Sample records for produktion von tumor-nekrose-faktor

  1. Zeitlicher Verlauf der avaskulären Nekrose des Hüftkopfes bei Patienten mit Pemphigus vulgaris.

    PubMed

    Balighi, Kamran; Daneshpazhooh, Maryam; Aghazadeh, Nessa; Saeidi, Vahide; Shahpouri, Farzam; Hejazi, Pardis; Chams-Davatchi, Cheyda

    2016-10-01

    Pemphigus vulgaris (PV) wird in der Regel mit systemischen Corticosteroiden und Immunsuppressiva behandelt. Avaskuläre Nekrose (AVN) des Hüftkopfes ist eine gut bekannte schwerere Komplikation einer Corticosteroid-Therapie. Die Charakteristika dieser schweren Komplikation bei PV sind nach wie vor unbekannt. Nicht kontrollierte, retrospektive Untersuchung aller PV-bedingten AVN-Fälle, die in einer iranischen Klinik für bullöse Autoimmunerkrankungen zwischen 1985 und 2013 diagnostiziert wurden. Anhand der Krankenakten von 2321 untersuchten PV-Patienten wurden 45 Fälle (1,93 %) von femoraler AVN identifiziert. Dreißig davon waren Männer. Das mittlere Alter bei der Diagnose der AVN betrug 47,4 ± 14,2 Jahre. Der mittlere Zeitraum zwischen der Diagnose des PV und dem Einsetzen der AVN lag bei 25,3 ± 18,3 Monaten. Mit Ausnahme von acht Fällen (17,8 %) setzte die AVN bei der Mehrheit der Patienten innerhalb von drei Jahren nach Diagnose des PV ein. Die mittlere kumulative Dosis von Prednisolon bei Patienten mit AVN betrug 13.115,8 ± 7041,1 mg. Zwischen der Prednisolon-Gesamtdosis und dem Zeitraum bis zum Einsetzen der AVN bestand eine starke Korrelation (p = 0,001). Bei Patienten mit Alendronateinnahme in der Vorgeschichte war dieser Zeitraum signifikant kürzer (p = 0,01). Die AVN ist eine schwere Komplikation einer Corticosteroid-Behandlung bei Patienten mit PV. Sie wird bei 2 % der Patienten beobachtet und tritt vor allem in den ersten drei Behandlungsjahren auf. Bei Patienten, die höhere Dosen von Prednisolon erhalten, setzt die AVN tendenziell früher ein. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  2. Developmentally arrested structures preceding cerebellar tumors in von Hippel–Lindau disease

    PubMed Central

    Shively, Sharon B; Falke, Eric A; Li, Jie; Tran, Maxine G B; Thompson, Eli R; Maxwell, Patrick H; Roessler, Erich; Oldfield, Edward H; Lonser, Russell R; Vortmeyer, Alexander O

    2011-01-01

    There is increasing evidence that suggests that knockout of tumor-suppressor gene function causes developmental arrest and protraction of cellular differentiation. In the peripheral nervous system of patients with the tumor-suppressor gene disorder, von Hippel–Lindau disease, we have demonstrated developmentally arrested structural elements composed of hemangioblast progenitor cells. Some developmentally arrested structural elements progress to a frank tumor, hemangioblastoma. However, in von Hippel–Lindau disease, hemangioblastomas are frequently observed in the cerebellum, suggesting an origin in the central nervous system. We performed a structural and topographic analysis of cerebellar tissues obtained from von Hippel–Lindau disease patients to identify and characterize developmentally arrested structural elements in the central nervous system. We examined the entire cerebella of five tumor-free von Hippel–Lindau disease patients and of three non-von Hippel–Lindau disease controls. In all, 9 cerebellar developmentally arrested structural elements were detected and topographically mapped in 385 blocks of von Hippel–Lindau disease cerebella. No developmentally arrested structural elements were seen in 214 blocks from control cerebella. Developmentally arrested structural elements are composed of poorly differentiated cells that express hypoxia-inducible factor (HIF)2α, but not HIF1α or brachyury, and preferentially involve the molecular layer of the dorsum cerebelli. For the first time, we identify and characterize developmentally arrested structural elements in the central nervous system of von Hippel–Lindau patients. We provide evidence that developmentally arrested structural elements in the cerebellum are composed of developmentally arrested hemangioblast progenitor cells in the molecular layer of the dorsum cerebelli. PMID:21499240

  3. XML-basierte Produkt- und Prozessdaten für die Leittechnik-Projektierung

    NASA Astrophysics Data System (ADS)

    Schleipen, Miriam

    Für die Überwachung und Steuerung hochkomplexer Produktionsprozesse werden Prozessleitsysteme eingesetzt. Ständige Veränderungen zwingen Produktionsbetriebe wandlungsfähig zu sein. Entsprechend muss auch die Technik diese Flexibilität unterstützen. Jede Veränderung des Produktionsprozesses muss eingeplant, die Anlagen neu konfiguriert und projektiert werden. Dabei müssen auch neue Prozessbilder für die Bedien- und Steuerungssysteme erstellt werden. Am Fraunhofer IITB wurde ein Engineering-Framework entwickelt, das das Leitsystem automatisch projektiert und die zugehörige Prozessvisualisierung generiert. In diesem Beitrag wird das Modul vorgestellt, dass die Prozessabbilder erstellt. Neben der Visualisierung von Anlagen werden auch laufende Prozesse und bearbeitete Produkte dargestellt. So können beispielsweise Identsysteme mit der Leittechnik gekoppelt werden.

  4. Von Hippel-Lindau Disease

    MedlinePlus

    What is Von Hippel-Lindau disease (VHL)? Von Hippel-Lindau disease (VHL) is a rare disease that causes tumors and cysts to grow in your body. They ... can become cancerous. What causes Von Hippel-Lindau disease (VHL)? Von Hippel-Lindau disease (VHL) is a ...

  5. Prognostischer Wert der Fläche und Dichte von Lymphgefäßen bei kutanem Plattenepithelkarzinom.

    PubMed

    Krediet, Jorien Tannette; Kanitakis, Jean; Bob, Adrienne; Schmitter, Julia; Carine Krediet, Annelot; Röwert, Joachim; Stockfleth, Eggert; Painsi, Clemens; Hügel, Rainer; Terhorst, Dorothea; Lange-Asschenfeldt, Bernhard

    2016-11-01

    Kutane Plattenepithelkarzinome (SCC) sind bekannt für ihre Fähigkeit, über Lymphgefäße zu metastasieren. In neueren Studien wird das Ausmaß der Lymphangiogenese als möglicher prognostischer Faktor bei einigen Hauttumoren genannt. Ziel dieser Studie war die Quantifizierung der Lymphangiogenese bei SCC entweder durch computergestützte Bildanalyse oder mithilfe der Zählmethode nach Chalkley. Gefäßparameter wurden im Hinblick auf ihre Vorhersagekraft für die Bildung von Tumormetastasen beurteilt und verglichen. In dieser Fallkontrollstudie wurden die klinischen und histologischen Daten von jeweils 15 SCC-Patienten mit bzw. ohne Metastasen retrospektiv analysiert. In den SCC-Proben wurde der für das Lymphendothel spezifische Marker D2-40 und der pan-vaskuläre Marker CD31 immunhistochemisch angefärbt und durch computergestützte morphometrische Bildanalyse in Hotspots sowie mithilfe der digitalisierten Zählmethode nach Chalkley analysiert. Die Dichte von Lymphgefäßen, die relative Lymphgefäßfläche und die mit der Chalkley-Methode ermittelte Zahl an Lymphgefäßen (Chalkley-Count) waren bei metastasierten SCC signifikant erhöht. Die Tumordicke war bei metastasierten SCC signifikant höher und besaß die höchste Vorhersagekraft für eine Metastasierung. Die Tumordicke war ein signifikanter Prädiktor für Lymphangiogeneseparameter. Die Lymphangiogenese ist bei metastasierten SCC erhöht, doch ihr Ausmaß wird von der Tumordicke beeinflusst. Die Tumordicke bildet weiterhin den zuverlässigsten prädiktiven Faktor für die Metastasierung. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  6. Pancreatic neuroendocrine tumor with complete replacement of the pancreas by serous cystic neoplasms in a patient with von Hippel-Lindau disease: a case report.

    PubMed

    Maeda, Shimpei; Motoi, Fuyuhiko; Oana, Shuhei; Ariake, Kyohei; Mizuma, Masamichi; Morikawa, Takanori; Hayashi, Hiroki; Nakagawa, Kei; Kamei, Takashi; Naitoh, Takeshi; Unno, Michiaki

    2017-09-25

    von Hippel-Lindau disease is a dominantly inherited multi-system syndrome with neoplastic hallmarks. Pancreatic lesions associated with von Hippel-Lindau include serous cystic neoplasms, simple cysts, and neuroendocrine tumors. The combination of pancreatic neuroendocrine tumors and serous cystic neoplasms is relatively rare, and the surgical treatment of these lesions must consider both preservation of pancreatic function and oncological clearance. We report a patient with von Hippel-Lindau disease successfully treated with pancreas-sparing resection of a pancreatic neuroendocrine tumor where the pancreas had been completely replaced by serous cystic neoplasms, in which pancreatic function was preserved. A 39-year-old female with von Hippel-Lindau disease was referred to our institution for treatment of a pancreatic neuroendocrine tumor. Abdominal computed tomography demonstrated a well-enhanced mass, 4 cm in diameter in the tail of the pancreas, and two multilocular tumors with several calcifications, 5 cm in diameter, in the head of the pancreas. There was complete replacement of the pancreas by multiple cystic lesions with diameters ranging from 1 to 3 cm. Magnetic resonance cholangiopancreatography showed innumerable cystic lesions on the whole pancreas and no detectable main pancreatic duct. Endoscopic ultrasound-guided fine-needle aspiration of the mass in the pancreatic tail showed characteristic features of a neuroendocrine tumor. A diagnosis of pancreatic neuroendocrine tumor in the tail of the pancreas and mixed-type serous cystic neoplasms replacing the whole pancreas was made and she underwent distal pancreatectomy while avoiding total pancreatectomy. The stump of the pancreas was sutured as firm as possible using a fish-mouth closure. The patient made a good recovery and was discharged on postoperative day 9. She is currently alive and well with no symptoms of endocrine or exocrine pancreatic insufficiency 8 months after surgery. A pancreas

  7. Increased metastatic potential of tumor cells in von Willebrand factor-deficient mice.

    PubMed

    Terraube, V; Pendu, R; Baruch, D; Gebbink, M F B G; Meyer, D; Lenting, P J; Denis, C V

    2006-03-01

    The key role played by von Willebrand factor (VWF) in platelet adhesion suggests a potential implication in various pathologies, where this process is involved. In cancer metastasis development, tumor cells interact with platelets and the vessel wall to extravasate from the circulation. As a potential mediator of platelet-tumor cell interactions, VWF could influence this early step of tumor spread and therefore play a role in cancer metastasis. To investigate whether VWF is involved in metastasis development. In a first step, we characterized the interaction between murine melanoma cells B16-BL6 and VWF in vitro. In a second step, an experimental metastasis model was used to compare the formation of pulmonary metastatic foci in C57BL/6 wild-type and VWF-null mice following the injection of B16-BL6 cells or Lewis lung carcinoma cells. In vitro adhesion assays revealed that VWF is able to promote a dose-dependent adhesion of B16-BL6 cells via its Arg-Gly-Asp (RGD) sequence. In the experimental metastasis model, we found a significant increase in the number of pulmonary metastatic foci in VWF-null mice compared with the wild-type mice, a phenotype that could be corrected by restoring VWF plasma levels. We also showed that increased survival of the tumor cells in the lungs during the first 24 h in the absence of VWF was the cause of this increased metastasis. These findings suggest that VWF plays a protective role against tumor cell dissemination in vivo. Underlying mechanisms remain to be investigated.

  8. Hypoxia and cell cycle regulation of the von Hippel-Lindau tumor suppressor

    PubMed Central

    Liu, Weijun; Xin, Hong; Eckert, David T.; Brown, Julie A.; Gnarra, James R.

    2010-01-01

    Inactivation of von Hippel-Lindau tumor suppressor protein (pVHL) is associated with von Hippel-Lindau disease, an inherited cancer syndrome, as well as the majority of patients with sporadic clear cell renal carcinoma (RCC). While the involvement of pVHL in oxygen sensing through targeting HIFα subunits to ubiquitin-dependent proteolysis has been well documented, less is known about pVHL regulation under both normoxic and hypoxic conditions. We found that pVHL levels decreased in hypoxia and that hypoxia-induced cell cycle arrest is associated with pVHL expression in RCC cells. pVHL levels fluctuate during the cell cycle, paralleling cyclin B1 levels, with decreased levels in mitosis and G1. pVHL contains consensus Destruction box sequences, and pVHL associates with Cdh1, an activator of the anaphase promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. We show that pVHL has a decreased half-life in G1, Cdh1 downregulation results in increased pVHL expression, while Cdh1 overexpression results in decreased pVHL expression. Taken together these results suggest that pVHL is a novel substrate of APC/CCdh1. Destruction box-independent pVHL degradation was also detected, indicating that other ubiquitin ligases are also activated for pVHL degradation. PMID:20802534

  9. [Emergent Caesarean Section in a Patient with a Mediastinal Tumor and Von Recklinghausen Disease: A Case Report].

    PubMed

    Owada, Mayuko; Inomata, Shinichi; Danmura, Masato; Yamada, Kumiko; Tanaka, Makoto

    2016-06-01

    It is rare to encounter a pregnant patient with a mediastinal tumor, and if the tumor size increases as the pregnancy progresses, this increase can cause complications such as airway constriction and vascular occlusion. We report a case of a pregnant patient diagnosed with von Recklinghausen disease at the age of seven and diagnosed with a mediastinal tumors just after her present admission. The impending suffocation progressed and fetal heart rate decreased during her hospitalization. Her trachea was intubated and she was moved to an operating room for an emergent cesarean section under general anesthesia. With this rapid response, we could rescue both patient and infant. If the size of mediastinal tumor increases as pregnancy progresses, the tumor will cause suffocation by airway compression from the outside, in addition to specific airway edema on the inward side. The present case demonstrates that appropriate desisoins must be made for airway manegement and initiation of surgery.

  10. Modulare und durchgängige Produktmodelle als Erfolgsfaktor zur Bedienung einer Omni-Channel-Architektur - PLM 4.0

    NASA Astrophysics Data System (ADS)

    Golovatchev, Julius; Felsmann, Marcus

    Mit der Transformation der Wertschöpfungsstrukturen von Utility 1.0 zu Utility 4.0 erfolgt offensichtlich auch eine Veränderung des Produkts. Vor dem Hintergrund disruptiver Technologien (IoT, Big Data, Cloud, Robotics etc.) und auch gesellschaftlicher Veränderungen entstehen ständig neue Geschäftsmodelle und Produkte, die über die reine Versorgungsdienstleistung (z. B. Strom) hinausgehen. Dabei muss der wertvolle Rohstoff Produktdaten für smarte Produkte durchgängiger und schneller nutzbar gemacht werden. Die modularen und durchgängigen Produktstrukturen leisten einen Beitrag zur Beherrschung von Komplexität und stellen somit einen wesentlichen Hebel für erfolgreiche Produktentwicklung und -management dar. In diesem Beitrag werden Ansätze beschrieben, wie es den vor der Herausforderung Utility 4.0 stehenden Unternehmen gelingen kann, Smart-Energy-Produkte so zu modellieren, dass sie die Interoperabilität der einzelnen Produktionsmodule sicherstellt und ein Ende-zu-Ende-Management ermöglicht.

  11. Von Start-ups lernen - Methoden und Entwicklungsprozesse, die Jungunternehmen erfolgreich machen

    NASA Astrophysics Data System (ADS)

    Böhme, Eckhart

    Die Start-up-Bewegung bringt beständig sog. Disruptoren hervor, die jede Branche betreffen und so gut wie keinen Lebensbereich auslassen. Diese Jungunternehmen, insbesondere aus der Softwarebranche, verfügen zwar nicht über Ressourcen wie etablierte Unternehmen, sie sind jedoch agil, "hungrig", können frei von "Ballast" agieren und treiben die Digitalisierung aller Branchen voran. Aber auch Start-ups können nicht einfach ungetestete Ideen in erfolgreiche Produkte oder Dienstleistungen umwandeln und ihren Erfolg dem Zufall überlassen. Erfolgreiche Jungunternehmen folgen vielmehr einem strukturierten Prozess, um marktgetestete Nutzenversprechen und Geschäftsmodelle zu entwickeln. Zunehmend adaptieren etablierte Unternehmen innovative Entwicklungsprozesse und Methoden. Die Fragestellung für Energieversorgungsunternehmen (EVUs) lautet, welche Methoden, Werkzeuge und Entwicklungsprozesse, die heute bei vielen Start-ups eingesetzt werden, sie aufgreifen können, um das Unternehmen gegenüber Disruptoren robust zu machen?

  12. Methoden der digitalen Planung

    NASA Astrophysics Data System (ADS)

    Westkämper, Engelbert; Niemann, Jörg; Warschat, Joachim; Scheer, August-Wilhelm; Thomas, Oliver

    Die industrielle Produktion ist das Herz der verarbeitenden Industrie in Deutschland. Mit einem Beitrag von rund 500 Mrd. EUR pro Jahr erwirtschaftet das verarbeitende Gewerbe etwa ein Viertel der gesamtwirtschaftlichen Wertschöpfung in Deutschland. Gemessen am Produktionswert der Gesamtwirtschaft betrug der industrielle Anteil sogar über ein Drittel. Der Erhalt und der Ausbau der Wettbewerbsfähigkeit unter den gegebenen Rahmenbedingungen der globalen Märkte ist eine der größten Herausforderungen der deutschen Wirtschaft [5, 8]. In diesem Beitrag soll - ausgehend von einer Strategie der Ausrüster von Fabriken in einer globalen Produktion - diskutiert werden, wie mit der digitalen Fabrik Potentiale in den Planungs- und Wandlungsprozessen erschlossen werden können.

  13. Preventive medicine for von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors.

    PubMed

    Krauss, Tobias; Ferrara, Alfonso Massimiliano; Links, Thera P; Wellner, Ulrich; Bancos, Irina; Kvachenyuk, Andrey; Villar Gómez de Las Heras, Karina; Yukina, Marina; Petrov, Roman; Bullivant, Garrett; von Duecker, Laura; Jadhav, Swati S; Ploeckinger, Ursula; Welin, Staffan; Schalin-Jantti, Camilla; Gimm, Oliver; Pfeifer, Marija; Ngeow, Joanne; Hasse-Lazar, Kornelia; Sanso, Gabriela; Qi, Xiao-Ping; Ugurlu, Umit; Diaz, Rene Eduardo; Wohllk, Nelson; Peczkowska, Mariola; Aberle, Jens; Lourenço, Delmar Muniz; Pereira, Maria Adelaide; Fragoso, Maria Candida Barisson Villares; Hoff, Ana O; Almeida, Madson Queiroz; Violante, Alice H D; Quidute, Ana R P; Zhang, Zheiwei; Recasens, Monica; Robles Diaz, Luis; Kunavisarut, Tada; Wannachalee, Taweesak; Sirinvaravong, Sirinart; Jonasch, Eric; Grozinsky-Glasberg, Simona; Fraenkel, Merav; Beltsevich, Dmitry; Egorov, Viacheslav I; Bausch, Dirk; Schott, Matthias; Tiling, Nikolaus; Pennelli, Gianmaria; Zschiedrich, Stefan; Därr, Roland; Ruf, Juri; Denecke, Timm; Link, Karl-Heinrich; Zovato, Stefania; von Dobschuetz, Ernst; Yaremchuk, Svetlana; Amthauer, Holger; Makay, Ozer; Patocs, Attila; Walz, Martin K; Huber, Tobias B; Seufert, Jochen; Hellman, Per; Kim, Raymond H; Kuchinskaya, Ekaterina; Schiavi, Francesca; Malinoc, Angelica; Reisch, Nicole; Jarzab, Barbara; Barontini, Marta; Januszewicz, Andrzej; Shah, Nalini; Young, William; Opocher, Giuseppe; Eng, Charis; Neumann, Hartmut P H; Bausch, Birke

    2018-05-10

    Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2,330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P<0.001) and tumor volume doubling time (TVDT) was faster (22 vs 126 months; P=0.001). All metastatic tumors were ≥2.8 cm. Codons 161 and 167 were hotspots for VHL germline mutations with enhanced risk for metastatic PanNETs. Multivariate prediction modeling disclosed maximum tumor diameter and TVDT as significant predictors for metastatic disease (positive and negative predictive values of 51% and 100% for diameter cutoff ≥2.8 cm, 44% and 91% for TVDT cutoff of ≤24 months). In 117/273 patients, PanNETs >1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs <2.8cm vs ≥2.8 cm (94% vs 85% by 10 years; P=0.020; 80% vs 50% at 10 years; P=0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.

  14. Shorter telomere length increases age-related tumor risks in von Hippel-Lindau disease patients.

    PubMed

    Wang, Jiang-Yi; Peng, Shuang-He; Ning, Xiang-Hui; Li, Teng; Liu, Sheng-Jie; Liu, Jia-Yuan; Hong, Bao-An; Qi, Nie-Nie; Peng, Xiang; Zhou, Bo-Wen; Zhang, Jiu-Feng; Cai, Lin; Gong, Kan

    2017-09-01

    Von Hippel-Lindau (VHL) disease is a rare autosomal dominant cancer syndrome caused by alterations of VHL gene. Patients are predisposed to develop pheochromocytomas and solid or cystic tumors of the central nervous system, kidney, pancreas, and retina. Remarkable phenotypic heterogeneity exits in organ involvement and tumor onset age between and within VHL families. However, no reliable markers have been found to predict the age-related tumor risks in VHL patients. A large Chinese cohort composed of 300 VHL patients and 92 healthy family controls was enrolled in our study. Blood relative telomere length was measured in 184 patients and all the controls available for genomic DNA samples. Age-related risks for the five major VHL-associated tumors were evaluated using Kaplan-Meier plots and Cox regression analysis. Differences in clinical phenotype were observed between Chinese cohort and the United Kingdom cohort. VHL patients showed significantly shorter telomere length than healthy family controls(P = 0.0183), and a positive correlation was found between telomere length and onset age of the five major tumors, respectively. Moreover, patients in the shorter telomere group (age-adjusted telomere length ≤ 0.44) suffered higher age-related risks for VHL-associated central nervous system hemangioblastomas (HR: 1.879, P = 0.004), renal cell carcinoma (HR: 2.126, P = 0.002) and pancreatic cyst and neuroendocrine tumors (HR: 2.093, P = 0.001). These results indicate that blood shorter telomere length is a new biomarker for age-related tumor risks in VHL patients, which will be crucial to genetic counseling and future research about the role of telomere shortening in the pathogenesis of VHL-associated tumors. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  15. Tumors in von Hippel-Lindau Syndrome: From Head to Toe-Comprehensive State-of-the-Art Review.

    PubMed

    Ganeshan, Dhakshinamoorthy; Menias, Christine O; Pickhardt, Perry J; Sandrasegaran, Kumaresan; Lubner, Meghan G; Ramalingam, Preetha; Bhalla, Sanjeev

    2018-01-01

    Von Hippel-Lindau syndrome (VHL) is an autosomal-dominant hereditary tumor disease that arises owing to germline mutations in the VHL gene, located on the short arm of chromosome 3. Patients with VHL may develop multiple benign and malignant tumors involving various organ systems, including retinal hemangioblastomas (HBs), central nervous system (CNS) HBs, endolymphatic sac tumors, pancreatic neuroendocrine tumors, pancreatic cystadenomas, pancreatic cysts, clear cell renal cell carcinomas, renal cysts, pheochromocytomas, paragangliomas, and epididymal and broad ligament cystadenomas. The VHL/hypoxia-inducible factor pathway is believed to play a key role in the pathogenesis of VHL-related tumors. The diagnosis of VHL can be made clinically when the characteristic clinical history and findings have manifested, such as the presence of two or more CNS HBs. Genetic testing for heterozygous germline VHL mutation may also be used to confirm the diagnosis of VHL. Imaging plays an important role in the diagnosis and surveillance of patients with VHL. Familiarity with the clinical and imaging manifestations of the various VHL-related tumors is important for early detection and guiding appropriate management. The purpose of this article is to discuss the molecular cytogenetics and clinical manifestations of VHL, review the characteristic multimodality imaging features of the various VHL-related tumors affecting multiple organ systems, and discuss the latest advances in management of VHL, including current recommendations for surveillance and screening. © RSNA, 2018 An earlier incorrect version of this article appeared online. This article was corrected on April 9, 2018.

  16. Spinal Cord Tumor

    MedlinePlus

    ... are linked to known inherited syndromes, such as neurofibromatosis 2 and von Hippel-Lindau disease. Risk factors ... tumors are more common in people who have: Neurofibromatosis 2. In this hereditary disorder, benign tumors develop ...

  17. Liquid Biopsy zur Überwachung von Melanompatienten.

    PubMed

    Gaiser, Maria Rita; von Bubnoff, Nikolas; Gebhardt, Christoffer; Utikal, Jochen Sven

    2018-04-01

    In den letzten sechs Jahren wurden verschiedene innovative systemische Therapien zur Behandlung des metastasierten malignen Melanoms (MM) entwickelt. Die konventionelle Chemotherapie wurde durch neuartige Primärtherapien abgelöst, darunter systemische Immuntherapien (Anti-CTLA4- und Anti-PD1-Antikörper; Zulassung von Anti-PDL1-Antikörpern erwartet) und Therapien, die gegen bestimmte Mutationen gerichtet sind (BRAF, NRAS und c-KIT). Daher stehen die behandelnden Ärzte neuen Herausforderungen gegenüber, beispielsweise der Stratifizierung von Patienten für geeignete Behandlungen und der Überwachung von Langzeit-Respondern auf Progression. Folglich werden zuverlässige Methoden zur Überwachung von Krankheitsprogression oder Behandlungsresistenz benötigt. Lokalisierte und fortgeschrittene Krebserkrankungen können zur Bildung zirkulierender Tumorzellen und Tumor-DNA (ctDNA) führen, die sich in Proben von peripherem Blut nachweisen und quantifizieren lassen (Liquid Biopsy). Im Fall von Melanompatienten können die Ergebnisse von Liquid Biopsy als neuartige prädiktive Biomarker bei therapeutischen Entscheidungen hilfreich sein, insbesondere im Zusammenhang mit mutationsbasierten zielgerichteten Therapien. Die Herausforderungen bei der Anwendung der Liquid Biopsy beinhalten strikte Kriterien für den Phänotyp der zirkulierenden MM-Zellen oder ihrer Fragmente und die Instabilität von ctDNA im Blut. In diesem Übersichtsartikel diskutieren wir die Beschränkungen der Liquid Biopsy hinsichtlich ihrer Anwendung in der Routinediagnostik. © 2018 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  18. Uptake of genetic testing and long-term tumor surveillance in von Hippel-Lindau disease

    PubMed Central

    2010-01-01

    Background von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome caused by germline mutations in the VHL gene. Patients have significant morbidity and mortality secondary to vascular tumors. Disease management is centered on tumor surveillance that allows early detection and treatment. Presymptomatic genetic testing is therefore recommended, including in at-risk children. Methods We tested 17 families (n = 109 individuals) for VHL mutations including 43 children under the age of 18. Personalized genetic counseling was provided pre and post-test and the individuals undergoing presymptomatic testing filled out questionnaires gathering socio-demographic, psychological and psychiatric data. Mutation analysis was performed by direct sequencing of the VHL gene. Mutation-carriers were screened for VHL disease-related tumors and were offered follow-up annual examinations. Results Mutations were identified in 36 patients, 17 of whom were asymptomatic. In the initial screening, we identified at least one tumor in five of 17 previously asymptomatic individuals. At the end of five years, only 38.9% of the mutation-carriers continued participating in our tumor surveillance program. During this time, 14 mutation carriers developed a total of 32 new tumors, three of whom died of complications. Gender, education, income, marital status and religiosity were not found to be associated with adherence to the surveillance protocol. Follow-up adherence was also independent of pre-test depression, severity of disease, or number of affected family members. The only statistically significant predictor of adherence was being symptomatic at the time of testing (OR = 5; 95% CI 1.2 - 20.3; p = 0.02). Pre-test anxiety was more commonly observed in patients that discontinued follow-up (64.7% vs. 35.3%; p = 0.01). Conclusions The high initial uptake rate of genetic testing for VHL disease, including in minors, allowed the discontinuation of unnecessary screening procedures in non

  19. GPU-basierte Smart Visibility Techniken für die Planung von Tumor-Operationen

    NASA Astrophysics Data System (ADS)

    Tietjen, Christian; Kubisch, Christoph; Hiller, Stefan; Preim, Bernhard

    Bei der Planung von Tumoroperationen ist die Einschätzung von Abständen und Infiltrationen zu vitalen Strukturen wichtig. Im Bereich der medizinischen Visualisierung wurden hierfür bereits zahlreiche Techniken entwickelt, die unter dem Begriff Smart Visibility zusammengefasst werden. Zu diesen zählen Ghost Views und Section Views. In diesem Beitrag wird eine GPU-basierte Realisierung dieser Techniken für polygonale Daten vorgestellt. Die Parametrisierung der Techniken erfolgt automatisch, um einen klinischen Einsatz ermöglichen zu können.

  20. Herstellung von Chitosan und einige Anwendungen

    NASA Astrophysics Data System (ADS)

    Struszczyk, Marcin Henryk

    2001-05-01

    . Die aus Chitosan-Dispersionen hergestellten MCChB-Filme weisen bessere mechanische Eigenschaften (Bruchfestigkeit, Dehnung) und eine höhere Wasseraufnahmefähigkeit auf als Filme, die nach herkömmlichen Methoden aus sauerer Lösung hergestellt werden. Die Einführung von Proteinen ändert die mechanischen Eigenschaften der MCChB-Filme abhängig von der Art, der Proteine sowie des DD und der Mv des eingesetzte Chitosan. Die Zugabe von Protein beschleunigt den biologischen Abbau der MCChB-Filme. Aus den untersuchten MCChB-Filmen mit Proteinzusatz können leichte, reißfeste und dennoch elastische Materialen hergestellt werden. 4. Mit Hilfe von MCChB-Dispersion kann Papier modifiziert werden. Dadurch werden die mechanischen Eigenschaften verbessert und die Wasseraufnahme wird verringert. Die Zugabe von Proteinen verringert das Wasseraufnahmevermögen noch weiter. Ein geringes Wasseraufnahmevermögen ist der bedeutendste Faktor bei der Papierherstellung. Auch Papier, das mit einem MCChB-Protein-Komplexe modifiziert wurde, zeigt gute mechanische Eigenschaften. 5. Wird Chitosan durch unmittelbare Einführung von MCChB auf Cellulose-Fasern aufgebracht, so erhält man eine netzartige Struktur, während durch Ausfällung aufgebrachtes Chitosan eine dünne Schicht auf den Cellulose-Fasern bildet. Die netzartige Struktur erleichtert die Bioabbaubarkeit, während die Schichtstruktur diese erschwert. 6. Die guten mechanischen Eigenschaften, die geringe Wasseraufnahmefähigkeit und die mit Cellulose vergleichbare Bioabbaubarkeit von Papier, das mit MCChB modifiziert wurde, lassen MCChB für die Veredlung von Papier nützlich erscheinen. 1. Deacetylation of the crustacean chitosan causes drastically decrease in the Mv with increasing reaction temperature and time as well as the concentration of sodium hydroxide. However, the DD are relatively less affected. Pandalus borealis is a good source for production of chitosan having high Mv and low DD, whereas chitosan of medium to low Mv

  1. Design and analysis of a Petri net model of the Von Hippel-Lindau (VHL) tumor suppressor interaction network.

    PubMed

    Minervini, Giovanni; Panizzoni, Elisabetta; Giollo, Manuel; Masiero, Alessandro; Ferrari, Carlo; Tosatto, Silvio C E

    2014-01-01

    Von Hippel-Lindau (VHL) syndrome is a hereditary condition predisposing to the development of different cancer forms, related to germline inactivation of the homonymous tumor suppressor pVHL. The best characterized function of pVHL is the ubiquitination dependent degradation of Hypoxia Inducible Factor (HIF) via the proteasome. It is also involved in several cellular pathways acting as a molecular hub and interacting with more than 200 different proteins. Molecular details of pVHL plasticity remain in large part unknown. Here, we present a novel manually curated Petri Net (PN) model of the main pVHL functional pathways. The model was built using functional information derived from the literature. It includes all major pVHL functions and is able to credibly reproduce VHL syndrome at the molecular level. The reliability of the PN model also allowed in silico knockout experiments, driven by previous model analysis. Interestingly, PN analysis suggests that the variability of different VHL manifestations is correlated with the concomitant inactivation of different metabolic pathways.

  2. Pazopanib therapy for cerebellar hemangioblastomas in von Hippel–Lindau disease

    PubMed Central

    Kim, Betty Y. S.; Jonasch, Eric

    2016-01-01

    von Hippel–Lindau (VHL) disease is a genetically acquired multisystem tumor syndrome of the viscera and central nervous system (CNS). The most common tumors associated with this disease are histologically benign, slow-growing CNS hemangioblastomas affecting the retina, cerebellum, brainstem, spinal cord or nerve roots. With mean age at diagnosis of 30 years, CNS hemangioblastomas are usually the first manifestation of the disease. Ongoing clinical and radiological surveillance is required, with symptomatic lesions necessitating treatment. As tumor growth is inevitable during the lifetime of most VHL patients, and the multiplicity of tumors may preclude surgical cure, the search for effective therapies is ongoing. Here we provide the first report demonstrating clinical and radiological anti-tumor response using pazopanib, a small molecule multi-receptor tyrosine kinase inhibitor, in a patient with treatment-refractory VHL-associated CNS hemangioblastoma. Treatment initiation with daily oral pazopanib (800 mg/day) resulted in significant neurologic improvement and radiologic tumor volume reduction. PMID:22374327

  3. Einsatz molekularer Methoden für Starterkulturen

    NASA Astrophysics Data System (ADS)

    Ehrmann, Matthias A.; Pavlovic, Melanie

    Unter Starterkulturen versteht man Mikroorganismen (Bakterien, Hefen, Pilze), die pflanzlichen bzw. tierischen Rohstoffen zur gezielten Veränderung ihrer chemischen Zusammensetzung zugesetzt werden. Sie dienen im Wesentlichen der Aromabildung, der Strukturveränderung und der Konservierung der Lebensmittel und werden aufgrund spezieller, funktioneller Eigenschaften selektiert. Die Zugabe von Starterkulturen erfolgt in der Regel in relativ hohen Keimzahlen in Form von Rein- oder Mischkulturen. Die zum Einsatz kommenden Mikroorganismen sind ebenso zahlreich wie die daraus resultierenden Produkte und reichen von der Fermentation von Milchprodukten, Fleisch und Gemüse durch Milchsäurebakterien über die Essigsäureherstellung bis hin zum Einsatz von Hefen in der Brau- und Weinindustrie. Hieraus ergibt sich auch eine zunehmende Bedeutung schneller und zuverlässiger Methoden zur taxonomischen Identifizierung, aber auch zur Charakterisierung des genetischen Potenzials der jeweiligen Starterkulturen.

  4. Organisationsaspekte in der Umsetzung

    NASA Astrophysics Data System (ADS)

    Balck, Henning; Bungard, Walter; Hofmann, Karsten; Ganz, Walter; Schwenker, Burkhard; Hanßen, Dirk; Meindl, Rudolf; Schloske, Alexander; Thieme, Paul; Teufel, Peter

    Strukturbrüche sind eine der Hauptursachen für die Schwierigkeiten vieler Unternehmen, ihre Organisationsform zu modernisieren und vor allem turbulenten Marktbedingungen anzupassen. Klassische Beispiele für Strukturbrüche finden sich in der Spaltung von Aufbau- und Ablauforganisation, der Spaltung von Produktion und Dienstleistung oder der Spaltung von Planung und Ausführung. Ein wirkungsvoller Ansatz zur Überwindung solcher Spaltungen ist eine Art Versöhnungsmuster: die Polare Organisation. Wesentliche Elemente dieser Organisationsform sind ihr Netzwerkcharakter, kooperatives Zusammenwirken, eine hohe Kommunikationsintensität und eine polare Koppelung der kommunizierenden Partner oder - in abstrahierter Form - die organisierte Balance erfolgskritischer Gegensätze, wie Kosten und Qualität.

  5. Wernher von Braun

    NASA Image and Video Library

    1959-01-01

    This photograph of Dr. von Braun, shown here to the left of General Bruce Medaris, was taken in the fall of 1959, immediately prior to Medaris' retirement from the Army. At the time, von Braun and his associates worked for the Army Ballistics Missile Agency in Huntsville, Alabama. Those in the photograph have been identified as Ernst Stuhlinger, Frederick von Saurma, Fritz Mueller, Hermarn Weidner, E.W. Neubert (partially hidden), W.A. Mrazek, Karl Heimburg, Arthur Rudolph, Otto Hoberg, von Braun, Oswald Lange, Medaris, Helmut Hoelzer, Hans Maus, E.D. Geissler, Hans Heuter, and George Constan.

  6. Wernher von Braun

    NASA Image and Video Library

    1977-06-16

    Dr. Wernher von Braun served as Marshall Space Flight Center's first director from July 1, 1960 until January 27, 1970, when he was appointed NASA Deputy Associate Administrator for Planning. Following World War II, Dr. von Braun and his German colleagues arrived in the United States under Project Paper Clip to continue their rocket development work. In 1950, von Braun and his rocket team were transferred from Ft. Bliss, Texas to Huntsville, Alabama to work for the Army's rocket program at Redstone Arsenal and later, NASA's Marshall Space Flight Center. Under von Braun's leadership, Marshall developed the Saturn V launch vehicle which took Apollo astronauts to the moon. Dr. von Braun died in Alexandria, Va., on June 16, 1977, seven years after his NASA appointment. This photo was taken at the site where he was laid to rest.

  7. Wernher von Braun

    NASA Image and Video Library

    1960-01-01

    Dr. Wernher von Braun served as Marshall Space Flight Center's first director from July 1, 1960 until January 27, 1970, when he was appointed NASA Deputy Associate Administrator for Plarning. Following World War II, Dr. von Braun and his German colleagues arrived in the United States under Project Paperclip to continue their rocket development work. In 1950, von Braun and his rocket team were transferred from Ft. Bliss, Texas to Huntsville, Alabama to work for the Army's rocket program at Redstone Arsenal and later, NASA's Marshall Space Flight Center. Under von Braun's leadership, Marshall developed the Saturn V launch vehicle which took Apollo astronauts to the moon.

  8. Pregnancy and delivery in women with von Willebrand's disease and different von Willebrand factor mutations.

    PubMed

    Castaman, Giancarlo; Tosetto, Alberto; Rodeghiero, Francesco

    2010-06-01

    Pregnancy in von Willebrand's disease may carry a significant risk of bleeding. Information on changes in factor VIII and von Willebrand factor and pregnancy outcome in relation to von Willebrand factor gene mutations are very scanty. We examined biological response to desmopressin, changes in factor VIII and von Willebrand factor and pregnancy outcome in a cohort of 23 women with von Willebrand's disease characterized at molecular level and prospectively followed during 2000-2007. Thirty-one pregnancies occurred during the study period. Remarkably, similar changes of factor VIII and von Willebrand factor were observed after desmopressin and during pregnancy in nine women with R854Q, R1374H, V1665E, V1822G and C2362F mutations. Women with von Willebrand's disease and R1205H and C1130F mutations (17 pregnancies in 12 women) had only a slight increase of factor VIII and von Willebrand factor during pregnancy while their response to desmopressin was marked but short-lived. For these women, two to three desmopressin administrations within the first 48 hours were sufficient to successfully manage vaginal delivery. Two women with recessive von Willebrand's disease due to compound heterozygosity for different gene mutations had a spontaneous, major increase in factor VIII while von Willebrand factor remained severely reduced. Desmopressin increased factor VIII and was clinically useful in the first case, while a factor VIII/von Willebrand factor concentrate was required in the second patient not responsive to the compound. Factor VIII/von Willebrand factor concentrate was also required for two women with type 2 A von Willebrand's disease with V1665E mutations who had no von Willebrand factor activity change during pregnancy. In one of them, delayed bleeding occurred 15 days later requiring treatment with Factor VIII/von Willebrand factor concentrate. No miscarriages or stillbirths occurred. Close follow-up and detailed guidelines for the management of parturition have

  9. Wernher von Braun

    NASA Image and Video Library

    1970-02-24

    In 1970 Marshall Space Flight Center (MSFC) Director Dr. Wernher von Braun (right) was reassigned to NASA Headquarters to serve as Deputy Associate Administrator for Plarning. Prior to his transfer, Dr. von Braun was honored for his career in Huntsville, Alabama, with the celebration of "Wernher von Braun Day." Among those participating were Alabama Governor Albert Brewer (left) and Alabama Senator John Sparkman (center). (Courtesy of Huntsville/Madison County Public library)

  10. Design and Analysis of a Petri Net Model of the Von Hippel-Lindau (VHL) Tumor Suppressor Interaction Network

    PubMed Central

    Minervini, Giovanni; Panizzoni, Elisabetta; Giollo, Manuel; Masiero, Alessandro; Ferrari, Carlo; Tosatto, Silvio C. E.

    2014-01-01

    Von Hippel-Lindau (VHL) syndrome is a hereditary condition predisposing to the development of different cancer forms, related to germline inactivation of the homonymous tumor suppressor pVHL. The best characterized function of pVHL is the ubiquitination dependent degradation of Hypoxia Inducible Factor (HIF) via the proteasome. It is also involved in several cellular pathways acting as a molecular hub and interacting with more than 200 different proteins. Molecular details of pVHL plasticity remain in large part unknown. Here, we present a novel manually curated Petri Net (PN) model of the main pVHL functional pathways. The model was built using functional information derived from the literature. It includes all major pVHL functions and is able to credibly reproduce VHL syndrome at the molecular level. The reliability of the PN model also allowed in silico knockout experiments, driven by previous model analysis. Interestingly, PN analysis suggests that the variability of different VHL manifestations is correlated with the concomitant inactivation of different metabolic pathways. PMID:24886840

  11. [A Case of Von Hippel-Lindau Disease with Nonfunctioning Pancreatic Neuroendocrine Tumors Treated by Duodenum-Preserving Resection of the Head of the Pancreas and Spleen-Preserving Resection of the Tail of the Pancreas].

    PubMed

    Umehara, Yutaka; Umehara, Minoru; Tokura, Tomohisa; Yachi, Takafumi; Takahashi, Kenichi; Morita, Takayuki; Hakamada, Kenichi

    2015-10-01

    A 26-year-old woman presented to our department with a diagnosis of multiple nonfunctioning pancreatic neuroendocrine tumors. She had a family history of pheochromocytoma and a medical history of bilateral adrenalectomy for pheochromocytoma at the age of 25 years. During follow-up treatment for adrenal insufficiency after the surgery, highly enhanced tumors in the pancreas were detected on contrast-enhanced CT. Other examinations found that the patient did not satisfy the clinical criteria for von Hippel-Lindau (VHL) disease. Considering her age and risk of developing multiple heterotopic and heterochronous tumors, we performed a duodenum-preserving resection of the head of the pancreas and spleen-preserving resection of the tail of the pancreas with informed consent. The histopathological findings revealed that all of the tumors were NET G1. She underwent genetic testing postoperatively and was diagnosed with VHL disease. This diagnosis meant that we were able to create an optimal treatment plan for the patient. If a tumor predisposition syndrome is suspected, VHL disease should be borne in mind and genetic testing after genetic counseling should be duly considered.

  12. Wernher von Braun

    NASA Image and Video Library

    1954-01-01

    Marshall Center Director Dr. Wernher Von Braun is pictured with Walt Disney during a visit to the Marshall Space Flight Center in 1954. In the 1950s, Dr. Von Braun while working in California on the Saturn project, also worked with Disney studios as a technical director in making three films about Space Exploration for television. Disney's tour of Marshall in 1965 was Von Braun's hope for a renewed public interest in the future of the Space Program at NASA.

  13. Dr. Wernher von Braun

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Dr. von Braun is looking out from a 10th floor window of building 4200 at the Marshall Space Flight Center (MSFC). He was the first Center Director and served as the Director from July 1960 through February 1970. Following World War II, Dr. von Braun and his German colleagues arrived in the United States under the Project Paperclip (American acquisition of German rocket experts) to continue their rocket development work. In 1950, von Braun and his German Rocket Team (also called the Peenemuende Team) were transferred from Ft. Bliss, Texas to Huntsville, Alabama to work for the Army's rocket program at Redstone Arsenal and later, NASA's Marshall Space Flight Center (MSFC). Under Dr. von Braun's leadership, MSFC developed the Saturn V launch vehicle, which placed the first men, two American astronauts, on the Moon. Wernher von Braun's life was dedicated to expanding man's knowledge through the exploration of space.

  14. Wernher von Braun

    NASA Image and Video Library

    1959-01-01

    Five of the seven original astronauts are seen with Dr. von Braun inspecting the Mercury-Redstone hardware in the Fabrication Laboratory of Army Ballistic Missile Agency (ABMA) in 1959. Left to right: Astronauts Walter Schirra, Alan Shepard, John Glenn, Scott Carpenter, Gordon Cooper, and Dr. von Braun.

