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Sample records for tumor development focusing

  1. Recent developments: Washington focus

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    Recent weeks have seen considerable Congressional activity on uranium enrichment legislation. On August 2, the Senate passed the Energy ampersand Water Development Appropriations Bill, which funds the DOE and NRC programs. A conference committee must be convened to work out the differences between the House and Senate versions of the Bill. The House Science, Space and Technology subcommittee held one hearing, and also a markup of HR 2480, the House bill to restructure the uranium enrichment program as a government corporation. Also in the House of Representatives, subcommittees of the Energy and Commerce Committee, and the Interior and Insular Affairs Committee held a joint hearing on the Smith Barney report on DOE restructuring. Lastly, the USCEA's Nuclear Fuel Supply Committee met in San Francisco near the end of July

  2. Cancer Associated Fibroblasts and Tumor Growth: Focus on Multiple Myeloma

    International Nuclear Information System (INIS)

    De Veirman, Kim; Rao, Luigia; De Bruyne, Elke; Menu, Eline; Van Valckenborgh, Els; Van Riet, Ivan; Frassanito, Maria Antonia; Di Marzo, Lucia; Vacca, Angelo; Vanderkerken, Karin

    2014-01-01

    Cancer associated fibroblasts (CAFs) comprise a heterogeneous population that resides within the tumor microenvironment. They actively participate in tumor growth and metastasis by production of cytokines and chemokines, and the release of pro-inflammatory and pro-angiogenic factors, creating a more supportive microenvironment. The aim of the current review is to summarize the origin and characteristics of CAFs, and to describe the role of CAFs in tumor progression and metastasis. Furthermore, we focus on the presence of CAFs in hypoxic conditions in relation to multiple myeloma disease

  3. Cancer Associated Fibroblasts and Tumor Growth: Focus on Multiple Myeloma

    Energy Technology Data Exchange (ETDEWEB)

    De Veirman, Kim, E-mail: kdeveirm@vub.ac.be [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium); Rao, Luigia [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium); Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine, University of Bari Medical School, Bari I-70124 (Italy); De Bruyne, Elke; Menu, Eline; Van Valckenborgh, Els [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium); Van Riet, Ivan [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium); Stem Cell Laboratory, Division of Clinical Hematology, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels 1090 (Belgium); Frassanito, Maria Antonia [Department of Biomedical Sciences and Human Oncology, Section of General Pathology, University of Bari Medical School, Bari I-70124 (Italy); Di Marzo, Lucia; Vacca, Angelo [Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine, University of Bari Medical School, Bari I-70124 (Italy); Vanderkerken, Karin, E-mail: kdeveirm@vub.ac.be [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium)

    2014-06-27

    Cancer associated fibroblasts (CAFs) comprise a heterogeneous population that resides within the tumor microenvironment. They actively participate in tumor growth and metastasis by production of cytokines and chemokines, and the release of pro-inflammatory and pro-angiogenic factors, creating a more supportive microenvironment. The aim of the current review is to summarize the origin and characteristics of CAFs, and to describe the role of CAFs in tumor progression and metastasis. Furthermore, we focus on the presence of CAFs in hypoxic conditions in relation to multiple myeloma disease.

  4. Review of juxtaglomerular cell tumor with focus on pathobiological aspect

    Directory of Open Access Journals (Sweden)

    Pan Chin-Chen

    2011-08-01

    Full Text Available Abstract Juxtaglomerular cell tumor (JGCT generally affects adolescents and young adults. The patients experience symptoms related to hypertension and hypokalemia due to renin-secretion by the tumor. Grossly, the tumor is well circumscribed with fibrous capsule and the cut surface shows yellow or gray-tan color with frequent hemorrhage. Histologically, the tumor is composed of monotonous polygonal cells with entrapped normal tubules. Immunohistochemically, tumor cells exhibit a positive reactivity for renin, vimentin and CD34. Ultrastructurally, neoplastic cells contain rhomboid-shaped renin protogranules. Genetically, losses of chromosomes 9 and 11 were frequently observed. Clinically, the majority of tumors showed a benign course, but rare tumors with vascular invasion or metastasis were reported. JGCT is a curable cause of hypertensive disease if it is discovered early and surgically removed, but may cause a fatal outcome usually by a cerebrovascular attack or may cause fetal demise in pregnancy. Additionally, pathologists and urologists need to recognize that this neoplasm in most cases pursues a benign course, but aggressive forms may develop in some cases.

  5. Impact of the Tumor Microenvironment on Tumor-Infiltrating Lymphocytes: Focus on Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ivan J Cohen

    2017-09-01

    Full Text Available Immunotherapy is revolutionizing cancer care across disciplines. The original success of immune checkpoint blockade in melanoma has already been translated to Food and Drug Administration–approved therapies in a number of other cancers, and a large number of clinical trials are underway in many other disease types, including breast cancer. Here, we review the basic requirements for a successful antitumor immune response, with a focus on the metabolic and physical barriers encountered by lymphocytes entering breast tumors. We also review recent clinical trials of immunotherapy in breast cancer and provide a number of interesting questions that will need to be answered for successful breast cancer immunotherapy.

  6. Focusing on key development challenges

    International Development Research Centre (IDRC) Digital Library (Canada)

    addresses today's pressing environmental, social, economic, and political ... telecentre.org. Harness science, technology, and innovation to promote sustainable development and reduce poverty. ... capacities, support research that would lead to better policies and ... country researchers, and the private sector to produce.

  7. Immunoperoxidase staining and radioimmunobinding of human tumor markers separated by direct tissue agarose isoelectric focusing

    International Nuclear Information System (INIS)

    Saravis, C.A.; Cunningham, C.G.; Marasco, P.V.; Cook, R.B.; Zamcheck, N.; FMC Corp., Rockland, ME

    1980-01-01

    The new technique of agarose isoelectric focusing is used to identify, quantitate, and characterize specific tumor markers. After fixation of the isoelectric focusing patterns these are reacted with specific anti-tumor marker antisera, then with second antibody either peroxidase conjugated or radiolabellad (radioiodine). (RB) [de

  8. Neuroendocrine Tumors: A Focus on Liver Metastatic Lesions

    Energy Technology Data Exchange (ETDEWEB)

    Limouris, Georgios S., E-mail: nucleard@aretaieio.uoa.gr [Athens University Medical Faculty, Nuclear Medicine Division, Radiology Department, Aretaieion University Hospital, Athens (Greece)

    2012-02-28

    Transhepatic radionuclide infusion has been introduced as a new treatment approach for unresectable liver neuroendocrine metastatic lesions with the prerequisite of a positive In-111 Pentetreotide (Octreoscan). Patients with multiple liver neuroendocrine metastases can be locally treated after selective hepatic artery catheterization and infusion of radiolabeled somatostatin analogs, and in case of extra-hepatic secondary spread, after simple i.v. application. According to the world wide references, the average dose per session to each patient is 6.3 ± 0.3 GBq (∼160–180 mCi) of In-111-DTPA-Phe1-Pentetreotide, 10- to 12-fold in total, administered monthly or of 4.1 ± 0.2 GBq (∼105–116 mCi) of Y-90 DOTA TOC, threefold in total, or of 7.0 ± 0.4 GBq (∼178–200 mCi) of Lu-177 DOTA TATE, fourfold to sixfold in total (the choice of which being based on the tumor size, assessed by CT or MRI). Follow-up at monthly intervals has to be performed by means of ultrasonography (US). Treatment response has to be assessed according to the WHO criteria (RECIST or SWOG).

  9. Cavitation-enhanced MR-guided focused ultrasound ablation of rabbit tumors in vivo using phase shift nanoemulsions

    OpenAIRE

    Kopechek, Jonathan A; Park, Eun-Joo; Zhang, Yong-Zhi; Vykhodtseva, Natalia I; McDannold, Nathan J; Porter, Tyrone M

    2014-01-01

    Advanced tumors are often inoperable due to their size and proximity to critical vascular structures. High intensity focused ultrasound (HIFU) has been developed to non-invasively thermally ablate inoperable solid tumors. However, the clinical feasibility of HIFU ablation therapy has been limited by the long treatment times (on the order of hours) and high acoustic intensities required. Studies have shown that inertial cavitation can enhance HIFU-mediated heating by generating broadband acous...

  10. Amide proton transfer imaging of high intensity focused ultrasound-treated tumor tissue

    NARCIS (Netherlands)

    Hectors, S.J.C.G.; Jacobs, I.; Strijkers, G.J.; Nicolay, K.

    2014-01-01

    Purpose: In this study, the suitability of amide proton transfer (APT) imaging as a biomarker for the characterization of high intensity focused ultrasound (HIFU)-treated tumor tissue was assessed. Methods: APT imaging was performed on tumor-bearing mice before (n=15), directly after (n=15) and at 3

  11. Amide Proton Transfer Imaging of High Intensity Focused Ultrasound-Treated Tumor Tissue

    NARCIS (Netherlands)

    Hectors, Stefanie J. C. G.; Jacobs, Igor; Strijkers, Gustav J.; Nicolay, Klaas

    2014-01-01

    PurposeIn this study, the suitability of amide proton transfer (APT) imaging as a biomarker for the characterization of high intensity focused ultrasound (HIFU)-treated tumor tissue was assessed. MethodsAPT imaging was performed on tumor-bearing mice before (n=15), directly after (n=15) and at 3

  12. T1 ρ mapping for the evaluation of high intensity focused ultrasound tumor treatment

    NARCIS (Netherlands)

    Hectors, Stefanie J. C. G.; Moonen, Rik P. M.; Strijkers, Gustav J.; Nicolay, Klaas

    2015-01-01

    This study was aimed to assess the effects of High Intensity Focused Ultrasound (HIFU) thermal ablation on tumor T1ρ . In vivo T1ρ measurements of murine tumors at various spin-lock amplitudes (B1 = 0-2000 Hz) were performed before (n = 13), directly after (n = 13) and 3 days (n = 7) after HIFU

  13. Professional Development: Focusing on Transition. Issue Brief

    Science.gov (United States)

    de Azúa, Ramón L.; Keleher, Julia

    2017-01-01

    In 2017, the National Technical Assistance Center for the Education of Neglected or Delinquent Children and Youth (NDTAC) released its first in a series of professional development briefs that focus on the professional development needs and interests of Neglected or Delinquent (N or D) State coordinators, correctional educators, and providers of…

  14. RNA-Sequencing of Primary Retinoblastoma Tumors Provides New Insights and Challenges Into Tumor Development

    Directory of Open Access Journals (Sweden)

    Sailaja V. Elchuri

    2018-05-01

    Full Text Available Retinoblastoma is rare tumor of the retina caused by the homozygous loss of the Retinoblastoma 1 tumor suppressor gene (RB1. Loss of the RB1 protein, pRB, results in de-regulated activity of the E2F transcription factors, chromatin changes and developmental defects leading to tumor development. Extensive microarray profiles of these tumors have enabled the identification of genes sensitive to pRB disruption, however, this technology has a number of limitations in the RNA profiles that they generate. The advent of RNA-sequencing has enabled the global profiling of all of the RNA within the cell including both coding and non-coding features and the detection of aberrant RNA processing events. In this perspective, we focus on discussing how RNA-sequencing of rare Retinoblastoma tumors will build on existing data and open up new area’s to improve our understanding of the biology of these tumors. In particular, we discuss how the RB-research field may be to use this data to determine how RB1 loss results in the expression of; non-coding RNAs, causes aberrant RNA processing events and how a deeper analysis of metabolic RNA changes can be utilized to model tumor specific shifts in metabolism. Each section discusses new opportunities and challenges associated with these types of analyses and aims to provide an honest assessment of how understanding these different processes may contribute to the treatment of Retinoblastoma.

  15. Does Tumor Development Follow a Programmed Path?

    Science.gov (United States)

    Austin, Robert

    2011-03-01

    The initiation and progression of a tumor is a complex process, resembling the growth of a embryo in terms of the stages of development and increasing differentiation and somatic evolution of constituent cells in the community of cells that constitute the tumor. Typically we view cancer cells as rogue individuals violating the rules of the games played within an organism, but I would suggest that what we see is a programmed and algorithmic process. I will then question If tumor progression is dominated by the random acquisition of successive survival traits, or by a systematic and sequential unpacking of ``weapons'' from a pre-adapted ``toolkit'' of genetic and epigenetic potentialities? Can we then address this hypothesis by data mining solid tumors layer by layer? Support of the NSF and the NCI is gratefully acknowledged.

  16. Cavitation-enhanced MR-guided focused ultrasound ablation of rabbit tumors in vivo using phase shift nanoemulsions

    Science.gov (United States)

    Kopechek, Jonathan A.; Park, Eun-Joo; Zhang, Yong-Zhi; Vykhodtseva, Natalia I.; McDannold, Nathan J.; Porter, Tyrone M.

    2014-07-01

    Advanced tumors are often inoperable due to their size and proximity to critical vascular structures. High intensity focused ultrasound (HIFU) has been developed to non-invasively thermally ablate inoperable solid tumors. However, the clinical feasibility of HIFU ablation therapy has been limited by the long treatment times (on the order of hours) and high acoustic intensities required. Studies have shown that inertial cavitation can enhance HIFU-mediated heating by generating broadband acoustic emissions that increase tissue absorption and accelerate HIFU-induced heating. Unfortunately, initiating inertial cavitation in tumors requires high intensities and can be unpredictable. To address this need, phase-shift nanoemulsions (PSNE) have been developed. PSNE consist of lipid-coated liquid perfluorocarbon droplets that are less than 200 nm in diameter, thereby allowing passive accumulation in tumors through leaky tumor vasculature. PSNE can be vaporized into microbubbles in tumors in order to nucleate cavitation activity and enhance HIFU-mediated heating. In this study, MR-guided HIFU treatments were performed on intramuscular rabbit VX2 tumors in vivo to assess the effect of vaporized PSNE on acoustic cavitation and HIFU-mediated heating. HIFU pulses were delivered for 30 s using a 1.5 MHz, MR-compatible transducer, and cavitation emissions were recorded with a 650 kHz ring hydrophone while temperature was monitored using MR thermometry. Cavitation emissions were significantly higher (P cavitation which correlates with enhanced HIFU-mediated heating in tumors. This suggests that PSNE could potentially be used to reduce the time and/or acoustic intensity required for HIFU-mediated heating, thereby increasing the feasibility and clinical efficacy of HIFU thermal ablation therapy.

  17. Extracellular matrix in canine mammary tumors with special focus on versican, a versatile extracellular proteoglycan

    NARCIS (Netherlands)

    Erdélyi, Ildikó

    2006-01-01

    The extracellular matrix (ECM) research has become fundamental to understand cancer. This thesis focuses on the exploration of ECM composition and organization in canine mammary tumors, with a special interest in the large chondroitin-sulfate proteoglycan (PG), versican. Chapter 1 gives an

  18. Magnetic resonance–guided interstitial high-intensity focused ultrasound for brain tumor ablation

    Science.gov (United States)

    MacDonell, Jacquelyn; Patel, Niravkumar; Rubino, Sebastian; Ghoshal, Goutam; Fischer, Gregory; Burdette, E. Clif; Hwang, Roy; Pilitsis, Julie G.

    2018-01-01

    Currently, treatment of brain tumors is limited to resection, chemotherapy, and radiotherapy. Thermal ablation has been recently explored. High-intensity focused ultrasound (HIFU) is being explored as an alternative. Specifically, the authors propose delivering HIFU internally to the tumor with an MRI-guided robotic assistant (MRgRA). The advantage of the authors’ interstitial device over external MRI-guided HIFU (MRgHIFU) is that it allows for conformal, precise ablation and concurrent tissue sampling. The authors describe their workflow for MRgRA HIFU delivery. PMID:29385926

  19. Clinicopathological characteristics of duodenal epithelial neoplasms: Focus on tumors with a gastric mucin phenotype (pyloric gland-type tumors.

    Directory of Open Access Journals (Sweden)

    Takehiro Mitsuishi

    Full Text Available Epithelial tumors less commonly occur in the duodenum than in the stomach or large intestine. The clinicopathological characteristics of duodenal epithelial tumors remain a matter of debate. We therefore studied resected specimens to investigate the clinicopathological characteristics of duodenal epithelial tumors.Among duodenal epithelial tumors resected endoscopically or surgically in our hospital, we studied the clinicopathological characteristics of 110 adenomas or intramucosal carcinomas. The grade of atypia of all tumors was classified into 3 groups according to the World Health Organization (WHO 2010 classification. The tumors were immunohistochemically evaluated to determine the frequency of differentiation toward fundic glands.As for patient characteristics, there were 76 men (75.2% and 25 women (24.8%, with a median age of 65 years (range, 34 to 84. The tumors most commonly arose in the first to second part of the duodenum. Many lesions were flat, and the median tumor diameter was 8.0 mm. The lesions were classified into 2 types according to mucin phenotype: intestinal-type tumors (98 lesions, 89.1% and gastric-type tumors (12 lesions, 10.9%. Intestinal-type tumors were subdivided into 2 groups: tubular-type tumors (91 lesions, 82.7% and tubulovillous-type tumors (7 lesions, 6.4%. Gastric-type tumors were classified into 2 types: foveolar type (3 lesions, 2.7% and pyloric gland-type (PG tumors (9 lesions, 8.2%. The grade of atypia was significantly higher in gastric-type tumors (p<0.01. PG tumors were gastric-type tumors characterized by pyloric glands and findings suggesting differentiation toward fundic glands.About 10% of the duodenal tumors had a gastric-type mucin phenotype. Gastric-type tumors showed high-grade atypia. In particular, PG tumors showed similarities to PG tumors of the stomach, such as differentiation toward fundic glands.

  20. Cavitation-enhanced MR-guided focused ultrasound ablation of rabbit tumors in vivo using phase shift nanoemulsions

    International Nuclear Information System (INIS)

    Kopechek, Jonathan A; Porter, Tyrone M; Park, Eun-Joo; Zhang, Yong-Zhi; Vykhodtseva, Natalia I; McDannold, Nathan J

    2014-01-01

    Advanced tumors are often inoperable due to their size and proximity to critical vascular structures. High intensity focused ultrasound (HIFU) has been developed to non-invasively thermally ablate inoperable solid tumors. However, the clinical feasibility of HIFU ablation therapy has been limited by the long treatment times (on the order of hours) and high acoustic intensities required. Studies have shown that inertial cavitation can enhance HIFU-mediated heating by generating broadband acoustic emissions that increase tissue absorption and accelerate HIFU-induced heating. Unfortunately, initiating inertial cavitation in tumors requires high intensities and can be unpredictable. To address this need, phase-shift nanoemulsions (PSNE) have been developed. PSNE consist of lipid-coated liquid perfluorocarbon droplets that are less than 200 nm in diameter, thereby allowing passive accumulation in tumors through leaky tumor vasculature. PSNE can be vaporized into microbubbles in tumors in order to nucleate cavitation activity and enhance HIFU-mediated heating. In this study, MR-guided HIFU treatments were performed on intramuscular rabbit VX2 tumors in vivo to assess the effect of vaporized PSNE on acoustic cavitation and HIFU-mediated heating. HIFU pulses were delivered for 30 s using a 1.5 MHz, MR-compatible transducer, and cavitation emissions were recorded with a 650 kHz ring hydrophone while temperature was monitored using MR thermometry. Cavitation emissions were significantly higher (P < 0.05) after PSNE injection and this was well correlated with enhanced HIFU-mediated heating in tumors. The peak temperature rise induced by sonication was significantly higher (P < 0.05) after PSNE injection. For example, the mean per cent change in temperature achieved at 5.2 W of acoustic power was 46 ± 22% with PSNE injection. The results indicate that PSNE nucleates cavitation which correlates with enhanced HIFU-mediated heating in tumors. This suggests that PSNE could

  1. Cavitation-enhanced delivery of a replicating oncolytic adenovirus to tumors using focused ultrasound.

    Science.gov (United States)

    Bazan-Peregrino, Miriam; Rifai, Bassel; Carlisle, Robert C; Choi, James; Arvanitis, Costas D; Seymour, Leonard W; Coussios, Constantin C

    2013-07-10

    Oncolytic viruses (OV) and ultrasound-enhanced drug delivery are powerful novel technologies. OV selectively self-amplify and kill cancer cells but their clinical use has been restricted by limited delivery from the bloodstream into the tumor. Ultrasound has been previously exploited for targeted release of OV in vivo, but its use to induce cavitation, microbubble oscillations, for enhanced OV tumor extravasation and delivery has not been previously reported. By identifying and optimizing the underlying physical mechanism, this work demonstrates that focused ultrasound significantly enhances the delivery and biodistribution of systemically administered OV co-injected with microbubbles. Up to a fiftyfold increase in tumor transgene expression was achieved, without any observable tissue damage. Ultrasound exposure parameters were optimized as a function of tumor reperfusion time to sustain inertial cavitation, a type of microbubble activity, throughout the exposure. Passive detection of acoustic emissions during treatment confirmed inertial cavitation as the mechanism responsible for enhanced delivery and enabled real-time monitoring of successful viral delivery. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Cancer vaccine development: Designing tumor cells for greater immunogenicity

    Science.gov (United States)

    Bozeman, Erica N.; Shashidharamurthy, Rangaiah; Paulos, Simon A.; Palaniappan, Ravi; D’Souza, Martin; Selvaraj, Periasamy

    2014-01-01

    Cancer vaccine development is one of the most hopeful and exhilarating areas in cancer research. For this reason, there has been a growing interest in the development and application of novel immunotherapies for the treatment of cancer with the focus being on stimulating the immune system to target tumor cells specifically while leaving normal cells unharmed. From such research has emerged a host of promising immunotherapies such as dendritic cell-based vaccines, cytokine therapies and gene transfer technology. These therapies seek to counteract the poor immunogenicity of tumors by augmenting the host’s immune system with a variety of immunostimulatory proteins such as cytokines and costimulatory molecules. While such therapies have proven effective in the induction of anti-tumor immunity in animal models, they are less than optimal and pose a high risk of clinical infeasibility. Herein, we further discuss these immunotherapies as well as a feasible and efficient alternative that, in pre-clinical animal models, allows for the expression of specific immunostimulatory molecules on the surface of tumor cells by a novel protein transfer technology. PMID:20036822

  3. Review of reasearch and technical development focused

    Directory of Open Access Journals (Sweden)

    Slavkovský Marián

    1998-12-01

    Full Text Available Treatment of flotation tetrahedrite concentrates produced from the of ore mined in the Rudňany and Rožňava ore deposits is a very complex technological problem. This problem has not been solved succesfuly so far. The presence and quality of undesired metal components such as antimony and mercury in the product of a wet ore dressing is a limiting factor for subsequent metalurgical process to obtain pure metal copper and/or silver in copper smelter plants. This factor has been the principal reason of a great effort provided in this respects by both, manufacturers and reaserchers mainly in the last 25 years. This article is focused on the summary of mentioned activities.

  4. New developments in transference focused psychotherapy.

    Science.gov (United States)

    Kernberg, Otto F

    2016-04-01

    This paper will summarize recent clinical developments in the treatment of borderline patients at the Personality Disorders Institute at Cornell. The experiences under review will include the careful, ongoing monitoring of developments in the patient's life outside the sessions, and their consideration in diagnosing affective dominance during the hours. Other issues include the discussion of a 'second chance' approach to contract violations; the assessment and concern with the patient's assumption of responsibility for himself; the contradictions between actual behavior patterns and life goals, and between personality potentials and present functioning; the technical implications of particular constellations of regressive narcissistic features; drug dependence and antisocial behavior; and life goals and treatment goals. Copyright © 2016 Institute of Psychoanalysis.

  5. [The development of novel tumor targeting delivery strategy].

    Science.gov (United States)

    Gao, Hui-le; Jiang, Xin-guo

    2016-02-01

    Tumor is one of the most serious threats for human being. Although many anti-tumor drugs are approved for clinical use, the treatment outcome is still modest because of the poor tumor targeting efficiency and low accumulation in tumor. Therefore, it is important to deliver anti-tumor drug into tumor efficiently, elevate drug concentration in tumor tissues and reduce the drug distribution in normal tissues. And it has been one of the most attractive directions of pharmaceutical academy and industry. Many kinds of strategies, especially various nanoparticulated drug delivery systems, have been developed to address the critical points of complex tumor microenvironment, which are partially or mostly satisfied for tumor treatment. In this paper, we carefully reviewed the novel targeting delivery strategies developed in recent years. The most powerful method is passive targeting delivery based on the enhanced permeability and retention(EPR) effect, and most commercial nanomedicines are based on the EPR effect. However, the high permeability and retention require different particle sizes, thus several kinds of size-changeable nanoparticles are developed, such as size reducible particles and assemble particles, to satisfy the controversial requirement for particle size and enhance both tumor retention and penetration. Surface charge reversible nanoparticles also shows a high efficiency because the anionic charge in blood circulation and normal organs decrease the unintended internalization. The charge can change into positive in tumor microenvironment, facilitating drug uptake by tumor cells. Additionally, tumor microenvironment responsive drug release is important to decrease drug side effect, and many strategies are developed, such as p H sensitive release and enzyme sensitive release. Except the responsive nanoparticles, shaping tumor microenvironment could attenuate the barriers in drug delivery, for example, decreasing tumor collagen intensity and normalizing tumor

  6. Simulations of adaptive temperature control with self-focused hyperthermia system for tumor treatment.

    Science.gov (United States)

    Hu, Jiwen; Ding, Yajun; Qian, Shengyou; Tang, Xiangde

    2013-01-01

    The control problem in ultrasound therapy is to destroy the tumor tissue while not harming the intervening healthy tissue with a desired temperature elevation. The objective of this research is to present a robust and feasible method to control the temperature distribution and the temperature elevation in treatment region within the prescribed time, which can improve the curative effect and decrease the treatment time for heating large tumor (≥2.0cm in diameter). An adaptive self-tuning-regulator (STR) controller has been introduced into this control method by adding a time factor with a recursive algorithm, and the speed of sound and absorption coefficient of the medium is considered as a function of temperature during heating. The presented control method is tested for a self-focused concave spherical transducer (0.5MHz, 9cm aperture, 8.0cm focal length) through numerical simulations with three control temperatures of 43°C, 50°C and 55°C. The results suggest that this control system has adaptive ability for variable parameters and has a rapid response to the temperature and acoustic power output in the prescribed time for the hyperthermia interest. There is no overshoot during temperature elevation and no oscillation after reaching the desired temperatures. It is found that the same results can be obtained for different frequencies and temperature elevations. This method can obtain an ellipsoid-shaped ablation region, which is meaningful for the treatment of large tumor. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Thermal and mechanical high-intensity focused ultrasound: perspectives on tumor ablation, immune effects and combination strategies.

    Science.gov (United States)

    van den Bijgaart, Renske J E; Eikelenboom, Dylan C; Hoogenboom, Martijn; Fütterer, Jurgen J; den Brok, Martijn H; Adema, Gosse J

    2017-02-01

    Tumor ablation technologies, such as radiofrequency-, cryo- or high-intensity focused ultrasound (HIFU) ablation will destroy tumor tissue in a minimally invasive manner. Ablation generates large volumes of tumor debris in situ, releasing multiple bio-molecules like tumor antigens and damage-associated molecular patterns. To initiate an adaptive antitumor immune response, antigen-presenting cells need to take up tumor antigens and, following activation, present them to immune effector cells. The impact of the type of tumor ablation on the precise nature, availability and suitability of the tumor debris for immune response induction, however, is poorly understood. In this review, we focus on immune effects after HIFU-mediated ablation and compare these to findings using other ablation technologies. HIFU can be used both for thermal and mechanical destruction of tissue, inducing coagulative necrosis or subcellular fragmentation, respectively. Preclinical and clinical results of HIFU tumor ablation show increased infiltration and activation of CD4 + and CD8 + T cells. As previously observed for other types of tumor ablation technologies, however, this ablation-induced enhanced infiltration alone appears insufficient to generate consistent protective antitumor immunity. Therapies combining ablation with immune stimulation are therefore expected to be key to boost HIFU-induced immune effects and to achieve systemic, long-lasting, antitumor immunity.

  8. The importance of time interval to development of second tumor in metachronous bilateral wilms' tumor

    International Nuclear Information System (INIS)

    Paulino, Arnold C.; Thakkar, Bharat; Henderson, William G.

    1997-01-01

    Purpose: To determine whether the time interval to development of second tumor is a prognostic factor for overall survival in children with metachronous bilateral Wilms' tumor and to give a recommendation regarding screening of the contralateral kidney in patients with Wilms' tumor. Materials and Management: A literature search using MEDLINE was performed of manuscripts in the English language from 1950-1996 and identified 108 children with metachronous bilateral Wilms' tumor. Children were classified according to time interval to development of a contralateral Wilms' tumor ( 78 mos (2), 78 - < 84 mos (1), 84 - < 90 mos (0), 90 - < 96 mos (1), ≥ 96 mos (0). Analysis of overall survival in patients with a time interval of < 18 months and ≥ 18 months showed a 10 year survival of 39.6% and 55.2%, respectively (p = 0.024, log-rank test). Conclusions: Children with metachronous bilateral Wilms' tumor who develop a contralateral tumor at a time interval of ≥ 18 months from the initial Wilms' tumor had a better overall survival than children with a time interval of < 18 months. Screening by abdominal ultrasound of the contralateral kidney for more than 5 years after initial diagnosis of Wilms' tumor may not be necessary since 102/106 (96.2%) of children had a time interval to second tumor of < 60 months

  9. Conjunctival Melanocytic Tumors-New Developments

    Directory of Open Access Journals (Sweden)

    Hülya Gökmen Soysal

    2014-09-01

    Full Text Available Melanocytic lesions of the conjunctiva represent a wide spectrum of tumors that include benign, premalignant, and malignant tumors. There are many ongoing arguments about the definition, classification, and therapeutic options of the conjunctival melanocytic tumors with many different suggestions. Conjunctival nevi are the most common melanocytic tumors and their risk of malignant transformation is less than1%. Primary acquired melanosis (PAM histopathologically includes various types of lesions from increased melanin pigmentation without melanocyte proliferation to melanoma in situ and is accepted as a clinical definition, so that a new classification is recommended which is based on more objective criteria than before. Although conjunctival melanoma is seen rarely, it is associated with a high mortality rate. Management of these tumors mainly involves surgery and adjuvant topical chemotherapy, cryotherapy, and radiation therapy that help improving the survival, however, new options are being investigated related to genetic and molecular researches. (Turk J Ophthalmol 2014; 44: Supplement 15-21

  10. Development of synchronous VHL syndrome tumors reveals contingencies and constraints to tumor evolution

    DEFF Research Database (Denmark)

    Fisher, Rosalie; Horswell, Stuart; Rowan, Andrew

    2014-01-01

    are contingent upon the nature of 3p loss of heterozygosity occurring early in tumorigenesis. However, despite distinct 3p events, genomic, proteomic and immunohistochemical analyses reveal evidence for convergence upon the PI3K-AKT-mTOR signaling pathway. Four germline tumors in this young patient...... a germline VHL mutation, the evolutionary principles of contingency and convergence in tumor development are complementary. In this small set of patients with early stage VHL-associated tumors, there is reduced mutation burden and limited evidence of intra-tumor heterogeneity....

  11. Targeted therapy of animal eyes with tumors by laser-generated focused ultrasound (Conference Presentation)

    Science.gov (United States)

    Lee, Taehwa; Luo, Wei; Demirci, Hakan; Guo, L. Jay

    2016-03-01

    Cavitation therapy based on high-amplitude focused ultrasound (e.g., Histotripsy) has shown great promise in clinical trials. The technique realizes localized treatments of tissues and diseased cells by controlling cavitation zones, which can be even smaller than its acoustic spot sizes. Also, the short pressure pulse used in the technique can minimize the unwanted heat accumulation, which the conventional piezoelectric transducers suffer from due to low operating frequencies and relatively long acoustic pulses. However, this modality requires bulky system composed of array of piezoelectric elements and electric amplifiers in order to obtain high pressure amplitude. Moreover, especially when treating an area much smaller than the acoustic spot size, this approach may be vulnerable to nucleation sites within the focal volume, which can potentially induce cavitation and thus enlarge the total treatment area. Here, we show targeted cell-level therapy by using laser generated ultrasound. By employing a concave lens coated by a carbon nanotube (CNT)-polymer composite, high-amplitude acoustic pressure can be obtained at a tight focal spot (small focal spot, comparable to cavitation zone, lead to controlled cavitation treatment. Such feature can be exploited for treating intraocular tumors but without harming other parts of the eye (e.g. healthy retina and choroid) and therefore preserve the vision of the patients. We demonstrate that the localized disruption effects can be used for cell-level surgery to remove cells and to kill cells. Some experimental examples are shown using animal eyeballs.

  12. The Effects of Radiation and Dose-Fractionation on Cancer and Non-Tumor Disease Development

    Directory of Open Access Journals (Sweden)

    Gayle E. Woloschak

    2012-12-01

    Full Text Available The Janus series of radiation experiments, conducted from 1970 to 1992, explored the effects of gamma and neutron radiation on animal lifespan and disease development. Data from these experiments presents an opportunity to conduct a large scale analysis of both tumor and non-tumor disease development. This work was focused on a subset of animals from the Janus series of experiments, comparing acute or fractionated exposures of gamma or neutron radiation on the hazards associated with the development of tumor and non-tumor diseases of the liver, lung, kidney or vascular system. This study also examines how the co-occurrence of non-tumor diseases may affect tumor-associated hazards. While exposure to radiation increases the hazard of dying with tumor and non-tumor diseases, dose fractionation modulates these hazards, which varies across different organ systems. Finally, the effect that concurrent non-cancer diseases have on the hazard of dying with a tumor also differs by organ system. These results highlight the complexity in the effects of radiation on the liver, lung, kidney and vascular system.

  13. Development of a focused ion beam micromachining system

    Energy Technology Data Exchange (ETDEWEB)

    Pellerin, J.G.; Griffis, D.; Russell, P.E.

    1988-12-01

    Focused ion beams are currently being investigated for many submicron fabrication and analytical purposes. An FIB micromachining system consisting of a UHV vacuum system, a liquid metal ion gun, and a control and data acquisition computer has been constructed. This system is being used to develop nanofabrication and nanomachining techniques involving focused ion beams and scanning tunneling microscopes.

  14. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    Energy Technology Data Exchange (ETDEWEB)

    Selle, F.; Gligorov, J. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France); Richard, S.; Khalil, A. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Alexandre, I. [Medical Oncology Department, Hospital Centre of Bligny, Briis-sous-Forges (France); Avenin, D.; Provent, S.; Soares, D.G. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Lotz, J.P. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France)

    2014-11-04

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis.

  15. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    International Nuclear Information System (INIS)

    Selle, F.; Gligorov, J.; Richard, S.; Khalil, A.; Alexandre, I.; Avenin, D.; Provent, S.; Soares, D.G.; Lotz, J.P.

    2014-01-01

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis

  16. A drug development perspective on targeting tumor-associated myeloid cells.

    Science.gov (United States)

    Majety, Meher; Runza, Valeria; Lehmann, Christian; Hoves, Sabine; Ries, Carola H

    2018-02-01

    Despite decades of research, cancer remains a devastating disease and new treatment options are needed. Today cancer is acknowledged as a multifactorial disease not only comprising of aberrant tumor cells but also the associated stroma including tumor vasculature, fibrotic plaques, and immune cells that interact in a complex heterotypic interplay. Myeloid cells represent one of the most abundant immune cell population within the tumor stroma and are equipped with a broad functional repertoire that promotes tumor growth by suppressing cytotoxic T cell activity, stimulating neoangiogenesis and tissue remodeling. Therefore, myeloid cells have become an attractive target for pharmacological intervention. In this review, we summarize the pharmacological approaches to therapeutically target tumor-associated myeloid cells with a focus on advanced programs that are clinically evaluated. In addition, for each therapeutic strategy, the preclinical rationale as well as advantages and challenges from a drug development perspective are discussed. © 2017 Federation of European Biochemical Societies.

  17. Liposomes and nanotechnology in drug development: focus on oncotargets

    Directory of Open Access Journals (Sweden)

    Kozako T

    2012-09-01

    Full Text Available Tomohiro Kozako,1 Naomichi Arima,2 Makoto Yoshimitsu,3 Shin-Ichro Honda,1 Shinji Soeda11Department of Biochemistry, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan; 2Division of Hematology and Immunology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan; 3Department of Hematology and Immunology, Kagoshima University Hospital, Kagoshima, JapanAbstract: Nanotechnology is the development of an engineered device at the atomic, molecular, and macromolecular level in the nanometer range. Advances in nanotechnology have proven beneficial in therapeutic fields such as drug-delivery and gene/protein delivery. Antigen delivery systems are important for inducing and modifying immune responses. In cellular immunity, cytotoxic T lymphocytes (CTLs are important in the host defense against tumors. Key to the development of CTL-inducible vaccines is the ability to deliver antigens to antigen-presenting cells efficiently and to induce the subsequent activation of T cell-mediated immunity without adjuvants, as they can induce excessive inflammation leading to systemic febrile disease. Since expression and cloning methods for tumor-associated antigens have been reported, cancer vaccines that induce effective cell immunity may be promising therapeutic candidates, but Th2 cells are undesirable for use in cancer immunotherapy. Peptide vaccines have immunological and economic advantages as cancer vaccines because CTL epitope peptides from tumor-associated antigens have high antigen-specificity. However, cancer vaccines have had limited effectiveness in clinical responses due to the ability of cancer cells to “escape” from cancer immunity and a low efficiency of antigen-specific CTL induction due to immunogenic-free synthetic peptides. In contrast, carbohydrate-decorated particles such as carbohydrate-coated liposomes with encapsulated antigens might be more suitable as

  18. Development of focused ion beam systems with various ion species

    International Nuclear Information System (INIS)

    Ji Qing; Leung, K.-N.; King, Tsu-Jae; Jiang Ximan; Appleton, Bill R.

    2005-01-01

    Conventional focused ion beam systems employ a liquid-metal ion source (LMIS) to generate high-brightness beams, such as Ga + beams. Recently there has been an increased need for focused ion beams in areas like biological studies, advanced magnetic-film manufacturing and secondary-ion mass spectroscopy (SIMS). In this article, status of development on focused ion beam systems with ion species such as O 2 + , P + , and B + will be reviewed. Compact columns for forming focused ion beams from low energy (∼3keV), to intermediate energy (∼35keV) are discussed. By using focused ion beams, a SOI MOSFET is fabricated entirely without any masks or resist

  19. A physical theory of focus development in plant disease

    NARCIS (Netherlands)

    Zawolek, M.W.

    1989-01-01

    Chapter 1. The 'diffusion theory' of focus development in plant disease is introduced. Foci develop in space and time. The theory applies primarily to air-borne fungal diseases of the foliage.

    Chapter 2. The contents of the present volume are outlined.

    Chapter 3. The

  20. Development of the focus system for heaven-I

    International Nuclear Information System (INIS)

    Xiang Yihuai; Zhou Chuangzhi; Gong Kun; Ma Jinglong; Dai Hui; Shan Yusheng; Wang Naiyan

    2003-01-01

    This paper introduces the method of guiding the six KrF laser beams into target chamber and the development of focus system in MOPA angular multiplex system for Heaven-I. The six beams are focused to the vacuum target chamber by six plane-convex lenses. The focal spot on the target is measured by UV CCD camera, the diameter of the focal spot of six beams is 290 μm, the focusing power density on the target is 8 x 10 12 W/cm 2

  1. Enhancement in blood-tumor barrier permeability and delivery of liposomal doxorubicin using focused ultrasound and microbubbles: evaluation during tumor progression in a rat glioma model

    Science.gov (United States)

    Aryal, Muna; Park, Juyoung; Vykhodtseva, Natalia; Zhang, Yong-Zhi; McDannold, Nathan

    2015-03-01

    Effective drug delivery to brain tumors is often challenging because of the heterogeneous permeability of the ‘blood tumor barrier’ (BTB) along with other factors such as increased interstitial pressure and drug efflux pumps. Focused ultrasound (FUS) combined with microbubbles can enhance the permeability of the BTB in brain tumors, as well as the blood-brain barrier in the surrounding tissue. In this study, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to characterize the FUS-induced permeability changes of the BTB in a rat glioma model at different times after implantation. 9L gliosarcoma cells were implanted in both hemispheres in male rats. At day 9, 14, or 17 days after implantation, FUS-induced BTB disruption using 690 kHz ultrasound and definity microbubbles was performed in one tumor in each animal. Before FUS, liposomal doxorubicin was administered at a dose of 5.67 mg kg-1. This chemotherapy agent was previously shown to improve survival in animal glioma models. The transfer coefficient Ktrans describing extravasation of the MRI contrast agent Gd-DTPA was measured via DCE-MRI before and after sonication. We found that tumor doxorubicin concentrations increased monotonically (823  ±  600, 1817  ±  732 and 2432  ±  448 ng g-1) in the control tumors at 9, 14 and 17 d. With FUS-induced BTB disruption, the doxorubicin concentrations were enhanced significantly (P benefit from FUS-induced drug enhancement. Corresponding enhancements in Ktrans were found to be variable in large/late-stage tumors and not significantly different than controls, perhaps reflecting the size mismatch between the liposomal drug (~100 nm) and Gd-DTPA (molecular weight: 938 Da; hydrodynamic diameter: ≃2 nm). It may be necessary to use a larger MRI contrast agent to effectively evaluate the sonication-induced enhanced permeabilization in large/late-stage tumors when a large drug carrier such as a liposome is used.

  2. Mechanic effect of pulsed focused ultrasound in tumor and muscle tissue evaluated by MRI, histology, and microarray analysis

    International Nuclear Information System (INIS)

    Hundt, Walter; Yuh, Esther L.; Steinbach, Silke; Bednarski, Mark D.; Guccione, Samira

    2010-01-01

    The purpose of this study was to investigate the effect of pulsed high-intensity focused ultrasound (HIFU) to tumor and muscle tissue. Pulsed HIFU was applied to tumor and muscle tissue in C3H/Km mice. Three hours after HIFU treatment pre- and post-contrast T1-wt, T2-wt images and a diffusion-wt STEAM-sequence were obtained. After MR imaging, the animals were euthenized and the treated tumor and muscle was taken out for histology and functional genomic analysis. In the tumor tissue a slight increase of the diffusion coefficient could be found. In the muscle tissue T2 images showed increased signal intensity and post-contrast T1 showed a decreased contrast uptake in the center and a severe contrast uptake in the surrounding muscle tissue. A significant increase of the diffusion coefficient was found. Gene expression analysis revealed profound changes in the expression levels of 29 genes being up-regulated and 3 genes being down-regulated in the muscle tissue and 31 genes being up-regulated and 15 genes being down-regulated in the SCCVII tumor tissue. Seven genes were up-regulated in both tissue types. The highest up-regulated gene in the tumor and muscle tissue encoded for Mouse histone H2A.1 gene (FC = 13.2 ± 20.6) and Apolipoprotein E (FC = 12.8 ± 27.4) respectively MHC class III (FC = 83.7 ± 67.4) and hsp70 (FC = 75.3 ± 85.0). Immunoblot confirmed the presence of HSP70 protein in the muscle tissue. Pulsed HIFU treatment on tumor and muscle tissue results in dramatic changes in gene expression, indicating that the effect of pulsed HIFU is in some regard dependent and also independent of the tissue type.

  3. Development and application of the variable focus laser leveling gage

    International Nuclear Information System (INIS)

    Gong Kun; Ma Jinglong

    2005-01-01

    The variable focus laser leveling gage was developed. The performance and structure were introduced. The several alignments and tests in KrF laser angle multi-path optical system were accomplished with them. Its application in other optical equipment was discussed too. (author)

  4. Non-invasive focused ultrasound-based synergistic treatment of brain tumors

    Directory of Open Access Journals (Sweden)

    Ya-Jui Lin

    2016-09-01

    The success of FUS BBB disruption in delivering a variety of therapeutic molecules into brain tumors has recently been demonstrated in an animal model. In this paper the authors review a number of critical studies that have demonstrated successful outcomes, including enhancement of the delivery of traditional clinically used chemotherapeutic agents or application of novel nanocarrier designs for actively transporting drugs, or extending drug half-lives to significantly improve treatment efficacy in preclinical animal models.

  5. Development of Antibody-Based Vaccines Targeting the Tumor Vasculature.

    Science.gov (United States)

    Zhuang, Xiaodong; Bicknell, Roy

    2016-01-01

    A functional vasculature is essential for tumor progression and malignant cell metastasis. Endothelial cells lining blood vessels in the tumor are exposed to a unique microenvironment, which in turn induces expression of specific proteins designated as tumor endothelial markers (TEMs). TEMs either localized at the plasma membrane or secreted into the extracellular matrix are accessible for antibody targeting, which can be either infused or generated de novo via vaccination. Recent studies have demonstrated vaccines against several TEMs can induce a strong antibody response accompanied by a potent antitumor effect in animal models. These findings present an exciting field for novel anticancer therapy development. As most of the TEMs are self-antigens, breaking tolerance is necessary for a successful vaccine. This chapter describes approaches to efficiently induce a robust antibody response against the tumor vasculature.

  6. In vivo effects of focused shock waves on tumor tissue visualized by fluorescence staining techniques

    Czech Academy of Sciences Publication Activity Database

    Lukeš, Petr; Zeman, J.; Horák, Vratislav; Hoffer, Petr; Poučková, P.; Holubová, Monika; Hosseini, S.H.R.; Akiyama, H.; Šunka, Pavel; Beneš, J.

    2015-01-01

    Roč. 103, June (2015), s. 103-110 ISSN 1567-5394 R&D Projects: GA MŠk ED2.1.00/03.0124 Grant - others:Rada Programu interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M100431203 Program:M Institutional support: RVO:61389021 ; RVO:67985904 Keywords : Electrical discharge * Shock waves * Tumor damage * Necrosis * Apoptosis Subject RIV: BO - Biophysics Impact factor: 3.556, year: 2015 http://dx.doi.org/10.1016/j.bioelechem.2014.08.019

  7. The Enigmatic Roles of Caspases in Tumor Development

    Energy Technology Data Exchange (ETDEWEB)

    Jäger, Richard; Zwacka, Ralf M., E-mail: ralf.zwacka@nuigalway.ie [National University of Ireland, Galway, National Centre for Biomedical Engineering Science and Apoptosis Research Centre, Molecular Therapeutics Group, Galway (Ireland)

    2010-11-24

    One function ascribed to apoptosis is the suicidal destruction of potentially harmful cells, such as cancerous cells. Hence, their growth depends on evasion of apoptosis, which is considered as one of the hallmarks of cancer. Apoptosis is ultimately carried out by the sequential activation of initiator and executioner caspases, which constitute a family of intracellular proteases involved in dismantling the cell in an ordered fashion. In cancer, therefore, one would anticipate caspases to be frequently rendered inactive, either by gene silencing or by somatic mutations. From clinical data, however, there is little evidence that caspase genes are impaired in cancer. Executioner caspases have only rarely been found mutated or silenced, and also initiator caspases are only affected in particular types of cancer. There is experimental evidence from transgenic mice that certain initiator caspases, such as caspase-8 and -2, might act as tumor suppressors. Loss of the initiator caspase of the intrinsic apoptotic pathway, caspase-9, however, did not promote cellular transformation. These data seem to question a general tumor-suppressive role of caspases. We discuss several possible ways how tumor cells might evade the need for alterations of caspase genes. First, alternative splicing in tumor cells might generate caspase variants that counteract apoptosis. Second, in tumor cells caspases might be kept in check by cellular caspase inhibitors such as c-FLIP or XIAP. Third, pathways upstream of caspase activation might be disrupted in tumor cells. Finally, caspase-independent cell death mechanisms might abrogate the selection pressure for caspase inactivation during tumor development. These scenarios, however, are hardly compatible with the considerable frequency of spontaneous apoptosis occurring in several cancer types. Therefore, alternative concepts might come into play, such as compensatory proliferation. Herein, apoptosis and/or non-apoptotic functions of caspases may

  8. The Enigmatic Roles of Caspases in Tumor Development

    International Nuclear Information System (INIS)

    Jäger, Richard; Zwacka, Ralf M.

    2010-01-01

    One function ascribed to apoptosis is the suicidal destruction of potentially harmful cells, such as cancerous cells. Hence, their growth depends on evasion of apoptosis, which is considered as one of the hallmarks of cancer. Apoptosis is ultimately carried out by the sequential activation of initiator and executioner caspases, which constitute a family of intracellular proteases involved in dismantling the cell in an ordered fashion. In cancer, therefore, one would anticipate caspases to be frequently rendered inactive, either by gene silencing or by somatic mutations. From clinical data, however, there is little evidence that caspase genes are impaired in cancer. Executioner caspases have only rarely been found mutated or silenced, and also initiator caspases are only affected in particular types of cancer. There is experimental evidence from transgenic mice that certain initiator caspases, such as caspase-8 and -2, might act as tumor suppressors. Loss of the initiator caspase of the intrinsic apoptotic pathway, caspase-9, however, did not promote cellular transformation. These data seem to question a general tumor-suppressive role of caspases. We discuss several possible ways how tumor cells might evade the need for alterations of caspase genes. First, alternative splicing in tumor cells might generate caspase variants that counteract apoptosis. Second, in tumor cells caspases might be kept in check by cellular caspase inhibitors such as c-FLIP or XIAP. Third, pathways upstream of caspase activation might be disrupted in tumor cells. Finally, caspase-independent cell death mechanisms might abrogate the selection pressure for caspase inactivation during tumor development. These scenarios, however, are hardly compatible with the considerable frequency of spontaneous apoptosis occurring in several cancer types. Therefore, alternative concepts might come into play, such as compensatory proliferation. Herein, apoptosis and/or non-apoptotic functions of caspases may

  9. Focus on the Development of Natural Gas Hydrate in China

    Directory of Open Access Journals (Sweden)

    Zhongfu Tan

    2016-05-01

    Full Text Available Natural gas hydrate, also known as combustible ice, and mainly composed of methane, is identified as a potential clean energy for the 21st century. Due to its large reserves, gas hydrate can ease problems caused by energy resource shortage and has gained attention around the world. In this paper, we focus on the exploration and development of gas hydrate as well as discussing its status and future development trend in China and abroad. We then analyze its opportunities and challenges in China from four aspects, resource, technology, economy and policy, with five forces model and Politics Economics Society Technology method. The results show China has abundance gas hydrate resource; however, backward technologies and inadequate investment have seriously hindered the future development of gas hydrate; thus, China should establish relevant cooperation framework and intuitional arrangement to attract more investment as well as breaking through technical difficulties to commercialization gas hydrate as soon as possible.

  10. A bioavailable cathepsin S nitrile inhibitor abrogates tumor development.

    Science.gov (United States)

    Wilkinson, Richard D A; Young, Andrew; Burden, Roberta E; Williams, Rich; Scott, Christopher J

    2016-04-21

    Cathepsin S has been implicated in a variety of malignancies with genetic ablation studies demonstrating a key role in tumor invasion and neo-angiogenesis. Thus, the application of cathepsin S inhibitors may have clinical utility in the treatment of cancer. In this investigation, we applied a cell-permeable dipeptidyl nitrile inhibitor of cathepsin S, originally developed to target cathepsin S in inflammatory diseases, in both in vitro and in vivo tumor models. Validation of cathepsin S selectivity was carried out by assaying fluorogenic substrate turnover using recombinant cathepsin protease. Complete kinetic analysis was carried out and true K i values calculated. Abrogation of tumour invasion using murine MC38 and human MCF7 cell lines were carried out in vitro using a transwell migration assay. Effect on endothelial tube formation was evaluated using primary HUVEC cells. The effect of inhibitor in vivo on MC38 and MCF7 tumor progression was evaluated using cells propagated in C57BL/6 and BALB/c mice respectively. Subsequent immunohistochemical staining of proliferation (Ki67) and apoptosis (TUNEL) was carried out on MCF7 tumors. We confirmed that this inhibitor was able to selectively target cathepsin S over family members K, V, L and B. The inhibitor also significantly reduced MC38 and MCF7 cell invasion and furthermore, significantly reduced HUVEC endothelial tubule formation in vitro. In vivo analysis revealed that the compound could significantly reduce tumor volume in murine MC38 syngeneic and MCF7 xenograft models. Immunohistochemical analysis of MCF7 tumors revealed cathepsin S inhibitor treatment significantly reduced proliferation and increased apoptosis. In summary, these results highlight the characterisation of this nitrile cathepsin S inhibitor using in vitro and in vivo tumor models, presenting a compound which may be used to further dissect the role of cathepsin S in cancer progression and may hold therapeutic potential.

  11. Developing New Treatments for Heart Failure: Focus on the Heart.

    Science.gov (United States)

    Gheorghiade, Mihai; Larson, Christopher J; Shah, Sanjiv J; Greene, Stephen J; Cleland, John G F; Colucci, Wilson S; Dunnmon, Preston; Epstein, Stephen E; Kim, Raymond J; Parsey, Ramin V; Stockbridge, Norman; Carr, James; Dinh, Wilfried; Krahn, Thomas; Kramer, Frank; Wahlander, Karin; Deckelbaum, Lawrence I; Crandall, David; Okada, Shunichiro; Senni, Michele; Sikora, Sergey; Sabbah, Hani N; Butler, Javed

    2016-05-01

    Compared with heart failure (HF) care 20 to 30 years ago, there has been tremendous advancement in therapy for ambulatory HF with reduced ejection fraction with the use of agents that block maladaptive neurohormonal pathways. However, during the past decade, with few notable exceptions, the frequency of successful drug development programs has fallen as most novel therapies have failed to offer incremental benefit or raised safety concerns (ie, hypotension). Moreover, no therapy has been approved specifically for HF with preserved ejection fraction or for worsening chronic HF (including acutely decompensated HF). Across the spectrum of HF, preliminary results from many phase II trials have been promising but are frequently followed by unsuccessful phase III studies, highlighting a disconnect in the translational process between basic science discovery, early drug development, and definitive clinical testing in pivotal trials. A major unmet need in HF drug development is the ability to identify homogeneous subsets of patients whose underlying disease is driven by a specific mechanism that can be targeted using a new therapeutic agent. Drug development strategies should increasingly consider therapies that facilitate reverse remodeling by directly targeting the heart itself rather than strictly focusing on agents that unload the heart or target systemic neurohormones. Advancements in cardiac imaging may allow for more focused and direct assessment of drug effects on the heart early in the drug development process. To better understand and address the array of challenges facing current HF drug development, so that future efforts may have a better chance for success, the Food and Drug Administration facilitated a meeting on February 17, 2015, which was attended by clinicians, researchers, regulators, and industry representatives. The following discussion summarizes the key takeaway dialogue from this meeting. © 2016 American Heart Association, Inc.

  12. Finding focus: a study of the historical development of focus in English

    NARCIS (Netherlands)

    Komen, E.R.

    2013-01-01

    This study reveals how two important focus articulations change over time in written English. Constituent focus, often accompanied by contrast, makes use of the clause-initial position in the oldest stages of English, but as this position comes to be used for the grammatical subject over time, the

  13. Development of Superconducting Focusing Quadrupoles for Heavy Ion Drivers

    Energy Technology Data Exchange (ETDEWEB)

    Martovetsky, N; Manahan, R; Lietzke, A F

    2001-09-10

    Heavy Ion Fusion (HIF) is exploring a promising path to a practical inertial-confinement fusion reactor. The associated heavy ion driver will require a large number of focusing quadrupole magnets. A concept for a superconducting quadrupole array, using many simple racetrack coils, was developed at LLNL. Two, single-bore quadrupole prototypes of the same design, with distinctly different conductor, were designed, built, and tested. Both prototypes reached their short sample currents with little or no training. Magnet design, and test results, are presented and discussed.

  14. Development of the FOCUS (Focus on the Outcomes of Communication under Six), a Communication Outcome Measure for Preschool Children

    Science.gov (United States)

    Thomas-Stonell, Nancy L.; Oddson, Bruce; Robertson, Bernadette; Rosenbaum, Peter L.

    2010-01-01

    Aim: Our aim was to develop an outcome measure, called Focus on the Outcomes of Communication Under Six (FOCUS), that captures real-world changes in preschool children's communication. Conceptually grounded in the World Health Organization International Classification of Functioning, Disability and Health framework, the FOCUS items were derived…

  15. Computer-Aided Sensor Development Focused on Security Issues

    Directory of Open Access Journals (Sweden)

    Andrzej Bialas

    2016-05-01

    Full Text Available The paper examines intelligent sensor and sensor system development according to the Common Criteria methodology, which is the basic security assurance methodology for IT products and systems. The paper presents how the development process can be supported by software tools, design patterns and knowledge engineering. The automation of this process brings cost-, quality-, and time-related advantages, because the most difficult and most laborious activities are software-supported and the design reusability is growing. The paper includes a short introduction to the Common Criteria methodology and its sensor-related applications. In the experimental section the computer-supported and patterns-based IT security development process is presented using the example of an intelligent methane detection sensor. This process is supported by an ontology-based tool for security modeling and analyses. The verified and justified models are transferred straight to the security target specification representing security requirements for the IT product. The novelty of the paper is to provide a patterns-based and computer-aided methodology for the sensors development with a view to achieving their IT security assurance. The paper summarizes the validation experiment focused on this methodology adapted for the sensors system development, and presents directions of future research.

  16. Computer-Aided Sensor Development Focused on Security Issues.

    Science.gov (United States)

    Bialas, Andrzej

    2016-05-26

    The paper examines intelligent sensor and sensor system development according to the Common Criteria methodology, which is the basic security assurance methodology for IT products and systems. The paper presents how the development process can be supported by software tools, design patterns and knowledge engineering. The automation of this process brings cost-, quality-, and time-related advantages, because the most difficult and most laborious activities are software-supported and the design reusability is growing. The paper includes a short introduction to the Common Criteria methodology and its sensor-related applications. In the experimental section the computer-supported and patterns-based IT security development process is presented using the example of an intelligent methane detection sensor. This process is supported by an ontology-based tool for security modeling and analyses. The verified and justified models are transferred straight to the security target specification representing security requirements for the IT product. The novelty of the paper is to provide a patterns-based and computer-aided methodology for the sensors development with a view to achieving their IT security assurance. The paper summarizes the validation experiment focused on this methodology adapted for the sensors system development, and presents directions of future research.

  17. Malignant melanoma in Ferrara, Northern Italy: epidemiologic survey focusing on tumor thickness.

    Science.gov (United States)

    Borghi, A; Corazza, M; Minghetti, S; Masarà, A; Virgili, A

    2015-12-01

    Estimates of malignant melanoma (MM) incidence and prognosis vary widely. The present study was performed to analyze epidemiologic and prognostic aspects of primary MM mainly in relation to tumor thickness. We conducted a retrospective study on a cohort of 435 patients with diagnosis of primary MM between 1997 and 2011. In the period 2009-2011, among the MM diagnosed 50.00% were thin, 32.43% in situ and 17.57% thicker while in 1997-1999 MM>1 mm accounted for 51.61% of diagnoses. Mean age of patients affected with thin MM was significantly lower than that of patients with MM>1 mm, and mean thickness resulted significantly lower in female patients than in males. Mean thickness of MM located on easily self-evaluable body areas was significantly lower than in those not accessible for skin self-examination. The commonest histogenetic type was superficially spreading melanoma. Mitotic rate, ulceration and vertical growth phase all resulted related to MM thickness. Out of 61 patients with thin MM who underwent SLNB, 3 resulted positive (4.92%): neither thickness >0.75 mm, nor ulceration, mitotic rate or Clark level were found to be associated with SLNB positivity. Five-year survival rate was 98.3% for thin MM patients and 76.4% for thick MM patients. Our trend analysis evidences a continuing increase of thinner primary MM throughout the study period, potentially enhancing patient prognosis. Regular skin self-examination could contribute to earlier recognition of MM. Identification of more powerful predictors of thin MM prognosis is necessary.

  18. On a computational study for investigating acoustic streaming and heating during focused ultrasound ablation of liver tumor

    International Nuclear Information System (INIS)

    Solovchuk, Maxim A.; Sheu, Tony W.H.; Thiriet, Marc; Lin, Win-Li

    2013-01-01

    The influences of blood vessels and focused location on temperature distribution during high-intensity focused ultrasound (HIFU) ablation of liver tumors are studied numerically. A three-dimensional acoustics-thermal-fluid coupling model is employed to compute the temperature field in the hepatic cancerous region. The model construction is based on the linear Westervelt and bioheat equations as well as the nonlinear Navier–Stokes equations for the liver parenchyma and blood vessels. The effect of acoustic streaming is also taken into account in the present HIFU simulation study. Different blood vessel diameters and focal point locations were investigated. We found from this three-dimensional numerical study that in large blood vessels both the convective cooling and acoustic streaming can considerably change the temperature field and the thermal lesion near blood vessels. If the blood vessel is located within the beam width, both acoustic streaming and blood flow cooling effects should be addressed. The temperature rise on the blood vessel wall generated by a 1.0 MHz focused ultrasound transducer with the focal intensity 327 W/cm 2 was 54% lower when acoustic streaming effect was taken into account. Subject to the applied acoustic power the streaming velocity in a 3 mm blood vessel is 12 cm/s. Thirty percent of the necrosed volume can be reduced, when taking into account the acoustic streaming effect. -- Highlights: • 3D three-field coupling physical model for focused ultrasound tumor ablation is presented. • Acoustic streaming and blood flow cooling effects on ultrasound heating are investigated. • Acoustic streaming can considerably affect the temperature distribution. • The lesion can be reduced by 30% due to the acoustic streaming effect. • Temperature on the blood vessel wall is reduced by 54% due to the acoustic streaming effect

  19. Tumor markers kits development for use in radioimmunometric assays

    International Nuclear Information System (INIS)

    Ahmed, B.

    1997-01-01

    The immunoassays such as RIA and IRMA are now widely used through the world for the quantitation of a variety of substances in the biological fluid for their high sensibility and specificity which required simple equipments. These techniques are also very used in Algeria for an effective amelioration of public heath The assays kits of RIA/IRMA of thyroid hormones are the most used, followed by peptidic hormones, steroids hormones and IRMA Tumor Markers (T.M) kits. In spite of the important demand, of tumor markers kits for the diagnosis and follow up of cancers their use are always insufficient due to the high cost. The research contract programme proposed by IAEA on the theme 'The Developments of IRMA Tumor Markers Kits' of prostate specific Antigen (PSA) and Tissue Polypeptide Specific Antigen (TPS) will allowed us to produce locally with best quality-price, the main reagents for PSA and TPS IRMA assays kits for diagnosis and follow up the prostate and breast cancers which are very spready in the country. This report include the following points: Generalities on the use of tumor markers in Algeria, programme for the Development of the PSA IRMA assay (schedule of protocols applied for each reagents; annual planning for assessing the programme activities) and conclusion

  20. Tumor Necrosis Factor-Alpha and Pregnancy: Focus on Biologics. An Updated and Comprehensive Review.

    Science.gov (United States)

    Alijotas-Reig, Jaume; Esteve-Valverde, Enrique; Ferrer-Oliveras, Raquel; Llurba, Elisa; Gris, Josep Maria

    2017-08-01

    Tumor necrosis factor-α (TNF-α) is a central regulator of inflammation, and TNF-α antagonists may be effective in treating inflammatory disorders in which TNF-α plays a major pathogenic role. TNF-α has also been associated with inflammatory mechanisms related to implantation, placentation, and pregnancy outcome. TNF-α is secreted by immune cells and works by binding to TNFR1 and TNFR2 cell receptors. TNF-α is also related to JAK/STAT pathways, which opens up hypothetical new targets for modifying. The accurate balance between Th1 cytokines, mainly TNF-α, Th17, and Th2, particularly IL-10 is essential to achieve good obstetric outcomes. TNF-α targeted therapy could be rational in treating women with obstetric complication related to overproduction of TNF-α, such as recurrent pregnancy loss, early and severe pre-eclampsia, and recurrent implantation failure syndrome, all "idiopathic" or related to aPL positivity. Along the same lines, Th1 cytokines, mainly TNF- α, play a leading pathogenic role in rheumatic and systemic autoimmune diseases occurring in women and, to a lesser extent, in men of reproductive age. These disorders have to be clinically silent before pregnancy can be recommended, which is usually only possible to achieve after intensive anti-inflammatory and immunosuppressive treatment, TNF-α blockers included. Physicians should be aware of the theoretic potential but low embryo-fetal toxicity risk of these drugs during pregnancy. From an updated review in May 2016, we can conclude that TNF-α blockers are useful in certain "refractory" cases of inflammatory disorders related to poor obstetric outcomes and infertility. Furthermore, TNF-α blockers can be safely used during the implantation period and pregnancy. Breastfeeding is also permitted with all TNF-α inhibitors. Since data on the actual mechanism of action of JAK-STAT in inflammatory obstetric disorders including embryo implantation are scarce, for the time being, therapeutic

  1. Transcriptional mutagenesis: causes and involvement in tumor development

    Science.gov (United States)

    Brégeon, Damien; Doetsch, Paul W.

    2013-01-01

    The majority of normal cells in a human do not multiply continuously but are quiescent and devote most of their energy to gene transcription. When DNA damages in the transcribed strand of an active gene are bypassed by an RNA polymerase, they can miscode at the damaged site and produce mutant transcripts. This process known as transcriptional mutagenesis can lead to the production of mutant proteins that could be important in tumor development. PMID:21346784

  2. Role for the Wilms tumor gene in genital development?

    International Nuclear Information System (INIS)

    van Heyningen, V.; Bickmore, W.A.; Seawright, A.; Fletcher, J.M.; Maule, J.; Hastie, N.D.; Fekete, G.; Gessler, M.; Bruns, G.A.P.; Huerre-Jeanpierre, C.; Junien, C.; Williams, B.R.G.

    1990-01-01

    Detailed molecular definition of the WAGR region at chromosome 11p13 has been achieved by chromosome breakpoint analysis and long-range restriction mapping. Here the authors describe the molecular detection of a cytogenetically invisible 1-megabase deletion in an individual with aniridia, cryptorchidism, and hypospadias but no Wilms tumor (WT). The region of overlap between this deletion and one associated with WT and similar genital anomalies but no aniridia covers a region of 350-400 kilobases, which is coincident with the extent of homozygous deletion detected in tumor tissue from a sporadic WT. A candidate WT gene located within this region has recently been isolated, suggesting nonpenetrance for tumor expression in the first individual. The inclusion within the overlap region of a gene for WT predisposition and a gene for the best-documented WT-associated genitourinary malformations leads to suggest that both of these anomalies result from a loss-of-function mutation at the same locus. This in turn implies that the WT gene exerts pleiotropic effect on both kidney and genitourinary development, a possibility supported by the observed expression pattern of the WT candidate gene in developing kidney and gonads

  3. Plutonium Focus Area research and development plan. Revision 1

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-11-01

    The Department of Energy (DOE) committed to a research and development program to support the technology needs for converting and stabilizing its nuclear materials for safe storage. The R and D Plan addresses five of the six material categories from the 94-1 Implementation Plan: plutonium (Pu) solutions, plutonium metals and oxides, plutonium residues, highly enriched uranium, and special isotopes. R and D efforts related to spent nuclear fuel (SNF) stabilization were specifically excluded from this plan. This updated plan has narrowed the focus to more effectively target specific problem areas by incorporating results form trade studies. Specifically, the trade studies involved salt; ash; sand, slag, and crucible (SS and C); combustibles; and scrub alloy. The plan anticipates possible disposition paths for nuclear materials and identifies resulting research requirements. These requirements may change as disposition paths become more certain. Thus, this plan represents a snapshot of the current progress and will continue to be updated on a regular basis. The paper discusses progress in safeguards and security, plutonium stabilization, special isotopes stabilization, highly-enriched uranium stabilization--MSRE remediation project, storage technologies, engineered systems, core technology, and proposed DOE/Russian technology exchange projects.

  4. Plutonium Focus Area research and development plan. Revision 1

    International Nuclear Information System (INIS)

    1996-11-01

    The Department of Energy (DOE) committed to a research and development program to support the technology needs for converting and stabilizing its nuclear materials for safe storage. The R and D Plan addresses five of the six material categories from the 94-1 Implementation Plan: plutonium (Pu) solutions, plutonium metals and oxides, plutonium residues, highly enriched uranium, and special isotopes. R and D efforts related to spent nuclear fuel (SNF) stabilization were specifically excluded from this plan. This updated plan has narrowed the focus to more effectively target specific problem areas by incorporating results form trade studies. Specifically, the trade studies involved salt; ash; sand, slag, and crucible (SS and C); combustibles; and scrub alloy. The plan anticipates possible disposition paths for nuclear materials and identifies resulting research requirements. These requirements may change as disposition paths become more certain. Thus, this plan represents a snapshot of the current progress and will continue to be updated on a regular basis. The paper discusses progress in safeguards and security, plutonium stabilization, special isotopes stabilization, highly-enriched uranium stabilization--MSRE remediation project, storage technologies, engineered systems, core technology, and proposed DOE/Russian technology exchange projects

  5. Understanding focused ion beam guided anodic alumina nanopore development

    International Nuclear Information System (INIS)

    Chen Bo; Lu, Kathy; Tian Zhipeng

    2011-01-01

    Graphical abstract: Display Omitted Highlights: → We study the effect of FIB patterning on pore evolution during anodization. → FIB patterned concaves with 1.5 nm depth can effectively guide nanopore growth. → The edge effect of FIB guided patterns causes nanopores to bend. → Anodization window is enlarged to 50-80 V for 150 nm interpore distance hexagonal arrays. - Abstract: Focused ion beam (FIB) patterning in combination with anodization has shown great promise in creating unique pore patterns. This work is aimed to understand the effect of the FIB patterned sites in guiding anodized pore development. Highly ordered porous anodic alumina has been created with the guidance of FIB created patterns on electropolished aluminum followed by oxalic acid anodization. Shallow concaves created by the FIB with only 1.5 nm depth can effectively guide the growth of ordered nanopore patterns. With the guidance of the FIB pattern, the anodization rate is much faster and the nanopore growth direction bends at the boundary of the FIB patterned and un-patterned regions. FIB patterning also enlarges the anodization window; ordered nanopore arrays with 150 nm interpore distances can be produced under an applied potential from 50 V to 80 V. The fundamental understanding of these unique processes is discussed.

