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Sample records for targeting ebv-expressing lymphoproliferative

  1. Epstein-Barr Virus-related post-transplant lymphoproliferative disorders: pathogenetic insights for targeted therapy.

    Science.gov (United States)

    Nourse, J P; Jones, K; Gandhi, M K

    2011-05-01

    Post-transplant lymphoproliferative disorder (PTLD) is a spectrum of major, life-threatening lymphoproliferative diseases occurring in the post-transplant setting. The majority of PTLD is of B-cell origin and is associated with several risk factors, the most significant being Epstein-Barr virus (EBV) infection. EBV's in vitro transforming abilities, distinctive latency, clonality within the malignant cells and response to targeted therapies implicate a critical role in the biology of PTLD. This minireview focuses on EBV-related PTLD pathogenesis, in particular the interplay between aspects of the EBV life cycle and latency with nonviral factors resulting in the wide spectrum of histology and clinical presentations encountered in PTLD. With the increased prevalence of transplantation a rise in the incidence of PTLD may be expected. Therefore the importance of laboratory and animal models in the understanding of PTLD and the development of novel therapeutic approaches is discussed. © 2011 The Authors Journal compilation © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

  2. Viral induction and targeted inhibition of galectin-1 in EBV+ posttransplant lymphoproliferative disorders.

    Science.gov (United States)

    Ouyang, Jing; Juszczynski, Przemyslaw; Rodig, Scott J; Green, Michael R; O'Donnell, Evan; Currie, Treeve; Armant, Myriam; Takeyama, Kunihiko; Monti, Stefano; Rabinovich, Gabriel A; Ritz, Jerome; Kutok, Jeffery L; Shipp, Margaret A

    2011-04-21

    Posttransplant lymphoproliferative disorders (PTLDs) are potentially fatal, EBV-driven B-cell malignancies that develop in immunocompromised solid organ or hematopoietic stem cell recipients. In PTLD, the expression of EBV proteins, including latent membrane protein 1 (LMP1) and LMP2A, viral immune evasion strategies, and impaired host immune surveillance foster the proliferation of EBV-transformed B cells. Current PTLD treatment strategies include reduction of immunosuppression, which increases the risk of graft rejection, anti-CD20 treatment, combination chemotherapy, and administration of EBV-specific cytotoxic T cells. In the present study, we report that EBV-transformed lymphoblastoid B-cell lines (LCLs) and primary PTLDs overexpress galectin-1 (Gal1), a carbohydrate-binding lectin that induces tolerogenic dendritic cells and triggers the selective apoptosis of CD4(+) Th1 and Th17 cells and cytotoxic T cells. In transcriptional reporter assays, LMP2A and LMP1 each increased Gal1-driven luciferase expression, and the combination of LMP2A and LMP1 was additive. In addition, small interfering RNA (siRNA)-mediated depletion of LMP2A decreased Gal1 protein abundance in EBV-transformed LCLs. Gal1 expression in LCLs was dependent on both activating protein 1 (AP-1) and PI3K. A newly developed neutralizing Gal1 mAb selectively inhibited Gal1-mediated apoptosis of EBV-specific CD8(+) T cells. Given the tolerogenic and immunosuppressive function of Gal1, antibody-mediated Gal1 neutralization may represent a novel immunotherapeutic strategy for PTLD and other Gal1-expressing tumors.

  3. Constitutive AP-1 activity and EBV infection induce PD-L1 in Hodgkin lymphomas and posttransplant lymphoproliferative disorders: implications for targeted therapy.

    Science.gov (United States)

    Green, Michael R; Rodig, Scott; Juszczynski, Przemyslaw; Ouyang, Jing; Sinha, Papiya; O'Donnell, Evan; Neuberg, Donna; Shipp, Margaret A

    2012-03-15

    Programmed cell death ligand 1 (PD-L1) is a molecule expressed on antigen-presenting cells that engages the PD-1 receptor on T cells and inhibits T-cell receptor signaling. The PD-1 axis can be exploited by tumor cells to dampen host antitumor immune responses and foster tumor cell survival. PD-1 blockade has shown promise in multiple malignancies but should be directed toward patients in whom it will be most effective. In recent studies, we found that the chromosome 9p24.1 amplification increased the gene dosage of PD-L1 and its induction by JAK2 in a subset of patients with classical Hodgkin lymphoma (cHL). However, cHLs with normal 9p24.1 copy numbers also expressed detectable PD-L1, prompting analyses of additional PD-L1 regulatory mechanisms. Herein, we utilized immunohistochemical, genomic, and functional analyses to define alternative mechanisms of PD-L1 activation in cHL and additional EBV(+) lymphoproliferative disorders. We identified an AP-1-responsive enhancer in the PD-L1 gene. In cHL Reed-Sternberg cells, which exhibit constitutive AP-1 activation, the PD-L1 enhancer binds AP-1 components and increases PD-L1 promoter activity. In addition, we defined Epstein-Barr virus (EBV) infection as an alternative mechanism for PD-L1 induction in cHLs with diploid 9p24.1. PD-L1 was also expressed by EBV-transformed lymphoblastoid cell lines as a result of latent membrane protein 1-mediated, JAK/STAT-dependent promoter and AP-1-associated enhancer activity. In addition, more than 70% of EBV(+) posttransplant lymphoproliferative disorders expressed detectable PD-L1. AP-1 signaling and EBV infection represent alternative mechanisms of PD-L1 induction and extend the spectrum of tumors in which to consider PD-1 blockade.

  4. Constitutive AP-1 Activity and EBV Infection Induce PD-L1 in Hodgkin Lymphomas and Post-transplant Lymphoproliferative Disorders: Implications for Targeted Therapy

    Science.gov (United States)

    Green, Michael R.; Rodig, Scott; Juszczynski, Przemyslaw; Ouyang, Jing; Sinha, Papiya; O’Donnell, Evan; Neuberg, Donna; Shipp, Margaret A.

    2012-01-01

    Purpose Programmed cell death ligand 1 (PD-L1) is a molecule expressed on antigen-presenting cells that engages the PD-1 receptor on T cells and inhibits T-cell receptor signaling. The PD-1 axis can be exploited by tumor cells to dampen host anti-tumor immune responses and foster tumor cell survival. PD-1 blockade has shown promise in multiple malignancies but should be directed towards patients in whom it will be most effective. In recent studies, we found that the chromosome 9p24.1 amplification increased the gene dosage of PD-L1 and its induction by JAK2 in a subset of patients with classical Hodgkin lymphoma (cHL). However, cHLs with normal 9p24.1 copy numbers also expressed detectable PD-L1, prompting analyses of additional PD-L1 regulatory mechanisms. Experimental Design Herein, we utilized immunohistochemical, genomic and functional analyses to define alternative mechanisms of PD-L1 activation in cHL and additional EBV+ lymphoproliferative disorders. Results We identified an AP-1-responsive enhancer in the PD-L1 gene. In cHL Reed Sternberg cells, which exhibit constitutive AP-1 activation, the PD-L1 enhancer binds AP-1 components and increases PD-L1 promoter activity. In addition, we defined EBV infection as an alternative mechanism for PD-L1 induction in cHLs with diploid 9p24.1. PD-L1 was also expressed by EBV-transformed lymphoblastoid cell lines as a result of latent membrane protein 1-mediated, JAK/STAT-dependent promoter and AP-1-associated enhancer activity. In addition, over 70% of EBV+ post-transplant lymphoproliferative disorders expressed detectable PD-L1. Conclusions AP-1 signaling and EBV infection represent alternative mechanisms of PD-L1 induction and extend the spectrum of tumors in which to consider PD-1 blockade. PMID:22271878

  5. Frequent hypermethylation of DBC1 in malignant lymphoproliferative neoplasms

    DEFF Research Database (Denmark)

    Grønbæk, Karin Elmegård; Ralfkiaer, U.; Dahl, C.

    2008-01-01

    Allelic loss at chromosome 9q31-34 is a frequent event in many lymphoproliferative malignancies. Here, we examined DBC1 at 9q33.1 as a potential target in lymphomagenesis. DBC1 is a putative tumor suppressor that has been shown to be involved in the regulation of cell growth and programmed cell d...

  6. Mapping the x-linked lymphoproliferative syndrome

    International Nuclear Information System (INIS)

    Skare, J.C.; Milunsky, A.; Byron, K.S.; Sullivan, J.L.

    1987-01-01

    The X-linked lymphoproliferative syndrome is triggered by Epstein-Barr virus infection and results in fatal mononucleosis, immunodeficiency, and lymphoproliferative disorders. This study shows that the mutation responsible for X-linked lymphoproliferative syndrome is genetically linked to a restriction fragment length polymorphism detected with the DXS42 probe (from Xq24-q27). The most likely recombination frequency between the loci is 4%, and the associated logarithm of the odds is 5.26. Haplotype analysis using flanking restriction fragment length polymorphism markers indicates that the locus for X-linked lymphoproliferative syndrome is distal to probe DXS42 but proximal to probe DXS99 (from Xq26-q27). It is now possible to predict which members of a family with X-linked lymphoproliferative syndrome are carrier females and to diagnose the syndrome prenatally

  7. Rapidly progressive post-transplant lymphoproliferative disease ...

    African Journals Online (AJOL)

    of patients, and just over half of these affect only the brain.1,2. Presentation is often late, with mortality rates in excess of 60%.2. PTLD comprises a heterogeneous group of lymphoproliferative diseases, ranging from the early indolent disorders that resemble infectious mononucleosis, through to polymorphic PTLD and onto.

  8. Posttransplant lymphoproliferative disorder: a pictorial review

    International Nuclear Information System (INIS)

    Burney, K.; Bradley, M.; Lyburn, I.; Hopkins, R.; Buckley, A.; Rye, A.

    2006-01-01

    Posttransplant lymphoproliferative disorder (PTLD) is a serious and potentially fatal complication after solid organ and haemopoietic stem cell transplantation. The frequency of PTLD varies with the type of organ transplant but overall it affects 2-10% of all solid organ transplant recipients. Most cases develop within 1 year after the transplant, although occasional cases present 5-10 years later. Posttransplant lymphoproliferative disorder is clinically and pathologically heterogeneous - the majority are of the non-Hodgkin's lymphoma type, whereas Hodgkin's lymphoma arising after transplantation is rare. We have retrospectively reviewed patients with a histological diagnosis of PTLD after a solid organ transplant. We present the imaging features and a clinical review of this condition. Early diagnosis of PTLD may alter the management and outcome of the disease. The radiologist can play a vital role in establishing the diagnosis by imaging features supplemented with percutaneous biopsy and also in monitoring the disease response to treatment

  9. Mutlifocal osseous posttransplantation lymphoproliferative disorder: case report

    Energy Technology Data Exchange (ETDEWEB)

    Lo, Ryan [University of Chicago, Department of Radiology, Chicago, IL (United States); Michalicek, Zachary [Northshore University Healthsystems, Department of Pathology, Evanston, IL (United States); Lazarus, Martin [Northshore University Healthsystems, Department of Radiology, Evanston, IL (United States)

    2015-02-14

    Posttransplant lymphoproliferative disorder (PTLD) is a known complication of organ transplantation, but musculoskeletal involvement of PTLD remains very rare. We present a case of recurrent PTLD of the bone in a heart transplant patient that was misdiagnosed as gout for several years. There are only a few cases of osseous PTLD in the literature, and we hope to better characterize its imaging findings on multiple imaging modalities. (orig.)

  10. Recurrent Oral Inflammation in Autoimmune Lymphoproliferative Syndrome

    OpenAIRE

    Pac, Malgorzata; Olczak-Kowalczyk, Dorota; Wolska-Kuśnierz, Beata; Piątosa, Barbara; Górska, Renata; Bernatowska, Ewa

    2014-01-01

    Abstract   Background and aim: Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of abnormal lymphocyte survival caused by dysregulation of the Fas apoptotic pathway. In ALPS defective lymphocyte apoptosis manifests as a chronic, nonmalignant lymphadenopathy and/or splenomegaly/hepatosplenomegaly, expansion of double negative T cell (DNTC) – CD4-CD8-TCRαβ+ T cells, autoimmune cytopenias and other autoimmune diseases.  Patients demonstrate oral lesions which have not yet been repo...

  11. Lacrimal sac lymphoproliferative lesion: case report.

    Science.gov (United States)

    Coloma-González, I; Ruíz-García, L; Ceriotto, A; Corredor-Casas, S; Salcedo-Casillas, G

    2015-03-01

    The case is presented of a 51 year-old woman with a firm mass at the medial canthus of the right eye of five years onset. A low-grade lymphoproliferative lesion (reactive lymphoid hyperplasia) was diagnosed from an excisional biopsy Lacrimal sac tumors are rare, with a peak incidence in the fifth decade of life. The initial clinical features are epiphora and medial canthus swelling. As it mimics nasolacrimal duct obstruction, up to 40% of these tumors are misdiagnosed until undergoing surgery. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  12. Lymphoproliferative disorders in Oxford renal transplant recipients.

    Science.gov (United States)

    Bates, W D; Gray, D W R; Dada, M A; Chetty, R; Gatter, K C; Davies, D R; Morris, P J

    2003-06-01

    Increased cancer incidence, particularly lymphoproliferative disease, is a complication of immunosuppression in organ transplantation. Non-Hodgkin's lymphomas (NHLs) occur frequently during the first year after transplantation, more so in North America than in Europe. This study audited and correlated the demographic, clinical, pathological, and outcome features of post-transplant lymphoproliferative disorders (PTLDs) in a large centre in Oxford, and assessed whether the time of onset fitted more with the European or North American pattern. There were 1383 renal transplants in the study period and 27 patients developed lymphoma: 26 NHLs and one Hodgkin's disease (1.95%). Four of the patients never received cyclosporin. The mean time of diagnosis after transplant was 46 months. Most tumours (21/27) presented extranodally. Management included reduction of immunosuppression, surgical excision, antiviral treatment, radiotherapy, and chemotherapy. Three patients presented in the first post-transplant year-0.34% of cyclosporin managed patients-similar to the North American incidence, although the incidence of extranodal late PTLDs was also high (mean onset, 36 months v 15 months international mean). Post-transplant lymphomas were the most common malignancy associated with death in transplant patients. PTLDs occurred in 2% of renal transplant patients, presenting both in the first year in association with cyclosporin use, as in North America, but also in subsequent years, giving an overall presentation time later than the international mean. The disease usually presented extranodally, accounting for the wide range of symptoms and signs. Despite awareness and active management, the disease contributed to death in more that 50% of patients with PTLDs.

  13. Tubulointerstitial Nephritis in a Patient With Probable Autoimmune Lymphoproliferative Syndrome

    DEFF Research Database (Denmark)

    Glerup, Mia; Herlin, Troels; Rittig, Søren

    2013-01-01

    Autoimmune lymphoproliferative syndrome (ALPS) is caused by a nonmalignant defective Fas-mediated apoptosis. The main clinical manifestations are chronic lymphadenopathy, splenomegaly, and autoimmune cytopenia. Most patients with ALPS have a FAS germline mutation. ALPS has occasionally been......-vessel vasculitis with normal glomeruli and inflammation in the interstitium. The patient responded to prednisolone treatment and obtained a full renal recovery. Symptoms of connective tissue disorder supervened and after the development of more pronounced splenomegaly, a diagnosis of ALPS was confirmed....

  14. Hepatitis C virus-related lymphoproliferative disorders: An overview

    OpenAIRE

    Zignego, Anna Linda; Giannini, Carlo; Ferri, Clodoveo

    2007-01-01

    Hepatitis C virus (HCV) is a global health problem affecting 3% of the world's population (about 180 million) and a cause of both hepatic and extrahepatic diseases. B-cell lymphoproliferative disorders, whose prototype is mixed cryoglobulinemia, represent the most closely related as well as the most investigated HCV-related extrahepatic disorder. The association between extrahepatic (lymphoma) as well as hepatic malignancies (hepatocellular carcinoma) has justified the inclusion of HCV among ...

  15. Post-kidney transplant large bowel lymphoproliferative disorder

    Directory of Open Access Journals (Sweden)

    Neeraj Singh

    2014-01-01

    Full Text Available Epstein-Barr virus (EBV-associated post-transplant lymphoproliferative disorder (PTLD is a serious complication of organ transplantation. The gastrointestinal (GI tract is a common site involved, but non-specific signs and symptoms often delay the diagnosis. We report a case of EBV-associated GI-PTLD in a 68-year-old kidney transplant patient who received the kidney ten months earlier. He presented with chronic diarrhea and developed massive pneumo-peritoneum secondary to multiple colonic perforations.

  16. Thymic Hyperplasia after Lung Transplantation Imitating Posttransplant Lymphoproliferative Disorder

    Science.gov (United States)

    Steger, Christina Maria; Semsroth, Severin; Hager, Thomas; Rieker, Ralf; Müller, Ludwig

    2011-01-01

    Thymic hyperplasia is usually associated with the treatment of malignant tumours and is sometimes linked with endocrine diseases. For the first time, we report a case of thymic hyperplasia in a patient 2 years after bilateral lung transplantation. Contrast-enhanced chest CT scan was highly suspicious for a posttransplant lymphoma or thymoma. Therefore, the patient received total thymectomy. Excised specimens were sent to the Department of Pathology. Unexpectedly, the histological examination revealed hyperplastic thymic tissue without evidence for a posttransplant lymphoproliferative disorder or malignancy. PMID:23213605

  17. Post-transplant lymphoproliferative disorder following kidney transplantation

    DEFF Research Database (Denmark)

    Maksten, Eva Futtrup; Vase, Maja Ølholm; Kampmann, Jan

    2016-01-01

    Post-transplant lymphoproliferative disorder (PTLD) incidence is difficult to determine, mainly because both early and other lesions may go unrecognized and unregistered. Few studies have included systematic pathology review to maximize case identification and decide more accurately PTLD frequency...... after long-term post-transplantation follow-up. A retrospective population-based cohort study including all kidney transplant recipients at two Danish centres (1990-2011; population covered 3.1 million; 2175 transplantations in 1906 patients). Pathology reports were reviewed for all patient biopsies...

  18. Thymic Hyperplasia after Lung Transplantation Imitating Posttransplant Lymphoproliferative Disorder

    Directory of Open Access Journals (Sweden)

    Christina Maria Steger

    2011-01-01

    Full Text Available Thymic hyperplasia is usually associated with the treatment of malignant tumours and is sometimes linked with endocrine diseases. For the first time, we report a case of thymic hyperplasia in a patient 2 years after bilateral lung transplantation. Contrast-enhanced chest CT scan was highly suspicious for a posttransplant lymphoma or thymoma. Therefore, the patient received total thymectomy. Excised specimens were sent to the Department of Pathology. Unexpectedly, the histological examination revealed hyperplastic thymic tissue without evidence for a posttransplant lymphoproliferative disorder or malignancy.

  19. Oncogenic Notch signaling in T-cell and B-cell lymphoproliferative disorders.

    Science.gov (United States)

    Chiang, Mark Y; Radojcic, Vedran; Maillard, Ivan

    2016-07-01

    This article highlights recent discoveries about Notch activation and its oncogenic functions in lymphoid malignancies, and discusses the therapeutic potential of Notch inhibition. NOTCH mutations arise in a broad spectrum of lymphoid malignancies and are increasingly scrutinized as putative therapeutic targets. In T-cell acute lymphoblastic leukemia (T-ALL), NOTCH1 mutations affect the extracellular negative regulatory region and lead to constitutive Notch activation, although mutated receptors remain sensitive to Notch ligands. Other NOTCH1 mutations in T-ALL and NOTCH1/2 mutations in multiple B-cell malignancies truncate the C-terminal proline (P), glutamic acid (E), serine (S), threonine (T)-rich (PEST) domain, leading to decreased Notch degradation after ligand-mediated activation. Thus, targeting Notch ligand-receptor interactions could provide therapeutic benefits. In addition, we discuss recent reports on clinical testing of Notch inhibitors in T-ALL that influenced contemporary thinking on the challenges of targeting Notch in cancer. We review advances in the laboratory to address these challenges in regards to drug targets, the Notch-driven metabolome, and the sophisticated protein-protein interactions at Notch-dependent superenhancers that underlie oncogenic Notch functions. Notch signaling is a recurrent oncogenic pathway in multiple T- and B-cell lymphoproliferative disorders. Understanding the complexity and consequences of Notch activation is critical to define optimal therapeutic strategies targeting the Notch pathway.

  20. Allogeneic hematopoietic stem cell transplantation in patients with advanced indolent lymphoproliferative disorders

    Directory of Open Access Journals (Sweden)

    Ana Marcela Rojas Fonseca-Hial

    2016-06-01

    Full Text Available ABSTRACT BACKGROUND: The role of allogeneic hematopoietic stem cell transplantation for advanced indolent lymphoproliferative disorders remains to be established. OBJECTIVE: This paper aims to describe the results of allogeneic hematopoietic stem cell transplantation in patients with advanced indolent lymphoproliferative disorders. METHODS: This article reports on 29 adult patients submitted to allogeneic transplantations from 1997 to 2010. RESULTS: Most had follicular non-Hodgkin lymphoma (n = 14 or chronic lymphocytic leukemia (n = 12. The median age was 44 years (range: 24-53 years and 65% of patients were male. Only 21% had had access to rituximab and 45% to fludarabine. All had advanced disease (stage IV with partial response or stable disease. Most underwent myeloablative conditioning n = 17 - 59%. In this scenario, refractory disease was observed in seven (24% patients, the 100-day mortality rate was 17% (n = 5 and relapse occurred in four patients (18%. The main cause of death throughout the follow up was refractory disease in six of the 12 patients who died. Moderate and severe chronic graft-versus-host disease was frequent; about 41% of 24 patients analyzed. The overall survival rates and disease free survival at 42 months were 56.7% and 45.4%, respectively. According to Kaplan-Meyer analysis, the median time from diagnosis to transplant predicted the overall survival; however age, gender and conditioning regimen did not predict the prognosis. It was impossible to reach other conclusions because of the small sample size in this study. CONCLUSIONS: The role of allogeneic transplantations should be re-evaluated in the era of targeted therapy.

  1. A Rare Presentation of Isolated CNS Posttransplantation Lymphoproliferative Disorder

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    Jaime Morris

    2017-01-01

    Full Text Available Posttransplantation lymphoproliferative disorder (PTLD is a recognized and extremely morbid complication of solid organ transplantation, but central nervous system involvement, particularly in isolation, is rare. There are no standardized treatment strategies for PTLD, though commonly used strategies include reduction of immunosuppression, chemotherapy, rituximab, radiation, and surgery. We present a case of an unusual morphologic variant of primary central nervous system PTLD with successful response to rituximab and cranial radiation. A 69-year-old Asian male, who underwent postrenal transplant nine years earlier, presented with a one-month history of new onset seizure activity. His evaluation revealed multiple brain lesions on magnetic resonance imaging (MRI, as well as serologic and cerebrospinal fluid studies which were positive for Epstein-Barr Virus (EBV infection. Ultimately, he underwent craniotomy with tissue biopsy with the final pathology report showing posttransplant lymphoproliferative disorder, polymorphic type. The patient was managed with reduction in immunosuppression, rituximab therapy, and cranial radiation treatments. He had demonstrated marked improvement in his neurologic function and was ultimately discharged to inpatient rehabilitation facility.

  2. Leflunomide/teriflunomide inhibit Epstein-Barr virus (EBV)- induced lymphoproliferative disease and lytic viral replication.

    Science.gov (United States)

    Bilger, Andrea; Plowshay, Julie; Ma, Shidong; Nawandar, Dhananjay; Barlow, Elizabeth A; Romero-Masters, James C; Bristol, Jillian A; Li, Zhe; Tsai, Ming-Han; Delecluse, Henri-Jacques; Kenney, Shannon C

    2017-07-04

    EBV infection causes mononucleosis and is associated with specific subsets of B cell lymphomas. Immunosuppressed patients such as organ transplant recipients are particularly susceptible to EBV-induced lymphoproliferative disease (LPD), which can be fatal. Leflunomide (a drug used to treat rheumatoid arthritis) and its active metabolite teriflunomide (used to treat multiple sclerosis) inhibit de novo pyrimidine synthesis by targeting the cellular dihydroorotate dehydrogenase, thereby decreasing T cell proliferation. Leflunomide also inhibits the replication of cytomegalovirus and BK virus via both "on target" and "off target" mechanisms and is increasingly used to treat these viruses in organ transplant recipients. However, whether leflunomide/teriflunomide block EBV replication or inhibit EBV-mediated B cell transformation is currently unknown. We show that teriflunomide inhibits cellular proliferation, and promotes apoptosis, in EBV-transformed B cells in vitro at a clinically relevant dose. In addition, teriflunomide prevents the development of EBV-induced lymphomas in both a humanized mouse model and a xenograft model. Furthermore, teriflunomide inhibits lytic EBV infection in vitro both by preventing the initial steps of lytic viral reactivation, and by blocking lytic viral DNA replication. Leflunomide/teriflunomide might therefore be clinically useful for preventing EBV-induced LPD in patients who have high EBV loads yet require continued immunosuppression.

  3. A typical aspects of intrathoracic posttransplantation lymphoproliferative disorders

    Energy Technology Data Exchange (ETDEWEB)

    Beigelman, C. [Dept. of Radiology, Hopital Pitie-Salpetriere, 75 Paris (France); Leblond, V. [Dept. of Hematology, Hopital Pitie-Salpetriere, 75 Paris (France); Suberbielle, C. [Dept. of Hematology, Hopital Pitie-Salpetriere, 75 Paris (France); Lenoir, S. [Dept. of Radiology, Hopital Pitie-Salpetriere, 75 Paris (France); Dorent, R. [Dept. of Thoracic Surgery, Hopital Pitie-Salpetriere, 75 Paris (France); Grenier, P. [Dept. of Radiology, Hopital Pitie-Salpetriere, 75 Paris (France)

    1995-11-01

    Posttransplant lymphoproliferative disorders (PTLD), developing after immunosuppressive therapy in human organ-graft recipients, are, for the most part, Epstein-Barr virus-induced. The earlier the diagnosis is made, the greater the potential for reversibility. The chest radiographs and CT scans of 10 patients with thoracic locations of PTLD were reviewed. Mediastinal and hilar adenopathy, pulmonary nodules, and pleural thickening or effusion were encountered. The incidence of partial resolution with clinical remission appears to be noteworthy, and in all likelihood is related to the extensive necrosis that is frequently seen. Slow regression, transitory deterioration in one case, and localization only on the graft side in two cases, were observed. These morphological and evolutionary peculiarities must be known in order to optimize the diagnosis, and thus the prognosis, of these very original disorders. (orig.)

  4. Post-transplantation lymphoproliferative disorder: the spectrum of imaging appearances

    Energy Technology Data Exchange (ETDEWEB)

    Scarsbrook, A.F. [Department of Radiology, John Radcliffe Hospital, Oxford (United Kingdom); Warakaulle, D.R. [Department of Radiology, John Radcliffe Hospital, Oxford (United Kingdom); Dattani, M. [Department of Radiology, John Radcliffe Hospital, Oxford (United Kingdom); Traill, Z. [Department of Radiology, Churchill Hospital, Oxford (United Kingdom)]. E-mail: zoe.traill@orh.nhs.uk

    2005-01-01

    Post-transplantation lymphoproliferative disorder (PTLD) is a serious complication of chronic immunosuppression following solid organ transplantation. Clinical presentation is non-specific and almost any organ can be affected. Early diagnosis is associated with a better prognosis but requires tissue sampling to ascertain the histopathological subtype of disease which cannot be predicted on imaging features alone. The radiologist has a key role in detecting the disorder, guiding biopsy and monitoring response to treatment which often only involves a reduction in immunosuppressive therapy. The aim of this paper is to illustrate the wide spectrum of imaging features in PTLD and emphasize the more specific findings which allow the diagnosis to be suggested at an early stage.

  5. Lymphoproliferative disorders after renal transplantation: role of medical imaging

    Energy Technology Data Exchange (ETDEWEB)

    Claudon, M.; Lefevre, F. [Service de Radiologie, Hopital de Brabois, Vandoeuvre les Nancy (France); Kessler, M.; Hestin, D.; Renoult, E. [Service de Nephrologie, Hopital de Brabois, Vandoeuvre les Nancy (France); Champigneulle, J. [Laboratoire d`Anatomopathologie, Hopital de Brabois, Vandoeuvre les Nancy (France)

    1998-12-01

    Post-transplantation lymphoproliferative disorders (PTLD) are a complication of immunosuppressed transplant recipients, and their incidence is reported to be 20-120 times greater than the rate in the general population. After kidney transplantation, PTLD more likely arise within the renal transplant fossa. Radiological patterns of these forms are presented and discussed, according to a review of the literature, and illustrated by cases from our institution. Ultrasound plays an essential role in the early diagnosis of PTLD by detecting a urinary obstruction associated with adenopathy or an ill-defined mass not previously seen. However, in the case of an inconclusive US examination, CT or MRI should be performed to confirm the presence of a mass. Both techniques are useful in evaluating the extension of the process within the transplantation fossa; MRI seems more accurate and can be used for the follow-up, especially after reduction in immunosuppressive therapy without transplant removal. (orig.) With 4 figs., 1 tab., 38 refs.

  6. Relative adrenal insufficiency in post-transplant lymphoproliferative disorder.

    Directory of Open Access Journals (Sweden)

    Cinclair R

    2003-01-01

    Full Text Available Post-transplant lymphoproliferative disorder is treated with rapid decrement of immunosuppressive therapy. This cannot be achieved with ease in patients on long-term glucocorticoid therapy, as chronically suppressed adrenal glands may not be capable of mounting adequate response to stress. A 52-year-old Caucasian male presented with fever, orthostatic hypotension, lymphadenopathy and hyponatraemia. Serum cortisol levels were within normal levels with a sub optimal response to stimulation by ACTH. Hyponatraemia and orthostasis responded poorly to fluid restriction, saline and salt repletion but corrected after increasing the steroid dose. The normal baseline cortisol levels represented a stimulated adrenal gland, however, the ACTH stimulation had inadequate response. This sub optimal stimulation and a good response to increased steroids suggest the presence of relative or occult adrenal insufficiency. Relative adrenal insufficiency must be considered in patients who have received prolonged glucocorticoid therapy and have symptoms such as hypotension and/or hyponatraemia.

  7. Familial Lymphoproliferative Malignancies and Tandem Duplication of NF1 Gene

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    Gustavo Fernandes

    2014-01-01

    Full Text Available Background. Neurofibromatosis type 1 is a genetic disorder caused by loss-of-function mutations in a tumor suppressor gene (NF1 which codifies the protein neurofibromin. The frequent genetic alterations that modify neurofibromin function are deletions and insertions. Duplications are rare and phenotype in patients bearing duplication of NF1 gene is thought to be restricted to developmental abnormalities, with no reference to cancer susceptibility in these patients. We evaluated a patient who presented with few clinical signs of neurofibromatosis type 1 and a conspicuous personal and familiar history of different types of cancer, especially lymphoproliferative malignancies. The coding region of the NF-1 gene was analyzed by real-time polymerase chain reaction and direct sequencing. Multiplex ligation-dependent probe amplification was performed to detect the number of mutant copies. The NF1 gene analysis showed the following alterations: mosaic duplication of NF1, TRAF4, and MYO1D. Fluorescence in situ hybridization using probes (RP5-1002G3 and RP5-92689 flanking NF1 gene in 17q11.2 and CEP17 for 17q11.11.1 was performed. There were three signals (RP5-1002G3conRP5-92689 in the interphases analyzed and two signals (RP5-1002G3conRP5-92689 in 93% of cells. These findings show a tandem duplication of 17q11.2. Conclusion. The case suggests the possibility that NF1 gene duplication may be associated with a phenotype characterized by lymphoproliferative disorders.

  8. Prevention of EBV lymphoma development by oncolytic myxoma virus in a murine xenograft model of post-transplant lymphoproliferative disease

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Manbok, E-mail: manbok66@dankook.ac.kr [Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610 (United States); Rahman, Masmudur M. [Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610 (United States); Cogle, Christopher R. [Department of Hematology/Oncology, University of Florida, Gainesville, FL 32610 (United States); McFadden, Grant [Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610 (United States)

    2015-07-10

    Epstein–Barr virus (EBV) has been associated with a variety of epithelial and hematologic malignancies, including B-, T- and NK cell-lymphomas, Hodgkin's disease (HD), post-transplant lymphoproliferative diseases (LPDs), nasopharyngeal and gastric carcinomas, smooth muscle tumors, and HIV-associated lymphomas. Currently, treatment options for EBV-associated malignancies are limited. We have previously shown that myxoma virus specifically targets various human solid tumors and leukemia cells in a variety of animal models, while sparing normal human or murine tissues. Since transplant recipients of bone marrow or solid organs often develop EBV-associated post-transplant LPDs and lymphoma, myxoma virus may be of utility to prevent EBV-associated malignancies in immunocompromised transplant patients where treatment options are frequently limited. In this report, we demonstrate the safety and efficacy of myxoma virus purging as a prophylactic strategy for preventing post-transplant EBV-transformed human lymphomas, using a highly immunosuppressed mouse xenotransplantation model. This provides support for developing myxoma virus as a potential oncolytic therapy for preventing EBV-associated LPDs following transplantation of bone marrow or solid organ allografts. - Highlights: • Myxoma virus effectively infects and purges EBV lymphoma cells in vivo. • Oncolytic myxoma virus effectively eradicates oncogenic EBV tumorigenesis. • Ex vivo pre-treatment of myxoma virus can be effective as a preventive treatment modality for post-transplant lymphoproliferative diseases.

  9. Early onset post-transplant lymphoproliferative disease is associated with allograft localization

    NARCIS (Netherlands)

    Bakker, NA; van Imhoff, GW; Verschuuren, EAM; van Son, WJ; van der Heide, JJH; Veeger, NJGM; Kluin, PM; Kluin-Nelemans, HC

    Post-transplant lymphoproliferative disease (PTLD) is a major complication after solid organ transplantation. We analyzed incidence, patient characteristics, clinical presentation, and prognostic factors for treatment outcome and survival of PTLD patients transplanted at our center. Records from

  10. Early onset post-transplant lymphoproliferative disease is associated with allograft localization

    NARCIS (Netherlands)

    Bakker, Nicolaas A.; van Imhoff, Gustaaf W.; Verschuuren, Erik A. M.; van Son, Willem J.; Homan van der Heide, Jaap J.; Veeger, Nic J. G. M.; Kluin, Philip M.; Kluin-Nelemans, Hanneke C.

    2005-01-01

    Post-transplant lymphoproliferative disease (PTLD) is a major complication after solid organ transplantation. We analyzed incidence, patient characteristics, clinical presentation, and prognostic factors for treatment outcome and survival of PTLD patients transplanted at our center. Records from

  11. Diagnosis of autoimmune lymphoproliferative syndrome caused by FAS deficiency in adults

    Science.gov (United States)

    Lambotte, Olivier; Neven, Bénédicte; Galicier, Lionel; Magerus-Chatinet, Aude; Schleinitz, Nicolas; Hermine, Olivier; Meyts, Isabelle; Picard, Capucine; Godeau, Bertrand; Fischer, Alain; Rieux-Laucat, Frédéric

    2013-01-01

    A diagnosis of autoimmune lymphoproliferative syndrome caused by FAS deficiency during adulthood is unusual. We analyzed 17 cases of autoimmune lymphoproliferative syndrome caused by FAS deficiency diagnosed during adulthood in French reference centers for hereditary immunodeficiencies and for immune cytopenias. Twelve of the 17 patients had developed their first symptoms during childhood. The diagnosis of autoimmune lymphopro-liferative syndrome had been delayed for a variety of reasons, including unusual clinical manifestations, late referral to a reference center, and the occurrence of somatic FAS mutations. The 5 other patients presented their first symptoms after the age of 16 years. In these patients, three germline heterozygous FAS mutations were predicted to be associated with haploinsufficiency and a somatic event on the second FAS allele was observed in 2 cases. Autoimmune lymphoproliferative syndrome may well be diagnosed in adulthood. The occurrence of additional genetic events may account for the delayed disease onset. PMID:22983577

  12. Cerebral Post-Transplant Lymphoproliferative Disorder Occurring after Renal Transplantation: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Suh, Jang Ho; Byun, Woo Mok; Kim, Hong Chul; Hwang, Min Su [Dept. of Radiology, Yeungnam University College of Medicine, Daegu (Korea, Republic of)

    2012-04-15

    Post-transplant lymphoproliferative disorder (PTLD) is a complication of organ transplantation and immunosuppression. A 36-year-old woman with a history of renal transplantation visited the hospital complaining of headache and on pathology was diagnosed with cerebral PTLD manifesting as multiple rim enhanced masses in both hemispheres. We report here a case of post-transplant lymphoproliferative disorder involving the cerebrum occurring after renal transplantation, and describe the MRI findings for this patient

  13. Cerebral Post-Transplant Lymphoproliferative Disorder Occurring after Renal Transplantation: A Case Report

    International Nuclear Information System (INIS)

    Suh, Jang Ho; Byun, Woo Mok; Kim, Hong Chul; Hwang, Min Su

    2012-01-01

    Post-transplant lymphoproliferative disorder (PTLD) is a complication of organ transplantation and immunosuppression. A 36-year-old woman with a history of renal transplantation visited the hospital complaining of headache and on pathology was diagnosed with cerebral PTLD manifesting as multiple rim enhanced masses in both hemispheres. We report here a case of post-transplant lymphoproliferative disorder involving the cerebrum occurring after renal transplantation, and describe the MRI findings for this patient

  14. Characterization of skin blister fluids from children with Epstein-Barr virus-associated lymphoproliferative disease.

    Science.gov (United States)

    Wada, Taizo; Toma, Tomoko; Miyazawa, Hanae; Koizumi, Eiko; Shirahashi, Tetsujiro; Matsuda, Yusuke; Yachie, Akihiro

    2018-01-20

    Epstein-Barr virus (EBV)-associated T- or natural killer (NK)-cell lymphoproliferative disease (LPD) is a heterogeneous group of disorders characterized by chronic proliferation of EBV-infected lymphocytes. Patients may present with severe skin manifestations, including hypersensitivity to mosquito bites (HMB) and hydroa vacciniforme (HV)-like eruption, which are characterized by blister formation and necrotic ulceration. Skin biopsy specimens show inflammatory reactions comprising EBV-infected lymphocytes. However, blister fluids have not been fully assessed in patients with this disease. Blister fluids were collected from three patients with EBV-associated LPD: two with HMB and one with HV. Immunophenotyping of blister lymphocytes and measurement of tumor necrosis factor (TNF)-α in blister fluids were performed. The patients with HMB and HV exhibited markedly increased percentages of NK and γδ T cells, respectively, in both peripheral blood and blister fluids. These NK and γδ T cells strongly expressed the activation marker human leukocyte antigen-DR and were considered to be cellular targets of EBV infections. TNF-α was highly elevated in all blister fluids. Severe local skin reactions of EBV-associated LPD may be associated with infiltrating EBV-infected lymphocytes and a high TNF-α concentration in blister fluids. © 2018 Japanese Dermatological Association.

  15. Molecular Surveillance for Lymphoproliferative Disease Virus in Wild Turkeys (Meleagris gallopavo from the Eastern United States.

    Directory of Open Access Journals (Sweden)

    Jesse M Thomas

    Full Text Available Lymphoproliferative disease virus (LPDV is a poorly understood, oncogenic avian retrovirus of domestic turkeys that has historically been restricted to Europe and Israel. However, a recent study reported LPDV in multiple wild turkey diagnostic cases from throughout the eastern United States of America (USA. To better understand the distribution of LPDV in the eastern USA, we surveyed 1,164 reportedly asymptomatic hunter-harvested wild turkeys from 17 states for the presence of LPDV proviral DNA by PCR. In total, 564/1,164 (47% turkeys were positive for LPDV. Wild turkeys from each state had a relatively high prevalence of LPDV, although statewide prevalence varied from 26 to 83%. Phylogenetic analysis revealed two major clades of LPDV in the USA, although one was at a low frequency suggesting restricted transmission, as well as significant clustering by state of isolation. To determine the best tissue to target for diagnostic purposes, liver, spleen, and bone marrow were tested from a subset of 15 hunter-harvested wild turkeys and 20 wild turkey diagnostic cases. Overall, bone marrow provided the highest level of detection for both hunter-harvested turkeys and diagnostic cases. The sensitivity of LPDV detection between tissues was not significantly different for diagnostic cases, but was for hunter-harvested birds. These results indicate that LPDV infection is common and widespread in wild turkey populations throughout the eastern USA, even without overt signs of disease.

  16. Indolent T-cell lymphoproliferative disease of the gastrointestinal tract

    Science.gov (United States)

    Perry, Anamarija M.; Warnke, Roger A.; Hu, Qinglong; Gaulard, Philippe; Copie-Bergman, Christiane; Alkan, Serhan; Wang, Huan-You; Cheng, Jason X.; Bacon, Chris M.; Delabie, Jan; Ranheim, Erik; Kucuk, Can; Hu, XiaoZhou; Weisenburger, Dennis D.

    2013-01-01

    Primary gastrointestinal (GI) T-cell lymphoma is an infrequent and aggressive disease. However, rare indolent clonal T-cell proliferations in the GI tract have been described. We report 10 cases of GI involvement by an indolent T-cell lymphoproliferative disease, including 6 men and 4 women with a median age of 48 years (range, 15-77 years). Presenting symptoms included abdominal pain, diarrhea, vomiting, food intolerance, and dyspepsia. The lesions involved oral cavity, esophagus, stomach, small intestine, and colon. The infiltrates were dense, but nondestructive, and composed of small, mature-appearing lymphoid cells. Eight cases were CD4−/CD8+, 1 was CD4+/CD8−, and another was CD4−/CD8−. T-cell receptor-γ chain gene rearrangement identified a clonal population in all 10 cases. There was no evidence of STAT3 SH2 domain mutation or activation. Six patients received chemotherapy because of an initial diagnosis of peripheral T-cell lymphoma, with little or no response, whereas the other 4 were followed without therapy. After a median follow-up of 38 months (range, 9-175 months), 9 patients were alive with persistent disease and 1 was free of disease. We propose the name “indolent T-LPD of the GI tract” for these lesions that can easily be mistaken for intestinal peripheral T-cell lymphoma, and lead to aggressive therapy. PMID:24009234

  17. Ultra-early onset post-transplantation Lymphoproliferative disease

    Directory of Open Access Journals (Sweden)

    Hossein Khedmat

    2013-01-01

    Full Text Available Post-transplant lymphoproliferative disease (PTLD can present as early as days to as late as several decades after transplantation. This study, however, tries to research PTLD characteristics including histopathological and clinical features, predictors and prognosis of the disease when occurring within the first month post-transplantation. We conducted a comprehensive search for the available data using the Pubmed and Google scholar search engines for reports indicating presentation time in PTLD patients. Data from 25 previously published studies were included in the analysis. Finally, we found 355 recipients of organs presenting with "ultra-early onset PTLD." Transplant recipients with ultra-early onset PTLD were significantly more likely to have kidney allografts (P = 0.032. Transplant recipients with ultra-early onset PTLD were comparable to their counterparts in the control group in their demographics, histopathological findings and survival. Patients with ultra-early onset PTLD were significantly more likely to receive induction therapy (100% vs. 49%, respectively; P = 0.013. Pancreas transplant recipients were at a significantly higher risk for development of ultra-early onset PTLD (20% vs. 1%, respectively; P <0.001. Our findings emphasize the importance of immunosuppression potency as well as the type of allograft transplanted on the incidence of PTLD in the early stages after transplantation. However, we found no histopathological or outcome disparities for patients with ultra-early PTLD compared with controls. Further prospective studies with more comparable approaches to the patients are needed to confirm our findings.

  18. Ultra-early onset post-transplantation lymphoproliferative disease.

    Science.gov (United States)

    Khedmat, Hossein; Taheri, Saeed

    2013-11-01

    Post-transplant lymphoproliferative disease (PTLD) can present as early as days to as late as several decades after transplantation. This study, however, tries to research PTLD characteristics including histopathological and clinical features, predictors and prognosis of the disease when occurring within the first month post-transplantation. We conducted a comprehensive search for the available data using the Pubmed and Google scholar search engines for reports indicating presentation time in PTLD patients. Data from 25 previously published studies were included in the analysis. Finally, we found 355 recipients of organs presenting with "ultra-early onset PTLD." Transplant recipients with ultra-early onset PTLD were significantly more likely to have kidney allografts (P = 0.032). Transplant recipients with ultra-early onset PTLD were comparable to their counterparts in the control group in their demographics, histopathological findings and survival. Patients with ultra-early onset PTLD were significantly more likely to receive induction therapy (100% vs. 49%, respectively; P = 0.013). Pancreas transplant recipients were at a significantly higher risk for development of ultra-early onset PTLD (20% vs. 1%, respectively; P <0.001). Our findings emphasize the importance of immunosuppression potency as well as the type of allograft transplanted on the incidence of PTLD in the early stages after transplantation. However, we found no histopathological or outcome disparities for patients with ultra-early PTLD compared with controls. Further prospective studies with more comparable approaches to the patients are needed to confirm our findings.

  19. A nuclear proliferation antigen in chronic lymphoproliferative disease

    International Nuclear Information System (INIS)

    Hassab, A.H.; Nafae, M.H.

    1998-01-01

    To determine whether the proliferation rates of tumour cells, in chronic lymphoproliferative disorders may reflect disease activity and relate to prognosis, we studied the expression of Ki-67% (a nuclear proliferation marker) by alkaline phosphatase anti-alkaline phosphatase technique (APAAP), in peripheral blood and bone marrow mononuclear cells (separated on ficoll-hypaque) and in lymph-node biopsies, from patients with chronic lymphatic leukemia (Cll), chronic lymphatic leukemia/prolymphocytic leukemia (CLL/PLL), prolymphocytic leukemia (PLL) and non-hodgkin's lymphoma with leukemic plase. The proliferation rate was determined for these patients at presentation and again two months after therapy (to detect any change with therapy). We found that the highest rate of proliferation in each group was parallel to the degree of malignancy i.e. PLL showed higher proliferation than CLL/PLL, and CLL/PLL showed higher proliferation than CLL. In the NHL group the highest proliferation rate was found in the high high-grade NHL, followed by intermediate grade NHL then the low grade NHL. Lymph node biopsies also showed the same relation between proliferation rates and degree of malignancy. Bone marrow cells did not show a particular pattern probably due to interference from the erythroid element and contamination by peripheral blood. Ki-67% was compared to other proliferation markers serum B2 microglobulin and lactate dehydrogenase. It was found to be an independent marker of proliferation it is unaffected by hepatic, renal and gastrointestinal elements and thus its specificity for the tumour proliferation

  20. Autoimmune Lymphoproliferative Syndrome: A Rare Cause of Disappearing HDL Syndrome

    Directory of Open Access Journals (Sweden)

    Swetha Sriram

    2016-01-01

    Full Text Available The term disappearing HDL syndrome refers to development of severe high density lipoprotein cholesterol (HDL-C deficiency in noncritically ill patients with previously normal HDL-C and triglyceride levels. Autoimmune lymphoproliferative syndrome (ALPS is a disorder of the immune system due to an inability to regulate lymphocyte homeostasis resulting in lymphadenopathy and hepatosplenomegaly. We describe a 17-year-old boy who was evaluated in the lipid clinic for history of undetectable or low HDL-C and low density lipoprotein cholesterol (LDL-C levels. Past medical history was significant for ALPS IA diagnosed at 10 years of age when he presented with bilateral cervical adenopathy. He was known to have a missense mutation in one allele of the FAS protein extracellular domain consistent with ALPS type 1A. HDL-C and LDL-C levels had been undetectable on multiple occasions, though lipids had not been measured prior to the diagnosis of ALPS. He had been receiving sirolimus for immunosuppression. The HDL-C and LDL-C levels correlated with disease activity and improved to normal levels during times when the activity of ALPS was controlled. This case highlights the importance of considering ALPS as a cause of low HDL-C and LDL-C levels in a child with evidence of lymphoproliferation.

  1. Approaches to managing cytopenias in Autoimmune Lymphoproliferative Syndrome (ALPS.

    Directory of Open Access Journals (Sweden)

    V. Koneti eRao

    2015-07-01

    Full Text Available Autoimmune Lymphoproliferative Syndrome (ALPS is a rare disorder frequently due to mutations in FAS (TNFRSF6 gene. Unlike most of the self limiting autoimmune cytopenias sporadically seen in childhood, multi lineage cytopenias due to ALPS are often refractory as their inherited genetic defect is not going to go away. Historically more ALPS patients have died due to overwhelming sepsis following splenectomy to manage their chronic cytopenias than due to any other cause, including malignancies. Hence current recommendations underscore the importance of avoiding splenectomy in ALPS, by long-term use of corticosteroid sparing immunosuppressive agents like mycophenolate mofetil and sirolimus. Paradigms learnt from managing ALPS patients in recent years is highlighted here and can be extrapolated to manage refractory cytopenias in patients with as yet undetermined genetic bases for their ailments. It is also desirable to develop international registries for children with rare and complex immune problems associated with chronic multilineage cytopenias in order to elucidate their natural history and long-term comorbidities due to their disease and its treatments.

  2. Rituximab for lymphoproliferative disease prior to haematopoietic stem cell transplantation for X-linked severe combined immunodeficiency.

    Science.gov (United States)

    Trahair, Toby N; Wainstein, Brynn; Manton, Nicholas; Bourne, Anthony J; Ziegler, John B; Rice, Michael; Russell, Susan J

    2008-02-01

    Lymphoproliferative disease (LPD) is a complication of congenital and acquired immunodeficiency states. There are a number of treatment options for LPD arising after haematopoietic stem cell or solid organ transplantation including reduction of immunosuppression, targeted therapies, such as the anti-CD20 monoclonal antibody, rituximab, and EBV specific cytotoxic lymphocytes. Treatment of LPD in children with congenital immunodeficiency syndromes remains unsatisfactory and is associated with a high mortality rate. We recently managed an infant found to have polymorphic LPD concurrent with X-linked severe combined immunodeficiency (SCID). Haematopoietic stem cell transplantation (HSCT) had to be deferred because of progressive LPD. Treatment with rituximab resulted in regression of the LPD following which the patient received a 5/6 HLA matched umbilical cord blood (UCB) transplant. The patient remains well 20 months following transplantation. Rituximab treatment may have a useful role in the control of LPD associated with congenital immunodeficiency prior to HSCT. (c) 2007 Wiley-Liss, Inc.

  3. Pulmonary lymphoproliferative disorders with affinity to lymphoma: a clinicopathoradiologic study of 16 cases

    International Nuclear Information System (INIS)

    Fernandez Cruz, J.; Gonzalez Garcia, A.; Escobar Casas, P.; Gomez Benitez, S.; Gonzalez Guirao, M.A.; Borderas, F.

    1993-01-01

    Pulmonary lymphoproliferative disorders include plasma cell granuloma, Castleman's disease, pseudolymphoma, lymphocytic interstitial pneumonia, angioimmunoblastic lymphadenopathy and lymphomatoid granulomatosis. We carried out a retrospective study for the purpose of analysing the clinical and radiological findings of 16 cases of pulmonary lymphoproliferative disorders seen during the decade 1980-1990. The cases comprised 8 lymphocytic interstitial pneumonia, 5 lymphomatoid granulomatosis, 2 plasma cell granuloma and 1 angioimmunoblastic lymphadenopathy. Owing to the overlap and low specificity of the radiological patterns in these processes, histopathological examination is required. In view of the frequent evolution of pulmonary lymphoproliferative disorders to malignant lymphoma (4 cases, 1 of lymphocytic interstitial pneumonia and 3 of lymphomatoid granulomatosis, in our series) we provide a description of the radiological changes that occur during this process. (orig.)

  4. Deregulation of Fas ligand expression as a novel cause of autoimmune lymphoproliferative syndrome-like disease.

    Science.gov (United States)

    Nabhani, Schafiq; Ginzel, Sebastian; Miskin, Hagit; Revel-Vilk, Shoshana; Harlev, Dan; Fleckenstein, Bernhard; Hönscheid, Andrea; Oommen, Prasad T; Kuhlen, Michaela; Thiele, Ralf; Laws, Hans-Jürgen; Borkhardt, Arndt; Stepensky, Polina; Fischer, Ute

    2015-09-01

    Autoimmune lymphoproliferative syndrome is frequently caused by mutations in genes involved in the Fas death receptor pathway, but for 20-30% of patients the genetic defect is unknown. We observed that treatment of healthy T cells with interleukin-12 induces upregulation of Fas ligand and Fas ligand-dependent apoptosis. Consistently, interleukin-12 could not induce apoptosis in Fas ligand-deficient T cells from patients with autoimmune lymphoproliferative syndrome. We hypothesized that defects in the interleukin-12 signaling pathway may cause a similar phenotype as that caused by mutations of the Fas ligand gene. To test this, we analyzed 20 patients with autoimmune lymphoproliferative syndrome of unknown cause by whole-exome sequencing. We identified a homozygous nonsense mutation (c.698G>A, p.R212*) in the interleukin-12/interleukin-23 receptor-component IL12RB1 in one of these patients. The mutation led to IL12RB1 protein truncation and loss of cell surface expression. Interleukin-12 and -23 signaling was completely abrogated as demonstrated by deficient STAT4 phosphorylation and interferon γ production. Interleukin-12-mediated expression of membrane-bound and soluble Fas ligand was lacking and basal expression was much lower than in healthy controls. The patient presented with the classical symptoms of autoimmune lymphoproliferative syndrome: chronic non-malignant, non-infectious lymphadenopathy, splenomegaly, hepatomegaly, elevated numbers of double-negative T cells, autoimmune cytopenias, and increased levels of vitamin B12 and interleukin-10. Sanger sequencing and whole-exome sequencing excluded the presence of germline or somatic mutations in genes known to be associated with the autoimmune lymphoproliferative syndrome. Our data suggest that deficient regulation of Fas ligand expression by regulators such as the interleukin-12 signaling pathway may be an alternative cause of autoimmune lymphoproliferative syndrome-like disease. Copyright© Ferrata Storti

  5. X-Linked Lymphoproliferative Disease Presenting as Pancytopenia in a 10-Month-Old Boy

    Directory of Open Access Journals (Sweden)

    S. Nicole Chadha

    2010-01-01

    Full Text Available X-linked lymphoproliferative disease, also known as Duncan's syndrome, is a rare genetic disorder that causes exaggerated immune responses to Epstein-Barr virus (EBV infection and often leads to death. Patient presentation varies but can include signs and symptoms typical of EBV, pancytopenia, and fulminant hepatitis.

  6. Nodal Involvement by CD30+ Cutaneous Lymphoproliferative Disorders and Its Challenging Differentiation From Classical Hodgkin Lymphoma.

    Science.gov (United States)

    Lezama, Lhara Sumarriva; Gratzinger, Dita

    2018-01-01

    Primary cutaneous lymphomas are defined as non-Hodgkin lymphomas that present in the skin with no evidence of extracutaneous disease at the time of diagnosis. Mycosis fungoides is the most common type of primary cutaneous T-cell lymphoma, representing almost 50% of primary cutaneous T-cell lymphomas, and primary cutaneous CD30 + T-cell lymphoproliferative disorders are the second most common group (30%). Transformed mycosis fungoides is usually CD30 + and can involve multiple nodal sites; other primary cutaneous CD30 + T-cell lymphoproliferative disorders can also involve draining regional nodes. Nodal involvement by CD30 + T-cell lymphoproliferative disorders can mimic classical Hodgkin lymphoma, which can aberrantly express T-cell antigens. The aim of this article is to briefly review salient clinical, histologic, immunophenotypic, and molecular features that can be used to distinguish lymph node involvement by CD30 + cutaneous T-cell lymphomas and lymphoproliferative disorders from classical Hodgkin lymphoma, a clinically important differential diagnosis that represents a challenging task for the pathologist.

  7. Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab in Treating Patients With Post-Transplant Lymphoproliferative Disorder

    Science.gov (United States)

    2013-01-24

    Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Waldenström Macroglobulinemia

  8. Presentation and early detection of post-transplant lymphoproliferative disorder after solid organ transplantation

    NARCIS (Netherlands)

    Bakker, Nicolaas A.; van Imhoff, Gustaaf W.; Verschuuren, Erik A. M.; van Son, Willem J.

    Post-transplant lymphoproliferative disorder (PTLD) is a serious and still frequently observed complication of solid organ transplantation. Despite the recent introduction of anti B-cell monoclonal antibody therapy (rituximab) for treatment of PTLD, mortality rates remain high. Because PTLD often

  9. Association of human leukocyte antigen haplotypes with posttransplant lymphoproliferative disease after solid organ transplantation

    NARCIS (Netherlands)

    Subklewe, Marion; Marquis, Rene; Choquet, Sylvain; Leblond, Veronique; Garnier, Jeanne-Luce; Hetzer, Roland; Swinnen, Lode J.; Oertel, Stephan; Papp-Vary, Matthias; Gonzalez-Barca, Eva; Hepkema, Bouke G.; Schoenemann, Constanze; May, Juergen; Pezzutto, Antonio; Riess, Hanno

    2006-01-01

    Background. Posttransplant lymphoproliferative disease (PTLD) after solid organ transplantation (SOT) is commonly characterized by Epstein-Barr virus (EBV)-driven proliferation of recipient B cells due to impaired immune surveillance in the context of immunosuppression. Because EBV-specific T-cell

  10. Extradural thoracic spinal cord compression : Unusual initial presentation of post-transplant lymphoproliferative disorder

    NARCIS (Netherlands)

    Bakker, Nicholas. A.; van Dijk, J. Marc C.; Slart, Riemer. H. J. A.; Coppes, Maarten. H.; van Imhoff, Gustaaf. W.; Verschuuren, Eric. A. M.

    2008-01-01

    Post-transplant lymphoproliferative disorder (PTLD) is a serious complication after solid-organ transplantation. We report a lung transplant recipient presenting with lower limb weakness as a result of extradural cord compression from PTLD. Diagnosis was made by laminectomy of T-3 with partial

  11. Donor Monoclonal Gammopathy May Cause Lymphoproliferative Disorders in Solid Organ Transplant Recipients.

    Science.gov (United States)

    Felldin, M; Ekberg, J; Polanska-Tamborek, D; Hansson, U; Sender, M; Rizell, M; Svanvik, J; Mölne, J

    2016-09-01

    Prior research on donor monoclonal gammopathy of undetermined significance (MGUS) has been inadequate regarding the risk for lymphoproliferative disease in solid organ transplantation recipients. Seven organ recipients from two different donors developed lymphoproliferative disease. The origin of the malignancy was determined by use of microsatellite analysis, and the plasma of the two donors was analyzed with the use of electrophoresis. The clinical courses of the seven recipients were followed for 36-60 months. One donor transmitted lymphoplasmacytic lymphoma to two kidney recipients and MGUS to a liver recipient, all IgMκ. A second donor caused IgGλ myeloma in two kidney and one liver recipient, and IgGλ gammopathy in a heart recipient. Transplant nephrectomy was performed in three kidney recipients and remission was achieved. The fourth kidney recipient has kept the graft and the disease has progressed. The liver recipient died from myeloma. There were no clinical signs of lymphoproliferative disease in the donors, but retrospective serum analyses showed M-components, IgMκ (37 g/L) and IgGλ (8 g/L). Donors with MGUS may cause donor-transmitted malignancies via passenger lymphocytes/plasma cells in solid organ recipients. The results call for a large register study of the incidence of donor MGUS and lymphoproliferative disease in their recipients. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  12. Prevalence and patterns of renal involvement in imaging of malignant lymphoproliferative diseases

    International Nuclear Information System (INIS)

    Bach, Andreas Gunter; Behrmann, Curd; Spielmann, Rolf Peter; Surov, Alexey; Holzhausen, Hans Jurgen; Katzer, Michaela; Arnold, Dirk

    2012-01-01

    Background: Renal involvement in patients with lymphoproliferative disease is an uncommon radiological finding. Purpose: To determine its prevalence and radiological appearances in a patient population. Material and Methods: All forms of lymphoproliferative disease (ICD: C81-C96) were considered. From January 2005 to January 2010, 668 consecutive patients with lymphoproliferative disease were identified with the help of the radiological database and patient records. Inclusion criteria were complete staging including appropriate CT scan and/or MRI. All stored images (initial staging and follow-up examinations) were reviewed. Results: Review of all stored images revealed renal infiltration in patients with non-Hodgkin lymphoma (11 of 364 = 3.0%; median age = 65 years, m:f = 6:5) but also multiple myeloma (2 of 162 = 1.2%; median age = 72 years; m:f = 1:1) and leukemia (5 of 101 4.9%; median age = 12 years; m:f = 2:3). There were no cases of renal infiltration in 41 patients with Hodgkin's disease. In total there were six patients with solitary lesions, five patients with diffuse renal enlargement, four patients with perirenal lesions, and two patients with direct invasion of the kidney. Conclusion: In leukemia the most common imaging pattern is diffuse enlargement. In the other subtypes of lymphoproliferative disease no specific correlation between typical CT patterns and subtype of lymphoproliferative disease can be found. The prevalence of renal involvement is in line with earlier studies. Contrary to earlier reports, multiple lesions were not found to be a common pattern

  13. Risk of Hematopoietic and Lymphoproliferative Malignancies among U. S. Radiologic Technologists

    International Nuclear Information System (INIS)

    Linet, M. S.; Fredman, D. M.; Mohan, A.; Morin Doody, M.; Ron, E.; Mabuchi, K.; Alexander, B. B.; Sigurdson, A.; Matanoski, G.; Hauptmann, M.