  15. Elemente moderner, schlanker Produktionssysteme

    NASA Astrophysics Data System (ADS)

    Bartholomay, Christian; Boppert, Julia; Dickmann, Eva; Dickmann, Philipp; Gröbner, Michael; Harting, Lothar; Leikep, Sabine; Michels, Friedhelm; Pfister, Johannes; Reitz, Andreas; Schedlbauer, Michael; Takeda, Hitoshi; Thews, Michael; Wilbert, Fred

    Meilensteine der modernen Produktion mit Lean Production, Total Quality Management, Six Sigma, Supply Chain Management, Lean Management und Lean Enterprise können zu effizienteren Abläufen führen. In der betrieblichen Praxis existiert jedoch eine Vielzahl von Zielkonflikten basierend auf Richtlinien von Material Requirements Planning- (MRP), Controlling- und anderen Systemen. Nur wenige Spezialisten in größeren Unternehmen sind im Stande, die Komplexität über die Grenzen eines Fachgebiets hinaus im Detail zu verstehen. Fachübergreifendes Verständnis scheitert an der Komplexität der Gesamtproblematik. Entscheidungen verschiedenster Fachbereiche begrenzen die maximal erreichbare Effizienz des Materialflusses. Logistik und Materialfluss werden daher in vielen Unternehmen als unabdingbare Kernkompetenz verstanden. Um eine schlanke Produktion, einen optimalen Materialfluss und somit minimale Produktkosten zu erreichen, sind folglich vielfältige andere Fachthemen als Vorraussetzungen zu beherrschen. Erst dann ist es in der Produktionslogistik möglich, im Vergleich zu einem Top-Benchmark erfolgreich zu sein. Um im täglichen Konkurrenzkampf die Nase auch morgen noch vorne zu haben" ist es nötig, über den Preis hinaus auch noch völlig andere Problemstellungen zu beherrschen.

  16. Titanisierung von Implantatoberflächen

    NASA Astrophysics Data System (ADS)

    Zimmermann, Hanngörg; Heinlein, Markus; Guldner, Norbert W.

    Titan gilt seit Jahrzehnten als einer der wichtigsten Implantatwerkstoffe in der Medizin. Neben den guten mechanischen Eigenschaften (Leichtigkeit, hohe Festigkeit etc.), besitzen Titanimplantate vor allem eine hervorragende Körperverträglichkeit, so dass die Implantate optimal in den humanen Organismus integriert werden [1]. Ist jedoch aufgrund der Anforderungen an das Implantat eine hohe Flexibilität und/ oder Elastizität gefragt, so scheidet der Werkstoff Titan aufgrund seiner spröden und unflexiblen Materialeigenschaften aus. Die Folge ist der Einsatz von Implantatmaterialien, sowohl künstlichen als auch biologischen Ursprungs, welche nicht selten eine unzureichende Biokompatibilität aufweisen und somit zu Fremdköper- und immunologischen Reaktionen und Einkapselung des Implantates führen können. Die Erhöhung der Körperverträglichkeit, eine Adaption an das biologische Umfeld und eine hohe Biokompatibilität sind demzufolge die wichtigsten Eigenschaften bei der bedarfsgerechten Herstellung von Implantaten und Implantatoberflächen. Zur Gestaltung von innovativen, biokompatiblen Oberflächen stehen unterschiedliche technische Lösungsansätze zur Verfügung. Zum einen besteht die Möglichkeit, geeignete Oberflächeneigenschaften aus dem Grundmaterial selbst zu optimieren. Dies geschieht unter anderem durch Modifikation der Werkstoffoberflächen in Form von Texturierungen und Oberflächenrauhigkeiten. Zum anderen können die Oberflächeneigenschaften unabhängig von denen des Trägermaterials gestaltet werden. Durch Funktionalisierung der Oberflächen mit geeigneten Beschichtungen oder der Zugabe von Medikamenten (Drug Eluting) werden die Kunststoffimplantate dahingehend verändert, dass eine Steigerung der Körperakzeptanz erreicht wird. Die Titanbeschichtung von Implantatoberflächen kombiniert die positiven Materialeigenschaften von Titan und Polymer.

  17. Wernher von Braun

    NASA Image and Video Library

    1968-01-22

    Dr. Wernher Von Braun, stands in front of a Saturn IB Launch Vehicle at Kennedy Space Center (KSC). Dr. Von Braun was Marshall's first Center Director (1960-1970). Under his leadership Marshall was responsible for the development of the Saturn rockets, the Skylab project and getting the United States into Space and landing on the moon with the Apollo missions.

  18. Wernher von Braun

    NASA Image and Video Library

    1970-02-24

    Dr. von Braun was honored with a series of farewell events and ceremonies prior to his reassignment to NASA Headquarters in Washington, D.C. Alabama Governor Brewer greets Dr. von Braun following his speech at the front of the Madison County Courthouse in Huntsville, Alabama on February 24, 1970. Behind are Madison County Commissioner James Record, Huntsville Mayor Joe Davis, and U.S. Senator Sparkman.

  19. Wernher von Braun

    NASA Image and Video Library

    1969-07-24

    Apollo 11 splashdown celebration in Huntsville, Alabama, on July 24, 1969. Huntsville Alabama is the home of the Marshall Space Flight Center which developed the Saturn vehicles under the direction of Dr. von Braun. The photo shows Dr. von Braun speaking to the crowd at the Madison County Courthouse as Mayor Joe Davis, Madison County Commissioner James Record and City Council President Ken Johnson look on.

  20. Wernher von Braun

    NASA Image and Video Library

    1969-07-24

    Dr. von Braun is carried aloft on the shoulders of Huntsville city officials during the Apollo 11 celebration in Huntsville, Alabama, on July 24, 1969. Huntsville, Alabama is the home of the Marshall Space Flight Center which developed the Saturn vehicles under the direction of Dr. von Braun. The Apollo 11 lifted off in July and made the first marned lunar landing on the Moon.

  1. Hypoxia-mediated sorafenib resistance can be overcome by EF24 through Von Hippel-Lindau tumor suppressor-dependent HIF-1α inhibition in hepatocellular carcinoma.

    PubMed

    Liang, Yingjian; Zheng, Tongsen; Song, Ruipeng; Wang, Jiabei; Yin, Dalong; Wang, Luoluo; Liu, Haitao; Tian, Lantian; Fang, Xiang; Meng, Xianzhi; Jiang, Hongchi; Liu, Jiaren; Liu, Lianxin

    2013-05-01

    The increasing incidence of hepatocellular carcinoma (HCC) is of great concern not only in the United States but throughout the world. Although sorafenib, a multikinase inhibitor with antiangiogenic and antiproliferative effects, currently sets the new standard for advanced HCC, tumor response rates are usually quite low. An understanding of the underlying mechanisms for sorafenib resistance is critical if outcomes are to be improved. In this study we tested the hypothesis that hypoxia caused by the antiangiogenic effects of sustained sorafenib therapy could induce sorafenib resistance as a cytoprotective adaptive response, thereby limiting sorafenib efficiency. We found that HCCs, clinically resistant to sorafenib, exhibit increased intratumor hypoxia compared with HCCs before treatment or HCCs sensitive to sorafenib. Hypoxia protected HCC cells against sorafenib and hypoxia-inducible factor 1 (HIF-1α) was required for the process. HCC cells acquired increased P-gp expression, enhanced glycolytic metabolism, and increased nuclear factor kappa B (NF-κB) activity under hypoxia. EF24, a molecule having structural similarity to curcumin, could synergistically enhance the antitumor effects of sorafenib and overcome sorafenib resistance through inhibiting HIF-1α by sequestering it in cytoplasm and promoting degradation by way of up-regulating Von Hippel-Lindau tumor suppressor (VHL). Furthermore, we found that sustained sorafenib therapy led to increased intratumor hypoxia, which was associated with sorafenib sensitivity in HCC subcutaneous mice tumor models. The combination of EF24 and sorafenib showed synergistically effects against metastasis both in vivo and in vitro. Synergistic tumor growth inhibition effects were also observed in subcutaneous and orthotopic hepatic tumors. Hypoxia induced by sustained sorafenib treatment confers sorafenib resistance to HCC through HIF-1α and NF-κB activation. EF24 overcomes sorafenib resistance through VHL-dependent HIF-1

  2. Diagnosis and management of von Willebrand's syndrome.

    PubMed

    Rick, M E

    1994-05-01

    von Willebrand's disease is the most common of the inherited bleeding disorders. It is caused by quantitative and/or qualitative abnormalities of von Willebrand factor, and it usually presents with bleeding from mucosal surfaces. The diagnosis is confirmed by measuring von Willebrand factor activity and antigen levels, factor VIII activity, and performing a multimer analysis of von Willebrand factor. Treatment may require plasma-derived concentrates, but can often be accomplished with DDAVP, a vasopressin analogue that causes transient release of von Willebrand factor from body storage sites.

  3. Paraneoplastic Cushing Syndrome Due To Wilm's Tumor.

    PubMed

    Faizan, Mahwish; Manzoor, Jaida; Saleem, Muhammad; Anwar, Saadia; Mehmood, Qaiser; Hameed, Ambreen; Ali, Agha Shabbir

    2017-05-01

    Paraneoplastic syndromes are rare disorders that are triggered by an altered immune system response to neoplasm. Paraneoplastic syndromes may be the first or the most prominent manifestations of cancer. Wilm's tumor is the most frequent pediatric renal malignancy and usually presents with abdominal mass. Unusual presentations like acquired von Willebrand disease, sudden death due to pulmonary embolism and Cushing syndrome have been described in the literature. Cushing syndrome, as the presenting symptom of a malignant renal tumor in children, is a very rare entity. Few case reports are available in the literature exploring the option of preoperative chemotherapy as well as upfront nephrectomy. We report a rare case of paraneoplastic Cushing syndrome due to a Wilm's tumor. Based on gradual decrease of postoperative weight, blood pressure, serum adrenocorticotropic hormone, and plasma cortisol levels, along with histological confirmation of Wilm's tumor, paraneoplastic Cushing syndrome due to Wilm's tumor was confirmed.

  4. A double commutant theorem for Murray–von Neumann algebras

    PubMed Central

    Liu, Zhe

    2012-01-01

    Murray–von Neumann algebras are algebras of operators affiliated with finite von Neumann algebras. In this article, we study commutativity and affiliation of self-adjoint operators (possibly unbounded). We show that a maximal abelian self-adjoint subalgebra of the Murray–von Neumann algebra associated with a finite von Neumann algebra is the Murray–von Neumann algebra , where is a maximal abelian self-adjoint subalgebra of and, in addition, is . We also prove that the Murray–von Neumann algebra with the center of is the center of the Murray–von Neumann algebra . Von Neumann’s celebrated double commutant theorem characterizes von Neumann algebras as those for which , where , the commutant of , is the set of bounded operators on the Hilbert space that commute with all operators in . At the end of this article, we present a double commutant theorem for Murray–von Neumann algebras. PMID:22543165

  5. Wernher von Braun

    NASA Image and Video Library

    1964-03-24

    Marshall Space Flight Center Director Dr. Wernher von Braun presents Lady Bird Johnson with an inscribed hard hat during the First Lady's March 24, 1964 visit. While at the Marshall Center, Mrs. Johnson addressed Center employees, toured facilities and witnessed test firings of a Saturn I first stage and an F-1 engine. Dr. von Braun is wearing a Texas hat presented to him months earlier by Lyndon Johnson during a visit to the Johnson ranch in Texas.

  6. Synchronous adrenocortical neoplasms, paragangliomas, and pheochromocytomas: syndromic considerations regarding an unusual constellation of endocrine tumors.

    PubMed

    LeBlanc, Melissa; Tabrizi, Mohsen; Kapsner, Patricia; Hanson, Joshua Anspach

    2014-12-01

    The most common clinical syndromes presenting with paragangliomas and/or pheochromocytomas as their endocrine components are multiple endocrine neoplasia type 2, neurofibromatosis, Von Hippel-Lindau syndrome, Carney-Stratakis syndrome, Carney triad, and the recently described hereditary paraganglioma syndrome. Only Carney triad is known to also present with adrenocortical adenomas, currently representing the only described syndrome in which all 3 of the aforementioned tumors are found together. In most cases, prototypical lesions of the triad such as gastrointestinal stromal tumor and pulmonary chondromas are also seen. We present a case of a young woman with synchronous paragangliomas, adrenal/extra-adrenal cortical neoplasms, and pheochromocytoma without genetic mutations for multiple endocrine neoplasia 2, Von Hippel-Lindau syndrome, neurofibromatosis, and succinate dehydrogenase. We speculate that this represents a previously undescribed presentation of Carney triad and, at the very least, indicates the need for monitoring for the development of other tumors of the triad. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Molecular-genetic diagnostics of von Hippel-Lindau syndrome (VHL) in Bulgaria: first complex mutation event in the VHL gene.

    PubMed

    Glushkova, Maria; Dimova, Petia; Yordanova, Iglika; Todorov, Tihomir; Tourtourikov, Ivan; Mitev, Vanyo; Todorova, Albena

    2018-02-01

    Von Hippel-Lindau syndrome is an autosomal-dominant disease characterized by the formation of various tumours and cysts in many different parts of the body. Von Hippel-Lindau syndrome is caused by VHL gene mutations leading to production of impaired tumor suppressor Von Hippel-Lindau syndrome protein or its complete absence. To study five patients with clinically suspected Von Hippel-Lindau syndrome, who were referred for molecular genetic testing. Sanger sequencing of the coding regions of the VHL gene. Five clinically relevant germline mutations were detected. One of the pathogenic variants has not been previously reported. This novel mutation is a complex mutation event combining a duplication and an indel, rearranging exon 3 of the VHL gene - c. [516_517dupGTCAAGCCT; 532_542delCTGGACATCGTinsATTA], p. (Glu173Serfs*4). Overall, our results showed that the diagnosis of Von Hippel-Lindau syndrome in our country is difficult most probably because of its heterogeneous clinical manifestation and insufficient knowledge on the diagnostic criteria for the disease. From genetic point of view our results add some novel data on the mutation profile of the VHL gene. In order to prove or revise the diagnosis, early genetic testing is strongly recommended in affected patients and their family members to ensure appropriate follow-up and treatment of the malignancies.

  8. Wernher von Braun

    NASA Image and Video Library

    1958-01-31

    Jet Propulsion Laboratory Director Dr. James Pickering, Dr. James van Allen of the State University of Iowa, and Army Ballistic missionile Agency Technical Director Dr. Wernher von Braun triumphantly display a model of the Explorer I, America's first satellite, shortly after the satellite's launch on January 31, 1958. The Jet Propulsion Laboratory packed and tested the payload, a radiation detection experiment designed by Dr. van Allen. Dr. von Braun's rocket team at Redstone Arsenal in Huntsville, Alabama, developed the Juno I launch vehicle, a modified Jupiter-C.

  9. Dr. von Braun Briefing Walt Disney

    NASA Technical Reports Server (NTRS)

    1965-01-01

    Dr. von Braun began his association with Walt Disney in the 1950s when the rocket scientist appeared in three Disney television productions related to the exploration of space. Years later, Dr. von Braun invited Disney and his associates to tour the Marshall Space Flight Center (MSFC) in Huntsville, Alabama. This photograph is dated April 13, 1965. From left are R.J. Schwinghamer from the MSFC, Disney, B.J. Bernight, and Dr. von Braun.

  10. Wernher von Braun

    NASA Image and Video Library

    1970-06-27

    This photograph was taken after Dr. von Braun moved from his post as Director of the Marshall Space Flight Center (MSFC) to Deputy Associate Administrator for Planning at NASA Headquarters. On June 27, 1970, he visited the MSFC again during the center’s 10th anniversary to look at a mockup of the spacecraft that would later be known as Skylab. With von Braun are (left to right): Herman K. Weidner, director of Science and Engineering at MSFC, and James R. Thompson of the center’s Astrionics Laboratory.

  11. Verbesserung der Symmetrie von Hirnaufnahmen entlang der Sagittalebene

    NASA Astrophysics Data System (ADS)

    Ens, Konstantin; Wenzel, Fabian; Fischer, Bernd

    Die lokale Symmetrie von Hirnscans entlang der Sagittalebene zu ermitteln und zu modizifieren, ist für eine Reihe neurologischer Anwendungen interessant. Beispielsweise kann der voxelweise Vergleich von rechter und linker Hirnhälfte nur dann Aufschluss über die Lokalisierung von Läsionen geben, wenn durch Transformation ein Hirnscan eine möglichst hohe Symmetrie aufweist. Ein weiteres Anwendungsgebiet ist die Visualisierung von medialen Hirnschnitten, für die die Trennfläche beider Hirnhälfte möglichst eben sein sollte. Diese Arbeit stellt die Entwicklung eines Verfahrens vor, mit dessen Hilfe die Symmetrie von Hirnaufnahmen entlang der Sagittalebene verbessert werden kann. Dies geschieht unter Verwendung von aktiven Konturen, die mit Hilfe einer neuartigen Kostenfunktion gesteuert werden. Experimente am Ende der Arbeit mit strukturellen Kernspinaufnahmen demonstrieren die Leistungsfähigkeit des Verfahrens.

  12. Cystic renal tumors: new entities and novel concepts.

    PubMed

    Moch, Holger

    2010-05-01

    Cystic renal neoplasms and renal epithelial stromal tumors are diagnostically challenging and represent some novel tumor entities. In this article, clinical and pathologic features of established and novel entities are discussed. Predominantly cystic renal tumors include cystic nephroma/mixed epithelial and stromal tumor, synovial sarcoma, and multilocular cystic renal cell carcinoma. These entities are own tumor entities of the 2004 WHO classification of renal tumors. Tubulocystic carcinoma and acquired cystic disease-associated renal cell carcinoma are neoplasms with an intrinsically cystic growth pattern. Both tumor types should be included in a future WHO classification as novel entities owing to their characteristic features. Cysts and clear cell renal cell carcinoma frequently coexist within the kidneys of patients with von Hippel-Lindau disease. Sporadic clear cell renal cell carcinomas often contain cysts, usually as a minor component. Some clear cell renal cell carcinomas have prominent cysts, and multilocular cystic renal cell carcinoma is composed almost exclusively of cysts. Recent molecular findings suggest that clear cell renal cancer may develop through cyst-dependent and cyst-independent molecular pathways.

  13. A note on derivations of Murray–von Neumann algebras

    PubMed Central

    Kadison, Richard V.; Liu, Zhe

    2014-01-01

    A Murray–von Neumann algebra is the algebra of operators affiliated with a finite von Neumann algebra. In this article, we first present a brief introduction to the theory of derivations of operator algebras from both the physical and mathematical points of view. We then describe our recent work on derivations of Murray–von Neumann algebras. We show that the “extended derivations” of a Murray–von Neumann algebra, those that map the associated finite von Neumann algebra into itself, are inner. In particular, we prove that the only derivation that maps a Murray–von Neumann algebra associated with a factor of type II1 into that factor is 0. Those results are extensions of Singer’s seminal result answering a question of Kaplansky, as applied to von Neumann algebras: The algebra may be noncommutative and may even contain unbounded elements. PMID:24469831

  14. A note on derivations of Murray-von Neumann algebras.

    PubMed

    Kadison, Richard V; Liu, Zhe

    2014-02-11

    A Murray-von Neumann algebra is the algebra of operators affiliated with a finite von Neumann algebra. In this article, we first present a brief introduction to the theory of derivations of operator algebras from both the physical and mathematical points of view. We then describe our recent work on derivations of Murray-von Neumann algebras. We show that the "extended derivations" of a Murray-von Neumann algebra, those that map the associated finite von Neumann algebra into itself, are inner. In particular, we prove that the only derivation that maps a Murray-von Neumann algebra associated with a factor of type II1 into that factor is 0. Those results are extensions of Singer's seminal result answering a question of Kaplansky, as applied to von Neumann algebras: The algebra may be noncommutative and may even contain unbounded elements.

  15. Adenomatous tumors of the middle ear and temporal bone: clinical, morphological and tumor biological characteristics of challenging neoplastic lesions.

    PubMed

    Duderstadt, M; Förster, Christine; Welkoborsky, H-J; Ostertag, H

    2012-03-01

    Adenomatous tumors of the middle ear and temporal bone are rare tumors. In this retrospective study, we examined nine patients who underwent surgery for an adenomatous tumor of the middle ear, mastoid cavity or eustachian tube. In seven patients, a middle ear adenoma (MEA) and in two patients an aggressive papillary tumor (APT) was diagnosed. We report the clinical, radiologic, morphologic, immunohistochemical and DNA image cytometrical characteristics that can help to correctly classify these tumors. Therapy consisted of surgical excision of the tumors in eight cases. In one elderly patient, only a large biopsy was taken, because this patient suffered from cardial and kidney disorders and was not suitable for an extended surgical approach. This patient received stereotactic radiotherapy. Seven patients underwent planned second look operation. Recurrences occurred in three patients (one with APT, two with MEA), whereas in two of these cases rather a residual tumor due to initial incomplete tumor resection occurred. By image analysis, DNA cytometry MEA were considered benign, whereas the appearance of aneuploid tumor cells in APT confirmed these tumors as low grade malignant lesions. The proliferation rates were equally low in both entities. APT and MEA are tumor entities which can only be correctly classified by a synopsis of histopathology, immunohistochemistry and DNA image cytometry. The recommended therapy is the complete tumor excision. In cases of APT, von Hippel-Lindau syndrome has to be excluded.

  16. Molecular analysis of the von hippel-lindau disease gene.

    PubMed

    Chernoff, A; Kasparcova, V; Linehan, W M; Stolle, C A

    2001-01-01

    Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that predisposes the affected individual to develop characteristic tumors. These include CNS hemangioblastoma, retinal angiomas, endolymphatic sac tumors, pancreatic cysts and tumors, epididymal cystadenomas, pheochromocytomas, renal cysts, and clear-cell renal carcinoma. The VHL gene was localized to 3p25 and then isolated by Latif et al. (1). The gene contains three exons with an open reading frame of 852 nucleotides, which encode a predicted protein of 284 amino acids. The VHL protein is believed to have several functions. It is involved in transcription regulation through its inhibition of elongation by binding to the B and C subunits of elongin. Mutations of VHL allow the B and C subunits to bind with the A subunit. This complex then overcomes "pausing" of RNA polymerase during mRNA transcription (2,3). Several studies suggest that the VHL protein is also involved in regulation of hypoxia-inducible transcripts, particularly vascular endothelial growth factor (VEGF), by altering mRNA stability (4,5). Therefore, VHL gene mutations permit the overexpression of VEGF under normoxic conditions, which leads to the angiogenesis believed to be required for tumor growth. The VHL-elongin BC complex (VBC) also binds two other proteins-CUL2 and Rbx1-in a complex that has structural similarity to other E3 ubiquitin ligase complexes (6). Such complexes mediate the degradation of cell-cycle regulatory proteins.

  17. Analyse der pharmazeutischen Versorgungssituation von Patienten mit Psoriasis-Arthritis auf Basis von Routinedaten der Gesetzlichen Krankenversicherung.

    PubMed

    Sondermann, Wiebke; Ventzke, Julia; Matusiewicz, David; Körber, Andreas

    2018-03-01

    Die Psoriasis-Arthritis (PsA) gehört zu den chronisch entzündlichen Gelenkerkrankungen. Trotz zahlreicher versorgungswissenschaftlicher Studien in Deutschland liegen zur pharmazeutischen Versorgungssituation von PsA-Patienten bisher kaum aktuelle Ergebnisse vor. Mit Hilfe einer systematischen Literaturrecherche sowie anhand von Routinedaten der Allgemeinen Ortskrankenkasse (AOK) Rheinland/Hamburg wird ein aktueller Überblick über die pharmazeutische Versorgung von PsA-Patienten in Deutschland gegeben. Selektiert wurden Versicherte aus dem ambulanten und stationären Bereich, die im 1. und 2. Quartal des Jahres 2014 die gesicherte Abrechnungsdiagnose Psoriasis-Arthritis L40.5+ aufwiesen. Anschließend wurden auf Basis dieser "vorab definierten" Kohorte die Arzneimitteldaten für 5 Jahre (01.01.2010-31.12.2014) abgerufen. Es konnten insgesamt n  =  3205 Versicherte (45 % männlich, 55 % weiblich) der AOK Rheinland/Hamburg mit einer gesicherten PsA-Diagnose selektiert werden. Das Durchschnittsalter betrug 58,9 Jahre. 53,7 % der PsA-Patienten wurden mit systemischen PsA-relevanten Arzneimitteln versorgt. Nichtsteroidale Antirheumatika (NSAR) wurden am häufigsten verordnet, gefolgt von systemischen Glucocorticoiden. Von den selektierten PsA-Patienten, die eine Systemtherapie erhielten, wurden 72,1 % mittels einer Disease-modifying-antirheumatic-Drug (DMARD)-Monotherapie behandelt, gefolgt von der Kombinationstherapie aus DMARDs und Biologika (20,9 %). Die pharmakologische Therapie der PsA muss eine Gewährleistung zwischen adäquater Versorgung der PsA mit Verhinderung der Krankheitsprogression und ökonomischer Verantwortung darstellen. © 2018 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  18. Versuche zur Gewinnung von katalytischen Antikörpern zur Hydrolyse von Arylcarbamaten und Arylharnstoffen. (English Title: Attempts to produce catalytic antibodies for hydrolysis of arylcarbamates and arylureas)

    NASA Astrophysics Data System (ADS)

    Werner, Deljana

    2002-05-01

    Im Rahmen dieser Arbeit gelang es, katalytische Antikörper zur Hydrolyse von Benzylphenylcarbamaten sowie zahlreiche monoklonale Antikörper gegen Haptene herzustellen. Es wurden verschiedene Hapten-Protein-Konjugate unter Verwendung unterschiedlicher Kopplungsmethoden hergestellt und charakterisiert. Zur Generierung der hydrolytisch aktiven Antikörper wurden Inzuchtmäuse mit KLH-Konjugaten von 4 Übergangszustandsanaloga (ÜZA) immunisiert. Mit Hilfe der Hybridomtechnik wurden verschiedene monoklonale Antikörper gegen diese ÜZA gewonnen. Dabei wurden sowohl verschiedene Immunisierungsschemata als auch verschiedene Inzuchtmausstämme und Fusionstechniken verwendet. Insgesamt wurden 32 monoklonale Antikörper gegen die verwendeten ÜZA selektiert. Diese Antikörper wurden in groen Mengen hergestellt und gereinigt. Zum Nachweis der Antikörper-vermittelten Katalyse wurden verschiedene Methoden entwickelt und eingesetzt, darunter immunologische Nachweismethoden mit Anti-Substrat- und Anti-Produkt-Antikörpern und eine photometrische Methode mit Dimethylaminozimtaldehyd. Der Nachweis der hydrolytischen Aktivität gelang mit Hilfe eines Enzymsensors, basierend auf immobilisierter Tyrosinase. Die Antikörper N1-BC1-D11, N1-FA7-C4, N1-FA7-D12 und R3-LG2-F9 hydrolysierten die Benzylphenylcarbamate POCc18, POCc19 und Substanz 27. Der Nachweis der hydrolytischen Aktivität dieser Antikörper gelang auch mit Hilfe der HPLC. Der katalytische Antikörper N1-BC1-D11 wurde kinetisch und thermodynamisch untersucht. Es wurde eine Michaelis-Menten-Kinetik mit Km von 210 µM, vmax von 3 mM/min und kcat von 222 min-1 beobachtet. Diese Werte korrelieren mit den Werten der wenigen bekannten Diphenylcarbamat-spaltenden Abzyme. Die Beschleunigungsrate des Antikörpers N1-BC1-D11 betrug 10. Das ÜZA Hei3 hemmte die hydrolytische Aktivität. Dies beweist, dass die Hydrolyse in der Antigenbindungsstelle stattfindet. Weiter wurde zwischen der Antikörperkonzentration und der

  19. The allele frequency of two single nucleotide polymorphisms in the von Hippel-Lindau (VHL) tumor suppressor gene in the Taiwanese population.

    PubMed

    Wang, Wen-Chung; Chen, Hui-Ju; Shu, Wei-Pang; Tsai, Yi-Chang; Lai, Yen-Chein

    2011-10-01

    The von Hippel-Lindau (VHL) tumor suppressor gene located on chromosome 3p25-26 is implicated in VHL disease. Two informative single nucleotide polymorphisms are at positions 19 and 1149 on the nucleotide sequence from Gene Bank NM_000551. In this study we examined the allele frequencies at these two loci in the Taiwanese population and compared the results to those from European ethnic populations. The allele frequency was examined in 616 healthy individuals including 301 university students and 315 neonates. Both A/G polymorphisms were investigated using restriction fragment length polymorphism analysis created by restriction enzymes, BsaJ I and Acc I. Among these subjects, the allele frequencies at 19 SNP and 1149 SNP for variant G were 0.130 and 0.133, respectively. And these results were significant differences from those of the Caucasian populations. In addition, 90% of the tested subjects had identical genotypes at these two loci suggesting the existence of nonrandom association of alleles. We found that the G allele frequency at these two loci in the Taiwanese population is much lower than that in people from Western countries. This phenomenon may be attributed to ethnic effects. Copyright © 2011. Published by Elsevier B.V.

  20. Clarifying the link between von Neumann and thermodynamic entropies

    NASA Astrophysics Data System (ADS)

    Deville, Alain; Deville, Yannick

    2013-01-01

    The state of a quantum system being described by a density operator ρ, quantum statistical mechanics calls the quantity - kTr( ρln ρ), introduced by von Neumann, its von Neumann or statistical entropy. A 1999 Shenker's paper initiated a debate about its link with the entropy of phenomenological thermodynamics. Referring to Gibbs's and von Neumann's founding texts, we replace von Neumann's 1932 contribution in its historical context, after Gibbs's 1902 treatise and before the creation of the information entropy concept, which places boundaries into the debate. Reexamining von Neumann's reasoning, we stress that the part of his reasoning implied in the debate mainly uses thermodynamics, not quantum mechanics, and identify two implicit postulates. We thoroughly examine Shenker's and ensuing papers, insisting upon the presence of open thermodynamical subsystems, imposing us the use of the chemical potential concept. We briefly mention Landau's approach to the quantum entropy. On the whole, it is shown that von Neumann's viewpoint is right, and why Shenker's claim that von Neumann entropy "is not the quantum-mechanical correlate of thermodynamic entropy" can't be retained.

  1. [Clinical study on patients with renal-cell carcinoma accompanied with Von Hippel-Lindau disease treated with radiofrequency ablation].

    PubMed

    Nao, Tomoya; Shimamoto, Tsutomu; Karashima, Takashi; Kamei, Maiko; Fukuhara, Hideo; Fukata, Satoshi; Satake, Hirofumi; Ashida, Shingo; Yamasaki, Ichiro; Kamata, Masayuki; Inoue, Keiji; Yamanishi, Tomoaki; Ogawa, Yasuhiro; Ito, Satoshi; Shuin, Taro

    2014-09-01

    We report 12 renal cell carcinomas in 6 patients with Von Hippel-Lindau (VHL) disease treated with radiofrequency ablation (RFA). The mean age of the patients was 46 (range 38-53) years (male : 4, female : 2). Computed tomography (CT)-guided transcutaneous RFA was performed under conscious sedation with local anesthetics. The mean size of the tumors was 2.4 (range 0.7-8.1) cm. Nine of the 12 tumors (75%) were locally well controlled. However, 3 tumors in 2 patients developed visceral metastases after RFA. While minimal flank pain, nausea, perinephritic hematoma and lumbago were observed, there was no major complication during or after the procedure. The therapy with CT-guided transcutaneous RFA is efficient and minimal invasive for renal cell carcinoma in patients with VHL, leading to preservation of renal function.

  2. An MRI Von Economo - Koskinas atlas.

    PubMed

    Scholtens, Lianne H; de Reus, Marcel A; de Lange, Siemon C; Schmidt, Ruben; van den Heuvel, Martijn P

    2018-04-15

    The cerebral cortex displays substantial variation in cellular architecture, a regional patterning that has been of great interest to anatomists for centuries. In 1925, Constantin von Economo and George Koskinas published a detailed atlas of the human cerebral cortex, describing a cytoarchitectonic division of the cortical mantle into over 40 distinct areas. Von Economo and Koskinas accompanied their seminal work with large photomicrographic plates of their histological slides, together with tables containing for each described region detailed morphological layer-specific information on neuronal count, neuron size and thickness of the cortical mantle. Here, we aimed to make this legacy data accessible and relatable to in vivo neuroimaging data by constructing a digital Von Economo - Koskinas atlas compatible with the widely used FreeSurfer software suite. In this technical note we describe the procedures used for manual segmentation of the Von Economo - Koskinas atlas onto individual T1 scans and the subsequent construction of the digital atlas. We provide the files needed to run the atlas on new FreeSurfer data, together with some simple code of how to apply the atlas to T1 scans within the FreeSurfer software suite. The digital Von Economo - Koskinas atlas is easily applicable to modern day anatomical MRI data and is made publicly available online. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Von Hippel–Lindau and myotonic dystrophy of Steinert along with pancreatic neuroendocrine tumor and renal clear cell carcinomal neoplasm: Case report and review of the literature

    PubMed Central

    Addeo, A.; Bini, R.; Viora, T.; Bonaccorsi, L.; Leli, R.

    2013-01-01

    INTRODUCTION Myotonic dystrophy of Steinert, DM1, is the most common adult muscular dystrophy and generally is not associated to development on multiple site neoplasm. Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome that is associated to tumors such as hemangioblastoma of the retina or central nervous system, clear-cell renal carcinoma (RCC) and endocrine tumors, most commonly pheochromocytoma and non-secretory pancreatic islet cell cancers. No data exist in literature describing the coexistence of both DM1 and VHL. PRESENTATION OF CASE Herein we report a case of renal and pancreatic neoplasm in a young adult female affected by DM1 and VHL simultaneously. DISCUSSION DM1 is due to an unstable trinucleotide (CTG) expansion in the 30 antranslated region of the dystrophia myotonica-protein kinase (DMPK) gene, located on chromosome 19q13.3. Several molecular mechanisms thought to be determining the classical DM phenotype have been shown. VHL disease is characterized by marked phenotypic variability and the most common tumors are hemangioblastomas of the retina or central nervous system, clear-cell renal carcinoma (RCC) and endocrine tumors, most commonly pheochromocytoma and non-secretory pancreatic islet cell cancers. The pancreatic manifestations seen in patients with VHL disease are divided into 2 categories: pancreatic neuroendocrine tumor (PNET) as solid tumors, and cystic lesions, including a simple cyst and serous cystadenoma. The surgical approach for these cistic lesions is to consider as golden standard. Blansfield has proposed 3 criteria to predict metastatic disease of PNET in patients with VHL disease: (1) tumor size greater than or equal to 3 cm; (2) presence of a mutation in exon 3; and (3) tumor doubling time less than 500 d. If the patient has none of these criteria the patient could be followed with physical examination and radiological surveillance on a 2/3 years base.4 If the patient has 1 criterion, the patient

  4. [Albert Reder Ritter von Schellmann (1826-1904)].

    PubMed

    Schmidt, G; Holubar, K

    1990-01-01

    Albert Reder von Schellmann (1826-1904) was an important syphilidologist of the Vienna Medical School in the second half of the nineteenth century. He went in for the dualistic concept of the origin of syphilis and ulcer caused by soft chancre. In 1870 - Reder became head of a third dermato-syphilidologic department in the "Josephinum" in Vienna, where military surgeons got their medical education. At the same time the two full professorships of dermatosyphilidology in the Vienna General Hospital were held by Ferdinand von Hebra (1816-1880) and Carl Ludwig Sigmund von Ilanor (1810-1883).

  5. von Willebrand's disease antigen II. A new plasma and platelet antigen deficient in severe von Willebrand's disease.

    PubMed Central

    Montgomery, R R; Zimmerman, T S

    1978-01-01

    Factor VIII-related antigen (VIIIag) is deficient in plasma and platelets of patients with severe von Willebrand's disease. This study reports a second von Willebrand's disease antigen (vWagII), distinct from VIIIag, that is also deficient in the platelets and plasma of patients with severe von Willebrand's disease. VIIIag and vWagII are separable by molecular exclusion chromatography, sucrose density gradient ultracentrifugation, and crossed immunoelectrophoresis. They show reactions of immunologic nonidentity with each other, and thus, do not share a precursor-product relationship. vWagII is released from normal platelets during blood clotting, accounting for a fourfold higher concentration of vWagII in serum over plasma. Images PMID:307007

  6. Pancreatic mixed serous neuroendocrine neoplasm with clear cells leading to diagnosis of von Hippel Lindau disease.

    PubMed

    Kakkar, Aanchal; Sharma, Mehar C; Yadav, Rajni; Panwar, Rajesh; Mathur, Sandeep R; Iyer, Venkateswaran K; Sahni, Peush

    2016-08-01

    Mixed serous neuroendocrine neoplasms are extremely rare tumors that are usually seen in female patients and are often associated with von Hippel Lindau (VHL) disease. We describe the case of a 38-year-old male who presented with complaints of anorexia, weight loss, and abdominal pain. CT abdomen showed a mass in the head of the pancreas, multiple small nodules in the body of pancreas, and bilateral adrenal masses. Fine needle aspiration cytology (FNAC) from the mass showed features of a neuroendocrine tumor, with many of the cells demonstrating abundant clear cytoplasm. Histopathological examination of the pancreaticoduodenectomy specimen showed a mixed serous neuroendocrine neoplasm with two components viz. serous cystadenoma and neuroendocrine tumor (NET) World Health Organization (WHO) grade 2. In addition, he was diagnosed to have bilateral pheochromocytomas and a paraganglioma. The synchronicity of these tumors suggested the possibility of VHL disease. Thus, identification of a NET with clear cells or of a mixed serous neuroendocrine neoplasm should raise suspicion of VHL disease. In a mixed tumor, FNAC may identify only one of the two components. Thorough processing of all pancreatic serous tumors for pathological examination is recommended, as NET may occur as a small nodule within the serous cystadenoma. Copyright © 2016 Elsevier GmbH. All rights reserved.

  7. Wernher von Braun

    NASA Image and Video Library

    1962-12-20

    Dr. von Braun, Major General Francis McMorrow, and Alabama Governor, John Patterson (far left) participated in the ground breaking ceremony for the University of Alabama Research Institute in Huntsville, December 20, 1962.

  8. Wernher von Braun

    NASA Image and Video Library

    1965-11-05

    In this photograph, Marshall Space Flight Center Director, Dr. Wernher von Braun, presents a Co-Inventor’s award to MSFC employee Martin Hall of the Mechanical Engineering Laboratory during the NASA Anniversary ceremony.

  9. Vergleich von rekombinanten Vaccinia- und DNA-Vektoren zur Tumorimmuntherapie im C57BL/6-Mausmodell

    NASA Astrophysics Data System (ADS)

    Johnen, Heiko

    2002-10-01

    antigenpräsentierender Zellen verantwortlich sein. Durch die Modifikation einer Methode zur intrazellulären IFN-gamma Färbung konnten in vakzinierten Mäusen tumorantigenspezifische CTL sensitiv und quantitativ detektiert werden. Die so bestimmte CTL-Frequenz, nicht jedoch die humorale Antwort, korrelierte mit der in vivo Wirksamkeit der verschiedenen Vakzinen: DNA vakzinierte Tiere entwickeln starke tumorantigenspezifische CTL-Antworten, wohingegen in MVA-vakzinierten Tieren überwiegend gegen virale Epitope gerichtete CD4 und CD8-T-Zellen detektiert wurden. Die Wirksamkeit der pCI-DNA-Vakzine spricht für die Weiterentwicklung in weiteren präklinischen Mausmodellen, beispielsweise unter Verwendung von MUC1 oder HLA-A2 transgenen Mäusen. Die Methoden zur Detektion Tumorantigen-spezifischer CTL in 96-Loch-Mikrotiterplatten können dabei zur systematischen Suche nach im Menschen immundominanten T-Zell-Epitopen im Muzin-Molekül genutzt werden. Der durchgeführte Vergleich der auf den Vektoren pCI und MVA basierenden Vakzinen und die Analyse neuerer Publikationen führen zu dem Ergebniss, daß vor allem DNA-Vakzinen in Zukunft eine wichtige Rolle bei der Entwicklung von aktiven Tumorimpfstoffen spielen werden. Rekombinante MVA-Viren, eventuell in Kombination mit DNA- oder anderen Vektoren, haben sich dagegen in zahlreichen Studien als wirksame Impfstoffe zur Kontrolle von durch Pathogene hervorgerufenen Infektionserkrankungen erwiesen. In this study, tumor vaccines based on the plasmid pCI, the attenuated vaccinia virus strain modified vaccinia virus Ankara (MVA) and MVA-infected dendritic cells were constructed and characterized by sequencing, Western blot and flow cytometric analysis. The efficiency to induce tumor immunity in vivo was compared in several C57BL/6 mouse tumor models. Naked DNA Vaccination based on the eukaryotic expression vector pCI did induce very effective, antigen-specific and long-term protection against tumor cell lines expressing mucin, CEA or

  10. Dr. Wernher Von Braun Memorial Dinner

    NASA Image and Video Library

    2017-10-26

    The annual Dr. Wernher Von Braun Memorial Dinner was held at the U.S. Space and Rocket Center's Davidson Center on October 26, 2017 with Keynote speaker General John Hyten, Commander of U.S. Strategic Command. Emcee was Mark Larson of Mark Larson Media Services, Inc. Dr. Wernher Von Braun Memorial Scholarships were presented to 8 college students by the National Space Club. Educator of the Year was awarded to Tammy Thorpe; Community Service award was presented to Huntsville, Al. Mayor Tommy Battle. The Communications Award was presented to retired astronaut Dr. Mike Massimino. The Distinguished Science Award was presented to Dr. Martin Weisskopf. The Astronautics Engineer Award was presented to Douglas R. Cooke. The Dr. Wernher Von Braun Space Flight Trophy was presented to Robert Lightfoot.

  11. Wernher von Braun

    NASA Image and Video Library

    1967-08-28

    Marshall Space Flight Center’s (MSFC) director, Dr. Wernher von Braun (right), inspects a component of a laser experiment being conducted in MSFC’s Space Sciences Laboratory during a tour on August 28, 1967.

  12. Wernher von Braun

    NASA Image and Video Library

    1962-09-11

    Marshall Space Flight Center Director Dr. Wernher von Braun explains a detail from a Saturn IB mockup and engine to President John F. Kennedy, Vice President Lyndon Johnson and other guests, September 11, 1962.

  13. Bewertung von Fahrzeuggeräuschen

    NASA Astrophysics Data System (ADS)

    Genuit, Klaus; Schulte-Fortkamp, Brigitte; Fiebig, André; Haverkamp, Michael

    Bei der Wahrnehmung und Beurteilung eines Automobils sind unzählige Merkmale und Eigenschaften von Bedeutung. Dabei können Merkmale objektiv-technisch beschrieben werden, wie Angaben zur Motorisierung, Höchstgeschwindigkeit, Drehmoment, zulässige Zuladung, Verbrauch usw. Daneben sind weitere Eigenschaften von Bedeutung, die sich einer einfachen objektiv-technischen Beschreibung entziehen. Hier sind Begriffe zu nennen, wie Sicherheit, allgemeine Qualitätsanmutung, Design, Ergonomie, Komfort, Haptik, Fahrdynamik, Zuverlässigkeit, die deutlich schwieriger objektiv erfassbar und beschreibbar sind (Abb. 4.1).

  14. Coexistence of sporadic cerebellar hemangioblastoma and pituitary null cell adenoma: simultaneous expression of von Hippel-Lindau gene product. Case report.

    PubMed

    Shimoda, Yoshiteru; Ogawa, Yoshikazu; Endo, Hidenori; Watanabe, Mika; Tominaga, Teiji

    2012-01-01

    Coexistence of brain tumors of different pathologies is rare, and the majority of the cases were related to genetic disorders or secondary tumors occurring after radiotherapy. A 73-year-old man was introduced to the outpatient department suffering from severe nausea and vertigo. Magnetic resonance imaging showed a cystic tumor in the left cerebellar hemisphere and another lesion in the sella turcica. There was no evident family history of von Hippel-Lindau (VHL) disease, and the systemic investigation failed to detect any other tumors or signs of VHL disease. Treatment was performed in two stages, and he was discharged with remaining slight ataxic gait. The diagnoses were cerebellar hemangioblastoma and pituitary null cell adenoma. Additional immunohistochemical investigation using VHL disease gene-related protein in both tumors showed minute granular positive staining in the cytoplasm of stromal cells in the former, and diffuse and strong granular cytoplasmic positive staining in the latter. Further analysis is required to confirm the true implication of the VHL gene mutation, and the possible involvement of VHL gene-related protein in the pathogenesis of these coexisting tumors.

  15. Baron von Zach's business relations with the Munich entrepreneur Joseph von Utzschneider (German Title: Geschäftsbeziehungen des Barons von Zach zu dem Münchner Unternehmer Joseph von Utzschneider)

    NASA Astrophysics Data System (ADS)

    Schneider, Ivo

    The relationship between the astronomer von Zach on the one side and the entrepreneur Joseph von Utzschneider and his partner Georg von Reichenbach on the other dates presumably from the year 1807 when Zach spent two months in Munich. Already in the same year Zach had ordered an instrument for himself and began to solicit business for the institute of Reichenbach, Utzschneider, and Liebherr, which was founded in 1804. One of the clients canvassed by Zach was the director of the observatory in Naples Zuccari. Zuccari had ordered the whole equipment for the new observatory from this institute in 1813. The instruments for Naples, which were completed in 1814, were sent accompanied by Reichenbach by land and sea to their destination where Reichenbach supervised their setup. At that time Reichenbach had separated from Utzschneider who kept the optical institute in Benediktbeuern with his new partner Joseph von Fraunhofer whereas Reichenbach became owner of the mathematical-mechanical institute in Munich. For personal and economical reasons Utzschneider began soon after to produce not only optical glass but also optical devices similar to those offered by Reichenbach. As soon as two institutes in Munich competed against each other on the market for sophisticated geodetical and astronomical instruments Zach sided with Utzschneider. Zach's main professional argument for this decision was that both competitors got the optical glass for their instruments from Utzschneider's optical institute in Benediktbeuern. This meant that Utzschneider had first choice and so the optical part of his instruments could be considered as better than that of Reichenbach`s instruments. Zach's role as an agent in Italy and France for the sale of products coming from Utzschneider's manufactories is highlighted by three of Zach's letters to Utzschneider from 1817 and 1818, two of which are reproduced here for the first time.

  16. Wernher von Braun

    NASA Image and Video Library

    1962-01-01

    Dr. Wernher von Braun, Director of the Marshall Space Flight Center (MSFC), during his tour of the Space information Division of North American Aviation (NAA) in Downey, California, where the Saturn SII stage was developed.

  17. Wernher von Braun

    NASA Image and Video Library

    1964-10-14

    This photograph, dated October 14, 1964, was taken at the Marned Spacecraft Center, now the Johnson Space Center in Houston, Texas. Dr. von Braun is shown looking over consoles in the Manned Spaceflight Control Center.