  6. Development of RIA kits for tumor-markers monitoring

    International Nuclear Information System (INIS)

    Suprarop, P.

    1997-01-01

    All reagents for tumor markers assays are imported from various manufacturers mainly CIS bio international. The average cost of these reagents is ranged from 80-150 bath/test (2-4 dollars test). The screening test for cancers could not be done especially in other regions of Thailand whose budgets and resources are so limited. If the reagents are made locally, many laboratories can perform the tests and use as primary diagnosis, screening or monitor the course of the disease following treatment. In addition, these reagents could help clinicians and give complementary information on the tumor status to improve quality of life in Thailand. Research objectives include: 1. Development of IRMA reagent kits suitable for diagnosing staging and monitoring prostrate and breast cancer. 2. Transfer of technology and reagent kits to relevant laboratories in Thailand. 3. Routine distribution of the reagents kits to the end users

  7. Development of TPF-1 plasma focus for education

    Science.gov (United States)

    Picha, R.; Promping, J.; Channuie, J.; Poolyarat, N.; Sangaroon, S.; Traikool, T.

    2017-09-01

    The plasma focus is a device that uses high voltage and electromagnetic force to induce plasma generation and acceleration, in order to cause nuclear reactions. Radiation of various types (X-ray, gamma ray, electrons, ions, neutrons) can be generated using this method during the pinch phase, thus making the plasma focus able to serve as a radiation source. Material testing, modification, and identification are among the current applications of the plasma focus. Other than being an alternative option to isotopic sources, the plasma focus, which requires multidisciplinary team of personnel to design, operate, and troubleshoot, can also serve as an excellent learning device for physics and engineering students in the fields including, but not limited to, plasma physics, nuclear physics, electronics engineering, and mechanical engineering. This work describes the parameters and current status of Thai Plasma Focus 1 (TPF-1) and the characteristics of the plasma being produced in the machine using a Rogowski coil.

  8. Immunotherapy for the treatment of colorectal tumors: focus on approved and in-clinical-trial monoclonal antibodies

    Directory of Open Access Journals (Sweden)

    Françoso A

    2017-01-01

    Full Text Available Alex Françoso,1 Patricia Ucelli Simioni1–3 1Department of Biomedical Science, Faculty of Americana, Americana, 2Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas, Campinas, 3Department of Biochemistry and Microbiology, Institute of Biosciences, Universidade Estadual Paulista, Rio Claro, São Paulo, Brazil Abstract: Colorectal cancer is considered a disease of the elderly population. Since the number of geriatric patients continues to rise, monoclonal antibody therapy is the most promising therapy in the recent research. Presently, the monoclonal antibodies most frequently used in the treatment of colorectal tumors are bevacizumab, cetuximab, panitumumab, and ramucirumab. Bevacizumab is a monoclonal antibody that acts on VEGF. Cetuximab and panitumumab act on EGFR. Ramucirumab binds directly to the ligand-binding pocket of VEGFR-2 to block the binding of VEGF-A, VEGF-C, and VEGF-D. These monoclonal antibodies, alone or in association with radiotherapy or chemotherapy, are presenting good results and are increasing patient survival, despite the side effects. Due to the limited number of molecules available, several studies are trying to develop new monoclonal antibodies for the treatment of colorectal tumors. Among those being studied, some recent molecules are in phase I and/or II trials and are yielding advantageous results, such as anti-DR5, anti-Fn14, anti-IGF-1R, anti-EGFR, anti-NRP1, and anti-A33 antibodies. This has been successful in reducing side effects and in treating nonresponsive patients. Keywords: monoclonal antibodies, colorectal tumor, bevacizumab, cetuximab, panitumumab, ramucirumab

  9. Development of precision elliptic neutron-focusing supermirror.

    Science.gov (United States)

    Hosobata, Takuya; Yamada, Norifumi L; Hino, Masahiro; Yamagata, Yutaka; Kawai, Toshihide; Yoshinaga, Hisao; Hori, Koichiro; Takeda, Masahiro; Takeda, Shin; Morita, Shin-Ya

    2017-08-21

    This paper details methods for the precision design and fabrication of neutron-focusing supermirrors, based on electroless nickel plating. We fabricated an elliptic mirror for neutron reflectometry, which is our second mirror improved from the first. The mirror is a 550-millimeter-long segmented mirror assembled using kinematic couplings, with each segment figured by diamond cutting, polished using colloidal silica, and supermirror coated through ion-beam sputtering. The mirror was evaluated with neutron beams, and the reflectivity was found to be 68-90% at a critical angle. The focusing width was 0.17 mm at the full width at half maximum.

  10. Islet Cell Tumors of the Pancreas: A Variety of Multiphase Dynamic Imaging Findings with Pathologic Correlations Focusing on Nonfunctioning Tumors and Insulinomas

    International Nuclear Information System (INIS)

    Hong, Yoo Jin; Yu, Jeong Sik; Park, Chan Il; Kwon, Ji Eun; Chung, Jae Joon; Kim, Joo Hee; Kim, Ki Whang

    2010-01-01

    Islet cell tumors (ICTs) are rare pancreatic neoplasms of neuroendocrine origin, posing a diagnostic challenge to radiologists. We illustrated a spectrum of features of pancreatic ICTs that could be found on multiphase dynamic CT or MRI, and elucidated the histopathologic characteristics by determining the contrast enhancement pattern of the lesions. Various enhancement patterns were dependant on the internal composition of the tumor, that is, the proportion of vascular densities for early enhancement and non-hypervascular interstitial tissue for late enhancement regardless of the size or functional behavior. This knowledge of the imaging-pathologic spectrum of ICTs could be helpful for the proper differential diagnosis from other pancreatic tumors

  11. Renal transplantation-related risk factors for the development of uterine adenomatoid tumors.

    Science.gov (United States)

    Mizutani, Teruyuki; Yamamuro, Osamu; Kato, Noriko; Hayashi, Kazumasa; Chaya, Junya; Goto, Norihiko; Tsuzuki, Toyonori

    2016-08-01

    •We analyzed the epidemiological factors for clinical manifestations of uterine adenomatoid tumors.•Renal transplantation with immunosuppression therapy is risk factor for the development of uterine adenomatoid tumors.•The length of time on dialysis is risk factor for the development of uterine adenomatoid tumors.

  12. Development of an acellular tumor extracellular matrix as a three-dimensional scaffold for tumor engineering.

    Directory of Open Access Journals (Sweden)

    Wei-Dong Lü

    Full Text Available Tumor engineering is defined as the construction of three-dimensional (3D tumors in vitro with tissue engineering approaches. The present 3D scaffolds for tumor engineering have several limitations in terms of structure and function. To get an ideal 3D scaffold for tumor culture, A549 human pulmonary adenocarcinoma cells were implanted into immunodeficient mice to establish xenotransplatation models. Tumors were retrieved at 30-day implantation and sliced into sheets. They were subsequently decellularized by four procedures. Two decellularization methods, Tris-Trypsin-Triton multi-step treatment and sodium dodecyl sulfate (SDS treatment, achieved complete cellular removal and thus were chosen for evaluation of histological and biochemical properties. Native tumor tissues were used as controls. Human breast cancer MCF-7 cells were cultured onto the two 3D scaffolds for further cell growth and growth factor secretion investigations, with the two-dimensional (2D culture and cells cultured onto the Matrigel scaffolds used as controls. Results showed that Tris-Trypsin-Triton multi-step treated tumor sheets had well-preserved extracellular matrix structures and components. Their porosity was increased but elastic modulus was decreased compared with the native tumor samples. They supported MCF-7 cell repopulation and proliferation, as well as expression of growth factors. When cultured within the Tris-Trypsin-Triton treated scaffold, A549 cells and human colorectal adenocarcinoma cells (SW-480 had similar behaviors to MCF-7 cells, but human esophageal squamous cell carcinoma cells (KYSE-510 had a relatively slow cell repopulation rate. This study provides evidence that Tris-Trypsin-Triton treated acellular tumor extracellular matrices are promising 3D scaffolds with ideal spatial arrangement, biomechanical properties and biocompatibility for improved modeling of 3D tumor microenvironments.

  13. Essential variables help to focus sustainable development goals monitoring

    CSIR Research Space (South Africa)

    Reyers, B

    2017-06-01

    Full Text Available indicators [1], each one of which relies on existing and new multiple data streams for its development (Figure 1a). Under this current proliferation logic, the process of developing an SDG monitoring system inexorably results in an ever-expanding set....sciencedirect.com Essential Sustainable Development Goal Variables Reyers et al. 99abstraction provides a degree of independence from observations, thus accommodating multiple diverse pri- mary data streams across regions and sections, as well as the flexibility to meet...

  14. COX-2 inhibition is neither necessary nor sufficient for celecoxib to suppress tumor cell proliferation and focus formation in vitro

    Directory of Open Access Journals (Sweden)

    Petasis Nicos A

    2008-05-01

    Full Text Available Abstract Background An increasing number of reports is challenging the notion that the antitumor potential of the selective COX-2 inhibitor celecoxib (Celebrex® is mediated primarily via the inhibition of COX-2. We have investigated this issue by applying two different analogs of celecoxib that differentially display COX-2-inhibitory activity: the first analog, called unmethylated celecoxib (UMC, inhibits COX-2 slightly more potently than its parental compound, whereas the second analog, 2,5-dimethyl-celecoxib (DMC, has lost the ability to inhibit COX-2. Results With the use of glioblastoma and pancreatic carcinoma cell lines, we comparatively analyzed the effects of celecoxib, UMC, and DMC in various short-term (≤48 hours cellular and molecular studies, as well as in long-term (≤3 months focus formation assays. We found that DMC exhibited the most potent antitumor activity; celecoxib was somewhat less effective, and UMC clearly displayed the overall weakest antitumor potential in all aspects. The differential growth-inhibitory and apoptosis-stimulatory potency of these compounds in short-term assays did not at all correlate with their capacity to inhibit COX-2, but was closely aligned with their ability to trigger endoplasmic reticulum stress (ERS, as indicated by the induction of the ERS marker CHOP/GADD153 and activation of the ERS-associated caspase 7. In addition, we found that these compounds were able to restore contact inhibition and block focus formation during long-term, chronic drug exposure of tumor cells, and this was achieved at sub-toxic concentrations in the absence of ERS or inhibition of COX-2. Conclusion The antitumor activity of celecoxib in vitro did not involve the inhibition of COX-2. Rather, the drug's ability to trigger ERS, a known effector of cell death, might provide an alternative explanation for its acute cytotoxicity. In addition, the newly discovered ability of this drug to restore contact inhibition and

  15. The development of CAR design for tumor CAR-T cell therapy.

    Science.gov (United States)

    Xu, Dandan; Jin, Guoliang; Chai, Dafei; Zhou, Xiaowan; Gu, Weiyu; Chong, Yanyun; Song, Jingyuan; Zheng, Junnian

    2018-03-02

    In recent years, the chimeric antigen receptor modified T cells (Chimeric antigen receptor T cells, CAR-T) immunotherapy has developed rapidly, which has been considered the most promising therapy. Efforts to enhance the efficacy of CAR-based anti-tumor therapy have been made, such as the improvement of structures of CAR-T cells, including the development of extracellular antigen recognition receptors, intracellular co-stimulatory molecules and the combination application of CARs and synthetic small molecules. In addition, effects on the function of the CAR-T cells that the space distance between the antigen binding domains and tumor targets and the length of the spacer domains have are also being investigated. Given the fast-moving nature of this field, it is necessary to make a summary of the development of CAR-T cells. In this review, we mainly focus on the present design strategies of CAR-T cells with the hope that they can provide insights to increase the anti-tumor efficacy and safety.

  16. Distributed Generation to Support Development-Focused Climate Action

    Energy Technology Data Exchange (ETDEWEB)

    Cox, Sadie; Gagnon, Pieter; Stout, Sherry; Zinaman, Owen; Watson, Andrea; Hotchkiss, Eliza

    2016-09-01

    This paper explores the role of distributed generation, with a high renewable energy contribution, in supporting low emission climate-resilient development. The paper presents potential impacts on development (via energy access), greenhouse gas emission mitigation, and climate resilience directly associated with distributed generation, as well as specific actions that may enhance or increase the likelihood of climate and development benefits. This paper also seeks to provide practical and timely insights to support distributed generation policymaking and planning within the context of common climate and development goals as the distributed generation landscape rapidly evolves globally. Country-specific distributed generation policy and program examples, as well as analytical tools that can inform efforts internationally, are also highlighted throughout the paper.

  17. in_focus - Competition and Development: The Power of Competitive ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2008-01-01

    Jan 1, 2008 ... This has brought about many changes in the economies of developing ... touching on issues of globalization, consumer welfare, cartels and monopolies ... citizens can promote and practice to limit the impact of such practices.

  18. in_focus - Competition and Development: The Power of Competitive ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    1 janv. 2008 ... This has brought about many changes in the economies of developing ... and an effective marketplace, touching on issues of globalization, ... and the policies that governments and citizens can promote and practice to limit the ...

  19. Proposal for product development model focused on ce certification methodology

    Directory of Open Access Journals (Sweden)

    Nathalia Marcia Goulart Pinheiro

    2015-09-01

    Full Text Available This paper presents a critical analysis comparing 21 product development models in order to identify whether these structures meet the demands Product Certification of the European Community (CE. Furthermore, it presents a product development model, comprising the steps in the models analyzed, including improvements in activities for referred product certification. The proposed improvements are justified by the growing quest for the internationalization of products and processes within companies.

  20. Focusing on dissociated motor development in Brazilian children

    OpenAIRE

    Minami, Maria Avanise Yumi; Funayama, Carolina A.R.; Daneluzzi, Julio Cesar

    2001-01-01

    Dissociated motor development (DMD) is considered when the baby starts independent walking late, with normality of the other fields of development. There is evidence that babies with DMD present an atypical crawling pattern and hypotonia. To investigate the frequency and characteristics of DMD, neurological examination was performed monthly in 177 healthy full-term babies from 6 months age, in urban and rural zone samples in Brazil. Among 20 children with atypical crawling, none presented hyp...

  1. Involvement of host stroma cells and tissue fibrosis in pancreatic tumor development in transgenic mice.

    Directory of Open Access Journals (Sweden)

    Itai Spector

    Full Text Available INTRODUCTION: Stroma cells and extracellular matrix (ECM components provide the pivotal microenvironment for tumor development. The study aimed to evaluate the importance of the pancreatic stroma for tumor development. METHODS: Pancreatic tumor cells were implanted subcutaneously into green fluorescent protein transgenic mice, and stroma cells invading the tumors were identified through immunohistochemistry. Inhibition of tumor invasion by stroma cells was achieved with halofuginone, an inhibitor of TGFβ/Smad3 signaling, alone or in combination with chemotherapy. The origin of tumor ECM was evaluated with species-specific collagen I antibodies and in situ hybridization of collagen α1(I gene. Pancreatic fibrosis was induced by cerulean injection and tumors by spleen injection of pancreatic tumor cells. RESULTS: Inhibition of stroma cell infiltration and reduction of tumor ECM levels by halofuginone inhibited development of tumors derived from mouse and human pancreatic cancer cells. Halofuginone reduced the number only of stroma myofibroblasts expressing both contractile and collagen biosynthesis markers. Both stroma myofibroblasts and tumor cells generated ECM that contributes to tumor growth. Combination of treatments that inhibit stroma cell infiltration, cause apoptosis of myofibroblasts and inhibit Smad3 phosphorylation, with chemotherapy that increases tumor-cell apoptosis without affecting Smad3 phosphorylation was more efficacious than either treatment alone. More tumors developed in fibrotic than in normal pancreas, and prevention of tissue fibrosis greatly reduced tumor development. CONCLUSIONS: The utmost importance of tissue fibrosis and of stroma cells for tumor development presents potential new therapy targets, suggesting combination therapy against stroma and neoplastic cells as a treatment of choice.

  2. Development and Climate Change in Fiji. Focus on Coastal Mangroves

    International Nuclear Information System (INIS)

    Agrawala, S.; Ota, Tomoko; Van Aalst, M.; Smith, J.; Hagenstad, M.; Risbey, J.; Koshy, K.; Prasad, B.

    2003-01-01

    This document is an output from the OECD Development and Climate Change project, an activity jointly overseen by the EPOC Working Party on Global and Structural Policies (WPGSP), and the DAC Network on Environment and Development Co-operation (ENVIRONET). The overall objective of the project is to provide guidance on how to mainstream responses to climate change within economic development planning and assistance policies, with natural resource management as an overarching theme. This report presents the integrated case study for Fiji carried out under an OECD project on Development and Climate Change. The report is structured around a three-tier framework. First, recent climate trends and climate change scenarios for Fiji are assessed, and key sectoral impacts are identified and ranked along multiple indicators to establish priorities for adaptation. Second, donor portfolios are analyzed to examine the proportion of donor activities affected by climate risks. A desk analysis of donor strategies and project documents as well as national plans is conducted to assess the degree of attention to climate change concerns in development planning and assistance. Third, an in-depth analysis is conducted for Fiji's coastal mangroves which help reduce coastal inundation and storm surge damages, but are also themselves vulnerable to climate change

  3. Development and Climate Change in Tanzania. Focus on Mount Kilimanjaro

    International Nuclear Information System (INIS)

    Agrawala, S.; Moehner, A.; Van Aalst, M.; Smith, J.; Hitz, S.; Hemp, A.; Meena, H.; Mwakifwamba, S.M.; Hyera, T.; Mwaipopo, O.U.

    2003-01-01

    This document is an output from the OECD Development and Climate Change project, an activity jointly overseen by the EPOC Working Party on Global and Structural Policies (WPGSP), and the DAC Network on Environment and Development Co-operation (ENVIRONET). The overall objective of the project is to provide guidance on how to mainstream responses to climate change within economic development planning and assistance policies, with natural resource management as an overarching theme. This report presents the integrated case study for Tanzania carried out under an OECD project on Development and Climate Change. The report is structured around a three-tiered framework. First, recent climate trends and climate change scenarios for Tanzania are assessed, and key sectoral impacts are identified and ranked along multiple indicators to establish priorities for adaptation. Second, donor portfolios in Tanzania are analyzed to examine the proportion of donor activities affected by climate risks. A desk analysis of donor strategies and project documents as well as national plans is conducted to assess the degree of attention to climate change concerns in development planning and assistance. Third, an in-depth analysis is conducted for climate change impacts and response strategies for Mount Kilimanjaro - a critical ecosystem, biodiversity hotspot, and source of freshwater. This part of the analysis draws upon extended field research by a case study consultant in collaboration with national and international partners

  4. Health Promotion: A developing focus area over the years.

    Science.gov (United States)

    Povlsen, Lene; Borup, Ina

    2015-08-01

    In 1953 when the Nordic School of Public Health was founded, the aim of public health programmes was disease prevention more than health promotion. This was not unusual, since at this time health usually was seen as the opposite of disease and illness. However, with the Ottawa Charter of 1986, the World Health Organization made a crucial change to view health not as a goal in itself but as the means to a full life. In this way, health promotion became a first priority and fundamental action for the modern society. This insight eventually reached NHV and in 2002 - 50 years after the foundation - an associate professorship was established with a focus on health promotion. Nevertheless, the concept of health promotion had been integrated with or mentioned in courses run prior to the new post. Subsequently, a wide spectrum of courses in health promotion was introduced, such as 'Empowerment for Child and Adolescent Health Promotion', 'Salutogenesis--from theory to practice' and 'Health, Stress and Coping'. More than half of all doctoral theses undertaken at NHV during these years had health promotion as their theme. As a derivative, the Nordic Health Promotion Research Network (NHPRN) was established in 2007 with bi-annual meetings at NHV. © 2015 the Nordic Societies of Public Health.

  5. Transition-Focused Professional Development: An Annotated Bibliography of Essential Elements and Features of Professional Development

    Science.gov (United States)

    Holzberg, Debra G.; Clark, Kelly A.; Morningstar, Mary E.

    2018-01-01

    Transition professional development (PD) has been identified as a way to improve transition services; however, there is a dearth of literature on transition-focused PD. To learn more about the essential features of effective PD, 73 published articles were evaluated in the area of PD in both secondary transition and special education. Articles were…

  6. IN_FOCUS COLLECTION Mini-websites on current development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2011-07-29

    Jul 29, 2011 ... FIGHTING POVERTY WITH FACTS: Community-Based Monitoring Systems · COMPETITION AND DEVELOPMENT: The Power of Competitive Markets · COMANAGEMENT OF NATURAL RESOURCES: Local Learning for Poverty Reduction · GROWING BETTER CITIES: Urban Agriculture for Sustainable ...

  7. Creaducation: A Focus on Dynamic Education for Development in ...

    African Journals Online (AJOL)

    Creaducation arouses, creates, and invigorates the latent elements within an individual to begin a fathomable process of creative thinking, problem solving, process improvement, and to actions leading to self-betterment and community development. This form of education calls forth the latent genie that lies within us, to a ...

  8. Mental health literacy: focus on developing countries | Ganasen ...

    African Journals Online (AJOL)

    ... is of particular concern in low and middle-income countries where mental health services are already scarce. It is likely that strategies for improvement will need to be comprehensive and innovative, taking advantage of opportunities and meeting challenges faced in the developing world. African Journal of Psychiatry Vol.

  9. Environmental migration and conflict dynamics: focus on developing regions.

    Science.gov (United States)

    Swain, A

    1996-12-01

    The world's population is increasing by 90-100 million every year, and it may double during the next half-century, with most of the added population coming from developing countries. 700 million people are malnourished and 40,000 die of hunger and hunger-related diseases each day. Most of the developing countries are extremely dependent on their renewable resource base to sustain their economic activities. Therefore, environmental changes and the loss of resources has dire implications for developing countries. This includes loss of arable land and lack of water, which lead to decreased food production. An area of about 1.2 billion hectares (almost the size of China and India taken together) has endured modest to severe soil degradation since World War II because of human activity. Air pollution can also directly affect crop production, lowering crop, wheat, soybean, and peanut harvests in the US. Rapid climate change triggered by the greenhouse effect would also inflict disproportionately more suffering on developing countries. The rise in sea levels caused by climatic change may severely affect densely populated coastal areas in China, Egypt, and Bangladesh. The loss of living space and livelihood could lead to the migration of people as it has happened throughout human history. The definition of environmental migrants is controversial and the other terms used include environmental refugees, ecological refugees, and resource refugees. Economic migrants are those who move to economically affluent regions responding to both the push and pull factors. In contrast, environmental migrants are forced to move--as a result of the loss of livelihood and space--to the nearest possible location. The scarcity induced by environmental migration may lead to acute conflict at three levels in the developing society: state vs. state (large-scale trans-border migration may trigger armed conflicts); state vs. group (rapid urbanization); and group vs. group (nativism).

  10. Development of a High Intensity Focused Ultrasound (HIFU) Hydrophone System

    International Nuclear Information System (INIS)

    Schafer, Mark E.; Gessert, James

    2009-01-01

    The growing clinical use of High Intensity Focused Ultrasound (HIFU) has driven a need for reliable, reproducible measurements of HIFU acoustic fields. We have previously presented data on a reflective scatterer approach, incorporating several novel features for improved bandwidth, reliability, and reproducibility [Proc. 2005 IEEE Ultrasonics Symposium, 1739-1742]. We now report on several design improvements which have increase the signal to noise ratio of the system, and potentially reduced the cost of implementation. For the scattering element, we now use an artificial sapphire material to provide a more uniform radiating surface. The receiver is a segmented, truncated spherical structure with a 10 cm radius; the scattering element is positioned at the center of the sphere. The receiver is made from 25 micron thick, biaxially stretched PVDF, with a Pt-Au electrode on the front surface. In the new design, a specialized backing material provides the stiffness required to maintain structural stability, while at the same time providing both electrical shielding and ultrasonic absorption. Compared with the previous version, the new receiver design has improved the noise performance by 8-12 dB; the new scattering sphere has reduced the scattering loss by another 14 dB, producing an effective sensitivity of -298 dB re 1 microVolt/Pa. The design trade-off still involves receiver sensitivity with effective spot size, and signal distortion from the scatter structure. However, the reduced cost and improved repeatability of the new scatter approach makes the overall design more robust for routine waveform measurements of HIFU systems.

  11. Developing Public Policy in Romania: Focusing Responsability, Authority and Capacity

    Directory of Open Access Journals (Sweden)

    David C. RINGSMUTH

    2002-02-01

    Full Text Available The model of foreign friends visiting fellow democracies to observe and participate in the civic culture, has a long and distinguished tradition. Tocqueville’s visit to and observations of the United States nearly 200 years ago provide a lofty exemplar to which few could pretend to or attempt to duplicate or approach. Nothing in the following observations is meant to make such a pretense1 My journey in Romania has been and will be substantially less noted and notable, but my observations are offered with similar intentions. Rather they are meant in the spirit and offered with the hope that they might, in some small way, begin to make a contribution to the dialogue about the development of democracy and democratic institutions in Romania. In particular, here, I am concerned with Romania’s ability, will and means to develop public policy.

  12. Focusing on dissociated motor development in Brazilian children

    Directory of Open Access Journals (Sweden)

    Minami Maria Avanise Yumi

    2001-01-01

    Full Text Available Dissociated motor development (DMD is considered when the baby starts independent walking late, with normality of the other fields of development. There is evidence that babies with DMD present an atypical crawling pattern and hypotonia. To investigate the frequency and characteristics of DMD, neurological examination was performed monthly in 177 healthy full-term babies from 6 months age, in urban and rural zone samples in Brazil. Among 20 children with atypical crawling, none presented hypotonia neither did they start independent walking late. The means of the ages at the begining of atypical crawling and independent walking acquisitions, 7.40mo (SD 1.4 and 12.76mo (SD 2.5 respectively, did not differ from the group with crossed crawling pattern. Thus, in this sample of Brazilian healthy children we did not find cases with DMD.

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

    International Nuclear Information System (INIS)

    Vignaud, J.; Doyon, D.

    1988-01-01

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

  14. Recent advances in canine leptospirosis: focus on vaccine development

    Directory of Open Access Journals (Sweden)

    Klaasen HLBM

    2015-06-01

    Full Text Available Henricus LBM (Eric Klaasen,1 Ben Adler2 1Global Companion Animals Research and Development, Merck Sharp and Dohme Animal Health, Boxmeer, the Netherlands; 2Department of Microbiology, Monash University, Clayton, VIC, Australia Abstract: Leptospirosis is a global infection of humans and animals caused by pathogenic Leptospira spp. Leptospirosis is a major zoonosis, with infection acquired from wild and domestic animals. It is also a significant cause of morbidity, mortality, and economic loss in production and companion animals. Leptospirosis in dogs is prevalent worldwide and as well as a cause of canine disease, it presents a zoonotic risk to human contacts. Canine leptospirosis does not differ greatly from the syndromes seen in other animal species, with hepatic, renal, and pulmonary involvement being the main manifestations. While the pathogenesis of disease is well documented at the whole animal level, the cellular and molecular basis remains obscure. Killed, whole-cell bacterin vaccines are licensed worldwide and have not changed greatly over the past several decades. Vaccine-induced immunity is restricted to serologically related serovars and is generally short-lived, necessitating annual revaccination. The appearance of new serovars as causes of canine leptospirosis requires constant epidemiological surveillance and tailoring of vaccines to cover emerging serovars. At the present time, there is no realistic prospect of alternative, non-bacterin vaccines in the foreseeable future. Keywords: canine leptospirosis, vaccines, diagnosis, epidemiology, pathogenesis

  15. Inflammasomes and Cancer: The Dynamic Role of the Inflammasome in Tumor Development

    Directory of Open Access Journals (Sweden)

    Melvin Kantono

    2017-09-01

    Full Text Available Chronic Inflammation in tumor microenvironments is not only associated with various stages of tumor development, but also has significant impacts on tumor immunity and immunotherapy. Inflammasome are an important innate immune pathway critical for the production of active IL-1β and interleukin 18, as well as the induction of pyroptosis. Although extensive studies have demonstrated that inflammasomes play a vital role in infectious and autoimmune diseases, their role in tumor progression remains elusive. Multiple studies using a colitis-associated colon cancer model show that inflammasome components provide protection against the development of colon cancer. However, very recent studies demonstrate that inflammasomes promote tumor progression in skin and breast cancer. These results indicate that inflammasomes can promote and suppress tumor development depending on types of tumors, specific inflammasomes involved, and downstream effector molecules. The complicated role of inflammasomes raises new opportunities and challenges to manipulate inflammasome pathways in the treatment of cancer.

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

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  17. Development of stereotactic mass spectrometry for brain tumor surgery.

    Science.gov (United States)

    Agar, Nathalie Y R; Golby, Alexandra J; Ligon, Keith L; Norton, Isaiah; Mohan, Vandana; Wiseman, Justin M; Tannenbaum, Allen; Jolesz, Ferenc A

    2011-02-01

    Surgery remains the first and most important treatment modality for the majority of solid tumors. Across a range of brain tumor types and grades, postoperative residual tumor has a great impact on prognosis. The principal challenge and objective of neurosurgical intervention is therefore to maximize tumor resection while minimizing the potential for neurological deficit by preserving critical tissue. To introduce the integration of desorption electrospray ionization mass spectrometry into surgery for in vivo molecular tissue characterization and intraoperative definition of tumor boundaries without systemic injection of contrast agents. Using a frameless stereotactic sampling approach and by integrating a 3-dimensional navigation system with an ultrasonic surgical probe, we obtained image-registered surgical specimens. The samples were analyzed with ambient desorption/ionization mass spectrometry and validated against standard histopathology. This new approach will enable neurosurgeons to detect tumor infiltration of the normal brain intraoperatively with mass spectrometry and to obtain spatially resolved molecular tissue characterization without any exogenous agent and with high sensitivity and specificity. Proof of concept is presented in using mass spectrometry intraoperatively for real-time measurement of molecular structure and using that tissue characterization method to detect tumor boundaries. Multiple sampling sites within the tumor mass were defined for a patient with a recurrent left frontal oligodendroglioma, World Health Organization grade II with chromosome 1p/19q codeletion, and mass spectrometry data indicated a correlation between lipid constitution and tumor cell prevalence. The mass spectrometry measurements reflect a complex molecular structure and are integrated with frameless stereotaxy and imaging, providing 3-dimensional molecular imaging without systemic injection of any agents, which can be implemented for surgical margins delineation of

  18. Androgen dependent mechanisms of pro-angiogenic networks in placental and tumor development.

    Science.gov (United States)

    Metzler, Veronika M; de Brot, Simone; Robinson, Robert S; Jeyapalan, Jennie N; Rakha, Emad; Walton, Thomas; Gardner, David S; Lund, Emma F; Whitchurch, Jonathan; Haigh, Daisy; Lochray, Jack M; Robinson, Brian D; Allegrucci, Cinzia; Fray, Rupert G; Persson, Jenny L; Ødum, Niels; Miftakhova, Regina R; Rizvanov, Albert A; Hughes, Ieuan A; Tadokoro-Cuccaro, Rieko; Heery, David M; Rutland, Catrin S; Mongan, Nigel P

    2017-08-01

    The placenta and tumors share important characteristics, including a requirement to establish effective angiogenesis. In the case of the placenta, optimal angiogenesis is required to sustain the blood flow required to maintain a successful pregnancy, whereas in tumors establishing new blood supplies is considered a key step in supporting metastases. Therefore the development of novel angiogenesis inhibitors has been an area of active research in oncology. A subset of the molecular processes regulating angiogenesis are well understood in the context of both early placentation and tumorigenesis. In this review we focus on the well-established role of androgen regulation of angiogenesis in cancer and relate these mechanisms to placental angiogenesis. The physiological actions of androgens are mediated by the androgen receptor (AR), a ligand dependent transcription factor. Androgens and the AR are essential for normal male embryonic development, puberty and lifelong health. Defects in androgen signalling are associated with a diverse range of clinical disorders in men and women including disorders of sex development (DSD), polycystic ovary syndrome in women and many cancers. We summarize the diverse molecular mechanisms of androgen regulation of angiogenesis and infer the potential significance of these pathways to normal and pathogenic placental function. Finally, we offer potential research applications of androgen-targeting molecules developed to treat cancer as investigative tools to help further delineate the role of androgen signalling in placental function and maternal and offspring health in animal models. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Recent development of fluorescent imaging for specific detection of tumors

    International Nuclear Information System (INIS)

    Nakata, Eiji; Morii, Takashi; Uto, Yoshihiro; Hori, Hitoshi

    2011-01-01

    Increasing recent studies on fluorescent imaging for specific detection of tumors are described here on strategies of molecular targeting, metabolic specificity and hypoxic circumstance. There is described an instance of a conjugate of antibody and pH-activable fluorescent ligand, which specifically binds to the tumor cells, is internalized in the cellular lysozomes where their pH is low, and then is activated to become fluorescent only in viable tumor cells. For the case of metabolic specificity, excessive loading of the precursor (5-aminolevulinic acid) of protoporphyrin IX (ppIX), due to their low activity to convert ppIX to heme B, results in making tumors observable in red as ppIX emits fluorescence (red, 585 nm) when excited by blue ray of 410 nm. Similarly, imaging with indocyanine green which is accumulated in hepatoma cells is reported in success in detection of small lesion and metastasis when the dye is administered during operation. Reductive reactions exceed in tumor hypoxic conditions, of which feature is usable for imaging. Conjugates of nitroimidazole and fluorescent dye are reported to successfully image tumors by nitro reduction. Authors' UTX-12 is a non-fluorescent nitroaromatic derivative of pH-sensitive fluorescent dye seminaphtharhodafluor (SNARF), and is designed for the nitro group, the hypoxia-responding sensor, to be reduced in tumor hypoxic conditions and then for the aromatic moiety to be cleaved to release free SNARF. Use of hypoxia-inducible factor-1 (HIF-1) for imaging has been also reported in many. As above, studies on fluorescent imaging for specific detection of tumors are mostly at fundamental step but its future is conceivably promising along with advances in other technology like fluorescent endoscopy and multimodal imaging. (author)

  20. Tanks Focus Area retrieval process development and enhancements FY96 technology development summary report

    International Nuclear Information System (INIS)

    Rinker, M.W.; Bamberger, J.A.; Hatchell, B.K.

    1996-09-01

    The Retrieval Process Development and Enhancements (RPD ampersand E) activities are part of the Retrieval and Closure Program of the U.S. Department of Energy (DOE) EM-50 Tanks Focus Area. The purposes of RPD ampersand E are to understand retrieval processes, including emerging and existing technologies, and to gather data on those processes, so that end users have the requisite technical basis to make retrieval decisions. Work has been initiated to support the need for multiple retrieval technologies across the DOE complex. Technologies addressed during FY96 focused on enhancements to sluicing, borehole mining, confined sluicing retrieval end effectors, the lightweight scarifier, and pulsed air mixing. Furthermore, a decision tool and database have been initiated to link retrieval processes with tank closure to assist end users in making retrieval decisions

  1. Development of a Prognostic Marker for Lung Cancer Using Analysis of Tumor Evolution

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-15-1-0243 TITLE: Development of a Prognostic Marker for Lung Cancer Using Analysis of Tumor Evolution PRINCIPAL...SUBTITLE 5a. CONTRACT NUMBER Development of a Prognostic Marker for Lung Cancer Using Analysis of Tumor Evolution 5b. GRANT NUMBER 5c. PROGRAM...derive a prognostic classifier. 15. SUBJECT TERMS NSCLC; tumor evolution ; whole exome sequencing 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF

  2. How real is the long-lasting effect of tumor necrosis factor α inhibitors? Focus on immunogenicity

    Directory of Open Access Journals (Sweden)

    D.E. Karateev

    2014-01-01

    Full Text Available Tumor necrosis factor (TNF α inhibitors are the most commonly used agents to treat rheumatoid arthritis (RA and other inflammatory arthropathies. Five drugs belonging to the family of TNFα inhibitors have been certified in Russia for treating RA: infliximab (INF, adali- mumab (ADA, golimumab, certolizumab pegol, and etanercept (ETN. These drugs have different compositions. ETN does not belong to the family of monoclonal antibodies (mAbs and has a different mechanism of action. It is a dimeric molecule of synthetic fusion protein contain- ing TNF receptor and bound to the Fc-fragment of human Ig1. ETN can inhibit both TNFα and lymphotoxin α. ETN contains only the pro- tein identical to human protein. All TNFα inhibitors exhibit a virtually identical anti-inflammatory activity. The data from the registries show that the risk of discontinuation of therapy with TNFα during the first 2–3 years is appreciably high; there is a trend toward increased frequency of therapy discontinuation because of loss of effectiveness. It was found that the risk of therapy discontinuation because of insufficient effectiveness and adverse events (AEs is minimal for ETN and maximal for INF. The structure of biological drugs (which also affects their immunogenicity has the key neg- ative effect on maintaining the response to therapy and frequency of AEs. However, since ETN is a fusion molecule and contains less poten- tially immunogenic epitopes compared to mAbs, the frequency of detecting anti-drug antibodies (ADAbs is appreciably lower. The fact that ETN has a lower immunogenicity can be used to explain the significantly lower probability of discontinuing therapy using this drug as compared to INF and ADA. The risk that the need to increase the dose because of gradual loss of effectiveness of therapy with ADA and INF, was 4.9- and 28-fold higher, respectively, as compared to ETN. Therapeutic algorithms make it possible to control therapy with TGFα inhibitors

  3. How real is the long-lasting effect of tumor necrosis factor α inhibitors? Focus on immunogenicity

    Directory of Open Access Journals (Sweden)

    D.E. Karateev

    2014-05-01

    Full Text Available Tumor necrosis factor (TNF α inhibitors are the most commonly used agents to treat rheumatoid arthritis (RA and other inflammatory arthropathies. Five drugs belonging to the family of TNFα inhibitors have been certified in Russia for treating RA: infliximab (INF, adali- mumab (ADA, golimumab, certolizumab pegol, and etanercept (ETN. These drugs have different compositions. ETN does not belong to the family of monoclonal antibodies (mAbs and has a different mechanism of action. It is a dimeric molecule of synthetic fusion protein contain- ing TNF receptor and bound to the Fc-fragment of human Ig1. ETN can inhibit both TNFα and lymphotoxin α. ETN contains only the pro- tein identical to human protein. All TNFα inhibitors exhibit a virtually identical anti-inflammatory activity. The data from the registries show that the risk of discontinuation of therapy with TNFα during the first 2–3 years is appreciably high; there is a trend toward increased frequency of therapy discontinuation because of loss of effectiveness. It was found that the risk of therapy discontinuation because of insufficient effectiveness and adverse events (AEs is minimal for ETN and maximal for INF. The structure of biological drugs (which also affects their immunogenicity has the key neg- ative effect on maintaining the response to therapy and frequency of AEs. However, since ETN is a fusion molecule and contains less poten- tially immunogenic epitopes compared to mAbs, the frequency of detecting anti-drug antibodies (ADAbs is appreciably lower. The fact that ETN has a lower immunogenicity can be used to explain the significantly lower probability of discontinuing therapy using this drug as compared to INF and ADA. The risk that the need to increase the dose because of gradual loss of effectiveness of therapy with ADA and INF, was 4.9- and 28-fold higher, respectively, as compared to ETN. Therapeutic algorithms make it possible to control therapy with TGFα inhibitors

  4. Rapid development of Leydig cell tumors in a Wistar rat substrain

    NARCIS (Netherlands)

    Teerds, K. J.; de rooij, D. G.; de Jong, F. H.; Rommerts, F. F.

    1991-01-01

    In 78% of the Wistar rats (substrain U) studied, spontaneous Leydig cell tumors developed between the ages of 12 and 30 months. The first signs of tumor development, in the form of nodules of Leydig cells, were already apparent in 1-month-old U-rats. These nodules of Leydig cells were found in all

  5. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: focus on the cancer hallmark of tumor angiogenesis.

    Science.gov (United States)

    Hu, Zhiwei; Brooks, Samira A; Dormoy, Valérian; Hsu, Chia-Wen; Hsu, Hsue-Yin; Lin, Liang-Tzung; Massfelder, Thierry; Rathmell, W Kimryn; Xia, Menghang; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Brown, Dustin G; Prudhomme, Kalan R; Colacci, Annamaria; Hamid, Roslida A; Mondello, Chiara; Raju, Jayadev; Ryan, Elizabeth P; Woodrick, Jordan; Scovassi, A Ivana; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Salem, Hosni K; Lowe, Leroy; Jensen, Lasse; Bisson, William H; Kleinstreuer, Nicole

    2015-06-01

    One of the important 'hallmarks' of cancer is angiogenesis, which is the process of formation of new blood vessels that are necessary for tumor expansion, invasion and metastasis. Under normal physiological conditions, angiogenesis is well balanced and controlled by endogenous proangiogenic factors and antiangiogenic factors. However, factors produced by cancer cells, cancer stem cells and other cell types in the tumor stroma can disrupt the balance so that the tumor microenvironment favors tumor angiogenesis. These factors include vascular endothelial growth factor, endothelial tissue factor and other membrane bound receptors that mediate multiple intracellular signaling pathways that contribute to tumor angiogenesis. Though environmental exposures to certain chemicals have been found to initiate and promote tumor development, the role of these exposures (particularly to low doses of multiple substances), is largely unknown in relation to tumor angiogenesis. This review summarizes the evidence of the role of environmental chemical bioactivity and exposure in tumor angiogenesis and carcinogenesis. We identify a number of ubiquitous (prototypical) chemicals with disruptive potential that may warrant further investigation given their selectivity for high-throughput screening assay targets associated with proangiogenic pathways. We also consider the cross-hallmark relationships of a number of important angiogenic pathway targets with other cancer hallmarks and we make recommendations for future research. Understanding of the role of low-dose exposure of chemicals with disruptive potential could help us refine our approach to cancer risk assessment, and may ultimately aid in preventing cancer by reducing or eliminating exposures to synergistic mixtures of chemicals with carcinogenic potential. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Jnk2 effects on tumor development, genetic instability and replicative stress in an oncogene-driven mouse mammary tumor model.

    Directory of Open Access Journals (Sweden)

    Peila Chen

    2010-05-01

    Full Text Available Oncogenes induce cell proliferation leading to replicative stress, DNA damage and genomic instability. A wide variety of cellular stresses activate c-Jun N-terminal kinase (JNK proteins, but few studies have directly addressed the roles of JNK isoforms in tumor development. Herein, we show that jnk2 knockout mice expressing the Polyoma Middle T Antigen transgene developed mammary tumors earlier and experienced higher tumor multiplicity compared to jnk2 wildtype mice. Lack of jnk2 expression was associated with higher tumor aneuploidy and reduced DNA damage response, as marked by fewer pH2AX and 53BP1 nuclear foci. Comparative genomic hybridization further confirmed increased genomic instability in PyV MT/jnk2-/- tumors. In vitro, PyV MT/jnk2-/- cells underwent replicative stress and cell death as evidenced by lower BrdU incorporation, and sustained chromatin licensing and DNA replication factor 1 (CDT1 and p21(Waf1 protein expression, and phosphorylation of Chk1 after serum stimulation, but this response was not associated with phosphorylation of p53 Ser15. Adenoviral overexpression of CDT1 led to similar differences between jnk2 wildtype and knockout cells. In normal mammary cells undergoing UV induced single stranded DNA breaks, JNK2 localized to RPA (Replication Protein A coated strands indicating that JNK2 responds early to single stranded DNA damage and is critical for subsequent recruitment of DNA repair proteins. Together, these data support that JNK2 prevents replicative stress by coordinating cell cycle progression and DNA damage repair mechanisms.

  7. Magnetic resonance guided focused ultrasound surgery (MRgFUS) of bone metastases: From primary pain palliation to local tumor control

    Science.gov (United States)

    Napoli, A.; Leonardi, A.; Andrani, F.; Boni, F.; Anzidei, M.; Catalano, C.

    2017-03-01

    Purpose: To evaluate the clinical performance of MRgFUS in primary pain palliation of painful bone metastases and in local tumor control. Materials and Methods: We enrolled 26 consecutive patients (female/male 12/14; age: 64.7±7.5yrs) with painful bone metastases. Before and 3 months after MRgFUS treatment pain severity and pain interference scores were assessed according to Brief Pain Inventory-Quality of Life (BPI-QoL) criteria and patients underwent both CT and MRI. Local tumor control was evaluated according to lesion size, density and perfusion at CT, dynamic contrast enhancement at MRI (Discovery 750HD, GE; Gd-Bopta, Bracco) and metabolic activity at PET or scintigraphy. Patients were classified as responders or non-responders. Results: No treatment-related adverse events were recorded during the study. As statistically significant difference between baseline and follow-up values for both pain severity and pain interference scores was observed (p<0.05). Increased bone density was observed in 9/26 (34.6%) patients. Non-Perfused Volume values ranged between 20% and 92%. There was no difference in NPV values between responders and non-responders (46.7±24.2% [25 - 90 %] vs. 45±24.9% [20 - 93 %]; p=0.7). In 6 patients (5 prostate and 1 breast primary cancer) there was nearly absence of metabolic activity after treatment (mean SUV=1.2). Conclusion: MRgFUS can be safely and effectively used as the primary treatment for pain palliation in patients with painful bone metastases; moreover our experience demonstrated also a potential role for the MRgFUS in local tumor control.

  8. FTIR spectro-imaging of collagen scaffold formation during glioma tumor development.

    Science.gov (United States)

    Noreen, Razia; Chien, Chia-Chi; Chen, Hsiang-Hsin; Bobroff, Vladimir; Moenner, Michel; Javerzat, Sophie; Hwu, Yeukuang; Petibois, Cyril

    2013-11-01

    Evidence has recently emerged that solid and diffuse tumors produce a specific extracellular matrix (ECM) for division and diffusion, also developing a specific interface with microvasculature. This ECM is mainly composed of collagens and their scaffolding appears to drive tumor growth. Although collagens are not easily analyzable by UV-fluorescence means, FTIR imaging has appeared as a valuable tool to characterize collagen contents in tissues, specially the brain, where ECM is normally devoid of collagen proteins. Here, we used FTIR imaging to characterize collagen content changes in growing glioma tumors. We could determine that C6-derived solid tumors presented high content of triple helix after 8-11 days of growth (typical of collagen fibrils formation; 8/8 tumor samples; 91 % of total variance), and further turned to larger α-helix (days 12-15; 9/10 of tumors; 94 % of variance) and β-turns (day 18-21; 7/8 tumors; 97 % of variance) contents, which suggest the incorporation of non-fibrillar collagen types in ECM, a sign of more and more organized collagen scaffold along tumor progression. The growth of tumors was also associated to the level of collagen produced (P < 0.05). This study thus confirms that collagen scaffolding is a major event accompanying the angiogenic shift and faster tumor growth in solid glioma phenotypes.

  9. EM-50 Tanks Focus Area retrieval process development and enhancements. FY97 technology development summary report

    International Nuclear Information System (INIS)

    Rinker, M.W.; Bamberger, J.A.; Alberts, D.G.

    1997-09-01

    The Retrieval Process Development and Enhancements (RPD and E) activities are part of the US Department of Energy (DOE) EM-50 Tanks Focus Area, Retrieval and Closure program. The purpose of RPD and E is to understand retrieval processes, including emerging and existing technologies, and to gather data on these processes, so that end users have requisite technical bases to make retrieval decisions. Technologies addressed during FY97 include enhancements to sluicing, the use of pulsed air to assist mixing, mixer pumps, innovative mixing techniques, confined sluicing retrieval end effectors, borehole mining, light weight scarification, and testing of Russian-developed retrieval equipment. Furthermore, the Retrieval Analysis Tool was initiated to link retrieval processes with tank waste farms and tank geometric to assist end users by providing a consolidation of data and technical information that can be easily assessed. The main technical accomplishments are summarized under the following headings: Oak Ridge site-gunite and associated tanks treatability study; pulsed air mixing; Oak Ridge site-Old Hydrofracture Facility; hydraulic testbed relocation; cooling coil cleaning end effector; light weight scarifier; innovative tank mixing; advanced design mixer pump; enhanced sluicing; Russian retrieval equipment testing; retrieval data analysis and correlation; simulant development; and retrieval analysis tool (RAT)

  10. Glucose-Modulated Mitochondria Adaptation in Tumor Cells: A Focus on ATP Synthase and Inhibitor Factor 1

    Directory of Open Access Journals (Sweden)

    Irene Mavelli

    2012-02-01

    Full Text Available Warburg’s hypothesis has been challenged by a number of studies showing that oxidative phosphorylation is repressed in some tumors, rather than being inactive per se. Thus, treatments able to shift energy metabolism by activating mitochondrial pathways have been suggested as an intriguing basis for the optimization of antitumor strategies. In this study, HepG2 hepatocarcinoma cells were cultivated with different metabolic substrates under conditions mimicking “positive” (activation/biogenesis or “negative” (silencing mitochondrial adaptation. In addition to the expected up-regulation of mitochondrial biogenesis, glucose deprivation caused an increase in phosphorylating respiration and a rise in the expression levels of the ATP synthase β subunit and Inhibitor Factor 1 (IF1. Hyperglycemia, on the other hand, led to a markedly decreased level of the transcriptional coactivator PGC-α suggesting down-regulation of mitochondrial biogenesis, although no change in mitochondrial mass and no impairment of phosphorylating respiration were observed. Moreover, a reduction in mitochondrial networking and in ATP synthase dimer stability was produced. No effect on β-ATP synthase expression was elicited. Notably, hyperglycemia caused an increase in IF1 expression levels, but it did not alter the amount of IF1 associated with ATP synthase. These results point to a new role of IF1 in relation to high glucose utilization by tumor cells, in addition to its well known effect upon mitochondrial ATP synthase regulation.

  11. Design of the Accounting Course Focusing on the Development of Competences

    Science.gov (United States)

    Ciudad-Gomez, Adelaida

    2011-01-01

    The aim of this work is to develop a proposal for a methodology in the university environment that enables us to design our course with an approach based on the development and acquisition of competences within the framework of the European Higher Education Area (EHEA), allowing a transition from a model focused on teaching to a model focused on…

  12. Noncontact measurement of elasticity for the detection of soft-tissue tumors using phase-sensitive optical coherence tomography combined with a focused air-puff system.

    Science.gov (United States)

    Wang, Shang; Li, Jiasong; Manapuram, Ravi Kiran; Menodiado, Floredes M; Ingram, Davis R; Twa, Michael D; Lazar, Alexander J; Lev, Dina C; Pollock, Raphael E; Larin, Kirill V

    2012-12-15

    We report on an optical noncontact method for the detection of soft-tissue tumors based on the measurement of their elasticity. A focused air-puff system is used to excite surface waves (SWs) on soft tissues with transient static pressure. A high-speed phase-sensitive optical coherence tomography system is used to measure the SWs as they propagate from the point of excitation. To evaluate the stiffness of soft tissues, the Young's modulus is quantified based on the group velocity of SWs. Pilot experiments were performed on ex vivo human myxoma and normal fat. Results demonstrate the feasibility of the proposed method to measure elasticity and differentiate soft-tissue tumors from normal tissues.

  13. Tumor Heterogeneity and Drug Resistance

    International Nuclear Information System (INIS)

    Kucerova, L.; Skolekova, S.; Kozovska, Z.

    2015-01-01

    New generation of sequencing methodologies revealed unexpected complexity and genomic alterations linked with the tumor subtypes. This diversity exists across the tumor types, histologic tumor subtypes and subsets of the tumor cells within the same tumor. This phenomenon is termed tumor heterogeneity. Regardless of its origin and mechanisms of development it has a major impact in the clinical setting. Genetic, phenotypic and expression pattern diversity of tumors plays critical role in the selection of suitable treatment and also in the prognosis prediction. Intratumoral heterogeneity plays a key role in the intrinsic and acquired chemoresistance to cytotoxic and targeted therapies. In this review we focus on the mechanisms of intratumoral and inter tumoral heterogeneity and their relationship to the drug resistance. Understanding of the mechanisms and spatiotemporal dynamics of tumor heterogeneity development before and during the therapy is important for the ability to design individual treatment protocols suitable in the given molecular context. (author)

  14. The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

    International Nuclear Information System (INIS)

    Rymaszewski, Amy L.; Tate, Everett; Yimbesalu, Joannes P.; Gelman, Andrew E.; Jarzembowski, Jason A.; Zhang, Hao; Pritchard, Kirkwood A. Jr.; Vikis, Haris G.

    2014-01-01

    Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting

  15. The role of neutrophil myeloperoxidase in models of lung tumor development.

    Science.gov (United States)

    Rymaszewski, Amy L; Tate, Everett; Yimbesalu, Joannes P; Gelman, Andrew E; Jarzembowski, Jason A; Zhang, Hao; Pritchard, Kirkwood A; Vikis, Haris G

    2014-05-09

    Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

  16. The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

    Energy Technology Data Exchange (ETDEWEB)

    Rymaszewski, Amy L.; Tate, Everett; Yimbesalu, Joannes P. [Department of Pharmacology and Toxicology and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Gelman, Andrew E. [Department of Surgery, Washington University in St. Louis, St. Louis, MO 63130 (United States); Jarzembowski, Jason A. [Department of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Zhang, Hao; Pritchard, Kirkwood A. Jr. [Department of Surgery and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Vikis, Haris G., E-mail: hvikis@mcw.edu [Department of Pharmacology and Toxicology and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States)

    2014-05-09

    Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

  17. The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

    Directory of Open Access Journals (Sweden)

    Amy L. Rymaszewski

    2014-05-01

    Full Text Available Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA-initiated, butylated hydroxytoluene (BHT-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC, a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

  18. Tumor development following internal exposures to radionuclides during the perinatal period

    International Nuclear Information System (INIS)

    Sikov, M.R.

    1988-07-01

    Exposure to radiation from internally deposited radionuclides during the prenatal and/or neonatal periods involves a distinct oncogenic potential. The fundamental mechanisms for perinatal radionuclide carcinogenesis seem to be generally similar to those that pertain to external radiation exposures and other carcinogenic agents, but unique interactions may be superimposed. Specific dose-effect relationships differ among radionuclides; many studies find dose-related increases in the incidence of tumors or decreases in age at tumor appearance following prenatal or neonatal radiation exposures. Tumor incidences may be decreased, especially at high dose levels; these are usually attributable to cell death, inhibited development of target tissues, or to endocrine malfunction. Age-related differences in predominant tumor types and/or sites of tumor development are often detected, and are explainable by the existence of nuclide-specific target organs or tissues, dosimetric factors, and developmental considerations. 34 refs

  19. Microdissecting the Genetic Events in Nephrogenic Rests and Wilms’ Tumor Development

    Science.gov (United States)

    Charles, Adrian K.; Brown, Keith W.; Berry, P. Jeremy

    1998-01-01

    Nephrogenic rests are precursor lesions associated with about 40% of Wilms’ tumors. This study identifies genetic steps occurring in the development of Wilms’ tumor. Thirty-four Wilms’ tumors with nephrogenic rests and/or areas of anaplasia were microdissected from paraffin sections to determine whether and at what stage loss of heterozygosity (LOH) occurred, using polymerase chain reaction-based polymorphic markers at 11p13, 11p15, and 16q. LOH at these loci have been identified in Wilms’ tumors and are associated with identified or putative tumor suppressor genes. Three cystic nephromas/cystic partially differentiated nephroblastomas were also examined. LOH was detected in six cases at 11p13 and in six cases at 11p15, and two of these cases had LOH at both loci. All intralobar rests showing LOH also showed LOH in the tumor. A case with a small perilobar rest showed LOH of 11p13 only in the tumor. Five cases showing LOH at 16q were identified (this was identified only in the tumor, and not in the associated rest), and three of these had recurrence of the tumor. Two cases had a WT1 mutation (one germline and the other somatic), as well as LOH in both the intralobar rest and the tumor. A cystic partially differentiated nephroblastoma showed loss at 11p13 and 11p15, as well as at 16q. This study suggests that LOH at 11p13 and 11p15 and WT1 mutations are early events but that LOH at 16q occurs late in the pathogenesis of Wilms’ tumor. Intralobar and perilobar nephrogenic rests are known to have different biological behaviors, and this study suggests that they are genetically different. A multistep model of Wilms’ tumor pathogenesis is supported by these findings. PMID:9736048

  20. Successful Use of Magnetic Resonance-Guided Focused Ultrasound Surgery for Long-Term Pain Palliation in a Patient Suffering from Metastatic Bone Tumor

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji Eun; Yoon, Sang Wook; Kim, Kyoung Ah; Lee, Jong Tae [Dept. of Diagnostic Radiology, CHA Bundang Medical Center, CHA University College of Medicine, Seongnam (Korea, Republic of); Shay, Lilach [InSightec. Ltd, Hifa, (Israel); Lee, Kyong Sik [Dept. of General Surgery, CHA Bundang Medical Center, CHA University College of Medicine, Seongnam (Korea, Republic of)

    2011-08-15

    Magnetic Resonance-guided Focused Ultrasound Surgery (MRgFUS) is a clinically effective, non-invasive treatment for thermal ablation of various soft tissue tumors, and is effective in pain palliation following radiation therapy, as has been demonstrated in the initial studies of bone metastases. The current study evaluated the safety and clinical efficacy of MRgFUS for pain palliation prior to radiation therapy, in a patient with a solitary metastatic bone lesion. This is the first case report of MRgFUS treatment with a 1-year follow-up in a patient.

  1. Successful Use of Magnetic Resonance-Guided Focused Ultrasound Surgery for Long-Term Pain Palliation in a Patient Suffering from Metastatic Bone Tumor

    International Nuclear Information System (INIS)

    Lee, Ji Eun; Yoon, Sang Wook; Kim, Kyoung Ah; Lee, Jong Tae; Shay, Lilach; Lee, Kyong Sik

    2011-01-01

    Magnetic Resonance-guided Focused Ultrasound Surgery (MRgFUS) is a clinically effective, non-invasive treatment for thermal ablation of various soft tissue tumors, and is effective in pain palliation following radiation therapy, as has been demonstrated in the initial studies of bone metastases. The current study evaluated the safety and clinical efficacy of MRgFUS for pain palliation prior to radiation therapy, in a patient with a solitary metastatic bone lesion. This is the first case report of MRgFUS treatment with a 1-year follow-up in a patient.

  2. Cell Death Conversion under Hypoxic Condition in Tumor Development and Therapy

    Directory of Open Access Journals (Sweden)

    Yu Qiu

    2015-10-01

    Full Text Available Hypoxia, which is common during tumor progression, plays important roles in tumor biology. Failure in cell death in response to hypoxia contributes to progression and metastasis of tumors. On the one hand, the metabolic and oxidative stress following hypoxia could lead to cell death by triggering signal cascades, like LKB1/AMPK, PI3K/AKT/mTOR, and altering the levels of effective components, such as the Bcl-2 family, Atg and p62. On the other hand, hypoxia-induced autophagy can serve as a mechanism to turn over nutrients, so as to mitigate the adverse condition and then avoid cell death potentially. Due to the effective role of hypoxia, this review focuses on the crosstalk in cell death under hypoxia in tumor progression. Additionally, the illumination of cell death in hypoxia could shed light on the clinical applications of cell death targeted therapy.

  3. 78 FR 29755 - Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...

    Science.gov (United States)

    2013-05-21

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0473] Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus Cure... an opportunity for public comment on human immunodeficiency virus (HIV) Patient-Focused Drug...

  4. 78 FR 46969 - Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...

    Science.gov (United States)

    2013-08-02

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0473] Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus Cure... for the notice of public meeting entitled ``Human Immunodeficiency Virus (HIV) Patient-Focused Drug...

  5. Cystatin C and lactoferrin concentrations in biological fluids as possible prognostic factors in eye tumor development

    Directory of Open Access Journals (Sweden)

    Mariya A. Dikovskaya

    2013-08-01

    Full Text Available Objectives. To investigate the possible role of cystatin C in eye biological fluids locally and in serum and lactoferrin revealing anti-tumor activity in eye tumor development. Background. The increased number of eye tumors was registered recently not only in the countries with high insolation, but also in the northern countries including Russia (11 cases per million of population. Search for new biological markers is important for diagnosis and prognosis in eye tumors. Cystatin C, an endogenous inhibitor of cysteine proteases, plays an important protective role in several tumors. Lactoferrin was shown to express anti-tumor and antiviral activities. It was hypothesized that cystatin C and lactoferrin could serve as possible biomarkers in the diagnosis of malignant and benign eye tumors. Study design. A total of 54 patients with choroidal melanoma and benign eye tumors were examined (part of them undergoing surgical treatment. Serum, tear fluid and intraocular fluid samples obtained from the anterior chamber of eyes in patients with choroidal melanoma were studied. Methods. Cystatin C concentration in serum and eye biological fluids was measured by commercial ELISA kits for human (BioVendor, Czechia; lactoferrin concentration – by Lactoferrin-strip D 4106 ELISA test systems (Vector-BEST, Novosibirsk Region, Russia. Results. Cystatin C concentration in serum of healthy persons was significantly higher as compared to tear and intraocular fluids. In patients with choroidal melanoma, increased cystatin C concentration was similar in tear fluid of both the eyes. Lactoferrin level in tear fluid of healthy persons was significantly higher than its serum level. Significantly increased lactoferrin concentration in tear fluid was noted in patients with benign and malignant eye tumors. Conclusion. Increased level of cystatin C in tear fluid seems to be a possible diagnostic factor in the eye tumors studied. However, it does not allow us to differentiate

  6. Predictors of health-related quality of life in neurosurgical brain tumor patients: focus on patient-centered perspective.

    Science.gov (United States)

    Bunevicius, Adomas; Tamasauskas, Sarunas; Deltuva, Vytenis; Tamasauskas, Arimantas; Radziunas, Andrius; Bunevicius, Robertas

    2014-02-01

    In brain tumor (BT) patients, the association between health-related quality of life (HRQoL) and psychological characteristics remains largely unknown. We evaluated the association of personality traits, clinical factors, psychological distress symptoms, and cognitive state with HRQoL in BT patients. On admission for BT surgery, 200 patients (69 % women; age 55.8 ± 14.5 years) were evaluated for HRQoL (SF-36 scale), Big-Five personality traits (Ten-Item Personality Inventory), psychological distress symptoms (Hospital Anxiety and Depression Scale or HADS), cognitive function (Mini-Mental State Examination or MMSE) and clinical characteristics, including functional status (Barthel index or BI). The most common BT diagnoses were meningioma (39 %) and high-grade glioma (18 %). Only factors significantly associated with SF-36 domains in univariable regression analyses were included in their respective multivariable models and predicted from 6 %-49 % of the total variance of SF-36 scores. Greater TIPI emotional stability score was independently associated with greater SF-36 emotional well-being (β = 0.23, p emotional well-being score (β = 0.13, p = 0.02). HADS-anxiety and HADS-depression scores were the strongest independent determinants of all, except physical functioning, SF-36 scores (β-values range from 0.14 to 0.56; p values ≤ 0.03). BI score was the strongest independent determinant of SF-36 physical functioning score (β = 0.36, p emotional well-being and social functioning SF-36 scores. Consciousness and emotional stability should be considered important personality-related determinants of HRQoL in BT patients. Psychological distress, functional disability, and cognitive impairment are also important predictors of HRQoL.

  7. Non-invasive thermal IR detection of breast tumor development in vivo

    Science.gov (United States)

    Case, Jason R.; Young, Madison A.; Dréau, D.; Trammell, Susan R.

    2015-03-01

    Lumpectomy coupled with radiation therapy and/or chemotherapy comprises the treatment of breast cancer for many patients. We are developing an enhanced thermal IR imaging technique that can be used in real-time to guide tissue excision during a lumpectomy. This novel enhanced thermal imaging method is a combination of IR imaging (8- 10 μm) and selective heating of blood (~0.5 °C) relative to surrounding water-rich tissue using LED sources at low powers. Post-acquisition processing of these images highlights temporal changes in temperature and is sensitive to the presence of vascular structures. In this study, fluorescent and enhanced thermal imaging modalities were used to estimate breast cancer tumor volumes as a function of time in 19 murine subjects over a 30-day study period. Tumor volumes calculated from fluorescent imaging follow an exponential growth curve for the first 22 days of the study. Cell necrosis affected the tumor volume estimates based on the fluorescent images after Day 22. The tumor volumes estimated from enhanced thermal imaging show exponential growth over the entire study period. A strong correlation was found between tumor volumes estimated using fluorescent imaging and the enhanced IR images, indicating that enhanced thermal imaging is capable monitoring tumor growth. Further, the enhanced IR images reveal a corona of bright emission along the edges of the tumor masses. This novel IR technique could be used to estimate tumor margins in real-time during surgical procedures.

  8. Effect of high-intensity focused ultrasound (HIFU combined with radiotherapy on tumor malignancy in patients with advanced pancreatic cancer and evaluation of side effects

    Directory of Open Access Journals (Sweden)

    Jing Li

    2017-02-01

    Full Text Available Objective: To study the effect of high-intensity focused ultrasound (HIFU combined with radiotherapy on tumor malignancy in patients with advanced pancreatic cancer and the corresponding side effects. Methods: A total of 84 patients with advanced pancreatic cancer treated in our hospital between May 2013 and March 2016 were selected and randomly divided into HIFU group and IGRT group, HIFU group accepted high-intensity focused ultrasound combined with radiotherapy and IGRT group received radiotherapy alone. 4 weeks after treatment, the levels of tumor markers, liver and kidney function indexes, perineural invasionrelated molecules and cytokines in serum as well as the levels of immune cells in peripheral blood were determined. Results: 4 weeks after treatment, serum CA199, CA242, OPN, NGAL, RBP4, NGF, TrkA, p75, BDNF and TrkB levels of HIFU group were significantly lower than those of IGRT group, serum IL-2, TNF-毩, IFN-γ and IL-13 levels as well as peripheral blood NKT cell and CD4+T cell levels were significantly higher than those of IGRT group, and serum ALT, AST, Cr and BUN levels were not significantly different from those of IGRT group. Conclusion: HIFU combined with radiotherapy treatment of advanced pancreatic cancer can more effectively kill cancer cells, inhibit pancreatic cancer cell invasion to the peripheral nerve and enhance the antitumor immune response mediated by NKT cells and CD4+T cells.

  9. Computerized Attention Training Program and Vocal Ensemble Classes – means of Adolescent Attention Focusing Ability Development

    OpenAIRE

    Trubina, Irēna; Sīle, Maruta; Vaļēviča, Evita; Voita, Daina

    2015-01-01

    Nowadays adolescents encounter difficulties focusing on particular, effective and long-term activities. These difficulties depend on their age group development regularities. The aim of the research is to evaluate computer attention training software in comparison with vocal ensemble classes on the subject of adolescent attention focusing ability development. Participants – 24 adolescents (both sexes, average age 14 ± 0,87 years) were divided into three experimental groups – experimental grou...

  10. Exome sequencing of bilateral testicular germ cell tumors suggests independent development lineages.

    Science.gov (United States)

    Brabrand, Sigmund; Johannessen, Bjarne; Axcrona, Ulrika; Kraggerud, Sigrid M; Berg, Kaja G; Bakken, Anne C; Bruun, Jarle; Fosså, Sophie D; Lothe, Ragnhild A; Lehne, Gustav; Skotheim, Rolf I

    2015-02-01

    Intratubular germ cell neoplasia, the precursor of testicular germ cell tumors (TGCTs), is hypothesized to arise during embryogenesis from developmentally arrested primordial germ cells (PGCs) or gonocytes. In early embryonal life, the PGCs migrate from the yolk sac to the dorsal body wall where the cell population separates before colonizing the genital ridges. However, whether the malignant transformation takes place before or after this separation is controversial. We have explored the somatic exome-wide mutational spectra of bilateral TGCT to provide novel insight into the in utero critical time frame of malignant transformation and TGCT pathogenesis. Exome sequencing was performed in five patients with bilateral TGCT (eight tumors), of these three patients in whom both tumors were available (six tumors) and two patients each with only one available tumor (two tumors). Selected loci were explored by Sanger sequencing in 71 patients with bilateral TGCT. From the exome-wide mutational spectra, no identical mutations in any of the three bilateral tumor pairs were identified. Exome sequencing of all eight tumors revealed 87 somatic non-synonymous mutations (median 10 per tumor; range 5-21), some in already known cancer genes such as CIITA, NEB, platelet-derived growth factor receptor α (PDGFRA), and WHSC1. SUPT6H was found recurrently mutated in two tumors. We suggest independent development lineages of bilateral TGCT. Thus, malignant transformation into intratubular germ cell neoplasia is likely to occur after the migration of PGCs. We reveal possible drivers of TGCT pathogenesis, such as mutated PDGFRA, potentially with therapeutic implications for TGCT patients. Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.

  11. Exome Sequencing of Bilateral Testicular Germ Cell Tumors Suggests Independent Development Lineages

    Directory of Open Access Journals (Sweden)

    Sigmund Brabrand

    2015-02-01

    Full Text Available Intratubular germ cell neoplasia, the precursor of testicular germ cell tumors (TGCTs, is hypothesized to arise during embryogenesis from developmentally arrested primordial germ cells (PGCs or gonocytes. In early embryonal life, the PGCs migrate from the yolk sac to the dorsal body wall where the cell population separates before colonizing the genital ridges. However, whether the malignant transformation takes place before or after this separation is controversial. We have explored the somatic exome-wide mutational spectra of bilateral TGCT to provide novel insight into the in utero critical time frame of malignant transformation and TGCT pathogenesis. Exome sequencing was performed in five patients with bilateral TGCT (eight tumors, of these three patients in whom both tumors were available (six tumors and two patients each with only one available tumor (two tumors. Selected loci were explored by Sanger sequencing in 71 patients with bilateral TGCT. From the exome-wide mutational spectra, no identical mutations in any of the three bilateral tumor pairs were identified. Exome sequencing of all eight tumors revealed 87 somatic non-synonymous mutations (median 10 per tumor; range 5-21, some in already known cancer genes such as CIITA, NEB, platelet-derived growth factor receptor α (PDGFRA, and WHSC1. SUPT6H was found recurrently mutated in two tumors. We suggest independent development lineages of bilateral TGCT. Thus, malignant transformation into intratubular germ cell neoplasia is likely to occur after the migration of PGCs. We reveal possible drivers of TGCT pathogenesis, such as mutated PDGFRA, potentially with therapeutic implications for TGCT patients.