    2004-01-01

    To evaluate risks of hematopoietic and lymphoproliferative malignancies among medical workers exposed to protracted low-to-moderate-dose radiation exposures, a follow-up investigation was conducted in a nation wide cohort of U. S. radiologic technologists. eligible for this study were 71.894 technologists (78% female) certified for at least 2 years during 1926-82, who had responded to a baseline mail questionnaire during 1983-89, were cancer-free except for non-melanoma skin cancer at completion of the questionnaire, and completed a second questionnaire during 1994-98 or died through August 1998. There were 241 technologists with hematopoietic or lymphoproliferative malignancies, including 41 with leukemia subtypes associated with radiation exposures (specifically acute myeloid, acute lymphoid and chronic myeloid leukemias, hereafter designated radiogenic leukemias), 23 with chronic lymphocytic leukemia, 28 with multiple myeloma, 118 with non-Hodgkin lymphoma, and 31 with Hodgkin lymphoma. Of the 241 hematopoietic or lymphoproliferative malignancies identified among radiologic technologists, 85 percent were confirmed by medical records or death certificates, including 98 percent of radiogenic leukemia. Risks of the hematopoietic or lymphoproliferative malignancies were evaluated in relation to questionnaire-derived information on employment as a radiologic technologist, including procedures, work practices, and protective measures. cox proportional hazards regression analysis was used to compute relative risks and 95% confidence intervals, using age at diagnosis as the response, stratifying at baseline for birth cohort in 5-year intervals, and adjusting for potential confounding. Risks were not increased for any of the hematopoietic or lymphoproliferative neoplasms according to year first worked or total duration of years worked as radiologic technologist. For the combined radiogenic leukemias, risks rose significantly with an increasing number of years worked

  14. Risk of Hematopoietic and Lymphoproliferative Malignancies among U. S. Radiologic Technologists

    Energy Technology Data Exchange (ETDEWEB)

    Linet, M. S.; Fredman, D. M.; Mohan, A.; Morin Doody, M.; Ron, E.; Mabuchi, K.; Alexander, B. B.; Sigurdson, A.; Matanoski, G.; Hauptmann, M.

    2004-07-01

    To evaluate risks of hematopoietic and lymphoproliferative malignancies among medical workers exposed to protracted low-to-moderate-dose radiation exposures, a follow-up investigation was conducted in a nation wide cohort of U. S. radiologic technologists. eligible for this study were 71.894 technologists (78% female) certified for at least 2 years during 1926-82, who had responded to a baseline mail questionnaire during 1983-89, were cancer-free except for non-melanoma skin cancer at completion of the questionnaire, and completed a second questionnaire during 1994-98 or died through August 1998. There were 241 technologists with hematopoietic or lymphoproliferative malignancies, including 41 with leukemia subtypes associated with radiation exposures (specifically acute myeloid, acute lymphoid and chronic myeloid leukemias, hereafter designated radiogenic leukemias), 23 with chronic lymphocytic leukemia, 28 with multiple myeloma, 118 with non-Hodgkin lymphoma, and 31 with Hodgkin lymphoma. Of the 241 hematopoietic or lymphoproliferative malignancies identified among radiologic technologists, 85 percent were confirmed by medical records or death certificates, including 98 percent of radiogenic leukemia. Risks of the hematopoietic or lymphoproliferative malignancies were evaluated in relation to questionnaire-derived information on employment as a radiologic technologist, including procedures, work practices, and protective measures. cox proportional hazards regression analysis was used to compute relative risks and 95% confidence intervals, using age at diagnosis as the response, stratifying at baseline for birth cohort in 5-year intervals, and adjusting for potential confounding. Risks were not increased for any of the hematopoietic or lymphoproliferative neoplasms according to year first worked or total duration of years worked as radiologic technologist. For the combined radiogenic leukemias, risks rose significantly with an increasing number of years worked

  15. Correlation between flow cytometry and histologic findings: ten year experience in the investigation of lymphoproliferative diseases

    OpenAIRE

    Bezerra, Alanna Mara Pinheiro Sobreira; Pasqualin, Denise da Cunha; Guerra, João Carlos de Campos; Colombini, Marjorie Paris; Velloso, Elvira Deolinda Rodrigues Pereira; Silveira, Paulo Augusto Achucarro; Mangueira, Cristovão Luis Pitangueira; Kanayama, Ruth Hissae; Nozawa, Sonia Tsukasa; Correia, Rodolfo; Apelle, Ana Carolina; Pereira, Welbert de Oliveira; Garcia, Rodrigo Gobbo; Bacal, Nydia Strachman

    2011-01-01

    Objective: To demonstrate the advantages of correlating flow cytometry immunophenotyping with the pathology/ immunohistochemistry of lymph nodes or nodules in the diagnosis of lymphoproliferative diseases. Methods: A retrospective study was carried out of 157 biopsy or fine-needle aspiration lymph nodes/ nodule specimens taken from 142 patients, from 1999 and 2009. The specimens were simultaneously studied with fow cytometry and pathology at Hospital Israelita Albert Einstein. The specimens ...

  16. Patogenetic correction of anemia with erythropoiesis-stimulating agents in lymphoproliferative disorders (literature review

    Directory of Open Access Journals (Sweden)

    N. A. Romanenko

    2014-07-01

    Full Text Available Literature review of anemia pathogenesis in patients with lymphatic system malignancies is presented. Advantages and disadvanta ges of eritropoiesis-stimulating preparations (ESP used for anemia correction are shown. Efficacy of anemia treatment with ESP in various types of lymphoproliferative disorders (LPD is presented. Prognostic factors that predict positive response on ESP in LPD pati ents and reduce treatment cost are identified.

  17. Patogenetic correction of anemia with erythropoiesis-stimulating agents in lymphoproliferative disorders (literature review

    Directory of Open Access Journals (Sweden)

    N. A. Romanenko

    2011-01-01

    Full Text Available Literature review of anemia pathogenesis in patients with lymphatic system malignancies is presented. Advantages and disadvanta ges of eritropoiesis-stimulating preparations (ESP used for anemia correction are shown. Efficacy of anemia treatment with ESP in various types of lymphoproliferative disorders (LPD is presented. Prognostic factors that predict positive response on ESP in LPD pati ents and reduce treatment cost are identified.

  18. HLA associations and risk of posttransplant lymphoproliferative disorder in Danish population-based cohort

    DEFF Research Database (Denmark)

    Vase, Maja Ølholm; Maksten, Eva Futtrup; Strandhave, Charlotte

    2015-01-01

    Background: Posttransplant lymphoproliferative disorder (PTLD) is a feared complication to organ transplantation, associated with substantial morbidity and inferior survival. Risk factors for PTLD include T cell–depleting induction therapy and primary infection or reactivation of Epstein-Barr virus....... Possible associations between certain HLA types and the risk of developing PTLD have been reported by other investigators; however, results are conflicting. Methods: We conducted a retrospective, population-based study on 4295 Danish solid organ transplant patients from the Scandiatransplant database...

  19. Post-transplant Lymphoproliferative Disorder Arising from Renal Allograft Parenchyma: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Byung Kwan; Kim, Chan Kyo; Kwon, Ghee Young [Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul (Korea, Republic of)

    2010-06-15

    Post-transplant lymphoproliferative disorder (PTLD) is a rare but serious complication that occurs in patients undergoing kidney transplantation. PTLD usually manifests as a renal hilar mass comprised of histologically B-lymphocytes. We report our experience of managing a patient with PTLD arising from renal parenchyma. Ultrasonographic and MR imaging features of this unusual PTLD suggested differentiated renal cell carcinoma arising from the renal allograft

  20. Occurrence and prognostic relevance of CD30 expression in post-transplant lymphoproliferative disorders

    DEFF Research Database (Denmark)

    Vase, Maja Ølholm; Maksten, Eva Futtrup; Bendix, Knud

    2015-01-01

    Post-transplant lymphoproliferative disorders (PTLDs) are potentiallyfatal, often Epstein-Barr virus (EBV)-driven neoplasias developing in immunocompromised hosts. Initial treatment usually consists of a reduction in immunosuppressive therapy and/or rituximab with or without chemotherapy. However...... favorable outcome. For diffuse large B-cell lymphoma (DLBCL)-type PTLD this was regardless of EBV status, and remained significant in multivariate analysis. Cell-of-origin had no independent prognostic value in our series of DLBCL PTLD....

  1. Patogenetic correction of anemia with erythropoiesis-stimulating agents in lymphoproliferative disorders (literature review)

    OpenAIRE

    N. A. Romanenko; K. M. Abdulkadyrov

    2014-01-01

    Literature review of anemia pathogenesis in patients with lymphatic system malignancies is presented. Advantages and disadvanta ges of eritropoiesis-stimulating preparations (ESP) used for anemia correction are shown. Efficacy of anemia treatment with ESP in various types of lymphoproliferative disorders (LPD) is presented. Prognostic factors that predict positive response on ESP in LPD pati ents and reduce treatment cost are identified.

  2. Association of severe myoclonic epilepsy of infancy (SMEI with probable autoimmune lymphoproliferative syndrome-variant

    Directory of Open Access Journals (Sweden)

    A. Berio

    2014-12-01

    Full Text Available The paper reported on a case of severe myoclonic epilepsy of infancy (SMEI associated with a probable autoimmune lymphoproliferative syndrome variant (Dianzani autoimmune lymphoproliferative disease (DALD. A male patient with typical features of SMEI and a SCN1A gene variant presented in the first year of life with multiple lymph nodes, palpable liver at 2 cm from the costal margin, neutropenia, dysgammaglobulinemia, relative and sometimes absolute lymphocytosis. Subsequently the patient presented with constantly raised IgA in serum and positive antinuclear and thyroid antimicrosomal antibodies. The diagnosis of probable autoimmune lymphoproliferative syndrome was made; arthritis, skin and throat blisters, which appeared subsequently led to the diagnosis of linear IgA disease. On the basis of these unique associations, the Authors hypothesized that autoimmunity may be partly responsible of the severe epileptic symptomatology, perhaps mediated by autoantibodies against sodium channels or by accompanying cytotoxic T-lymphocytes. Corticosteroid treatment ameliorated the epilepsy and laboratory tests. Future studies will be necessary to evaluate the relevance of autoimmunity in SMEI.

  3. ROLE OF SERUM EOSINOPHILIC CATIONIC PROTEIN AND TRYPTASE IN MYELOPROLIFERATIVE AND LYMPHOPROLIFERATIVE DISORDERS

    Directory of Open Access Journals (Sweden)

    L. S. Komarova

    2008-01-01

    Full Text Available Abstract. A role of intracellular proteins of eosinophils and mast cells remains unclear in the patients with hematological neoplasia. There is a substantial evidence that eosinophils possess some common mechanisms of cooperation with mast cells. Therapeutic interventions into key events controlling eosinophil migration may be a leading factor in treatment of hypereosinophylic states in onco-hematological disorders. Due to unknown functions of eosinophils in majority of eosinophilia-associated diseases, it would be useful to establish an algorithm of accurate diagnostics in the patients with eosinophilia, in order to choose more effective treatment in future.We studied serum levels of secretable eosinophil and mast cells proteins in oncohematological patients with increased eosinophil counts. The aim of our study was to test a significance of quantitative assay for tryptase and ECP in the patients with myelo- and lymphoproliferative diseases. The study group included thirty-eight patients with oncohematological diseases, accompanied by a marked eosinophilia (> 0.4 x 109/L. Eighteen patients with bronchial asthma (BA, and eight cases of solid tumors comprised a reference group for polyclonal eosinophilia. The levels of ECP and tryptase were measured in blood serum using a commercial fluoroimmunoenzyme assay («Pharmacia», Uppsala, Sweden. Total ECP levels were markedly increased in general group with hematological malignancies (p < 0.03, , and in cases of chronic GvHD (p < 0.03, and in a sub-group with lymphoproliferative disorders (р = 0.007 as compared to the group of non-hematological diseases.Serum levels of tryptase were significantly increased in the patients with chronic GvHD after allo-HSCT and lymphoproliferative diseases, as compared to the group of patients with solid tumors (р = 0.03, as well in GvHD compared with lymphoproliferative disorders (р < 0.05.A direct correlation was found between serum ECP levels and absolute

  4. Understanding Drug Resistance to Targeted Therapeutics in Malignant B-Cell Lymphoproliferative Disorders (B-LPDs)

    Science.gov (United States)

    2014-10-01

    Thompson SA et al. B-cell reconstitution and BAFF after alemtuzumab (Campath-1H) treatment of multiple sclerosis . J Clin Immunol. 2010 Jan;30(1):99-105...minor stipulations in language . Once formally approved, work can resume on approval of this proposal, award number W81XWH-13-1-0358. B. TASK...proteins. Novel flow based assays are planned that can concurrently quantify multiple mRNA transcripts on a cellular cell enabling correct ratio

  5. Prevention of Human Lymphoproliferative Tumor Formation in Ovarian Cancer Patient-Derived Xenografts

    Directory of Open Access Journals (Sweden)

    Kristina A. Butler

    2017-08-01

    Full Text Available Interest in preclinical drug development for ovarian cancer has stimulated development of patient-derived xenograft (PDX or tumorgraft models. However, the unintended formation of human lymphoma in severe combined immunodeficiency (SCID mice from Epstein-Barr virus (EBV–infected human lymphocytes can be problematic. In this study, we have characterized ovarian cancer PDXs which developed human lymphomas and explore methods to suppress lymphoproliferative growth. Fresh human ovarian tumors from 568 patients were transplanted intraperitoneally in SCID mice. A subset of PDX models demonstrated atypical patterns of dissemination with mediastinal masses, hepatosplenomegaly, and CD45-positive lymphoblastic atypia without ovarian tumor engraftment. Expression of human CD20 but not CD3 supported a B-cell lineage, and EBV genomes were detected in all lymphoproliferative tumors. Immunophenotyping confirmed monoclonal gene rearrangements consistent with B-cell lymphoma, and global gene expression patterns correlated well with other human lymphomas. The ability of rituximab, an anti-CD20 antibody, to suppress human lymphoproliferation from a patient's ovarian tumor in SCID mice and prevent growth of an established lymphoma led to a practice change with a goal to reduce the incidence of lymphomas. A single dose of rituximab during the primary tumor heterotransplantation process reduced the incidence of CD45-positive cells in subsequent PDX lines from 86.3% (n = 117 without rituximab to 5.6% (n = 160 with rituximab, and the lymphoma rate declined from 11.1% to 1.88%. Taken together, investigators utilizing PDX models for research should routinely monitor for lymphoproliferative tumors and consider implementing methods to suppress their growth.

  6. Long-term follow-up of kidney transplant patients with posttransplant lymphoproliferative disorder

    DEFF Research Database (Denmark)

    Birkeland, S A; Hamilton-Dutoit, Stephen Jacques; Bendtzen, K

    2003-01-01

    Posttransplant lymphoproliferative disorder (PTLD) can be resolved in many transplant patients by the reduction or cessation of immunosuppression, after which many grafts continue to function as the result of a form of operational tolerance. When graft function deteriorates, retransplantation may...... be an option. Cytokines such as interleukin (IL)-10 and IL-18 may play a role in PTLD tolerance induction and tumor regression. We report long-term follow-up on the duration of graft tolerance and the course of retransplantation in a series of patients who underwent kidney transplantation and demonstrated PTLD...

  7. EBV-Associated Lymphoproliferative Disorder and Hemophagocytic Lymphohistiocytosis in a Patient with Severe Celiac Disease

    Directory of Open Access Journals (Sweden)

    John Jacob Kinross-Wright

    2018-01-01

    Full Text Available Background. Epstein-Barr virus- (EBV- associated lymphoproliferative disease (LPD is a rare condition, usually occurring in immunocompromised patients. We report a case of EBV-associated LPD in a patient with severe celiac disease, the first report to describe this syndrome in a patient with this diagnosis. Case Summary. A 69-year-old Caucasian woman with recent diagnosis of celiac sprue presented to our hospital with persistent diarrhea, abdominal pain, weight loss, and fatigue despite adherence to gluten-free diet for a number of weeks prior to presentation. She underwent evaluation for occult malignancy and was found to have diffuse intra-abdominal mesenteric lymphadenopathy on CT scan. Biopsy of mesenteric nodes revealed an EBV positive, CD20 positive mixed lymphoproliferative process with T-cell predominance, but without a monoclonal cell population felt to be consistent with EBV-associated LPD. Bone marrow biopsy revealed hemophagocytic lymphohistiocytosis, complicating her course. She was treated with steroids and rituximab but continued to decline, eventually developing MSSA bacteremia and succumbing to her disease. Conclusion. To our knowledge, this is the first report of the constellation of celiac sprue, EBV-associated LPD, and hemophagocytic lymphohistiocytosis. Providers caring for patients with severe, uncontrolled celiac disease and adenopathy should consider EBV-associated LPD.

  8. Lymphoproliferative disorders in inflammatory bowel disease patients on immunosuppression: Lessons from other inflammatory disorders.

    Science.gov (United States)

    Lam, Grace Y; Halloran, Brendan P; Peters, Anthea C; Fedorak, Richard N

    2015-11-15

    Immunosuppressive agents, such as thiopurines, methotrexate, and biologics, have revolutionized the treatment of inflammatory bowel disease (IBD). However, a number of case reports, case control studies and retrospective studies over the last decade have identified a concerning link between immunosuppression and lymphoproliferative disorders (LPDs), the oncological phenomenon whereby lymphocytes divide uncontrollably. These LPDs have been associated with Epstein-Barr virus (EBV) infection in which the virus provides the impetus for malignant transformation while immunosuppression hampers the immune system's ability to detect and clear these malignant cells. As such, the use of immunosuppressive agents may come at the cost of increased risk of developing LPD. While little is known about the LPD risk in IBD, more is known about immunosuppression in the post-transplantation setting and the development of EBV associated post-transplantation lymphoproliferative disorders (PTLD). In review of the PTLD literature, evidence is available to demonstrate that certain immune suppressants such as cyclosporine and T-lymphocyte modulators in particular are associated with an increased risk of PTLD development. As well, high doses of immunosuppressive agents and multiple immunosuppressive agent use are also linked to increased PTLD development. Here, we discuss these findings in context of IBD and what future studies can be taken to understand and reduce the risk of EBV-associated LPD development from immunosuppression use in IBD.

  9. POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDERS: ROLE OF VIRAL INFECTION, GENETIC LESIONS AND ANTIGEN STIMULATION IN THE PATHOGENESIS OF THE DISEASE

    Directory of Open Access Journals (Sweden)

    Daniela Capello

    2009-11-01

    Full Text Available Post-transplant lymphoproliferative disorders (PTLD are a life-threatening complication of solid organ transplantation or, more rarely, hematopoietic stem cell transplantation. The majority of PTLD is of B-cell origin and associated with Epstein–Barr virus (EBV infection. PTLD generally display involvement of extranodal sites, aggressive histology and aggressive clinical behavior. The molecular pathogenesis of PTLD involves infection by oncogenic viruses, namely Epstein-Barr virus, as well as genetic or epigenetic alterations of several cellular genes. At variance with lymphoma arising in immunocompetent hosts, whose genome is relatively stable, a fraction of PTLD are characterized by microsatellite instability as a consequence of defects in the DNA mismatch repair mechanism. Apart from microsatellite instability, molecular alterations of cellular genes recognized in PTLD include alterations of cMYC, BCL6, TP53, DNA hypermethylation, and aberrant somatic hypermutation of protooncogenes. The occurrence of IGV mutations in the overwhelming majority of PTLD documents that malignant transformation targets germinal centre (GC B-cells and their descendants both in EBV–positive and EBV–negative cases. Analysis of phenotypic markers of B-cell histogenesis, namely BCL6, MUM1 and CD138, allows further distinction of PTLD histogenetic categories. PTLD expressing the BCL6+/MUM1+/-/CD138- profile reflect B-cells actively experiencing the GC reaction, and comprise diffuse large B-cell lymphoma (DLBCL centroblastic and Burkitt lymphoma. PTLD expressing the BCL6-/MUM1+/CD138- phenotype putatively derive from B-cells that have concluded the GC reaction, and comprise the majority of polymorphic PTLD and a fraction of DLBCL immunoblastic. A third group of PTLD is reminiscent of post-GC and preterminally differentiated B-cells that show the BCL6-/MUM1+/CD138+ phenotype, and are morphologically represented by either polymorphic PTLD or DLBCL immunoblastic.

  10. Bone Marrow and Peripheral Blood Leptin Levels in Lymphoproliferative Diseases - Relation to the Bone Marrow Fat and Infiltration

    Czech Academy of Sciences Publication Activity Database

    Gaja, A.; Churý, Z.; Pecen, Ladislav; Fraňková, H.; Jandáková, H.; Hejlová, N.

    2000-01-01

    Roč. 47, č. 5 (2000), s. 307-312 ISSN 0028-2685 Institutional research plan: AV0Z1030915 Keywords : leptin * bone marrow fat * bone marrow infiltration * lymphoproliferative disease Subject RIV: BA - General Mathematics Impact factor: 0.579, year: 2000

  11. The role of molecular analysis of immunoglobulin and T cell receptor gene rearrangements in the diagnosis of lymphoproliferative disorders

    NARCIS (Netherlands)

    Langerak, AW; van Krieken, JHJM; Wolvers-Tettero, ILM; Kerkhof, E; Mulder, AH; Vrints, LWMA; Coebergh, JW; Schuuring, E; Kluin, PM; van Dongen, JJM

    Aims-To investigate whether the analysis of immunoglobulin (Ig)/T cell receptor (TCR) rearrangements is useful in the diagnosis of lymphoproliferative disorders. Methods-In a series of 107 consecutive cases with initial suspicion of non-Hodgkin's lymphoma (NHL), Southern blot (SB) analysis of Ig/TCR

  12. Treatment of the X-linked lymphoproliferative, Griscelli and Chédiak-Higashi syndromes by HLH directed therapy

    DEFF Research Database (Denmark)

    Trottestam, Helena; Beutel, Karin; Meeths, Marie

    2009-01-01

    BACKGROUND: Griscelli syndrome type 2 (GS2), the X-linked lymphoproliferative (XLP) and the Chédiak-Higashi (CHS) syndromes are diseases that all may develop hemophagocytic syndromes. We wanted to investigate whether the treatment protocols for hemophagocytic lymphohistiocytosis (HLH) can also...

  13. Epstein-Barr Virus-Positive Posttransplant Lymphoproliferative Disease After Solid Organ Transplantation: Pathogenesis, Clinical Manifestations, Diagnosis, and Management

    NARCIS (Netherlands)

    Nijland, Marieke L.; Kersten, Marie José; Pals, Steven T.; Bemelman, Frederike J.; ten Berge, Ineke J. M.

    2016-01-01

    Posttransplant lymphoproliferative disease (PTLD) is a potentially fatal complication after (solid organ) transplantation, which is highly associated with Epstein-Barr virus (EBV). The EBV-specific cytotoxic T cell response that is essential in controlling the virus in healthy individuals is

  14. Effect of anti-CD 20 antibody rituximab in patients with post-transplant lymphoproliferative disorder (PTLD)

    NARCIS (Netherlands)

    Oertel, SHK; Verschuuren, E; Reinke, P; Zeidler, K; Papp-Vary, M; Babel, N; Trappe, RU; Jonas, S; Hummel, M; Anagnostopoulos, [No Value; Dorken, B; Riess, HB

    2005-01-01

    Post-transplant lymphoproliferative disorders (PTLD) are a life-threatening complication following solid organ transplantation. Treatment with rituximab, a humanized anti-CD20 monoclonal antibody, has proved to be a promising approach and shown a low toxicity profile. Between February 1999 and April

  15. Development of an Epstein-Barr virus-associated lymphoproliferative disorder in a patient treated with azacitidine for chronic myelomonocytic leukaemia.

    Science.gov (United States)

    Menter, T; Schlageter, M; Bastian, L; Haberthür, R; Rätz Bravo, A E; Tzankov, A

    2014-03-01

    Some chemotherapeutic agents can cause iatrogenic lymphoproliferative disorders. In analogy to what has been observed with other nucleoside analogues such as cladribine and fludarabine, we document the first case of an Epstein-Barr virus-positive, iatrogenic immunodeficiency-associated, lymphoproliferative disease, formally resembling polymorphic post-transplant lymphoproliferative disease in a patient treated with azacitidine (Vidaza) for chronic myelomonocytic leukaemia (CMML). A 78-year-old female patient was diagnosed with CMML in January 2012, and treatment with azacitidine was initiated, which lasted for five cycles from February until June 2012. The patient was hospitalized in June 2012 under the suspicion of pneumonia. Transformation of the CMML was suspected at that time too. During hospitalization, a generalized enlargement of the lymph nodes and the spleen was noticed. The patient rapidly deteriorated and finally died of respiratory insufficiency. At autopsy, an Epstein-Barr virus-associated lymphoproliferative disorder, resembling polymorphic post-transplant lymphoproliferative disease with involvement of the lymph nodes, the spleen and the lung and causing necrotizing pneumonia, was diagnosed. Diagnostic criteria for diffuse large B-cell lymphoma or infectious mononucleosis-like lymphoproliferative disease were not met. This is the first documented case of an azacitidine-associated lymphoproliferative disease, raising awareness for possible not yet known side effects of this drug, which should be kept in mind by oncologists and pathologists. Copyright © 2013 John Wiley & Sons, Ltd.

  16. Diagnostic and functional imaging of thymic and mediastinal involvement in lymphoproliferative disorders.

    Science.gov (United States)

    Priola, Adriano Massimiliano; Galetto, Giorgio; Priola, Sandro Massimo

    2014-01-01

    Lymphoproliferative disorders of the anterior mediastinum may involve the thymus or lymph nodes as part of disseminated disease or as an isolated site. Imaging is crucial in managing patients with mediastinal lymphoma and is employed in pretreatment assessment, midtreatment evaluation of response, posttreatment restaging, and surveillance during follow-up. For decades, computed tomography (CT) has been the standard imaging technique, although in the last years, positron emission tomography (PET)-CT and magnetic resonance imaging (MRI) have been introduced. We discuss the role of different imaging techniques in the assessment of patients with mediastinal lymphoma, focusing on novel aspects of PET-CT and diffusion-weighted/MRI. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Posttransplant Lymphoproliferative Disorder in a Patient with Worsening Ascites after Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Harsh D. Patel

    2017-01-01

    Full Text Available Posttransplant lymphoproliferative disorder (PTLD is a spectrum of diseases that involves abnormal lymphoid and/or plasmacytic proliferation in patients with solid organ or hematopoietic cell transplantation. It is a condition with a low incidence of 3.5–4.3% in liver transplant (LT recipients. This case involves a 63-year-old male with history of LT for chronic HCV induced cirrhosis who presented with abdominal distension related to worsening ascites. Cytological ascitic fluid analysis revealed EBV (+ malignant cells without a malignant focal point on imaging. Diagnosis of monomorphic PTLD with primary effusion lymphoma-like morphology and immunophenotype was established. This case highlights the complexity in diagnosis, different diagnostic modalities, and rare clinical presentations of PTLD.

  18. Diagnosis of post-transplant lymphoproliferative disorder in solid organ transplant recipients - BCSH and BTS Guidelines.

    Science.gov (United States)

    Parker, Anne; Bowles, Kristin; Bradley, J Andrew; Emery, Vincent; Featherstone, Carrie; Gupte, Girish; Marcus, Robert; Parameshwar, Jayan; Ramsay, Alan; Newstead, Charles

    2010-06-01

    A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Transplantation Society (BTS) has reviewed the available literature and made recommendations for the diagnosis and management of post-transplant lymphoproliferative disorder (PTLD) in adult recipients of solid organ transplants. This review details the risk factors predisposing to development, initial features and diagnosis. It is important that the risk of developing PTLD is considered when using post transplant immunosuppression and that the appropriate investigations are carried out when there are suspicions of the diagnosis. These must include tissue for histology and computed tomography scan to assess the extent of disease. These recommendations have been made primarily for adult patients, there have been some comments made with regard to paediatric practice.

  19. Suppressed peripheral and placental blood lymphoproliferative responses in first pregnancies: relevance to malaria

    DEFF Research Database (Denmark)

    Rasheed, F N; Bulmer, J N; Dunn, D T

    1993-01-01

    .003, and 190N P = 0.10). Reduced proliferative capacity of placental mononuclear cells may contribute to heavy parasite colonization of this organ. Proliferation to malarial and PPD but not Candida antigens was selectively suppressed in peripheral and placental blood of primiparae relative to multiparae (F32 P...... protein derivative [PPD]) were examined in the peripheral and placental blood of 102 Gambian women at the time of delivery. The lymphoproliferative responses of placental cells were poor to all antigens compared with those of peripheral blood (Candida P ... comparable among women of different parities and between peripheral and placental blood. Primigravidae may be more susceptible to malaria because of unique physiologic factors, such as higher levels of circulating immunosuppressive corticosteroids (P

  20. Autoimmune lymphoproliferative syndrome: more than a FAScinating disease [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Karen Bride

    2017-11-01

    Full Text Available Autoimmune lymphoproliferative syndrome (ALPS is an inherited syndrome characterized by abnormal lymphocyte survival caused by failure of apoptotic mechanisms to maintain lymphocyte homeostasis. This failure leads to the clinical manifestations of non-infectious and non-malignant lymphadenopathy, splenomegaly, and autoimmune pathology, most commonly, autoimmune cytopenias. Since ALPS was first characterized in the early 1990s, insights in disease biology have improved both diagnosis and management of this syndrome. Sirolimus is the best-studied and most effective corticosteroid-sparing therapy for ALPS and should be considered first-line for patients in need of chronic treatment. This review highlights practical clinical considerations for the diagnosis and management of ALPS. Further studies could reveal new proteins and regulatory pathways that are critical for lymphocyte activation and apoptosis.

  1. Use of flow cytometry in the diagnosis of lymphoproliferative disorders in fluid specimens.

    Science.gov (United States)

    Yu, Gordon H; Vergara, Norge; Moore, Erika M; King, Rebecca L

    2014-08-01

    The diagnostic evaluation of fluid specimens, including serous effusions and cerebrospinal fluids (CSFs), can be challenging for a number of reasons. The evaluation of lymphoid proliferations in these specimens can be particularly problematic, given the frequent presence of coexisting inflammatory conditions and the manner in which these specimens are processed. As a result, immunophenotypic analysis of hematopoietic cell populations by flow cytometry has emerged as a useful ancillary study in the diagnosis of these specimens, both in patients with and without a previous history of a lymphoproliferative disorder. In this study, we review our experience with flow cytometry in fluid specimens over a four-year period. Flow cytometry was performed in 184 of 6,925 total cases (2.7% of all fluids). Flow cytometry was performed in 4.8% of pleural fluids (positive findings in 38%, negative in 40%, and atypical in 18%), 1.1% of peritoneal fluids (positive in 40%, negative in 50%, and atypical in 10%), 1.9% of pericardial fluids (positive in 67%, negative in 33%), and 1.9% of CSFs (positive in 23%, negative in 55%, atypical in 3%). The specimen submitted was inadequate for analysis in 9.2% of cases, most commonly with CSF specimens, but was not related to the volume of fluid submitted. Atypical flow cytometry findings and atypical morphologic findings in the context of negative flow cytometry results led to the definitive diagnosis of a lymphoproliferative disorder in a significant number of cases when repeat procedures and ancillary studies were performed. Copyright © 2014 Wiley Periodicals, Inc.

  2. Expression of proliferation markers and cell cycle regulators in T cell lymphoproliferative skin disorders.

    Science.gov (United States)

    Gambichler, Thilo; Bischoff, Stefan; Bechara, Falk G; Altmeyer, Peter; Kreuter, Alexander

    2008-02-01

    Abnormal cell proliferation, which results from deregulation of the cell cycle, is fundamental in tumorigenesis. To investigate the expression of proliferation markers and cell cycle regulators in a range of T cell lymphoproliferative skin diseases. We studied skin specimens of 51 patients with parapsoriasis (PP), mycosis fungiodes (MF), or lymphomatoid papulosis (LyP). Immunohistochemistry was performed for Ki-67, proliferating cell nuclear antigen (PCNA), minichromosome maintenance protein 7 (MCM7), and p21. MF with stage IIB-IV and LyP showed a significantly greater number of Ki-67-positive cells than PP (P=0.02 and 0.001) and MF I-IIA (P=0.019 and 0.003), respectively. MCM7 staining revealed significantly higher labeling indices for MF IIB-IV and LyP when compared to PP (P=0.002 and 0.04) and MF I-IIA (P=0.0005 and 0.01), respectively. Compared to PP and MF I-IIA, MF IIB-IV was associated with significantly higher labeling indices for PCNA (P=0.006 and 0.0004). p21 staining was significantly increased in MF IIB-IV and LyP when compared to PP (P=0.006 and 0.003) and MF I-IIA (P=0.003). However, p21 staining was all in all very weak. Ki-67 and PCNA seem to be useful immunohistological parameters for the correlation with the clinical stage of MF. In the differentiation and prognostication of T cell lymphoproliferative skin disorders, MCM7 may serve as a novel biomarker which is, in contrast to Ki-67 and PCNA, stable throughout the cell cycle.

  3. EBV-positive mucocutaneous ulcer in organ transplant recipients: a localized indolent posttransplant lymphoproliferative disorder.

    Science.gov (United States)

    Hart, Melissa; Thakral, Beenu; Yohe, Sophia; Balfour, Henry H; Singh, Charanjeet; Spears, Michael; McKenna, Robert W

    2014-11-01

    Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBV MCU) is a B-cell lymphoproliferative disorder occurring in elderly or iatrogenic immunocompromised patients. It has not been reported in solid organ transplant recipients. We observed 7 patients with EBV MCU in a cohort of 70 transplant recipients with EBV posttransplant lymphoproliferative disorder (PTLD). Transplants included: 5 renal, 1 heart, and 1 lung. Median patient age was 61; 5 were male. EBV MCU was observed in oral mucosa in 4 and gastrointestinal tract in 3. Duration of immunosuppressive therapy before EBV MCU was 0.6 to 13 years. Ulcers were undermined by inflammatory cells and polymorphic or monomorphic large cell lymphoproliferation. Reed-Sternberg-like cells were present in 5/7. Large B cells were CD20, CD30, and EBV-encoded RNA positive in all cases. Diagnosis in 3 recent patients was EBV MCU; 4 patients diagnosed before familiarity with EBV MCU were classified as monomorphic large cell (n=3) and polymorphic (n=1) PTLD. None of the patients had EBV DNA in their blood (<1000 copies/mL) at diagnosis or follow-up versus 35/44 transplant patients with systemic PTLD (P<0.001). All lesions resolved with reduced immunosuppression (7/7), change in immunosuppression (2/7), and rituximab (3/7). Five patients are living: 4 healthy, 1 awaiting second renal transplant. Two patients died 3 and 5 years after resolution of EBV MCU. No patient recurred with EBV MCU or other PTLDs. EBV MCU mimics more aggressive categories of PTLD but lacks EBV DNA in blood, which may be a useful distinguishing feature. Lesions are likely to resolve with conservative management. Awareness of EBV MCU in the posttransplant setting is necessary for appropriate diagnosis and treatment.

  4. Analysis of incidence of thromboembolic complications in patients with chronic lymphoproliferative diseases

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    Nikolovski Srđan

    2015-01-01

    Full Text Available Introduction: An increased risk for thromboembolism in cancer patients has been observed in patients with solid tumours, whereas little data exist on malignant lymphoma. Aim: Determination of the incidence of TE in patients with non Hodgkin lymphoma (NHL, Hodgkin lymphoma (HL and chronic lymphocytic leukemia (CLL treated in our institution. Material and methods: We reviewed medical records of patients with NHL, HL and CLL diagnosed according to the WHO classification and treated at our institution between January 2006. and December 2014. Results: A total of 1054 patients, 48.4% had high-grade NHL, 20.0% low-grade NHL, 14.5% HL, 7.1% other forms of lymphoma and 10.0% CLL. In group of lymphoma patients, 72 (6.8 % had at least one TE. TE included deep vein thrombosis (38.9%, jugular vein thrombosis (12.5%, pulmonary embolism (11.1%, CNS thrombosis (6.9%, superficial vein thrombosis (2.8%, acute myocardial infarction (1.4% and other (26.4%. In 49 patients thrombosis occurred during treatment or up to three months after therapy completion, whereas in 23 patients thrombosis was diagnosed prior to therapy. Patients with aggressive NHL and CLL had significantly higher incidence of TE (8.63%, 8.57% compared to other types of lymphoma patients (p = 0.009. There is no statistical significance of impact of different types of lymphoproliferative diseases on increased risk for TE. Conclusion: This study confirmed findings of some earlier studies of increased risk of thromboembolic events (TE in patients with aggressive forms of chronic lymphoproliferative diseasses, but there is no significantly impact of gender or age on that risk.

  5. Post-transplant lymphoproliferative disorder in the pelvis successfully treated with consolidative radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Habibeh, Omar; Elsayad, Khaled; Kriz, Jan; Haverkamp, Uwe; Eich, Hans Theodor [University Hospital of Muenster, Department of Radiation Oncology, Muenster (Germany)

    2017-01-15

    Post-transplant lymphoproliferative disorders (PTLDs) are aggressive malignancies which represent one of the major post-transplant complications. However, treatment options vary significantly and localized disease may be curatively treated with radiotherapy (RT) or surgery. We report a case of recurrent rectal PTLD, which was successfully treated by chemoimmunotherapy followed by RT. We describe a patient who developed a rectal lymphoproliferative lesion 11 years after kidney transplant, which was successfully treated with consolidative RT using 25.4 Gy sequential to chemoimmunotherapy (R-CHOP). RT was well tolerated and the patient showed no signs of grade 3 or 4 toxicity. This patient is free of recurrence 52 months after RT, with an overall survival of 62 months since diagnosis. Conventionally fractionated moderate-dose RT appears to be a tolerable and effective treatment option for localized PTLD if a sufficient systemic treatment cannot be applied. (orig.) [German] Posttransplantationslymphoproliferative Erkrankungen (PTLDs) sind eine haeufige Komplikation nach einer Organtransplantation. Nichtdestotrotz unterscheiden sich die Behandlungsmoeglichkeiten signifikant und vor allem lokalisierte Stadien koennen kurativ entweder mit Strahlentherapie (RT) und/oder Operation behandelt werden. Wir berichten ueber einen Fall einer rezidivierten rektalen PTLD, die erfolgreich mit einer Chemoimmuntherapie mit anschliessender RT behandelt wurde. Wir beschreiben einen Patienten der 11 Jahre nach einer Nierentransplantation eine PTLD entwickelte. Diese wurde erfolgreich mit konsolidierender RT (25,4 Gy) im Anschluss an eine Chemoimmuntherapie (R-CHOP) behandelt. Die RT wurde komplikationslos vertragen und es zeigten sich keine Nebenwirkungen. Das rezidivfreie Ueberleben betrug zum Zeitpunkt der letzten Nachsorgeuntersuchung 52 Monate mit einer Gesamtueberlebenszeit von 62 Monaten seit der Diagnose. Die konventionelle fraktionierte moderat dosierte RT scheint eine gut

  6. Small intestinal involvement by lymphoproliferative disorders post-renal transplantation: A report from the post-transplant lymphoproliferative disorder international survey

    Directory of Open Access Journals (Sweden)

    Hossein Khedmat

    2013-01-01

    Full Text Available In this study, data on post-renal transplant lymphoproliferative disorders (PTLD collected from the existing literature were pooled and analyzed to compare the characteristics, predictors and prognosis of small intestinal PTLDs. We performed a comprehensive search for the available data by Pubmed and Google scholar search engines for reports on this subject. Data from 18 previously published studies, comprising 120 renal allograft recipients, were included in the analysis. Renal transplant recipients with intestinal PTLD were significantly less likely to have Hogkin′s and Hogkin′s-like lesions (P = 0.044 and to be younger at the time of transplan-tation (P = 0.07. Except for Hodgkin′s-like lesions, histopathological evaluations elsewhere were comparable between the group with PTLD in the small intestine and age- and sex-matched renal transplant recipients with PTLD in other sites. The overall mortality was relatively higher in the control group (P = 0.09. When death only due to PTLD was used as the outcome, a trend toward better outcome was seen for the intestinal PTLD group compared with the other localizations (P = 0.1. The 1- and 5-year survival rates for intestinal PTLD patients were 57% and 37%, respectively, compared with 54% and 21%, respectively, for the control group. According to our findings based on analysis of international data, renal transplant patients with small intestinal PTLD are more likely to be of younger age but less frequently represent Hodgkin′s and Hodgkin′s-like lesions. They also have better patient survival compared with transplant recipients with PTLD in other locations. Further multi-center prospective studies are needed to confirm our results.

  7. POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDERS: ROLE OF VIRAL INFECTION, GENETIC LESIONS AND ANTIGEN STIMULATION IN THE PATHOGENESIS OF THE DISEASE

    Directory of Open Access Journals (Sweden)

    Gianluca Gaidano

    2009-11-01

    Full Text Available

    Post-transplant lymphoproliferative disorders (PTLD are a life-threatening complication of solid organ transplantation or, more rarely, hematopoietic stem cell transplantation. The majority of PTLD is of B-cell origin and associated with Epstein–Barr virus (EBV infection. PTLD generally display involvement of extranodal sites, aggressive histology and aggressive clinical behavior. The molecular pathogenesis of PTLD involves infection by oncogenic viruses, namely Epstein-Barr virus, as well as genetic or epigenetic alterations of several cellular genes. At variance with lymphoma arising in immunocompetent hosts, whose genome is relatively stable, a fraction of PTLD are characterized by microsatellite instability as a consequence of defects in the DNA mismatch repair mechanism. Apart from microsatellite instability, molecular alterations of cellular genes recognized in PTLD include alterations of cMYC, BCL6, TP53, DNA hypermethylation, and aberrant somatic hypermutation of protooncogenes. The occurrence of IGV mutations in the overwhelming majority of PTLD documents that malignant transformation targets germinal centre (GC B-cells and their descendants both in EBV–positive and EBV–negative cases. Analysis of phenotypic markers of B-cell histogenesis, namely BCL6, MUM1 and CD138, allows further distinction of PTLD histogenetic categories. PTLD expressing the BCL6+/MUM1+/-/CD138- profile reflect B-cells actively experiencing the GC reaction, and comprise diffuse large B-cell lymphoma (DLBCL centroblastic and Burkitt lymphoma. PTLD expressing the BCL6-/MUM1+/CD138- phenotype putatively derive from B-cells that have concluded the GC reaction, and comprise the majority of polymorphic PTLD and a fraction of

  8. PTEN and PI-3 kinase inhibitors control LPS signaling and the lymphoproliferative response in the CD19+ B cell compartment

    International Nuclear Information System (INIS)

    Singh, Alok R.; Peirce, Susan K.; Joshi, Shweta; Durden, Donald L.

    2014-01-01

    Pattern recognition receptors (PRRs), e.g. toll receptors (TLRs) that bind ligands within the microbiome have been implicated in the pathogenesis of cancer. LPS is a ligand for two TLR family members, TLR4 and RP105 which mediate LPS signaling in B cell proliferation and migration. Although LPS/TLR/RP105 signaling is well-studied; our understanding of the underlying molecular mechanisms controlling these PRR signaling pathways remains incomplete. Previous studies have demonstrated a role for PTEN/PI-3K signaling in B cell selection and survival, however a role for PTEN/PI-3K in TLR4/RP105/LPS signaling in the B cell compartment has not been reported. Herein, we crossed a CD19cre and PTEN fl/fl mouse to generate a conditional PTEN knockout mouse in the CD19+ B cell compartment. These mice were further crossed with an IL-14α transgenic mouse to study the combined effect of PTEN deletion, PI-3K inhibition and expression of IL-14α (a cytokine originally identified as a B cell growth factor) in CD19+ B cell lymphoproliferation and response to LPS stimulation. Targeted deletion of PTEN and directed expression of IL-14α in the CD19+ B cell compartment (IL-14+PTEN-/-) lead to marked splenomegaly and altered spleen morphology at baseline due to expansion of marginal zone B cells, a phenotype that was exaggerated by treatment with the B cell mitogen and TLR4/RP105 ligand, LPS. Moreover, LPS stimulation of CD19+ cells isolated from these mice display increased proliferation, augmented AKT and NFκB activation as well as increased expression of c-myc and cyclinD1. Interestingly, treatment of LPS treated IL-14+PTEN-/- mice with a pan PI-3K inhibitor, SF1126, reduced splenomegaly, cell proliferation, c-myc and cyclin D1 expression in the CD19+ B cell compartment and normalized the splenic histopathologic architecture. These findings provide the direct evidence that PTEN and PI-3K inhibitors control TLR4/RP105/LPS signaling in the CD19+ B cell compartment and that pan PI-3

  9. PTEN and PI-3 kinase inhibitors control LPS signaling and the lymphoproliferative response in the CD19+ B cell compartment

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Alok R. [UCSD Department of Pediatrics, Moores UCSD Cancer Center, University of California School of Medicine, San Diego, CA 92093 (United States); Peirce, Susan K. [Department of Pediatrics, Emory University School of Medicine, Atlanta, GA (United States); Joshi, Shweta [UCSD Department of Pediatrics, Moores UCSD Cancer Center, University of California School of Medicine, San Diego, CA 92093 (United States); Durden, Donald L., E-mail: ddurden@ucsd.edu [UCSD Department of Pediatrics, Moores UCSD Cancer Center, University of California School of Medicine, San Diego, CA 92093 (United States); Division of Pediatric Hematology-Oncology, UCSD Rady Children' s Hospital, La Jolla, CA (United States)

    2014-09-10

    Pattern recognition receptors (PRRs), e.g. toll receptors (TLRs) that bind ligands within the microbiome have been implicated in the pathogenesis of cancer. LPS is a ligand for two TLR family members, TLR4 and RP105 which mediate LPS signaling in B cell proliferation and migration. Although LPS/TLR/RP105 signaling is well-studied; our understanding of the underlying molecular mechanisms controlling these PRR signaling pathways remains incomplete. Previous studies have demonstrated a role for PTEN/PI-3K signaling in B cell selection and survival, however a role for PTEN/PI-3K in TLR4/RP105/LPS signaling in the B cell compartment has not been reported. Herein, we crossed a CD19cre and PTEN{sup fl/fl} mouse to generate a conditional PTEN knockout mouse in the CD19+ B cell compartment. These mice were further crossed with an IL-14α transgenic mouse to study the combined effect of PTEN deletion, PI-3K inhibition and expression of IL-14α (a cytokine originally identified as a B cell growth factor) in CD19+ B cell lymphoproliferation and response to LPS stimulation. Targeted deletion of PTEN and directed expression of IL-14α in the CD19+ B cell compartment (IL-14+PTEN-/-) lead to marked splenomegaly and altered spleen morphology at baseline due to expansion of marginal zone B cells, a phenotype that was exaggerated by treatment with the B cell mitogen and TLR4/RP105 ligand, LPS. Moreover, LPS stimulation of CD19+ cells isolated from these mice display increased proliferation, augmented AKT and NFκB activation as well as increased expression of c-myc and cyclinD1. Interestingly, treatment of LPS treated IL-14+PTEN-/- mice with a pan PI-3K inhibitor, SF1126, reduced splenomegaly, cell proliferation, c-myc and cyclin D1 expression in the CD19+ B cell compartment and normalized the splenic histopathologic architecture. These findings provide the direct evidence that PTEN and PI-3K inhibitors control TLR4/RP105/LPS signaling in the CD19+ B cell compartment and that pan PI

  10. Systemic Epstein-Barr Virus-positive T-Cell Lymphoproliferative Disease of Childhood With Good Response to Steroid Therapy.

    Science.gov (United States)

    Kim, Do-Hoon; Kim, Myungshin; Kim, Yonggoo; Han, Kyungja; Han, Eunhee; Lee, Jae Wook; Chung, Nack-Gyun; Cho, Bin

    2017-11-01

    Systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disease of childhood is a rare disease and has a very fulminant clinical course with high mortality. A 21-month-old female patient was referred to our hospital with a 1 week history of fever and was subsequently diagnosed with systemic Epstein-Barr virus-positive T-cell lymphoproliferative disease of childhood. After starting treatment with dexamethasone, she showed early defervescence and improvement of laboratory parameters, and has remained disease-free after stopping steroid treatment, although longer follow-up is necessary. Our report underscores the possibility that this disease entity may be heterogenous in terms of prognosis.

  11. Very late onset lymphoproliferative disorders occurring over 10 years post-renal transplantation: PTLD.Int. Survey.

    Science.gov (United States)

    Khedmat, Hossein; Taheri, Saeed

    2011-01-01

    Knowledge of the significance of post-transplant lymphoproliferative disorders (PTLD) that occur "very late" or more 10 years after renal transplantation is limited. thus, we analysed and compared characteristics and prognosis of the disease in renal transplant patients with very late onset PTLD vs. early- and late-onset PTLD. Retrospective study of data obtained from comprehensive search of medical literature We searched for available data using the Pubmed and Google scholar search engines for reports of lymphoproliferative disorders occurring in renal transplant patients by disease presentation time. We analyzed data from 27 studies that included 303 patients with lymphoproliferative disorders after renal transplantation. Renal graft recipients with very late onset PTLD were significantly less likely to be under mycophenolate mofetil (MMF)- and/or tacrolimus (FK-506) (vs. azathioprine) -based immunosuppression (P=.035) and less likely to have a history of antibody induction immunosuppression (P.1 for all). Older renal transplant patients are at increased risk for development of very late onset PTLD, and should be strictly followed. further multi-institutional prospective studies are needed to confirm our results.

  12. Treatment of post-transplantation lymphoproliferative disorders after kidney transplant with rituximab and conversion to m-TOR inhibitor.

    Science.gov (United States)

    Nieto-Rios, John Fredy; Gómez de Los Ríos, Sandra Milena; Serna-Higuita, Lina María; Ocampo-Kohn, Catalina; Aristizabal-Alzate, Arbey; Gálvez-Cárdenas, Kenny Mauricio; Zuluaga-Valencia, Gustavo Adolfo

    2016-12-30

    Post-transplantation lymphoproliferative disorders are serious complications of organ transplantation which treatment is not yet standardized. To describe the clinical response, overall and graft survival of patients in our center with this complication after kidney transplantation, which received rituximab as part of their treatment as well as conversion to m-TOR. Retrospective study, which included patients, diagnosed with post-transplant lymphoproliferative disorders after kidney transplantation from January 2011 to July 2014. Eight cases were found with a wide spectrum of clinical presentations. Most had monomorphic histology, 85% were associated with Epstein-Barr virus, 25% of patients had tumor involvement of the renal graft, and 12.5% ​​had primary central nervous system lymphoma. All patients were managed with reduction of immunosuppression, conversion to m-TOR (except one who lost the graft at diagnosis) and rituximab-based therapy. The overall response rate was 87.5% (62.5% complete response, 25% partial response). Survival was 87.5% with a median follow-up of 34 months. An additional patient lost the graft, with chronic nephropathy already known. All the remaining patients had stable renal function. There are no standardized treatment regimens for lymphoproliferative disorders after kidney transplantation, but these patients can be managed successfully with reduction of immunosuppression, conversion to m-TOR and rituximab-based schemes.

  13. Correlation between flow cytometry and histologic findings: ten year experience in the investigation of lymphoproliferative diseases

    Directory of Open Access Journals (Sweden)

    Alanna Mara Pinheiro Sobreira Bezerra

    2011-06-01

    Full Text Available Objective: To demonstrate the advantages of correlatingflow cytometry immunophenotyping with the pathology/immunohistochemistry of lymph nodes or nodules in the diagnosisof lymphoproliferative diseases. Methods: A retrospective studywas carried out of 157 biopsy or fine-needle aspiration lymph nodes/nodule specimens taken from 142 patients, from 1999 and 2009.The specimens were simultaneously studied with flow cytometryand pathology at Hospital Israelita Albert Einstein. The specimenswere prepared in hematoxylin/eosin, Giemsa, or monoclonal antibodystained slides for detecting specific antibodies for the purposesof pathology/immunohistochemical analysis. The samples werehemolyzed and marked with different monoclonal antibody panels fordifferent antigens in flow cytometry immunophenotyping. Results:The diagnostic results of pathology/immunohistochemical studiesand flow cytometry immunophenotyping agreed in 115 patients(81%, corresponding to 127 specimens, as follows according tothe pathologic diagnosis: 63 patients with non-Hodgkin’s B-celllymphoma; 26 patients with reactive lymphoid hyperplasia; 5 patientswith non-Hodgkin’s T-cell lymphoma; 4 patients with atypical lymphoidproliferation; 5 patients with a chronic granulomatous inflammatoryprocess; 5 patients with a non-hematologic diagnosis; 2 patientswith granulocytic sarcoma; 2 patients with thymoma; 1 patientwith byphenotypic leukemia; 1 patient with kappa plasmocytoma;1 patient with Hodgkin’s lymphoma. Subtypes of lymphomas couldbe classified by associating the two techniques: 19 patients withfollicular lymphoma; 15 patients with diffuse large B-cell lymphoma; 7patients with small lymphocytic B-cell lymphoma/chronic lymphocyticleukemia; 3 patients with mantle cell lymphoma; 1 patient withBurkitt’s lymphoma; 1 patient with MALT type lymphoma; 1 patientwith post-transplant lymphoproliferative disease; 2 patients with highgrade non-Hodgkin’s B-cell lymphoma; 1 patient with low grade

  14. Recurrent posttransplant lymphoproliferative disorder involving the larynx and trachea: case report and review of the literature.

    Science.gov (United States)

    Banks, Caroline A; Meier, Jeremy D; Stallworth, Christina R; White, David R

    2012-05-01

    Posttransplant lymphoproliferative disorder (PTLD) is a well-recognized complication of solid organ transplantation and commonly affects upper airway lymphoid tissue. Tracheal and laryngeal involvement in patients with PTLD, however, is rare. We present one such case. We report the case of a patient with recurrent PTLD involving the larynx and trachea and describe the presentation, evaluation, management, and outcome. An 11-year-old boy who underwent bilateral nephrectomy and renal transplantation as an infant was admitted to the hospital with chronic cough, fever, stridor, and dyspnea. His post-transplantation course was complicated by PTLD in cervical lymph nodes at 9 years of age that was successfully treated with chemotherapy. A computed tomographic scan during his present admission revealed supraglottic swelling, a distal tracheal mass, and paratracheal lymph node enlargement. The patient underwent laryngoscopy and bronchoscopy with biopsy specimens taken from the right laryngeal ventricle and distal trachea. Pathologic examination yielded a diagnosis of Epstein-Barr virus-positive PTLD. The patient was treated with chemotherapy, which resulted in resolution of the airway lesions, as seen on repeat bronchoscopy. This is the first report, to our knowledge, of recurrent PTLD involving simultaneous lesions in the larynx and the trachea. PTLD in the head and neck can present as lymphoid hypertrophy, airway obstruction, stridor, or cough. A high degree of clinical suspicion is essential for prompt diagnosis of this life-threatening complication.

  15. LYMPHO-PROLIFERATIVE RESPONSES TO VARIOUS FASCIOLA HEPATICA WORM'S ANTIGENS: AN IN VITRO STUDY.

    Science.gov (United States)

    Sharaf, Osama F; Amir, Elamir M; Hawash, Yousry A

    2016-04-01

    Fascioliasis is an important zoonotic disease with approximately 2-4 million people infected worldwide and a further 180 million at risk of infection. F. hepatica can survive within the bile ducts for many years through its ability to suppress the host immunity with Fasciola cathepsin L1 cysteine protease and Glutathione S transferase playing an important role. The aim of the present study is to investigate the in vitro lympho-proliferative responses of hepatic hilar lymphocytes (HLN) of infected sheep in response to different F. hepatica antigens. The suppressive effects of Fasciola excretory/secretory (ES) and tegument (TEG) and their fractions were also investigated. Our results showed that both ES and TEG had significant suppressive effects on lympho-proliferation, up to 74% and 92%, respectively. When these antigens were fractionated, fraction 3 (MW of >10000-30000) of both ES (64%) and TEG (59%) in addition to fraction 4 (MW of ≤ 10000) of TEG (38%) inherited the suppressive effects. Identification of the potential molecule(s) with such suppressive effects on lymphocytes in TEG fraction 4 could reveal vaccine candidates.

  16. Posttransplant Lymphoproliferative Disorder After Clinical Islet Transplantation: Report of the First Two Cases.

    Science.gov (United States)

    Peters, A; Olateju, T; Deschenes, J; Shankarnarayan, S H; Chua, N; Shapiro, A M J; Senior, P

    2017-09-01

    We report the first two cases of posttransplant lymphoproliferative disorder (PTLD) in recipients of islet transplants worldwide. First, a 44-year-old recipient of three islet infusions developed PTLD 80 months after his initial transplantation, presenting with abdominal pain and diffuse terminal ileum thickening on imaging. He was treated with surgical excision, reduction of immunosuppression, and rituximab. Seven months later, he developed central nervous system PTLD, presenting with vertigo and diplopia; immunosuppression was discontinued, resulting in graft loss, and he was given high-dose methotrexate and underwent consolidative autologous stem cell transplantation. He remains in remission 37 months after the initial diagnosis. Second, a 58-year-old female recipient of two islet infusions developed PTLD 24 months after initial islet infusion, presenting with pancytopenia secondary to extensive bone marrow involvement. Immunosuppression was discontinued, resulting in graft loss, and she received rituximab and chemotherapy, achieving complete remission. Both patients were monomorphic B cell PTLD subtype by histology and negative for Epstein-Barr virus in tissue or blood. These cases document the first occurrences of this rare complication in islet transplantation, likely secondary to prolonged, intensive immunosuppression, and highlight the varying clinical manifestations of PTLD. Further studies are needed to determine incidence rate and risk factors in islet transplantation. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  17. Clonality assessment of lymphoproliferative lesions using the polymerase chain reaction: An analysis of two methods

    Directory of Open Access Journals (Sweden)

    Nikhil Moorchung

    2011-01-01

    Full Text Available Background: Lymphoid malignancies are a heterogeneous group of disorders which may be difficult to differentiate from reactive proliferations even after immunohistochemistry. Polymerase chain reaction (PCR is believed to be a good adjunct tool for diagnosis. Materials and Methods: We examined 24 cases of neoplastic and non-neoplastic lymphoproliferative lesions in this study and evaluated the PCR as an additional tool in the confirmation of the diagnosis. Two different PCR methodologies were evaluated. Results: In the evaluation of the T-cell PCR, it was seen that the correlation using both the commercial kits and the custom-synthesized primers was highly significant at a P value of 0.05. Conclusions: Both the methods showed an excellent concordance for T-cell γ gene rearrangements, However, the same was not seen in the B-cell receptor rearrangements. This may be because of the small sample size or the inability of consensus V primers to recognize complementary DNA sequences in all of the V segments.