  18. Wernher von Braun

    NASA Image and Video Library

    1959-03-03

    Dr. von Braun, Director of the Development Operations Divisons, and Dr. Debus, Director of the Missile Firing Laboratory; Army Ballistic Missile Agency (ABMA), in the blockhouse during the launch of the Pioneer IV, March 3, 1959.

  19. Wernher von Braun

    NASA Image and Video Library

    1960-11-03

    Marshall Space Flight Center’s (MSFC) Director, Dr. Wernher von Braun, is pictured here with Army Ballistic Missile Agency’s (ABMA) Commanding General, J.B. Medaris, before a display of Army missles at the ABMA test lab.

  20. Kanban - der Weg ist das Ziel

    NASA Astrophysics Data System (ADS)

    Aull, Florian; Berlak, Joachim; Dickmann, Eva; Dickmann, Philipp; Fischäder, Holm; Gerlach, Joachim; Henneberg, Jens; Kapalla, Klaus; Kress, Oliver; Kuttler, Robert; Schneider, Herfried M.; Schürle, Philipp; Stellpflug, Franz-Josef; Wannenwetsch, Ralph; Wulz, Johannes; Zäh, Michael F.

    Wenn man aktuell Produktionsbereiche in Deutschland und Europa besucht, fallen im Zusammenhang mit modernen Produktionsmethoden immer öfter die Begriffe Kanban (jap. Karte, Signal) und Pull-Produktion, und dies nicht ohne Stolz, da diese mit dem schillernden Vorbild des Toyota Produktionssystems in Zusammenhang stehen. Tatsächlich ist Kanban ein integraler Bestandteil moderner Produktionssysteme. Blickt man aber im Rahmen von Prozessanalysen hinter die Fassaden", d. h. in die tägliche Praxis der Arbeitsprozesse, wird man schnell desillusioniert - die viel gepriesenen klassischen Kanban-Regeln werden im Tagesgeschäft nicht eingehalten.

  1. Childhood Picture of Dr. von Braun

    NASA Technical Reports Server (NTRS)

    1912-01-01

    This is a childhood picture of Dr. von Braun (center) with his brothers. Dr. Wernher von Braun was born in Wirsitz, Germany, March 23, 1912. His childhood dreams of marned space flight were fulfilled when giant Saturn rockets, developed under his direction at NASA's Marshall Space Flight Center, boosted the manned Apollo spacecraft to the Moon. His life was dedicated to expanding man's knowledge through the exploration of space.

  2. Laboratory diagnosis of von Willebrand's disease.

    PubMed

    Rick, M E

    1994-12-01

    The diagnosis of von Willebrand's disease is becoming complex as more is understood about the disease. Clinical information and laboratory data are necessary for the diagnosis because of the overlap of normal and abnormal laboratory values. A complete evaluation including von Willebrand factor multimers, ristocetin-induced platelet aggregation, factor VIII activity level, and a template bleeding time is necessary to correctly classify the patient so that optimal treatment may be given.

  3. Wernher von Braun

    NASA Image and Video Library

    1959-01-01

    Marshall Space Flight Center Director Wernher von Braun presents General J.B. Medaris with a new golf bag. General Medaris, (left) was a Commander of the Army Ballistic Missile Agency (ABMA) in Redstone Arsenal, Alabama during 1955 to 1958.

  4. Dr. von Braun Tries Out the NBS

    NASA Technical Reports Server (NTRS)

    1967-01-01

    Marshall Space Flight Center (MSFC) Director, Dr. von Braun, is shown fitted with suit and diving equipment as he prepares for a tryout in the MSFC Neutral Buoyancy Simulator (NBS). Weighted to a neutrally buoyant condition, Dr. von Braun was able to perform tasks underwater which simulated weightless conditions found in space.

  5. Wernher von Braun

    NASA Image and Video Library

    1950-01-01

    Dr. von Braun stands beside a model of the upper stage (Earth-returnable stage) of the three-stage launch vehicle built for the series of the motion picture productions of space flight produced by Walt Disney in the mid-1950's.

  6. Wernher von Braun

    NASA Image and Video Library

    1959-01-01

    In this picture, Dr. Wernher von Braun, who was serving as Director of the Army Ballistic Missile Agency's (ABMA) Development Operations Division, is shown posed with his Mercedes 220SE automobile in front of Redstone Building 4488, which houses the ABMA.

  7. Von Neumann was not a Quantum Bayesian.

    PubMed

    Stacey, Blake C

    2016-05-28

    Wikipedia has claimed for over 3 years now that John von Neumann was the 'first quantum Bayesian'. In context, this reads as stating that von Neumann inaugurated QBism, the approach to quantum theory promoted by Fuchs, Mermin and Schack. This essay explores how such a claim is, historically speaking, unsupported. © 2016 The Author(s).

  8. Locally Compact Quantum Groups. A von Neumann Algebra Approach

    NASA Astrophysics Data System (ADS)

    Van Daele, Alfons

    2014-08-01

    In this paper, we give an alternative approach to the theory of locally compact quantum groups, as developed by Kustermans and Vaes. We start with a von Neumann algebra and a comultiplication on this von Neumann algebra. We assume that there exist faithful left and right Haar weights. Then we develop the theory within this von Neumann algebra setting. In [Math. Scand. 92 (2003), 68-92] locally compact quantum groups are also studied in the von Neumann algebraic context. This approach is independent of the original C^*-algebraic approach in the sense that the earlier results are not used. However, this paper is not really independent because for many proofs, the reader is referred to the original paper where the C^*-version is developed. In this paper, we give a completely self-contained approach. Moreover, at various points, we do things differently. We have a different treatment of the antipode. It is similar to the original treatment in [Ann. Sci. & #201;cole Norm. Sup. (4) 33 (2000), 837-934]. But together with the fact that we work in the von Neumann algebra framework, it allows us to use an idea from [Rev. Roumaine Math. Pures Appl. 21 (1976), 1411-1449] to obtain the uniqueness of the Haar weights in an early stage. We take advantage of this fact when deriving the other main results in the theory. We also give a slightly different approach to duality. Finally, we collect, in a systematic way, several important formulas. In an appendix, we indicate very briefly how the C^*-approach and the von Neumann algebra approach eventually yield the same objects. The passage from the von Neumann algebra setting to the C^*-algebra setting is more or less standard. For the other direction, we use a new method. It is based on the observation that the Haar weights on the C^*-algebra extend to weights on the double dual with central support and that all these supports are the same. Of course, we get the von Neumann algebra by cutting down the double dual with this unique

  9. Dr. von Braun and Army Ballistics Missile Agency (ABMA) Group

    NASA Technical Reports Server (NTRS)

    1959-01-01

    This photograph of Dr. von Braun, shown here to the left of General Bruce Medaris, was taken in the fall of 1959, immediately prior to Medaris' retirement from the Army. At the time, von Braun and his associates worked for the Army Ballistics Missile Agency in Huntsville, Alabama. Those in the photograph have been identified as Ernst Stuhlinger, Frederick von Saurma, Fritz Mueller, Hermarn Weidner, E.W. Neubert (partially hidden), W.A. Mrazek, Karl Heimburg, Arthur Rudolph, Otto Hoberg, von Braun, Oswald Lange, Medaris, Helmut Hoelzer, Hans Maus, E.D. Geissler, Hans Heuter, and George Constan.

  10. Color constancy: enhancing von Kries adaption via sensor transformations

    NASA Astrophysics Data System (ADS)

    Finlayson, Graham D.; Drew, Mark S.; Funt, Brian V.

    1993-09-01

    Von Kries adaptation has long been considered a reasonable vehicle for color constancy. Since the color constancy performance attainable via the von Kries rule strongly depends on the spectral response characteristics of the human cones, we consider the possibility of enhancing von Kries performance by constructing new `sensors' as linear combinations of the fixed cone sensitivity functions. We show that if surface reflectances are well-modeled by 3 basis functions and illuminants by 2 basis functions then there exists a set of new sensors for which von Kries adaptation can yield perfect color constancy. These new sensors can (like the cones) be described as long-, medium-, and short-wave sensitive; however, both the new long- and medium-wave sensors have sharpened sensitivities -- their support is more concentrated. The new short-wave sensor remains relatively unchanged. A similar sharpening of cone sensitivities has previously been observed in test and field spectral sensitivities measured for the human eye. We present simulation results demonstrating improved von Kries performance using the new sensors even when the restrictions on the illumination and reflectance are relaxed.

  11. Dr. von Braun With Management Team

    NASA Technical Reports Server (NTRS)

    1961-01-01

    Dr. von Braun is shown in this photograph, which was probably taken in the early 1960s, with members of his management team. Pictured from left to right are, Werner Kuers, Director of the Manufacturing Engineering Division; Dr. Walter Haeussermarn, Director of the Astrionics Division; Dr. William Mrazek, Propulsion and Vehicle Engineering Division; Dr. von Braun; Dieter Grau, Director of the Quality Assurance Division; Dr. Oswald Lange, Director of the Saturn Systems Office; and Erich Neubert , Associate Deputy Director for Research and Development.

  12. Portrait of Dr. Von Braun with Walt Disney, 1954.

    NASA Technical Reports Server (NTRS)

    1954-01-01

    Marshall Center Director Dr. Wernher Von Braun is pictured with Walt Disney during a visit to the Marshall Space Flight Center in 1954. In the 1950s, Dr. Von Braun while working in California on the Saturn project, also worked with Disney studios as a technical director in making three films about Space Exploration for television. Disney's tour of Marshall in 1965 was Von Braun's hope for a renewed public interest in the future of the Space Program at NASA.

  13. Alexander von Humboldt and the concept of animal electricity.

    PubMed

    Kettenmann, H

    1997-06-01

    More than two hundred years ago, Alexander von Humboldt helped to establish Galvani's view that muscle and nerve tissue are electrically excitable. His 1797 publication was a landmark for establishing the concept of animal electricity. Almost half a century later, von Humboldt became the mentor of the young du Bois-Reymond. With the help of von Humboldt's promotion, du Bois-Reymond demonstrated convincingly that animal tissue has the intrinsic capacity to generate electrical activity, and thus laid the ground for modern electrophysiology.

  14. Dr. von Braun With German Rocket Experimenters

    NASA Technical Reports Server (NTRS)

    1930-01-01

    Dr. von Braun was among a famous group of rocket experimenters in Germany in the 1930s. This photograph is believed to be made on the occasion of Herman Oberth's Kegelduese liquid rocket engine being certified as to performance during firing. From left to right are R. Nebel, Dr. Ritter, Mr. Baermueller, Kurt Heinish, Herman Oberth, Klaus Riedel, Wernher von Braun, and an unidentified person.

  15. Two Dimensional Drug Diffusion Between Nanoparticles and Fractal Tumors

    NASA Astrophysics Data System (ADS)

    Samioti, S. E.; Karamanos, K.; Tsiantis, A.; Papathanasiou, A.; Sarris, I.

    2017-11-01

    Drug delivery methods based on nanoparticles are some of the most promising medical applications in nanotechnology to treat cancer. It is observed that drug released by nanoparticles to the cancer tumors may be driven by diffusion. A fractal tumor boundary of triangular Von Koch shape is considered here and the diffusion mechanism is studied for different drug concentrations and increased fractality. A high order Finite Elements method based on the Fenics library is incorporated in fine meshes to fully resolve these irregular boundaries. Drug concentration, its transfer rates and entropy production are calculated in an up to forth order fractal iteration boundaries. We observed that diffusion rate diminishes for successive prefractal generations. Also, the entropy production around the system changes greatly as the order of the fractal curve increases. Results indicate with precision where the active sites are, in which most of the diffusion takes place and thus drug arrives to the tumor.

  16. Reproductive disturbances in multiple neuroendocrine tumor syndromes.

    PubMed

    Lytras, Aristides; Tolis, George

    2009-12-01

    In the context of multiple neuroendocrine tumor syndromes, reproductive abnormalities may occur via a number of different mechanisms, such as hyperprolactinemia, increased GH/IGF-1 levels, hypogonadotropic hypogonadism, hypercortisolism, hyperandrogenism, hyperthyroidism, gonadotropin hypersecretion, as well as, tumorigenesis or functional disturbances in gonads or other reproductive organs. Precocious puberty and/or male feminization is a feature of McCune-Albright syndrome (MAS), neurofibromatosis type 1 (NF1), Carney complex (CNC), and Peutz-Jeghers syndrome (PJS), while sperm maturation and ovulation defects have been described in MAS and CNC. Although tumorigenesis of reproductive organs due to a multiple neuroendocrine tumor syndrome is very rare, certain lesions are characteristic and very unusual in the general population. Awareness leading to their recognition is important especially when other endocrine abnormalities coexist, as occasionally they may even be the first manifestation of a syndrome. Lesions such as certain types of ovarian cysts (MAS, CNC), pseudogynecomastia due to neurofibromas of the nipple-areola area (NF1), breast disease (CNC and Cowden disease (CD)), cysts and 'hypernephroid' tumors of the epididymis or bilateral papillary cystadenomas (mesosalpinx cysts) and endometrioid cystadenomas of the broad ligament (von Hippel-Lindau disease), testicular Sertoli calcifying tumors (CNC, PJS) monolateral or bilateral macroochidism and microlithiasis (MAS) may offer diagnostic clues. In addition, multiple neuroendocrine tumor syndromes may be complicated by reproductive malignancies including ovarian cancer in CNC, breast and endometrial cancer in CD, breast malignancies in NF1, and malignant sex-cord stromal tumors in PJS.

  17. Von Neumann's impossibility proof: Mathematics in the service of rhetorics

    NASA Astrophysics Data System (ADS)

    Dieks, Dennis

    2017-11-01

    According to what has become a standard history of quantum mechanics, in 1932 von Neumann persuaded the physics community that hidden variables are impossible as a matter of principle, after which leading proponents of the Copenhagen interpretation put the situation to good use by arguing that the completeness of quantum mechanics was undeniable. This state of affairs lasted, so the story continues, until Bell in 1966 exposed von Neumann's proof as obviously wrong. The realization that von Neumann's proof was fallacious then rehabilitated hidden variables and made serious foundational research possible again. It is often added in recent accounts that von Neumann's error had been spotted almost immediately by Grete Hermann, but that her discovery was of no effect due to the dominant Copenhagen Zeitgeist. We shall attempt to tell a story that is more historically accurate and less ideologically charged. Most importantly, von Neumann never claimed to have shown the impossibility of hidden variables tout court, but argued that hidden-variable theories must possess a structure that deviates fundamentally from that of quantum mechanics. Both Hermann and Bell appear to have missed this point; moreover, both raised unjustified technical objections to the proof. Von Neumann's argument was basically that hidden-variables schemes must violate the ;quantum principle; that physical quantities are to be represented by operators in a Hilbert space. As a consequence, hidden-variables schemes, though possible in principle, necessarily exhibit a certain kind of contextuality. As we shall illustrate, early reactions to Bohm's theory are in agreement with this account. Leading physicists pointed out that Bohm's theory has the strange feature that pre-existing particle properties do not generally reveal themselves in measurements, in accordance with von Neumann's result. They did not conclude that the ;impossible was done; and that von Neumann had been shown wrong.

  18. Wernher von Braun

    NASA Image and Video Library

    1964-10-14

    This photograph is dated October 14, 1964, and shows Dr. von Braun, left, during a tour of the NASA Marned Spacecraft Center, now the Johnson Space Center. He is with Dr. J.P. Kuettner, center, from the Marshall Space Flight Center, and Warren J. North from the Manned Spacecraft Center.

  19. Dr. von Braun with Seven Original Mercury Astronauts

    NASA Technical Reports Server (NTRS)

    1959-01-01

    In this photo, Dr. Wernher von Braun, Director of the U.S. Army Ballistic Missile Agency's (ABMA) Development Operations Division, is shown briefing the seven original Mercury astronauts in ABMA's Fabrication Laboratory. (Left to right) Guss Grissom, Walter Schirra, Alan Shepard, John Glenn, Scott Carpenter, Gordon Cooper, Donald Slayton, and Dr. von Braun.

  20. Ein Konzept für den energieeffizienten Betrieb von Mobilfunknetzen

    NASA Astrophysics Data System (ADS)

    Bayer, N.; von Hugo, D.

    2015-11-01

    Der flächendeckende Betrieb mehrerer Mobilfunknetze unterschiedlicher Technologie in einem Land sorgt aufgrund der ständigen Bereithaltung von Übertragungskapazität für Dienste mit zunehmend höherem Datenvolumenbedarf für einen erheblichen Energieverbrauch. Das Forschungsförderungsprojekt ComGreen hat sich zur Aufgabe gesetzt, durch lastadaptiven Betrieb und intelligente dynamische Rekonfiguration des Funkzugangsnetzes zur Energieeinsparung beizutragen. Konzept, Herausforderungen, ausgewählte Ergebnisse von Simulationen und prototypischem Betrieb werden ebenso wie typische Erwartungswerte des künftigen Energieverbrauchs im Mobilfunkbereich vorgestellt. Sowohl Berechnungen als auch Messungen zeigen, dass durch kontext-basierte dynamische Rekonfiguration von zellularen Funknetzen Energieeinsparungen im Bereich von 25-40 % ermöglicht werden.

  1. Wernher von Braun

    NASA Image and Video Library

    1959-03-04

    Dr. Wernher von Braun, Director of the U.S. Army Ballistic Missile Agency's (ABMA) Development Operations Division, talks to Huntsville Mayor R. B. "Speck" Searcy, center, and Army Ordnance Missile Command (ARMC) Major General John B. Medaris, right, during "Moon Day" celebrations in downtown Huntsville, Alabama. (Courtesy of Huntsville/Madison County Public Library)

  2. Wernher von Braun

    NASA Image and Video Library

    1965-05-25

    In this photo, Dr. von Braun anxiously awaits the launch of the Saturn I vehicle (SA-8) in the Launch Complex Control Center at the Kennedy Space Center in Florida on May 25, 1965. The SA-8 mission made the first night launch and deployed the Pegasus II micro meteoroid detection satellite.

  3. [Hereditary pheochromocytoma--a family affected by von Hippel-Lindau disease].

    PubMed

    Mertl, J; Rovný, A; Krepelová, A; Prásek, J

    2003-07-01

    The authors present a case of a 37 year old male (proband) with a 13 year history of progressive sight impairment leading to blindness and a 4 year history of a mild hypertension. He was incidentally found to have large adrenal tumors after an ultrasound kidney examination. The tumors were confirmed with CT scan and magnetic resonance imaging. A bilateral pheochromocytoma was biochemically demonstrated and successfully removed. The eye diagnosis of angiomatosis retinae von Hippel-Lindau was ascertained after a search of the patient files in other medical departments, which led to a family screening. Proband's brother, having hypertension and a history of a cerebellar astrocytoma operation, was also diagnosed with CT scan to have a bilateral pheochromocytoma. Unfortunately, at the same time he was found to have a large irremovable neuroendocrine pancreatic carcinoma, which caused complications and his eventual death. Both proband and his brother were affected by the same CGG(Arg167)->CAG(Gln) mutation in the exon 3 of the VHL gene. Other living and examined family members were not affected, which was confirmed by negative genetic testing. One year after the pheochromocytoma operation, proband was diagnosed to have a retroperitoneal tumor left to the aorta, clinically silent, with slightly and non-constantly elevated urine norepinephrine and normetanephrine. Metaiodobenzylguanidine scintigraphy showed that it was a paraganglioma. The old CT and magnetic resonance picture review demonstrated that the tumor had already been present at the time of the operation. It was surgically removed and histologically verified. It is a pity that proband had not been sent by his ophthalmologist for an endocrine examination when the eye diagnosis was determined. Affection of the family would have been discovered earlier, and proband's brother might have possibly been saved.

  4. The Opposing Roles of Nucleophosmin and the ARF Tumor Suppressor in Breast Cancer

    DTIC Science & Technology

    2006-04-01

    born to be weak. Trends Cell Biol. 15:121–124. 26. Li, Y. P ., R. K. Busch, B. C. Valdez, and H. Busch. 1996 . C23 interacts with B23, a putative...peptides in vivo. Injection of a peptide from the von Hippel -Lindau (VHL) tumor suppressor inhibited the growth and invasiveness of renal tumor...NPM IB: NPM IB: p19ARF 1° 2° 3° 4° 5° s up er na ta nt 2 5 % i n p u t 28S 18S WT Arf -/- 120 240 120 240chase (min) N C N CN C N C

  5. Dr. von Braun with Original Mercury Astronauts

    NASA Technical Reports Server (NTRS)

    1959-01-01

    Dr. Wernher von Braun, Director of the Army Ballistic Missile Agency's (ABMA) Development Operations Division, poses with the original Mercury astronauts in ABMA's Fabrication Laboratory during a 1959 visit. Inspecting Mercury-Redstone hardware are from left to right, Alan Shepard, Donald Deke Slayton, Virgil Gus Grissom, von Braun, Gordon Cooper, Wally Schirra, John Glenn, and Scott Carpenter. Project Mercury officially began October 7, 1958 as the United States' first manned space program.

  6. Platelet-independent adhesion of calcium-loaded erythrocytes to von Willebrand factor

    PubMed Central

    Bierings, Ruben; Meems, Henriet; Mul, Frederik P. J.; Geerts, Dirk; Vlaar, Alexander P. J.; Voorberg, Jan; Hordijk, Peter L.

    2017-01-01

    Adhesion of erythrocytes to endothelial cells lining the vascular wall can cause vaso-occlusive events that impair blood flow which in turn may result in ischemia and tissue damage. Adhesion of erythrocytes to vascular endothelial cells has been described in multiple hemolytic disorders, especially in sickle cell disease, but the adhesion of normal erythrocytes to endothelial cells has hardly been described. It was shown that calcium-loaded erythrocytes can adhere to endothelial cells. Because sickle erythrocyte adhesion to ECs can be enhanced by ultra-large von Willebrand factor multimers, we investigated whether calcium loading of erythrocytes could promote binding to endothelial cells via ultra-large von Willebrand factor multimers. We used (immunofluorescent) live-cell imaging of washed erythrocytes perfused over primary endothelial cells at venular flow rate. Using this approach, we show that calcium-loaded erythrocytes strongly adhere to histamine-stimulated primary human endothelial cells. This adhesion is mediated by ultra-large von Willebrand factor multimers. Von Willebrand factor knockdown or ADAMTS13 cleavage abolished the binding of erythrocytes to activated endothelial cells under flow. Platelet depletion did not interfere with erythrocyte binding to von Willebrand factor. Our results reveal platelet-independent adhesion of calcium-loaded erythrocytes to endothelium-derived von Willebrand factor. Erythrocyte adhesion to von Willebrand factor may be particularly relevant for venous thrombosis, which is characterized by the formation of erythrocyte-rich thrombi. PMID:28249049

  7. Wernher von Braun

    NASA Image and Video Library

    1965-04-13

    Walt Disney toured the West Test Area during his visit to the Marshall Space Flight Center on April 13, 1965. The three in center foreground are Karl Heimburg, Director, Test Division; Dr. von Braun, Director, MSFC; and Walt Disney. The Dynamic Test Stand with the S-1C stage being installed is in the background.

  8. [Successful treatment with rituximab in a patient with primary thymic MALT lymphoma complicated with acquired von Willebrand syndrome and Sjögren syndrome].

    PubMed

    Iwabuchi, Tamiko; Kimura, Yukihiko; Suzuki, Takashi; Hayashi, Haeru; Fujimoto, Hiroaki; Hashimoto, Yuko; Ogawa, Takashi; Kusama, Hiroshi; Fukutake, Katsuyuki; Ohyashiki, Kazuma

    2011-04-01

    A 53-year-old female developed epigastric discomfort and back pain in 2007. Diagnostic imaging studies demonstrated a soft tissue tumor with heterogeneous enhancement in the anterior mediastinum and multiple nodules in the right lung. She underwent expanded thymectomy with subtotal resection of the right lung. The pathological diagnosis was primary thymic mucosa-associated lymphoid tissue (MALT) lymphoma. The patient complained of ocular discomfort, oral dryness and continuous nasal bleeding in 2007. Detailed examination led to a diagnosis of Sjögren syndrome and acquired von Willebrand syndrome. Rituximab treatment for residual disease achieved not only a reduction of the lung MALT lymphoma but also clinical and hematological remission of both syndromes. This is, to our knowledge, the first reported case of primary thymic MALT lymphoma accompanied by Sjögren and acquired von Willebrand syndromes.

  9. Wernher von Braun

    NASA Image and Video Library

    1961-10-19

    Dr. Wernher von Braun holds the coveted Hermarn Oberth award presented to him by Professor Oberth during the banquet hosted by the Alabama Section of the American Rocket Society (ARS), on October 19, 1961. The Oberth award was given for outstanding technical contributions to the field of astronautics or for the promotion and advancement of astronautical sciences.

  10. Dr. von Braun With Five of the Original Astronauts

    NASA Technical Reports Server (NTRS)

    1959-01-01

    Five of the seven original astronauts are seen with Dr. von Braun inspecting the Mercury-Redstone hardware in the Fabrication Laboratory of Army Ballistic Missile Agency (ABMA) in 1959. Left to right: Astronauts Walter Schirra, Alan Shepard, John Glenn, Scott Carpenter, Gordon Cooper, and Dr. von Braun.

  11. Von Kármán between Aachen and Pasadena

    NASA Astrophysics Data System (ADS)

    Krause, Egon; Kalkmann, Ulrich

    2013-05-01

    In the Introduction the reader is referred back to the academic ceremonials held after Theodore von Kármán's death in Aachen in May 1963. His work as the first director of the Aerodynamisches Institut (Institute of Aerodynamics) of the RWTH Aachen University of Technology from 1913 on and his initiative to re-establish international cooperation after World War I, resulting in the International Union of Theoretical and Applied Mechanics (IUTAM), are commented on. The following chapter describes von Kármán's relation to his former teacher Ludwig Prandtl. Some of von Kármán's scientific contributions during his time in Aachen are briefly reviewed. Thereafter, his first contacts to the California Institute of Technology are covered. Finally, the scientific and political circumstances, which led to von Kármán's decision to leave Germany in the early thirties, are elucidated in some detail. The English translation of the titles of the Aachen papers is given in Appendix I.

  12. Mittelwert- und Arbeitstaktsynchrone Simulation von Dieselmotoren

    NASA Astrophysics Data System (ADS)

    Zahn, Sebastian

    Getrieben durch die immer restriktiveren Anforderungen an das Emissions- und Verbrauchsverhalten moderner Verbrennungsmotoren steigt die Komplexität von Motormanagementsystemen mit jeder Modellgeneration an. Damit geht nicht nur eine Zunahme des Softwareumfangs von Steuergeräten sondern zugleich ein deutlicher Anstieg des Applikations-, Vermessungs- und Testaufwandes einher. Zur Effizienzsteigerung des Software- und Funktionsentwicklungsprozesses haben sich daher in der Automobilindustrie sowie in Forschungsinstituten verschiedene modell- und simulationsbasierte Methoden wie die Model-in-the-Loop (MiL) Simulation, die Software-in-the-Loop (SiL) Simulation, das Rapid Control Prototyping (RCP) sowie die Hardware-in-the-Loop (HiL) Simulation etabliert.

  13. von Braun and German Publisher

    NASA Technical Reports Server (NTRS)

    1969-01-01

    In this photograph, Guenter Ogger of Capitol Magazine, West Germany, greets Marshall Space Flight Center Director, Dr. Wernher von Braun. Mr. Ogger interviewed the famous rocket scientist for his magazine.

  14. Eine selbstkonsistente Carleman Linearisierung zur Analyse von Oszillatoren

    NASA Astrophysics Data System (ADS)

    Weber, Harry; Mathis, Wolfgang

    2017-09-01

    Die Analyse nichtlinearer dynamischer Schaltungen ist bis heute eine herausfordernde Aufgabe, da nur selten analytische Lösungen angegeben werden können. Daher wurden eine Vielzahl von Methoden entwickelt, um eine qualitative oder quantitative Näherung für die Lösungen der Netzwerkgleichung zu erhalten. Oftmals wird beispielsweise eine Kleinsignalanalyse mit Hilfe einer Taylorreihe in einem Arbeitspunkt durchgeführt, die nach den Gliedern erster Ordnung abgebrochen wird. Allerdings ist diese Linearisierung nur in der Nähe des stabilen Arbeitspunktes für hyperbolische Systeme gültig. Besonders für die Analyse des dynamischen Verhaltens von Oszillatoren treten jedoch nicht-hyperbolische Systeme auf, sodass diese Methode nicht angewendet werden kann Mathis (2000). Carleman hat gezeigt, dass nichtlineare Differentialgleichungen mit polynomiellen Nichtlinearitäten in ein unendliches System von linearen Differentialgleichungen transformiert werden können Carleman (1932). Wird das unendlichdimensionale Gleichungssystem für numerische Zwecke abgebrochen, kann bei Oszillatoren der Übergang in eine stationäre Schwingung (Grenzzyklus) nicht wiedergegeben werden. In diesem Beitrag wird eine selbstkonsistente Carleman Linearisierung zur Untersuchung von Oszillatoren vorgestellt, die auch dann anwendbar ist, wenn die Nichtlinearitäten keinen Polynomen entsprechen. Anstelle einer linearen Näherung um einen Arbeitspunkt, erfolgt mit Hilfe der Carleman Linearisierung eine Approximation auf einem vorgegebenen Gebiet. Da es jedoch mit der selbstkonsistenten Technik nicht möglich ist, das stationäre Verhalten von Oszillatoren zu beschreiben, wird die Berechnung einer Poincaré-Abbildung durchgeführt. Mit dieser ist eine anschließende Analyse des Oszillators möglich.

  15. Monte Carlo turbulence simulation using rational approximations to von Karman spectra

    NASA Technical Reports Server (NTRS)

    Campbell, C. W.

    1986-01-01

    Turbulence simulation is computationally much simpler using rational spectra, but turbulence falls off as f exp -5/3 in frequency ranges of interest to aircraft response and as predicted by von Karman's model. Rational approximations to von Karman spectra should satisfy three requirements: (1) the rational spectra should provide a good approximation to the von Karman spectra in the frequency range of interest; (2) for stability, the resulting rational transfer function should have all its poles in the left half-plane; and (3) at high frequencies, the rational spectra must fall off as an integer power of frequency, and since the -2 power is closest to the -5/3 power, the rational approximation should roll off as the -2 power at high frequencies. Rational approximations to von Karman spectra that satisfy these three criteria are presented, along with spectra from simulated turbulence. Agreement between the spectra of the simulated turbulence and von Karman spectra is excellent.

  16. Wernher von Braun

    NASA Image and Video Library

    1959-01-21

    In this photo, (left to right) Army Ballistic Missile Agency (ABMA) Missile Firing Laboratory Chief Dr. Kurt Debus, Director of the ABMA Development Operations Division, Dr. von Braun and an unidentified individual in blockhouse during the CM-21 (Jupiter) firing. The Jupiter missile CM-21 became the first Chrysler production qualification missile to be fired and in March 1959 launched the Pioneer IV.

  17. Von Karman Vortices

    NASA Image and Video Library

    2017-12-08

    July 4th, 2002: Description: As air flows over and around objects in its path, spiraling eddies, known as Von Karman vortices, may form. The vortices in this image were created when prevailing winds sweeping east across the northern Pacific Ocean encountered Alaska’s Aleutian Islands. Source: Landsat 7 To learn more about the Landsat satellite go to: landsat.gsfc.nasa.gov/

  18. Wernher von Braun

    NASA Image and Video Library

    1954-07-01

    Dr. Wernher von Braun (center), then Chief of the Guided Missile Development Division at Redstone Arsenal, Alabama, discusses a "bottle suit" model with Dr. Heinz Haber (left), an expert on aviation medicine, and Willey Ley, a science writer on rocketry and space exploration. The three men were at the Disney studios appearing in the motion picture, entitled "Man in Space."

  19. Expression of hypoxia-inducible carbonic anhydrases in brain tumors

    PubMed Central

    Proescholdt, Martin A.; Mayer, Christina; Kubitza, Marion; Schubert, Thomas; Liao, Shu-Yuan; Stanbridge, Eric J.; Ivanov, Sergey; Oldfield, Edward H.; Brawanski, Alexander; Merrill, Marsha J.

    2005-01-01

    Malignant brain tumors exhibit distinct metabolic characteristics. Despite high levels of lactate, the intracellular pH of brain tumors is more alkaline than normal brain. Additionally, with increasing malignancy, brain tumors display intratumoral hypoxia. Carbonic anhydrase (CA) IX and XII are transmembrane isoenzymes that are induced by tissue hypoxia. They participate in regulation of pH homeostasis by catalyzing the reversible hydration of carbon dioxide. The aim of our study was to investigate whether brain tumors of different histology and grade of malignancy express elevated levels of CA IX and XII as compared to normal brain. We analyzed 120 tissue specimens from brain tumors (primary and metastatic) and normal brain for CA IX and XII expression by immunohistochemistry, Western blot, and in situ hybridization. Whereas normal brain tissue showed minimal levels of CA IX and XII expression, expression in tumors was found to be upregulated with increased level of malignancy. Hemangioblastomas, from patients with von Hippel–Lindau disease, also displayed high levels of CA IX and XII expression. Comparison of CA IX and XII staining with HIF-1α staining revealed a similar microanatomical distribution, indicating hypoxia as a major, but not the only, induction factor. The extent of CA IX and XII staining correlated with cell proliferation, as indicated by Ki67 labeling. The results demonstrate that CA IX and XII are upregulated in intrinsic and metastatic brain tumors as compared to normal brain tissue. This may contribute to the management of tumor-specific acid load and provide a therapeutic target. PMID:16212811

  20. Dr. Wernher Von Braun

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Shown viewing the Apollo telescope mockup are, from left to right, Charles Donlan, deputy associate administrator for manned space flight; Dr. Wernher Von Braun, Marshall Space Flight Center director; William Horton, astrionics lab; Dr. Thomas Paine, NASA deputy administrator; Warner Kuers, director of the ME lab.

  1. PT2385 for the Treatment of Von Hippel-Lindau Disease-Associated Clear Cell Renal Cell Carcinoma

    ClinicalTrials.gov

    2017-08-23

    VHL Gene Mutation; VHL; VHL Syndrome; VHL Gene Inactivation; Von Hippel; Von Hippel-Lindau Disease; Von Hippel's Disease; Von Hippel-Lindau Syndrome, Modifiers of; Clear Cell Renal Cell Carcinoma; Clear Cell RCC; ccRCC

  2. Wernher von Braun

    NASA Image and Video Library

    1963-03-28

    Dr. von Braun, Director of the Marshall Space Flight Center (MSFC), and Dr. Debus, Director of the Launch Operations Center, at Complex 34 prior to the Launch of the SA-4 (the fourth flight of Saturn I), March 28, 1963. The mission conducted the second "Project Highwater" experiment, which the upper stage ejected 30,000 gallons of ballast water in the upper atmosphere for a physics experiment.

  3. Wernher von Braun

    NASA Image and Video Library

    1968-10-01

    Dr. von Braun, Director of the Marshall Space Flight Center (MSFC), greets Commander of Apollo 7 mission, Walter M. Schirra, Jr., during the mission briefing at Kennedy Space Center (KSC). The Apollo 7 mission, boosted by a Saturn IB launch vehicle on October 11, 1968, was the first flight of the Apollo spacecraft with crew. Other crew members were Astronaut Donn Eisele and Astronaut Walter Cunningham.

  4. Measurements in Quantum Mechanics and von NEUMANN's Model

    NASA Astrophysics Data System (ADS)

    Mello, Pier A.; Johansen, Lars M.

    2010-12-01

    Many textbooks on Quantum Mechanics are not very precise as to the meaning of making a measurement: as a consequence, they frequently make assertions which are not based on a dynamical description of the measurement process. A model proposed by von Neumann allows a dynamical description of measurement in Quantum Mechanics, including the measuring instrument in the formalism. In this article we apply von Neumann's model to illustrate the measurement of an observable by means of a measuring instrument and show how various results, which are sometimens postulated without a dynamical basis, actually emerge. We also investigate the more complex, intriguing and fundamental problem of two successive measurements in Quantum Mechanics, extending von Neumann's model to two measuring instruments. We present a description which allows obtaining, in a unified way, various results that have been given in the literature.

  5. Test of Von Baer's law of the conservation of early development.

    PubMed

    Poe, Steven

    2006-11-01

    One of the oldest and most pervasive ideas in comparative embryology is the perceived evolutionary conservation of early ontogeny relative to late ontogeny. Karl Von Baer first noted the similarity of early ontogeny across taxa, and Ernst Haeckel and Charles Darwin gave evolutionary interpretation to this phenomenon. In spite of a resurgence of interest in comparative embryology and the development of mechanistic explanations for Von Baer's law, the pattern itself has been largely untested. Here, I use statistical phylogenetic approaches to show that Von Baer's law is an unnecessarily complex explanation of the patterns of ontogenetic timing in several clades of vertebrates. Von Baer's law suggests a positive correlation between ontogenetic time and amount of evolutionary change. I compare ranked position in ontogeny to frequency of evolutionary change in rank for developmental events and find that these measures are not correlated, thus failing to support Von Baer's model. An alternative model that postulates that small changes in ontogenetic rank are evolutionarily easier than large changes is tentatively supported.

  6. E2-EPF UCP targets pVHL for degradation and associates with tumor growth and metastasis.

    PubMed

    Jung, Cho-Rok; Hwang, Kyung-Sun; Yoo, Jinsang; Cho, Won-Kyung; Kim, Jin-Man; Kim, Woo Ho; Im, Dong-Soo

    2006-07-01

    The von Hippel-Lindau tumor suppressor, pVHL, forms part of an E3 ubiquitin ligase complex that targets specific substrates for degradation, including hypoxia-inducible factor-1alpha (HIF-1alpha), which is involved in tumor progression and angiogenesis. It remains unclear, however, how pVHL is destabilized. Here we show that E2-EPF ubiquitin carrier protein (UCP) associates with and targets pVHL for ubiquitin-mediated proteolysis in cells, thereby stabilizing HIF-1alpha. UCP is detected coincidently with HIF-1alpha in human primary liver, colon and breast tumors, and metastatic cholangiocarcinoma and colon cancer cells. UCP level correlates inversely with pVHL level in most tumor cell lines. In vitro and in vivo, forced expression of UCP boosts tumor-cell proliferation, invasion and metastasis through effects on the pVHL-HIF pathway. Our results suggest that UCP helps stabilize HIF-1alpha and may be a new molecular target for therapeutic intervention in human cancers.

  7. Dr. von Braun Tries Out the Neutral Buoyancy Simulator (NBS)

    NASA Technical Reports Server (NTRS)

    1967-01-01

    Marshall Space Flight Center (MSFC) Director, Dr. von Braun, submerges after spending some time under water in the MSFC Neutral Buoyancy Simulator (NBS). Weighted to a neutrally buoyant condition, Dr. von Braun was able to perform tasks underwater which simulated weightless conditions found in space.

  8. Valence bond and von Neumann entanglement entropy in Heisenberg ladders.

    PubMed

    Kallin, Ann B; González, Iván; Hastings, Matthew B; Melko, Roger G

    2009-09-11

    We present a direct comparison of the recently proposed valence bond entanglement entropy and the von Neumann entanglement entropy on spin-1/2 Heisenberg systems using quantum Monte Carlo and density-matrix renormalization group simulations. For one-dimensional chains we show that the valence bond entropy can be either less or greater than the von Neumann entropy; hence, it cannot provide a bound on the latter. On ladder geometries, simulations with up to seven legs are sufficient to indicate that the von Neumann entropy in two dimensions obeys an area law, even though the valence bond entanglement entropy has a multiplicative logarithmic correction.

  9. Cystic tumors of the liver: A practical approach

    PubMed Central

    Poggio, Paolo Del; Buonocore, Marco

    2008-01-01

    Biliary cyst tumors (cystadenoma and cystadeno-carcinoma) are an indication for liver resection. They account for only 5% of all solitary cystic lesions of the liver, but differential diagnosis with multiloculated or complicated biliary cysts, atypical hemangiomas, hamartomas and lymphangiomas may be difficult. The most frequent challenge is to differentiate biliary cyst tumors from hemorrhagic cysts. Computerized tomography (CT) and magnetic resonance imaging (MRI) are often not diagnostic and in these cases fine needle aspiration (FNA) is used to confirm the presence of atypical biliary cells. FNA, however, lacks adequate sensitivity and specificity and should always be used in conjunction with imaging. Pre-operative differentiation of cystadenoma from cystadenocarcinoma is impossible and surgery must be performed if a biliary cyst tumor is suspected. When multiple cystic lesions are observed throughout the liver parenchyma, it is important to exclude liver metastasis, of which colonic cancer is the most common primary site. Multiple biliary hamartomas (von Meyenburg complex) can appear as a mixture of solid and cystic lesions and can be confused with cystic metastasis. Strong and uniform T2 hyperintensity on MRI is usually diagnostic, but occasionally a percutaneous biopsy may be required. PMID:18595127

  10. Wernher von Braun with German Officers and Others

    NASA Technical Reports Server (NTRS)

    1942-01-01

    General Erich Fellgiebel, head of the German Army Information Service during World War II, congratulates members of the von Braun rocket team from Peenemunde for their October 3, 1942 A4 flight. Pictured front center is General Erich Fellgiebel. Shaking hands are General Walter Dornberger (left) and General Janssen, commanding officer of Peenemuende with Rudolph Hermarn to their right. Picture left to right in the back row are Wernher von Braun, Captain Stoelzel, Luftwaffe, and Dr. Gerhard Reisig.

  11. Pediatric living donor liver transplantation for congenital hepatic fibrosis using a mother's graft with von Meyenburg complex: A case report.

    PubMed

    Yamada, Naoya; Sanada, Yukihiro; Katano, Takumi; Tashiro, Masahisa; Hirata, Yuta; Okada, Noriki; Ihara, Yoshiyuki; Miki, Atsushi; Sasanuma, Hideki; Urahashi, Taizen; Sakuma, Yasunaru; Mizuta, Koichi

    2016-11-28

    This is the first report of living donor liver transplantation (LDLT) for congenital hepatic fibrosis (CHF) using a mother's graft with von Meyenburg complex. A 6-year-old girl with CHF, who suffered from recurrent gastrointestinal bleeding, was referred to our hospital for liver transplantation. Her 38-year-old mother was investigated as a living donor and multiple biliary hamartoma were seen on her computed tomography and magnetic resonance imaging scan. The mother's liver function tests were normal and she did not have any organ abnormality, including polycystic kidney disease. LDLT using the left lateral segment (LLS) graft from the donor was performed. The donor LLS graft weighed 250 g; the graft recipient weight ratio was 1.19%. The operation and post-operative course of the donor were uneventful and she was discharged on post-operative day (POD) 8. The graft liver function was good, and the recipient was discharged on POD 31. LDLT using a graft with von Meyenburg complex is safe and useful. Long-term follow-up is needed with respect to graft liver function and screening malignant tumors.

  12. Renal Cell Carcinoma Programmed Death-ligand 1, a New Direct Target of Hypoxia-inducible Factor-2 Alpha, is Regulated by von Hippel-Lindau Gene Mutation Status.

    PubMed

    Messai, Yosra; Gad, Sophie; Noman, Muhammad Zaeem; Le Teuff, Gwenael; Couve, Sophie; Janji, Bassam; Kammerer, Solenne Florence; Rioux-Leclerc, Nathalie; Hasmim, Meriem; Ferlicot, Sophie; Baud, Véronique; Mejean, Arnaud; Mole, David Robert; Richard, Stéphane; Eggermont, Alexander M M; Albiges, Laurence; Mami-Chouaib, Fathia; Escudier, Bernard; Chouaib, Salem

    2016-10-01

    Clear cell renal cell carcinomas (ccRCC) frequently display a loss of function of the von Hippel-Lindau (VHL) gene. To elucidate the putative relationship between VHL mutation status and immune checkpoint ligand programmed death-ligand 1 (PD-L1) expression. A series of 32 renal tumors composed of 11 VHL tumor-associated and 21 sporadic RCCs were used to evaluate PD-L1 expression levels after sequencing of the three exons and exon-intron junctions of the VHL gene. The 786-O, A498, and RCC4 cell lines were used to investigate the mechanisms of PD-L1 regulation. Fisher's exact test was used for VHL mutation and Kruskal-Wallis test for PD-L1 expression. If no covariate accounted for the association of VHL and PD-L1, then a Kruskal-Wallis test was used; otherwise Cochran-Mantel-Haenzsel test was used. We also used the Fligner-Policello test to compare two medians when the distributions had different dispersions. We demonstrated that tumors from ccRCC patients with VHL biallelic inactivation (ie, loss of function) display a significant increase in PD-L1 expression compared with ccRCC tumors carrying one VHL wild-type allele. Using the inducible VHL 786-O-derived cell lines with varying hypoxia-inducible factor-2 alpha (HIF-2α) stabilization levels, we showed that PD-L1 expression levels positively correlate with VHL mutation and HIF-2α expression. Targeting HIF-2α decreased PD-L1, while HIF-2α overexpression increased PD-L1 mRNA and protein levels in ccRCC cells. Interestingly, chromatin immunoprecipitation and luciferase assays revealed a direct binding of HIF-2α to a transcriptionally active hypoxia-response element in the human PD-L1 proximal promoter in 786-O cells. Our work provides the first evidence that VHL mutations positively correlate with PD-L1 expression in ccRCC and may influence the response to ccRCC anti-PD-L1/PD-1 immunotherapy. We investigated the relationship between von Hippel-Lindau mutations and programmed death-ligand 1 expression. We

  13. Die Kosmogonie Anton von Zachs.

    NASA Astrophysics Data System (ADS)

    Brosche, P.

    In his "Cosmogenische Betrachtungen" (1804), Anton von Zach rediscovered - probably independently - some aspects of the theories of Kant and Laplace. More originally, he envisaged also the consequences of an era of heavy impacts in the early history of the Earth.

  14. Dr. von Braun Tries Out the Neutral Buoyancy Simulator (NBS)

    NASA Technical Reports Server (NTRS)

    1967-01-01

    Marshall Space Flight Center (MSFC) Director, Dr. von Braun, is shown leaving the suiting-up van wearing a pressure suit prepared for a tryout in the MSFC Neutral Buoyancy Simulator (NBS). Weighted to a neutrally buoyant condition, Dr. von Braun was able to perform tasks underwater which simulated weightless conditions found in space.