  12. Development of cell-cycle checkpoint therapy for solid tumors.

    Science.gov (United States)

    Tamura, Kenji

    2015-12-01

    Cellular proliferation is tightly controlled by several cell-cycle checkpoint proteins. In cancer, the genes encoding these proteins are often disrupted and cause unrestrained cancer growth. The proteins are over-expressed in many malignancies; thus, they are potential targets for anti-cancer therapies. These proteins include cyclin-dependent kinase, checkpoint kinase, WEE1 kinase, aurora kinase and polo-like kinase. Cyclin-dependent kinase inhibitors are the most advanced cell-cycle checkpoint therapeutics available. For instance, palbociclib (PD0332991) is a first-in-class, oral, highly selective inhibitor of CDK4/6 and, in combination with letrozole (Phase II; PALOMA-1) or with fulvestrant (Phase III; PALOMA-3), it has significantly prolonged progression-free survival, in patients with metastatic estrogen receptor-positive, HER2-negative breast cancer, in comparison with that observed in patients using letrozole, or fulvestrant alone, respectively. In this review, we provide an overview of the current compounds available for cell-cycle checkpoint protein-directed therapy for solid tumors. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. A comparison of two clinical correlation models used for real-time tumor tracking of semi-periodic motion: A focus on geometrical accuracy in lung and liver cancer patients

    International Nuclear Information System (INIS)

    Poels, Kenneth; Dhont, Jennifer; Verellen, Dirk; Blanck, Oliver; Ernst, Floris; Vandemeulebroucke, Jef; Depuydt, Tom; Storme, Guy; De Ridder, Mark

    2015-01-01

    Purpose: A head-to-head comparison of two clinical correlation models with a focus on geometrical accuracy for internal tumor motion estimation during real-time tumor tracking (RTTT). Methods and materials: Both the CyberKnife (CK) and the Vero systems perform RTTT with a correlation model that is able to describe hysteresis in the breathing motion. The CK dual-quadratic (DQ) model consists of two polynomial functions describing the trajectory of the tumor for inhale and exhale breathing motion, respectively. The Vero model is based on a two-dimensional (2D) function depending on position and speed of the external breathing signal to describe a closed-loop tumor trajectory. In this study, 20 s of internal motion data, using an 11 Hz (on average) full fluoroscopy (FF) sequence, was used for training of the CK and Vero models. Further, a subsampled set of 15 internal tumor positions (15p) equally spread over the different phases of the breathing motion was used for separate training of the CK DQ model. Also a linear model was trained using 15p and FF tumor motion data. Fifteen liver and lung cancer patients, treated on the Vero system with RTTT, were retrospectively evaluated comparing the CK FF, CK 15p and Vero FF models using an in-house developed simulator. The distance between estimated target position and the tumor position localized by X-ray imaging was measured in the beams-eye view (BEV) to calculate the 95th percentile BEV modeling errors (ME 95,BEV ). Additionally, the percentage of ME 95,BEV smaller than 5 mm (P 5mm ) was determined for all correlation models. Results: In general, no significant difference (p > 0.05, paired t-test) was found between the CK FF and Vero models. Based on patient-specific evaluation of the geometrical accuracy of the linear, CK DQ and Vero correlation models, no statistical necessity (p > 0.05, two-way ANOVA) of including hysteresis in correlation models was proven, although during inhale breathing motion, the linear model

  14. Mammary Gland Tumor Development in Transgenic Mice Overexpressing Different Isoforms of the CDP/Cux Transcription Factor

    National Research Council Canada - National Science Library

    Cadieux, Chantal

    2008-01-01

    Short CUX1 isoforms were found to be overexpressed in breast cancer cell lines, in human breast tumors and in uterine leiomyomas, suggesting that these proteins play a key role in tumor development and progression...

  15. Mammary Gland Tumor Development in Transgenic Mice Overexpressing Different Isoforms of the CDP/Cux Transcription Factor

    National Research Council Canada - National Science Library

    Cadieux, Chantal

    2007-01-01

    Short CDP/Cux isoforms were found to be overexpressed in breast cancer cell lines, in human breast tumors and in uterine leiomyomas, suggesting that these proteins play a key role in tumor development and progression...

  16. In ovo method for evaluating the effect of nutritional therapies on tumor development, growth and vascularization

    OpenAIRE

    Dupertuis, Yves M.; Delie, Florence; Cohen, Marie; Pichard, Claude

    2015-01-01

    In the state of the art evaluation of nutritional therapy on tumor development, growth and vascularization requires tedious and expensive in vivo assays in which a significant number of animals undergo invasive treatments. Therefore, new alternative methods to avoid animal suffering and sacrifice are welcome. This review presents a rapid and low-cost method of experimental radio/chemotherapy in tumor xenografted chicken chorioallantoic membrane (CAM), which may contribute to implement the 3R ...

  17. Diet-induced obesity promotes colon tumor development in azoxymethane-treated mice.

    Directory of Open Access Journals (Sweden)

    Iina Tuominen

    Full Text Available Obesity is an important risk factor for colon cancer in humans, and numerous studies have shown that a high fat diet enhances colon cancer development. As both increased adiposity and high fat diet can promote tumorigenesis, we examined the effect of diet-induced obesity, without ongoing high fat diet, on colon tumor development. C57BL/6J male mice were fed regular chow or high fat diet for 8 weeks. Diets were either maintained or switched resulting in four experimental groups: regular chow (R, high fat diet (H, regular chow switched to high fat diet (RH, and high fat diet switched to regular chow (HR. Mice were then administered azoxymethane to induce colon tumors. Tumor incidence and multiplicity were dramatically smaller in the R group relative to all groups that received high fat diet at any point. The effect of obesity on colon tumors could not be explained by differences in aberrant crypt foci number. Moreover, diet did not alter colonic expression of pro-inflammatory cytokines tumor necrosis factor-α, interleukin-6, interleukin-1β, and interferon-γ, which were measured immediately after azoxymethane treatment. Crypt apoptosis and proliferation, which were measured at the same time, were increased in the HR relative to all other groups. Our results suggest that factors associated with obesity - independently of ongoing high fat diet and obesity - promote tumor development because HR group animals had significantly more tumors than R group, and these mice were fed the same regular chow throughout the entire carcinogenic period. Moreover, there was no difference in the number of aberrant crypt foci between these groups, and thus the effect of obesity appears to be on subsequent stages of tumor development when early preneoplastic lesions transition into adenomas.

  18. Development of tumor-targeted near infrared probes for fluorescence guided surgery.

    Science.gov (United States)

    Kelderhouse, Lindsay E; Chelvam, Venkatesh; Wayua, Charity; Mahalingam, Sakkarapalayam; Poh, Scott; Kularatne, Sumith A; Low, Philip S

    2013-06-19

    Complete surgical resection of malignant disease is the only reliable method to cure cancer. Unfortunately, quantitative tumor resection is often limited by a surgeon's ability to locate all malignant disease and distinguish it from healthy tissue. Fluorescence-guided surgery has emerged as a tool to aid surgeons in the identification and removal of malignant lesions. While nontargeted fluorescent dyes have been shown to passively accumulate in some tumors, the resulting tumor-to-background ratios are often poor, and the boundaries between malignant and healthy tissues can be difficult to define. To circumvent these problems, our laboratory has developed high affinity tumor targeting ligands that bind to receptors that are overexpressed on cancer cells and deliver attached molecules selectively into these cells. In this study, we explore the use of two tumor-specific targeting ligands (i.e., folic acid that targets the folate receptor (FR) and DUPA that targets prostate specific membrane antigen (PSMA)) to deliver near-infrared (NIR) fluorescent dyes specifically to FR and PSMA expressing cancers, thereby rendering only the malignant cells highly fluorescent. We report here that all FR- and PSMA-targeted NIR probes examined bind cultured cancer cells in the low nanomolar range. Moreover, upon intravenous injection into tumor-bearing mice with metastatic disease, these same ligand-NIR dye conjugates render receptor-expressing tumor tissues fluorescent, enabling their facile resection with minimal contamination from healthy tissues.

  19. A Multimodal Imaging Approach for Longitudinal Evaluation of Bladder Tumor Development in an Orthotopic Murine Model.

    Directory of Open Access Journals (Sweden)

    Chantal Scheepbouwer

    Full Text Available Bladder cancer is the fourth most common malignancy amongst men in Western industrialized countries with an initial response rate of 70% for the non-muscle invasive type, and improving therapy efficacy is highly needed. For this, an appropriate, reliable animal model is essential to gain insight into mechanisms of tumor growth for use in response monitoring of (new agents. Several animal models have been described in previous studies, but so far success has been hampered due to the absence of imaging methods to follow tumor growth non-invasively over time. Recent developments of multimodal imaging methods for use in animal research have substantially strengthened these options of in vivo visualization of tumor growth. In the present study, a multimodal imaging approach was addressed to investigate bladder tumor proliferation longitudinally. The complementary abilities of Bioluminescence, High Resolution Ultrasound and Photo-acoustic Imaging permit a better understanding of bladder tumor development. Hybrid imaging modalities allow the integration of individual strengths to enable sensitive and improved quantification and understanding of tumor biology, and ultimately, can aid in the discovery and development of new therapeutics.

  20. Designing and Developing a Programme-Focused Assessment Strategy: A Case Study

    Science.gov (United States)

    Brunton, James; Brown, Mark; Costello, Eamon; Walsh, Elaine

    2016-01-01

    This case study describes the process that the Humanities Programme Team, in Dublin City University's Open Education Unit, has undertaken with regard to developing a systematic, programme-focused assessment strategy. It charts the development of an Assessment Matrix that facilitated the enhancement of programme coherence in the context of a…

  1. Cofimvaba: Innovative and systemic technology application in rural, education focused, agri-based development initiatives

    CSIR Research Space (South Africa)

    Van Rensburg, J

    2012-10-01

    Full Text Available In this presentation the author shares current learning on the use of more targeted and systemic ICT for development as well as broader technology for development education and LED-focused interventions in the science, engineering and technology...

  2. The Pitfalls of Focusing on Instructional Strategies in Professional Development for Teachers of English Learners

    Science.gov (United States)

    Molle, Daniella

    2013-01-01

    For more than a decade, the professional development literature has shown that most teachers are not adequately prepared to teach English learners (ELs)--that holds true for both specialist and mainstream teachers (see, for example, August & Hakuta, 1997; Beykont, 2002). Research that focuses on professional development for teachers of ELs,…

  3. Lessons for tumor biomarker trials: vicious cycles, scientific method & developing guidelines.

    Science.gov (United States)

    Hayes, Daniel; Raison, Claire

    2015-02-01

    Interview with Daniel Hayes, by Claire Raison (Commissioning Editor) Daniel F Hayes, M.D. is the Stuart A Padnos Professor of Breast Cancer Research and co-Director of the Breast Oncology Program at the University of Michigan Comprehensive Cancer Center (Ann Arbor, MI, USA). Dr Hayes has extensive experience in clinical and translational breast cancer biomarker research, and in drug development and clinical trials. Around 30 years ago, he led the discovery of the circulating breast tumor biomarker, CA15-3, which started his career into further tumor biomarker work. The main thrust of his work since then has been in clinical trials, tumor biomarkers and trying to integrate the two. Dr Hayes is Chair of the Correlative Sciences Committee of the North American Breast Cancer Group (now called the Breast Cancer Steering Committee), and co-chairs the Expert Panel for Tumor Biomarker Practice Guidelines for the American Society of Clinical Oncology.

  4. PTEN C-Terminal Deletion Causes Genomic Instability and Tumor Development

    Directory of Open Access Journals (Sweden)

    Zhuo Sun

    2014-03-01

    Full Text Available Tumor suppressor PTEN controls genomic stability and inhibits tumorigenesis. The N-terminal phosphatase domain of PTEN antagonizes the PI3K/AKT pathway, but its C-terminal function is less defined. Here, we describe a knockin mouse model of a nonsense mutation that results in the deletion of the entire Pten C-terminal region, referred to as PtenΔC. Mice heterozygous for PtenΔC develop multiple spontaneous tumors, including cancers and B cell lymphoma. Heterozygous deletion of the Pten C-terminal domain also causes genomic instability and common fragile site rearrangement. We found that Pten C-terminal disruption induces p53 and its downstream targets. Simultaneous depletion of p53 promotes metastasis without influencing the initiation of tumors, suggesting that p53 mainly suppresses tumor progression. Our data highlight the essential role of the PTEN C terminus in the maintenance of genomic stability and suppression of tumorigenesis.

  5. In vivo preclinical photoacoustic imaging of tumor vasculature development and therapy

    Science.gov (United States)

    Laufer, Jan; Johnson, Peter; Zhang, Edward; Treeby, Bradley; Cox, Ben; Pedley, Barbara; Beard, Paul

    2012-05-01

    The use of a novel all-optical photoacoustic scanner for imaging the development of tumor vasculature and its response to a therapeutic vascular disrupting agent is described. The scanner employs a Fabry-Perot polymer film ultrasound sensor for mapping the photoacoustic waves and an image reconstruction algorithm based upon attenuation-compensated acoustic time reversal. The system was used to noninvasively image human colorectal tumor xenografts implanted subcutaneously in mice. Label-free three-dimensional in vivo images of whole tumors to depths of almost 10 mm with sub-100-micron spatial resolution were acquired in a longitudinal manner. This enabled the development of tumor-related vascular features, such as vessel tortuosity, feeding vessel recruitment, and necrosis to be visualized over time. The system was also used to study the temporal evolution of the response of the tumor vasculature following the administration of a therapeutic vascular disrupting agent (OXi4503). This revealed the well-known destruction and recovery phases associated with this agent. These studies illustrate the broader potential of this technology as an imaging tool for the preclinical and clinical study of tumors and other pathologies characterized by changes in the vasculature.

  6. Combined effect of carcinogenic n-nitrosodimethylamine precursors and fractioned γ-irradiation on tumor development in rats

    International Nuclear Information System (INIS)

    Galenko, P.M.; Nedopitanskaya, N.N.

    1996-01-01

    The influence of combined action of N-nitrosodimethylamine (NDMA) and fractioned γ-irradiation on tumor development in rats was investigated. Both the tumor frequency and tumor plurality coefficient have been studied for two types of treatment: precursors of NDMA (amidopyrine and/or sodium nitrite (SN)) alone and the combination 'precursors plus radiation'. Tumor frequency decreased by about 11% after combination of γ-irradiation and precursors in comparison with precursors alone. Nevertheless, treatment with SN and γ-irradiation did not change tumor frequency in comparison with SN alone. Irradiation of rats treated with precursors led to an increased tumor plurality coefficient

  7. Focusing on What Counts: Using Exploratory Focus Groups to Enhance the Development of an Electronic Survey in a Mixed-Methods Research Design

    Science.gov (United States)

    Galliott, Natal'ya; Graham, Linda J.

    2016-01-01

    This paper illustrates the use of exploratory focus groups to inform the development of a survey instrument in a sequential phase mixed-methods study investigating differences in secondary students' career choice capability. Five focus groups were conducted with 23 Year 10 students in the state of New South Wales, Australia. Analysis of the focus…

  8. Toward the development of intrafraction tumor deformation tracking using a dynamic multi-leaf collimator

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Yuanyuan; O’Brien, Ricky T.; Shieh, Chun-Chien; Keall, Paul J., E-mail: paul.keall@sydney.edu.au [Radiation Physics Laboratory, University of Sydney, NSW 2006 (Australia); Booth, Jeremy T. [Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, NSW 2065 (Australia)

    2014-06-15

    Purpose: Intrafraction deformation limits targeting accuracy in radiotherapy. Studies show tumor deformation of over 10 mm for both single tumor deformation and system deformation (due to differential motion between primary tumors and involved lymph nodes). Such deformation cannot be adapted to with current radiotherapy methods. The objective of this study was to develop and experimentally investigate the ability of a dynamic multi-leaf collimator (DMLC) tracking system to account for tumor deformation. Methods: To compensate for tumor deformation, the DMLC tracking strategy is to warp the planned beam aperture directly to conform to the new tumor shape based on real time tumor deformation input. Two deformable phantoms that correspond to a single tumor and a tumor system were developed. The planar deformations derived from the phantom images in beam's eye view were used to guide the aperture warping. An in-house deformable image registration software was developed to automatically trigger the registration once new target image was acquired and send the computed deformation to the DMLC tracking software. Because the registration speed is not fast enough to implement the experiment in real-time manner, the phantom deformation only proceeded to the next position until registration of the current deformation position was completed. The deformation tracking accuracy was evaluated by a geometric target coverage metric defined as the sum of the area incorrectly outside and inside the ideal aperture. The individual contributions from the deformable registration algorithm and the finite leaf width to the tracking uncertainty were analyzed. Clinical proof-of-principle experiment of deformation tracking using previously acquired MR images of a lung cancer patient was implemented to represent the MRI-Linac environment. Intensity-modulated radiation therapy (IMRT) treatment delivered with enabled deformation tracking was simulated and demonstrated. Results: The first

  9. Effectiveness of solution focus brief counseling approach (SFBC in developing student career adaptability

    Directory of Open Access Journals (Sweden)

    Mulawarman Mulawarman

    2016-12-01

    Full Text Available Career adaptability is the preparedness role in work and adjustman to changes in working situation in the future. The purpose of this study was to examine Solution Focused Brief Counseling (SFBC approach in developing career adaptability of students.The method used in this study was a mix method . Subjects selected through a purposive sampling method that is focused on graduate students at the beginning of the semester with a major in Guidance and Counseling Faculty of Education, Semarang State University. Career adaptability in this study consists of four dimensions, concern, control, curiosity and confidence. Stages of Solution Focused Brief Counseling (SFBC implemented include establishing relationships, Identifying a solvable complaint, Establishing goals, Designing and Implementing Intervention, and termination, evaluation, and follow-up. The results of this study showed Solution Focused Brief Counseling (SFBC is effective in improving the adaptability of student career both qualitatively and quantitatively.

  10. [A NATURAL PLAGUE FOCUS. IN GORNYI ALTAI: FORMATION, DEVELOPMENT, AND FUNCTIONING].

    Science.gov (United States)

    Korzun, V M; Balakhoiov, S V; Chpanin, E V; Denisov, A V; Mikhailov, E P; Mischenko, A J; Yarygina, M B; Rozhdestvensky, E N; Fomina, L A

    2016-01-01

    The paper gives the results of analyzing the data of long-term studies of the natural focal pattern of plague in the Gornyi Altai natural focus. It describes a wide range of biological processes occurring in the focus and shows the most important patterns of its functioning as a complex multilevel ecological system. The key features of the formation of the focus have been revealed. The plague focus in South-Western Altai has formed relatively, recently, about half a century ago, then it has intensively developed and its enzootic area and the activity of epizootic manifestations have considerably increased. This process is due to the space-time transformations of the basic ecological and population characteristics of Pallas' pika (Ochotoma pallasi), the principal vector of the pathogen of plague and fleas parasitizing the mammal, which is in turn related to the aridization of mountain steppes in South-Western Altai.

  11. When Science is Not Enough: A Framework Towards More Customer-Focused Drug Development.

    Science.gov (United States)

    Oraiopoulos, Nektarios; Dunlop, William C N

    2017-07-01

    The purpose of this study was to identify the key barriers to a customer-focused drug development process and develop a comprehensive framework to overcome them. The paper draws on existing literature, both academic and practitioner, across a range of disciplines (innovation management, marketing, organizational behavior, behavioral economics, health economics, industry reports). On the basis of this extensive review, a conceptual framework is developed that offers concrete suggestions on how organizations can overcome the barriers and enable a more customer-focused development process. The barriers to collaboration are organized into three distinct categories (economic, behavioral, organizational), and within each category, a one-to-one mapping between barriers and solutions is developed. The framework is specifically designed with the objective of offering actionable and practical advice to executives who face these challenges in their organizations. The paper provides a unique theoretical contribution by synthesizing findings from several academic disciplines with concrete examples from the pharmaceutical industry. Mundipharma International Limited.

  12. Recent developments in the nanostructured materials functionalized with ruthenium complexes for targeted drug delivery to tumors

    Directory of Open Access Journals (Sweden)

    Thangavel P

    2017-04-01

    Full Text Available Prakash Thangavel,1 Buddolla Viswanath,1 Sanghyo Kim1,2 1Department of Bionanotechnology, Gachon University, Bokjeong-Dong, Sujeong-Gu, Seongnam-Si, Gyeonggi-Do, 2Graduate Gachon Medical Research Institute, Gil Medical Center, Incheon, Republic of Korea Abstract: In recent years, the field of metal-based drugs has been dominated by other existing precious metal drugs, and many researchers have focused their attention on the synthesis of various ruthenium (Ru complexes due to their potential medical and pharmaceutical applications. The beneficial properties of Ru, which make it a highly promising therapeutic agent, include its variable oxidation states, low toxicity, high selectivity for diseased cells, ligand exchange properties, and the ability to mimic iron binding to biomolecules. In addition, Ru complexes have favorable adsorption properties, along with excellent photochemical and photophysical properties, which make them promising tools for photodynamic therapy. At present, nanostructured materials functionalized with Ru complexes have become an efficient way to administer Ru-based anticancer drugs for cancer treatment. In this review, the recent developments in the nanostructured materials functionalized with Ru complexes for targeted drug delivery to tumors are discussed. In addition, information on “traditional” (ie, non-nanostructured Ru-based cancer therapies is included in a precise manner. Keywords: metallodrugs, nanotechnology, cancer treatment, cell apoptosis, DNA damage, toxicity

  13. Focused attention, heart rate deceleration, and cognitive development in preterm and full-term infants.

    Science.gov (United States)

    Petrie Thomas, Julianne H; Whitfield, Michael F; Oberlander, Tim F; Synnes, Anne R; Grunau, Ruth E

    2012-05-01

    The majority of children who are born very preterm escape major impairment, yet more subtle cognitive and attention problems are very common in this population. Previous research has linked infant focused attention during exploratory play to later cognition in children born full-term and preterm. Infant focused attention can be indexed by sustained decreases in heart rate (HR). However there are no preterm studies that have jointly examined infant behavioral attention and concurrent HR response during exploratory play in relation to developing cognition. We recruited preterm infants free from neonatal conditions associated with major adverse outcomes, and further excluded infants with developmental delay (Bayley Mental Development Index [MDI attention and concurrent HR response were compared in 83 preterm infants (born 23-32 weeks gestational age [GA]) who escaped major impairment to 46 full-term infants. Focused attention and HR response were then examined in relation to Bayley MDI, after adjusting for neonatal risk. MDI did not differ by group, yet full-term infants displayed higher global focused attention ratings. Among the extremely preterm infants born attention episodes, accounted for 49% of adjusted variance in predicting concurrent MDI. There were no significant associations for later-born gestational age (29-32 weeks) or full-term infants. Among extremely preterm infants who escape major impairment, our findings suggest unique relationships between focused attention, HR deceleration, and developing cognition. Copyright © 2011 Wiley Periodicals, Inc.

  14. Mixed waste focus area Department of Energy technology development needs identification and prioritization

    International Nuclear Information System (INIS)

    Roach, J.A.

    1995-11-01

    The Assistant Secretary for the Office of Environmental Management (EM) at the US DOE initiated a new approach in August, 1993 to environmental research and technology development. The key features of this new approach included establishment of five focus areas and three crosscutting technology programs, which overlap the boundaries of the focus areas. The five focus areas include the Contaminant Plumes Containment and Remediation; Mixed Waste Characterization, Treatment, and Disposal; High-Level Waste Tank Remediation, Landfill Stabilization, and Decontamination and Decommissioning Focus Areas. The three crosscutting technologies programs include Characterization, Monitoring, and Sensor Technology; Efficient Separations and Processing; and Robotics. The DOE created the Mixed Waste Characterization, Treatment, and Disposal Focus Area (MWFA) to develop and facilitate implementation of technologies required to meet its commitments for treatment of mixed wastes. To accomplish this goal, the technology deficiencies must be identified and categorized, the deficiencies and needs must be prioritized, and a technical baseline must be established that integrates the requirements associated with these needs into the planned and ongoing environmental research and technology development activities supported by the MWFA. These steps are described

  15. Microwave ablation of renal tumors: state of the art and development trends.

    Science.gov (United States)

    Floridi, Chiara; De Bernardi, Irene; Fontana, Federico; Muollo, Alessandra; Ierardi, Anna Maria; Agostini, Andrea; Fonio, Paolo; Squillaci, Ettore; Brunese, Luca; Fugazzola, Carlo; Carrafiello, Gianpaolo

    2014-07-01

    In the last decades an increased incidence of new renal tumor cases has been for clinically localized, small tumors elderly patients, with medical comorbidities whom the risk of surgical complications may pose a greater risk of death than that due to the tumor itself. In these patients, unsuitable for surgical approach, thermal ablation represents a valid alternative to traditional surgery. Thermal ablation is a less invasive, less morbid treatment option thanks to reduced blood loss, lower incidence of complications during the procedure and a less long convalescence. At present, the most widely used thermal ablative techniques are cryoablation, radiofrequency ablation and microwave ablation (MWA). MWA offers many benefits of other ablation techniques and offers several other advantages: higher intratumoral temperatures, larger tumor ablation volumes, faster ablation times, the ability to use multiple applicators simultaneously, optimal heating of cystic masses and tumors close to the vessels and less procedural pain. This review aims to provide the reader with an overview about the state of the art of microwave ablation for renal tumors and to cast a glance on the new development trends of this technique.

  16. Tumor imaging using Tc(V)-99m dimercaptosuccinic acid, a newly developed radiopharmaceutical

    International Nuclear Information System (INIS)

    Ohta, Hitoya; Endo, Keigo; Koizumi, Mitsuru

    1985-01-01

    Being aware of the ideal nuclear properties of Tc-99m, we have developed a new tumor seeking agent, Tc-99m (V) dimercaptosuccinic acid (Tc(V)-DMS). In order to evaluate its clinical usefulness of Tc(V)-DMS, 400 untreated patients with histologically proven diagnoses were studied, and, in some selected cases, the results were compared with those of Ga-67 citrate. The Tc(V)-DMS scintigraphy was found especially useful in patients with head and neck tumors, medullary thyroid carcinomas, soft tissue tumors and bone tumors. But in patients with lung tumors, liver tumors, malignant melanoma or malignant lymphomas, it revealed no obvious advantage over Ga-67 scintigraphy, the results seemed to the different uptake mechanism of Tc(V)-DMS from that of Ga-67 citrate. Nevertheless the superiority of physical properties of Tc-99m, pharmacological advantage that may enable satisfactory imaging, and lower supply cost, Tc(V)-DMS would certainly offer good clinical applicability in some regions. (author)

  17. Development of oral cancer vaccine using recombinant Bifidobacterium displaying Wilms' tumor 1 protein.

    Science.gov (United States)

    Kitagawa, Koichi; Oda, Tsugumi; Saito, Hiroki; Araki, Ayame; Gonoi, Reina; Shigemura, Katsumi; Hashii, Yoshiko; Katayama, Takane; Fujisawa, Masato; Shirakawa, Toshiro

    2017-06-01

    Several types of vaccine-delivering tumor-associated antigens (TAAs) have been developed in basic and clinical research. Wilms' tumor 1 (WT1), identified as a gene responsible for pediatric renal neoplasm, is one of the most promising TAA for cancer immunotherapy. Peptide and dendritic cell-based WT1 cancer vaccines showed some therapeutic efficacy in clinical and pre-clinical studies but as yet no oral WT1 vaccine can be administrated in a simple and easy way. In the present study, we constructed a novel oral cancer vaccine using a recombinant Bifidobacterium longum displaying WT1 protein. B. longum 420 was orally administered into mice inoculated with WT1-expressing tumor cells for 4 weeks to examine anti-tumor effects. To analyze the WT1-specific cellular immune responses to oral B. longum 420, mice splenocytes were isolated and cytokine production and cytotoxic activities were determined. Oral administrations of B. longum 420 significantly inhibited WT1-expressing tumor growth and prolonged survival in mice. Immunohistochemical study and immunological assays revealed that B. longum 420 substantially induced tumor infiltration of CD4 + T and CD8 + T cells, systemic WT1-specific cytokine production, and cytotoxic activity mediated by WT1-epitope specific cytotoxic T lymphocytes, with no apparent adverse effects. Our novel oral cancer vaccine safely induced WT1-specific cellular immunity via activation of the gut mucosal immune system and achieved therapeutic efficacy with several practical advantages over existing non-oral vaccines.

  18. A LOCAL DEVELOPMENT PROJECT IN THE FRAMEWORK OF PUBLIC POLICIES FOCUSED ON REGIONAL DEVELOPMENT STRATEGIES

    Directory of Open Access Journals (Sweden)

    George Schin

    2013-12-01

    Full Text Available This paper aims at outlining a successful implementation of a project within LEADER framework, which is a local development method which allows local actors to develop an area by using its endogenous development potential. After a brief presentation of the characteristics of regional development strategies in Romania, there were emphasized the objectives and activities encompassed in a local development plan, managed by the leaders of the local action group called ‘Vrancea County’. In order to reinforce the strengths of Vrancea County and implicitly to assure a sustainable development of this area from the South-East part of Romania, a LAG constituted through a partnership between public and private actors settled a set of priorities to be exploited by means of specific actions. The goal of this paper is to highlight these priorities, by integrating them in a project management approach. The paper concludes with specifications about how Microsoft Project software could support project management initiatives that will be developed by the LAG Vrancea County in the next period.

  19. Interplay between TGF-β signaling and receptor tyrosine kinases in tumor development.

    Science.gov (United States)

    Shi, Qiaoni; Chen, Ye-Guang

    2017-10-01

    Transforming growth factor-β (TGF-β) signaling regulates cell proliferation, differentiation, migration and death, and plays a critical role in embryogenesis and tissue homeostasis. Its deregulation results in various diseases including tumor formation. Receptor tyrosine kinases (RTKs), such as epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR), vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR), also play key roles in the development and progression of many types of tumors. It has been realized that TGF-β signaling and RTK pathways interact with each other and their interplay is important for cancer development. They are mutually regulated and cooperatively modulate cell survival and migration, epithelial-mesenchymal transition, and tumor microenvironment to accelerate tumorigenesis and tumor metastasis. RTKs can modulate Smad-dependent transcription or cooperate with TGF-β to potentiate its oncogenic activity, while TGF-β signaling can in turn control RTK signaling by regulating their activities or expression. This review summarizes current understandings of the interplay between TGF-β signaling and RTKs and its influence on tumor development.

  20. Pediatric brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Poussaint, Tina Y. [Department of Radiology, Boston, MA (United States); Panigrahy, Ashok [Children' s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Department of Radiology, Pittsburgh, PA (United States); Huisman, Thierry A.G.M. [Charlotte R. Bloomberg Children' s Center, Johns Hopkins Hospital, Division of Pediatric Radiology and Pediatric Neuroradiology, Baltimore, MD (United States)

    2015-09-15

    Among all causes of death in children from solid tumors, pediatric brain tumors are the most common. This article includes an overview of a subset of infratentorial and supratentorial tumors with a focus on tumor imaging features and molecular advances and treatments of these tumors. Key to understanding the imaging features of brain tumors is a firm grasp of other disease processes that can mimic tumor on imaging. We also review imaging features of a common subset of tumor mimics. (orig.)

  1. Motivation and Career-Development Training Programs: Use of Regulatory Focus to Determine Program Effectiveness

    Science.gov (United States)

    Anthony, Peter J.; Weide, Jeffrey

    2015-01-01

    The purpose of this study was to focus on the relationship between career-development training programs and the motivation of employees. The study used a qualitative method and a phenomenological design using semistructured interviews conducted with a script of open-ended questions. Two main components of the research design were the modified van…

  2. 78 FR 63223 - Fibromyalgia Public Meeting on Patient-Focused Drug Development; Correction

    Science.gov (United States)

    2013-10-23

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-N-2013-1041] Fibromyalgia Public Meeting on Patient-Focused Drug Development; Correction AGENCY: Food and Drug... 23, 2013 (78 FR 58313). The document announced a public meeting entitled ``Fibromyalgia Public...

  3. Improving Primary Teachers' Attitudes toward Science by Attitude-Focused Professional Development

    Science.gov (United States)

    van Aalderen-Smeets, Sandra I.; van der Molen, Juliette H. Walma

    2015-01-01

    This article provides a description of a novel, attitude-focused, professional development intervention, and presents the results of an experimental pretest-posttest control group study investigating the effects of this intervention on primary teachers' personal attitudes toward science, attitudes toward teaching science, and their science…

  4. Improving primary teachers’ attitudes toward science by attitude-focused professional development

    NARCIS (Netherlands)

    van Aalderen-Smeets, Sandra; Walma van der Molen, Julie Henriëtte

    2015-01-01

    This article provides a description of a novel, attitude-focused, professional development intervention, and presents the results of an experimental pretest-posttest control group study investigating the effects of this intervention on primary teachers’ personal attitudes toward science, attitudes

  5. Developing L2 Listening Fluency through Extended Listening-Focused Activities in an Extensive Listening Programme

    Science.gov (United States)

    Chang, Anna C-S.; Millett, Sonia

    2016-01-01

    This study investigates the effects on developing L2 listening fluency through doing extended listening-focused activities after reading and listening to audio graded readers. Seventy-six EFL university students read and listened to a total of 15 graded readers in a 15-week extensive listening programme. They were divided into three groups (Group…

  6. Implications for Focusing Research in Career and Technical Education and Workforce Development

    Science.gov (United States)

    Lambeth, Jeanea M.; Joerger, Richard M.; Elliot, Jack

    2009-01-01

    Education and educational research is shaped by philosophy, psychology, practice, and ever changing educational policies. Previous studies have expressed a need for a relevant and focused research agenda for career and technical education (CTE), workforce development education and career and technical education. A need for a relevant and timely…

  7. Using Focus Groups to Develop a Nutrition Education Video for High School Students.

    Science.gov (United States)

    James, Delores C. S.; Rienzo, Barbara A.; Frazee, Carol

    1997-01-01

    Study used focus group interviews with ninth graders to help develop a nutrition education video and teacher's guide for Florida high schools. Students believed a video would be successful, expressed interest in 10 nutrition topics, recommended using teen actors with varying body types, and suggested no more than three or four topics per video.…

  8. Numerical Study for Optimizing Parameters of High-Intensity Focused Ultrasound-Induced Thermal Field during Liver Tumor Ablation: HIFU Simulator

    Directory of Open Access Journals (Sweden)

    Somayeh gharloghi

    2017-03-01

    Full Text Available Introduction High intensity focused ultrasound (HIFU is considered a noninvasive and effective technique for tumor ablation. Frequency and acoustic power are the most effective parameters for temperature distribution and the extent of tissue damage. The aim of this study was to optimize the operating transducer parameters such as frequency and input power in order to acquire suitable temperature and thermal dose distribution in the course of a numerical assessment. Materials and Methods To model the sound propagation, the Khokhlov-Zabolotskava-Kuznetsov (KZK nonlinear wave equation was used and simulation was carried out using MATLAB HIFU toolbox. Bioheat equation was applied to calculate the transient temperature in the liver tissue. Frequency ranges of 2, 3, 4, and 5 MHz and power levels of 50 and 100 W were applied using an extracorporeal transducer. Results Using a frequency of 2 MHz, the maximum temperatures reached 53°C and 90°C in the focal point for power levels of 50 W and 100 W, respectively. With the same powers and using a frequency of 3 MHz, the temperature reached to 71°C and 170°C, respectively. In addition, for these power levels at the frequency of 4 MHz, the temperature reached to 72°C and 145°C, respectively. However, at the 5 MHz frequency, the temperature in the focal spot was either 57°C or 79°C. Conclusion Use of frequency of 2 MHz and power of 100 W led to higher thermal dose distribution, and subsequently, reduction of the treatment duration and complications at the same exposure time in ablation of large tumors.

  9. Brain tumors and synchrotron radiation: Methodological developments in quantitative brain perfusion imaging and radiation therapy

    International Nuclear Information System (INIS)

    Adam, Jean-Francois

    2005-01-01

    High-grade gliomas are the most frequent type of primary brain tumors in adults. Unfortunately, the management of glioblastomas is still mainly palliative and remains a difficult challenge, despite advances in brain tumor molecular biology and in some emerging therapies. Synchrotron radiation opens fields for medical imaging and radiation therapy by using monochromatic intense x-ray beams. It is now well known that angiogenesis plays a critical role in the tumor growth process and that brain perfusion is representative of the tumor mitotic activity. Synchrotron radiation quantitative computed tomography (SRCT) is one of the most accurate techniques for measuring in vivo contrast agent concentration and thus computing precise and accurate absolute values of the brain perfusion key parameters. The methodological developments of SRCT absolute brain perfusion measurements as well as their preclinical validation are detailed in this thesis. In particular, absolute cerebral volume and blood brain barrier permeability high-resolution (pixel size 2 ) parametric maps were reported. In conventional radiotherapy, the treatment of these tumors remains a delicate challenge, because the damages to the surrounding normal brain tissue limit the amount of radiation that can be delivered. One strategy to overcome this limitation is to infuse an iodinated contrast agent to the patient during the irradiation. The contrast agent accumulates in the tumor, through the broken blood brain barrier, and the irradiation is performed with kilovoltage x rays, in tomography mode, the tumor being located at the center of rotation and the beam size adjusted to the tumor dimensions. The dose enhancement results from the photoelectric effect on the heavy element and from the irradiation geometry. Synchrotron beams, providing high intensity, tunable monochromatic x rays, are ideal for this treatment. The beam properties allow the selection of monochromatic irradiation, at the optimal energy, for a

  10. Nanomedicine developments in the treatment of metastatic pancreatic cancer: focus on nanoliposomal irinotecan

    Directory of Open Access Journals (Sweden)

    Ko AH

    2016-03-01

    Full Text Available Andrew H KoDivision of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA Abstract: Nanoliposomal irinotecan (nal-IRI was originally developed using an efficient and high-loading capacity system to encapsulate irinotecan within a liposomal carrier, producing a therapeutic agent with improved biodistribution and pharmacokinetic characteristics compared to free drug. Specifically, administration of nal-IRI results in prolonged exposure of SN-38, the active metabolite of irinotecan, within tumors, while at the same time offering the advantage of less systemic toxicity than traditional irinotecan. These favorable properties of nal-IRI, confirmed in a variety of tumor xenograft models, led to its clinical evaluation in a number of disease indications for which camptothecins have proven activity, including in colorectal, gastric, and pancreatic cancers. The culmination of these clinical trials was the NAPOLI-1 (Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy trial, an international Phase III study evaluating nal-IRI both alone and in combination with 5-fluorouracil and leucovorin in patients with metastatic pancreatic adenocarcinoma following progression on gemcitabine-based chemotherapy. Positive results from NAPOLI-1 led to approval of nal-IRI (with 5-fluorouracil/leucovorin in October 2015 by the US Food and Drug Administration specifically for the treatment of metastatic pancreatic cancer in the second-line setting and beyond, a clinical context in which there had previously been no accepted standard of care. As such, nal-IRI represents an important landmark in cancer drug development, and potentially ushers in a new era where a greater number of patients with advanced pancreatic cancer can be sequenced through multiple lines of therapy translating into meaningful improvements in

  11. Development and Validation of the Body-Focused Shame and Guilt Scale

    Science.gov (United States)

    Weingarden, Hilary; Renshaw, Keith D.; Tangney, June P.; Wilhelm, Sabine

    2015-01-01

    Body shame is described as central in clinical literature on body dysmorphic disorder (BDD). However, empirical investigations of body shame within BDD are rare. One potential reason for the scarcity of such research may be that existing measures of body shame focus on eating and weight-based content. Within BDD, however, body shame likely focuses more broadly on shame felt in response to perceived appearance flaws in one’s body parts. We describe the development and validation of the Body-Focused Shame and Guilt Scale (BF-SGS), a measure of BDD-relevant body shame, across two studies: a two time-point study of undergraduates, and a follow-up study in two Internet-recruited clinical samples (BDD, obsessive compulsive disorder) and healthy controls. Across both studies, the BF-SGS shame subscale demonstrated strong reliability and construct validity, with Study 2 providing initial clinical norms. PMID:26640760

  12. The Role of gsp Mutations on the Development of Adrenal Cortical Tumors and Adrenal Hyperplasias

    Directory of Open Access Journals (Sweden)

    Maria Candida Barisson Villares Fragoso

    2016-07-01

    Full Text Available Somatic GNAS point mutations, commonly known as gsp mutations, are involved in the pathogenesis of McCune Albright syndrome and have also been described in autonomous hormone-producing tumors, such as somatotropinoma, corticotrophoma, thyroid cancer, ovarian and testicular Leydig cell tumors and primary macronodular adrenocortical hyperplasia (PMAH. [1-3]The involvement of gsp mutations in adrenal tumors was first described by Lyons et al. in 1990. Since then, several studies have detected the presence of gsp mutations in adrenal tumors, but none of them could explain its presence along or the mechanism that leads to tumor formation and hormone hypersecretion. As a result, the molecular pathogenesis of the majority of sporadic adrenocortical tumors remains unclear. [3] PMAH has also been reported with gsp somatic mutations in a few cases. Fragoso et al. in 2003 identified two distinct gsp somatic mutations affecting arginine residues on codon 201 of GNAS in a few patients with PMAH who lacked any features or manifestations of McCune Albright syndrome. Followed by this discovery, other studies have continued looking for gsp mutations based on strong prior evidence demonstrating that increased cAMP signaling is sufficient for cell proliferation and cortisol production. [2, 4] With consideration for the previously reported findings, we conjecture that although somatic activating mutations in GNAS are a rare molecular event, these mutations could probably be sufficient to induce the development of macronodule hyperplasia and variable cortisol secretion.In this manuscript, we revised the presence of gsp mutations associated with adrenal cortical tumors and hyperplasia.

  13. Clinical applications of PD-1-based therapy: a focus on pembrolizumab (MK-3475 in the management of melanoma and other tumor types

    Directory of Open Access Journals (Sweden)

    Gangadhar TC

    2015-04-01

    Full Text Available Tara C Gangadhar,1 April KS Salama2 1Division of Hematology/Oncology, Department of Medicine, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA; 2Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC, USA Abstract: Preclinical work has led to an increased understanding of the immunomodulatory mechanisms involved in the regulation of the antitumor response in a variety of tumor types. PD-1 (programmed death 1 appears to be a key checkpoint involved in immune suppression in the tumor microenvironment, even in diseases not previously thought to be sensitive to immune manipulation. More recently, the subsequent clinical development of PD-1-based therapy has resulted in a major breakthrough in the field of oncology. Pembrolizumab, a humanized highly selective IgG4 anti-PD-1 monoclonal antibody, was recently approved for the treatment of advanced melanoma based on promising early-phase clinical data. Encouraging results have also been seen in other malignancies, and PD-1-targeted therapies are likely to markedly change the treatment landscape. Future work will center on rationally designed combination strategies in order to potentiate the antitumor immune response and overcome mechanisms of resistance. Keywords: PD-1, cancer, pembrolizumab, nivolumab, immunotherapy, antitumor activity 

  14. Effect of Arrabidaea chica extracts on the Ehrlich solid tumor development

    Directory of Open Access Journals (Sweden)

    Ana Flávia C. Ribeiro

    2012-04-01

    Full Text Available The aim of this study was to investigate the effect of Arrabidaea chica (Humb. & Bonpl. B. Verl., Bignoniaceae, extracts on Ehrlich solid tumor development in Swiss mice. Leaves of A. chica were extracted with two distinct solvents, ethanol and water. The phytochemical analysis of the extracts indicated different classes of secondary metabolites like as anthocyanidins, flavonoids, tannins and saponins. Ethanol (EE and aqueous (AE extracts at 30 mg/kg reduced the development of Ehrlich solid tumor after ten days of oral treatment. The EE group presented increase in neutrophil count, α1 and β globulin values, and decrease of α2 globulin values. Furthermore, EE reduced the percentage of CD4+ T cells in blood but did not alter the percentage of inflammatory mononuclear cells associated with tumor suggesting a direct action of EE on tumor cells. Reduced tumor development observed in AE group was accompanied by a lower percentage of CD4+ T lymphocytes in blood. At the tumor microenvironment, this treatment decreased the percentage of CD3+ T cells, especially due to a reduction of CD8+ T subpopulation and NK cells. The antitumor activity presented by the AE is possibly related to an anti-inflammatory activity. None of the extracts produced toxic effects in animals. In conclusion, the ethanol and aqueous extracts of A. chica have immunomodulatory and antitumor activities attributed to the presence of flavonoids, such as kaempferol. These effects appear to be related to different mechanisms of action for each extract. This study demonstrates the potential of A. chica as an antitumor agent confirming its use in traditional popular medicine.

  15. Consequences of Collective-Focused Leadership and Differentiated Individual-Focused Leadership : Development and Testing of an Organizational-Level Model

    OpenAIRE

    Kunze, Florian; de Jong, Simon Barend; Bruch, Heike

    2016-01-01

    Recent advances in leadership research suggest that collective-focused leadership climate and differentiated individual-focused leadership might simultaneously, yet oppositely, affect collective outcomes. The present study extends this literature by addressing open questions regarding theory, methods, statistics, and level of analysis. Therefore, a new and more parsimonious theoretical model is developed on the organizational-level of analysis. Drawing on the commitment literature, we argue f...

  16. Tanks Focus Area Alternative Salt Processing Research and Development Program Plan

    Energy Technology Data Exchange (ETDEWEB)

    Harmon, Harry D.

    2000-05-15

    In March 2000, DOE-Headquarters (HQ) requested the Tanks Focus Area (TFA)to assume management responsibility for the Salt Processing Project technology development program at Savannah River Site. The TFA was requested to conduct several activities, including review and revision of the technology development roadmaps, development of down-selection criteria, and preparation of a comprehensive Research and Development (R&D) Program Plan for three candidate cesium removal technologies, as well as the Alpha and strontium removal processes that must also be carried out. The three cesium removal candidate technologies are Crystalline Silicotitanate (CST) Non-Elutable Ion Exchange, Caustic Side Solvent Extraction (CSSX), and Small Tank Tetraphenylborate Precipitation (STTP). This plan describes the technology development needs for each process that must be satisfied in order to reach a down-selection decision, as well as continuing technology development required to support conceptual design activities.

  17. Tanks Focus Area Alternative Salt Processing Research and Development Program Plan

    Energy Technology Data Exchange (ETDEWEB)

    Harmon, Harry D.

    2000-11-30

    In March 2000, DOE-Headquarters (HQ) requested the Tanks Focus Area (TFA) to assume management responsibility for the Salt Processing Project technology development program at Savannah River Site. The TFA was requested to conduct several activities, including review and revision of the technology development roadmaps, development of down-selection criteria, and preparation of a comprehensive Research and Development (R&D) Program Plan for three candidate cesium removal technologies, as well as the Alpha and strontium removal processes that must also be carried out. The three cesium removal candidate technologies are Crystalline Silicotitanate (CST) Non-Elutable Ion Exchange, Caustic Side Solvent Extraction (CSSX), and Small Tank Tetraphenylborate Precipitation (STTP). This plan describes the technology development needs for each process that must be satisfied in order to reach a down-selection decision, as well as continuing technology development required to support conceptual design activities.

  18. Aberrant crypt foci in the colo-rectal mucosa as reliable markers of tumor development

    DEFF Research Database (Denmark)

    Thorup, Inger

    connection exists between occurrence of ACF (neither qualitatively nor quantita- tively) and later development of tumors. However, the literature has shown that part of the ACF show morphologic and genetic features characteristic for the tumorigenic process and a recent investigation indicate that all ACF...

  19. Selenium prevents tumor development in a rat model for chemical carcinogenesis

    DEFF Research Database (Denmark)

    Bjorkhem-Bergman, L.; Torndal, U. B.; Eken, S.

    2005-01-01

    Previous studies in animals and humans have shown that selenium compounds can prevent cancer development. In this work we studied the tumor preventive effect of selenium supplementation, administrated as selenite, in the initiation, promotion and progression phases in a synchronized rat model for...

  20. Do External or Internal Factors Lead to Tumor Development? It Is Still Unknown.

    Science.gov (United States)

    Manskikh, V N

    2017-01-01

    Arguments supporting the "bad luck" hypothesis presented by C. Tomasetti and B. Vogelstein ((2015) Science, 347, 78-81) and A. V. Lichtenstein ((2017) Biochemistry (Moscow), 82, 75-80) are critically discussed. Those arguments are not sufficient for recognition of the "bad luck" hypothesis and the leading role of internal factors in spontaneous tumor development.

  1. Development of model plans in three dimensional conformal radiotherapy for brain tumors

    International Nuclear Information System (INIS)

    Pyo, Hongryull; Kim, Gwieon; Keum, Kichang; Chang, Sekyung; Suh, Changok; Lee, Sanghoon

    2002-01-01

    Three dimensional conformal radiotherapy planning is being used widely for the treatment of patients with brain tumor. However, it takes much time to develop an optimal treatment plan, therefore, it is difficult to apply this technique to all patients. To increase the efficiency of this technique, we need to develop standard radiotherapy plans for each site of the brain. Therefore we developed several 3 dimensional conformal radiotherapy plans (3D plans) for tumors at each site of brain, compared them with each other, and with 2 dimensional radiotherapy plans. Finally model plans for each site of the brain were decided. Imaginary tumors, with sizes commonly observed in the clinic, were designed for each site of the brain and drawn on CT images. The planning target volumes (PTVs) were as follows; temporal tumor-5.7 x 8.2 x 7.6 cm, suprasellar tumor-3 x 4 x 4.1 cm, thalamic tumor-3.1 x 5.9 x 3.7 cm, frontoparietal tumor-5.5 x 7 x 5.5 cm, and occipitoparietal tumor-5 x 5.5 x 5 cm. Plans using parallel opposed 2-portals and/or 3 portals including fronto-vertex and 2 lateral fields were developed manually as the conventional 2D plans, and 3D noncoplanar conformal plans were developed using beam's eye view and the automatic block drawing tool. Total tumor dose was 54 Gy for a suprasellar tumor, 59.4 Gy and 72 Gy for the other tumors. All dose plans (including 2D plans) were calculated using 3D plan software. Developed plans were compared with each other using dose-volume histograms (DVH), normal tissue complication probabilities (NTCP) and variable dose statistic values (minimum, maximum and mean dose, D5, V83, V85 and V95). Finally a best radiotherapy plan for each site of brain was selected. 1) Temporal tumor; NTCPs and DVHs of the normal tissue of all 3D plans were superior to 2D plans and this trend was more definite when total dose was escalated to 72 Gy (NTCPs of normal brain 2D plans: 27%, 8% → 3D plans: 1%, 1%). Various dose statistic values did not show any

  2. Cancer vaccines: the challenge of developing an ideal tumor killing system.

    Science.gov (United States)

    Mocellin, Simone

    2005-09-01

    Despite the evidence that the immune system plays a significant role in controlling tumor growth in natural conditions and in response to therapeutic vaccination, cancer cells can survive their attack as the disease progresses and no vaccination regimen should be currently proposed to patients outside experimental clinical trials. Clinical results show that the immune system can be actively polarized against malignant cells by means of a variety of vaccination strategies, and that in some cases this is associated with tumor regression. This implies that under some unique circumstances, the naturally "dormant" immune effectors can actually be put at work and used as endogenous weapons against malignant cells. Consequently, the main challenge of tumor immunologists appears to lie on the ability of reproducing those conditions in a larger set of patients. The complexity of the immune network and the still enigmatic host-tumor interactions make these tasks at the same time challenging and fascinating. Recent tumor immunology findings are giving new impetus to the development of more effective vaccination strategies and might revolutionize the way of designing the next generation of cancer vaccines. In the near future, the implementation of these insights in the clinical setting and the completion/conduction of comparative randomized phase III trials will allow oncologists to define the actual role of cancer vaccines in the fight against malignancy.

  3. Towards the development of tumor necrosis factor (TNF) sensitizers: making TNF work against cancer.

    Science.gov (United States)

    Mocellin, Simone; Pilati, Pierluigi; Nitti, Donato

    2007-01-01

    Although TNF antitumor activity has been demonstrated in many preclinical models and in non-comparative clinical trials, no evidence exists that TNF-based treatments increase patient survival. Moreover, due to systemic toxicity, TNF can only be administered through sophisticated locoregional drug-delivery systems in patients with some types of organ-confined solid tumors; as a corollary, the impossibility to administer TNF through the systemic route does not allow to test the effectiveness of this cytokine in other clinical settings for the treatment of a broader spectrum of tumor types. A challenge many researchers are tackling is to dissect the cascade of molecular events underlying tumor sensitivity to TNF so to fully explore the anticancer potential of this molecule. The rationale for the development of strategies aimed at sensitizing malignant cells to TNF is to exploit tumor-specific molecular derangements to modulate TNF biological activities and ultimately maximize its tumor-selective cytotoxicity. This would not only enhance the anticancer activity of current TNF-based locoregional regimens, but would also open the avenue to the systemic administration of this cytokine and thus to a much wider clinical experimentation of TNF in the oncology field. In this review we first summarize the molecular biology of TNF and its cancer-related properties; then, the available findings regarding some among the most promising and best characterized TNF sensitizers are overviewed.

  4. In ovo method for evaluating the effect of nutritional therapies on tumor development, growth and vascularization

    Directory of Open Access Journals (Sweden)

    Yves M. Dupertuis

    2015-10-01

    Full Text Available In the state of the art evaluation of nutritional therapy on tumor development, growth and vascularization requires tedious and expensive in vivo assays in which a significant number of animals undergo invasive treatments. Therefore, new alternative methods to avoid animal suffering and sacrifice are welcome. This review presents a rapid and low-cost method of experimental radio/chemotherapy in tumor xenografted chicken chorioallantoic membrane (CAM, which may contribute to implement the 3R principle (Reduce, Refine, Replace. Advantages and limitations of the CAM as an experimental model in cancer research are discussed. Improving the CAM model by using tumor spheroid grafting and positron emission and computed tomography imaging would help to overcome the drawbacks of poor tumor grafting efficiency and restrained 2-D tumor growth measurement to the CAM surface. Such a simple, reliable, reproducible and quantitative method for obtaining dose–response analysis and estimating treatment schedule (i.e. type, route, dose and timing would provide an alternative to the time-consuming and expensive evaluation step in animals before initiating clinical trials.

  5. Autoclaved Tumor Bone for Skeletal Reconstruction in Paediatric Patients: A Low Cost Alternative in Developing Countries

    Directory of Open Access Journals (Sweden)

    Masood Umer

    2013-01-01

    Full Text Available We reviewed in this series forty patients of pediatric age who underwent resection for malignant tumors of musculoskeletal system followed by biological reconstruction. Our surgical procedure for reconstruction included (1 wide en bloc resection of the tumor; (2 curettage of tumor from the resected bone; (3 autoclaving for 8 minutes (4 bone grafting from the fibula (both vascularized and nonvascularized fibular grafts used; (5 reimplantation of the autoclaved bone into the host bone defect and fixation with plates. Functional evaluation was done using MSTS scoring system. At final followup of at least 18 months (mean 29.2 months, 31 patients had recovered without any complications. Thirty-eight patients successfully achieved a solid bony union between the graft and recipient bone. Three patients had surgical site infection. They were managed with wound debridement and flap coverage of the defect. Local recurrence and nonunion occurred in two patients each. One patient underwent disarticulation at hip due to extensive local disease and one died of metastasis. For patients with non-union, revision procedure with bone graft and compression plates was successfully used. The use of autoclaved tumor grafts provides a limb salvage option that is inexpensive and independent of external resources and is a viable option for musculoskeletal tumor management in developing countries.

  6. Albumin-bound paclitaxel in solid tumors: clinical development and future directions.

    Science.gov (United States)

    Kundranda, Madappa N; Niu, Jiaxin

    2015-01-01

    Albumin-bound paclitaxel (nab-paclitaxel) is a solvent-free formulation of paclitaxel that was initially developed more than a decade ago to overcome toxicities associated with the solvents used in the formulation of standard paclitaxel and to potentially improve efficacy. Nab-paclitaxel has demonstrated an advantage over solvent-based paclitaxel by being able to deliver a higher dose of paclitaxel to tumors and decrease the incidence of serious toxicities, including severe allergic reactions. To date, nab-paclitaxel has been indicated for the treatment of three solid tumors in the USA. It was first approved for the treatment of metastatic breast cancer in 2005, followed by locally advanced or metastatic non-small-cell lung cancer in 2012, and most recently for metastatic pancreatic cancer in 2013. Nab-paclitaxel is also under investigation for the treatment of a number of other solid tumors. This review highlights key clinical efficacy and safety outcomes of nab-paclitaxel in the solid tumors for which it is currently indicated, discusses ongoing trials that may provide new data for the expansion of nab-paclitaxel's indications into other solid tumors, and provides a clinical perspective on the use of nab-paclitaxel in practice.

  7. DNA methylation mediated control of gene expression is critical for development of crown gall tumors.

    Directory of Open Access Journals (Sweden)

    Jochen Gohlke

    Full Text Available Crown gall tumors develop after integration of the T-DNA of virulent Agrobacterium tumefaciens strains into the plant genome. Expression of the T-DNA-encoded oncogenes triggers proliferation and differentiation of transformed plant cells. Crown gall development is known to be accompanied by global changes in transcription, metabolite levels, and physiological processes. High levels of abscisic acid (ABA in crown galls regulate expression of drought stress responsive genes and mediate drought stress acclimation, which is essential for wild-type-like tumor growth. An impact of epigenetic processes such as DNA methylation on crown gall development has been suggested; however, it has not yet been investigated comprehensively. In this study, the methylation pattern of Arabidopsis thaliana crown galls was analyzed on a genome-wide scale as well as at the single gene level. Bisulfite sequencing analysis revealed that the oncogenes Ipt, IaaH, and IaaM were unmethylated in crown galls. Nevertheless, the oncogenes were susceptible to siRNA-mediated methylation, which inhibited their expression and subsequently crown gall growth. Genome arrays, hybridized with methylated DNA obtained by immunoprecipitation, revealed a globally hypermethylated crown gall genome, while promoters were rather hypomethylated. Mutants with reduced non-CG methylation developed larger tumors than the wild-type controls, indicating that hypermethylation inhibits plant tumor growth. The differential methylation pattern of crown galls and the stem tissue from which they originate correlated with transcriptional changes. Genes known to be transcriptionally inhibited by ABA and methylated in crown galls became promoter methylated upon treatment of A. thaliana with ABA. This suggests that the high ABA levels in crown galls may mediate DNA methylation and regulate expression of genes involved in drought stress protection. In summary, our studies provide evidence that epigenetic processes

  8. Self-Concept Development in Inclusive Classroom Settings focusing on Children with and without Visual Impairment

    OpenAIRE

    Sarah Wieckert

    2013-01-01

    The encouragement of the development of a realistic self-concept of the children in their classes is an important challenge for school teachers. Children who know about their strengths and weaknesses can work on the competences, which need to be improved, more effectively. This contribution presents a study which focuses on the special time of first-grade when primary school children get to know their new learning environment. In that context a survey takes place in Germany and accompanies ch...

  9. Information paradox of new product development: A case of decision-makers' focus of attention

    DEFF Research Database (Denmark)

    Jespersen, Kristina Risom

    Drawing on theory of bounded rationality and the attention-based view of the company, decision-makers' focus of attention is examined within the new product development process. Attention, defined as something which occupies individual consciousness, should be directed at selecting development...... activities and applying information resulting from these activities to go/no-go decision-making. Based on the information behavior of 42 development managers collected through a virtual role-play simulation of new product development, this research finds two information paradoxes of new product development....... First, competitive behavior makes decision-makers apply logic of reassurances in their implementation of NPD activities. Second, the information processing competence of decision-makers is unbalanced as information increases uncertainty in the concrete decision-making situation....

  10. Merkel Cell Polyomavirus Small T Antigen Initiates Merkel Cell Carcinoma-like Tumor Development in Mice.

    Science.gov (United States)

    Verhaegen, Monique E; Mangelberger, Doris; Harms, Paul W; Eberl, Markus; Wilbert, Dawn M; Meireles, Julia; Bichakjian, Christopher K; Saunders, Thomas L; Wong, Sunny Y; Dlugosz, Andrzej A

    2017-06-15

    Merkel cell carcinoma (MCC) tumor cells express several markers detected in normal Merkel cells, a nonproliferative population of neuroendocrine cells that arise from epidermis. MCCs frequently contain Merkel cell polyomavirus (MCPyV) DNA and express viral transforming antigens, sT and tLT, but the role of these putative oncogenes in MCC development, and this tumor's cell of origin, are unknown. Using a panel of preterm transgenic mice, we show that epidermis-targeted coexpression of sT and the cell fate-determinant atonal bHLH transcription factor 1 (ATOH1) leads to development of widespread cellular aggregates, with histology and marker expression mimicking that of human intraepidermal MCC. The MCC-like tumor phenotype was dependent on the FBXW7-binding domain of sT, but not the sT-PP2A binding domain. Coexpression of MCPyV tLT did not appreciably alter the phenotype driven by either sT or sT combined with ATOH1. MCPyV sT, when coexpressed with ATOH1, is thus sufficient to initiate development of epidermis-derived MCC-like tumors in mice. Cancer Res; 77(12); 3151-7. ©2017 AACR . ©2017 American Association for Cancer Research.

  11. Design and development of permanent magnet based focusing lens for J-Band Klystron

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Kumud; Itteera, Janvin; Ukarde, Priti; Malhotra, Sanjay; Taly, Y.K., E-mail: kumuds@barc.gov.in [Control Instrumentation Division, Bhabha Atomic Research Centre, Mumbai (India); Bandyopadhay, Ayan; Meena, Rakesh; Rawat, Vikram; Joshi, L.M [Microwave Tubes Division, Central Electronics Engineering Research Institute, Pilani (India)

    2014-07-01

    Applying permanent magnet technology to beam focusing in klystrons can reduce their power consumption and increase their reliability of operation. Electromagnetic design of the beam focusing elements, for high frequency travelling wave tubes, is very critical. The magnitude and profile of the magnetic field need to match the optics requirement from beam dynamics studies. The rise of the field from cathode gun region to the uniform field region (RF section) is important as the desired transition from zero to peak axial field must occur over a short axial distance. Confined flow regime is an optimum choice to minimize beam scalloping but demands an axial magnetic field greater than 2 - 3 times the Brillouin flow field. This necessitates optimization in the magnet design achieve high magnetic field within given spatial constraints. Electromagnetic design and simulations were done using 3D Finite element method (FEM) analysis software. A permanent magnet based focusing lens for a miniature J-Band klystron has been designed and developed at Control Instrumentation Division, BARC. This paper presents the design, simulation studies, beam transmission and RF tests results for J Band klystron with permanent magnet focusing lens. (author)

  12. Effects of pulsed magnetic stimulation on tumor development and immune functions in mice.

    Science.gov (United States)

    Yamaguchi, Sachiko; Ogiue-Ikeda, Mari; Sekino, Masaki; Ueno, Shoogo

    2006-01-01

    We investigated the effects of pulsed magnetic stimulation on tumor development processes and immune functions in mice. A circular coil (inner diameter = 15 mm, outer diameter = 75 mm) was used in the experiments. Stimulus conditions were pulse width = 238 micros, peak magnetic field = 0.25 T (at the center of the coil), frequency = 25 pulses/s, 1,000 pulses/sample/day and magnetically induced eddy currents in mice = 0.79-1.54 A/m(2). In an animal study, B16-BL6 melanoma model mice were exposed to the pulsed magnetic stimulation for 16 days from the day of injection of cancer cells. A tumor growth study revealed a significant tumor weight decrease in the stimulated group (54% of the sham group). In a cellular study, B16-BL6 cells were also exposed to the magnetic field (1,000 pulses/sample, and eddy currents at the bottom of the dish = 2.36-2.90 A/m(2)); however, the magnetically induced eddy currents had no effect on cell viabilities. Cytokine production in mouse spleens was measured to analyze the immunomodulatory effect after the pulsed magnetic stimulation. tumor necrosis factor (TNF-alpha) production in mouse spleens was significantly activated after the exposure of the stimulus condition described above. These results showed the first evidence of the anti-tumor effect and immunomodulatory effects brought about by the application of repetitive magnetic stimulation and also suggested the possible relationship between anti-tumor effects and the increase of TNF-alpha levels caused by pulsed magnetic stimulation.

  13. Gamified systems development focused on edutertainment and player: an analysis of Bartle and Marczewski archetipes

    Directory of Open Access Journals (Sweden)

    Shelley Navari Christianini

    2016-05-01

    Full Text Available This paper presents a development methodology about gamification systems, in which discuss the learning in these media from entertainment, concept defined as Edutertainment. By employing gamification in this type of production, it is believed that the investigation must be focused only on the playing techniques. However, from a literature review, it was found that the focus should be on the player, considering their feelings and real motivations to stay in the system. As a result, it is providing a comparative overview on the theories of Bartle (1996, 2005 and Marczewski (2015 with the main differences between player types in gaming environments and gamification systems, especially with regard to motivational strategies in the context of education.

  14. Application of Underwater Shock Wave Focusing to the Development of Extracorporeal Shock Wave Lithotripsy

    Science.gov (United States)

    Takayama, Kazuyoshi

    1993-05-01

    This paper describes a summary of a research project for the development of extracorporeal shock wave lithotripsy (ESWL), which has been carried out, under close collaboration between the Shock Wave Research Center of Tohoku University and the School of Medicine, Tohoku University. The ESWL is a noninvasive clinical treatment of disintegrating human calculi and one of the most peaceful applications of shock waves. Underwater spherical shock waves were generated by explosion of microexplosives. Characteristics of the underwater shock waves and of ultrasound focusing were studied by means of holographic interferometric flow visualization and polyvinyliden-difluoride (PVDF) pressure transducers. These focused pressures, when applied to clinical treatments, could effectively and noninvasively disintegrate urinary tract stones or gallbladder stones. However, despite clincal success, tissue damage occurs during ESWL treatments, and the possible mechanism of tissue damage is briefly described.

  15. Prognostic Factors Influencing the Development of an Iatrogenic Pneumothorax for Computed Tomography-Guided Radiofrequency Ablation of Upper Renal Tumor

    International Nuclear Information System (INIS)

    Park, B.K.; Kim, C.K.

    2008-01-01

    Background: Percutaneous radiofrequency (RF) ablation of upper renal tumors is considered a minimally invasive treatment, but this technique may cause pneumothorax. Purpose: To assess retrospectively the prognostic factors influencing the development of iatrogenic pneumothorax for RF ablation of upper renal tumors. Material and Methods: Computed tomography (CT)-guided RF ablation was performed in 24 patients (21 men, three women; age range 31-77 years, mean age 53.3 years) with 28 upper renal tumors. Various factors for pneumothorax-complicated (PC) upper renal tumors and non-pneumothoracic (NP) upper renal tumors were compared during RF ablation to determine which of the factors were involved in the development of pneumothorax. Results: Among 28 upper renal tumors in 24 patients, a pneumothorax occurred accidentally in six patients with eight tumors and intentionally in two patients with two tumors. This complication was treated with conservative management, instead of tube drainage. PC upper renal tumors had shorter distance from the lung or from the costophrenic line to the tumor, a larger angle between the costophrenic line and the tumor, and a higher incidence of intervening lung tissue than NP upper renal tumors (P<0.01). Intervening lung tissue was more frequently detected on CT images obtained with the patient in the prone position than on CT images obtained with the patient in the supine position. Conclusion: The presence of intervening lung tissue and the close proximity between an upper renal tumor and the lung are high risk factors for developing an iatrogenic pneumothorax. Pre-ablation CT scan should be performed in the prone position to exactly evaluate intervening lung tissue

  16. LANGUAGE, HUMAN DEVELOPMENT AND EDUCATION: FOCUS ON CHILDREN’S EDUCATION

    Directory of Open Access Journals (Sweden)

    Solange Maria Alves

    2010-06-01

    Full Text Available Based on theoretical patterns of historical-cultural approach, this text proposes a critical discussion about the relation among the process of human development, the role of language and scholar education as elements of specific and intentional mediation, directed to the development of typical human ways of thinking, or, as preferred by Vygotsky, superior psychological functions. Under this focus, the author points some characteristics to be assumed by scholar organization, committed with pedagogic praxis for childhood, approaching the playful of social roles and the game as linguistic elements itself, and, thus, owners of social content, fundamental symbolic contents to be taken as start element for the educative action of change. KEYWORDS: Language and play. Human development. Education. Childhood. AUTORA

  17. Development of the compact proton beam therapy system dedicated to spot scanning with real-time tumor-tracking technology

    Science.gov (United States)

    Umezawa, Masumi; Fujimoto, Rintaro; Umekawa, Tooru; Fujii, Yuusuke; Takayanagi, Taisuke; Ebina, Futaro; Aoki, Takamichi; Nagamine, Yoshihiko; Matsuda, Koji; Hiramoto, Kazuo; Matsuura, Taeko; Miyamoto, Naoki; Nihongi, Hideaki; Umegaki, Kikuo; Shirato, Hiroki

    2013-04-01

    Hokkaido University and Hitachi Ltd. have started joint development of the Gated Spot Scanning Proton Therapy with Real-Time Tumor-Tracking System by integrating real-time tumor tracking technology (RTRT) and the proton therapy system dedicated to discrete spot scanning techniques under the "Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program)". In this development, we have designed the synchrotron-based accelerator system by using the advantages of the spot scanning technique in order to realize a more compact and lower cost proton therapy system than the conventional system. In the gated irradiation, we have focused on the issues to maximize irradiation efficiency and minimize the dose errors caused by organ motion. In order to understand the interplay effect between scanning beam delivery and target motion, we conducted a simulation study. The newly designed system consists of the synchrotron, beam transport system, one compact rotating gantry treatment room with robotic couch, and one experimental room for future research. To improve the irradiation efficiency, the new control function which enables multiple gated irradiations per synchrotron cycle has been applied and its efficacy was confirmed by the irradiation time estimation. As for the interplay effect, we confirmed that the selection of a strict gating width and scan direction enables formation of the uniform dose distribution.