  18. Low incidence of lymphoproliferative disease post kidney transplantation with prevalent use of alemtuzumab

    Directory of Open Access Journals (Sweden)

    John Fredy Nieto-Ríos

    2014-01-01

    Full Text Available Introduction: It is well known that the incidence of malignancy is significantly higher in transplanted patients than in general population. The incidence of lymphoproliferative disease post-transplantation (PTLD is approximately of 1% to 2% in kidney transplantation recipients. Objective: The main objective of this study was to evaluate the PTLD incidence when monitoring kidney transplanted patients between the years 2005 and 2010. Methods: Kidney transplanted patients’ data was retrospectively taken between the years 2005 to 2010 in order to determine the number of PTLD cases according to the inductor scheme used. Results: 425 patients were transplanted between 2005 and 2010. They received alemtuzumab 76.2%, daclizumab 10.7%, basiliximab 3.6% and thymoglobulin 2.4%. The 7% did not receive antibody induction. During this period 2 cases of PTLD ocurred: One with multiple myeloma and the other with lymphoma. One of them had been treated with alemtuzumab and the other with thymoglobulin. Conclusions: The PTLD incidence in our group, where alemtuzumab was used predominantly as inductor, was very low; this might suggest that alemtuzumab is a medication that does not increase the risk of this kind of neoplasia.

  19. Fine-needle aspiration biopsy of lymphoproliferative disorders--interpretations based on morphologic criteria alone: results from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology.

    Science.gov (United States)

    Young, Nancy A; Moriarty, Ann T; Haja, Jennifer C; Wilbur, David C

    2006-12-01

    Diagnosis of lymphoproliferative disorders is one of the most challenging tasks faced by the cytologist. The initial cytomorphologic evaluation of lymphoproliferative lesions directs the choice of ancillary studies that ultimately lead to a diagnosis based on the World Health Organization classification system using a composite of clinical, morphologic, immunophenotypic, and molecular features. To evaluate the ability of participating laboratories in the College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytopathology to appropriately categorize lymphoproliferative lesions based solely on cytomorphologic criteria. Laboratory responses for lymph node aspirates were examined. All responses were based on review of glass slides without ancillary immunologic or molecular data available. The benchmarking data provided for each specific diagnosis were analyzed, with a focus on the performance for evaluation of lymphoproliferative lesions. Based on morphology alone, responses for lymph node aspirates in the Non-Gynecologic Cytopathology program were correct to the exact reference diagnosis for 87.1% of Hodgkin lymphoma. Non-Hodgkin lymphoma was identified in 69.5% of the large cell non-Hodgkin lymphoma cases, of which 66.8% were correctly classified as large cell type. Non-Hodgkin lymphoma was identified in 68.1% of non-Hodgkin lymphoma, other than large cell cases, and of these, 94.7% were identified as other than large cell type. The spectrum of specific responses was consistent for lymphoproliferative lesions, with a reasonable differential diagnosis based on cytomorphology alone, which, in practice, facilitates the appropriate choice of immunophenotypic markers and other ancillary studies.

  20. Long-term follow-up of kidney transplant patients with posttransplant lymphoproliferative disorder: duration of posttransplant lymphoproliferative disorder-induced operational graft tolerance, interleukin-18 course, and results of retransplantation

    DEFF Research Database (Denmark)

    Birkeland, Søren; Dutoit, Stephen Jacques Hamilton; Bendtzen, K

    2003-01-01

    Posttransplant lymphoproliferative disorder (PTLD) can be resolved in many transplant patients by the reduction or cessation of immunosuppression, after which many grafts continue to function as the result of a form of operational tolerance. When graft function deteriorates, retransplantation may...... be an option. Cytokines such as interleukin (IL)-10 and IL-18 may play a role in PTLD tolerance induction and tumor regression. We report long-term follow-up on the duration of graft tolerance and the course of retransplantation in a series of patients who underwent kidney transplantation and demonstrated PTLD...

  1. Epstein-Barr virus load in transplant patients: Early detection of post-transplant lymphoproliferative disorders.

    Science.gov (United States)

    Fellner, María Dolores; Durand, Karina A; Solernou, Veronica; Bosaleh, Andrea; Balbarrey, Ziomara; García de Dávila, María T; Rodríguez, Marcelo; Irazu, Lucía; Alonio, Lidia V; Picconi, María A

    2016-01-01

    High levels of circulating EBV load are used as a marker of post-transplant lymphoproliferative disorders (PTLD). There is no consensus regarding the threshold level indicative of an increase in peripheral EBV DNA. The aim of the study was to clinically validate a developed EBV quantification assay for early PTLD detection. Transversal study: paired peripheral blood mononuclear cells (PBMC), plasma and oropharyngeal lymphoid tissue (OLT) from children undergoing a solid organ transplant with (n=58) and without (n=47) PTLD. Retrospective follow-up: 71 paired PBMC and plasma from recipients with (n=6) and without (n=6) PTLD history. EBV load was determined by real-time PCR. The diagnostic ability to detect all PTLD (categories 1-4), advanced PTLD (categories 2-4) or neoplastic PTLD (categories 3 and 4) was estimated by analyzing the test performance at different cut-off values or with a load variation greater than 0.5log units. The higher diagnostic performance for identifying all, advanced or neoplastic PTLD, was achieved with cut-off values of 1.08; 1.60 and 2.47log EBVgEq/10(5) PBMC or 2.30; 2.60; 4.47loggEq/10(5) OLT cells, respectively. EBV DNA detection in plasma showed high specificity but low (all categories) or high (advanced/neoplastic categories) sensitivity for PTLD identification. Diagnostic performance was greater when: (1) a load variation in PBMC or plasma was identified; (2) combining the measure of EBV load in PBMC and plasma. The best diagnostic ability to identify early PTLD stages was achieved by monitoring EBV load in PBMC and plasma simultaneously; an algorithm was proposed. Copyright © 2016 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Subcutaneous immunoglobulin in lymphoproliferative disorders and rituximab-related secondary hypogammaglobulinemia: a single-center experience in 61 patients.

    Science.gov (United States)

    Compagno, Nicolò; Cinetto, Francesco; Semenzato, Gianpietro; Agostini, Carlo

    2014-06-01

    Intravenous immunoglobulin replacement therapy represents the standard treatment for hypogammaglobulinemia secondary to B-cell lymphoproliferative disorders. Subcutaneous immunoglobulin infusion is an effective, safe and well-tolerated treatment approach in primary immunodeficiencies but no extensive data are available on their use in secondary hypogammaglobulinemia, a frequent phenomenon occurring after treatment with anti-CD20 monoclonal antibodies in lymphoproliferative disorders. In this retrospective study we evaluated efficacy (serum IgG trough levels, incidence of infections per year, need for antibiotics) and safety (number of adverse events) of intravenous (300 mg/kg/4 weeks) versus subcutaneous (75 mg/kg/week) immunoglobulin replacement therapy in 61 patients. In addition, the impact of the infusion methods on quality of life was compared. All patients were treated with subcutaneous immunoglobulin, and 33 out of them had been previously treated with intravenous immunoglobulin. Both treatments appeared to be effective in replacing Ig production deficiency and in reducing the incidence of infectious events and the need for antibiotics. Subcutaneous immunoglobulin obtained a superior benefit when compared to intravenous immunoglobulin achieving higher IgG trough levels, lower incidence of overall infection and need for antibiotics. The incidence of serious bacterial infections was similar with both infusion ways. As expected, a lower number of adverse events was registered with subcutaneous immunoglobulin, compared to intravenous immunoglobulin, with no serious adverse events. Finally, we observed an improvement in health-related quality of life parameters after the switch to subcutaneous immunoglobulin. Our results suggest that subcutaneous immunoglobulin is safe and effective in patients with hypogammaglobulinemia associated to lymphoproliferative disorders. Copyright© Ferrata Storti Foundation.

  3. Isolated Post-Transplantation Lymphoproliferative Disease Involving the Breast and Axilla as Peripheral T-cell Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Ji-Young [Department of Radiology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul 150-950 (Korea, Republic of); Cha, Eun Suk; Lee, Jee Eun [Department of Radiology, Ewha Womans University School of Medicine, Seoul 158-710 (Korea, Republic of); Sung, Sun Hee [Department of Pathology, Ewha Womans University School of Medicine, Seoul 158-710 (Korea, Republic of)

    2013-07-01

    Post-transplantation lymphoproliferative disorders (PTLDs) are a heterogeneous group of diseases that represent serious complications following immunosuppressive therapy for solid organ or hematopoietic-cell recipients. In contrast to B-cell PTLD, T-cell PTLD is less frequent and is not usually associated with Epstein Barr Virus infection. Moreover, to our knowledge, isolated T-cell PTLD involving the breast is extremely rare and this condition has never been reported previously in the literature. Herein, we report a rare case of isolated T-cell PTLD of the breast that occurred after a patient had been treated for allogeneic peripheral blood stem cell transplantation due to acute myeloblastic leukemia.

  4. [A case of lymphoproliferative disorder in the entire small intestine after renal transplantation detected by wireless capsule endoscopy].

    Science.gov (United States)

    Sonoda, Akira; Katsuta, Makoto; Yada, Mika; Mizukami, Kazuhiro; Okamoto, Kazuhisa; Ogawa, Ryo; Okimoto, Tadayoshi; Kodama, Masaaki; Murakami, Kazunari

    2015-04-01

    A 42-year-old woman underwent renal transplantation in 200X. After the transplant, she received tacrolimus as immunosuppressant therapy. Eleven years after the transplant, diffuse large B-cell lymphomas were detected in the duodenum and terminal ileum. Wireless capsule endoscopy (WCE) revealed multiple lymphoma lesions in the entire small intestine. The patient achieved complete response through the administration of R-CHOP therapy and discontinuation of immunosuppressant therapy. Post-transplant lymphoproliferative disorder (PTLD) is a rare complication and WCE may be useful for diagnosing PTLD of the small intestine.

  5. Management of post-transplant lymphoproliferative disorder in adult solid organ transplant recipients - BCSH and BTS Guidelines.

    Science.gov (United States)

    Parker, Anne; Bowles, Kristin; Bradley, J Andrew; Emery, Vincent; Featherstone, Carrie; Gupte, Girish; Marcus, Robert; Parameshwar, Jayan; Ramsay, Alan; Newstead, Charles

    2010-06-01

    A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Transplantation Society (BTS) has reviewed the available literature and made recommendations for the diagnosis and management of post-transplant lymphoproliferative disorder in adult recipients of solid organ transplants. This review details the therapeutic options recommended including reduction in immunosuppression (RIS), transplant organ resection, radiotherapy and chemotherapy. Effective therapy should be instituted before progressive disease results in declining performance status and multi-organ dysfunction. The goal of treatment should be a durable complete remission with retention of transplanted organ function with minimal toxicity.

  6. Clinicopathologic Assessment of Ocular Adnexal Lymphoproliferative Lesions at a Tertiary Eye Hospital in Iran.

    Science.gov (United States)

    Asadi-Amoli, Fahimeh; Nozarian, Zohreh; Bonaki, Hirbod Nasiri; Mehrtash, Vahid; Entezari, Samaneh

    2016-01-01

    The most common type of ocular lymphoma is non-Hodgkin lymphoma (NHL), categorized into two groups: indolent (slow growing) and aggressive (rapid growing). Differentiating benign reactive lymphoid hyperplasia (RLH) from malignant ocular adnexal lymphoma (OAL) is challenging. Histopathology, immunohistochemistry (IHC) and ow cytometry have been used as diagnostic tools in such cases. In this retrospective case series, from 2002 to 2013 at Farabi Eye Center, 110 patients with ocular lymphoproliferative disease were enrolled. Prevalence, anatomical locations, mean age at diagnosis and the nal diagnosis of the disease with IHC were assessed. Comparison between previous pathologic diagnoses and results of IHC was made. Immunoglobulin light chains and B-cell and T-cell markers and other immuno-phenotyping markers including CD20, CD3, CD5, CD23, CD10, CYCLIND1 and BCL2 were evaluated to determine the most accurate diagnosis. The lymphomas were categorized based on revised European-American lymphoma (REAL) classi cation. Mean age±SD (years) of the patients was 55.6 ±19.3 and 61% were male. Patients with follicular lymphoma, large B-cell lymphoma or chronic lymphocytic leukemia/small cell lymphoma (CLL/SLL) tended to be older. Nine patients with previous diagnoses of low grade B-cell lymphoma were re-evaluated by IHC and the new diagnoses were as follows: extranodal marginal zone lymphoma(EMZL) (n=1), SLL(n=1), mantle cell lymphoma (MCL) (n=3), reactive lymphoid hyperplasia RLH (n=2). Two cases were excluded due to poor blocks. Flow cytometry reports in these seven patients revealed SLL with positive CD5 and CD23, MCL with positive CD5 and CyclinD1 and negative CD23, EMZL with negative CD5,CD23 and CD10. One RLH patient was negative for Kappa/Lambda and positive for CD3 and CD20 and the other was positive for all of the light chains, CD3 and CD20. Orbit (49.1%), conjunctiva (16.1%) and lacrimal glands (16.1%) were the most common sites of involvement. Accurate

  7. Clinical, laboratory, and morphological characteristics of kidney damage in lymphoproliferative disorders

    Directory of Open Access Journals (Sweden)

    B. T. Dzhumabaeva

    2017-01-01

    Full Text Available Kidney involvement in the onset of lymphoproliferative diseases (LPD detected rarely, observed mainly at tumor progression or relapse.Objective: to determine the clinical and morphological features of kidney damage in the initial manifestation of LPD.Materials and methods: 19 patients with LPD and kidney damage were included in the study. The diagnosis of non-Hodgkin’s lymphomas was established according to 2008 WHO classification. Histological and immunohistochemical, immunofluorescent and electron microscopic studies of nephrobiopsy have been performed.Results. Patients were aged 46-83 years (median 63 years, of which 13 were men and 6 women. Chronic lymphocytic leukemia / small cell lymphocytic lymphoma was established in 12 patients, marginal zone lymphoma – in 4 pts, follicular lymphoma – in 1 patient, Waldenstrom's macroglobulinemia – in 1 patient and diffuse large B-cell lymphoma (DLBCL in 1 patient. Proteinuria was observed in 18 patients, microhematuria – in 6 pts, arterial hypertension – in 8 pts, nephrotic syndrome – in 3 pts and renal failure in 18 patients. The mean creatinine level was 330.9 ± 52.3 µmol/L, the average glomerular filtration rate was 25.7 ± 12.9 ml/min. Monoclonal IgMκ secretion was detected in 6 patients, BJκ protein – in 9 pts, increased free light chain level – in 4 pts, cryoglobulin – in 4 pts (type II cryoglobulin in 3 of them, type I – in 1 patient.Morphological study of nephrobiopsy revealed tumor lymphoid infiltration of kidney interstitium in 10 (52.6 % cases. Diffuse small cell lymphoid proliferation was detected in 1 patient, local infiltration – in 9 pts, in 3 of them in combination with glomerulonephritis, and in 4 cases with kidney carcinoma. Local large cell lymphoid proliferation was found in 1 patient with DLBCL. Amyloidosis was detected in 2 pts and thrombotic microangiopathy – in 2 patients. Glomerulopathy was revealed in 10 patients (52.6 %: mesangioproliferative

  8. Incidence of post-transplantation lymphoproliferative disease in Andalusia (1990-2009).

    Science.gov (United States)

    Govantes, M A Gentil; Esteve, A Franco; Ramos, M Toro; Gracia De Guindo, M C; Sánchez, L Fuentes; Blanca, M A Mazuecos; Rodríguez-Benot, A; Blandino, M Vidal; De la Nuez, P Castro; Rodríguez, D Burgos

    2013-01-01

    Post-transplantation lymphoproliferative disease (PTLD) is a severe complication of renal transplantation (RT) but information about its incidence and predisposing factors is diverse, varying according to geographic area and study period. We analyzed the incidence of PTLD after all RT performed at adult transplantation centers in Andalusia from January 1, 1990 to December 31, 2009, recorded in the Andalusian Transplant Co-ordination Information System (SICATA) regional computerized database (n = 5577). We calculated the risk of PTLD using the Kaplan-Meier curve, censoring for organ failure and incidence rate per patient-year of exposure. Log-rank comparisons were made by center (n = 5), decade (1990-1999 vs 2000-2009), age group, recipient gender, hepatitis C virus (HCV) serology, transplantation number, and duration of pre-RT replacement therapy (per quartiles). We identified 60 cases of PTLD. The pre-RT treatment time was 48.2 ± 60 months; 11.7% were retransplantations, and 10.4% had a positive HCV serology. The median post-RT time before diagnosis of PTLD was 5.98 years. At the time of the database analysis, only 11 patients (18%) were alive with a functioning transplant; 10% had returned to dialysis and 72% had died. The actuarial incidence of PTLD at 1, 5, 10, and 20 years post-RT was 0.2%, 0.5%, 1.6%, and 2.9%, respectively; the exposure rate was 14.71 PTLD/10,000 patient-years (95% confidence interval [CI], 12.3-17.1). Although the incidence tended to be higher in 1990-1999 than 2000-2009 (16.8 vs 12.1 cases/10,000 patient-years), in the actuarial study the difference was far from significant (at 7.5 years, 1.2 vs 0.8%; P = .4). Nor were there significant differences in the curves of incidence per RT center (1%-1.2% of patients) or recipient characteristics. The cumulative incidence of PTLD in Andalusia in patients with a functioning kidney transplant during 1990-2009 was 2.9% at 20 years. There was no significant variation between the RT centers or over

  9. Recent advances in the risk factors, diagnosis and management of Epstein-Barr virus post-transplant lymphoproliferative disease

    Directory of Open Access Journals (Sweden)

    Paibel Aguayo-Hiraldo

    2016-01-01

    Full Text Available Fifty years after the first reports of Epstein-Barr virus (EBV-associated endemic Burkitt's lymphoma, EBV has emerged as the third most prevalent oncogenic virus worldwide. EBV infection is associated with various malignancies including Hodgkin and non-Hodgkin lymphoma, NK/T-cell lymphoma and nasopharyngeal carcinoma. Despite the highly specific immunologic control in the immunocompetent host, EBV can cause severe complications in the immunocompromised host (namely, post-transplant lymphoproliferative disease. This is particularly a problem in patients with delayed immune reconstitution post-hematopoietic stem cell transplant or solid organ transplant. Despite advances in diagnostic techniques and treatment algorithms allowing earlier identification and treatment of patients at highest risk, mortality rates remain as high as 90% if not treated early. The cornerstones of treatment include reduction in immunosuppression and in vivo B cell depletion with an anti-CD20 monoclonal antibody. However, these treatment modalities are not always feasible due to graft rejection, emergence of graft vs. host disease, and toxicity. Newer treatment modalities include the use of adoptive T cell therapy, which has shown promising results in various EBV-related malignancies. In this article we will review recent advances in risk factors, diagnosis and management of EBV-associated malignancies, particularly post-transplant lymphoproliferative disease. We will also discuss new and innovative treatment options including adoptive T cell therapy as well as management of special situations such as chronic active EBV and EBV-associated hemophagocytic lymphohistiocytosis.

  10. Risk factors, diagnosis, and management of posttransplant lymphoproliferative disorder: improving patient outcomes with a multidisciplinary treatment approach

    Directory of Open Access Journals (Sweden)

    Ligeti K

    2017-01-01

    Full Text Available Kinga Ligeti, Lutz P Müller, Carsten Müller-Tidow, Thomas Weber Department of Hematology and Oncology, University Hospital Halle (Saale and Martin-Luther-University Halle-Wittenberg, Halle (Saale, Germany Abstract: Posttransplant lymphoproliferative disease (PTLD is a major complication after solid organ transplantation and allogeneic hematopoietic stem cell transplantation. The spectrum of PTLD ranges from benign hyperplasia to malignant lymphoma, representing one of the most relevant malignancies in these patients. Most PTLDs are driven by latent Epstein–Barr virus infections. The backbone of treatment is reduction of immunosuppression. Further treatment depends on the type of PTLD and the type of transplantation. A multidisciplinary approach involving transplant team, hematologists, and other disciplines is crucial for the diagnosis and treatment of PTLD and for concurrent preservation of the transplant function. In this study, known pathomechanisms, risk factors, preemptive management, and especially emerging treatment algorithms in PTLD were reviewed. Keywords: lymphoproliferative disease, Epstein-Barr virus, management, rituximab, ­preemptive therapy

  11. Epstein-Barr Virus-Negative Post-Transplant Lymphoproliferative Diseases: Three Distinct Cases from a Single Center

    Directory of Open Access Journals (Sweden)

    Şule Mine Bakanay

    2014-03-01

    Full Text Available Three cases of Epstein-Barr virus (EBV-negative post-transplant lymphoproliferative disease that occurred 6 to 8 years after renal transplantation are reported. The patients respectively had gastric mucosa-associated lymphoid tissue lymphoma, gastric diffuse large B-cell lymphoma, and atypical Burkitt lymphoma. Absence of EBV in the tissue samples was demonstrated by both in situ hybridization for EBV early RNA and polymerase chain reaction for EBV DNA. Patients were treated with reduction in immunosuppression and combined chemotherapy plus an anti-CD20 monoclonal antibody, rituximab. Despite the reduction in immunosuppression, patients had stable renal functions without loss of graft functions. The patient with atypical Burkitt lymphoma had an abnormal karyotype, did not respond to treatment completely, and died due to disease progression. The other patients are still alive and in remission 5 and 3 years after diagnosis, respectively. EBV-negative post-transplant lymphoproliferative diseases are usually late-onset and are reported to have poor prognosis. Thus, reduction in immunosuppression is usually not sufficient for treatment and more aggressive approaches like rituximab with combined chemotherapy are required.

  12. Frequent monitoring of Epstein-Barr virus DNA load in unfractionated whole blood is essential for early detection of posttransplant lymphoproliferative disease in high-risk patients

    NARCIS (Netherlands)

    Stevens, SJC; Verschuuren, EAM; Pronk, [No Value; van der Bij, W; Harmsen, MC; The, TH; Meijer, CJLM; van den Brule, AJC; Middeldorp, JM

    2001-01-01

    Posttransplant lymphoproliferative disease (PTLD) is a frequent and severe Epstein-Barr virus (EBV)-associated complication in transplantation recipients that is caused by iatrogenic suppression of T-cell function, The diagnostic value of weekly EBV DNA load monitoring was investigated in

  13. [Two families of X-linked lymphoproliferative disease type 1 characterized by agammaglobulinemia].

    Science.gov (United States)

    Li, W Y; Chen, J S; Zhao, Q; Dai, R X; Wang, Y P; Zhao, H Y; Chen, X M; Xue, X H; Sun, X Y; Tang, X M; Zhang, Y; Ding, Y; Zhao, X D; Zhang, Z Y

    2017-05-04

    Objective: To investigate the clinical and immunological laboratory features, mutations in SH2D1A gene and SAP protein expression in four children of two families with X-linked lymphoproliferative disease type 1(XLP-1). Method: Four patients (Family A including Patient 1 and Patient 2, Family B including Patient 3 and Patient 4) and their maternal relatives were enrolled in this study. The clinical manifestation, EBV infection status and chest CT scan were analyzed. The absolute and relative numbers of lymphocyte subsets, T lymphocyte proliferative response, SAP protein expression were assessed by flow cytometry. Quantification of signal joint TCR rearrangementexcision circle (sjTRECs), CDR3 spectratyping of TCRvβ and gene mutation of SH2D1A were detected by PCR based on genomic DNA or cDNA. Result: Four male patients from two families were diagnosed with XLP-1. The ages of disease onset were more than 1 year, more than 1 year, more than 1 month and 6 months. The ages at diagnosis were nine years and ten months, sixteen years and eight months, fourteen years and ten months, four years and nine months. All patients had recurrent infections and EBV infection. Patients 1, 2, and 3 had agammaglobulinemia and Patient 4 had hypogammaglobulinemia. Chest CT scan showed all patients had atelectasis and pneumonia, and Patient 3 had bronchiectasis. Patient 3 was diagnosised as Burkitt lymphoma. For immunological function, all patients exhibited reduced CD4/CD8 ratios, increased numbers of exhausted T lymphocyte, decreased number of NK cell. The numbers of total B lymphocyte and naïve B lymphocyte were normal, but the number of memory B lymphocyte declined in all cases. Four patients' copy numbers of sjTRECs were low and CDR3 spectratypings of TCRvβ showed mildly skewed. But their T lymphocyte proliferative response was normal. SAP protein expression in four cases were measured by flow cytometry. Two patients from Family A were absent and two patients from Family B showed

  14. Hairy B-cell lymphoproliferative disorder and its differential diagnosis: a case with long-term follow-up

    Directory of Open Access Journals (Sweden)

    Kensuke Matsuda

    2017-09-01

    Full Text Available Hairy B-cell lymphoproliferative disorder (HBLD is one of chronic polyclonal B-cell lymphocytosis. We report a 47-year-old female Japanese patient diagnosed as having HBLD based on lymphocytosis with hairy cell appearance and characteristic phenotypes including CD11c+, and without B-cell monoclonalities. She was a non-smoker, and possessed HLA-DR4. She has been closely followed up without treatment and lymphoma development for over five years. Although this disease is quite rare and has been reported, to our knowledge, in only 13 Japanese cases, an accurate diagnosis, particularly differential diagnosis from persistent polyclonal B-cell lymphocytosis or hairy cell leukemia-Japanese variant is essential for the prevention of unnecessary treatments.

  15. Clinical Aspects of IgG4-Related Orbital Inflammation in a Case Series of Ocular Adnexal Lymphoproliferative Disorders

    Directory of Open Access Journals (Sweden)

    Masayuki Takahira

    2012-01-01

    Full Text Available The most frequent ocular adnexal tumors and simulating lesions are lymphoproliferative disorders (LPDs, including malignant lymphomas and orbital inflammation with lymphoid hyperplasia or infiltration. IgG4-related orbital inflammation (IgG4-ROI often involves lacrimal glands and other orbital tissues and is an important differential diagnosis. The present study evaluated clinical aspects of IgG4-ROI in a case series of orbital LPD. Sixty-two consecutive cases of orbital LPD, pathologically diagnosed from November, 2004, through March, 2011, were investigated. Histological types were 22 cases with MALT lymphoma, 11 cases with diffuse large B-cell lymphoma (DLBCL, 3 cases with other malignant lymphomas, 16 cases with IgG4-ROI, and 10 cases with non-IgG4-ROI. Ages of the IgG4-ROI group (56±10?yrs were significantly lower than the MALT lymphoma (71±12?yrs and DLBCL (75±14?yrs groups. Orbital lesions other than lacrimal glands were present in six cases including extraocular muscle swelling, mass lesions surrounding the optic nerve, and supraorbital and infraorbital nerves enlargements. Although none of the malignant lymphomas were related to IgG4, previous evidence suggested that malignant lymphomas can arise from IgG4-ROI. Based on this study (26% and another report (33%, it is likely that nearly a quarter of orbital LPD are IgG4-ROI.

  16. P-glycoprotein is expressed and causes resistance to chemotherapy in EBV-positive T-cell lymphoproliferative diseases

    International Nuclear Information System (INIS)

    Yoshimori, Mayumi; Takada, Honami; Imadome, Ken-Ichi; Kurata, Morito; Yamamoto, Kouhei; Koyama, Takatoshi; Shimizu, Norio; Fujiwara, Shigeyoshi; Miura, Osamu; Arai, Ayako

    2015-01-01

    Epstein–Barr virus-positive T-cell lymphoproliferative diseases (EBV-T-LPDs) are rare lymphomas with poor prognosis. Although chemotherapeutic strategies such as CHOP have been often selected, they have exhibited only limited efficacy. To clarify the mechanism of chemoresistance, we examined P-glycoprotein (P-gp) expression. P-gp acts as an energy-dependent efflux pump that excretes drugs from the cytoplasm, resulting in low-intracellular drug concentrations and poor sensitivity to chemotherapy. We examined P-gp expression in EBV-positive cells by immunohistochemistry staining in three patients of EBV-T-LPDs and the expression was detected in all patients. We also examined mdr1 mRNA expression by reverse-transcriptase polymerase-chain reaction (RT-PCR) in EBV-positive tumor cells from these patients and additional three patients. The expression was detected in all examined patients. In five EBV-T-LPDs patients, P-gp function was detected by Rhodamine-123 efflux assay in these cells. The efflux was inhibited by treatment with a P-gp inhibitor, cyclosporine A (CsA). We also examined and detected P-gp expression in EBV-positive T-cell lines SNT8 and SNT16 established from EBV-T-LPDs patients, by RT-PCR and western blotting. The function was also detected by Rhodamine-123 efflux in these cell lines. Inhibition and knock down of P-gp by CsA and siRNA, respectively, enhanced etoposide- and doxorubicin-induced cell death in the EBV-positive T-cell lines. Finally, we infected the T-cell line MOLT4 with EBV, and found that mdr1 mRNA expression and Rhodamine 123 efflux were upregulated after infection. These results indicated that enhanced P-gp expression contributed to the chemoresistance of EBV-T-LPDs

  17. Preliminary experience on the use of PET/CT in the management of pediatric post-transplant lymphoproliferative disorder.

    Science.gov (United States)

    Guerra-García, Pilar; Hirsch, Steffen; Levine, Daniel S; Taj, Mary M

    2017-12-01

    Post-transplant lymphoproliferative disorder (PTLD) is a well-known complication following prolonged immunosuppression. Contrary to other lymphomas, there is no standardized imaging approach to assess PTLD either at staging or for response to therapy. Positron emission tomography/computed tomography (PET/CT) is an imaging modality that has proven to be useful in lymphoma. However, there is still limited data concerning its use in pediatric PTLD. Our study evaluates the use of PET/CT in pediatric PTLD at our institution. To assess the role of PET/CT in pediatric PTLD, we reviewed the pediatric patients with PTLD who had undergone PET/CT at our institution between 2000 and 2016. Nine patients were identified. Six had PET/CT at diagnosis. All lesions seen on CT were identified with PET/CT. Fourteen PET/CTs were done during treatment. Eight PET/CTs were negative, including three where CT showed areas of uncertain significance. In these cases, PET/CT helped us to stop treatment and the patients remain in remission after a long follow-up (mean 74.3 months; range 12.4-180.9 months). PET/CT revealed additional disease in two cases, therefore treatment was intensified. Six biopsies and close follow-up was done to confirm PET/CT results. In one case, PET/CT did not identify central nervous system involvement demonstrated on magnetic resonance imaging. PET/CT may have an important role in the staging and follow-up of pediatric PTLD. In our cohort, PET/CT was helpful in staging and assessing treatment response and in clarifying equivocal findings on other imaging modalities. © 2017 Wiley Periodicals, Inc.

  18. Immunoglobulin heavy-chain fluorescence in situ hybridization-chromogenic in situ hybridization DNA probe split signal in the clonality assessment of lymphoproliferative processes on cytological samples.

    Science.gov (United States)

    Zeppa, Pio; Sosa Fernandez, Laura Virginia; Cozzolino, Immacolata; Ronga, Valentina; Genesio, Rita; Salatiello, Maria; Picardi, Marco; Malapelle, Umberto; Troncone, Giancarlo; Vigliar, Elena

    2012-12-25

    The human immunoglobulin heavy-chain (IGH) locus at chromosome 14q32 is frequently involved in different translocations of non-Hodgkin lymphoma (NHL), and the detection of any breakage involving the IGH locus should identify a B-cell NHL. The split-signal IGH fluorescence in situ hybridization-chromogenic in situ hybridization (FISH-CISH) DNA probe is a mixture of 2 fluorochrome-labeled DNAs: a green one that binds the telomeric segment and a red one that binds the centromeric segment, both on the IGH breakpoint. In the current study, the authors tested the capability of the IGH FISH-CISH DNA probe to detect IGH translocations and diagnose B-cell lymphoproliferative processes on cytological samples. Fifty cytological specimens from cases of lymphoproliferative processes were tested using the split-signal IGH FISH-CISH DNA probe and the results were compared with light-chain assessment by flow cytometry (FC), IGH status was tested by polymerase chain reaction (PCR), and clinicohistological data. The signal score produced comparable results on FISH and CISH analysis and detected 29 positive, 15 negative, and 6 inadequate cases; there were 29 true-positive cases (66%), 9 true-negative cases (20%), 6 false-negative cases (14%), and no false-positive cases (0%). Comparing the sensitivity of the IGH FISH-CISH DNA split probe with FC and PCR, the highest sensitivity was obtained by FC, followed by FISH-CISH and PCR. The split-signal IGH FISH-CISH DNA probe is effective in detecting any translocation involving the IGH locus. This probe can be used on different samples from different B-cell lymphoproliferative processes, although it is not useful for classifying specific entities. Cancer (Cancer Cytopathol) 2012;. © 2012 American Cancer Society. Copyright © 2012 American Cancer Society.

  19. Preventing acute rejection, Epstein-Barr virus infection, and posttransplant lymphoproliferative disorders after kidney transplantation: Use of aciclovir and mycophenolate mofetil in a steroid-free immunosuppressive protocol

    DEFF Research Database (Denmark)

    Birkeland, S.A.; Andersen, H.K.; Hamilton-Dutoit, Stephen Jacques

    1999-01-01

    Background: A widely held view is that any increase in the potency of an immunosuppressive agent will lead to an increase in infection and malignancy, such as life-threatening Epstein-Barr virus (EBV) induced posttransplant lymphoproliferative disorders (PTLD), We tested this paradigm by studying......; the effect of adding mofetil to a steroid-free protocol under cover of high-dose aciclovir prophylaxis on the number of acute rejections, EBV infections and PTLDs after kidney transplantation. Methods: EBV serology was performed in 267 consecutive renal transplantations (1990-1997), All were treated...

  20. Outpatient management of steroid-induced hyperglycaemia and steroid-induced diabetes in people with lymphoproliferative disorders treated with intermittent high dose steroids

    Directory of Open Access Journals (Sweden)

    Jennifer Vidler

    2017-09-01

    Eighty-three people were diagnosed with a lymphoproliferative disorder, of whom 6 had known Type 2 diabetes. Fifty-three people without known diabetes were screened by HbA1c and random venous plasma glucose. All patients (n = 34 subsequently prescribed HDS checked capillary blood glucose (CBG pre-breakfast and pre-evening meal. Treatment algorithms used initiation and/or dose titration of gliclazide or human NPH insulin, aiming for pre-meal CBG 5–11 mmol/l. Type 2 diabetes was identified in 4/53 people screened (7.5%. Of 34 people treated with HDS, 17 (44% developed SIH/SID. All 7 people with Type 2 diabetes developed SIH and 3 required insulin. Of 27 people without known diabetes, 8 (30% developed SID and 1 required insulin. Pre-treatment HbA1c was higher in people who developed SID compared to those that did not (p = 0.002. This is the first report of a SID/SIH detection and treatment protocol for use in people with lymphoproliferative disorders receiving intermittent HDS, demonstrating its feasibility and safety.

  1. Autoimmune Lymphoproliferative Syndrome (ALPS)

    Science.gov (United States)

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  2. Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation (SCT) and quantitatively predicts EBV-lymphoproliferative disease following T-cell--depleted SCT

    NARCIS (Netherlands)

    van Esser, J W; van der Holt, B; Meijer, E; Niesters, H G; Trenschel, R; Thijsen, S F; van Loon, A M; Frassoni, F; Bacigalupo, A; Schaefer, U W; Osterhaus, A D; Gratama, J W; Löwenberg, B; Verdonck, L F; Cornelissen, J J

    2001-01-01

    Reactivation of the Epstein-Barr virus (EBV) after allogeneic stem cell transplantation (allo-SCT) may evoke a protective cellular immune response or may be complicated by the development of EBV-lymphoproliferative disease (EBV-LPD). So far, very little is known about the incidence, recurrence, and

  3. Epstein-Barr virus-positive post-transplant lymphoproliferative disorder of the central nervous system, after renal transplantation with a discrepancy in viral load between peripheral blood and cerebrospinal fluid

    NARCIS (Netherlands)

    Boersma, Marijke Nynke; van der Zanden, Adri; Laverman, Gozewijn Dirk; Sanders, Jan Stephan; de Vries, Peter Alexander Marcel

    2012-01-01

    A 43-year-old female developed an EpsteinBarr virus (EBV)-positive post-transplant lymphoproliferative disorder (PTLD) in the central nervous system (CNS), 14 years after renal transplantation. One year prior to presentation, the patients treatment regimen was altered from cyclosporine,

  4. Primary and secondary cutaneous CD30(+) lymphoproliferative disorders: a report from the Dutch Cutaneous Lymphoma Group on the long-term follow-up data of 219 patients and guidelines for diagnosis and treatment

    NARCIS (Netherlands)

    Bekkenk, M. W.; Geelen, F. A.; van Voorst Vader, P. C.; Heule, F.; Geerts, M. L.; van Vloten, W. A.; Meijer, C. J.; Willemze, R.

    2000-01-01

    To evaluate our diagnostic and therapeutic guidelines, clinical and long-term follow-up data of 219 patients with primary or secondary cutaneous CD30(+) lymphoproliferative disorders were evaluated. The study group included 118 patients with lymphomatoid papulosis (LyP; group 1), 79 patients with

  5. Oral cyclophosphamide was effective for Coombs-negative autoimmune hemolytic anemia in CD16+CD56- chronic lymphoproliferative disorder of NK-cells.

    Science.gov (United States)

    Sekiguchi, Nodoka; Nishina, Sayaka; Kawakami, Toru; Sakai, Hitoshi; Senoo, Noriko; Senoo, Yasushi; Ito, Toshiro; Saito, Hiroshi; Nakazawa, Hideyuki; Koizumi, Tomonobu; Ishida, Fumihiro

    2017-06-01

    An 84-year-old woman was referred to our hospital presenting anemia. Her hemoglobin level was 5.8 g/dL, and white blood cell count was 9400/μL, consisting of 82% lymphocytes. Given the lymphocyte phenotype (CD2+, CD3-, CD16+, and CD56-) and negative whole blood EBV viral load, we made a diagnosis of chronic lymphoproliferative disorder of NK cells (CLPD-NK). We suspected hemolytic anemia because of the high levels of reticulocytes in the peripheral blood and the low haptoglobin value. Although the direct Coombs test was negative and there was no cold agglutination, we examined her red-blood-cell-bound IgG (RBC-IgG), which was elevated. She was diagnosed as having as Coombs-negative autoimmune hemolytic anemia (AIHA). We report the effectiveness of oral cyclophosphamide for Coombs-negative autoimmune hemolytic anemia in CLPD-NK.

  6. Desordem linfoproliferativa pós-transplante em paciente pediátrico Post-transplantation lymphoproliferative disorder in pediatric patient

    Directory of Open Access Journals (Sweden)

    Paulo Manuel Pêgo Fernandes

    2006-10-01

    Full Text Available Terapias de imunossupressão, a que pacientes transplantados devem ser submetidos, os expõe a um alto risco de desenvolver desordens linfoproliferativas pós-transplante (PTLD. Descrevemos o caso de uma criança submetida a transplante cardíaco aos sete meses de idade e que acabou desenvolvendo PTLD, aos nove anos, diagnosticada por meio de retirada de nódulo pulmonar.Immunosuppressive therapy for transplanted patients exposes them to a high risk of developing posttransplantation lymphoproliferative disorders (PTLD. We report the case of a child undergoing heart transplantation at seven months of age who developed PTLD at nine years of age, diagnosed by resection of a pulmonary nodule.

  7. T-Cell lymphoproliferative disorder of hand-mirror cell morphology presenting in an eosinophilic loculated peritoneal effusion, with omental "caking"

    Directory of Open Access Journals (Sweden)

    Tufankjian Dearon

    2006-01-01

    Full Text Available Abstract Background Cells with "hand mirror" morphology have not, to the best of our knowledge, been described in a primary effusion sample. This paper describes a case of T-cell lymphoma with eosinophilia in a patient with suspected peritoneal carcinomatosis. Rarely, a T-cell lymphoproliferative process may mimic primary peritoneal carcinomatosis, clinically suggested by a presentation in CT imaging of omental caking with bilateral massive loculated effusions in a patient without lymphadenopathy or splenomegaly. Methods A 60 year old caucasian male presented with vague abdominal discomfort and increasing abdominal girth. Computed tomography showed a two centimeter thick omental cake and a small loculated effusion. The clinical presentation and imaging findings were most consistent with peritoneal carcinomatosis. Cytologic evaluation of the effusion was undertaken for diagnostic study. Results Rapid intraprocedural interpretation of the effusion sample showed a monomorphic population of cells with "hand-mirror" cell morphology exhibiting cytoplasmic extensions (uropodia with 3–5 course dark cytoplasmic granules and a rim of vacuolated cytoplasm capping the opposing "mirror head" side. These cells were seen within a background of mature eosinophils. Flow cytometric evaluation of the ascites fluid demonstrated an atypical T-cell population with the following immunophenotype: CD2-, CD3+, CD4-, CD5-, CD7-, CD8+, CD56+. T-cell receptor (TCR gene rearrangement was positive for clonal TCR-gamma gene rearrangement, supporting the diagnosis of a T-lymphoprolifereative disorder. Conclusion A T-cell lymphoproliferative process may present with "hand mirror" morphology in an effusion sample. These cells may show polar cytoplasmic vacuolization and 3–5 course granules within the "handle" of these unique cells. Cytoplasm shows peripheral constriction around the nucleus.

  8. The Epstein-Barr virus microRNA BART11-5p targets the early B-cell transcription factor EBF1.

    Science.gov (United States)

    Ross, Nathan; Gandhi, Maher K; Nourse, Jamie P

    2013-01-01

    Epstein-Barr virus (EBV) is a ubiquitous B-cell trophic herpesvirus associated with a variety of histologically diverse B-cell lymphomas, each associated with specific viral-latency gene expression programs. Initial infection drives resting B-cells to differentiate via an atypical germinal centre reaction into memory B-cells, where the virus resides in a latent state. The mechanisms that underpin this process have yet to be fully elucidated. EBV expresses more than 40 microRNAs (miRNAs). The alternatively spliced BamHI A rightward transcripts (BARTs) are the template for two large miRNA clusters (BARTs A and B), that comprise the majority of all known EBV-miRNAs. Although BART-miRNAs are abundantly expressed in all latency programs, few BART-miRNA targets have been identified and their function is poorly understood. The early B-cell factor 1 (EBF1) was identified using bioinformaticss analysis as a novel target of EBV-miRNA BART11-5p, encoded by BART cluster B. EBF1 is an important B-cell transcription factor that regulates many B-cell specific genes including Pax5, BCR and CD40 and is critical for germinal centre formation. Using luciferase reporter assays and a series of BART-constructs, we confirmed silencing via the EBF1 3' untranslated region (UTR) and identified the target site as 2137-2159 bp after the stop codon. Results were confirmed following transfection of a BART11-5p mimic, which was able to silence via the predicted target site. Our findings highlight a potential role of BART-miRNAs in the regulation of B-cell differentiation.

  9. A meta-analysis of potential relationship between Epstein-Barr-Encoded-RNA (EBER and onset time of post-transplant lymphoproliferative disorders

    Directory of Open Access Journals (Sweden)

    Hossein Khedmat

    2015-01-01

    Full Text Available Epstein-Barr virus (EBV encodes two non-polyadenylated RNAs termed EBV-encoded RNAs (EBERs. In this study, we tried to find series in which data of EBER and onset time of post-transplant lymphoproliferative disorder (PTLD for patients have been documented to conduct a meta-analysis. A comprehensive search of the literature was performed by Pubmed and Google scholar to find reports indicating test results for EBER and PTLD onset in transplant patients. PTLD was considered "early onset" when it develops within the first post-transplant year. Finally, 265 patients from 15 studies have been included in the meta-analysis. The overall meta-analysis also showed a significant relation between EBER test positivity and early-onset PTLD development [relative risk (RR: 1.36; 95% CI: 1.16-1.59; P <0.001]. The i2 index was 49.8%. Our study suggests that PTLD lesions with positive EBER test are more likely to develop within the early post-transplant period. Since early-onset PTLD is supposed to have better prognosis, having a positive EBER test might not be a bad news. However, for having a precise conclusion, prospective studies are needed to be conducted.

  10. Early Gastric Post-Transplant Lymphoproliferative Disorder and H pylori Detection after Kidney Transplantation: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    CL Nash

    2000-01-01

    Full Text Available The incidence of post-transplantation lymphoproliferative disorder (PTLD in the adult renal transplant population ranges from 0.7% to 4%. The majority of cases involve a single site and arise, on average, seven months after transplantation. Histopathology usually reveals B-cell proliferative disease and has been standardized into its own classification. Treatment modalities consist of decreased immunosuppression, eradication of Epstein-Barr virus, surgical resection, systemic chemotherapy and monoclonal antibody therapy; however, mortality remains high, typically with a short survival time. In patients who have undergone renal transplantation, approximately 10% of those with PTLDs present with gastrointestinal symptomatology and disease. Reported sites include the stomach, and small and large bowel. Very few cases of Helicobacter pylori or mucosal-associated lymphoid tissue have been described in association with PTLD. In the era of cyclosporine immunosuppression, the incidence of PTLD affecting the gastrointestinal tract may be increasing in comparison with the incidence seen with the use of older immunosuppression regimens. A case of antral PTLD and H pylori infection occurring three months after renal transplantation is presented, and the natural history and management of gastric PTLD are reviewed.

  11. Epstein-Barr Virus-Positive Extranodal Marginal Zone Lymphoma of Bronchial-Associated Lymphoid Tissue in the Posttransplant Setting: An Immunodeficiency-Related (Posttransplant) Lymphoproliferative Disorder?

    Science.gov (United States)

    Cassidy, Daniel P; Vega, Francisco; Chapman, Jennifer R

    2017-12-20

    Posttransplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of hematolymphoid proliferations arising in the context of chronic immunosuppression. The common and indolent B-cell lymphomas, including extranodal marginal zone lymphomas (ENMZLs) of mucosa-associated lymphoid tissue (MALT), are excluded from the category of PTLD in the current World Health Organization classification. We report a case of Epstein-Barr virus (EBV)-positive bronchial-associated lymphoid tissue (BALT) lymphoma involving the lungs of a transplant patient. Aside from history of cardiac transplant, young patient age, and EBV positivity, the histopathologic findings were indistinguishable from usual BALT lymphoma. We review the literature of ENMZL occurring in immunocompromised patients and present this case for consideration that this specific entity is a PTLD. We believe that additional studies might lend strength to the hypothesis that this particular group of EBV-positive, posttransplant ENMZLs merits classification and management as PTLDs. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  12. Post transplant lymphoproliferative disease in pediatric solid organ transplant patients: A possible role for [18F]-FDG-PET(/CT) in initial staging and therapy monitoring

    International Nuclear Information System (INIS)

    Falck, C. von; Maecker, B.; Schirg, E.; Boerner, A.R.; Knapp, W.H.; Klein, C.; Galanski, M.

    2007-01-01

    Post transplant lymphoproliferative disease (PTLD) is a severe complication after solid organ or bone marrow transplantation. In pediatric transplant recipients PTLD is the most common malignancy. The aim of this study was to evaluate a possible role for positron emission tomography with [ 18 F]-2-fluoro-2-desoxy-glucose (FDG) in the initial staging and in therapy monitoring of pediatric patients suffering from biopsy-proven CD20-positive PTLD after solid organ transplantation. Seven pediatric patients were included. All available imaging studies - CT (n = 15), MRI (n = 16) and PET/PETCT (n = 16) - were reviewed on a lesion by lesion base. The performance of FDG-PET in the initial staging and during therapy with a chimeric anti-CD20 antibody was compared to conventional cross sectional imaging and correlated with the clinical outcome. FDG-PET identified all sites of disease as shown by CT/MRI and helped to clarify the significance of equivocal findings. The initial stage of disease was correctly identified by FDG-PET alone when compared to CT/MRI. During therapy, FDG-PET was superior to conventional cross-sectional imaging in the early evaluation of response

  13. Post-Transplant Lymphoproliferative Disorder (PTLD) Manifesting in the Oral Cavity of a 13-Year-Old Liver Transplant Recipient (LTx).

    Science.gov (United States)

    Krasuska-Sławińska, Ewa; Minko-Chojnowska, Izabela; Pawłowska, Joanna; Dembowska-Bagińska, Bożenna; Pronicki, Maciej; Olczak-Kowalczyk, Dorota

    2015-08-18

    BACKGROUND Post-transplant lymphoproliferative disorder (PTLD) is a potential complication of solid organ or bone marrow transplants. The main PTLD risk factors are: the Epstein-Barr virus (EBV), transplant type, and use of immunosuppressants. It mainly consists of an uncontrolled growth of lymphocytes in transplant recipients under chronic immunosuppressive therapy. About 85% of PTLDs are EBV-containing B-cell proliferations; 14% are T-cell proliferations, of which only 40% contain EBV; and the remaining 1% is NK-cell or plasmocyte proliferations. PTLD may present various clinical manifestations, from non-specific mononucleosis-like syndrome to graft or other organ damage resulting from pathologic lymphocyte infiltration. PTLD may manifest in the oral cavity. CASE REPORT The objective of this study was to present the case of a 13-year-old female living-donor liver transplant recipient, resulting from biliary cirrhosis caused by congenital biliary atresia, with exophytic fibrous lesions on buccal mucosa and tongue. Exophytic and hyperplastic lesion of oral mucosa were removed and histopathological examination revealed polymorphic PTLD. The patient underwent 6 cycles of CHOP chemotherapy and all the oral lesions regressed completely. CONCLUSIONS All oral pathological lesions in organ transplant recipients need to be surgically removed and histopathologically examined because they present an increased risk of neoplastic transformations such as PTLD.

  14. Post transplant lymphoproliferative disease in pediatric solid organ transplant patients: A possible role for [{sup 18}F]-FDG-PET(/CT) in initial staging and therapy monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Falck, C. von [Department of Diagnostic Radiology, Medizinische Hochschule Hannover (Medical School Hanover), Carl-Neuberg-Strasse 1, 30625 Hannover (Germany)], E-mail: Falck.Christian.von@mh-hannover.de; Maecker, B. [Department of Pediatric Hematology and Oncology, Medizinische Hochschule Hannover (Medical School Hanover), Carl-Neuberg-Strasse 1, 30625 Hannover (Germany); Schirg, E. [Department of Diagnostic Radiology, Medizinische Hochschule Hannover (Medical School Hanover), Carl-Neuberg-Strasse 1, 30625 Hannover (Germany); Boerner, A.R.; Knapp, W.H. [Department of Nuclear Medicine, Medizinische Hochschule Hannover (Medical School Hanover), Carl-Neuberg-Strasse 1, 30625 Hannover (Germany); Klein, C. [Department of Pediatric Hematology and Oncology, Medizinische Hochschule Hannover (Medical School Hanover), Carl-Neuberg-Strasse 1, 30625 Hannover (Germany); Galanski, M. [Department of Diagnostic Radiology, Medizinische Hochschule Hannover (Medical School Hanover), Carl-Neuberg-Strasse 1, 30625 Hannover (Germany)

    2007-09-15

    Post transplant lymphoproliferative disease (PTLD) is a severe complication after solid organ or bone marrow transplantation. In pediatric transplant recipients PTLD is the most common malignancy. The aim of this study was to evaluate a possible role for positron emission tomography with [{sup 18}F]-2-fluoro-2-desoxy-glucose (FDG) in the initial staging and in therapy monitoring of pediatric patients suffering from biopsy-proven CD20-positive PTLD after solid organ transplantation. Seven pediatric patients were included. All available imaging studies - CT (n = 15), MRI (n = 16) and PET/PETCT (n = 16) - were reviewed on a lesion by lesion base. The performance of FDG-PET in the initial staging and during therapy with a chimeric anti-CD20 antibody was compared to conventional cross sectional imaging and correlated with the clinical outcome. FDG-PET identified all sites of disease as shown by CT/MRI and helped to clarify the significance of equivocal findings. The initial stage of disease was correctly identified by FDG-PET alone when compared to CT/MRI. During therapy, FDG-PET was superior to conventional cross-sectional imaging in the early evaluation of response.

  15. Target Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — [Part of the ATLAS user facility.] The Physics Division operates a target development laboratory that produces targets and foils of various thickness and substrates,...

  16. Dynamic contrast-enhanced MRI in orbital lymphoproliferative disorders: Effects of region of interest selection methods on time efficiency, measurement reproducibility, and diagnostic ability.

    Science.gov (United States)

    Qian, Wen; Xu, Xiao-Quan; Hu, Hao; Su, Guo-Yi; Wu, Jiang-Fen; Shi, Hai-Bin; Wu, Fei-Yun

    2017-09-18

    Previous studies indicated that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) could serve as a useful biomarker for differentiating malignant from benign orbital lymphoproliferative disorders (OLPDs). To investigate the influence of different region of interest (ROI) selection methods on the measurements of DCE-MRI parameters, and their diagnostic ability in discriminating malignant from benign OLPDs. Retrospective study. In all, 46 patients with OLPDs (22 benign and 24 malignant). 3.T DCE-MRI using a 2D turbo fast low angle shot sequence postcontrast. DCE-MRI data were analyzed using three different ROI selection methods, including whole-tumor ROI (ROI WT ), single-slice ROI (ROI SS ) and hot-spot ROI (ROI HS ). Quantitative parameters (K trans , K ep , V e ) were calculated based on a modified Tofts model. Analysis of variance test, intraclass correlation coefficient (ICC), Bland-Altman plots, independent t-test, and receiver operating characteristic curve analyses were used for statistical analyses. The time required for outlining ROI WT was significantly longer than ROI SS and ROI HS (P measurements of DCE-MRI-derived parameters based on ROI HS demonstrated lowest ICC, followed by ROI SS and ROI WT . Malignant OLPDs showed significantly higher K ep than benign mimics (P methods could have an influence on the measurements of DCE-MRI parameters. Taking measurement time, reproducibility, and diagnostic ability into account, we suggest single-slice ROI to be used for differentiating malignant from benign OLPDs in clinical practice. 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017. © 2017 International Society for Magnetic Resonance in Medicine.

  17. Construction of a YAC contig and STS map spanning 2.5 Mbp in Xq25, the critical region for the X-linked lymphoproliferative (XLP) gene

    Energy Technology Data Exchange (ETDEWEB)

    Lanyi, A.; Li, B.F.; Li, S. [Univ. of Nebraska Medical Center, Omaha, NE (United States)] [and others

    1994-09-01

    X-linked lymphoproliferative disease (XLP) is characterized by a marked vulnerability in Epstein-Barr virus (EBV) infection. Infection of XLP patients with EBV invariably results in fatal mononucleosis, agammaglobulinemia or B-cell lymphoma. The XLP gene lies within a 10 cM region in Xq25 between DXS42 and DXS10. Initial chromosome studies revealed an interstitial, cytogenetically visible deletion in Xq25 in one XLP family (43-004). We estimated the size of the Xq25 deletion by dual laser flow karyotyping to involve 2% of the X chromosome, or approximately 3 Mbp of DNA sequences. To further delineate the deletion we performed a series of pulsed field gel electrophoresis (PFGE) analyses which showed that DXS6 and DXS100, two Xq25-specific markers, are missing from 45-004 DNA. Five yeast artificial chromosomes (YACs) from a chromosome X specific YAC library containing sequences deleted in patient`s 43-004 DNA were isolated. These five YACs did not overlap, and their end fragments were used to screen the CEPH MegaYAC library. Seven YACs were isolated from the CEPH MegaYAC library. They could be arranged into a contig which spans between DXS6 and DXS100. The contig contains a minimum of 2.5 Mbp of human DNA. A total of 12 YAC end clone, lambda subclones and STS probes have been used to order clones within the contig. These reagents were also used in Southern blot and patients showed interstitial deletions in Xq25. The size of these deletions range between 0.5 and 2.5 Mbp. The shortest deletion probably represents the critical region for the XLP gene.

  18. The value of DNA storage and pedigree analysis in rare diseases: a 17-year-old boy with X-linked lymphoproliferative disease (XLP) caused by a de novo SH2D1A mutation.

    Science.gov (United States)

    Overwater, E; Smulders, Y; van der Burg, M; Lombardi, M P; Meijers-Heijboer, H E; Kuijpers, T W; Houweling, A C

    2014-12-01

    We present a case of a fatal Epstein-Barr infection in a 17-year-old male patient suspected to be caused by X-linked lymphoproliferative disease. At the time of hospitalization, DNA diagnostics was not available. The suspected diagnosis was confirmed several years later when a SH2D1A missense mutation was identified in stored patient DNA. Extended pedigree analysis showed that this mutation occurred de novo in his mother. In addition, we provide a summary of the currently listed SH2D1A mutations. This case report underlines the importance of DNA storage, pedigree analysis, and multidisciplinary care in patients with rare diseases and their families.

  19. Composite cutaneous lymphoma (iatrogenic immunodeficiency-associated lymphoproliferative disorder) in a patient with rheumatoid arthritis treated with methotrexate: Staging and evaluation of response to therapy with 1'8F-FDG PET/CT

    International Nuclear Information System (INIS)

    Makis, William; Ciarallo, Anthony; Gonzalez-Verdecia, Milene; Wang, Beatrice; Probst, Stehan

    2017-01-01

    A 67 year old woman with a 10 year history of rheumatoid arthritis (RA) treated with methotrexate and prednisone, presented with a 2 year history of worsening multiple cutaneous plaques of variable appearance. Two distinct skin lesions were biopsied to reveal a composite cutaneous lymphoma, possibly caused by long term methotrexate therapy. An [18F] fluoro-2-deoxy-D-glucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) was performed to stage the malignancy, and was later repeated to evaluate response to chemotherapy, which guided subsequent management. We present the PET/CT imaging findings of this very rare iatrogenic (methotrexate induced) immunodeficiency-associated lymphoproliferative disorder

  20. Frequency of a FAS ligand gene variant associated with inherited feline autoimmune lymphoproliferative syndrome in British shorthair cats in New Zealand.

    Science.gov (United States)

    Aberdein, D; Munday, J S; Dittmer, K E; Heathcott, R W; Lyons, L A

    2017-11-01

    AIMS To determine the frequency of the FAS-ligand gene (FASLG) variant associated with feline autoimmune lymphoproliferative syndrome (FALPS) and the proportion of carriers of the variant in three British shorthair (BSH) breeding catteries in New Zealand. METHODS Buccal swabs were collected from all cats in two BSH breeding catteries from the South Island and one from the North Island of New Zealand. DNA was extracted and was tested for the presence of the FASLG variant using PCR. Cats with the FASLG variant were identified and the frequency of the FASLG variant allele calculated. Pedigree analysis was performed and inbreeding coefficients were calculated for cats with the FASLG variant. RESULTS Of 32 BSH cats successfully tested for the presence of the FASLG variant, one kitten (3%) was homozygous (FALPS-affected), and seven (22%) cats were heterozygous (carriers) for the FASLG variant allele, and 24 (75%) cats were homozygous for the wild type allele. The overall frequency of the FASLG variant allele in these 32 cats was 0.14. Cats carrying the FASLG variant were from all three breeding catteries sampled, including two catteries that had not previously reported cases of FALPS. Pedigree analysis revealed common ancestry of FALPS-affected and carrier cats within six generations, as well as frequent inbreeding, with inbreeding coefficients >0.12 for five cats with the FASLG variant. CONCLUSIONS AND CLINICAL RELEVANCE There was a high frequency of the FASLG variant allele (0.14) in this small sample of BSH cats, with 22% of healthy cats identified as carriers of the FASLG variant. For an inherited disease, lethal at a young age, in a small population in which inbreeding is common, these results are significant. To prevent future cases of disease and stop further spread of the FASLG variant allele within the BSH population in New Zealand, it is recommended that all BSH and BSH-cross cats be tested for the presence of the FASLG variant before mating. Cats identified as

  1. Response to rituximab-based therapy and risk factor analysis in epstein barr virus-related lymphoproliferative disorder after hematopoietic stem cell transplant in children and adults: a study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.