  15. Spectrum of magnetic resonance imaging findings in pancreatic and other abdominal manifestations of Von Hippel-Lindau disease in a series of 23 patients: a pictorial review.

    PubMed

    Graziani, Rossella; Mautone, Simona; Vigo, Mario; Manfredi, Riccardo; Opocher, Giuseppe; Falconi, Massimo

    2014-01-10

    Von Hippel Lindau disease is a rare autosomal dominantly inherited multisystem disorder characterized by development of benign and malignant tumors. The abdominal manifestation of the syndrome are protean. Magnetic resonance plays an important role in identification of abdominal abnormalities and follow-up of lesions. To describe magnetic resonance imaging findings and patterns of pancreatic and other principal abdominal manifestations in a series of von Hippel-Lindau (VHL) disease patients and to review literature. We retrospectively reviewed abdominal magnetic resonance studies performed in 23 patients (10 males, 13 females) diagnosed of VHL. In all examined patients abdominal involvement was present. The pancreatic imaging findings detected were: unilocular cystic lesions (6/23: 26.1%); serous cystadenomas (11/23: 47.8%), including diffuse lesions (8/23: 34.8%); solid neuroendocrine tumors (8/23: 34.8%); cystic neuroendocrine tumors (1/23: 4.3%). The renal findings detected were: simple renal cysts (18/23: 78.3%); complex renal cysts (13/23: 56.5%), including benign lesions (10/23: 43.5%) and malignant lesions (3/23: 13.0%); renal carcinomas (11/23: 47.8%) and 5 of these (45.5%) were multiple and bilateral. Five patients (21.7%) presented pheochromocytoma (4 of these were bilateral; 80.0%) and 1 patient (4.3%) presented cystadenoma of the epididymis. In VHL disease patients, magnetic resonance imaging plays an essential role in the identification of pancreatic and other abdominal lesions, in their follow-up, in the screening of asymptomatic gene carriers, and in their long-term surveillance.

  16. Dr. Wernher Von Braun

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Marshall Space Flight Center director Wernher Von Braun and his family were honored with a series of events prior to his relocation to Washington, D.C. where he was assigned duties at NASA headquarters as deputy associate administrator for planning. Here he is shown with General Richard Drury and Hazel Toftoy, widow of General H.N. Toftoy.

  17. Evaluation of the Utility of von Willebrand Factor Propeptide in the Differential Diagnosis of von Willebrand Disease and Acquired von Willebrand Syndrome.

    PubMed

    Stufano, Francesca; Boscarino, Marco; Bucciarelli, Paolo; Baronciani, Luciano; Maino, Alberto; Cozzi, Giovanna; Peyvandi, Flora

    2018-06-18

    An increased von Willebrand factor propeptide (VWFpp) to VWF antigen (VWF:Ag) ratio (VWFpp/VWF:Ag) indicates an enhanced clearance of VWF. This finding has been described in von Willebrand disease (VWD) and in acquired von Willebrand syndrome (AVWS). A distinction between these two diseases, one congenital and the other acquired, is primarily based on family and personal history of bleeding. However, if this information is scanty, the diagnosis might be challenging due to the lack of an effective diagnostic biomarker. In this cross-sectional study, we assessed the ability of VWFpp/VWF:Ag for the differential diagnosis between VWD and AVWS. VWFpp/VWF:Ag was measured in a group of 153 patients (125 with VWD and 28 with AVWS). Most patients with AVWS and VWD showed an increased VWFpp/VWF:Ag, although to variable degrees. A marked increase of VWFpp/VWF:Ag was mainly associated with the diagnosis of AVWS and VWD type 1 Vicenza. A receiver operating characteristic curve was used to identify the optimal cutoff of VWFpp/VWF:Ag for discrimination of patients with a modestly increased (most VWD cases) versus those with a markedly increased clearance (AVWS and VWD type 1 Vicenza), and this cutoff was identified at the value of 3.9 (sensitivity: 0.70, specificity: 0.97). The ROC curve sorting from a logistic model containing VWFpp/VWF:Ag, age, and sex had an area under the curve (AUC) of 0.88 (95% confidence interval: 0.80-0.95). A subsequent molecular evaluation discriminated VWD type 1 Vicenza from AVWS. In conclusion, VWFpp/VWF:Ag appears helpful to discriminate patients with a markedly increase VWF clearance (AVWS or VWD type 1 Vicenza) from those with a modestly increased clearance (most VWD patients). Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  18. Zuverlässigkeit digitaler Schaltungen unter Einfluss von intrinsischem Rauschen

    NASA Astrophysics Data System (ADS)

    Kleeberger, V. B.; Schlichtmann, U.

    2011-08-01

    Die kontinuierlich fortschreitende Miniaturisierung in integrierten Schaltungen führt zu einem Anstieg des intrinsischen Rauschens. Um den Einfluss von intrinsischem Rauschen auf die Zuverlässigkeit zukünftiger digitaler Schaltungen analysieren zu können, werden Methoden benötigt, die auf CAD-Verfahren wie Analogsimulation statt auf abschätzenden Berechnungen beruhen. Dieser Beitrag stellt eine neue Methode vor, die den Einfluss von intrinsischem Rauschen in digitalen Schaltungen für eine gegebene Prozesstechnologie analysieren kann. Die Amplituden von thermischen, 1/f und Schrotrauschen werden mit Hilfe eines SPICE Simulators bestimmt. Anschließend wird der Einfluss des Rauschens auf die Schaltungszuverlässigkeit durch Simulation analysiert. Zusätzlich zur Analyse werden Möglichkeiten aufgezeigt, wie die durch Rauschen hervorgerufenen Effekte im Schaltungsentwurf mit berücksichtigt werden können. Im Gegensatz zum Stand der Technik kann die vorgestellte Methode auf beliebige Logikimplementierungen und Prozesstechnologien angewendet werden. Zusätzlich wird gezeigt, dass bisherige Ansätze den Einfluss von Rauschen bis um das Vierfache überschätzen.

  19. mRNAs for PRPs, statherin, and histatins in von Ebner's gland tissues.

    PubMed

    Azen, E A; Hellekant, G; Sabatini, L M; Warner, T F

    1990-11-01

    A search was made for expression of genes for proline-rich proteins (PRPs) and other salivary-type proteins, including statherin and histatins, in taste-bud tissues of mice and primates because of previous genetic findings in mice (Azen et al., 1986) that Prp and taste genes for certain bitter substances are either the same or closely linked. Taste-bud tissues and other tissues were tested for specific mRNAs with labeled DNA probes by Northern blotting and in situ hybridization. It was found that PRP mRNAs were present in von Ebner's glands of mice and macaques, and that there was a much greater degree of PRP mRNA induction in mouse parotid (16-fold) than in von Ebner's gland (two-fold) after in vivo isoproterenol stimulation. This difference may be due, in part, to differences in autonomic nerve innervation. Statherin and histatin mRNAs were found in macaque taste-bud tissues containing von Ebner's gland, and statherin protein was found in human von Ebner's gland by immunohistochemistry. The finding of PRP gene expression in von Ebner's gland, whose secretions have been suggested to play a role in taste stimulation, adds further support to a possible function of PRPs in bitter tasting. The possible functions of statherin and histatins in von Ebner's gland secretions may be related to statherin's regulation of salivary calcium and histatins' antibacterial and antifungal properties.

  20. Victor or Villain? Wernher von Braun and the Space Race

    ERIC Educational Resources Information Center

    O'Brien, Jason L.; Sears, Christine E.

    2011-01-01

    Set during the Cold War and space race, this historical role-play focuses on Wernher von Braun's involvement in and culpability for the use of slave laborers to produce V-2 rockets for Nazi Germany. Students will grapple with two central questions. Should von Braun have been allowed to emigrate to the United States given his affiliation with the…

  1. Wernher von Braun

    NASA Image and Video Library

    1966-06-21

    Dr. Joseph Randall, a laser expert at Marshall Space Flight Center (MSFC), explains one of the projects he is working on to a group composed of Federal Republic of Germany and MSFC officials. From left are: Dr. Randall; Minister for Scientific Research of Federal Republic of Germany, Dr. Gerhard Stolenberg; Director of MSFC Astrionics Lab, Dr. Walter Haeusserman; Head of Space Research Federal Republic of Germany, Max Mayer; MSFC Director Dr. von Braun; MSFC Deputy Director Dr. Elberhard Rees.

  2. Wernher von Braun

    NASA Image and Video Library

    1968-10-01

    Dr. von Braun inside the KC-135 in flight. The KC-135 provide NASA's Reduced-Gravity Program the unique weightlessness or zero-g environment of space flight for testing and training of human and hardware reactions. The recent version, KC-135A, is a specially modified turbojet transport which flies parabolic arcs to produce weightlessness periods of 20 to 25 seconds and its cargo bay test area is approximately 60 feet long, 10 feet wide, and 7 feet high.

  3. Physik gestern und heute Von der Metallstange zum Hochenergielaser

    NASA Astrophysics Data System (ADS)

    Heering, Peter

    2002-05-01

    Im Mai 1752 wurde in Marly bei Paris auf Anregung des amerikanischen Forschers und Politikers Benjamin Franklin erstmals die elektrische Natur des Blitzes nachgewiesen. Damals beschrieb Franklin auch eine technische Vorrichtung, die als Schutz von Gebäuden vor Blitzschlägen dienen sollte: den Blitzableiter. Diese aus heutiger Sicht scheinbar triviale Vorrichtung wurde aber keineswegs unmittelbar akzeptiert. Und bis heute ist die Forschung zum Schutz von Einrichtungen vor Blitzschlägen nicht abgeschlossen.

  4. von Baer's law for the ages: lost and found principles of developmental evolution.

    PubMed

    Abzhanov, Arhat

    2013-12-01

    In 1828, Karl Ernst von Baer formulated a series of empirically defined rules, which became widely known as the 'Law of Development' or 'von Baer's law of embryology'. This was one the most significant attempts to define the principles that connected morphological complexity and embryonic development. Understanding this relation is central to both evolutionary biology and developmental genetics. Von Baer's ideas have been both a source of inspiration to generations of biologists and a target of continuous criticism over many years. With advances in multiple fields, including paleontology, cladistics, phylogenetics, genomics, and cell and developmental biology, it is now possible to examine carefully the significance of von Baer's law and its predictions. In this review, I argue that, 185 years after von Baer's law was first formulated, its main concepts after proper refurbishing remain surprisingly relevant in revealing the fundamentals of the evolution-development connection, and suggest that their explanation should become the focus of renewed research. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Dr. von Braun Tries Out the Neutral Buoyancy Simulator (NBS)

    NASA Technical Reports Server (NTRS)

    1967-01-01

    Astronaut L. Gordon Cooper checks the neck ring of a space suit worn by Marshall Space Flight Center (MSFC) Director, Dr. von Braun before he submerges into the water of the MSFC Neutral Buoyancy Simulator (NBS). Wearing a pressurized suit and weighted to a neutrally buoyant condition, Dr. von Braun was able to perform tasks underwater which simulated weightless conditions found in space.

  6. Wernher von Braun

    NASA Image and Video Library

    1960-01-01

    In this photo, Director of the US Army Ballistic Missile Agency (ABMA) Development Operations Division, Dr. Wernher von Braun, is standing before a display of Army missiles celebrating ABMA's Fourth Open House. The missiles in the background include (left to right) a satellite on a Juno II shroud with a Nike Ajax pointing left in front of a Jupiter missile. The Lacrosse is in front of the Juno II. The Nike Hercules points skyward in front of the Juno II and the Redstone.

  7. Molecular quantum control landscapes in von Neumann time-frequency phase space

    NASA Astrophysics Data System (ADS)

    Ruetzel, Stefan; Stolzenberger, Christoph; Fechner, Susanne; Dimler, Frank; Brixner, Tobias; Tannor, David J.

    2010-10-01

    Recently we introduced the von Neumann representation as a joint time-frequency description for femtosecond laser pulses and suggested its use as a basis for pulse shaping experiments. Here we use the von Neumann basis to represent multidimensional molecular control landscapes, providing insight into the molecular dynamics. We present three kinds of time-frequency phase space scanning procedures based on the von Neumann formalism: variation of intensity, time-frequency phase space position, and/or the relative phase of single subpulses. The shaped pulses produced are characterized via Fourier-transform spectral interferometry. Quantum control is demonstrated on the laser dye IR140 elucidating a time-frequency pump-dump mechanism.

  8. Molecular quantum control landscapes in von Neumann time-frequency phase space.

    PubMed

    Ruetzel, Stefan; Stolzenberger, Christoph; Fechner, Susanne; Dimler, Frank; Brixner, Tobias; Tannor, David J

    2010-10-28

    Recently we introduced the von Neumann representation as a joint time-frequency description for femtosecond laser pulses and suggested its use as a basis for pulse shaping experiments. Here we use the von Neumann basis to represent multidimensional molecular control landscapes, providing insight into the molecular dynamics. We present three kinds of time-frequency phase space scanning procedures based on the von Neumann formalism: variation of intensity, time-frequency phase space position, and/or the relative phase of single subpulses. The shaped pulses produced are characterized via Fourier-transform spectral interferometry. Quantum control is demonstrated on the laser dye IR140 elucidating a time-frequency pump-dump mechanism.

  9. [Precocious puberty and von Recklinghausen's disease].

    PubMed

    Barg, Ewa; Wikiera, Beata; Basiak, Aleksander; Głab, Ewa

    2006-01-01

    Von Recklinghausen's disease belongs to a group of neurocutaneous syndromes and is characterised by skin, nerve and bone abnormalities. We present a case of von Recklinghausen's disease and precocious puberty in 7-year-old boy. At the age of three café au lait spots on the skin and an incranial tumour situated near the optic chiasm--qualified as inoperable--were discovered. At the age of 7 first signs of precocious puberty appeared (pubic hair P3 and enlargement of the testes (15 ml) and penis). Laboratory measurements included: LH 7.5 mIU/ml, FSH 1.1 mIU/ml, testosterone 183 ng/ml, assessment of bone age: 9 years. The response to LHRH stimulation was characteristic for true precocious puberty (LH 15.9 mIU/ml and FSH 1.5 mIU/ml after 30 minutes). The MRI of the brain showed a tumour of the suprasellar region with compression of pituitary stalk. True precocious puberty was diagnosed. Treatment with Diphereline was introduced. At present the boy is 9 years old and has been treated with Diphereline for 16 months. The volume of the testicles has decreased to 7 ml and loss of pubic hair was noted. The MRI does not show any progression in tumour growth. The authors would like to underline the need of close observation of children with von Reclinghausen disease with regard to possibility of uncovering true precocious puberty which is critical for rapid diagnosis and introduction of correct treatment.

  10. VHL-regulated miR-204 Suppresses Tumor Growth through Inhibition of LC3B-mediated Autophagy in Renal Clear Cell Carcinoma

    PubMed Central

    Mikhaylova, Olga; Stratton, Yiwen; Hall, Daniel; Kellner, Emily; Ehmer, Birgit; Drew, Angela F.; Gallo, Catherine A.; Plas, David R.; Biesiada, Jacek; Meller, Jarek; Czyzyk-Krzeska, Maria F.

    2012-01-01

    Summary The von Hippel-Lindau tumor-suppressor gene (VHL) is lost in most clear cell renal cell carcinomas (ccRCC). Here, using human ccRCC specimens, VHL-deficient cells, and xenograft models, we show that miR-204 is a VHL-regulated tumor suppressor acting by inhibiting macroautophagy, with MAP1LC3B (LC3B) as a direct and functional target. Importantly, higher tumor grade of human ccRCC was correlated with a concomitant decrease in miR-204 and increase in LC3B levels, indicating that LC3B-mediated macroautophagy is necessary for RCC progression. VHL, in addition to inducing endogenous miR-204, triggered the expression of LC3C, an HIF-regulated LC3B paralog, that suppressed tumor growth. These data reveal a function of VHL as a tumor suppressing regulator of autophagic programs. PMID:22516261

  11. The smooth entropy formalism for von Neumann algebras

    NASA Astrophysics Data System (ADS)

    Berta, Mario; Furrer, Fabian; Scholz, Volkher B.

    2016-01-01

    We discuss information-theoretic concepts on infinite-dimensional quantum systems. In particular, we lift the smooth entropy formalism as introduced by Renner and collaborators for finite-dimensional systems to von Neumann algebras. For the smooth conditional min- and max-entropy, we recover similar characterizing properties and information-theoretic operational interpretations as in the finite-dimensional case. We generalize the entropic uncertainty relation with quantum side information of Tomamichel and Renner and discuss applications to quantum cryptography. In particular, we prove the possibility to perform privacy amplification and classical data compression with quantum side information modeled by a von Neumann algebra.

  12. The smooth entropy formalism for von Neumann algebras

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

    Berta, Mario, E-mail: berta@caltech.edu; Furrer, Fabian, E-mail: furrer@eve.phys.s.u-tokyo.ac.jp; Scholz, Volkher B., E-mail: scholz@phys.ethz.ch

    2016-01-15

    We discuss information-theoretic concepts on infinite-dimensional quantum systems. In particular, we lift the smooth entropy formalism as introduced by Renner and collaborators for finite-dimensional systems to von Neumann algebras. For the smooth conditional min- and max-entropy, we recover similar characterizing properties and information-theoretic operational interpretations as in the finite-dimensional case. We generalize the entropic uncertainty relation with quantum side information of Tomamichel and Renner and discuss applications to quantum cryptography. In particular, we prove the possibility to perform privacy amplification and classical data compression with quantum side information modeled by a von Neumann algebra.

  13. Von Bertalanffy's dynamics under a polynomial correction: Allee effect and big bang bifurcation

    NASA Astrophysics Data System (ADS)

    Leonel Rocha, J.; Taha, A. K.; Fournier-Prunaret, D.

    2016-02-01

    In this work we consider new one-dimensional populational discrete dynamical systems in which the growth of the population is described by a family of von Bertalanffy's functions, as a dynamical approach to von Bertalanffy's growth equation. The purpose of introducing Allee effect in those models is satisfied under a correction factor of polynomial type. We study classes of von Bertalanffy's functions with different types of Allee effect: strong and weak Allee's functions. Dependent on the variation of four parameters, von Bertalanffy's functions also includes another class of important functions: functions with no Allee effect. The complex bifurcation structures of these von Bertalanffy's functions is investigated in detail. We verified that this family of functions has particular bifurcation structures: the big bang bifurcation of the so-called “box-within-a-box” type. The big bang bifurcation is associated to the asymptotic weight or carrying capacity. This work is a contribution to the study of the big bang bifurcation analysis for continuous maps and their relationship with explosion birth and extinction phenomena.

  14. Hazardous Waste Cleanup: Von Roll Isola USA Incorporated in Schenectady, New York

    EPA Pesticide Factsheets

    The Riverview facility is a 52-acre manufacturing facility located on Von Roll Drive in Schenectady, New York. The facility is owned and operated by Von Roll Isola USA, Inc., and produces solid and liquid insulating materials and tapes for the electrical

  15. Die nuklearen Anlagen von Hanford (1943-1987) Eine Fallstudie über die Schnittstellen von Physik, Biologie und die US-amerikanische Gesellschaft zur Zeit des Kalten Krieges

    NASA Astrophysics Data System (ADS)

    Macuglia, Daniele

    Die Geschichte des Kalten Krieges eröffnet viele Möglichkeiten, sich näher mit den Schnittstellen von Physik und Biologie während des 20. Jahrhunderts zu befassen. Nicht nur das Unglück in Tschernobyl aus dem Jahr 1986, auch das Beispiel der nuklearen Anlagen in Hanford in den Vereinigten Staaten zeigt die biologischen Folgen von nuklearer Physik.

  16. Von Neumann entropy in a Rashba-Dresselhaus nanodot; dynamical electronic spin-orbit entanglement

    NASA Astrophysics Data System (ADS)

    Safaiee, Rosa; Golshan, Mohammad Mehdi

    2017-06-01

    The main purpose of the present article is to report the characteristics of von Neumann entropy, thereby, the electronic hybrid entanglement, in the heterojunction of two semiconductors, with due attention to the Rashba and Dresselhaus spin-orbit interactions. To this end, we cast the von Neumann entropy in terms of spin polarization and compute its time evolution; with a vast span of applications. It is assumed that gate potentials are applied to the heterojunction, providing a two dimensional parabolic confining potential (forming an isotropic nanodot at the junction), as well as means of controlling the spin-orbit couplings. The spin degeneracy is also removed, even at electronic zero momentum, by the presence of an external magnetic field which, in turn, leads to the appearance of Landau states. We then proceed by computing the time evolution of the corresponding von Neumann entropy from a separable (spin-polarized) initial state. The von Neumann entropy, as we show, indicates that electronic hybrid entanglement does occur between spin and two-dimensional Landau levels. Our results also show that von Neumann entropy, as well as the degree of spin-orbit entanglement, periodically collapses and revives. The characteristics of such behavior; period, amplitude, etc., are shown to be determined from the controllable external agents. Moreover, it is demonstrated that the phenomenon of collapse-revivals' in the behavior of von Neumann entropy, equivalently, electronic hybrid entanglement, is accompanied by plateaus (of great importance in quantum computation schemes) whose durations are, again, controlled by the external elements. Along these lines, we also make a comparison between effects of the two spin-orbit couplings on the entanglement (von Neumann entropy) characteristics. The finer details of the electronic hybrid entanglement, which may be easily verified through spin polarization measurements, are also accreted and discussed. The novel results of the present

  17. The Opposing Roles of Nucleophosmin and the ARF Tumor Suppressor in Breast Cancer

    DTIC Science & Technology

    2007-04-01

    P ., R. K. Busch, B. C. Valdez, and H. Busch. 1996 . C23 interacts with B23, a putative nucleolar...beneficial anti-cancer activity of peptides in vivo. Injection of a peptide from the von Hippel -Lindau (VHL) tumor suppressor inhibited the growth and... 240 WT Arf -/- 1 2 3 4 5 0 C y to s o lic 3 H -M e th y l M e th io n in e c p m ( x 1 0 3 ) A 28S 18S WT chase (min): Arf -/- 120 240 120 240 N

  18. The molecular genetics of von Willebrand disease.

    PubMed

    Berber, Ergül

    2012-12-01

    Quantitative and/or qualitative deficiency of von Willebrand factor (vWF) is associated with the most common inherited bleeding disease von Willebrand disease (vWD). vWD is a complex disease with clinical and genetic heterogeneity. Incomplete penetrance and variable expression due to genetic and environmental factors contribute to its complexity. vWD also has a complex molecular pathogenesis. Some vWF gene mutations are associated with the affected vWF biosynthesis and multimerization, whereas others are associated with increased clearance and functional impairment. Moreover, in addition to a particular mutation, type O blood may result in the more severe phenotype. The present review aimed to provide a summary of the current literature on the molecular genetics of vWD. None declared.

  19. Wernher von Braun

    NASA Image and Video Library

    1965-05-25

    This image depicts the tension in the Launch Control Center of the Launch Complex 37 at Cape Canaveral, Florida, during the SA-8 on May 25, 1965. Pointing, center is Dr. Kurt Debus, Director, Launch Operations Directorate, MSFC. To the right is Dr. Hans Gruene, Deputy Director, Launch Operations Directorate, MSFC; Dr. von Braun, Director, Marshall Space Flight Center (MSFC); and leaning, Dr. Eberhard Rees, Director, Deputy Director for Research and Development, MSFC. The SA-8 mission, with a Saturn I launch vehicle, made the first night launch and deployed Pegasus II, micrometeoroid detection satellite.

  20. Fibroblast growth factor-10 signals development of von Brunn's nests in the exstrophic bladder

    PubMed Central

    Eastman, Rocky; Leaf, Elizabeth M.; Zhang, Dianzhong; True, Lawrence D.; Sweet, Robert M.; Seidel, Kristy; Siebert, Joseph R.; Grady, Richard; Mitchell, Michael E.

    2010-01-01

    von Brunn's nests have long been recognized as precursors of benign lesions of the urinary bladder mucosa. We report here that von Brunn's nests are especially prevalent in the exstrophic bladder, a birth defect that predisposes the patient to formation of bladder cancer. Cells of von Brunn's nest were found to coalesce into a stratified, polarized epithelium which surrounds itself with a capsule-like structure rich in types I, III, and IV collagen. Histocytochemical analysis and keratin profiling demonstrated that nested cells exhibited a phenotype similar, but not identical, to that of urothelial cells of transitional epithelium. Immunostaining and in situ hybridization analysis of exstrophic tissue demonstrated that the FGF-10 receptor is synthesized and retained by cells of von Brunn's nest. In contrast, FGF-10 is synthesized and secreted by mesenchymal fibroblasts via a paracrine pathway that targets basal epithelial cells of von Brunn's nests. Small clusters of 10pRp cells, positive for both FGF-10 and its receptor, were observed both proximal to and inside blood vessels in the lamina propria. The collective evidence points to a mechanism where von Brunn's nests develop under the control of the FGF-10 signal transduction system and suggests that 10pRp cells may be the original source of nested cells. PMID:20719973

  1. Deletion of the von Hippel-Lindau Gene in Hemangioblasts Causes Hemangioblastoma-like Lesions in Murine Retina.

    PubMed

    Wang, Herui; Shepard, Matthew J; Zhang, Chao; Dong, Lijin; Walker, Dyvon; Guedez, Liliana; Park, Stanley; Wang, Yujuan; Chen, Shida; Pang, Ying; Zhang, Qi; Gao, Chun; Wong, Wai T; Wiley, Henry; Pacak, Karel; Chew, Emily Y; Zhuang, Zhengping; Chan, Chi-Chao

    2018-03-01

    von Hippel-Lindau (VHL) disease is an autosomal-dominant tumor predisposition syndrome characterized by the development of highly vascularized tumors and cysts. LOH of the VHL gene results in aberrant upregulation of hypoxia-inducible factors (HIF) and has been associated with tumor formation. Hemangioblastomas of the central nervous system and retina represent the most prevalent VHL-associated tumors, but no VHL animal model has reproduced retinal capillary hemangioblastomas (RCH), the hallmark lesion of ocular VHL. Here we report our work in developing a murine model of VHL-associated RCH by conditionally inactivating Vhl in a hemangioblast population using a Scl -Cre-ERT2 transgenic mouse line. In transgenic mice carrying the conditional allele and the Scl -Cre-ERT2 allele, 64% exhibited various retinal vascular anomalies following tamoxifen induction. Affected Vhl -mutant mice demonstrated retinal vascular lesions associated with prominent vasculature, anomalous capillary networks, hemorrhage, exudates, and localized fibrosis. Histologic analyses showed RCH-like lesions characterized by tortuous, dilated vasculature surrounded by "tumorlet" cell cluster and isolated foamy stromal cells, which are typically associated with RCH. Fluorescein angiography suggested increased vascular permeability of the irregular retinal vasculature and hemangioblastoma-like lesions. Vhl deletion was detected in "tumorlet" cells via microdissection. Our findings provide a phenotypic recapitulation of VHL-associated RCH in a murine model that may be useful to study RCH pathogenesis and therapeutics aimed at treating ocular VHL. Significance: This study describes a model that phenotypically recapitulates a form of retinal pathogenesis that is driven by genetic loss of the VHL tumor suppressor, providing a useful tool for its study and therapeutic intervention. Cancer Res; 78(5); 1266-74. ©2018 AACR . ©2018 American Association for Cancer Research.

  2. Genetics Home Reference: von Hippel-Lindau syndrome

    MedlinePlus

    ... more common in particular ethnic groups? Genetic Changes Mutations in the VHL gene cause von Hippel-Lindau ... dividing too rapidly or in an uncontrolled way. Mutations in this gene prevent production of the VHL ...

  3. A rapid method to visualize von willebrand factor multimers by using agarose gel electrophoresis, immunolocalization and luminographic detection.

    PubMed

    Krizek, D R; Rick, M E

    2000-03-15

    A highly sensitive and rapid clinical method for the visualization of the multimeric structure of von Willebrand Factor in plasma and platelets is described. The method utilizes submerged horizontal agarose gel electrophoresis, followed by transfer of the von Willebrand Factor onto a polyvinylidine fluoride membrane, and immunolocalization and luminographic visualization of the von Willebrand Factor multimeric pattern. This method distinguishes type 1 from types 2A and 2B von Willebrand disease, allowing timely evaluation and classification of von Willebrand Factor in patient plasma. It also allows visualization of the unusually high molecular weight multimers present in platelets. There are several major advantages to this method including rapid processing, simplicity of gel preparation, high sensitivity to low concentrations of von Willebrand Factor, and elimination of radioactivity.

  4. Wernher von Braun: Reflections on His Contributions to Space Exploration

    NASA Technical Reports Server (NTRS)

    Goldman, Arthur E.

    2012-01-01

    In 1950, Dr. Wernher von Braun and approximately 100 of his team members came to Huntsville, Alabama, to begin work with the Army on what would later become America's historic space program. He would later serve as the first director of the Marshall Space Flight Center and led the development of the Saturn V launch vehicle that launched seven crewed American mission to the moon, as well as America s first space station, Skylab. Von Braun is best known for his team s technical achievements. He realized his dream of exploring outer space by helping place humans on the moon. His engineering and managerial talent during the Apollo era had contributed to a technological revolution. He was by all accounts a good engineer, but he was only one among many. What set Von Braun apart were his charisma, his vision, and his leadership skills. He inspired loyalty and dedication in the people around him. He understood the importance of communicating his vision to his team, to political and business leaders and the public. Today, the Marshall Center continues his vision by pursuing engineering and scientific projects that will continue to open space to exploration. This presentation will discuss Von Braun's impact on Huntsville, the Marshall Center, the nation and the world and look at his contributions in context of where world space exploration is today.

  5. Update zum klinischen Einsatz von Inhibitoren mutierter Phosphokinasen beim Melanom.

    PubMed

    Cosgarea, Ioana; Ritter, Cathrin; Becker, Jürgen C; Schadendorf, Dirk; Ugurel, Selma

    2017-09-01

    Die Behandlungsstrategie beim metastasierten Melanom hat sich mit der Identifizierung therapeutisch angreifbarer molekularer Zielstrukturen innerhalb zellulärer Signalwege radikal geändert. Durch die Zulassung von Substanzen, die gezielt an den zentralen Schaltmolekülen, den Phosphokinasen, angreifen, können diese Signalwege selektiv abgeschaltet werden. Dies ist insbesondere bei denjenigen Tumoren von Interesse, deren Signalwege durch aktivierende Mutationen der für die Schaltmoleküle kodierenden Gene konstitutiv aktiviert sind. Aktuell ist diese therapeutische Strategie insbesondere für Patienten bedeutsam, deren Melanome eine Mutation im BRAF-Gen aufweisen. Diese Patienten können durch eine Kombinationstherapie aus Inhibitoren der Phosphokinasen BRAF und MEK langfristig mit sehr guter Krankheitskontrolle behandelt werden. Unter dieser Kombinationstherapie wird aktuell ein progressionsfreies Überleben von über zehn Monaten und ein Gesamtüberleben von mehr als zwei Jahren bei guter Lebensqualität erzielt. Da unter längerfristiger Therapie mit Kinaseinhibitoren jedoch bei einem Großteil der Patienten eine Resistenzbildung auftritt, sind aktuelle klinische Therapiestudien auf die Suche nach geeigneten Kombinationspartnern unter Blockierung anderer Signalwege oder unter Aktivierung der T-Zell-vermittelten Immunantwort ausgerichtet. Der vorliegende Übersichtsartikel stellt sowohl die aktuell verfügbaren als auch die in der klinischen Testung befindlichen zukünftigen Optionen der zielgerichteten Therapie des Melanoms dar. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  6. Wernher von Braun

    NASA Image and Video Library

    1959-03-01

    In this photo, Director of the U.S. Army Ballistic Missile Agency's (ABMA) Development Operations Division, Dr. Wernher von Braun, and Director of Missile Firing Division, Dr. Kurt Debus, are shown with unidentified individuals, discussing two components that would make up the Pioneer IV Lunar Probe. The mercury batteries (left) were used to power the radio transmitter, cosmic radiation counter and other instruments in Pioneer IV. The conical shroud placed over the instruments of Pioneer IV was plated with gold to improve conductivity. The metal surface also served as the anterna for the probe's instruments signaling back to the Earth receiving stations.

  7. The British Interplanetary Society - Val Cleaver and Wernher von Braun

    NASA Astrophysics Data System (ADS)

    Willhite, I. P.

    This article is concerned with the early relationship between Wernher von Braun and the British Interplanetary Society (BIS). The BIS/Wernher von Braun/Val Cleaver correspondence files located here at the US Space & Rocket Center in Huntsville, Alabama are unparalleled. As one reads the stimulating comments between Cleaver and von Braun, the need to share their thoughts prevails. Following is an excerpt from one letter that whets ones appetite for more. 10 June 1951 Cleaver writes, “I'm so glad you enjoyed my last letter, and look forward to your promised further contribution to our discussion of the ethics of science in general and astronautics in particu- lar. As regards the one particular point on which you found yourself unable to hold your fire, I should say there are really two distinct issues at stake:. . .” This article attempts to represent the best of the letters as they goad each other on scientific principles, means to prevent wars, and other philosophic ideas.

  8. Virchow's triad: Kussmaul, Quincke and von Recklinghausen.

    PubMed

    Stanifer, John W

    2016-02-01

    For most of the 19th century, Germany was the centre of the medical world. From there the most innovating research came and many of the physicians of that era are known to nearly every medical student and physician of today. Virchow, Kussmaul, Quincke, von Recklinghausen, Müller and Schönlein are familiar names in today's medicine but insofar as they are merely eponyms associated with signs, symptoms, disease and anatomy. The story of their lives, their research and their influence on each other has been little examined. This is an essay about Virchow's relationship with his mentors Müller and Schönlein and how these relationships shaped the development of Kussmaul, Quincke and von Recklinghausen as students of Virchow and their work in medicine and clinical observation after leaving Virchow's laboratory. © The Author(s) 2014.

  9. Von eingebetteten Systemen zu Cyber-Physical Systems

    NASA Astrophysics Data System (ADS)

    Wedde, Rorst F.; Lehnhoff, Sebastian; Rehtanz, Christian; Krause, Olav

    Das Hauptanliegen des Papiers ist, ein Paradigma für Probleme mit neuartigen Integrationsanforderungen für Forschung und Entwicklung in verteilten eingebetteten Echtzeitsystemen zu motivieren und vorzustellen, nämlich den Begriff Cyber-Physical Systems. Bei einer in letzter Zeit stark zunehmenden Anzahl von Realzeitanwendungen können ohne die Berücksichtigung solcher Forderungen keine praktisch brauchbaren Lösungen erwartet werden. Einige Anwendungsfelder werden angesprochen. Im Einzelnen werden dann für Elektroautos, die mit erneuerbaren Energien betrieben werden sollen, einerseits die Management-, verteilte Verhandlungs- und Verteilungsprobleme der benötigten Energie in einem bottom-up Ansatz gelöst. Andererseits wird als Teil unserer Projektarbeit die Bereitstellung von Reserveenergie für den allgemeinen Bedarf durch Autobatterien vorgestellt. Es zeigt sich, dass dies effizienter und wesentlich kurzfristiger in unserem verteilten Vorgehen geschehen kann als in traditionellen Verfahren.

  10. Aufnahme, Analyse und Visualisierung von Bewegungen nativer Herzklappen in-vitro

    NASA Astrophysics Data System (ADS)

    Weiß, Oliver; Friedl, Sven; Kondruweit, Markus; Wittenberg, Thomas

    Die hohe Zahl an Transplantationen von Herzklappen und viele nötige Re-Operationen machen eine detaillierte Analyse der Strömungen und Klappenbewegungen klinisch interessant. Ein neuer Ansatz ist hierbei der Einsatz von Hochgeschwindigkeitskameras um Bewegungsabl äufe der Herzklappen beobachten und auswerten zu können. Die hohen Datenraten erfordern allerdings eine möglichst automatisierte Analyse und möglichst komprimierte Darstellung des Schwingungsverhaltens. In dieser Arbeit wird ein Ansatz vorgestellt, bei dem Bewegungen nativer Herzklappen in-vitro aufgenommen, analysiert und kompakt visualisiert werden.

  11. The von Hippel-Lindau (VHL) tumor-suppressor gene is down-regulated by selenium deficiency in Caco-2 cells and rat colon mucosa.

    PubMed

    Uthus, Eric; Begaye, Adrienne; Ross, Sharon; Zeng, Huawei

    2011-08-01

    To test the hypothesis that selenium affects DNA methylation and hence gene regulation, we employed a methylation array (Panomics) in the human colonic epithelial Caco-2 cell model. The array profiles DNA methylation from promoter regions of 82 human genes. After conditioning cells to repeatedly reduced concentrations of fetal bovine serum, a serum-free culture was established. Se-methylselenocysteine (SeMSC) was added at 0 (deficient Se) or 250 (control Se) nM to cells maintained in DMEM. After 7 days, cells were collected and stored at -80 °C until analysis; experiments were replicated three times. Glutathione peroxidase activity was significantly decreased in cells grown in low SeMSC. Cells grown in 250 nM SeMSC had maximal GPx activity. Genomic DNA from cells grown in the low-SeMSC media and media containing 250 nM SeMSC was incubated with methylation-binding protein followed by isolation of methylated DNA. The methylated DNA was labeled with biotin and hybridized to the methylation array. Thus, genes with promoter methylation will produce a higher chemiluminescence signal than those genes with no promoter methylation. Of the genes profiled, the von Hippel-Lindau (VHL) gene was most different as indicated by quantification following chemiluminescence detection demonstrating that the promoter region of VHL was hypermethylated in cells from the low-SeMSC media. To determine whether promoter methylation affected transcription, we isolated RNA from replicate samples and performed real-time RT PCR. VHL (mRNA) was down-regulated (fold change significantly <1) in cells grown in low SeMSC compared to cells grown in 250 nM SeMSC (control; fold change = 1). We also show that (mRNA) Vhl expression is significantly reduced in mucosa from rats fed a diet deficient in Se. Our results suggest that low Se status affects DNA promoter region methylation and that this can result in down-regulation of the tumor suppressor gene VHL.

  12. Quantitative Analyse und Visualisierung der Herzfunktionen

    NASA Astrophysics Data System (ADS)

    Sauer, Anne; Schwarz, Tobias; Engel, Nicole; Seitel, Mathias; Kenngott, Hannes; Mohrhardt, Carsten; Loßnitzer, Dirk; Giannitsis, Evangelos; Katus, Hugo A.; Meinzer, Hans-Peter

    Die computergestützte bildbasierte Analyse der Herzfunktionen ist mittlerweile Standard in der Kardiologie. Die verfügbaren Produkte erfordern meist ein hohes Maß an Benutzerinteraktion und somit einen erhöhten Zeitaufwand. In dieser Arbeit wird ein Ansatz vorgestellt, der dem Kardiologen eine größtenteils automatische Analyse der Herzfunktionen mittels MRT-Bilddaten ermöglicht und damit Zeitersparnis schafft. Hierbei werden alle relevanten herzphysiologsichen Parameter berechnet und mithilfe von Diagrammen und Graphen visualisiert. Diese Berechnungen werden evaluiert, indem die ermittelten Werte mit manuell vermessenen verglichen werden. Der hierbei berechnete mittlere Fehler liegt mit 2,85 mm für die Wanddicke und 1,61 mm für die Wanddickenzunahme immer noch im Bereich einer Pixelgrösse der verwendeten Bilder.

  13. The genetic locus NRC-1 within chromosome 3p12 mediates tumor suppression in renal cell carcinoma independently of histological type, tumor microenvironment, and VHL mutation.

    PubMed

    Lovell, M; Lott, S T; Wong, P; El-Naggar, A; Tucker, S; Killary, A M

    1999-05-01

    Human chromosome 3p cytogenetic abnormalities and loss of heterozygosity have been observed at high frequency in the nonpapillary form of sporadic renal cell carcinoma (RCC). The von Hippel-Lindau (VHL) gene has been identified as a tumor suppressor gene for RCC at 3p25, and functional studies as well as molecular genetic and cytogenetic analyses have suggested as many as two or three additional regions of 3p that could harbor tumor suppressor genes for sporadic RCC. We have previously functionally defined a novel genetic locus nonpapillary renal carcinoma-1 (NRC-1) within chromosome 3p12, distinct from the VHL gene, that mediates tumor suppression and rapid cell death of RCC cells in vivo. We now report the suppression of tumorigenicity of RCC cells in vivo after the transfer of a defined centric 3p fragment into different histological types of RCC. Results document the functional involvement of NRC-1 in not only different cell types of RCC (i.e., clear cell, mixed granular cell/clear cell, and sarcomatoid types) but also in papillary RCC, a less frequent histological type of RCC for which chromosome 3p LOH and genetic aberrations have only rarely been observed. We also report that the tumor suppression observed in functional genetic screens was independent of the microenvironment of the tumor, further supporting a role for NRC-1 as a more general mediator of in vivo growth control. Furthermore, this report demonstrates the first functional evidence for a VHL-independent pathway to tumorigenesis in the kidney via the genetic locus NRC-1.

  14. Von Donuts und Zucker: Mit Neutronen biologische Makromoleküle erforschen

    NASA Astrophysics Data System (ADS)

    May, Roland P.

    2003-05-01

    Für die Erforschung von Biomolekülen bieten Neutronen einzigartige Eigenschaften. Vor allem ihre unterschiedliche Wechselwirkung mit dem natürlichen Wasserstoff und seinem schweren Isotop Deuterium ermöglicht tiefe Einblicke in Struktur, Funktion und Dynamik von Proteinen, Nukleinsäuren und Biomembranen. Bei vielen Fragestellungen zur Strukturaufklärung gibt es kaum oder keine Alternative zum Neutron. Das Institut Laue-Langevin trägt Bahnbrechendes zum Erfolg der Neutronen-Methoden in der Biologie bei.

  15. The von Auwers reaction - history and synthetic applications.

    PubMed

    Dumeunier, Raphaël; Jaeckh, Simon

    2014-01-01

    Dienones obtained from the facile dearomatization of phenols, can be further transformed to semi-benzenes prone to rearomatize in clean, but sometimes unexpected, fashion. Over a hundred years ago, K. von Auwers found that adding Grignards on dienones would lead spontaneously to subsequent dehydration and a novel aromatizing rearrangement. This reaction was ignored for 50 years before Melvin Newman re-investigated these findings, studied the mechanism, and developed variations on the same theme. Since then, despite the tremendous potential of the reactions, those studies were only rarely mentioned, before finally falling into oblivion. This review aims to provide the reader with a detailed history and comprehensive bibliography of the von Auwers rearrangement, some of its synthetic applications, and new unpublished material in the hope to open new perspectives on this forgotten reaction.

  16. Sentinel-Lymphknoten-Biopsie des Melanoms mittels Indocyaningrün und "FOVIS"-System.

    PubMed

    Göppner, Daniela; Nekwasil, Stephan; Jellestad, Anne; Sachse, Alexander; Schönborn, Karl-Heinz; Gollnick, Harald

    2017-02-01

    Der Nachweis metastatischer Infiltrate im Sentinel-Lymphkoten (SLN) gilt als wesentlicher prognostischer Faktor des Melanoms. Alternativ zur Farbstoffmethode mit Patentblau zum Goldstandard der SLN-Biopsie (SLNB) mittels Radiokolloid wird die fluoreszenzoptische Darstellung mit Hilfe von Indocyaningrün (ICG) und Nahinfrarot (NIR)-Kamerasystem kommuniziert. Im Vergleich zur konventionellen Methode wurde die Wertigkeit des ICG-/NIR-Verfahrens in Abhängigkeit vom Body-Mass-Index (BMI) des Patienten und der Konzentration von ICG bezüglich der Visualisierung des Lymphabstroms und des SLNs untersucht. An zehn Patienten wurde die SLNB mittels Technetium-99m, Patentblau und ICG durchgeführt. Die Fluoreszenz-Darstellung von Lymphbahnen und SLN erfolgte in Echtzeit mittels der NIR-Kameratechnik "FOVIS". Je nach erzielter Bildqualität wurde ICG in einer Dosis von 0,25 mg bis 2,5 mg intrakutan appliziert. Neun der zehn SLN wurden fluoreszenzoptisch identifiziert (90 %), alle zehn radioaktiv (100 %), nur acht (80 %) mittels ICG-Grünfärbung bzw. Patenblau-Markierung. Transdermal wurde ein SLN dargestellt (10 %). In Korrelation zum BMI waren höhere ICG-Mengen, bis zu 2,5 mg intrakutan absolut, in der Darstellung der Lymphbahnen von Vorteil. Die SLN-Fluoreszenzmarkierung mit dem ICG/NIR-Kamera-System "FOVIS" stellt eine sichere Alternative zur Farbstoffmethode mit Patentblau ergänzend zur Radiokolloidmethode mit Technetium-99m dar. Weitere Studien zur optimalen Dosierung von ICG und transdermalen Bildgebung in Relation zum BMI sind notwendig. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  17. Dr. von Braun Tours the North American Aviation

    NASA Technical Reports Server (NTRS)

    1962-01-01

    Dr. Wernher von Braun, Director of the Marshall Space Flight Center (MSFC), during his tour of the Space information Division of North American Aviation (NAA) in Downey, California, where the Saturn SII stage was developed.

  18. Dr. von Braun tours the North American Aviation

    NASA Technical Reports Server (NTRS)

    1962-01-01

    Dr. Wernher von Braun, Director of the Marshall Space Flight Center (MSFC), during his tour of the Space Information Division of North American Aviation (NAA) in Downey, California, where the Saturn SII stage was developed.

  19. Design of inside cut von koch fractal UWB MIMO antenna

    NASA Astrophysics Data System (ADS)

    Tharani, V.; Shanmuga Priya, N.; Rajesh, A.

    2017-11-01

    An Inside Cut Hexagonal Von Koch fractal MIMO antenna is designed for UWB applications and its characteristics behaviour are studied. Self-comparative and space filling properties of Koch fractal structure are utilized in the antenna design which leads to the desired miniaturization and wideband characteristics. The hexagonal shaped Von Koch Fractal antenna with Defected Ground Structure (DGS) is designed on FR4 substrate with a compact size of 30mm x 20mm x 1.6mm. The antenna achieves a maximum of -44dB and -51dB at 7.1GHz for 1-element and 2-element case respectively.