  18. Development of the PedsQL™ Epilepsy Module: Focus group and cognitive interviews.

    Science.gov (United States)

    Follansbee-Junger, Katherine W; Mann, Krista A; Guilfoyle, Shanna M; Morita, Diego A; Varni, James W; Modi, Avani C

    2016-09-01

    Youth with epilepsy have impaired health-related quality of life (HRQOL). Existing epilepsy-specific HRQOL measures are limited by not having parallel self- and parent-proxy versions, having a restricted age range, not being inclusive of children with developmental disabilities, or being too lengthy for use in a clinical setting. Generic HRQOL measures do not adequately capture the idiosyncrasies of epilepsy. The purpose of the present study was to develop items and content validity for the PedsQL™ Epilepsy Module. An iterative qualitative process of conducting focus group interviews with families of children with epilepsy, obtaining expert input, and conducting cognitive interviews and debriefing was utilized to develop empirically derived content for the instrument. Eleven health providers with expertise in pediatric epilepsy from across the country provided feedback on the conceptual model and content, including epileptologists, nurse practitioners, social workers, and psychologists. Ten pediatric patients (age 4-16years) with a diagnosis of epilepsy and 11 parents participated in focus groups. Thirteen pediatric patients (age 5-17years) and 17 parents participated in cognitive interviews. Focus groups, expert input, and cognitive debriefing resulted in 6 final domains including restrictions, seizure management, cognitive/executive functioning, social, sleep/fatigue, and mood/behavior. Patient self-report versions ranged from 30 to 33 items and parent proxy-report versions ranged from 26 to 33 items, with the toddler and young child versions having fewer items. Standardized qualitative methodology was employed to develop the items and content for the novel PedsQL™ Epilepsy Module. The PedsQL™ Epilepsy Module has the potential to enhance clinical decision-making in pediatric epilepsy by capturing and monitoring important patient-identified contributors to HRQOL. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Self-Concept Development in Inclusive Classroom Settings focusing on Children with and without Visual Impairment

    Directory of Open Access Journals (Sweden)

    Sarah Wieckert

    2013-08-01

    Full Text Available The encouragement of the development of a realistic self-concept of the children in their classes is an important challenge for school teachers. Children who know about their strengths and weaknesses can work on the competences, which need to be improved, more effectively. This contribution presents a study which focuses on the special time of first-grade when primary school children get to know their new learning environment. In that context a survey takes place in Germany and accompanies children with and without special needs in the field of vision which learn together in school.

  20. Micro product development methods – how do we focus on the right issues?

    DEFF Research Database (Denmark)

    De Grave, Arnaud

    2005-01-01

    The development of micro and nano products or systems is considered to be a very difficult and challenging task. The manufacturing technologies used are emerging or pushed to the limits of their capabilities. The physical working principle is often not in the same area as common engineering...... is to focus on the right issues for each required part of the design steps and have the available knowledge and technologies. To that extent, both a technology pushed approach and a product/customer driven approach have to be used in order to conduct to a level of knowledge which can lead to actual production...

  1. Dietary quercetin exacerbates the development of estrogen-induced breast tumors in female ACI rats

    International Nuclear Information System (INIS)

    Singh, Bhupendra; Mense, Sarah M.; Bhat, Nimee K.; Putty, Sandeep; Guthiel, William A.; Remotti, Fabrizio; Bhat, Hari K.

    2010-01-01

    Phytoestrogens are plant compounds that structurally mimic the endogenous estrogen 17β-estradiol (E 2 ). Despite intense investigation, the net effect of phytoestrogen exposure on the breast remains unclear. The objective of the current study was to examine the effects of quercetin on E 2 -induced breast cancer in vivo. Female ACI rats were given quercetin (2.5 g/kg food) for 8 months. Animals were monitored weekly for palpable tumors, and at the end of the experiment, rats were euthanized, breast tumor and different tissues excised so that they could be examined for histopathologic changes, estrogen metabolic activity and oxidant stress. Quercetin alone did not induce mammary tumors in female ACI rats. However, in rats implanted with E 2 pellets, co-exposure to quercetin did not protect rats from E 2 -induced breast tumor development with 100% of the animals developing breast tumors within 8 months of treatment. No changes in serum quercetin levels were observed in quercetin and quercetin + E 2 -treated groups at the end of the experiment. Tumor latency was significantly decreased among rats from the quercetin + E 2 group relative to those in the E 2 group. Catechol-O-methyltransferase (COMT) activity was significantly downregulated in quercetin-exposed mammary tissue. Analysis of 8-isoprostane F 2α (8-iso-PGF 2α ) levels as a marker of oxidant stress showed that quercetin did not decrease E 2 -induced oxidant stress. These results indicate that quercetin (2.5 g/kg food) does not confer protection against breast cancer, does not inhibit E 2 -induced oxidant stress and may exacerbate breast carcinogenesis in E 2 -treated ACI rats. Inhibition of COMT activity by quercetin may expose breast cells chronically to E 2 and catechol estrogens. This would permit longer exposure times to the carcinogenic metabolites of E 2 and chronic exposure to oxidant stress as a result of metabolic redox cycling to estrogen metabolites, and thus quercetin may exacerbate E 2 -induced

  2. Therapeutics targeting tumor immune escape: towards the development of new generation anticancer vaccines.

    Science.gov (United States)

    Mocellin, Simone; Nitti, Donato

    2008-05-01

    Despite the evidence that immune effectors can play a significant role in controlling tumor growth under natural conditions or in response to therapeutic manipulation, it is clear that malignant cells evade immune surveillance in most cases. Considering that anticancer vaccination has reached a plateau of results and currently no vaccination regimen is indicated as a standard anticancer therapy, the dissection of the molecular events underlying tumor immune escape is the necessary condition to make anticancer vaccines a therapeutic weapon effective enough to be implemented in the routine clinical setting. Recent years have witnessed significant advances in our understanding of the molecular mechanisms underlying tumor immune escape. These mechanistic insights are fostering the development of rationally designed therapeutics aimed at reverting the immunosuppressive circuits that undermine an effective antitumor immune response. In this review, the best characterized mechanisms that allow cancer cells to evade immune surveillance are overviewed and the most debated controversies constellating this complex field are highlighted. In addition, the latest therapeutic strategies devised to overcome tumor immune escape are described, with special regard to those entering clinical phase investigation. Copyright (c) 2007 Wiley-Periodicals, Inc.

  3. Development of real-time tumor tracking system for stereotactic radiotherapy

    International Nuclear Information System (INIS)

    Yamanaka, Seiji; Sasagawa, Tsuyoshi; Uno, Yukimichi

    2011-01-01

    We are now developing the real-time tumor tracking system for stereotactic radiotherapy (SRT) to provide precise information on the location of a tumor and to reduce the irradiation to healthy tissue in a patient. The system has the following features: A motion tracking and processing unit recognizes a gold marker inserted in or near a tumor in real time by the pattern matching of a predetermined template image and acquired X-ray fluoroscopic images. When the gold marker is within a planned area, that is to say, when a tumor enters a target irradiation area, a gate signal is sent to a linear accelerator. A railway unit is equipped with two X-ray tubes and two detectors, which are controlled separately with their own drive mechanism. They travel with high accuracy and reproducibility to the best position for monitoring the gold marker. A synchronization controller controls the timing for X-ray fluoroscopy and the gate signals to the linear accelerator. The controller works for two types of detectors: a color X-ray detector and a flat panel detector (FPD). (author)

  4. [High-intensity focused ultrasound (HIFU) for tumor pain relief in inoperable pancreatic cancer : Evaluation with the pain sensation scale (SES)].

    Science.gov (United States)

    Marinova, M; Strunk, H M; Rauch, M; Henseler, J; Clarens, T; Brüx, L; Dolscheid-Pommerich, R; Conrad, R; Cuhls, H; Radbruch, L; Schild, H H; Mücke, M

    2017-02-01

    High-intensity focused ultrasound (HIFU) in combination with palliative standard therapy is an innovative and effective treatment option for pain reduction in patients with inoperable pancreatic cancer. Evaluation of the effects of additive ultrasound (US)-guided HIFU treatment in inoperable pancreatic cancer on the sensory and affective pain perception using validated questionnaries. In this study 20 patients with locally advanced inoperable pancreatic cancer and tumor-related pain were treated by US-guided HIFU (6 stage III, 12 stage IV according to UICC and 2 with local recurrence after surgery). Ablation was performed using the JC HIFU system (HAIFU, Chongqing, China) with an ultrasonic device for real-time imaging. Clinical assessment included evaluation of pain severity using validated questionnaires with particular attention to the pain sensation scale (SES) with its affective and sensory component and the numeric rating scale (NRS). The average pain reduction after HIFU was 2.87 points on the NRS scale and 57.3 % compared to the mean baseline score (n = 15, 75 %) in 19 of 20 treated patients. Four patients did not report pain relief, however, the previous opioid medication could be stopped (n = 2) or the analgesic dosage could be reduced (n = 2). No pain reduction was achieved in one patient. Furthermore, after HIFU emotional as well as sensory pain aspects were significantly reduced (before vs. 1 week after HIFU, p pain scales). US-guided HIFU can be used for effective and early pain relief and reduction of emotional and sensory pain sensation in patients with locally advanced pancreatic cancer.

  5. US Department of Energy mixed waste characterization, treatment, and disposal focus area technical baseline development process

    International Nuclear Information System (INIS)

    Roach, J.A.; Gombert, D.

    1996-01-01

    The US Department of Energy (DOE) created the Mixed Waste Characterization, Treatment, and Disposal Focus Area (MWFA) to develop and facilitate implementation of technologies required to meet its commitments for treatment of mixed wastes under the Federal Facility Compliance Act (FFCA), and in accordance with the Land Disposal Restrictions (LDR) of the Resource Conservation and Recovery Act (RCRA). Mixed wastes include both mixed low-level waste (MLLW) and mixed transuranic (MTRU) waste. The goal of the MWFA is to develop mixed waste treatment systems to the point of implementation by the Environmental Management (EM) customer. To accomplish this goal, the MWFA is utilizing a three step process. First, the treatment system technology deficiencies were identified and categorized. Second, these identified needs were prioritized. This resulted in a list of technical deficiencies that will be used to develop a technical baseline. The third step, the Technical Baseline Development Process, is currently ongoing. When finalized, the technical baseline will integrate the requirements associated with the identified needs into the planned and ongoing environmental research and technology development activities supported by the MWFA. Completion of this three-step process will result in a comprehensive technology development program that addresses customer identified and prioritized needs. The MWFA technical baseline will be a cost-effective, technically-defensible tool for addressing and resolving DOE's mixed waste problems

  6. [Recent developments in biopsy diagnosis of early and undefined liver tumors].

    Science.gov (United States)

    Longerich, T; Schirmacher, P

    2009-01-01

    Biopsy diagnosis of early and highly differentiated liver tumors is difficult and complex. Modern pathology has met this challenge by several different means; elaborate morphological algorithms and novel immunohistological markers support the differential diagnosis of highly differentiated HCC and a new, predictive molecular pathological and histological classification of liver cell adenoma was developed. By these new diagnostic tools together with the so-called 'matrix diagnosis' a reliable diagnostic classification is now feasible in the vast majority of these difficult cases.

  7. Developing a plasma focus research training system for the fusion energy age

    International Nuclear Information System (INIS)

    Lee, S.

    2014-01-01

    The 3 kJ UNU/ICTP Plasma Focus Facility is the most significant device associated with the AAAPT (Asian African Association for Plasma Training). In original and modified/upgraded form it has trained generations of plasma focus (PF) researchers internationally, producing many PhD theses and peer-reviewed papers. The Lee Model code was developed for the design of this PF. This code has evolved to cover all PF machines for design, interpretation and optimization, for derivation of radiation scaling laws; and to provide insights into yield scaling limitations, radiative collapse, speed-enhanced and current-stepped PF variants. As example of fresh perspectives derivable from this code, this paper presents new results on energy transfers of the axial and radial phases of generalized PF devices. As the world moves inexorably towards the Fusion Energy Age it becomes ever more important to train plasma fusion researchers. A recent workshop in Nepal shows that demand for such training continues. Even commercial project development consultants are showing interest. We propose that the AAAPT-proven research package be upgraded, by modernizing the small PF for extreme modes of operation, switchable from the typical strong-focus mode to a slow-mode which barely pinches, thus producing a larger, more uniform plasma stream with superior deposition properties. Such a small device would be cost-effective and easily duplicated, and have the versatility of a range of experiments from intense multi-radiation generation and target damage studies to superior advanced-materials deposition. The complementary code is used to reference experiments up to the largest existing machine. This is ideal for studying machine limitations and scaling laws and to suggest new experiments. Such a modernized versatile PF machine complemented by the universally versatile code would extend the utility of the PF experience; so that AAAPT continues to provide leadership in pulsed plasma research training in

  8. Effect of a mouse mammary tumor virus-derived protein vaccine on primary tumor development in mice

    NARCIS (Netherlands)

    Creemers, P.; Ouwehand, J.; Bentveizen, P.

    1978-01-01

    The vaccines used in this study were derived from purified murine mammary tumor virus (MuMTV) preparations. Approximately 60% of the protein fractions consisted of the major viral membrane glycoprotein gp52. Inoculation sc of 10 pg MuMTV-S-derived vaccine significantly delayed the appearance of

  9. Obesity and the metabolic syndrome in developing countries: focus on South Asians.

    Science.gov (United States)

    Misra, Anoop; Bhardwaj, Swati

    2014-01-01

    With improvement in the economic situation, an increasing prevalence of obesity and the metabolic syndrome is seen in developing countries in South Asia. Particularly vulnerable population groups include women and children, and intra-country and inter-country migrants. The main causes are increasing urbanization, nutrition transition, reduced physical activity, and genetic predisposition. Some evidence suggests that widely prevalent perinatal undernutrition and childhood 'catch-up' obesity may play a role in adult-onset metabolic syndrome and type 2 diabetes. Data show that atherogenic dyslipidemia, glucose intolerance, thrombotic tendency, subclinical inflammation, and endothelial dysfunction are higher in South Asians than white Caucasians. Many of these manifestations are more severe even at an early age in South Asians than white Caucasians. Metabolic and cardiovascular risks in South Asians are also heightened by their higher body fat, truncal subcutaneous fat, intra-abdominal fat, and ectopic fat deposition (liver fat, muscle fat, etc.). Further, cardiovascular risk cluster manifests at a lower level of adiposity and abdominal obesity. The cutoffs of body mass index and waist circumference for defining obesity and abdominal obesity, respectively, have been lowered for Asians, and same has been endorsed for South Asians in the UK. The economic cost of obesity and related diseases in developing countries, having meager health budget, is enormous. Increasing awareness of these noncommunicable diseases and how to prevent them should be focus of population-wide prevention strategies in South Asian developing countries. Community intervention programs focusing on increased physical activity and healthier food options for schoolchildren are urgently required. Data from such a major intervention program conducted by us on adolescent urban schoolchildren in north India (project MARG) have shown encouraging results and could serve as a model for initiating such

  10. Small heterodimer partner overexpression partially protects against liver tumor development in farnesoid X receptor knockout mice

    International Nuclear Information System (INIS)

    Li, Guodong; Kong, Bo; Zhu, Yan; Zhan, Le; Williams, Jessica A.; Tawfik, Ossama; Kassel, Karen M.; Luyendyk, James P.; Wang, Li; Guo, Grace L.

    2013-01-01

    Farnesoid X receptor (FXR, Nr1h4) and small heterodimer partner (SHP, Nr0b2) are nuclear receptors that are critical to liver homeostasis. Induction of SHP serves as a major mechanism of FXR in suppressing gene expression. Both FXR −/− and SHP −/− mice develop spontaneous hepatocellular carcinoma (HCC). SHP is one of the most strongly induced genes by FXR in the liver and is a tumor suppressor, therefore, we hypothesized that deficiency of SHP contributes to HCC development in the livers of FXR −/− mice and therefore, increased SHP expression in FXR −/− mice reduces liver tumorigenesis. To test this hypothesis, we generated FXR −/− mice with overexpression of SHP in hepatocytes (FXR −/− /SHP Tg ) and determined the contribution of SHP in HCC development in FXR −/− mice. Hepatocyte-specific SHP overexpression did not affect liver tumor incidence or size in FXR −/− mice. However, SHP overexpression led to a lower grade of dysplasia, reduced indicator cell proliferation and increased apoptosis. All tumor-bearing mice had increased serum bile acid levels and IL-6 levels, which was associated with activation of hepatic STAT3. In conclusion, SHP partially protects FXR −/− mice from HCC formation by reducing tumor malignancy. However, disrupted bile acid homeostasis by FXR deficiency leads to inflammation and injury, which ultimately results in uncontrolled cell proliferation and tumorigenesis in the liver. - Highlights: • SHP does not prevent HCC incidence nor size in FXR KO mice but reduces malignancy. • Increased SHP promotes apoptosis. • Bile acids and inflammation maybe critical for HCC formation with FXR deficiency

  11. Interaction of tumor cells with the microenvironment

    Directory of Open Access Journals (Sweden)

    Lehnert Hendrik

    2011-09-01

    Full Text Available Abstract Recent advances in tumor biology have revealed that a detailed analysis of the complex interactions of tumor cells with their adjacent microenvironment (tumor stroma is mandatory in order to understand the various mechanisms involved in tumor growth and the development of metastasis. The mutual interactions between tumor cells and cellular and non-cellular components (extracellular matrix = ECM of the tumor microenvironment will eventually lead to a loss of tissue homeostasis and promote tumor development and progression. Thus, interactions of genetically altered tumor cells and the ECM on the one hand and reactive non-neoplastic cells on the other hand essentially control most aspects of tumorigenesis such as epithelial-mesenchymal-transition (EMT, migration, invasion (i.e. migration through connective tissue, metastasis formation, neovascularisation, apoptosis and chemotherapeutic drug resistance. In this mini-review we will focus on these issues that were recently raised by two review articles in CCS.

  12. Quercetin as an Emerging Anti-Melanoma Agent: A four-focus area therapeutic development strategy

    Directory of Open Access Journals (Sweden)

    Zoey Harris

    2016-10-01

    Full Text Available Replacing current refractory treatments for melanoma with new prevention and therapeutic approaches is crucial in order to successfully treat this aggressive cancer form. Melanoma develops from neural crest cells, which express tyrosinase -- a key enzyme in the pigmentation pathway. The tyrosinase enzyme is highly active in melanoma cells and metabolizes polyphenolic compounds; tyrosinase expression thus makes a feasible a target for polyphenol-based therapies. For example, quercetin (3,3′,4′,5,7-pentahydroxyflavone is a highly ubiquitous and well-classified dietary polyphenol found in various fruits, vegetables and other plant products including onions, broccoli, kale, oranges, blueberries, apples, and tea. Quercetin has demonstrated anti-proliferative and pro-apoptotic activity in various cancer cell types. Quercetin is readily metabolized by tyrosinase into various compounds that promote anti-cancer activity; additionally, given that tyrosinase expression increases during tumorigenesis, and its activity is associated with pigmentation changes in both early- and late-stage melanocytic lesions, it suggests that quercetin can be used to target melanoma. In this review we explore the potential of Quercetin as an anti-melanoma agent utilizing and extrapolating on evidence from previous in vitro studies in various human malignant cell lines and propose a four-focus area strategy to develop quercetin as a targeted anti-melanoma compound for use as either a preventative or therapeutic agent. The four areas of focus include utilizing quercetin to i modulate cellular bioreduction potential and associated signaling cascades, ii affect transcription of relevant genes, iii regulate epigenetic processes, and iv develop effective combination therapies and delivery modalities/protocols. In general, quercetin could be used to exploit tyrosinase activity to prevent, and/or treat, melanoma with minimal additional side effects.

  13. Developing an Environmental Performance Index (EPI: a focus on impacts of information and communication technology use

    Directory of Open Access Journals (Sweden)

    C Mbohwa

    2011-07-01

    Full Text Available There is a growing need for environmental performance measures that can be used by all stakeholders like surrounding communities, customers, suppliers and shareholders to gauge the environmental performance of organizations. The environmental performance measures that are used worldwide are normally not suitable for benchmarking organizations. This paper develops an environmental performance index using indicator and weight matrices of the full life cycle phases of an organization’s energy use for environmental management system activities. This work is transdisciplinary in nature and applies mathematical matrices and environmental productivity approaches, and borrows from the development of quality indices to consider a variety of impacts that cut across various phases of a product life cycle and different functions within an organization. The focus is on information and communication technology use in these systems. The model is applied to the Japanese automotive industry and the findings show that it is feasible and effective for comparing the environmental performance of companies in the same sector using the same weight matrices and indicators agreed to. The work informs decision making on the development of environmental performance measures that have worldwide applications, across many disciplines, in situations where suitable data are recorded. It also contributes to efforts on economic and social sustainability. Research efforts in similar areas in Southern Africa can benefit from the development and improvement of the proposed methodology. Keywords: Environmental performance index, indicator and weight matrices, benchmarking Disciplines: Information and Communications Technology Studies (ICT, Environmental Studies, Economics, Sustainability Studies

  14. Development and experimental study of oil-free capacitor module for plasma focus device

    Science.gov (United States)

    Sharma, Ravindra Kumar; Sharma, Archana

    2017-03-01

    This development is concerned with the compact capacitor module for a plasma focus device. Oil-free, non-standard geometry capacitors are designed and developed for high current delivery in sub-microseconds time. Metalized dielectric film based pulse capacitor becomes progressively less viable at currents above 10 kA. It is due to reliability and energy scaling difficulties, based on effects such as vaporization, high resistivity, and end connection. Bipolar electrolytic capacitors are also not preferred due to their limited life and comparatively low peak current delivery. Bi-axially oriented polypropylene (BOPP) film with extended aluminum foil is a combination to deliver moderately high power. But, electrically weak points, relative permittivity, and the edge gap margins have made its adoption difficult. A concept has been developed in lab for implementing the above combination in a less complex and costly manner. This paper concerns the development and testing process techniques for quite different hollow cylindrical, oil-free capacitors (4 μ F , 10 kV, 20 nH). Shot life of 1000 has been experimentally performed on the test bed at its rated energy density level. The technological methods and engineering techniques are now available and utilized for manufacturing and testing of BOPP film based oil-free capacitors.

  15. Developing public affairs counseling skills to support a public participation focus at Fernald

    Energy Technology Data Exchange (ETDEWEB)

    Hoopes, J. [Fernald Environmental Restoration Management Corp., Cincinnati, OH (United States)

    1994-03-01

    To provide closer coordination between the Public Affairs Division and environmental restoration management and technical staff, the Fernald Environmental Restoration Management Corporation (FERMCO) matrixed Public Affairs staffers as counselors to project teams within FERMCO. Close coordination between technical staff and public affairs staff is essential for effective public communication in a public participation, environmental risk communication environment. Two-way symmetrical communication (public participation) represents a paradigm shift for public affairs staff who have developed skills primarily in a public information (asymmetrical communication) environment. While there has been much focus in the literature and workshops on management changes needed to support a public participation environment, less attention has been paid to identifying and developing the skills needed by public affairs professionals to support public participation. To support the new counseling role of public affairs staffers, FERMCO used a public affairs training consultant to design and deliver a workshop to initiate development of the skills needed for the public affairs counseling role. This paper describes FERMCO`s matrixed counseling program and the training to develop public affairs counseling skills for the public participation environment.

  16. Development of a flexible and potent hypoxia-inducible promoter for tumor-targeted gene expression in attenuated Salmonella

    NARCIS (Netherlands)

    Mengesha, Asferd; Dubois, Ludwig; Lambin, Philippe; Landuyt, Willy; Chiu, Roland K; Wouters, Bradly G; Theys, Jan

    To increase the potential of attenuated Salmonella as gene delivery vectors for cancer treatment, we developed a hypoxia-inducible promoter system to limit gene expression specifically to the tumor. This approach is envisaged to not only increase tumor specificity, but also to target those cells

  17. Patient input into the development and enhancement of ED discharge instructions: a focus group study.

    Science.gov (United States)

    Buckley, Barbara A; McCarthy, Danielle M; Forth, Victoria E; Tanabe, Paula; Schmidt, Michael J; Adams, James G; Engel, Kirsten G

    2013-11-01

    Previous research indicates that patients have difficulty understanding ED discharge instructions; these findings have important implications for adherence and outcomes. The objective of this study was to obtain direct patient input to inform specific revisions to discharge documents created through a literacy-guided approach and to identify common themes within patient feedback that can serve as a framework for the creation of discharge documents in the future. Based on extensive literature review and input from ED providers, subspecialists, and health literacy and communication experts, discharge instructions were created for 5 common ED diagnoses. Participants were recruited from a federally qualified health center to participate in a series of 5 focus group sessions. Demographic information was obtained and a Rapid Estimate of Adult Literacy in Medicine (REALM) assessment was performed. During each of the 1-hour focus group sessions, participants reviewed discharge instructions for 1 of 5 diagnoses. Participants were asked to provide input into the content, organization, and presentation of the documents. Using qualitative techniques, latent and manifest content analysis was performed to code for emergent themes across all 5 diagnoses. Fifty-seven percent of participants were female and the average age was 32 years. The average REALM score was 57.3. Through qualitative analysis, 8 emergent themes were identified from the focus groups. Patient input provides meaningful guidance in the development of diagnosis-specific discharge instructions. Several themes and patterns were identified, with broad significance for the design of ED discharge instructions. Copyright © 2013 Emergency Nurses Association. Published by Mosby, Inc. All rights reserved.

  18. Genetically engineered mouse models of craniopharyngioma: an opportunity for therapy development and understanding of tumor biology.

    Science.gov (United States)

    Apps, John Richard; Martinez-Barbera, Juan Pedro

    2017-05-01

    Adamantinomatous craniopharyngioma (ACP) is the commonest tumor of the sellar region in childhood. Two genetically engineered mouse models have been developed and are giving valuable insights into ACP biology. These models have identified novel pathways activated in tumors, revealed an important function of paracrine signalling and extended conventional theories about the role of organ-specific stem cells in tumorigenesis. In this review, we summarize these mouse models, what has been learnt, their limitations and open questions for future research. We then discussed how these mouse models may be used to test novel therapeutics against potentially targetable pathways recently identified in human ACP. © 2017 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

  19. Recent Developments in Active Tumor Targeted Multifunctional Nanoparticles for Combination Chemotherapy in Cancer Treatment and Imaging

    Science.gov (United States)

    Glasgow, Micah D. K.; Chougule, Mahavir B.

    2016-01-01

    Nanotechnology and combination therapy are two major fields that show great promise in the treatment of cancer. The delivery of drugs via nanoparticles helps to improve drug’s therapeutic effectiveness while reducing adverse side effects associated with high dosage by improving their pharmacokinetics. Taking advantage of molecular markers over-expressing on tumor tissues compared to normal cells, an “active” molecular marker targeted approach would be beneficial for cancer therapy. These actively targeted nanoparticles would increase drug concentration at the tumor site, improving efficacy while further reducing chemo-resistance. The multidisciplinary approach may help to improve the overall efficacy in cancer therapy. This review article summarizes recent developments of targeted multifunctional nanoparticles in the delivery of various drugs for a combinational chemotherapy approach to cancer treatment and imaging. PMID:26554150

  20. Eosinophilia in routine blood samples as a biomarker for solid tumor development

    DEFF Research Database (Denmark)

    Andersen, Christen Bertel L; Siersma, V.D.; Hasselbalch, H.C.

    2014-01-01

    eosinophilia in routine blood samples as a potential biomarker of solid tumor development in a prospective design. MATERIAL AND METHODS: From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356 196 individuals with at least one differential cell count (DIFF) encompassing...... was increased with mild eosinophilia [OR 1.93 (CI 1.29-2.89), p = 0.0013]. No associations with eosinophilia were observed for the remaining solid cancers. CONCLUSION: We demonstrate that eosinophilia in routine blood samples associates with an increased risk of bladder cancer. Our data emphasize...... that additional preclinical studies are needed in order to shed further light on the role of eosinophils in carcinogenesis, where it is still unknown whether the cells contribute to tumor immune surveillance or neoplastic evolution....

  1. Development of laser-induced grating spectroscopy for underwater temperature measurement in shock wave focusing regions

    Science.gov (United States)

    Gojani, Ardian B.; Danehy, Paul M.; Alderfer, David W.; Saito, Tsutomu; Takayama, Kazuyoshi

    2004-02-01

    In Extracorporeal Shock Wave Lithotripsy (ESWL) underwater shock wave focusing generates high pressures at very short duration of time inside human body. However, it is not yet clear how high temperatures are enhanced at the spot where a shock wave is focused. The estimation of such dynamic temperature enhancements is critical for the evaluation of tissue damages upon shock loading. For this purpose in the Interdisciplinary Shock Wave Research Center a technique is developed which employs laser induced thermal acoustics or Laser Induced Grating Spectroscopy. Unlike most of gas-dynamic methods of measuring physical quantities this provides a non-invasive one having spatial and temporal resolutions of the order of magnitude of 1.0 mm 3 and 400 ns, respectively. Preliminary experiments in still water demonstrated that this method detected sound speed and hence temperature in water ranging 283 K to 333 K with errors of 0.5%. These results are used to empirically establish the equation of states of water, gelatin or agar cell which will work as alternatives of human tissues.

  2. New developments in management of gastrointestinal stromal tumors: regorafenib, the new player in the team

    Directory of Open Access Journals (Sweden)

    Boichuk S

    2013-12-01

    Full Text Available Sergei Boichuk,1,2 Jessica L Rausch,1 Anette Duensing1,31Cancer Virology Program, University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, PA, USA; 2Department of Pathology, Kazan State Medical University, Kazan, Russia; 3Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USAAbstract: Gastrointestinal stromal tumors (GISTs are the most common mesenchymal tumors of the gastrointestinal tract and the most frequent single type of sarcoma, at least in some geographical regions. They arise from the interstitial cells of Cajal (or a common progenitor cell. The vast majority of GISTs are characterized by oncogenically activating mutations in the KIT or platelet-derived growth factor receptor alpha (PDGFRA receptor tyrosine kinase genes. This molecular feature has been successfully exploited for therapeutic purposes, and as of a decade ago, GISTs have become the prototype of a solid tumor that can be targeted with small molecule kinase inhibitors. Imatinib mesylate (Gleevec®/Glivec® benefits more than 85% of patients with unresectable and/or metastatic GIST. Unfortunately, the majority of patients develop resistance to imatinib within the first 2 years of treatment and new therapeutic options are needed. Although the broad-range kinase inhibitor sunitinib malate (Sutent® has been the second-line therapy approved by the US Food and Drug Administration since 2006, it was not until recently (February 2013 that regorafenib (Stivarga® was approved as a third-line therapeutic agent for GIST. This review summarizes the development process of regorafenib for GIST and highlights its biochemical, pharmacologic, and clinical properties.Keywords: gastrointestinal stromal tumors, GIST, regorafenib

  3. Novel allelic mutations in murine Serca2 induce differential development of squamous cell tumors

    Energy Technology Data Exchange (ETDEWEB)

    Toki, Hideaki; Minowa, Osamu; Inoue, Maki; Motegi, Hiromi; Karashima, Yuko; Ikeda, Ami [Team for Advanced Development and Evaluation of Human Disease Models, Riken BioResource Center (BRC), Tsukuba, Ibaraki (Japan); Kaneda, Hideki [Technology and Development Team for Mouse Phenotype Analysis, Riken BRC, Tsukuba, Ibaraki (Japan); Sakuraba, Yoshiyuki [Mutagenesis and Genomics Team, Riken BRC, Tsukuba, Ibaraki (Japan); Saiki, Yuriko [Department of Molecular Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi (Japan); Wakana, Shigeharu [Technology and Development Team for Mouse Phenotype Analysis, Riken BRC, Tsukuba, Ibaraki (Japan); Suzuki, Hiroshi [Department of Biochemistry, Asahikawa Medical University, Asahikawa, Hokkaido (Japan); Gondo, Yoichi [Mutagenesis and Genomics Team, Riken BRC, Tsukuba, Ibaraki (Japan); Shiroishi, Toshihiko [Mammalian Genetics Laboratory, National Institute of Genetics, Mishima, Shizuoka (Japan); Noda, Tetsuo, E-mail: tnoda@jfcr.or.jp [Team for Advanced Development and Evaluation of Human Disease Models, Riken BioResource Center (BRC), Tsukuba, Ibaraki (Japan); Department of Cell Biology, Cancer Institute, The Japanese Foundation for Cancer Research, Tokyo (Japan)

    2016-08-05

    Dominant mutations in the Serca2 gene, which encodes sarco(endo)plasmic reticulum calcium-ATPase, predispose mice to gastrointestinal epithelial carcinoma [1–4] and humans to Darier disease (DD) [14–17]. In this study, we generated mice harboring N-ethyl-N-nitrosourea (ENU)-induced allelic mutations in Serca2: three missense mutations and one nonsense mutation. Mice harboring these Serca2 mutations developed tumors that were categorized as either early onset squamous cell tumors (SCT), with development similar to null-type knockout mice [2,4] (aggressive form; M682, M814), or late onset tumors (mild form; M1049, M1162). Molecular analysis showed no aberration in Serca2 mRNA or protein expression levels in normal esophageal cells of any of the four mutant heterozygotes. There was no loss of heterozygosity at the Serca2 locus in the squamous cell carcinomas in any of the four lines. The effect of each mutation on Ca{sup 2+}-ATPase activity was predicted using atomic-structure models and accumulated mutated protein studies, suggesting that putative complete loss of Serca2 enzymatic activity may lead to early tumor onset, whereas mutations in which Serca2 retains residual enzymatic activity result in late onset. We propose that impaired Serca2 gene product activity has a long-term effect on squamous cell carcinogenesis from onset to the final carcinoma stage through an as-yet unrecognized but common regulatory pathway. -- Highlights: •Novel mutations in murine Serca2 caused early onset or late onset of tumorigenesis. •They also caused higher or lower incidence of Darier Disease phenotype. •3D structure model suggested the former mutations led to severer defect on ATPase. •Driver gene mutations via long-range effect on Ca2+ distributions are suggested.

  4. Focused ultrasound in ophthalmology

    Directory of Open Access Journals (Sweden)

    Silverman RH

    2016-09-01

    Full Text Available Ronald H Silverman1,2 1Department of Ophthalmology, Columbia University Medical Center, 2F.L. Lizzi Center for Biomedical Engineering, Riverside Research, New York, NY, USA Abstract: The use of focused ultrasound to obtain diagnostically significant information about the eye goes back to the 1950s. This review describes the historical and technological development of ophthalmic ultrasound and its clinical application and impact. Ultrasound, like light, can be focused, which is crucial for formation of high-resolution, diagnostically useful images. Focused, single-element, mechanically scanned transducers are most common in ophthalmology. Specially designed transducers have been used to generate focused, high-intensity ultrasound that through thermal effects has been used to treat glaucoma (via cilio-destruction, tumors, and other pathologies. Linear and annular transducer arrays offer synthetic focusing in which precise timing of the excitation of independently addressable array elements allows formation of a converging wavefront to create a focus at one or more programmable depths. Most recently, linear array-based plane-wave ultrasound, in which the array emits an unfocused wavefront and focusing is performed solely on received data, has been demonstrated for imaging ocular anatomy and blood flow. While the history of ophthalmic ultrasound extends back over half-a-century, new and powerful technologic advances continue to be made, offering the prospect of novel diagnostic capabilities. Keywords: ophthalmic ultrasound, ultrasound biomicroscopy (UBM, high-intensity focused ultrasound (HIFU, ultrafast imaging, Doppler imaging 

  5. Genomic selection to improve livestock production in developing countries with a focus on India

    DEFF Research Database (Denmark)

    Kadarmideen, Haja; Do, Duy Ngoc

    2015-01-01

    growth will increase the demand for food as well as animal products, particularly in emerging economic giants like India. Moreover, the urbanization has considerable impact on patterns of food consumption in general and on demand for livestock products, in particular and the increased income growth led......Global livestock production has increased substantially during the last decades, in both number of animals and productivity. Meanwhile, the human population is projected to reach 9.6 billions by 2050 and most of the increase in the projection takes place in developing countries. Rapid population...... production (OPU-IVP) of embryos will have a considerable impact in the future. This paper attempts to provide basic concepts of using genomic tools for livestock production with the focus on genomic prediction and selection methods and discuss about the potential application of genomic selection to increase...

  6. DEVELOPMENT OF A WATER SPOUT FOR THE ACTIVE EXTINGUISHING OF THE FOCUS OF AN INTENSE FLAME

    Directory of Open Access Journals (Sweden)

    Stanislav LICHOROBIEC

    2017-12-01

    Full Text Available The topic of the article is devoted to the experimental development of directional charges, which have a front part filled with water and are thus capable of forming a high velocity water jet, which has intense cooling effects and is accompanied by a shock wave created by the explosion of the charge. The water jet can then be used to extinguish the flame from an intense fire epicenter caused, for example, by a gas pipe failure, a tank with flammable liquid or an oil well. The text is accompanied with the visual design of the water spout prototype, including the experimental test of extinguishing the focus of an intense flame caused by various sources.

  7. The Effects of Language- and Literacy-Focused Professional Development on Early Educators and Children

    DEFF Research Database (Denmark)

    Markussen-Brown, Justin; Juhl, Carsten Bogh; Piasta, Shayne B.

    2017-01-01

    Professional development (PD) is increasingly used to improve early childhood educators' skills and lcnowledge in providing quality language and emergent literacy environments for children. However, the literature does not clearly indicate the extent to which such efforts reach their goals......, or whether improvements in educator outcomes translate to learning gains for children. In the current synthesis, we conducted meta-analyses to evaluate the effects of language- and literacy-focused PD on process quality, structural quality, and educator knowledge as primary outcomes. Furthermore, we...... estimated effects for three child outcomes: receptive vocabulary, phonological awareness, and alphabet knowledge. PD produced a medium effect for process quality and a large effect for structural quality but no effect for educator knowledge. PD also produced a small to medium effect for phonological...

  8. Travel industry as a focus on regional development: Case study of the Mediterranean France

    Directory of Open Access Journals (Sweden)

    Terzić Aleksandra

    2015-01-01

    Full Text Available This paper presents a regionalization of the Mediterranean France with regard to tourism, as well as basic economic sectors present in the region. The study included three administrative regions of this part of France: Provence - Alpes - Cote d'Azur, Languedoc - Roussillon and the Island of Corsica, where the travel industry is defined as dominant. The subject of this research is to study the area of the Mediterranean France, primarily from the aspect of tourism. Special attention is focused on the identification of economic and socioeconomic importance that tourism has on the overall economic development of the region, in order to enable the implementation of tourism regionalization. In order to tourism regionalization of this area carried out, it is necessary to include research components, such as geographic environment, tourist motives and attractions that are located in this area, as well as other elements relevant to the separation of the region from the neighboring regions of France.

  9. Development of a work improvement checklist for occupational mental health focused on requests from workers.

    Science.gov (United States)

    Tahara, Hiroyuki; Yamada, Tatsuji; Nagafuchi, Keiko; Shirakawa, Chie; Suzuki, Kiyomi; Mafune, Kosuke; Kubota, Shinya; Hiro, Hisanori; Mishima, Norio; Nagata, Shoji

    2009-01-01

    To develop tools offering definite orientation for managers and employees to support their work improvement through occupational mental health. This research was a part of the Mental Health Improvement & Reinforcement Study (MIR study), conducted from October 2004 to March 2006. We developed a trial version named the Kaizen Check List (KCL) by referring to problem solving methods for quality management. Then we improved it for a formal version named MIR Research of Recognition (MIRROR). A feedback form named MIR Action Guidance (MIRAGe) was also developed. We analyzed data from 1,953 respondents at five manufacturing enterprises in Japan using MIRROR and the Brief Job Stress Questionnaire (BJSQ) to determine whether or not the workers requesting work improvement had more stress than other workers. The KCL had 47 items, which indicated desirable working conditions for mental health at work, and four answer categories. MIRROR has 45 selected items and improved answer categories. MIRAGe displays the results of MIRROR and step-by-step guidance for work improvement. Respondents with request had significantly higher scores in stressor and lower scores in buffer factors compared with respondents without request in many items of MIRROR. A combinational use of MIRROR and stress scales is useful for finding worksites with high risk factors for mental health and for directing focus on work improvement at these worksites according to workers' requests.

  10. Mixed Waste Focus Area alternative oxidation technologies development and demonstration program

    International Nuclear Information System (INIS)

    Borduin, L.C.; Fewell, T.; Gombert, D.; Priebe, S.

    1998-01-01

    The Mixed Waste Focus Area (MWFA) is currently supporting the development and demonstration of several alternative oxidation technology (AOT) processes for treatment of combustible mixed low-level wastes. The impetus for this support derives from regulatory and political hurdles frequently encountered by traditional thermal techniques, primarily incinerators. AOTs have been defined as technologies that destroy organic material without using open-flame reactions. Whether thermal or nonthermal, the processes have the potential advantages of relatively low-volume gaseous emissions, generation of few or no dioxin/furan compounds, and operation at low enough temperatures that metals (except mercury) and most radionuclides are not volatilized. Technology development and demonstration are needed to confirm and realize the potential of AOTs and to compare them on an equal basis with their fully demonstrated thermal counterparts. AOTs include both thermal and nonthermal processes that oxidize organic wastes but operate under significantly different physical and chemical conditions than incinerators. Nonthermal processes currently being studied include Delphi DETOX and acid digestion at the Savannah River Site, and direct chemical oxidation at Lawrence Livermore National Laboratory. All three technologies are at advanced stages of development or are entering the demonstration phase. Nonflame thermal processes include catalytic chemical oxidation, which is being developed and deployed at Lawrence Berkeley National Laboratory, and team reforming, a commercial process being supported by Department of Energy. Related technologies include two low-flow, secondary oxidation processes (Phoenix and Thermatrix units) that have been tested at MSE, Inc., in Butte, Montana. Although testing is complete on some AOT technologies, most require additional support to complete some or all of the identified development objectives. Brief descriptions, status, and planned paths forward for each

  11. Universities in capacity building in sustainable development: focus on solid waste management and technology.

    Science.gov (United States)

    Agamuthu, P; Hansen, Jens Aage

    2007-06-01

    This paper analyses some of the higher education and research capacity building experiences gained from 1998-2006 by Danish and Malaysian universities. The focus is on waste management, directly relating to both the environmental and socio-economic dimensions of sustainable development. Primary benefits, available as an educational legacy to universities, were obtained in terms of new and enhanced study curricula established on Problem-oriented Project-based Learning (POPBL) pedagogy, which strengthened academic environmental programmes at Malaysian and Danish universities. It involved more direct and mutually beneficial cooperation between academia and businesses in both countries. This kind of university reach-out is considered vital to development in all countries actively striving for global and sustainable development. Supplementary benefits were accrued for those involved directly in activities such as the 4 months of field studies, workshops, field courses and joint research projects. For students and academics, the gains have been new international dimensions in university curricula, enhanced career development and research collaboration based on realworld cases. It is suggested that the area of solid waste management offers opportunities for much needed capacity building in higher education and research, contributing to sustainable waste management on a global scale. Universities should be more actively involved in such educational, research and innovation programmes to make the necessary progress. ISWA can support capacity building activities by utilizing its resources--providing a lively platform for debate, securing dissemination of new knowledge, and furthering international networking beyond that which universities already do by themselves. A special challenge to ISWA may be to improve national and international professional networks between academia and business, thereby making education, research and innovation the key driving mechanisms in

  12. Contrast-Enhanced Ultrasonography of Hepatocellular Carcinoma After Chemoembolisation Using Drug-Eluting Beads: A Pilot Study Focused on Sustained Tumor Necrosis

    International Nuclear Information System (INIS)

    Moschouris, Hippocrates; Malagari, Katerina; Papadaki, Marina Georgiou; Kornezos, Ioannis; Matsaidonis, Dimitrios

    2010-01-01

    The purpose of this study was to assess the use of contrast-enhanced ultrasonography (CEUS) and the sustained antitumor effect of drug-eluting beads used for transarterial chemoembolisation (TACE) of unresectable hepatocellular carcinoma (HCC). Ten patients with solitary, unresectable HCC underwent CEUS before, 2 days after, and 35 to 40 days after TACE using a standard dose (4 ml) of drug-eluting beads (DC Beads; Biocompatibles, Surrey, UK) preloaded with doxorubicin (25 mg doxorubicin/ml hydrated beads). For CEUS, a second-generation contrast agent (SonoVue, Bracco, Milan, Italy) and a low mechanical-index technique were used. A part of the tumor was characterized as necrotic if it showed complete lack of enhancement. The percentage of necrosis was calculated at the sonographic section that depicted the largest diameter of the tumor. Differences in the extent of early (2 days after TACE) and delayed (35 to 40 days after TACE) necrosis were quantitatively and subjectively assessed. Early post-TACE tumor necrosis ranged from 21% to 70% (mean 43.5% ± 19%). There was a statistically significant (p = 0.0012, paired Student t test) higher percentage of delayed tumor necrosis, which ranged from 24% to 88% (mean 52.3% ± 20.3%). Subjective evaluation showed a delayed obvious increase of the necrotic areas in 5 patients. In 2 patients, tumor vessels that initially remained patent disappeared on the delayed follow-up. A part of tumor necrosis after chemoembolisation of HCC with DEB seems to take place later than 2 days after TACE. CEUS may provide evidence for the sustained antitumor effect of DEB-TACE. Nevertheless, the ideal time for the imaging evaluation of tumor response remains to be defined.

  13. Development of respiratory motion reduction device system (RMRDs) for radiotherapy in moving tumors

    International Nuclear Information System (INIS)

    Lee, Suk; Yang, Dae-Sik; Choil, Myung-Sun; Kim, Chui-Yong

    2004-01-01

    The internal target volume (ITV) for tumors in the abdomen or thorax includes sufficient margin for breathing-related movement of tumor volumes during treatment. Depending on the location of the tumor, the magnitude of the ITV margin extends from 1 to 3 cm, which increases substantially the volume of the irradiated normal tissue, hence resulting in an increase in normal tissue complication probability (NTCP). We developed a simple and handy method which can reduce ITV margins in patients with moving tumors: the respiratory motion reduction device system (RMRDs). The patient's clinical database was structured for moving tumor patients and patient set-up error measurement and immobilization device effects were investigated. The system is composed of the respiration presser device (RPD) utilized in the prone position and the abdominal strip device (ASD) utilized in the supine position, and the analysis program, which enables analysis of patient set-up reproducibility. It was tested for analyzing the diaphragm movement from patients with RMRDs, the magnitude of the ITV margin was determined and the dose-volume histogram (DVH) was computed using treatment planning software. The dose to normal tissue in patients with and without RMRDs was analyzed by comparing the fraction of the normal liver receiving 50% of the isocenter dose. Average diaphragm movement due to respiration was 16±1.9 mm in the case of the supine position, and 12±1.9 mm in the case of the prone position. When utilizing the RMRDs, which was personally developed in our hospital, the value was reduced to 5±1.4 mm, and in the case in which the belt immobilization device was utilized, the value was reduced to 3±0.9 mm. In the case where the strip device was utilized, the value was proven to reduce to 4±0.3 mm. As a result of analyzing the volume of normal liver where 50% of the prescription dose is irradiated in DVH according to the radiation treatment planning, the use of the RMRD can create a reduction

  14. The Dual Role of Cellular Senescence in Developing Tumors and Their Response to Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Markus Schosserer

    2017-11-01

    Full Text Available Cellular senescence describes an irreversible growth arrest characterized by distinct morphology, gene expression pattern, and secretory phenotype. The final or intermediate stages of senescence can be reached by different genetic mechanisms and in answer to different external and internal stresses. It has been maintained in the literature but never proven by clearcut experiments that the induction of senescence serves the evolutionary purpose of protecting the individual from development and growth of cancers. This hypothesis was recently scrutinized by new experiments and found to be partly true, but part of the gene activities now known to happen in senescence are also needed for cancer growth, leading to the view that senescence is a double-edged sword in cancer development. In current cancer therapy, cellular senescence is, on the one hand, intended to occur in tumor cells, as thereby the therapeutic outcome is improved, but might, on the other hand, also be induced unintentionally in non-tumor cells, causing inflammation, secondary tumors, and cancer relapse. Importantly, organismic aging leads to accumulation of senescent cells in tissues and organs of aged individuals. Senescent cells can occur transiently, e.g., during embryogenesis or during wound healing, with beneficial effects on tissue homeostasis and regeneration or accumulate chronically in tissues, which detrimentally affects the microenvironment by de- or transdifferentiation of senescent cells and their neighboring stromal cells, loss of tissue specific functionality, and induction of the senescence-associated secretory phenotype, an increased secretory profile consisting of pro-inflammatory and tissue remodeling factors. These factors shape their surroundings toward a pro-carcinogenic microenvironment, which fuels the development of aging-associated cancers together with the accumulation of mutations over time. We are presenting an overview of well-documented stress

  15. Development and testing of the improved focusing quadrupole for heavy ion fusion accelerators

    Energy Technology Data Exchange (ETDEWEB)

    Manahan, R R; Martovetsky, N N; Meinke, R B; Chiesa, L; Lietzke, A F; Sabbi, G L; Seidl, P A

    2003-10-23

    An improved version of the focusing magnet for a Heavy Ion Fusion (HIF) accelerator was designed, built and tested in 2002-2003. This quadrupole has higher focusing power and lower error field than the previous version of the focusing quadrupoles successfully built and tested in 2001. We discuss the features of the new design, selected fabrication issues and test results.

  16. Development and evaluation of a radiobromine-labeled sigma ligand for tumor imaging

    International Nuclear Information System (INIS)

    Ogawa, Kazuma; Kanbara, Hiroya; Kiyono, Yasushi; Kitamura, Yoji; Kiwada, Tatsuto; Kozaka, Takashi; Kitamura, Masanori; Mori, Tetsuya; Shiba, Kazuhiro; Odani, Akira

    2013-01-01

    Introduction: Sigma receptors are appropriate targets for tumor imaging because they are highly expressed in a variety of human tumors. Previously, we synthesized a vesamicol analog, (+)-2-[4-(4-iodophenyl)piperidino]cyclohexanol ((+)-pIV), with high affinity for sigma receptors, and prepared radioiodinated (+)-pIV. In this study, to develop a radiobromine-labeled vesamicol analog as a sigma receptor imaging agent for PET, nonradioactive and radiobromine-labeled (+)-2-[4-(4-bromophenyl)piperidino]cyclohexanol ((+)-pBrV) was prepared and evaluated in vitro and in vivo. In these initial studies, 77 Br was used because of its longer half-life. Methods: (+)-[ 77 Br]pBrV was prepared by a bromodestannylation reaction with radiochemical purity of 98.8% after HPLC purification. The partition coefficient of (+)-[ 77 Br]pBrV was measured. In vitro binding characteristics of (+)-pBrV to sigma receptors were assayed. Biodistribution experiments were performed by intravenous administration of a mixed solution of (+)-[ 77 Br]pBrV and (+)-[ 125 I]pIV into DU-145 tumor-bearing mice. Results: The lipophilicity of (+)-[ 77 Br]pBrV was lower than that of (+)-[ 125 I]pIV. As a result of in vitro binding assay to sigma receptors, the affinities of (+)-pBrV to sigma receptors were competitive to those of (+)-pIV. In biodistribution experiments, (+)-[ 77 Br]pBrV and (+)-[ 125 I]pIV showed high uptake in tumor via sigma receptors. The biodistributions of both radiotracers showed similar patterns. However, the accumulation of radioactivity in liver after injection of (+)-[ 77 Br]pBrV was significantly lower compared to that of (+)-[ 125 I]pIV. Conclusion: These results indicate that radiobromine-labeled pBrV possesses great potential as a sigma receptor imaging agent for PET

  17. Development and evaluation of a radiobromine-labeled sigma ligand for tumor imaging.

    Science.gov (United States)

    Ogawa, Kazuma; Kanbara, Hiroya; Kiyono, Yasushi; Kitamura, Yoji; Kiwada, Tatsuto; Kozaka, Takashi; Kitamura, Masanori; Mori, Tetsuya; Shiba, Kazuhiro; Odani, Akira

    2013-05-01

    Sigma receptors are appropriate targets for tumor imaging because they are highly expressed in a variety of human tumors. Previously, we synthesized a vesamicol analog, (+)-2-[4-(4-iodophenyl)piperidino]cyclohexanol ((+)-pIV), with high affinity for sigma receptors, and prepared radioiodinated (+)-pIV. In this study, to develop a radiobromine-labeled vesamicol analog as a sigma receptor imaging agent for PET, nonradioactive and radiobromine-labeled (+)-2-[4-(4-bromophenyl)piperidino]cyclohexanol ((+)-pBrV) was prepared and evaluated in vitro and in vivo. In these initial studies, (77)Br was used because of its longer half-life. (+)-[(77)Br]pBrV was prepared by a bromodestannylation reaction with radiochemical purity of 98.8% after HPLC purification. The partition coefficient of (+)-[(77)Br]pBrV was measured. In vitro binding characteristics of (+)-pBrV to sigma receptors were assayed. Biodistribution experiments were performed by intravenous administration of a mixed solution of (+)-[(77)Br]pBrV and (+)-[(125)I]pIV into DU-145 tumor-bearing mice. The lipophilicity of (+)-[(77)Br]pBrV was lower than that of (+)-[(125)I]pIV. As a result of in vitro binding assay to sigma receptors, the affinities of (+)-pBrV to sigma receptors were competitive to those of (+)-pIV. In biodistribution experiments, (+)-[(77)Br]pBrV and (+)-[(125)I]pIV showed high uptake in tumor via sigma receptors. The biodistributions of both radiotracers showed similar patterns. However, the accumulation of radioactivity in liver after injection of (+)-[(77)Br]pBrV was significantly lower compared to that of (+)-[(125)I]pIV. These results indicate that radiobromine-labeled pBrV possesses great potential as a sigma receptor imaging agent for PET. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. The skill development temporary location with focus professional on the formation of the primary master

    Directory of Open Access Journals (Sweden)

    Carlos Alberto Rojas González

    2018-01-01

    Full Text Available The development of skills as part of the integral formation of the primary teacher is today one of the main challenges in initial formation. In particular, to promote the development of the temporal location skill, it becomes a learning problem at the same time as a professional problem, so that they can understand the past, to understand the present and project the future, with modes of action consistent with social demands. The objective of this paper is to present the results of the study carried out on the current state of this process of development of the temporary location skill with a professional focus in the career Degree in Primary Education, at the University of Pinar del Río. For this, methods such as the historical-logical, the documentary analysis, the interview with teachers, the survey of teachers in training and the observation of classes were used, which allowed to verify the current state of said process in the initial formation of the primary teacher, taking as a methodological basis the dialectical-materialist method. From the systematization carried out it was possible to know that the subject has been little addressed, in the particular context of this professional in the undergraduate. In the historical evolution of the various curricula, the appropriation of the internal structure of this skill on the part of the students has not yet been achieved, which significantly limits the pertinence of the training process, negatively affecting the fact that students appropriate historical content and develop historical reasoning.

  19. Beneficial effects of a woman-focused development programme on child survival: evidence from rural Bangladesh.

    Science.gov (United States)

    Bhuiya, Abbas; Chowdhury, Mushtaque

    2002-11-01

    This paper reports results from a prospective study of the impact of a woman-focused development programme on child survival in Matlab, a rural area of Bangladesh. The programme was targeted to households owning less than 50 decimals of land and members selling more than 100 days of labour for living in a year. Programme components included formation of women's groups for saving and credit, training on skill development, functional literacy including legal and social awareness, and technical and marketing support to projects undertaken with the loan money from the organization. A total of 13,549 children born alive during 1988-97 in the study area were included in the study. Hazards of mortality during pre- and post-intervention periods were compared among the programme participants and non-participants controlling the effects of other relevant variables. There has been a substantial reduction in mortality during the post-intervention period; however, the reduction was much greater for infants whose mothers participated in the development programme compared to infants of non-participant mothers from similar socioeconomic background. In a relative sense, there has been a 52% reduction of the pre-intervention level hazard of death of children during infancy of participant mothers compared to 31% reduction for the infants of non-participant mothers from similar socioeconomic background. There had also been a substantial reduction in hazard of death during childhood (1-4 year age group), however, the reduction was statistically similar for all groups of children irrespective of their mothers' participation in the development programmes.

  20. Development of an optical displacement transducer for CO2 laser auto-focusing

    International Nuclear Information System (INIS)

    Brown, D.P.D.

    1986-01-01

    The PCMWP has partially funded the development of an optical displacement transducer by UKAEA Culham Laboratory (Laser Applications Group). This report covers all work which was done up to the end of the 1984/5 financial year. The purpose of the transducer is to sense automatically the standoff gap between the workpiece and a laser cutting head and subsequently to control an auto-focusing head for the CO 2 laser cutting process. Development of the transducer has reached a stage where it can be mounted on an industrial robot and incorporated into a closed loop servo control system so that standoff gap can be closely controlled whilst traversing variable geometry workpieces. The transducer has been shown to be insensitive to angular displacement of the workpiece (within limits) and to workpiece type or surface finish with the exception of transparent materials. Separate trials have shown it to be unaffected by CO 2 laser light and it has been used, with a motorised laser head, to control standoff whilst the laser cuts a range of contoured materials. The scientific principle of the transducer has thus been proved and a laboratory system has been successfully tested. Its performance has matched the specification with the exception of its ability to sense transparent materials. (author)

  1. Recent developments in sensing methods for eutrophying nutrients with a focus on automation for environmental applications.

    Science.gov (United States)

    Duffy, G; Regan, F

    2017-11-20

    The demand for autonomous sensors for unattended, continuous nutrient monitoring in water is rapidly growing with the increasing need for more frequent and widespread environmental pollution monitoring. Legislative bodies, local authorities and industries all require frequent water quality monitoring, however, this is time and labour intensive, and an expensive undertaking. Autonomous sensors allow for frequent, unattended data collection. While this solves the time and labour intensive aspects of water monitoring, sensors can be very expensive. Development of low-cost sensors is essential to realise the concept of Internet of Things (IoT). However there is much work yet to be done in this field. This article reviews current literature on the research and development efforts towards deployable autonomous sensors for phosphorus (in the form of phosphate) and nitrogen (in the form of nitrate), with a focus on analytical performance and cost considerations. Additionally, some recent sensing approaches that could be automated in the future are included, along with an overview of approaches to monitoring both nutrients. These approaches are compared with standard laboratory methods and also with commercially available sensors for both phosphate and nitrate. Application of nutrient sensors in agriculture is discussed as an example of how sensor networks can provide improvements in decision making.

  2. Development of NMR imaging using CEST agents: application to brain tumor in a rodent model

    International Nuclear Information System (INIS)

    Flament, J.

    2012-01-01

    The study aimed at developing saturation transfer imaging of lipoCEST contrast agents for the detection of angiogenesis in a U87 mouse brain tumor model. A lipoCEST with a sensitivity threshold of 100 pM in vitro was optimized in order to make it compatible with CEST imaging in vivo. Thanks to the development of an experimental setup dedicated to CEST imaging, we evaluated lipoCEST to detect specifically tumor angiogenesis. We demonstrated for the first time that lipoCEST visualization was feasible in vivo in a mouse brain after intravenous injection. Moreover, the integrin α v β 3 over expressed during tumor angiogenesis can be specifically targeted using a functionalized lipoCEST with RGD peptide. The specific association between the RGD-lipoCEST and its target α v β 3 was confirmed by immunohistochemical data and fluorescence microscopy. Finally, in order to tend to a molecular imaging protocol by CEST-MRI, we developed a quantification tool of lipoCEST contrast agents. This tool is based on modeling of proton exchange processes in vivo. By taking into account both B0 and B1 fields inhomogeneities which can dramatically alter CEST contrast, we showed that the accuracy of our quantification tool was 300 pM in vitro. The tool was applied on in vivo data acquired on the U87 mouse model and the maximum concentration of RGD-lipoCEST linked to their molecular targets was evaluated to 1.8 nM. (author) [fr

  3. Brain Tumor Image Segmentation in MRI Image

    Science.gov (United States)

    Peni Agustin Tjahyaningtijas, Hapsari

    2018-04-01

    Brain tumor segmentation plays an important role in medical image processing. Treatment of patients with brain tumors is highly dependent on early detection of these tumors. Early detection of brain tumors will improve the patient’s life chances. Diagnosis of brain tumors by experts usually use a manual segmentation that is difficult and time consuming because of the necessary automatic segmentation. Nowadays automatic segmentation is very populer and can be a solution to the problem of tumor brain segmentation with better performance. The purpose of this paper is to provide a review of MRI-based brain tumor segmentation methods. There are number of existing review papers, focusing on traditional methods for MRI-based brain tumor image segmentation. this paper, we focus on the recent trend of automatic segmentation in this field. First, an introduction to brain tumors and methods for brain tumor segmentation is given. Then, the state-of-the-art algorithms with a focus on recent trend of full automatic segmentaion are discussed. Finally, an assessment of the current state is presented and future developments to standardize MRI-based brain tumor segmentation methods into daily clinical routine are addressed.

  4. Development, fundamentals and objective of half-body irradiation as a method of systematic tumor therapy

    International Nuclear Information System (INIS)

    Eichhorn, H.J.

    1988-01-01

    A review is given on (1) the development of systemic radiotherapy - total body irradiation as well as sequential half-body irradiation in cases of palliative and curative treatment, resp., (2) radiobiological fundamentals of action and limits of the method, (3) clinical results of upper and lower half-body irradiation, resp., as palliative treatment of solid tumors, (4) studies of the prevention of radiation pneumonitis without decreasing radiation dose and (5) proposals for modification, improvement and combination of upper and lower half-body irradiation with other procedures such as hyperthermia and chemotherapy. 48 refs

  5. Myeloid leukemias and virally induced lymphomas in miniature inbred swine; development of a large animal tumor model

    Directory of Open Access Journals (Sweden)

    RAIMON eDURAN-STRUUCK

    2015-11-01

    Full Text Available The lack of a large animal transplantable tumor model has limited the study of novel therapeutic strategies for the treatment of liquid cancers. Swine as a species provide a natural option based on their similarities with humans and their already extensive use in biomedical research. Specifically, the MGH miniature swine herd retains unique genetic characteristics that facilitate the study of hematopoietic cell and solid organ transplantation. Spontaneously arising liquid cancers in these swine, specifically myeloid leukemias and B cell lymphomas, closely resemble human malignancies. The ability to establish aggressive tumor cell lines in vitro from these naturally occurring malignancies makes a transplantable tumor model a close reality. Here, we discuss our experience with myeloid and lymphoid tumors in MHC characterized miniature swine and future approaches regarding the development of a large animal transplantable tumor model.

  6. Imaging study of lymphoreticular tumor development in ataxia-telangiectasia and Nijmegen breakage syndrome

    International Nuclear Information System (INIS)

    Martinez-Leon, M. I.; Ceres-Ruiz, L.; Cuesta, M. A.; Garcia-Martin, F. J.

    2003-01-01

    Ataxia-telangiectasia (AT), or Louis-Bar syndrome, is an autosomal recessive illness characterized by progressive cerebellar ataxia, oculo-cutaneous telangiectasia, immunodeficiency combined with susceptibility to sinopulmonary infections and high incidence of neoplastic development. Nijmegen breakage syndrome (NBS) is a variant of AT, is also an autosomal recessive illness that presents cerebellar ataxia, as well as combined immunodeficiency and a tendency toward tumor development. Contrary to Louis-Bar syndrome, it doesn't present telangiectasia and exhibits a characteristics phenotype (short stature, bird-like face and microcephaly). Both entities are classified as syndrome of chromosomal instability or chromosomal fragility, a group which also includes Bloom syndrome and Fanconi anemia. All of these show an increase in the frequency of neoplastic pathologies, mainly lymphoid tumors. We present three patients,two with AT and one with NBS, who developed different lymphoma types in the course of the illness. We highlight the most outstanding aspects from a clinical-radiological point of view. (Author) 17 refs

  7. Library Assessment and Quality Assurance - Creating a Staff-Driven and User-Focused Development Process

    Directory of Open Access Journals (Sweden)

    Håkan Carlsson

    2016-09-01

    Full Text Available Objective – Gothenburg University Library has implemented a process with the goal to combine quality assurance and strategic planning activities. The process has bottom-up and top-down features designed to generate strong staff-involvement and long-term strategic stability. Methods – In 2008 the library started implementing a system in which each library team should state a number of improvement activities for the upcoming year. In order to focus the efforts, the system has gradually been improved by closely coupling a number of assessment activities, such as surveys and statistics, and connecting the activities to the long-term strategic plan of the library. Results – The activities of the library are now more systematically guided by both library staff and users. The system has resulted in increased understanding within different staff groups of changing external and internal demands, as well as the need for continuous change to library activities. Conclusion – Library assessment and external intelligence are important for tracking and improving library activities. Quality assurance and strategic planning are intricate parts in sustainable development of better and more effective services. The process becomes more effective when staff-driven and built upon systematic knowledge of present activities and users.

  8. Motivation and career-development training programs: Use of regulatory focus to determine program effectiveness

    Directory of Open Access Journals (Sweden)

    Peter John Anthony

    2015-06-01

    Full Text Available The purpose of this study was to focus on the relationship between career-development training programs and the motivation of employees. The study used a qualitative method and a phenomenological design using semistructured interviews conducted with a script of open-ended questions. Two main components of the research design were the modified van Kaam method for exploration of experiences and the purposive selection of the participants. The 20 participants in the sample were project managers and consultants from south-central Texas, all of whom had experience with governmental projects. Based on interview responses, the findings of this study highlighted a concern from the participants that training programs have a major influence on workplace productivity and morale. Furthermore, the findings suggest the training program’s quality may influence workplace productivity. The authors conclude by pointing out the analysis of the answers showed that not only does workplace productivity decline from the changes in a training program, but employee motivation is altered as well. DOI: 10.18870/hlrc.v5i2.214 

  9. The use of focus groups in the development of the PROMIS pediatrics item bank.

    Science.gov (United States)

    Walsh, Tasanee R; Irwin, Debra E; Meier, Andrea; Varni, James W; DeWalt, Darren A

    2008-06-01

    To understand differences in perceptions of patient-reported outcome domains between children with asthma and children from the general population. We used this information in the development of patient-reported outcome items for the Patient-Reported Outcomes Measurement Information System Pediatrics project. We conducted focus groups composed of ethnically, racially, and geographically diverse youth (8-12, 13-17 years) from the general population and youth with asthma. We performed content analysis to identify important themes. We identified five unique and different challenges that may confront youth with asthma as compared to general population youth: (1) They experience more difficulties when participating in physical activities; (2) They may experience anxiety about having an asthma attack at anytime and anywhere; (3) They may experience sleep disturbances and fatigue secondary to their asthma symptoms; (4) Their health condition has a greater effect on their emotional well-being and interpersonal relationships; and (5) Youth with asthma report that asthma often leaves them with insufficient energy to complete their school activities, especially physical activities. The results confirm unique experiences for children with asthma across a broad range of health domains and enhance the breadth of all domains when creating an item bank.

  10. PCMs for Residential Building Applications: A Short Review Focused on Disadvantages and Proposals for Future Development

    Directory of Open Access Journals (Sweden)

    Ashley Bland

    2017-08-01

    Full Text Available Phase change materials (PCMs offer great potential as a latent heat energy storage technique to provide energy efficient systems in new and existing residential buildings. Due to their unique characteristic of high storage densities and latent heat properties, PCMs provide opportunities for greater energy storage in many applications for residential buildings. These applications include, but are not limited to, solar water heating, space heating/cooling, and waste heat recovery. This study reviews PCM systems in residential building applications, with a focus on their major disadvantages and concludes with proposals for future development. Several disadvantages of PCM use in the given application have been identified and include; super cooling, low thermal conductivity, phase segregation, fire safety, and cost. The issues caused by super cooling and phase segregation lead to thermal cycling degradation, limiting the useful lifecycle of the material. These issues could limit their potential in building applications, which require systems of a long lifespan. Low thermal conductivities can slow down the rate at which heat is distributed or absorbed from the building, which affect the occupants comfort and as well as the efficiency of the system. Ideas based on the current research on ways to limit these disadvantages are included in the study. This study also identifies that further research is required on novel maintenance ways for the PCM systems after they have been installed.

  11. Quality of leadership in multidisciplinary cancer tumor boards: development and evaluation of a leadership assessment instrument (ATLAS).

    Science.gov (United States)

    Jalil, Rozh; Soukup, Tayana; Akhter, Waseem; Sevdalis, Nick; Green, James S A

    2018-03-03

    High-quality leadership and chairing skills are vital for good performance in multidisciplinary tumor boards (MTBs), but no instruments currently exist for assessing and improving these skills. To construct and validate a robust instrument for assessment of MTB leading and chairing skills. We developed an observational MTB leadership assessment instrument (ATLAS). ATLAS includes 12 domains that assess the leadership and chairing skills of the MTB chairperson. ATLAS has gone through a rigorous process of refinement and content validation prior to use to assess the MTB lead by two urological surgeons (blinded to each other) in 7 real-live (n = 286 cases) and 10 video-recorded (n = 131 cases) MTBs. ATLAS domains were analyzed via descriptive statistics. Instrument content was evaluated for validity using the content validation index (CVI). Intraclass correlation coefficients (ICCs) were used to assess inter-observer reliability. Instrument refining resulted in ATLAS including the following 12 domains: time management, communication, encouraging contribution, ability to summarize, ensuring all patients have treatment plan, case prioritization, keeping meeting focused, facilitate discussion, conflict management, leadership, creating good working atmosphere, and recruitment for clinical trials. CVI was acceptable and inter-rater agreement adequate to high for all domains. Agreement was somewhat higher in real-time MTBs compared to video ratings. Concurrent validation evidence was derived via positive and significant correlations between ATLAS and an established validated brief MTB leadership assessment scale. ATLAS is an observational assessment instrument that can be reliably used for assessing leadership and chairing skills in cancer MTBs (both live and video-recorded). The ability to assess and feedback on team leader performance provides the ground for promotion of good practice and continuing professional development of tumor board leaders.