    NARCIS (Netherlands)

    Styczynski, J.; Gil, L.; Tridello, G.; Ljungman, P.; Donnelly, J.P.; Velden, W. van der; Omar, H.; Martino, R.; Halkes, C.; Faraci, M.; Theunissen, K.; Kalwak, K.; Hubacek, P.; Sica, S.; Nozzoli, C.; Fagioli, F.; Matthes, S.; Diaz, M.A.; Migliavacca, M.; Balduzzi, A.; Tomaszewska, A.; amara Rde, L. C; Biezen, A. van; Hoek, J. van den; Iacobelli, S.; Einsele, H.; Cesaro, S.

    2013-01-01

    BACKGROUND: The objective of this analysis was to investigate prognostic factors that influence the outcome of Epstein-Barr virus (EBV)-related posttransplant lymphoproliferative disorder (PTLD) after a rituximab-based treatment in the allogeneic hematopoietic stem cell transplant (HSCT) setting.

  2. Antiproton Target

    CERN Multimedia

    1980-01-01

    Antiproton target used for the AA (antiproton accumulator). The first type of antiproton production target used from 1980 to 1982 comprised a rod of copper 3mm diameter and 120mm long embedded in a graphite cylinder that was itself pressed into a finned aluminium container. This assembly was air-cooled and it was used in conjunction with the Van der Meer magnetic horn. In 1983 Fermilab provided us with lithium lenses to replace the horn with a view to increasing the antiproton yield by about 30%. These lenses needed a much shorter target made of heavy metal - iridium was chosen for this purpose. The 50 mm iridium rod was housed in an extension to the original finned target container so that it could be brought very close to the entrance to the lithium lens. Picture 1 shows this target assembly and Picture 2 shows it mounted together with the lithium lens. These target containers had a short lifetime due to a combination of beam heating and radiation damage. This led to the design of the water-cooled target in...

  3. Autoimmune lymphoproliferative syndrome and non-Hodgkin lymphoma: what 18F-fluorodeoxyglucose positron emission tomography/computed tomography can do in the management of these patients? Suggestions from a case report.

    Science.gov (United States)

    Cistaro, A; Pazè, F; Durando, S; Cogoni, M; Faletti, R; Vesco, S; Vallero, S; Quartuccio, N; Treglia, G; Ramenghi, U

    2014-01-01

    A young patient with undefined autoimmune lymphoproliferative syndrome (ALPS-U) and low back pain underwent a CT and MRI study that showed enhancing vertebral lesions, some pulmonary nodules and diffuse latero-cervical lymphadenopathy. A (18)F-FDG-PET/CT scan showed many areas of intense (18)F-FDG uptake in multiple vertebrae, in some ribs, in the sacrum, in the liver, in both lungs, in multiple lymph nodes spread in the cervical, thoracic and abdominal chains. A bone marrow biopsy showed a "lymphomatoid granulomatosis", a rare variant of B-cell non-Hodgkin lymphoma (NHL). After the treatment, the (18)F-FDG-PET/CT scan showed a complete metabolic response. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

  4. Composite cutaneous lymphoma (iatrogenic immunodeficiency-associated lymphoproliferative disorder) in a patient with rheumatoid arthritis treated with methotrexate: Staging and evaluation of response to therapy with {sup 1}'8F-FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Makis, William [Dept. of Diagnostic Imaging, CCI, Diagnostic Imaging, Edmonton (Canada); Ciarallo, Anthony; Gonzalez-Verdecia, Milene [MUHC Glen Site, Montreal (Canada); Wang, Beatrice [MUHC, Dermatology, Westmount (Canada); Probst, Stehan [MUHC Jewish General Hospital, Nuclear Medicine, Montreal (Canada)

    2017-09-15

    A 67 year old woman with a 10 year history of rheumatoid arthritis (RA) treated with methotrexate and prednisone, presented with a 2 year history of worsening multiple cutaneous plaques of variable appearance. Two distinct skin lesions were biopsied to reveal a composite cutaneous lymphoma, possibly caused by long term methotrexate therapy. An [18F] fluoro-2-deoxy-D-glucose ({sup 18}F-FDG) positron emission tomography/computed tomography (PET/CT) was performed to stage the malignancy, and was later repeated to evaluate response to chemotherapy, which guided subsequent management. We present the PET/CT imaging findings of this very rare iatrogenic (methotrexate induced) immunodeficiency-associated lymphoproliferative disorder.

  5. Targeted Learning

    CERN Document Server

    van der Laan, Mark J

    2011-01-01

    The statistics profession is at a unique point in history. The need for valid statistical tools is greater than ever; data sets are massive, often measuring hundreds of thousands of measurements for a single subject. The field is ready to move towards clear objective benchmarks under which tools can be evaluated. Targeted learning allows (1) the full generalization and utilization of cross-validation as an estimator selection tool so that the subjective choices made by humans are now made by the machine, and (2) targeting the fitting of the probability distribution of the data toward the targe

  6. Accelerator target

    Science.gov (United States)

    Schlyer, David J.; Ferrieri, Richard A.; Koehler, Conrad

    1999-01-01

    A target includes a body having a depression in a front side for holding a sample for irradiation by a particle beam to produce a radioisotope. Cooling fins are disposed on a backside of the body opposite the depression. A foil is joined to the body front side to cover the depression and sample therein. A perforate grid is joined to the body atop the foil for supporting the foil and for transmitting the particle beam therethrough. A coolant is circulated over the fins to cool the body during the particle beam irradiation of the sample in the depression.

  7. New targeted treatments for cutaneous T-cell Lymphomas

    Directory of Open Access Journals (Sweden)

    Martine Bagot

    2017-01-01

    Full Text Available Cutaneous T-cell lymphomas (CTCLs represent a group of rare and heterogeneous diseases that are very difficult to treat at advanced stages. The development of monoclonal antibodies is a new hope for the treatment of these diseases. Alemtuzumab (Campath is a humanized IgG1 kappa monoclonal antibody specific for CD52, an antigen expressed by most T and B lymphocytes. Alemtuzumab may frequently induce long-term remissions in patients with Sezary syndrome but high-dose treatments lead to severe cytopenia, immune depletion, and opportunistic infections. This treatment is less efficient in mycosis fungoides (MF. Brentuximab vedotin is a chimeric anti-CD30 monoclonal antibody conjugated to monomethyl auristatin E, a cytotoxic antitubulin agent. Brentuximab vedotin is a very interesting new treatment for advanced tumor MF, Sezary syndrome, and primary cutaneous CD30+ lymphoproliferative disorders. The main limiting adverse event is neurosensitive peripheral neuropathy. Mogamulizumab is a humanized anti-C-C chemokine receptor Type 4 monoclonal antibody with a defucosylated Fc region leading to increased antibody-dependent cellular cytotoxicity. Mogamulizumab is very efficient on aggressive peripheral T-cell lymphomas, particularly adult T-cell leukemia/lymphoma and CTCLs, especially on the blood component of tumor cells. The main limiting events are related to the concomitant depletion of regulatory T-cells. IPH4102 is a humanized monoclonal antibody that targets the immune receptor KIR3DL2/CD158k. Preclinical results with this antibody offer proofs of concept for the clinical development of IPH4102 to treat patients with advanced CTCL.

  8. Targets and teamwork

    DEFF Research Database (Denmark)

    Skinner, Timothy C.; Lange, Karin S.; Hoey, Hilary

    2017-01-01

    with less disagreement about recommended targets. Multiple regression analysis indicated that teams reporting higher HbA1c targets and more target disagreement had parents reporting higher treatment targets. This seemed to partially account for center differences in Hb1Ac. Conclusions: The diabetes care...

  9. Genetics Home Reference: autoimmune lymphoproliferative syndrome

    Science.gov (United States)

    ... NBK1108/ Citation on PubMed Dowdell KC, Niemela JE, Price S, Davis J, Hornung RL, Oliveira JB, Puck JM, ... on PubMed or Free article on PubMed Central Price S, Shaw PA, Seitz A, Joshi G, Davis J, ...

  10. Rapidly progressive post-transplant lymphoproliferative disease ...

    African Journals Online (AJOL)

    Sirolimus, a potent inhibitor of B- and T-cell activation, is a commonly used immunosuppressant after renal transplantation. Withdrawal of sirolimus from the immunosuppression regimen may reduce B-cell surveillance. We present a case of rapidly progressive central nervous system (CNS) polymorphic Epstein-Barr virus ...

  11. X-Linked Lymphoproliferative Disease (XLP)

    Science.gov (United States)

    ... Publications Help Archive Site Map Información en español Employee Information Connect with NIAID Facebook Twitter Linkedin Google+ Youtube Flickr Instagram Pinterest Email Website Policies & Notices ...

  12. Molecular Targets for Targeted Radionuclide Therapy

    International Nuclear Information System (INIS)

    Mather, S.J.

    2009-01-01

    Molecular targeted radionuclide cancer therapy is becoming of increasing importance, especially for disseminated diseases. Systemic chemotherapies often lack selectivity while targeted radionuclide therapy has important advantages as the radioactive cytotoxic unit of the targeting vector is specifically directed to the cancer, sparing normal tissues. The principle strategy to improve cancer selectivity is to couple therapeutic agents to tumour-targeting vectors. In targeted radionuclide therapy (TRT), the cytotoxic portion of the conjugates normally contains a therapeutic radiometal immobilised by a bifunctional chelator. The aim is therefore to use as ligand-targeted therapeutics vectors coupled to Auger-, alpha- and/or beta-emitting radionuclides. An advantage of using radiation instead of chemotherapeutics as the cytotoxic agent is the so called 'crossfire effect'. This allows sterilisation of tumour cells that are not directly targeted due to heterogeneity in target molecule expression or inhomogeneous vector delivery. However, before the targeting ligands can be selected, the target molecule on the tumour has to be selected. It should be uniquely expressed, or at least highly overexpressed, on or in the target cells relative to normal tissues. The target should be easily accessible for ligand delivery and should not be shed or down- regulated after ligand binding. An important property of a receptor (or antigen) is its potential to be internalized upon binding of the ligand. This provides an active uptake mechanism and allows the therapeutic agent to be trapped within the tumour cells. Molecular targets of current interest include: Receptors: G-protein coupled receptors are overexpressed on many major human tumours. The prototype of these receptors are somatostatin receptors which show very high density in neuroendocrine tumours, but there are many other most interesting receptors to be applied for TRT. The targeting ligands for these receptors are

  13. Human target acquisition performance

    Science.gov (United States)

    Teaney, Brian P.; Du Bosq, Todd W.; Reynolds, Joseph P.; Thompson, Roger; Aghera, Sameer; Moyer, Steven K.; Flug, Eric; Espinola, Richard; Hixson, Jonathan

    2012-06-01

    The battlefield has shifted from armored vehicles to armed insurgents. Target acquisition (identification, recognition, and detection) range performance involving humans as targets is vital for modern warfare. The acquisition and neutralization of armed insurgents while at the same time minimizing fratricide and civilian casualties is a mounting concern. U.S. Army RDECOM CERDEC NVESD has conducted many experiments involving human targets for infrared and reflective band sensors. The target sets include human activities, hand-held objects, uniforms & armament, and other tactically relevant targets. This paper will define a set of standard task difficulty values for identification and recognition associated with human target acquisition performance.

  14. MYC as therapeutic target in leukemia and lymphoma

    Directory of Open Access Journals (Sweden)

    Cortiguera MG

    2015-07-01

    Full Text Available Maria G Cortiguera,1 Ana Batlle-López,1,2 Marta Albajar,1,2 M Dolores Delgado,1,3 Javier León1,3 1Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC, CSIC-University of Cantabria, 2Department of Hemathology, Hospital Universitario Marqués de Valdecilla, 3Department of Molecular Biology, University of Cantabria, Santander, Spain Abstract: MYC is a transcription factor that is involved in the expression of many genes. Deregulated MYC is found in about half of human tumors, being more prevalent in hematological neoplasms. Deregulation mechanisms include chromosomal translocation (particularly in lymphoma, amplification, and hyperactivation of MYC transcription. Here we review MYC involvement in the major types of leukemia and lymphoma. MYC rearrangements appear in all Burkitt lymphomas and are common in other lymphoma types, whereas in acute lymphoblastic leukemia, acute myeloid leukemia, lymphoproliferative, and myeloproferative diseases, they are less frequent. However, MYC overexpression is present in all types of hematological malignancies and often correlates with a worse prognosis. Data in leukemia-derived cells and in animal models of lymphomagenesis and leukemogenesis suggest that MYC would be a good therapeutic target. Several MYC-directed therapies have been assayed in preclinical settings and even in clinical trials. First, peptides and small molecules that interrupt the MYC–MAX interaction impair MYC-mediated tumorogenesis in several mouse models of solid tumors, although not yet in lymphoma and leukemia models. Second, there are a number of small molecules inhibiting the interaction of MYC–MAX heterodimers with DNA, still in the preclinical research phase. Third, inhibitors of MYC expression via the inhibition of BRD4 (a reader of acetylated histones have been shown to control the growth of MYC-transformed leukemia and lymphoma cells and are being used in clinic trials. Finally, we review a number of promising MYC

  15. Targeted therapies for cancer

    Science.gov (United States)

    ... Kummar S, Murgo AJ, Tomaszewski JE, Doroshow JH. Therapeutic targeting of cancer cells: era of molecularly targeted agents. ... ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow ...

  16. Reflectance Reference Targets (OTTER)

    Data.gov (United States)

    National Aeronautics and Space Administration — ABSTRACT: Spectral reflectance measurements of flat field targets as reference points representative of pseudo-invariant targets as measured by Spectron SE590...

  17. Reflectance Reference Targets (OTTER)

    Data.gov (United States)

    National Aeronautics and Space Administration — Spectral reflectance measurements of flat field targets as reference points representative of pseudo-invariant targets as measured by Spectron SE590 spectrophotometer

  18. TARGET COSTING FUNCTIONS

    OpenAIRE

    OFILEANU Dimi

    2015-01-01

    This article aims to highlight the concept of Target Costing. Based on the characteristics of Target Costing, identified in specialized literature, the article presents its main advantages and disadvantages. Also, a comparison is being made between Target Cost and Traditional Cost (in its traditional form, the cost represents an independent variable on the basis of which the sell price is established; and in the Target Cost form the cost represents a dependent variable which is determined on ...

  19. Targeting outcomes redux

    OpenAIRE

    Coady, David P.; Grosh, Margaret; Hoddinott, John

    2002-01-01

    "...There are sharply divergent views as to how much narrowly targeted interventions actually benefit the poor. These result from differing assessments of three issues: whether better targeting outcomes are likely to be achieved, whether such methods are cost-effective, and whether the living standards of the poor are improved by such targeted interventions. This paper focuses on the first issue. Using a newly constructed database of targeted interventions, it addresses three questions: (1) W...

  20. Graphite targets at LAMPF

    International Nuclear Information System (INIS)

    Brown, R.D.; Grisham, D.L.

    1983-01-01

    Rotating polycrystalline and stationary pyrolytic graphite target designs for the LAMPF experimental area are described. Examples of finite element calculations of temperatures and stresses are presented. Some results of a metallographic investigation of irradiated pyrolytic graphite target plates are included, together with a brief description of high temperature bearings for the rotating targets

  1. Síndrome linfoproliferativo ligado al cromosoma X, infección por el virus EBV y defectos en la regulación de la citotoxicidad linfocitaria X-linked lymphoproliferative syndrome, EBV infection and impaired regulation of cell-mediated cytotoxicity

    Directory of Open Access Journals (Sweden)

    A. Malbrán

    2003-01-01

    Full Text Available La deficiencia del gen SH2D1A que codifica para la proteína reguladora SAP trae aparejada la activación incontrolada de la vía de activación linfocitaria señalizada por SLAM (molécula señaladora de la activación linfocitaria. Es una inmunodeficiencia ligada al cromosoma X (XLP que se pone en evidencia cuando los pacientes portadores de mutaciones en el gen se enfrentan con el virus de Epstein Barr, desarrollando una mononucleosis infecciosa fulminante. Algunos pacientes desarrollan un síndrome linfoproliferativo fatal; los que sobreviven pueden presentar hipogammaglobulinemia severa y mayor frecuencia de neoplasia hematológica que la población normal. En esta revisión se discuten los mecanismos inmuno-regulatorios involucrados en el desarrollo de la patología mencionada, así como la participación de diferentes células efectoras de la respuesta inmune (linfocitos CD8 citotóxicos, células NK.Mutations in SH2D1A, a gene that codifies for the regulatory protein SAP, result in uncontrolled activation of the SLAM (signaling lymphocyte-activation molecule pathway. This X-linked immunodeficiency becomes evident when the patients are infected with Epstein Barr virus (EBV and develop a fulminant form of infectious mononucleosis leading to a lymphoproliferative syndrome that is often fatal (X-linked lymphoproliferative syndrome, XLP. In those who survive, hypogammaglobulinemia and oncohematologic diseases are frequently observed. In this revision, the immuno-regulatory mechanisms involved in XLP immunopathology and the role of different effector cells (CD8 T lymphocytes, NK cells are discussed.

  2. Development of distributed target

    CERN Document Server

    Yu Hai Jun; Li Qin; Zhou Fu Xin; Shi Jin Shui; Ma Bing; Chen Nan; Jing Xiao Bing

    2002-01-01

    Linear introduction accelerator is expected to generate small diameter X-ray spots with high intensity. The interaction of the electron beam with plasmas generated at the X-ray converter will make the spot on target increase with time and debase the X-ray dose and the imaging resolving power. A distributed target is developed which has about 24 pieces of thin 0.05 mm tantalum films distributed over 1 cm. due to the structure adoption, the distributed target material over a large volume decreases the energy deposition per unit volume and hence reduces the temperature of target surface, then reduces the initial plasma formalizing and its expansion velocity. The comparison and analysis with two kinds of target structures are presented using numerical calculation and experiments, the results show the X-ray dose and normalized angle distribution of the two is basically the same, while the surface of the distributed target is not destroyed like the previous block target

  3. Bar coded retroreflective target

    Science.gov (United States)

    Vann, Charles S.

    2000-01-01

    This small, inexpensive, non-contact laser sensor can detect the location of a retroreflective target in a relatively large volume and up to six degrees of position. The tracker's laser beam is formed into a plane of light which is swept across the space of interest. When the beam illuminates the retroreflector, some of the light returns to the tracker. The intensity, angle, and time of the return beam is measured to calculate the three dimensional location of the target. With three retroreflectors on the target, the locations of three points on the target are measured, enabling the calculation of all six degrees of target position. Until now, devices for three-dimensional tracking of objects in a large volume have been heavy, large, and very expensive. Because of the simplicity and unique characteristics of this tracker, it is capable of three-dimensional tracking of one to several objects in a large volume, yet it is compact, light-weight, and relatively inexpensive. Alternatively, a tracker produces a diverging laser beam which is directed towards a fixed position, and senses when a retroreflective target enters the fixed field of view. An optically bar coded target can be read by the tracker to provide information about the target. The target can be formed of a ball lens with a bar code on one end. As the target moves through the field, the ball lens causes the laser beam to scan across the bar code.

  4. Business Targets and Compliance

    OpenAIRE

    Albers, Felicitas G.

    2014-01-01

    The finding and setting of a business target is the starting point whenever dealing with corporate governance; the autonomy of companies to define those targets is one constitutive characteristic of any market economy. Regulatory demands as the standardization of the German ‘Unternehmensinteresse’ (interest of the company) in the German stock corporation laws as well as ethical-theoretical approaches in the process of forming targets gain relevance both in theory and practice in the context o...

  5. The ISOLDE target robots

    CERN Multimedia

    Maximilein Brice

    2002-01-01

    ISOLDE targets need to be changed frequently, around 80 times per year. The high radiation levels do not permit this to be done by human hands and the target changes are effected by 2 industrial robots (picture _01). On the left, in the distance, the front-end of the GPS (General Purpose Separator) is seen, while the HRS (High Resolution Separator) is at the right. Also seen are the doors to the irradiated-target storage.

  6. Targeting and Persuasive Advertising

    OpenAIRE

    Egli, Alain (Autor/in)

    2015-01-01

    Firms face a prisoner's dilemma when advertising in a competitive environment. In a Hotelling framework with persuasive advertisingfirms counteract this prisoner's dilemma with targeting. The firms even solve the prisoner's problem if targeted advertising is effective enough. Advertising turns from wasteful competition into profits. This is in contrast to wasteful competition as argument for regulations. A further result is maximum advertising differentiation: thefirms target their advertisin...

  7. Targeted Radionuclide Therapy

    International Nuclear Information System (INIS)

    Ersahin, Devrim; Doddamane, Indukala; Cheng, David

    2011-01-01

    Targeted radiotherapy is an evolving and promising modality of cancer treatment. The killing of cancer cells is achieved with the use of biological vectors and appropriate radionuclides. Among the many advantages of this approach are its selectiveness in delivering the radiation to the target, relatively less severe and infrequent side effects, and the possibility of assessing the uptake by the tumor prior to the therapy. Several different radiopharmaceuticals are currently being used by various administration routes and targeting mechanisms. This article aims to briefly review the current status of targeted radiotherapy as well as to outline the advantages and disadvantages of radionuclides used for this purpose

  8. Targeting the tumor microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Kenny, P.A.; Lee, G.Y.; Bissell, M.J.

    2006-11-07

    Despite some notable successes cancer remains, for the most part, a seemingly intractable problem. There is, however, a growing appreciation that targeting the tumor epithelium in isolation is not sufficient as there is an intricate mutually sustaining synergy between the tumor epithelial cells and their surrounding stroma. As the details of this dialogue emerge, new therapeutic targets have been proposed. The FDA has already approved drugs targeting microenvironmental components such as VEGF and aromatase and many more agents are in the pipeline. In this article, we describe some of the 'druggable' targets and processes within the tumor microenvironment and review the approaches being taken to disrupt these interactions.

  9. Target Assembly Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Target Assembly Facility integrates new armor concepts into actual armored vehicles. Featuring the capability ofmachining and cutting radioactive materials, it...

  10. Targeting the PI3K/mTOR Pathway in Pediatric Hematologic Malignancies

    Directory of Open Access Journals (Sweden)

    Sarah K Tasian

    2014-05-01

    Full Text Available A complex interplay of intracellular signaling networks orchestrates normal cell growth and survival, including translation, transcription, proliferation, and cell cycle progression. Dysregulation of such signals occurs commonly in many malignancies, thereby giving the cancer cell a survival advantage, but also providing possible targets for therapeutic intervention. Activation of the phosphatidylinositol 3-kinase (PI3K/protein kinase B (Akt/mammalian target of rapamycin (mTOR signaling pathway contributes to the proliferative advantage of malignant cells and may confer resistance to chemotherapy in various hematologic malignancies. The initial mTOR inhibitor, sirolimus (also known as rapamycin, was first discovered in 1975 in the soil of Easter Island. Sirolimus was originally developed as an anti-fungal agent given its macrolide properties, but was approved by the Food and Drug Administration (FDA in 1999 as an immunosuppressive agent for renal transplantation patients once its T cell suppression characteristics were recognized. Shortly thereafter, recognition of sirolimus’s ability to inhibit cellular proliferation and cell cycle progression brought sirolimus to the forefront as a possible inhibitor of mTOR. In the subsequent decade, the functional roles of the mTOR protein have been more fully elucidated, and this protein is now known to be a key regulator in a highly complex signaling pathway that controls cell growth, proliferation, metabolism, and apoptosis. This article discusses the dysregulation of PI3K/mTOR signaling in hematologic malignancies, including acute and chronic leukemias, lymphomas, and lymphoproliferative disorders. The current repertoire of PI3K/mTOR pathway inhibitors in development and clinical trials to date are described with emphasis upon pediatric hematologic malignancies (Figure 1. Investigation of small molecule inhibitors of this complex signaling network is an active area of oncology drug development.

  11. The CNGS target

    CERN Multimedia

    Patrice Loïez

    2005-01-01

    The CERN Neutrinos to Gran Sasso (CNGS) target ‘magazine’ of five target units. Each unit contains a series of 10-cm long graphite rods distributed over a length of 2 m. It is designed to maximize the number of secondary particles produced and hence the number of neutrinos. One unit is used at a time to prevent over heating.

  12. Modelling Recycling Targets

    DEFF Research Database (Denmark)

    Hill, Amanda Louise; Leinikka Dall, Ole; Andersen, Frits M.

    2014-01-01

    % for household waste, and sets an ambitious goal of a 50% recycling rate by 2020. This study integrates the recycling target into the FRIDA model to project how much waste and from which streams should be diverted from incineration to recycling in order to achieve the target. Furthermore, it discusses how...

  13. Strategic Targeted Advertising

    NARCIS (Netherlands)

    A. Galeotti; J.L. Moraga-Gonzalez (José Luis)

    2003-01-01

    textabstractWe present a strategic game of pricing and targeted-advertising. Firms can simultaneously target price advertisements to different groups of customers, or to the entire market. Pure strategy equilibria do not exist and thus market segmentation cannot occur surely. Equilibria exhibit

  14. Seedling root targets

    Science.gov (United States)

    Diane L. Haase

    2011-01-01

    Roots are critical to seedling performance after outplanting. Although root quality is not as quick and simple to measure as shoot quality, target root characteristics should be included in any seedling quality assessment program. This paper provides a brief review of root characteristics most commonly targeted for operational seedling production. These are: root mass...

  15. Internal targets for LEAR

    International Nuclear Information System (INIS)

    Kilian, K.; Gspann, J.; Mohl, D.; Poth, H.

    1984-01-01

    This chapter considers the use of thin internal targets in conjunction with phase-space cooling at the Low-Energy Antiproton Ring (LEAR). Topics considered include the merits of internal target operation; the most efficient use of antiprotons and of proton synchrotron (PS) protons, highest center-of-mass (c.m.) energy resolution; highest angular resolution and access to extreme angles; the transparent environment for all reaction products; a windowless source and pure targets; highest luminosity and count rates; access to lowest energies with increasing resolution; internal target thickness and vacuum requirements; required cooling performance; and modes of operation. It is demonstrated that an internal target in conjunction with phase-space cooling has the potential of better performance in terms of the economic use of antiprotons and consequently of PS protons; energy resolution; angular resolution; maximum reaction rate capability (statistical precision); efficient parasitic operation; transparency of the target for reaction products; access to low energies; and the ease of polarized target experiments. It is concluded that all p - experiments which need high statistics and high p - flux, such as studies of rare channels or broad, weak resonance structures, would profit from internal targets

  16. Advanced Targeted Nanomedicine

    Science.gov (United States)

    Arachchige, Mohan C M; Reshetnyak, Yana K.; Andreev, Oleg A.

    2015-01-01

    Targeted drug delivery has been the major topic in drug formulation and delivery. As nanomedicine emerges to create nano scale therapeutics and diagnostics, it is still essential to embed targeting capability to these novel systems to make them useful. Here we discuss various targeting approaches for delivery of therapeutic and diagnostic nano materials in view of search for more universal methods to target diseased tissues. Many diseases are accompanied with hypoxia and acidosis. Coating nanoparticles with pH Low Insertion Peptides (pHLIPs) increases efficiency of targeting acidic diseased tissues. It has been showing promising results to create future nanotheranostics for cancer and other diseases which are dominating in the present world. PMID:25615945

  17. Electron beam fusion targets

    International Nuclear Information System (INIS)

    Clauser, M.J.; Sweeney, M.A.

    1975-01-01

    R The behavior of the DT filled gold shells when irradiated by a variety of pulse shapes was studied. In these pulses the power (and beam current) was varied, but the voltage was kept constant at 1 MeV. In general the performance of the target, for a given peak power, was not significantly affected by the pulse shape. Pulses with rise times of up to half the implosion time do not significantly degrade the target performance. The use of the ''optimal pulse'' of laser fusion with a fixed peak power does not appear to improve the performance of these targets. The main function of the ''optimal pulse'' is to produce a large rho r of the target during the thermonuclear burn. In e-beam targets a total rho r of 5--10 g/cm 2 can be obtained without pulse shaping; the problem here is one of achieving high enough temperatures to ignite the DT. (U.S.)

  18. Targeted therapy in lymphoma

    Directory of Open Access Journals (Sweden)

    Cavalli Franco

    2010-11-01

    Full Text Available Abstract Discovery of new treatments for lymphoma that prolong survival and are less toxic than currently available agents represents an urgent unmet need. We now have a better understanding of the molecular pathogenesis of lymphoma, such as aberrant signal transduction pathways, which have led to the discovery and development of targeted therapeutics. The ubiquitin-proteasome and the Akt/mammalian target of rapamycin (mTOR pathways are examples of pathological mechanisms that are being targeted in drug development efforts. Bortezomib (a small molecule protease inhibitor and the mTOR inhibitors temsirolimus, everolimus, and ridaforolimus are some of the targeted therapies currently being studied in the treatment of aggressive, relapsed/refractory lymphoma. This review will discuss the rationale for and summarize the reported findings of initial and ongoing investigations of mTOR inhibitors and other small molecule targeted therapies in the treatment of lymphoma.

  19. Adaptive Target Tracking for Underwater Maneuvering Targets.

    Science.gov (United States)

    1979-12-01

    concenetrate on the bearings-only approach. In this method the Observer monitors his bearing to the Source, over a period of time. Usually the Observer must...developed in [ 5] was earlier applied with much success to tracking maneuvering air targets. This approach will now be applied in the underwater environment...April 1977. [11] A. H. Jazwinski, Stochastic Processes and Filtering Theory, Academic Press, New York, 1970. [12] D. H. Halliday, and R. Resnick, Physics, John Wiley & Sons, Inc., New York, 1966. hI

  20. AA antiproton production target

    CERN Multimedia

    CERN PhotoLab

    1979-01-01

    The first version of the antiproton production target was a tungsten rod, 11 cm long and 3 mm in diameter. The rod was embedded in graphite, pressure-seated into an outer casing of stainless steel. At the entrance to the target assembly was a scintillator screen, imprinted with circles every 5 mm in radius, which allowed to precisely aim the 26 GeV high-intensity proton beam from the PS onto the centre of the target rod. The scintillator screen was a 1 mm thick plate of Cr-doped alumina. See also 7903034 and 7905091.

  1. Biological targeting of radionuclides

    International Nuclear Information System (INIS)

    Wheldon, T.E.; Glasgow Univ.

    1993-01-01

    Targeted radionuclide therapy in several forms has now been investigated in the clinic for more than 10 years. Despite some promising indications, targeted radiotherapy has not yet had a large impact on cancer therapy. Theoretical analysis shows that tumour cure would not often be expected using existing treatments. Addition of external-beam irradiation appears to be a robust strategy, which is appropriate in a wide range of situations. In future, many new agents will be made available by progress in molecular biology. However, integration of targeted radionuclide therapy with other modalities, especially radiotherapy, may still be required. (Author)

  2. Shiva target irradiation facility

    International Nuclear Information System (INIS)

    Manes, K.R.; Ahlstrom, H.G.; Coleman, L.W.; Storm, E.K.; Glaze, J.A.; Hurley, C.A.; Rienecker, F.; O'Neal, W.C.

    1977-01-01

    The first laser/plasma studies performed with the Shiva laser system will be two sided irradiations extending the data obtained by other LLL lasers to higher powers. The twenty approximately 1 TW laser pulses will reach the target simultaneously from above and below in nested pentagonal clusters. The upper and lower clusters of ten beams each are radially polarized so that they strike the target in p-polarization and maximize absorption. This geometry introduces laser system isolation problems which will be briefly discussed. The layout and types of target diagnostics will be described and a brief status report on the facility given

  3. STANFORD: Internal targets

    International Nuclear Information System (INIS)

    Riordan, Michael

    1989-01-01

    Of burgeoning interest to many nuclear and particle physicists is a storage ring technique for fixed target experiments. It hinges on the use of gas-jet targets, shooting a narrow stream of atoms through a circulating beam of electrons or protons. Pioneered at CERN and the Soviet Novosibirsk Laboratory, more such 'internal targets' are being built or contemplated for storage rings in Europe, the Soviet Union, and the United States. From 9-12 January, physicists from around the world met at the Stanford Linear Accelerator Center (SLAC) to discuss prospects and problems in this expanding field

  4. Internal polarized targets

    Energy Technology Data Exchange (ETDEWEB)

    Kinney, E.R.; Coulter, K.; Gilman, R.; Holt, R.J.; Kowalczyk, R.S.; Napolitano, J.; Potterveld, D.H.; Young, L. (Argonne National Lab., IL (USA)); Mishnev, S.I.; Nikolenko, D.M.; Popov, S.G.; Rachek, I.A.; Temnykh, A.B.; Toporkov, D.K.; Tsentalovich, E.P.; Wojtsekhowski, B.B. (AN SSSR, Novosibirsk (USSR). Inst. Yadernoj Fiziki)

    1989-01-01

    Internal polarized targets offer a number of advantages over external targets. After a brief review of the basic motivation and principles behind internal polarized targets, the technical aspects of the atomic storage cell will be discussed in particular. Sources of depolarization and the means by which their effects can be ameliorated will be described, especially depolarization by the intense magnetic fields arising from the circulating particle beam. The experience of the Argonne Novosibirsk collaboration with the use of a storage cell in a 2 GeV electron storage ring will be the focus of this technical discussion. 17 refs., 11 figs.

  5. Exploring Terrorist Targeting Preferences

    National Research Council Canada - National Science Library

    Libicki, Martin C; Chalk, Peter; Sisson, Melanie

    2007-01-01

    ... that reflect the value and vulnerability of each potential target. Yet those buildings, institutions, and icons perceived as being of utmost value to the United States may not be perceived as such to its potential attackers...

  6. Targeting radiation to tumours

    International Nuclear Information System (INIS)

    Wheldon, T.E.; Greater Glasgow Health Board, Glasgow

    1994-01-01

    Biologically targeted radiotherapy entails the preferential delivery of radiation to solid tumours or individual tumour cells by means of tumour-seeking delivery vehicles to which radionuclides can be conjugated. Monoclonal antibodies have attracted attention for some years as potentially selective targeting agents, but advances in tumour and molecular biology are now providing a much wider choice of molecular species. General radiobiological principles may be derived which are applicable to most forms of targeted radiotherapy. These principles provide guidelines for the appropriate choice of radionuclide in specific treatment situations and its optimal combination with other treatment modalities. In future, the availability of gene targeting agents will focus attention on the use of Auger electron emitters whose high potency and short range selectivity makes them attractive choices for specific killing of cancer cells whose genetic peculiarities are known. (author)

  7. Optimal exploration target zones

    CSIR Research Space (South Africa)

    Debba, Pravesh

    2008-09-01

    Full Text Available This research describes a quantitative methodology for deriving optimal exploration target zones based on a probabilistic mineral prospectivity map. In order to arrive at out objective, we provide a plausible answer to the following question: "Which...

  8. Target Price Accuracy

    Directory of Open Access Journals (Sweden)

    Alexander G. Kerl

    2011-04-01

    Full Text Available This study analyzes the accuracy of forecasted target prices within analysts’ reports. We compute a measure for target price forecast accuracy that evaluates the ability of analysts to exactly forecast the ex-ante (unknown 12-month stock price. Furthermore, we determine factors that explain this accuracy. Target price accuracy is negatively related to analyst-specific optimism and stock-specific risk (measured by volatility and price-to-book ratio. However, target price accuracy is positively related to the level of detail of each report, company size and the reputation of the investment bank. The potential conflicts of interests between an analyst and a covered company do not bias forecast accuracy.

  9. Targets and special materials

    International Nuclear Information System (INIS)

    Blanc, R.; Bouriant, M.; Richaud, J.P.

    1997-01-01

    The target preparation group supplied a large number of samples to nuclear physicists for experiments using SARA and also other accelerators throughout the world. Particular preparation and projects include: 208 Pb, 116 Cd, 6 LiF, 123 Sb, In and Ta targets, strippers for SARA and GANIL, optical silicone disks for POLDER and GRAAL experiments, active participations for the AMS project and finally filament preparation for the GENEPI project. (authors)

  10. An ISOLDE target unit

    CERN Multimedia

    Maximilien Brice

    2002-01-01

    A good dozen different targets are available for ISOLDE, made of different materials and equipped with different kinds of ion-sources, according to the needs of the experiments. Each separator (GPS: general purpose; HRS: high resolution) has its own target. Because of the high radiation levels, robots effect the target changes, about 80 times per year. In the standard unit shown in picture _01, the target is the cylindrical object in the front. It contains uranium-carbide kept at a temperature of 2200 deg C, necessary for the isotopes to be able to escape. At either end, one sees the heater current leads, carrying 700 A. The Booster beam, some 3E13 protons per pulse, enters the target from left. The evaporated isotope atoms enter a hot-plasma ion source (the black object behind the target). The whole unit sits at 60 kV potential (pulsed in synchronism with the arrival of the Booster beam) which accelerates the ions (away from the viewer) towards one of the 2 separators.

  11. Laser targets: introduction

    International Nuclear Information System (INIS)

    Rosen, M.D.

    1985-01-01

    The laser target design group was engaged in three main tasks in 1984: (1) analyzing Novette implosion and hohlraum-scaling data, (2) planning for the first experiments on Nova, and (3) designing laboratory x-ray laser targets and experiments. The Novette implosion and hohlraum scaling data are mostly classified and are therefore not discussed in detail here. The authors achieved average final/initial pusher pr ratios of about 50, some 3 times higher than the value achieved in the best Shiva shots. These pr values imply a fuel compression to 100 times liquid density, although this figure and other aspects of the experiments are subject to further interpretation because of detailed questions of target symmetry and stability. Their main long-term goal for Nova is to produce a so-called hydrodynamically equivalent target (HET) - that is, a target whose hydrodynamic behavior (implosion velocity, convergence ratio, symmetry and stability requirements, etc.) is very much like that of a high-gain target, but one that is scaled down in size to match the energy available from Nova and is too small to achieve enough hot-spot pr to ignite the cold, near-Fermi-degenerate fuel around it. Their goal for Nova's first year is to do experiments that will teach them how to achieve the symmetry and stability conditions required by an HET

  12. Argus target chamber

    International Nuclear Information System (INIS)

    Rienecker, F. Jr.; Glaros, S.S.; Kobierecki, M.

    1975-01-01

    A target chamber for application in the laser fusion program must satisfy some very basic requirements. (1) Provide a vacuum on the order of 10 -6 torr. (2) Support a microscopically small target in a fixed point in space and verify its location within 5 micrometers. (3) Contain an adjustable beam focusing system capable of delivering a number of laser beams onto the target simultaneously, both in time and space. (4) Provide access for diagnostics to evaluate the results of target irradiation. (5) Have flexibility to allow changes in targets, focusing optics and number of beams. The ARGUS laser which is now under construction at LLL will have a target chamber which meets these requirements in a simple economic manner. The chamber and auxiliary equipment are described, with reference to two double beam focusing systems; namely, lenses and ellipsoidal mirrors. Provision is made for future operation with four beams, using ellipsoidal mirrors for two-sided illumination and lens systems for tetragonal and tetrahedral irradiation

  13. Burglar Target Selection

    Science.gov (United States)

    Townsley, Michael; Bernasco, Wim; Ruiter, Stijn; Johnson, Shane D.; White, Gentry; Baum, Scott

    2015-01-01

    Objectives: This study builds on research undertaken by Bernasco and Nieuwbeerta and explores the generalizability of a theoretically derived offender target selection model in three cross-national study regions. Methods: Taking a discrete spatial choice approach, we estimate the impact of both environment- and offender-level factors on residential burglary placement in the Netherlands, the United Kingdom, and Australia. Combining cleared burglary data from all study regions in a single statistical model, we make statistical comparisons between environments. Results: In all three study regions, the likelihood an offender selects an area for burglary is positively influenced by proximity to their home, the proportion of easily accessible targets, and the total number of targets available. Furthermore, in two of the three study regions, juvenile offenders under the legal driving age are significantly more influenced by target proximity than adult offenders. Post hoc tests indicate the magnitudes of these impacts vary significantly between study regions. Conclusions: While burglary target selection strategies are consistent with opportunity-based explanations of offending, the impact of environmental context is significant. As such, the approach undertaken in combining observations from multiple study regions may aid criminology scholars in assessing the generalizability of observed findings across multiple environments. PMID:25866418

  14. The Sinuous Target

    Energy Technology Data Exchange (ETDEWEB)

    Zwaska, R. [Fermilab

    2015-06-01

    We report on the concept for a target material comprised of a multitude of interlaced wires of small dimension. This target material concept is primarily directed at high-power neutrino targets where the thermal shock is large due to small beam sizes and short durations; it also has applications to other high-power targets, particularly where the energy deposition is great or a high surface area is preferred. This approach ameliorates the problem of thermal shock by engineering a material with high strength on the micro-scale, but a very low modulus of elasticity on the meso-scale. The low modulus of elasticity is achieved by constructing the material of spring-like wire segments much smaller than the beam dimension. The intrinsic bends of the wires will allow them to absorb the strain of thermal shock with minimal stress. Furthermore, the interlaced nature of the wires provides containment of any segment that might become loose. We will discuss the progress on studies of analogue materials and fabrication techniques for sinuous target materials.

  15. Setting reference targets

    International Nuclear Information System (INIS)

    Ruland, R.E.

    1997-04-01

    Reference Targets are used to represent virtual quantities like the magnetic axis of a magnet or the definition of a coordinate system. To explain the function of reference targets in the sequence of the alignment process, this paper will first briefly discuss the geometry of the trajectory design space and of the surveying space, then continue with an overview of a typical alignment process. This is followed by a discussion on magnet fiducialization. While the magnetic measurement methods to determine the magnetic centerline are only listed (they will be discussed in detail in a subsequent talk), emphasis is given to the optical/mechanical methods and to the task of transferring the centerline position to reference targets

  16. LANSCE target calculations

    International Nuclear Information System (INIS)

    Grisham, D.L.; Brown, R.D.

    1989-01-01

    The LANSCE target operates at a beam current of 30 microamps. We present here the results of the finite-element calculations for the temperatures and stresses in the present target operated at 100 microamps. The calculations were run using the ABAQUS finite-element code. All finite-element codes require as input both the boundary conditions for the material being heated, and such material properties as the thermal conductivity, specific heat, and the elastic modulus. For the LANSCE target, the boundary conditions involve knowing the power deposition from the beam, and the heat transfer coefficients between the tungsten-alloy cylinder and the cooling water. We believe that these numbers are quite well established. 5 refs., 6 figs

  17. Cooled particle accelerator target

    Science.gov (United States)

    Degtiarenko, Pavel V.

    2005-06-14

    A novel particle beam target comprising: a rotating target disc mounted on a retainer and thermally coupled to a first array of spaced-apart parallel plate fins that extend radially inwardly from the retainer and mesh without physical contact with a second array of spaced-apart parallel plate fins that extend radially outwardly from and are thermally coupled to a cooling mechanism capable of removing heat from said second array of spaced-apart fins and located within the first array of spaced-apart parallel fins. Radiant thermal exchange between the two arrays of parallel plate fins provides removal of heat from the rotating disc. A method of cooling the rotating target is also described.

  18. Modelling Recycling Targets

    DEFF Research Database (Denmark)

    hill, amanda; Leinikka Dall, Ole; Andersen, Frits Møller

    2014-01-01

    Within the European Union (EU) a paradigm shift is currently occurring in the waste sector, where EU waste directives and national waste strategies are placing emphasis on resource efficiency and recycling targets. The most recent Danish resource strategy calculates a national recycling rate of 22......% for household waste, and sets an ambitious goal of a 50% recycling rate by 2020. This study integrates the recycling target into the FRIDA model to project how much waste and from which streams should be diverted from incineration to recycling in order to achieve the target. Furthermore, it discusses how...... the existing technological, organizational and legislative frameworks may affect recycling activities. The results of the analysis show that with current best practice recycling rates, the 50% recycling rate cannot be reached without recycling of household biowaste. It also shows that all Danish municipalities...

  19. Fine target of deuterium

    International Nuclear Information System (INIS)

    Diaz Diaz, J.; Granados Gonzalez, C. E.; Gutierrez Bernal, R.

    1959-01-01

    A fine target of deuterium on a tantalum plate by the absorption method is obtained. In order to obtain the de gasification temperature an induction generator of high frequency is used and the deuterium pass is regulated by means of a palladium valve. Two vacuum measures are available, one to measure the high vacuum in the de gasification process of the tantalum plate and the other, for low vacuum, to measure the deuterium inlet in the installation and the deuterium pressure change in the installation after the absorption in the tantalum plate. A target of 48 μ gr/cm 2 thick is obtained. (Author) 1 refs

  20. AA antiproton production target

    CERN Multimedia

    CERN PhotoLab

    1979-01-01

    The first version of the antiproton production target was a tungsten rod, 11 cm long (actually a row of 11 rods, each 1 cm long) and 3 mm in diameter. The rod was embedded in graphite, pressure-seated into an outer casing made of stainless steel. The casing had fins for forced-air cooling. In this picture, the 26 GeV high-intensity beam from the PS enters from the right, where a scintillator screen, with circles every 5 mm in radius, permits precise aim at the target centre. See also 7903034 and 7905094.

  1. Targets and tactics

    DEFF Research Database (Denmark)

    Woo, V; Shestakova, M V; Ørskov, C

    2008-01-01

    BACKGROUND: The incidence of type 2 diabetes is reaching pandemic proportions, impacting patients and healthcare systems across the globe. Evidence suggests that a majority of patients are not achieving recommended blood glucose targets resulting in an increased risk of micro- and macro-vascular ......BACKGROUND: The incidence of type 2 diabetes is reaching pandemic proportions, impacting patients and healthcare systems across the globe. Evidence suggests that a majority of patients are not achieving recommended blood glucose targets resulting in an increased risk of micro- and macro...... diabetes has never been more compelling; with a clear focus on strategies for glycaemic control, the impact of the diabetes pandemic can be limited....

  2. Targeted Therapy for Melanoma

    International Nuclear Information System (INIS)

    Quinn, Thomas; Moore, Herbert

    2016-01-01

    The research project, entitled ''Targeted Therapy for Melanoma,'' was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the 212Pb/203 Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg 11 )CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of 212 Pb labeled DOTA-Re(Arg 11 )CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter 212 Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

  3. Targets of curcumin

    Science.gov (United States)

    Zhou, Hongyu; Beevers, Christopher S.; Huang, Shile

    2010-01-01

    Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of the plant Curcuma longa. For centuries, curcumin has been used in some medicinal preparation or used as a food-coloring agent. In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (such as nuclear factor-κB), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase). Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, curcumin has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, arthritis, allergies, Alzheimer’s disease, and other inflammatory illnesses. This review summarizes various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms. The recently identified molecular targets and signaling pathways modulated by curcumin are also discussed here. PMID:20955148

  4. Targeted Therapy for Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Quinn, Thomas [Alphamed, Jackson, TN (United States); Moore, Herbert [Alphamed, Jackson, TN (United States)

    2016-12-05

    The research project, entitled ”Targeted Therapy for Melanoma,” was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the 212Pb/203Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg11)CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of 212Pb labeled DOTA-Re(Arg11)CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter 212Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

  5. Antibodies Targeting EMT

    Science.gov (United States)

    2017-10-01

    determine their targets on the cell. The newly discovered antibodies will then be engineered for utility as new highly specific drugs and diagnostics in...are from the aldo-keto reductase family (AKRs). Remarkably, 3 of the top 10 genes with induction in the mesenchymal TES2b cells Figure 1. Amino

  6. ISOLDE back on target

    CERN Multimedia

    Anaïs Schaeffer

    2014-01-01

    Today, Friday 1 August, the ISOLDE installation, supplied by the beams of the PS Booster, restarted its physics programme. After a shutdown of almost a year and a half, there was a real buzz in the air as the first beam of protons hit the target of the first post-LS1 ISOLDE experiment.   One of the new target-handling robots installed by ISOLDE during LS1. Many improvements have been made to the ISOLDE installation during LS1. One of the main projects was the installation of new robots for handling the targets (see photo 1). “Our targets are bombarded by protons from the PS Booster’s beams and become very radioactive,” explains Maria Jose Garcia Borge, spokesperson for the ISOLDE collaboration. “They therefore need to be handled carefully, which is where the robots come in. The robots we had until now were already over 20 years old and were starting to suffer from the effects of radiation. So LS1 was a perfect opportunity to replace them with more moder...

  7. Target Chamber Manipulator

    Science.gov (United States)

    Tantillo, Anthony; Watson, Matthew

    2015-11-01

    A system has been developed to allow remote actuation of sensors in a high vacuum target chamber used with a particle accelerator. Typically, sensors of various types are placed into the target chamber at specific radial and angular positions relative to the beam line and target. The chamber is then evacuated and the experiments are performed for those sensor positions. Then, the chamber is opened, the sensors are repositioned to new angles or radii, and the process is repeated, with a separate pump-down cycle for each set of sensor positions. The new sensor positioning system allows scientists to pre-set the radii of up to a dozen sensors, and then remotely actuate their angular positions without breaking the vacuum of the target chamber. This reduces the time required to reposition sensors from 6 hours to 1 minute. The sensors are placed into one of two tracks that are separately actuated using vacuum-grade stepping motors. The positions of the sensors are verified using absolute optical rotary encoders, and the positions are accurate to 0.5 degrees. The positions of the sensors are electronically recorded and time-stamped after every change. User control is through a GUI using LabVIEW.

  8. Physics of polarized targets

    CERN Document Server

    Niinikoski, Tapio

    2014-01-01

    For developing, building and operating solid polarized targets we need to understand several fields of physics that have seen sub stantial advances during the last 50 years. W e shall briefly review a selection of those that are important today. These are: 1) quantum statistical methods to describe saturation and relaxation in magnetic resonance; 2) equal spin temperature model for dy namic nuclear polarization; 3 ) weak saturation during NMR polarization measurement; 4 ) refrigeration using the quantum fluid properties of helium isotopes. These, combined with superconducting magnet technologies, permit today to reach nearly complete pola rization of almost any nuclear spins. Targets can be operated in frozen spin mode in rather low and inhomogeneous field of any orientation, and in DNP mode in beams of high intensity. Beyond such experiments of nuclear and particle physics, applications a re also emerging in macromolecular chemistry and in magnetic resonance imaging. This talk is a tribute to Michel Borghini...

  9. Aquaporin-2 membrane targeting

    DEFF Research Database (Denmark)

    Olesen, Emma T B; Fenton, Robert A

    2017-01-01

    The targeting of the water channel aquaporin-2 (AQP2) to the apical plasma membrane of kidney collecting duct principal cells is regulated mainly by the antidiuretic peptide hormone arginine vasopressin (AVP). This process is of crucial importance for the maintenance of body water homeostasis....... In this brief review we assess the role of cyclic adenosine monophosphate (cAMP) and discuss the emerging concept that type 2 AVP receptor (V2R)-mediated AQP2 trafficking is cAMP-independent. the ability of the kidney to concentrate the urine and thereby maintain body water homeostasis depends on targeting....... For example, 1) stimulation with the nonspecific AC activator forskolin increases AQP2 membrane accumulation in a mouse cortical collecting duct cell line [e.g., Norregaard et al. (16)]; 2) cAMP increases CD water permeability (15); 3) the cAMP-activated protein kinase A (PKA) can phosphorylate AQP2 on its...

  10. Protein targeting protocols

    National Research Council Canada - National Science Library

    Clegg, Roger A

    1998-01-01

    ... of intracellular environment. Because the concept of protein targeting is intuitive rather than explicitly defined, it has been variously used by different groups of researchers in cell biology, biochemistry, and molecular biology. For those working in the field of intracellular signaling, an influential introduction to the topic was the seminal article by Hubbard & Cohen (TIBS [1993] 18, 172- 177), which was based on the work of Cohen's laboratory on protein phosphatases. Subsequently, the ideas that t...

  11. CDTI target selection criteria

    Science.gov (United States)

    Britt, C. L.; Davis, C. M.; Jackson, C. B.; Mcclellan, V. A.

    1984-01-01

    A Cockpit Display of Traffic Information (CDTI) is a cockpit instrument which provides information to the aircrew on the relative location of aircraft traffic in the vicinity of their aircraft (township). In addition, the CDTI may provide information to assist in navigation and in aircraft control. It is usually anticipated that the CDTI will be integrated with a horizontal situation indicator used for navigational purposes and/or with a weather radar display. In this study, several sets of aircraft traffic data are analyzed to determine statistics on the number of targets that will be displayed on a CDTI using various target selection criteria. Traffic data were obtained from an Atlanta Terminal Area Simulation and from radar tapes recorded at the Atlanta and Miami terminal areas. Results are given in the form of plots showing the average percentage of time (or probability) that an aircraft equipped with a CDTI would observe from 0 to 10 other aircraft on the display for range settings on the CDTI up to 30 n. mi. and using various target discrimination techniques.

  12. The Bochum Polarized Target

    International Nuclear Information System (INIS)

    Reicherz, G.; Goertz, S.; Harmsen, J.; Heckmann, J.; Meier, A.; Meyer, W.; Radtke, E.

    2001-01-01

    The Bochum 'Polarized Target' group develops the target material 6 LiD for the COMPASS experiment at CERN. Several different materials like alcohols, alcanes and ammonia are under investigation. Solid State Targets are polarized in magnetic fields higher than B=2.5T and at temperatures below T=1K. For the Dynamic Nuclear Polarization process, paramagnetic centers are induced chemically or by irradiation with ionizing beams. The radical density is a critical factor for optimization of polarization and relaxation times at adequate magnetic fields and temperatures. In a high sensitive EPR--apparatus, an evaporator and a dilution cryostat with a continuous wave NMR--system, the materials are investigated and optimized. To improve the polarization measurement, the Liverpool NMR-box is modified by exchanging the fixed capacitor for a varicap diode which not only makes the tuning very easy but also provides a continuously tuned circuit. The dependence of the signal area upon the circuit current is measured and it is shown that it follows a linear function

  13. Implementing Target Value Design.

    Science.gov (United States)

    Alves, Thais da C L; Lichtig, Will; Rybkowski, Zofia K

    2017-04-01

    An alternative to the traditional way of designing projects is the process of target value design (TVD), which takes different departure points to start the design process. The TVD process starts with the client defining an allowable cost that needs to be met by the design and construction teams. An expected cost in the TVD process is defined through multiple interactions between multiple stakeholders who define wishes and others who define ways of achieving these wishes. Finally, a target cost is defined based on the expected profit the design and construction teams are expecting to make. TVD follows a series of continuous improvement efforts aimed at reaching the desired goals for the project and its associated target value cost. The process takes advantage of rapid cycles of suggestions, analyses, and implementation that starts with the definition of value for the client. In the traditional design process, the goal is to identify user preferences and find solutions that meet the needs of the client's expressed preferences. In the lean design process, the goal is to educate users about their values and advocate for a better facility over the long run; this way owners can help contractors and designers to identify better solutions. This article aims to inform the healthcare community about tools and techniques commonly used during the TVD process and how they can be used to educate and support project participants in developing better solutions to meet their needs now as well as in the future.

  14. WRN-targeted therapy using inhibitors NSC 19630 and NSC 617145 induce apoptosis in HTLV-1-transformed adult T-cell leukemia cells

    Directory of Open Access Journals (Sweden)

    R. Moles

    2016-11-01

    Full Text Available Abstract Background Human T-cell leukemia virus type 1 (HTLV-1 infection is associated with adult T-cell leukemia/lymphoma (ATLL, a lymphoproliferative malignancy with a dismal prognosis and limited therapeutic options. Recent evidence shows that HTLV-1-transformed cells present defects in both DNA replication and DNA repair, suggesting that these cells might be particularly sensitive to treatment with a small helicase inhibitor. Because the “Werner syndrome ATP-dependent helicase” encoded by the WRN gene plays important roles in both cellular proliferation and DNA repair, we hypothesized that inhibition of WRN activity could be used as a new strategy to target ATLL cells. Methods Our analysis demonstrates an apoptotic effect induced by the WRN helicase inhibitor in HTLV-1-transformed cells in vitro and ATL-derived cell lines. Inhibition of cellular proliferation and induction of apoptosis were demonstrated with cell cycle analysis, XTT proliferation assay, clonogenic assay, annexin V staining, and measurement of mitochondrial transmembrane potential. Results Targeted inhibition of the WRN helicase induced cell cycle arrest and apoptosis in HTLV-1-transformed leukemia cells. Treatment with NSC 19630 (WRN inhibitor induces S-phase cell cycle arrest, disruption of the mitochondrial membrane potential, and decreased expression of anti-apoptotic factor Bcl-2. These events were associated with activation of caspase-3-dependent apoptosis in ATL cells. We identified some ATL cells, ATL-55T and LMY1, less sensitive to NSC 19630 but sensitive to another WRN inhibitor, NSC 617145. Conclusions WRN is essential for survival of ATL cells. Our studies suggest that targeting the WRN helicase with small inhibitors is a novel promising strategy to target HTLV-1-transformed ATL cells.

  15. Inflation targeting and core inflation

    OpenAIRE

    Julie Smith

    2005-01-01

    This paper examines the interaction of core inflation and inflation targeting as a monetary policy regime. Interest in core inflation has grown because of inflation targeting. Core inflation is defined in numerous ways giving rise to many potential measures; this paper defines core inflation as the best forecaster of inflation. A cross-country study finds before the start of inflation targeting, but not after, core inflation differs between non-inflation targeters and inflation targeters. Thr...

  16. Targeted therapy for sarcomas

    Directory of Open Access Journals (Sweden)

    Forscher C

    2014-03-01

    Full Text Available Charles Forscher,1 Monica Mita,2 Robert Figlin3 1Sarcoma Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 2Experimental Therapeutics Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 3Academic Development Program, Samuel Oschin Comprehensive Cancer Institute, and Division of Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA Abstract: Sarcomas are tumors of mesenchymal origin that make up approximately 1% of human cancers. They may arise as primary tumors in either bone or soft tissue, with approximately 11,280 soft tissue tumors and 2,650 bone tumors diagnosed each year in the United States. There are at least 50 different subtypes of soft tissue sarcoma, with new ones described with ever-increasing frequency. One way to look at sarcomas is to divide them into categories on the basis of their genetic make-up. One group of sarcomas has an identifiable, relatively simple genetic signature, such as the X:18 translocation seen in synovial sarcoma or the 11:22 translocation seen in Ewing's sarcoma. These specific abnormalities often lead to the presence of fusion proteins, such as EWS-FLI1 in Ewing's sarcoma, which are helpful as diagnostic tools and may become therapeutic targets in the future. Another group of sarcomas is characterized by complex genetic abnormalities as seen in leiomyosarcoma, osteosarcoma, and undifferentiated sarcoma. It is important to keep these distinctions in mind when contemplating the development of targeted agents for sarcomas. Different abnormalities in sarcoma could be divided by tumor subtype or by the molecular or pathway abnormality. However, some existing drugs or drugs in development may interfere with or alter more than one of the presented pathways. Keywords: sarcoma, targeted agents, tyrosine kinase inhibitors, mTor inhibition

  17. Polarized scintillator targets

    Science.gov (United States)

    van den Brandt, B.; Bunyatova, E. I.; Hautle, P.; Konter, J. A.; Mango, S.

    2000-05-01

    The hydrogen nuclei in an organic scintillator have been polarized to more than 80% and the deuterons in its fully deuterated version to 24%. The scintillator, doped with TEMPO, has been polarized dynamically in a field of 2.5 T in a vertical dilution refrigerator in which a plastic lightguide transports the scintillation light from the sample in the mixing chamber to a photomultiplier outside the cryostat. Sizeable solid samples with acceptable optical properties and light output have been prepared and successfully operated as "live" polarized targets in nuclear physics experiments.

  18. Polarized scintillator targets

    Energy Technology Data Exchange (ETDEWEB)

    Brandt, B. van den E-mail: vandenbrandt@psi.ch; Bunyatova, E.I.; Hautle, P.; Konter, J.A.; Mango, S

    2000-05-21

    The hydrogen nuclei in an organic scintillator have been polarized to more than 80% and the deuterons in its fully deuterated version to 24%. The scintillator, doped with TEMPO, has been polarized dynamically in a field of 2.5 T in a vertical dilution refrigerator in which a plastic lightguide transports the scintillation light from the sample in the mixing chamber to a photomultiplier outside the cryostat. Sizeable solid samples with acceptable optical properties and light output have been prepared and successfully operated as 'live' polarized targets in nuclear physics experiments.