  20. Von recklinghausens disease: a series of four cases with variable expression.

    PubMed

    Arun, K P; Thomas Joseph, P; Jaishankar, H P; Abhinethra, M S

    2015-03-01

    Though neurofibromatosis type I (NFI) is a fairly common condition, it has a variable expressivity and penetrance. Here we present a series of cases with striking differences in the presentation especially in the oral cavity. NFI, also known as von Recklinghausen's neurofibromatosis, is an autosomal dominantly inherited neurogenetic disorder affecting 1:3000 newborn (Bongiorno et al., Oral Dis 12:125-129, 2006). About 50 % of NFI patients have no family history of the disease. There is no prevalence for gender or race in NFI. Expressivity in NFI is tremendously variable, but subtle phenotypic patterns may exist within subgroups of affected patients. Furthermore, 50 % of cases are sporadic and arise from germ cell mutation (Bongiorno et al., Oral Dis 12:125-129, 2006). The precise constellation of findings in any one individual is extremely variable, both within a family and between different families (Batsakis, Tumors of the head and neck: clinical and pathological considerations, 2nd edn. Williams and Wilkins, Baltimore, pp 313-333, 1979). Only 4-7 % of patients affected by neurofibromatosis exhibit oral manifestations (Güneri et al., Turk J Pediatr 48(2):155-158, 2006).

  1. Elliptical Instability of Rotating Von Karman Street

    NASA Astrophysics Data System (ADS)

    Stegner, A.; Pichon, T.; Beunier, M.

    Clouds often reveal a meso-scale vortex shedding in the wake of mountainous islands. Unlike the classical bi-dimensional Von-Karman street, these observed vortex street are affected by the earth rot ation and vertical stratification. Theses effects could induce a selective destabilization of anticyclonic vortices. It is well known that inertial instability (also called centrifugal instability) induce a three- dimensional destabilization of anticyclonic structures when the absolute vorticity is larger than the local Coriolis parameter. However, we have shown, by the mean of laboratory experiments, that it is a different type of instability which is mainly responsible for asymmetric rotating Von-Karman street. A serie of experiments were performed to study the wake of a cylinder in a rotating fluid, at medium Reynolds number and order one Rossby number. We have shown that the vertical structure of unstable anticyclonic vortices is characteristic of an elliptical instability. Besides, unlike the inertial instability, the vertical unstable wavelength depends on the Rossby number.

  2. Inattentional blindness and the von Restorff effect.

    PubMed

    Schmidt, Stephen R; Schmidt, Constance R

    2015-02-01

    Sometimes we fail to notice distinctive or unusual items (inattentional blindness), while other times we remember distinctive items more than expected items (the von Restorff effect). A three-factor framework is presented and tested in two experiments in an attempt to reconcile these seemingly contradictory phenomena. Memory for different types of unexpected stimuli was tested after an easy or difficult Stroop color-naming task. Highly arousing taboo words were well remembered even when the difficult Stroop task limited attentional resources. However, a conceptual isolation effect was only observed when the nature of the category change was highlighted by the Stroop task, the Stroop task was easy, and/or the isolated targets enjoyed a retrieval advantage relative to comparison targets. As proposed in the three-factor framework, the arousing qualities of the stimuli, the attentional demands of the primary task, and the relevance of isolated features at encoding and retrieval combine to produce inattentional blindness and the von Restorff effect.

  3. Von Willebrand's disease: case report and review of literature.

    PubMed

    Echahdi, Hanae; El Hasbaoui, Brahim; El Khorassani, Mohamed; Agadr, Aomar; Khattab, Mohamed

    2017-01-01

    Von Willebrand Disease (VWD) is the most common human inherited bleeding disorder due to a defect of Von Willebrand Factor (VWF), which a glycoprotein crucial for platelet adhesion to the subendothelium after vascular injury. VWD include quantitative defects of VWF, either partial (type 1 with VWF levels < 50 IU/dL) or virtually total (type 3 with undetectable VWF levels) and also qualitative defects of VWF (type 2 variants with discrepant antigenic and functional VWF levels). The most bleeding forms of VWD usually do not concern type 1 patients with the mildest VWF defects (VWF levels between 30 and 50IU/dL). Von willebrand factor is a complex multimeric protein with two functions: it forms a bridge between the platelets and areas of vascular damage and it binds to and stabilizes factor VIII, which is necessary for the clotting cascade. By taking a clinical history of bleeding (mucocutaneous bleeding symptoms suggestive of a primary haemostatic disorder, a quantitative or qualitative abnormality of VWF is possible) it is important to think about VWD and to make the appropriate diagnosis. If the VWD is suspected diagnostic tests should include an activated partial thromboplastin time, bleeding time, factor VIII: C Ristocetin cofactor and vWF antigen. Additional testing of ristocetin induced plattlet adhesion (RIPA) the multimeric structure and collagen binding test and genanalysis allow diagnosing the different types of von. Willebrand Disease. The treatment of choice in mild forms is the synthetic agent desmopressin. In patients with severe type 1, type 2B, 2N and type 3 or in people who do not response to desmopressin, the appropriate treatment is a factor VIII concentrate that is rich of VWF. We report a case of infant in 27-month-old boy who had been referred due to haemorrhagic shock. His birth histories, his familie's social history and developmental milestones were unremarkable. He was born at full term with no antenatal or perinatal complications. Prior to

  4. Segmentierung von Aortenaneurysmen in CTA-Bildern mit dem statistischen Verfahren der Active Appearance Models

    NASA Astrophysics Data System (ADS)

    Greiner, Katharina; Egger, Jan; Großkopf, Stefan; Kaftan, Jens N.; Dörner, Ralf; Freisleben, Bernd

    In diesem Beitrag werden Active Appearance Models (AAMs) zur Segmentierung der äußeren Kontur von Aortenaneurysmen eingesetzt. Diese Aufgabe ist wegen des geringen Kontrastes zum umliegenden Gewebe und des Aufbaus der teils thrombotisierten oder kalzifizierten Gefäßwände im Bereich eines Aneurysmas so komplex, dass sie aufgrund der Vielgestalt der Kontur in CT-Angiographie-Bildern die Verwendung eines statistischen Modells für Form und eingeschlossene Textur rechtfertigt. Für die Evaluation des Verfahrens wurden verschiedene statistische Modelle aus Schichten von neun CTA-Datensätzen trainiert und die Segmentierung anhand von Leave-One-Out-Tests überprüft.

  5. Dr. von Braun Visits Huntsville Boys Club

    NASA Technical Reports Server (NTRS)

    1961-01-01

    Dr. von Braun, Director of Marshall Space Flight Center (MSFC) and chairman of this year's United Givers Fund (UGF) drive at MSFC, takes time out from the problems of sending a man to the Moon to talk baseball with 11-year-old Randy Smith at the Huntsville Boys Club.

  6. Gebrauch von Komplementärmedizin bei Patienten mit metastasierendem Melanom unter Therapie mit Ipilimumab innerhalb einer klinischen Studie.

    PubMed

    Huebner, Jutta; Mohr, Peter; Simon, Jan-Christoph; Fluck, Michael; Berking, Carola; Zimmer, Lisa; Loquai, Carmen

    2016-05-01

    In Deutschland wenden 40-90 % aller Krebspatienten Methoden der komplementären and alternativen Medizin (KAM) an. Bis dato gibt es kein Datenmaterial zum Einsatz der KAM bei Melanompatienten. Das Ziel unserer Studie war es, Daten über den Gebrauch, die Informationsquellen und Ziele von Patienten mit metastasierendem Melanom zu erfassen. Einhundertsechsundfünfzig Patienten aus 25 Studienzentren nahmen an der DecOG-MM-PAL Multibasket Studie teil. Die beteiligten Personen wurden auch gebeten, an einer Nebenstudie teilzunehmen, die ihren Gebrauch von KAM erfassen sollte. Dazu wurde während der Behandlung ein standardisierter Fragebogen zu genau festgelegten Zeitpunkten ausgeteilt. Insgesamt gingen 55 Fragebögen von 32 (21 %) Melanompatienten ein. Von diesen gaben 17 (53 %) ein Interesse an KAM an, und sieben (22 %) machten von KAM Gebrauch. Die Hauptinformationsquellen (31 %) waren Familienmitglieder und Freunde, gefolgt von Ärzten (19 %). Die Hauptgründe für die Anwendung von KAM waren die Stärkung des Immunsystems (41 %) und des Körpers (34 %). Nahrungsergänzungsmittel (Vitamine und Spurenelemente) wurden am häufigsten angewendet (28 %). Eine relativ hohe Anzahl an Patienten mit metastasierendem Melanom machte trotz Teilnahme an einer klinischen Studie von KAM Gebrauch. Wechselwirkungen könnten durch biologisch basierte KAM auftreten, und hier besonders bei immunmodulierenden KAM- Strategien. Um Risiken zu vermeiden, sollte die Kommunikation zwischen den Ärzten und den Patienten verbessert werden. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  7. Trizentrische Analyse von Kofaktoren und Komorbidität des Pyoderma gangraenosum.

    PubMed

    Jockenhöfer, Finja; Herberger, Katharina; Schaller, Jörg; Hohaus, Katja Christina; Stoffels-Weindorf, Maren; Ghazal, Philipp Al; Augustin, Matthias; Dissemond, Joachim

    2016-10-01

    Das Pyoderma gangraenosum (PG) ist eine seltene, inflammatorische destruktiv-ulzerierende neutrophile Erkrankung mit weitgehend unklarer Pathophysiologie. In dieser Studie wurden die potenziell relevanten Kofaktoren und Begleiterkrankungen von Patienten mit PG aus drei dermatologischen Wundzentren in Deutschland differenziert ausgewertet. Von den insgesamt 121 analysierten Patienten waren Frauen (66,9 %) häufiger betroffen als Männer. Das Alter der Patienten war 18-96 Jahre (Mittelwert [MW]: 59,8); die Wunden hatten eine Größe von 1-600 cm² (MW: 65,6 cm²) und waren überwiegend sehr schmerzhaft (VAS 1-10, MW: 7). Die Unterschenkel waren am häufigsten (71,9 %) betroffen. Bei 12 (9,9 %) Patienten bestanden chronisch entzündliche Darmerkrankungen (5,8 % Colitis ulcerosa; 4,1 % Morbus Crohn), bei 14,1 % der Patienten wurde eine Begleiterkrankung aus dem rheumatischen Formenkreis beschrieben. Neoplasien bestanden bei 20,6 % der Patienten, von denen 6,6 % als hämatologische und 14,1 % als solide Neoplasien klassifiziert wurden. Aus dem Kreis des metabolischen Syndroms wurde bei 69,4 % Patienten eine Adipositas, bei 57,9 % eine arterielle Hypertonie und bei 33,9 % ein Diabetes mellitus diagnostiziert. Diese Datenanalyse bestätigt Assoziationen des PG mit dem metabolischen Syndrom und mit Neoplasien, die zukünftig frühzeitig bei einer zielgerichteten Diagnostik der Patienten beachtet und behandelt werden sollten. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  8. (Never) Mind your p's and q's: Von Neumann versus Jordan on the foundations of quantum theory

    NASA Astrophysics Data System (ADS)

    Duncan, A.; Janssen, M.

    2013-03-01

    In 1927, in two papers entitled "On a new foundation [Neue Begründung] of quantum mechanics," Pascual Jordan presented his version of what came to be known as the Dirac-Jordan statistical transformation theory. Jordan and Paul Dirac arrived at essentially the same theory independently of one another at around the same time. Later in 1927, partly in response to Jordan and Dirac and avoiding the mathematical difficulties facing their approach, John von Neumann developed the modern Hilbert space formalism of quantum mechanics. We focus on Jordan and von Neumann. Central to the formalisms of both are expressions for conditional probabilities of finding some value for one quantity given the value of another. Beyond that Jordan and von Neumann had very different views about the appropriate formulation of problems in quantum mechanics. For Jordan, unable to let go of the analogy to classical mechanics, the solution of such problems required the identification of sets of canonically conjugate variables, i.e., p's and q's. For von Neumann, not constrained by the analogy to classical mechanics, it required only the identification of a maximal set of commuting operators with simultaneous eigenstates. He had no need for p's and q's. Jordan and von Neumann also stated the characteristic new rules for probabilities in quantum mechanics somewhat differently. Jordan and Dirac were the first to state those rules in full generality. Von Neumann rephrased them and, in a paper published a few months later, sought to derive them from more basic considerations. In this paper we reconstruct the central arguments of these 1927 papers by Jordan and von Neumann and of a paper on Jordan's approach by Hilbert, von Neumann, and Nordheim. We highlight those elements in these papers that bring out the gradual loosening of the ties between the new quantum formalism and classical mechanics. This paper was written as part of a joint project in the history of quantum physics of the Max Planck

  9. Beyond victimhood. The struggle of Munich anatomist Titus von Lanz during National Socialism.

    PubMed

    Schütz, Mathias; Waschke, Jens; Marckmann, Georg; Steger, Florian

    2015-09-01

    The article analyzes the life and career of the anatomist Titus von Lanz (1897-1967) of Munich focusing on the period of National Socialism (NS). Von Lanz lost his position as an associate professor at the Anatomical Institute of Munich University because of his marriage to a "half-Jewish" woman in 1938. In contrast to most of his colleagues affected by National Socialist measures, von Lanz had opportunities to save his career and made extensive use of them. His story is that of a complicated struggle for the continuation of his work, involving a wide range of supporters from prestigious physicians to high-ranking National Socialist officials as well as the alienation of his colleagues at the Munich department of anatomy. The article tries to clarify these developments through the presentation of his social background, his supporters, his enemies, the research he conducted during NS and von Lanz' own remembrance of these developments from the post-war period. It aims at laying out a critical appreciation of his motives and actions, thereby contributing to the understanding of individual behavior of anatomists under NS. Copyright © 2015 Elsevier GmbH. All rights reserved.

  10. An Alternative Perspective on von Winterfeldt et al.'s (1997) Test of Consequence Monotonicity

    ERIC Educational Resources Information Center

    Ho, Moon-Ho R.; Regenwetter, Michel; Niederee, Reinhard; Heyer, Dieter

    2005-01-01

    D. von Winterfeldt, N.-K. Chung, R. D. Luce, and Y. Cho (see record 1997-03378-008) provided several tests for consequence monotonicity of choice or judgment, using certainty equivalents of gambles. The authors reaxiomatized consequence monotonicity in a probabilistic framework and reanalyzed von Winterfeldt et al.'s main experiment via a…

  11. [Scientific theoretical founding of medicine as a natural science by Hermann von Helmholtz (1821-1894)].

    PubMed

    Neumann, J N

    1994-01-01

    In this study an attempt will be made to discuss the epistemological problems in the theory and practice of modern technical medicine in the writings of Hermann von Helmholz. An inquiry into the relationship between von Helmholtz' thinking and the critical philosophy of Immanuel Kant is followed by the characteristics of von Helmholtz' philosophy of science which he himself called "empirical theory". The question of medicine as a science finally leads to the main problem of medical epistemology, viz., the relationship between theoretical knowledge and practice in medicine. In this context the anthropological dimension is brought into consideration.

  12. Physical Realization of von Neumann Lattices in Rotating Bose Gases with Dipole Interatomic Interactions.

    PubMed

    Cheng, Szu-Cheng; Jheng, Shih-Da

    2016-08-22

    This paper reports a novel type of vortex lattice, referred to as a bubble crystal, which was discovered in rapidly rotating Bose gases with long-range interactions. Bubble crystals differ from vortex lattices which possess a single quantum flux per unit cell, while atoms in bubble crystals are clustered periodically and surrounded by vortices. No existing model is able to describe the vortex structure of bubble crystals; however, we identified a mathematical lattice, which is a subset of coherent states and exists periodically in the physical space. This lattice is called a von Neumann lattice, and when it possesses a single vortex per unit cell, it presents the same geometrical structure as an Abrikosov lattice. In this report, we extend the von Neumann lattice to one with an integral number of flux quanta per unit cell and demonstrate that von Neumann lattices well reproduce the translational properties of bubble crystals. Numerical simulations confirm that, as a generalized vortex, a von Neumann lattice can be physically realized using vortex lattices in rapidly rotating Bose gases with dipole interatomic interactions.

  13. The Nephrologist’s Tumor: Basic Biology and Management of Renal Cell Carcinoma

    PubMed Central

    Hu, Susie L.; Chang, Anthony; Perazella, Mark A.; Okusa, Mark D.; Jaimes, Edgar A.

    2016-01-01

    Kidney cancer, or renal cell carcinoma (RCC), is a disease of increasing incidence that is commonly seen in the general practice of nephrology. However, RCC is under-recognized by the nephrology community, such that its presence in curricula and research by this group is lacking. In the most common form of RCC, clear cell renal cell carcinoma (ccRCC), inactivation of the von Hippel–Lindau tumor suppressor is nearly universal; thus, the biology of ccRCC is characterized by activation of hypoxia-relevant pathways that lead to the associated paraneoplastic syndromes. Therefore, RCC is labeled the internist’s tumor. In light of this characterization and multiple other metabolic abnormalities recently associated with ccRCC, it can now be viewed as a metabolic disease. In this review, we discuss the basic biology, pathology, and approaches for treatment of RCC. It is important to distinguish between kidney confinement and distant spread of RCC, because this difference affects diagnostic and therapeutic approaches and patient survival, and it is important to recognize the key interplay between RCC, RCC therapy, and CKD. Better understanding of all aspects of this disease will lead to optimal patient care and more recognition of an increasingly prevalent nephrologic disease, which we now appropriately label the nephrologist’s tumor. PMID:26961346

  14. Identifikationsverfahren zur Analyse von EEG-Signalen bei Epilepsie mit Reaktions-Diffusions Netzwerken

    NASA Astrophysics Data System (ADS)

    Gollas, F.; Tetzlaff, R.

    2007-06-01

    Partielle Differentialgleichungen des Reaktions-Diffusions-Typs beschreiben Phänomene wie Musterbildung, nichtlineare Wellenausbreitung und deterministisches Chaos und werden oft zur Untersuchung komplexer Vorgänge auf den Gebieten der Biologie, Chemie und Physik herangezogen. Zellulare Nichtlineare Netzwerke (CNN) sind eine räumliche Anordnung vergleichsweise einfacher dynamischer Systeme, die eine lokale Kopplung untereinander aufweisen. Durch eine Diskretisierung der Ortsvariablen können Reaktions-Diffusions-Gleichungen häufig auf CNN mit nichtlinearen Gewichtsfunktionen abgebildet werden. Die resultierenden Reaktions-Diffusions-CNN (RD-CNN) weisen dann in ihrer Dynamik näherungsweise gleiches Verhalten wie die zugrunde gelegten Reaktions-Diffusions-Systeme auf. Werden RD-CNN zur Identifikation neuronaler Strukturen anhand von EEG-Signalen herangezogen, so besteht die Möglichkeit festzustellen, ob das gefundene Netzwerk lokale Aktivität aufweist. Die von Chua eingeführte Theorie der lokalen Aktivität Chua (1998); Dogaru und Chua (1998) liefert eine notwendige Bedingung für das Auftreten von emergentem Verhalten in zellularen Netzwerken. Änderungen in den Parametern bestimmter RD-CNN könnten auf bevorstehende epileptische Anfälle hinweisen. In diesem Beitrag steht die Identifikation neuronaler Strukturen anhand von EEG-Signalen durch Reaktions-Diffusions-Netzwerke im Vordergrund der dargestellten Untersuchungen. In der Ergebnisdiskussion wird insbesondere auch die Frage nach einer geeigneten Netzwerkstruktur mit minimaler Komplexität behandelt.

  15. Interaktive Visualisierung von Abständen und Ausdehnungen anatomischer Strukturen für die Interventionsplanung

    NASA Astrophysics Data System (ADS)

    Rössling, Ivo; Cyrus, Christian; Dornheim, Lars; Hahn, Peter; Preim, Bernhard; Boehm, Andreas

    Im Rahmen der Interventionsplanung muss der Chirurg therapierelevante Entscheidungen auf Basis räumlicher Relationen anatomischer Strukturen treffen. Interaktive 3D-Visualisierungen unterstützen diesen Prozess qualitativ. Quantitative Fragestellungen (Tumorausdehnung, Infiltrationstiefe, etc.) erfordern die Integration einer Bemaßung, deren Nutzen wesentlich von einer geeigneten Darstellung abhängt. In dieser Arbeit haben wir allgemeine Kriterien für die Eignung von Visualisierungen von Bemaßungen in interaktiven 3D-Szenen erarbeitet. Daran orientierend haben wir verschiedene Varianten der Darstellung von Abständen und Ausdehnungen anatomischer Strukturen betrachtet und ihr Erscheinungsbild hierzu zweckmäßig parametrisiert. Die Ausprägungen dieser Darstellungsparameter wurden in einer Studie auf ihre visuellen Wirkung hin an Chirurgen evaluiert. Es zeigte sich, dass die befragten Mediziner höchsten Wert auf Kohärenz und klare Zuordnung der Bemaßung setzten und überraschenderweise dafür sogar Abstriche in der direkten Lesbarkeit in Kauf nahmen.

  16. Einstellung und Wissen von Lehramtsstudierenden zur Evolution - ein Vergleich zwischen Deutschland und der Türkei

    NASA Astrophysics Data System (ADS)

    Graf, Dittmar; Soran, Haluk

    Es wird eine Untersuchung vorgestellt, in der Wissen und Überzeugungen von Lehramtsstudierenden aller Fächer zum Thema Evolution an zwei Universitäten in Deutschland und der Türkei erhoben worden sind. Die Befragung wurde in Dortmund und in Ankara durchgeführt. Es stellte sich heraus, dass ausgeprägte Defizite im Verständnis der Evolutionsmechanismen herrschen. Viele Studierende, insbesondere aus der Türkei, sind nicht von der Faktizität der Evolution überzeugt. Dies gilt sowohl für Studierende mit Fach Biologie als auch für Studierende mit anderen Fächern. Näher untersucht worden sind die Faktoren, die die Überzeugungen zur Evolution beeinflussen können, was ja in Anbetracht der hohen Ablehnungsrate der Evolution von besonderem Interesse ist. Das Vertrauen in die Wissenschaft spielt hierbei eine besondere Rolle: Wer der Wissenschaft vertraut, ist auch eher von der Evolution überzeugt, als diejenigen, die skeptisch gegenüber der Wissenschaft sind.

  17. Identification of a His54Gln substitution in von Willebrand factor from a patient with defective binding of factor VIII.

    PubMed

    Rick, M E; Krizek, D M

    1996-04-01

    A patient with type 2N ("Normandy" variant) von Willebrand's disease is described. Her von Willebrand factor level was borderline low, while her factor VIII was markedly decreased to 7%. Her plasma von Willebrand factor demonstrated a decreased ability to complex with factor VIII in vitro, binding less than 10% when compared to normal plasma von Willebrand factor. The factor VIII released into the circulation after the patient received DDAVP had a shortened survival in vivo. Nucleotide sequence analysis revealed a T-to-A transition at nucleotide 2451 on both alleles. This transition results in a substitution of Gln for His at amino acid 54 in the mature subunit of von Willebrand factor.

  18. Guido von Pirquet: Austrian pioneer of astronautics

    NASA Technical Reports Server (NTRS)

    Sykora, F.

    1977-01-01

    The works of Guido von Pirquet, Austrian pioneer of rocketry, were assessed. Major emphasis was given to Pirquet's calculation of the route to Venus which in fact was followed by the first Russian rocket to Venus. Of interest also is Pirquet's valuable construction of a space station and his analysis of interstellar space flight.

  19. Von Willebrand factor regulation of blood vessel formation.

    PubMed

    Randi, Anna M; Smith, Koval E; Castaman, Giancarlo

    2018-06-04

    Several important physiological processes, from permeability to inflammation to haemostasis, take place at the vessel wall and are regulated by endothelial cells (EC). Thus, proteins that have been identified as regulators of one process are increasingly found to be involved in other vascular functions. Such is the case for Von Willebrand Factor (VWF), a large glycoprotein best known for its critical role in haemostasis. In vitro and in vivo studies have shown that lack of VWF causes enhanced vascularisation, both constitutively and following ischemia. This evidence is supported by studies on blood outgrowth endothelial cells (BOEC) from patients with lack of VWF synthesis (type 3 von Willebrand disease [VWD]). The molecular pathways are likely to involve VWF binding partners, such as integrin αvβ3, and components of Weibel Palade bodies (WPB), such as Angiopoietin-2 and Galectin-3, whose storage is regulated by VWF; these converge on the master regulator of angiogenesis and endothelial homeostasis, vascular endothelial growth factor (VEGF) signalling. Recent studies suggest that the roles of VWF may be tissue-specific. The ability of VWF to regulate angiogenesis has clinical implications for a subset of VWD patients with severe, intractable gastrointestinal bleeding due to vascular malformations. In this article, we review the evidence showing that VWF is involved in blood vessel formation, discuss the role of VWF high molecular weight multimers in regulating angiogenesis, and the value of studies on BOEC in developing a precision medicine approach to validate novel treatments for angiodysplasia in congenital VWD and acquired von Willebrand syndrome. Copyright © 2018 American Society of Hematology.

  20. Anwendungsorientierte Funktionswerkstoffe mittels Walzplattieren

    NASA Astrophysics Data System (ADS)

    Reichelt, Stephan; Schmidt, J.-F.; Neubauer, M.; Schade, A.; Andler, G.; Buerkle, G.; Hansen, H.; Hofmann, L.; Stiehler, J.; Janisch, S. D.

    Obwohl walzplattierte Werkstoffe in der allgemeinen Öffentlichkeit nur wenig beachtet und behandelt werden, besitzen sie bereits heute eine hohe Bedeutung, um unterschiedliche Güter des täglichen Bedarfs realisieren und produzieren zu können. Durch eine hohe Produktivität und ein umfangreiches technologisches Wissen lassen sich bereits heute sehr anspruchsvolle und aufwändige Funktionswerkstoffe mittels Plattierverfahren herstellen, die maßgeschneiderte Produkteigenschaften für viele Halbzeuge und Fertigprodukte garantieren. Bedingt durch die konstruktiven Trends im Bereich von Automotive, Luft- und Raumfahrt sowie dem allgemeinen konstruktiven und materiellem Leichtbau ist davon auszugehen, dass die Bedeutung maßgeschneiderter Funktionswerkstoffe für spezifische Anwendungsfelder in naher Zukunft weiter wachsen und die Bedeutung einzelner Plattierverfahren für eine wirtschaftliche Produktionskette verschiedener Produkte wachsen wird.

  1. Untersuchung der Störwirkung von LTE auf SRD Anwendungen bei 868 MHz

    NASA Astrophysics Data System (ADS)

    Welpot, M.; Wunderlich, S.; Gaspard, I.

    2014-11-01

    Moderne Hausautomatisierungssysteme, Alarmanlagen oder auch Funk-Zugangssysteme in Haus und Automobil setzen auf frei nutzbare Frequenzen in ISM/SRD-Bändern. Die rasante Zunahme an privaten und kommerziell genutzten Applikationen im SRD-Band bei 868 MHz und der Ausbau der LTE-Mobilfunknetze im Frequenzbereich unterhalb von 1 GHz ("Digital Dividend") wirft zunehmend die Frage nach der Funkverträglichkeit dieser Systeme untereinander auf. Während die SRD-Funkmodule auf eine geringe Sendeleistung von ~ +14 dBm beschränkt sind (Ralf and Thomas, 2009), beträgt die maximale LTE-Sendeleistung im Uplink nach (ETSI-Norm, 2011) +23 dBm. Zusammen mit der Einführung von LTE im Frequenzbereich unterhalb 1 GHz als DSL-Ersatz vor allem in ländlichen Gebieten, ergibt sich damit als mögliches Störszenario, dass durch die Aussendung des LTE-Endgerätes im Bereich von ca. 850 MHz die SRD-Funkverbindungen bei 868 MHz insbesondere dann gestört werden, wenn die Antennen beider Funksysteme räumlich nahe zueinander angeordnet sind und folglich nur eine geringe zusätzliche Entkopplung der Systeme bieten. In der vorliegenden Arbeit wird das LTE-Störpotential auf SRD-Empfänger praxisnah untersucht.

  2. Planungsunterstützung für Pankreasoperationen bei Hyperinsulinismus von Kindern

    NASA Astrophysics Data System (ADS)

    Dornheim, J.; Preim, B.; Preim, U.; Mohnike, K.; Blankenstein, O.; Füchtner, F.; Mohnike, W.; Empting, S.; Mohnike, K.

    Auf Basis von sechs PET/CT-Datensätzen des Pankreas wird eine Computerunterstützung für die Teilresektion der Bauchspeicheldr üse (Pankreas) bei fokalem Hyperinsulinismus von Kindern entwickelt. Ziel ist es, die Lokalisation des krankhaften Fokus im Pankreasgewebe präoperativ dreidimensional zu visualisieren, um so die Sicherheit des Eingriffs zu erhöhen. Die relevanten anatomischen Strukturen werden im CT segmentiert und anschließend dreidimensional visualisiert. Der im PET erkennbare Fokus wird in diese anatomische 3D-Visualisierung eingeblendet. Es zeigt sich eine klare Erkennbarkeit des Fokus in allen sechs Fällen.

  3. Visualisierung analoger Schaltungen durch 3-D Animation von transienten SPICE-Simulationen

    NASA Astrophysics Data System (ADS)

    Becker, J.; Manoli, Y.

    2007-06-01

    Für das Zeichnen analoger Schaltpläne wird oft versucht, die Potentialverteilung in der entsprechenden Schaltung auszunutzen, um eine Platzierung der Bauteile nach abfallendem Potential vorzunehmen. Mit Hilfe von Computerunterstützung gelingt es, eine verallgemeinerte dreidimensionale Platzierungsstrategie anzuwenden, die allein auf Grund der Potentialwerte einer Schaltung die automatische Generierung einer technisch exakten Potentialdarstellung erlaubt. Somit ist es möglich, die Ergebnisse von transienten SPICE-Simulationen in jedem Zeitschritt darzustellen und eine Animation des zeitlichen Verhaltens zu erzeugen. Die Umsetzung dieser Methode zur Einbettung in eine webbasierte Lern - und Arbeitsplattform wird im Folgenden erläutert.

  4. In memory of Eugene (Jenő) von Gothard: a pioneering nineteenth century Hungarian astrophysicist

    NASA Astrophysics Data System (ADS)

    Vincze, Ildikő J.; Jankovics, István

    2012-07-01

    Eugene von Gothard was a Hungarian engineer/scientist, instrument-maker and astrophysicist who founded the Herény Astrophysical Observatory in 1881 and carried out pioneering work in astronomical photography and spectroscopy. In this paper we provide biographical material about von Gothard and describe his observatory, before discussing his astronomical observations and the contribution that hemade to the early development of astrophysics.

  5. Cyclin D1 down-regulation is essential for DBC2's tumor suppressor function

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

    Yoshihara, Takashi; Collado, Denise; Hamaguchi, Masaaki

    2007-07-13

    The expression of tumor suppressor gene DBC2 causes certain breast cancer cells to stop growing [M. Hamaguchi, J.L. Meth, C. Von Klitzing, W. Wei, D. Esposito, L. Rodgers, T. Walsh, P. Welcsh, M.C. King, M.H. Wigler, DBC2, a candidate for a tumor suppressor gene involved in breast cancer, Proc. Natl. Acad. Sci. USA 99 (2002) 13647-13652]. Recently, DBC2 was found to participate in diverse cellular functions such as protein transport, cytoskeleton regulation, apoptosis, and cell cycle control [V. Siripurapu, J.L. Meth, N. Kobayashi, M. Hamaguchi, DBC2 significantly influences cell cycle, apoptosis, cytoskeleton, and membrane trafficking pathways. J. Mol. Biol. 346more » (2005) 83-89]. Its tumor suppression mechanism, however, remains unclear. In this paper, we demonstrate that DBC2 suppresses breast cancer proliferation through down-regulation of Cyclin D1 (CCND1). Additionally, the constitutional overexpression of CCND1 prevented the negative impact of DBC2 expression on their growth. Under a CCND1 promoter, the expression of CCNE1 exhibited the same protective effect. Our results indicate that the down-regulation of CCND1 is an essential step for DBC2's growth suppression of cancer cells. We believe that this discovery contributes to a better understanding of DBC2's tumor suppressor function.« less

  6. Inherited pancreatic endocrine tumor syndromes: advances in molecular pathogenesis, diagnosis, management and controversies

    PubMed Central

    Jensen, Robert T.; Berna, Marc J.; Bingham, David B; Norton, Jeffrey A.

    2008-01-01

    Pancreatic endocrine tumors (PETs) can occur in as part of four inherited disorders including: Multiple Endocrine Neoplasia type 1 (MEN1), von Hippel-Lindau disease (VHL), neurofibromatosis 1(NF-1) [von Recklinghausen’s disease] and the tuberous sclerosis complex (TSC). The relative frequency with which patients with these disorders develop PETs is MEN1>VHL>NF-1>TSC. Over the last few years there have been major advances in the understanding of the genetics and molecular pathogenesis of these disorders as well in the localization, medical and surgical treatment of the PETs in these patients. The study of the PETs in these disorders has not only provided insights into the possible pathogenesis of sporadic PETs, but have also presented a number of unique management and treatment issues, some of which are applicable to patients with sporadic PETs. Therefore the study of PETs in these uncommon disorders has provided valuable insights that in many cases are applicable to the general group of patients with sporadic PETs. In this article these areas are briefly reviewed as well as the current state of knowledge of the PETs in these disorders and the controversies that exist in their management are briefly summarized and discussed. PMID:18798544

  7. Dr. Wernher Von Braun

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Dr. Thomas Paine, Deputy Administrator of the National Aeronautics and Space Administration, examines an ordinary man's shoe outfitted for use in the Saturn I workshop. Pictured from the left in the Saturn I workshop mockup are William Brooksbank, propulsion and vehicle engineering laboratory; Dr. Paine; Dr. Wernher Von Braun, Marshall Center director; Colonel Clare F. Farley, Executive Officer in the Office Of The Administrator; and Charles J. Donlan, Deputy Associate Administrator for Manned Space Flight, Technical. the shoe Dr. Paine is holding has a unique fastener built into the sole to allow an astronaut to move about on the workshop floor and to remain in one position if he desires.

  8. Von Braun Rocket Team at Fort Bliss, Texas

    NASA Technical Reports Server (NTRS)

    1940-01-01

    The German Rocket Team, also known as the Von Braun Rocket Team, poses for a group photograph at Fort Bliss, Texas. After World War II ended in 1945, Dr. Wernher von Braun led some 120 of his Peenemuende Colleagues, who developed the V-2 rocket for the German military during the War, to the United Sttes under a contract to the U.S. Army Corps as part of Operation Paperclip. During the following five years the team worked on high altitude firings of the captured V-2 rockets at the White Sands Missile Range in New Mexico, and a guided missile development unit at Fort Bliss, Texas. In April 1950, the group was transferred to the Army Ballistic Missile Agency (ABMA) at Redstone Arsenal in Huntsville, Alabama, and continued to work on the development of the guided missiles for the U.S. Army until transferring to a newly established field center of the National Aeronautic and Space Administration (NASA), George C. Marshall Space Flight Center (MSFC).

  9. Wernher von Braun

    NASA Image and Video Library

    2004-04-15

    A pioneer of America's space program, Dr. von Braun stands by the five F-1 engines of the Saturn V launch vehicle. This Saturn V vehicle is an actual test vehicle which has been displayed at the U.S. Space Rocket Center in Huntsville, Alabama. Designed and developed by Rocketdyne under the direction of the Marshall Space Flight Center, a cluster of five F-1 engines was mounted on the Saturn V S-IC (first) stage. The engines measured 19-feet tall by 12.5-feet at the nozzle exit and burned 15 tons of liquid oxygen and kerosene each second to produce 7,500,000 pounds of thrust. The S-IC stage is the first stage, or booster, of a 364-foot long rocket that ultimately took astronauts to the Moon.

  10. The natural history of occult or angiodysplastic gastrointestinal bleeding in von Willebrand disease.

    PubMed

    Makris, M; Federici, A B; Mannucci, P M; Bolton-Maggs, P H B; Yee, T T; Abshire, T; Berntorp, E

    2015-05-01

    Recurrent gastrointestinal bleeding is one of the most challenging complications encountered in the management of patients with von Willebrand disease (VWD). The commonest cause is angiodysplasia, but often no cause is identified due to the difficulty in making the diagnosis. The optimal treatment to prevent recurrences remains unknown. We performed a retrospective study of VWD patients with occult or angiodysplastic bleeding within the setting of the von Willebrand Disease Prophylaxis Network (VWD PN) to describe diagnostic and treatment strategies. Centres participating in the VWD PN recruited subjects under their care with a history of congenital VWD and gastrointestinal (GI) bleeding due to angiodysplasia, or cases in which the cause was not identified despite investigation. Patients with acquired von Willebrand syndrome or those for whom the GI bleeding was due to another cause were excluded. Forty-eight patients from 18 centres in 10 countries were recruited. Seven individuals had a family history of GI bleeding and all VWD types except 2N were represented. Angiodysplasia was confirmed in 38%, with video capsule endoscopy and GI tract endoscopies being the most common methods of making the diagnosis. Recurrent GI bleeding in VWD is associated with significant morbidity and required hospital admission on up to 30 occasions. Patients were treated with multiple pharmacological agents with prophylactic von Willebrand factor concentrate being the most efficient in preventing recurrence of the GI bleeding. The diagnosis and treatment of recurrent GI bleeding in congenital VWD remains challenging and is associated with significant morbidity. Prophylactic treatment with von Willebrand factor concentrate was the most effective method of preventing recurrent bleeding but its efficacy remains to be confirmed in a prospective study. © 2014 John Wiley & Sons Ltd.

  11. Clinical and Molecular Features of Renal and Pheochromocytoma/Paraganglioma Tumor Association Syndrome (RAPTAS): Case Series and Literature Review.

    PubMed

    Casey, Ruth T; Warren, Anne Y; Martin, Jose Ezequiel; Challis, Benjamin G; Rattenberry, Eleanor; Whitworth, James; Andrews, Katrina A; Roberts, Thomas; Clark, Graeme R; West, Hannah; Smith, Philip S; Docquier, France M; Rodger, Fay; Murray, Vicki; Simpson, Helen L; Wallis, Yvonne; Giger, Olivier; Tran, Maxine; Tomkins, Susan; Stewart, Grant D; Park, Soo-Mi; Woodward, Emma R; Maher, Eamonn R

    2017-11-01

    The co-occurrence of pheochromocytoma (PC) and renal tumors was linked to the inherited familial cancer syndrome von Hippel-Lindau (VHL) disease more than six decades ago. Subsequently, other shared genetic causes of predisposition to renal tumors and to PC, paraganglioma (PGL), or head and neck paraganglioma (HNPGL) have been described, but case series of non-VHL-related cases of renal tumor and pheochromocytoma/paraganglioma tumor association syndrome (RAPTAS) are rare. To determine the clinical and molecular features of non-VHL RAPTAS by literature review and characterization of a case series. A review of the literature was performed and a retrospective study of referrals for investigation of genetic causes of RAPTAS. Literature review revealed evidence of an association, in addition to VHL disease, between germline mutations in SDHB, SDHC, SDHD, TMEM127, and MAX genes and RAPTAS [defined here as the co-occurrence of tumors from both classes (PC/PGL/HNPGL and renal tumors) in the same individual or in first-degree relatives]. In both the literature review and our case series of 22 probands with non-VHL RAPTAS, SDHB mutations were the most frequent cause of non-VHL RAPTAS. A genetic cause was identified in 36.3% (8/22) of kindreds. Renal tumors and PC/PGL/HNPGL tumors share common molecular features and their co-occurrence in an individual or family should prompt genetic investigations. We report a case of MAX-associated renal cell carcinoma and confirm the role of TMEM127 mutations with renal cell carcinoma predisposition. Copyright © 2017 Endocrine Society

  12. Johann Bernhard Aloys von Gudden and the Mad King of Bavaria

    PubMed Central

    Bhattacharyya, Kalyan B.

    2017-01-01

    Bernhard von Gudden was a psychiatrist in Prussia and he was summoned in March 1886 to examine King Ludwig II for his apparently insane activities like, profligate spending and erratic behaviour. A team of four estimable psychiatrists pronounced that he was not capable ruling. Consequently, he was dethroned and kept in a castle under supervision of von Gudden. Gudden championed the idea of 'no restraint' and advocated free movement of insane persons and one evening in June, he accompanied the King during an evening stroll to a lake. A few hours later, the corpus of both of them were recovered under mysterious circumstances. Autopsy suggested that the King was drowned but no post-mortem examination was performed on von Gudden. There are plenty of controversies regarding their death like, murder, accidental death or even natural death from cardiac arrest following immersion in cold water, but no incontrovertible conclusion could be arrived at, even after scrupulous analysis by historians and even the diagnosis of insanity of the King has been doubted. Some even suggested that the opinion of psychiatrists were sought as a pretense in order to depose the King. PMID:29184335

  13. Director von Braun Presents General Medaris With Golf Bag

    NASA Technical Reports Server (NTRS)

    1959-01-01

    Marshall Space Flight Center Director Wernher von Braun presents General J.B. Medaris with a new golf bag. General Medaris, (left) was a Commander of the Army Ballistic Missile Agency (ABMA) in Redstone Arsenal, Alabama during 1955 to 1958.

  14. A phase I study of ABT-510 plus bevacizumab in advanced solid tumors.

    PubMed

    Uronis, Hope E; Cushman, Stephanie M; Bendell, Johanna C; Blobe, Gerard C; Morse, Michael A; Nixon, Andrew B; Dellinger, Andrew; Starr, Mark D; Li, Haiyan; Meadows, Kellen; Gockerman, Jon; Pang, Herbert; Hurwitz, Herbert I

    2013-06-01

    Targeting multiple regulators of tumor angiogenesis have the potential to improve treatment efficacy. Bevacizumab is a monoclonal antibody directed against vascular endothelial growth factor and ABT-510 is a synthetic analog of thrombospondin, an endogenous angiogenesis inhibitor. Dual inhibition may result in additional benefit. We evaluated the safety, tolerability, and efficacy of the combination of bevacizumab plus ABT-510 in patients with refractory solid tumors. We also explored the effects of these agents on plasma-based biomarkers and wound angiogenesis. Thirty-four evaluable subjects were enrolled and received study drug. Therapy was well tolerated; minimal treatment-related grade 3/4 toxicity was observed. One patient treated at dose level 1 had a partial response and five other patients treated at the recommended phase II dose had prolonged stable disease for more than 1 year. Biomarker evaluation revealed increased levels of D-dimer, von Willebrand factor, placental growth factor, and stromal-derived factor 1 in response to treatment with the combination of bevacizumab and ABT-510. Data suggest that continued evaluation of combination antiangiogenesis therapies may be clinically useful.

  15. Classical Mathematical Models for Description and Prediction of Experimental Tumor Growth

    PubMed Central

    Benzekry, Sébastien; Lamont, Clare; Beheshti, Afshin; Tracz, Amanda; Ebos, John M. L.; Hlatky, Lynn; Hahnfeldt, Philip

    2014-01-01

    Despite internal complexity, tumor growth kinetics follow relatively simple laws that can be expressed as mathematical models. To explore this further, quantitative analysis of the most classical of these were performed. The models were assessed against data from two in vivo experimental systems: an ectopic syngeneic tumor (Lewis lung carcinoma) and an orthotopically xenografted human breast carcinoma. The goals were threefold: 1) to determine a statistical model for description of the measurement error, 2) to establish the descriptive power of each model, using several goodness-of-fit metrics and a study of parametric identifiability, and 3) to assess the models' ability to forecast future tumor growth. The models included in the study comprised the exponential, exponential-linear, power law, Gompertz, logistic, generalized logistic, von Bertalanffy and a model with dynamic carrying capacity. For the breast data, the dynamics were best captured by the Gompertz and exponential-linear models. The latter also exhibited the highest predictive power, with excellent prediction scores (≥80%) extending out as far as 12 days in the future. For the lung data, the Gompertz and power law models provided the most parsimonious and parametrically identifiable description. However, not one of the models was able to achieve a substantial prediction rate (≥70%) beyond the next day data point. In this context, adjunction of a priori information on the parameter distribution led to considerable improvement. For instance, forecast success rates went from 14.9% to 62.7% when using the power law model to predict the full future tumor growth curves, using just three data points. These results not only have important implications for biological theories of tumor growth and the use of mathematical modeling in preclinical anti-cancer drug investigations, but also may assist in defining how mathematical models could serve as potential prognostic tools in the clinic. PMID:25167199

  16. Classical mathematical models for description and prediction of experimental tumor growth.

    PubMed

    Benzekry, Sébastien; Lamont, Clare; Beheshti, Afshin; Tracz, Amanda; Ebos, John M L; Hlatky, Lynn; Hahnfeldt, Philip

    2014-08-01

    Despite internal complexity, tumor growth kinetics follow relatively simple laws that can be expressed as mathematical models. To explore this further, quantitative analysis of the most classical of these were performed. The models were assessed against data from two in vivo experimental systems: an ectopic syngeneic tumor (Lewis lung carcinoma) and an orthotopically xenografted human breast carcinoma. The goals were threefold: 1) to determine a statistical model for description of the measurement error, 2) to establish the descriptive power of each model, using several goodness-of-fit metrics and a study of parametric identifiability, and 3) to assess the models' ability to forecast future tumor growth. The models included in the study comprised the exponential, exponential-linear, power law, Gompertz, logistic, generalized logistic, von Bertalanffy and a model with dynamic carrying capacity. For the breast data, the dynamics were best captured by the Gompertz and exponential-linear models. The latter also exhibited the highest predictive power, with excellent prediction scores (≥80%) extending out as far as 12 days in the future. For the lung data, the Gompertz and power law models provided the most parsimonious and parametrically identifiable description. However, not one of the models was able to achieve a substantial prediction rate (≥70%) beyond the next day data point. In this context, adjunction of a priori information on the parameter distribution led to considerable improvement. For instance, forecast success rates went from 14.9% to 62.7% when using the power law model to predict the full future tumor growth curves, using just three data points. These results not only have important implications for biological theories of tumor growth and the use of mathematical modeling in preclinical anti-cancer drug investigations, but also may assist in defining how mathematical models could serve as potential prognostic tools in the clinic.