  12. Development of [18F]afatinib as new TKI-PET tracer for EGFR positive tumors

    International Nuclear Information System (INIS)

    Slobbe, Paul; Windhorst, Albert D.; Walsum, Marijke Stigter-van; Schuit, Robert C.; Smit, Egbert F.; Niessen, Heiko G.; Solca, Flavio; Stehle, Gerd; Dongen, Guus A.M.S. van; Poot, Alex J.

    2014-01-01

    Introduction: Afatinib is an irreversible ErbB family blocker that was approved for the treatment of EGFR mutated non-small cell lung cancer in 2013. Positron emission tomography (PET) with fluorine-18 labeled afatinib provides a means to obtain improved understanding of afatinib tumor disposition in vivo. PET imaging with [ 18 F]afatinib may also provide a method to select treatment responsive patients. The aim of this study was to label afatinib with fluorine-18 and evaluate its potential as TKI-PET tracer in tumor bearing mice. Methods: A radiochemically novel coupling, using peptide coupling reagent BOP, was explored and optimized to synthesize [ 18 F]afatinib, followed by a metabolite analysis and biodistribution studies in two clinically relevant lung cancer cell lines, xenografted in nude mice. Results: A reliable [ 18 F]afatinib radiosynthesis was developed and the tracer could be produced in yields of 17.0 ± 2.5% calculated from [ 18 F]F − and >98% purity. The identity of the product was confirmed by co-injection on HPLC with non-labeled afatinib. Metabolite analysis revealed a moderate rate of metabolism, with >80% intact tracer in plasma at 45 min p.i. Biodistribution studies revealed rapid tumor accumulation and good retention for a period of at least 2 hours, while background tissues showed rapid clearance of the tracer. Conclusion: We have developed a method to synthesize [ 18 F]afatinib and related fluorine-18 labeled 4-anilinoquinazolines. [ 18 F]Afatinib showed good stability in vivo, justifying further evaluation as a TKI-PET tracer

  13. Locally Appropriate Energy Strategies for the Developing World: A focus on Clean Energy Opportunities in Borneo

    Science.gov (United States)

    Shirley, Rebekah Grace

    This dissertation focuses on an integration of energy modeling tools to explore energy transition pathways for emerging economies. The spate of growth in the global South has led to a global energy transition, evidenced in part by a surge in the development of large scale energy infrastructure projects for the provision of reliable electricity service. The rational of energy security and exigency often usher these large scale projects through to implementation with minimal analysis of costs: social and environmental impact, ecological risk, or opportunity costs of alternative energy transition pathways foregone. Furthermore, development of energy infrastructure is inherently characterized by the involvement of a number of state and non-state actors, with varying interests, objectives and access to authority. Being woven through and into social institutions necessarily impacts the design, control and functionality of infrastructure. In this dissertation I therefore conceptualize energy infrastructure as lying at the intersection, or nexus, of people, the environment and energy security. I argue that energy infrastructure plans and policy should, and can, be informed by each of these fields of influence in order to appropriately satisfy local development needs. This case study explores the socio-techno-environmental context of contemporary mega-dam development in northern Borneo. I describe the key actors of an ongoing mega-dam debate and the constellation of their interaction. This highlights the role that information may play in public discourse and lends insight into how inertia in the established system may stymie technological evolution. I then use a combination of power system simulation, ecological modeling and spatial analysis to analyze the potential for, and costs and tradeoffs of, future energy scenarios. In this way I demonstrate reproducible methods that can support energy infrastructure decision making by directly addressing data limitation barriers. I

  14. Neuroendocrine tumors and smoking

    Directory of Open Access Journals (Sweden)

    Tanja Miličević

    2016-12-01

    Full Text Available Neuroendocrine cells are dispersed around the body and can be found within the gastrointestinal system, lungs, larynx, thymus, thyroid, adrenal, gonads, skin and other tissues. These cells form the so-called ''diffuse neuroendocrine system'' and tumors arising from them are defined as neuroendocrine tumors (NETs. The traditional classification of NETs based on their embryonic origin includes foregut tumors (lung, thymus, stomach, pancreas and duodenum, midgut tumors (beyond the ligament of Treitz of the duodenum to the proximal transverse colon and hindgut tumors (distal colon and rectum. NETs at each site are biologically and clinically distinct from their counterparts at other sites. Symptoms in patients with early disease are often insidious in onset, leading to a delay in diagnosis. The majority of these tumors are thus diagnosed at a stage at which the only curative treatment, radical surgical intervention, is no longer an option. Due to the increasing incidence and mortality, many studies have been conducted in order to identify risk factors for the development of NETs. Still, little is known especially when it comes to preventable risk factors such as smoking. This review will focus on smoking and its contribution to the development of different subtypes of NETs.

  15. Considerations in the development of circulating tumor cell technology for clinical use

    Directory of Open Access Journals (Sweden)

    Parkinson David R

    2012-07-01

    Full Text Available Abstract This manuscript summarizes current thinking on the value and promise of evolving circulating tumor cell (CTC technologies for cancer patient diagnosis, prognosis, and response to therapy, as well as accelerating oncologic drug development. Moving forward requires the application of the classic steps in biomarker development–analytical and clinical validation and clinical qualification for specific contexts of use. To that end, this review describes methods for interactive comparisons of proprietary new technologies, clinical trial designs, a clinical validation qualification strategy, and an approach for effectively carrying out this work through a public-private partnership that includes test developers, drug developers, clinical trialists, the US Food & Drug Administration (FDA and the US National Cancer Institute (NCI.

  16. Development of New Generation of Ceramics for Environmentally Focused Chemical Separations

    Science.gov (United States)

    Ramakrishnan, Girish

    of this thesis focuses on development of a new generation of ceramic membranes utilizing thermal spray techniques to produce highly scalable and extremely cost effective filtration membranes. Thermal spray method of membrane manufacturing has the advantage of economic scalability (up to tens of square meters) along with performance enhancement as compared to conventional wet casting process. In addition to developing a proof of concept for this approach, several strategies on how to improve ceramic membranes' performance via spraying process optimization are also described. Specifically, several thermal sprayed Alumina membrane samples were prepared by varying different process parameters. These samples were characterized using known techniques and subjected to permeability and size exclusion tests to correlate spraying parameters with membranes' performance. The membrane samples showed excellent clean water flux comparable to commercially available membranes and had rejection rates up to 96%. These results show that the membranes produced in this research achieve outstanding performance at a fraction of the cost of commercially produced membrane, enabling the use of membrane filtrations units in developing countries.

  17. Development of Surface-Variable Polymeric Nanoparticles for Drug Delivery to Tumors.

    Science.gov (United States)

    Han, Ning; Pang, Liang; Xu, Jun; Hyun, Hyesun; Park, Jinho; Yeo, Yoon

    2017-05-01

    To develop nanoparticle drug carriers that interact with cells specifically in the mildly acidic tumor microenvironment, we produced polymeric nanoparticles modified with amidated TAT peptide via a simple surface modification method. Two types of core poly(lactic-co-glycolic acid) nanoparticles (NL and NP) were prepared with a phospholipid shell as an optional feature and covered with polydopamine that enabled the conjugation of TAT peptide on the surface. Subsequent treatment with acid anhydrides such as cis-aconitic anhydride (CA) and succinic anhydride (SA) converted amines of lysine residues in TAT peptide to β-carboxylic amides, introducing carboxylic groups that undergo pH-dependent protonation and deprotonation. The nanoparticles modified with amidated TAT peptide (NLpT-CA and NPpT-CA) avoided interactions with LS174T colon cancer cells and J774A.1 macrophages at pH 7.4 but restored the ability to interact with LS174T cells at pH 6.5, delivering paclitaxel efficiently to the cells following a brief contact time. In LS174T tumor-bearing nude mice, NPpT-CA showed less accumulation in the lung than NPpT, reflecting the shielding effect of amidation, but tumor accumulation of NPpT and NPpT-CA was equally minimal. Comparison of particle stability and protein corona formation in media containing sera from different species suggests that NPpT-CA has been activated and opsonized in mouse blood to a greater extent than those in bovine serum-containing medium, thus losing the benefits of pH-sensitivity expected from in vitro experiments.

  18. Engaging the optics community in the development of informative, accessible resources focusing on careers

    Science.gov (United States)

    Poulin-Girard, Anne-Sophie; Gingras, F.; Zambon, V.; Thériault, G.

    2014-09-01

    Young people often have biased and pre-conceived ideas about scientists and engineers that can dissuade them from considering a career in optics. This situation is compounded by the fact that existing resources on careers in optics are not suitable since they mostly focus on more general occupations such as a physicist and an electrical engineer. In addition, the linguistic register is not adapted for students, and many of these resources are only available to guidance counselors. To create appropriate resources that will inform high school students on different career opportunities in optics and photonics, we sought the collaboration of our local optics community. We selected seven specific occupations: entrepreneur in optics, university professor, teacher, technician, research and development engineer, sales representative and graduate student in optics. For each career, a list of daily tasks was created from the existing documentation by a guidance counselor and was validated by an expert working in the field of optics. Following a process of validation, we built surveys in which professionals were asked to select the tasks that best represented their occupation. The surveys were also used to gather other information such as level of education and advice for young people wishing to pursue careers in optics. Over 175 professionals answered the surveys. With these results, we created a leaflet and career cards that are available online and depict the activities of people working in optics and photonics. We hope that these resources will help counter the negative bias against scientific careers and inform teenagers and young adults on making career choices that are better suited to their preferences and aspirations.

  19. Growth and development of children with a special focus on sleep.

    Science.gov (United States)

    Danker-Hopfe, Heidi

    2011-12-01

    The first two decades of life are characterised complex biological processes involving growth and maturation as well as differentiation. The Central Nervous System (CNS) where among others internal and external stimuli are integrated and responses of the body are prepared starts to evolve quite early during ontogenesis. One of the complex behaviours, which are regulated by the brain, is the sleep-wake cycle. The discussion of age-related changes in sleep comprises changes at the physiological level (e.g. changes in the frequency and amplitude of EEG signal, as well as development and distribution of sleep stages), changes in the corresponding behaviour (e.g. changes in the absolute amount of sleep and its distribution in 24h perspective), and finally the subjective perception of sleep and sleep as a measure of well-being. Studies on the impact of a specific factor on sleep during childhood and adolescence have to consider chronological and biological age as well as sex as relevant biological parameters. Even when these factors are controlled for large interindividual differences persist, that is why prospective instead of cross-sectional approaches should be used whenever possible. Furthermore, it has to be distinguished between sleep assessed at the level of brain functioning (i.e. by polysomnography), which gives information on effects at the physiological level and at the level of self-assessment, which focuses on behaviour. Both, sleep at the subjective as well as at the objective level, can to a considerable degree be affected by life style factors, which hence have to be considered as potential confounders. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. A Value Focused Thinking Model for the Development and Selection of Electrical Energy Source Alternatives at Military Installations

    National Research Council Canada - National Science Library

    Schanding, Gregory

    2004-01-01

    .... This thesis presents a Value Focused Thinking approach to the development of a decision analysis model to assist a decision maker at a military installation in the generation and selection of back...

  1. Developments in the treatment of moderate to severe ulcerative colitis: focus on adalimumab

    Directory of Open Access Journals (Sweden)

    Freeman HJ

    2013-11-01

    Full Text Available Hugh J FreemanDepartment of Medicine (Gastroenterology, University of British Columbia, Vancouver, BC, Canada Abstract: In selected patients with moderate to severe active ulcerative colitis who have failed to respond or are poorly responsive to standard pharmacologic forms of treatment with corticosteroids and immunosuppressive agents, therapy with a biological agent may be considered. While infliximab is an established tumor necrosis factor blocker and has a longer history of clinical use, adalimumab is an alternative in the same class and may be employed as an initial biological agent, if indicated for treatment of the disease. Adalimumab may have special appeal to stable users able to self-inject in a home setting rather than a centralized infusion center. Short-term adverse effects have been limited, but long-term adverse events can be serious and remain less well defined. Recently, another agent, subcutaneous golimumab, has also been reported to induce and maintain clinical response and remission in clinical trials, but a large experience has not been accumulated to date in clinical practice. In the future, other biological agents with novel and distinct mechanisms of therapeutic action may become available. Keywords: ulcerative colitis, anti-tumor necrosis factor inhibitors, biological therapy, infliximab, adalimumab

  2. Two cases of acute leukemia developed after therapeutic radiation for malignant tumors

    International Nuclear Information System (INIS)

    Takahashi, Naoki; Matsuo, Kakaru; Yamaguchi, Hiroshi; Tsuno, Sumio; Toyoda, Shigeki

    1978-01-01

    Report was made as to two cases of acute leukemia developed after therapeutic radiation for malignant tumors. Both cases were exposed to atomic-bomb at the places 4 and 3 km far from the center of explosion, and they did not suffer from injuries and acute symptoms due to radiation. Case 1. -A 78 year old man had a mass in a right hypogastric region in April of 1975. In March of 1976, he received laparotomy and was diagnosed as malignant schwannoma. He received radiation therapy with 4,600 R and MFC therapy. In February of 1977, a clinical diagnosis of erythroleukemia was made according to the findings by bone marrow puncture, and he died in March. Postmortem examination revealed that main lesions were malignant schwannoma, its metastases, and leukemia. Case 2. -A 51 year old woman had a finger-tip sized tumor in the left breast in November of 1965, and had a radical operation on the basis of a diagnosis of comedo sarcoma. After that she received 60 Co irradiation with 18,800 R, and she was admitted in December of 1971, because she was suspected of having leukemia. She died in January of 1972. Postmortem examination revealed acute myelocytic leukemia. It is suspected that the onset of erythroleukemia within one year after irradiation would be influenced by MFC therapy in addition to radiotherapy. It was thought that leukemia in Case 2 was influenced by radiotherapy rather than atomic-bomb radioactivity. (Serizawa, K.)

  3. Development of a cell microarray chip for detection of circulating tumor cells

    Science.gov (United States)

    Yamamura, S.; Yatsushiro, S.; Abe, K.; Baba, Y.; Kataoka, M.

    2012-03-01

    Detection of circulating tumor cells (CTCs) in the peripheral blood of metastatic cancer patients has clinical significance in earlier diagnosis of metastases. In this study, a novel cell microarray chip for accurate and rapid detection of tumor cells from human leukocytes was developed. The chip with 20,944 microchambers (105 μm diameter and 50 μm depth) was made from polystyrene, and the surface was rendered to hydrophilic by means of reactive-ion etching, which led to the formation of mono-layers of leukocytes on the microchambers. As the model of CTCs detection, we spiked human bronchioalveolar carcinoma (H1650) cells into human T lymphoblastoid leukemia (CEM) cells suspension and detected H1650 cells using the chip. A CEM suspension contained with H1650 cells was dispersed on the chip surface, followed by 10 min standing to allow the cells to settle down into the microchambers. About 30 CEM cells were accommodated in each microchamber, over 600,000 CEM cells in total being on a chip. We could detect 1 H1650 cell per 106 CEM cells on the microarray by staining with fluorescence-conjugated antibody (Anti-Cytokeratin) and cell membrane marker (DiD). Thus, this cell microarray chip has highly potential to be a novel tool of accurate and rapid detection of CTCs.

  4. Developing high-frequency ultrasound tomography for testicular tumor imaging in rats: An in vitro study

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chih-Chung, E-mail: cchuang@mail.ncku.edu.tw [Department of Biomedical Engineering, National Cheng Kung University, Tainan 701, Taiwan (China); Chen, Wei-Tsen [Department of Electrical Engineering, Fu Jen Catholic University, New Taipei City 24205, Taiwan (China)

    2014-01-15

    Purpose: This paper describes a feasibility study for developing a 35-MHz high-frequency ultrasound computed-tomography (HFUCT) system for imaging rat testicles. Methods: The performances of two kinds of HFUCT-attenuation and sound-speed UCT-based on transmission and pulse-echo modes were investigated in this study. Experiments were carried out using phantoms and actual rat testiclesin vitro. HFUCT images were reconstructed using a filtered backprojection algorithm. Results: The phantom experimental results indicated that all types of HFUCT can determine the dimensions of a plastic cylinder with a diameter of 500μm. Compared to sound-speed HFUCT, attenuation HFUCT exhibited a better performance in recognizing a tiny sclerosed region in a gelatin phantom. Therefore, the in vitro testicular experiments were performed using attenuation HFUCT based on transmission and pulse-echo modes. The experimentally measured attenuation coefficient and sound speed for healthy rat testicles were 2.92 ± 0.25 dB/mm and 1537 ± 25 m/s, respectively. Conclusions: A homogeneous texture was evident for healthy testicles using both modes. An artificial sclerosed tumor could also be clearly observed using two- and three-dimensional attenuation HFUCT in both modes. However, an object artifact was apparent in pulse-echo mode because of ultrasound beam refraction. All of the obtained experimental results indicate the potential of using HFUCT as a novel tool for monitoring the preclinical responses of testicular tumors in small animals.

  5. Developing high-frequency ultrasound tomography for testicular tumor imaging in rats: An in vitro study

    International Nuclear Information System (INIS)

    Huang, Chih-Chung; Chen, Wei-Tsen

    2014-01-01

    Purpose: This paper describes a feasibility study for developing a 35-MHz high-frequency ultrasound computed-tomography (HFUCT) system for imaging rat testicles. Methods: The performances of two kinds of HFUCT-attenuation and sound-speed UCT-based on transmission and pulse-echo modes were investigated in this study. Experiments were carried out using phantoms and actual rat testiclesin vitro. HFUCT images were reconstructed using a filtered backprojection algorithm. Results: The phantom experimental results indicated that all types of HFUCT can determine the dimensions of a plastic cylinder with a diameter of 500μm. Compared to sound-speed HFUCT, attenuation HFUCT exhibited a better performance in recognizing a tiny sclerosed region in a gelatin phantom. Therefore, the in vitro testicular experiments were performed using attenuation HFUCT based on transmission and pulse-echo modes. The experimentally measured attenuation coefficient and sound speed for healthy rat testicles were 2.92 ± 0.25 dB/mm and 1537 ± 25 m/s, respectively. Conclusions: A homogeneous texture was evident for healthy testicles using both modes. An artificial sclerosed tumor could also be clearly observed using two- and three-dimensional attenuation HFUCT in both modes. However, an object artifact was apparent in pulse-echo mode because of ultrasound beam refraction. All of the obtained experimental results indicate the potential of using HFUCT as a novel tool for monitoring the preclinical responses of testicular tumors in small animals

  6. Rational design of an EGF-IL18 fusion protein: Implication for developing tumor therapeutics

    International Nuclear Information System (INIS)

    Lu Jianxin; Peng Ying; Meng Zhefeng; Jin Liqin; Lu Yongsui; Guan Minxin

    2005-01-01

    Interleukin-18 (IL-18) is a proinflammatory cytokine. This protein has a role in regulating immune responses and exhibits significant anti-tumor activities. Epidermal growth factor (EGF) is an important growth factor that plays a central role in the regulation of cell cycle and differentiation. It was proposed that a targeted delivery of IL-18 by generation of IL-18-EGF fusion protein might decrease adverse effects and result in enhancing cytotoxic and antitumor activities. In the present study, a fusion protein, consisting of EGFR binding domain fused to human IL-18 mature peptide via a linker peptide of (Gly 4 Ser) 3, was constructed and expressed in the insect cell line Sf9 using Bac-to-Bac baculovirus expression system. We showed that the purified recombinant fusion protein induced similar levels of IFN-γ to that of native IL-18 protein in human PBMC in the presence of ConA. Furthermore, EGF receptor competitive test in human epithelial cancer A431 cell line showed that EGF-IL18 fusion protein can specifically bind with EGFR by competing with native EGF protein. These suggest that this rationally designed protein can be further developed as novel tumor therapeutics

  7. Cell surface fucosylation does not affect development of colon tumors in mice with germline Smad3 mutation

    Science.gov (United States)

    Domino, Steven E.; Karnak, David M.; Hurd, Elizabeth A.

    2006-01-01

    Background/Aims: Neoplasia-related alterations in cell surface α(1,2)fucosylated glycans have been reported in multiple tumors including colon, pancreas, endometrium, cervix, bladder, lung, and choriocarcinoma. Spontaneous colorectal tumors from mice with a germline null mutation of transforming growth factor-β signaling gene Smad3 (Madh3) were tested for α(1,2)fucosylated glycan expression. Methods: Ulex Europaeus Agglutinin-I lectin staining, fucosyltransferase gene northern blot analysis, and a cross of mutant mice with Fut2 and Smad3 germline mutations were performed. Results: Spontaneous colorectal tumors from Smad3 (-/-) homozygous null mice were found to express α(1,2)fucosylated glycans in an abnormal pattern compared to adjacent nonneoplastic colon. Northern blot analysis of α(1,2)fucosyltransferase genes Fut1 and Fut2 revealed that Fut2, but not Fut1, steady-state mRNA levels were significantly increased in tumors relative to adjacent normal colonic mucosa. Mutant mice with a Fut2-inactivating germline mutation were crossed with Smad3 targeted mice. In Smad3 (-/-)/Fut2 (-/-) double knock-out mice, UEA-I lectin staining was eliminated from colon and colon tumors, however, the number and size of tumors present by 24 weeks of age did not vary regardless of the Fut2 genotype. Conclusions: In this model of colorectal cancer, cell surface α(1,2)fucosylation does not affect development of colon tumors. PMID:17264540

  8. Ovarian germ cell tumors with rhabdomyosarcomatous components and later development of growing teratoma syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Al-Jumaily Usama

    2012-01-01

    Full Text Available Abstract Introduction Development of a sarcomatous component in a germ cell tumor is an uncommon phenomenon. Most cases reported have a grim prognosis. Growing teratoma syndrome is also an uncommon phenomenon and occurs in approximately 2% to 7% of non seminomatous germ cell tumors and should be treated surgically. Case presentation We report the case of a 12-year-old Asian girl with an ovarian mixed germ cell tumor containing a rhabdomyosarcomatous component. She was treated with a germ cell tumor chemotherapy regimen and rhabdomyosarcoma-specific chemotherapy. Towards the end of her treatment, she developed a retroperitoneal mass that was increasing in size. It was completely resected, revealing a mature teratoma, consistent with growing teratoma syndrome. She is still in complete remission approximately three years after presentation. Conclusion The presence of rhabdomyosarcoma in a germ cell tumor should be treated by a combined chemotherapy regimen (for germ cell tumor and rhabdomyosarcoma. In addition, development of a mass during or after therapy with normal serum markers should raise the possibility of growing teratoma syndrome that should be treated surgically.

  9. How to Initiate and Develop the Market of DME - With Focus on Bio-DME?

    Energy Technology Data Exchange (ETDEWEB)

    Baudin, Anders; Nordvall, Hans-Olof (School of Engineering, Linnaeus Univ., Vaexjoe (Sweden))

    2010-01-15

    The theme of this study is how to initiate and develop the market for DME with focus on Bio-DME. In particular, the view considered is that DME can replace diesel and LPG. Initiating and market development for other application is not included here. Regional diesel prices are highly correlated. One can even argue that there seems to be a world market price. Furthermore, they are strongly volatile, which can be traced to the relationship to crude oil. The volatility in diesel - and oil - prices is taken care of in a well developed market for financial instruments (e.g. futures, options). Similar financial risk handling is not yet available for the unit price of DME. A considerable amount of structured information exists in companies, also with consultants and researchers, on how different end-use sectors are expected to react to variation in diesel prices. Knowledge of the end-use sectors' likely reaction to the introduction of DME prices in comparison to diesel prices is generally unknown and is thus only subject to discussion. Obtaining information on this process is, however, the crucial point in the introduction of the market for (bio-)DME. In the short term the introduction phase might be shorter if DME could be mixed with diesel (cf. DME in LPG). This would imply unaltered infrastructure. The advantage of leaving aside adaptation of engines and changing infrastructure would imply that the thresholds for introduction of DME are reduced - the consequence would be that larger production volumes of DME would be obtained quicker. The business risk would also be reduced. But is it possible to mix DME (fossil and bio) with diesel? One standpoint is that this is impossible. Other researchers argue that mix is possible up to 25 per cent - some claim even higher. The problem is that viscosity tends to be too low. Further studies will cast light on this problem. Parallel efforts should be initiated to introduce systems with 100 per cent DME. This requires adaptation

  10. Development of Epitope-Focused Tumor Vaccine to Prevent Escape from Immune Surveillance by the NKG2D Pathway

    Science.gov (United States)

    2017-12-01

    critical issues were discussed during weekly meetings with my mentor and joint monthly meetings with both my mentor and co- mentor . The excellent...researcher in this rapid growing field of cancer research. I also had the opportunity to mentor 3 undergraduate summer students and a master’s student during...Funding Support: None 13 Has there been a change in the active other support of the PD/PI(s) or senior /key personnel since the last reporting

  11. Developing population interventions with migrant women for maternal-child health: a focused ethnography.

    Science.gov (United States)

    Gagnon, Anita J; Carnevale, Franco; Mehta, Praem; Rousseau, Hélène; Stewart, Donna E

    2013-05-14

    Literature describing effective population interventions related to the pregnancy, birth, and post-birth care of international migrants, as defined by them, is scant. Hence, we sought to determine: 1) what processes are used by migrant women to respond to maternal-child health and psychosocial concerns during the early months and years after birth; 2) which of these enhance or impede their resiliency; and 3) which population interventions they suggest best respond to these concerns. Sixteen international migrant women living in Montreal or Toronto who had been identified in a previous study as having a high psychosocial-risk profile and subsequently classified as vulnerable or resilient based on indicators of mental health were recruited. Focused ethnography including in-depth interviews and participant observations were conducted. Data were analyzed thematically and as an integrated whole. Migrant women drew on a wide range of coping strategies and resources to respond to maternal-child health and psychosocial concerns. Resilient and vulnerable mothers differed in their use of certain coping strategies. Social inclusion was identified as an overarching factor for enhancing resiliency by all study participants. Social processes and corresponding facilitators relating to social inclusion were identified by participants, with more social processes identified by the vulnerable group. Several interventions related to services were described which varied in type and quality; these were generally found to be effective. Participants identified several categories of interventions which they had used or would have liked to use and recommended improvements for and creation of some programs. The social determinants of health categories within which their suggestions fell included: income and social status, social support network, education, personal health practices and coping skills, healthy child development, and health services. Within each of these, the most common

  12. New developments in the treatment of osteoarthritis – focus on biologic agents

    Directory of Open Access Journals (Sweden)

    Torrero JI

    2015-07-01

    Full Text Available Jose Ignacio Torrero,1 Carlos Martínez2 1BioTrauma Centre, Escaldes, Principality of Andorra; 2University of Illinois Hospital and Health Sciences System, Chicago, IL, USA Abstract: Osteoarthritis (OA is one of the most common diseases around the world. Medical, social, and financial consequences oblige clinicians, surgeons, and researchers to focus on finding the best treatment option, to eradicate and stop this degenerative joint disease, in order to avoid surgical options which in many instances are over-indicated. Noninvasive treatments, such as anti-inflammatory drugs, physiotherapy, orthotic devices, dietary supplements, have demonstrated lack of effectiveness. The possibility to perform intra-articular injections with hyaluronic acid, corticosteroids, or the newest but criticized treatment based on platelet-rich plasma (PRP has changed the management of OA disease. The use of PRP has led to many differences in treatment since there is a lack of consensus about protocols, indications, number of doses, cost-effectiveness, and duration of the treatment. Many publications have suggested efficacy in tendon injuries, but when PRP has been indicated to treat cartilage injuries, things are more inconsistent. Some authors have reported their experience treating OA with PRP, and it seems that, if well indicated, it is an option as a supplementary therapy. Therefore, we need to understand that OA is a mechanical disease which not only produces changes in radiographs, but also affects the quality of life. Pathogenesis of OA has been well explained, providing us new knowledge and future possibilities to improve the clinical approach. From basic science to surgery, there is a great field we all need to contribute to, because the general population is aging and total joint replacements should not be the only solution for OA. So herein is an actual review of the developments for treating OA with biologics, intended to be useful for the population inside

  13. Role of hormonal factor in development of primary and secondary tumorous process in the brain

    Directory of Open Access Journals (Sweden)

    O. I. Kit

    2016-01-01

    Full Text Available Introduction. Causes of the development onset of primary malignant cerebral neoplasms have not yet been determined. Not excluded is a possibility of unfavorable effect of the environment, genetic abnormalities, changes alterations in the hormonal background as well as metabolism, ionizing radiation: possible is also the role of viral infections and injuries. One of the main most severest complications of malignant tumors remain are metastatic lesions of the central nervous system whose proportion increases as with the patients’ longlivity. Cerebral metastases of malignant tumors are encountered more often than primary neoplasms of the central nervous system. The brain is not only a hormone-dependent organ the effect of sex hormones as early the embryonic state conditions normal development of the body as a whole and controls the sex related differentiation. It is known that neurons and glyocites like gonads and adrenal glands are able to produce steroid hormones. The enzymes responsible for the synthesis of neurosteroids were detected in the brain tissue in the embryonic period of the development. The human brain is not only a hormone-dependent organ effect influence of sex hormones as early as in the embrional state conditiones normal development of the body as a whole and controls sexual gender differentiation. It is known that neurons and glyocytes like gonads and adrenal glands are able to produce steroid hormones. Enzymes responsible for synthesis of neurosteroids were revealed in cerebral tissue both in during the embryonic period of the development and in adult condition. Besides there are have been obtained large amount of data on the presence in the cerebral cells of receptors to steroidal hormones. In various periods of life the influence effect exerted by steroids on nervous cells can change the morphofunctional state of the brain and manifests as altering myelinization, neuronal growth, and differentiation of nerve cells

  14. Pituitary Tumors

    Science.gov (United States)

    ... Association (ABTA) International RadioSurgery Association National Brain Tumor Society National Institute of Child Health and Human Development ... Definition The pituitary is a small, bean-sized gland ...

  15. The Role of Regulatory Focus in Determining Career-Development Training Program Effectiveness

    Science.gov (United States)

    Weide, Jeffrey Lee

    2014-01-01

    American organizations spend over $135 billion annually on training with an unknown return on investment. When budgets decline, leaders typically reduce training, despite the known influence of such training on employee motivation. To explore the perceptions of government-focused project managers regarding the effect of a lack of standardized…

  16. Linking Teacher Evaluation to Professional Development: Focusing on Improving Teaching and Learning. Research & Policy Brief

    Science.gov (United States)

    Goe, Laura; Biggers, Kietha; Croft, Andrew

    2012-01-01

    Recently, teacher evaluation has become a major focus in educational policy debates and research efforts. This increased attention to teacher evaluation has raised questions about the relationship between evaluation and student outcomes. Rivkin, Hanushek, and Kain (2005) and others have demonstrated with value-added research that there are…

  17. Development and optimization of targeted radionuclide tumor therapy using folate based radiopharmaceuticals

    CERN Document Server

    Reber, Josefine Astrid

    The folate receptor (FR) has been used for a quarter of a century as a tumor-associated target for selective delivery of drugs and imaging agents to cancer cells. While several folic acid radioconjugates have been successfully employed for imaging purposes in (pre)clinical studies, a therapeutic application of folic acid radioconjugates has not yet reached the critical stage which would allow a clinical translation. Due to a substantial expression of the FR in the proximal tubule cells, radiofolates accumulate in the kidneys which are at risk of damage by particle-radiation. To improve this situation, we aimed to develop and evaluate strategies for the performance of FR-targeted radionuclide therapy by decreasing the renal uptake of radiofolates and thereby reducing potential nephrotoxic effects. Two different strategies were investigated. First, the combination of radiofolates with chemotherapeutic agents such as pemetrexed (PMX) and 5-fluorouracil (5-FU) and secondly, an approach based on radioiodinated fol...

  18. Late sarcoma development after curettage and bone grafting of benign bone tumors

    International Nuclear Information System (INIS)

    Picci, Piero; Sieberova, Gabriela; Alberghini, Marco; Balladelli, Alba; Vanel, Daniel; Hogendoorn, Pancras C.W.; Mercuri, Mario

    2011-01-01

    Background and aim: Rarely sarcomas develop in previous benign lesions, after a long term disease free interval. We report the experience on these rare cases observed at a single Institution. Patients and methods: 12 cases curetted and grafted, without radiotherapy developed sarcomas, between 1970 and 2005, 6.5-28 years from curettage (median 18, average 19). Age ranged from 13 to 55 years (median 30, average 32) at first diagnosis; tumors were located in the extremities (9 GCT, benign fibrous histiocytoma, ABC, and solitary bone cyst). Radiographic and clinic documentation, for the benign and malignant lesions, were available. Histology was available for 7 benign and all malignant lesions. Results: To fill cavities, autogenous bone was used in 4 cases, allograft in 2, allograft and tricalcium-phosphate/hydroxyapatite in 1, autogenous/allograft in 1, heterogenous in 1. For 3 cases the origin was not reported. Secondary sarcomas, all high grade, were 8 osteosarcoma, 3 malignant fibrous histiocytoma, and 1 fibrosarcoma. Conclusions: Recurrences with progression from benign tumors are possible, but the very long intervals here reported suggest a different cancerogenesis for these sarcomas. This condition is extremely rare accounting for only 0.26% of all malignant bone sarcomas treated in the years 1970-2005 and represents only 8.76% of all secondary bone sarcomas treated in the same years. This incidence is the same as that of sarcomas arising on fibrous dysplasia, and is lower than those arising on bone infarcts or on Paget's disease. This possible event must be considered during follow-up of benign lesions.

  19. Late sarcoma development after curettage and bone grafting of benign bone tumors

    Energy Technology Data Exchange (ETDEWEB)

    Picci, Piero, E-mail: piero.picci@ior.it [Bone Tumor Center, Istituto Ortopedico Rizzoli, Bologna (Italy); Sieberova, Gabriela [Dept. of Pathology, National Cancer Institute, Bratislava (Slovakia); Alberghini, Marco; Balladelli, Alba; Vanel, Daniel [Bone Tumor Center, Istituto Ortopedico Rizzoli, Bologna (Italy); Hogendoorn, Pancras C.W. [Dept. of Pathology, Leiden University Medical Center, Leiden (Netherlands); Mercuri, Mario [Bone Tumor Center, Istituto Ortopedico Rizzoli, Bologna (Italy)

    2011-01-15

    Background and aim: Rarely sarcomas develop in previous benign lesions, after a long term disease free interval. We report the experience on these rare cases observed at a single Institution. Patients and methods: 12 cases curetted and grafted, without radiotherapy developed sarcomas, between 1970 and 2005, 6.5-28 years from curettage (median 18, average 19). Age ranged from 13 to 55 years (median 30, average 32) at first diagnosis; tumors were located in the extremities (9 GCT, benign fibrous histiocytoma, ABC, and solitary bone cyst). Radiographic and clinic documentation, for the benign and malignant lesions, were available. Histology was available for 7 benign and all malignant lesions. Results: To fill cavities, autogenous bone was used in 4 cases, allograft in 2, allograft and tricalcium-phosphate/hydroxyapatite in 1, autogenous/allograft in 1, heterogenous in 1. For 3 cases the origin was not reported. Secondary sarcomas, all high grade, were 8 osteosarcoma, 3 malignant fibrous histiocytoma, and 1 fibrosarcoma. Conclusions: Recurrences with progression from benign tumors are possible, but the very long intervals here reported suggest a different cancerogenesis for these sarcomas. This condition is extremely rare accounting for only 0.26% of all malignant bone sarcomas treated in the years 1970-2005 and represents only 8.76% of all secondary bone sarcomas treated in the same years. This incidence is the same as that of sarcomas arising on fibrous dysplasia, and is lower than those arising on bone infarcts or on Paget's disease. This possible event must be considered during follow-up of benign lesions.

  20. Horses and At-Risk Youth: An Equine Facilitated Learning Program Focusing on Authentic Leadership Skill Development

    Directory of Open Access Journals (Sweden)

    Brittany L. Adams-Pope

    2014-12-01

    Full Text Available Interesting and innovative youth development programs are important to further youth education. Programs focused on developing leadership skills in youth, specifically at-risk youth, are important when thinking of the future of our communities. The primary purpose of the study was to determine the impact of an equine facilitated, authentic leadership program on at-risk youth. Youth participated in a three-day equine facilitated learning program based on authentic leadership with focus groups conducted three days before and three days after the program. In this article, we describe the development and methodology of the program and specific implications for practice.

  1. Osteoprotegerin inhibits bone resorption and prevents tumor development in a xenogenic model of Ewing's sarcoma by inhibiting RANKL

    Science.gov (United States)

    Picarda, Gaëlle; Matous, Etienne; Amiaud, Jérôme; Charrier, Céline; Lamoureux, François; Heymann, Marie-Françoise; Tirode, Franck; Pitard, Bruno; Trichet, Valérie; Heymann, Dominique; Redini, Françoise

    2013-01-01

    Ewing's sarcoma (ES) associated with high osyeolytic lesions typically arises in the bones of children and adolescents. The development of multi-disciplinary therapy has increased current long-term survival rates to greater than 50% but only 20% for high risk group patients (relapse, metastases, etc.). Among new therapeutic approaches, osteoprotegerin (OPG), an anti-bone resorption molecule may represent a promising candidate to inhibit RANKL-mediated osteolytic component of ES and consequently to limit the tumor development. Xenogenic orthotopic models of Ewing's sarcoma were induced by intra-osseous injection of human TC-71 ES cells. OPG was administered in vivo by non-viral gene transfer using an amphiphilic non ionic block copolymer. ES bearing mice were assigned to controls (no treatment, synthetic vector alone or F68/empty pcDNA3.1 plasmid) and hOPG treated groups. A substantial but not significant inhibition of tumor development was observed in the hOPG group as compared to control groups. Marked bone lesions were revealed by micro-computed tomography analyses in control groups whereas a normal bone micro-architecture was preserved in the hOPG treated group. RANKL over-expressed in ES animal model was expressed by tumor cells rather than by host cells. However, TRAIL present in the tumor microenvironment may interfere with OPG effect on tumor development and bone remodeling via RANKL inhibition. In conclusion, the use of a xenogenic model of Ewing's sarcoma allowed discriminating between the tumor and host cells responsible for the elevation of RANKL production observed in this tumor and demonstrated the relevance of blocking RANKL by OPG as a promising therapy in ES. PMID:26909278

  2. The combined status of ATM and p53 link tumor development with therapeutic response

    DEFF Research Database (Denmark)

    Jiang, Hai; Reinhardt, H Christian; Bartkova, Jirina

    2009-01-01

    commonly used by tumors to bypass early neoplastic checkpoints ultimately determine chemotherapeutic response and generate tumor-specific vulnerabilities that can be exploited with targeted therapies. Specifically, evaluation of the combined status of ATM and p53, two commonly mutated tumor suppressor...... genes, can help to predict the clinical response to genotoxic chemotherapies. We show that in p53-deficient settings, suppression of ATM dramatically sensitizes tumors to DNA-damaging chemotherapy, whereas, conversely, in the presence of functional p53, suppression of ATM or its downstream target Chk2...... actually protects tumors from being killed by genotoxic agents. Furthermore, ATM-deficient cancer cells display strong nononcogene addiction to DNA-PKcs for survival after DNA damage, such that suppression of DNA-PKcs in vivo resensitizes inherently chemoresistant ATM-deficient tumors to genotoxic...

  3. Distance Learning as a Tool for Poverty Reduction and Economic Development: A Focus on China and Mexico

    Science.gov (United States)

    Larson, Richard C.; Murray, M. Elizabeth

    2008-01-01

    This paper uses case studies to focus on distance learning in developing countries as an enabler for economic development and poverty reduction. To provide perspective, we first review the history of telecottages, local technology-equipped facilities to foster community-based learning, which have evolved into "telecenters" or…

  4. Development of refractive X-ray focusing optics at Diamond Light Source

    Science.gov (United States)

    Alianelli, L.; Sawhney, K. J. S.; Loader, I. M.; Jenkins, D. W. K.; Stevens, R.; Snigirev, A.; Snigireva, I.

    2007-09-01

    The Diamond Optics & Metrology Group and the collaborators at the STFC Central Microstructure Facility have initiated a program for the design and fabrication of in-line micro- and nano-focusing optics for synchrotron radiation beamlines. The first type of optics fabricated is a kinoform lens in silicon on the same model proposed by K. Evans- Lutterodt et al [Opt. Expr. 11 (2003) 919.]. The fabrication utilised ultra high resolution electron beam lithographic patterning of an electron sensitive SU8 polymer and deep reactive ion etching of silicon. The first test of the focusing properties was performed at the ESRF BM5 optics beamline. In this paper we present details on the design and fabrication, and discuss the test results.

  5. Preliminary study on development of 300 Kv compact focused gaseous ion beam system

    Energy Technology Data Exchange (ETDEWEB)

    Ohkubo, T.; Ishii, Y.; Kamiya, T. [Takasaki Advanced Radiation Research Institute, Japan Atomic Energy Agency (JAEA) 1233 Watanuki-machi, Takasaki, Gunma, 370-1292 (Japan); Miyake, Y. [Beam Seiko Instruments Inc., 2-10-1 Kamata, Ohta-ku, Tokyo, 144-0052 (Japan)

    2013-04-19

    A new 300 kV compact focused gaseous ion beam (gas-FIB) system with three-stage acceleration lens was constructed at JAEA. The preliminary experiments of formation of the focused gaseous ion beams were carried out to show the availability of the gas-FIB system as a writing tool for 3D proton lithography. As a result of the experiments, it was proved that the focal point was kept at the same position under changing the kinetic energy but with keeping the kinetic energy ratio constant, which was defined as the ratio of kinetic energy in object side to that in image side for the third acceleration lens. This characteristic of the gas-FIB is a good point to advance the 3D proton lithography changing penetration depth in a sample by varying the beam energy.

  6. Preliminary study on development of 300 Kv compact focused gaseous ion beam system

    International Nuclear Information System (INIS)

    Ohkubo, T.; Ishii, Y.; Kamiya, T.; Miyake, Y.

    2013-01-01

    A new 300 kV compact focused gaseous ion beam (gas-FIB) system with three-stage acceleration lens was constructed at JAEA. The preliminary experiments of formation of the focused gaseous ion beams were carried out to show the availability of the gas-FIB system as a writing tool for 3D proton lithography. As a result of the experiments, it was proved that the focal point was kept at the same position under changing the kinetic energy but with keeping the kinetic energy ratio constant, which was defined as the ratio of kinetic energy in object side to that in image side for the third acceleration lens. This characteristic of the gas-FIB is a good point to advance the 3D proton lithography changing penetration depth in a sample by varying the beam energy.

  7. Development of 68Ga-Glycopeptide as an Imaging Probe for Tumor Angiogenesis

    Directory of Open Access Journals (Sweden)

    Ning Tsao

    2011-01-01

    Full Text Available Objective. This study was aimed to study tissue distribution and tumor imaging potential of 68Ga-glycopeptide (GP in tumor-bearing rodents by PET. Methods. GP was synthesized by conjugating glutamate peptide and chitosan. GP was labeled with 68Ga chloride for in vitro and in vivo studies. Computer outlined region of interest (counts per pixel of the tumor and muscle (at the symmetric site was used to determine tumor-to-muscle count density ratios. To ascertain the feasibility of 68Ga-GP in tumor imaging in large animals, PET/CT imaging of 68Ga-GP and 18F-FDG were conducted in New Zealand white rabbits bearing VX2 tumors. Standard uptake value of tumors were determined by PET up to 45 min. To determine blood clearance and half-life of 68Ga-GP, blood samples were collected from 10 seconds to 20 min. Results. Radiochemical purity of 68Ga-GP determined by instant thin-layer chromatography was >95%. Tumor uptake values (SUV for 68Ga-GP and 18F-FDG in New Zealand white rabbits bearing VX2 tumors were 3.25 versus 7.04. PET images in tumor-bearing rats and rabbits confirmed that 68Ga-GP could assess tumor uptake. From blood clearance curve, the half-life of 68Ga-GP was 1.84 hr. Conclusion Our data indicate that it is feasible to use 68Ga-GP to assess tumor angiogenesis.

  8. Petroleum activity in ice covered waters - development and operation phase. Focus of eventual consequential explanation

    International Nuclear Information System (INIS)

    Thomassen, J.; Andresen, K.H.; Moe, K.A.

    1996-06-01

    This report from a seminar relates to the petroleum activities in the Barentshavet north. The focal point was to put on petroleum activities in ice covered waters covering the drilling and operation phase, to identify discharges from various technical solutions, and to classify possible research requirements when mapping the impacts of such components. In addition to this approach, the seminar also focused on other factors regarding drilling and production activities in ice covered waters. 3 refs., 13 figs., 25 tabs

  9. Denis Goulet and the project of development ethics : Choices in methodology, focus and organization

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2008-01-01

    textabstractDenis Goulet (1931-2006) was a pioneer of human development theory and the main founder of work on “development ethics” as a self-conscious field that, by his definition, treats the ethical and value questions posed by development theory, planning, and practice. The paper looks at

  10. Denis Goulet and the Project of Development Ethics: Choices in Methodology, Focus and Organization

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2008-01-01

    markdownabstractAbstract: Denis Goulet (1931-2006) was a pioneer of human development theory and a founder of work on ‘development ethics’ as a self-conscious field that treats the ethical and value questions posed by development theory, planning, and practice. The paper looks at aspects of

  11. Adiponectin haploinsufficiency promotes mammary tumor development in MMTV-PyVT mice by modulation of phosphatase and tensin homolog activities.

    Directory of Open Access Journals (Sweden)

    Janice B B Lam

    Full Text Available Adiponectin is an adipokine possessing beneficial effects on obesity-related medical complications. A negative association of adiponectin levels with breast cancer development has been demonstrated. However, the precise role of adiponectin deficiency in mammary carcinogenesis remains elusive.In the present study, MMTV-polyomavirus middle T antigen (MMTV-PyVT transgenic mice with reduced adiponectin expressions were established and the stromal effects of adiponectin haploinsufficiency on mammary tumor development evaluated. In mice from both FVB/N and C57BL/6J backgrounds, insufficient adiponectin production promoted mammary tumor onset and development. A distinctive basal-like subtype of tumors, with a more aggressive phenotype, was derived from adiponectin haplodeficient MMTV-PyVT mice. Comparing with those from control MMTV-PyVT mice, the isolated mammary tumor cells showed enhanced tumor progression in re-implanted nude mice, accelerated proliferation in primary cultures, and hyperactivated phosphatidylinositol-3-kinase (PI3K/Akt/beta-catenin signaling, which at least partly attributed to the decreased phosphatase and tensin homolog (PTEN activities. Further analysis revealed that PTEN was inactivated by a redox-regulated mechanism. Increased association of PTEN-thioredoxin complexes was detected in tumors derived from mice with reduced adiponectin levels. The activities of thioredoxin (Trx1 and thioredoxin reductase (TrxR1 were significantly elevated, whereas treatment with either curcumin, an irreversible inhibitor of TrxR1, or adiponectin largely attenuated their activities and resulted in the re-activation of PTEN in these tumor cells. Moreover, adiponectin could inhibit TrxR1 promoter-mediated transcription and restore the mRNA expressions of TrxR1.Adiponectin haploinsufficiency facilitated mammary tumorigenesis by down-regulation of PTEN activity and activation of PI3K/Akt signalling pathway through a mechanism involving Trx1/TrxR1

  12. Effect of troglitazone on tumor growth and pulmonary metastasis development of the mouse osteosarcoma cell line LM8

    International Nuclear Information System (INIS)

    Aizawa, Junichi; Sakayama, Kenshi; Kamei, Setsuya; Kidani, Teruki; Yamamoto, Haruyasu; Norimatsu, Yoshiaki; Masuno, Hiroshi

    2010-01-01

    Osteosarcoma often develops micrometastases in the lung prior to diagnosis, causing a fatal outcome. Therefore, the prevention of pulmonary metastases is critical for the improvement of the prognosis of patients with osteosarcoma. The purpose of this study was to investigate whether troglitazone (TGZ) is considered as possible therapeutics in the treatment of growth and metastasis of osteosarcoma. LM8 cells were treated for 3 days with various concentrations of TGZ. The effect of TGZ on cell proliferation was determined by DNA measurement in the cultures and 5-bromo-2'-deoxyuridine incorporation study. The assay of cell invasion and motility was performed using either the Matrigel-coated cell culture inserts or the uncoated cell culture inserts in the invasion chambers. The effect of TGZ on Akt signaling was assessed by Western blot analysis of Akt and p-Akt. The effects of oral administration of either TGZ (TGZ group) or ethanol (control group) on the growth of primary tumor and the development of pulmonary metastasis were examined in nude mice implanted with LM8 cells on their backs. The expression and activity of matrix metalloproteinase 2 (MMP-2) within the tumor were determined by immunohistochemistry and zymography. The microvessel density (MVD) within the tumor was determined by immunohistochemistry for CD34. TGZ dose-dependently inhibits cell proliferation. TGZ-treated cells were less invasive and less motile than untreated cells. The activity of MMP-2 secreted by TGZ-treated cells was lower than that secreted by untreated cells. TGZ decreased the level of p-Akt. The primary tumor mass was smaller in the TGZ group than in the control group. The TGZ group had less metastatic tumors in the lung compared with the control group. The expression and activity of MMP-2 within the tumor of the TGZ group were lower than those of the control group. The MVD within the tumor of the TGZ group was lower than that of the control group. Inhibition of Akt signaling by

  13. Effect of troglitazone on tumor growth and pulmonary metastasis development of the mouse osteosarcoma cell line LM8

    Directory of Open Access Journals (Sweden)

    Kidani Teruki

    2010-02-01

    Full Text Available Abstract Background Osteosarcoma often develops micrometastases in the lung prior to diagnosis, causing a fatal outcome. Therefore, the prevention of pulmonary metastases is critical for the improvement of the prognosis of patients with osteosarcoma. The purpose of this study was to investigate whether troglitazone (TGZ is considered as possible therapeutics in the treatment of growth and metastasis of osteosarcoma. Methods LM8 cells were treated for 3 days with various concentrations of TGZ. The effect of TGZ on cell proliferation was determined by DNA measurement in the cultures and 5-bromo-2'-deoxyuridine incorporation study. The assay of cell invasion and motility was performed using either the Matrigel-coated cell culture inserts or the uncoated cell culture inserts in the invasion chambers. The effect of TGZ on Akt signaling was assessed by Western blot analysis of Akt and p-Akt. The effects of oral administration of either TGZ (TGZ group or ethanol (control group on the growth of primary tumor and the development of pulmonary metastasis were examined in nude mice implanted with LM8 cells on their backs. The expression and activity of matrix metalloproteinase 2 (MMP-2 within the tumor were determined by immunohistochemistry and zymography. The microvessel density (MVD within the tumor was determined by immunohistochemistry for CD34. Results TGZ dose-dependently inhibits cell proliferation. TGZ-treated cells were less invasive and less motile than untreated cells. The activity of MMP-2 secreted by TGZ-treated cells was lower than that secreted by untreated cells. TGZ decreased the level of p-Akt. The primary tumor mass was smaller in the TGZ group than in the control group. The TGZ group had less metastatic tumors in the lung compared with the control group. The expression and activity of MMP-2 within the tumor of the TGZ group were lower than those of the control group. The MVD within the tumor of the TGZ group was lower than that of the

  14. A novel mouse model of human prostate cancer to study intraprostatic tumor growth and the development of lymph node metastases.

    Science.gov (United States)

    Linxweiler, Johannes; Körbel, Christina; Müller, Andreas; Hammer, Markus; Veith, Christian; Bohle, Rainer M; Stöckle, Michael; Junker, Kerstin; Menger, Michael D; Saar, Matthias

    2018-06-01

    In this study, we aimed to establish a versatile in vivo model of prostate cancer, which adequately mimics intraprostatic tumor growth, and the natural routes of metastatic spread. In addition, we analyzed the capability of high-resolution ultrasonography (hrUS), in vivo micro-CT (μCT), and 9.4T MRI to monitor tumor growth and the development of lymph node metastases. A total of 5 × 10 5 VCaP cells or 5 × 10 5 cells of LuCaP136- or LuCaP147 spheroids were injected into the prostate of male CB17-SCID mice (n = 8 for each cell type). During 12 weeks of follow-up, orthotopic tumor growth, and metastatic spread were monitored by repetitive serum-PSA measurements and imaging studies including hrUS, μCT, and 9.4T MRI. At autopsy, primary tumors and metastases were harvested and examined by histology and immunohistochemistry (CK5, CK8, AMACR, AR, Ki67, ERG, and PSA). From imaging results and PSA-measurements, tumor volume doubling time, tumor-specific growth rate, and PSA-density were calculated. All 24 mice developed orthotopic tumors. The tumor growth could be reliably monitored by a combination of hrUS, μCT, MRI, and serum-PSA measurements. In most animals, lymph node metastases could be detected after 12 weeks, which could also be well visualized by hrUS, and MRI. Immunohistochemistry showed positive signals for CK8, AMACR, and AR in all xenograft types. CK5 was negative in VCaP- and focally positive in LuCaP136- and LuCaP147-xenografts. ERG was positive in VCaP- and negative in LuCaP136- and LuCaP147-xenografts. Tumor volume doubling times and tumor-specific growth rates were 21.2 days and 3.9 %/day for VCaP-, 27.6 days and 3.1 %/day for LuCaP136- and 16.2 days and 4.5 %/day for LuCaP147-xenografts, respectively. PSA-densities were 433.9 ng/mL per milliliter tumor for VCaP-, 6.5 ng/mL per milliliter tumor for LuCaP136-, and 11.2 ng/mL per milliliter tumor for LuCaP147-xenografts. By using different monolayer and 3D spheroid cell cultures in an

  15. Tumor necrosis factor alpha inhibits in vitro bovine embryo development through a prostaglandin mediated mechanism

    Directory of Open Access Journals (Sweden)

    Jackson Lauren R

    2012-03-01

    Full Text Available Abstract Mastitis or other infectious diseases have been related to reduced fertility in cattle. Inflammatory cytokines such as tumor necrosis factor α (TNFα are released in response to infection and may have negative effects on embryo development. In the current study the effect of exposure to TNFα on the development of in vitro fertilized bovine embryos was examined. Indomethacin, a prostaglandin synthesis inhibitor, was used to determine if blockade of prostaglandin synthesis would alter the effects of TNFα. Ovaries were obtained from a local abattoir and immature COC were isolated from 2-10 mm follicles, in vitro matured and fertilized. After fertilization, groups of presumptive zygotes were randomly placed into either control development medium, medium containing 25 ng/mL TNFα or medium containing 25 ng/mL TNFα plus 1 μg/mL indomethacin. The proportion of blastocysts formed was assessed at day 7 of culture. Fewer embryos exposed to TNFα alone reached the blastocyst stage (17.5 ± 2.4%, P

  16. Development and characterisation of iridium-192 seeds for brachytherapy treatment of ocular tumors

    International Nuclear Information System (INIS)

    Peleias Jr, F.S.; Zeituni, C.A.; Souza, C.D.; Rostelato, M.E.CM.; Mattos, F.R.; Banega, M.A.G.; Rodrigues, B.T.; Tiezzi, R.; Oliveira, T.B.; Feher, A.; Moura, J.A.; Costa, O.L.

    2014-01-01

    Even ocular tumors are not amongst the cases with a high incidence, they affect the population, particularly children. The Institute of Energy and Nuclear Research (IPEN-CNEN/SP) in partnership with Escola Paulista de Medicina (UNIFESP), created a project to develop an alternative treatment for ophthalmic cancer that uses iridium-192 seeds in brachytherapy. This work aims to study and develop a seed of iridium-192 from a platinum-iridium alloy The prototype seed has a 3.0 mm long core sealed by a titanium capsule of 0.8 mm of outer diameter, 0.05 mm of wall thickness and 4.5 mm long. We developed a methodology that covered: characterisation of the material used in the core, creation of a device for neutron activation of the cores and leakage tests. The results show that this methodology is feasible. As a suggestion for future work, studies regarding metrology and dosimetry of these sources should be carried out. (authors)

  17. Development of effective tumor immunotherapy using a novel dendritic cell-targeting Toll-like receptor ligand.

    Directory of Open Access Journals (Sweden)

    Nadeeka H De Silva

    Full Text Available Although dendritic cell (DC-based immunotherapy shows little toxicity, improvements should be necessary to obtain satisfactory clinical outcome. Using interferon-gamma injection along with DCs, we previously obtained significant clinical responses against small or early stage malignant tumors in dogs. However, improvement was necessary to be effective to largely developed or metastatic tumors. To obtain effective methods applicable to those tumors, we herein used a DC-targeting Toll-like receptor ligand, h11c, and examined the therapeutic effects in murine subcutaneous and visceral tumor models and also in the clinical treatment of canine cancers. In murine experiments, most and significant inhibition of tumor growth and extended survival was observed in the group treated with the combination of h11c-activated DCs in combination with interferon-gamma and a cyclooxygenase2 inhibitor. Both monocytic and granulocytic myeloid-derived suppressor cells were significantly reduced by the combined treatment. Following the successful results in mice, the combined treatment was examined against canine cancers, which spontaneously generated like as those in human. The combined treatment elicited significant clinical responses against a nonepithelial malignant tumor and a malignant fibrous histiocytoma. The treatment was also successful against a bone-metastasis of squamous cell carcinoma. In the successful cases, the marked increase of tumor-responding T cells and decrease of myeloid-derived suppressor cells and regulatory T cells was observed in their peripheral blood. Although the combined treatment permitted the growth of lung cancer of renal carcinoma-metastasis, the marked elevated and long-term maintaining of the tumor-responding T cells was observed in the patient dog. Overall, the combined treatment gave rise to emphatic amelioration in DC-based cancer therapy.

  18. Development of a scheffler fixed focus concentrator for the processing of medicinal plants and fruits

    International Nuclear Information System (INIS)

    Munir, A.; Hensel, O.

    2011-01-01

    With the increasing population and industrialization, there is need to cut down the load of fossil fuels and to reduce environmental pollution. A large part of industrial process heat lies from low to medium temperature range which can be supplied by solar energy. Scheffler fixed focus concentrators are successfully used for medium temperature applications in different parts of the world. These concentrators are taken as lateral sections of paraboloids and provide fixed focus away from the path of incident beam radiations throughout the year. The paper presents description and experimental results of medicinal and fruit processing using an 8 m/sup 2/ surface area Scheffler solar concentrator installed at solar campus, university of Kassel, Witzenhausen Germany. The research was focused to promote solar renewable energy in rural and remote locations. The solar system was equipped with Pyranometer and thermocouples to evaluate real time data which was used for performance evaluation of the solar system during processing of different products. In the first phase of the research, several trials were made to evaluate the performance of the system. Within the solar radiations range of 700- 800 W m-2, the receiver temperatures were recorded between 300 - 400 deg. C. The average power was found to be 1.55 kW and system efficiency was found to be 32.34%. Different medicinal plants like Melissa, Peppermint, Rosemary, Cumin, and Cloves buds were successfully processed by using solar energy. Different fruit and vegetables like Apples, Plums, cherries, tomatoes were also processed by using solar energy. Research results have showed that solar energy can be successfully used for the post harvest and fruit processing at rural location. (author)

  19. Development of Focused Ion Beam technique for high speed steel 3D-SEM artefact fabrication

    DEFF Research Database (Denmark)

    Carli, Lorenzo; MacDonald, A. Nicole; De Chiffre, Leonardo

    2009-01-01

    The work describes preliminary manufacture by grinding, followed by machining on a Focused Ion Beam (FIB), of a high speed steel step artefact for 3D-SEM calibration. The FIB is coupled with a SEM in the so called dual beam instrument. The milling capabilities of FIB were checked from a qualitative...... point of view, using the dual beam SEM imaging, and quantitatively using a reference stylus instrument, to establish traceability. A triangular section having a depth of about 10 μm was machined, where the 50 μm curvature radius due to grinding was reduced to about 2 μm by FIB milling...

  20. Cluster analysis of DCE-MRI data identifies regional tracer-kinetic changes after tumor treatment with high intensity focused ultrasound

    NARCIS (Netherlands)

    Jacobs, Igor; Hectors, Stefanie J. C. G.; Schabel, Matthias C.; Grüll, Holger; Strijkers, Gustav J.; Nicolay, Klaas

    2015-01-01

    Evaluation of high intensity focused ultrasound (HIFU) treatment with MRI is generally based on assessment of the non-perfused volume from contrast-enhanced T1-weighted images. However, the vascular status of tissue surrounding the non-perfused volume has not been extensively investigated with MRI.

  1. Development of FOCUS-GC: Framework for Outcomes of Clinical Communication Services in Genetic Counseling.

    Science.gov (United States)

    Cragun, Deborah; Zierhut, Heather

    2018-02-01

    Conceptual frameworks bring together existing theories and models in order to identify, consolidate, and fill in gaps between theory, practice, and evidence. Given the vast number of possible outcomes that could be studied in genetic counseling, a framework for organizing outcomes and postulating relationships between communication services and genetic counseling outcomes was sought. Through an iterative approach involving literature review, thematic analysis, and consolidation, outcomes and processes were categorized to create and define components of a conceptual framework. The final product, "Framework for Outcomes of Clinical commUnication Services" (FOCUS) contains the following domains: communication strategy; communication process measures; patient care experience, patient changes, patient health; and family changes. A website was created to allow easier access and ongoing modifications to the framework. In addition, a step-by-step guide and two examples were created to show flexibility in how the framework can be used. FOCUS may help in conceptualizing, organizing and summarizing outcomes research related to risk communication and counseling in genetic service delivery as well as other healthcare settings.

  2. Developing a Laue Lens for Nuclear Astrophysics: The Challenge of Focusing Soft Gamma-rays

    Science.gov (United States)

    Barriere, Nicolas

    Soft gamma rays provide a unique window on the high-energy Universe, especially for studying nuclear astrophysics through nuclear line emission. However, the sensitivity of state-of-the-art gamma-ray telescopes is severely limited by the intense instrumental background when flown in space. A solution is to decouple the photon collection area from the photon detection area. Focusing source photons from a large collection area onto a small detector volume would dramatically improve the signal-to-noise ratio, and hence provide the long awaited sensitivity leap in this challenging energy band. Laue crystal diffraction can be utilized to focus soft gamma rays when configured in a Laue lens. While this technology has been demonstrated on balloon flights, the type of crystals used and the process of assembling many crystals into a lens have not been optimized yet. We propose to address all the technical aspects of the construction of a scientifically exploitable Laue lens in order to bring this technology to TRL-6. To this end, two small prototypes representative of the diversity of Laue lenses will be built and tested in relevant environments, leveraging the work accomplished under a previous APRA grant. This project will establish the real performances, the cost, and the construction duration of a full-scale lens, allowing us to propose a Laue lens telescope for suborbital or satellite missions.

  3. Development in High-Density Cobra Fiber Positioners for the Subaru Telescope's Prime Focus Spectrometer

    Science.gov (United States)

    Fisher, Charles D.; Braun, David F.; Kaluzny, Joel V.; Seiffert, Mic D.; Dekany, Richard G.; Ellis, Richard S.; Smith, Roger S.

    2012-01-01

    The Prime Focus Spectrograph (PFS) is a fiber fed multi-object spectrometer for the Subaru Telescope that will conduct a variety of targeted surveys for studies of dark energy, galaxy evolution, and galactic archaeology. The key to the instrument is a high density array of fiber positioners placed at the prime focus of the Subaru Telescope. The system, nicknamed "Cobra", will be capable of rapidly reconfiguring the array of 2394 optical fibers to the image positions of astronomical targets in the focal plane with high accuracy. The system uses 2394 individual "SCARA robot" mechanisms that are 7.7mm in diameter and use 2 piezo-electric rotary motors to individually position each of the optical fibers within its patrol region. Testing demonstrates that the Cobra positioner can be moved to within 5 micrometers of an astronomical target in 6 move iterations with a success rate of 95%. The Cobra system is a key aspect of PFS that will enable its unprecedented combination of high-multiplex factor and observing efficiency on the Subaru telescope. The requirements, design, and prototyping efforts for the fiber positioner system for the PFS are described here as are the plans for modular construction, assembly, integration, functional testing, and performance validation.

  4. Endothelial cell marker PAL-E reactivity in brain tumor, developing brain, and brain disease

    NARCIS (Netherlands)

    Leenstra, S.; Troost, D.; Das, P. K.; Claessen, N.; Becker, A. E.; Bosch, D. A.

    1993-01-01

    The endothelial cell marker PAL-E is not reactive to vessels in the normal brain. The present study concerns the PAL-E reactivity in brain tumors in contrast to normal brain and nonneoplastic brain disease. A total of 122 specimens were examined: brain tumors (n = 94), nonneoplastic brain disease (n

  5. Development of oligoclonal nanobodies for targeting the tumor-associated glycoprotein 72 antigen

    DEFF Research Database (Denmark)

    Sharifzadeh, Zahra; Rahbarizadeh, Fatemeh; Shokrgozar, Mohammad Ali

    2013-01-01

    The tumor-associated glycoprotein 72 (TAG-72) is a membrane mucin whose over-expression is correlated with advanced tumor stage and increased invasion and metastasis. In this study, we identified a panel of four nanobodies, single variable domains of dromedary heavy-chain antibodies that specific...

  6. T Cell-Tumor Interaction Directs the Development of Immunotherapies in Head and Neck Cancer

    Directory of Open Access Journals (Sweden)

    A. E. Albers

    2010-01-01

    Full Text Available The competent immune system controls disease effectively due to induction, function, and regulation of effector lymphocytes. Immunosurveillance is exerted mostly by cytotoxic T-lymphocytes (CTLs while specific immune suppression is associated with tumor malignancy and progression. In squamous cell carcinoma of the head and neck, the presence, activity, but also suppression of tumor-specific CTL have been demonstrated. Functional CTL may exert a selection pressure on the tumor cells that consecutively escape by a combination of molecular and cellular evasion mechanisms. Certain of these mechanisms target antitumor effector cells directly or indirectly by affecting cells that regulate CTL function. This results in the dysfunction or apoptosis of lymphocytes and dysregulated lymphocyte homeostasis. Another important tumor-escape mechanism is to avoid recognition by dysregulation of antigen processing and presentation. Thus, both induction of functional CTL and susceptibility of the tumor and its microenvironment to become T cell targets should be considered in CTL-based immunotherapy.

  7. Development of an automated extraction method for liver tumors in three dimensional multiphase multislice CT images

    International Nuclear Information System (INIS)

    Nakagawa, Junya; Shimizu, Akinobu; Kobatake, Hidefumi

    2004-01-01

    This paper proposes a tumor detection method using four phase three dimensional (3D) CT images of livers, i.e. non-contrast, early, portal, and late phase images. The method extracts liver regions from the four phase images and enhances tumors in the livers using a 3D adaptive convergence index filter. Then it detects local maximum points and extracts tumor candidates by a region growing method. Subsequently several features of the candidates are measured and each candidate is classified into true tumor or normal tissue based on Mahalanobis distances. Above processes except liver region extraction are applied to four phase images, independently and four resultant images are integrated into one. We applied the proposed method to 3D abdominal CT images of ten patients obtained with multi-detector row CT scanner and confirmed that tumor detection rate was 100% without false positives, which was quite promising results. (author)

  8. Focus on focusing

    International Nuclear Information System (INIS)

    Anon.

    1985-01-01

    The discovery and impact of the principle of strong focusing was celebrated at a history Symposium at Stanford on 25 July in the course of the 1985 US Summer School on Particle Accelerators. Burt Richter, Stanford Linac Director, who introduced all the speakers with well chosen reminders about their various contributions related to the theme of the symposium, remarked that it was an appropriate time to be lauding the great contributions of accelerator physicists following the Nobel Prize award to Simon van der Meer for outstanding achievements in accelerator physics

  9. Focus on focusing

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1985-10-15

    The discovery and impact of the principle of strong focusing was celebrated at a history Symposium at Stanford on 25 July in the course of the 1985 US Summer School on Particle Accelerators. Burt Richter, Stanford Linac Director, who introduced all the speakers with well chosen reminders about their various contributions related to the theme of the symposium, remarked that it was an appropriate time to be lauding the great contributions of accelerator physicists following the Nobel Prize award to Simon van der Meer for outstanding achievements in accelerator physics.

  10. Search Strategy Development in a Flipped Library Classroom: A Student-Focused Assessment

    Science.gov (United States)

    Goates, Michael C.; Nelson, Gregory M.; Frost, Megan

    2017-01-01

    Librarians at Brigham Young University compared search statement development between traditional lecture and flipped instruction sessions. Students in lecture sessions scored significantly higher on developing search statements than those in flipped sessions. However, student evaluations show a strong preference for pedagogies that incorporate…

  11. Protease-Sensitive Liposomes in Chemotherapy & Chemoradiotherapy: From Material Development to In Vivo Application in Tumor-Bearing Mice

    DEFF Research Database (Denmark)

    Brogaard, Rikke Yding; Melander, Fredrik

    to enhance therapeutic efficacies. In this thesis, the development, characterization, and evaluation of an advanced liposomal DDS and its potential in chemoradiotherapy is presented from material development to in vivo application in tumor*bearing mice. In the first part of the thesis, we report the design...... concept of the liposomal DDS, which leads to rapid cellular uptake. Various lipid compositions are tested in uptake and cytotoxicity experiments in vitro, followed by in vivo experiments where the ability of the liposomal DDS to accumulate in tumors together with its anti*cancer activity is explored...... in tumor*bearing mice. The in vivo data demonstrates superior anti*cancer activity relative to the free drug and to conventional, long circulating liposomes. This indicates that the MMP*sensitive liposomal DDS holds potential in therapeutic applications. In the second part of the thesis, the potential...

  12. The development of fluoroandrogens and fluoroprogestins as potential imaging agents for receptor-positive prostate and breast tumors

    International Nuclear Information System (INIS)

    Brandes, S.J.; Katzenellenbogen, J.A.