  19. Targeting proteins for degradation.

    Science.gov (United States)

    Schrader, Erin K; Harstad, Kristine G; Matouschek, Andreas

    2009-11-01

    Protein degradation plays a central role in many cellular functions. Misfolded and damaged proteins are removed from the cell to avoid toxicity. The concentrations of regulatory proteins are adjusted by degradation at the appropriate time. Both foreign and native proteins are digested into small peptides as part of the adaptive immune response. In eukaryotic cells, an ATP-dependent protease called the proteasome is responsible for much of this proteolysis. Proteins are targeted for proteasomal degradation by a two-part degron, which consists of a proteasome binding signal and a degradation initiation site. Here we describe how both components contribute to the specificity of degradation.

  20. Fixed target beams

    CERN Document Server

    Kain, V; Cettour-Cave, S; Cornelis, K; Fraser, M A; Gatignon, L; Goddard, B; Velotti, F

    2017-01-01

    The CERN SPS (Super Proton Synchrotron) serves asLHC injector and provides beam for the North Area fixedtarget experiments. At low energy, the vertical acceptancebecomes critical with high intensity large emittance fixed tar-get beams. Optimizing the vertical available aperture is a keyingredient to optimize transmission and reduce activationaround the ring. During the 2016 run a tool was developed toprovide an automated local aperture scan around the entirering.The flux of particles slow extracted with the1/3inte-ger resonance from the Super Proton Synchrotron at CERNshould ideally be constant over the length of the extractionplateau, for optimum use of the beam by the fixed target ex-periments in the North Area. The extracted intensity is con-trolled in feed-forward correction of the horizontal tune viathe main SPS quadrupoles. The Mains power supply noiseat 50 Hz and harmonics is also corrected in feed-forwardby small amplitude tune modulation at the respective fre-quencies with a dedicated additional quad...

  1. Non-Targeted Analysis Challenge (Non-targeted screening workshop)

    Science.gov (United States)

    This brief presentation is intended to motivate discussion of the "Non-Targeted Analysis Challenge" at the Advancing Non-Targeted Analyses of Xenobiotics in Environmental and Biological Media workshop held at the EPA RTP campus.

  2. Low intensity beam target unit

    CERN Multimedia

    CERN PhotoLab

    1976-01-01

    This is a wheel fitted with many targets around its periphery (each with three longitudinally arranged thin rods) of which one is placed into the beam via a rotation of the wheel. Upstream of each target is placed a luminescent screen, aligbed on each target axis and viewed with a TV camera, to make sure that one is hitting the target. This target unit was probably used to study target's behaviour (like beam heating). Gualtiero Del Torre stands on the left, Pierre Gerdil on the right.

  3. ORION laser target diagnostics

    International Nuclear Information System (INIS)

    Bentley, C. D.; Edwards, R. D.; Andrew, J. E.; James, S. F.; Gardner, M. D.; Comley, A. J.; Vaughan, K.; Horsfield, C. J.; Rubery, M. S.; Rothman, S. D.; Daykin, S.; Masoero, S. J.; Palmer, J. B.; Meadowcroft, A. L.; Williams, B. M.; Gumbrell, E. T.; Fyrth, J. D.; Brown, C. R. D.; Hill, M. P.; Oades, K.

    2012-01-01

    The ORION laser facility is one of the UK's premier laser facilities which became operational at AWE in 2010. Its primary mission is one of stockpile stewardship, ORION will extend the UK's experimental plasma physics capability to the high temperature, high density regime relevant to Atomic Weapons Establishment's (AWE) program. The ORION laser combines ten laser beams operating in the ns regime with two sub ps short pulse chirped pulse amplification beams. This gives the UK a unique combined long pulse/short pulse laser capability which is not only available to AWE personnel but also gives access to our international partners and visiting UK academia. The ORION laser facility is equipped with a comprehensive suite of some 45 diagnostics covering optical, particle, and x-ray diagnostics all able to image the laser target interaction point. This paper focuses on a small selection of these diagnostics.

  4. ORION laser target diagnostics.

    Science.gov (United States)

    Bentley, C D; Edwards, R D; Andrew, J E; James, S F; Gardner, M D; Comley, A J; Vaughan, K; Horsfield, C J; Rubery, M S; Rothman, S D; Daykin, S; Masoero, S J; Palmer, J B; Meadowcroft, A L; Williams, B M; Gumbrell, E T; Fyrth, J D; Brown, C R D; Hill, M P; Oades, K; Wright, M J; Hood, B A; Kemshall, P

    2012-10-01

    The ORION laser facility is one of the UK's premier laser facilities which became operational at AWE in 2010. Its primary mission is one of stockpile stewardship, ORION will extend the UK's experimental plasma physics capability to the high temperature, high density regime relevant to Atomic Weapons Establishment's (AWE) program. The ORION laser combines ten laser beams operating in the ns regime with two sub ps short pulse chirped pulse amplification beams. This gives the UK a unique combined long pulse/short pulse laser capability which is not only available to AWE personnel but also gives access to our international partners and visiting UK academia. The ORION laser facility is equipped with a comprehensive suite of some 45 diagnostics covering optical, particle, and x-ray diagnostics all able to image the laser target interaction point. This paper focuses on a small selection of these diagnostics.

  5. Next Generation Target Control System

    National Research Council Canada - National Science Library

    1995-01-01

    Our objective was to evaluate the allegations concerning the Next Generation Target Control System Program and to determine whether the Program is the most cost effective solution to meet the target...

  6. Scaling of exploding pusher targets

    International Nuclear Information System (INIS)

    Nuckolls, J.H.

    1977-01-01

    A theory of exploding pusher laser pusher targets is compared to results of LASNEX calculations and to Livermore experiments. A scaling relationship is described which predicts the optimum target/pulse combinations as a function of the laser power

  7. Bradycardia During Targeted Temperature Management

    DEFF Research Database (Denmark)

    Thomsen, Jakob Hartvig; Nielsen, Niklas; Hassager, Christian

    2016-01-01

    OBJECTIVES: Bradycardia is common during targeted temperature management, likely being a physiologic response to lower body temperature, and has recently been associated with favorable outcome following out-of-hospital cardiac arrest in smaller observational studies. The present study sought...... to confirm this finding in a large multicenter cohort of patients treated with targeted temperature management at 33°C and explore the response to targeted temperature management targeting 36°C. DESIGN: Post hoc analysis of a prospective randomized study. SETTING: Thirty-six ICUs in 10 countries. PATIENTS......: We studied 447 (targeted temperature management = 33°C) and 430 (targeted temperature management = 36°C) comatose out-of-hospital cardiac arrest patients with available heart rate data, randomly assigned in the targeted temperature management trial from 2010 to 2013. INTERVENTIONS: Targeted...

  8. Some Issues in Inflation Targeting

    OpenAIRE

    Andrew Haldane

    1997-01-01

    This paper discusses some of the operational issues relevant to the implementation of an inflation-targeting regime. In particular it focuses on: whether inflation targeting is 'new'; whether (and how) the forward-looking nature of inflation-targeting helps to prevent instabilities in inflation; whether inflation-targeting potentially destabilises output; and whether it requires too much knowledge on the part of the authorities. The paper argues that none of these propositions is in general c...

  9. Inflation targeting in dollarized economies

    OpenAIRE

    Dokle, Eda

    2013-01-01

    Inflation targeting has become an increasingly popular regime among emerging markets. Focusing on the experience of inflation targeting adoption in the countries in Central and Eastern Europe and Commonwealth of Independent States, this thesis highlights the main features of the inflation targeting framework. A clear economic condition bringing these countries together is considered the dollarization issue which gains importance when designing the inflation targeting framework. The empirical ...

  10. Solid Polarized Targets and Applications

    International Nuclear Information System (INIS)

    Crabb, D. G.

    2008-01-01

    Examples are given of dynamically polarized targets in use today and how the subsystems have changed to meet the needs of todays experiments. Particular emphasis is placed on target materials such as ammonia and lithium deuteride. Recent polarization studies of irradiated materials such as butanol, deuterated butanol, polyethylene, and deuterated polyethylene are presented. The operation of two non-DNP target systems as well as applications of traditional DNP targets are briefly discussed

  11. Nova target diagnostics control system

    International Nuclear Information System (INIS)

    Severyn, J.R.

    1985-01-01

    During the past year the Nova target diagnostics control system was finished and put in service. The diagnostics loft constructed to the north of the target room provides the environmental conditions required to collect reliable target diagnostic data. These improvements include equipment cooling and isolation of the power source with strict control of instrumentation grounds to eliminate data corruption due to electromagnetic pulses from the laser power-conditioning system or from target implosion effects

  12. Fabrication of mercury target vessel

    International Nuclear Information System (INIS)

    Wakui, Takashi; Kogawa, Hiroyuki; Haga, Katsuhiro; Futakawa, Masatoshi; Hayashi, Ryoichi; Uchiyama, Naoyoshi; Okamoto, Yoshinao; Nakamura, Koji

    2010-03-01

    The construction of materials and life science experimental facility in J-PARC (Japan Proton Accelerator Complex) project had been completed and accepted pulsed proton beams with low power. Since 2003, the detailed design, fabrication and examination for the mercury target vessel as a pulsed neutron source were carried out by the vender. The mercury target vessel consists of triple-walled structure in order to prevent the leak of mercury to outside at the failure of the mercury vessel and to remove the heat of the safety hull, which covers the mercury vessel, due to the injection of the pulsed proton beams. The high fabrication accuracy is required for the mercury target vessel assembled by the welding, because there are the relationships between the mercury target vessel and other components (target trolley, target storage container, flange of helium vessel, reflector and water-cooled shield). At each fabrication step, the examinations for the mercury target vessel with multi-walled structure were required. In this report, the required specification and basic structure of parts in the mercury target vessel are described and the fabrication procedure of the mercury target vessel by the vender is reported. In the fabrication of the mercury target vessel, there were many troubles such as large deformation due to the welding and then the vender repaired and brought the mercury target vessel to completion. Furthermore, improvements for the design and fabrication of the mercury target are reported. (author)

  13. Targets for heavy ion fusion

    International Nuclear Information System (INIS)

    Clauser, M.J.

    1978-01-01

    This paper describes some of the basic principles of fusion target implosions, using some simple targets designed for irradiation by ion beams. Present estimates are that ion beams with 1-5 MJ, and 100-500 TW will be required to ignite high gain targets. (orig.) [de

  14. Isomeric Targets and Beams

    International Nuclear Information System (INIS)

    Oganesyan, Yu.Ts.; Karamyan, S.A.

    1994-01-01

    One of the main topics of modern nuclear physics is the investigation of exotic nuclei including hyper-nuclei, trans fermium elements, proton and neutron rich isotopes near drip lines as well as high-spin excited states and states with anomalous deformation. The isomerism of nuclei is closely related with such phenomena as the alignment of single-particle orbitals, the coexistence of various deformations and the manifestation of intruder-levels from neighbouring shells. The investigation of electromagnetic and nuclear interactions of isomers could give important information on their shell structure and its role in the mechanism of nuclear reactions. For such experiments one can either make isomeric targets (sufficiently long-lived) or use the methods of acceleration of isomeric nuclei. Recently, an exotic 16 + four-quasiparticle isomer of 178 Hf m 2 was produced in a micro weight quantity and the first nuclear reactions on it were successfully observed. The talk describes these experiments as well as new ideas for the continuation of the studies and some advantageous ways for the isomeric beams production by the method of direct acceleration or by the secondary beam method. 35 refs., 15 figs., 8 tabs

  15. Magnetic targeted drug delivery

    Directory of Open Access Journals (Sweden)

    Timothy Wiedmann

    2009-10-01

    Full Text Available Lung cancer is the most common cause of death from cancer in both men and women. Treatment by intravenous or oral administration of chemotherapy agents results in serious and often treatment-limiting side effects. Delivery of drugs directly to the lung by inhalation of an aerosol holds the promise of achieving a higher concentration in the lung with lower blood levels. To further enhance the selective lung deposition, it may be possible to target deposition by using external magnetic fields to direct the delivery of drug coupled to magnetic particles. Moreover, alternating magnetic fields can be used to induce particle heating, which in turn controls the drug release rate with the appropriate thermal sensitive material.With this goal, superparamagetic nanoparticles (SPNP were prepared and characterized, and enhanced magnetic deposition was demonstrated in vitro and in vivo. SPNPs were also incorporated into a lipid-based/SPNP aerosol formulation, and drug release was shown to be controlled by thermal activation. Because of the inherent imaging potential of SPNPs, this use of nanotechnology offers the possibility of coupling the diagnosis of lung cancer to drug release, which perhaps will ultimately provide the “magic bullet” that Paul Ehrlich originally sought.

  16. Meeting the Aichi targets

    DEFF Research Database (Denmark)

    Funk, Stephan M; Conde, Dalia Amor; Lamoreux, John

    2017-01-01

    Effective protection of the *19 000 IUCNlisted threatened species has never been more pressing. Ensuring the survival of the most vulnerable and irreplaceable taxa and places, such as those identified by the Alliance for Zero Extinction (AZE) species and their associated sites (AZEs&s), is an exc......Effective protection of the *19 000 IUCNlisted threatened species has never been more pressing. Ensuring the survival of the most vulnerable and irreplaceable taxa and places, such as those identified by the Alliance for Zero Extinction (AZE) species and their associated sites (AZEs......&s), is an excellent opportunity to achieve the Aichi 2020 Targets T11 (protected areas) and T12 (preventing species extinctions). AZE taxa have small, single-site populations that are especially vulnerable to human-induced extinctions, particularly for the many amphibians. We show that AZEs&s can be protected...... feasibly and cost-effectively, but action is urgent. We argue that the Alliance, whose initial main aim was to identify AZEs&s, must be followed up by a second-generation initiative that directs and co-ordinates AZE conservation activities on the ground. The prominent role of zoos, conservation NGOs...

  17. The target effect: visual memory for unnamed search targets.

    Science.gov (United States)

    Thomas, Mark D; Williams, Carrick C

    2014-01-01

    Search targets are typically remembered much better than other objects even when they are viewed for less time. However, targets have two advantages that other objects in search displays do not have: They are identified categorically before the search, and finding them represents the goal of the search task. The current research investigated the contributions of both of these types of information to the long-term visual memory representations of search targets. Participants completed either a predefined search or a unique-object search in which targets were not defined with specific categorical labels before searching. Subsequent memory results indicated that search target memory was better than distractor memory even following ambiguously defined searches and when the distractors were viewed significantly longer. Superior target memory appears to result from a qualitatively different representation from those of distractor objects, indicating that decision processes influence visual memory.

  18. Facility target insert shielding assessment

    Energy Technology Data Exchange (ETDEWEB)

    Mocko, Michal [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-10-06

    Main objective of this report is to assess the basic shielding requirements for the vertical target insert and retrieval port. We used the baseline design for the vertical target insert in our calculations. The insert sits in the 12”-diameter cylindrical shaft extending from the service alley in the top floor of the facility all the way down to the target location. The target retrieval mechanism is a long rod with the target assembly attached and running the entire length of the vertical shaft. The insert also houses the helium cooling supply and return lines each with 2” diameter. In the present study we focused on calculating the neutron and photon dose rate fields on top of the target insert/retrieval mechanism in the service alley. Additionally, we studied a few prototypical configurations of the shielding layers in the vertical insert as well as on the top.

  19. Oxide Fiber Targets at ISOLDE

    CERN Document Server

    Köster, U; Carminati, D; Catherall, R; Cederkäll, J; Correia, J G; Crepieux, B; Dietrich, M; Elder, K; Fedosseev, V; Fraile-Prieto, L M; Franchoo, S; Fynbo, H O U; Georg, U; Giles, T; Joinet, A; Jonsson, O C; Kirchner, R; Lau, C; Lettry, Jacques; Maier, H J; Mishin, V I; Oinonen, M; Peräjärvi, K; Ravn, H L; Rinaldi, T; Santana-Leitner, M; Wahl, U; Weissman, L

    2003-01-01

    Many elements are rapidly released from oxide matrices. Some oxide powder targets show a fast sintering, thus losing their favorable release characteristics. Loosely packed oxyde fiber targets are less critical since they may maintain their open structure even when starting to fuse together at some contact points. The experience with various oxyde fiber targets (titania, zirconia, ceria and thoria) used in the last years at ISOLDE is reviewed. For short-lived isotopes of Cu, Ga and Xe the zirconia and ceria targets respectively provided significantly higher yields than any other target (metal foils, oxide powders, etc.) tested before. Titania fibers, which were not commercially available, were produced in a relic process by impregnation of a rayon felt in a titanium chloride solution and subsequent calcination by heating the dried felt in air. Thoria fibers were obtained either by the same process or by burning commercial gas lantern mantle cloth. In the future a beryllia fiber target could be used to produce...

  20. The Bering Target Tracking Instrumentation

    DEFF Research Database (Denmark)

    Denver, Troelz; Jørgensen, John Leif; Betto, Maurizio

    2003-01-01

    's pointing direction. To achieve fast tracking over a large solid angle, the telescope pointing is achieved by means of a folding mirror in the optical pathway. When a prospective target approaches the telescope FOV, the ASC on the secondary will guide the folding mirror into position such that the target...... is inside the telescope FOV. During the telescope observation time, the ASC will constantly control the folding mirror to correctly position the target at the center of the telescope, basically performing a standard telescope tracking service. The telescope will alter the initial target acquisition track...

  1. Targeted nanotechnology for cancer imaging.

    Science.gov (United States)

    Toy, Randall; Bauer, Lisa; Hoimes, Christopher; Ghaghada, Ketan B; Karathanasis, Efstathios

    2014-09-30

    Targeted nanoparticle imaging agents provide many benefits and new opportunities to facilitate accurate diagnosis of cancer and significantly impact patient outcome. Due to the highly engineerable nature of nanotechnology, targeted nanoparticles exhibit significant advantages including increased contrast sensitivity, binding avidity and targeting specificity. Considering the various nanoparticle designs and their adjustable ability to target a specific site and generate detectable signals, nanoparticles can be optimally designed in terms of biophysical interactions (i.e., intravascular and interstitial transport) and biochemical interactions (i.e., targeting avidity towards cancer-related biomarkers) for site-specific detection of very distinct microenvironments. This review seeks to illustrate that the design of a nanoparticle dictates its in vivo journey and targeting of hard-to-reach cancer sites, facilitating early and accurate diagnosis and interrogation of the most aggressive forms of cancer. We will report various targeted nanoparticles for cancer imaging using X-ray computed tomography, ultrasound, magnetic resonance imaging, nuclear imaging and optical imaging. Finally, to realize the full potential of targeted nanotechnology for cancer imaging, we will describe the challenges and opportunities for the clinical translation and widespread adaptation of targeted nanoparticles imaging agents. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Targeted Nanotechnology for Cancer Imaging

    Science.gov (United States)

    Toy, Randall; Bauer, Lisa; Hoimes, Christopher; Ghaghada, Ketan B.; Karathanasis, Efstathios

    2014-01-01

    Targeted nanoparticle imaging agents provide many benefits and new opportunities to facilitate accurate diagnosis of cancer and significantly impact patient outcome. Due to the highly engineerable nature of nanotechnology, targeted nanoparticles exhibit significant advantages including increased contrast sensitivity, binding avidity and targeting specificity. Considering the various nanoparticle designs and their adjustable ability to target a specific site and generate detectable signals, nanoparticles can be optimally designed in terms of biophysical interactions (i.e., intravascular and interstitial transport) and biochemical interactions (i.e., targeting avidity towards cancer-related biomarkers) for site-specific detection of very distinct microenvironments. This review seeks to illustrate that the design of a nanoparticle dictates its in vivo journey and targeting of hard-to-reach cancer sites, facilitating early and accurate diagnosis and interrogation of the most aggressive forms of cancer. We will report various targeted nanoparticles for cancer imaging using X-ray computed tomography, ultrasound, magnetic resonance imaging, nuclear imaging and optical imaging. Finally, to realize the full potential of targeted nanotechnology for cancer imaging, we will describe the challenges and opportunities for the clinical translation and widespread adaptation of targeted nanoparticles imaging agents. PMID:25116445

  3. Internal Targeting and External Control: Phototriggered Targeting in Nanomedicine.

    Science.gov (United States)

    Arrue, Lily; Ratjen, Lars

    2017-12-07

    The photochemical control of structure and reactivity bears great potential for chemistry, biology, and life sciences. A key feature of photochemistry is the spatiotemporal control over secondary events. Well-established applications of photochemistry in medicine are photodynamic therapy (PDT) and photopharmacology (PP). However, although both are highly localizable through the application of light, they lack cell- and tissue-specificity. The combination of nanomaterial-based drug delivery and targeting has the potential to overcome limitations for many established therapy concepts. Even more privileged seems the merger of nanomedicine and cell-specific targeting (internal targeting) controlled by light (external control), as it can potentially be applied to many different areas of medicine and pharmaceutical research, including the aforementioned PDT and PP. In this review a survey of the interface of photochemistry, medicine and targeted drug delivery is given, especially focusing on phototriggered targeting in nanomedicine. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Target support for inertial confinement fusion

    International Nuclear Information System (INIS)

    Schultz, K.R.

    1995-08-01

    General Atomics (GA) plays an important industrial support role for the US Inertial Confinement Fusion (ICF) program in the area of target technology. This includes three major activities: target fabrication support, target handling systems development, and target chamber design. The work includes target fabrication for existing ICF experiments, target and target system development for future experiments, and target research and target chamber design for experiments on future machines, such as the National Ignition Facility (NIF)

  5. The impact of targeting repetitive BamHI-W sequences on the sensitivity and precision of EBV DNA quantification.

    Directory of Open Access Journals (Sweden)

    Armen Sanosyan

    Full Text Available Viral load monitoring and early Epstein-Barr virus (EBV DNA detection are essential in routine laboratory testing, especially in preemptive management of Post-transplant Lymphoproliferative Disorder. Targeting the repetitive BamHI-W sequence was shown to increase the sensitivity of EBV DNA quantification, but the variability of BamHI-W reiterations was suggested to be a source of quantification bias. We aimed to assess the extent of variability associated with BamHI-W PCR and its impact on the sensitivity of EBV DNA quantification using the 1st WHO international standard, EBV strains and clinical samples.Repetitive BamHI-W- and LMP2 single- sequences were amplified by in-house qPCRs and BXLF-1 sequence by a commercial assay (EBV R-gene™, BioMerieux. Linearity and limits of detection of in-house methods were assessed. The impact of repeated versus single target sequences on EBV DNA quantification precision was tested on B95.8 and Raji cell lines, possessing 11 and 7 copies of the BamHI-W sequence, respectively, and on clinical samples.BamHI-W qPCR demonstrated a lower limit of detection compared to LMP2 qPCR (2.33 log10 versus 3.08 log10 IU/mL; P = 0.0002. BamHI-W qPCR underestimated the EBV DNA load on Raji strain which contained fewer BamHI-W copies than the WHO standard derived from the B95.8 EBV strain (mean bias: - 0.21 log10; 95% CI, -0.54 to 0.12. Comparison of BamHI-W qPCR versus LMP2 and BXLF-1 qPCR showed an acceptable variability between EBV DNA levels in clinical samples with the mean bias being within 0.5 log10 IU/mL EBV DNA, whereas a better quantitative concordance was observed between LMP2 and BXLF-1 assays.Targeting BamHI-W resulted to a higher sensitivity compared to LMP2 but the variable reiterations of BamHI-W segment are associated with higher quantification variability. BamHI-W can be considered for clinical and therapeutic monitoring to detect an early EBV DNA and a dynamic change in viral load.

  6. The impact of targeting repetitive BamHI-W sequences on the sensitivity and precision of EBV DNA quantification.

    Science.gov (United States)

    Sanosyan, Armen; Fayd'herbe de Maudave, Alexis; Bollore, Karine; Zimmermann, Valérie; Foulongne, Vincent; Van de Perre, Philippe; Tuaillon, Edouard

    2017-01-01

    Viral load monitoring and early Epstein-Barr virus (EBV) DNA detection are essential in routine laboratory testing, especially in preemptive management of Post-transplant Lymphoproliferative Disorder. Targeting the repetitive BamHI-W sequence was shown to increase the sensitivity of EBV DNA quantification, but the variability of BamHI-W reiterations was suggested to be a source of quantification bias. We aimed to assess the extent of variability associated with BamHI-W PCR and its impact on the sensitivity of EBV DNA quantification using the 1st WHO international standard, EBV strains and clinical samples. Repetitive BamHI-W- and LMP2 single- sequences were amplified by in-house qPCRs and BXLF-1 sequence by a commercial assay (EBV R-gene™, BioMerieux). Linearity and limits of detection of in-house methods were assessed. The impact of repeated versus single target sequences on EBV DNA quantification precision was tested on B95.8 and Raji cell lines, possessing 11 and 7 copies of the BamHI-W sequence, respectively, and on clinical samples. BamHI-W qPCR demonstrated a lower limit of detection compared to LMP2 qPCR (2.33 log10 versus 3.08 log10 IU/mL; P = 0.0002). BamHI-W qPCR underestimated the EBV DNA load on Raji strain which contained fewer BamHI-W copies than the WHO standard derived from the B95.8 EBV strain (mean bias: - 0.21 log10; 95% CI, -0.54 to 0.12). Comparison of BamHI-W qPCR versus LMP2 and BXLF-1 qPCR showed an acceptable variability between EBV DNA levels in clinical samples with the mean bias being within 0.5 log10 IU/mL EBV DNA, whereas a better quantitative concordance was observed between LMP2 and BXLF-1 assays. Targeting BamHI-W resulted to a higher sensitivity compared to LMP2 but the variable reiterations of BamHI-W segment are associated with higher quantification variability. BamHI-W can be considered for clinical and therapeutic monitoring to detect an early EBV DNA and a dynamic change in viral load.

  7. Possibilistic approach to target classification

    NARCIS (Netherlands)

    Huizing, A.G.; Groen, F.C.A.

    2000-01-01

    Abstract: This chapter describes an alternative to the Bayesian approach to target classification that is based on possibility theory. A possibilistic classifier minimizes the maximum cost of the classification decision taking into account the a posteriori possibilities of the target classes given

  8. Spinning targets for laser fusion

    International Nuclear Information System (INIS)

    Baldwin, D.E.; Ryutov, D.D.

    1995-09-01

    Several techniques for spinning the ICF targets up prior to or in the course of their compression are suggested. Interference of the rotational shear flow with Rayleigh-Taylor instability is briefly discussed and possible consequences for the target performance are pointed out

  9. Target recognition by wavelet transform

    CERN Document Server

    Li Zheng Dong; He Wu Liang; Pei Chun Lan; Peng Wen; SongChen; Zheng Xiao Dong

    2002-01-01

    Wavelet transform has an important character of multi-resolution power, which presents pyramid structure, and this character coincides the way by which people distinguish object from coarse to fineness and from large to tiny. In addition to it, wavelet transform benefits to reducing image noise, simplifying calculation, and embodying target image characteristic point. A method of target recognition by wavelet transform is provided

  10. Dual targeting of peroxisomal proteins

    Directory of Open Access Journals (Sweden)

    Julia eAst

    2013-10-01

    Full Text Available Cellular compartmentalization into organelles serves to separate biological processes within the environment of a single cell. While some metabolic reactions are specific to a single organelle, others occur in more than one cellular compartment. Specific targeting of proteins to compartments inside of eukaryotic cells is mediated by defined sequence motifs. To achieve multiple targeting to different compartments cells use a variety of strategies. Here, we focus on mechanisms leading to dual targeting of peroxisomal proteins. In many instances, isoforms of peroxisomal proteins with distinct intracellular localization are encoded by separate genes. But also single genes can give rise to differentially localized proteins. Different isoforms can be generated by use of alternative transcriptional start sites, by differential splicing or ribosomal read-through of stop codons. In all these cases different peptide variants are produced, of which only one carries a peroxisomal targeting signal. Alternatively, peroxisomal proteins contain additional signals that compete for intracellular targeting. Dual localization of proteins residing in both the cytoplasm and in peroxisomes may also result from use of inefficient targeting signals. The recent observation that some bona fide cytoplasmic enzymes were also found in peroxisomes indicates that dual targeting of proteins to both the cytoplasm and the peroxisome might be more widespread. Although current knowledge of proteins exhibiting only partial peroxisomal targeting is far from being complete, we speculate that the metabolic capacity of peroxisomes might be larger than previously assumed.

  11. Treating rheumatoid arthritis to target

    DEFF Research Database (Denmark)

    Smolen, Josef S; Breedveld, Ferdinand C; Burmester, Gerd R

    2016-01-01

    BACKGROUND: Reaching the therapeutic target of remission or low-disease activity has improved outcomes in patients with rheumatoid arthritis (RA) significantly. The treat-to-target recommendations, formulated in 2010, have provided a basis for implementation of a strategic approach towards this t...

  12. Treating rheumatoid arthritis to target

    DEFF Research Database (Denmark)

    Smolen, Josef S; Aletaha, Daniel; Bijlsma, Johannes W J

    2010-01-01

    BACKGROUND: Aiming at therapeutic targets has reduced the risk of organ failure in many diseases such as diabetes or hypertension. Such targets have not been defined for rheumatoid arthritis (RA). OBJECTIVE: /st> To develop recommendations for achieving optimal therapeutic outcomes in RA. METHODS...

  13. Detection of a distributed target

    NARCIS (Netherlands)

    Spek, G.A. van der

    1971-01-01

    The influence of increasing range resolution on the detectability of targets with dimensions greater than the resolution cell is studied. An N-cell target model is assumed, which contains k reflecting cells, each reflecting independently according to the same Rayleigh amplitude distribution. It will

  14. High speed cryogenic monodisperse targets

    Science.gov (United States)

    Boukharov, A.; Vishnevkii, E.

    2017-11-01

    The basic possibility of creation of high speed cryogenic monodisperse targets is shown. According to calculations at input of thin liquid cryogenic jets with a velocity of bigger 100 m/s in vacuum the jets don’t manage to freeze at distance to 1 mm and can be broken into monodisperse drops. Drops due to evaporation are cooled and become granules. High speed cryogenic monodisperse targets have the following advantages: direct input in vacuum (there is no need for a chamber of a triple point chamber and sluices), it is possible to use the equipment of a cluster target, it is possible to receive targets with a diameter of D 100m/s), exact synchronization of the target hitting moment in a beam with the moment of sensors turning on.

  15. Oxide fiber targets at ISOLDE

    DEFF Research Database (Denmark)

    Köster, U.; Bergmann, U.C.; Carminati, D.

    2003-01-01

    Many elements are rapidly released from oxide matrices. Some oxide powder targets show a fast sintering, thus losing their favorable release characteristics. Loosely packed oxide fiber targets are less critical since they may maintain their open structure even when starting to fuse together at some...... contact points. The experience with various oxide fiber targets (titania, zirconia, ceria and thoria) used in the last years at ISOLDE is reviewed. For short-lived isotopes of Cu, Ga and Xe the zirconia and ceria targets respectively provided significantly higher yields than any other target (metal foils......, oxide powders, etc.) tested before. Titania fibers, which were not commercially available, were produced in a relic process by impregnation of a rayon felt in a titanium chloride solution and subsequent calcination by heating the dried felt in air. Thoria fibers were obtained either by the same process...

  16. Targeted marketing and public health.

    Science.gov (United States)

    Grier, Sonya A; Kumanyika, Shiriki

    2010-01-01

    Targeted marketing techniques, which identify consumers who share common needs or characteristics and position products or services to appeal to and reach these consumers, are now the core of all marketing and facilitate its effectiveness. However, targeted marketing, particularly of products with proven or potential adverse effects (e.g., tobacco, alcohol, entertainment violence, or unhealthful foods) to consumer segments defined as vulnerable raises complex concerns for public health. It is critical that practitioners, academics, and policy makers in marketing, public health, and other fields recognize and understand targeted marketing as a specific contextual influence on the health of children and adolescents and, for different reasons, ethnic minority populations and other populations who may benefit from public health protections. For beneficial products, such understanding can foster more socially productive targeting. For potentially harmful products, understanding the nature and scope of targeted marketing influences will support identification and implementation of corrective policies.

  17. Target-Searching on Percolation

    International Nuclear Information System (INIS)

    Yang Shijie

    2005-01-01

    We study target-searching processes on a percolation, on which a hunter tracks a target by smelling odors it emits. The odor intensity is supposed to be inversely proportional to the distance it propagates. The Monte Carlo simulation is performed on a 2-dimensional bond-percolation above the threshold. Having no idea of the location of the target, the hunter determines its moves only by random attempts in each direction. For lager percolation connectivity p ∼> 0.90, it reveals a scaling law for the searching time versus the distance to the position of the target. The scaling exponent is dependent on the sensitivity of the hunter. For smaller p, the scaling law is broken and the probability of finding out the target significantly reduces. The hunter seems trapped in the cluster of the percolation and can hardly reach the goal.

  18. Gas target neutron generator studies

    International Nuclear Information System (INIS)

    Chatoorgoon, V.

    1978-01-01

    The need for an intense neutron source for the study of radiation damage on materials has resulted in the proposal of various solid, liquid, and gas targets. Among the gas targets proposed have been the transonic gas target, two types of hypersonic gas target, and the subsonic gas target (SGT). It has been suggested that heat deposition in a subsonic channel might create a gas density step which would constitute an attractive gas target type. The first part of the present study examines this aspect of the SGT and shows that gas density gradients are indeed formed by heat deposition in subsonic flow. The variation of beam voltage, gas density, gas pressure, and gas temperature within the channel have been calculated as functions of the system parameters: beam voltage, beam current, channel diameter, stagnation tank temperature and pressure. The analysis is applicable to any beam particle and target gas. For the case of T + on D 2 , which is relevant to the fusion application, the 14 MeV neutron profiles are presented as a function of system parameters. It is found that the SGT is compatible with concentrated intense source operation. The possibility of instability was investigated in detail using a non-linear analysis which made it possible to follow the complete time development of the SGT. It was found that the SGT is stable against all small perturbations and certain types of large perturbations. It appears that the SGT is the most advantageous type of gas target, operating at a lower mass flow and less severe stagnation tank conditions than the other types. The second part of the thesis examines a problem associated with the straight hypersonic target, the deuterium spill into the tritium port. The regime of practical operation for this target is established. (auth)

  19. Preparation of thin nuclear targets

    International Nuclear Information System (INIS)

    Muggleton, A.H.F.

    1979-03-01

    Thin film backings, sources and targets are needed for many applications in low energy nuclear physics and nuclear chemistry experiments. A survey of techniques used in the preparation of nuclear targets is first briefly discussed. These are classified as chemical, mechanical and physical preparations. Vacuum evaporation, being the most generally used technique, is discussed in detail. It is highly desirable to monitor the film thickness and control the deposition rate during evaporation and to measure the final target thickness after deposition has concluded. The relative merits of various thickness measuring techniques are described. Stages in the fabrication and mounting of self-supporting foils are described in detail, with emphasis given to the preparation of thin self-supporting carbon foils used as target backings and stripper foils. Various target backings, and the merits of the more generally used release agents are described in detail. The preparations of more difficult elemental targets are discussed, and a comprehensive list of the common targets is presented

  20. Simulations of effusion from ISOL target/ion source systems

    International Nuclear Information System (INIS)

    Mustapha, B.; Nolen, J.A.

    2004-01-01

    Monte Carlo simulations of the low- and high-conductivity Target/Ion Source systems used at Oak Ridge National Laboratory for effusion measurements are performed. Comparisons with the corresponding experimental data for the different geometries are presented and discussed. Independent checks of the simulation using data for simple geometries and using the conductance approach well known in vacuum technology are performed. A simulation-based comparison between the low- and high-conductivity systems is also presented

  1. PENETAPAN TARGET TERHADAP STICKINESS COST

    Directory of Open Access Journals (Sweden)

    Windyastuti Windyastuti

    2017-03-01

    Full Text Available This study aimed to analyze the influence of manager targeting to the stickiness cost. The research data was amanufacturing company’s financial statements during 1999-2011 published at BEI. The research data includedcost of sales, administration and general, net sales and Price Earnings Ratio (PER. This study used adynamic panel data regression analysis. The results showed that cost of sales, administration and general weresticky. Furthermore, manager targeting caused the stickiness degree of sales, administration and general costlower. Manager targeting changed the manager’s behavior. When the net sales declined, manager reduced theresource use drastically so the cost of sales, administration and general also decreased drastically.

  2. Development of targeted radiotherapy systems

    International Nuclear Information System (INIS)

    Ferro, Guillermina; Villarreal, Jose E.; Garcia, Laura; Tendilla, Jose I.; Paredes, Lydia; Murphy, Consuelo A.; Pedraza, Martha

    2001-01-01

    Conventional or external beam radiotherapy, has been a viable alternative for cancer treatment. Although this technique is effective, its use is limited if the patient has multiple malignant lesions (metastases). An alternative approach is based on the design of radiopharmaceuticals that, to be administered in the patient, are directed specifically toward the target cell producing a selective radiation delivery. This treatment is known as targeted radiotherapy. We have summarized and discussed some results related to our investigations on the development of targeted radiotherapy systems, including aspects of internal dosimetry

  3. Obstacles to Effective Joint Targeting

    National Research Council Canada - National Science Library

    Patch, John

    2007-01-01

    No foe can beat the modern-day American military machine in combined arms warfare, yet this machine is subject to strategic targeting vulnerabilities that military and policy leaders would do well to appreciate...

  4. Targeted Treatment of Brain Metastases.

    Science.gov (United States)

    Shonka, Nicole; Venur, Vyshak Alva; Ahluwalia, Manmeet S

    2017-04-01

    Brain metastases are the most common intracranial tumors in adults. Historically, the median survival after the diagnosis of brain metastases has been dismal and medical therapies had a limited role in the management of these patients. The advent of targeted therapy has ushered in an era of increased hope for patients with brain metastases. The most common malignancies that result in brain metastases-melanoma, lung cancer, and breast cancer, often have actionable mutations, which make them good candidates for targeted systemic therapy. These brain metastases have been shown to have relevant and sometimes divergent genetic alterations, and there has been a resurgence of interest in targeted drug delivery to the brain by using standard or pulsatile dosing to achieve adequate concentration in the brain. An increased understanding of oncogenic alterations, a surge in targeted drug development with good blood barrier penetration, and inclusion of patients with active brain metastases on clinical trials have led to improved outcomes for patients with brain metastases.

  5. Targeted intraoperative radiotherapy in oncology

    CERN Document Server

    Keshtgar, Mohammed; Wenz, Frederik

    2014-01-01

    Targeted intraoperative radiotherapy is a major advance in the management of cancer patients. With an emphasis on practical aspects, this book offers an ideal introduction to this innovative  technology for clinicians.

  6. Immunotherapy Targets Common Cancer Mutation

    Science.gov (United States)

    In a study of an immune therapy for colorectal cancer that involved a single patient, researchers identified a method for targeting the cancer-causing protein produced by a mutant form of the KRAS gene.

  7. Performance Targets and External Benchmarking

    DEFF Research Database (Denmark)

    Friis, Ivar; Hansen, Allan; Vámosi, Tamás S.

    Research on relative performance measures, transfer pricing, beyond budgeting initiatives, target costing, piece rates systems and value based management has for decades underlined the importance of external benchmarking in performance management. Research conceptualises external benchmarking...

  8. Physics of Automatic Target Recognition

    CERN Document Server

    Sadjadi, Firooz

    2007-01-01

    Physics of Automatic Target Recognition addresses the fundamental physical bases of sensing, and information extraction in the state-of-the art automatic target recognition field. It explores both passive and active multispectral sensing, polarimetric diversity, complex signature exploitation, sensor and processing adaptation, transformation of electromagnetic and acoustic waves in their interactions with targets, background clutter, transmission media, and sensing elements. The general inverse scattering, and advanced signal processing techniques and scientific evaluation methodologies being used in this multi disciplinary field will be part of this exposition. The issues of modeling of target signatures in various spectral modalities, LADAR, IR, SAR, high resolution radar, acoustic, seismic, visible, hyperspectral, in diverse geometric aspects will be addressed. The methods for signal processing and classification will cover concepts such as sensor adaptive and artificial neural networks, time reversal filt...

  9. National Ignition Facility Target Chamber

    International Nuclear Information System (INIS)

    Wavrik, R W; Cox, J R; Fleming, P J

    2000-01-01

    On June 11, 1999 the Department of Energy dedicated the single largest piece of the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory (LLNL) in Livermore, California. The ten (10) meter diameter aluminum target high vacuum chamber will serve as the working end of the largest laser in the world. The output of 192 laser beams will converge at the precise center of the chamber. The laser beams will enter the chamber in two by two arrays to illuminate 10 millimeter long gold cylinders called hohlraums enclosing 2 millimeter capsule containing deuterium, tritium and isotopes of hydrogen. The two isotopes will fuse, thereby creating temperatures and pressures resembling those found only inside stars and in detonated nuclear weapons, but on a minute scale. The NIF Project will serve as an essential facility to insure safety and reliability of our nation's nuclear arsenal as well as demonstrating inertial fusion's contribution to creating electrical power. The paper will discuss the requirements that had to be addressed during the design, fabrication and testing of the target chamber. A team from Sandia National Laboratories (SNL) and LLNL with input from industry performed the configuration and basic design of the target chamber. The method of fabrication and construction of the aluminum target chamber was devised by Pitt-Des Moines, Inc. (PDM). PDM also participated in the design of the chamber in areas such as the Target Chamber Realignment and Adjustment System, which would allow realignment of the sphere laser beams in the event of earth settlement or movement from a seismic event. During the fabrication of the target chamber the sphericity tolerances had to be addressed for the individual plates. Procedures were developed for forming, edge preparation and welding of individual plates. Construction plans were developed to allow the field construction of the target chamber to occur parallel to other NIF construction activities. This was

  10. Nanotechnology of emerging targeting systems.

    Science.gov (United States)

    Smith, S S

    2008-09-01

    Recent developments in the design and testing of complex nanoscale payload-carrying systems (i.e. systems with payloads that do not exceed 100 nm in size) are the focus of this brief review. Emerging systems include targeted single-walled nanotubes, viral capsids, dendrimers, gold nanoparticles, milled boron carbide nanoparticles, and protein nucleic acid assemblies. Significant advances are emerging with each of these bionanotechnological approaches to cellular targeting.

  11. Polarized atomic beams for targets

    International Nuclear Information System (INIS)

    Grueebler, W.

    1984-01-01

    The basic principle of the production of polarized atomic hydrogen and deuterium beams are reviewed. The status of the present available polarization, density and intensity are presented. The improvement of atomic beam density by cooling the hydrogen atoms to low velocity is discussed. The possible use of polarized atomic beams as targets in storage rings is shown. It is proposed that polarized atomic beams can be used to produce polarized gas targets with high polarization and greatly improved density

  12. Targeted immunotherapy in Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Hutchings, Martin

    2015-01-01

    In this issue of Blood, Rothe et al introduce a new principle of targeted Hodgkin lymphoma (HL) immunotherapy in their report from a phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13.......In this issue of Blood, Rothe et al introduce a new principle of targeted Hodgkin lymphoma (HL) immunotherapy in their report from a phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13....

  13. X-ray tube target

    International Nuclear Information System (INIS)

    Weber, R.G.

    1980-01-01

    A target with an improved heat emissive surface for use in a rotating anode type x-ray tube is described. The target consists of a body having a first surface portion made of x-ray emissive material and a second surface portion made of a heat emissive material comprising at least one of hafnium boride, hafnium oxide, hafnium nitride, hafnium silicide, and hafnium aluminide. (U.K.)

  14. Market segmentation, targeting and positioning

    OpenAIRE

    Camilleri, Mark Anthony

    2017-01-01

    Businesses may not be in a position to satisfy all of their customers, every time. It may prove difficult to meet the exact requirements of each individual customer. People do not have identical preferences, so rarely does one product completely satisfy everyone. Many companies may usually adopt a strategy that is known as target marketing. This strategy involves dividing the market into segments and developing products or services to these segments. A target marketing strategy is focused on ...

  15. Model organisms and target discovery.

    Science.gov (United States)

    Muda, Marco; McKenna, Sean

    2004-09-01

    The wealth of information harvested from full genomic sequencing projects has not generated a parallel increase in the number of novel targets for therapeutic intervention. Several pharmaceutical companies have realized that novel drug targets can be identified and validated using simple model organisms. After decades of service in basic research laboratories, yeasts, worms, flies, fishes, and mice are now the cornerstones of modern drug discovery programs.: © 2004 Elsevier Ltd . All rights reserved.

  16. Theoretical aspects of inflation targeting

    Directory of Open Access Journals (Sweden)

    Obradović Jelena

    2014-01-01

    Full Text Available Inflation targeting is one of the possible strategies used by central banks during conducting monetary policy. The basic characteristics, advantages and disadvantages of inflation targeting will be presented in this paper. The focus is on the the presentation and interpretation of the understanding of this strategy from the perspective of monetarist and Keynesian theory, the theory of rational expectations, and methodological analysis of the strategy in light of the game theory using payoff matrix.

  17. Genetics Home Reference: X-linked lymphoproliferative disease

    Science.gov (United States)

    ... PubMed Central Woon ST, Ameratunga R, Croxson M, Taylor G, Neas K, Edkins E, Browett P, Gane ... RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from http:// ...

  18. Interleukin-10 and posttransplant lymphoproliferative disorder after kidney transplantation

    DEFF Research Database (Denmark)

    Birkeland, S.A.; Bendtzen, K.; Moller, B.

    1999-01-01

    , and the type and duration of immunosuppression. Interleukin-10 (IL-10) is a pleiotropic cytokine, produced primarily by T-helper 2 (Th2) lymphocytes in the later stages of T-cell activation, suggested to play a role in EBV-associated PTLD, We recently reported preliminary findings on IL-10 in relation...... human recombinant IL-10 was employed; the assay is specific for human natural and viral IL-10, Results, Three patients experienced primary EBV infection, five reactivated EBV infections, and one did not change EBV status. Three patients had a fulminant course and died with EBV-associated PTLD; confirmed...... immunosuppression and are now in a state of operational tolerance. In three of four cases with initial lymphoma, EBV infection (primary or reactivation) preceded the increase in IL-10, In all four cases, the IL-10 increase preceded the PTLD diagnosis. In six cases, IL-10 could be followed after treatment showing...

  19. Therapeutic approach to metastatic myelo-lymphoproliferative malignancies in spine

    Directory of Open Access Journals (Sweden)

    Mauricio Dominguez

    2016-02-01

    Full Text Available Introduction Myeloproliferative metastatic tumors (leukemia, multiple myeloma and lymphoma are a problem that the spinal surgeon faces increasingly due to longer survival periods associated with their slower growth rates and improved oncological treatments available.Currently there is not consensus about any classifications that establish a prognosis and a treatment plan for the management of these pathologiesObjectiveTo apply and evaluate specific survival scale (ECOG and SCMMM and treatment (Sins for this type of spinal metastases. Material and MethodsPatients with diagnosis of metastatic spine myeloproliferative diseases had the above scale applied and also adding visual analog scale (VAS and Oswestry (ODI to quantify the evolution of treatment. Were included in this sample 5 patients with a minimum follow up of 6 months. ResultsOf the patients sampled 4 patients had a diagnosis of multiple myeloma and one a diagnosis of leukemia, 2 were operated and 3 were treated with radiotherapy, chemotherapy and corset; all improved EVA and Oswestry except one who died at 7 days by an extraspinal complication. ConclusionThe scales used are very useful for therapeutic decision of these patients to be more specific for these metastases.

  20. Lymphoproliferative disorders in non-AIDS associated Kaposi's ...

    African Journals Online (AJOL)

    The association of the non-AIDS-related, classic fonn of Kaposi's sarcoma (KS) with secondary malignancies, especially Iymphoproliferative disorders, has frequently been noted. However, in endemic: African-type KS, such an association has been reported only rarely. A review of 62 non-AIDS-related cases of KS treated ...

  1. Frequent hypermethylation of DBC1 in malignant lymphoproliferative neoplasms

    DEFF Research Database (Denmark)

    Grønbæk, Karin Elmegård; Ralfkiaer, U.; Dahl, C.

    2008-01-01

    follicular lymphomas, 5 of 5 mantle cell lymphomas, 4 of 4 small lymphocytic lymphomas, 1 of 2 lymphoplasmacytoid lymphomas, and in 12 of 12 acute lymphoblastic leukemias, but was unmethylated in 1 case of splenic marginal zone lymphoma, in 12 of 12 multiple myelomas, in 24 of 24 reactive lymph nodes...

  2. Lymphoproliferative disorders in non-AIDS- associated Kaposi's ...

    African Journals Online (AJOL)

    62 non-AiDS-related cases of KS treated and followed up at Johannesburg General Hospital between 1980 ... Non-AIDS-associated Kaposi's sarcoma (KS) is a rare vascular tumour, affecting mainly the skin but also ..... Further investigation of patients may well show the occurrence of common pathogenetic mechanisms.

  3. Human immunodeficiency virus negative Kaposi sarcoma and lymphoproliferative disorders

    NARCIS (Netherlands)

    Fossati, S; Boneschi, [No Value; Ferrucci, S; Brambilla, L

    1999-01-01

    BACKGROUND. The concomitant occurrence of more than one primary neoplasm in the same individual has led researchers to seek possible common etiopathogenetic factors. Kaposi sarcoma (KS) is a multicentric neoplasm of vascular origin and perhaps viral etiology. Four forms of KS are known: classic or

  4. CD8+mycosis fungoides: A low-grade lymphoproliferative disorder.

    Science.gov (United States)

    Martinez-Escala, Maria Estela; Kantor, Robert W; Cices, Ahuva; Zhou, Xiaolong A; Kaplan, Jason B; Pro, Barbara; Choi, Jaehyuk; Guitart, Joan

    2017-09-01

    The prognosis of the CD8 + subtype of mycosis fungoides (MF) is controversial. Although most authors believe that determining the presence of this cell surface antigen has no prognostic value, others have observed a more indolent course for CD8 + MF compared with CD4 + MF. To review the cases of CD8 + MF in the pediatric and adult populations seen at our institution. This is a retrospective review of clinical and pathologic data. Age, stage at presentation, and outcomes of patients at our institution were compared with those of 2 large MF cohorts that predominantly were CD4 + from the relevant literature. Sixty-seven patients of a median age of 46 years were included. A higher frequency of early-stage disease was observed for CD8 + MF patients at diagnosis when compared with other cohorts, including 31 (47%) patients with stage IA, 33 (50%) with stage IB, and 2 (3%) with stage IIB (P = .001, P = .001, and P = .002, respectively). With a median follow-up (5.5 years, range 0.2-21 years) similar to other cohorts, a higher rate of complete remission was achieved (65.5%, P = .001), and a lower rate of progression was observed (P = .004). This is a retrospective review. Our experience with CD8 + MF confirms a more indolent course of disease with this MF variant. Our results warrant a conservative treatment approach limited to skin-directed therapies and observation in most patients. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  5. Yersinia enterocolitica Infection Simulating Lymphoproliferative Disease, after Liver Transplant

    Directory of Open Access Journals (Sweden)

    E. Jakobovich

    2014-01-01

    Full Text Available We describe a 14-year-old girl, who was 13 y after liver transplantation for biliary atresia with an unremarkable postoperative course. She presented with fever of up to 40°C, extreme fatigue, malaise, anorexia, and occasional vomiting. On physical examination the only finding was splenomegaly. Lab results showed hyperglobulinemia and an elevated sedimentation rate. Liver function tests were normal except for mild elevation of γGTP. Abdominal U/S and CT demonstrated an enlarged spleen with retroperitoneal and mesenteric lymph nodes enlargement. An exhaustive evaluation for infectious causes, autoimmune conditions, and malignancy was negative. A full recovery after 5 months prompted testing for self-limited infectious etiologies. Yersinia enterocolitica infection was diagnosed.

  6. Emerging targeted therapies for melanoma.

    Science.gov (United States)

    Johnson, Douglas B; Pollack, Megan H; Sosman, Jeffrey A

    2016-06-01

    Melanoma is an aggressive cutaneous malignancy associated with poor response to traditional therapies. Recent regulatory approval for immune checkpoint inhibitors and agents targeting mutated BRAF has led to a tremendous expansion of effective treatment options for patients with advanced melanoma. Unfortunately, primary or acquired resistance develops in most patients, highlighting the need for additional therapies. Numerous genetic and other molecular features of this disease may provide effective targets for therapy development. This article reviews available melanoma treatments, including immune and molecularly-targeted therapies. We then discuss agents in development, with a focus on targeted (rather than immune) therapies. In particular, we discuss agents that block mitogen-activated protein kinase (MAPK) signaling, as well as other emerging approaches such as antibody-drug conjugates, cell-cycle targeting, and novel genetically-informed clinical trials. Despite the incredible advances in melanoma therapeutics over the last several years, a clear need to develop more effective therapies remains. Molecularly-targeted therapy approaches will likely remain a cornerstone of melanoma treatment in parallel to immune therapy strategies.

  7. Killing cells by targeting mitosis.

    Science.gov (United States)

    Manchado, E; Guillamot, M; Malumbres, M

    2012-03-01

    Cell cycle deregulation is a common feature of human cancer. Tumor cells accumulate mutations that result in unscheduled proliferation, genomic instability and chromosomal instability. Several therapeutic strategies have been proposed for targeting the cell division cycle in cancer. Whereas inhibiting the initial phases of the cell cycle is likely to generate viable quiescent cells, targeting mitosis offers several possibilities for killing cancer cells. Microtubule poisons have proved efficacy in the clinic against a broad range of malignancies, and novel targeted strategies are now evaluating the inhibition of critical activities, such as cyclin-dependent kinase 1, Aurora or Polo kinases or spindle kinesins. Abrogation of the mitotic checkpoint or targeting the energetic or proteotoxic stress of aneuploid or chromosomally instable cells may also provide further benefits by inducing lethal levels of instability. Although cancer cells may display different responses to these treatments, recent data suggest that targeting mitotic exit by inhibiting the anaphase-promoting complex generates metaphase cells that invariably die in mitosis. As the efficacy of cell-cycle targeting approaches has been limited so far, further understanding of the molecular pathways modulating mitotic cell death will be required to move forward these new proposals to the clinic.

  8. Advances in Tumor Targeted Liposomes.

    Science.gov (United States)

    Jain, A; Jain, S K

    2018-04-15

    Cancer remains a deadly disease for effective treatment. Although anomalous tumor microenvironment is now widely exploited for targeted chemotherapy, safe and efficacious drug delivery to tumor cells is not still warranted. Liposomes are promising biodegradable and biocompatible nanocarriers having potential amenability for surface and internal modifications, and extraordinary capability to carry both hydrophilic as well as hydrophobhic drugs. Meticulous fabrication of liposomes with tumor selective ligand(s) and PEGylation reduces immunogenicity and increase target-specificity. This chapter focuses on critical developmental aspects of liposomes to target cancer cells exploiting Enhanced Permeability and Retention (EPR) effect and tumor-selective ligands such as folate, transferrin, peptides etc. Moreover, stimuli-responsive smart liposomes (triggers: pH, temperature, enzymes, magnetic field, ultrasound, and redox potential etc.) are also investigated for enhancement of drug delivery to tumors. This review summarizes advances in tumor-targeted liposomes via various means of targeting. This knowledgeable assemblage of advances in liposomal approaches will render new insights to formulators and budding scientists to design cancer targeted liposomes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Target detectability in acoustic elastography.

    Science.gov (United States)

    Bilgen, M

    1999-01-01

    The clinically relevant task of visually detecting low contrast targets in noisy strain images estimated from ultrasonic signals is studied. Detectability is measured quantitatively using contrast-to-noise ratio (CNR) analysis. Contrast in strain images is generated by a complex interaction among the soft tissue elasticity shear modulus distribution, target shape and location in the stress field, and external boundary conditions. Although a large strain variation is preferred for enhancing the contrast, this also increases the signal-dependent noise in strain estimates in a nonlinear fashion. Therefore, understanding the tradeoffs between contrast and noise is necessary for improving the diagnostic performance of strain imaging. In this paper, targets with slab, cylindrical, and spherical geometries are studied. Strains in the target and background and the precision of their estimates are described in terms of the corresponding shear modulus values for each geometry. These results are then incorporated into the CNR expression to investigate the changes in target detectability with the variation of shear modulus in the target and the ultrasonic signal parameters (echo signal-to-noise ratio and inverse fractional bandwidth) as well as the signal processing variables (time-bandwidth product and fractional window overlap).

  10. Unification of automatic target tracking and automatic target recognition

    Science.gov (United States)

    Schachter, Bruce J.

    2014-06-01

    The subject being addressed is how an automatic target tracker (ATT) and an automatic target recognizer (ATR) can be fused together so tightly and so well that their distinctiveness becomes lost in the merger. This has historically not been the case outside of biology and a few academic papers. The biological model of ATT∪ATR arises from dynamic patterns of activity distributed across many neural circuits and structures (including retina). The information that the brain receives from the eyes is "old news" at the time that it receives it. The eyes and brain forecast a tracked object's future position, rather than relying on received retinal position. Anticipation of the next moment - building up a consistent perception - is accomplished under difficult conditions: motion (eyes, head, body, scene background, target) and processing limitations (neural noise, delays, eye jitter, distractions). Not only does the human vision system surmount these problems, but it has innate mechanisms to exploit motion in support of target detection and classification. Biological vision doesn't normally operate on snapshots. Feature extraction, detection and recognition are spatiotemporal. When vision is viewed as a spatiotemporal process, target detection, recognition, tracking, event detection and activity recognition, do not seem as distinct as they are in current ATT and ATR designs. They appear as similar mechanism taking place at varying time scales. A framework is provided for unifying ATT and ATR.

  11. Polymeric micelles for drug targeting.

    Science.gov (United States)

    Mahmud, Abdullah; Xiong, Xiao-Bing; Aliabadi, Hamidreza Montazeri; Lavasanifar, Afsaneh

    2007-11-01

    Polymeric micelles are nano-delivery systems formed through self-assembly of amphiphilic block copolymers in an aqueous environment. The nanoscopic dimension, stealth properties induced by the hydrophilic polymeric brush on the micellar surface, capacity for stabilized encapsulation of hydrophobic drugs offered by the hydrophobic and rigid micellar core, and finally a possibility for the chemical manipulation of the core/shell structure have made polymeric micelles one of the most promising carriers for drug targeting. To date, three generations of polymeric micellar delivery systems, i.e. polymeric micelles for passive, active and multifunctional drug targeting, have arisen from research efforts, with each subsequent generation displaying greater specificity for the diseased tissue and/or targeting efficiency. The present manuscript aims to review the research efforts made for the development of each generation and provide an assessment on the overall success of polymeric micellar delivery system in drug targeting. The emphasis is placed on the design and development of ligand modified, stimuli responsive and multifunctional polymeric micelles for drug targeting.

  12. China's energy efficiency target 2010

    International Nuclear Information System (INIS)

    Yang Ming

    2008-01-01

    The Chinese government has set an ambitious target: reducing China's energy intensity by 20%, or 4.36% each year between 2006 and 2010 on the 2005 level. Real data showed that China missed its target in 2006, having reduced its energy intensity only by 1.3%. The objective of this study is to evaluate the feasibility and potential of the Chinese to achieve the target. This paper presents issues of macro-economy, population migration, energy savings, and energy efficiency policy measures to achieve the target. A top-down approach was used to analyse the relationship between the Chinese economic development and energy demand cycles and to identify the potentials of energy savings in sub-sectors of the Chinese economy. A number of factors that contribute to China's energy intensity are identified in a number of energy-intensive sectors. This paper concludes that China needs to develop its economy at its potential GDP growth rate; strengthen energy efficiency auditing, monitoring and verification; change its national economy from a heavy-industry-dominated mode to a light industry or a commerce-dominated mode; phase out inefficient equipment in industrial sectors; develop mass and fast railway transportation; and promote energy-efficient technologies at the end use. This paper transfers key messages to policy makers for designing their policy to achieve China's energy efficiency target

  13. Target-Centric Network Modeling

    DEFF Research Database (Denmark)

    Mitchell, Dr. William L.; Clark, Dr. Robert M.

