markers. Speaking in general, the tumor markers are the specific molecules appearing in the blood or tissues and the occurrence of which is associated with cancer. According to their application, tumor markers can be roughly divided as markers in clinical oncology and markers in pathology. In this review, only tumor markers in clinical oncology are going to be discussed. Current tumor markers in clinical oncology include (i) oncofetal antigens, (ii) placental proteins, (iii) hormones, (iv) enzymes, (v) tumor-associated antigens, (vi) special serum proteins, (vii) catecholamine metabolites, and (viii) miscellaneous markers. As to the literature, an ideal tumor marker should fulfil certain criteria - when using it as a test for detection of cancer disease: (1) positive results should occur in the early stages of the disease, (2) positive results should occur only in the patients with a specific type of malignancy, (3) positive results should occur in all patients with the same malignancy, (4) the measured values should correlate with the stage of the disease, (5) the measured values should correlate to the response to treatment, (6) the marker should be easy to measure. Most tumor markers available today meet several, but not all criteria. As a consequence of that, some criteria were chosen for the validation and proper selection of the most appropriate marker in a particular malignancy, and these are: (1) markers' sensitivity, (2) specificity, and (3) predictive values. Sensitivity expresses the mean probability of determining an elevated tumor

  14. Combined tumor therapy

    International Nuclear Information System (INIS)

    Wrba, H.

    1990-01-01

    This comprehensive survey of current methods and achievements first takes a look at the two basic therapies, devoting a chapter each to the surgery and radiotherapy of tumors. The principal subjects of the book, however, are the systemic, adjuvant therapy, biological therapies, hyperthermia and various other therapies (as e.g. treatment with ozone, oxygen, or homeopathic means), and psychotherapy. (MG) With 54 figs., 86 tabs [de

  15. "Cancer tumor".

    Science.gov (United States)

    Bronshtehn, V. A.

    The title is a phrase borrowed from a speech by a Leningrad pressman, V. E. Lvov, who called upon those attending a theoretical conference on ideological issues in astronomy held by the Leningrad Branch of the All-Union Astronomic and Geodetic Society (13 - 4 December 1948), "to make a more radical emphasis on the negative role of relativistic cosmology which is a cancer tumor disintegrating the contemporary astronomy theory, and a major ideological enemy of a materialist astronomy".

  16. SPHINGOSINE-1 PHOSPHATE: A NEW MODULATOR OF IMMUNE PLASTICITY IN THE TUMOR MICROENVIRONMENT

    Directory of Open Access Journals (Sweden)

    Yamila I Rodriguez

    2016-10-01

    Full Text Available In the last 15 years, increasing evidences demonstrate a strong link between sphingosine-1-phosphate (S1P in both normal physiology and progression of different diseases, including cancer and inflammation. Indeed, numerous studies show that tissue levels of this sphingolipid metabolite are augmented in many cancers, affecting survival, proliferation, angiogenesis and metastatic spread. Recent insights into the possible role of S1P as a therapeutic target has attracted enormous attention and opened new opportunities in this evolving field. In this review we will focus on the role of S1P in cancer with particular emphasis in new developments that highlight the many functions of this sphingolipid in the tumor microenvironment. We will discuss how S1P modulates phenotypic plasticity of macrophages and mast cells, tumor-induced immune evasion, differentiation and survival of immune cells in the tumor milieu, interaction between cancer and stromal cells and hypoxic response.

  17. Pituitary gland tumors; Hypophysentumoren

    Energy Technology Data Exchange (ETDEWEB)

    Jesser, J.; Schlamp, K.; Bendszus, M. [Radiologische Klinik, Universitaetsklinikum Heidelberg, Abteilung fuer Neuroradiologie, Heidelberg (Germany)

    2014-10-15

    This article gives an overview of the most common tumors of the pituitary gland and the differential diagnostics with special emphasis on radiological diagnostic criteria. A selective search of the literature in PubMed was carried out. Pituitary adenomas constitute 10-15 % of all intracranial tumors and are the most common tumors of the sellar region. Tumors smaller than 1 cm in diameter are called microadenomas while those larger than 1 cm in diameter are called macroadenomas. Approximately 65 % of pituitary gland adenomas secrete hormones whereby approximately 50 % secrete prolactin, 10 % secrete growth hormone (somatotropin) and 6 % secrete corticotropin. Other tumors located in the sella turcica can also cause endocrinological symptoms, such as an oversecretion of pituitary hormone or pituitary insufficiency by impinging on the pituitary gland or its stalk. When tumors spread into the space cranial to the sella turcica, they can impinge on the optic chiasm and cause visual disorders. A common differential diagnosis of a sellar tumor is a craniopharyngeoma. In children up to 10 % of all intracranial tumors are craniopharyngeomas. Other differential diagnoses for sellar tumors are metastases, meningiomas, epidermoids and in rare cases astrocytomas, germinomas or Rathke cleft cysts As these tumors are located in an anatomically complex region of the skull base and are often very small, a highly focused imaging protocol is required. The currently favored modality is magnetic resonance imaging (MRI) with the administration of a contrast agent. The sellar region should be mapped in thin slices. In cases of suspected microadenoma the imaging protocol should also contain a sequence with dynamic contrast administration in order to assess the specific enhancement characteristics of the tumor and the pituitary gland. (orig.) [German] Diese Arbeit ist eine Uebersicht ueber die haeufigsten Hypophysentumoren und deren Differenzialdiagnosen mit Augenmerk auf die

  18. mRNA-based vaccines synergize with radiation therapy to eradicate established tumors

    International Nuclear Information System (INIS)

    Fotin-Mleczek, Mariola; Zanzinger, Kai; Heidenreich, Regina; Lorenz, Christina; Kowalczyk, Aleksandra; Kallen, Karl-Josef; Huber, Stephan M

    2014-01-01

    The eradication of large, established tumors by active immunotherapy is a major challenge because of the numerous cancer evasion mechanisms that exist. This study aimed to establish a novel combination therapy consisting of messenger RNA (mRNA)-based cancer vaccines and radiation, which would facilitate the effective treatment of established tumors with aggressive growth kinetics. The combination of a tumor-specific mRNA-based vaccination with radiation was tested in two syngeneic tumor models, a highly immunogenic E.G7-OVA and a low immunogenic Lewis lung cancer (LLC). The molecular mechanism induced by the combination therapy was evaluated via gene expression arrays as well as flow cytometry analyses of tumor infiltrating cells. In both tumor models we demonstrated that a combination of mRNA-based immunotherapy with radiation results in a strong synergistic anti-tumor effect. This was manifested as either complete tumor eradication or delay in tumor growth. Gene expression analysis of mouse tumors revealed a variety of substantial changes at the tumor site following radiation. Genes associated with antigen presentation, infiltration of immune cells, adhesion, and activation of the innate immune system were upregulated. A combination of radiation and immunotherapy induced significant downregulation of tumor associated factors and upregulation of tumor suppressors. Moreover, combination therapy significantly increased CD4 + , CD8 + and NKT cell infiltration of mouse tumors. Our data provide a scientific rationale for combining immunotherapy with radiation and provide a basis for the development of more potent anti-cancer therapies. The online version of this article (doi:10.1186/1748-717X-9-180) contains supplementary material, which is available to authorized users

  19. Understanding Brain Tumors

    Science.gov (United States)

    ... to Know About Brain Tumors . What is a Brain Tumor? A brain tumor is an abnormal growth
 ... Tumors” from Frankly Speaking Frankly Speaking About Cancer: Brain Tumors Download the full book Questions to ask ...

  20. Brain tumor - primary - adults

    Science.gov (United States)

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...