    1986-01-01

    The assay of progesterone receptor (PR) concentration in breast tumors and androgen receptor (AR) concentration in prostate tumors enables hormone responsive neoplasms to be distinguished from those that are non-responsive. In principle, a positron-emitting progestin or androgen with suitably high affinity and selectivity for PR and AR, respectively, and an adequately high specific activity might provide a means for imaging receptor-positive tumors and quantifying their receptor content in vivo. The use of fluorine-18 as a radiolabel, coupled with the use of positron emission transaxial tomography, appears to be a most favorable approach in the development of receptor binding radiopharmaceuticals for in vivo imaging. Therefore, we have begun a systematic investigation of the development of fluorine-substituted androgens and progestins that might be prepared in F-18 labeled form as probes for AR and PR. (author)

  13. Development of Coagulation Factor Probes for the Identification of Procoagulant Circulating Tumor Cells

    Energy Technology Data Exchange (ETDEWEB)

    Tormoen, Garth W.; Cianchetti, Flor A. [Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR (United States); Bock, Paul E. [Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN (United States); McCarty, Owen J. T., E-mail: tormoeng@ohsu.edu [Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR (United States); Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, OR (United States); Division of Hematology and Medical Oncology, Department of Medicine, Oregon Health and Science University, Portland, OR (United States)

    2012-09-06

    Metastatic cancer is associated with a hypercoagulable state, and pathological venous thromboembolic disease is a significant source of morbidity and the second leading cause of death in patients with cancer. Here we aimed to develop a novel labeling strategy to detect and quantify procoagulant circulating tumor cells (CTCs) from patients with metastatic cancer. We hypothesize that the enumeration of procoagulant CTCs may be prognostic for the development of venous thrombosis in patients with cancer. Our approach is based on the observation that cancer cells are capable of initiating and facilitating cell-mediated coagulation in vitro, whereby activated coagulation factor complexes assemble upon cancer cell membrane surfaces. Binding of fluorescently labeled, active site-inhibited coagulation factors VIIa, Xa, and IIa to the metastatic breast cancer cell line, MDA-MB-231, non-metastatic colorectal cell line, SW480, or metastatic colorectal cell line, SW620, was characterized in a purified system, in anticoagulated blood and plasma, and in plasma under conditions of coagulation. We conclude that a CTC labeling strategy that utilizes coagulation factor-based fluorescent probes may provide a functional assessment of the procoagulant potential of CTCs, and that this strategy is amenable to current CTC detection platforms.

  14. Self-consistent beam halo studies ampersand halo diagnostic development in a continuous linear focusing channel

    International Nuclear Information System (INIS)

    Jameson, R.A.

    1994-01-01

    Beam halos are formed via self-consistent motion of the beam particles. Interactions of single particles with time-varying density distributions of other particles are a major source of halo. Aspects of these interactions are studied for an initially equilibrium distribution in a radial, linear, continuous focusing system. When there is a mismatch, it is shown that in the self-consistent system, there is a threshold in space-charge and mismatch, above which a halo is formed that extends to ∼1.5 times the initial maximum mismatch radius. Tools are sought for characterizing the halo dynamics. Testing the particles against the width of the mismatch driving resonance is useful for finding a conservative estimate of the threshold. The exit, entering and transition times, and the time evolution of the halo, are also explored using this technique. Extension to higher dimensions is briefly discussed

  15. Treatment of antisocial personality disorder: Development of a practice focused framework.

    Science.gov (United States)

    van den Bosch, L M C; Rijckmans, M J N; Decoene, S; Chapman, A L

    There is little to no evidence of effective treatment methods for patients with an antisocial personality disorder (ASPD). One of the reasons could be the fact that they are often excluded from mental healthcare and thus from studies. A treatment framework based on 'state of the art' methods and best practices, offering guidelines on the treatment of ASP and possibilities for more systematical research, is urgently needed. This research involved a literature search and an international Delphi-study (N = 61 experts in research, management and clinical practice focused on ASPD). The results suggested important preconditions with regard to organization of care, healthcare workers and therapy. Conclusions are that there are many ways to coordinate effective treatment and management and work toward the increased availability of evidence based care for persons with ASPD. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. B Lymphocytes: Development, Tolerance, and Their Role in Autoimmunity—Focus on Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Gabriel J. Tobón

    2013-01-01

    Full Text Available B lymphocytes are the effectors of humoral immunity, providing defense against pathogens through different functions including antibody production. B cells constitute approximately 15% of peripheral blood leukocytes and arise from hemopoietic stem cells in the bone marrow. It is here that their antigen receptors (surface immunoglobulin are assembled. In the context of autoimmune diseases defined by B and/or T cell autoreactive that upon activation lead to chronic tissue inflammation and often irreversible structural and functional damage, B lymphocytes play an essential role by not only producing autoantibodies but also functioning as antigen-presenting cells (APC and as a source of cytokines. In this paper, we describe B lymphocyte functions in autoimmunity and autoimmune diseases with a special focus on their abnormalities in systemic lupus erythematosus.

  17. Regulatory odour model development: Survey of modelling tools and datasets with focus on building effects

    DEFF Research Database (Denmark)

    Olesen, H. R.; Løfstrøm, P.; Berkowicz, R.

    dispersion models for estimating local concentration levels in general. However, the report focuses on some particular issues, which are relevant for subsequent work on odour due to animal production. An issue of primary concern is the effect that buildings (stables) have on flow and dispersion. The handling...... of building effects is a complicated problem, and a major part of the report is devoted to the treatment of building effects in dispersion models......A project within the framework of a larger research programme, Action Plan for the Aquatic Environment III (VMP III) aims towards improving an atmospheric dispersion model (OML). The OML model is used for regulatory applications in Denmark, and it is the candidate model to be used also in future...

  18. [Sustainability focus in the health plans of the autonomous communities: sustainable development as an opportunity].

    Science.gov (United States)

    Moyano-Santiago, Miguel A; Rivera-Lirio, Juana M

    2016-01-01

    To determine the degree to which the health plans of the autonomous communities focus on the usual three dimensions of sustainability: economic, social and environmental, both in the general level of discourse and in the different areas of intervention. A qualitative study was conducted through content analysis of a large sample of documents. The specific methodology was analysis of symbolic and operational sensitivity in a sample of eleven health plans of the Spanish state. Social aspects, such as social determinants or vulnerable groups, are receiving increasing attention from the health planner, although there is room to strengthen attention to environmental issues and to provide specific interventions in economic terms. The analysis demonstrates the incipient state of health plans as strategic planning documents that integrate economic, social and environmental aspects and contribute to the sustainability of the different health systems of the country. Copyright © 2016 SESPAS. Published by Elsevier Espana. All rights reserved.

  19. Targeting oncomiRNAs and mimicking tumor suppressor miRNAs: New trends in the development of miRNA therapeutic strategies in oncology (Review)

    Science.gov (United States)

    GAMBARI, ROBERTO; BROGNARA, ELEONORA; SPANDIDOS, DEMETRIOS A.; FABBRI, ENRICA

    2016-01-01

    MicroRNA (miRNA or miR) therapeutics in cancer are based on targeting or mimicking miRNAs involved in cancer onset, progression, angiogenesis, epithelial-mesenchymal transition and metastasis. Several studies conclusively have demonstrated that miRNAs are deeply involved in tumor onset and progression, either behaving as tumor-promoting miRNAs (oncomiRNAs and metastamiRNAs) or as tumor suppressor miRNAs. This review focuses on the most promising examples potentially leading to the development of anticancer, miRNA-based therapeutic protocols. The inhibition of miRNA activity can be readily achieved by the use of miRNA inhibitors and oligomers, including RNA, DNA and DNA analogues (miRNA antisense therapy), small molecule inhibitors, miRNA sponges or through miRNA masking. On the contrary, the enhancement of miRNA function (miRNA replacement therapy) can be achieved by the use of modified miRNA mimetics, such as plasmid or lentiviral vectors carrying miRNA sequences. Combination strategies have been recently developed based on the observation that i) the combined administration of different antagomiR molecules induces greater antitumor effects and ii) some anti-miR molecules can sensitize drug-resistant tumor cell lines to therapeutic drugs. In this review, we discuss two additional issues: i) the combination of miRNA replacement therapy with drug administration and ii) the combination of antagomiR and miRNA replacement therapy. One of the solid results emerging from different independent studies is that miRNA replacement therapy can enhance the antitumor effects of the antitumor drugs. The second important conclusion of the reviewed studies is that the combination of anti-miRNA and miRNA replacement strategies may lead to excellent results, in terms of antitumor effects. PMID:27175518

  20. Development and Climate Change in Egypt. Focus on Coastal Resources and the Nile

    International Nuclear Information System (INIS)

    Agrawala, S.; Moehner, A.; Gagnon-Lebrun, F.; Van Aalst, M.; Smith, J.; Hagenstad, M.; El Raey, M.; Conway, D.

    2004-01-01

    This document is an output from the OECD Development and Climate Change project, an activity jointly overseen by the EPOC Working Party on Global and Structural Policies (WPGSP), and the DAC Network on Environment and Development Co-operation (ENVIRONET). The overall objective of the project is to provide guidance on how to mainstream responses to climate change within economic development planning and assistance policies, with natural resource management as an overarching theme. This report presents the integrated case study for Tanzania carried out under an OECD project on Development and Climate Change. This report presents the integrated case study for Egypt carried out under an OECD project on Development and Climate Change. The report is structured around a three-tiered framework. First, recent climate trends and climate change scenarios for Egypt are assessed and key sectoral impacts are identified and ranked along multiple indicators to establish priorities for adaptation. Second, donor portfolios are analyzed to examine the proportion of development assistance activities affected by climate risks. A desk analysis of donor strategies and project documents as well as national plans is conducted to assess the degree of attention to climate change concerns in development planning and assistance. Third, an in-depth analysis is conducted for coastal zones as well as water resource management on the Nile

  1. Development and Climate Change in Uruguay. Focus on Coastal Zones, Agriculture and Forestry

    International Nuclear Information System (INIS)

    Agrawala, S.; Moehner, A.; Gagnon-Lebrun, F.; Van Aalst, M.; Smith, J.; Hagenstad, M.; Baethgen, W.E.; Martino, D.L.; Lorenzo, E.

    2004-01-01

    This document is an output from the OECD Development and Climate Change project, an activity jointly overseen by the EPOC Working Party on Global and Structural Policies (WPGSP), and the DAC Network on Environment and Development Co-operation (ENVIRONET). The overall objective of the project is to provide guidance on how to mainstream responses to climate change within economic development planning and assistance policies, with natural resource management as an overarching theme. This report presents the integrated case study for Tanzania carried out under an OECD project on Development and Climate Change. This report presents the integrated case study for Uruguay carried out under an OECD project on Development and Climate Change. The report is structured around a three-tiered framework. First, recent climate trends and climate change scenarios for Uruguay are assessed and key sectoral impacts are identified and ranked along multiple indicators to establish priorities for adaptation. Second, donor portfolios are analyzed to examine the proportion of development assistance activities affected by climate risks. A desk analysis of donor strategies and project documents as well as national plans is conducted to assess the degree of attention to climate change concerns in development planning and assistance. Third, an in-depth analysis is conducted for adaptation in coastal zones as well as for mainstreaming carbonsequestration within the agriculture and forestry sectors

  2. Focused development of advanced practice nurse roles for specific patient groups in a Swiss university hospital

    Science.gov (United States)

    Spichiger, Elisabeth; Zumstein-Shaha, Maya; Schubert, Maria; Herrmann, Luzia

    2018-02-01

    Background: To cover future health care needs of the population, new care models are necessary. The development of advanced nursing practice (ANP) offers the opportunity to meet these challenges with novel services. At the Inselspital, Bern University Hospital, ANP services and corresponding advanced practice nurse (APN) roles have been developed since 2011. Purpose: The aim is to develop innovative and evidence based ANP services to supplement health care for specific patient groups and their family members with the goal to improve safety and achieve better outcomes. Methods: Project-based ANP services are developed in close collaboration of clinical departments and the Nursing Development Unit (NDU) of the Directorate of Nursing. Structure, process and outcome data are collected for evaluation. Findings: Currently, five ANP services are established and running, eight more are in the developmental phase. Most services address the long term care of patients with chronic illnesses and their family members. Ten APNs work between 10 % and 80 %, three are leading an ANP-team. APNs work over 50 % in direct clinical practice, primarily in counselling. An ANP network connects APNs and NDU, promoting synergy and exchange. Conclusions: The available resources often constitute a challenge for the development of ANP services. Vital for the long-term success are an adequate extent of the position, the support by department directorate, the conceptual framework that is implemented across the whole hospital, and the development within project structures.

  3. Development of a center for light ion therapy and accurate tumor diagnostics at karolinska institutet and hospital

    Science.gov (United States)

    Brahme, Anders; Lind, Bengt K.

    2002-04-01

    Radiation therapy is today in a state of very rapid development with new intensity modulated treatment techniques continuously being developed. This has made intensity modulated electron and photon beams almost as powerful as conventional uniform beam proton therapy. To be able to cure also the most advanced hypoxic and radiation resistant tumors of complex local spread, intensity modulated light ion beams are really the ultimate tool and only slightly more expensive than proton therapy. The aim of the new center for ion therapy and tumor diagnostics in Stockholm is to develop radiobiologically optimized 3-dimensional pencil beam scanning techniques. Beside the "classical" approaches using low ionization density hydrogen ions (protons, but also deuterons and tritium nuclei) and high ionization density carbon ions, two new approaches will be developed. In the first one lithium or beryllium ions, that induce the least detrimental biological effect to normal tissues for a given biological effect in a small volume of the tumor, will be key particles. In the second approach, referred patients will be given a high-dose high-precision "boost" treatment with carbon or oxygen ions during one week preceding the final treatment with conventional radiations in the referring hospital. The rationale behind these approaches is to reduce the high ionization density dose to the normal tissue stroma inside the tumor and to ensure a microscopically uniform dose delivery. The principal idea of the center is to closely integrate ion therapy into the clinical routine and research of a large radiotherapy department. The light ion therapy center will therefore be combined with advanced tumor diagnostics including MR and PET-CT imaging to facilitate efficient high-precision high-dose boost treatment of remitted patients. The possibility to do 3D tumor diagnostics and 3D dose delivery verification with the same PET camera will be the ultimate step in high quality adaptive radiation therapy

  4. Pharmaceutical development of investigational anticancer agents: focus on EO-9, AP5346, and GMP implications

    NARCIS (Netherlands)

    Schoot, Sabina Cornelia van der

    2006-01-01

    The development of new anticancer drugs can be divided into six phases: characterization of the API (structural and analytical), solubility- and stability studies, design of the formulation, manufacturing, quality control analysis, and (bio)compatibility studies. Structural and analytical

  5. 78 FR 40485 - Lung Cancer Patient-Focused Drug Development; Extension of Comment Period

    Science.gov (United States)

    2013-07-05

    ... effects of the treatments? (Common side effects could include nausea, loss of appetite fatigue, diarrhea... risks associated with the treatments? (Examples of less common but serious risks are developing a hole...

  6. NIMROD: A Customer Focused, Team Driven Approach for Fusion Code Development

    Science.gov (United States)

    Karandikar, H. M.; Schnack, D. D.

    1996-11-01

    NIMROD is a new code that will be used for the analysis of existing fusion experiments, prediction of operational limits, and design of future devices. An approach called Integrated Product Development (IPD) is being used for the development of NIMROD. It is a dramatic departure from existing practice in the fusion program. Code development is being done by a self-directed, multi-disciplinary, multi-institutional team that consists of experts in plasma theory, experiment, computational physics, and computer science. Customer representatives (ITER, US experiments) are an integral part of the team. The team is using techniques such as Quality Function Deployment (QFD), Pugh Concept Selection, Rapid Prototyping, and Risk Management, during the design phase of NIMROD. Extensive use is made of communication and internet technology to support collaborative work. Our experience with using these team techniques for such a complex software development project will be reported.

  7. A Review of Particulate Matter and Health: Focus on Developing Countries.

    OpenAIRE

    L. Panyacosit

    2000-01-01

    The burden of ill human health attributable to particulate air pollution is a critical problem of growing concern. In developing countries it is not uncommon to experience today the same particulate matter levels that characterized the devastating "London fog episodes" of the 1950s which resulted in over 4000 cases of premature mortality and countless cases of exacerbated morbidity related health endpoints. This literature review gives an overview of the situation in developing countries...

  8. Review and discussion of the development of synthetic aperture focusing technique for ultrasonic testing (SAFT-UT)

    International Nuclear Information System (INIS)

    Busse, L.J.; Collins, H.D.; Doctor, S.R.

    1984-03-01

    The development and capabilities of synthetic aperture focusing techniques for ultrasonic testing (SAFT-UT) are presented. The purpose of SAFT-UT is to produce high-resolution images of the interior of opaque objects. The goal of this work is to develop and implement methods which can be used to detect and to quantify the extent of defects and cracks in critical components of nuclear reactors (pressure vessels, primary piping systems, and nozzles). This report places particular emphasis upon the practical experimental results that have been obtained using SAFT-UT as well as the theoretical background that underlies synthetic aperture focusing. A discussion regarding high-speed and real-time implementations of two- and three-dimensional synthetic aperture focusing is also presented

  9. Development and Climate Change in Bangladesh. Focus on Coastal Flooding and the Sundarbans

    International Nuclear Information System (INIS)

    Agrawala, S.; Ota, Tomoko; Uddin Ahmed, Ahsan; Van Aalst, M.; Smith, J.

    2003-01-01

    This document is an output from the OECD Development and Climate Change project, an activity jointly overseen by the EPOC Working Party on Global and Structural Policies (WPGSP), and the DAC Network on Environment and Development Co-operation (ENVIRONET). The overall objective of the project is to provide guidance on how to mainstream responses to climate change within economic development planning and assistance policies, with natural resource management as an overarching theme. This report presents the integrated case study for Bangladesh carried out under an OECD project on Development and Climate Change. The report is structured around a three-tiered framework. First, recent climate trends and climate change scenarios for Bangladesh are assessed and key sectoral impacts are identified and ranked along multiple indicators to establish priorities for adaptation. Second, donor portfolios in Bangladesh are analyzed to examine the proportion of development assistance activities affected by climate risks. A desk analysis of donor strategies and project documents as well as national plans is conducted to assess the degree of attention to climate change concerns in development planning and assistance. Third, an in-depth analysis is conducted for coastal zones, particularly the coastal mangroves - the Sundarbans - which have been identified as particularly vulnerable to climate change

  10. Tumor-specific CD4+ T cells develop cytotoxic activity and eliminate virus-induced tumor cells in the absence of regulatory T cells.

    Science.gov (United States)

    Akhmetzyanova, Ilseyar; Zelinskyy, Gennadiy; Schimmer, Simone; Brandau, Sven; Altenhoff, Petra; Sparwasser, Tim; Dittmer, Ulf

    2013-02-01

    The important role of tumor-specific cytotoxic CD8(+) T cells is well defined in the immune control of the tumors, but the role of effector CD4(+) T cells is poorly understood. In the current research, we have used a murine retrovirus-induced tumor cell line of C57BL/6 mouse origin, namely FBL-3 cells, as a model to study basic mechanisms of immunological control and escape during tumor formation. This study shows that tumor-specific CD4(+) T cells are able to protect against virus-induced tumor cells. We show here that there is an expansion of tumor-specific CD4(+) T cells producing cytokines and cytotoxic molecule granzyme B (GzmB) in the early phase of tumor growth. Importantly, we demonstrate that in vivo depletion of regulatory T cells (Tregs) and CD8(+) T cells in FBL-3-bearing DEREG transgenic mice augments IL-2 and GzmB production by CD4(+) T cells and increases FV-specific CD4(+) T-cell effector and cytotoxic responses leading to the complete tumor regression. Therefore, the capacity to reject tumor acquired by tumor-reactive CD4(+) T cells largely depends on the direct suppressive activity of Tregs. We suggest that a cytotoxic CD4(+) T-cell immune response may be induced to enhance resistance against oncovirus-associated tumors.

  11. Basic study for development of new tumor specific agents for neutron capture therapy

    International Nuclear Information System (INIS)

    Matsumura, Akira; Nakagawa, Kunio; Yoshii, Yoshihiko; Nose, Tadao

    1994-01-01

    New tissue specific agents for neutron capture therapy was studied. Monoclonal labeled gadolinium-DTPA (Gd-MoAb) and porphyrin (ATN-10)-Gd-DTPA (Gd-ATN10) were studied as possible agents by using 9-L experimental brain tumor model. The tissue concentration were analyzed with magnetic resonance imaging (MRI) and inductively coupled plasma (ICP) analyzer. Gd-MoAb showed persistent retention in the tumor on MRI, but tissue gadolinium concentration was not detectable in the tumor by ICP analyzer, while there was high accumulation of Gd-MoAb in the liver. Gd-ATN10 showed prolonged and high accumulation in the tumor up to 48 hours on MRI. Gadolinium concentration reached up to 9 ppm in the tumor by 0.02 mmol/kg administration, but it disappeared within 6 hours after administration. This dissociation between MRI and ICP analysis was due to separation of ATN-10 and Gd-DTPA. As conclusions, the porphyrin compounds are potential agents for delivering gadolinium or boron specific to the tumor tissue, thus further improvement such as more stable conjugation between porphyrinfic to the tumor tissue, thus further improvement such as more stable conjugation between porphyrin and Gd-DTPA is needed. (author)

  12. Development and Climate Change in Nepal. Focus on Water Resources and Hydropower

    International Nuclear Information System (INIS)

    Agrawala, S.; Raksakulthai, V.; Van Aalst, M.; Larsen, P.; Smith, J.; Reynolds, J.

    2003-01-01

    This document is an output from the OECD Development and Climate Change project, an activity jointly overseen by the EPOC Working Party on Global and Structural Policies (WPGSP), and the DAC Network on Environment and Development Co-operation (ENVIRONET). The overall objective of the project is to provide guidance on how to mainstream responses to climate change within economic development planning and assistance policies, with natural resource management as an overarching theme. This report presents the integrated case study for Nepal carried out under an OECD project on Development and Climate Change. The report is structured around a three-tier framework. First, recent climate trends and climate change scenarios for Nepal are assessed, and key sectoral impacts are identified and ranked along multiple indicators to establish priorities for adaptation. Second, donor portfolios in Nepal are analyzed to examine the proportion of donor activities affected by climate risks. A desk analysis of donor strategies and project documents as well as national plans is conducted to assess the degree of attention to climate change concerns in development planning and assistance. Third, an in-depth analysis is conducted for Nepal's water resources sector which was identified as most vulnerable to climate change. This part of the analysis also involved stakeholder consultation through an in-country workshop to identify key synergies and conflicts between climate change concerns and sectoral projects and plans

  13. Development of the dense plasma focus for short-pulse applications

    Science.gov (United States)

    Bennett, N.; Blasco, M.; Breeding, K.; Constantino, D.; DeYoung, A.; DiPuccio, V.; Friedman, J.; Gall, B.; Gardner, S.; Gatling, J.; Hagen, E. C.; Luttman, A.; Meehan, B. T.; Misch, M.; Molnar, S.; Morgan, G.; O'Brien, R.; Robbins, L.; Rundberg, R.; Sipe, N.; Welch, D. R.; Yuan, V.

    2017-01-01

    The dense plasma focus (DPF) has long been considered a compact source for pulsed neutrons and has traditionally been optimized for the total neutron yield. In this paper, we describe the efforts to optimize the DPF for short-pulse applications by introducing a reentrant cathode at the end of the coaxial plasma gun. The resulting neutron pulse widths are reduced by an average of 21 ±9 % from the traditional long-drift DPF design. Pulse widths and yields achieved from deuterium-tritium fusion at 2 MA are 61.8 ±30.7 ns FWHM and 1.84 ±0.49 ×1012 neutrons per shot. Simulations were conducted concurrently to elucidate the DPF operation and confirm the role of the reentrant cathode. A hybrid fluid-kinetic particle-in-cell modeling capability demonstrates correct sheath velocities, plasma instabilities, and fusion yield rates. Consistent with previous findings that the DPF is dominated by beam-target fusion from superthermal ions, we estimate that the thermonuclear contribution is at the 1% level.

  14. Development of X-ray and ion diagnostic methods for plasma focus research

    International Nuclear Information System (INIS)

    Sadowski, M.

    1986-12-01

    A review of experimental methods used for investigation of X-rays and ion-beams emmited from plasma focus facilities is presented. The research program has been realized at the Institute for Nuclear Studies in Swierk and at the Institut fuer Plasmaforschung in Stuttgart, within the frames of an international co-operation. The studies on ion emission from different PF facilities are reviewed. The application of CN-films with Al-filters and of different ion-pinhole cameras is described. The use of a Thomson mass-spectrometer adopted for plasma studies is presented. The time-resolved measurements combined with a simultaneous mass- and energy-analysis of the ion beams are also described. The most important results of these studies are summarized. Particular attention is also paid to the studies of the X-ray emission. The use of stereoscopic sets of vacuum pinhole cameras with thin Be-filters is described. The application of X-ray pinhole cameras equipped with miniature scintillators for time-resolved measurements is also presented. The most important results of the X-ray emission studies are summarized. 35 refs., 12 figs. (author)

  15. The Development of Curricular Guidelines for Introductory Microbiology that Focus on Understanding

    Directory of Open Access Journals (Sweden)

    Susan Merkel

    2012-02-01

    Full Text Available The number of students who leave majors in science, technology, engineering, and mathematics (STEM due to a perception that courses are poorly taught is evidence that education reform in STEM is overdue. Despite decades of research that argues for student-centered teaching approaches, most introductory STEM courses are still taught in the large lecture format, focusing on rote memorization. While individual efforts in STEM educational reform are important, solutions will most certainly need to include institutional and cultural change. In biology, numerous national reports have called for educational reform to better prepare future scientists. We describe here a new, concept-based curriculum for Introductory Microbiology courses, designed to promote deep understanding of core concepts. Supported by the American Society for Microbiology (ASM and based on the overarching concepts and competencies presented in the AAAS/NSF report Vision and Change in Undergraduate Biology Education: A Call to Action, we hope it will empower instructors to adapt student-centered approaches so that students in Introductory Microbiology courses can leave the course with a core set of enduring understandings of microbiology.

  16. The Development of Curricular Guidelines for Introductory Microbiology that Focus on Understanding.

    Science.gov (United States)

    Merkel, Susan

    2012-01-01

    The number of students who leave majors in science, technology, engineering, and mathematics (STEM) due to a perception that courses are poorly taught is evidence that education reform in STEM is overdue. Despite decades of research that argues for student-centered teaching approaches, most introductory STEM courses are still taught in the large lecture format, focusing on rote memorization. While individual efforts in STEM educational reform are important, solutions will most certainly need to include institutional and cultural change. In biology, numerous national reports have called for educational reform to better prepare future scientists. We describe here a new, concept-based curriculum for Introductory Microbiology courses, designed to promote deep understanding of core concepts. Supported by the American Society for Microbiology (ASM) and based on the overarching concepts and competencies presented in the AAAS/NSF report Vision and Change in Undergraduate Biology Education: A Call to Action, we hope it will empower instructors to adapt student-centered approaches so that students in Introductory Microbiology courses can leave the course with a core set of enduring understandings of microbiology.

  17. Cellullar insights into cerebral cortical development: focusing on the locomotion mode of neuronal migration

    Directory of Open Access Journals (Sweden)

    Takeshi eKawauchi

    2015-10-01

    Full Text Available The mammalian brain consists of numerous compartments that are closely connected with each other via neural networks, comprising the basis of higher order brain functions. The highly specialized structure originates from simple pseudostratified neuroepithelium-derived neural progenitors located near the ventricle. A long journey by neurons from the ventricular side is essential for the formation of a sophisticated brain structure, including a mammalian-specific six-layered cerebral cortex. Neuronal migration consists of several contiguous steps, but the locomotion mode comprises a large part of the migration. The locomoting neurons exhibit unique features; a radial glial fiber-dependent migration requiring the endocytic recycling of N-cadherin and a neuron-specific migration mode with dilation/swelling formation that requires the actin and microtubule organization possibly regulated by cyclin-dependent kinase 5 (Cdk5, Dcx, p27kip1, Rac1 and POSH. Here I will introduce the roles of various cellular events, such as cytoskeletal organization, cell adhesion and membrane trafficking, in the regulation of the neuronal migration, with particular focus on the locomotion mode.

  18. Water in the Solar System: The Development of Science Education Curriculum Focused on Planetary Exploration

    Science.gov (United States)

    Edgar, L. A.; Anderson, R. B.; Gaither, T. A.; Milazzo, M. P.; Vaughan, R. G.; Rubino-Hare, L.; Clark, J.; Ryan, S.

    2017-12-01

    "Water in the Solar System" is an out-of-school time (OST) science education activity for middle school students that was developed as part of the Planetary Learning that Advances the Nexus of Engineering, Technology, and Science (PLANETS) project. The PLANETS project was selected in support of the NASA Science Mission Directorate's Science Education Cooperative Agreement Notice, with the goal of developing and disseminating OST curriculum and related professional development modules that integrate planetary science, technology, and engineering. "Water in the Solar System" is a science activity that addresses the abundance and availability of water in the solar system. The activity consists of three exercises based on the following guiding questions: 1) How much water is there on the Earth? 2) Where can you find water in the solar system? and 3) What properties affect whether or not water can be used by astronauts? The three exercises involve a scaling relationship demonstration about the abundance of useable water on Earth, a card game to explore where water is found in the solar system, and a hands-on exercise to investigate pH and salinity. Through these activities students learn that although there is a lot of water on Earth, most of it is not in a form that is accessible for humans to use. They also learn that most water in the solar system is actually farther from the sun, and that properties such as salinity and pH affect whether water can be used by humans. In addition to content for students, the activity includes background information for educators, and links to in-depth descriptions of the science content. "Water in the Solar System" was developed through collaboration between subject matter experts at the USGS Astrogeology Science Center, and curriculum and professional development experts in the Center for Science Teaching and Learning at Northern Arizona University. Here we describe our process of curriculum development, education objectives of

  19. Catalyzing Gender Equality-Focused Clean Energy Development in West Africa

    Energy Technology Data Exchange (ETDEWEB)

    2016-06-01

    The Economic Community of West African States (ECOWAS) Regional Center for Renewable Energy and Energy Efficiency (ECREEE) partnered with the Clean Energy Solutions Center (Solutions Center), the African Development Bank and other institutions to develop a Situation Analysis of Energy and Gender Issues in ECOWAS Member States. Through a systematic approach to assess interlinked gender and energy issues in the region, the report puts forth a number of key findings. This brochure highlights ECREEE's partnership with the Solutions Center and key findings from the report.

  20. Differences in microRNA expression during tumor development in the transition and peripheral zones of the prostate

    International Nuclear Information System (INIS)

    Carlsson, Jessica; Helenius, Gisela; Karlsson, Mats G; Andrén, Ove; Klinga-Levan, Karin; Olsson, Björn

    2013-01-01

    The prostate is divided into three glandular zones, the peripheral zone (PZ), the transition zone (TZ), and the central zone. Most prostate tumors arise in the peripheral zone (70-75%) and in the transition zone (20-25%) while only 10% arise in the central zone. The aim of this study was to investigate if differences in miRNA expression could be a possible explanation for the difference in propensity of tumors in the zones of the prostate. Patients with prostate cancer were included in the study if they had a tumor with Gleason grade 3 in the PZ, the TZ, or both (n=16). Normal prostate tissue was collected from men undergoing cystoprostatectomy (n=20). The expression of 667 unique miRNAs was investigated using TaqMan low density arrays for miRNAs. Student’s t-test was used in order to identify differentially expressed miRNAs, followed by hierarchical clustering and principal component analysis (PCA) to study the separation of the tissues. The ADtree algorithm was used to identify markers for classification of tissues and a cross-validation procedure was used to test the generality of the identified miRNA-based classifiers. The t-tests revealed that the major differences in miRNA expression are found between normal and malignant tissues. Hierarchical clustering and PCA based on differentially expressed miRNAs between normal and malignant tissues showed perfect separation between samples, while the corresponding analyses based on differentially expressed miRNAs between the two zones showed several misplaced samples. A classification and cross-validation procedure confirmed these results and several potential miRNA markers were identified. The results of this study indicate that the major differences in the transcription program are those arising during tumor development, rather than during normal tissue development. In addition, tumors arising in the TZ have more unique differentially expressed miRNAs compared to the PZ. The results also indicate that separate mi

  1. Germ cell tumors in patients with disorders of sex development: Risk factors, initial developmental stages and targets for early diagnosis

    NARCIS (Netherlands)

    M.B.C.M. Cools (Martine)

    2006-01-01

    textabstractThis thesis describes the origin, identification and correct diagnosis of the earliest stages of malignant germ cell tumors, i.e. intra tubular germ cell neoplasia unclassified (ITGNU) and gonadoblastoma, in patients with disorders of sex development. Special attention is given to the

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  3. Suppression of tumor development and metastasis formation in mice lacking the S100A4(mts1) gene

    DEFF Research Database (Denmark)

    Grum-Schwensen, Birgitte; Klingelhofer, Jörg; Berg, Christian Hededam

    2005-01-01

    distribution of host-derived stroma cells. Coinjection of CSML100 cells with immortalized S100A4(+/+) fibroblasts partially restored the dynamics of tumor development and the ability to form metastasis. These fibroblasts were characterized by an enhanced motility and invasiveness in comparison with S100A4...

  4. Project Excel: A Model for an Individually Focused Staff Development Program.

    Science.gov (United States)

    Minix, Nancy A.; Pearce, Winston Thomas

    A description is given of the development and implementation of an inservice program, "Project Excel," which was designed in accordance with andragogical theory. This theory is based upon four major assumptions: (1) as people grow, they become increasingly self-directed; (2) as people grow, a reservoir of experiences which provide a…

  5. Developing an Undergraduate International Business Program: Context, Rationale, Process and Focus

    Science.gov (United States)

    Bell, Jim; Gray, Brendan; McNaughton, Rod

    2003-01-01

    This paper discusses the recent development of a new undergraduate international business program at the University of Otago in New Zealand. Firstly, it describes the context of the initiative in terms of the New Zealand business environment, the university sector in New Zealand and recent global trends in international business education.…

  6. 78 FR 33851 - Lung Cancer Patient-Focused Drug Development; Public Meeting

    Science.gov (United States)

    2013-06-05

    ... effects could include nausea, loss of appetite fatigue, diarrhea, rash.) 4.3 How do you weigh potential benefits of these treatments versus the less common but serious risks associated with the treatments? (Examples of less common but serious risks are developing a hole in the stomach or intestine, liver failure...

  7. Development and Deployment of a Library of Industrially Focused Advanced Immersive VR Learning Environments

    Science.gov (United States)

    Cameron, Ian; Crosthwaite, Caroline; Norton, Christine; Balliu, Nicoleta; Tadé, Moses; Hoadley, Andrew; Shallcross, David; Barton, Geoff

    2008-01-01

    This work presents a unique education resource for both process engineering students and the industry workforce. The learning environment is based around spherical imagery of real operating plants coupled with interactive embedded activities and content. This Virtual Reality (VR) learning tool has been developed by applying aspects of relevant…

  8. Development and Implementation of Worksite Health and Wellness Programs: A Focus on Non-Communicable Disease.

    Science.gov (United States)

    Cahalin, Lawrence P; Kaminsky, Leonard; Lavie, Carl J; Briggs, Paige; Cahalin, Brendan L; Myers, Jonathan; Forman, Daniel E; Patel, Mahesh J; Pinkstaff, Sherry O; Arena, Ross

    2015-01-01

    The development and implementation of worksite health and wellness programs (WHWPs) in the United States (US) hold promise as a means to improve population health and reverse current trends in non-communicable disease incidence and prevalence. However, WHWPs face organizational, economic, systematic, legal, and logistical challenges which have combined to impact program availability and expansion. Even so, there is a burgeoning body of evidence indicating WHWPs can significantly improve the health profile of participating employees in a cost effective manner. This foundation of scientific knowledge justifies further research inquiry to elucidate optimal WHWP models. It is clear that the development, implementation and operation of WHWPs require a strong commitment from organizational leadership, a pervasive culture of health and availability of necessary resources and infrastructure. Since organizations vary significantly, there is a need to have flexibility in creating a customized, effective health and wellness program. Furthermore, several key legal issues must be addressed to facilitate employer and employee needs and responsibilities; the US Affordable Care Act will play a major role moving forward. The purposes of this review are to: 1) examine currently available health and wellness program models and considerations for the future; 2) highlight key legal issues associated with WHWP development and implementation; and 3) identify challenges and solutions for the development and implementation of as well as adherence to WHWPs. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. The use of focus groups in the development of the KIDSCREEN HRQL questionnaire

    NARCIS (Netherlands)

    Detmar, S.B.; Bruil, J.; Ravens-Sieberer, U.; Gosch, A.; Bisegger, C.

    2006-01-01

    There is increasing interest in the public health sector in the health-related quality of life (HRQL) of healthy children. However, most HRQL instruments are developed for children with a chronic illness. In addition, existing questionnaires are mostly based on expert opinion about what constitutes

  10. Appropriate school starting age: A focus on the cognitive and social development of a child

    Directory of Open Access Journals (Sweden)

    Mahwish Ali Baber

    2016-12-01

    Full Text Available The early years are the most important in the emotional, social, physical and cognitive development of a child.. A child’s early experiences have an immense impact on the development of his/ her physical, emotional and cognitive skills. Therefore, it is very important to understand the kind of environment children need in the early years for their healthy development and also to understand when it is appropriate to begin their schooling in order to optimize their social, cognitive and emotional well-being. It is observed that the number of formal pre-schools have increased drastically in the past few years. Children between the ages of one to five are attending these pre-schools. This paper attempts to look into the various researches conducted to find out how early childhood experiences affect children; how their emotional and cognitive development occurs; and most importantly, whether or not starting school at an age earlier than seven years, benefits their academic achievement in the long run. The findings of the various researches indicate that children in the early years need to spend time in free play rather than in structured and scheduled school environments. This will also help them in their future academic success. Thus, starting school earlier than seven years of age is not beneficial socially or academically in the long run.

  11. The metodical approaches to analysis of sustainable regional development with a focus on agritourism

    Directory of Open Access Journals (Sweden)

    Barbora Kysilková

    2006-01-01

    Full Text Available Economies in rural regions are characterised by a wide range of economic activities and that in 1990 even in the most rural regions of economically developed countries the agricultural sector accounted for less than 20% of regional labour force (OECD. Non-agricultural activities become dominant in rural regions. Among others, rural tourism and agri-tourism belong to the most frequent types of these activities in rural areas. However prerequisites and conditions for sustainable regional development and rural and agri-tourism differ between countries economy with long tradition of market economy and countries with transition economies. There are many factors behind this difference, when intensive character of agricultural production even in less favourite areas, which was typical for these areas in transition economies still a few years ago, is one of decisive.The article addresses the problem of evaluation of sustainable regional development and evaluation of rural and agritourism in the context of various world regions. The three dimensions of sustainable development, the environmental, the economic and the social dimension are equally important and should not be ranked or separated.Indicator systems and evaluation methods have the potential to play a significant role in the decision making process at a regional level. They can form the basic information that is necessary to allow strategic planning as well as informed participatory processes for the decision among different pathways into the future.

  12. Information management in civil engineering infrastructural development : With focus on geological and geotechnical information

    NARCIS (Netherlands)

    Tegtmeier, W.; Zlatanova, S.; Van Oosterom, P.J.M.; Hack, H.R.G.K.

    2009-01-01

    In civil engineering infrastructural projects, information exchange and (re-) use in and between involved parties is difficult. This is mainly caused by a lack of information harmonization. Various specialists are working together on the development of an infrastructural project and are all using

  13. Evaluation of endourological tools to improve the diagnosis and therapy of ureteral tumors – from model development to clinical application

    Directory of Open Access Journals (Sweden)

    Wagner D.

    2015-09-01

    Full Text Available Adequate diagnosis of upper urinary tract (UUT tumors is essential for successful local treatment. Organsparing approaches are technically difficult and require consistent further development. Appropriate models for investigating new diagnostic and therapeutic methods are not yet available. This study demonstrates the incorporation of a fresh sample model into five different test levels (I-V for improving the diagnosis and therapy of ureteral tumors. In these test levels, new diagnostic and ablation techniques are evaluated for feasibility, application safety, efficacy and accuracy. An assessment of their suitability for broad preclinical and clinical application also took economic aspects into account.

  14. Development of a magnetic beam guiding system for tumor-specific radiotherapy using heavy, charged particles

    International Nuclear Information System (INIS)

    Haberer, T.

    1994-06-01

    An active, magnetic beam guiding system was developed and tested for the purpose of enhanced and tumor-specific irradiation of irregularly shaped target volumina. Combining intensity-controlled wobbling in rapidly changing magnetic fields with the heavy-ion synchrotron's capacity of fast energy variation achieved a new technique allowing good range modulation. This technique allows the calculated dose distribution to be exactly matched to target contours, and at the same time guarantees best possible quality of the radiation beam, since there is no need for use of mechanical beam shaping members. The components of the scanning system and a specifically designed instrumentation and control concept for this configuration were integrated into the synchrotron's control system, so that there is now a system available offering free selection of beam characteristics combined with energy variation along with the pulsed operation of the accelerator. The system was tested at the biophysical measuring unit of the GSI implementing an elaborated irradiation method at this unit equipped with tools for physico-technical irradiation planning and performance. Methods were designed and tested for optimizing the beam path within a given contour, the optimization taking into account the effects of transmission functions of the scanner components on the results of radiation treatments. (orig.) [de

  15. Development of radioinmunoconjugate 90Y-DOTA-nimotuzumab-Fab for therapy of EGFR over expressing tumors

    International Nuclear Information System (INIS)

    Rodriguez, A. M.; Alonso, L. M.; Gongora, M.; Leyva, R.; Solana, A.

    2015-01-01

    Many monoclonal antibodies conjugated with 1,4,7,10-tetraaza cyclododecane-N, N', N'', N'''-tetraacetic acid (DOTA) and radiolabeled with 90 Y, have been used for radioimmunotherapy. As know IgG molecules are heavy proteins with a molecular weight of approximately 150 kDa. Accordingly, intact IgG antibodies may have significant slow kinetics biodistribution and severely limited properties of tissue penetration. Antibody fragments labeled with radio metals could be promising radiopharmaceuticals for imaging and non-invasive therapy due to its high affinity to the tumor, the lack of effector function and rapid pharmacokinetic. In this work, the nimotuzumab Fab fragment was obtained by cleavage with papain in molar excess. After separating the reaction mixture in three steps using affinity, size exclusion and ion exchange chromatography; the Fab fragment showed high values of purity, integrity and identity. The Fab fragment was derivatized with DOTA and labeled with 90 Y. The radioimmunoconjugate with high radiochemical yield was assessed by in vitro stability with an excess of 50mM DTPA. The development of 90 Y-DOTA-Nimotuzumab-Fab radioimmunoconjugate allows to count on as a potential agent for radioimmunotherapy. (Author)

  16. New developments in the treatment of hypoactive sexual desire disorder – a focus on Flibanserin

    Directory of Open Access Journals (Sweden)

    Jayne CJ

    2017-04-01

    Full Text Available Christopher J Jayne,1 Michael J Heard,2 Sarah Zubair,3 Dustie L Johnson4 1Greater Houston Urogyn, 2Department of Ob/Gyn, St Joseph Medical Center, The Heard Institute, 3Department of Natural Sciences, The University of Houston – Downtown, Houston, 4Reproductive Solutions Inc., Midland, TX, USA Abstract: The objective of the authors is to highlight the historical complexities for the diagnosis and treatment of hypoactive sexual desire disorder (HSDD with a focus on Flibanserin. A systematic review of the medical literature published in PubMed using the search terms HSDD and Flibanserin was conducted. Each author reviewed the results of the systematic review for articles to include in this study. HSDD is defined as a persistent or recurrent deficiency or absence of sexual fantasies and desire for sexual activity causing marked distress or interpersonal difficulty that is not better accounted for by another diagnosis. Until 2015, only homeopathic products and off-label use of prescription medications were medical treatment options for women with HSDD. Flibanserin, approved by the US Food and Drug Administration (FDA in 2015, is the first to target female HSDD in premenopausal women. Flibanserin is a centrally acting nonhormonal oral medication taken once daily that affects serotonin, dopamine and norepinephrine levels, the key neurotransmitters in the biology of desire. Understanding prescribing guidelines and awareness of black box warnings is paramount for prescribers. Adherence to proper oversight will ensure Flibanserin can fulfil an unmet need for an FDA approved prescription medication for the treatment of HSDD in premenopausal women. Keywords: flibanserin, hypoactive sexual desire, women’s sexual health

  17. Factors Influencing Participation in Continuing Professional Development: A Focus on Motivation Among Pharmacists.

    Science.gov (United States)

    Tjin A Tsoi, Sharon L N M; de Boer, Anthonius; Croiset, Gerda; Koster, Andries S; Kusurkar, Rashmi A

    2016-01-01

    The interest in continuing education (CE) for pharmacists has increased because of patient safety issues, advancing science and the quick changes in the profession. Therefore, contemporary pharmaceutical care requires an effective and sustainable system for pharmacists to maintain and improve competencies. Although motivation plays an important role both as a facilitator (desire to learn) and a barrier (lack of motivation), there is little investigated about this specific factor. The aim of the study was to explore what factors influence pharmacists' participation in CE with a focus on motivation. The theoretical framework was self-determination theory (SDT), which describes autonomous motivation (AM) representing motivation from an internal locus of causality, controlled motivation (CM) originating from an external locus of causality, and relative autonomous motivation (RAM) that measures the AM in an individual after correcting for the CM. The relationship between pharmacists' characteristics, especially their motivation (AM, CM and RAM) in CE, and their participation in CE activities was explored using the AMS-questionnaire and the Dutch online portfolio system. RAM was positively correlated with CE participation of pharmacists and explained 7.8% of the variance. The correlations between the independent variables AM and CM and CE hours were negative (-0.301 and -0.476, respectively). Other factors influencing CE participation were pharmacy school (6.8%), traineeship (10.9%), and work experience (7.8%). Pharmacists participated for 27.0 hours on average in CE during 11 months and preferred face-to-face-learning (85.5%) above e-learning (13.8%). Our findings show a positive relationship between RAM and CE participation. The current CE system is probably not conducive to stimulation of AM. Further research is needed to understand the factors that stimulate pharmacists' motivation and participation in CE.

  18. Central focused convolutional neural networks: Developing a data-driven model for lung nodule segmentation.

    Science.gov (United States)

    Wang, Shuo; Zhou, Mu; Liu, Zaiyi; Liu, Zhenyu; Gu, Dongsheng; Zang, Yali; Dong, Di; Gevaert, Olivier; Tian, Jie

    2017-08-01

    Accurate lung nodule segmentation from computed tomography (CT) images is of great importance for image-driven lung cancer analysis. However, the heterogeneity of lung nodules and the presence of similar visual characteristics between nodules and their surroundings make it difficult for robust nodule segmentation. In this study, we propose a data-driven model, termed the Central Focused Convolutional Neural Networks (CF-CNN), to segment lung nodules from heterogeneous CT images. Our approach combines two key insights: 1) the proposed model captures a diverse set of nodule-sensitive features from both 3-D and 2-D CT images simultaneously; 2) when classifying an image voxel, the effects of its neighbor voxels can vary according to their spatial locations. We describe this phenomenon by proposing a novel central pooling layer retaining much information on voxel patch center, followed by a multi-scale patch learning strategy. Moreover, we design a weighted sampling to facilitate the model training, where training samples are selected according to their degree of segmentation difficulty. The proposed method has been extensively evaluated on the public LIDC dataset including 893 nodules and an independent dataset with 74 nodules from Guangdong General Hospital (GDGH). We showed that CF-CNN achieved superior segmentation performance with average dice scores of 82.15% and 80.02% for the two datasets respectively. Moreover, we compared our results with the inter-radiologists consistency on LIDC dataset, showing a difference in average dice score of only 1.98%. Copyright © 2017. Published by Elsevier B.V.

  19. Giant Subependymoma Developed in a Patient with Aniridia: Analyses of PAX6 and Tumor-relevant Genes

    Science.gov (United States)

    Maekawa, Motoko; Fujisawa, Hironori; Iwayama, Yoshimi; Tamase, Akira; Toyota, Tomoko; Osumi, Noriko; Yoshikawa, Takeo

    2010-01-01

    We observed an unusually large subependymoma in a female patient with congenital aniridia. To analyze the genetic mechanisms of tumorigenesis, we first examined the paired box 6 (PAX6) gene using both tumor tissue and peripheral lymphocytes. Tumor suppressor activity has been proposed for PAX6 in gliomas, in addition to its well-known role in the eye development. Using genomic quantitative PCR and loss of heterozygosity analysis, we identified hemizygous deletions in the 5′-region of PAX6. In lymphocytes, the deletion within PAX6 spanned from between exons 6 and 7 to the 5′-upstream region of the gene, but did not reach the upstream gene, RNC1, which is reported to be associated with tumors. The subependymoma had an additional de novo deletion spanning from the intron 4 to intron 6 of PAX6, although we could not completely determine whether these two deletions are on the same chromosome or not. We also examined other potentially relevant tumor suppressor genes: PTEN, TP53 and SOX2. However, we detected no exonic mutations or deletions in these genes. Collectively, we speculate that the defect in PAX6 may have contributed to the extremely large size of the subependymoma, due to a loss of tumor suppressor activity in glial cell lineage. PMID:20500513

  20. Potential Development of Tumor-Targeted Oral Anti-Cancer Prodrugs: Amino Acid and Dipeptide Monoester Prodrugs of Gemcitabine.

    Science.gov (United States)

    Tsume, Yasuhiro; Drelich, Adam J; Smith, David E; Amidon, Gordon L

    2017-08-10

    One of the main obstacles for cancer therapies is to deliver medicines effectively to target sites. Since stroma cells are developed around tumors, chemotherapeutic agents have to go through stroma cells in order to reach tumors. As a method to improve drug delivery to the tumor site, a prodrug approach for gemcitabine was adopted. Amino acid and dipeptide monoester prodrugs of gemcitabine were synthesized and their chemical stability in buffers, resistance to thymidine phosphorylase and cytidine deaminase, antiproliferative activity, and uptake/permeability in HFF cells as a surrogate to stroma cells were determined and compared to their parent drug, gemcitabine. The activation of all gemcitabine prodrugs was faster in pancreatic cell homogenates than their hydrolysis in buffer, suggesting enzymatic action. All prodrugs exhibited great stability in HFF cell homogenate, enhanced resistance to glycosidic bond metabolism by thymidine phosphorylase, and deamination by cytidine deaminase compared to their parent drug. All gemcitabine prodrugs exhibited higher uptake in HFF cells and better permeability across HFF monolayers than gemcitabine, suggesting a better delivery to tumor sites. Cell antiproliferative assays in Panc-1 and Capan-2 pancreatic ductal cell lines indicated that the gemcitabine prodrugs were more potent than their parent drug gemcitabine. The transport and enzymatic profiles of gemcitabine prodrugs suggest their potential for delayed enzymatic bioconversion and enhanced resistance to metabolic enzymes, as well as for enhanced drug delivery to tumor sites, and cytotoxic activity in cancer cells. These attributes would facilitate the prolonged systemic circulation and improved therapeutic efficacy of gemcitabine prodrugs.

  1. 78 FR 50425 - Prospective Grant of Exclusive License: Development of Brachyury Tumor Associated Antigens as...

    Science.gov (United States)

    2013-08-19

    ... relating to the contemplated exclusive license should be directed to: Sabarni K. Chatterjee, Ph.D., M.B.A... target for human T-cell mediated cancer immunotherapy, such as for tumors of the lung, intestine, stomach...

  2. 75 FR 16490 - Prospective Grant of Exclusive License: Development of PANVAC and Tumor Associated Antigens as...

    Science.gov (United States)

    2010-04-01

    ... exclusive license should be directed to: Sabarni K. Chatterjee, Ph.D. Licensing and Patenting Associate... indicates that Brachyury is aberrantly expressed on tumors of the lung, intestine, stomach, kidney, bladder...

  3. Development of brain tumor at six years after the onset of acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Kumazaki, Hisami; Hanada, Ryoji; Kikuti, Akira; Ichikawa, Masataka; Yamamoto, Keiko; Aihara, Toshinori; Ogawa, Yoshihiro

    1996-01-01

    In October 1994, a 16-year-old boy was diagnosed as having a brain tumor in the left fronto-temporal region 5 years after completing treatment for acute lymphoblastic leukemia (ALL). The patient had been treated for ALL starting in 1988 when he was 10-year-old. He had received systemic chemotherapy and central nervous system prophylaxis, consisting of cranial irradiation (24 Gy) and intrathecal methotrexate. When the brain tumor was detected he was still in complete remission. The patient received only supportive therapy mainly for relief of increased intracranial pressure because the tumor was too large to resect in addition to being inappropriate for surgical treatment. He died in December 1994. On autopsy, pathological diagnosis of the brain tumor was anaplastic astrocytoma, which is a rare secondary malignancy though glioma is common. (author)

  4. Development and validation of a microRNA based diagnostic assay for primary tumor site classification of liver core biopsies

    DEFF Research Database (Denmark)

    Perell, Katharina; Vincent, Martin; Vainer, Ben

    2015-01-01

    for normal liver tissue contamination. Performance was estimated by cross-validation, followed by independent validation on 55 liver core biopsies with a tumor content as low as 10%. A microRNA classifier developed, using the statistical contamination model, showed an overall classification accuracy of 74...... on classification. MicroRNA profiling was performed using quantitative Real-Time PCR on formalin-fixed paraffin-embedded samples. 278 primary tumors and liver metastases, representing nine primary tumor classes, as well as normal liver samples were used as a training set. A statistical model was applied to adjust.......5% upon independent validation. Two-thirds of the samples were classified with high-confidence, with an accuracy of 92% on high-confidence predictions. A classifier trained without adjusting for liver tissue contamination, showed a classification accuracy of 38.2%. Our results indicate that surrounding...

  5. Iron Deficiency Anemia: Focus on Infectious Diseases in Lesser Developed Countries

    Science.gov (United States)

    Shaw, Julia G.; Friedman, Jennifer F.

    2011-01-01

    Iron deficiency anemia is thought to affect the health of more than one billion people worldwide, with the greatest burden of disease experienced in lesser developed countries, particularly women of reproductive age and children. This greater disease burden is due to both nutritional and infectious etiologies. Individuals in lesser developed countries have diets that are much lower in iron, less access to multivitamins for young children and pregnant women, and increased rates of fertility which increase demands for iron through the life course. Infectious diseases, particularly parasitic diseases, also lead to both extracorporeal iron loss and anemia of inflammation, which decreases bioavailability of iron to host tissues. This paper will address the unique etiologies and consequences of both iron deficiency anemia and the alterations in iron absorption and distribution seen in the context of anemia of inflammation. Implications for diagnosis and treatment in this unique context will also be discussed. PMID:21738863

  6. Conceptual design and development of GEM based detecting system for tomographic tungsten focused transport monitoring

    Science.gov (United States)

    Chernyshova, M.; Czarski, T.; Malinowski, K.; Kowalska-Strzęciwilk, E.; Poźniak, K.; Kasprowicz, G.; Zabołotny, W.; Wojeński, A.; Kolasiński, P.; Mazon, D.; Malard, P.

    2015-10-01

    Implementing tungsten as a plasma facing material in ITER and future fusion reactors will require effective monitoring of not just its level in the plasma but also its distribution. That can be successfully achieved using detectors based on Gas Electron Multiplier (GEM) technology. This work presents the conceptual design of the detecting unit for poloidal tomography to be tested at the WEST project tokamak. The current stage of the development is discussed covering aspects which include detector's spatial dimensions, gas mixtures, window materials and arrangements inside and outside the tokamak ports, details of detector's structure itself and details of the detecting module electronics. It is expected that the detecting unit under development, when implemented, will add to the safe operation of tokamak bringing the creation of sustainable nuclear fusion reactors a step closer. A shorter version of this contribution is due to be published in PoS at: 1st EPS conference on Plasma Diagnostics

  7. Intimate partner violence against women: experiences from a woman-focused development programme in Matlab, Bangladesh.

    Science.gov (United States)

    Ahmed, Syed Masud

    2005-03-01

    This paper explores the association between microcredit-based development programmes and domestic violence against women perpetrated by their husbands. A sub-set of cross-sectional data collected in 1999 from 60 BRAC-ICDDR,B study villages in Matlab, Bangladesh, was used. Data were analyzed to characterize group-level differences among study women regarding the reported occurrence of violence (physical and/or mental) and to identify its predictors. About 17.5% of women had experienced violence from their husbands in the past four months, the proportion being greater among BRAC households (p = 0.05). Results of logistic regression identified age, schooling, age of household head, and self-rated poverty status of household as important predictors of violence, but not level of BRAC membership. The study concludes that the greater level of domestic violence reported during the initial stages of BRAC membership subsided with the introduction of skill-development training among participant women over time.

  8. Iron Deficiency Anemia: Focus on Infectious Diseases in Lesser Developed Countries

    Directory of Open Access Journals (Sweden)

    Julia G. Shaw

    2011-01-01

    Full Text Available Iron deficiency anemia is thought to affect the health of more than one billion people worldwide, with the greatest burden of disease experienced in lesser developed countries, particularly women of reproductive age and children. This greater disease burden is due to both nutritional and infectious etiologies. Individuals in lesser developed countries have diets that are much lower in iron, less access to multivitamins for young children and pregnant women, and increased rates of fertility which increase demands for iron through the life course. Infectious diseases, particularly parasitic diseases, also lead to both extracorporeal iron loss and anemia of inflammation, which decreases bioavailability of iron to host tissues. This paper will address the unique etiologies and consequences of both iron deficiency anemia and the alterations in iron absorption and distribution seen in the context of anemia of inflammation. Implications for diagnosis and treatment in this unique context will also be discussed.

  9. Present status of accelerator-based BNCT: Focus on developments in Argentina

    International Nuclear Information System (INIS)

    Cartelli, D.; Capoulat, M.E.; Bergueiro, J.; Gagetti, L.; Suárez Anzorena, M.; Grosso, M.F. del; Baldo, M.; Castell, W.; Padulo, J.; Suárez Sandín, J.C.; Igarzabal, M.; Erhardt, J.; Mercuri, D.

    2015-01-01

    In this work we provide some information on the present status of accelerator-based BNCT (AB-BNCT) worldwide and subsequently concentrate on the recent accelerator technology developments in Argentina. - Highlights: • The current status of projects and associated facilities for AB-BNCT worldwide is shown. • Only low (few MeV) energy accelerators are included. • The recent progress of the Argentine AB-BNCT program is described.

  10. The Determinants of Research and Development Investment in the Pharmaceutical Industry: Focus on Financial Structures

    OpenAIRE

    Lee, Munjae; Choi, Mankyu

    2015-01-01

    Objectives This study analyzes the influence of the financial structure of pharmaceutical companies on R&D investment to create a next-generation profit source or develop relatively cost-effective drugs to maximize enterprise value. Methods The period of the empirical analysis is from 2000 to 2012. Financial statements and comments in general and internal transactions were extracted from TS-2000 of the Korea Listed Company Association (KLCA), and data related to stock price is extracted from ...

  11. Pharmacy resident-led student mentoring program: A focus on developing mentoring skills.

    Science.gov (United States)

    Howard, Meredith L; Steuber, Taylor D; Nisly, Sarah A; Wilhoite, Jessica; Saum, Lindsay

    2017-11-01

    Formalized mentoring programs are often credited for influencing professional development of mentees. Unfortunately, little information exists regarding advancement of mentoring skills. We report the development and evaluation of a program to cultivate mentoring skills in pharmacy residents. Advanced pharmacy practice experience students and pharmacy residents were contacted for program participation. Resident mentors were paired with a student mentee for the program. Mentors were provided resources and support throughout the program. Sessions were held to facilitate mentoring relationships and to discuss professional development topics. Pre- and post-perception surveys were administered to mentors to measure changes in mentoring comfort and ability. Only matched pre- and post-surveys were included for analysis. The program was held and evaluated over two separate academic years FINDINGS: Fifty-three residents mentored 54 students over two cycles of the program. Mentors' matched perception surveys (n = 26) reported increased comfort in mentoring (p effectiveness in provision of written and oral feedback (p = 0.004 and p = 0.013 respectively). Mentors also reported heightened belief that serving as a student mentor will be beneficial to their long-term career goals (p = 0.034). Overall, this formal resident-led student mentoring program improved resident comfort serving in a mentoring role. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Development and evaluation of copper-67 and samarium-153 labeled conjugates for tumor radioimmunotherapy

    International Nuclear Information System (INIS)

    Srivastava, S.C.; Mausner, L.F.; Mease, R.C.; Meinken, G.E.; Joshi, V.; Kolsky, K.; Sweet, M.; Steplewski, Z.

    1995-01-01

    The potential of utilizing receptor-specific agents such as monoclonal antibodies (MAb), and MAb-derived smaller molecules, as carriers of radionuclides for the selective destruction of tumors has stimulated much research activity. The success of such applications depends on many factors, especially the tumor binding properties of the antibody reagent, the efficiency of labeling and in-vivo stability of the radioconjugate and, on the careful choice of the radionuclide best suited to treat the tumor under consideration. The radiolabeled antibody technique for radioimmunotherapy (RIT), however, has experienced many limitations, and its success has not matched the expectations that were raised more than a decade ago. The problems that have been identified include: (i) degradation of antibody immunoreactivity resulting from chemical manipulations required for labeling; (ii) lack of suitable radioisotopes and methods for stable attachment of the radiolabel; (iii) in-vivo instability of the radioimmunoconjugates; (iv) excessive accumulation of activity in non-target locations; and (v) lack of radioimmunoconjugate accessibility to cells internal to a tumor mass. A careful choice of the radionuclide(s) best suited to treat the tumor under consideration is one of the most important requirements for successful radioimmunotherapy. This study evaluates copper 67 and samarium 153 for tumor radioimmunotherapy

  13. Peculiarities of antioxidant system and iron metabolism in organism during development of tumor resistance to cisplatin.

    Science.gov (United States)

    Chekhun, V F; Lozovska, Y V; Burlaka, A P; Lukyanova, N Y; Todor, I N; Naleskina, L A

    2014-09-01

    To study in vivo the peculiarities of changes of iron metabolism and antioxidant system in dynamics of growth of Guerin carcinoma with different sensitivity to cisplatin. In order to evaluate the content of metallothionein-1 (MT-1) in tumor homogenates and blood serum of rats with cisplatin-sensitive and cisplatin-resistant Guerin carcinoma the immunoenzyme method was used. The evaluation of ceruloplasmin activity, content of "free iron" complexes, superoxide and NO-generating acti-vity of NADPH-oxidase and iNOS activity in neutrophils, blood serum and tumor homogenates was measured by EPR-spectro-scopy. Maximal accumulation of MT-1 in blood serum and tumor, more pronounced in resistant strain, at the border of latent and exponential phase of growth has been shown that is the evidence of protective role of this protein in the respect to the generation of free radical compounds. It has been determined that in animals with cisplatin-resistant strain of Guerin carcinoma, increase of "free iron" complexes is more apparent both on the level of tumor and organism on the background on increase of CP/TR ratio that is the consequence of organism antioxidant protection system disorder. Mentioned changes in metabolism of iron with its accumulation in tumor and further reprogramming of mitochondria metabolism and activity of NADPH-oxidase for non-transformed cells are favorable conditions for the formation of oxidative phenotype of tumor.

  14. Developing a yearlong Next Generation Science Standard (NGSS) learning sequence focused on climate solutions: opportunities, challenges and reflections

    Science.gov (United States)

    Cordero, E.; Centeno, D.

    2015-12-01

    Over the last four years, the Green Ninja Project (GNP) has been developing educational media (e.g., videos, games and online lessons) to help motivate student interest and engagement around climate science and solutions. Inspired by the new emphasis in NGSS on climate change, human impact and engineering design, the GNP is developing a technology focused, integrative, and yearlong science curriculum focused around solutions to climate change. Recognizing the importance of teacher training on the successful implementation of NGSS, we have also integrated teacher professional development into our curriculum. During the presentation, we will describe the design philosophy around our middle school curriculum and share data from a series of classes that are piloting the curriculum during Fall 2015. We will also share our perspectives on how data, media creation and engineering can be used to create educational experiences that model the type of 'three-dimensional learning' encouraged by NGSS.

  15. Bone tumor

    Science.gov (United States)

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

  16. Exploring the Influence of Student Focus Groups in Their Professional and Personal Development

    Science.gov (United States)

    Hosseini, S.; Hut, R.

    2014-12-01

    A scientific career is often more than a 9-to-5 commitment, both in terms of time and passion. An important factor that fuels this passion is engaging with the community on many levels. In the history of education and professional development, there are numerous studies that emphasis the importance of surrounding groups and like-minded peers in one's professional and personal development in a less constrained environment. In our experience, in modern days where students are surrounded with too much information and yet too little clear signal, the idea of mentor and advisor can no longer limit to one or two people. We strongly feel it is imperative to have the opportunity to share expertise on scientific issues, career options, develop presenting and writing skills, participate in professional volunteer activities with alike and advanced colleagues, share future opportunities, and successfully navigating life both inside and outside of graduate school in a relaxed environment. Most of the professional scientific and engineering communities put a lot of effort to create and maintain professional groups in masters and Ph.D. levels but the dynamics within these groups prove it to be very different and it is challenging to maintain both momentum and productivity. Authors of this report would present their experience in creating, running and maintaining various student groups in the discipline of physics, astronomy, planetary science, hydrology, and optical engineering in US, Europe and Middle East. The common factors and differences based on the supportive community, location, and the educational level would be discussed. An outline of potential helpful factors within the academic institutes and professional communities would be presented based on the examination on various successful and unsuccessful experiences.

  17. A Study on the PRC-DPRK Alliance: Focusing on Historical Development of Alliance

    Science.gov (United States)

    2015-06-12

    since the end of Cold War, the PRC-DPRK “blood- shared alliance” has been branded as a “relic of a bygone age,” and some Chinese officers even argued...sanctions beyond those targeting luxury goods. Beijing managed to persuade Pyongyang to resume the Six-Party Talks in 2007. In February 2007, during...called Six-Party Talks. The resolutions also imposed embargoes on large-scale arms, weapons-related research and development materials, and luxury

  18. Community Development Strategic Planning with a Focus on Social Variables, Case study: Tollab Community of Mashhad

    OpenAIRE

    E. Mafi; M.M. Razavi

    2012-01-01

    Extended abstract1- IntroductionThe world has encountered an urban revolution in the past 200 years. In 1800, the cities were a small island in rural ocean, now in 2000; half of world populations were living in cities. It has been stated that it reaches to 65 percent in 2025, While they occupied just 2 percent of the earth, and upon UN forecast, 80 percent of next decade population growth take place in cities, 90 percent from this rate will occur in cities of developing countries. Urbanizatio...

  19. NNSA Laboratory Directed Research and Development Program 2008 Symposium--Focus on Energy Security

    Energy Technology Data Exchange (ETDEWEB)

    Kotta, P R; Sketchley, J A

    2008-08-20

    The Laboratory Directed Research and Development (LDRD) Program was authorized by Congress in 1991 to fund leading-edge research and development central to the national laboratories core missions. LDRD anticipates and engages in projects on the forefront of science and engineering at the Department of Energy (DOE) national laboratories, and has a long history of addressing pressing national security needs at the National Nuclear Security Administration (NNSA) laboratories. LDRD has been a scientific success story, where projects continue to win national recognition for excellence through prestigious awards, papers published and cited in peer-reviewed journals, mainstream media coverage, and patents granted. The LDRD Program is also a powerful means to attract and retain top researchers from around the world, to foster collaborations with other prominent scientific and technological institutions, and to leverage some of the world's most technologically advanced assets. This enables the LDRD Program to invest in high-risk and potentially high-payoff research that creates innovative technical solutions for some of our nation's most difficult challenges. Worldwide energy demand is growing at an alarming rate, as developing nations continue to expand their industrial and economic base on the back of limited global resources. The resulting international conflicts and environmental consequences pose serious challenges not only to this nation, but to the international community as well. The NNSA and its national security laboratories have been increasingly called upon to devote their scientific and technological capabilities to help address issues that are not limited solely to the historic nuclear weapons core mission, but are more expansive and encompass a spectrum of national security missions, including energy security. This year's symposium highlights some of the exciting areas of research in alternative fuels and technology, nuclear power, carbon

  20. Developing an iPhone application with focus on the user interface

    OpenAIRE

    Kannan, Naryanan

    2012-01-01

    Smartphones are becoming increasingly popular day by day. The reason why they are called ‘Smart phones’ is that they can perform advanced computing and have a better connectivity to the Internet. Smartphones usually run a complete operating system. For example, iOS runs on Apple Inc.’s mobile devices like iPhone, iPod Touch and iPad [1]. A Smartphone allows the user to run applications. These applications are aimed at making life simpler for the users. This Master Thesis aims at developing on...

  1. Neuromuscular Structure, Evolution and Development in Meiofaunal Annelids with Special Focus on Dinophilus gyrociliatus (Dinophilidae)

    DEFF Research Database (Denmark)

    Kerbl, Alexandra

    less complex sensory structures. Yet, very little is still known on how these small brains are organized to fulfil basic functions. This study addresses the structure, evolution and development of neuromuscular systems within two exclusively meiofaunal lineages Lobatocerebridae and Dinophilidae....... RESULTS: Both families were shown to be nested within annelids in phylogenomic analyses based on transcriptomic data, which also suggest the Spiralian ancestor to be meiofaunal (Manuscript 4). The annelid affinity of the enigmatic Lobatocerebridae was further tested by detailed morphological examinations...... warranting further studies to uncover how the genetic domains influence the configuration of the brain...

  2. Does cell phone use increase the chances of parotid gland tumor development? A systematic review and meta-analysis.

    Science.gov (United States)

    de Siqueira, Elisa Carvalho; de Souza, Fabrício Tinoco Alvim; Gomez, Ricardo Santiago; Gomes, Carolina Cavalieri; de Souza, Renan Pedra

    2017-08-01

    Prior epidemiological studies had examined the association between cell phone use and the development of tumors in the parotid glands. However, there is no consensus about the question of whether cell phone use is associated with increased risk of tumors in the parotid glands. We performed a meta-analysis to evaluate the existing literature about the mean question and to determine their statistical significance. Primary association studies. Papers that associated cell phone use and parotid gland tumors development were included, with no restrictions regarding publication date, language, and place of publication. Systematic literature search using PubMed, SciELO and Embase followed by meta-analysis. Initial screening included 37 articles, and three were included in meta-analysis. Using three independent samples including 5087 subjects from retrospective case-control studies, cell phone use seems to be associated with greater odds (1.28, 95%- confidence interval: 1.09-1.51) to develop salivary gland tumor. Results should be read with caution due to the limited number of studies available and their retrospective design. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Preclinical development of a novel class of CXCR4 antagonist impairing solid tumors growth and metastases.