    In Target-Centric Network Modeling: Case Studies in Analyzing Complex Intelligence Issues, authors Robert Clark and William Mitchell take an entirely new approach to teaching intelligence analysis. Unlike any other book on the market, it offers case study scenarios using actual intelligence...... reporting formats, along with a tested process that facilitates the production of a wide range of analytical products for civilian, military, and hybrid intelligence environments. Readers will learn how to perform the specific actions of problem definition modeling, target network modeling......, and collaborative sharing in the process of creating a high-quality, actionable intelligence product. The case studies reflect the complexity of twenty-first century intelligence issues by dealing with multi-layered target networks that cut across political, economic, social, technological, and military issues...

  14. Pharmacogenomics of GPCR Drug Targets

    DEFF Research Database (Denmark)

    Hauser, Alexander Sebastian; Chavali, Sreenivas; Masuho, Ikuo

    2018-01-01

    Natural genetic variation in the human genome is a cause of individual differences in responses to medications and is an underappreciated burden on public health. Although 108 G-protein-coupled receptors (GPCRs) are the targets of 475 (∼34%) Food and Drug Administration (FDA)-approved drugs...... and account for a global sales volume of over 180 billion US dollars annually, the prevalence of genetic variation among GPCRs targeted by drugs is unknown. By analyzing data from 68,496 individuals, we find that GPCRs targeted by drugs show genetic variation within functional regions such as drug......- and effector-binding sites in the human population. We experimentally show that certain variants of μ-opioid and Cholecystokinin-A receptors could lead to altered or adverse drug response. By analyzing UK National Health Service drug prescription and sales data, we suggest that characterizing GPCR variants...

  15. Materials considerations in accelerator targets

    International Nuclear Information System (INIS)

    Peacock, H.B. Jr.; Iyer, N.C.; Louthan, M.R. Jr.

    1994-01-01

    Future nuclear materials production and/or the burn-up of long lived radioisotopes may be accomplished through the capture of spallation produced neutrons in accelerators. Aluminum clad-lead and/or lead alloys has been proposed as a spallation target. Aluminum was the cladding choice because of the low neutron absorption cross section, fast radioactivity decay, high thermal conductivity, and excellent fabricability. Metallic lead and lead oxide powders were considered for the target core with the fabrication options being casting or powder metallurgy (PM). Scoping tests to evaluate gravity casting, squeeze casting, and casting and swaging processes showed that, based on fabricability and heat transfer considerations, squeeze casting was the preferred option for manufacture of targets with initial core cladding contact. Thousands of aluminum clad aluminum-lithium alloy core targets and control rods for tritium production have been fabricated by coextrusion processes and successfully irradiated in the SRS reactors. Tritium retention in, and release from the coextruded product was modeled from experimental and operational data. Newly produced tritium atoms were trapped by lithium atoms to form a lithium tritide. The effective tritium pressure required for trap or tritide stability was the equilibrium decomposition pressure of tritium over a lithium tritide-aluminum mixture. The temperature dependence of tritium release was determined by the permeability of the cladding to tritium and the local equilibrium at the trap sites. The model can be used to calculate tritium release from aluminum clad, aluminum-lithium alloy targets during postulated accelerator operational and accident conditions. This paper describes the manufacturing technologies evaluated and presents the model for tritium retention in aluminum clad, aluminum-lithium alloy tritium production targets

  16. Materials considerations in accelerator targets

    International Nuclear Information System (INIS)

    Peacock, H. B. Jr.; Iyer, N. C.; Louthan, M. R. Jr.

    1995-01-01

    Future nuclear materials production and/or the burn-up of long lived radioisotopes may be accomplished through the capture of spallation produced neutrons in accelerators. Aluminum clad-lead and/or lead alloys has been proposed as a spallation target. Aluminum was the cladding choice because of the low neutron absorption cross section, fast radioactivity decay, high thermal conductivity, and excellent fabricability. Metallic lead and lead oxide powders were considered for the target core with the fabrication options being casting or powder metallurgy (PM). Scoping tests to evaluate gravity casting, squeeze casting, and casting and swaging processes showed that, based on fabricability and heat transfer considerations, squeeze casting was the preferred option for manufacture of targets with initial core cladding contact. Thousands of aluminum clad aluminum-lithium alloy core targets and control rods for tritium production have been fabricated by coextrusion processes and successfully irradiated in the SRS reactors. Tritium retention in, and release from, the coextruded product was modeled from experimental and operational data. The model assumed that tritium atoms, formed by the 6Li(n,a)3He reaction, were produced in solid solution in the Al-Li alloy. Because of the low solubility of hydrogen isotopes in aluminum alloys, the irradiated Al-Li rapidly became supersaturated in tritium. Newly produced tritium atoms were trapped by lithium atoms to form a lithium tritide. The effective tritium pressure required for trap or tritide stability was the equilibrium decomposition pressure of tritium over a lithium tritide-aluminum mixture. The temperature dependence of tritium release was determined by the permeability of the cladding to tritium and the local equilibrium at the trap sites. The model can be used to calculate tritium release from aluminum clad, aluminum-lithium alloy targets during postulated accelerator operational and accident conditions. This paper describes

  17. Harnessing off-target effects

    DEFF Research Database (Denmark)

    Saginc, Gaye; Voellmy, Franziska; Linding, Rune

    2017-01-01

    The 'off-targets' of a drug are often poorly characterized yet could be harnessed in the treatment of complex diseases. A recent study used a small-molecule screening in non-small-cell lung cancer to repurpose an FDA-approved ALK/IGF1R inhibitor and uncover its mechanism of action.......The 'off-targets' of a drug are often poorly characterized yet could be harnessed in the treatment of complex diseases. A recent study used a small-molecule screening in non-small-cell lung cancer to repurpose an FDA-approved ALK/IGF1R inhibitor and uncover its mechanism of action....

  18. Target-Centric Network Modeling

    DEFF Research Database (Denmark)

    Mitchell, Dr. William L.; Clark, Dr. Robert M.

    reporting formats, along with a tested process that facilitates the production of a wide range of analytical products for civilian, military, and hybrid intelligence environments. Readers will learn how to perform the specific actions of problem definition modeling, target network modeling......, and collaborative sharing in the process of creating a high-quality, actionable intelligence product. The case studies reflect the complexity of twenty-first century intelligence issues by dealing with multi-layered target networks that cut across political, economic, social, technological, and military issues...

  19. The Bering Autonomous Target Detection

    DEFF Research Database (Denmark)

    Jørgensen, John Leif; Denver, Troelz; Betto, Maurizio

    2003-01-01

    An autonomous asteroid target detection and tracking method has been developed. The method features near omnidirectionality and focus on high speed operations and completeness of search of the near space rather than the traditional faint object search methods, employed presently at the larger...... telescopes. The method has proven robust in operation and is well suited for use onboard spacecraft. As development target for the method and the associated instrumentation the asteroid research mission Bering has been used. Onboard a spacecraft, the autonomous detection is centered around the fully...

  20. Nuclear target making and development

    International Nuclear Information System (INIS)

    Klimczak, G.W.; Thomas, G.E.

    1985-01-01

    The Physics Division operates a facility which produces and coordinates production of thin targets for charged-particle induced experiments, primarily at the Tandem-Linac and Dynamitron accelerators. In addition, these thin films are occasionally prepared for other scientific purposes. The services of the nuclear target-making facility are available to the Physics Division, other divisions of the Laboratory, and other scientific institutions. In addition to the typical production requirements, research work is performed in this facility to develop new techniques, as well as to implement and advance new state-of-the-art techniques developed at other institutions. Several new facilities and items of equipment are described

  1. The OPERA experiment Target Tracker

    CERN Document Server

    Adam, T; Borer, K.; Campagne, Jean-Eric; Con-Sen, N.; de La Taille, C.; Dick, N.; Dracos, M.; Gaudiot, G.; Goeltzenlichter, T.; Gornushkin, Y.; Grapton, J.-N.; Guyonnet, J.-L.; Hess, M.; Igersheim, R.; Janicsko Csathy, J.; Jollet, C.; Juget, F.; Kocher, H.; Krasnoperov, A.; Krumstein, Z.; Martin-Chassard, G.; Moser, U.; Nozdrin, A.; Olchevski, A.; Porokhovoi, S.; Raux, L.; Sadovski, A.; Schuler, J.; Schutz, H.-U.; Schwab, C.; Smolnikov, A.; Van Beek, G.; Vilain, P.; Walchli, T.; Wilquet, G.; Wurtz, J.

    2007-01-01

    The main task of the Target Tracker detector of the long baseline neutrino oscillation OPERA experiment is to locate in which of the target elementary constituents, the lead/emulsion bricks, the neutrino interactions have occurred and also to give calorimetric information about each event. The technology used consists in walls of two planes of plastic scintillator strips, one per transverse direction. Wavelength shifting fibres collect the light signal emitted by the scintillator strips and guide it to both ends where it is read by multi-anode photomultiplier tubes. All the elements used in the construction of this detector and its main characteristics are described.

  2. Nuclear Security: Target Analysis-rev

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Surinder Paul [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Gibbs, Philip W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bultz, Garl A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2014-03-01

    The objectives of this presentation are to understand target identification, including roll-up and protracted theft; evaluate target identification in the SNRI; recognize the target characteristics and consequence levels; and understand graded safeguards.

  3. Targeted Therapies in Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Selen Dogan

    2014-04-01

    Full Text Available Endometrial cancer is the most common genital cancer in developed world. It is generally diagnosed in early stage and it has a favorable prognosis. However, advanced staged disease and recurrences are difficult to manage. There are some common genetic alterations related to endometrial carcinogenesis in similar fashion to other cancers. Personalized medicine, which means selection of best suited treatment for an individual, has gain attention in clinical care of patients in recent years. Targeted therapies were developed as a part of personalized or %u201Ctailored%u201D medicine and specifically acts on a target or biologic pathway. There are quite a number of molecular alteration points in endometrial cancer such as PTEN tumor suppressor genes, DNA mismatch repair genes, PI3K/AKT/mTOR pathway and p53 oncogene which all might be potential candidates for tailored targeted therapy. In recent years targeted therapies has clinical application in ovarian cancer patients and in near future with the advent of new agents these %u201Ctailored%u201D drugs will be in market for routine clinical practice in endometrial cancer patients, in primary disease and recurrences as well.

  4. Raw eggs-moving target

    Science.gov (United States)

    Forrest, Doug

    1999-09-01

    High school physics students often have difficulty with understanding when and where to use an appropriate calculation to solve a problem. In this activity students have to solve a real problem using formulas they have seen before, but in a context with which they are unfamiliar; namely dropping a raw egg on a moving target-their instructor.

  5. Tracking Target and Spiral Waves

    DEFF Research Database (Denmark)

    Jensen, Flemming G.; Sporring, Jon; Nielsen, Mads

    2002-01-01

    A new algorithm for analyzing the evolution of patterns of spiral and target waves in large aspect ratio chemical systems is introduced. The algorithm does not depend on finding the spiral tip but locates the center of the pattern by a new concept, called the spiral focus, which is defined by the...

  6. Exploring targeted therapies in oncology

    NARCIS (Netherlands)

    Mom, Constantijne Helene

    2007-01-01

    Targeted therapy in oncology is treatment directed at specific biological pathways and processes that play a critical role in carcinogenesis. Increased knowledge regarding the molecular changes underlying tumor progression and metastatis has resulted in the development of agents that are designed to

  7. Targeted nanoparticles for colorectal cancer

    DEFF Research Database (Denmark)

    Cisterna, Bruno A.; Kamaly, Nazila; Choi, Won Il

    2016-01-01

    Colorectal cancer (CRC) is highly prevalent worldwide, and despite notable progress in treatment still leads to significant morbidity and mortality. The use of nanoparticles as a drug delivery system has become one of the most promising strategies for cancer therapy. Targeted nanoparticles could...

  8. Uranium briquettes for irradiation target

    Energy Technology Data Exchange (ETDEWEB)

    Saliba-Silva, Adonis Marcelo; Garcia, Rafael Henrique Lazzari; Martins, Ilson Carlos; Carvalho, Elita Fontenele Urano de; Durazzo, Michelangelo, E-mail: saliba@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    Direct irradiation on targets inside nuclear research or multiple purpose reactors is a common route to produce {sup 99}Mo-{sup 99m}Tc radioisotopes. Nevertheless, since the imposed limits to use LEU uranium to prevent nuclear armament production, the amount of uranium loaded in target meats has physically increased and new processes have been proposed for production. Routes using metallic uranium thin film and UAl{sub x} dispersion have been used for this purpose. Both routes have their own issues, either by bringing difficulties to disassemble the aluminum case inside hot cells or by generating great amount of alkaline radioactive liquid rejects. A potential route might be the dispersion of powders of LEU metallic uranium and nickel, which are pressed as a blend inside a die and followed by pulse electroplating of nickel. The electroplating provides more strength to the briquettes and creates a barrier for gas evolution during neutronic disintegration of {sup 235}U. A target briquette platted with nickel encapsulated in an aluminum case to be irradiated may be an alternative possibility to replace other proposed targets. This work uses pulse Ni-electroplating over iron powder briquette to simulate the covering of uranium by nickel. The following parameters were applied 10 times for each sample: 900Hz, -0.84A/square centimeters with duty cycle of 0.1 in Watts Bath. It also presented the optical microscopy analysis of plated microstructure section. (author)

  9. Particle physics using nuclear targets

    International Nuclear Information System (INIS)

    Ferbel, T.

    1978-01-01

    The use of nuclear targets in particle physics is discussed and some recent results obtained in studies of hadronic interactions on nuclei summarized. In particular experimental findings on inclusive production and on coherent dissociation of mesons and baryons at high energies are presented. 41 references

  10. Downstream targets of WRKY33

    DEFF Research Database (Denmark)

    Petersen, Klaus; Fiil, Berthe Katrine; Mundy, John

    2008-01-01

    . Transcriptome analysis of a wrky33 loss-of-function mutant identified a subset of defense-related genes as putative targets of WRKY33. These genes include PAD3 and CYP71A13, which encode cytochrome P450 monoxygenases required for synthesis of the antimicrobial phytoalexin camalexin. Chromatin...

  11. Communicating to heterogeneous target groups

    DEFF Research Database (Denmark)

    Pedersen, Karsten

    very often have to communicate to rather heterogeneous target groups that have little more in common than a certain geographical habitat. That goes against most schoolbook teaching in the field of communication, but is none the less the terms with which that kind of communication has to live...... will be able to make a much stronger case....

  12. Polarized Scintillating Targets at Psi

    Science.gov (United States)

    van den Brandt, B.; Bunyatova, E. I.; Hautle, P.; Konter, J. A.; Mango, S.

    2001-02-01

    Scintillating polarized targets are now routinely available: blocks of 18×18×5 mm scintillating organic polymer, doped with TEMPO, polarized dynamically in a field of 2.5 T in a vertical 3He-4He dilution refrigerator. A 19 mm diameter plastic lightguide transports the scintillation light from the sample in the mixing chamber to a photomultiplier outside the cryostat.

  13. Targeted Advertising and Social Status

    NARCIS (Netherlands)

    N. Vikander (Nick)

    2010-01-01

    textabstractThis paper shows how a firm can use non-targeted advertising to exploit consumers' desire for social status. A monopolist sells multiple varieties of a good to consumers who each care about what others believe about his wealth. Advertising allows consumers both to buy different varieties

  14. Target selection for direct marketing.

    NARCIS (Netherlands)

    Bult, Jan Roelf

    1993-01-01

    In this thesis we concentrated on the use ol direct mail for targeting potential buyers. The major characteristics that influences the success of a plomotional direct mail campaign are the of-fbr,the communication elements, the timing or sequence of these communication elements, and the list of

  15. Targeted drugs in radiation therapy

    International Nuclear Information System (INIS)

    Favaudon, V.; Hennequin, C.; Hennequin, C.

    2004-01-01

    New drugs aiming at the development of targeted therapies have been assayed in combination with ionizing radiation over the past few years. The rationale of this concept comes from the fact that the cytotoxic potential of targeted drugs is limited, thus requiring concomitant association with a cytotoxic agent for the eradication of tumor cells. Conversely a low level of cumulative toxicity is expected from targeted drugs. Most targeted drugs act through inhibition of post-translational modifications of proteins, such as dimerization of growth factor receptors, prenylation reactions, or phosphorylation of tyrosine or serine-threonine residues. Many systems involving the proteasome, neo-angiogenesis promoters, TGF-β, cyclooxygenase or the transcription factor NF-κB, are currently under investigation in hopes they will allow a control of cell proliferation, apoptosis, cell cycle progression, tumor angiogenesis and inflammation. A few drugs have demonstrated an antitumor potential in particular phenotypes. In most instances, however, radiation-drug interactions proved to be strictly additive in terms of cell growth inhibition or induced cell death. Strong potentiation of the response to radiotherapy is expected to require interaction with DNA repair mechanisms. (authors)

  16. CERN neutrino project on target

    CERN Multimedia

    2005-01-01

    Scientists at CERN announced the completion of the target assembly for the CERN neutrinos to Gran Sasso project, CNGS. On schedule for start-up in May 2006, CNGS will send a beam of neutrinos through the Earth to the Gran Sasso laboratory 730 km away in Italy in a bid to unravel the mysteries of nature's most elusive particles (½ page)

  17. Tumor targeting via integrin ligands

    Directory of Open Access Journals (Sweden)

    Udaya Kiran eMarelli

    2013-08-01

    Full Text Available Selective and targeted delivery of drugs to tumors is a major challenge for an effective cancer therapy and also to overcome the side effects associated with current treatments. Overexpression of various receptors on tumor cells is a characteristic structural and biochemical aspect of tumors and distinguishes them from physiologically normal cells. This abnormal feature is therefore suitable for selectively directing anticancer molecules to tumors by using ligands that can preferentially recognize such receptors. Several subtypes of integrin receptors that are crucial for cell adhesion, cell signaling, cell viability and motility have been shown to have an upregulated expression on cancer cells. Thus, ligands that recognize specific integrin subtypes represent excellent candidates to be conjugated to drugs or drug carrier systems and be targeted to tumors. In this regard, integrins recognizing the RGD cell adhesive sequence have been extensively targeted for tumor specific drug delivery. Here we review key recent examples on the presentation of RGD-based integrin ligands by means of distinct drug delivery systems, and discuss the prospects of such therapies to specifically target tumor cells.

  18. The Automatic Measurement of Targets

    DEFF Research Database (Denmark)

    Höhle, Joachim

    1997-01-01

    The automatic measurement of targets is demonstrated by means of a theoretical example and by an interactive measuring program for real imagery from a réseau camera. The used strategy is a combination of two methods: the maximum correlation coefficient and the correlation in the subpixel range...... interactive software is also part of a computer-assisted learning program on digital photogrammetry....

  19. Uranium briquettes for irradiation target

    International Nuclear Information System (INIS)

    Saliba-Silva, Adonis Marcelo; Garcia, Rafael Henrique Lazzari; Martins, Ilson Carlos; Carvalho, Elita Fontenele Urano de; Durazzo, Michelangelo

    2011-01-01

    Direct irradiation on targets inside nuclear research or multiple purpose reactors is a common route to produce 99 Mo- 99m Tc radioisotopes. Nevertheless, since the imposed limits to use LEU uranium to prevent nuclear armament production, the amount of uranium loaded in target meats has physically increased and new processes have been proposed for production. Routes using metallic uranium thin film and UAl x dispersion have been used for this purpose. Both routes have their own issues, either by bringing difficulties to disassemble the aluminum case inside hot cells or by generating great amount of alkaline radioactive liquid rejects. A potential route might be the dispersion of powders of LEU metallic uranium and nickel, which are pressed as a blend inside a die and followed by pulse electroplating of nickel. The electroplating provides more strength to the briquettes and creates a barrier for gas evolution during neutronic disintegration of 235 U. A target briquette platted with nickel encapsulated in an aluminum case to be irradiated may be an alternative possibility to replace other proposed targets. This work uses pulse Ni-electroplating over iron powder briquette to simulate the covering of uranium by nickel. The following parameters were applied 10 times for each sample: 900Hz, -0.84A/square centimeters with duty cycle of 0.1 in Watts Bath. It also presented the optical microscopy analysis of plated microstructure section. (author)

  20. How are inflation targets set?

    Czech Academy of Sciences Publication Activity Database

    Horváth, R.; Matějů, Jakub

    -, č. 426 (2010), s. 1-35 ISSN 1211-3298 Grant - others:MŠk(CZ) SVV-2010-261801 Institutional research plan: CEZ:MSM0021620846 Keywords : inflation targeting * central bank * credibility Subject RIV: AH - Economics http://www.cerge-ei.cz/pdf/wp/Wp426.pdf

  1. TARGET Imbalances at Record Levels

    DEFF Research Database (Denmark)

    Hallett, Andrew Hughes

    TARGET is the payments system for making settlements between euro area economies and five other EU economies. Cross-border transactions generate claims/surpluses and liabilities/deficits among national central banks which “net out” for the system as a whole. These imbalances are manageable...

  2. Other targeted drugs in melanoma.

    Science.gov (United States)

    González-Cao, María; Rodón, Jordi; Karachaliou, Niki; Sánchez, Jesús; Santarpia, Mariacarmela; Viteri, Santiago; Pilotto, Sara; Teixidó, Cristina; Riso, Aldo; Rosell, Rafael

    2015-10-01

    Targeted therapy drugs are developed against specific molecular alterations on cancer cells. Because they are "targeted" to the tumor, these therapies are more effective and better tolerated than conventional therapies such as chemotherapy. In the last decade, great advances have been made in understanding of melanoma biology and identification of molecular mechanisms involved in malignant transformation of cells. The identification of oncogenic mutated kinases involved in this process provides an opportunity for development of new target therapies. The dependence of melanoma on BRAF-mutant kinase has provided an opportunity for development of mutation-specific inhibitors with high activity and excellent tolerance that are now being used in clinical practice. This marked a new era in the treatment of metastatic melanoma and much research is now ongoing to identify other "druggable" kinases and transduction signaling networking. It is expected that in the near future the spectrum of target drugs for melanoma treatment will increase. Herein, we review the most relevant potential novel drugs for melanoma treatment based on preclinical data and the results of early clinical trials.

  3. Realism and Effectiveness of Robotic Moving Targets

    Science.gov (United States)

    2017-04-01

    balloons hanging from a pulley on an angled cable. Target movement is provided by human or mechanical power and targets have to be manually reset... mechanical power. For both types of targets speed varies based on human or mechanical strength. Walking targets. Walking targets are used in a...their shots . The current moving target systems are limited in terms of realism and effectiveness. Movement for two systems is limited to bi

  4. Cellular Targets of Dietary Polyphenol Resveratrol

    National Research Council Canada - National Science Library

    Wu, Joseph M

    2006-01-01

    To test the hypothesis that resveratrol, a grape derived polyphenol, exerts its chemopreventive properties against prostate cancer by interacting with specific cellular targets, denoted resveratrol targeting proteins (RTPs...

  5. North Pacific Targets Program Environmental Assessment

    National Research Council Canada - National Science Library

    2001-01-01

    .... The STPO would provide the Strategic Target System launch vehicle for strategic target launch services from Kodiak Launch Complex, Kodiak Island, Alaska, a commercial rocket launch facility operated...

  6. Adaptive Maneuvering Target Tracking Algorithm

    Directory of Open Access Journals (Sweden)

    Chunling Wu

    2014-07-01

    Full Text Available Based on the current statistical model, a new adaptive maneuvering target tracking algorithm, CS-MSTF, is presented. The new algorithm keep the merits of high tracking precision that the current statistical model and strong tracking filter (STF have in tracking maneuvering target, and made the modifications as such: First, STF has the defect that it achieves the perfect performance in maneuvering segment at a cost of the precision in non-maneuvering segment, so the new algorithm modified the prediction error covariance matrix and the fading factor to improve the tracking precision both of the maneuvering segment and non-maneuvering segment; The estimation error covariance matrix was calculated using the Joseph form, which is more stable and robust in numerical. The Monte- Carlo simulation shows that the CS-MSTF algorithm has a more excellent performance than CS-STF and can estimate efficiently.

  7. Targeting Wnt Pathways in Disease

    Science.gov (United States)

    Zimmerman, Zachary F.; Moon, Randall T.

    2012-01-01

    Wnt-mediated signal transduction pathways have long been recognized for their roles in regulating embryonic development, and have more recently been linked to cancer, neurologic diseases, inflammatory diseases, and disorders of endocrine function and bone metabolism in adults. Although therapies targeting Wnt signaling are attractive in theory, in practice it has been difficult to obtain specific therapeutics because many components of Wnt signaling pathways are also involved in other cellular processes, thereby reducing the specificity of candidate therapeutics. New technologies, and advances in understanding the mechanisms of Wnt signaling, have improved our understanding of the nuances of Wnt signaling and are leading to promising new strategies to target Wnt signaling pathways. PMID:23001988

  8. Multishell inertial confinement fusion target

    International Nuclear Information System (INIS)

    Holland, J.R.; Del Vecchio, R.M.

    1984-01-01

    A method of fabricating multishell fuel targets for inertial confinement fusion usage. Sacrificial hemispherical molds encapsulate a concentric fuel pellet which is positioned by fiber nets stretched tautly across each hemispherical mold section. The fiber ends of the net protrude outwardly beyond the mold surfaces. The joint between the sacrificial hemispheres is smoothed. A ceramic or glass cover is then deposited about the finished mold surfaces to produce an inner spherical surface having continuously smooth surface configuration. The sacrificial mold is removed by gaseous reaction accomplished through the porous ceramic cover prior to enclosing of the outer sphere by addition of an outer coating. The multishell target comprises the inner fuel pellet concentrically arranged within a surrounding coated cover or shell by fiber nets imbedded within the cover material

  9. Swimbladder on Fish Target Strength

    Directory of Open Access Journals (Sweden)

    Sunardi

    2008-08-01

    Full Text Available This paper discusses of target strength (TS for the Selar boops (Oxeye scad and Megalaspis cordyla (Torpedo scad, the most commercially fish in Malaysia. TS can be determined from in situ measurements and acoustic calculation of fish model. TS value, depth, and position (x-y-z of targeted fish can be viewed from echogram using FQ-80 Analyzer by in situ measurement. X-ray imaged can be deployed to develop the acoustic fish model. The percentage of length and upper surface area for swimbladder to body fish of Selar boops more than Megalaspis cordyla can be measured after X-ray process. The percentage of width and volume of swimbladders to its each body are no significantly difference for both fish. These data of swimbladder physic support the result of in situ measurement which TS of Megalaspis cordyla stronger Selar boops.

  10. Super liquid density target designs

    International Nuclear Information System (INIS)

    Pan, Y.L.; Bailey, D.S.

    1976-01-01

    The success of laser fusion depends on obtaining near isentropic compression of fuel to very high densities and igniting this fuel. To date, the results of laser fusion experiments have been based mainly on the exploding pusher implosion of fusion capsules consisting of thin glass microballoons (wall thickness of less than 1 micron) filled with low density DT gas (initial density of a few mg/cc). Maximum DT densities of a few tenths of g/cc and temperatures of a few keV have been achieved in these experiments. We will discuss the results of LASNEX target design calculations for targets which: (a) can compress fuel to much higher densities using the capabilities of existing Nd-glass systems at LLL; (b) allow experimental measurement of the peak fuel density achieved

  11. Recurring Utterances - Targeting a Breakthrough

    Directory of Open Access Journals (Sweden)

    Jacqueline Stark

    2014-05-01

    The most interesting phenomenon is KB’s production of words from former sessions indicating that they are still ‘active’ and the production of completely novel incorrect words. The observable features indicate that immediate auditory processing is possible in the form of repeating target words. However, as soon as KB must retrieve information from the (semantic lexicon, even after being able to correctly ‘repeat’ the target word several times, he responds with a RU, perseveration, or paraphasia. Several of his productions can be characterized as aphasic confabulations which stem from a memory gap. Thus, although KB’s language impairment is severe, his responses across time indicate that step-by-step a breakthrough is being made.

  12. Targeted Learning in Healthcare Research.

    Science.gov (United States)

    Gruber, Susan

    2015-12-01

    The increasing availability of Big Data in healthcare encourages investigators to seek answers to big questions. However, nonparametric approaches to analyzing these data can suffer from the curse of dimensionality, and traditional parametric modeling does not necessarily scale. Targeted learning (TL) combines semiparametric methodology with advanced machine learning techniques to provide a sound foundation for extracting information from data. Predictive models, variable importance measures, and treatment benefits and risks can all be addressed within this framework. TL has been applied in a broad range of healthcare settings, including genomics, precision medicine, health policy, and drug safety. This article provides an introduction to the two main components of TL, targeted minimum loss-based estimation and super learning, and gives examples of applications in predictive modeling, variable importance ranking, and comparative effectiveness research.

  13. Targeting vaccines to dendritic cells

    DEFF Research Database (Denmark)

    Foged, Camilla; Sundblad, Anne; Hovgaard, Lars

    2002-01-01

    are considered to play a central role for the provocation of primary immune responses by vaccination. A rational way of improving the potency and safety of new and already existing vaccines could therefore be to direct vaccines specifically to DC. There is a need for developing multifunctional vaccine drug...... to be far superior to that of B-cells and macrophages. DC are localized at strategic places in the body at sites used by pathogens to enter the organism, and are thereby in an optimal position to capture antigens. In general, vaccination strategies try to mimic the invasiveness of the pathogens. DC...... delivery systems (DDS) with adjuvant effect that target DC directly and induce optimal immune responses. This paper will review the current knowledge of DC physiology as well as the progress in the field of novel vaccination strategies that directly or indirectly aim at targeting DC....

  14. Fixed target flammable gas upgrades

    International Nuclear Information System (INIS)

    Schmitt, R.; Squires, B.; Gasteyer, T.; Richardson, R.

    1996-12-01

    In the past, fixed target flammable gas systems were not supported in an organized fashion. The Research Division, Mechanical Support Department began to support these gas systems for the 1995 run. This technical memo describes the new approach being used to supply chamber gasses to fixed target experiments at Fermilab. It describes the engineering design features, system safety, system documentation and performance results. Gas mixtures provide the medium for electron detection in proportional and drift chambers. Usually a mixture of a noble gas and a polyatomic quenching gas is used. Sometimes a small amount of electronegative gas is added as well. The mixture required is a function of the specific chamber design, including working voltage, gain requirements, high rate capability, aging and others. For the 1995 fixed target run all the experiments requested once through gas systems. We obtained a summary of problems from the 1990 fixed target run and made a summary of the operations logbook entries from the 1991 run. These summaries primarily include problems involving flammable gas alarms, but also include incidents where Operations was involved or informed. Usually contamination issues were dealt with by the experimenters. The summaries are attached. We discussed past operational issues with the experimenters involved. There were numerous incidents of drift chamber failure where contaminated gas was suspect. However analyses of the gas at the time usually did not show any particular problems. This could have been because the analysis did not look for the troublesome component, the contaminant was concentrated in the gas over the liquid and vented before the sample was taken, or that contaminants were drawn into the chambers directly through leaks or sub-atmospheric pressures. After some study we were unable to determine specific causes of past contamination problems, although in argon-ethane systems the problems were due to the ethane only

  15. Targeting phenotypically tolerant Mycobacterium tuberculosis

    Science.gov (United States)

    Gold, Ben; Nathan, Carl

    2016-01-01

    While the immune system is credited with averting tuberculosis in billions of individuals exposed to Mycobacterium tuberculosis, the immune system is also culpable for tempering the ability of antibiotics to deliver swift and durable cure of disease. In individuals afflicted with tuberculosis, host immunity produces diverse microenvironmental niches that support suboptimal growth, or complete growth arrest, of M. tuberculosis. The physiological state of nonreplication in bacteria is associated with phenotypic drug tolerance. Many of these host microenvironments, when modeled in vitro by carbon starvation, complete nutrient starvation, stationary phase, acidic pH, reactive nitrogen intermediates, hypoxia, biofilms, and withholding streptomycin from the streptomycin-addicted strain SS18b, render M. tuberculosis profoundly tolerant to many of the antibiotics that are given to tuberculosis patients in a clinical setting. Targeting nonreplicating persisters is anticipated to reduce the duration of antibiotic treatment and rate of post-treatment relapse. Some promising drugs to treat tuberculosis, such as rifampicin and bedaquiline, only kill nonreplicating M. tuberculosis in vitro at concentrations far greater than their minimal inhibitory concentrations against replicating bacilli. There is an urgent demand to identify which of the currently used antibiotics, and which of the molecules in academic and corporate screening collections, have potent bactericidal action on nonreplicating M. tuberculosis. With this goal, we review methods of high throughput screening to target nonreplicating M. tuberculosis and methods to progress candidate molecules. A classification based on structures and putative targets of molecules that have been reported to kill nonreplicating M. tuberculosis revealed a rich diversity in pharmacophores. However, few of these compounds were tested under conditions that would exclude the impact of adsorbed compound acting during the recovery phase of

  16. Theranostics Targeting Metastatic Breast Cancer

    Science.gov (United States)

    2017-10-01

    is ideal for optical imaging in vivo. In cell studies on a high-power fluorescent microscope we can see that the targeted dye 3 has a higher...theranostic. Currently we are scaling up the synthesis of this molecule, for photophysical measurements, cellular assays particularly light /dark...absorbs light optimally at a wavelength (around 500 nm) that is too short for efficient penetration of more than a few mm in tis- sue.43,44 To circumvent

  17. Targeted Advertising in Magazine Markets

    OpenAIRE

    Ambarish Chandra; Ulrich Kaiser

    2010-01-01

    We examine the scope and value of targeted advertising in the magazine industry. We use data on reader characteristics at individual media, in contrast to previous work that has needed to infer this information from aggregate data. Our results show a strong relationship between subscriber characteristics and advertising prices. Advertisers clearly value more homogenous groups of readers, measured according to income, gender and age. Our results explain recent trends of declining advertising e...

  18. Peptide-targeted polymer cancerostatics

    Czech Academy of Sciences Publication Activity Database

    Böhmová, Eliška; Pola, Robert

    2016-01-01

    Roč. 65, Suppl. 2 (2016), S153-S164 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : HPMA copolymers * tumor targeting * peptides Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.461, year: 2016 http://www.biomed.cas.cz/physiolres/pdf/65%20Suppl%202/65_S153.pdf

  19. Medium size polarised deuteron target

    Energy Technology Data Exchange (ETDEWEB)

    Kiselev, Yu.F.; Polyakov, V.V.; Kovalev, A.I.; Bunyatova, E.I.; Borisov, N.S.; Trautman, V.Yu.; Werner, K.; Kozlenko, N.G.

    1984-03-01

    A frozen polarised deuteron target based on ethanediol with a high percentage of deuterium is described. Analytical expressions for the NMR spectrum correction for non-linearity of the Q-meter are obtained and a method for the determination of the asymmetry is developed. Experimental results confirm the thermal mixing theory for deuteron and proton spin systems with a dipole-dipole reservoir of electron spins.

  20. CATAMARAN targeted at innovative radiopharmacy

    Energy Technology Data Exchange (ETDEWEB)

    Impens, N.; Aerts, A.

    2010-07-01

    In cancer therapy there is a great need for specific treatments: therapies that kill cancer cells selectively without affecting the healthy cells. In the CATAMARAN project (Cancer Targeting Molecules Attached to Radionuclides) SCK-CEN develops, in a preclinical trial, products that deliver the right radiation doses at the right place in the human body. With the new multidisciplinary expertise that has been built up in the project, SCK-CEN is contributing to new medical applications of radiation.

  1. CATAMARAN targeted at innovative radiopharmacy

    International Nuclear Information System (INIS)

    Impens, N.; Aerts, A.

    2010-01-01

    In cancer therapy there is a great need for specific treatments: therapies that kill cancer cells selectively without affecting the healthy cells. In the CATAMARAN project (Cancer Targeting Molecules Attached to Radionuclides) SCK-CEN develops, in a preclinical trial, products that deliver the right radiation doses at the right place in the human body. With the new multidisciplinary expertise that has been built up in the project, SCK-CEN is contributing to new medical applications of radiation.

  2. Fixed Target Collisions at STAR

    Energy Technology Data Exchange (ETDEWEB)

    Meehan, Kathryn C.

    2016-12-15

    The RHIC Beam Energy Scan (BES) program was proposed to look for the turn-off of signatures of the quark gluon plasma (QGP), search for a possible QCD critical point, and study the nature of the phase transition between hadronic and partonic matter. Previous results have been used to claim that the onset of deconfinement occurs at a center-of-mass energy of 7 GeV. Data from lower energies are needed to test if this onset occurs. The goal of the STAR Fixed-Target Program is to extend the collision energy range in BES II to energies that are likely below the onset of deconfinement. Currently, STAR has inserted a gold target into the beam pipe and conducted test runs at center-of-mass energies of 3.9 and 4.5 GeV. Tests have been done with both Au and Al beams. First physics results from a Coulomb potential analysis of Au + Au fixed-target collisions are presented and are found to be consistent with results from previous experiments. Furthermore, the Coulomb potential, which is sensitive to the Z of the projectile and degree of baryonic stopping, will be compared to published results from the AGS.

  3. Therapeutic targets in liver fibrosis.

    Science.gov (United States)

    Fallowfield, Jonathan A

    2011-05-01

    Detailed analysis of the cellular and molecular mechanisms that mediate liver fibrosis has provided a framework for therapeutic approaches to prevent, slow down, or even reverse fibrosis and cirrhosis. A pivotal event in the development of liver fibrosis is the activation of quiescent hepatic stellate cells (HSCs) to scar-forming myofibroblast-like cells. Consequently, HSCs and the factors that regulate HSC activation, proliferation, and function represent important antifibrotic targets. Drugs currently licensed in the US and Europe for other indications target HSC-related components of the fibrotic cascade. Their deployment in the near future looks likely. Ultimately, treatment strategies for liver fibrosis may vary on an individual basis according to etiology, risk of fibrosis progression, and the prevailing pathogenic milieu, meaning that a multiagent approach could be required. The field continues to develop rapidly and starts to identify exciting potential targets in proof-of-concept preclinical studies. Despite this, no antifibrotics are currently licensed for use in humans. With epidemiological predictions for the future prevalence of viral, obesity-related, and alcohol-related cirrhosis painting an increasingly gloomy picture, and a shortfall in donors for liver transplantation, the clinical urgency for new therapies is high. There is growing interest from stakeholders keen to exploit the market potential for antifibrotics. However, the design of future trials for agents in the developmental pipeline will depend on strategies that enable equal patient stratification, techniques to reliably monitor changes in fibrosis over time, and the definition of clinically meaningful end points.

  4. Fixed-Target Electron Accelerators

    International Nuclear Information System (INIS)

    Brooks, William K.

    2001-01-01

    A tremendous amount of scientific insight has been garnered over the past half-century by using particle accelerators to study physical systems of sub-atomic dimensions. These giant instruments begin with particles at rest, then greatly increase their energy of motion, forming a narrow trajectory or beam of particles. In fixed-target accelerators, the particle beam impacts upon a stationary sample or target which contains or produces the sub-atomic system being studied. This is in distinction to colliders, where two beams are produced and are steered into each other so that their constituent particles can collide. The acceleration process always relies on the particle being accelerated having an electric charge; however, both the details of producing the beam and the classes of scientific investigations possible vary widely with the specific type of particle being accelerated. This article discusses fixed-target accelerators which produce beams of electrons, the lightest charged particle. As detailed in the report, the beam energy has a close connection with the size of the physical system studied. Here a useful unit of energy is a GeV, i.e., a giga electron-volt. (ne GeV, the energy an electron would have if accelerated through a billion volts, is equal to 1.6 x 10 -10 joules.) To study systems on a distance scale much smaller than an atomic nucleus requires beam energies ranging from a few GeV up to hundreds of GeV and more

  5. Targeting the Brain with Nanomedicine.

    Science.gov (United States)

    Rueda, Felix; Cruz, Luis J

    2017-01-01

    Herein, we review innovative nanomedicine-based approaches for treating, preventing and diagnosing neurodegenerative diseases. We focus on nanoscale systems such as polymeric nanoparticles (NPs), liposomes, micelles and other vehicles (e.g. dendrimers, nanogels, nanoemulsions and nanosuspensions) for targeted delivery of bioactive molecules to the brain. To ensure maximum selectivity for optimal therapeutic or diagnostic results, researchers must employ delivery systems that are non-toxic, biodegradable and biocompatible. This entails: (i) use of "safe" materials, such as polymers or lipids; (ii) targeting to the brain and, specifically, to the desired active site within the brain; (iii) controlled release of the loaded agent; and (iv) use of agents that, once released into the brain, will exhibit the desired pharmacologic activity. Here, we explore the design and preclinical use of representative delivery systems that have been proposed to date. We then analyze the principal challenges that have delayed clinical application of these and other approaches. Lastly, we look at future developments in this area, addressing the needs for increased penetration of the blood brain barrier (BBB), enhanced targeting of specific brain sites, improved therapeutic efficacy and lower neurotoxicity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Development of Helios target insertion mechanism

    International Nuclear Information System (INIS)

    Day, R.D.; Cummings, C.E.; Tucker, H.E.

    1979-01-01

    A system for precisely positioning a DT-filled target in the Helios target vacuum chamber is described. The target insertion mechanism (TIM), which is designed to insert either a target or a surrogate sphere into the vacuum chamber through an airlock to prevent loss of vacuum, is discussed in detail and its performance is evaluated

  7. Identification of Small Ligands Targeting Breast Cancer by In Vivo Screening of Peptide Libraries in Breast Cancer Patients

    Science.gov (United States)

    2000-09-01

    association between hyposplenism and immunodeficiency in patients with coeliac disease . J British Soc Gastroenterol 16:538-542, 1975 73. Hamblin TJ, Jones...enlargement, or lymphoproliferative disease , beginning around 8 weeks of age. Because their lymph nodes become markedly enlarged (tumors) these mice were...34Breast Disease . LIMITED DISTRIBUTION 1997 83 Crews KA Kuhn JA, Fisher TL, Grant MD, Peters GN, Knox SM, Kraq DN. Sentinel node biopsy for breast

  8. Targeted Therapy in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Murray Baron

    2016-10-01

    Full Text Available Targeted therapies use an understanding of the pathophysiology of a disease in an individual patient. Although targeted therapy for systemic sclerosis (SSc, scleroderma has not yet reached the level of patient-specific treatments, recent developments in the understanding of the global pathophysiology of the disease have led to new treatments based on the cells and pathways that have been shown to be involved in the disease pathogenesis. The presence of a B cell signature in skin biopsies has led to the trial of rituximab, an anti-CD20 antibody, in SSc. The well-known properties of transforming growth factor (TGF-β in promoting collagen synthesis and secretion has led to a small trial of fresolimumab, a human IgG4 monoclonal antibody capable of neutralizing TGF-β. Evidence supporting important roles for interleukin-6 in the pathogenesis of SSc have led to a large trial of tocilizumab in SSc. Soluble guanylate cyclase (sGC is an enzyme that catalyzes the production of cyclic guanosine monophosphate (cGMP upon binding of nitric oxide (NO to the sGC molecule. Processes such as cell growth and proliferation are regulated by cGMP. Evidence that sGC may play a role in SSc has led to a trial of riociguat, a molecule that sensitizes sGC to endogenous NO. Tyrosine kinases (TKs are involved in a wide variety of physiologic and pathological processes including vascular remodeling and fibrogenesis such as occurs in SSc. This has led to a trial of nintedanib, a next-generation tyrosine-kinase (TK inhibitor which targets multiple TKs, in SSc.

  9. Target cells in radiation pneumopathy

    International Nuclear Information System (INIS)

    Trott, Klaus Ruediger; Herrmann, Thomas; Kasper, Michael

    2004-01-01

    Radiation pneumopathy is the reaction of the organ lung to radiation effects in various target cells. It starts as an exudative inflammation, with the clinical picture of interstitial pneumonia 6-12 weeks after irradiation, and proceeds to a productive chronic inflammation lasting several months and terminating, as other chronic inflammations do, in scar formation, called lung fibrosis. Lung fibrosis is the common end point after lung damage from a wide range of damaging agents. The pathogenetic process leading to the signs and symptoms of radiation pneumopathy is an integrated response of the complex organization of lung tissue. Clinical and pathologic data in patients do not support the hypothesis that the early inflammatory phase of radiation 'pneumonitis' and late 'radiation fibrosis' are independent pathogenetic processes in the same way as acute radiodermatitis and subcutaneous fibrosis are separate pathologic entities. The target cell population that initiates the pathogenetic process in the lung is not known, and it has been suggested that no single identifiable target exists. The entire process is the result of complex functional alterations in endothelial cells, pneumocytes, macrophages, and other resident and transient cells. No evidence has been found for a role of stem cell sterilization, for impaired transit cell proliferation, or for hypoplasia, which is the hallmark of other acute inflammatory normal tissue damage (i.e., in the mucosa). The radiobiologic concepts developed in cellular radiobiology are not adequate for the quantitative analysis of radiation pneumopathy. A new analytical framework based on structurally defined intercellular interaction by signaling molecules and their activation needs to be developed. This would not be only an abstract radiobiologic paradigm but would be the key to the development of potential therapeutic interventions in irradiated patients

  10. Hospitals: Soft Target for Terrorism?

    Science.gov (United States)

    De Cauwer, Harald; Somville, Francis; Sabbe, Marc; Mortelmans, Luc J

    2017-02-01

    In recent years, the world has been rocked repeatedly by terrorist attacks. Arguably, the most remarkable were: the series of four coordinated suicide plane attacks on September 11, 2001 on buildings in New York, Virginia, and Pennsylvania, USA; and the recent series of two coordinated attacks in Brussels (Belgium), on March 22, 2016, involving two bombings at the departure hall of Brussels International Airport and a bombing at Maalbeek Metro Station located near the European Commission headquarters in the center of Brussels. This statement paper deals with different aspects of hospital policy and disaster response planning that interface with terrorism. Research shows that the availability of necessary equipment and facilities (eg, personal protective clothing, decontamination rooms, antidotes, and anti-viral drugs) in hospitals clearly is insufficient. Emergency teams are insufficiently prepared: adequate and repetitive training remain necessary. Unfortunately, there are many examples of health care workers and physicians or hospitals being targeted in both political or religious conflicts and wars. Many health workers were kidnapped and/or killed by insurgents of various ideology. Attacks on hospitals also could cause long-term effects: hospital units could be unavailable for a long time and replacing staff could take several months, further compounding hospital operations. Both physical and psychological (eg, posttraumatic stress disorder [PTSD]) after-effects of a terrorist attack can be detrimental to health care services. On the other hand, physicians and other hospital employees have shown to be involved in terrorism. As data show that some offenders had a previous history with the location of the terror incident, the possibility of hospitals or other health care services being targeted by insiders is discussed. The purpose of this report was to consider how past terrorist incidents can inform current hospital preparedness and disaster response planning

  11. Introduction to radar target recognition

    CERN Document Server

    Tait, P

    2006-01-01

    This new text provides an overview of the radar target recognition process and covers the key techniques being developed for operational systems. It is based on the fundamental scientific principles of high resolution radar, and explains how the techniques can be used in real systems, taking into account the characteristics of practical radar system designs and component limitations. It also addresses operational aspects, such as how high resolution modes would fit in with other functions such as detection and tracking. Mathematics is kept to a minimum and the complex techniques and issues are

  12. Nova target chamber decontamination study

    International Nuclear Information System (INIS)

    1979-05-01

    An engineering study was performed to determine the most effective method for decontamination of the Nova target chamber. Manual and remote decontamination methods currently being used were surveyed. In addition, a concept that may not require in-situ decontamination was investigated. Based on the presently available information concerning material and system compatibility and particle penetration, it is recommended that a system of removable aluminum shields be considered. It is also recommended that a series of tests be performed to more precisely determine the vacuum compatibility and penetrability of other materials discussed in this report

  13. Acoustic target models and phenomenology

    Science.gov (United States)

    Neiswander, Paul R.; Kaiser, Stephen G.

    2000-07-01

    Ground-based and airborne acoustic systems often target vehicles that are powered by reciprocating internal combustion engines. Typically the far-field acoustic spectra of these vehicles are dominated by a few narrow spectral lines that are harmonically related. The dominant harmonics change with engine speed and also with emission angle. This paper describes a simple model that recreates some of this variability. The model breaks the far-field signature into two components: the generation of a train of pressure pulses at each exhaust outlet, and the radiation of sound pressures from the outlet(s) to the far field. Predictions are compared with field test data for two ground vehicles.

  14. Biomimetic nanoparticles for inflammation targeting

    Directory of Open Access Journals (Sweden)

    Kai Jin

    2018-01-01

    Full Text Available There have been many recent exciting developments in biomimetic nanoparticles for biomedical applications. Inflammation, a protective response involving immune cells, blood vessels, and molecular mediators directed against harmful stimuli, is closely associated with many human diseases. As a result, biomimetic nanoparticles mimicking immune cells can help achieve molecular imaging and precise drug delivery to these inflammatory sites. This review is focused on inflammation-targeting biomimetic nanoparticles and will provide an in-depth look at the design of these nanoparticles to maximize their benefits for disease diagnosis and treatment.

  15. LIFE Target Fabrication Research Plan Sept 2008

    Energy Technology Data Exchange (ETDEWEB)

    Miles, R; Biener, J; Kucheyev, S; Montesanti, R; Satcher, J; Spadaccini, C; Rose, K; Wang, M; Hamza, A; Alexander, N; Brown, L; Hund, J; Petzoldt, R; Sweet, W; Goodin, D

    2008-11-10

    The target-system for the baseline LIFE fast-ignition target was analyzed to establish a preliminary estimate for the costs and complexities involved in demonstrating the technologies needed to build a prototype LIFE plant. The baseline fast-ignition target upon which this analysis was developed is shown in Figure 1.0-1 below. The LIFE target-system incorporates requirements for low-cost, high throughput manufacture, high-speed, high accuracy injection of the target into the chamber, production of sufficient energy from implosion and recovery and recycle of the imploded target material residue. None of these functions has been demonstrated to date. Existing target fabrication techniques which lead to current 'hot spot' target costs of {approx}$100,000 per target and at a production rate of 2/day are unacceptable for the LIFE program. Fabrication techniques normally used for low-cost, low accuracy consumer products such as toys must be adapted to the high-accuracy LIFE target. This will be challenge. A research program resulting is the demonstration of the target-cycle technologies needed for a prototype LIFE reactor is expected to cost {approx}$51M over the course of 5 years. The effort will result in targets which will cost an estimated $0.23/target at a rep-rate of 20 Hz or about 1.73M targets/day.

  16. Mammalian target of rapamycin as a therapeutic target in osteoporosis.

    Science.gov (United States)

    Shen, Gengyang; Ren, Hui; Qiu, Ting; Zhang, Zhida; Zhao, Wenhua; Yu, Xiang; Huang, Jinjing; Tang, Jingjing; Liang, De; Yao, Zhensong; Yang, Zhidong; Jiang, Xiaobing

    2018-05-01

    The mechanistic target of rapamycin (mTOR) plays a key role in sensing and integrating large amounts of environmental cues to regulate organismal growth, homeostasis, and many major cellular processes. Recently, mounting evidences highlight its roles in regulating bone homeostasis, which sheds light on the pathogenesis of osteoporosis. The activation/inhibition of mTOR signaling is reported to positively/negatively regulate bone marrow mesenchymal stem cells (BMSCs)/osteoblasts-mediated bone formation, adipogenic differentiation, osteocytes homeostasis, and osteoclasts-mediated bone resorption, which result in the changes of bone homeostasis, thereby resulting in or protect against osteoporosis. Given the likely importance of mTOR signaling in the pathogenesis of osteoporosis, here we discuss the detailed mechanisms in mTOR machinery and its association with osteoporosis therapy. © 2017 Wiley Periodicals, Inc.

  17. 26 CFR 1.430(d)-1 - Determination of target normal cost and funding target.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Determination of target normal cost and funding... of target normal cost and funding target. (a) In general—(1) Overview. This section sets forth rules for determining a plan's target normal cost and funding target under sections 430(b) and 430(d...

  18. Kidney–targeted drug delivery systems

    Directory of Open Access Journals (Sweden)

    Peng Zhou

    2014-02-01

    Full Text Available Kidney-targeted drug delivery systems represent a promising technology to improve drug efficacy and safety in the treatment of renal diseases. In this review, we summarize the strategies that have been employed to develop kidney-targeted drug delivery systems. We also describe how macromolecular carriers and prodrugs play crucial roles in targeting drugs to particular target cells in the kidney. New technologies render it possible to create renal targeting conjugates and other delivery systems including nanoparticles and liposomes present promising strategies to achieve the goal of targeting drugs to the kidney.

  19. Preliminary results of accelerator targets cooling

    International Nuclear Information System (INIS)

    Silverman, I.; Nagler, A.; Kijel, D.

    2004-01-01

    Accelerator targets, both for radioisotope production and for high neutron flux sources generate very high thermal power in the target material, which absorbs the particles beam. Generally, the geometric size of the targets is very small and the power density is high. The design of these targets requires dealing with very high heat fluxes and very efficient heat removal techniques in order to preserve the integrity of the target. Normal heat fluxes from these targets are in the order of 1 kW/cm 2 and may reach levels of an order of magnitude higher

  20. QUIKVIS- CELESTIAL TARGET AVAILABILITY INFORMATION

    Science.gov (United States)

    Petruzzo, C.

    1994-01-01

    QUIKVIS computes the times during an Earth orbit when geometric requirements are satisfied for observing celestial objects. The observed objects may be fixed (stars, etc.) or moving (sun, moon, planets). QUIKVIS is useful for preflight analysis by those needing information on the availability of celestial objects to be observed. Two types of analyses are performed by QUIKVIS. One is used when specific objects are known, the other when targets are unknown and potentially useful regions of the sky must be identified. The results are useful in selecting candidate targets, examining the effects of observation requirements, and doing gross assessments of the effects of the orbit's right ascension of the ascending node (RAAN). The results are not appropriate when high accuracy is needed (e.g. for scheduling actual mission operations). The observation duration is calculated as a function of date, orbit node, and geometric requirements. The orbit right ascension of the ascending node can be varied to account for the effects of an uncertain launch time of day. The orbit semimajor axis and inclination are constant throughout the run. A circular orbit is assumed, but a simple program modification will allow eccentric orbits. The geometric requirements that can be processed are: 1) minimum separation angle between the line of sight to the object and the earth's horizon; 2) minimum separation angle between the line of sight to the object and the spacecraft velocity vector; 3) maximum separation angle between the line of sight to the object and the zenith direction; and 4) presence of the spacecraft in the earth's shadow. The user must supply a date or date range, the spacecraft orbit and inclination, up to 700 observation targets, and any geometric requirements to be met. The primary output is the time per orbit that conditions are satisfied, with options for sky survey maps, time since a user-specified orbit event, and bar graphs illustrating overlapping requirements. The

  1. Bioengineering Strategies for Designing Targeted Cancer Therapies

    Science.gov (United States)

    Wen, Xuejun

    2014-01-01

    The goals of bioengineering strategies for targeted cancer therapies are (1) to deliver a high dose of an anticancer drug directly to a cancer tumor, (2) to enhance drug uptake by malignant cells, and (3) to minimize drug uptake by nonmalignant cells. Effective cancer-targeting therapies will require both passive- and active targeting strategies and a thorough understanding of physiologic barriers to targeted drug delivery. Designing a targeted therapy includes the selection and optimization of a nanoparticle delivery vehicle for passive accumulation in tumors, a targeting moiety for active receptor-mediated uptake, and stimuli-responsive polymers for control of drug release. The future direction of cancer targeting is a combinatorial approach, in which targeting therapies are designed to use multiple targeting strategies. The combinatorial approach will enable combination therapy for delivery of multiple drugs and dual ligand targeting to improve targeting specificity. Targeted cancer treatments in development and the new combinatorial approaches show promise for improving targeted anticancer drug delivery and improving treatment outcomes. PMID:23768509

  2. Dendritic Cell-Targeted Vaccines

    Science.gov (United States)

    Cohn, Lillian; Delamarre, Lélia

    2014-01-01

    Despite significant effort, the development of effective vaccines inducing strong and durable T-cell responses against intracellular pathogens and cancer cells has remained a challenge. The initiation of effector CD8+ T-cell responses requires the presentation of peptides derived from internalized antigen on class I major histocompatibility complex molecules by dendritic cells (DCs) in a process called cross-presentation. A current strategy to enhance the effectiveness of vaccination is to deliver antigens directly to DCs. This is done via selective targeting of antigen using monoclonal antibodies directed against endocytic receptors on the surface of the DCs. In this review, we will discuss considerations relevant to the design of such vaccines: the existence of DC subsets with specialized functions, the impact of the antigen intracellular trafficking on cross-presentation, and the influence of maturation signals received by DCs on the outcome of the immune response. PMID:24910635

  3. Targeting α-synuclein oligomers

    DEFF Research Database (Denmark)

    van Diggelen, Femke

    Parkinson’s Disease (PD) is a complex disease, characterised by degeneration of neocortical, limbic and nigrostriatal neurons. It is unknown what initiates neurodegeneration, but soluble oligomers of the protein α-synuclein (αSn) seem to be particularly toxic, compared to insoluble fibrils...... unique characteristics, e.g. they were recognized by different conformational antibodies and DHA–αSOs also formed a second elongated species in addition to the dominant spherical species. Although further functional testing is needed, this suggests that each species has its own distinct toxic mechanism......+/K+ ATPase, V-type ATPase, VDAC, CaMKII and Rab-3A. The identification of these targets is a first step towards unravelling the toxic pathways which are activated upon synaptic binding of extracellularly added αSOs, and hopefully will contribute to the discovery of new disease modifying compounds, which can...

  4. Nuclear spin polarization of targets

    International Nuclear Information System (INIS)

    Happer, W.

    1990-01-01

    Lasers can be used to produce milligrams to grams of noble gas nuclei with spin polarizations in excess of 50%. These quantities are sufficient to be very useful targets in nuclear physics experiments. Alkali-metal atoms are used to capture the angular momentum of circularly polarized laser photons, and the alkali-metal atoms transfer their angular momentum to noble gas atoms in binary or three-body collisions. Non-radiative collisions between the excited alkali atoms and molecular quenching gases are essential to avoid radiation trapping. The spin exchange can involve gas-phase van der Waals molecules, consisting of a noble gas atom and an alkali metal atom. Surface chemistry is also of great importance in determining the wall-induced relaxation rates of the noble gases

  5. BAD: a good therapeutic target?

    International Nuclear Information System (INIS)

    Motoyama, Andrea B; Hynes, Nancy E

    2003-01-01

    The major goal in cancer treatment is the eradication of tumor cells. Under stress conditions, normal cells undergo apoptosis; this property is fortunately conserved in some tumor cells, leading to their death as a result of chemotherapeutic and/or radiation-induced stress. Many malignant cells, however, have developed ways to subvert apoptosis, a characteristic that constitutes a major clinical problem. Gilmore et al. recently described the ability of ZD1839, a small-molecule inhibitor of the epidermal growth factor receptor (EGFR), to induce apoptosis of mammary cells that are dependent upon growth factors for survival. Furthermore, they showed that the major effector of the EGFR-targeted therapy is BAD, a widely expressed BCL-2 family member. These results are promising in light of the role of the EGFR in breast cancer development

  6. Gene Therapy Targeting HIV Entry

    Directory of Open Access Journals (Sweden)

    Chuka Didigu

    2014-03-01

    Full Text Available Despite the unquestionable success of antiretroviral therapy (ART in the treatment of HIV infection, the cost, need for daily adherence, and HIV-associated morbidities that persist despite ART all underscore the need to develop a cure for HIV. The cure achieved following an allogeneic hematopoietic stem cell transplant (HSCT using HIV-resistant cells, and more recently, the report of short-term but sustained, ART-free control of HIV replication following allogeneic HSCT, using HIV susceptible cells, have served to both reignite interest in HIV cure research, and suggest potential mechanisms for a cure. In this review, we highlight some of the obstacles facing HIV cure research today, and explore the roles of gene therapy targeting HIV entry, and allogeneic stem cell transplantation in the development of strategies to cure HIV infection.