  17. Alexander von Humboldt and the Origins of Landscape Archaeology.

    ERIC Educational Resources Information Center

    Mathewson, Kent

    1986-01-01

    Reviews the life, theories, and influence of Alexander von Humboldt, the early nineteenth century founder of modern geography. Maintains that Humboldt's novel approaches to the study of landscape antiquities have value for contemporary students in cultural and historical geography. (JDH)

  18. Wernher von Braun

    NASA Image and Video Library

    1971-07-26

    During the Apollo 15 launch activities in the launch control center's firing room 1 at Kennedy Space Center, Dr. Wernher von Braun, NASA's Deputy Associate Administrator for planning, takes a closer look at the launch pad through binoculars. The fifth manned lunar landing mission, Apollo 15 (SA-510), carrying a crew of three astronauts: Mission commander David R. Scott, Lunar Module pilot James B. Irwin, and Command Module pilot Alfred M. Worden Jr., lifted off on July 26, 1971. Astronauts Scott and Irwin were the first to use a wheeled surface vehicle, the Lunar Roving Vehicle, or the Rover, which was designed and developed by the Marshall Space Flight Center, and built by the Boeing Company. Astronauts spent 13 days, nearly 67 hours, on the Moon's surface to inspect a wide variety of its geological features.

  19. Long-term outcome after resection of brainstem hemangioblastomas in von Hippel-Lindau disease

    PubMed Central

    Wind, Joshua J.; Bakhtian, Kamran D.; Sweet, Jennifer A.; Mehta, Gautam U.; Thawani, Jayesh P.; Asthagiri, Ashok R.; Oldfield, Edward H.; Lonser, Russell R.

    2016-01-01

    Object Brainstem hemangioblastomas are frequently encountered in patients with von Hippel-Lindau (VHL) disease. These tumors can cause significant morbidity, and their optimal management has not been defined. To better define the outcome and management of these tumors, the authors analyzed the long-term results in patients who underwent resection of brainstem hemangioblastomas. Methods Consecutive patients with VHL disease who underwent resection of brainstem hemangioblastomas with a follow-up of 12 months or more were included in this study. Serial functional assessments, radiographic examinations, and operative records were analyzed. Results Forty-four patients (17 male and 27 female) underwent 51 operations for resection of 71 brainstem hemangioblastomas. The most common presenting symptoms were headache, swallowing difficulties, singultus, gait difficulties, and sensory abnormalities. The mean follow-up was 5.9 ± 5.0 years (range 1.0–20.8 years). Immediately after 34 operations (66.7%), the patients remained at their preoperative functional status; they improved after 8 operations (15.7%) and worsened after 9 operations (17.6%) as measured by the McCormick scale. Eight (88.9%) of the 9 patients who were worse immediately after resection returned to their preoperative status within 6 months. Two patients experienced functional decline during long-term follow-up (beginning at 2.5 and 5 years postoperatively) caused by extensive VHL disease–associated CNS disease. Conclusions Generally, resection of symptomatic brainstem hemangioblastomas is a safe and effective management strategy in patients with VHL disease. Most patients maintain their preoperative functional status, although long-term decline in functional status may occur due to VHL disease–associated progression. PMID:20932100

  20. The Influence of Field Marshal Colmar Von Der Goltz on Ottoman Military Effectiveness in Mesopotamia: December 1915 to April 1916

    DTIC Science & Technology

    2012-02-23

    SUBTITLE The Influence of Field Marshal Colmar Von Der Goltz on Ottoman Military Effectiveness in Mesopotamia: December 1915 to April 1916 5a...SUPPLEMENTARY NOTES N/A 14. ABSTRACT This paper discusses the contributions made by Field Marshal Colmar von der Goltz on the development of Ottoman...Kut. 15. SUBJECT TERMS Colmar von der Goltz ; Military advisor; Mesopotamian Campaign; Ottoman; Ottoman military effectiveness; British; Kut; World

  1. Laboratory Testing for von Willebrand Disease: The Past, Present, and Future State of Play for von Willebrand Factor Assays that Measure Platelet Binding Activity, with or without Ristocetin.

    PubMed

    Just, Sarah

    2017-02-01

    von Willebrand disease (VWD) was first described nearly a century ago in 1924 by Erik Adolf von Willebrand. Diagnostic testing at the time was very limited and it was not until the mid to late 1900s that more tests became available to assist with the diagnosis and classification of VWD. Two of these tests are based on ristocetin, one being ristocetin-induced platelet aggregation (RIPA) and the other the von Willebrand factor (VWF) ristocetin cofactor assay (VWF:RCo). The VWF:RCo assay provides functional assessment of in vitro VWF binding to the platelet glycoprotein (Gp) complex, GPIb-IX-V. Despite some advancements and newer technologies utilizing the principles of the original VWF:RCo assay, the original assay is still referred to as the gold standard for measurement of VWF activity. This article will review the history of VWD diagnostic assays, including RIPA and VWF:RCo over the past 40 years, as well as the newer assays that measure platelet binding with or without ristocetin, and which have been developed with the aim to potentially replace platelet-based ristocetin-dependent assays. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  2. Potential supplementary utility of combined PFA-100 and functional von Willebrand factor testing for the laboratory assessment of desmopressin and factor concentrate therapy in von Willebrand disease.

    PubMed

    Favaloro, Emmanuel J; Thom, Jim; Patterson, David; Just, Sarah; Baccala, Maria; Dixon, Tracy; Meiring, Muriel; Koutts, Jerry; Rowell, John; Baker, Ross

    2009-09-01

    We performed a retrospective audit of cross-laboratory testing of desmopressin and factor concentrate therapy to assess the potential utility of supplementary testing using the PFA-100 with functional von Willebrand factor (VWF) activity testing. Data were evaluated for a large number of patients with von Willebrand disease of type 1, type 2A or type 2M, as well as a comparative subset of individuals with haemophilia or carriers of haemophilia. Laboratory testing comprised pre and postdesmopressin, or pre and postconcentrate, evaluation of factor VIII, VWF antigen (VWF:Ag) and VWF ristocetin cofactor activity as traditionally performed, supplemented with collagen-binding (VWF:CB) testing and PFA-100 closure times. In brief, both therapies tended to normalize VWF test parameters and closure times in individuals with type 1 von Willebrand disease, with the level of correction in closure times related to the level of normalization of VWF, particularly the VWF:CB. However, although occasional correction of closure times was observed in patients with type 2A or type 2M von Willebrand disease, these did not in general normalize PFA-100 closure times either with desmopressin or factor concentrate therapy. In these patients, improvement in closure times was more likely in those in whom VWF:CB values normalized or when VWF:CB/VWF:Ag ratios normalized. This study confirms that there is a strong relationship between the presenting levels of plasma VWF and PFA-100 closure times, and that the supplementary combination of PFA-100 and VWF:CB testing might provide added clinical utility to current broadly applied testing strategies limited primarily to VWF:Ag, VWF ristocetin cofactor and factor VIII:coagulant. Future prospective investigations are warranted to validate these relationships and to investigate their therapeutic implications.

  3. A comparative study of results of the von Langenbeck and the V-Y pushback palatoplasties.

    PubMed

    Krause, C J; Tharp, R F; Morris, H L

    1976-01-01

    The incidence of velopharyngeal competence noted in 267 cleft palate patients following palatoplsty has been reviewed. Comparisons have been drawn with regard to the cleft type and the surgical technique performed. Since there were relatively small numbers of subjects in some categories, differences in age at last examination between the von Langenbeck and V-Y palatoplasty groups, some patients were very young at time of evaluation, and a number of different surgeons at different levels of training and experience performed the surgery, the differences in velopharyngeal competence found should be viewed as trends and this report as preliminary. In general, there was a trend toward smaller percentages of patients attaining acceptable velopharyngeal competence as the severity of the cleft increased. Of those with clefts of the soft palate only 86 per cent achieved competence. Among those patients with clefts of the palate only, 67 per cent achieved competence, whereas only 57 per cent of those with clefts of the lip and palate were able to do so. When comparing all cleft types, the V-Y palatoplasty resulted in a significantly higher percentage of velopharyngeal competence (74 per cent) than did the von Langenbeck method (56 per cent), although the data for the V-Y group are probably less reliable than those for the von Langenbeck group. In the soft palate only category, the results were slightly better with the von Langenbeck technique, though not significantly so. In all other cleft types, the results with the V-Y method were better than those with the von Langenbeck.

  4. Confounding of the association between radiation exposure from CT scans and risk of leukemia and brain tumors by cancer susceptibility syndromes.

    PubMed

    Meulepas, Johanna M; Ronckers, Cécile M; Merks, Johannes; Weijerman, Michel E; Lubin, Jay H; Hauptmann, Michael

    2016-12-01

    Recent studies linking radiation exposure from pediatric computed tomography (CT) to increased risks of leukemia and brain tumors lacked data to control for cancer susceptibility syndromes (CSS). These syndromes might be confounders because they are associated with an increased cancer risk and may increase the likelihood of pediatric CT scans. We identify CSS predisposing to leukemia and brain tumors through a systematic literature search and summarize prevalence and risk. Since empirical evidence is lacking in published literature on patterns of CT use for most types of CSS, we estimate confounding bias of relative risks (RR) for categories of radiation exposure based on expert opinion about patterns of CT scans among CSS patients. We estimate that radiation-related RRs for leukemia are not meaningfully confounded by Down syndrome, Noonan syndrome and other CSS. Moreover, tuberous sclerosis complex, von Hippel-Lindau disease, neurofibromatosis type 1 and other CSS do not meaningfully confound RRs for brain tumors. Empirical data on the use of CT scans among CSS patients is urgently needed. Our assessment indicates that associations with radiation exposure from pediatric CT scans and leukemia or brain tumors reported in previous studies are unlikely to be substantially confounded by unmeasured CSS.

  5. Wilhelm von Humboldt's Idea of "Bildung" and Education.

    ERIC Educational Resources Information Center

    Stubbs, Elsina

    The importance of Wilhelm von Humboldt's work in educational philosophy is little known outside of Germany and even there he is more often criticized than praised. This is unfortunate because his contributions to education and other areas had an important impact on other philosophers of his period and are well worth considering today. In his main…

  6. [Hildegards von Bingen 'Liber simplicis medicinae' in the Mainz 'Garden of Health'].

    PubMed

    Riethe, Peter

    2005-01-01

    The "Garden of Health" (Gart der Gesundheit) is the first illustrated book of herbs in German language. Its author, Johann Wonnecke from Kaub on the Rhine, was born in 1430 and worked as a city doctor in Frankfurt/Main until his death in 1503 or 1504. In his book, he refers to "proven Greek, Latin and Arabic masters of medicine" (bewerte meister in der artzeney), whose writings he was instructed to collect by Bernard von Breidenbach in 1480. Wonnecke carried out he task in a special way, deceiving five generations of historians of science, who proceeded from the false assumption, that the Gart der Gesundheit was compiled and translated from Latin sources. Wonnecke established the desired authors skilfully in his report, but under a more detailed investigation they reveal themselves as not taken from Latin sources but copied off from native language scriptures, e.g. Alterer deutscher Macer and Buch der Natur by Konrad von Megenberg. To these hitherto known sources used by him now the Speyrer Kräuterbuch is added, which supplied the medical knowledge of Hildegard von Bingen to the "Gart".

  7. "'And They Lived Happily Ever After": The Fairy Tale of Radical Constructivism and Von Glasersfeld's Ethical Disengagement

    ERIC Educational Resources Information Center

    d'Agnese, Vasco

    2015-01-01

    Is von Glasersfeld's constructivism actually radical? In this article, I respond to this question by analyzing von Glasersfeld's main works. I argue that the essential theoretical move of radical constructivism--namely the assertion that reality is the construction of a human mind that only responds to the subjective perception of "what…

  8. Report on von Willebrand Disease in Malaysia

    PubMed Central

    Periayah, Mercy Halleluyah; Halim, Ahmad Sukari; Saad, Arman Zaharil Mat; Yaacob, Nik Soriani; Karim, Faraizah Abdul

    2016-01-01

    BACKGROUND: Von Willebrand disease (vWD) is an inherited hemostatic disorder that affects the hemostasis pathway. The worldwide prevalence of vWD is estimated to be 1% of the general population but only 0.002% in Malaysia. AIM: Our present paper has been written to disclose the statistical counts on the number of vWD cases reported from 2011 to 2013. MATERIAL AND METHODS: This article is based on sociodemographic data, diagnoses and laboratory findings of vWD in Malaysia. A total of 92 patients were reported to have vWD in Malaysia from 2011 to 2013. RESULTS: Sociodemographic-analysis revealed that 60% were females, 63% were of the Malay ethnicity, 41.3% were in the 19-44 year old age group and 15.2% were from Sabah, with the East region having the highest registered number of vWD cases. In Malaysia, most patients are predominately affected by vWD type 1 (77.2%). Factor 8, von Willebrand factor: Antigen and vWF: Collagen-Binding was the strongest determinants in the laboratory profiles of vWD. CONCLUSION: This report has been done with great interest to provide an immense contribution from Malaysia, by revealing the statistical counts on vWD from 2011-2013. PMID:27275342

  9. Gesellschaft, Lebensgemeinschaft, Ökosystem - Über die Kongruenz von politischen und ökologischen Theorien der Entwicklung

    NASA Astrophysics Data System (ADS)

    Voigt, Annette

    Im Jahr 1859 veröffentlichte Charles Darwin "On the Origin of Species“. Seine Evolutionstheorie ist das wohl spektakulärste Beispiel einer naturwissenschaftlichen Theorie großer gesellschaftlicher Relevanz. Ihre verschiedenen Facetten wurden in der Öffentlichkeit kontrovers diskutiert, unter anderem auch ihre Anwendung zur Erklärung von Zuständen und Prozessen menschlicher Gesellschaften. Zum Teil wurde die Seiensweise der Natur - scheinbar unabhängig von gesellschaftlichen Interessen - für die Erklärung und Legitimation gesellschaftlicher Zustände oder die Legitimation von politischen Ideologien herangezogen (Sozialdarwinismus). Denn Gesellschaft funktioniere ja so, wie Darwin die Natur erklärt habe: es herrsche z. B. Konkurrenzkampf, Auslese und Arbeitsteilung, Erfolg hätten diejenigen, die sich an die Bedingungen am Besten anpassten.

  10. Ernst von Glasersfeld's Radical Constructivism and Truth as Disclosure

    ERIC Educational Resources Information Center

    Joldersma, Clarence W.

    2011-01-01

    In this essay Clarence Joldersma explores radical constructivism through the work of its most well-known advocate, Ernst von Glasersfeld, who combines a sophisticated philosophical discussion of knowledge and truth with educational practices. Joldersma uses Joseph Rouse's work in philosophy of science to criticize the antirealism inherent in…

  11. Spin torque oscillator neuroanalog of von Neumann's microwave computer.

    PubMed

    Hoppensteadt, Frank

    2015-10-01

    Frequency and phase of neural activity play important roles in the behaving brain. The emerging understanding of these roles has been informed by the design of analog devices that have been important to neuroscience, among them the neuroanalog computer developed by O. Schmitt and A. Hodgkin in the 1930s. Later J. von Neumann, in a search for high performance computing using microwaves, invented a logic machine based on crystal diodes that can perform logic functions including binary arithmetic. Described here is an embodiment of his machine using nano-magnetics. Electrical currents through point contacts on a ferromagnetic thin film can create oscillations in the magnetization of the film. Under natural conditions these properties of a ferromagnetic thin film may be described by a nonlinear Schrödinger equation for the film's magnetization. Radiating solutions of this system are referred to as spin waves, and communication within the film may be by spin waves or by directed graphs of electrical connections. It is shown here how to formulate a STO logic machine, and by computer simulation how this machine can perform several computations simultaneously using multiplexing of inputs, that this system can evaluate iterated logic functions, and that spin waves may communicate frequency, phase and binary information. Neural tissue and the Schmitt-Hodgkin, von Neumann and STO devices share a common bifurcation structure, although these systems operate on vastly different space and time scales; namely, all may exhibit Andronov-Hopf bifurcations. This suggests that neural circuits may be capable of the computational functionality as described by von Neumann. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Recombinant von Willebrand factor: preclinical development.

    PubMed

    Plaimauer, B; Schlokat, U; Turecek, P L; Mitterer, A; Mundt, W; Auer, W; Pichler, L; Gritsch, H; Schwarz, H P

    2001-08-01

    Von Willebrand factor (vWF) is a multimeric glycoprotein (GP) that attracts platelets to the site of vascular injury, mediates platelet-platelet interaction, and stabilizes factor VIII (FVIII) in the circulation. Quantitative and qualitative defects of vWF result in von Willebrand disease (vWD), manifested by modest to severe bleeding episodes. Substitution therapy, with plasma-derived FVIII/vWF complex concentrates, is used for patients suffering the more severe forms of vWD. Efficacy of these preparations is often unsatisfactory because inadvertent proteolytic degradation during the manufacturing process causes them to lack the hemostatically most active high-molecular-weight multimers. In contrast, recombinant vWF (r-vWF), which is constitutively expressed at high yields in Chinese hamster ovary (CHO) cells and secreted into the conditioned medium under perfusion fermentation in "protein-free" medium, has high-molecular-weight multimers of extraordinary structural integrity. Functional analysis has shown that r-vWF promotes ristocetin cofactor-mediated platelet aggregation, collagen interaction and FVIII binding, and platelet-collagen adhesion under shear stress. Infusing vWF-deficient animals with r-vWF corrected vWF concentration and reduced blood loss, subsequently stabilizing endogenous FVIII associated with the reduction of bleeding time. Compared with plasma-derived vWF preparations, r-vWF was found to have a prolonged half-life, further enhancing the potential value of r-vWF as a therapeutic agent for treating patients suffering from vWD.

  13. Dr. Wernher Von Braun near the mobile launcher.

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Dr. George Mueller, NASA associate administrator for manned space flight, and Dr. Wernher Von Braun (right), director of the Marshall Space Flight Center, are seen near the mobile launcher carrying a 363 foot tall Saturn V space launch vehicle as the rocket is rolled from the vehicle assembly building at KSC for its three mile trip to the launch pad.

  14. Dr. von Braun With a Model of a Launch Vehicle

    NASA Technical Reports Server (NTRS)

    1950-01-01

    Dr. von Braun stands beside a model of the upper stage (Earth-returnable stage) of the three-stage launch vehicle built for the series of the motion picture productions of space flight produced by Walt Disney in the mid-1950's.

  15. Remembrances of Ulf Svante von Euler.

    PubMed

    Igić, Rajko

    2018-05-21

    I first met Ulf Svante von Euler when he came to Belgrade, in 1968, to attend an international symposium on the occasion of the 50 th anniversary of the Medical Faculty. I was at that time a graduate student at the Medical Faculty in Sarajevo, and a new researcher. I had finished medical school in Belgrade and had worked for two years as a physician in the northern part of Serbia. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Robuste Verzweigungserkennung von Gefäßen in CTA-Datensätzen zur modellbasierten Extraktion der Centerline

    NASA Astrophysics Data System (ADS)

    Beck, Thomas; Fritz, Dominik; Biermann, Christina; Dillmann, Rüdiger

    Bei der Befundung und Visualisierung von Blutgefäßen ist deren Centerline von zentraler Bedeutung. Die Unterscheidung zwischen unverzweigten Abschnitten des Gefäßes und Verzweigungsbereichen ermöglicht den Einsatz spezialisierter und sehr effizienter Algorithmen zur modellbasierten Extraktion der Centerline. In diesem Artikel wird ein robustes Verfahren zur Verzweigungserkennung vorgestellt. Das Verfahren beruht auf einem Front-Propagation-Ansatz mit dynamisch angepassten Schwellwerten und einer anschließenden Clusteranalyse. Die vorgestellte Methode zur Verzweigungserkennung wurde als Komponente einer Architektur zur Extraktion der Centerline auf handannotierten Datensätzen getestet. Erste Ergebnisse sind sehr vielversprechend und ermöglichen auch bei pathologischen Gefäßen eine robuste Detektion von Gefäßverzweigungen.

  17. Haemangioblastoma of a cervical sensory nerve root in Von Hippel-Lindau syndrome.

    PubMed

    McEvoy, A W; Benjamin, E; Powell, M P

    2000-10-01

    Spinal haemangioblastomas are rare, accounting for only about 7% of all central nervous system cases. The case of a 40-year-old woman with a haemangioblastoma arising solely from a cervical sensory nerve root is presented. At operation via a cervical laminectomy, it was possible to resect the tumour en masse with the sensory ramus, by extending the laminectomy through the exit foramen for C6. Haemangioblastomas are commonly intramedullary, and have only been reported in this location on one previous occasion. The patient has Von Hippel-Lindau syndrome and a history of multiple solid tumours. The possible role of the Von Hippel-Lindau tumour suppressor gene in the pathogenesis of these neoplasms is discussed.

  18. Screening for somatic mutations of the neurofibromatosis genes in nervous system and other solid tumors

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

    Rangaratnam, S.; Narod, S.; Ruttledge, M.

    Von Recklinghausen neurofibromatosis (NF1) and neurofibromatosis type 2 (NF2) are autosomal dominant inherited disorders which predispose carriers to various benign and malignant tumors. Both genes are thought to act as tumor suppressors with inactivation of both alleles resulting in abnormal cell growth. By inference from other hereditary cancer syndromes, it has been hypothesized that somatic mutation at the NF1 and NF2 loci is involved in the development of sporadic tumors of the types found with increased prevalence in these disorders. In addition to other malignancies, individuals with NF1 are at increased risk to develop astrocytomas and rhabdomyosarcomas. We have thereforemore » screened 40 astrocytomas for LOH using three NF1-derived cDNA probes, and have found no abnormalities. Single-strand conformation polymorphism (SSCP) analysis of exons of the NF1 GAP-related domain has also failed to show any variants in a total of 70 astrocytomas and 14 rhabdomyosarcomas (7 each of embryonal and alveolar types). LOH of chromosome 22 markers is known to occur in meningioma, malignant melanoma, breast cancer, and ependymoma. SSCP of all 17 exons of the NF2 gene in 27 melanoma cell lines, 42 breast cancers, and 27 pendymomas revealed no alterations. In a screen of 151 menigiomas, 26 new variants have been found, bringing our total to 50 variants in this sample. These represent inactivating mutations (frameshift, splice-site, and nonsense), determined by direct sequencing. Since the majority of these changes occur in tumors previously shown to have LOH at chromosome 22 markers flanking NF2, our results support a tumor sequence role for this gene in meningiomas. In addition, given that 40% of our tumors do not show LOH over this region, we propose that other genes are involved in the development of this latter subset of meningiomas.« less

  19. The education of Ehrenfried Walther von Tschirnhaus (1651-1708).

    PubMed

    Adler, Jacob

    2015-02-01

    Ehrenfried Walther von Tschirnhaus, mathematician, inventor, and correspondent of Spinoza, is often thought to have studied medicine at Leiden, though documentation of this fact has been lacking. Tschirnhaus' medical education is here documented, along with the nature of his medical practice. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  20. S2k-Leitlinie zum Gebrauch von Präparationen zur lokalen Anwendung auf der Haut (Topika).

    PubMed

    Wohlrab, Johannes; Staubach, Petra; Augustin, Matthias; Eisert, Lisa; Hünerbein, Andreas; Nast, Alexander; Reimann, Holger; Strömer, Klaus; Mahler, Vera

    2018-03-01

    Diese Leitlinie richtet sich an Assistenz- und Fachärzte der Dermatologie sowie an Kostenträger und politische Entscheidungsgremien. Die Leitlinie wurde im formellen Konsensusverfahren (S2k) von Dermatologen unter Einbindung von Apothekern erstellt. Die Leitlinie stellt allgemeine Aspekte der Pharmakokinetik sowie der regulatorischen Begrifflichkeiten dar. Es werden Empfehlungen zur Indikation von Magistralrezepturen sowie deren Qualitätssicherung gegeben. Die Bedeutung der galenischen Grundlagen und die Problematik bei einer Substitution gegeneinander verschiedener Grundlagen werden dargestellt. Die Leitlinie umfasst Kriterien zur Auswahl einer adäquaten Grundlage sowie spezifische Aspekte zur Therapieplanung. Die Leitlinie gibt Empfehlungen zum Management bei Unverträglichkeiten gegenüber Bestandteilen der Grundlagen oder Hilfsstoffe. © 2018 The Authors | Journal compilation © Blackwell Verlag GmbH, Berlin.

  1. Superfluid high REynolds von Kármán experiment.

    PubMed

    Rousset, B; Bonnay, P; Diribarne, P; Girard, A; Poncet, J M; Herbert, E; Salort, J; Baudet, C; Castaing, B; Chevillard, L; Daviaud, F; Dubrulle, B; Gagne, Y; Gibert, M; Hébral, B; Lehner, Th; Roche, P-E; Saint-Michel, B; Bon Mardion, M

    2014-10-01

    The Superfluid High REynolds von Kármán experiment facility exploits the capacities of a high cooling power refrigerator (400 W at 1.8 K) for a large dimension von Kármán flow (inner diameter 0.78 m), which can work with gaseous or subcooled liquid (He-I or He-II) from room temperature down to 1.6 K. The flow is produced between two counter-rotating or co-rotating disks. The large size of the experiment allows exploration of ultra high Reynolds numbers based on Taylor microscale and rms velocity [S. B. Pope, Turbulent Flows (Cambridge University Press, 2000)] (Rλ > 10000) or resolution of the dissipative scale for lower Re. This article presents the design and first performance of this apparatus. Measurements carried out in the first runs of the facility address the global flow behavior: calorimetric measurement of the dissipation, torque and velocity measurements on the two turbines. Moreover first local measurements (micro-Pitot, hot wire,…) have been installed and are presented.

  2. Superfluid high REynolds von Kármán experiment

    NASA Astrophysics Data System (ADS)

    Rousset, B.; Bonnay, P.; Diribarne, P.; Girard, A.; Poncet, J. M.; Herbert, E.; Salort, J.; Baudet, C.; Castaing, B.; Chevillard, L.; Daviaud, F.; Dubrulle, B.; Gagne, Y.; Gibert, M.; Hébral, B.; Lehner, Th.; Roche, P.-E.; Saint-Michel, B.; Bon Mardion, M.

    2014-10-01

    The Superfluid High REynolds von Kármán experiment facility exploits the capacities of a high cooling power refrigerator (400 W at 1.8 K) for a large dimension von Kármán flow (inner diameter 0.78 m), which can work with gaseous or subcooled liquid (He-I or He-II) from room temperature down to 1.6 K. The flow is produced between two counter-rotating or co-rotating disks. The large size of the experiment allows exploration of ultra high Reynolds numbers based on Taylor microscale and rms velocity [S. B. Pope, Turbulent Flows (Cambridge University Press, 2000)] (Rλ > 10000) or resolution of the dissipative scale for lower Re. This article presents the design and first performance of this apparatus. Measurements carried out in the first runs of the facility address the global flow behavior: calorimetric measurement of the dissipation, torque and velocity measurements on the two turbines. Moreover first local measurements (micro-Pitot, hot wire,…) have been installed and are presented.

  3. Kinematic α tensors and dynamo mechanisms in a von Kármán swirling flow.

    PubMed

    Ravelet, F; Dubrulle, B; Daviaud, F; Ratié, P-A

    2012-07-13

    We provide experimental and numerical evidence of in-blades vortices in the von Kármán swirling flow. We estimate the associated kinematic α-effect tensor and show that it is compatible with recent models of the von Kármán sodium (VKS) dynamo. We further show that depending on the relative frequency of the two impellers, the dominant dynamo mechanism may switch from α2 to α - Ω dynamo. We discuss some implications of these results for VKS experiments.

  4. Clinical and laboratory diagnosis of von Willebrand disease: A synopsis of the 2008 NHLBI/NIH guidelines

    PubMed Central

    Nichols, William L.; Rick, Margaret E.; Ortel, Thomas L.; Montgomery, Robert R.; Sadler, J. Evan; Yawn, Barbara P.; James, Andra H.; Hultin, Mae B.; Manco-Johnson, Marilyn J.; Weinstein, Mark

    2017-01-01

    Von Willebrand factor (VWF) mediates blood platelet adhesion and accumulation at sites of blood vessel injury, and also carries coagulation factor VIII (FVIII) that is important for generating procoagulant activity. Von Willebrand disease (VWD), the most common inherited bleeding disorder, affects males and females, and reflects deficiency or defects of VWF that may also cause decreased FVIII. It may also occur less commonly as an acquired disorder (acquired von Willebrand syndrome). This article briefly summarizes selected features of the March 2008 evidence-based clinical and laboratory diagnostic recommendations from the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel for assessment for VWD or other bleeding disorders or risks. Management of VWD is also addressed in the NHLBI guidelines, but is not summarized here. The VWD guidelines are available at the NHLBI Web site (http://www.nhlbi.nih.gov/guidelines/vwd). PMID:19415721

  5. Measuring Changes in Tactile Sensitivity in the Hind Paw of Mice Using an Electronic von Frey Apparatus

    PubMed Central

    Martinov, Tijana; Mack, Madison; Sykes, Akilah; Chatterjea, Devavani

    2013-01-01

    Measuring inflammation-induced changes in thresholds of hind paw withdrawal from mechanical pressure is a useful technique to assess changes in pain perception in rodents. Withdrawal thresholds can be measured first at baseline and then following drug, venom, injury, allergen, or otherwise evoked inflammation by applying an accurate force on very specific areas of the skin. An electronic von Frey apparatus allows precise assessment of mouse hind paw withdrawal thresholds that are not limited by the available filament sizes in contrast to classical von Frey measurements. The ease and rapidity of measurements allow for incorporation of assessment of tactile sensitivity outcomes in diverse models of rapid-onset inflammatory and neuropathic pain as multiple measurements can be taken within a short time period. Experimental measurements for individual rodent subjects can be internally controlled against individual baseline responses and exclusion criteria easily established to standardize baseline responses within and across experimental groups. Thus, measurements using an electronic von Frey apparatus represent a useful modification of the well-established classical von Frey filament-based assays for rodent mechanical allodynia that may also be applied to other nonhuman mammalian models. PMID:24378519

  6. Professor Oberth and Dr. von Braun at ARS Banquet

    NASA Technical Reports Server (NTRS)

    1961-01-01

    Dr. Wernher von Braun holds the coveted Hermarn Oberth award presented to him by Professor Oberth during the banquet hosted by the Alabama Section of the American Rocket Society (ARS), on October 19, 1961. The Oberth award was given for outstanding technical contributions to the field of astronautics or for the promotion and advancement of astronautical sciences.

  7. Phenotypic correction of von Willebrand disease type 3 blood-derived endothelial cells with lentiviral vectors expressing von Willebrand factor

    PubMed Central

    De Meyer, Simon F.; Vanhoorelbeke, Karen; Chuah, Marinee K.; Pareyn, Inge; Gillijns, Veerle; Hebbel, Robert P.; Collen, Désiré; Deckmyn, Hans; VandenDriessche, Thierry

    2006-01-01

    Von Willebrand disease (VWD) is an inherited bleeding disorder, caused by quantitative (type 1 and 3) or qualitative (type 2) defects in von Willebrand factor (VWF). Gene therapy is an appealing strategy for treatment of VWD because it is caused by a single gene defect and because VWF is secreted into the circulation, obviating the need for targeting specific organs or tissues. However, development of gene therapy for VWD has been hampered by the considerable length of the VWF cDNA (8.4 kb [kilobase]) and the inherent complexity of the VWF protein that requires extensive posttranslational processing. In this study, a gene-based approach for VWD was developed using lentiviral transduction of blood-outgrowth endothelial cells (BOECs) to express functional VWF. A lentiviral vector encoding complete human VWF was used to transduce BOECs isolated from type 3 VWD dogs resulting in high-transduction efficiencies (95.6% ± 2.2%). Transduced VWD BOECs efficiently expressed functional vector-encoded VWF (4.6 ± 0.4 U/24 hour per 106 cells), with normal binding to GPIbα and collagen and synthesis of a broad range of multimers resulting in phenotypic correction of these cells. These results indicate for the first time that gene therapy of type 3 VWD is feasible and that BOECs are attractive target cells for this purpose. PMID:16478886

  8. Meta-analysis of Clear Cell Renal Cell Carcinoma Gene Expression Defines a Variant Subgroup and Identifies Gender Influences on Tumor Biology

    PubMed Central

    Brannon, A. Rose; Haake, Scott M.; Hacker, Kathryn E.; Pruthi, Raj S.; Wallen, Eric M.; Nielsen, Matthew E.; Rathmell, W. Kimryn

    2011-01-01

    Background Clear cell renal cell carcinoma (ccRCC) displays molecular and histologic heterogeneity. Previously described subsets of this disease, ccA and ccB, were defined based on multigene expression profiles, but it is unclear whether these subgroupings reflect the full spectrum of disease or how these molecular subtypes relate to histologic descriptions or gender. Objective Determine whether additional subtypes of ccRCC exist and whether these subtypes are related to von Hippel-Lindau (VHL) inactivation, hypoxia-inducible factor (HIF) 1 and 2 expression, tumor histology, or gender. Design, setting, and participants Six large, publicly available ccRCC gene expression databases were identified that cumulatively provided data for 480 tumors for meta-analysis via meta-array compilation. Measurements Unsupervised consensus clustering was performed on the meta-arrays. Tumors were examined for the relationship of multigene-defined consensus subtypes and expression signatures of VHL mutation and HIF status, tumor histology, and gender. Results and limitations Two dominant subsets of ccRCC were observed. However, a minor third cluster was revealed that correlated strongly with a wild type (WT) VHL expression profile and indications of variant histologies. When variant histologies were removed, ccA tumors naturally divided by gender. This technique is limited by the potential for persistent batch effect, tumor sampling bias, and restrictions of annotated information. Conclusions The ccA and ccB subsets of ccRCC are robust in meta-analysis among histologically conventional ccRCC tumors. A third group of tumors was identified that may represent a new variant of ccRCC. Within definitively clear cell tumors, gender may delineate tumors in such a way that it could have implications regarding current treatments and future drug development. PMID:22030119

  9. Interpolatability distinguishes LOCC from separable von Neumann measurements

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

    Childs, Andrew M.; Leung, Debbie; Mančinska, Laura

    2013-11-15

    Local operations with classical communication (LOCC) and separable operations are two classes of quantum operations that play key roles in the study of quantum entanglement. Separable operations are strictly more powerful than LOCC, but no simple explanation of this phenomenon is known. We show that, in the case of von Neumann measurements, the ability to interpolate measurements is an operational principle that sets apart LOCC and separable operations.

  10. Hardware-Abbildung eines videobasierten Verfahrens zur echtzeitfähigen Auswertung von Winkelhistogrammen auf eine modulare Coprozessor-Architektur

    NASA Astrophysics Data System (ADS)

    Flatt, H.; Tarnowsky, A.; Blume, H.; Pirsch, P.

    2010-10-01

    Dieser Beitrag behandelt die Abbildung eines videobasierten Verfahrens zur echtzeitfähigen Auswertung von Winkelhistogrammen auf eine modulare Coprozessor-Architektur. Die Architektur besteht aus mehreren dedizierten Recheneinheiten zur parallelen Verarbeitung rechenintensiver Bildverarbeitungsverfahren und ist mit einem RISC-Prozessor verbunden. Eine konfigurierbare Architekturerweiterung um eine Recheneinheit zur Auswertung von Winkelhistogrammen von Objekten ermöglicht in Verbindung mit dem RISC eine echtzeitfähige Klassifikation. Je nach Konfiguration sind für die Architekturerweiterung auf einem Xilinx Virtex-5-FPGA zwischen 3300 und 12 000 Lookup-Tables erforderlich. Bei einer Taktfrequenz von 100 MHz können unabhängig von der Bildauflösung pro Einzelbild in einem 25-Hz-Videodatenstrom bis zu 100 Objekte der Größe 256×256 Pixel analysiert werden. This paper presents the mapping of a video-based approach for real-time evaluation of angular histograms on a modular coprocessor architecture. The architecture comprises several dedicated processing elements for parallel processing of computation-intensive image processing tasks and is coupled with a RISC processor. A configurable architecture extension, especially a processing element for evaluating angular histograms of objects in conjunction with a RISC processor, provides a real-time classification. Depending on the configuration of the architecture extension, 3 300 to 12 000 look-up tables are required for a Xilinx Virtex-5 FPGA implementation. Running at a clock frequency of 100 MHz and independently of the image resolution per frame, 100 objects of size 256×256 pixels are analyzed in a 25 Hz video stream by the architecture.

  11. Cloning and characterization of a mouse gene with homology to the human von Hippel-Lindau disease tumor suppressor gene: implications for the potential organization of the human von Hippel-Lindau disease gene.

    PubMed

    Gao, J; Naglich, J G; Laidlaw, J; Whaley, J M; Seizinger, B R; Kley, N

    1995-02-15

    The human von Hippel-Lindau disease (VHL) gene has recently been identified and, based on the nucleotide sequence of a partial cDNA clone, has been predicted to encode a novel protein with as yet unknown functions [F. Latif et al., Science (Washington DC), 260: 1317-1320, 1993]. The length of the encoded protein and the characteristics of the cellular expressed protein are as yet unclear. Here we report the cloning and characterization of a mouse gene (mVHLh1) that is widely expressed in different mouse tissues and shares high homology with the human VHL gene. It predicts a protein 181 residues long (and/or 162 amino acids, considering a potential alternative start codon), which across a core region of approximately 140 residues displays a high degree of sequence identity (98%) to the predicted human VHL protein. High stringency DNA and RNA hybridization experiments and protein expression analyses indicate that this gene is the most highly VHL-related mouse gene, suggesting that it represents the mouse VHL gene homologue rather than a related gene sharing a conserved functional domain. These findings provide new insights into the potential organization of the VHL gene and nature of its encoded protein.

  12. Space: The Long-Range Future: An Interview with Jesco von Puttkamer.

    ERIC Educational Resources Information Center

    Lawler, Andrew

    1985-01-01

    Jesco von Puttkamer manages long-range planning in NASA's Office of Space Flight. He believes that space offers the opportunity to ease global tensions, help the developing world, and create a new global culture off the planet. (Author/RM)

  13. MicroRNAs Associated with Von Hippel-Lindau Pathway in Renal Cell Carcinoma: A Comprehensive Review.

    PubMed

    Schanza, Lisa-Maria; Seles, Maximilian; Stotz, Michael; Fosselteder, Johannes; Hutterer, Georg C; Pichler, Martin; Stiegelbauer, Verena

    2017-11-22

    Renal cell carcinoma (RCC) are the most common renal neoplasia and can be divided into three main histologic subtypes, among which clear cell RCC is by far the most common form of kidney cancer. Despite substantial advances over the last decade in the understanding of RCC biology, surgical treatments, and targeted and immuno-therapies in the metastatic setting, the prognosis for advanced RCC patients remains poor. One of the major problems with RCC treatment strategies is inherent or acquired resistance towards therapeutic agents over time. The discovery of microRNAs (miRNAs), a class of small, non-coding, single-stranded RNAs that play a crucial role in post-transcriptional regulation, has added new dimensions to the development of novel diagnostic and treatment tools. Because of an association between Von Hippel-Lindau (VHL) genes with chromosomal loss in 3p25-26 and clear cell RCC, miRNAs have attracted considerable scientific interest over the last years. The loss of VHL function leads to constitutional activation of the hypoxia inducible factor (HIF) pathway and to consequent expression of numerous angiogenic and carcinogenic factors. Since miRNAs represent key players of carcinogenesis, tumor cell invasion, angiogenesis, as well as in development of metastases in RCC, they might serve as potential therapeutic targets. Several miRNAs are already known to be dysregulated in RCC and have been linked to biological processes involved in tumor angiogenesis and response to anti-cancer therapies. This review summarizes the role of different miRNAs in RCC angiogenesis and their association with the VHL gene, highlighting their potential role as novel drug targets.

  14. Transferrin receptor 1 upregulation in primary tumor and downregulation in benign kidney is associated with progression and mortality in renal cell carcinoma patients

    PubMed Central

    Greene, Christopher J.; Attwood, Kristopher; Sharma, Nitika J.; Gross, Kenneth W.; Smith, Gary J.; Xu, Bo; Kauffman, Eric C.

    2017-01-01

    The central dysregulated pathway of clear cell (cc) renal cell carcinoma (RCC), the von Hippel Lindau/hypoxia inducible factor-α axis, is a key regulator of intracellular iron levels, however the role of iron uptake in human RCC tumorigenesis and progression remains unknown. We conducted a thorough, large-scale investigation of the expression and prognostic significance of the primary iron uptake protein, transferrin receptor 1 (TfR1/CD71/TFRC), in RCC patients. TfR1 immunohistochemistry was performed in over 1500 cores from 574 renal cell tumor patient tissues (primary tumors, matched benign kidneys, metastases) and non-neoplastic tissues from 36 different body sites. TfR1 levels in RCC tumors, particularly ccRCC, were significantly associated with adverse clinical prognostic features (anemia, lower body mass index, smoking), worse tumor pathology (size, stage, grade, multifocality, sarcomatoid dedifferentiation) and worse survival outcomes, including after adjustments for tumor pathology. Highest TfR1 tissue levels in the non-gravid body were detected in benign renal tubule epithelium. Opposite to TfR1 changes in the primary tumor, TfR1 levels in benign kidney dropped during tumor progression and were inversely associated with worse survival outcomes, independent of tumor pathology. Quantitative measurement of TfR1 subcellular localization in cell lines demonstrated mixed cytoplasmic and membranous expression with increased TfR1 in clusters in ccRCC versus benign renal cell lines. Results of this study support an important role for TfR1 in RCC progression and identify TfR1 as a novel RCC biomarker and therapeutic target. PMID:29291011

  15. Genetic screening for von Hippel-Lindau gene mutations in non-syndromic pheochromocytoma: low prevalence and false-positives or misdiagnosis indicate a need for caution.

    PubMed

    Eisenhofer, G; Vocke, C D; Elkahloun, A; Huynh, T-T; Prodanov, T; Lenders, J W M; Timmers, H J; Benhammou, J N; Linehan, W M; Pacak, K

    2012-05-01

    Genetic testing of tumor susceptibility genes is now recommended in most patients with pheochromocytoma or paraganglioma (PPGL), even in the absence of a syndromic presentation. Once a mutation is diagnosed there is rarely follow-up validation to assess the possibility of misdiagnosis. This study prospectively examined the prevalence of von Hippel-Lindau (VHL) gene mutations among 182 patients with non-syndromic PPGLs. Follow-up in positive cases included comparisons of biochemical and tumor gene expression data in 64 established VHL patients, with confirmatory genetic testing in cases with an atypical presentation. VHL mutations were detected by certified laboratory testing in 3 of the 182 patients with non-syndromic PPGLs. Two of the 3 had an unusual presentation of diffuse peritoneal metastases and substantial increases in plasma metanephrine, the metabolite of epinephrine. Tumor gene expression profiles in these 2 patients also differed markedly from those associated with established VHL syndrome. One patient was diagnosed with a partial deletion by Southern blot analysis and the other with a splice site mutation. Quantitative polymerase chain reaction, multiplex ligation-dependent probe amplification, and comparative genomic hybridization failed to confirm the partial deletion indicated by certified laboratory testing. Analysis of tumor DNA in the other patient with a splice site alteration indicated no loss of heterozygosity or second hit point mutation. In conclusion, VHL germline mutations represent a minor cause of non-syndromic PPGLs and misdiagnoses can occur. Caution should therefore be exercised in interpreting positive genetic test results as the cause of disease in patients with non-syndromic PPGLs. © Georg Thieme Verlag KG Stuttgart · New York.

  16. Structure and Reversibility of 2D von Neumann Cellular Automata Over Triangular Lattice

    NASA Astrophysics Data System (ADS)

    Uguz, Selman; Redjepov, Shovkat; Acar, Ecem; Akin, Hasan

    2017-06-01

    Even though the fundamental main structure of cellular automata (CA) is a discrete special model, the global behaviors at many iterative times and on big scales could be a close, nearly a continuous, model system. CA theory is a very rich and useful phenomena of dynamical model that focuses on the local information being relayed to the neighboring cells to produce CA global behaviors. The mathematical points of the basic model imply the computable values of the mathematical structure of CA. After modeling the CA structure, an important problem is to be able to move forwards and backwards on CA to understand their behaviors in more elegant ways. A possible case is when CA is to be a reversible one. In this paper, we investigate the structure and the reversibility of two-dimensional (2D) finite, linear, triangular von Neumann CA with null boundary case. It is considered on ternary field ℤ3 (i.e. 3-state). We obtain their transition rule matrices for each special case. For given special triangular information (transition) rule matrices, we prove which triangular linear 2D von Neumann CAs are reversible or not. It is known that the reversibility cases of 2D CA are generally a much challenged problem. In the present study, the reversibility problem of 2D triangular, linear von Neumann CA with null boundary is resolved completely over ternary field. As far as we know, there is no structure and reversibility study of von Neumann 2D linear CA on triangular lattice in the literature. Due to the main CA structures being sufficiently simple to investigate in mathematical ways, and also very complex to obtain in chaotic systems, it is believed that the present construction can be applied to many areas related to these CA using any other transition rules.