    Directory of Open Access Journals (Sweden)

    Luigi Portella

    Full Text Available The CXCR4/CXCL12 axis plays a role in cancer metastases, stem cell mobilization and chemosensitization. Proof of concept for efficient CXCR4 inhibition has been demonstrated in stem cell mobilization prior to autologous transplantation in hematological malignancies. Nevertheless CXCR4 inhibitors suitable for prolonged use as required for anticancer therapy are not available. To develop new CXCR4 antagonists a rational, ligand-based approach was taken, distinct from the more commonly used development strategy. A three amino acid motif (Ar-Ar-X in CXCL12, also found in the reverse orientation (X-Ar-Ar in the vMIP-II inhibitory chemokine formed the core of nineteen cyclic peptides evaluated for inhibition of CXCR4-dependent migration, binding, P-ERK1/2-induction and calcium efflux. Peptides R, S and I were chosen for evaluation in in vivo models of lung metastases (B16-CXCR4 and KTM2 murine osteosarcoma cells and growth of a renal cells xenograft. Peptides R, S, and T significantly reduced the association of the 12G5-CXCR4 antibody to the receptor and inhibited CXCL12-induced calcium efflux. The four peptides efficiently inhibited CXCL12-dependent migration at concentrations as low as 10 nM and delayed CXCL12-mediated wound healing in PES43 human melanoma cells. Intraperitoneal treatment with peptides R, I or S drastically reduced the number of B16-CXCR4-derived lung metastases in C57/BL mice. KTM2 osteosarcoma lung metastases were also reduced in Balb/C mice following CXCR4 inhibition. All three peptides significantly inhibited subcutaneous growth of SN12C-EGFP renal cancer cells. A novel class of CXCR4 inhibitory peptides was discovered. Three peptides, R, I and S inhibited lung metastases and primary tumor growth and will be evaluated as anticancer agents.

  4. An "Evidence-Based" Professional Development Program for Physics Teachers Focusing on Knowledge Integration

    Science.gov (United States)

    Berger, Hana

    This dissertation is concerned with the design and study of an evidence-based approach to the professional development of high-school physics teachers responding to the need to develop effective continuing professional development programs (CPD) in domains that require genuine changes in teachers' views, knowledge, and practice. The goals of the thesis were to design an evidence-based model for the CPD program, to implement it with teachers, and to study its influence on teachers' knowledge, views, and practice, as well as its impact on students' learning. The program was developed in three consecutive versions: a pilot, first, and second versions. Based on the pilot version (that was not part of this study), we developed the first version of the program in which we studied difficulties in employing the evidence-based and blended-learning approaches. According to our findings, we modified the strategies for enacting these approaches in the second version of the program. The influence of the program on the teachers and students was studied during the enactment of the second version of the program. The model implemented in the second version of the program was characterized by four main design principles: 1. The KI and evidence aspects are acquired simultaneously in an integrated manner. 2. The guidance of the teachers follows the principles of cognitive apprenticeship both in the evidence and the KI aspects. 3. The teachers experience the innovative activities as learners. 4. The program promotes continuity of teachers' learning through a structured "blended learning" approach. The results of our study show that this version of the program achieved its goals; throughout the program the teachers progressed in their knowledge, views, and practice concerning the knowledge integration, and in the evidence and learner-centered aspects. The results also indicated that students improved their knowledge of physics and knowledge integration skills that were developed

  5. Poverty, energy, and resource use in developing countries: focus on Africa.

    Science.gov (United States)

    Kammen, Daniel M; Kirubi, Charles

    2008-01-01

    Energy poverty affects poor communities and poor nations far more severely, and more directly, than in developed nations. Poor rural communities are particularly vulnerable, and the poor globally spend by far the largest percentage of income on energy. To make matters worse, record-high oil prices combined with sharp decline in foreign exchange earnings are key processes influencing the energy sector in Africa. These increases cause tremendous local hardships, but can be used to steer development decisions toward renewable energy technologies. At the same time, breaking up of public monopolies and liberalizing generation and distribution provides an opportunity for a new approach to rural electrification. Given the right incentives and institutional framework, a new set of players (e.g., private entrepreneurs, cooperatives, nongovernmental organizations, and communities) are likely to emerge and dominate reformed rural electricity markets in the future. Through technological and institutional "leap-frogging," Africa stands to gain significantly by augmenting current initiatives with experience and lessons recently gained in South Asia and Latin America. In these regions, a number of remarkable recent strides to seed and grow rural electricity markets while stimulating and encouraging private investments. Examples of innovative regulatory tools to address poverty include licensing, standards and guidelines, metering, tariffs, transmission charges, and performance-based contracting for energy services.

  6. Football coaches’ development in Brazil: a focus on the content of learning

    Directory of Open Access Journals (Sweden)

    Alexandre Vinicius Bobato Tozetto

    2017-12-01

    Full Text Available Abstract AIM The aim of the study was to analyze the lifelong content of learning of coaches. METHODS Eight coaches inserted in an Elite Football Club participated. Rappaport Time Line and semi-structured interviews were used to obtain the data. The coaches’ learning was organized according to the theory of Lifelong Learning.1-4 RESULTS The coaches presented in their personal experiences, with their families and as athletes, content of learning such as “leadership development” and “formation of values”. In professional experiences, such as in academic training, coach assistants and even coaching, they are also reported as essential in obtaining content of learning (general and specific knowledge, training methods, leadership development, self-control. Finally, the reflexive process is considered by most coaches as a potentiator of learning, with interference on the “coach-athlete relationship”, “activity adjustment,” among other content of learning. CONCLUSION The content learned throughout the life were defined in certain episodes for presenting different meanings in the life of the coaches, in which they related to a new experience according to their biographies. Therefore, the various episodes offer coaches new experiences, in which they can incorporate, reinforce or renew the content about the coaching process and are responsible for the development of the coach.

  7. Household water treatment and the millennium development goals: keeping the focus on health.

    Science.gov (United States)

    Clasen, Thomas F

    2010-10-01

    Waterborne diseases such as diarrhea are a major killer in low-income settings, particularly of young children. For those without access to safe drinking water, household water treatment, such as boiling, chlorinating, and filtering water in the home, when combined with safe storage (HWTS) can significantly improve water quality and prevent disease, thereby contributing to the child survival and other health priorities encompassed within the Millennium Development Goals (MDGs). There is uncertainly, however, about whether HWTS should count toward the MDG water target, which promotes "sustainable access to safe drinking water". This paper reviews the relevant research and concludes that it should not. Although HWTS can significantly improve water quality, it does not improve water quantity and access-key aspects of the MDG water target that are essential for optimal improvements in health and development. A policy that excludes HWTS from the MDG water target will discourage governments from diverting scarce public resources from comprehensive and long-term improvements in water supplies. At the same time, the health-oriented MDGs provide a sufficient case for scaling up effective and appropriate HWTS among target populations. Moreover, a health-based strategy for HWTS will help ensure that promotion of the intervention is driven by measurable improvements in outcomes rather than inputs, thus encouraging advances in both hardware and programmatic delivery that will make HWTS more effective, appropriate, and accessible to vulnerable populations.

  8. Decision support methodology for national energy planning in developing countries: an implementation focused approach

    Science.gov (United States)

    Lee, Nathan Coenen

    The work described in this PhD Thesis focuses on the post-processing of optical fibers and their enhancement as sensing element. Since the majority of sensors presented are based in Fabry-Perot interferometers, an historical overview of this category of optical fiber sensors is firstly presented. This review considers the works published since the early years, in the beginning of the 1980s, until the middle of 2015. The incorporation of microcavities at the tip of a single mode fiber was extensively studied, particularly for the measurement of nitrogen and methane gas pressure. These cavities were fabricated using hollow core silica tubes and a hollow core photonic crystal fiber. Following a different approach, the microcavities were incorporated between two sections of single mode fiber. In this case, the low sensitivity to temperature makes these microcavities highly desirable for the measurement of strain at high temperatures. Competences in post-processing techniques such as the chemical etching and the writing of periodical structures in the fiber core by means of an excimer or a femtosecond laser were also acquired in the course of the PhD programme. One of the works consisted in the design and manufacturing of a double clad optical fiber. The refractive index of the inner cladding was higher than the one of the outer cladding and the core. Thus, light was guided in the inner cladding instead of propagating in the core. This situation was overcome by applying chemical etching, thus removing the inner cladding. The core, surrounded by air, was then able to guide light. Two different applications were found for this fiber, as a temperature sensor and as an optical refractometer. In the last, the optical phase changes with the liquid refractive index. Two different types of fiber Bragg gratings were characterized in strain and temperature. Sensing structures obtained through the phase mask technique at the tip of an optical fiber were subjected to chemical

  9. Proton acceleration: new developments for focusing and energy selection, and applications in plasma physics

    Science.gov (United States)

    Audebert, P.

    2007-11-01

    In the last few years, intense research has been conducted on laser-accelerated ion sources and their applications. These sources have exceptional properties, i.e. high brightness and high spectral cut-off, high directionality and laminarity, short burst duration. We have shown that for proton energies >10 MeV, the transverse and longitudinal emittance are respectively example point-projection radiography with unprecedented resolution. We will show example of such time and space-resolved radiography of fast evolving fields, either of associated with the expansion of a plasma in vacuum [*] or with the propagation of a ICF-relevant laser beam in an underdense plasma. These proton sources also open new opportunities for ion beam generation and control, and could stimulate development of compact ion accelerators for many applications.

  10. Development and implementation of IT require focus on user participation, acceptance and workflow

    DEFF Research Database (Denmark)

    Sølling, Ina Koldkjær; Carøe, Per; Mathiesen, Kirsten Siggaard

    Abstract. The study ”Online Care” follows a municipal project ”Online Welfare” where a nurse’s presence in the citizen's own home was replaced by online communication. The paper is based on a citizen’s perspective and seeks to develop meaningful workflow for the benefit of citizens with medical...... approved by the Danish System of Ethics in Science and is conducted in collaboration with Aalborg University, Aalborg Municipality and DanAge, (NGO). The municipality's goal of efficiency and financial savings regarding ”Online Welfare” was not honored due to insufficient network infrastructure...... to participate. Citizens, who were included in the study accepted and adopted the technology however, "Online Welfare" could not replace the care they used to receive. Therefore, the offer was perceived as an "appendix" which tended to meaninglessness by some of the citizens.The nurses' perception of nursing...

  11. Recent developments and emergent challenges in Ecohydrology: Focus on the belowground frontier

    Science.gov (United States)

    Mackay, D. S.

    2017-12-01

    The broad spectrum of ecohydrology issues touch on many areas of research in hydrology. But what are the emerging themes and challenges that represent the core of ecohydrology as a maturing discipline? To answer this question the ecohydrology lens was applied to manuscripts published in Water Resources Research over period of 2015 through July 2017. The 235 manuscripts retrieved can be broadly grouped into catchment hydrology, riparian-hyporheic-stream processes, critical zone, land-atmosphere exchange, wetlands, and sustainability. Three dominant crosscutting themes (i.e., coevolution, interfaces, and energy exchange) account for more than half the papers retrieved. In the context of ecohydrology, coevolution refers to the development of physical systems in concert with biological systems and their interactions. In an ecohydrology context, interfaces refer to subsurface, and sometime surface connections that influence transport (e.g., solutes concentration-discharge) influenced by vegetative plumbing, ecophysiology, animal behavior, and microbial processes. Energy exchange in ecohydrology connects vegetative processes to movement of water to the atmosphere through evapotranspiration. Across these themes there is emerging theory and methodology that emphasizes the integrated roles of biology and hydrology in the subsurface. In particular, there is a notable surge of interest in the role of plant roots on subsurface processes. But these are hard to observe and remain challenging to model. By adopting principles of coevolution, in particular, significant advances will be made in modeling plant roots and their depths, corroborated with new geophysical and tracer tools, for improving understanding of critical zone development, subsurface flow processes, and land-atmosphere energy exchange.

  12. Titanium dioxide nanoparticles: some aspects of toxicity/focus on the development.

    Science.gov (United States)

    Rollerova, E; Tulinska, J; Liskova, A; Kuricova, M; Kovriznych, J; Mlynarcikova, A; Kiss, A; Scsukova, S

    2015-04-01

    Nanosized titanium dioxide (TiO2) particles belong to the most widely manufactured nanoparticles (NPs) on a global scale because of their photocatalytic properties and the related surface effects. TiO2 NPs are in the top five NPs used in consumer products. Ultrafine TiO2 is widely used in the number of applications, including white pigment in paint, ceramics, food additive, food packaging material, sunscreens, cosmetic creams, and, component of surgical implants. Data evidencing rapid distribution, slow or ineffective elimination, and potential long-time tissue accumulation are especially important for the human risk assessment of ultrafine TiO2 and represent new challenges to more responsibly investigate potential adverse effects by the action of TiO2 NPs considering their ubiquitous exposure in various doses. Transport of ultrafine TiO2 particles in systemic circulation and further transition through barriers, especially the placental and blood-brain ones, are well documented. Therefore, from the developmental point of view, there is a raising concern in the exposure to TiO2 NPs during critical windows, in the pregnancy or the lactation period, and the fact that human mothers, women and men in fertile age and last but not least children may be exposed to high cumulative doses. In this review, toxicokinetics and particularly toxicity of TiO2 NPs in relation to the developing processes, oriented mainly on the development of the central nervous system, are discussed Keywords: nanoparticles, nanotoxicity, nanomaterials, titanium dioxide, reproductive toxicity, developmental toxicity, blood brain barrier, placental barrier.

  13. Polytomous diagnosis of ovarian tumors as benign, borderline, primary invasive or metastatic: development and validation of standard and kernel-based risk prediction models

    Directory of Open Access Journals (Sweden)

    Testa Antonia C

    2010-10-01

    Full Text Available Abstract Background Hitherto, risk prediction models for preoperative ultrasound-based diagnosis of ovarian tumors were dichotomous (benign versus malignant. We develop and validate polytomous models (models that predict more than two events to diagnose ovarian tumors as benign, borderline, primary invasive or metastatic invasive. The main focus is on how different types of models perform and compare. Methods A multi-center dataset containing 1066 women was used for model development and internal validation, whilst another multi-center dataset of 1938 women was used for temporal and external validation. Models were based on standard logistic regression and on penalized kernel-based algorithms (least squares support vector machines and kernel logistic regression. We used true polytomous models as well as combinations of dichotomous models based on the 'pairwise coupling' technique to produce polytomous risk estimates. Careful variable selection was performed, based largely on cross-validated c-index estimates. Model performance was assessed with the dichotomous c-index (i.e. the area under the ROC curve and a polytomous extension, and with calibration graphs. Results For all models, between 9 and 11 predictors were selected. Internal validation was successful with polytomous c-indexes between 0.64 and 0.69. For the best model dichotomous c-indexes were between 0.73 (primary invasive vs metastatic and 0.96 (borderline vs metastatic. On temporal and external validation, overall discrimination performance was good with polytomous c-indexes between 0.57 and 0.64. However, discrimination between primary and metastatic invasive tumors decreased to near random levels. Standard logistic regression performed well in comparison with advanced algorithms, and combining dichotomous models performed well in comparison with true polytomous models. The best model was a combination of dichotomous logistic regression models. This model is available online

  14. Early-in-life dietary zinc deficiency and supplementation and mammary tumor development in adulthood female rats.

    Science.gov (United States)

    da Silva, Flávia R M; Grassi, Tony F; Zapaterini, Joyce R; Bidinotto, Lucas T; Barbisan, Luis F

    2017-06-01

    Zinc deficiency during pregnancy and postnatal life can adversely increase risk of developing human diseases at adulthood. The present study was designed to evaluate whether dietary zinc deficiency or supplementation during the pregnancy, lactation and juvenile stages interferes in the development of mammary tumors induced by 7,12-dimethylbenzanthracene (DMBA) in female Sprague-Dawley (SD) rats. Pregnant female SD rats were allocated into three groups: zinc-adequate diet (ZnA - 35-mg/kg chow), zinc-deficient diet (ZnD - 3-mg/kg chow) or zinc-supplemented diet (ZnS - 180-mg/kg chow) during gestational day 10 (GD 10) until the litters' weaning. Female offspring received the same diets as their dams until postnatal day (PND) 51. At PND 51, the animals received a single dose of DMBA (50 mg/kg, ig) and zinc-adequate diets. At PND 180, female were euthanized, and tumor samples were processed for histological evaluation and gene expression microarray analysis. The ZnD induced a significant reduction in female offspring body weight evolution and in mammary gland development. At late in life, the ZnD or ZnS did not alter the latency, incidence, multiplicity, volume or histological types of mammary tumors in relation to the ZnA group. However, the total tumor number in ZnS group was higher than in ZnA group, accompanied by distinct expression of 4 genes up- and 15 genes down-regulated. The present findings indicate that early-in-life dietary zinc supplementation, differently to zinc deficiency, has a potential to modify the susceptibility to the development of mammary tumors induced by DMBA. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Rosiglitazone inhibits metastasis development of a murine mammary tumor cell line LMM3

    International Nuclear Information System (INIS)

    Magenta, Gabriela; Borenstein, Ximena; Rolando, Romina; Jasnis, María Adela

    2008-01-01

    Activation of peroxisome proliferator-activated receptors γ (PPARγ) induces diverse effects on cancer cells. The thiazolidinediones (TZDs), such as troglitazone and ciglitazone, are PPARγ agonists exhibiting antitumor activities; however, the underlying mechanism remains inconclusive. Rosiglitazone (RGZ), a synthetic ligand of PPARγ used in the treatment of Type 2 diabetes, inhibits growth of some tumor cells and is involved in other processes related to cancer progression. Opposing results have also been reported with different ligands on tumor cells. The purpose of this study was to determine if RGZ and 15d-PGJ 2 induce antitumor effects in vivo and in vitro on the murine mammary tumor cell line LMM3. The effect on LMM3 cell viability and nitric oxide (NO) production of different doses of RGZ, 15-dPGJ 2 , BADGE and GW9662 were determined using the MTS colorimetric assay and the Griess reaction respectively. In vivo effect of orally administration of RGZ on tumor progression was evaluated either on s.c. primary tumors as well as on experimental metastasis. Cell adhesion, migration (wound assay) and invasion in Transwells were performed. Metalloproteinase activity (MMP) was determined by zymography in conditioned media from RGZ treated tumor cells. PPARγ expression was detected by inmunohistochemistry in formalin fixed tumors and by western blot in tumor cell lysates. RGZ orally administered to tumor-bearing mice decreased the number of experimental lung metastases without affecting primary s.c. tumor growth. Tumor cell adhesion and migration, as well as metalloproteinase MMP-9 activity, decreased in the presence of 1 μM RGZ (non-cytotoxic dose). RGZ induced PPARγ protein expression in LMM3 tumors. Although metabolic activity -measured by MTS assay- diminished with 1–100 μM RGZ, 1 μM-treated cells recovered their proliferating capacity while 100 μM treated cells died. The PPARγ antagonist Biphenol A diglicydyl ether (BADGE) did not affect RGZ activity

  16. Hypoxic exosomes facilitate bladder tumor growth and development through transferring long non-coding RNA-UCA1.

    Science.gov (United States)

    Xue, Mei; Chen, Wei; Xiang, An; Wang, Ruiqi; Chen, He; Pan, Jingjing; Pang, Huan; An, Hongli; Wang, Xiang; Hou, Huilian; Li, Xu

    2017-08-25

    To overcome the hostile hypoxic microenvironment of solid tumors, tumor cells secrete a large number of non-coding RNA-containing exosomes that facilitate tumor development and metastasis. However, the precise mechanisms of tumor cell-derived exosomes during hypoxia are unknown. Here, we aim to clarify whether hypoxia affects tumor growth and progression by transferring long non-coding RNA-urothelial cancer-associated 1 (lncRNA-UCA1) enriched exosomes secreted from bladder cancer cells. We used bladder cancer 5637 cells with high expression of lncRNA-UCA1 as exosome-generating cells and bladder cancer UMUC2 cells with low expression of lncRNA-UCA1 as recipient cells. Exosomes derived from 5637 cells cultured under normoxic or hypoxic conditions were isolated and identified by transmission electron microscopy, nanoparticle tracking analysis and western blotting analysis. These exosomes were co-cultured with UMUC2 cells to evaluate cell proliferation, migration and invasion. We further investigated the roles of exosomal lncRNA-UCA1 derived from hypoxic 5637 cells by xenograft models. The availability of lncRNA-UCA1 in serum-derived exosomes as a biomarker for bladder cancer was also assessed. We found that hypoxic exosomes derived from 5637 cells promoted cell proliferation, migration and invasion, and hypoxic exosomal RNAs could be internalized by three bladder cancer cell lines. Importantly, lncRNA-UCA1 was secreted in hypoxic 5637 cell-derived exosomes. Compared with normoxic exosomes, hypoxic exosomes derived from 5637 cells showed the higher expression levels of lncRNA-UCA1. Moreover, Hypoxic exosomal lncRNA-UCA1 could promote tumor growth and progression though epithelial-mesenchymal transition, in vitro and in vivo. In addition, the expression levels of lncRNA-UCA1 in the human serum-derived exosomes of bladder cancer patients were higher than that in the healthy controls. Together, our results demonstrate that hypoxic bladder cancer cells remodel tumor

  17. Material focus

    DEFF Research Database (Denmark)

    Sokoler, Tomas; Vallgårda, Anna K. A.

    2009-01-01

    In this paper we build on the notion of computational composites, which hold a material perspective on computational technology. We argue that a focus on the material aspects of the technology could be a fruitful approach to achieve new expressions and to gain a new view on the technology's role...... in design. We study two of the computer's material properties: computed causality and connectability and through developing two computational composites that utilize these properties we begin to explore their potential expressions....

  18. Development and testing of a double-focusing, static, axisymmetric mass spectrometer

    International Nuclear Information System (INIS)

    Ritter, G.

    1979-04-01

    The developed mass spectrometer affords very high acceptance (cm 2 sr) compared with conventional mass spectrometers owing to its large solid angle of 0.178 sr. The ion optical properties of the instrument were tested by bombarding various targets (Al, Ni, Ti, Cu, Si) with potassium or caesium ions from a thermionic ion source with energies of 1, 2 and 3 keV and recording mass spectra of positive and negative sputtered ions. The ion optical beam path was calculated analytically (magnet system) in part and numerically in part (energy analyzer, einzel lenses and detector system) and represented in graph form. The results obtained from the mass spectra showed that the magnet system with its twelve permanent magnets is too irregular to produce mass linses with good resolution. Furthermore, it was found that the maximum primary energy of the alkali ions that was possible in this mass spectrometer owing to the breakdown strength was not sufficient to record surface-specific mass spectra since the target surface was covered within a very short time with an at least monatomic layer of alkali ions from the thermionic ion source. (orig./HP) [de

  19. Use and records of child health handbook focused on growth and development.

    Science.gov (United States)

    Palombo, Claudia Nery Teixeira; Duarte, Luciane Simões; Fujimori, Elizabeth; Toriyama, Aurea Tamami Minagawa

    2014-08-01

    Objective To evaluate the use and records of the Child Health Handbook (CHH), especially growth and development. Method Cross-sectional study with 358 mother-child pairs registered in 12 Primary Health Centers (PHCs) of a small municipality. Mothers were interviewed at the PHC from February to April 2013 using a questionnaire. Data analysis was done using WHO Anthro software, Epi InfoTM and Stata. Results Fifty-three percent of the mothers were carrying the CHH at the time of the interview, similar to the proportion of mothers who were instructed to bring the CHH to health appointments. Annotations in the CHH during the visits were reported by 49%. The vaccination schedule was completed in 97% of the CHH, but only 9% and 8% of the CHH, respectively, contained growth charts and properly completed developmental milestones. Conclusion Low rates of use and unsatisfactory record-keeping in the CHH reinforce the need for investment in professional training and community awareness for the CHH to become an effective instrument of promotion of child health.

  20. Use and records of child health handbook focused on growth and development

    Directory of Open Access Journals (Sweden)

    Claudia Nery Teixeira Palombo

    2014-08-01

    Full Text Available Objective To evaluate the use and records of the Child Health Handbook (CHH, especially growth and development. Method Cross-sectional study with 358 mother-child pairs registered in 12 Primary Health Centers (PHCs of a small municipality. Mothers were interviewed at the PHC from February to April 2013 using a questionnaire. Data analysis was done using WHO Anthro software, Epi InfoTM and Stata. Results Fifty-three percent of the mothers were carrying the CHH at the time of the interview, similar to the proportion of mothers who were instructed to bring the CHH to health appointments. Annotations in the CHH during the visits were reported by 49%. The vaccination schedule was completed in 97% of the CHH, but only 9% and 8% of the CHH, respectively, contained growth charts and properly completed developmental milestones. Conclusion Low rates of use and unsatisfactory record-keeping in the CHH reinforce the need for investment in professional training and community awareness for the CHH to become an effective instrument of promotion of child health.

  1. Research as an event: a novel approach to promote patient-focused drug development

    Directory of Open Access Journals (Sweden)

    Tsai JH

    2018-05-01

    Full Text Available Jui-Hua Tsai, Ellen Janssen, John FP Bridges Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA Abstract: Patient groups are increasingly engaging in research to understand patients’ preferences and incorporate their perspectives into drug development and regulation. Several models of patient engagement have emerged, but there is little guidance on how to partner with patient groups to engage the disease community. Our group has been using an approach to engage patient groups that we call research as an event. Research as an event is a method for researchers to use a community-centered event to engage patients in their own environment at modest incremental cost. It is a pragmatic solution to address the challenges of engaging patients in research to minimize patients’ frustration, decrease the time burden, and limit the overall cost. The community, the event, and the research are the three components that constitute the research as an event framework. The community represents a disease-specific community. The event is a meeting of common interest for patients and other stakeholders, such as a patient advocacy conference. The research describes activities in engaging the community for the purpose of research. Research as an event follows a six-step approach. A case study is used to demonstrate the six steps followed by recommendations for future implementation. Keywords: patients’ perspectives, decision making, drug approval, patient engagement, patient organization, patients’ preference

  2. The Determinants of Research and Development Investment in the Pharmaceutical Industry: Focus on Financial Structures

    Science.gov (United States)

    Lee, Munjae; Choi, Mankyu

    2015-01-01

    Objectives This study analyzes the influence of the financial structure of pharmaceutical companies on R&D investment to create a next-generation profit source or develop relatively cost-effective drugs to maximize enterprise value. Methods The period of the empirical analysis is from 2000 to 2012. Financial statements and comments in general and internal transactions were extracted from TS-2000 of the Korea Listed Company Association (KLCA), and data related to stock price is extracted from KISVALUE-Ⅲ of NICE Information Service Co., Ltd. Stata 12.0 was used as the statistical package for panel analysis. Results The current ratio had a positive influence on R&D investment, the debt ratio had a negative influence on R&D investment, and return on investment and net sales growth rate did not have a significant influence on R&D investment. Conclusion It was found in this study that the higher liquidity ratio, the greater the R&D investment. The stability of pharmaceutical companies has a negative influence on R&D investment. This finding is consistent with the prediction that if a company faces a financial risk, it will be passive in R&D investment due to its financial difficulties. PMID:26730355

  3. A New Development in Audiovisual Translation Studies: Focus on Target Audience Perception

    Directory of Open Access Journals (Sweden)

    John Denton

    2013-03-01

    Full Text Available Audiovisual translation is now a well-established sub-discipline of Translation Studies (TS: a position that it has reached over the last twenty years or so. Italian scholars and professionals in the field have made a substantial contribution to this successful development, a brief overview of which will be given in the first part of this article, inevitably concentrating on dubbing in the Italian context. Special attention will be devoted to the question of target audience perception, an area where researchers in the University of Bologna at Forlì have excelled. The second part of the article applies the methodology followed by the above mentioned researchers in a case study of how Italian end users perceive the dubbed version of the British film The History Boys (2006, which contains a plethora of culture-specific verbal and visual references to the English education system. The aim of the study was to ascertain: a whether translation/adaptation allows the transmission in this admittedly constrained medium of all the intended culture-bound issues, only too well known to the source audience, and, if so, to what extent, and b whether the target audience respondents to the e-questionnaire used were aware that they were missing information. The linked, albeit controversial, issue of quality assessment will also be addressed.

  4. Using print focused collections development policies (CDPs) in digitally born libraries

    KAUST Repository

    Buck, Stephen

    2016-11-03

    The King Abdullah University of Science & Technology (KAUST) library is a ‘born digital’ library. The core, and vast majority, of library resources was acquired in electronic form and a smaller print collection, which complemented the wider collection, was acquired contemporaneously. The purpose of this paper is to determine whether, in conjunction with our specific print collections development policy, we need a complementary E-Resources policy. The writing of such a policy utilizes valuable resources (both staff and time) and involves itself with the sometimes vaguely defined and complex concept of collection evaluation. Issues in e-resources are constantly changing and updates will be necessary to reflect this. How, and how often, do we update our E-Resources CDP? While Biblarz (2001) maintains that the main argument for the existence of a print CDP is to prevent the library from being driven by events or by individual enthusiasms and from purchasing a random set of resources, which may not support the mission of the library this paper explores issues in maintaining a joint print and ‘E’ CDP.

  5. New developments in the combination treatment of COPD: focus on umeclidinium/vilanterol

    Directory of Open Access Journals (Sweden)

    Cazzola M

    2013-10-01

    Full Text Available Mario Cazzola,1 Andrea Segreti,1 Maria Gabriella Matera2 1Department of System Medicine, University of Rome 'Tor Vergata', Rome, Italy; 2Department of Experimental Medicine, Second University, Naples, Italy Abstract: An increasing body of evidence suggests that the long-acting muscarinic antagonist (LAMA/long-acting β2-agonist (LABA combination appears to play an important role in maximizing bronchodilation, with studies to date indicating that combining different classes of bronchodilators may result in significantly greater improvements in lung function compared to the use of a single drug, and that these combinations are well tolerated in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD. An inhaled, fixed-dose combination of two 24-hour bronchodilators, the LAMA umeclidinium and the LABA vilanterol, is under development as a once-daily treatment for COPD. The efficacy of both mono-components has already been demonstrated. The information currently available suggests that umeclidinium/vilanterol is an effective once-daily dual bronchodilator fixed-dose combination in the treatment of COPD. However, it remains to be seen if it compares favorably with current therapies. Moreover, the question remains whether umeclidinium/vilanterol fixed-dose combination, which significantly improves FEV1, is also associated with improvements in other outcome measures that are important to COPD patients. Keywords: muscarinic antagonist, dual bronchodilation, COPD

  6. Triassic Sequence Geological Development of the Arctic with focus on Svalbard and the Barents Shelf

    Energy Technology Data Exchange (ETDEWEB)

    Moerk, Atle

    1998-12-31

    Triassic rocks are of great interest for exploration in Arctic areas as they have proved to include both good hydrocarbon source rocks and potential hydrogen reservoir rocks. In this thesis, the stratigraphy and sedimentology of the Arctic Triassic successions are studied within a sequence stratigraphical framework. Inter-regional comparisons throughout the Arctic are based on comparisons of transgressive-regressive sequences. Improved dating of the studied sequences, and the recognition and correlation of sequence boundaries of second and third order, facilitate interpretation of facies distribution and the geological development both within and between the studied areas. Main emphasis is given to the Triassic succession of Svalbard and the Barents Shelf, which through this study is integrated within a circum-Arctic sequence stratigraphical framework. Good correspondence of the Triassic sequence boundaries between the different Arctic areas indicate that they are mainly controlled by eustacy, while decreasing correspondence of the sequence boundaries in the Jurassic and Cretaceous periods indicate that local and large scale tectonism becomes progressively more dominant in the circum-Arctic Realm through the Mesozoic Era. These hypotheses are further discussed. 701 refs., 110 figs., 12 tabs.

  7. The Determinants of Research and Development Investment in the Pharmaceutical Industry: Focus on Financial Structures.

    Science.gov (United States)

    Lee, Munjae; Choi, Mankyu

    2015-10-01

    This study analyzes the influence of the financial structure of pharmaceutical companies on R&D investment to create a next-generation profit source or develop relatively cost-effective drugs to maximize enterprise value. The period of the empirical analysis is from 2000 to 2012. Financial statements and comments in general and internal transactions were extracted from TS-2000 of the Korea Listed Company Association (KLCA), and data related to stock price is extracted from KISVALUE-Ⅲ of NICE Information Service Co., Ltd. Stata 12.0 was used as the statistical package for panel analysis. The current ratio had a positive influence on R&D investment, the debt ratio had a negative influence on R&D investment, and return on investment and net sales growth rate did not have a significant influence on R&D investment. It was found in this study that the higher liquidity ratio, the greater the R&D investment. The stability of pharmaceutical companies has a negative influence on R&D investment. This finding is consistent with the prediction that if a company faces a financial risk, it will be passive in R&D investment due to its financial difficulties.

  8. Using print focused collections development policies (CDPs) in digitally born libraries

    KAUST Repository

    Buck, Stephen; Vijayakumar, J.K.

    2016-01-01

    The King Abdullah University of Science & Technology (KAUST) library is a ‘born digital’ library. The core, and vast majority, of library resources was acquired in electronic form and a smaller print collection, which complemented the wider collection, was acquired contemporaneously. The purpose of this paper is to determine whether, in conjunction with our specific print collections development policy, we need a complementary E-Resources policy. The writing of such a policy utilizes valuable resources (both staff and time) and involves itself with the sometimes vaguely defined and complex concept of collection evaluation. Issues in e-resources are constantly changing and updates will be necessary to reflect this. How, and how often, do we update our E-Resources CDP? While Biblarz (2001) maintains that the main argument for the existence of a print CDP is to prevent the library from being driven by events or by individual enthusiasms and from purchasing a random set of resources, which may not support the mission of the library this paper explores issues in maintaining a joint print and ‘E’ CDP.

  9. Genes and genetic variations involved in the development of hypertension: focusing on a Greek patient cohort.

    Science.gov (United States)

    Kouremenos, Nikolaos; Zacharopoulou, Ioanna V; Triantafyllidi, Helen; Zacharopoulos, Georgios V; Mornos, Cristian; Filippatos, Gerasimos; Lekakis, John; Kremastinos, Dimitrios; Manolis, Athanasios I; Gavras, Haralambos

    2014-01-01

    Essential hypertension (HTN) is a multifactorial disease involving environmental, genetic and other factors. Over the past years, genetic studies of essential HTN have increased dramatically but the molecular mechanisms involved are still unknown. As part of a research program coordinated by Boston university (USA), we studied the role of various genes and single nucleotide polymorphisms (SNPs) in the inheritance or the onset of HTN in African-American, Caucasian-American and Greek families. Among 128 Greek families with a history of HTN, we studied 1474 people. Of the total examined, 273 men and 286 women were hypertensive. Based on 410 DNA samples from the hypertensive subjects, different SNPs were examined. An overall meta-analysis of the results from the Greek families, as well as a comparison with the 2 other groups (African-Americans and Caucasian-Americans), was performed. We report SNPs that are associated with the inheritance of HTN and are located either at the promoters of N-methyltransferase and catalase genes, or within the coding region of NEDD4L ubiquitin ligase gene, or SNPs in mitochondrial DNA of hypertensive probands. Furthermore, we clarified the role of hereditary predisposition in the development of HTN, showing that the presence of maternal HTN was significantly higher in African-Americans and Greeks compared to Caucasian-Americans (81.7%, 84.8%, and 65%), while the paternal HTN showed no such difference (50%, 48.3% and 44.9%), respectively. Although genetic factors that were correlated with HTN were identified, it was not possible to identify a single gene that should be targeted for the treatment of HTN. Nevertheless, the important role of the maternal hereditary predisposition to HTN in the Greek patients and the responsible genetic factors involved should be further examined.

  10. Development of orodispersible polymer films with focus on the solid state characterization of crystalline loperamide.

    Science.gov (United States)

    Woertz, Christina; Kleinebudde, Peter

    2015-08-01

    The formulation of active pharmaceutical ingredients (API) as orodispersible films is gaining interest among novel oral drug delivery systems due to their small size, enhanced flexibility and improved patient compliance. The aim of this work was the preparation and characterization of orodispersible films containing loperamide hydrochloride (LPH) as model drug. As loperamide hydrochloride is poorly soluble in water it was used in crystalline form with a loading of 2mg/6cm(2) film. Hydroxypropyl methylcellulose (HPMC) and different types of hydroxypropyl cellulose (HPC) in different concentrations were used as film forming polymers whereas arabic gum, xanthan gum and tragacanth served as thickening agents. Films were characterized with respect to the content uniformity, morphology, thermal behavior and crystallinity. Suspensions were investigated regarding their viscosity using a rotational rheometer and the crystal structure of the Active Pharmaceutical Ingredient (API) was analyzed using polarized light microscopy. The development of flexible, non-brittle and homogeneous films of LPH was feasible. Two polymorphic forms of LPH appeared in the film formulations dependent on the utilized polymer. While in presence of HPMC the original polymorphic form I remained stable in suspension and films, the polymorphic form II occurred in presence of HPC. Both polymorphic forms were prepared separately and a solid state characterization was performed. Polymorph I showed isometric crystals whereas polymorph II showed needle shaped crystals. Tragacanth was able to prevent the transformation to polymorph II, if it was dissolved first before HPC. When HPC was added first to the suspension, the conversion to form II occurred irreversibly also after further addition of tragacanth. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Development and statistical assessment of a paper-based immunoassay for detection of tumor markers

    Energy Technology Data Exchange (ETDEWEB)

    Mazzu-Nascimento, Thiago [Instituto de Química de São Carlos, Universidade de São Paulo, 13566-590, São Carlos, SP (Brazil); Instituto Nacional de Ciência e Tecnologia de Bioanalítica, Campinas, SP (Brazil); Morbioli, Giorgio Gianini [Instituto de Química de São Carlos, Universidade de São Paulo, 13566-590, São Carlos, SP (Brazil); Instituto Nacional de Ciência e Tecnologia de Bioanalítica, Campinas, SP (Brazil); School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332 (United States); Milan, Luis Aparecido [Departamento de Estatística, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Donofrio, Fabiana Cristina [Instituto de Ciências da Saúde, Universidade Federal de Mato Grosso, 78557-267, Sinop, MT (Brazil); Mestriner, Carlos Alberto [Wama Produtos para Laboratório Ltda, 13560-971, São Carlos, SP (Brazil); Carrilho, Emanuel, E-mail: emanuel@iqsc.usp.br [Instituto de Química de São Carlos, Universidade de São Paulo, 13566-590, São Carlos, SP (Brazil); Instituto Nacional de Ciência e Tecnologia de Bioanalítica, Campinas, SP (Brazil)

    2017-01-15

    Paper-based assays are an attractive low-cost option for clinical chemistry testing, due to characteristics such as short time of analysis, low consumption of samples and reagents, and high portability of assays. However, little attention has been given to the evaluation of the performance of these simple tests, which should include the use of a statistical approach to define the choice of best cut-off value for the test. The choice of the cut-off value impacts on the sensitivity and specificity of the bioassay. Here, we developed a paper-based immunoassay for the detection of the carcinoembryonic antigen (CEA) and performed a statistical assessment to establish the assay's cut-off value using the Youden's J index (68.28 A.U.), what allowed for a gain in sensibility (0.86) and specificity (1.0). We also discuss about the importance of defining a gray zone as a safety margin for test (±12% over the cut-off value), eliminating all false positives and false negatives outcomes and avoiding misleading results. The test accuracy was calculated as the area under the curve (AUC) of the receiver operating characteristic (ROC) curve, presenting a value of 0.97, what classifies this test as highly accurate. We propose here a low-cost method capable of detecting carcinoembryonic antigen (CEA) in human serum samples, highlighting the importance of statistical tools to evaluate a new low-cost diagnostic method. - Highlights: • A paper-based sandwich immunoassay protocol for detection of tumor markers. • A statistical approach to define cut-off values and measuring test's sensitivity, specificity and accuracy. • A simple way to create a gray zone, avoiding false positive and false negative outcomes.

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

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  13. [Development of a Computer-aided Diagnosis System to Distinguish between Benign and Malignant Mammary Tumors in Dynamic Magnetic Resonance Images: Automatic Detection of the Position with the Strongest Washout Effect in the Tumor].

    Science.gov (United States)

    Miyazaki, Yoshiaki; Tabata, Nobuyuki; Taroura, Tomomi; Shinozaki, Kenji; Kubo, Yuichiro; Tokunaga, Eriko; Taguchi, Kenichi

    We propose a computer-aided diagnostic (CAD) system that uses time-intensity curves to distinguish between benign and malignant mammary tumors. Many malignant tumors show a washout pattern in time-intensity curves. Therefore, we designed a program that automatically detects the position with the strongest washout effect using the technique, such as the subtraction technique, which extracts only the washout area in the tumor, and by scanning data in 2×2 pixel region of interest (ROI). Operation of this independently developed program was verified using a phantom system that simulated tumors. In three cases of malignant tumors, the washout pattern detection rate in images with manually set ROI was ≤6%, whereas the detection rate with our novel method was 100%. In one case of a benign tumor, when the same method was used, we checked that there was no washout effect and detected the persistent pattern. Thus, the distinction between benign and malignant tumors using our method was completely consistent with the pathological diagnoses made. Our novel method is therefore effective for differentiating between benign and malignant mammary tumors in dynamic magnetic resonance images.

  14. The role of mirror focus in the surgical outcome of patients with indolent temporal lobe tumors Epilepsia do lobo temporal por processos expansivos e epileptogênese secundária

    Directory of Open Access Journals (Sweden)

    Leticia Sampaio

    2004-03-01

    Full Text Available PURPOSE: To review the clinical and neurophysiological data of 21 patients with epilepsy due to temporal lobe tumors and who had undergone evaluation and surgery at the Hospital das Clínicas da Universidade de São Paulo. The aim of this study was to investigate whether the occurrence of a mirror focus was influenced either by certain clinical factors or if the surgical outcome was influenced by the presence of a mirror focus. METHOD: We included these 21 patients who had undergone at least one interictal electroencephalogram in the pre- and post-surgical periods. They had had a minimum follow-up of one year. RESULTS: Eight patients had mirror focus (Group 1 and 13 did not (Group 2. The mean age at seizure onset, duration of epilepsy disorder and total number of seizures did not vary statistically between the two groups of patients. Generalized tonic-clonic seizures occurred more frequently in the mirror focus group. All, but one patient, with a mirror focus were seizure free at follow- up. The mirror focus disappeared in all eight patients in the post-surgical electroencephalogram. In this group, the patient who was not seizure - free had a seizure recorded in his post-surgical electroencephalogram with seizure onset ipsilateral to the resected tumor. The patients who were not seizure-free had either been submitted to an incomplete resection of the tumor or showed evidence of associated cortical dysplasia. CONCLUSION: The occurrence of mirror focus is not a contraindication to surgery even when interictal epileptiform activity predominates contralaterally to the tumor and neither when seizures appear to arise from the mirror focus on scalp EEG. Good surgical outcome is expected despite EEG findings that may conflict with tumor location.INTRODUÇÃO: A epileptogênese secundária é descrita como fenômeno em que, uma área epileptogênica primária, geradora de descargas, através de conexões neuroniais com outra área não acometida, pode

  15. [Pure gonad dysgenesia or Swyer sindrome. A case report having tumoral development: melanoma].

    Science.gov (United States)

    Russo, D; Blanco, M; Falke, G; Rocca Rivarola, M; Séller, R; Puigdevall, J C; Bergada, C

    2006-10-01

    A 14 year old girl having 10-days lumbar pain, polaquiuria and moderate pain to palpation is reported. Blood and urine analysis were normal. Abdominal ultrasound scan showed cavity free and solid, rounded, heterogeneous, intrapelvic mass compressing bladder and uterus. Magnetic resonance image was performed showing right gonad compromise with extensive liver and sacro-lumbar spine invasion. Tumoral markers were ruled out. During surgery, primary tumor mass localizad in the right gonad was completely excised. Melanotic peritoneal and hepatic disemination were observed. The patient had left streak gonad and infantile uterus (2 x 3 cm). As gonad dysgenesia was suspected, high resolution cromosomic study was performed and resulted in cariotype 46 XY. Microscopy of the resected gonad showed primary gonad melanoma. Chemotherapy was instituted with no tumor response and the patient died two month later.

  16. [Specific features of mammographic visualization of "small" breast tumors developing on the background of fibrocystic disease].

    Science.gov (United States)

    Bukharin, D G; Velichko, S A; Slonimskaia, E M; Frolova, I G; Luneva, S V; Garbukov, E Iu; Doroshenko, A V

    2011-01-01

    All complications diagnosed at early stages of breast cancer were associated with small tumors, especially with those arising in the aftermath of fibrocystic disease. Hence, our task was to study the XR-semiotics of lesions of less than 15 mm in diameter and of the same origin. 100 mammograms of breast cancer patients with benign disease of the breast were studied. The presence of moderate-to-severe fibrocystic disease significantly affected the visualization of lesions of less than 10 mm in diameter. Since the XR-semiotics of small tumors failed to reveal malignancy features, all lesions visualized by mammography required additional diagnostic procedures using ultrasound and invasive radiology.

  17. The evaluation of a clinical development unit leadership preparation program by focus group interviews - part 2: negative aspects.

    Science.gov (United States)

    Greenwood, Jennifer; Parsons, Myra

    2002-10-01

    In Western Sydney, Australia, in 1996, the Area Health Service and the University of Western Sydney entered a strategic alliance to develop a nursing research culture in the health services. One of the strategies implemented to achieve this was the establishment of a network of research-receptive environments known as Clinical Development Units (CDUs). In terms of research receptivity, evidence at the time suggested that it could only be developed in units where the leadership style is democratic and participatory. In terms of CDUs, evidence suggested that their successful development depended critically on the effective management of CDU leadership stressors. In light of this, it was agreed to conduct a CDU leadership preparation program in Western Sydney. The program aimed to furnish CDU leaders with the participatory leadership skills required to develop and manage their units. It was expected that the acquisition of such leadership skills would serve to minimize the leadership stessors they could expect to experience. This is the second of two papers which report course evaluation data. The first focused on the more positive evaluation data; this paper focuses on the negative evaluation data and outlines how the current program has been modified in light of these data. In addition, it discusses two themes which emerged during data analysis. These were nurses' apparent mutual lack of trust and their pressing needs to be recognized as valuable and merit-worthy.

  18. Resolving tumor heterogeneity: genes involved in chordoma cell development identified by low-template analysis of morphologically distinct cells.

    Directory of Open Access Journals (Sweden)

    Amin El-Heliebi

    Full Text Available The classical sacrococcygeal chordoma tumor presents with a typical morphology of lobulated myxoid tumor tissue with cords, strands and nests of tumor cells. The population of cells consists of small non-vacuolated cells, intermediate cells with a wide range of vacuolization and large heavily vacuolated (physaliferous cells. To date analysis was only performed on bulk tumor mass because of its rare incidence, lack of suited model systems and technical limitations thereby neglecting its heterogeneous composition. We intended to clarify whether the observed cell types are derived from genetically distinct clones or represent different phenotypes. Furthermore, we aimed at elucidating the differences between small non-vacuolated and large physaliferous cells on the genomic and transcriptomic level. Phenotype-specific analyses of small non-vacuolated and large physaliferous cells in two independent chordoma cell lines yielded four candidate genes involved in chordoma cell development. UCHL3, coding for an ubiquitin hydrolase, was found to be over-expressed in the large physaliferous cell phenotype of MUG-Chor1 (18.7-fold and U-CH1 (3.7-fold cells. The mannosyltransferase ALG11 (695-fold and the phosphatase subunit PPP2CB (18.6-fold were found to be up-regulated in large physaliferous MUG-Chor1 cells showing a similar trend in U-CH1 cells. TMEM144, an orphan 10-transmembrane family receptor, yielded contradictory data as cDNA microarray analysis showed up- but RT-qPCR data down-regulation in large physaliferous MUG-Chor1 cells. Isolation of few but morphologically identical cells allowed us to overcome the limitations of bulk analysis in chordoma research. We identified the different chordoma cell phenotypes to be part of a developmental process and discovered new genes linked to chordoma cell development representing potential targets for further research in chordoma tumor biology.

  19. Development of new mouse lung tumor models expressing EGFR T790M mutants associated with clinical resistance to kinase inhibitors.

    Science.gov (United States)

    Regales, Lucia; Balak, Marissa N; Gong, Yixuan; Politi, Katerina; Sawai, Ayana; Le, Carl; Koutcher, Jason A; Solit, David B; Rosen, Neal; Zakowski, Maureen F; Pao, William

    2007-08-29

    The EGFR T790M mutation confers acquired resistance to kinase inhibitors in human EGFR mutant lung adenocarcinoma, is occasionally detected before treatment, and may confer genetic susceptibility to lung cancer. To study further its role in lung tumorigenesis, we developed mice with inducible expression in type II pneumocytes of EGFR(T790M) alone or together with a drug-sensitive L858R mutation. Both transgenic lines develop lung adenocarcinomas that require mutant EGFR for tumor maintenance but are resistant to an EGFR kinase inhibitor. EGFR(L858R+T790M)-driven tumors are transiently targeted by hsp90 inhibition. Notably, EGFR(T790M)-expressing animals develop tumors with longer latency than EGFR(L858R+T790M)-bearing mice and in the absence of additional kinase domain mutations. These new mouse models of mutant EGFR-dependent lung adenocarcinomas provide insight into clinical observations. The models should also be useful for developing improved therapies for patients with lung cancers harboring EGFR(T790M) alone or in conjunction with drug-sensitive EGFR kinase domain mutations.

  20. Development of new mouse lung tumor models expressing EGFR T790M mutants associated with clinical resistance to kinase inhibitors.

    Directory of Open Access Journals (Sweden)

    Lucia Regales

    2007-08-01

    Full Text Available The EGFR T790M mutation confers acquired resistance to kinase inhibitors in human EGFR mutant lung adenocarcinoma, is occasionally detected before treatment, and may confer genetic susceptibility to lung cancer.To study further its role in lung tumorigenesis, we developed mice with inducible expression in type II pneumocytes of EGFR(T790M alone or together with a drug-sensitive L858R mutation. Both transgenic lines develop lung adenocarcinomas that require mutant EGFR for tumor maintenance but are resistant to an EGFR kinase inhibitor. EGFR(L858R+T790M-driven tumors are transiently targeted by hsp90 inhibition. Notably, EGFR(T790M-expressing animals develop tumors with longer latency than EGFR(L858R+T790M-bearing mice and in the absence of additional kinase domain mutations.These new mouse models of mutant EGFR-dependent lung adenocarcinomas provide insight into clinical observations. The models should also be useful for developing improved therapies for patients with lung cancers harboring EGFR(T790M alone or in conjunction with drug-sensitive EGFR kinase domain mutations.

  1. Recent developments: Washington focus

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    Congress continued to work on the budget during April with small breaks to attend Earth Day activities to acknowledge the public's growing environmental conscience. The House Budget Committee once again raised to 100 percent the portion of the Nuclear Regulatory Commission's (NRC) budget to be funded through user fees. However, the Senate Budget Committee authorized continuation of the current 45-percent user fee funding. The full House approved the budget resolution on May 1. The Senate may act sometime in May

  2. Recent developments: Washington focus

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    Congress has made progress on key legislation this summer. The House of Representatives passed an appropriations bill which authorizes spending for DOE and the NRC for FY91. The Senate has yet to consider an energy appropriations bill, but as the House bill exceeds the administration request for funding by $575 million, it will likely experience substantial cuts before its final passage. At the end of the month, the Senate Energy ampersand Natural Resources Committee held a hearing on the Smith Barney report on the Uranium Enrichment Enterprise. Since the Senate has already passed a uranium enrichment restructuring bill, attention has shifted to the House where some Representatives have expressed interest in holding a hearing on the report. After almost a month's delay, the House has named its representatives to the Clean Air Act Conference Committee. The Senate will have nine committee members, and the House will have 142 conferees from seven committees. Final action on the clean air bill is likely before November's Congressional elections. Finally, although it appeared the utilities had a chance to hold their payment of NRC user fees at 45 percent of the NRC's budget level, President Bush's decision to discuss taxes as part of the budget negotiations increases the likelihood of higher user fees-possibly as high as 100 percent of the NRC budget. The American Nuclear Energy Council (ANEC) estimates that the President's proposal to recover 100 percent of the NRC's budget through user fees is the second largest revenue item among the user fees proposed

  3. Recent developments: Washington focus

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    November was a quiet month in Washington. Although Congress has recessed until 1991, the Senate filled vacancies in party leadership positions created by November's elections. The House is expected to proceed with its changes in early December. The Nuclear Energy Forum was held in Washington, DC on November 11-14 to discuss the status of the nuclear industry in the USA. The Forum, held in conjunction with the American Nuclear Society's annual meeting, assembled a large number of CEO's from US, European, and Far Eastern utilities and vendors. The meeting concluded with an announcement by Philip Bayne, President of NYPA and chairman of the Nuclear Power Oversight Committee (NPOC), of the results of a year-long NPOC study entitled a open-quotes Strategic Plan for Building New Nuclear Power Plants.close quotes

  4. Recent developments: Washington focus

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    Congress reconvened on January 23, but most of Washington's January new involves the Administration. DOE sent two letters to USEC customers, awarded a contract for the independent financial review of the enrichment program, and released a plan for demonstrating AVLIS by 1992. A General Accounting Office (GAO) report investigating the impact of imports of Soviet EUP into the US was made public. Both Congress and the administration are reportedly considering a full-scope US-Soviet Agreement for Nuclear Cooperation. Finally, published reports indicate Congress may consider ending the customs user fee which levies a charge of 0.17% on the value of all imported goods. The fee is felt to violate the General Agreement on Tariffs and Trade (GATT) and is not based on recovering actual Customs costs for processing a good. The fee brings the Treasury over $700 million per year, but the business community plans to lobby hard for its outright elimination or a change in authority to collect the fee based on actual costs

  5. A clinical reasoning model focused on clients' behaviour change with reference to physiotherapists: its multiphase development and validation.

    Science.gov (United States)

    Elvén, Maria; Hochwälder, Jacek; Dean, Elizabeth; Söderlund, Anne

    2015-05-01

    A biopsychosocial approach and behaviour change strategies have long been proposed to serve as a basis for addressing current multifaceted health problems. This emphasis has implications for clinical reasoning of health professionals. This study's aim was to develop and validate a conceptual model to guide physiotherapists' clinical reasoning focused on clients' behaviour change. Phase 1 consisted of the exploration of existing research and the research team's experiences and knowledge. Phases 2a and 2b consisted of validation and refinement of the model based on input from physiotherapy students in two focus groups (n = 5 per group) and from experts in behavioural medicine (n = 9). Phase 1 generated theoretical and evidence bases for the first version of a model. Phases 2a and 2b established the validity and value of the model. The final model described clinical reasoning focused on clients' behaviour change as a cognitive, reflective, collaborative and iterative process with multiple interrelated levels that included input from the client and physiotherapist, a functional behavioural analysis of the activity-related target behaviour and the selection of strategies for behaviour change. This unique model, theory- and evidence-informed, has been developed to help physiotherapists to apply clinical reasoning systematically in the process of behaviour change with their clients.

  6. Development of a Prognostic Marker for Lung Cancer Using Analysis of Tumor Evolution

    Science.gov (United States)

    2016-08-01

    Bambanker cell freezing medium (Lymphotec Inc., Tokyo, Japan ). Prior to FACS, isolated tumor cells were stained with mouse anti-human CD45RA PE/Cy7... clone L48, BD Biosciences, San Jose, CA) and Aqua Vital Dye (Invitrogen, Carlsbad, CA). CD45 is a blood cell marker used to separate blood cells from

  7. A case of mesodermic mixed tumor of the uterus developing after the treatment of myoma with x-ray irradiation

    International Nuclear Information System (INIS)

    Hiura, Masamichi; Mano, Atsuo; Egawa, Kenshi; Katsube, Yasuhiro; Sasaki, Takahiro

    1975-01-01

    A case of mesodermic mixed tumor primarily developing in the endometrium was reported with some discussion. The anamnesis was interesting that the patient had been exposed to the secondary radioactivity of the atomic bomb in Hiroshima and to X-ray for the treatment of myoma. Histological examination revealed adenoma as the epithelial element and fibromyxoma-like tissues, cartilage tissues, vascular tissues, and endometrial interstitium-like tissues as the non-epithelial elements. (Chiba, N.)

  8. Case of mesodermic mixed tumor of the uterus developing after the treatment of myoma with x-ray irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Hiura, M; Mano, A; Egawa, K; Katsube, Y; Sasaki, T [Hiroshima Univ. (Japan). School of Medicine

    1975-06-01

    A case of mesodermic mixed tumor primarily developing in the endometrium was reported with some discussion. The anamnesis was interesting that the patient had been exposed to the secondary radioactivity of the atomic bomb in Hiroshima and to X-ray for the treatment of myoma. Histological examination revealed adenoma as the epithelial element and fibromyxoma-like tissues, cartilage tissues, vascular tissues, and endometrial interstitium-like tissues as the non-epithelial elements.

  9. Focus: Digital

    DEFF Research Database (Denmark)

    Technology has been an all-important and defining element within the arts throughout the 20th century, and it has fundamentally changed the ways in which we produce and consume music. With this Focus we investigate the latest developments in the digital domain – and their pervasiveness and rapid...... production and reception of contemporary music and sound art. With ‘Digital’ we present four composers' very different answers to how technology impact their work. To Juliana Hodkinson it has become an integral part of her sonic writing. Rudiger Meyer analyses the relationships between art and design and how...

  10. Development of nano radiopharmaceutical based on Bevacizumab labelled with Technetium-99m for early diagnosis of gastrointestinal stromal tumor

    International Nuclear Information System (INIS)

    Braga, Thais Ligiero

    2015-01-01

    The development of new radiopharmaceuticals is an essential activity to improve nuclear medicine, and essential for the early and effective diagnosis of oncological diseases. Among the various possibilities current research in the world, the radiopharmaceuticals to chemotherapeutic base may be the most effective in detecting tumors, particularly Gastrointestinal Stromal Tumor (GIST), the Metastatic Renal Cell Carcinoma and neuroendocrine pancreatic tumors. However, difficulties in directing, as well as adhesion of the radiopharmaceutical in the desired location, are currently the main problems in the early detection and treatment of some of these tumors. Advances in the field of nanotechnology, particularly in recent years, indicate significant contribution to overcoming these obstacles, particularly in the implementation of molecular barriers as well as the functionalization of the nanoparticles, thereby improving targeting by the use of surface nucleotides, and the increased adhesion, which facilitates the release of the drug and therefore increases the chances of early diagnosis and more effective treatment. This study aimed to the production, characterization and evaluation of cytotoxicity, as well as in vivo biodistribution test Bevacizumab nanoparticles labeled with Technetium-99m radionuclide for detection of type GIST tumors. Bevacizumab was encapsulated in the form of nanoparticles by the emulsification method using double poly-acetic acid and polyvinyl alcohol polymers (PLA / PVA) at a concentration of 2% of the monoclonal antibody. The characterization of the nanoparticles was performed by the technique of scanning electron microscopy (SEM). The cytotoxicity assessment was performed by XTT assay with various cell lines of solid tumor cells. The labeling with technetium-99m was done by the direct method, and its yield determined by paper chromatography using paper Whatmam 1 as the stationary phase and acetone as mobile phase. In the biodistribution study

  11. Alterations of the Blood-Brain Barrier and Regional Perfusion in Tumor Development: MRI Insights from a Rat C6 Glioma Model.

    Science.gov (United States)

    Huhndorf, Monika; Moussavi, Amir; Kramann, Nadine; Will, Olga; Hattermann, Kirsten; Stadelmann, Christine; Jansen, Olav; Boretius, Susann

    2016-01-01

    Angiogenesis and anti-angiogenetic medications play an important role in progression and therapy of glioblastoma. In this context, in vivo characterization of the blood-brain-barrier and tumor vascularization may be important for individual prognosis and therapy optimization. We analyzed perfusion and capillary permeability of C6-gliomas in rats at different stages of tumor-growth by contrast enhanced MRI and dynamic susceptibility contrast (DSC) MRI at 7 Tesla. The analyses included maps of relative cerebral blood volume (CBV) and signal recovery derived from DSC data over a time period of up to 35 days after tumor cell injections. In all rats tumor progression was accompanied by temporal and spatial changes in CBV and capillary permeability. A leakage of the blood-brain barrier (slow contrast enhancement) was observed as soon as the tumor became detectable on T2-weighted images. Interestingly, areas of strong capillary permeability (fast signal enhancement) were predominantly localized in the center of the tumor. In contrast, the tumor rim was dominated by an increased CBV and showed the highest vessel density compared to the tumor center and the contralateral hemisphere as confirmed by histology. Substantial regional differences in the tumor highlight the importance of parameter maps in contrast or in addition to region-of-interest analyses. The data vividly illustrate how MRI including contrast-enhanced and DSC-MRI may contribute to a better understanding of tumor development.

  12. Tumor immunology.

    Science.gov (United States)

    Mocellin, Simone; Lise, Mario; Nitti, Donato

    2007-01-01

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

  13. DEVELOPING ONLINE CO-CREATION INSTRUMENTS BASED ON A FOCUS GROUP APPROACH: THE E-PICUS CASE

    Directory of Open Access Journals (Sweden)

    ALEXA Lidia

    2016-09-01

    Full Text Available The current business environment is in constant change, characterized by increased competition and in order to remain relevant and to create products and services that respond better to the customers’ needs and expectations, companies need to become more innovative and proactive. To address the competitive challenges, more and more companies are using innovation co-creation where all the relevant stakeholders are participating across the value chain, from idea generation, selection, development and eventually, even to marketing the new products or services.The paper presents the process of developing an online cocreation. The platform, within the framework of a research project, underlying the importance of using a focus group approach for requirements elicitation in IT instruments development.

  14. Bone tumors

    International Nuclear Information System (INIS)

    Unni, K.K.

    1988-01-01

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

  15. Factors influencing the development of end-of-life communication skills: A focus group study of nursing and medical students.

    Science.gov (United States)

    Gillett, Karen; O'Neill, Bernadette; Bloomfield, Jacqueline G

    2016-01-01

    Poor communication between health care professionals and dying patients and their families results in complaints about end-of-life care. End-of-life communication skills should be a core part of nursing and medical education but research suggests that qualified doctors and nurses find this a challenging area of practice. The aim of this study was to explore factors influencing the development of end-of-life communication skills by nursing and medical students. A qualitative study comprising five focus groups. Second year undergraduate nursing (n=9 across 2 focus groups) and fourth year undergraduate medical students (n=10 across 3 focus groups) from a London University. Barriers and facilitators influenced nursing and medical students' experience of communication with dying patients and their families in clinical practice. Extrinsic barriers included gatekeeping by qualified staff and lack of opportunity to make sense of experiences through discussion. Intrinsic barriers included not knowing what to say, dealing with emotional responses, wasting patients' time, and concerns about their own ability to cope with distressing experiences. Facilitating factors included good role models, previous experience, and classroom input. In addition to clinical placements, formal opportunities for reflective discussion are necessary to facilitate the development of students' confidence and skills in end-of-life communication. For students and mentors to view end-of-life communication as a legitimate part of their learning it needs to be specified written practice-learning outcome. Mentors and supervisors may require training to enable them to facilitate students to develop end-of-life communication skills. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Development of novel murine mammary imaging windows to examine wound healing effects on leukocyte trafficking in mammary tumors with intravital imaging.

    Science.gov (United States)

    Sobolik, Tammy; Su, Ying-Jun; Ashby, Will; Schaffer, David K; Wells, Sam; Wikswo, John P; Zijlstra, Andries; Richmond, Ann

    2016-01-01

    We developed mammary imaging windows (MIWs) to evaluate leukocyte infiltration and cancer cell dissemination in mouse mammary tumors imaged by confocal microscopy. Previous techniques relied on surgical resection of a skin flap to image the tumor microenvironment restricting imaging time to a few hours. Utilization of mammary imaging windows offers extension of intravital imaging of the tumor microenvironment. We have characterized strengths and identified some previously undescribed potential weaknesses of MIW techniques. Through iterative enhancements of a transdermal portal we defined conditions for improved quality and extended confocal imaging time for imaging key cell-cell interactions in the tumor microenvironment.

  17. Development of a prototype clinical decision support tool for osteoporosis disease management: a qualitative study of focus groups

    Directory of Open Access Journals (Sweden)

    Newton David

    2010-07-01

    Full Text Available Abstract Background Osteoporosis affects over 200 million people worldwide, and represents a significant cost burden. Although guidelines are available for best practice in osteoporosis, evidence indicates that patients are not receiving appropriate diagnostic testing or treatment according to guidelines. The use of clinical decision support systems (CDSSs may be one solution because they can facilitate knowledge translation by providing high-quality evidence at the point of care. Findings from a systematic review of osteoporosis interventions and consultation with clinical and human factors engineering experts were used to develop a conceptual model of an osteoporosis tool. We conducted a qualitative study of focus groups to better understand physicians' perceptions of CDSSs and to transform the conceptual osteoporosis tool into a functional prototype that can support clinical decision making in osteoporosis disease management at the point of care. Methods The conceptual design of the osteoporosis tool was tested in 4 progressive focus groups with family physicians and general internists. An iterative strategy was used to qualitatively explore the experiences of physicians with CDSSs; and to find out what features, functions, and evidence should be included in a working prototype. Focus groups were conducted using a semi-structured interview guide using an iterative process where results of the first focus group informed changes to the questions for subsequent focus groups and to the conceptual tool design. Transcripts were transcribed verbatim and analyzed using grounded theory methodology. Results Of the 3 broad categories of themes that were identified, major barriers related to the accuracy and feasibility of extracting bone mineral density test results and medications from the risk assessment questionnaire; using an electronic input device such as a Tablet PC in the waiting room; and the importance of including well-balanced information in

  18. Some regularities in the development of radiation tumors of the stomach and intestine

    International Nuclear Information System (INIS)

    Lebedeva, G.A.

    1978-01-01

    It was shown on dogs and rats that gastric and intestinal neoplasms arise under the influence of different kinds of radiation, these may be located in all portions of the stomach and bowel and are of a different histological origin. They are not infrequently primary multiple, mostly benign neoplasms which show multicentric growth. The frequency of tumors appearence, their localization, an average latent period, the degree of malignancy and multiplicity are conditioned by the amount of tissue dosage, the topography of their distribution in the alimentary tract and the level of whole-body irradiation. With the increased dosage of local irradiation the latent period and multiplicity are decreased, while the incidence of malignancy raises. The optimum levels of the tissue dosage and the time of maximum tumor appearance were determined for each type of radiation

  19. Focusing horn

    CERN Multimedia

    1980-01-01

    This was the first magnetic horn developed by Simon Van der Meer to collect antiprotons in the AD complex. It was used for the AA (antiproton accumulator). Making an antiproton beam took a lot of time and effort. Firstly, protons were accelerated to an energy of 26 GeV/c (protons at 26GeV/c, antiprotons at 3.6GeV/c) in the PS and ejected onto a metal target. From the spray of emerging particles, a magnetic horn picked out 3.6 GeV antiprotons for injection into the AA through a wide-aperture focusing quadrupole magnet. For a million protons hitting the target, just one antiproton was captured, 'cooled' and accumulated. It took 3 days to make a beam of 3 x 10^11 -, three hundred thousand million - antiprotons. The development of this technology was a key step to the functioning of CERN's Super Proton Synchrotron as a proton - antiproton collider.

  20. Focus groups for developing a peer mentoring program to improve self-management in pediatric inflammatory bowel disease.

    Science.gov (United States)

    Mackner, Laura M; Ruff, Jessica M; Vannatta, Kathryn

    2014-10-01

    Inflammatory bowel disease (IBD) presents challenges for self-management in many areas. A peer mentoring program may offer advantages over other forms of self-management interventions because youth may be more receptive to learning self-management skills from a peer than from a parent or professional. The purpose of the present study was to identify themes from focus groups to inform development of a peer mentoring program for improving self-management in pediatric IBD. Focus groups were conducted for youth ages 12 to 17, stratified by age (3 groups; n = 14), young adults ages 18 to 20 (1 group; n = 5), and parents of the youth (3 groups; n = 17). Broad questions covered program goals, general program characteristics, mentor/mentee characteristics, and family involvement, and transcriptions were analyzed via directed content analysis, with the a priori codes specified as the broad questions above. Participants identified the primary goals of a program as support, role model, information/education, and fun. They described a program that would include a year-long, 1-on-1 mentor relationship with a peer who has had IBD for at least a year, educational group activities, fun activities that are not focused on IBD, expectations for in-person contact 1 to 2 times per month, and mentor-to-mentor and parent support. Many of the suggestions from the focus groups correspond with research findings associated with successful mentoring programs. Using participants' suggestions and empirically based best practices for mentoring may result in an effective peer mentoring program for improving self-management in youth with IBD.