  7. TARGET 2 and Settlement Finality

    Directory of Open Access Journals (Sweden)

    Ivan MANGATCHEV

    2011-03-01

    Full Text Available This article examines how TARGET 2 as system implements the idea of settlement finality regulated by Directive 98/26 EC of the European parliament and of the Council of 19 May 1998 on settlement finality in payment and securities settlement systems (Settlement Finality Directive and Directive 2009/44/EC of the European parliament and of the Council of 6 May 2009 amending Directive 98/26/EC on settlement finality in payment and securities settlement systems and Directive 2002/47/EC on financial collateral arrangements as regards linked systems and credit claims (Directive 2009/44/EC. As the title of the arti and finality of the settlement in this system.

  8. Therapeutic target for protozoal diseases

    Science.gov (United States)

    Rathore, Dharmendar [Blacksburg, VA; Jani, Dewal [Blacksburg, VA; Nagarkatti, Rana [Blacksburg, VA

    2008-10-21

    A novel Fasciclin Related Adhesive Protein (FRAP) from Plasmodium and related parasites is provided as a target for therapeutic intervention in diseases caused by the parasites. FRAP has been shown to play a critical role in adhesion to, or invasion into, host cells by the parasite. Furthermore, FRAP catalyzes the neutralization of heme by the parasite, by promoting its polymerization into hemozoin. This invention provides methods and compositions for therapies based on the administration of protein, DNA or cell-based vaccines and/or antibodies based on FRAP, or antigenic epitopes of FRAP, either alone or in combination with other parasite antigens. Methods for the development of compounds that inhibit the catalytic activity of FRAP, and diagnostic and laboratory methods utilizing FRAP are also provided.

  9. Electrostatic mask for active targets

    International Nuclear Information System (INIS)

    Pancin, J; Gangnant, P; Libin, J-F; Raabe, R; Roger, T; Roussel-Chomaz, P; Gibelin, J; Goth, M

    2012-01-01

    Active gas targets have been used in nuclear physics since 30 years. They are promising systems in view of the new exotic beams soon available at facilities like SPIRAL2 or FAIR, but the system can still be improved. One of the main limitation is the dynamic range in energy deposition. The energy deposited per unit length can be 3 decades higher for the beam than for the light reaction products and the risk to saturate the electronics or that the detector spark are not negligible. A simple solution using a wire plane to mask partially the beam is presented here. Some simulation has been realized and some experimental results are shown confirming the feasibility of this wire tunable mask. The mask can be used from full transparency to full opacity without degrading neither the drift electric field of the chamber nor the performances of detection of the beam or the light products.

  10. Moringa oleifera Lam: Targeting Chemoprevention.

    Science.gov (United States)

    Karim, Nurul Ashikin Abd; Ibrahim, Muhammad Din; Kntayya, Saie Brindha; Rukayadi, Yaya; Hamid, Hazrulizawati Abd; Razis, Ahmad Faizal Abdull

    2016-01-01

    Moringa oleifera Lam, family Moringaceae, is a perennial plant which is called various names, but is locally known in Malaysia as "murungai" or "kelor". Glucomoringin, a glucosinolate with from M. oleifera is a major secondary metabolite compound. The seeds and leaves of the plant are reported to have the highest amount of glucosinolates. M. oleifera is well known for its many uses health and benefits. It is claimed to have nutritional, medicinal and chemopreventive potentials. Chemopreventive effects of M. oleifera are expected due to the existence of glucosinolate which it is reported to have the ability to induce apoptosis in anticancer studies. Furthermore, chemopreventive value of M. oleifera has been demonstrated in studies utilizing its leaf extract to inhibit the growth of human cancer cell lines. This review highlights the advantages of M. oleifera targeting chemoprevention where glucosinolates could help to slow the process of carcinogenesis through several molecular targets. It is also includes inhibition of carcinogen activation and induction of carcinogen detoxification, anti-inflammatory, anti-tumor cell proliferation, induction of apoptosis and inhibition of tumor angiogenesis. Finally, for synergistic effects of M. oleifera with other drugs and safety, essential for chemoprevention, it is important that it safe to be consumed by human body and works well. Although there is promising evidence about M. oleifera in chemoprevention, extensive research needs to be done due to the expected rise of cancer in coming years and to gain more information about the mechanisms involved in M. oleifera influence, which could be a good source to inhibit several major mechanisms involved in cancer development.

  11. Polarized few-nucleon targets: new developments

    International Nuclear Information System (INIS)

    Haeusser, O.

    1992-09-01

    We discuss recent improvements in producing polarized few-nucleon targets for nuclear and particle physics experiments. The emphasis is on progress with polarized gas targets intended for experiments at electron and proton storage rings. (author) 54 refs., 1 tab

  12. Counter-Leadership Targeting and Conflict Termination

    National Research Council Canada - National Science Library

    Taylor, Bradly

    1999-01-01

    .... Can the leader be found? And, is it legal and ethical to attack the leader? Analysis rarely has been conducted to determine whether the targeted organization is vulnerable to Counter Leadership Targeting (CLT...

  13. Targets and processes for fabricating same

    Science.gov (United States)

    Adams, Jesse D; Malekos, Steven; Le Galloudec, Nathalie; Korgan, Grant; Cowan, Thomas; Sentoku, Yasuhiko

    2016-05-17

    In particular embodiments, the present disclosure provides targets including a metal layer and defining a hollow inner surface. The hollow inner surface has an internal apex. The distance between at least two opposing points of the internal apex is less than about 15 .mu.m. In particular examples, the distance is less than about 1 .mu.m. Particular implementations of the targets are free standing. The targets have a number of disclosed shaped, including cones, pyramids, hemispheres, and capped structures. The present disclosure also provides arrays of such targets. Also provided are methods of forming targets, such as the disclosed targets, using lithographic techniques, such as photolithographic techniques. In particular examples, a target mold is formed from a silicon wafer and then one or more sides of the mold are coated with a target material, such as one or more metals.

  14. Ground Moving Target Engagement by Cooperative UAVs

    National Research Council Canada - National Science Library

    Schumacher, Corey

    2005-01-01

    .... MultiUAV has been used to simulate a Cooperative Moving Target Engagement (CMTE) scenario, with a team of UAVs acting as a sensor and communication network to cooperatively track and attack moving ground targets...

  15. On the large COMPASS polarized deuteron target

    CERN Document Server

    Finger, M; Baum, G; Doshita, N; Finger, M Jr; Gautheron, F; Goertz, St; Hasegawa, T; Heckmann, J; Hess, Ch; Horikawa, N; Ishimoto, S; Iwata, T; Kisselev, Y; Koivuniemi, J; Kondo, K; Le Goff, J-M; Magnon, A; Marchand, C; Matsuda, T; Meyer, W; Reicherz, G; Srnka, A

    2006-01-01

    The spin structure of the nucleons is investigated in deep inelastic scattering of a polarized muon beam and a polarized nucleon target in the COMPASS experiment at CERN since 2001. To achieve high luminosities a large solid polarized target is used. The COMPASS polarized target consists of a high cooling power $^{3}$He/$^{4}$He dilution refrigerator capable to maintain working temperature of the target material at about 50mK, a superconducting solenoid and dipole magnet system for longitudinal and transversal magnetic field on the target material, respectively, target cells containing polarizable material, microwave cavities and high power microwave radiation systems for dynamic nuclear polarization and the nuclear magnetic resonance system for nuclear spin polarization measurements. During 2001–2004 experiments superconducting magnet system with opening angle $\\pm$69 mrad, polarized target holder with two target cells and corresponding microwave and NMR systems have been used. For the data taking from 200...

  16. Targets development at Sandia National Laboratories

    International Nuclear Information System (INIS)

    Smith, M.L.; Hebron, D.; Derzon, M.; Olson, R.; Alberts, T.

    1997-01-01

    For many years, Sandia National Laboratories under contract to the Department of Energy has produced targets designed to understand complex ion beam and z-pinch plasma physics. This poster focuses on the features of target designs that make them suitable for Z-pinch plasma physics applications. Precision diagnostic targets will prove critical in understanding the plasma physics model needed for future ion beam and z-pinch design. Targets are designed to meet specific physics needs; in this case the authors have fabricated targets to maximize information about the end-on versus side-on x-ray emission and z-pinch hohlraum development. In this poster, they describe the fabrication and characterization techniques. They include discussion of current targets under development as well as target fabrication capabilities. Advanced target designs are fabricated by Sandia National Laboratories in cooperation with General Atomics of San Diego, CA and W.J. Schafer Associates, Inc. of Livermore, CA

  17. Linking Target Selection to Political Objectives

    National Research Council Canada - National Science Library

    Tew, Scott

    2002-01-01

    ... up for effect, Our goal is to find and effect the targets that will ultimately lead to attainment of our political objectives Yet, how do we logically link a target to the desired political objectives...

  18. Progress on the SNS target station

    International Nuclear Information System (INIS)

    Carne, A.

    1983-01-01

    This review gives progress and modifications covering the last eighteen months, under the five broad areas of target, target assembly, control system, bulk shield and remote handling. Finally a discussion of additional facilities to the SNS is presented

  19. Cooperative tumour cell membrane targeted phototherapy

    Science.gov (United States)

    Kim, Heegon; Lee, Junsung; Oh, Chanhee; Park, Ji-Ho

    2017-06-01

    The targeted delivery of therapeutics using antibodies or nanomaterials has improved the precision and safety of cancer therapy. However, the paucity and heterogeneity of identified molecular targets within tumours have resulted in poor and uneven distribution of targeted agents, thus compromising treatment outcomes. Here, we construct a cooperative targeting system in which synthetic and biological nanocomponents participate together in the tumour cell membrane-selective localization of synthetic receptor-lipid conjugates (SR-lipids) to amplify the subsequent targeting of therapeutics. The SR-lipids are first delivered selectively to tumour cell membranes in the perivascular region using fusogenic liposomes. By hitchhiking with extracellular vesicles secreted by the cells, the SR-lipids are transferred to neighbouring cells and further spread throughout the tumour tissues where the molecular targets are limited. We show that this tumour cell membrane-targeted delivery of SR-lipids leads to uniform distribution and enhanced phototherapeutic efficacy of the targeted photosensitizer.

  20. Targeted Radionuclide Therapy of Human Tumors

    OpenAIRE

    Gudkov, Sergey V.; Shilyagina, Natalya Yu.; Vodeneev, Vladimir A.; Zvyagin, Andrei V.

    2015-01-01

    Targeted radionuclide therapy is one of the most intensively developing directions of nuclear medicine. Unlike conventional external beam therapy, the targeted radionuclide therapy causes less collateral damage to normal tissues and allows targeted drug delivery to a clinically diagnosed neoplastic malformations, as well as metastasized cells and cellular clusters, thus providing systemic therapy of cancer. The methods of targeted radionuclide therapy are based on the use of molecular carrier...

  1. Targeted integration of genes in Xenopus tropicalis

    DEFF Research Database (Denmark)

    Shi, Zhaoying; Tian, Dandan; Xin, Huhu

    2017-01-01

    With the successful establishment of both targeted gene disruption and integration methods in the true diploid frog Xenopus tropicalis, this excellent vertebrate genetic model now is making a unique contribution to modelling human diseases. Here, we summarize our efforts on establishing homologous...... recombination-mediated targeted integration in Xenopus tropicalis, the usefulness, and limitation of targeted integration via the homology-independent strategy, and future directions on how to further improve targeted gene integration in Xenopus tropicalis....

  2. Design of the FMIT lithium target

    International Nuclear Information System (INIS)

    Hassberger, J.A.; Annese, C.E.; Greenwell, R.K.; Ingham, J.G.; Miles, R.R.; Miller, W.C.

    1981-01-01

    Development of the liquid lithium target for the Fusion Materials Irradiation Test (FMIT) Facility is described. The target concept, major design goals and design requirements are presented. Progress made in the research and development areas leading to detailed design of the target is discussed. This progress, including experimental and analytic results, demonstrates that the FMIT target design is capable of meeting its major design goals and requirements

  3. Current progress in NIF target concepts

    International Nuclear Information System (INIS)

    Gobby, P.L.; Foreman, L.R.; Thoma, D.J.; Jacobson, L.A.; Hollis, R.V.; Barrera, J.; Mitchell, M.A.; Salazar, M.A.; Salzer, L.J.

    1996-01-01

    Target concepts for the National Ignition Facility (NIF) require progress in the art and science of target fabrication. Three distinct issues are addressed: beryllium fuel capsules, foam-buffered direct drive, and high-density gas-filled hohlraums. In all cases experiments on the existing Nova laser at LLNL are either in progress or planned for the near future to test the various concepts. Consequently, target fabrication must be able to deliver targets appropriate for each

  4. Target 5000: Target Capture Sequencing for Inherited Retinal Degenerations.

    Science.gov (United States)

    Dockery, Adrian; Stephenson, Kirk; Keegan, David; Wynne, Niamh; Silvestri, Giuliana; Humphries, Peter; Kenna, Paul F; Carrigan, Matthew; Farrar, G Jane

    2017-11-03

    There are an estimated 5000 people in Ireland who currently have an inherited retinal degeneration (IRD). It is the goal of this study, through genetic diagnosis, to better enable these 5000 individuals to obtain a clearer understanding of their condition and improved access to potentially applicable therapies. Here we show the current findings of a target capture next-generation sequencing study of over 750 patients from over 520 pedigrees currently situated in Ireland. We also demonstrate how processes can be implemented to retrospectively analyse patient datasets for the detection of structural variants in previously obtained sequencing reads. Pathogenic or likely pathogenic mutations were detected in 68% of pedigrees tested. We report nearly 30 novel mutations including three large structural variants. The population statistics related to our findings are presented by condition and credited to their respective candidate gene mutations. Rediagnosis rates of clinical phenotypes after genotyping are discussed. Possible causes of failure to detect a candidate mutation are evaluated. Future elements of this project, with a specific emphasis on structural variants and non-coding pathogenic variants, are expected to increase detection rates further and thereby produce an even more comprehensive representation of the genetic landscape of IRDs in Ireland.

  5. Target manifold formation using a quadratic SDF

    Science.gov (United States)

    Hester, Charles F.; Risko, Kelly K. D.

    2013-05-01

    Synthetic Discriminant Function (SDF) formulation of correlation filters provides constraints for forming target subspaces for a target set. In this paper we extend the SDF formulation to include quadratic constraints and use this solution to form nonlinear manifolds in the target space. The theory for forming these manifolds will be developed and demonstrated with data.

  6. Behavioral targeting: a European legal perspective

    NARCIS (Netherlands)

    Zuiderveen Borgesius, F.

    2013-01-01

    Behavioral targeting, or online profiling, is a hotly debated topic. Much of the collection of personal information on the Internet is related to behavioral targeting, although research suggests that most people don't want to receive behaviorally targeted advertising. The World Wide Web Consortium

  7. Targeted alpha therapy for cancer

    Energy Technology Data Exchange (ETDEWEB)

    Allen, Barry J [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Raja, Chand [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Rizvi, Syed [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Li Yong [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Tsui, Wendy [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Zhang, David [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Song, Emma [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Qu, C F [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Kearsley, John [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Graham, Peter [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Thompson, John [Sydney Melanoma Unit, Royal Prince Alfred Hospital, Camperdown 2050 NSW (Australia)

    2004-08-21

    Targeted alpha therapy (TAT) offers the potential to inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The practicality and efficacy of TAT is tested by in vitro and in vivo studies in melanoma, leukaemia, colorectal, breast and prostate cancers, and by a phase 1 trial of intralesional TAT for melanoma. The alpha-emitting radioisotope used is Bi-213, which is eluted from the Ac-225 generator and chelated to a cancer specific monoclonal antibody (mab) or protein (e.g. plasminogen activator inhibitor-2 PAI2) to form the alpha-conjugate (AC). Stable alpha-ACs have been produced which have been tested for specificity and cytotoxicity in vitro against melanoma (9.2.27 mab), leukaemia (WM60), colorectal (C30.6), breast (PAI2, herceptin), ovarian (PAI2, herceptin, C595), prostate (PAI2, J591) and pancreatic (PAI2, C595) cancers. Subcutaneous inoculation of 1-1.5 million human cancer cells into the flanks of nude mice causes tumours to grow in all mice. Tumour growth is compared for untreated controls, nonspecific AC and specific AC, for local (subcutaneous) and systemic (tail vein or intraperitoneal) injection models. The {sup 213}Bi-9.2.27 AC is injected into secondary skin melanomas in stage 4 patients in a dose escalation study to determine the effective tolerance dose, and to measure kinematics to obtain the equivalent dose to organs. In vitro studies show that TAT is one to two orders of magnitude more cytotoxic to targeted cells than non-specific ACs, specific beta emitting conjugates or free isotopes. In vivo local TAT at 2 days post-inoculation completely prevents tumour formation for all cancers tested so far. Intra-lesional TAT can completely regress advanced sc melanoma but is less successful for breast and prostate cancers. Systemic TAT inhibits the growth of sc melanoma xenografts and gives almost complete control of breast and prostate cancer tumour growth. Intralesional doses up to 450 {mu

  8. Epstein - Barr virus expression in Hodgkin's disease: Correlation withhistologic subtypes and T and B lymphocyte distribution

    International Nuclear Information System (INIS)

    Mourad, W.; Bazerbashi, S.; Alsohaibani, Mohamed O.; Saddik, M.

    1998-01-01

    The pathogenesis of Hodgkin's disease is linked to Epstein-Barr virus(EBV). Some histologic subtypes show a high level of viral expression. Theseinclude mixed cellularity (MCHD) and nodular sclerosis (NSHD) subtypes. GradeII NSHD is a more aggressive variant of HD. Lymphocyte predominant (LPHD) isa B cell lymphoproliferative disorder that has not been associated with EBVexpression. Infiltrating lymphocytes in HD are predominantly T lymphocytes,with minor component of B lymphocytes. In the current study, EBV expressionwas tested in cases of HD in relation to histologic subtypes. An attempt wasmade at correlating EBV expression with T and B lymphocyte distribution inlymph nodes involved by HD. Formalin-fixed paraffin-embedded tissue from 62cases of HD were tested for EBV and mRNA expression, using the EBER-1 probeand in situ hybridization. T and B lymphocyte distribution and their ratioswere evaluated using antibodies to T and B lymphocytes (UCHL-1 [CD45RO] andCD20, respectively), and the immunoperoxidase technique. The cases were seenin 38 male and 24 female patients, with an age range of 3 to 72 years (median25 years). There were 30 cases of grade I and 15 cases of grade II NSHD, 9cases of MCHD and 8 cases of LPHD. EBV mRNA expression was seen in 29 cases(46%). This expression was seen in 8 cases of grade I NSHD (26%), 13 cases ofgrade II NSHD (86%) and 8 cases of MCHD (88%). None of the cases of LPHDshowed viral expression. T to B lymphocytes ratios in EBV-positive casesranged from 1/6 to 8/1 and ranged from 2/1 to 20/1 in EBV-negative cases(P=0.06). Nine of the 29 positive cases (31%) showed equal T/B lymphocyteratios (n=4), or predominance of B lymphocytes (n=5). None of theEBV-negative cases showed predominance of B lymphocytes. Our study confirmedpreviously reported findings of the prevalence of EBV expression in MCHD andNSHD. Our findings also suggest that EBV expression may be more commonly seenin aggressive forms of HD. Decreased number of T lymphocytes in

  9. PLUTONIUM-238 PRODUCTION TARGET DESIGN STUDIES

    Energy Technology Data Exchange (ETDEWEB)

    Hurt, Christopher J [ORNL; Wham, Robert M [ORNL; Hobbs, Randall W [ORNL; Owens, R Steven [ORNL; Chandler, David [ORNL; Freels, James D [ORNL; Maldonado, G Ivan [ORNL

    2014-01-01

    A new supply chain is planned for plutonium-238 using existing reactors at the Oak Ridge National Laboratory (ORNL) and Idaho National Laboratory (INL) and existing chemical recovery facilities at ORNL. Validation and testing activities for new irradiation target designs have been conducted in three phases over a 2 year period to provide data for scale-up to production. Target design, qualification, target fabrication, and irradiation of fully-loaded targets have been accomplished. Data from post-irradiation examination (PIE) supports safety analysis and irradiation of future target designs.

  10. Drug-induced regulation of target expression

    DEFF Research Database (Denmark)

    Iskar, Murat; Campillos, Monica; Kuhn, Michael

    2010-01-01

    . In 1290 drug-target relations, corresponding to 466 drugs acting on 167 drug targets studied, 8% of the targets are subject to regulation at the mRNA level. We confirmed systematically that in particular G-protein coupled receptors, when serving as known targets, are regulated upon drug treatment. We...... further newly identified drug-induced differential regulation of Lanosterol 14-alpha demethylase, Endoplasmin, DNA topoisomerase 2-alpha and Calmodulin 1. The feedback regulation in these and other targets is likely to be relevant for the success or failure of the molecular intervention....

  11. Graphite target for the spiral project

    Energy Technology Data Exchange (ETDEWEB)

    Putaux, J.C.; Ducourtieux, M.; Ferro, A.; Foury, P.; Kotfila, L.; Mueller, A.C.; Obert, J.; Pauwels, N.; Potier, J.C.; Proust, J. [Paris-11 Univ., 91 - Orsay (France). Inst. de Physique Nucleaire; Bertrand, P. [Grand Accelerateur National d`Ions Lourds (GANIL), 14 - Caen (France); Loiselet, M. [Universite Catholique de Louvain, Louvain-La-Neuve (Belgium)] [and others

    1996-12-31

    A study of the thermal and physical properties of graphite targets for the SPIRAL project is presented. The main objective is to develop an optimized set-up both mechanically and thermally resistant, presenting good release properties (hot targets with thin slices). The results of irradiation tests concerning the mechanical and thermal resistance of the first prototype of SPIRAL target with conical geometry are presented. The micro-structural properties of the graphite target is also studied, in order to check that the release properties are not deteriorated by the irradiation. Finally, the results concerning the latest pilot target internally heated by an electrical current are shown. (author). 5 refs.

  12. Improved Targeting of Cancers with Nanotherapeutics

    DEFF Research Database (Denmark)

    Foster, Christian; Watson, Andre; Kaplinsky, Joseph John

    2017-01-01

    Targeted cancer nanotherapeutics offers numerous opportunities for the selective uptake of toxic chemotherapies within tumors and cancer cells. The unique properties of nanoparticles, such as their small size, large surface-to-volume ratios, and the ability to achieve multivalency of targeting...... ligands on their surface, provide superior advantages for nanoparticle-based drug delivery to a variety of cancers. This review highlights various key concepts in the design of targeted nanotherapeutics for cancer therapy, and discusses physicochemical parameters affecting nanoparticle targeting, along...... with recent developments for cancer-targeted nanomedicines....

  13. Nanotechnology based targeted drug delivery.

    Science.gov (United States)

    Ruggiero, Carmelina; Pastorino, Laura; Herrera, Oscar L

    2010-01-01

    NANOTECHNOLOGY is having a great impact on many industrial applications, such as manufacturing, semiconductors, nanostructured materials and biotechnology. As relates to the latter, nanobiotechnology focuses on the ability to work at the molecular and atomic level to fabricate structures combining biological materials and synthetic materials, taking into account engineering, physics, chemistry, genomics and proteomics. The main goals relate to biosensors, nanosized microchips, and more generally to medical applications at the molecular level. Nanotechnology has been recently extensively applied to treatment and diagnosis of diseases and the new term nanomedicine has been introduced, for which several definitions have so far been proposed [1]-[3] which focus on the use of engineered nano-devices and nanostructures for diagnosis and treatment. One of the key aspects of nanomedicine is targeted drug delivery by nanoscale drug carriers. At present, 95 % of all new potential therapeutics have poor pharmaco kinetics and biopharmaceutical properties, there is therefore a great need to develop drug delivery [4] systems that convey the therapeutically active molecules only to the site of action, without affecting other organs and tissues [5]. This allows to lower required doses of drugs and to increase their therapeutic indices and safety profiles. It is possible to fabricate nanoparticles or nanocapsules with different properties as relates to drug encapsulation and release. A great amount of nanoscale systems for drug delivery has been investigated; they include liposomes, dendrimers, quantum dots, nanotubes, polymeric biodegradable nanoparticles and nanocapsules [6].

  14. The utility target market model

    International Nuclear Information System (INIS)

    Leng, G.J.; Martin, J.

    1994-01-01

    A new model (the Utility Target Market Model) is used to evaluate the economic benefits of photovoltaic (PV) power systems located at the electrical utility customer site. These distributed PV demand-side generation systems can be evaluated in a similar manner to other demand-side management technologies. The energy and capacity values of an actual PV system located in the service area of the New England Electrical System (NEES) are the two utility benefits evaluated. The annual stream of energy and capacity benefits calculated for the utility are converted to the installed cost per watt that the utility should be willing to invest to receive this benefit stream. Different discount rates are used to show the sensitivity of the allowable installed cost of the PV systems to a utility's average cost of capital. Capturing both the energy and capacity benefits of these relatively environmentally friendly distributed generators, NEES should be willing to invest in this technology when the installed cost per watt declines to ca $2.40 using NEES' rated cost of capital (8.78%). If a social discount rate of 3% is used, installation should be considered when installed cost approaches $4.70/W. Since recent installations in the Sacramento Municipal Utility District have cost between $7-8/W, cost-effective utility applications of PV are close. 22 refs., 1 fig., 2 tabs

  15. Tensor Target Polarization at TRIUMF

    Energy Technology Data Exchange (ETDEWEB)

    Smith, G

    2014-10-27

    The first measurements of tensor observables in $\\pi \\vec{d}$ scattering experiments were performed in the mid-80's at TRIUMF, and later at SIN/PSI. The full suite of tensor observables accessible in $\\pi \\vec{d}$ elastic scattering were measured: $T_{20}$, $T_{21}$, and $T_{22}$. The vector analyzing power $iT_{11}$ was also measured. These results led to a better understanding of the three-body theory used to describe this reaction. %Some measurements were also made in the absorption and breakup channels. A direct measurement of the target tensor polarization was also made independent of the usual NMR techniques by exploiting the (nearly) model-independent result for the tensor analyzing power at 90$^\\circ _{cm}$ in the $\\pi \\vec{d} \\rightarrow 2p$ reaction. This method was also used to check efforts to enhance the tensor polarization by RF burning of the NMR spectrum. A brief description of the methods developed to measure and analyze these experiments is provided.

  16. Millimeter radar improves target identification

    Science.gov (United States)

    McAulay, Alastair D.

    2011-06-01

    Recently developed millimeter wave radar has advantages for target identification over conventional microwave radar which typically use lower frequencies. We describe the pertinent features involved in the construction of the new millimeter wave radar, the pseudo-optical cavity source and the quasi-optical duplexer. The long wavelength relative to light allows the radar beam to penetrate through most weather because the wavelength is larger than the particle size for dust, drizzle rain, fog. Further the mm wave beam passes through an atmospheric transmission window that provides a dip in attenuation. The higher frequency than conventional radar provides higher Doppler frequencies, for example, than X-band radar. We show by simulation that small characteristic vibrations and slow turns of an aircraft become visible so that the Doppler signature improves identification. The higher frequency also reduces beam width, which increases transmit and receive antenna gains. For the same power the transmit beam extends to farther range and the increase in receive antenna gain increases signal to noise ratio for improved detection and identification. The narrower beam can also reduce clutter and reject other noise more readily. We show by simulation that the radar can be used at lower elevations over the sea than conventional radar.

  17. Targeting dendritic cells--why bother?

    Science.gov (United States)

    Kreutz, Martin; Tacken, Paul J; Figdor, Carl G

    2013-04-11

    Vaccination is among the most efficient forms of immunotherapy. Although sometimes inducing lifelong protective B-cell responses, T-cell-mediated immunity remains challenging. Targeting antigen to dendritic cells (DCs) is an extensively explored concept aimed at improving cellular immunity. The identification of various DC subsets with distinct functional characteristics now allows for the fine-tuning of targeting strategies. Although some of these DC subsets are regarded as superior for (cross-) priming of naive T cells, controversies still remain about which subset represents the best target for immunotherapy. Because targeting the antigen alone may not be sufficient to obtain effective T-cell responses, delivery systems have been developed to target multiple vaccine components to DCs. In this Perspective, we discuss the pros and cons of targeting DCs: if targeting is beneficial at all and which vaccine vehicles and immunization routes represent promising strategies to reach and activate DCs.

  18. Liquid Hydrogen Target Experience at SLAC

    International Nuclear Information System (INIS)

    Weisend, J. G. II; Boyce, R.; Candia, A.; Kaminskas, W.; Mark, J.; Racine, M.; St Lorant, S.; Weber, T.; Arnold, R.; Bosted, P.; Carr, R.; Gao, J.; Jones, C. E.; McKeown, R.

    2006-01-01

    Liquid hydrogen targets have played a vital role in the physics program at SLAC for the past 40 years. These targets have ranged from small 'beer can' targets to the 1.5 m long E158 target that was capable of absorbing up to 800 W without any significant density changes. Successful use of these targets has required the development of thin-wall designs, liquid hydrogen pumps, remote positioning and alignment systems, safety systems, control and data acquisition systems, cryogenic cooling circuits and heat exchangers. Detailed operating procedures have been created to ensure safety and operational reliability.This paper surveys the evolution of liquid hydrogen targets at SLAC and discusses advances in several of the enabling technologies that made these targets possible

  19. Using the Dual-Target Cost to Explore the Nature of Search Target Representations

    Science.gov (United States)

    Stroud, Michael J.; Menneer, Tamaryn; Cave, Kyle R.; Donnelly, Nick

    2012-01-01

    Eye movements were monitored to examine search efficiency and infer how color is mentally represented to guide search for multiple targets. Observers located a single color target very efficiently by fixating colors similar to the target. However, simultaneous search for 2 colors produced a dual-target cost. In addition, as the similarity between…

  20. Quinoline: a promising antitubercular target.

    Science.gov (United States)

    Keri, Rangappa S; Patil, Siddappa A

    2014-10-01

    Tuberculosis (TB) remains a global public health problem in recent years. TB originated mainly from various strains of Mycobacterium tuberculosis, is a highly infectious and chronic disease with high infection rate since ancient times. Since the last 50 years, the same long-duration, multidrug treatment plan is being followed for the treatment of tuberculosis. Due to the development of resistance to conventional antibiotics there is a need for new therapeutic strategies to combat M. tuberculosis. Subsequently, there is an urgent need for the development of new drug molecules with newer targets and with an alternative mechanism of action. Among hetrocyclic compounds, quinoline compounds are important privileged structure in medicinal chemistry, are widely used as "parental" compounds to synthesize molecules with medical benefits, especially with anti-malarial and anti-microbial activities. Certain, quinoline-based compounds, also show effective anti-TB activity. This broad spectrum of biological and biochemical activities has been further facilitated by the synthetic versatility of quinoline, which allows the generation of a large number of structurally diverse derivatives. To pave the way for future research, there is a need to collect the latest information in this promising area. In the present review, we have collated published reports on this versatile core to provide an insight so that its full therapeutic potential can be utilized for the treatment tuberculosis. It is hoped that, this review will be helpful for new thoughts in the quest for rational designs of more active and less toxic quinoline-based anti-TB drugs. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  1. Target definition for shipwreck hunting

    Directory of Open Access Journals (Sweden)

    Kim Paul Kirsner

    2015-10-01

    Full Text Available The research described in the present article was implemented to define the locations of two World War II shipwrecks, the German raider Kormoran, and the Australian light cruiser HMAS Sydney. The paper describes the long and complex trail that led through inefficient oceanographic prediction to ambiguous historical prediction involving a single report and on to precise cognitive prediction based on nine reports from more than 70 survivors, a process that yielded a single target position or ‘mean’ just 2.7 NM (nautical miles from the wreck of Kormoran. Prediction for the position of the wreck of Sydney opened with wishful thinking that she had somehow reached the coast more than 100 NM away when cognitive analysis of the survivor’s reports actually provided the basis for accurate prediction in a position near to the wreck of Kormoran. In the account provided below, the focus on cognitive procedures emerged from, first, a review of a sample of the shipwreck hunts, and, second, growing awareness of the extraordinarily rich database available for this search, and the extent to which it was open to cognitive analysis. This review touches on both the trans-disciplinary and the cognitive or intra-disciplinary issues that so challenged the political entities responsible for supervising of the search for the wrecks of Kormoran and Sydney. One of the theoretical questions that emerged from these debate concerns the model of expertise advanced by Collins (2013. The decomposability of alleged forms of expertise is revealed as a fundamental problem for research projects that might or might not benefit from trans-disciplinary research. Where expertise can be decomposed for operational purposes, the traditional dividing lines between experts and novices, and fools for that matter, are much harder to discern, and require advanced and scientifically informed review.

  2. Cytomegalovirus protease targeted prodrug development.

    Science.gov (United States)

    Sabit, Hairat; Dahan, Arik; Sun, Jing; Provoda, Chester J; Lee, Kyung-Dall; Hilfinger, John H; Amidon, Gordon L

    2013-04-01

    Human cytomegalovirus (HCMV) is a prevalent virus that infects up to 90% of the population. The goal of this research is to determine if small molecular prodrug substrates can be developed for a specific HCMV encoded protease and thus achieve site-specific activation. HCMV encodes a 256 amino acid serine protease that is responsible for capsid assembly, an essential process for herpes virus production. The esterase activity of the more stable HCMV A143T/A144T protease mutant was evaluated with model p-nitrophenol (ONp) esters, Boc-Xaa-ONp (Ala, Leu, Ile, Val, Gln, Phe at the Xaa position). We demonstrate that the A143T/A144T mutant has esterase activity toward specific small ester compounds, e.g., Boc-L-Ala-ONp. Mono amino acid and dipeptide prodrugs of ganciclovir (GCV) were also synthesized and evaluated for hydrolysis by the A143T/A144T protease mutant in solution. Hydrolysis of these prodrugs was also evaluated in Caco-2 cell homogenates, human liver microsomes (HLMs), and rat and human plasma. For the selectivity potential of the prodrugs, the hydrolysis ratio was evaluated as a percentage of prodrug hydrolyzed by the HCMV protease over the percentages of prodrug hydrolyses by Caco-2 cell homogenates, HLMs, and human/rat plasma. A dipeptide prodrug of ganciclovir, Ac-l-Gln-l-Ala-GCV, emerged as a potential selective prodrug candidate. The results of this research demonstrate that targeting prodrugs for activation by a specific protease encoded by the infectious HCMV pathogen may be achievable.

  3. Target detection and tracking in infrared video

    Science.gov (United States)

    Deng, Zhihui; Zhu, Jihong

    2017-07-01

    In this paper, we propose a method for target detection and tracking in infrared video. The target is defined by its location and extent in a single frame. In the initialization process, we use an adaptive threshold to segment the target and then extract the fern feature and normalize it as a template. The detector uses the random forest and fern to detect the target in the infrared video. The random forest and fern is a random combination of 2bit Binary Pattern, which is robust to infrared targets with blurred and unknown contours. The tracker uses the gray-value weighted mean-Shift algorithm to track the infrared target which is always brighter than the background. And the tracker can track the deformed target efficiently and quickly. When the target disappears, the detector will redetect the target in the coming infrared image. Finally, we verify the algorithm on the real-time infrared target detection and tracking platform. The result shows that our algorithm performs better than TLD in terms of recall and runtime in infrared video.

  4. Memory for found targets interferes with subsequent performance in multiple-target visual search.

    Science.gov (United States)

    Cain, Matthew S; Mitroff, Stephen R

    2013-10-01

    Multiple-target visual searches--when more than 1 target can appear in a given search display--are commonplace in radiology, airport security screening, and the military. Whereas 1 target is often found accurately, additional targets are more likely to be missed in multiple-target searches. To better understand this decrement in 2nd-target detection, here we examined 2 potential forms of interference that can arise from finding a 1st target: interference from the perceptual salience of the 1st target (a now highly relevant distractor in a known location) and interference from a newly created memory representation for the 1st target. Here, we found that removing found targets from the display or making them salient and easily segregated color singletons improved subsequent search accuracy. However, replacing found targets with random distractor items did not improve subsequent search accuracy. Removing and highlighting found targets likely reduced both a target's visual salience and its memory load, whereas replacing a target removed its visual salience but not its representation in memory. Collectively, the current experiments suggest that the working memory load of a found target has a larger effect on subsequent search accuracy than does its perceptual salience. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  5. Polarized targets in high energy physics

    Energy Technology Data Exchange (ETDEWEB)

    Cates, G.D. Jr. [Princeton Univ., NJ (United States)

    1994-12-01

    Various approaches are discussed for producing polarized nuclear targets for high energy physics experiments. As a unifying theme, examples are drawn from experiments to measure spin dependent structure functions of nucleons in deep inelastic scattering. This single physics goal has, over roughly two decades, been a driving force in advances in target technology. Actual or planned approaches have included solid targets polarized by dynamic nuclear polarization (DNP), several types of internal targets for use in storage rings, and gaseous {sup 3}He targets polarized by spin-exchange optical pumping. This last approach is the type of target adopted for SLAC E-142, an experiment to measure the spin structure function of the neutron, and is described in detail.

  6. Protection Related to High-power Targets

    CERN Document Server

    Plum, M.A.

    2016-01-01

    Target protection is an important part of machine protection. The beam power in high-intensity accelerators is high enough that a single wayward pulse can cause serious damage. Today's high-power targets operate at the limit of available technology, and are designed for a very narrow range of beam parameters. If the beam pulse is too far off centre, or if the beam size is not correct, or if the beam density is too high, the target can be seriously damaged. We will start with a brief introduction to high-power targets and then move to a discussion of what can go wrong, and what are the risks. Next we will discuss how to control the beam-related risk, followed by examples from a few different accelerator facilities. We will finish with a detailed example of the Oak Ridge Spallation Neutron Source target tune up and target protection.

  7. Target production for inertial fusion energy

    International Nuclear Information System (INIS)

    Woodworth, J.G.; Meier, W.

    1995-03-01

    Inertial fusion energy (IFE) power plants will require the ignition and burn of 5-10 fusion fuel targets every second. The technology to economically mass produce high-quality, precision targets at this rate is beyond the current state of the art. Techniques that are scalable to high production rates, however, have been identified for all the necessary process steps, and many have been tested in laboratory experiments or are similar to current commercial manufacturing processes. In this paper, we describe a baseline target factory conceptual design and estimate its capital and operating costs. The result is a total production cost of ∼16 cents per target. At this level, target production represents about 6% of the estimated cost of electricity from a 1-GW e IFE power plant. Cost scaling relationships are presented and used to show the variation in target cost with production rate and plant power level

  8. Polarized gas targets for storage rings

    International Nuclear Information System (INIS)

    Holt, R.J.

    1990-01-01

    It is widely recognized that polarized gas targets in electron storage rings represent a new opportunity for precision nuclear physics studies. New developments in polarized target technology specific to internal applications will be discussed. In particular, polarized gas targets have been used in the VEPP-3 electron ring in Novosibirsk. A simple storage cell was used to increase the total target thickness by a factor of 15 over the simple gas jet target from an atomic beam source. Results from the initial phase of this project will be reported. In addition, the plans for increasing the luminosity by an additional order or magnitude will be presented. The application of this work to polarized hydrogen and deuterium targets for the HERA ring will be noted. The influence of beam-induced depolarization, a phenomena encountered in short-pulse electron storage rings, will be discussed. Finally, the performance tests of laser-driven sources will be presented. 8 refs., 12 figs., 1 tab

  9. Accelerator and neutron targets: a survey

    International Nuclear Information System (INIS)

    Kobisk, E.H.

    1974-01-01

    Although advances in electronics, ion source physics, detector technology, and other technical aspects of accelerator science have resulted in the capability of making highly sophisticated and accurate measurements of nuclear and atomic properties, the significance of such measurements is frequently dictated by the form, composition, and other characteristics of the target containing the nuclear species being studied. Consideration must be given to the impurity content, number of isotope nuclei per unit area, uniformity of nuclei distribution in the target, physical strength of the target, and myriad other factors. Most target characteristics are related to the mode(s) of preparation and to the quality of isotopic material used. A wide variety of target types and associated preparative methods are described and evaluated, together with methods of target characterization

  10. Inflation targeting and product market deregulation

    OpenAIRE

    Moretti, Laura

    2012-01-01

    I evaluate the effect of inflation targeting on inflation and how it interacts with product market deregulation during the disinflationary process in the 1990s. Using a sample of 21 OECD countries, I show that, after controlling for product market deregulation, the effect of inflation targeting is quantitatively important and statistically significant. Moreover, product market deregulation also matters in particular in countries that adopted an inflation targeting regime. I propose a New Keyn...

  11. Visualizing Energy on Target: Molecular Dynamics Simulations

    Science.gov (United States)

    2017-12-01

    ARL-TR-8234 ● DEC 2017 US Army Research Laboratory Visualizing Energy on Target: Molecular Dynamics Simulations by DeCarlos E...return it to the originator. ARL-TR-8234● DEC 2017 US Army Research Laboratory Visualizing Energy on Target: Molecular Dynamics...REPORT TYPE Technical Report 3. DATES COVERED (From - To) 1 October 2015–30 September 2016 4. TITLE AND SUBTITLE Visualizing Energy on Target

  12. ENTERPRISE RESOURCE STRATEGIC PLANNING: TARGET CHOICE TECHNIQUES

    Directory of Open Access Journals (Sweden)

    A. S. Lankin

    2011-01-01

    Full Text Available Choice of the targets is one of most important elements of the resource planning system. Particular feature of the strategic planning is development of future alternatives for the enterprise. Main resource strategic planning cycle elements: examination of principal external and internal environment components; forming the company mission; development of long-term targets; concretization of the long-term targets through short-term aims; examination of strategies and final choice.

  13. Promoting target models by potential measures

    OpenAIRE

    Dubiel, Joerg

    2010-01-01

    Direct marketers use target models in order to minimize the spreading loss of sales efforts. The application of target models has become more widespread with the increasing range of sales efforts. Target models are relevant for offline marketers sending printed mails as well as for online marketers who have to avoid intensity. However business has retained its evaluation since the late 1960s. Marketing decision-makers still prefer managerial performance measures of the economic benefit of a t...

  14. Bioinformatics for cancer immunotherapy target discovery

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn; Campos, Benito; Barnkob, Mike Stein

    2014-01-01

    cancer immunotherapies has yet to be fulfilled. The insufficient efficacy of existing treatments can be attributed to a number of biological and technical issues. In this review, we detail the current limitations of immunotherapy target selection and design, and review computational methods to streamline...... therapy target discovery in a bioinformatics analysis pipeline. We describe specialized bioinformatics tools and databases for three main bottlenecks in immunotherapy target discovery: the cataloging of potentially antigenic proteins, the identification of potential HLA binders, and the selection epitopes...

  15. Safety targets for nuclear power plants

    International Nuclear Information System (INIS)

    Herttrich, P.M.

    1985-01-01

    By taking as an example the safety targets of the American nuclear energy authority US-NRC, this paper explains what is meant by global, quantitative safety targets for nuclear power plants and what expectations are associated with the selecton of such safety targets. It is shown how probabilistic methods can be an appropriate completion of proven deterministic methods and what are the sectors where their application may become important in future. (orig./HP) [de

  16. A new transfer system for solid targets

    Science.gov (United States)

    Klug, J.; Buckley, K. R.; Zeisler, S. K.; Dodd, M.; Tsao, P.; Hoehr, C.; Economou, C.; Corsaut, J.; Appiah, J. P.; Kovacs, M. S.; Valliant, J. F.; Benard, F.; Ruth, T. J.; Schaffer, P.

    2012-12-01

    As part of a collaborative research project funded by Natural Resources Canada, TRIUMF has designed and manufactured solid target and solid target processing systems for the production of technetium-99m using small medical cyclotrons. The system described herein is capable of transporting the target from a hotcell, where the target is loaded and processed, to the cyclotron and back again. The versatility of the transfer system was demonstrated through the successful installation and operation on the ACSI TR 19 at the BC Cancer Agency, the GE PETtrace cyclotrons at Lawson Health Research (LHRI) and the Centre for Probe Development and Commercialization (CDPC).

  17. Target studies for surface muon production

    Directory of Open Access Journals (Sweden)

    F. Berg

    2016-02-01

    Full Text Available Meson factories are powerful drivers of diverse physics programs. With beam powers already in the MW-regime attention has to be turned to target and beam line design to further significantly increase surface muon rates available for experiments. For this reason we have explored the possibility of using a neutron spallation target as a source of surface muons by performing detailed Geant4 simulations with pion production cross sections based on a parametrization of existing data. While the spallation target outperforms standard targets in the backward direction by more than a factor 7 it is not more efficient than standard targets viewed under 90°. Not surprisingly, the geometry of the target plays a large role in the generation of surface muons. Through careful optimization, a gain in surface muon rate of between 30% and 60% over the standard “box-like” target used at the Paul Scherrer Institute could be achieved by employing a rotated slab target. An additional 10% gain could also be possible by utilizing novel target materials such as, e.g., boron carbide.

  18. An Empirical Study of Mobile Ad Targeting

    OpenAIRE

    Book, Theodore; Wallach, Dan S.

    2015-01-01

    Advertising, long the financial mainstay of the web ecosystem, has become nearly ubiquitous in the world of mobile apps. While ad targeting on the web is fairly well understood, mobile ad targeting is much less studied. In this paper, we use empirical methods to collect a database of over 225,000 ads on 32 simulated devices hosting one of three distinct user profiles. We then analyze how the ads are targeted by correlating ads to potential targeting profiles using Bayes' rule and Pearson's ch...

  19. Two target localization using passive monopulse radar

    KAUST Repository

    Jardak, Seifallah

    2016-02-19

    The simultaneous lobing technique, also known as monopulse technique, has been widely used for fast target localization and tracking purposes. Many works focused on accurately localizing one or two targets laying within a narrow beam centered around the monopulse antenna boresight direction. In this work, however, a new approach uses the outputs of a four quadrant antenna receiver to rapidly localize two point targets present in the hemisphere. A second set of antennas can be required to localize two targets sharing the same elevation or azimuth angles. To combine the outputs of both antenna sets and enhance the estimation performance of the algorithm, two methods are presented and compared.

  20. Resource implications of a national health target

    DEFF Research Database (Denmark)

    Jones, Peter; Sopina, Liza Elizaveta; Ashton, Toni

    2014-01-01

    of clinical/service managers in ED throughout New Zealand determined the type and cost of resources used for the target. Responses to the target were classified according to their impact in ED, the hospital and the community. Quantifiable resource changes were assigned a financial value and grouped...... into categories: structure (facilities/beds), staff and processes. Simple statistics were used to describe the data, and the correlation between expenditure and target performance was determined. Results There was 100% response to the survey. Most DHBs reported some expenditure specifically on the target...

  1. Drug-Target Kinetics in Drug Discovery.

    Science.gov (United States)

    Tonge, Peter J

    2018-01-17

    The development of therapies for the treatment of neurological cancer faces a number of major challenges including the synthesis of small molecule agents that can penetrate the blood-brain barrier (BBB). Given the likelihood that in many cases drug exposure will be lower in the CNS than in systemic circulation, it follows that strategies should be employed that can sustain target engagement at low drug concentration. Time dependent target occupancy is a function of both the drug and target concentration as well as the thermodynamic and kinetic parameters that describe the binding reaction coordinate, and sustained target occupancy can be achieved through structural modifications that increase target (re)binding and/or that decrease the rate of drug dissociation. The discovery and deployment of compounds with optimized kinetic effects requires information on the structure-kinetic relationships that modulate the kinetics of binding, and the molecular factors that control the translation of drug-target kinetics to time-dependent drug activity in the disease state. This Review first introduces the potential benefits of drug-target kinetics, such as the ability to delineate both thermodynamic and kinetic selectivity, and then describes factors, such as target vulnerability, that impact the utility of kinetic selectivity. The Review concludes with a description of a mechanistic PK/PD model that integrates drug-target kinetics into predictions of drug activity.

  2. A polarized target for the CLAS detector

    CERN Document Server

    Keith, C D; Battaglieri, M; Bosted, P; Branford, D; Bültmann, S; Burkert, V D; Comer, S A; Crabb, D G; De Vita, R; Dodge, G; Fatemi, R; Kashy, D; Kuhn, S E; Prok, Y; Ripani, M; Seely, M L; Taiuti, M; Witherspoon, S

    2003-01-01

    We describe the design, construction, and performance of a polarized solid target for use in electron scattering experiments with the CEBAF Large Acceptance Spectrometer. Protons and deuterons are continuously polarized by microwave-induced spin-flip transitions at 1 K and 5 T. The target operated successfully during two cycles in 1998 and 2000, providing proton and deuteron polarizations as high as 96% and 46%, respectively. The unique features of the target which permit its use inside a 4 pi spectrometer are stressed. Comparison is made between the target polarization measured by the traditional method of NMR and by electron elastic scattering.

  3. Public debt and changing inflation targets

    OpenAIRE

    Krause, Michael U.; Moyen, Stéphane

    2013-01-01

    What are the effects of a higher central bank inflation target on the burden of real public debt? Several recent proposals have suggested that even a moderate increase in the inflation target can have a pronounced effect on real public debt. We consider this question in a New Keynesian model with a maturity structure of public debt and an imperfectly observed inflation target. We find that moderate changes in the inflation target only have significant effects on real public debt if they are e...

  4. Sputtering target made by hot isostatic compaction

    International Nuclear Information System (INIS)

    Wright, R.J.; Hecht, R.J.; Fenton, R.J.

    1979-01-01

    In a method of making a cooled sputtering target assembly, material to be sputtered is in powder form which is isostatically hot-pressed in a toroidal metallic container under conditions which promote compaction and bonding of the powder particles to form a dense material. Parts of the container are then removed from the target material except for a remnant around the outer surface of the target material. A cooling jacket is then fabricated and attached around the remnant of the container. The targets specified are made from MCrAlY type alloys where M is Fe, Co or Ni. (U.K.)

  5. Project Plan Remote Target Fabrication Refurbishment Project

    International Nuclear Information System (INIS)

    Bell, Gary L.; Taylor, Robin D.

    2009-01-01

    In early FY2009, the DOE Office of Science - Nuclear Physics Program reinstated a program for continued production of 252 Cf and other transcurium isotopes at the Radiochemical Engineering Development Center (REDC) at Oak Ridge National Laboratory (ORNL). The FY2009 major elements of the workscope are as follows: (1) Recovery and processing of seven transuranium element targets undergoing irradiation at the High Flux Isotope Reactor (HFIR) at ORNL; (2) Development of a plan to manufacture new targets for irradiation beginning in early- to mid-FY10 to supply irradiated targets for processing Campaign 75 (TRU75); and (3) Refurbishment of the target manufacturing equipment to allow new target manufacture in early FY10 The 252 Cf product from processing Campaign 74 (recently processed and currently shipping to customers) is expected to supply the domestic demands for a period of approximately two years. Therefore it is essential that new targets be introduced for irradiation by the second quarter of FY10 (HFIR cycle 427) to maintain supply of 252 Cf; the average irradiation period is ∼10 HFIR cycles, requiring about 1.5 calendar years. The strategy for continued production of 252 Cf depends upon repairing and refurbishing the existing pellet and target fabrication equipment for one additional target production campaign. This equipment dates from the mid-1960s to the late 1980s, and during the last target fabrication campaign in 2005- 2006, a number of component failures and operations difficulties were encountered. It is expected that following the target fabrication and acceptance testing of the targets that will supply material for processing Campaign 75 a comprehensive upgrade and replacement of the remote hot-cell equipment will be required prior to subsequent campaigns. Such a major refit could start in early FY 2011 and would take about 2 years to complete. Scope and cost estimates for the repairs described herein were developed, and authorization for the work

  6. Selective targeting of epigenetic reader domains.

    Science.gov (United States)

    Greschik, Holger; Schüle, Roland; Günther, Thomas

    2017-05-01

    Epigenetic regulators including writers, erasers, and readers of chromatin marks have been implicated in numerous diseases and are therefore subject of intense academic and pharmaceutical research. While several small-molecule inhibitors targeting writers or erasers are either approved drugs or are currently being evaluated in clinical trials, the targeting of epigenetic readers has lagged behind. Proof-of-principle that epigenetic readers are also relevant drug targets was provided by landmark discoveries of selective inhibitors targeting the BET family of acetyl-lysine readers. More recently, high affinity chemical probes for non-BET acetyl- and methyl-lysine reader domains have also been developed. Areas covered: This article covers recent advances with the identification and validation of inhibitors and chemical probes targeting epigenetic reader domains. Issues related to epigenetic reader druggability, quality requirements for chemical probes, interpretation of cellular action, unexpected cross-talk, and future challenges are also discussed. Expert opinion: Chemical probes provide a powerful means to unravel biological functions of epigenetic readers and evaluate their potential as drug targets. To yield meaningful results, potency, selectivity, and cellular target engagement of chemical probes need to be stringently validated. Future chemical probes will probably need to fulfil additional criteria such as strict target specificity or the targeting of readers within protein complexes.

  7. Folate receptor-targeted liposomes enhanced the antitumor potency of imatinib through the combination of active targeting and molecular targeting

    Science.gov (United States)

    Ye, Peng; Zhang, Wendian; Yang, Tan; Lu, Yao; Lu, Miao; Gai, Yongkang; Ma, Xiang; Xiang, Guangya

    2014-01-01

    Purpose Imatinib inhibits platelet-derived growth factor receptor (PDGFR), and evidence shows that PDGFR participates in the development and progression of cervical cancer. Although imatinib has exhibited preclinical activity against cervical cancer, only minimal clinical therapeutic efficacy was observed. This poor therapeutic efficacy may be due to insufficient drug delivery to the tumor cells and plasma protein binding. Therefore, the purpose of this study was to explore a novel folate receptor (FR)-targeted delivery system via imatinib-loaded liposomes to enhance drug delivery to tumor cells and to reduce plasma protein binding. Methods Imatinib was remote-loaded into FR-targeted liposomes which were prepared by thin film hydration followed by polycarbonate membrane extrusion. Encapsulation efficiency, mean size diameter, and drug retention were characterized and cellular uptake, cell cytotoxicity, and cell apoptosis on cervical cancer HeLa cells were evaluated. Comparative pharmacokinetic studies were also carried out with FR-targeted imatinib liposomes, simple imatinib liposomes, and free imatinib. Results High encapsulation efficiency (>90%), appropriate mean particle size (143.5 nm), and zeta potential (−15.97 mV) were obtained for FR-targeted imatinib liposomes. The drug release profile showed minimal imatinib leakage (25%) was observed in PBS at pH =5.5. This indicates that these liposomes possess a certain degree of pH sensitivity. Cytotoxicity assays demonstrated that the FR-targeted imatinib liposomes promoted a six-fold IC50 reduction on the non-targeted imatinib liposomes from 910 to 150 μM. In addition, FR-targeted imatinib liposomes enhanced HeLa cell apoptosis in vitro compared to the non-targeted imatinib liposomes. Pharmacokinetic parameters indicated that both targeted and non-targeted liposomes exhibited long circulation properties in Kunming mice. Conclusion These findings indicate that the nano-sized FR-targeted PDGFR antagonist imatinib

  8. Logarithm laws and shrinking target properties

    Indian Academy of Sciences (India)

    and shrinking target properties for various families of dynamical systems. We discuss connections to geometry, diophantine approximation and probability theory. Keywords. Logarithm laws; shrinking target properties; diophantine approximation. 1. Introduction. A common theme in the study of (deterministic) dynamical ...

  9. Teaching Case: Security Breach at Target

    Science.gov (United States)

    Plachkinova, Miloslava; Maurer, Chris

    2018-01-01

    This case study follows the security breach that affected Target at the end of 2013 and resulted in the loss of financial data for over 70 million customers. The case provides an overview of the company and describes the reasons that led to one of the biggest security breaches in history. It offers a discussion on Target's vendor management…

  10. Small volume target for F-18 production

    Science.gov (United States)

    Pellicioli, M.; Schuler, J.; Marchand, P.; Brasse, D.

    2017-05-01

    In order to reduce the volume of O-18 enriched water used for each F-18 production for research a small volume target of 1 ml has been designed at IPHC. The designed is derived from ACSI 3.8ml F-18 target and uses both water and Helium cooling. After one year of use production yield is reported.

  11. Outdoor Synthetic Aperture Acoustic Ground Target Measurements

    Science.gov (United States)

    2010-04-19

    Dolphin Echolocation Clicks For Target Discrimination,” The Journal Of The Acoustical Society Of America 124(1), 657-666 (2008). [20] Y. Nakamura...22] H. Uberall, "History Of Resonance Scattering Theory In Acoustics And Its Applications To Target Recognition." Proc. SPIE 1960, 350-361 (1993

  12. Target system materials and engineering problems

    International Nuclear Information System (INIS)

    Fischer, W.E.

    1989-01-01

    This paper discusses the common problems of target design. As a model for the discussion, the author considers a spallation source which is fed by a high power proton beam of the order of one megawatt. The materials used for the target station and particularly for the spallation target itself depend on whether the source is built for pulsed, modulated or continuous operation. The difference of materials used is mainly determined by the neutronics considerations. Depending on the choice of materials for the target systems, the characters of material problems met, are of somewhat different nature. It is recognized that for each target version quite specific difficulties have to be overcome. On the other hand, there is a whole set of problems which is common to all target versions. These are: heat load in region of proton beam interactions; thermal stress and cycling; and radiation damage. It is shown that solutions to the whole package of problems up to a beam power of 0 (1MW) have been found. The whole effort concentrates onto the region of the first few centimeters of beam penetration. Two solutions have been proposed: (1) Keep the power of proton beam limited and produce neutrons elsewhere in the target. and (2) Dilute the power by moving mechanically the target and the window. 8 refs., 11 figs

  13. Targets for high power neutral beams

    International Nuclear Information System (INIS)

    Kim, J.

    1980-01-01

    Stopping high-power, long-pulse beams is fast becoming an engineering challenge, particularly in neutral beam injectors for heating magnetically confined plasmas. A brief review of neutral beam target technology is presented along with heat transfer calculations for some selected target designs

  14. Target discrimination strategies in optics detection

    Science.gov (United States)

    Sjöqvist, Lars; Allard, Lars; Henriksson, Markus; Jonsson, Per; Pettersson, Magnus

    2013-10-01

    Detection and localisation of optical assemblies used for weapon guidance or sniper rifle scopes has attracted interest for security and military applications. Typically a laser system is used to interrogate a scene of interest and the retro-reflected radiation is detected. Different system approaches for area coverage can be realised ranging from flood illumination to step-and-stare or continuous scanning schemes. Independently of the chosen approach target discrimination is a crucial issue, particularly if a complex scene such as in an urban environment and autonomous operation is considered. In this work target discrimination strategies in optics detection are discussed. Typical parameters affecting the reflected laser radiation from the target are the wavelength, polarisation properties, temporal effects and the range resolution. Knowledge about the target characteristics is important to predict the target discrimination capability. Two different systems were used to investigate polarisation properties and range resolution information from targets including e.g. road signs, optical reflexes, rifle sights and optical references. The experimental results and implications on target discrimination will be discussed. If autonomous operation is required target discrimination becomes critical in order to reduce the number of false alarms.

  15. Targeting the endocannabinoid system : future therapeutic strategies

    NARCIS (Netherlands)

    Aizpurua-Olaizola, Oier; Elezgarai, Izaskun; Rico-Barrio, Irantzu; Zarandona, Iratxe; Etxebarria, Nestor; Usobiaga, Aresatz

    2017-01-01

    The endocannabinoid system (ECS) is involved in many physiological regulation pathways in the human body, which makes this system the target of many drugs and therapies. In this review, we highlight the latest studies regarding the role of the ECS and the drugs that target it, with a particular

  16. Terrorist targeting, information and secret coalitions

    NARCIS (Netherlands)

    Koster, M.; Lindner, I.; McCormick, G.; Owen, G.

    2010-01-01

    We consider a game played by a state sponsor of terrorism, a terrorist group, and the target of terrorist attacks. The sponsoring state wishes to see as much damage inflicted on the target of attack as possible, but wishes to avoid retaliation. To do so, his relationship with the terrorist group

  17. Thin Scintillating Polarized Targets for Spin Physics

    Science.gov (United States)

    van den Brandt, B.; Bunyatova, E. I.; Hautle, P.; Konter, J. A.