  17. Inzidenz von bullösen Autoimmunerkrankungen in Serbien: eine retrospektive Studie über 20 Jahre.

    PubMed

    Milinković, Mirjana; Janković, Slavenka; Medenica, Ljiljana; Nikolić, Miloš; Reljić, Vesna; Popadić, Svetlana; Janković, Janko

    2016-10-01

    Die meisten früheren Arbeiten zu den klinisch-epidemiologischen Merkmalen von bullösen Autoimmunerkrankungen (AIBD) konzentrierten sich vor allem auf eine einzige Krankheitsentität oder nur eine Krankheitsgruppe; nur in wenigen Studien wurde die Inzidenz verschiedener AIBD untersucht. Bei der vorliegenden Studie war es unser Ziel, das gesamte Spektrum der AIBD zu betrachten, die Inzidenz der häufigsten AIBD zu ermitteln und die zeitlichen Trends ihres Auftretens in Zentralserbien über einen Zeitraum von 20 Jahren zu untersuchen. Wir rekrutierten retrospektiv 1161 AIBD-Fälle, die in Zentralserbien von Januar 1991 bis Dezember 2010 neu diagnostiziert wurden. Die Diagnose stützte sich auf eine strikte klinische, histologische und immunhistologische Beurteilung. Folgende Inzidenzraten wurden für die einzelnen Erkrankungen ermittelt: 4,35 pro eine Million Einwohner/Jahr (pME/Jahr) für Pemphigus, 4,47 pME/Jahr für Pemphigoid, 1,42 pME/Jahr für Dermatitis herpetiformis (DH), 0,25 pME/Jahr IgA-Dermatose und 0,08 pME/Jahr für Epidermolysis bullosa acquisita. Im betrachteten Zeitraum stieg die altersbereinigte Inzidenzrate für Pemphigus und insbesondere für Pemphigoid signifikant an, während sie für DH, allerdings nicht signifikant, abnahm. Unsere Studie befasst sich zum ersten Mal mit den Inzidenzraten des gesamten Spektrums der AIBD in Serbien und untersucht die zeitlichen Trends ihres Auftretens über einen Zeitraum von 20 Jahren. Nach unserem besten Wissen wurde ein ähnlicher Befund wie der unsere, dass nämlich die Inzidenzraten von Pemphigus und Pemphigoid vergleichbar sind, bisher noch nicht publiziert. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  18. Hypoxia and hypoxia-inducible factor (HIF) downregulate antigen-presenting MHC class I molecules limiting tumor cell recognition by T cells

    PubMed Central

    Nguyen, Thao; Hatfield, Stephen M.; Ohta, Akio; Sitkovsky, Michail V.

    2017-01-01

    Human cancers are known to downregulate Major Histocompatibility Complex (MHC) class I expression thereby escaping recognition and rejection by anti-tumor T cells. Here we report that oxygen tension in the tumor microenvironment (TME) serves as an extrinsic cue that regulates antigen presentation by MHC class I molecules. In support of this view, hypoxia is shown to negatively regulate MHC expression in a HIF-dependent manner as evidenced by (i) lower MHC expression in the hypoxic TME in vivo and in hypoxic 3-dimensional (3D) but not 2-dimensional (2D) tumor cell cultures in vitro; (ii) decreased MHC in human renal cell carcinomas with constitutive expression of HIF due to genetic loss of von Hippel-Lindau (VHL) function as compared with isogenically paired cells with restored VHL function, and iii) increased MHC in tumor cells with siRNA-mediated knockdown of HIF. In addition, hypoxia downregulated antigen presenting proteins like TAP 1/2 and LMP7 that are known to have a dominant role in surface display of peptide-MHC complexes. Corroborating oxygen-dependent regulation of MHC antigen presentation, hyperoxia (60% oxygen) transcriptionally upregulated MHC expression and increased levels of TAP2, LMP2 and 7. In conclusion, this study reveals a novel mechanism by which intra-tumoral hypoxia and HIF can potentiate immune escape. It also suggests the use of hyperoxia to improve tumor cell-based cancer vaccines and for mining novel immune epitopes. Furthermore, this study highlights the advantage of 3D cell cultures in reproducing hypoxia-dependent changes observed in the TME. PMID:29155844

  19. Generalization of von Neumann analysis for a model of two discrete half-spaces: The acoustic case

    USGS Publications Warehouse

    Haney, M.M.

    2007-01-01

    Evaluating the performance of finite-difference algorithms typically uses a technique known as von Neumann analysis. For a given algorithm, application of the technique yields both a dispersion relation valid for the discrete time-space grid and a mathematical condition for stability. In practice, a major shortcoming of conventional von Neumann analysis is that it can be applied only to an idealized numerical model - that of an infinite, homogeneous whole space. Experience has shown that numerical instabilities often arise in finite-difference simulations of wave propagation at interfaces with strong material contrasts. These interface instabilities occur even though the conventional von Neumann stability criterion may be satisfied at each point of the numerical model. To address this issue, I generalize von Neumann analysis for a model of two half-spaces. I perform the analysis for the case of acoustic wave propagation using a standard staggered-grid finite-difference numerical scheme. By deriving expressions for the discrete reflection and transmission coefficients, I study under what conditions the discrete reflection and transmission coefficients become unbounded. I find that instabilities encountered in numerical modeling near interfaces with strong material contrasts are linked to these cases and develop a modified stability criterion that takes into account the resulting instabilities. I test and verify the stability criterion by executing a finite-difference algorithm under conditions predicted to be stable and unstable. ?? 2007 Society of Exploration Geophysicists.

  20. [Papillary cystadenoma of the epididymis. 2 case reports].

    PubMed

    Raimoldi, A; Berti, G L; Canclini, L; Giola, V; Leidi, G L; Maccaroni, A; Sironi, M; Veneroni, L; Bacchioni, A M; Assi, A

    1997-12-01

    Tumors of the epididymis are very rare. They are benign tumors in 75 per cent of the cases. Papillary cystadenoma represents 4-9 per cent of epididymal benign tumors. Often associated with the syndrome of von Hippel Lindau and infertility, histologically it can be confused with metastatic renal cell carcinoma. We report two cases of papillary cystadenoma located in the head of the right epididymis, with no concomitance with the syndrome of von Hippel Lindau, cured by the removal of the neoplastic nodule. There was no recidivation, in confirmation of the neoplastic benignity.

  1. Von recklinghausen neurofibromatosis-pachydermatocele causing lower limb gigantism: a case report.

    PubMed

    Rekha, Arcot; Gopalan, T R

    2006-03-01

    Gigantism of the lower limb can occur because of plexiform neurofibromas. This condition is seen with café au lait patches and multiple neurofibromatosis in this case of von Recklinghausen neurofibromatosis. We report our patient and review literature of this uncommon condition.

  2. Morbidity and mortality of aggressive resection in patients with advanced neuroendocrine tumors.

    PubMed

    Norton, Jeffrey A; Kivlen, Maryann; Li, Michelle; Schneider, Darren; Chuter, Timothy; Jensen, Robert T

    2003-08-01

    There is considerable controversy about the treatment of patients with malignant advanced neuroendocrine tumors of the pancreas and duodenum. Aggressive surgery remains a potentially efficacious antitumor therapy but is rarely performed because of its possible morbidity and mortality. Aggressive resection of advanced neuroendocrine tumors can be performed with acceptable morbidity and mortality rates and may lead to extended survival. The medical records of patients with advanced neuroendocrine tumors who underwent surgery between 1997 and 2002 by a single surgeon at the University of California, San Francisco, were reviewed in an institutional review board-approved protocol. Surgical procedure, pathologic characteristics, complications, mortality rates, and disease-free and overall survival rates were recorded. Disease-free survival was defined as no tumor identified on radiological imaging studies and no detectable abnormal hormone levels. Proportions were compared statistically using the Fisher exact test. Kaplan-Meier curves were used to estimate survival rates. Twenty patients were identified (11 men and 9 women). Of these, 10 (50%) had gastrinoma, 1 had insulinoma, and the remainder had nonfunctional tumors; 2 had multiple endocrine neoplasia type 1, and 1 had von Hippel-Lindau disease. The mean age was 55 years (range, 34-72 years). In 10 patients (50%), tumors were thought to be unresectable according to radiological imaging studies because of multiple bilobar liver metastases (n = 6), superior mesenteric vein invasion (n = 3), and extensive nodal metastases (n = 1). Tumors were completely removed in 15 patients (75%). Surgical procedures included 8 proximal pancreatectomies (pancreatoduodenectomy or whipple procedure), 3 total pancreatectomies, 9 distal pancreatectomies, and 3 tumor enucleations from the pancreatic head. Superior mesenteric vein reconstruction was done in 3 patients. Liver resections were done in 6 patients, and an extended periaortic node

  3. Delboeuf and Janet as influences in Freud's treatment of Emmy von N.

    PubMed

    Macmillan, M B

    1979-10-01

    An analysis is made of Freud's treatment of the patient known as Emmy von N. in which for the first time he used what he called "Breuer's technique of investigation under hypnosis." It is shown that the main component of Freud's therapy owed nothing to Breuer: the patient's traumatic memories were altered by direct suggestion under hypnosis. The abreaction which did take place seems to have resulted from Freud's expectation that it should occur. Two cases published by Delboeuf and Janet in late 1888 and early 1889 were treated by a then unusual method which analysis demonstrates to have been virtually identical to the technique used by Freud. Evidence is presented that the Delboeuf and Janet cases could have been known to Freud before he began his treatment of Emmy von N.

  4. Recurrent haematomas of the thigh: a case of von Willebrand's disease presenting to a sports clinic

    PubMed Central

    Owens, S.; Baglin, T.

    2000-01-01

    Von Willebrand's disease is a relatively common mild form of haemophilia. It should be suspected in assessing sports injuries when excessive bleeding occurs in response to relatively mild trauma. Those with the disease should remain active but avoid contact sports. They should not take aspirin or non-steroidal anti-inflammatory drugs, which may exacerbate bleeding, and should be given supportive treatment to cover dental extraction, surgery, or significant bleeding episodes. Key Words: von Willebrand's disease; haemophilia; haematoma; sports clinic PMID:10786868

  5. Salivary histatins in human deep posterior lingual glands (of von Ebner).

    PubMed

    Piludu, Marco; Lantini, Maria Serenella; Cossu, Margherita; Piras, Monica; Oppenheim, Frank G; Helmerhorst, Eva J; Siqueira, Walter; Hand, Arthur R

    2006-11-01

    Human saliva contains a family of low molecular weight histidine-rich proteins, named histatins, characterised by bactericidal and fungicidal activities in vitro against several microbial pathogens, such as Streptococcus mutans and Candida albicans. They represent a major component of an innate host non-immune defense system. In an earlier study we described the distribution of histatins in the glandular parenchyma of human major salivary glands, confirming that all human major salivary glands are involved in the secretion of histatins into saliva. In the present study we determined the expression and localisation of histatins in human posterior deep lingual glands (von Ebner's glands) by means of immunoelectron microscopy. Thin sections of normal human salivary glands, embedded in Epon resin, were incubated with rabbit polyclonal antibodies specific for human histatins and successively with a gold conjugated goat anti-rabbit IgG used as secondary antibody. Sections incubated with medium devoid of primary antibody or containing non-immune serum were used as controls. The serous secreting cells represented the main source of histatins in the glandular parenchyma of von Ebner's glands. At the electron microscopic level, labeling was associated with rough endoplasmic reticulum, Golgi complex and secretory granules that represented the main cytoplasmic site of histatin localisation. However, variability in the intensity of labeling was observed among adjacent cells. The present results show for the first time that human von Ebner's glands produce and represent a significant source of histatins, supporting the hypothesis of their important role in preventing microbial assaults on the tissues in the posterior region of the tongue and in the circumvallate papillae.

  6. Von Hippel-Lindau Disease (VHL)

    MedlinePlus

    ... tumors can be treated with focused high-dose irradiation. Individuals with VHL need careful monitoring by a ... tumors can be treated with focused high-dose irradiation. Individuals with VHL need careful monitoring by a ...

  7. Optimal spinneret layout in Von Koch curves of fractal theory based needleless electrospinning process

    NASA Astrophysics Data System (ADS)

    Yang, Wenxiu; Liu, Yanbo; Zhang, Ligai; Cao, Hong; Wang, Yang; Yao, Jinbo

    2016-06-01

    Needleless electrospinning technology is considered as a better avenue to produce nanofibrous materials at large scale, and electric field intensity and its distribution play an important role in controlling nanofiber diameter and quality of the nanofibrous web during electrospinning. In the current study, a novel needleless electrospinning method was proposed based on Von Koch curves of Fractal configuration, simulation and analysis on electric field intensity and distribution in the new electrospinning process were performed with Finite element analysis software, Comsol Multiphysics 4.4, based on linear and nonlinear Von Koch fractal curves (hereafter called fractal models). The result of simulation and analysis indicated that Second level fractal structure is the optimal linear electrospinning spinneret in terms of field intensity and uniformity. Further simulation and analysis showed that the circular type of Fractal spinneret has better field intensity and distribution compared to spiral type of Fractal spinneret in the nonlinear Fractal electrospinning technology. The electrospinning apparatus with the optimal Von Koch fractal spinneret was set up to verify the theoretical analysis results from Comsol simulation, achieving more uniform electric field distribution and lower energy cost, compared to the current needle and needleless electrospinning technologies.

  8. Dreams of death: Von Weizsäcker's Dreams in so-called endogenic anorexia: a research note.

    PubMed

    Jackson, C; Beumont, P J; Thornton, C; Lennerts, W

    1993-04-01

    Viktor Von Weizsäcker's paper "Dreams in so-called endogenic Magersucht (anorexia," first published in the Deutsche Medizinische Wochenschrift in 1937 (translation in M. Kaufman & M. Heiman [1964]. Evolution of psychosomatic concepts: Anorexia nervosa: A paradigm (pp. 181-197), New York: International Universities Press, has been described as a noteworthy and historically important contribution to the recognition of anorexia nervosa as a psychosomatic illness. Von Weizsäcker analyzed the dreams of patients he was treating for "endogenous anorexia" (magersucht). He claimed that in the bulimic phase his patients experienced nightmares dealing with themes of death, but that in the anorectic phases of restricted eating more pleasant dreams dealt with themes of blissful contentment. The authors draw current attention to his work as another early example of the treatment of the theme of death and death symbolism in the literature on eating disorders, and suggest some reappraisal of von Weizsäcker's interpretations of his own material.

  9. A reappraisal of hemangiopericytoma of bone; analysis of cases reclassified as synovial sarcoma and solitary fibrous tumor of bone.

    PubMed

    Verbeke, Sofie L J; Fletcher, Christopher D M; Alberghini, Marco; Daugaard, Søren; Flanagan, Adrienne M; Parratt, Tim; Kroon, Herman M; Hogendoorn, Pancras C W; Bovée, Judith V M G

    2010-06-01

    Hemangiopericytoma (HPC) was first described as a neoplasm with distinct morphologic features, presumably composed of pericytes. In soft tissue, it is accepted that most such lesions are solitary fibrous tumors (SFTs), monophasic synovial sarcomas (SSs), or myofibromatoses. It is unclear whether HPC of bone exists. We reviewed 9 primary "HPC" of bone from 4 institutions diagnosed between 1952 and 2002. Immunohistochemistry was performed for CD31, CD34, von Willebrand factor, smooth muscle actin, keratin AE1/AE3, and epithelial membrane antigen. There were 4 male and 5 female patients between 21 and 73 years. All tumors were located within bone, either sited within spine or extremities. All tumors showed thin-walled branching vessels surrounded by undifferentiated spindle or round cells. These cells showed variation in their morphologic pattern: 6 tumors showed a pattern-less architecture and varying cellularity, consistent with SFT; 3 of 5 cases examined were CD34-positive. Three tumors showed more densely packed sheets and fascicles of poorly differentiated cells, resembling SS, of which 2 showed focal staining for keratin AE1/AE3 or epithelial membrane antigen. Fluorescent in-situ hybridization confirmed the presence of SS18 rearrangement in 1 of 2 tumors examined. In conclusion, similar to their soft-tissue counterpart, HPC-like features in bone are a nonspecific growth pattern rather than a true diagnosis. We confirm the existence of 2 entities: SFT and SS of bone. Both are characterized by distinct morphology and immunohistochemical profile. SFT of bone is located within spine and has a better prognosis, whereas SS of bone is located within long bones having a poor prognosis.

  10. Wirksamkeit und Sicherheit von Fumarsäureestern in Kombination mit Phototherapie bei Patienten mit moderater bis schwerer Plaque-Psoriasis (FAST).

    PubMed

    Weisenseel, Peter; Reich, Kristian; Griemberg, Wiebke; Merten, Katharina; Gröschel, Christine; Gomez, Natalie Nunez; Taipale, Kirsi; Bräu, Beate; Zschocke, Ina

    2017-02-01

    Die Behandlung von Psoriasis-Patienten mit einer Kombination aus Fumarsäureestern (FSE, Fumaderm ® ) und Phototherapie (UV) ist verbreitet, wurde aber im Rahmen von Studien wenig untersucht. Bisher liegen lediglich Daten aus einer kleinen Pilotstudie vor. Intention dieser Studie war, eine FSE/UV-Kombinationsbehandlung an einem größeren Patientenkollektiv mit mittelschwerer bis schwerer Psoriasis zu untersuchen. In dieser prospektiven, multizentrischen, nichtinterventionellen Studie wurden Daten von Patienten mit FSE/UV-Kombinationstherapie hinsichtlich der Wirksamkeit (PGA' PASI, DLQI, EQ-5D), Sicherheit und Dosierung über einen Zeitraum von zwölf Monaten erfasst und mit Daten einer retrospektiven Studie mit FSE-Monotherapie verglichen. Es wurden Daten von 363 Patienten ausgewertet. Unter der Kombinationstherapie verbesserten sich alle Wirksamkeitsparameter deutlich. Im Vergleich zur Monotherapie mit FSE konnte durch die Kombination mit UV ein schnellerer Wirkeintritt erzielt werden, wobei nach zwölf Monaten kein Unterschied in der Wirksamkeit bestand. Die Dauer und Art der Phototherapie zeigte keinen Einfluss auf die Wirksamkeitsparameter. Allgemein wurde die Kombinationstherapie gut vertragen. Unerwünschte Ereignisse wurden bei 7 % der Patienten berichtet. Die FSE/UV Kombinationstherapie zeigt eine gute Wirksamkeit und Verträglichkeit und kann zu einem schnelleren Wirkeintritt führen. Eine Kombinationstherapie erscheint vor allem in den ersten drei Monaten der FSE Behandlung sinnvoll. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  11. Optimal projection method determination by Logdet Divergence and perturbed von-Neumann Divergence.

    PubMed

    Jiang, Hao; Ching, Wai-Ki; Qiu, Yushan; Cheng, Xiao-Qing

    2017-12-14

    Positive semi-definiteness is a critical property in kernel methods for Support Vector Machine (SVM) by which efficient solutions can be guaranteed through convex quadratic programming. However, a lot of similarity functions in applications do not produce positive semi-definite kernels. We propose projection method by constructing projection matrix on indefinite kernels. As a generalization of the spectrum method (denoising method and flipping method), the projection method shows better or comparable performance comparing to the corresponding indefinite kernel methods on a number of real world data sets. Under the Bregman matrix divergence theory, we can find suggested optimal λ in projection method using unconstrained optimization in kernel learning. In this paper we focus on optimal λ determination, in the pursuit of precise optimal λ determination method in unconstrained optimization framework. We developed a perturbed von-Neumann divergence to measure kernel relationships. We compared optimal λ determination with Logdet Divergence and perturbed von-Neumann Divergence, aiming at finding better λ in projection method. Results on a number of real world data sets show that projection method with optimal λ by Logdet divergence demonstrate near optimal performance. And the perturbed von-Neumann Divergence can help determine a relatively better optimal projection method. Projection method ia easy to use for dealing with indefinite kernels. And the parameter embedded in the method can be determined through unconstrained optimization under Bregman matrix divergence theory. This may provide a new way in kernel SVMs for varied objectives.

  12. Synesthesia and memory: color congruency, von Restorff, and false memory effects.

    PubMed

    Radvansky, Gabriel A; Gibson, Bradley S; McNerney, M Windy

    2011-01-01

    In the current study, we explored the influence of synesthesia on memory for word lists. We tested 10 grapheme-color synesthetes who reported an experience of color when reading letters or words. We replicated a previous finding that memory is compromised when synesthetic color is incongruent with perceptual color. Beyond this, we found that, although their memory for word lists was superior overall, synesthetes did not exhibit typical color- or semantic-defined von Restorff isolation effects (von Restorff, 1933) compared with control participants. Moreover, our synesthetes exhibited a reduced Deese-Roediger-McDermott false memory effect (Deese, 1959; Roediger & McDermott, 1995). Taken as a whole, these findings are consistent with the idea that color-grapheme synesthesia can lead people to place a greater emphasis on item-specific processing and surface form characteristics of words in a list (e.g., the letters that make them up) relative to relational processing and more meaning-based processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

  13. von Willebrand factor, Jedi knight of the bloodstream.

    PubMed

    Springer, Timothy A

    2014-08-28

    When blood vessels are cut, the forces in the bloodstream increase and change character. The dark side of these forces causes hemorrhage and death. However, von Willebrand factor (VWF), with help from our circulatory system and platelets, harnesses the same forces to form a hemostatic plug. Force and VWF function are so closely intertwined that, like members of the Jedi Order in the movie Star Wars who learn to use "the Force" to do good, VWF may be considered the Jedi knight of the bloodstream. The long length of VWF enables responsiveness to flow. The shape of VWF is predicted to alter from irregularly coiled to extended thread-like in the transition from shear to elongational flow at sites of hemostasis and thrombosis. Elongational force propagated through the length of VWF in its thread-like shape exposes its monomers for multimeric binding to platelets and subendothelium and likely also increases affinity of the A1 domain for platelets. Specialized domains concatenate and compact VWF during biosynthesis. A2 domain unfolding by hydrodynamic force enables postsecretion regulation of VWF length. Mutations in VWF in von Willebrand disease contribute to and are illuminated by VWF biology. I attempt to integrate classic studies on the physiology of hemostatic plug formation into modern molecular understanding, and point out what remains to be learned. © 2014 by The American Society of Hematology.

  14. The Digital Von Fahrenheid Pyramid

    NASA Astrophysics Data System (ADS)

    Bura, M.; Janowski, J.; Wężyk, P.; Zięba, K.

    2017-08-01

    3D Scanners Lab from Digital Humanities Laboratory at the University of Warsaw initiated the scientific project, the purpose of which was to call attention to systematically penetrated and devastated pyramid-shaped tomb from the XVIII/XIX century, of family von Fahrenheid in Rapa in Banie Mazurskie commune (NE Poland). By conducting a series of non-invasive studies, such as 3D inventory using terrestrial laser scanning (TLS), thermal imaging, georadar measurements (around and inside the tomb) and anthropological research of mummified remains as well - the complete dataset was collected. Through the integration of terrestrial (TLS) and airborne laser scanning (ALS) authors managed to analyse the surroundings of Fahrenheid pyriamid and influence of some objects (like trees) on the condition and visibility of the Pyramids in the landscape.

  15. On the history of Ludwig von Bertalanffy's "general systemology", and on its relationship to cybernetics - Part II: Contexts and developments of the systemological hermeneutics instigated by von Bertalanffy

    NASA Astrophysics Data System (ADS)

    Pouvreau, David

    2014-02-01

    The history of "general system theory" is investigated in order to clarify its meanings, vocations, foundations and achievements. It is characterized as the project of a science of the systemic interpretation of the "real", renamed here "general systemology". The contexts and modes of its elaboration, publication and implementation are discussed. The paper mostly focuses on the works of its instigator: Ludwig von Bertalanffy. However, general systemology was a collective project: the main contributions of other "systemologists", from the 1950s until the 1970s, are hence also considered. Its solidarity with the history of the Society for General Systems Research is notably discussed. A reconstruction of the systemological hermeneutics is undertaken on this basis. It finds out the potential systematic unity underlying the diversity of the contributions to this both scientific and philosophical project. Light is thus shed on the actual scope of von Bertalanffy's works.

  16. Von Willebrand's disease with spontaneous platelet aggregation induced by an abnormal plasma von Willebrand factor.

    PubMed Central

    Grainick, H R; Williams, S B; McKeown, L P; Rick, M E; Maisonneuve, P; Jenneau, C; Sultan, Y

    1985-01-01

    We have investigated and characterized the abnormalities in four unrelated patients with von Willebrand's disease (vWd) who have (a) enhanced ristocetin-induced platelet aggregation (RIPA) at low ristocetin concentrations, (b) absence of the largest plasma von Willebrand factor (vWf) multimers, and (c) thrombocytopenia. The platelet-rich plasma of these patients aggregates spontaneously without the addition of any agonists. When isolated normal platelets are resuspended in patient plasma spontaneous aggregation occurs; however, the patients' plasmas did not induce platelet aggregation of normal washed formalinized platelets. When the patients' platelets are suspended in normal plasma, spontaneous aggregation is not observed. The spontaneous platelet aggregation (SPA) is associated with dense granule secretion as measured by ATP release and alpha granule release as measured by beta-thromboglobulin and platelet factor 4 release. The SPA is totally inhibited by 5 mM EDTA, prostaglandin I2, and dibutryl cyclic AMP, while it is only partially inhibited by 1 mM EDTA, acetylsalicylic acid, or apyrase. A monoclonal antibody directed against glycoprotein Ib (GPIb) and/or a monoclonal antibody against the glycoprotein IIb/IIIa (GPIIb/IIIa) complex totally inhibits the SPA. The vWf was isolated from the plasma of one of these patients. The purified vWf induced platelet aggregation of normal platelets resuspended in either normal or severe vWd plasma, but the vWf did not induce platelet aggregation of normal platelets resuspended in afibrinognemic plasma. Sialic acid and galactose quantification of the patient's vWf revealed approximately a 50% reduction compared with normal vWf. These studies indicate that a form of vWd exists, which is characterized by SPA that is induced by the abnormal plasma vWf. The SPA is dependent on the presence of plasma fibrinogen, and the availability of the GPIb and the GPIIb/IIIa complex. In this variant form of vWd the abnormal vWf causes

  17. Albert Einstein and Wernher von Braun - the two great German-American physicists seen in a historical perspective.

    NASA Astrophysics Data System (ADS)

    Winterberg, Friedwardt

    2008-04-01

    It was Albert Einstein who for the first time changed our view of the universe to be a non-euclidean curved space-time. And it was Wernher von Braun who blazed the trail to take us into this universe, leaving for the first time the gravitational field of our planet earth, with the landing a man on the moon the greatest event in human history. Both these great physicists did this on the shoulders of giants. Albert Einstein on the shoulders of his landsman, the mathematician Bernhard Riemann, and Wernher von Braun on the shoulders of Goddard and Oberth. Both Einstein and von Braun made a Faustian pact with the devil, von Braun by accepting research funds from Hitler, and Einstein by urging Roosvelt to build the atom bomb (against Hitler). Both of these great men later regretted the use of their work for the killing of innocent bystanders, even though in the end the invention of nuclear energy and space flight is for the benefit of man. Their example serves as a warning for all of us. It can be formulated as follows: ``Can I in good conscience accept research funds from the military to advance scientific knowledge, for weapons developed against an abstract enemy I never have met in person?'' Weapons if used do not differentiate between the scientist, who invented these weapons, and the non-scientist.

  18. Spontaneous haemothorax: a cause of sudden death in von Recklinghausen's disease.

    PubMed Central

    Griffiths, A. P.; White, J.; Dawson, A.

    1998-01-01

    Vasculopathy is a relatively frequent but poorly recognised manifestation of von Recklinghausen's neurofibromatosis. One of its more dramatic presentations is as spontaneous haemothorax. Clinicians and pathologists should be aware of this syndrome as a cause of sudden death in patients with neurofibromatosis. Images Figure 1 Figure 2 PMID:10197217

  19. The role of the cilium in hereditary tumor predisposition syndromes

    PubMed Central

    Klasson, Timothy D.; Giles, Rachel H.

    2014-01-01

    The primary cilium is a highly conserved cell organelle that is closely connected to processes involved in cell patterning and replication. Amongst their many functions, cilia act as “signal towers” through which cell-cell signaling cascades pass. Dysfunction of cilia or the myriad processes that are connected with cilium function can lead to disease. Due to the sheer number of cellular processes that at some point involve the primary cilium, the effects of misregulation are highly heterogeneous between different cell populations. However, because of the importance of primary cilia in the development, growth, patterning and orientation of cells and tissues, a common thread has emerged in which defective cilia can lead to disorganization, which can contribute to the growth of neoplasms, including cancer and pre-cancerous phenotypes. Because cilia are so vital for signaling during cell replication and the cell fate decisions that are important in childhood growth, symptoms often arise early in life. Here we review recent work connecting misregulation of the primary cilium with tumor formation in a variety of tissues in the developing body, with a particular focus on the syndromes in which classic tumor genes are mutated, including von Hippel-Lindau disease (OMIM 193300), adenomatous polyposis coli (OMIM 175100), tuberous sclerosis (OMIM 191100) and Birt-Hogg-Dubé syndrome (OMIM 135150). Timely diagnosis of these syndromes is essential for entry into appropriate screening protocols, which have been shown to effectively prolong life expectancy in these cohorts of patients. PMID:27625869

  20. Peri-tumoral leakage during intra-tumoral convection-enhanced delivery has implications for efficacy of peri-tumoral infusion before removal of tumor.

    PubMed

    Yang, Xiaoliang; Saito, Ryuta; Nakamura, Taigen; Zhang, Rong; Sonoda, Yukihiko; Kumabe, Toshihiro; Forsayeth, John; Bankiewicz, Krystof; Tominaga, Teiji

    2016-01-01

    In cases of malignant brain tumors, infiltrating tumor cells that exist at the tumor-surrounding brain tissue always escape from cytoreductive surgery and, protected by blood-brain barrier (BBB), survive the adjuvant chemoradiotherapy, eventually leading to tumor recurrence. Local interstitial delivery of chemotherapeutic agents is a promising strategy to target these cells. During our effort to develop effective drug delivery methods by intra-tumoral infusion of chemotherapeutic agents, we found consistent pattern of leakage from the tumor. Here we describe our findings and propose promising strategy to cover the brain tissue surrounding the tumor with therapeutic agents by means of convection-enhanced delivery. First, the intracranial tumor isograft model was used to define patterns of leakage from tumor mass after intra-tumoral infusion of the chemotherapeutic agents. Liposomal doxorubicin, although first distributed inside the tumor, distributed diffusely into the surrounding normal brain once the leakage happen. Trypan blue dye was used to evaluate the distribution pattern of peri-tumoral infusions. When infused intra- or peri-tumorally, infusates distributed robustly into the tumor border. Subsequently, volume of distributions with different infusion scheduling; including intra-tumoral infusion, peri-tumoral infusion after tumor resection, peri-tumoral infusion without tumor removal with or without systemic infusion of steroids, were compared with Evans-blue dye. Peri-tumoral infusion without tumor removal resulted in maximum volume of distribution. Prior use of steroids further increased the volume of distribution. Local interstitial drug delivery targeting tumor surrounding brain tissue before tumor removal should be more effective when targeting the invading cells.

  1. Two errors in enteric epidemiology: the stories of Austin Flint and Max von Pettenkofer.

    PubMed

    Evans, A S

    1985-01-01

    The misconceptions of two physicians, Austin Flint and Max von Pettenkofer, in interpreting epidemiologic data on the water transmission of enteric disease are reviewed. Austin Flint failed to recognize the transmission of typhoid fever from well water in an epidemic he investigated in North Boston, New York, in 1843. He later discovered and freely admitted his error. Max von Pettenkofer, who had studied cholera in the 1854 outbreak and in many subsequent outbreaks, failed to confirm John Snow's observations in England on the water transmission of cholera. Pettenkofer eventually swallowed live cholera bacilli and did not develop cholera. He remained convinced to the end of his life that cholera is not directly transmitted by drinking water.

  2. Effects of Turbulence Model and Numerical Time Steps on Von Karman Flow Behavior and Drag Accuracy of Circular Cylinder

    NASA Astrophysics Data System (ADS)

    Amalia, E.; Moelyadi, M. A.; Ihsan, M.

    2018-04-01

    The flow of air passing around a circular cylinder on the Reynolds number of 250,000 is to show Von Karman Vortex Street Phenomenon. This phenomenon was captured well by using a right turbulence model. In this study, some turbulence models available in software ANSYS Fluent 16.0 was tested to simulate Von Karman vortex street phenomenon, namely k- epsilon, SST k-omega and Reynolds Stress, Detached Eddy Simulation (DES), and Large Eddy Simulation (LES). In addition, it was examined the effect of time step size on the accuracy of CFD simulation. The simulations are carried out by using two-dimensional and three- dimensional models and then compared with experimental data. For two-dimensional model, Von Karman Vortex Street phenomenon was captured successfully by using the SST k-omega turbulence model. As for the three-dimensional model, Von Karman Vortex Street phenomenon was captured by using Reynolds Stress Turbulence Model. The time step size value affects the smoothness quality of curves of drag coefficient over time, as well as affecting the running time of the simulation. The smaller time step size, the better inherent drag coefficient curves produced. Smaller time step size also gives faster computation time.

  3. Richard von Volkmann

    PubMed Central

    Willy, Christian; Schneider, Peter; Engelhardt, Michael; Hargens, Alan R.

    2008-01-01

    Richard von Volkmann (1830–1889), one of the most important surgeons of the 19th century, is regarded as one of the fathers of orthopaedic surgery. He was a contemporary of Langenbeck, Esmarch, Lister, Billroth, Kocher, and Trendelenburg. He was head of the Department of Surgery at the University of Halle, Germany (1867–1889). His popularity attracted doctors and patients from all over the world. He was the lead physician for the German military during two wars. From this experience, he compared the mortality of civilian and war injuries and investigated the general poor hygienic conditions in civilian hospitals. This led him to introduce the “antiseptic technique” to Germany that was developed by Lister. His powers of observation and creativity led him to findings and achievements that to this day bear his name: Volkmann’s contracture and the Hueter-Volkmann law. Additionally, he was a gifted writer; he published not only scientific literature but also books of children’s fairy tales and poems under the pen name of Richard Leander, assuring him a permanent place in the world of literature as well as orthopaedics. PMID:18196438

  4. N-linked glycan truncation causes enhanced clearance of plasma-derived von Willebrand factor.

    PubMed

    O'Sullivan, J M; Aguila, S; McRae, E; Ward, S E; Rawley, O; Fallon, P G; Brophy, T M; Preston, R J S; Brady, L; Sheils, O; Chion, A; O'Donnell, J S

    2016-12-01

    Essentials von Willebrands factor (VWF) glycosylation plays a key role in modulating in vivo clearance. VWF glycoforms were used to examine the role of specific glycan moieties in regulating clearance. Reduction in sialylation resulted in enhanced VWF clearance through asialoglycoprotein receptor. Progressive VWF N-linked glycan trimming resulted in increased macrophage-mediated clearance. Click to hear Dr Denis discuss clearance of von Willebrand factor in a free presentation from the ISTH Academy SUMMARY: Background Enhanced von Willebrand factor (VWF) clearance is important in the etiology of both type 1 and type 2 von Willebrand disease (VWD). In addition, previous studies have demonstrated that VWF glycans play a key role in regulating in vivo clearance. However, the molecular mechanisms underlying VWF clearance remain poorly understood. Objective To define the molecular mechanisms through which VWF N-linked glycan structures influence in vivo clearance. Methods By use of a series of exoglycosidases, different plasma-derived VWF (pd-VWF) glycoforms were generated. In vivo clearance of these glycoforms was then assessed in VWF -/- mice in the presence or absence of inhibitors of asialoglycoprotein receptor (ASGPR), or following clodronate-induced macrophage depletion. Results Reduced amounts of N-linked and O-linked sialylation resulted in enhanced pd-VWF clearance modulated via ASGPR. In addition to this role of terminal sialylation, we further observed that progressive N-linked glycan trimming also resulted in markedly enhanced VWF clearance. Furthermore, these additional N-linked glycan effects on clearance were ASGPR-independent, and instead involved enhanced macrophage clearance that was mediated, at least in part, through LDL receptor-related protein 1. Conclusion The carbohydrate determinants expressed on VWF regulate susceptibility to proteolysis by ADAMTS-13. In addition, our findings now further demonstrate that non-sialic acid carbohydrate

  5. Gravity Effects in Diffusive Coarsening of Bubble Lattices: von Neumann's Law

    NASA Technical Reports Server (NTRS)

    Noever, David A.

    2000-01-01

    von Neumann modelled the evolution of two-dimensional soap froths as a purely diffusive phenomenon; the area growth of a given cell was found to depend only on the geometry of the bubble lattice. In the model, hexagons are stable, pentagons shrink and heptagons grow. The simplest equivalent to the area growth law is / approximately t(sub beta). The result depends on assuming (1) an incompressible gas; (2) bubble walls which meet at 120 deg and (3) constant wall thickness and curvature. Each assumption is borne out in experiments except the last one: bubble wall thickness between connecting cells varies in unit gravity because of gravity drainage. The bottom part of the soap membrane is thickened, the top part is thinned, such that gas diffusion across the membrane shows a complex dependence on gravity. As a result, experimental tests of von Neumann's law have been influenced by effects of gravity; fluid behavior along cell borders can give non-uniform wall thicknesses and thus alter the effective area and gas diffusion rates between adjacent bubbles. For area plotted as a function of time, Glazier (J.A. Glazier, S.P. Gross, and I. Stavans, Phys. Rev. A. 36, 306 (1987); J. Stavans, J.A, Glazier, Phys. Rev. Lett. 62, 1318 (1989).) suggest that in some cases their failure to observe von Neumann's predicted growth exponent ((sup beta)theor(sup =1; beta)exp(sup =0.70 + 0.10)) may have been the result of such "fluid drainage onto the lower glass plate". Additional experiments which varied plate spacing gave different beta exponents in a fashion consistent with this suggestion. During preliminary long duration experiments (approximately 100 h) aboard Spacelab-J, a low-gravity test of froth coarsening has examined (1) power law scaling of von Neumann's law (beta values) in the appropriate diffusive limits; (2) new bubble lattice dynamics such as greater fluid wetting behavior on froth membranes in low gravity; and (3) explicit relations for the gravity

  6. Book Review: John von Neumann and the foundations of quantum physics. (Vienna Circle Institute yearbook (2000), 8) Miklos Redei and Michael Stoltzner (Eds.); Kluwer Academic Publishers, Dordrecht, 2001, pp., US 125, ISBN 0792368126

    NASA Astrophysics Data System (ADS)

    Lupher, Tracy

    2003-12-01

    Some people may be surprised to learn that John von Neumann's work on the foundations of quantum physics went far beyond what is contained within the pages of his Mathematical Foundations of Quantum Mechanics (MFQM) (von Neumann, 1955). However, this narrow focus often ignores von Neumann's later work on quantum logic and what are now called in his honor, von Neumann algebras. This volume honoring von Neumann's contributions to physics is unique in that, while it contains 12 papers that examine various aspects of von Neumann's work, it also contains two of his previously unpublished papers and some of his previously unpublished correspondence.

  7. Epidemiological study of a von Hippel-Lindau family in northwest China.

    PubMed

    Zhang, Jingyao; Wu, Dapeng; Ai, Hong; Bai, Jigang; Dong, Shunbin; Yang, Qinling; Qu, Kai; Zhou, Lei; Xu, Xinsen; Liu, Chang

    2013-09-01

    von Hippel-Lindau (VHL) disease is a rare, inherited neoplastic disease characterized by hemangioblastomas (HBL) of the central nervous system (CNS), retinal angiomas, renal cell carcinomas (RCC), pancreatic endocrine tumors (PETs), pheochromocytomas, paragangliomas, and visceral cysts. We encountered a large VHL family in northwest China and conducted a systematic screening of the family members based on their epidemiological and clinical characteristics. A self-designed questionnaire was used to collect the general sociodemographic and health information of the family members. For the preliminary family screening, physical examination and abdomen B ultrasonography were performed. The suspected patients were subjected to cranial computerized tomography and fundus examination. The clinical data of the patients with confirmed VHL disease were collected from hospital records. A total of 63 lineal descendants in six generations were observed in the family (generations O, A, B, C, D, E), including 9 dead suspected cases (6 males, 3 females) and 10 living cases (2 males, 8 females). Among the 10 living cases, 4, 2, 1, 3, 4, 8, and 2 manifested HBLs of the CNS, PETs, RCC, pancreatic cysts, renal cysts, pheochromocytomas (4 hemi and 4 bilateral), and paragangliomas, respectively. Data showed that the morbidity of VHL disease in generation C was lower than that in generation B, but the age of onset was younger. This study is the first to report VHL disease in northwest China and VHL-associated PET cases in Chinese. Therefore, follow-up checkups of the family should be focused on younger generations. Proper family screening protocols should be followed for the treatment of patients with VHL disease.

  8. [Urology and National Socialism: the fate of Alexander von Lichtenberg 1880-1949].

    PubMed

    Moll, F H; Krischel, M; Rathert, P; Fangerau, H

    2010-09-01

    Alexander von Lichtenberg (1880-1949) was one of the famous members of the German Urological Society (DGU) in pre-war Germany. He introduced excretion urography and a special TURP Instrument. In 1928 he was president of the 8th meeting held in the German capital Berlin. His Handbook of Urology, released by Ferdinand Springer publishing house, was a trendsetter in establishing urology as a specialty in Germany and bringing together the whole wisdom of all aspects of urology. He was the founder of the famous Maximilian Nitze Award of the DGU. As a Jew he-like many others-was forced to leave Nazi Germany after 1933. Even in Hungary, his native country, he again had to resist anti-Semitic hostility. Later on he lived in Mexico. Alexander von Lichtenberg has to be remembered with special focus on the exodus of German Jewish scientists during the Nazi time.

  9. Tumor cell-derived microparticles polarize M2 tumor-associated macrophages for tumor progression.

    PubMed

    Ma, Ruihua; Ji, Tiantian; Chen, Degao; Dong, Wenqian; Zhang, Huafeng; Yin, Xiaonan; Ma, Jingwei; Liang, Xiaoyu; Zhang, Yi; Shen, Guanxin; Qin, Xiaofeng; Huang, Bo

    2016-04-01

    Despite identification of macrophages in tumors (tumor-associated macrophages, TAM) as potential targets for cancer therapy, the origin and function of TAM in the context of malignancy remain poorly characterized. Here, we show that microparticles (MPs), as a by-product, released by tumor cells act as a general mechanism to mediate M2 polarization of TAM. Taking up tumor MPs by macrophages is a very efficient process, which in turn results in the polarization of macrophages into M2 type, not only leading to promoting tumor growth and metastasis but also facilitating cancer stem cell development. Moreover, we demonstrate that the underlying mechanism involves the activation of the cGAS/STING/TBK1/STAT6 pathway by tumor MPs. Finally, in addition to murine tumor MPs, we show that human counterparts also possess consistent effect on human M2 polarization. These findings provide new insights into a critical role of tumor MPs in remodeling of tumor microenvironment and better understanding of the communications between tumors and macrophages.

  10. von Kármán swirling flow between a rotating and a stationary smooth disk: Experiment

    NASA Astrophysics Data System (ADS)

    Mukherjee, Aryesh; Steinberg, Victor

    2018-01-01

    Precise measurements of the torque in a von Kármán swirling flow between a rotating and a stationary smooth disk in three Newtonian fluids with different dynamic viscosities are reported. From these measurements the dependence of the normalized torque, called the friction coefficient, on Re is found to be of the form Cf=1.17 (±0.03 ) Re-0.46±0.003 where the scaling exponent and coefficient are close to that predicted theoretically for an infinite, unshrouded, and smooth rotating disk which follows from an exact similarity solution of the Navier-Stokes equations, obtained by von Kármán. An error analysis shows that deviations from the theory can be partially caused by background errors. Measurements of the azimuthal Vθ and axial velocity profiles along radial and axial directions reveal that the flow core rotates at Vθ/r Ω ≃0.22 (up to z ≈4 cm from the rotating disk and up to r0/R ≃0.25 in the radial direction) in spite of the small aspect ratio of the vessel. Thus the friction coefficient shows scaling close to that obtained from the von Kármán exact similarity solution, but the observed rotating core provides evidence of the Batchelor-like solution [Q. J. Mech. Appl. Math. 4, 29 (1951), 10.1093/qjmam/4.1.29] different from the von Kármán [Z. Angew. Math. Mech. 1, 233 (1921), 10.1002/zamm.19210010401] or Stewartson [Proc. Camb. Philos. Soc. 49, 333 (1953), 10.1017/S0305004100028437] one.

  11. Prenatal stress-induced increases in hippocampal von Willebrand factor expression are prevented by concurrent prenatal escitalopram

    PubMed Central

    Neigh, Gretchen N.; Nemeth, Christina L; Kelly, Sean D.; Hardy, Emily E.; Bourke, Chase; Stowe, Zachary N.; Owens, Michael J.

    2016-01-01

    Prenatal stress has been linked to deficits in neurological function including deficient social behavior, alterations in learning and memory, impaired stress regulation, and susceptibility to adult disease. In addition, prenatal environment is known to alter cardiovascular health; however, limited information is available regarding the cerebrovascular consequences of prenatal stress exposure. Vascular disturbances late in life may lead to cerebral hypoperfusion which is linked to a variety of neurodegenerative and psychiatric diseases. The known impact of cerebrovascular compromise on neuronal function and behavior highlights the importance of characterizing the impact of stress on not just neurons and glia, but also cerebrovasculature. Von Willebrand factor has previously been shown to be impacted by prenatal stress and is predictive of cerebrovascular health. Here we assess the impact of prenatal stress on von Willebrand factor and related angiogenic factors. Furthermore, we assess the potential protective effects of concurrent anti-depressant treatment during in utero stress exposure on the assessed cerebrovascular endpoints. Prenatal stress augmented expression of von Willebrand factor which was prevented by concurrent in utero escitalopram treatment. The functional implications of this increase in von Willebrand factor remain elusive, but the presented data demonstrate that although prenatal stress did not independently impact total vascularization, exposure to chronic stress in adulthood decreased blood vessel length. In addition, the current study demonstrates that production of reactive oxygen species in the hippocampus is decreased by prenatal exposure to escitalopram. Collectively, these findings demonstrate that the prenatal experience can cause complex changes in adult cerebral vascular structure and function. PMID:27422674

  12. Determining the von Mises stress power spectral density for frequency domain fatigue analysis including out-of-phase stress components

    NASA Astrophysics Data System (ADS)

    Bonte, M. H. A.; de Boer, A.; Liebregts, R.

    2007-04-01

    This paper provides a new formula to take into account phase differences in the determination of an equivalent von Mises stress power spectral density (PSD) from multiple random inputs. The obtained von Mises PSD can subsequently be used for fatigue analysis. The formula was derived for use in the commercial vehicle business and was implemented in combination with Finite Element software to predict and analyse fatigue failure in the frequency domain.