  1. Breast cancer instructs dendritic cells to prime interleukin 13–secreting CD4+ T cells that facilitate tumor development

    Science.gov (United States)

    Aspord, Caroline; Pedroza-Gonzalez, Alexander; Gallegos, Mike; Tindle, Sasha; Burton, Elizabeth C.; Su, Dan; Marches, Florentina; Banchereau, Jacques; Palucka, A. Karolina

    2007-01-01

    We previously reported (Bell, D., P. Chomarat, D. Broyles, G. Netto, G.M. Harb, S. Lebecque, J. Valladeau, J. Davoust, K.A. Palucka, and J. Banchereau. 1999. J. Exp. Med. 190: 1417–1426) that breast cancer tumors are infiltrated with mature dendritic cells (DCs), which cluster with CD4+ T cells. We now show that CD4+ T cells infiltrating breast cancer tumors secrete type 1 (interferon γ) as well as high levels of type 2 (interleukin [IL] 4 and IL-13) cytokines. Immunofluorescence staining of tissue sections revealed intense IL-13 staining on breast cancer cells. The expression of phosphorylated signal transducer and activator of transcription 6 in breast cancer cells suggests that IL-13 actually delivers signals to cancer cells. To determine the link between breast cancer, DCs, and CD4+ T cells, we implanted human breast cancer cell lines in nonobese diabetic/LtSz-scid/scid β2 microglobulin–deficient mice engrafted with human CD34+ hematopoietic progenitor cells and autologous T cells. There, CD4+ T cells promote early tumor development. This is dependent on DCs and can be partially prevented by administration of IL-13 antagonists. Thus, breast cancer targets DCs to facilitate its development. PMID:17438063

  2. A rationally designed combined treatment with an alphavirus-based cancer vaccine, sunitinib and low-dose tumor irradiation completely blocks tumor development

    NARCIS (Netherlands)

    Draghiciu, Oana; Boerma, Annemarie; Hoogeboom, Baukje Nynke; Nijman, Hans W.; Daemen, Toos

    2015-01-01

    The clinical efficacy of therapeutic cancer vaccines remains limited. For effective immunotherapeutic responses in cancer patients, multimodal approaches capable of both inducing antitumor immune responses and bypassing tumor-mediated immune escape seem essential. Here, we report on a combination

  3. Molecular pathways undergoing dramatic transcriptomic changes during tumor development in the human colon

    Directory of Open Access Journals (Sweden)

    Maglietta Rosalia

    2012-12-01

    Full Text Available Abstract Background The malignant transformation of precancerous colorectal lesions involves progressive alterations at both the molecular and morphologic levels, the latter consisting of increases in size and in the degree of cellular atypia. Analyzing preinvasive tumors of different sizes can therefore shed light on the sequence of these alterations. Methods We used a molecular pathway-based approach to analyze transcriptomic profiles of 59 colorectal tumors representing early and late preinvasive stages and the invasive stage of tumorigenesis. Random set analysis was used to identify biological pathways enriched for genes differentially regulated in tumors (compared with 59 samples of normal mucosa. Results Of the 880 canonical pathways we investigated, 112 displayed significant tumor-related upregulation or downregulation at one or more stages of tumorigenesis. This allowed us to distinguish between pathways whose dysregulation is probably necessary throughout tumorigenesis and those whose involvement specifically drives progression from one stage to the next. We were also able to pinpoint specific changes within each gene set that seem to play key roles at each transition. The early preinvasive stage was characterized by cell-cycle checkpoint activation triggered by DNA replication stress and dramatic downregulation of basic transmembrane signaling processes that maintain epithelial/stromal homeostasis in the normal mucosa. In late preinvasive lesions, there was also downregulation of signal transduction pathways (e.g., those mediated by G proteins and nuclear hormone receptors involved in cell differentiation and upregulation of pathways governing nuclear envelope dynamics and the G2>M transition in the cell cycle. The main features of the invasive stage were activation of the G1>S transition in the cell cycle, upregulated expression of tumor-promoting microenvironmental factors, and profound dysregulation of metabolic pathways (e

  4. Development of Y-shaped peptide for constructing nanoparticle systems targeting tumor-associated macrophages in vitro and in vivo

    International Nuclear Information System (INIS)

    Yan, Lu; Gao, Yunxiang; Pierce, Ryan; Dai, Liming; Kim, Julian; Zhang, Mei

    2014-01-01

    Tumor-associated macrophage (TAM) is increasingly being viewed as a target of great interest in tumor microenvironment due to its important role in the progression and metastasis of cancers. It has been shown that TAM indeed overexpresses unique surface marker legumain. In this study, we designed and synthesized a Y-shaped legumain-targeting peptide (Y-Leg) with functional groups allowing for further conjugation with imaging and therapeutic moieties (vide infra). The in vitro cell experiments using FITC-conjugated Y-Leg revealed its specific and selective interaction with M2-polarized macrophages (i.e., TAMs) with preference to M1 macrophages, and that the interaction was not interfered with by conjugating FITC to its functional group. Further, we constructed a nanotube system by grafting Y-Leg onto oxidized carbon nanotubes (OCNTs) loaded with paramagnetic Fe 3 O 4 nanoparticles. The intravenous injection of the resultant Y-Leg-OCNT/Fe 3 O 4 nanotubes to 4T1 mammary tumor-bearing mouse led to the magnetic resonance imaging (MRI) of TAM-infiltrated tumor microenvironment, revealing the targeting specificity of Y-Leg-conjugated nanotubes in vivo. The Y shape of peptide and its functional groups containing amines and imidazole can protonate at different pHs, contributing to the in vitro and in vivo targeting specificity. This study represents the first development of novel peptide and peptide-grafted nanotube system targeting M2-polarized TAMs in vivo. The methodology developed in this study is applicable to the construction of various multifunctional nanoparticle systems for selectively targeting, imaging and manipulating of TAMs for the diagnosis and treatment of cancers and inflammatory diseases identified with macrophage-infiltrated disease tissue. (papers)

  5. Using Exploratory Focus Groups to Inform the Development of Targeted COPD Self-Management Education DVDs for Rural Patients

    Directory of Open Access Journals (Sweden)

    Michael Stellefson

    2010-01-01

    Full Text Available This exploratory study assessed the self-management learning needs, experiences, and perspectives of COPD patients treated at a Certified Federal Rural Health Clinic to inform the development of a COPD self-management DVD. A purposive, homogeneous sample of COPD patients participated in focus group interviews. Data from these interviews were referenced to edit a library of Rvision COPD self-management DVDs into a single condensed DVD containing only the most pertinent self-management topics. Patients reported a lack of knowledge and skill development related to purse lipped breathing, controlled coughing, and stress management; while medication management skills were found to be quite adequate. Engaging rural communities in formal qualitative inquiries to describe COPD specific needs for self-management may lead to future use of educational technologies aimed at improving quality of life for these rural, hard to reach populations.

  6. Development of nanometer resolution C-Band radio frequency beam position monitors in the Final Focus Test Beam

    International Nuclear Information System (INIS)

    Slaton, T.; Mazaheri, G.

    1998-08-01

    Using a 47 GeV electron beam, the Final Focus Test Beam (FFTB) produces vertical spot sizes around 70 nm. These small beam sizes introduce an excellent opportunity to develop and test high resolution Radio Frequency Beam Position Monitors (RF-BPMs). These BPMs are designed to measure pulse to pulse beam motion (jitter) at a theoretical resolution of approximately 1 nm. The beam induces a TM 110 mode with an amplitude linearly proportional to its charge and displacement from the BPM's (cylindrical cavity) axis. The C-band (5,712 MHz) TM 110 signal is processed and converted into beam position for use by the Stanford Linear Collider (SLC) control system. Presented are the experimental procedures, acquisition, and analysis of data demonstrating resolution of jitter near 25 nm. With the design of future e + e - linear colliders requiring spot sizes close to 3 nm, understanding and developing RF-BPMs will be essential in resolving and controlling jitter

  7. Tumor suppressors: enhancers or suppressors of regeneration?

    Science.gov (United States)

    Pomerantz, Jason H.; Blau, Helen M.

    2013-01-01

    Tumor suppressors are so named because cancers occur in their absence, but these genes also have important functions in development, metabolism and tissue homeostasis. Here, we discuss known and potential functions of tumor suppressor genes during tissue regeneration, focusing on the evolutionarily conserved tumor suppressors pRb1, p53, Pten and Hippo. We propose that their activity is essential for tissue regeneration. This is in contrast to suggestions that tumor suppression is a trade-off for regenerative capacity. We also hypothesize that certain aspects of tumor suppressor pathways inhibit regenerative processes in mammals, and that transient targeted modification of these pathways could be fruitfully exploited to enhance processes that are important to regenerative medicine. PMID:23715544

  8. Targeted deletion of Nrf2 reduces urethane-induced lung tumor development in mice.

    Directory of Open Access Journals (Sweden)

    Alison K Bauer

    Full Text Available Nrf2 is a key transcription factor that regulates cellular redox and defense responses. However, permanent Nrf2 activation in human lung carcinomas promotes pulmonary malignancy and chemoresistance. We tested the hypothesis that Nrf2 has cell survival properties and lack of Nrf2 suppresses chemically-induced pulmonary neoplasia by treating Nrf2(+/+ and Nrf2(-/- mice with urethane. Airway inflammation and injury were assessed by bronchoalveolar lavage analyses and histopathology, and lung tumors were analyzed by gross and histologic analysis. We used transcriptomics to assess Nrf2-dependent changes in pulmonary gene transcripts at multiple stages of neoplasia. Lung hyperpermeability, cell death and apoptosis, and inflammatory cell infiltration were significantly higher in Nrf2(-/- mice compared to Nrf2(+/+ mice 9 and 11 wk after urethane. Significantly fewer lung adenomas were found in Nrf2(-/- mice than in Nrf2(+/+ mice at 12 and 22 wk. Nrf2 modulated expression of genes involved cell-cell signaling, glutathione metabolism and oxidative stress response, and immune responses during early stage neoplasia. In lung tumors, Nrf2-altered genes had roles in transcriptional regulation of cell cycle and proliferation, carcinogenesis, organismal injury and abnormalities, xenobiotic metabolism, and cell-cell signaling genes. Collectively, Nrf2 deficiency decreased susceptibility to urethane-induced lung tumorigenesis in mice. Cell survival properties of Nrf2 were supported, at least in part, by reduced early death of initiated cells and heightened advantage for tumor cell expansion in Nrf2(+/+ mice relative to Nrf2(-/- mice. Our results were consistent with the concept that Nrf2 over-activation is an adaptive response of cancer conferring resistance to anti-cancer drugs and promoting malignancy.

  9. Development and Validity of a Silicone Renal Tumor Model for Robotic Partial Nephrectomy Training.

    Science.gov (United States)

    Monda, Steven M; Weese, Jonathan R; Anderson, Barrett G; Vetter, Joel M; Venkatesh, Ramakrishna; Du, Kefu; Andriole, Gerald L; Figenshau, Robert S

    2018-04-01

    To provide a training tool to address the technical challenges of robot-assisted laparoscopic partial nephrectomy, we created silicone renal tumor models using 3-dimensional printed molds of a patient's kidney with a mass. In this study, we assessed the face, content, and construct validity of these models. Surgeons of different training levels completed 4 simulations on silicone renal tumor models. Participants were surveyed on the usefulness and realism of the model as a training tool. Performance was measured using operation-specific metrics, self-reported operative demands (NASA Task Load Index [NASA TLX]), and blinded expert assessment (Global Evaluative Assessment of Robotic Surgeons [GEARS]). Twenty-four participants included attending urologists, endourology fellows, urology residents, and medical students. Post-training surveys of expert participants yielded mean results of 79.2 on the realism of the model's overall feel and 90.2 on the model's overall usefulness for training. Renal artery clamp times and GEARS scores were significantly better in surgeons further in training (P ≤.005 and P ≤.025). Renal artery clamp times, preserved renal parenchyma, positive margins, NASA TLX, and GEARS scores were all found to improve across trials (P <.001, P = .025, P = .024, P ≤.020, and P ≤.006, respectively). Face, content, and construct validity were demonstrated in the use of a silicone renal tumor model in a cohort of surgeons of different training levels. Expert participants deemed the model useful and realistic. Surgeons of higher training levels performed better than less experienced surgeons in various study metrics, and improvements within individuals were observed over sequential trials. Future studies should aim to assess model predictive validity, namely, the association between model performance improvements and improvements in live surgery. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Tumor macroenvironment and metabolism.

    Science.gov (United States)

    Al-Zoughbi, Wael; Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

    2014-04-01

    In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organs. Amino acids, and distinct lipid and lipoprotein species can be essential for further tumor growth. The role of glucose in tumor metabolism has been studied extensively. Cancer-associated cachexia is the most important tumor-associated systemic syndrome and not only affects the quality of life of patients with various malignancies but is estimated to be the cause of death in 15%-20% of all cancer patients. On the other hand, systemic metabolic diseases such as obesity and diabetes are known to influence tumor development. Furthermore, the clinical implications of the tumor macroenvironment are explored in the context of the patient's outcome with special consideration for pediatric tumors. Finally, ways to target the tumor macroenvironment that will provide new approaches for therapeutic concepts are described. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Development and preclinical evaluation of new 124I-folate conjugates for PET imaging of folate receptor-positive tumors

    International Nuclear Information System (INIS)

    AlJammaz, I.; Al-Otaibi, B.; Al-Rumayan, F.; Al-Yanbawi, S.; Amer, S.; Okarvi, S.M.

    2014-01-01

    In an attempt to develop new folate radiotracers with favorable biochemical properties for detecting folate receptor-positive cancers, we have synthesized [ 124 I]-SIB- and [ 124 I]-SIP-folate conjugates using a straightforward and two-step simple reactions. Radiochemical yields for [ 124 I]-SIB- and [ 124 I]-SIP-folate conjugates were greater than 90 and 60% respectively, with total synthesis time of 30–40 min. Radiochemical purities were always greater than 98% without HPLC purification. These synthetic approaches hold considerable promise as rapid and simple method for 124 I-folate conjugate preparation with high radiochemical yield in short synthesis time. In vitro tests on KB cell line showed that the significant amounts of the radioconjugates were associated with cell fractions. In vivo characterization in normal Balb/c mice revealed rapid blood clearance of these radioconjugates and favorable biodistribution profile for [ 124 I]-SIP-folate conjugate over [ 124 I]-SIB-folate conjugate. Biodistribution studies of [ 124 I]-SIP-folate conjugate in nude mice bearing human KB cell line xenografts, demonstrated significant tumor uptake. The uptake in the tumors was blocked by excess injection of folic acid, suggesting a receptor-mediated process. These results demonstrate that [ 124 I]-SIP-folate conjugate may be useful as a molecular probe for detecting and staging of folate receptor-positive cancers, such as ovarian cancer and their metastasis as well as monitoring tumor response to treatment

  12. Development of a double-antibody radioimmunoassay for detecting ovarian tumor-associated antigen fraction OCA in plasma

    International Nuclear Information System (INIS)

    Knauf, S.; Urbach, G.I.

    1978-01-01

    Ovarian tumor-associated antigen isolated from human tumor tissue was shown to have a different mobility from that of carcinoembryonic antigen (CEA) in both acrylamide gel electrophoresis and immunoelectrophoresis in agarose. The ovarian tumor antigen is composed of six species with different electrophoretic mobility in acrylamide gel electrophoresis. Three of these species were detected in Sephadex G-100 ovarian fraction OCA (from the void volume peak) and the other three species of lower apparent molecular weight were detected in fraction OCD (from the second peak). Fractions OCA and OCD did not share common antigenic determinants as determined by immunodiffusion. CEA was shown to share antigenic determinants with both OCA and OCD. A double-antibody radioimmunoassay capable of detecting nanogram quantities of plasma OCA was developed. In a preliminary study of ovarian cancer patients, OCA appeared to be a more sensitive marker for ovarian cancer than CEA. There was virtually no correlation (r 2 = 0.1) between OCA and CEA levels in these patients, as determined by radioimmunoassay

  13. Development and Evaluation of an Open-Source Software Package “CGITA” for Quantifying Tumor Heterogeneity with Molecular Images

    Directory of Open Access Journals (Sweden)

    Yu-Hua Dean Fang

    2014-01-01

    Full Text Available Background. The quantification of tumor heterogeneity with molecular images, by analyzing the local or global variation in the spatial arrangements of pixel intensity with texture analysis, possesses a great clinical potential for treatment planning and prognosis. To address the lack of available software for computing the tumor heterogeneity on the public domain, we develop a software package, namely, Chang-Gung Image Texture Analysis (CGITA toolbox, and provide it to the research community as a free, open-source project. Methods. With a user-friendly graphical interface, CGITA provides users with an easy way to compute more than seventy heterogeneity indices. To test and demonstrate the usefulness of CGITA, we used a small cohort of eighteen locally advanced oral cavity (ORC cancer patients treated with definitive radiotherapies. Results. In our case study of ORC data, we found that more than ten of the current implemented heterogeneity indices outperformed SUVmean for outcome prediction in the ROC analysis with a higher area under curve (AUC. Heterogeneity indices provide a better area under the curve up to 0.9 than the SUVmean and TLG (0.6 and 0.52, resp.. Conclusions. CGITA is a free and open-source software package to quantify tumor heterogeneity from molecular images. CGITA is available for free for academic use at http://code.google.com/p/cgita.

  14. Avoiding Pitfalls in the Statistical Analysis of Heterogeneous Tumors

    Directory of Open Access Journals (Sweden)

    Judith-Anne W. Chapman

    2009-01-01

    Full Text Available Information about tumors is usually obtained from a single assessment of a tumor sample, performed at some point in the course of the development and progression of the tumor, with patient characteristics being surrogates for natural history context. Differences between cells within individual tumors (intratumor heterogeneity and between tumors of different patients (intertumor heterogeneity may mean that a small sample is not representative of the tumor as a whole, particularly for solid tumors which are the focus of this paper. This issue is of increasing importance as high-throughput technologies generate large multi-feature data sets in the areas of genomics, proteomics, and image analysis. Three potential pitfalls in statistical analysis are discussed (sampling, cut-points, and validation and suggestions are made about how to avoid these pitfalls.

  15. A case study of the changing nature of a non-government organisation: a focus on disability and development.

    Science.gov (United States)

    Yoshida, Karen K; Parnes, Penny; Brooks, Dina; Cameron, Deb

    2009-01-01

    The purpose of this article is to describe the changing nature, process and structure of an international non-governmental organisation (NGO) in response to internal and external factors. This article is based on the interview data collected for the study which focussed on the experiences and perception of key informants on trends related to official development assistance, local governments' perspective of the NGO as a development partner and the NGO's perception of corporate and foundation support. Qualitative descriptive data analysis was used. Three main themes were developed with the interview data. Our analysis indicated shifts in the: (1) vision/nature (single to cross disability focus), (2) structure (building internal and external relationships) and (3) process (from ad hoc to systemic evaluations). These broader issues of vision, structure (relationships) and evaluation within and outside of the organisation, needs to be addressed to provide a foundation upon which funding initiatives can be developed. A closer relationship between funders and projects/programmes would do much to enhance the partnership and would ensure that the projects are able to measure and report results in a manner that is conducive to increasing support.

  16. Development of tumor-reactive T cells after nonmyeloablative allogeneic hematopoietic stem cell transplant for chronic lymphocytic leukemia.

    Science.gov (United States)

    Nishida, Tetsuya; Hudecek, Michael; Kostic, Ana; Bleakley, Marie; Warren, Edus H; Maloney, David; Storb, Rainer; Riddell, Stanley R

    2009-07-15

    Allogeneic nonmyeloablative hematopoietic stem cell transplant (NM-HSCT) can result in durable remission of chronic lymphocytic leukemia (CLL). It is thought that the efficacy of NM-HSCT is mediated by recognition of tumor cells by T cells in the donor stem cell graft. We evaluated the development of CTLs specific for CLL after NM-HSCT to determine if their presence correlated with antitumor efficacy. Peripheral blood mononuclear cells obtained from 12 transplant recipients at intervals after NM-HSCT were stimulated in vitro with CLL cells. Polyclonal T-cell lines and CD8(+) T-cell clones were derived from these cultures and evaluated for lysis of donor and recipient target cells including CLL. The presence and specificity of responses was correlated with clinical outcomes. Eight of the 12 patients achieved remission or a major antitumor response and all 8 developed CD8(+) and CD4(+) T cells specific for antigens expressed by CLL. A clonal analysis of the CD8(+) T-cell response identified T cells specific for multiple minor histocompatibility (H) antigens expressed on CLL in six of the responding patients. A significant fraction of the CD8(+) T-cell response in some patients was also directed against nonshared tumor-specific antigens. By contrast, CLL-reactive T cells were not detected in the four patients who had persistent CLL after NM-HSCT, despite the development of graft-versus-host disease. The development of a diverse T-cell response specific for minor H and tumor-associated antigens expressed by CLL predicts an effective graft-versus-leukemia response after NM-HSCT.

  17. Development of the automated circulating tumor cell recovery system with microcavity array.

    Science.gov (United States)

    Negishi, Ryo; Hosokawa, Masahito; Nakamura, Seita; Kanbara, Hisashige; Kanetomo, Masafumi; Kikuhara, Yoshihito; Tanaka, Tsuyoshi; Matsunaga, Tadashi; Yoshino, Tomoko

    2015-05-15

    Circulating tumor cells (CTCs) are well recognized as useful biomarker for cancer diagnosis and potential target of drug discovery for metastatic cancer. Efficient and precise recovery of extremely low concentrations of CTCs from blood has been required to increase the detection sensitivity. Here, an automated system equipped with a microcavity array (MCA) was demonstrated for highly efficient and reproducible CTC recovery. The use of MCA allows selective recovery of cancer cells from whole blood on the basis of differences in size between tumor and blood cells. Intra- and inter-assays revealed that the automated system achieved high efficiency and reproducibility equal to the assay manually performed by well-trained operator. Under optimized assay workflow, the automated system allows efficient and precise cell recovery for non-small cell lung cancer cells spiked in whole blood. The automated CTC recovery system will contribute to high-throughput analysis in the further clinical studies on large cohort of cancer patients. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Toll-like receptor 2 signaling protects mice from tumor development in a mouse model of colitis-induced cancer.

    Directory of Open Access Journals (Sweden)

    Emily L Lowe

    2010-09-01

    Full Text Available Inflammatory bowel disease (IBD is a disorder of chronic inflammation with increased susceptibility to colorectal cancer. The etiology of IBD is unclear but thought to result from a dysregulated adaptive and innate immune response to microbial products in a genetically susceptible host. Toll-like receptor (TLR signaling induced by intestinal commensal bacteria plays a crucial role in maintaining intestinal homeostasis, innate immunity and the enhancement of intestinal epithelial cell (IEC integrity. However, the role of TLR2 in the development of colorectal cancer has not been studied. We utilized the AOM-DSS model for colitis-associated colorectal cancer (CAC in wild type (WT and TLR2(-/- mice. Colons harvested from WT and TLR2(-/- mice were used for histopathology, immunohistochemistry, immunofluorescence and cytokine analysis. Mice deficient in TLR2 developed significantly more and larger colorectal tumors than their WT controls. We provide evidence that colonic epithelium of TLR2(-/- mice have altered immune responses and dysregulated proliferation under steady-state conditions and during colitis, which lead to inflammatory growth signals and predisposition to accelerated neoplastic growth. At the earliest time-points assessed, TLR2(-/- colons exhibited a significant increase in aberrant crypt foci (ACF, resulting in tumors that developed earlier and grew larger. In addition, the intestinal microenvironment revealed significantly higher levels of IL-6 and IL-17A concomitant with increased phospho-STAT3 within ACF. These observations indicate that in colitis, TLR2 plays a protective role against the development of CAC.

  19. Development of a Checklist for Assessing Good Hygiene Practices of Fresh-Cut Fruits and Vegetables Using Focus Group Interviews.

    Science.gov (United States)

    Araújo, Jane A M; Esmerino, Erick A; Alvarenga, Verônica O; Cappato, Leandro P; Hora, Iracema C; Silva, Marcia Cristina; Freitas, Monica Q; Pimentel, Tatiana C; Walter, Eduardo H M; Sant'Ana, Anderson S; Cruz, Adriano G

    2018-03-01

    This study aimed to develop a checklist for good hygiene practices (GHP) for raw material of vegetable origin using the focus groups (FGs) approach (n = 4). The final checklist for commercialization of horticultural products totaled 28 questions divided into six blocks, namely: water supply; hygiene, health, and training; waste control; control of pests; packaging and traceability; and hygiene of facilities and equipment. The FG methodology was efficient to elaborate a participatory and objective checklist, based on minimum hygiene requirements, serving as a tool for diagnosis, planning, and training in GHP of fresh vegetables, besides contributing to raise awareness of the consumers' food safety. The FG methodology provided useful information to establish the final checklist for GHP, with easy application, according to the previous participants' perception and experience.

  20. Current status and prospect on the radioactive waste management program in the Republic of Korea. Focusing on recent development

    International Nuclear Information System (INIS)

    Park, Hyun-Soo; Chang, In-Soon

    1996-01-01

    Since its first commercial operation at Kori near the city of Pusan in 1978, nuclear energy has become one of the prime resources for the electricity. However, proper treatment of its byproducts, radioactive wastes, has been the national concern. Despite vigorous effort by the Korean Government and NEMAC(Nuclear Environment Management Center), the series of attempts for the site selection to build the national radioactive waste complex has been ruined. After the failure at Guleop Island, the Government recently amended its policy so that the major tasks on the management program of radioactive wastes shall be transferred to KEPCO(Korea Electric Power Corporation), sole national electric utility, while the current authority, KAERI(Korea Atomic Energy Research Institute)/NEMAC is limited to focus on the research and development in the safe management of spent fuels. Detailed plan to support the Government redirection is under discussion among concerned institutes. (author)

  1. Focusing on sustainable energy ambitions in the area development process. 2. ed.; Centraal stellen van duurzame energieambities in het gebiedsontwikkelingsproces

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-03-15

    Many local authorities have established firm energy ambitions. Making the built environment more sustainable, both by means of energy saving measures and by making the remaining energy use sustainable, are important focus points. The question rises how sustainable energy ambitions can be embedded in the area development process. Area developments related to new buildings or demolition/new building projects often involve lengthy and complex projects. Projects in which many parties and interests play a role, in which many instruments can be used and energy concepts can be applied. This report provides an overview of the area development process and the corresponding instruments and concepts. [Dutch] Veel gemeenten hebben stevige energieambities vastgesteld. Verduurzaming van de gebouwde omgeving, zowel door energiebesparingsmaatregelen als door het duurzaam invullen van het resterende energieverbruik, zijn daarbij belangrijke aangrijpingspunten. De vraag is hoe duurzame energieambities goed verankerd kunnen worden in het gebiedsontwikkelingsproces. Bij gebiedsontwikkeling van nieuwbouw of sloop/nieuwbouw projecten gaat het vaak om langdurige complexe projecten. Projecten waarbij vele partijen en belangen een rol spelen, diverse instrumenten kunnen worden gebruikt en energieconcepten kunnen worden toegepast. Dit rapport geeft een overzicht van het gebiedsontwikkelingsproces en de bijbehorende instrumenten en concepten.

  2. Stochastic models for tumoral growth

    OpenAIRE

    Escudero, Carlos

    2006-01-01

    Strong experimental evidence has indicated that tumor growth belongs to the molecular beam epitaxy universality class. This type of growth is characterized by the constraint of cell proliferation to the tumor border, and surface diffusion of cells at the growing edge. Tumor growth is thus conceived as a competition for space between the tumor and the host, and cell diffusion at the tumor border is an optimal strategy adopted for minimizing the pressure and helping tumor development. Two stoch...

  3. Tissue engineered tumor models.

    Science.gov (United States)

    Ingram, M; Techy, G B; Ward, B R; Imam, S A; Atkinson, R; Ho, H; Taylor, C R

    2010-08-01

    Many research programs use well-characterized tumor cell lines as tumor models for in vitro studies. Because tumor cells grown as three-dimensional (3-D) structures have been shown to behave more like tumors in vivo than do cells growing in monolayer culture, a growing number of investigators now use tumor cell spheroids as models. Single cell type spheroids, however, do not model the stromal-epithelial interactions that have an important role in controlling tumor growth and development in vivo. We describe here a method for generating, reproducibly, more realistic 3-D tumor models that contain both stromal and malignant epithelial cells with an architecture that closely resembles that of tumor microlesions in vivo. Because they are so tissue-like we refer to them as tumor histoids. They can be generated reproducibly in substantial quantities. The bioreactor developed to generate histoid constructs is described and illustrated. It accommodates disposable culture chambers that have filled volumes of either 10 or 64 ml, each culture yielding on the order of 100 or 600 histoid particles, respectively. Each particle is a few tenths of a millimeter in diameter. Examples of histological sections of tumor histoids representing cancers of breast, prostate, colon, pancreas and urinary bladder are presented. Potential applications of tumor histoids include, but are not limited to, use as surrogate tumors for pre-screening anti-solid tumor pharmaceutical agents, as reference specimens for immunostaining in the surgical pathology laboratory and use in studies of invasive properties of cells or other aspects of tumor development and progression. Histoids containing nonmalignant cells also may have potential as "seeds" in tissue engineering. For drug testing, histoids probably will have to meet certain criteria of size and tumor cell content. Using a COPAS Plus flow cytometer, histoids containing fluorescent tumor cells were analyzed successfully and sorted using such criteria.

  4. Teacher Characteristics and School-Based Professional Development in Inclusive STEM-focused High Schools: A Cross-case Analysis

    Science.gov (United States)

    Spillane, Nancy Kay

    Within successful Inclusive Science, Technology, Engineering, and Mathematics (STEM)-focused High Schools (ISHSs), it is not only the students who are learning. Teachers, with diverse backgrounds, training, and experience, share and develop their knowledge through rich, embedded professional development to continuously shape their craft, improve their teaching, and support student success. This study of four exemplars of ISHSs (identified by experts in STEM education as highly successful in preparing students underrepresented in STEM for STEM majors in college and future STEM careers) provides a rich description of the relationships among the characteristics of STEM teachers, their professional development, and the school cultures that allow teachers to develop professionally and serve the needs of students. By providing a framework for the development of teaching staffs in ISHSs and contributing to the better understanding of STEM teaching in any school, this study offers valuable insight, implications, and information for states and school districts as they begin planning improvements to STEM education programs. A thorough examination of an existing data set that included site visits to four ISHSs along with pre- and post-visit data, provided the resource for this multiple case study with cross-case analysis of the teachers and their teacher professional development experiences. Administrators in these ISHSs had the autonomy to hire teachers with strong content backgrounds, philosophical alignment with the school missions, and a willingness to work collaboratively toward achieving the schools' goals. Ongoing teacher professional development began before school started and continued throughout the school day and year through intense and sustained, formal and informal, active learning experiences. Flexible professional development systems varied, but aligned with targeted school reforms and teacher and student needs. Importantly, collaborative teacher learning

  5. Spatial Positioning of RET and H4 Following Radiation Exposure Leads to Tumor Development

    Directory of Open Access Journals (Sweden)

    Yuri E. Nikiforov

    2001-01-01

    Full Text Available Exposure to ionizing radiation is a well-known risk factor for a number of human cancers, including leukemia, thyroid cancer, soft tissue sarcomas, and many others. Although it has been known for a long time that radiation exposure to the cell results in extensive DNA damage, including double strand DNA breaks, the exact mechanisms of radiation-induced carcinogenesis remain unknown. Recently, a large increase in incidence of thyroid cancer was observed in children exposed to radiation after the Chernobyl nuclear accident [1]. A high prevalence of chromosomal rearrangements involving the RET gene was found among these radiation-induced thyroid tumors [2,3]. As a result of such rearrangement, a portion of the RET gene is fused with another gene, typically with the H4 or ELE1. However, since the DNA targets of ionizing radiation are randomly distributed throughout the cell nucleus, the reason for predilection for the RET rearrangements in thyroid cells was unclear.

  6. Microspheres labelled with short-lived isotopes: Development and application for tumors treatment (Experimental study)

    International Nuclear Information System (INIS)

    Drozdovsky, B.Y.; Rosiev, R.A.; Goncharova, A.Y.; Skvortsov, V.G.; Petriev, V.M.; Grigoriev, A.N.; Schischkanov, N.G.

    1997-01-01

    Analysis of the conducted studies strongly suggests the possibility of usage of the domestic protein microspheres as a vehicle for radionuclide. The neutron-activating method of RPP production enables to utilize a broad spectrum of short-living isotopes that can be delivered into the target organ and anchored there for a long time. Good treatment results were obtained in case of the experimentally induced rheumatoid arthritis in rats after intraarticular loading of 165 Dy-hMSA. Mathematical calculations show that homogeneous distribution of RPP in human articulation cavity with the square of 100 cm 2 can be achieved when the quantity of administered particles exceeds 3000. On the example of 165 Dy-hMSA energy characteristic distribution we demonstrated that the absorbed dose for damaged cells at 2mm distance from the radioactive source is 7 times less than the one for a sphere of 2mm diameter. Analysis of dosimetric data in case of intratumoral loading of 165 Dy-hMSA also point out the necessity of the absorbed dose calculation methods taking into account the distance from the source and possible heterogeneity of RPP distribution inside the tumor to be employed. The prolonged RPP detention in the target causing no essential morphological and functional changes was achieved by embolization on the level of septal and interlobular arteries and of efferent arterioles in the animal's renal. The uniformity of microsphere distribution in the organ and their accumulation in tumors depends on the number of particles being administered. Investigations carried out suggest the efficacy of radionuclide therapy application for treatment of oncological and heavy somatic diseases. They also indicate the necessity of further investigations aimed to optimize the usage of microspheres as a radionuclide carrier usage and to work out the criteria of dosimetric planning

  7. Microspheres labelled with short-lived isotopes: Development and application for tumors treatment (Experimental study)

    Energy Technology Data Exchange (ETDEWEB)

    Drozdovsky, B.Y.; Rosiev, R.A.; Goncharova, A.Y.; Skvortsov, V.G.; Petriev, V.M.; Grigoriev, A.N.; Schischkanov, N.G. [Medical Radiological Research Centre RAMS, Kaluga Region, (Russian Federation)

    1997-10-01

    Analysis of the conducted studies strongly suggests the possibility of usage of the domestic protein microspheres as a vehicle for radionuclide. The neutron-activating method of RPP production enables to utilize a broad spectrum of short-living isotopes that can be delivered into the target organ and anchored there for a long time. Good treatment results were obtained in case of the experimentally induced rheumatoid arthritis in rats after intraarticular loading of {sup 165}Dy-hMSA. Mathematical calculations show that homogeneous distribution of RPP in human articulation cavity with the square of 100 cm{sup 2} can be achieved when the quantity of administered particles exceeds 3000. On the example of {sup 165}Dy-hMSA energy characteristic distribution we demonstrated that the absorbed dose for damaged cells at 2mm distance from the radioactive source is 7 times less than the one for a sphere of 2mm diameter. Analysis of dosimetric data in case of intratumoral loading of {sup 165}Dy-hMSA also point out the necessity of the absorbed dose calculation methods taking into account the distance from the source and possible heterogeneity of RPP distribution inside the tumor to be employed. The prolonged RPP detention in the target causing no essential morphological and functional changes was achieved by embolization on the level of septal and interlobular arteries and of efferent arterioles in the animal`s renal. The uniformity of microsphere distribution in the organ and their accumulation in tumors depends on the number of particles being administered. Investigations carried out suggest the efficacy of radionuclide therapy application for treatment of oncological and heavy somatic diseases. They also indicate the necessity of further investigations aimed to optimize the usage of microspheres as a radionuclide carrier usage and to work out the criteria of dosimetric planning 25 refs.

  8. Clinical relevance and biology of circulating tumor cells

    Science.gov (United States)

    2011-01-01

    Most breast cancer patients die due to metastases, and the early onset of this multistep process is usually missed by current tumor staging modalities. Therefore, ultrasensitive techniques have been developed to enable the enrichment, detection, isolation and characterization of disseminated tumor cells in bone marrow and circulating tumor cells in the peripheral blood of cancer patients. There is increasing evidence that the presence of these cells is associated with an unfavorable prognosis related to metastatic progression in the bone and other organs. This review focuses on investigations regarding the biology and clinical relevance of circulating tumor cells in breast cancer. PMID:22114869

  9. Is upregulation of BCL2 a determinant of tumor development driven by inactivation of CDH1/E-cadherin?

    Directory of Open Access Journals (Sweden)

    Inga Karch

    Full Text Available Inactivation of CDH1, encoding E-cadherin, promotes cancer initiation and progression. According to a newly proposed molecular mechanism, loss of E-cadherin triggers an upregulation of the anti-apoptotic oncoprotein BCL2. Conversely, reconstitution of E-cadherin counteracts overexpression of BCL2. This reciprocal regulation is thought to be critical for early tumor development. We determined the relevance of this new concept in human infiltrating lobular breast cancer (ILBC, the prime tumor entity associated with CDH1 inactivation. BCL2 expression was examined in human ILBC cell lines (IPH-926, MDA-MB-134, SUM-44 harboring deleterious CDH1 mutations. To test for an intact regulatory axis between E-cadherin and BCL2, wild-type E-cadherin was reconstituted in ILBC cells by ectopic expression. Moreover, BCL2 and E-cadherin were evaluated in primary invasive breast cancers and in synchronous lobular carcinomas in situ (LCIS. MDA-MB-134 and IPH-926 showed little or no BCL2 expression, while SUM-44 ILBC cells were BCL2-positive. Reconstitution of E-cadherin failed to impact on BCL2 expression in all cell lines tested. Primary ILBCs were almost uniformly E-cadherin-negative (97% and were frequently BCL2-negative (46%. When compared with an appropriate control group, ILBCs showed a trend towards an increased frequency of BCL2-negative cases (P = 0.064. In terminal duct-lobular units affected by LCIS, the E-cadherin-negative neoplastic component showed a similar or a reduced BCL2-immunoreactivity, when compared with the adjacent epithelium. In conclusion, upregulation of BCL2 is not involved in lobular breast carcinogenesis and is unlikely to represent an important determinant of tumor development driven by CDH1 inactivation.

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  11. Development of nanometer resolution C-Band radio frequency beam position monitors in the Final Focus Test Beam

    Energy Technology Data Exchange (ETDEWEB)

    Slaton, T.; Mazaheri, G. [Stanford Univ., CA (US). Stanford Linear Accelerator Center; Shintake, T. [National Lab. for High Energy Physics, Tsukuba, Ibaraki (Japan)

    1998-08-01

    Using a 47 GeV electron beam, the Final Focus Test Beam (FFTB) produces vertical spot sizes around 70 nm. These small beam sizes introduce an excellent opportunity to develop and test high resolution Radio Frequency Beam Position Monitors (RF-BPMs). These BPMs are designed to measure pulse to pulse beam motion (jitter) at a theoretical resolution of approximately 1 nm. The beam induces a TM{sub 110} mode with an amplitude linearly proportional to its charge and displacement from the BPM's (cylindrical cavity) axis. The C-band (5,712 MHz) TM{sub 110} signal is processed and converted into beam position for use by the Stanford Linear Collider (SLC) control system. Presented are the experimental procedures, acquisition, and analysis of data demonstrating resolution of jitter near 25 nm. With the design of future e{sup +}e{sup -} linear colliders requiring spot sizes close to 3 nm, understanding and developing RF-BPMs will be essential in resolving and controlling jitter.

  12. Quantification of tumor infiltrating Foxp3+ regulatory T cells enables the identification of high-risk patients for developing synchronous cancers over upper aerodigestive tract.

    Science.gov (United States)

    Wang, Wen-Lun; Chang, Wei-Lun; Yang, Hsiao-Bai; Chang, I-Wei; Lee, Ching-Tai; Chang, Chi-Yang; Lin, Jaw-Town; Sheu, Bor-Shyang

    2015-07-01

    Patients with squamous cell carcinomas (SCC) of upper aerodigestive tract, either over head and neck (HNSCC) or esophagus (ESCC), frequently developed synchronous multiple cancers, leading to worse prognosis. This study validated whether suppression of host cancer immunosurveillance mediated by regulatory T cells (Treg) may predispose to the development of synchronous cancers. Tumor tissues of 200 patients (100 ESCC only, 50 HNSCC only, and 50 synchronous SCCs) were quantitatively accessed for the tumor infiltrating Treg by immunohistochemistry. The density of Treg was also correlated to the level of Treg-associated inhibitory cytokines (IL-10, IL-35 and TGF-β1), and chemokine (CCL22). The density of tumor infiltrating Treg in the index tumor (i.e. the first malignancy diagnosed) of synchronous SCC group was higher than those of HNSCC or ESCC only (prisk of synchronous cancer development to initiate a proper surveillance program. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Development of a Method to Implement Whole-Genome Bisulfite Sequencing of cfDNA from Cancer Patients and a Mouse Tumor Model

    Directory of Open Access Journals (Sweden)

    Elaine C. Maggi

    2018-01-01

    Full Text Available The goal of this study was to develop a method for whole genome cell-free DNA (cfDNA methylation analysis in humans and mice with the ultimate goal to facilitate the identification of tumor derived DNA methylation changes in the blood. Plasma or serum from patients with pancreatic neuroendocrine tumors or lung cancer, and plasma from a murine model of pancreatic adenocarcinoma was used to develop a protocol for cfDNA isolation, library preparation and whole-genome bisulfite sequencing of ultra low quantities of cfDNA, including tumor-specific DNA. The protocol developed produced high quality libraries consistently generating a conversion rate >98% that will be applicable for the analysis of human and mouse plasma or serum to detect tumor-derived changes in DNA methylation.

  14. Development of the SyncTraX FX4 version real-time tumor tracking system for radiation therapy

    International Nuclear Information System (INIS)

    Ishiyama, Tomoharu; Torigoe, Yui; Nagae, Koudai; Kajiki, Shunsuke; Sano, Takayuki

    2017-01-01

    Based on the current SyncTraX that was developed jointly with Hokkaido University, we have developed the SyncTraX FX4 version, which features not only tumor tracking but also patient positioning. The SyncTraX FX4 version is configured with four fixed x-ray tubes an detectors and eliminated the rail that is used to move the x-ray tube and detector as in the current SyncTraX. This development simplifies limitations on facility construction. We also adopted a distortion free flat panel detector instead of a color I.I., and the additional patient positioning feature will enable the SyncTraX FX4 version to become more widely applied in clinical cases. (author)

  15. Creating psychological connections between intervention recipients: development and focus group evaluation of a group singing session for people with aphasia.

    Science.gov (United States)

    Tarrant, Mark; Warmoth, Krystal; Code, Chris; Dean, Sarah; Goodwin, Victoria A; Stein, Ken; Sugavanam, Thavapriya

    2016-02-23

    The study sought to identify key design features that could be used to create a new framework for group-based health interventions. We designed and tested the first session of a group intervention for stroke survivors with aphasia which was aimed at nurturing new psychological connections between group members. The intervention session, a participant focus group and interviews with intervention facilitators were held in a local community music centre in the South West of England. A convenience sample of 10 community-dwelling people with poststroke aphasia participated in the session. Severity of aphasia was not considered for inclusion. Participants took part in a 90-min group singing session which involved singing songs from a specially prepared song book. Musical accompaniment was provided by the facilitators. Participants and group facilitators reported their experiences of participating in the session, with a focus on activities within the session related to the intervention aims. Researcher observations of the session were also made. Two themes emerged from the analysis, concerning experiences of the session ('developing a sense of group belonging') and perceptions of its design and delivery ('creating the conditions for engagement'). Participants described an emerging sense of shared social identity as a member of the intervention group and identified fixed (eg, group size, session breaks) and flexible (eg, facilitator responsiveness) features of the session which contributed to this emergence. Facilitator interviews and researcher observations corroborated and expanded participant reports. Engagement with health intervention content may be enhanced in group settings when intervention participants begin to establish positive and meaningful psychological connections with other group members. Understanding and actively nurturing these connections should be a core feature of a general framework for the design and delivery of group interventions. Published by the

  16. Creating psychological connections between intervention recipients: development and focus group evaluation of a group singing session for people with aphasia

    Science.gov (United States)

    Tarrant, Mark; Warmoth, Krystal; Code, Chris; Dean, Sarah; Goodwin, Victoria A; Stein, Ken; Sugavanam, Thavapriya

    2016-01-01

    Objectives The study sought to identify key design features that could be used to create a new framework for group-based health interventions. We designed and tested the first session of a group intervention for stroke survivors with aphasia which was aimed at nurturing new psychological connections between group members. Setting The intervention session, a participant focus group and interviews with intervention facilitators were held in a local community music centre in the South West of England. Participants A convenience sample of 10 community-dwelling people with poststroke aphasia participated in the session. Severity of aphasia was not considered for inclusion. Intervention Participants took part in a 90-min group singing session which involved singing songs from a specially prepared song book. Musical accompaniment was provided by the facilitators. Primary and secondary outcome measures Participants and group facilitators reported their experiences of participating in the session, with a focus on activities within the session related to the intervention aims. Researcher observations of the session were also made. Results Two themes emerged from the analysis, concerning experiences of the session (‘developing a sense of group belonging’) and perceptions of its design and delivery (‘creating the conditions for engagement’). Participants described an emerging sense of shared social identity as a member of the intervention group and identified fixed (eg, group size, session breaks) and flexible (eg, facilitator responsiveness) features of the session which contributed to this emergence. Facilitator interviews and researcher observations corroborated and expanded participant reports. Conclusions Engagement with health intervention content may be enhanced in group settings when intervention participants begin to establish positive and meaningful psychological connections with other group members. Understanding and actively nurturing these connections

  17. Boron neutron capture therapy (BNCT) inhibits tumor development from precancerous tissue: An experimental study that supports a potential new application of BNCT

    International Nuclear Information System (INIS)

    Monti Hughes, A.; Heber, E.M.; Pozzi, E.; Nigg, D.W.; Calzetta, O.; Blaumann, H.; Longhino, J.; Nievas, S.I.; Aromando, R.F.; Itoiz, M.E.; Trivillin, V.A.; Schwint, A.E.

    2009-01-01

    We previously demonstrated the efficacy of boron neutron capture therapy (BNCT) mediated by boronophenylalanine (BPA), GB-10 (Na 2 10 B 10 H 10 ) and (GB-10+BPA) to control tumors, with no normal tissue radiotoxicity, in the hamster cheek pouch oral cancer model. Herein we developed a novel experimental model of field-cancerization and precancerous lesions (globally termed herein precancerous tissue) in the hamster cheek pouch to explore the long-term potential inhibitory effect of the same BNCT protocols on the development of second primary tumors from precancerous tissue. Clinically, second primary tumor recurrences occur in field-cancerized tissue, causing therapeutic failure. We performed boron biodistribution studies followed by in vivo BNCT studies, with 8 months follow-up. All 3 BNCT protocols induced a statistically significant reduction in tumor development from precancerous tissue, reaching a maximum inhibition of 77-100%. The inhibitory effect of BPA-BNCT and (GB-10+BPA)-BNCT persisted at 51% at the end of follow-up (8 months), whereas for GB-10-BNCT it faded after 2 months. Likewise, beam-only elicited a significant but transient reduction in tumor development. No normal tissue radiotoxicity was observed. At 8 months post-treatment with BPA-BNCT or (GB-10+BPA)-BNCT, the precancerous pouches that did not develop tumors had regained the macroscopic and histological appearance of normal (non-cancerized) pouches. A potential new clinical application of BNCT would lie in its capacity to inhibit local regional recurrences.

  18. Focusing ethnography

    DEFF Research Database (Denmark)

    Woermann, Niklas

    2018-01-01

    underpinnings of focusing ethnographic research by comparing different schools of thought and suggesting a practice theory-based approach. It argues that many research projects are focused but do not reflect on the process of focusing, describes how to identify focal settings or practices, and introduces......Building theory with ethnography and filmic research increasingly requires focussing on key practices or settings, instead of painting a broad panorama of a culture. But few authors discuss why and how to focus. This article provides a systematic discussion of the theoretical and methodological...

  19. Early-life experiences and the development of adult diseases with a focus on mental illness: The Human Birth Theory.

    Science.gov (United States)

    Maccari, Stefania; Polese, Daniela; Reynaert, Marie-Line; Amici, Tiziana; Morley-Fletcher, Sara; Fagioli, Francesca

    2017-02-07

    In mammals, early adverse experiences, including mother-pup interactions, shape the response of an individual to chronic stress or to stress-related diseases during adult life. This has led to the elaboration of the theory of the developmental origins of health and disease, in particular adult diseases such as cardiovascular and metabolic disorders. In addition, in humans, as stated by Massimo Fagioli's Human Birth Theory, birth is healthy and equal for all individuals, so that mental illness develop exclusively in the postnatal period because of the quality of the relationship in the first year of life. Thus, this review focuses on the importance of programming during the early developmental period on the manifestation of adult diseases in both animal models and humans. Considering the obvious differences between animals and humans we cannot systematically move from animal models to humans. Consequently, in the first part of this review, we will discuss how animal models can be used to dissect the influence of adverse events occurring during the prenatal and postnatal periods on the developmental trajectories of the offspring, and in the second part, we will discuss the role of postnatal critical periods on the development of mental diseases in humans. Epigenetic mechanisms that cause reversible modifications in gene expression, driving the development of a pathological phenotype in response to a negative early postnatal environment, may lie at the core of this programming, thereby providing potential new therapeutic targets. The concept of the Human Birth Theory leads to a comprehension of the mental illness as a pathology of the human relationship immediately after birth and during the first year of life. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Endocrine tumors other than thyroid tumors

    International Nuclear Information System (INIS)

    Takeichi, Norio; Dohi, Kiyohiko

    1992-01-01

    This paper discusses the tendency for the occurrence of tumors in the endocrine glands, other than the thyroid gland, in A-bomb survivors using both autopsy and clinical data. ABCC-RERF sample data using 4136 autopsy cases (1961-1977) revealed parathyroid tumors in 13 A-bomb survivors, including 3 with the associated hyperparathyroidism, with the suggestion of dose-dependent increase in the occurrence of tumors. Based on clinical data from Hiroshima University, 7 (46.7%) of 15 parathyroid tumors cases were A-bomb survivors. Data (1974-1987) from the Tumor Registry Committee (TRC) in Hiroshima Prefecture revealed that a relative risk of parathyroid tumors was 5.6 times higher in the entire group of A-bomb survivors and 16.2 times higher in the group of heavily exposed A-bomb survivors, suggesting the dose-dependent increase in their occurrence. Adrenal tumors were detected in 47 of 123 cases from the TRC data, and 15 (31.5%) of these 47 were A-bomb survivors. Particularly, 11 cases of adrenal tumors associated with Cushing syndrome included 6 A-bomb survivors (54.5%). The incidence of multiple endocrine gonadial tumors (MEGT) tended to be higher with increasing exposure doses; and the 1-9 rad group, the 10-99 rad group, and the 100 or more rad group had a risk of developing MEGT of 4.1, 5.7, and 7.1, respectively, relative to both the not-in the city group and the 0 rad group. These findings suggested that there is a correlation between A-bomb radiation and the occurrence of parathyroid tumors (including hyperparathyroidism), adrenal tumors associated with Cushing syndrome and MEGT (especially, the combined thyroid and ovarian tumors and the combined thyroid and parathyroid tumors). (N.K.)

  1. Chlorinated Water Modulates the Development of Colorectal Tumors with Chromosomal Instability and Gut Microbiota in Apc-Deficient Mice.

    Science.gov (United States)

    Sasada, Tatsunari; Hinoi, Takao; Saito, Yasufumi; Adachi, Tomohiro; Takakura, Yuji; Kawaguchi, Yasuo; Sotomaru, Yusuke; Sentani, Kazuhiro; Oue, Naohide; Yasui, Wataru; Ohdan, Hideki

    2015-01-01

    The gastrointestinal tract is continuously exposed to a variety of chemicals and commensal bacteria. Recent studies have shown that changes in gut microbial populations caused by chlorine or other chemicals in the drinking water influence the development of human colorectal cancer, although the mechanism of tumorigenesis in the gut epithelium is obfuscated by the diversity of microflora and complexity of the tumor microenvironment. In this regard, mouse models that recapitulate human colorectal cancer are an invaluable tool. In this study, we used two conditional adenomatous polyposis coli (Apc) knockout mouse models to investigate the effect of chlorinated water on tumorigenesis in the digestive tract. Mice with colon-specific carcinoma--caused by either chromosomal (CDX2P 9.5-NLS Cre;Apc(+/flox), abbreviated to CPC;Apc) or microsatellite (CDX2P9.5-G19Cre;Apc(flox/flox) and CDX2P9.5-G22Cre;Apc(flox/flox)) instability, respectively--were administered chlorinated (10.0 mg/L chlorine) or tap (0.7 mg/L chlorine) water and evaluated for colon polyp formation. In CPC;Apc mice given chlorinated drinking water, tumors tended to develop in the colon, whereas in those that drank tap water, tumors were mostly observed in the small intestine. There was no difference in the rate of tumor formation of CDX2P9.5-G19Cre;Apc(flox/flox) and CDX2P9.5-G22Cre;Apc(flox/flox) mice consuming chlorinated as compared to tap water, suggesting that microsatellite instability in the Apc gene does not significantly affect tumorigenesis. Chlorinated water altered the enteric environment by reducing the fecal populations of the obligatory anaerobes Clostridium perfringens and C. difficile, as well as species belonging to the Atopobium cluster, including Enterobacteriaceae and Staphylococcus sp., which was associated with colon tumorigenesis in CPC;Apc mice. These results suggest that differences in tumorigenesis among CPC;Apc mice consuming chlorinated versus tap water may be due to differences

  2. Updates in the Development of ImmunoRNases for the Selective Killing of Tumor Cells

    Directory of Open Access Journals (Sweden)

    Sandra Jordaan

    2018-03-01

    Full Text Available Targeted cancer therapy includes, amongst others, antibody-based delivery of toxic payloads to selectively eliminate tumor cells. This payload can be either a synthetic small molecule drug composing an antibody-drug conjugate (ADC or a cytotoxic protein composing an immunotoxin (IT. Non-human cytotoxic proteins, while potent, have limited clinical efficacy due to their immunogenicity and potential off-target toxicity. Humanization of the cytotoxic payload is essential and requires harnessing of potent apoptosis-inducing human proteins with conditional activity, which rely on targeted delivery to contact their substrate. Ribonucleases are attractive candidates, due to their ability to induce apoptosis by abrogating protein biosynthesis via tRNA degradation. In fact, several RNases of the pancreatic RNase A superfamily have shown potential as anti-cancer agents. Coupling of a human RNase to a humanized antibody or antibody derivative putatively eliminates the immunogenicity of an IT (now known as a human cytolytic fusion protein, hCFP. However, RNases are tightly regulated in vivo by endogenous inhibitors, controlling the ribonucleolytic balance subject to the cell’s metabolic requirements. Endogenous inhibition limits the efficacy with which RNase-based hCFPs induce apoptosis. However, abrogating the natural interaction with the natural inhibitors by mutation has been shown to significantly enhance RNase activity, paving the way toward achieving cytolytic potency comparable to that of bacterial immunotoxins. Here, we review the immunoRNases that have undergone preclinical studies as anti-cancer therapeutic agents.

  3. Updates in the Development of ImmunoRNases for the Selective Killing of Tumor Cells.

    Science.gov (United States)

    Jordaan, Sandra; Akinrinmade, Olusiji A; Nachreiner, Thomas; Cremer, Christian; Naran, Krupa; Chetty, Shivan; Barth, Stefan

    2018-03-05

    Targeted cancer therapy includes, amongst others, antibody-based delivery of toxic payloads to selectively eliminate tumor cells. This payload can be either a synthetic small molecule drug composing an antibody-drug conjugate (ADC) or a cytotoxic protein composing an immunotoxin (IT). Non-human cytotoxic proteins, while potent, have limited clinical efficacy due to their immunogenicity and potential off-target toxicity. Humanization of the cytotoxic payload is essential and requires harnessing of potent apoptosis-inducing human proteins with conditional activity, which rely on targeted delivery to contact their substrate. Ribonucleases are attractive candidates, due to their ability to induce apoptosis by abrogating protein biosynthesis via tRNA degradation. In fact, several RNases of the pancreatic RNase A superfamily have shown potential as anti-cancer agents. Coupling of a human RNase to a humanized antibody or antibody derivative putatively eliminates the immunogenicity of an IT (now known as a human cytolytic fusion protein, hCFP). However, RNases are tightly regulated in vivo by endogenous inhibitors, controlling the ribonucleolytic balance subject to the cell's metabolic requirements. Endogenous inhibition limits the efficacy with which RNase-based hCFPs induce apoptosis. However, abrogating the natural interaction with the natural inhibitors by mutation has been shown to significantly enhance RNase activity, paving the way toward achieving cytolytic potency comparable to that of bacterial immunotoxins. Here, we review the immunoRNases that have undergone preclinical studies as anti-cancer therapeutic agents.

  4. Molecular signature of the radioinduction in the thyroid tumors developed after radiotherapy

    International Nuclear Information System (INIS)

    Mallard, Ch.

    2005-10-01

    Several epidemiological studies enlightens an increase of the number of thyroid cancers among children and adolescents exposed to ionizing radiation after an internal exposure ( Chernobylsk accident) or external one as a radiotherapy. No increase arose for adults.The analysis of the transcriptome was realised with micro arrays prepared on the genomic platform of the Cea at Evry that allow to study simultaneously the expression of 6000 genes. this study allows to enlighten a signature of radioinduction constituted by series of genes specifically expressed in one or other type of cancer in function of its etiology. This signature includes 59 genes expressed differentially between the sporadic carcinomas and 45 genes in the case of adenomas. with this signature an analysis in principal components allowed to determine correctly the etiology of 12 tumors among 13, the etiology of a sporadic adenoma was not determined. Besides, the study of the expression of genes specific to thyroid (TSHR, TG, TPO, TTF1, TTF2, PAX8) in relation with the presence of arrangements RET/PTC or mutations of BRAF was made. It allowed to enlighten the loss of TPO expression in the cancers changed for BRAF as well as a new mechanism of BRAF activation. (N.C.)

  5. Development of a virtual multidisciplinary lung cancer tumor board in a community setting.

    Science.gov (United States)

    Stevenson, Marvaretta M; Irwin, Tonia; Lowry, Terry; Ahmed, Maleka Z; Walden, Thomas L; Watson, Melanie; Sutton, Linda

    2013-05-01

    Creating an effective platform for multidisciplinary tumor conferences can be challenging in the rural community setting. The Duke Cancer Network created an Internet-based platform for a multidisciplinary conference to enhance the care of patients with lung cancer. This conference incorporates providers from different physical locations within a rural community and affiliated providers from a university-based cancer center 2 hours away. An electronic Web conferencing tool connects providers aurally and visually. Conferences were set up using a commercially available Web conferencing platform. The video platform provides a secure Web site coupled with a secure teleconference platform to ensure patient confidentiality. Multiple disciplines are invited to participate, including radiology, radiation oncology, thoracic surgery, pathology, and medical oncology. Participants only need telephone access and Internet connection to participate. Patient histories and physicals are presented, and the Web conferencing platform allows radiologic and histologic images to be reviewed. Treatment plans for patients are discussed, allowing providers to coordinate care among the different subspecialties. Patients who need referral to the affiliated university-based cancer center for specialized services are identified. Pertinent treatment guidelines and journal articles are reviewed. On average, there are 10 participants with one to two cases presented per session. The use of a Web conferencing platform allows subspecialty providers throughout the community and hours away to discuss lung cancer patient cases. This platform increases convenience for providers, eliminating travel to a central location. Coordination of care for patients requiring multidisciplinary care is facilitated, shortening evaluation time before definitive treatment plan.

  6. Focused Ethnography

    Directory of Open Access Journals (Sweden)

    Hubert Knoblauch

    2005-09-01

    Full Text Available In this paper I focus on a distinctive kind of sociological ethnography which is particularly, though not exclusively, adopted in applied research. It has been proposed that this branch of ethno­graphy be referred to as focused ethnography. Focused ethnography shall be delineated within the context of other common conceptions of what may be called conventional ethnography. However, rather than being opposed to it, focused ethno­graphy is rather complementary to conventional ethnography, particularly in fields that are charac­teristic of socially and functionally differentiated contemporary society. The paper outlines the back­ground as well as the major methodological features of focused ethnography, such as short-term field visits, data intensity and time intensity, so as to provide a background for future studies in this area. URN: urn:nbn:de:0114-fqs0503440

  7. 78 FR 11895 - Prospective Grant of Exclusive License: Development of MUC-1 Tumor Associated Antigens as Cancer...

    Science.gov (United States)

    2013-02-20

    ... recent approach where tumor associated antigens (TAAs), which are primarily expressed in human tumor cells, and not expressed or minimally expressed in normal tissues, are employed to generate a tumor... royalty bearing and will comply with the terms and conditions of 35 U.S.C. 209 and 37 CFR Part 404.7. The...

  8. Exploring views on long term rehabilitation for people with stroke in a developing country: findings from focus group discussions

    Science.gov (United States)

    2014-01-01

    Background The importance of long term rehabilitation for people with stroke is increasingly evident, yet it is not known whether such services can be materialised in countries with limited community resources. In this study, we explored the perception of rehabilitation professionals and people with stroke towards long term stroke rehabilitation services and potential approaches to enable provision of these services. Views from providers and users are important in ensuring whatever strategies developed for long term stroke rehabilitations are feasible and acceptable. Methods Focus group discussions were conducted involving 15 rehabilitation professionals and eight long term stroke survivors. All recorded conversations were transcribed verbatim and analysed using the principles of qualitative research. Results Both groups agreed that people with stroke may benefit from more rehabilitation compared to the amount of rehabilitation services presently provided. Views regarding the unavailability of long term rehabilitation services due to multi-factorial barriers were recognised. The groups also highlighted the urgent need for the establishment of community-based stroke rehabilitation centres. Family-assisted home therapy was viewed as a potential approach to continued rehabilitation for long term stroke survivors, given careful planning to overcome several family-related issues. Conclusions Barriers to the provision of long term stroke rehabilitation services are multi-factorial. Establishment of community-based stroke rehabilitation centres and training family members to conduct home-based therapy are two potential strategies to enable the continuation of rehabilitation for long term stroke survivors. PMID:24606911

  9. Meditation Breath Attention Scores (MBAS): Development and investigation of an internet-based assessment of focused attention during meditation practice.

    Science.gov (United States)

    Frewen, Paul; Hargraves, Heather; DePierro, Jonathan; D'Andrea, Wendy; Flodrowski, Les

    2016-07-01

    Meditation Breath Attention Scores (MBAS) represent a self-report, state measure of focused attention (FA) during the practice of meditation. The MBAS assessment procedure involves sounding a bell at periodic intervals during meditation practice, at which times participants indicate if they were attending toward breathing (scored 1) or if instead they had become distracted (e.g., by mind wandering; scored 0); scores are then tallied to yield participants' MBAS for that meditation. The current study developed and evaluated a fully automated and Internet-based version of MBAS in 1,101 volunteers. Results suggested that: (a) MBAS are internally consistent across bell rings; (b) MBAS total scores exhibit a non-normal distribution identifying subgroups of participants with particularly poor or robust FA during meditation; (c) MBAS decrease linearly with the duration of meditation practices, indicating that participants tend to experience less FA later as opposed to earlier in the meditation; (d) in the case of eyes-open meditation, MBAS are higher when the amount of time between bells is shorter; (e) MBAS correlate with various self-reported subjective experiences occurring during meditation; and (f) MBAS are weakly associated with higher trait mindful "acting with awareness," lesser ADHD-related symptoms of inattentiveness, and estimated minutes of meditation practiced in the past month. In sum, results provide further support for the construct validity of MBAS and serve to further characterize the dynamics of individual differences in FA during meditation. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  10. Development of Functional Surfaces on High-Density Polyethylene (HDPE) via Gas-Assisted Etching (GAE) Using Focused Ion Beams.

    Science.gov (United States)

    Sezen, Meltem; Bakan, Feray

    2015-12-01

    Irradiation damage, caused by the use of beams in electron and ion microscopes, leads to undesired physical/chemical material property changes or uncontrollable modification of structures. Particularly, soft matter such as polymers or biological materials is highly susceptible and very much prone to react on electron/ion beam irradiation. Nevertheless, it is possible to turn degradation-dependent physical/chemical changes from negative to positive use when materials are intentionally exposed to beams. Especially, controllable surface modification allows tuning of surface properties for targeted purposes and thus provides the use of ultimate materials and their systems at the micro/nanoscale for creating functional surfaces. In this work, XeF2 and I2 gases were used in the focused ion beam scanning electron microscope instrument in combination with gallium ion etching of high-density polyethylene surfaces with different beam currents and accordingly different gas exposure times resulting at the same ion dose to optimize and develop new polymer surface properties and to create functional polymer surfaces. Alterations in the surface morphologies and surface chemistry due to gas-assisted etching-based nanostructuring with various processing parameters were tracked using high-resolution SEM imaging, complementary energy-dispersive spectroscopic analyses, and atomic force microscopic investigations.

  11. Engaging Community Leaders in the Development of a Cardiovascular Health Behavior Survey Using Focus Group–Based Cognitive Interviewing

    Directory of Open Access Journals (Sweden)

    Gwenyth R Wallen

    2017-04-01

    Full Text Available Establishing the validity of health behavior surveys used in community-based participatory research (CBPR in diverse populations is often overlooked. A novel, group-based cognitive interviewing method was used to obtain qualitative data for tailoring a survey instrument designed to identify barriers to improved cardiovascular health in at-risk populations in Washington, DC. A focus group–based cognitive interview was conducted to assess item comprehension, recall, and interpretation and to establish the initial content validity of the survey. Thematic analysis of verbatim transcripts yielded 5 main themes for which participants (n = 8 suggested survey modifications, including survey item improvements, suggestions for additional items, community-specific issues, changes in the skip logic of the survey items, and the identification of typographical errors. Population-specific modifications were made, including the development of more culturally appropriate questions relevant to the community. Group-based cognitive interviewing provided an efficient and effective method for piloting a cardiovascular health survey instrument using CBPR.

  12. Developing Community-Focused Solutions using a Food-Energy-Water Calculator, with Initial Application to Western Kansas

    Science.gov (United States)

    Hill, M. C.; Pahwa, A.; Rogers, D.; Roundy, J. K.; Barron, R. W.

    2017-12-01

    Many agricultural areas are facing difficult circumstances. Kansas is one example, with problems that are typical. Past agricultural and hydrologic data document how irrigation in western Kansas has produced a multi-billion-dollar agricultural economy that is now threatened by pumping-induced declines in groundwater levels. Although reduced pumping could mitigate much of the threat and preserve much of Kansas' agricultural economy (albeit at a reduced level) in the long term, a primary disincentive for reducing pumping is the immediate economic impact of diminished irrigation. One alternative to continued unsustainable groundwater use is a water-energy tradeoff program that seeks to reduce pumping from the Ogallala aquifer to sustainable rates while maintaining local income levels. This program would allow development of the region's rich wind and solar energy resources in a way that focuses on local economic benefits, in exchange for water rights concessions from affected stakeholders. In considering this alternative, most citizens are currently unable to address a key question, "What could this mean for me?" Answering this question requires knowledge of agriculture, energy, water, economics, and drought probabilities, knowledge that is available at Kansas universities. This talk presents a joint University of Kansas - Kansas State University effort to address this need through development of the Food-Energy-Water Calculator. This talk will present the idea and discuss how the calculator would work. It is suggested that the framework created provides a powerful way to organize data and analysis results, and thus to seek solutions to difficult problems in many regions of the US and the world.

  13. Child- And Family-Focused Cognitive-Behavioral Therapy for Pediatric Bipolar Disorder: Development and Preliminary Results.

    Science.gov (United States)

    Pavuluri, Mani N.; Graczyk, Patricia A.; Henry, David B.; Carbray, Julie A.; Heidenreich, Jodi; Miklowitz, David J.

    2004-01-01

    Objective: To describe child- and family-focused cognitive-behavioral therapy (CFF-CBT), a new developmentally sensitive psychosocial intervention for pediatric bipolar disorder (PBD) that is intended for use along with medication. CFF-CBT integrates principles of family-focused therapy with those of CBT. The theoretical framework is based on (1)…

  14. How and when Does Complex Reasoning Occur? Empirically Driven Development of a Learning Progression Focused on Complex Reasoning about Biodiversity

    Science.gov (United States)

    Songer, Nancy Butler; Kelcey, Ben; Gotwals, Amelia Wenk

    2009-01-01

    In order to compete in a global economy, students are going to need resources and curricula focusing on critical thinking and reasoning in science. Despite awareness for the need for complex reasoning, American students perform poorly relative to peers on international standardized tests measuring complex thinking in science. Research focusing on…

  15. Development of a mouse-feline chimeric antibody against feline tumor necrosis factor-alpha

    Science.gov (United States)

    DOKI, Tomoyoshi; TAKANO, Tomomi; HOHDATSU, Tsutomu

    2016-01-01

    Feline infectious peritonitis (FIP) is a fatal inflammatory disease caused by FIP virus infection. Feline tumor necrosis factor (fTNF)-alpha is closely involved in the aggravation of FIP pathology. We previously described the preparation of neutralizing mouse anti-fTNF-alpha monoclonal antibody (mAb 2–4) and clarified its role in the clinical condition of cats with FIP using in vitro systems. However, administration of mouse mAb 2–4 to cat may lead to a production of feline anti-mouse antibodies. In the present study, we prepared a mouse-feline chimeric mAb (chimeric mAb 2–4) by fusing the variable region of mouse mAb 2–4 to the constant region of feline antibody. The chimeric mAb 2–4 was confirmed to have fTNF-alpha neutralization activity. Purified mouse mAb 2–4 and chimeric mAb 2–4 were repeatedly administered to cats, and the changes in the ability to induce feline anti-mouse antibody response were investigated. In the serum of cats treated with mouse mAb 2–4, feline anti-mouse antibody production was induced, and the fTNF-alpha neutralization effect of mouse mAb 2–4 was reduced. In contrast, in cats treated with chimeric mAb 2–4, the feline anti-mouse antibody response was decreased compared to that of mouse mAb 2–4-treated cats. PMID:27264736

  16. Tumor necrosis factor receptor- associated factor 6 (TRAF6) regulation of development, function, and homeostasis of the immune system.

    Science.gov (United States)

    Walsh, Matthew C; Lee, JangEun; Choi, Yongwon

    2015-07-01

    Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) is an adapter protein that mediates a wide array of protein-protein interactions via its TRAF domain and a RING finger domain that possesses non-conventional E3 ubiquitin ligase activity. First identified nearly two decades ago as a mediator of interleukin-1 receptor (IL-1R)-mediated activation of NFκB, TRAF6 has since been identified as an actor downstream of multiple receptor families with immunoregulatory functions, including members of the TNFR superfamily, the Toll-like receptor (TLR) family, tumor growth factor-β receptors (TGFβR), and T-cell receptor (TCR). In addition to NFκB, TRAF6 may also direct activation of mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), an