    2003-07-01

    At PSI polarized scintillating targets are available since 1996. Proton polarizations of more than 80%, and deuteron polarizations of 25% in polystyrene-based scintillators can be reached under optimum conditions in a vertical dilution refrigerator with optical access, suited for nuclear and particle physics experiments. New preparation procedures allow to provide very thin polarizable scintillating targets and widen the spectrum of conceivable experiments.

  18. The History of Target-Controlled Infusion

    NARCIS (Netherlands)

    Struys, Michel M. R. F.; De Smet, Tom; Glen, John (Iain) B.; Vereecke, Hugo E. M.; Absalom, Anthony R.; Schnider, Thomas W.

    Target-controlled infusion (TCI) is a technique of infusing IV drugs to achieve a user-defined predicted (target) drug concentration in a specific body compartment or tissue of interest. In this review, we describe the pharmacokinetic principles of TCI, the development of TCI systems, and technical

  19. Screening for Novel Drug Targets in Cancer

    NARCIS (Netherlands)

    Nijwening, J.H.

    2012-01-01

    Most cancer drugs are not specific enough, causing unwanted side effects and recurrence of treated tumors. Some modern cancer drugs, the so-called targeted therapeutics, specifically target tumor cells, while leaving normal and healthy cells unharmed. The aim of the research described in this thesis

  20. Polarized proton target-IV. Operations manual

    International Nuclear Information System (INIS)

    Hill, D.; Fletcher, O.; Moretti, A.; Onesto, F.

    1976-01-01

    Standard operating procedures are presented for the vacuum, cryogenic, and electronic systems of a polarized proton target. The systems are comprised of (1) a target cryostat; (2) a 4 He pumping system; (3) a 3 He pumping system; (4) a microwave system; (5) a magnet and power supply; (6) a computerized polarization monitor; and (7) miscellaneous auxiliary equipment

  1. NIF Target Assembly Metrology Methodology and Results

    Energy Technology Data Exchange (ETDEWEB)

    Alger, E. T. [General Atomics, San Diego, CA (United States); Kroll, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Dzenitis, E. G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Montesanti, R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Hughes, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Swisher, M. [IAP, Livermore, CA (United States); Taylor, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Segraves, K. [IAP, Livermore, CA (United States); Lord, D. M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Reynolds, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Castro, C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Edwards, G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2011-01-01

    During our inertial confinement fusion (ICF) experiments at the National Ignition Facility (NIF) we require cryogenic targets at the 1-cm scale to be fabricated, assembled, and metrologized to micron-level tolerances. During assembly of these ICF targets, there are physical dimensmetrology is completed using optical coordinate measurement machines that provide repeatable measurements with micron precision, while also allowing in-process data collection for absolute accuracy in assembly. To date, 51 targets have been assembled and metrologized, and 34 targets have been successfully fielded on NIF relying on these metrology data. In the near future, ignition experiments on NIF will require tighter tolerances and more demanding target assembly and metrology capability. Metrology methods, calculations, and uncertainty estimates will be discussed. Target diagnostic port alignment, target position, and capsule location results will be reviewed for the 2009 Energetics Campaign. The information is presented via control charts showing the effect of process improvements that were made during target production. Certain parameters, including capsule position, met the 2009 campaign specifications but will have much tighter requirements in the future. Finally, in order to meet these new requirements assembly process changes and metrology capability upgrades will be necessary.

  2. Moeller polarimetry with atomic hydrogen targets

    International Nuclear Information System (INIS)

    Chudakov, E.; Luppov, V.

    2005-01-01

    A novel proposal of using polarized atomic hydrogen gas, stored in an ultra-cold magnetic trap, as the target for electron beam polarimetry based on Moeller scattering is discussed. Such a target of practically 100% polarized electrons could provide a superb systematic accuracy of about 0.5% for beam polarization measurements. Feasibility studies for the CEBAF electron beam have been performed. (orig.)

  3. Technical Design Report, Second Target Station

    Energy Technology Data Exchange (ETDEWEB)

    Galambos, John D. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Anderson, David E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bechtol, D. [HDR, Inc., Chattanooga, TN (United States); Bethea, Katie L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Brown, N. [Barge Waggoner Sumner & Cannon, Inc., Nashville, TN (United States); Carden, W. F. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Chae, Steven M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Clark, A. [Barge Waggoner Sumner & Cannon, Inc., Nashville, TN (United States); Counce, Deborah M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Craft, K. [Barge Waggoner Sumner & Cannon, Inc., Nashville, TN (United States); Crofford, Mark T. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Collins, Richard M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Cousineau, Sarah M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Curry, Douglas E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Cutler, Roy I. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Dayton, Michael J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Dean, Robert A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Deibele, Craig E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Doleans, Marc [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Dye, T. [HDR, Inc., Chattanooga, TN (United States); Eason, Bob H. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Eckroth, James A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Fincrock, C. [HDR, Inc., Chattanooga, TN (United States); Fritts, S. [Barge Waggoner Sumner & Cannon, Inc., Nashville, TN (United States); Gallmeier, Franz X. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Gawne, Ken R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Hartman, Steven M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Herwig, Kenneth W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Hess, S. [HDR, Inc., Chattanooga, TN (United States); Holmes, Jeffrey A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Horak, Charlie M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Howell, Matthew P. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Iverson, Erik B. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Jacobs, Lorelei L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Jones, Larry C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Johnson, B. [HDR, Inc., Chattanooga, TN (United States); Johnson, S. [HDR, Inc., Chattanooga, TN (United States); Kasemir, Kay [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Kim, Sang-Ho [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Laughon, Gregory J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Lu, W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Mahoney, Kelly L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Mammosser, John [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); McManamy, T. [McManamy Consulting, Inc., Knoxville, TN (United States); Michilini, M. [HDR, Inc., Chattanooga, TN (United States); Middendorf, Mark E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); O' Neal, Ed [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Nemec, B. [Barge Waggoner Sumner & Cannon, Inc., Nashville, TN (United States); Peters, Roy Cecil [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Plum, Michael A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Reagan, G. [Barge Waggoner Sumner & Cannon, Inc., Nashville, TN (United States); Remec, Igor [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Rennich, Mark J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Riemer, Bernie [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Saethre, Robert B. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Schubert, James Phillip [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Shishlo, Andrei P. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Smith, C. Craig [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Strong, William Herb [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Tallant, Kathie M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Tennant, David Alan [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Thibadeau, Barbara M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Trumble, S. [HDR, Inc., Chattanooga, TN (United States); Trotter, Steven M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Wang, Z. [Institute of Modern Physics (IMP), Chinese Academy of Sciences (China); Webb, Steven B. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Williams, Derrick C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); White, Karen S. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Zhao, Jinkui [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-01-01

    The Second Target Station (STS) is a proposed upgrade for SNS. It includes a doubling of the accelerator power and an additional instrument hall. The new instrument hall will receive a 467 kW 10 Hz beam. The parameters and preliminary design aspects of the STS are presented for the accelerator, target systems, instrument hall, instruments and civil construction aspects.

  4. Targeting nominal income growth or inflation?

    DEFF Research Database (Denmark)

    Jensen, Henrik

    2002-01-01

    Within a simple New Keynesian model emphasizing forward-looking behavior of private agents, I evaluate optimal nominal income growth targeting versus optimal inflation targeting. When the economy is mainly subject to shocks that do not involve monetary policy trade-offs for society, inflation...

  5. Automatic target identification using neural networks

    Science.gov (United States)

    Abdallah, Mahmoud A.; Samu, Tayib I.; Grissom, William A.

    1995-10-01

    Neural network theories are applied to attain human-like performance in areas such as speech recognition, statistical mapping, and target recognition or identification. In target identification, one of the difficult tasks has been the extraction of features to be used to train the neural network which is subsequently used for the target's identification. The purpose of this paper is to describe the development of an automatic target identification system using features extracted from a specific class of targets. The extracted features were the graphical representations of the silhouettes of the targets. Image processing techniques and some Fast Fourier Transform (FFT) properties were implemented to extract the features. The FFT eliminates variations in the extracted features due to rotation or scaling. A Neural Network was trained with the extracted features using the Learning Vector Quantization paradigm. An identification system was set up to test the algorithm. The image processing software was interfaced with MATLAB Neural Network Toolbox via a computer program written in C language to automate the target identification process. The system performed well as at classified the objects used to train it irrespective of rotation, scaling, and translation. This automatic target identification system had a classification success rate of about 95%.

  6. Dynamic nuclear polarization of irradiated target materials

    International Nuclear Information System (INIS)

    Seely, M.L.

    1982-01-01

    Polarized nucleon targets used in high energy physics experiments usually employ the method of dynamic nuclear polarization (DNP) to polarize the protons or deuterons in an alcohol. DNP requires the presence of paramagnetic centers, which are customarily provided by a chemical dopant. These chemically doped targets have a relatively low polarizable nucleon content and suffer from loss of polarization when subjected to high doses of ionizing radiation. If the paramagnetic centers formed when the target is irradiated can be used in the DNP process, it becomes possible to produce targets using materials which have a relatively high polarizable nucleon content, but which are not easily doped by chemical means. Furthermore, the polarization of such targets may be much more radiation resistant. Dynamic nuclear polarization in ammonia, deuterated ammonia, ammonium hydroxide, methylamine, borane ammonia, butonal, ethane and lithium borohydride has been studied. These studies were conducted at the Stanford Linear Accelerator Center using the Yale-SLAC polarized target system. Results indicate that the use of ammonia and deuterated ammonia as polarized target materials would make significant increases in polarized target performance possible

  7. Targeted Gene Therapy for Breast Cancer

    Science.gov (United States)

    1999-08-01

    or immunotoxin therapy, natural vector-host tropisms must be altered. Recent improvements in monoclonal antibody (mAb) engineering have expanded the...endocytosis. To achieve targeted gene therapy or immunotoxin therapy, natural vector-host tropisms must be altered. Recent improvements in monoclonal...trafficking of monoclonal antibody- antigen to an endolysosomal pathway is important. After altering targeting specificities, prokaryotic and plant

  8. Generation of Modified Pestiviruses by Targeted Recombination

    DEFF Research Database (Denmark)

    Rasmussen, Thomas Bruun; Friis, Martin Barfred; Risager, Peter Christian

    involves targeted modification of viral cDNA genomes, cloned within BACs, by Red/ET recombination-mediated mutagenesis in E.coli DH10B cells. Using recombination-mediated mutagenesis for the targeted design, the work can be expedited and focused in principal on any sequence within the viral genome...

  9. Receptor-targeted metalloradiopharmaceuticals. Final technical report

    International Nuclear Information System (INIS)

    Green, Mark A.

    2000-01-01

    Copper (II) and platinum (II) coordination complexes were prepared and characterized. These complexes were designed to afford structural homology with steroidal and non-steroidal estrogens for possible use as receptor-targeted radiopharmaceuticals. While weak affinity for the estrogen receptor was detectable, none would appear to have sufficient receptor-affinity for estrogen-receptor-targeted imaging or therapy

  10. Misattribution of sensory input reflected in dysfunctional target:non-target ERPs in schizophrenia.

    Science.gov (United States)

    Brown, K; Gordon, E; Williams, L; Bahramali, H; Harris, A; Gray, J; Gonsalvez, C; Meares, R

    2000-11-01

    While numerous studies have found disturbances in the Event-Related Potentials (ERPs) of patients with schizophrenia linked to task relevant target stimuli (most notably a reduction in P300 amplitude), few have examined ERPs to task irrelevant non-targets. We hypothesize, from current models of dysfunction in information processing in schizophrenia, that there will be less difference between ERPs to targets and non-targets in patients with schizophrenia than in controls. EEGs were recorded for 40 subjects with schizophrenia and 40 age and sex matched controls during an auditory oddball reaction time task. ERPs to the targets and non-targets immediately preceding the targets were averaged separately. There was a disturbance in ERPs to targets but also to non-targets (reduced N100 amplitude and earlier P200 latency) and the difference between target and non-target ERP components (N100 and P200 amplitude and P200 latency), was significantly reduced in the schizophrenic group compared with controls. These findings suggest a disturbance in processing task relevant and irrelevant stimuli, consistent with Gray's (1998) hypothesis of misattributions in the 'match:mismatch' of novel (target) and familiar (non-target) sensory input compared with stored information.

  11. Predicting the Reliability of Drug-target Interaction Predictions with Maximum Coverage of Target Space.

    Science.gov (United States)

    Peón, Antonio; Naulaerts, Stefan; Ballester, Pedro J

    2017-06-19

    Many computational methods to predict the macromolecular targets of small organic molecules have been presented to date. Despite progress, target prediction methods still have important limitations. For example, the most accurate methods implicitly restrict their predictions to a relatively small number of targets, are not systematically validated on drugs (whose targets are harder to predict than those of non-drug molecules) and often lack a reliability score associated with each predicted target. Here we present a systematic validation of ligand-centric target prediction methods on a set of clinical drugs. These methods exploit a knowledge-base covering 887,435 known ligand-target associations between 504,755 molecules and 4,167 targets. Based on this dataset, we provide a new estimate of the polypharmacology of drugs, which on average have 11.5 targets below IC 50 10 µM. The average performance achieved across clinical drugs is remarkable (0.348 precision and 0.423 recall, with large drug-dependent variability), especially given the unusually large coverage of the target space. Furthermore, we show how a sparse ligand-target bioactivity matrix to retrospectively validate target prediction methods could underestimate prospective performance. Lastly, we present and validate a first-in-kind score capable of accurately predicting the reliability of target predictions.

  12. The drug target genes show higher evolutionary conservation than non-target genes.

    Science.gov (United States)

    Lv, Wenhua; Xu, Yongdeng; Guo, Yiying; Yu, Ziqi; Feng, Guanglong; Liu, Panpan; Luan, Meiwei; Zhu, Hongjie; Liu, Guiyou; Zhang, Mingming; Lv, Hongchao; Duan, Lian; Shang, Zhenwei; Li, Jin; Jiang, Yongshuai; Zhang, Ruijie

    2016-01-26

    Although evidence indicates that drug target genes share some common evolutionary features, there have been few studies analyzing evolutionary features of drug targets from an overall level. Therefore, we conducted an analysis which aimed to investigate the evolutionary characteristics of drug target genes. We compared the evolutionary conservation between human drug target genes and non-target genes by combining both the evolutionary features and network topological properties in human protein-protein interaction network. The evolution rate, conservation score and the percentage of orthologous genes of 21 species were included in our study. Meanwhile, four topological features including the average shortest path length, betweenness centrality, clustering coefficient and degree were considered for comparison analysis. Then we got four results as following: compared with non-drug target genes, 1) drug target genes had lower evolutionary rates; 2) drug target genes had higher conservation scores; 3) drug target genes had higher percentages of orthologous genes and 4) drug target genes had a tighter network structure including higher degrees, betweenness centrality, clustering coefficients and lower average shortest path lengths. These results demonstrate that drug target genes are more evolutionarily conserved than non-drug target genes. We hope that our study will provide valuable information for other researchers who are interested in evolutionary conservation of drug targets.

  13. Targeted Radionuclide Therapy of Human Tumors

    Directory of Open Access Journals (Sweden)

    Sergey V. Gudkov

    2015-12-01

    Full Text Available Targeted radionuclide therapy is one of the most intensively developing directions of nuclear medicine. Unlike conventional external beam therapy, the targeted radionuclide therapy causes less collateral damage to normal tissues and allows targeted drug delivery to a clinically diagnosed neoplastic malformations, as well as metastasized cells and cellular clusters, thus providing systemic therapy of cancer. The methods of targeted radionuclide therapy are based on the use of molecular carriers of radionuclides with high affinity to antigens on the surface of tumor cells. The potential of targeted radionuclide therapy has markedly grown nowadays due to the expanded knowledge base in cancer biology, bioengineering, and radiochemistry. In this review, progress in the radionuclide therapy of hematological malignancies and approaches for treatment of solid tumors is addressed.

  14. Electrostatics, small particles, and laser fusion targets

    International Nuclear Information System (INIS)

    Hendricks, C.D.

    1978-01-01

    The success of any Inertial Confinement Fusion system for the production of useful power depends critically on the production of suitable targets. This is true whether the arrangement is that proposed by Nuckolls et al. or some other arrangement. The target must have characteristics such as material composition, structure, and surface finish which are tailored to the laser pulse length, energy, peak and average power and pulse shape. To provide useful power on a continuous basis, it is likely that the repetition rate will be 1.0 to 10 per second. Thus, in a 24 hour running period 864,000 targets may be necessary and one must be placed at the focal point of the laser every tenth of a second. For economic operation it is necessary that the targets be produced at costs of less than $1.00 per target

  15. Progress on LMJ targets for ignition

    International Nuclear Information System (INIS)

    Cherfils-Clerouin, C; Boniface, C; Bonnefille, M; Dattolo, E; Galmiche, D; Gauthier, P; Giorla, J; Laffite, S; Liberatore, S; Loiseau, P; Malinie, G; Masse, L; Masson-Laborde, P E; Monteil, M C; Poggi, F; Seytor, P; Wagon, F; Willien, J L

    2009-01-01

    Targets designed to produce ignition on the Laser Megajoule (LMJ) are being simulated in order to set specifications for target fabrication. The LMJ experimental plans include the attempt of ignition and burn of an ICF capsule with 160 laser beams, delivering up to 1.4 MJ and 380 TW. New targets needing reduced laser energy with only a small decrease in robustness have then been designed for this purpose. Working specifically on the coupling efficiency parameter, i.e. the ratio of the energy absorbed by the capsule to the laser energy, has led to the design of a rugby-ball shaped cocktail hohlraum; with these improvements, a target based on the 240-beam A1040 capsule can be included in the 160-beam laser energy-power space. Robustness evaluations of these different targets shed light on critical points for ignition, which can trade off by tightening some specifications or by preliminary experimental and numerical tuning experiments.

  16. Progress on LMJ targets for ignition

    Energy Technology Data Exchange (ETDEWEB)

    Cherfils-Clerouin, C; Boniface, C; Bonnefille, M; Dattolo, E; Galmiche, D; Gauthier, P; Giorla, J; Laffite, S; Liberatore, S; Loiseau, P; Malinie, G; Masse, L; Masson-Laborde, P E; Monteil, M C; Poggi, F; Seytor, P; Wagon, F; Willien, J L, E-mail: catherine.cherfils@cea.f [CEA, DAM, DIF, F-91297 Arpajon (France)

    2009-12-15

    Targets designed to produce ignition on the Laser Megajoule (LMJ) are being simulated in order to set specifications for target fabrication. The LMJ experimental plans include the attempt of ignition and burn of an ICF capsule with 160 laser beams, delivering up to 1.4 MJ and 380 TW. New targets needing reduced laser energy with only a small decrease in robustness have then been designed for this purpose. Working specifically on the coupling efficiency parameter, i.e. the ratio of the energy absorbed by the capsule to the laser energy, has led to the design of a rugby-ball shaped cocktail hohlraum; with these improvements, a target based on the 240-beam A1040 capsule can be included in the 160-beam laser energy-power space. Robustness evaluations of these different targets shed light on critical points for ignition, which can trade off by tightening some specifications or by preliminary experimental and numerical tuning experiments.

  17. Radiochemical aspects of liquid mercury spallation targets

    CERN Document Server

    Neuhausen, Joerg; Eichler, Bernd; Eller, Martin; Horn, Susanne; Schumann, Dorothea; Stora, Thierry

    2012-01-01

    Liquid metal spallation targets using mercury as target material are used in state-of-the-art high power pulsed neutron sources that have been constructed in the USA and Japan within the last decade. Similar target concepts were also proposed for next generation ISOL, beta-beam and neutrino facilities. A large amount of radioactivity will be induced in the liquid metal during operation caused by the interaction of the target material with the intense proton beam. This radioactivity - carried by a wide range of radioisotopes of all the elements of the periodic table from hydrogen up to thallium - must be considered for the assessment of safe operation and maintenance procedures as well as for a final disposal of the used target material and components. This report presents an overview on chemical investigations performed in our laboratory that deal with the behavior of radionuclides in proton irradiated mercury samples. The solubility of elements in mercury was calculated using thermodynamical data obtained by...

  18. Performance Targets and External Market Prices

    DEFF Research Database (Denmark)

    Hansen, Allan; Friis, Ivar; Vámosi, Tamás S.

    In this paper we explore the processes of ‘bringing the market inside the firm’ to set performance targets and benchmark production workers productivity. We analyze attempts to use external suppliers’ bids in target setting in a Danish manufacturing company. The case study illustrates how...... the implementation of external market information in target setting – well known in transfer pricing, relative performance evaluation, beyond budgeting, target costing, piece rates systems and value based management – relate to challenging motivation and information problem. The analysis and discussion of those...... problems, in particular those related to accounting for the internal performance (that are going to be compared with the external target), calculating the ‘inside’ costs and defining controllability, contributes to the management accounting as well as the piece-rate literature....

  19. The Jefferson Lab Frozen Spin Target

    Energy Technology Data Exchange (ETDEWEB)

    Christopher Keith, James Brock, Christopher Carlin, Sara Comer, David Kashy, Josephine McAndrew, David Meekins, Eugene Pasyuk, Joshua Pierce, Mikell Seely

    2012-08-01

    A frozen spin polarized target, constructed at Jefferson Lab for use inside a large acceptance spectrometer, is described. The target has been utilized for photoproduction measurements with polarized tagged photons of both longitudinal and circular polarization. Protons in TEMPO-doped butanol were dynamically polarized to approximately 90% outside the spectrometer at 5 T and 200-300 mK. Photoproduction data were acquired with the target inside the spectrometer at a frozen-spin temperature of approximately 30 mK with the polarization maintained by a thin, superconducting coil installed inside the target cryostat. A 0.56 T solenoid was used for longitudinal target polarization and a 0.50 T dipole for transverse polarization. Spin relaxation times as high as 4000 hours were observed. We also report polarization results for deuterated propanediol doped with the trityl radical OX063.

  20. Performance Targets and External Market Prices

    DEFF Research Database (Denmark)

    Hansen, Allan; Friis, Ivar; Vámosi, Tamás S.

    2012-01-01

    the implementation of external market information in target setting – well known in transfer pricing, relative performance evaluation, beyond budgeting, target costing, piece rates systems and value based management – relate to challenging motivation and information problem. The analysis and discussion of those......In this paper we explore the processes of ‘bringing the market inside the firm’ to set performance targets and benchmark production workers productivity. We analyze attempts to use external suppliers’ bids in target setting in a Danish manufacturing company. The case study illustrates how...... problems, in particular those related to accounting for the internal performance (that are going to be compared with the external target), calculating the ‘inside’ costs and defining controllability, contributes to the management accounting as well as the piece-rate literature....

  1. Remote handling for an ISIS target change

    International Nuclear Information System (INIS)

    Broome, T.A.; Holding, M.

    1989-01-01

    During 1987 two ISIS targets were changed. This document describes the main features of the remote handling aspects of the work. All the work has to be carried out using remote handling techniques. The radiation level measured on the surface of the reflector when the second target had been removed was about 800 mGy/h demonstrating that hands on operations on any part of the target reflector moderator assembly is not practical. The target changes were the first large scale operations in the Target Station Remote Handling Cell and a great deal was learned about both equipment and working practices. Some general principles emerged which are applicable to other active handling tasks on facilities like ISIS and these are discussed below. 8 figs

  2. Cooperative target convergence using multiple agents

    Energy Technology Data Exchange (ETDEWEB)

    Kwok, K.S.; Driessen, B.J.

    1997-10-01

    This work considers the problem of causing multiple (100`s) autonomous mobile robots to converge to a target and provides a follow-the-leader approach to the problem. Each robot has only a limited-range sensor for sending the target and also larger but also limited-range robot-to-robot communication capability. Because of the small amount of information available to the robots, a practical approach to improve convergence to the target is to have a robot follow the robot with the best quality of information. Specifically, each robot emits a signal that informs in-range robots what its status is. A robot has a status value of 0 if it is itself in range of the target. A robot has a status of 1 if it is not in range of the target but is in communication range of a robot that is in range of the target. A robot has a status of 2 if it is not in range of the target but is within range of another robot that has status 1, and so on. Of all the mobile robots that any given robot is in range of, it follows the one with the best status. The emergent behavior is the ant-like trails of robots following each other toward the target. If the robot is not in range of another robot that is either in range of the target or following another robot, the robot will assign-1 to its quality-of-information, and will execute an exhaustive search. The exhaustive search will continue until it encounters either the target or another robot with a nonnegative quality-of-information. The quality of information approach was extended to the case where each robot only has two-bit signals informing it of distance to in-range robots.

  3. Targeted Brain Tumor Treatment: Current Perspectives

    Directory of Open Access Journals (Sweden)

    Ningaraj N.S

    2007-01-01

    Full Text Available Brain tumor is associated with poor prognosis. The treatment option is severely limited for a patient with brain tumor, despite great advances in understanding the etiology and molecular biology of brain tumors that have lead to breakthroughs in developing pharmaceutical strategies, and ongoing NCI/Pharma-sponsored clinical trials. We reviewed the literature on molecular targeted agents in preclinical and clinical studies in brain tumor for the past decade, and observed that the molecular targeting in brain tumors is complex. This is because no single gene or protein can be affected by single molecular agent, requiring the use of combination molecular therapy with cytotoxic agents. In this review, we briefly discuss the potential molecular targets, and the challenges of targeted brain tumor treatment. For example, glial tumors are associated with over-expression of calcium-dependent potassium (KCa channels, and high grade glioma express specific KCa channel gene (gBK splice variants, and mutant epidermal growth factor receptors (EGFRvIII. These specific genes are promising targets for molecular targeted treatment in brain tumors. In addition, drugs like Avastin and Gleevec target the molecular targets such as vascular endothelial cell growth factor receptor, platelet-derived growth factor receptors, and BRC-ABL/Akt. Recent discovery of non-coding RNA, specifically microRNAs could be used as potential targeted drugs. Finally, we discuss the role of anti-cancer drug delivery to brain tumors by breaching the blood-brain tumor barrier. This non-invasive strategy is particularly useful as novel molecules and humanized monoclonal antibodies that target receptor tyrosine kinase receptors are rapidly being developed.

  4. Targeted Brain Tumor Treatment-Current Perspectives

    Directory of Open Access Journals (Sweden)

    N.S. Ningaraj

    2007-01-01

    Full Text Available Brain tumor is associated with poor prognosis. The treatment option is severely limited for a patient with brain tumor, despite great advances in understanding the etiology and molecular biology of brain tumors that have lead to breakthroughs in developing pharmaceutical strategies, and ongoing NCI/Pharma-sponsored clinical trials. We reviewed the literature on molecular targeted agents in preclinical and clinical studies in brain tumor for the past decade, and observed that the molecular targeting in brain tumors is complex. This is because no single gene or protein can be affected by single molecular agent, requiring the use of combination molecular therapy with cytotoxic agents. In this review, we briefly discuss the potential molecular targets, and the challenges of targeted brain tumor treatment. For example, glial tumors are associated with over-expression of calcium-dependent potassium (K Ca channels, and high grade glioma express specific K Ca channel gene (gBK splice variants, and mutant epidermal growth factor receptors (EGFRvIII. These specific genes are promising targets for molecular targeted treatment in brain tumors. In addition, drugs like Avastin and Gleevec target the molecular targets such as vascular endothelial cell growth factor receptor, platelet-derived growth factor receptors, and BRC-ABL/Akt. Recent discovery of non-coding RNA, specifically microRNAs could be used as potential targeted drugs. Finally, we discuss the role of anti-cancer drug delivery to brain tumors by breaching the blood-brain tumor barrier. This non-invasive strategy is particularly useful as novel molecules and humanized monoclonal antibodies that target receptor tyrosine kinase receptors are rapidly being developed.

  5. Cooperative target convergence using multiple agents

    International Nuclear Information System (INIS)

    Kwok, K.S.; Driessen, B.J.

    1997-01-01

    This work considers the problem of causing multiple (100''s) autonomous mobile robots to converge to a target and provides a follow-the-leader approach to the problem. Each robot has only a limited-range sensor for sending the target and also larger but also limited-range robot-to-robot communication capability. Because of the small amount of information available to the robots, a practical approach to improve convergence to the target is to have a robot follow the robot with the best quality of information. Specifically, each robot emits a signal that informs in-range robots what its status is. A robot has a status value of 0 if it is itself in range of the target. A robot has a status of 1 if it is not in range of the target but is in communication range of a robot that is in range of the target. A robot has a status of 2 if it is not in range of the target but is within range of another robot that has status 1, and so on. Of all the mobile robots that any given robot is in range of, it follows the one with the best status. The emergent behavior is the ant-like trails of robots following each other toward the target. If the robot is not in range of another robot that is either in range of the target or following another robot, the robot will assign-1 to its quality-of-information, and will execute an exhaustive search. The exhaustive search will continue until it encounters either the target or another robot with a nonnegative quality-of-information. The quality of information approach was extended to the case where each robot only has two-bit signals informing it of distance to in-range robots

  6. Target-to-Target Repetition Cost and Location Negative Priming Are Dissociable: Evidence for Different Mechanisms

    Science.gov (United States)

    Chao, Hsuan-Fu

    2011-01-01

    In a location-selection task, the repetition of a prior distractor location as the target location would slow down the response. This effect is termed the location negative priming (NP) effect. Recently, it has been demonstrated that repetition of a prior target location as the current target location would also slow down response. Because such…

  7. The Cost of Search for Multiple Targets: Effects of Practice and Target Similarity

    Science.gov (United States)

    Menneer, Tamaryn; Cave, Kyle R.; Donnelly, Nick

    2009-01-01

    With the use of X-ray images, performance in the simultaneous search for two target categories was compared with performance in two independent searches, one for each category. In all cases, displays contained one target at most. Dual-target search, for both categories simultaneously, produced a cost in accuracy, although the magnitude of this…

  8. High or Low Target Prevalence Increases the Dual-Target Cost in Visual Search

    Science.gov (United States)

    Menneer, Tamaryn; Donnelly, Nick; Godwin, Hayward J.; Cave, Kyle R.

    2010-01-01

    Previous studies have demonstrated a dual-target cost in visual search. In the current study, the relationship between search for one and search for two targets was investigated to examine the effects of target prevalence and practice. Color-shape conjunction stimuli were used with response time, accuracy and signal detection measures. Performance…

  9. Search for Two Categories of Target Produces Fewer Fixations to Target-Color Items

    Science.gov (United States)

    Menneer, Tamaryn; Stroud, Michael J.; Cave, Kyle R.; Li, Xingshan; Godwin, Hayward J.; Liversedge, Simon P.; Donnelly, Nick

    2012-01-01

    Searching simultaneously for metal threats (guns and knives) and improvised explosive devices (IEDs) in X-ray images is less effective than 2 independent single-target searches, 1 for metal threats and 1 for IEDs. The goals of this study were to (a) replicate this dual-target cost for categorical targets and to determine whether the cost remains…

  10. Hitting moving targets : A dissociation between the use of the target's speed and direction of motion

    NARCIS (Netherlands)

    Brouwer, Anne Marie; Middelburg, Tom; Smeets, Jeroen B J; Brenner, Eli

    2003-01-01

    Previous work has indicated that people do not use their judgment of a target's speed to determine where to hit it. Instead, they use their judgment of the target's changing position and an expected speed (based on the speed of previous targets). In the present study we investigate whether people

  11. Detection of CD5 in B-cell chronic lymphoproliferative diseases by flow cytometry: a strong expression in B-cell chronic lymphocytic leukemia Detecção do CD5 em doenças linfoproliferativas crônicas de células B por citometria de fluxo: uma importante expressão em leucemia linfocítica crônica

    Directory of Open Access Journals (Sweden)

    Geraldo Barroso Cavalcanti Júnior

    2005-01-01

    Full Text Available PURPOSE: CD5 is a T cell marker, aberrantly express in B cell chronic lymphocytic leukemia (B-CLL and mantle cell lymphoma (MCL. Other chronic B cell malignancies including hairy cell leukemia (HCL and B cell prolymphocytic leukemia (B-PLL are CD5 negative or express this antigen in a weak way. In this study, CD5 expression was investigated in leukemic cells from 42 patients with chronic B cell lymphoproliferative disease. METHODS: We studied the CD5 expression in leukemic cells from 42 patients with chronic B-cell malignancies by flow cytometry. Demographic features such as age, sex and clinical date were also analyzed. RESULTS: There were 22 males and 20 females. The immunophenotyping showed that 35 cases were B-CLL, 3 B-PLL and HCL and one patient was MCL. CD5 expression was present in all B-CLL and MCL. Low expression of CD5 was observed in one patient with B-PLL and negative in all cases of HCL. CONCLUSION: Our date demonstrated that CD5 expression can help distinguish among B-CLL from HCL and B-PLL, but is similar expressed in MCL.OBJETIVOS: CD5 é um marcador normalmente expresso nas células T e de forma aberrante nas células B da leucemia linfocítica crônica (LLC e no linfoma de células do manto (LCM. Outras doenças linfoproliferativas crônicas como a hairy cell leukemia (HCL e leukemia prolinfocítica de células B (LPL-B, são geralmente CD5 negativas ou expressam fracamente este antígeno. Neste trabalho investigou-se o padrão de expressão do CD5 em 42 pacientes com doenças linfoproliferativas crônicas de células B (DLC-B. METODOS: Investigamos a expressão de CD5 em células leucêmicas de 42 pacientes com DLC-B através da citometria de fluxo. Dados demográficos, tais como idade e sexo, bem como dados clínicos e laboratoriais também foram analisados. RESULTADOS: A imunofenotipagem mostrou que 35 casos foram LLC, 3 LPL-B, 3 HCL e um caso de LMC. O CD5 mostrou-se fortemente expresso em todos os casos de LLC e LMC. Baixa

  12. COMPASS polarized target for Drell-Yan

    CERN Document Server

    Pešek, M

    2014-01-01

    In the COMPASS Drell–Yan experiment the pion beam with momen tum of 190 GeV/ c and in- tensity up to 10 8 pions/s will interact with transversely polarized proton t arget producing muon pair via Drell–Yan process. The solid-state NH 3 will be polarized by dynamic nuclear polar- ization. Maximum polarization reached during data taking i s expected to be up to 90%. The non-interacting beam and other particles produced inside t he target will be stopped in the hadron absorber after the target. Two target cells, sepparated by a 20 cm gap in between, each 55 cm long and 4 cm in diameter give the target material volume about 691 cm 3 . The target platform needs to be moved by 2.3 m in upstream dire ction from the position used in previous experiments in order to accomodate the absorber. D uring the beam time higher radiation is expected in the area of the control room. Thus a new target r emote control system is needed. The target magnet is undergoing a substantial upgrade. Drell–Yan data taking is expected t...

  13. Hypersonic sliding target tracking in near space

    Directory of Open Access Journals (Sweden)

    Xiang-yu Zhang

    2015-12-01

    Full Text Available To improve the tracking accuracy of hypersonic sliding target in near space, the influence of target hypersonic movement on radar detection and tracking is analyzed, and an IMM tracking algorithm is proposed based on radial velocity compensating and cancellation processing of high dynamic biases under the earth centered earth fixed (ECEF coordinate. Based on the analysis of effect of target hypersonic movement, a measurement model is constructed to reduce the filter divergence which is caused by the model mismatch. The high dynamic biases due to the target hypersonic movement are approximately compensated through radial velocity estimation to achieve the hypersonic target tracking at low systematic biases in near space. The high dynamic biases are further eliminated by the cancellation processing of different radars, in which the track association problem can be solved when the dynamic biases are low. An IMM algorithm based on constant acceleration (CA, constant turning (CT and Singer models is used to achieve the hypersonic sliding target tracking in near space. Simulation results show that the target tracking in near space can be achieved more effectively by using the proposed algorithm.

  14. Target discovery from data mining approaches.

    Science.gov (United States)

    Yang, Yongliang; Adelstein, S James; Kassis, Amin I

    2012-02-01

    Data mining of available biomedical data and information has greatly boosted target discovery in the 'omics' era. Target discovery is the key step in the biomarker and drug discovery pipeline to diagnose and fight human diseases. In biomedical science, the 'target' is a broad concept ranging from molecular entities (such as genes, proteins and miRNAs) to biological phenomena (such as molecular functions, pathways and phenotypes). Within the context of biomedical science, data mining refers to a bioinformatics approach that combines biological concepts with computer tools or statistical methods that are mainly used to discover, select and prioritize targets. In response to the huge demand of data mining for target discovery in the 'omics' era, this review explicates various data mining approaches and their applications to target discovery with emphasis on text and microarray data analysis. Two emerging data mining approaches, chemogenomic data mining and proteomic data mining, are briefly introduced. Also discussed are the limitations of various data mining approaches found in the level of database integration, the quality of data annotation, sample heterogeneity and the performance of analytical and mining tools. Tentative strategies of integrating different data sources for target discovery, such as integrated text mining with high-throughput data analysis and integrated mining with pathway databases, are introduced. Published by Elsevier Ltd.

  15. Bacterial proteases, untapped antimicrobial drug targets.

    Science.gov (United States)

    Culp, Elizabeth; Wright, Gerard D

    2017-04-01

    Bacterial proteases are an extensive collection of enzymes that have vital roles in cell viability, stress response and pathogenicity. Although their perturbation clearly offers the potential for antimicrobial drug development, both as traditional antibiotics and anti-virulence drugs, they are not yet the target of any clinically used therapeutics. Here we describe the potential for and recent progress in the development of compounds targeting bacterial proteases with a focus on AAA+ family proteolytic complexes and signal peptidases (SPs). Caseinolytic protease (ClpP) belongs to the AAA+ family of proteases, a group of multimeric barrel-shaped complexes whose activity is tightly regulated by associated AAA+ ATPases. The opportunity for chemical perturbation of these complexes is demonstrated by compounds targeting ClpP for inhibition, activation or perturbation of its associated ATPase. Meanwhile, SPs are also a proven antibiotic target. Responsible for the cleavage of targeting peptides during protein secretion, both type I and type II SPs have been successfully targeted by chemical inhibitors. As the threat of pan-antibiotic resistance continues to grow, these and other bacterial proteases offer an arsenal of novel antibiotic targets ripe for development.

  16. Bounded Target Cascading in Hierarchical Design Optimization

    Directory of Open Access Journals (Sweden)

    Xiaoling Zhang

    2014-06-01

    Full Text Available For large scale systems, as a hierarchical multilevel decomposed design optimization method, analytical target cascading coordinates the inconsistency between the assigned targets and response in each level by a weighted-sum formulation. To avoid the problems associated with the weighting coefficients, single objective functions in the hierarchical design optimization are formulated by a bounded target cascading method in this paper. In the BTC method, a single objective optimization problem is formulated in the system level, and two kinds of coordination constraints are added: one is bound constraint for the design points based on the response from each subsystem level and the other is linear equality constraint for the common variables based on their sensitivities with respect to each subsystem. In each subsystem level, the deviation with target for design point is minimized in the objective function, and the common variables are constrained by target bounds. Therefore, in the BTC method, the targets are coordinated based on the optimization iteration information in the hierarchical design problem and the performance of the subsystems, and BTC method will converge to the global optimum efficiently. Finally, comparisons of the results from BTC method and the weighted-sum analytical target cascading method are presented and discussed.

  17. Targeted assembly of short sequence reads.

    Directory of Open Access Journals (Sweden)

    René L Warren

    Full Text Available As next-generation sequence (NGS production continues to increase, analysis is becoming a significant bottleneck. However, in situations where information is required only for specific sequence variants, it is not necessary to assemble or align whole genome data sets in their entirety. Rather, NGS data sets can be mined for the presence of sequence variants of interest by localized assembly, which is a faster, easier, and more accurate approach. We present TASR, a streamlined assembler that interrogates very large NGS data sets for the presence of specific variants by only considering reads within the sequence space of input target sequences provided by the user. The NGS data set is searched for reads with an exact match to all possible short words within the target sequence, and these reads are then assembled stringently to generate a consensus of the target and flanking sequence. Typically, variants of a particular locus are provided as different target sequences, and the presence of the variant in the data set being interrogated is revealed by a successful assembly outcome. However, TASR can also be used to find unknown sequences that flank a given target. We demonstrate that TASR has utility in finding or confirming genomic mutations, polymorphisms, fusions and integration events. Targeted assembly is a powerful method for interrogating large data sets for the presence of sequence variants of interest. TASR is a fast, flexible and easy to use tool for targeted assembly.

  18. Detecting targets hidden in random forests

    Science.gov (United States)

    Kouritzin, Michael A.; Luo, Dandan; Newton, Fraser; Wu, Biao

    2009-05-01

    Military tanks, cargo or troop carriers, missile carriers or rocket launchers often hide themselves from detection in the forests. This plagues the detection problem of locating these hidden targets. An electro-optic camera mounted on a surveillance aircraft or unmanned aerial vehicle is used to capture the images of the forests with possible hidden targets, e.g., rocket launchers. We consider random forests of longitudinal and latitudinal correlations. Specifically, foliage coverage is encoded with a binary representation (i.e., foliage or no foliage), and is correlated in adjacent regions. We address the detection problem of camouflaged targets hidden in random forests by building memory into the observations. In particular, we propose an efficient algorithm to generate random forests, ground, and camouflage of hidden targets with two dimensional correlations. The observations are a sequence of snapshots consisting of foliage-obscured ground or target. Theoretically, detection is possible because there are subtle differences in the correlations of the ground and camouflage of the rocket launcher. However, these differences are well beyond human perception. To detect the presence of hidden targets automatically, we develop a Markov representation for these sequences and modify the classical filtering equations to allow the Markov chain observation. Particle filters are used to estimate the position of the targets in combination with a novel random weighting technique. Furthermore, we give positive proof-of-concept simulations.

  19. Systemic Targeted Alpha Radiotherapy for Cancer

    Directory of Open Access Journals (Sweden)

    Allan B. J.

    2013-09-01

    Full Text Available Background: The fundamental principles of internal targeted alpha therapy for cancer were established many decades ago.The high linear energy transfer (LET of alpha radiation to the targeted cancer cellscauses double strand breaks in DNA. At the same time, the short range radiation spares adjacent normal tissues. This targeted approach complements conventional external beam radiotherapy and chemotherapy. Such therapies fail on several fronts, such as lack of control of some primary cancers (e.g.glioblastoma multiformeand to inhibit the development of lethal metastatic cancer after successful treatment of the primary cancer. Objective: This review charts the developing role of systemic high LET, internal radiation therapy. Method: Targeted alpha therapy is a rapidly advancing experimental therapy that holds promise to deliver high cytotoxicity to targeted cancer cells. Initially thought to be indicated for leukemia and micrometastases, there is now evidence that solid tumors can also be regressed. Results: Alpha therapy may be molecular or physiological in its targeting. Alpha emitting radioisotopes such as Bi-212, Bi-213, At-211 and Ac-225 are used to label monoclonal antibodies or proteins that target specifc cancer cells. Alternatively, Radium-233 is used for palliative therapy of breast and prostate cancers because of its bone seeking properties. Conclusion: Preclinical studies and clinical trials of alpha therapy are discussed for leukemia, lymphoma, melanoma, glioblastoma multiforme, bone metastases, ovarian cancer, pancreatic cancer and other cancers.

  20. Design of the LBNF Beamline Target Station

    Energy Technology Data Exchange (ETDEWEB)

    Tariq, S. [Fermilab; Ammigan, K. [Fermilab; Anderson, K.; ; Buccellato, S. A. [Fermilab; Crowley, C. F. [Fermilab; Hartsell, B. D. [Fermilab; Hurh, P. [Fermilab; Hylen, J. [Fermilab; Kasper, P. [Fermilab; Krafczyk, G. E. [Fermilab; Lee, A. [Fermilab; Lundberg, B. [Fermilab; Reitzner, S. D. [Fermilab; Sidorov, V. [Fermilab; Stefanik, A. M. [Fermilab; Tropin, I. S. [Fermilab; Vaziri, K. [Fermilab; Williams, K. [Fermilab; Zwaska, R. M. [Fermilab; Densham, C. [RAL, Didcot

    2016-10-01

    The Long Baseline Neutrino Facility (LBNF) project will build a beamline located at Fermilab to create and aim an intense neutrino beam of appropriate energy range toward the DUNE detectors at the SURF facility in Lead, South Dakota. Neutrino production starts in the Target Station, which consists of a solid target, magnetic focusing horns, and the associated sub-systems and shielding infrastructure. Protons hit the target producing mesons which are then focused by the horns into a helium-filled decay pipe where they decay into muons and neutrinos. The target and horns are encased in actively cooled steel and concrete shielding in a chamber called the target chase. The reference design chase is filled with air, but nitrogen and helium are being evaluated as alternatives. A replaceable beam window separates the decay pipe from the target chase. The facility is designed for initial operation at 1.2 MW, with the ability to upgrade to 2.4 MW, and is taking advantage of the experience gained by operating Fermilab’s NuMI facility. We discuss here the design status, associated challenges, and ongoing R&D and physics-driven component optimization of the Target Station.

  1. Macros in microRNA target identification

    Science.gov (United States)

    Tarang, Shikha; Weston, Michael D

    2014-01-01

    MicroRNAs (miRNAs) are short RNA molecules that modulate post-transcriptional gene expression by partial or incomplete base-pairing to the complementary sequences on their target genes. Sequence-based miRNA target gene recognition enables the utilization of computational methods, which are highly informative in identifying a subset of putative miRNA targets from the genome. Subsequently, single miRNA–target gene binding is evaluated experimentally by in vitro assays to validate and quantify the transcriptional or post-transcriptional effects of miRNA–target gene interaction. Although ex vivo approaches are instructive in providing a basis for further analyses, in vivo genetic studies are critical to determine the occurrence and biological relevance of miRNA targets under physiological conditions. In the present review, we summarize the important features of each of the experimental approaches, their technical and biological limitations, and future challenges in light of the complexity of miRNA target gene recognition. PMID:24717361

  2. Exploring model-based target discrimination metrics

    Science.gov (United States)

    Witus, Gary; Weathersby, Marshall

    2004-08-01

    Visual target discrimination has occurred when the observer can say "I see a target THERE!" and can designate the target location. Target discrimination occurs when a perceived shape is sufficiently similar one or more of the instances the observer has been trained on. Marr defined vision as "knowing what is where by seeing." Knowing "what" requires prior knowledge. Target discrimination requires model-based visual processing. Model-based signature metrics attempt to answer the question "to what extent does the target in the image resemble a training image?" Model-based signature metrics attempt to represent the effects of high-level top-down visual cognition, in addition to low-level bottom-up effects. Recent advances in realistic 3D target rendering and computer-vision object recognition have made model-based signature metrics more practical. The human visual system almost certainly does NOT use the same processing algorithms as computer vision object recognition, but some processing elements and the overall effects are similar. It remains to be determined whether model-based metrics explain the variance in human performance. The purpose of this paper is to explain and illustrate the model-based approach to signature metrics.

  3. Degradable Polymersomes for Targeted Drug Delivery

    Science.gov (United States)

    Petersen, Matthew Alan

    Chemotherapy today is often accompanied by major side effects due to delivery of toxic drugs to healthy tissue in addition to diseased cells. Targeted drug delivery offers the possibility of minimizing these side effects by specific delivery to cancer cells using targeted nanocarriers that enhance drug accumulation in tumors and facilitate target-specific cellular uptake. Polymersomes, vesicles self-assembled from polymeric amphiphiles, are an attractive targeted vehicle, as they are capable of encapsulating both hydrophobic and hydrophilic drugs, have lengthy circulation times in vivo, and can employ degradable functionality for triggered release of payload and clearance from the body. This thesis reports on efforts to enhance the capabilities of degradable polymersomes for targeted delivery. First, targeting functionality is incorporated into polymersomes of the block copolymer poly(ethylene oxide)-b-poly(gamma-methyl-epsilon-caprolactone) by incorporating the reactive vinyl sulfone group into the amphiphile's hydrophilic terminus, allowing site-selective reaction with cysteine-functionalized targeting peptides following self-assembly. The performance of targeted delivery using this polymersome is then evaluated in vitro. Binding and delivery to model cell lines for targeted and bystander cells is tracked using nontargeted polymersomes and compared to that for polymersomes using a high- or low-affinity ligand. Polymer degradation is also tracked both in simple media and during cellular delivery. Finally, a new monomer is developed incorporating acid-labile acetal functionality into a cyclic polyester. The polymerization of this monomer to two distinct polymers is also characterized and the degradation behavior of both polymers evaluated.

  4. Peptide-Targeted Radionuclide Therapy for Melanoma

    Science.gov (United States)

    Miao, Yubin; Quinn, Thomas P.

    2011-01-01

    Melanocortin-1 receptor (MC1-R) and melanin are two attractive melanoma-specific targets for peptide-targeted radionuclide therapy for melanoma. Radiolabeled peptides targeting MC1-R/melanin can selectively and specifically target cytotoxic radiation generated from therapeutic radionuclides to melanoma cells for cell killing, while sparing the normal tissues and organs. This review highlights the recent advances of peptide-targeted radionuclide therapy of melanoma targeting MC1R and melanin. The promising therapeutic efficacies of 188Re-(Arg11)CCMSH (188Re-[Cys3,4,10, d-Phe7, Arg11]-α-MSH3-13), 177Lu- and 212Pb-labeled DOTA-Re(Arg11)CCMSH (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[ReO-(Cys3,4,10, d-Phe7, Arg11)]-α-MSH3-13) and 188Re-HYNIC-4B4 (188Re-hydrazinonicotinamide-Tyr-Glu-Arg-Lys-Phe-Trp-His-Gly-Arg-His) in preclinical melanoma-bearing models demonstrate an optimistic outlook for peptide-targeted radionuclide therapy for melanoma. Peptide-targeted radionuclide therapy for melanoma will likely contribute in an adjuvant setting, once the primary tumor has been surgically removed, to treat metastatic deposits and for treatment of end-stage disease. The lack of effective treatments for metastatic melanoma and end stage disease underscores the necessity to develop and implement new treatment strategies, such as peptide-targeted radionuclide therapy. PMID:18387816

  5. The 1994 Fermilab Fixed Target Program

    International Nuclear Information System (INIS)

    Conrad, J.

    1994-11-01

    This paper highlights the results of the Fermilab Fixed Target Program that were announced between October, 1993 and October, 1994. These results are drawn from 18 experiments that took data in the 1985, 1987 and 1990/91 fixed target running periods. For this discussion, the Fermilab Fixed Target Program is divided into 5 major topics: hadron structure, precision electroweak measurements, heavy quark production, polarization and magnetic moments, and searches for new phenomena. However, it should be noted that most experiments span several subtopics. Also, measurements within each subtopic often affect the results in other subtopics. For example, parton distributions from hadron structure measurements are used in the studies of heavy quark production

  6. Prospect of polarized targets in electron rings

    International Nuclear Information System (INIS)

    Holt, R.J.

    1984-01-01

    The feasibility of performing electron scattering experiments with polarized targets in electron storage rings is discussed. Three examples of the physics which would be accessible with this novel method are given. It is noted that this new method is compatible with recent proposals for linac-stretcher-ring accelerator designs. A new method for producing a polarized hydrogen or deuterium target is proposed and some preliminary results are described. A brief summary of laser-driven polarized targets as well as conventionally-produced polarized atomic beams is included

  7. Neutron performance analysis for ESS target proposal

    International Nuclear Information System (INIS)

    Magán, M.; Terrón, S.; Thomsen, K.; Sordo, F.; Perlado, J.M.; Bermejo, F.J.

    2012-01-01

    In the course of discussing different target types for their suitability in the European Spallation Source (ESS) one main focus was on neutronics' performance. Diverse concepts have been assessed baselining some preliminary engineering and geometrical details and including some optimization. With the restrictions and resulting uncertainty imposed by the lack of detailed designs optimizations at the time of compiling this paper, the conclusion drawn is basically that there is a little difference in the neutronic yield of the investigated targets. Other criteria like safety, environmental compatibility, reliability and cost will thus dominate the choice of an ESS target.

  8. Sputtering yield calculation for binary target

    International Nuclear Information System (INIS)

    Jimenez-Rodriguez, J.J.; Rodriguez-Vidal, M.; Valles-Abarca, J.A.

    1979-01-01

    The generalization for binary targets, of the ideas proposed by Sigmund for monoatomic targets, leads to a set of coupled intergrodifferential equations for the sputtering functions. After moment decomposition, the final formulae are obtained by the standard method based on the Laplace Transform, where the inverse transform is made with the aid of asymptotic expansions in the limit of very high projectile energy as compared to the surface binding energy. The possible loss of stoichiometry for binary targets is analyzed. Comparison of computed values of sputtering yield for normal incidence, with experimental results shows good agreement. (author)

  9. Targets for a Neutral Kaon Beam

    Energy Technology Data Exchange (ETDEWEB)

    Keith, Christopher [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States)

    2016-04-01

    A secondary beam of neutral Kaons is under consideration for Hall D at Jefferson Lab to perform spectroscopic studies of hyperons produced by K 0 L particles scattering from proton and deuteron targets. The proposed physics program would utilize the GlueX detector package currently installed in Hall D. This contribution looks at potential targets for use in the new facility, paying close attention to the existing infrastructure of GlueX and Hall D. Unpolarized cryotargets of liquid hydrogen and deuerium, as well as polarized solid targets of protons and deuterons are examined.

  10. Targeting engineering synchronization in chaotic systems

    Science.gov (United States)

    Bhowmick, Sourav K.; Ghosh, Dibakar

    2016-07-01

    A method of targeting engineering synchronization states in two identical and mismatch chaotic systems is explained in detail. The method is proposed using linear feedback controller coupling for engineering synchronization such as mixed synchronization, linear and nonlinear generalized synchronization and targeting fixed point. The general form of coupling design to target any desire synchronization state under unidirectional coupling with the help of Lyapunov function stability theory is derived analytically. A scaling factor is introduced in the coupling definition to smooth control without any loss of synchrony. Numerical results are done on two mismatch Lorenz systems and two identical Sprott oscillators.

  11. Thickness and uniformity measurements of nuclear targets

    International Nuclear Information System (INIS)

    Xu Guoji; Meng Xiangjin; Luo Xinghua; Guan Shouren

    1987-06-01

    This paper introduces the methods of target thickness and uniformity measurements including weighing, α-particle thickness gauge, quartz thickness gauge, optical transmittance and Rutherford backscattering. An α-particle gauging which measures target thicknesses up to several μm is metioned. A fast thickness measurements for C, Au and Cu targets by spectrophotometer is given. A high sensitive quartz gauge which can measure minimum deposit of 0.04 μg/cm 2 is described. Thickness and impurity determinations by RBS with accuracy better than 5% are summarized

  12. A windowless frozen hydrogen target system

    International Nuclear Information System (INIS)

    Knowles, P.E.; Beer, G.A.; Beveridge, J.L.

    1995-06-01

    A cryogenic target system has been constructed in which gaseous mixtures of all three hydrogen isotopes have been frozen onto a thin, 65 mm diameter gold foil. The foil is cooled to 3 K while inside a 70 K radiation shield, all of which is mounted in a vacuum system maintained at 10 -9 torr. Stable multi-layer hydrogen targets of known uniformity and thickness have been maintained for required measurement times of up to several days. To date, hundreds of targets have been successfully used in muon-catalyzed fusion experiments at TRIUMF. (author). 12 refs., 6 figs

  13. 29 mm Diameter Target Test Report

    Energy Technology Data Exchange (ETDEWEB)

    Woloshun, Keith Albert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Olivas, Eric Richard [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Dale, Gregory E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Naranjo, Angela Carol [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Romero, Frank Patrick [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Chemerisov, Sergey [Argonne National Lab. (ANL), Argonne, IL (United States); Gromov, Roman [Argonne National Lab. (ANL), Argonne, IL (United States)

    2017-10-23

    After numerous delays, the test of the 29 mm diameter target was conducted on 8/18/2017. The complete target design report, dated 8/15/2016, is reproduced below for completeness. This describes in detail the 10 disk target with varying thickness disks. The report presents and discusses the test results. In brief summary, there appears to have been multiple instrumentation errors. Measured temperatures, pressures and IR camera window temperature measurement are all suspect. All tests were done at 35 MeV, with 171 μA current, or 6 kW of beam power.

  14. Antiproton production target of the AA

    CERN Multimedia

    Photographic Service; CERN PhotoLab

    1980-01-01

    The target rods were initially of tungsten, later of iridium. Diameters were around 3 mm and the lengths 60-110 mm. The rod is embedded in graphite, pressed into an aluminium body with cooling fins for forced air cooling. The 26 GeV proton beam from the PS was focused to the dimension of the rod. To aim precisely at its centre, the target was fitted with a scintillator screen, with circles at every 5 mm radius. Both scintillator and target had to stand pulses of 1.4E13 protons every 4.8 s, without interruption for many months.

  15. Radar automatic target recognition (ATR) and non-cooperative target recognition (NCTR)

    CERN Document Server

    Blacknell, David

    2013-01-01

    The ability to detect and locate targets by day or night, over wide areas, regardless of weather conditions has long made radar a key sensor in many military and civil applications. However, the ability to automatically and reliably distinguish different targets represents a difficult challenge. Radar Automatic Target Recognition (ATR) and Non-Cooperative Target Recognition (NCTR) captures material presented in the NATO SET-172 lecture series to provide an overview of the state-of-the-art and continuing challenges of radar target recognition. Topics covered include the problem as applied to th

  16. TargetMine, an integrated data warehouse for candidate gene prioritisation and target discovery.

    Directory of Open Access Journals (Sweden)

    Yi-An Chen

    Full Text Available Prioritising candidate genes for further experimental characterisation is a non-trivial challenge in drug discovery and biomedical research in general. An integrated approach that combines results from multiple data types is best suited for optimal target selection. We developed TargetMine, a data warehouse for efficient target prioritisation. TargetMine utilises the InterMine framework, with new data models such as protein-DNA interactions integrated in a novel way. It enables complicated searches that are difficult to perform with existing tools and it also offers integration of custom annotations and in-house experimental data. We proposed an objective protocol for target prioritisation using TargetMine and set up a benchmarking procedure to evaluate its performance. The results show that the protocol can identify known disease-associated genes with high precision and coverage. A demonstration version of TargetMine is available at http://targetmine.nibio.go.jp/.

  17. Selective Nanoparticle Targeting of the Renal Tubules.

    Science.gov (United States)

    Williams, Ryan M; Shah, Janki; Tian, Helen S; Chen, Xi; Geissmann, Frederic; Jaimes, Edgar A; Heller, Daniel A

    2018-01-01

    Direct targeting to the kidneys is a promising strategy to improve drug therapeutic index for the treatment of kidney diseases. We sought to investigate the renal selectivity and safety of kidney-targeted mesoscale nanoparticle technology. We found that direct intravenous administration of these particles resulted in 26-fold renal selectivity and localized negligibly in the liver or other organs. The nanoparticles targeted the renal proximal tubular epithelial cells, as evidenced by intravital microscopy and ex vivo imaging. Mice treated with the nanoparticles exhibited no negative systemic consequences, immune reaction, liver impairment, or renal impairment. The localization of material selectively to the renal tubules is uncommon, and this work portends the development of renal-targeted drugs for the treatment of kidney diseases. © 2017 American Heart Association, Inc.

  18. RNA as a small molecule druggable target.

    Science.gov (United States)

    Rizvi, Noreen F; Smith, Graham F

    2017-12-01

    Small molecule drugs have readily been developed against many proteins in the human proteome, but RNA has remained an elusive target for drug discovery. Increasingly, we see that RNA, and to a lesser extent DNA elements, show a persistent tertiary structure responsible for many diverse and complex cellular functions. In this digest, we have summarized recent advances in screening approaches for RNA targets and outlined the discovery of novel, drug-like small molecules against RNA targets from various classes and therapeutic areas. The link of structure, function, and small-molecule Druggability validates now for the first time that RNA can be the targets of therapeutic agents. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Logarithm Laws and Shrinking Target Properties

    Indian Academy of Sciences (India)

    Abstract. We survey some of the recent developments in the study of logarithm laws and shrinking target properties for various families of dynamical systems. We discuss connections to geometry, diophantine approximation and probability theory.

  20. Crime clocks and target performance maps

    CSIR Research Space (South Africa)

    Cooper, Antony K

    1999-12-01

    Full Text Available for the prevention and management of crime. This paper describes two innovative techniques that were developed by CSIR for analysing crime: "crime clocks" and "target performance maps"....