  13. Platelet von Willebrand factor in Hermansky-Pudlak syndrome.

    PubMed

    McKeown, L P; Hansmann, K E; Wilson, O; Gahl, W; Gralnick, H R; Rosenfeld, K E; Rosenfeld, S J; Horne, M K; Rick, M E

    1998-10-01

    The Hermansky-Pudlak Syndrome (HPS) is an autosomal recessive inherited disorder characterized by oculocutaneous albinism, tissue accumulation of ceroid pigment, and a mild to moderate bleeding diathesis attributed to storage-pool deficient (SPD) platlets. Patients have platelet aggregation and release abnormalities. In addition, low levels of plasma von Willebrand factor (vWF) antigen in some HPS patients have been associated with a greater bleeding tendency than would be predicted from either condition alone. Other HPS patients have severe bleeding despite normal levels of plasma vWF, suggesting that at least one additional factor is responsible for their bleeding diathesis. Because platelet vWF levels have been well correlated with clinical bleeding times in patients with von Willebrand's disease, we have measured the platelet vWF activity and antigen levels in 30 HPS patients and have attempted to correlate their clinical bleeding with these values. The platelet vWF activity levels in patients was significantly lower than that of normal subjects (P < 0.0001). The patients as a group also had slightly lower values of plasma vWF activity when compared with normals (P-0.03). In 11 of the HPS patients, the multimeric structure of plasma vWF showed a decrease in the high molecular weight multimers and an increase in the low molecular weight multimers. In correlating the platelet and plasma vWF values with the bleeding histories, we were not able to show a predictable relationship in the majority of the patients.

  14. Expression of von Willebrand factor and caldesmon in the placental tissues of pregnancies complicated with intrauterine growth restriction.

    PubMed

    Göksever Çelik, Hale; Uhri, Mehmet; Yildirim, Gökhan

    2017-11-02

    The decreased placental perfusion is the underlying reason for intrauterine growth restriction that in turn leads to reduced placental perfusion and ischemia. However, there are several issues to be understood in the pathophysiology of intrauterine growth restriction. We aimed to study whether any compensatory response in placental vascular bed occur in pregnancies complicated with intrauterine growth restriction by the immunohistochemical staining of von Willebrand factor and caldesmon in placental tissues. A total of 103 pregnant women was enrolled in the study including 50 patients who were complicated with IUGR and 50 uncomplicated control patients. The study was designed in a prospective manner. All placentas were also stained with von Willebrand factor and caldesmon monoclonal kits. The immunohistochemical staining of von Willebrand factor and caldesmon expressions in placental tissues were different between normal and intrauterine growth restriction group. The percentages of 2+ and 3+ von Willebrand factor expression were higher in the intrauterine growth restriction group comparing with the normal group, although the difference was not statistically significant. The intensity of caldesmon expression was significantly lower in the intrauterine growth restriction group in comparison with the normal group (p < .001). Angiogenesis occurs as a placental response to intrauterine growth restriction which is a hypoxic condition. But newly formed vessels are immature and not strong enough. Our study is important to clarify the pathophysiology and placental compensatory responses in intrauterine growth restriction.

  15. Platelet Dysfunction and a High Bone Mass Phenotype in a Murine Model of Platelet-Type von Willebrand Disease

    PubMed Central

    Suva, Larry J.; Hartman, Eric; Dilley, Joshua D.; Russell, Susan; Akel, Nisreen S.; Skinner, Robert A.; Hogue, William R.; Budde, Ulrich; Varughese, Kottayil I.; Kanaji, Taisuke; Ware, Jerry

    2008-01-01

    The platelet glycoprotein Ib-IX receptor binds surface-bound von Willebrand factor and supports platelet adhesion to damaged vascular surfaces. A limited number of mutations within the glycoprotein Ib-IX complex have been described that permit a structurally altered receptor to interact with soluble von Willebrand factor, and this is the molecular basis of platelet-type von Willebrand disease. We have developed and characterized a mouse model of platelet-type von Willebrand disease (G233V) and have confirmed a platelet phenotype mimicking the human disorder. The mice have a dramatic increase in splenic megakaryocytes and splenomegaly. Recent studies have demonstrated that hematopoetic cells can influence the differentiation of osteogenic cells. Thus, we examined the skeletal phenotype of mice expressing the G233V variant complex. At 6 months of age, G233V mice exhibit a high bone mass phenotype with an approximate doubling of trabecular bone volume in both the tibia and femur. Serum measures of bone resorption were significantly decreased in G233V animals. With decreased bone resorption, cortical thickness was increased, medullary area decreased, and consequently, the mechanical strength of the femur was significantly increased. Using ex vivo bone marrow cultures, osteoclast-specific staining in the G233V mutant marrow was diminished, whereas osteoblastogenesis was unaffected. These studies provide new insights into the relationship between the regulation of megakaryocytopoiesis and bone mass. PMID:18187573

  16. MSFC Director welcomes attendees to the 10th Annual Wernher von

    NASA Image and Video Library

    2017-10-26

    Marshall Space Flight Center director Todd May welcomes attendees to the 10th annual Dr. Wernher von Braun Memorial Symposium held at the University of Alabama, Huntsville, Alabama. The three-day symposium brought together experts for discussion panels on science, engineering and technology under the theme “Gateways in Space: Exploration, Security, and Commerce.”

  17. Einheit von Forschung und Lehre: Implications for State Funding of Universities

    ERIC Educational Resources Information Center

    Frolich, Nicoline; Coate, Kelly; Mignot-Gerard, Stephanie; Knill, Christoph

    2010-01-01

    The Humboldtian educational ideal is based on the idea of the unity of teaching and research in universities ("Einheit von Forschung und Lehre"). The role of the state, according to Humboldt, was to fund universities in such a way that their autonomy was maintained. Much has changed in the funding mechanisms of higher education systems…

  18. Confounding of the Association between Radiation Exposure from CT Scans and Risk of Leukemia and Brain Tumors by Cancer Susceptibility Syndromes.

    PubMed

    Meulepas, Johanna M; Ronckers, Cécile M; Merks, Johannes; Weijerman, Michel E; Lubin, Jay H; Hauptmann, Michael

    2016-01-01

    Recent studies linking radiation exposure from pediatric computed tomography (CT) to increased risks of leukemia and brain tumors lacked data to control for cancer susceptibility syndromes (CSS). These syndromes might be confounders because they are associated with an increased cancer risk and may increase the likelihood of CT scans performed in children. We identify CSS predisposing to leukemia and brain tumors through a systematic literature search and summarize prevalence and risk estimates. Because there is virtually no empirical evidence in published literature on patterns of CT use for most types of CSS, we estimate confounding bias of relative risks (RR) for categories of radiation exposure based on expert opinion about the current and previous patterns of CT scans among CSS patients. We estimate that radiation-related RRs for leukemia are not meaningfully confounded by Down syndrome, Noonan syndrome, or other CSS. In contrast, RRs for brain tumors may be overestimated due to confounding by tuberous sclerosis complex (TSC) while von Hippel-Lindau disease, neurofibromatosis type 1, or other CSS do not meaningfully confound. Empirical data on the use of CT scans among CSS patients are urgently needed. Our assessment indicates that associations with leukemia reported in previous studies are unlikely to be substantially confounded by unmeasured CSS, whereas brain tumor risks might have been overestimated due to confounding by TSC. Future studies should identify TSC patients in order to avoid overestimation of brain tumor risks due to radiation exposure from CT scans. ©2015 American Association for Cancer Research.

  19. POTASSIUM BROMATE-INDUCED RAT CLEAR CELL RENAL TUMOR IS INDEPENDENT OF CODING REGION MUTATIONS IN THE VON HIPPEL- LINDAU GENE

    EPA Science Inventory

    Potassium bromate (KBr03) is a rat renal carcinogen and a major drinking water disinfection by-product from ozonization. While KBr03 is a human nephro- and neuro-toxicant, its carcinogenicity in humans is unknown. Clear cell renal tumors, the common form of human renal carcinomas...

  20. L'atteinte vésicale au cours de la neurofibromatose de Von Recklinghausen

    PubMed Central

    Benazzouz, Mohamed Hicham; Hajjad, Tilila; Essatara, Younes; El Sayegh, Hachem; Iken, Ali; Benslimane, Lounis; Nouini, Yassine

    2014-01-01

    La neurofibromatose de type 1 ou maladie de Von Recklinghausen est une maladie génétique autosomique dominante en rapport avec des mutations dans le gène suppresseur de tumeur NF1. L'atteinte uro-génitale au cours de cette maladie est rare et moins de 80 cas ont été rapportés à ce jour dans la littérature mondiale. Les auteurs rapportent un nouveau cas d'atteinte vésicale découverte fortuitement au cours du suivi d'une patiente atteinte de la maladie de Von Recklinghausen. A travers cette observation et une revue de la littérature les auteurs discutent également les difficultés diagnostiques, thérapeutiques ainsi que les modalités de suivi dans cette maladie. PMID:25328590

  1. Galerkin analysis of kinematic dynamos in the von Kármán geometry

    NASA Astrophysics Data System (ADS)

    Marié, L.; Normand, C.; Daviaud, F.

    2006-01-01

    We investigate dynamo action by solving the kinematic dynamo problem for velocity fields of the von Kármán type between two coaxial counter-rotating propellers in a cylinder. A Galerkin method is implemented that takes advantage of the symmetries of the flow and their subsequent influence on the nature of the magnetic field at the dynamo threshold. Distinct modes of instability have been identified that differ by their spatial and temporal behaviors. Our calculations give the result that a stationary and antisymmetric mode prevails at the dynamo threshold. We then present a quantitative analysis of the results based on the parametric study of four interaction coefficients obtained by reduction of our initially large eigenvalue problem. We propose these coefficients to measure the relative importance of the different mechanisms at play in the von Kármán kinematic dynamo.

  2. Quantitative conditions for time evolution in terms of the von Neumann equation

    NASA Astrophysics Data System (ADS)

    Wang, WenHua; Cao, HuaiXin; Chen, ZhengLi; Wang, Lie

    2018-07-01

    The adiabatic theorem describes the time evolution of the pure state and gives an adiabatic approximate solution to the Schödinger equation by choosing a single eigenstate of the Hamiltonian as the initial state. In quantum systems, states are divided into pure states (unite vectors) and mixed states (density matrices, i.e., positive operators with trace one). Accordingly, mixed states have their own corresponding time evolution, which is described by the von Neumann equation. In this paper, we discuss the quantitative conditions for the time evolution of mixed states in terms of the von Neumann equation. First, we introduce the definitions for uniformly slowly evolving and δ-uniformly slowly evolving with respect to mixed states, then we present a necessary and sufficient condition for the Hamiltonian of the system to be uniformly slowly evolving and we obtain some upper bounds for the adiabatic approximate error. Lastly, we illustrate our results in an example.

  3. Estimating age at a specified length from the von Bertalanffy growth function

    USGS Publications Warehouse

    Ogle, Derek H.; Isermann, Daniel A.

    2017-01-01

    Estimating the time required (i.e., age) for fish in a population to reach a specific length (e.g., legal harvest length) is useful for understanding population dynamics and simulating the potential effects of length-based harvest regulations. The age at which a population reaches a specific mean length is typically estimated by fitting a von Bertalanffy growth function to length-at-age data and then rearranging the best-fit equation to solve for age at the specified length. This process precludes the use of standard frequentist methods to compute confidence intervals and compare estimates of age at the specified length among populations. We provide a parameterization of the von Bertalanffy growth function that has age at a specified length as a parameter. With this parameterization, age at a specified length is directly estimated, and standard methods can be used to construct confidence intervals and make among-group comparisons for this parameter. We demonstrate use of the new parameterization with two data sets.

  4. von Neumann's Law: Theoretical and Microgravity Experimental Comparison for Coarsening Diffusion in Bubble Lattices

    NASA Technical Reports Server (NTRS)

    Noever, David A.

    2000-01-01

    The effects of gravity in influencing the theoretical limit for bubble lattice coarsening and aging behavior, otherwise called von Neumann's law, is examined theoretically and experimentally. Preliminary microgravity results will be discussed.

  5. Detailed von Willebrand factor multimer analysis in patients with von Willebrand disease in the European study, molecular and clinical markers for the diagnosis and management of type 1 von Willebrand disease (MCMDM-1VWD).

    PubMed

    Budde, U; Schneppenheim, R; Eikenboom, J; Goodeve, A; Will, K; Drewke, E; Castaman, G; Rodeghiero, F; Federici, A B; Batlle, J; Pérez, A; Meyer, D; Mazurier, C; Goudemand, J; Ingerslev, J; Habart, D; Vorlova, Z; Holmberg, L; Lethagen, S; Pasi, J; Hill, F; Peake, I

    2008-05-01

    Type 1 von Willebrand disease (VWD) is a congenital bleeding disorder characterized by a partial quantitative deficiency of plasma von Willebrand factor (VWF) in the absence of structural and/or functional VWF defects. Accurate assessment of the quantity and quality of plasma VWF is difficult but is a prerequisite for correct classification. To evaluate the proportion of misclassification of patients historically diagnosed with type 1 VWD using detailed analysis of the VWF multimer structure. Previously diagnosed type 1 VWD families and healthy controls were recruited by 12 expert centers in nine European countries. Phenotypic characterization comprised plasma VWF parameters and multimer analysis using low- and intermediate-resolution gels combined with an optimized visualization system. VWF genotyping was performed in all index cases (ICs). Abnormal multimers were present in 57 out of 150 ICs; however, only 29 out of these 57 (51%) had VWF ristocetin cofactor to antigen ratio below 0.7. In most cases multimer abnormalities were subtle, and only two cases had a significant loss of the largest multimers. Of the cases previously diagnosed as type 1 VWD, 38% showed abnormal multimers. Depending on the classification criteria used, 22 out of these 57 cases (15% of the total cohort) may be reclassified as type 2, emphasizing the requirement for multimer analysis compared with a mere ratio of VWF functional parameters and VWF:Ag. This is further supported by the finding that even slightly aberrant multimers are highly predictive for the presence of VWF mutations.

  6. Analysis of nuclear accumulation of influenza NP antigen in von Magnus virus-infected cells.

    PubMed

    Maeno, K; Aoki, H; Hamaguchi, M; Iinuma, M; Nagai, Y; Matsumoto, T; Takeura, S; Shibata, M

    1981-01-01

    When 1-5C-4 cells were infected with von Magnus virus derived from influenza A/RI/5+ virus by successive undiluted passages in chick embryos, virus-specific proteins were synthesized but production of infectious virus was inhibited. In these cells the synthesis of viral RNA was suppressed and the nucleoprotein (NP) antigen was found predominantly in the nucleus in contrast to standard virus-infected cells in which the antigen was distributed throughout the whole cell. The intracellular location and migration of NP were determined by isotope labeling and sucrose gradient centrifugation of subcellular fractions. In standard virus-infected cell NP polypeptide was present predominantly in the cytoplasm in the form of viral ribonucleoprotein (RNP) and intranuclear RNP was detected in reduced amounts. In contrast, in von Magnus virus-infected cells NP polypeptide was present predominantly in the nucleus in a nonassembled, soluble from and the amount of cytoplasmic RNP was considerably reduced. After short-pulse labeling NP was detected exclusively in the cytoplasm in a soluble form and after a chase a large proportion of such soluble NP was seen in the nucleus. It is suggested that a large proportion of the NP synthesized in von Magnus virus-infected cells in not assembled into cytoplasmic RNP because of the lack of available RNA and the NP migrated into the nucleus and remained there.

  7. How Alexander von Humboldt's life story can inspire innovative soil research in developing countries

    NASA Astrophysics Data System (ADS)

    Bouma, Johan

    2017-09-01

    The pioneering vision of Alexander von Humboldt of science and society of the early 1800s is still highly relevant today. His open mind and urge to make many measurements characterizing the interconnected web of life are crucial ingredients as we now face the worldwide challenge of the UN Sustainable Development Goals. Case studies in the Philippines, Vietnam, Kenya, Niger, and Costa Rica demonstrate, in Alexander's spirit, interaction with stakeholders and attention to unique local conditions, applying modern measurement and modeling methods and allowing inter- and transdisciplinary research approaches. But relations between science and society are increasingly problematic, partly as a result of the information revolution and post-truth, fact-free thinking. Overly regulated and financially restricted scientific communities in so-called developed countries may stifle intellectual creativity. Researchers in developing countries are urged to leapfrog these problems in the spirit of Alexander von Humboldt as they further develop their scientific communities. Six suggestions to the science community are made with particular attention to soil science. (The Humboldt lecture, presented by the 2017 recipient of the Alexander von Humboldt lecture, Johan Bouma, can be accessed at http://client.cntv.at/egu2017/ml1.)

  8. Critical assessment of von Mises distribution and an infinite series ansatz for self-propelled particles

    NASA Astrophysics Data System (ADS)

    Kürsten, Rüdiger; Ihle, Thomas

    2017-03-01

    We consider a Vicsek model of self-propelled particles with bounded confidence, where each particle interacts only with neighbors that have a similar direction. Depending on parameters, the system exhibits a continuous or discontinuous polar phase transition from the isotropic phase to a phase with a preferred direction. In a recent paper (Lam, Schindler and Dauchot 2015 J. Stat. Mech. P10017) the von Mises distribution was proposed as an ansatz for polar ordering. In the present system the time evolution of the angular distribution can be solved in Fourier space. We compare the results of the Fourier analysis with the ones obtained by using the von Mises distribution ansatz. In the latter case the qualitative behavior of the system is recovered correctly. However, quantitatively there are serious deviations. We introduce an extended von Mises distribution ansatz such that a second term takes care of the next two Fourier modes. With the extended ansatz we find much better quantitative agreement. As an alternative approach we also use a Gaussian and a geometric series ansatz in Fourier space. The geometric series ansatz is analytically handable but fails for very weak noise, the Gaussian ansatz yields better results but it is not analytically treatable.

  9. A visit paid to Jung by Alwine von Keller.

    PubMed

    Bernardini, Riccardo; Quaglino, Gian Piero; Romano, Augusto

    2011-04-01

    In the winter of 1943-1944, Jung had suffered a coronary thrombosis which almost cost him his life. During his illness, Jung experienced a series of visions, described in his Memories, Dreams, Reflections, which were also to influence significantly the development of his theoretical thinking. On 27(th) September 1944, Alwine von Keller (1878-1965) paid a visit to Jung, while he was still convalescing, in Zurich and documented her meeting with him in a series of notes, recently discovered, which testify to the fact that, at the time of their meeting, Jung was engaged in writing the 'Salt' chapter of Mysterium coniunctionis and investigating the alchemistic symbolism of the 'sea'. This theme seems to testify to a continuity of interests on Jung's part with the seminar he held at Eranos the previous year on the cartographic art of Opicinus de Canistris (1296-c.1352). With its addition of many unpublished details, Alwine von Keller's notes supplement the report which Jung made of his visions experienced during his sickness in MDR. In particular, these attest to the fact that Jung had attributed the terrible experience which he had endured to the problem of the conjunctio, which was confronting him from the theoretical point of view in his writing of Mysterium coniunctionis. © 2011, The Society of Analytical Psychology.

  10. The (re)-introduction of semiotics into medical education: on the works of Thure von Uexküll.

    PubMed

    Tredinnick-Rowe, John

    2017-03-01

    Thure von Uexküll's reputation as a pioneer in biosemiotics and also in psychosomatic medicine is well documented. It is easy to see these disciplines reflected in his notable publications, both in English and in German. However, if one spares the time to filter through all of his articles, monographs, conference papers and editorials in English and in German, a notable gap arises in his English language publications: that of clinical education. This gap in the English language literature may seem unimportant in and of itself, but it speaks volumes when we consider the total absence of medical semiotics in the curriculum of medical schools in the English speaking world. This runs in stark contrast to the strong traditions of psychosomatic medicine in Germany, which Thure von Uexküll largely helped to instil. Do the works of Thure von Uexküll offer a possible step towards a resurrection of medical semiotics in clinical education? This chapter attempts to explore the lesser known German literature on clinical education that Thure von Uexküll produced, and explore the role semiotics can play in Medical Education in the English speaking world. While also seeking to contrast this literature with other existing approaches in British and American medical schools who have attempted to reintroduce medical humanities and reflexive thinking into clinical education. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  11. Hemophilia and von Willebrand's disease: 2. Management. Association of Hemophilia Clinic Directors of Canada.

    PubMed Central

    1995-01-01

    OBJECTIVE: To present current strategies for the treatment of hemophilia and von Willebrand's disease. OPTIONS: Prophylactic and corrective therapy with hemostatic and adjunctive agents: DDAVP (1-desamino-8-D-arginine vasopressin [desmopressin acetate]), recombinant coagulation products (human Factor VIII and human Factor VIIa) or virally inactivated plasma-derived products (high- or ultra-high-purity human Factor VIII or human Factor VIII concentrate containing von Willebrand factor activity, porcine Factor VIII, high-purity human Factor IX, human prothrombin-complex concentrate, human activated prothrombin-complex concentrate), adjunctive antifibrinolytic agents, topical thrombin and fibrin sealant. The induction of immune tolerance in patients in whom inhibitors develop should also be considered. OUTCOMES: Morbidity and quality of life associated with bleeding and treatment. EVIDENCE: Relevant clinical studies and reports published from 1974 to 1994 were examined. A search was conducted of our reprint files, MEDLINE, citations in the articles reviewed and references provided by colleagues. In the MEDLINE search the following terms were used singly or in combination: "hemophilia," "von Willebrand's disease," "Factor VIII," "Factor IX," "von Willebrand factor," "diagnosis," "management," "home care," "comprehensive care," "inhibitor," "AIDS," "hepatitis," "life expectancy," "complications," "practice guidelines," "consensus statement" and "controlled trial." The in-depth review included only articles written in English from North America and Europe that were relevant to human disease and pertinent to a predetermined outline. The availability of treatment products in Canada was also considered. VALUES: Minimizing morbidity and maximizing functional status and quality of life were given a high value. BENEFITS, HARMS AND COSTS: Proper prophylactic or early treatment with appropriate hemostatic agents minimizes morbidity and functional disability and improves quality

  12. Werner von Braun relaxes after successful Apollo 11 Saturn V launch

    NASA Technical Reports Server (NTRS)

    1969-01-01

    Dr. Wernher von Braun, director of the Marshall Space Flight Center, Huntsville, Alabama, relaxes after the successful launch of Apollo 11 astronauts Neil A. Armstrong, Michael Collins and Edwin Aldrin Jr. today. Their historic lunar landing mission began at 9:32 a.m. EDT, July 16, 1969, when an Apollo/Saturn V space vehicle lifted off from the spaceport's Launch Complex 39A.

  13. Dr. von Braun Relaxes After the Successful Launch of Apollo 11

    NASA Technical Reports Server (NTRS)

    1969-01-01

    Dr. Wernher von Braun, first director of the Marshall Space Flight Center, relaxes following the successful launch of the Saturn V carrying Apollo 11 to the moon. The towering 363-foot Saturn V was a multi-stage, multi-engine launch vehicle standing taller than the Statue of Liberty. Altogether, the Saturn V engines produced as much power as 85 Hoover Dams.

  14. Bone tumor

    MedlinePlus

    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 ...

  15. Displacements Of Brownian Particles In Terms Of Marian Von Smoluchowski's Heuristic Model

    ERIC Educational Resources Information Center

    Klein, Hermann; Woermann, Dietrich

    2005-01-01

    Albert Einstein's theory of the Brownian motion, Marian von Smoluchowski's heuristic model, and Perrin's experimental results helped to bring the concept of molecules from a state of being a useful hypothesis in chemistry to objects existing in reality. Central to the theory of Brownian motion is the relation between mean particle displacement and…

  16. Otto von Guericke and 17th century cosmology

    NASA Astrophysics Data System (ADS)

    Knobloch, Eberhard

    Otto von Guericke's scientific method was based on reason and experimental science. His cosmology was embedded in theology and can be interpreted as a refutation of Descartes' worldview. He used Nicolaus Cusanus' theory of quantities in order to characterize space. The notion of space has to be distinguished from that of world or heaven. Forces play a crucial role in this respect described by Athanasius Kircher in his "Celestial Journey". Guericke read this work very diligently. In spite of some obvious similarities between Guericke's and Newton's scientific aims and methods there are crucial differences between the scientific convictions and results of these scholars.

  17. Wnt5a suppresses tumor formation and redirects tumor phenotype in MMTV-Wnt1 tumors.

    PubMed

    Easter, Stephanie L; Mitchell, Elizabeth H; Baxley, Sarah E; Desmond, Renee; Frost, Andra R; Serra, Rosa

    2014-01-01

    Wnt5a is a non-canonical signaling Wnt that has been implicated in tumor suppression. We previously showed that loss of Wnt5a in MMTV-PyVmT tumors resulted in a switch in tumor phenotype resulting in tumors with increased basal phenotype and high Wnt/β-catenin signaling. The object of this study was to test the hypothesis that Wnt5a can act to inhibit tumors formed by activation of Wnt/β-catenin signaling. To this end, we characterized tumor and non-tumor mammary tissue from MMTV-Wnt1 and double transgenic MMTV-Wnt1;MMTV-Wnt5a mice. Wnt5a containing mice demonstrated fewer tumors with increased latency when compared to MMTV-Wnt1 controls. Expression of markers for basal-like tumors was down-regulated in the tumors that formed in the presence of Wnt5a indicating a phenotypic switch. Reduced canonical Wnt signaling was detected in double transgenic tumors as a decrease in active β-catenin protein and a decrease in Axin2 mRNA transcript levels. In non-tumor tissues, over-expression of Wnt5a in MMTV-Wnt1 mammary glands resulted in attenuation of phenotypes normally observed in MMTV-Wnt1 glands including hyperbranching and increased progenitor and basal cell populations. Even though Wnt5a could antagonize Wnt/β-catenin signaling in primary mammary epithelial cells in culture, reduced Wnt/β-catenin signaling was not detected in non-tumor MMTV-Wnt1;Wnt5a tissue in vivo. The data demonstrate that Wnt5a suppresses tumor formation and promotes a phenotypic shift in MMTV-Wnt1 tumors.

  18. Kamera-basierte Erkennung von Geschwindigkeitsbeschränkungen auf deutschen Straen

    NASA Astrophysics Data System (ADS)

    Nienhüser, Dennis; Ziegenmeyer, Marco; Gumpp, Thomas; Scholl, Kay-Ulrich; Zöllner, J. Marius; Dillmann, Rüdiger

    An Fahrerassistenzsysteme im industriellen Einsatz werden hohe Anforderungen bezüglich Zuverlässigkeit und Robustheit gestellt. In dieser Arbeit wird die Kombination robuster Verfahren wie der Hough-Transformation und Support-Vektor-Maschinen zu einem Gesamtsystem zur Erkennung von Geschwindigkeitsbeschränkungen beschrieben. Es setzt eine Farbvideokamera als Sensorik ein. Die Evaluation auf Testdaten bestätigt durch die ermittelte hohe Korrektklassifikationsrate bei gleichzeitig geringer Zahl Fehlalarme die Zuverlässigkeit des Systems.

  19. Collecting Tumor Samples From Patients With Gynecological Tumors

    ClinicalTrials.gov

    2016-10-26

    Borderline Ovarian Clear Cell Tumor; Borderline Ovarian Serous Tumor; Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Childhood Embryonal Rhabdomyosarcoma; Childhood Malignant Ovarian Germ Cell Tumor; Endometrioid Stromal Sarcoma; Gestational Trophoblastic Tumor; Malignant Mesothelioma; Malignant Ovarian Epithelial Tumor; Melanoma; Neoplasm of Uncertain Malignant Potential; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Paget Disease of the Vulva; Recurrent Cervical Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Recurrent Vaginal Carcinoma; Recurrent Vulvar Carcinoma; Stage I Ovarian Cancer; Stage I Uterine Corpus Cancer; Stage I Vaginal Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Cervical Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage II Uterine Corpus Cancer; Stage II Vaginal Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Cervical Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage III Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage III Cervical Cancer; Stage III Uterine Corpus Cancer; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell

  20. IR studies of the impact of Ge doping on the successive conversion of VOn defects in Czochralski-Si containing carbon

    NASA Astrophysics Data System (ADS)

    Londos, C. A.; Andrianakis, A.; Sgourou, E. N.; Emtsev, V. V.; Ohyama, H.

    2011-02-01

    We report infrared absorption studies of oxygen-related defects in electron-irradiated Ge-doped Czochralski-Si. Our investigation was mainly focused on the reaction channel leading to the formation of VOn (1≤n≤6) defects. The VOn defects form mainly upon annealing, as a result of the successive aggregation of oxygen atoms in the initial VO defect produced by the irradiation: (VO+Oi→VO2+Oi→VO3+Oi→VO4,…). It was found that the ratio of the conversion of VOn to VOn+1 defects is sensitive to the Ge content of the material. In particular, the ratio of the conversion of the VO to the VO2 defects was found to decrease with the increase in Ge concentration of the samples, although the opposite trend was observed for the VO3 to VO4 conversion. However, the VO2 to VO3 conversion changes only slightly with Ge content, being practically unaffected for Ge concentrations up to 2×1020 cm-3. In the case of VO2 formation, the phenomenon was attributed to the elastic strains induced in the lattice due to the Ge presence which affects the balance between the reactions VO+Oi→VO2, VO+SiI→Oi, mainly involved in the decay of the VO and the growth of the VO2 defects. In the case of VO4 formation, the phenomenon was discussed by taking into account the enhancement of the diffusivity of the Oi atoms in the Ge-doped Si, which could lead to an enhancement of the rate of the reaction VO3+Oi→VO4. For the VO3 formation this effect is practically negligible due to the fact that at the temperatures of VO2 to VO3 conversion oxygen diffusivity is quite small. The exhibited behavior in the conversion of the VOn to VOn+1 defects (n=1,2,3) was similar in Ge-doped samples with low carbon content ([Cs]<2×1016 cm-3) and in Ge-doped samples with high carbon content ([Cs]≥1×1017 cm-3). The impact of C as well as its role in the conversion efficiency of VO to VO2 was studied by comparing the spectra in low carbon and high carbon Ge free Si material. Furthermore, a pair of bands at

  1. Citizenship Ceremony for Dr. von Braun and German-Born Scientists and Engineers

    NASA Technical Reports Server (NTRS)

    1955-01-01

    In a swearing-in ceremony held at Huntsville High School, one hundred and three German-born scientists and engineers, along with family members, took the oath of citizenship to become United States citizens. Among those taking the oath was Dr. Wernher von Braun, located in the second row, right side, third from the end.

  2. Differential tumor microenvironment in human ovarian cystic tumors.

    PubMed

    Tavares Murta, Beatriz Martins; Cunha, Fernando de Queiróz; Miranda, Rodrigo; Adad, Sheila Jorge; Murta, Eddie Fernando Candido

    2004-01-01

    Cells and soluble mediators obtained from tumor effusions are useful in evaluating the tumor microenvironment. Our aim was to examine cytologically and to quantify the leukocyte infiltrate, nitric oxide, cytokines and tumor markers in the intracystic fluid from patients with a cystic adnexal mass, for a possible differentiation between benign and malignant findings. Sixty-six women who had their cystic fluids collected were prospectively divided into benign tumor (22, 33.3%), malignant tumor (10, 15.2%) or other gynecological alterations (34, 51.5%). Cytology, total and differential leukocyte counts were determined by light microscopy. Tumor markers, cytokines and nitric oxide were assayed in the supernatants using the Immulite system, ELISA and Griess reaction, respectively. The sensitivity and specificity of the cytological analysis was 66.7% and 97.7%, respectively. The levels of CA 19.9, CA 15.3, alpha-fetoprotein, carcinoembryonic antigen, progesterone and beta-HCG were significantly higher in the benign and/or malignant group than in the other gynecological alterations. Also, the local concentrations of CA 15.3 and beta-HCG were significantly higher in malignant than in benign tumors. In malignant tumors, increased leukocyte counts and higher concentrations of IL-6, IL-10 and nitric oxide were detected than in benign tumors or other gynecological alterations. In malignant tumors, the microenvironment could be differentiated from benign tumors or other gynecological alterations by cystic fluid analysis.

  3. Identification of Langmuir wave turbulence-supercontinuum transition by application of von Neumann entropy

    NASA Astrophysics Data System (ADS)

    Kawamori, Eiichirou

    2017-09-01

    A transition from Langmuir wave turbulence (LWT) to coherent Langmuir wave supercontinuum (LWSC) is identified in one-dimensional particle-in-cell simulations as the emergence of a broad frequency band showing significant temporal coherence of a wave field accompanied by a decrease in the von Neumann entropy of classical wave fields. The concept of the von Neumann entropy is utilized for evaluation of the phase-randomizing degree of the classical wave fields, together with introduction of the density matrix of the wave fields. The transition from LWT to LWSC takes place when the energy per one plasmon (one wave quantum) exceeds a certain threshold. The coherent nature, which Langmuir wave systems acquire through the transition, is created by four wave mixings of the plasmons. The emergence of temporal coherence and the decrease in the phase randomization are considered as the development of long-range order and spontaneous symmetry breaking, respectively, indicating that the LWT-LWSC transition is a second order phase transition phenomenon.

  4. The astronomer of the duchess -- Life and work of Franz Xaver von Zach 1754-1832. (German Title: Der Astronom der Herzogin -- Leben und Werk von Franz Xaver von Zach 1754-1832)

    NASA Astrophysics Data System (ADS)

    Brosche, Peter

    The astronomer, geodesist, geographer and historian of science Franz Xaver von Zach (1754-1832) lived and worked in several European countries. Duke Ernst II of Saxe-Gotha-Altenburg appointed him as the founding scientist of his Seeberg Observatory. This was the place of his strongest activity. Why should we have an interest in him today? There is a rational and an emotional answer. First, he has rendered organisational services to his sciences which are equivalent to a great scientific achievement. Second, Zach was a very colourful character, travelled across many states in a time of radical changes and had connections with many colleagues and public figures. Images from his life therefore provide outlooks, insights and relations.

  5. THE TUMOR MACROENVIRONMENT: CANCER-PROMOTING NETWORKS BEYOND TUMOR BEDS

    PubMed Central

    Rutkowski, Melanie R.; Svoronos, Nikolaos; Puchalt, Alfredo Perales; Conejo-Garcia, Jose R.

    2015-01-01

    During tumor progression, alterations within the systemic tumor environment, or macroenvironment, result in the promotion of tumor growth, tumor invasion to distal organs, and eventual metastatic disease. Distally produced hormones, commensal microbiota residing within mucosal surfaces, and myeloid cells and even the bone marrow impact the systemic immune system, tumor growth, and metastatic spread. Understanding the reciprocal interactions between the cells and soluble factors within the macroenvironment and the primary tumor will enable the design of specific therapies that have the potential to prevent dissemination and metastatic spread. This chapter will summarize recent findings detailing how the primary tumor and systemic tumor macroenvironment coordinate malignant progression. PMID:26216635

  6. Haploinsufficiency in tumor predisposition syndromes: altered genomic transcription in morphologically normal cells heterozygous for VHL or TSC mutation

    PubMed Central

    Peri, Suraj; Caretti, Elena; Tricarico, Rossella; Devarajan, Karthik; Cheung, Mitchell; Sementino, Eleonora; Menges, Craig W.; Nicolas, Emmanuelle; Vanderveer, Lisa A.; Howard, Sharon; Conrad, Peggy; Crowell, James A.; Campbell, Kerry S.; Ross, Eric A.; Godwin, Andrew K.; Yeung, Anthony T.; Clapper, Margie L.; Uzzo, Robert G.; Henske, Elizabeth P.; Ricketts, Christopher J.; Vocke, Cathy D.; Linehan, W. Marston; Testa, Joseph R.; Bellacosa, Alfonso; Kopelovich, Levy; Knudson, Alfred G.

    2017-01-01

    Tumor suppressor genes and their effector pathways have been identified for many dominantly heritable cancers, enabling efforts to intervene early in the course of disease. Our approach on the subject of early intervention was to investigate gene expression patterns of morphologically normal one-hit cells before they become hemizygous or homozygous for the inherited mutant gene which is usually required for tumor formation. Here, we studied histologically non-transformed renal epithelial cells from patients with inherited disorders that predispose to renal tumors, including von Hippel-Lindau (VHL) disease and Tuberous Sclerosis (TSC). As controls, we studied histologically normal cells from non-cancerous renal epithelium of patients with sporadic clear cell renal cell carcinoma (ccRCC). Gene expression analyses of VHLmut/wt or TSC1/2mut/wt versus wild-type (WT) cells revealed transcriptomic alterations previously implicated in the transition to precancerous renal lesions. For example, the gene expression changes in VHLmut/wt cells were consistent with activation of the hypoxia response, associated, in part, with the Warburg effect. Knockdown of any remaining VHL mRNA using shRNA induced secondary expression changes, such as activation of NF?B and interferon pathways, that are fundamentally important in the development of RCC. We posit that this is a general pattern of hereditary cancer predisposition, wherein haploinsufficiency for VHL or TSC1/2, or potentially other tumor susceptibility genes, is sufficient to promote development of early lesions, while cancer results from inactivation of the remaining normal allele. The gene expression changes identified here are related to the metabolic basis of renal cancer and may constitute suitable targets for early intervention. PMID:27682873

  7. Systemic Sunitinib Malate Treatment for Advanced Juxtapapillary Retinal Hemangioblastomas Associated with von Hippel-Lindau Disease.

    PubMed

    Knickelbein, Jared E; Jacobs-El, Naima; Wong, Wai T; Wiley, Henry E; Cukras, Catherine A; Meyerle, Catherine B; Chew, Emily Y

    2017-01-01

    To describe the clinical course of advanced juxtapapillary retinal capillary hemangioblastomas (RCH) associated with von Hippel-Lindau (VHL) disease treated with systemic sunitinib malate, an agent that inhibits both anti-vascular endothelial growth factor and anti-platelet-derived growth factor signaling. Observational case review. Three patients with advanced VHL-related juxtapapillary RCH treated with systemic sunitinib malate. Patient 1 was followed routinely every 4 months while on systemic sunitinib prescribed by her oncologist for metastatic pancreatic neuroendocrine and kidney tumors. Patients 2 and 3 were part of a prospective clinical trial evaluating the use of systemic sunitinib for ocular VHL lesions during a period of 9 months. Visual acuity, size of RCH, and degree of exudation were recorded at each visit. Optical coherence tomography (OCT) and fluorescein angiography were also obtained at some visits. Visual acuity, size of RCH, and degree of exudation. Three patients with advanced VHL-associated juxtapapillary RCH were treated with systemic sunitinib malate. While none of the patients lost vision during therapy, treatment with sunitinib malate did not improve visual acuity or reduce the size of RCH. Improvements in RCH-associated retinal edema were observed in two patients. All patients experienced multiple adverse effects, including thyroid toxicity, thrombocytopenia, nausea, fatigue, jaundice, and muscle aches. Two of the three patients had to discontinue treatment prematurely and the third required dose reduction. Systemic sunitinib malate may be useful in slowing progression of ocular disease from VHL-associated RCH. However, significant systemic adverse effects limited its use in this small series, and systemic sunitinib malate may not be safe for treatment of RCH when used at the doses described in this report. Further studies are required to determine if this medication used at lower doses with different treatment strategies, other

  8. Systemic Sunitinib Malate Treatment for Advanced Juxtapapillary Retinal Hemangioblastomas Associated with von Hippel-Lindau Disease

    PubMed Central

    Knickelbein, Jared E.; Jacobs-El, Naima; Wong, Wai T.; Wiley, Henry E.; Cukras, Catherine A.; Meyerle, Catherine B.; Chew, Emily Y.

    2016-01-01

    Purpose To describe the clinical course of advanced juxtapapillary retinal capillary hemangioblastomas (RCH) associated with von Hippel-Lindau (VHL) disease treated with systemic sunitinib malate, an agent that inhibits both anti-vascular endothelial growth factor and anti-platelet-derived growth factor signaling. Design Observational case review. Participants Three patients with advanced VHL-related juxtapapillary RCH treated with systemic sunitinib malate. Methods Patient 1 was followed routinely every 4 months while on systemic sunitinib prescribed by her oncologist for metastatic pancreatic neuroendocrine and kidney tumors. Patients 2 and 3 were part of a prospective clinical trial evaluating the use of systemic sunitinib for ocular VHL lesions during a period of 9 months. Visual acuity, size of RCH, and degree of exudation were recorded at each visit. Optical coherence tomography (OCT) and fluorescein angiography were also obtained at some visits. Main Outcome Measures Visual acuity, size of RCH, and degree of exudation. Results Three patients with advanced VHL-associated juxtapapillary RCH were treated with systemic sunitinib malate. While none of the patients lost vision during therapy, treatment with sunitinib malate did not improve visual acuity or reduce the size of RCH. Improvements in RCH-associated retinal edema were observed in two patients. All patients experienced multiple adverse effects, including thyroid toxicity, thrombocytopenia, nausea, fatigue, jaundice, and muscle aches. Two of the three patients had to discontinue treatment prematurely and the third required dose reduction. Conclusions Systemic sunitinib malate may be useful in slowing progression of ocular disease from VHL-associated RCH. However, significant systemic adverse effects limited its use in this small series, and systemic sunitinib malate may not be safe for treatment of RCH when used at the doses described in this report. Further studies are required to determine if this

  9. Perfecting the Individual: Wilhelm von Humboldt's Concept of Anthropology, "Bildung" and Mimesis

    ERIC Educational Resources Information Center

    Wulf, Christoph

    2003-01-01

    In the works of Wilhelm von Humboldt education took on a new quality, focusing firmly on the importance of the individual. "Bildung" was to become the principal task with a view to preparing the individual for the requirements of future life. In this article, the author investigates two aspects relating to the "Bildung" of the individual. First,…

  10. The Tumor Macroenvironment: Cancer-Promoting Networks Beyond Tumor Beds.

    PubMed

    Rutkowski, Melanie R; Svoronos, Nikolaos; Perales-Puchalt, Alfredo; Conejo-Garcia, Jose R

    2015-01-01

    During tumor progression, alterations within the systemic tumor environment, or macroenvironment, result in the promotion of tumor growth, tumor invasion to distal organs, and eventual metastatic disease. Distally produced hormones, commensal microbiota residing within mucosal surfaces, myeloid cells and even the bone marrow impact the systemic immune system, tumor growth, and metastatic spread. Understanding the reciprocal interactions between the cells and soluble factors within the macroenvironment and the primary tumor will enable the design of specific therapies that have the potential to prevent dissemination and metastatic spread. This chapter will summarize recent findings detailing how the primary tumor and systemic tumor macroenvironment coordinate malignant progression. © 2015 Elsevier Inc. All rights reserved.

  11. "The captain and canon" C. W. A. von Wahl (1760-1846) (German Title: "Der Hauptmann und Kanonikus" C. W. A. von Wahl (1760-1846) )

    NASA Astrophysics Data System (ADS)

    Brosche, Peter

    Von Wahl was an active member of the group of independent scholars, who were working in the German states within Goethe's time, and who performed astrometric and geodetic observations and calculations. Here we present some cornerstones of his life; longer intervals of it took place in Allstedt south of the Harz and in Halberstadt. Small scientific assets have been preserved at the Universitäts-Sternwarte Bonn. Therein, a lecture on secular variations of the ecliptic is of singular nature.

  12. [Carl Friedrich von Weizsäcker's philosophy of the mind].

    PubMed

    Lyre, Holger

    2014-01-01

    The paper deals with Carl Friedrich von Weizsäcker's position within the philosophy of mind. It turns out that Weizsäcker's ontology is based on an unorthodox conception both in the philosophy of physics and in the philosophy of mind. His quantum information theoretic reductionism is based on a subtle combination of atomism and holism, his philosophy of mind connected to this is a neutral monism, which proposes a bold intertwining of mind, matter, and space.

  13. Entwicklung von umwelt- und naturschutzgerechten Verfahren der landwirtschaftlichen Landnutzung für das Biosphärenreservat Schorfheide-Chorin

    NASA Astrophysics Data System (ADS)

    Meyer-Aurich, Andreas

    1999-11-01

    Mit der vorliegenden Arbeit werden exemplarisch Chancen und Grenzen der Integration von Umwelt- und Naturschutz in Verfahren der ackerbaulichen Landnutzung aufgezeigt. Die Umsetzung von Zielen des Umwelt- und Naturschutzes in Verfahren der Landnutzung ist mit verschiedenen Schwierigkeiten verbunden. Diese liegen zum einen in der Konkretisierung der Ziele, um diese umsetzen zu können, zum anderen in vielfach unzulänglichem Wissen über den Zusammenhang zwischen unterschiedlichen Formen der Landnutzung und insbesondere den biotischen Naturschutzzielen. Zunächst wird die Problematik der Zielfestlegung und Konkretisierung erörtert. Das Umweltqualitätszielkonzept von Fürst et al. (1992) stellt einen Versuch dar, Ziele des Umwelt- und Naturschutzes zu konkretisieren. Dieses Konzept haben Heidt et al. (1997) auf einen Landschaftsausschnitt von ca. 6000 ha im Biosphärenreservat Schorfheide-Chorin im Nordosten Brandenburgs angewendet. Eine Auswahl der von Heidt et al. (1997) formulierten Umweltqualitätsziele bildet die Basis dieser Arbeit. Für die ausgewählten Umweltqualitätsziele wurden wesentliche Einflussfaktoren der Landnutzung identifiziert und ein Bewertungssystem entwickelt, mit dem die Auswirkungen von landwirtschaftlichen Anbauverfahren auf diese Umweltqualitätsziele abgebildet werden können. Die praktizierte Landnutzung von 20 Betrieben im Biosphärenreservat Schorfheide-Chorin wurde von 1994 bis 1997 hinsichtlich ihrer Auswirkungen auf die Umweltqualitätsziele analysiert. Die Analyse ergab ein sehr differenziertes Bild, das zum Teil Unterschiede in der Auswirkung auf die Umweltqualitätsziele für den Anbau einzelner Kulturen oder für bestimmte Betriebstypen zeigte. Es zeigte sich aber auch, dass es bei der Gestaltung des Anbaus einzelner Kulturarten große Unterschiede gab, die für Umweltqualitätsziele Bedeutung haben. Neben der Analyse der Landnutzung im Biosphärenreservat Schorfheide-Chorin wurde ein System entwickelt, mit dem die modellhafte

  14. Microbial anaerobic methane cycling in the subseafloor at the Von Damm hydrothermal vent field, Mid-Cayman Rise

    NASA Astrophysics Data System (ADS)

    Huber, J. A.; Reveillaud, J. C.; Stepanauskas, R.; McDermott, J. M.; Sylva, S. P.; Seewald, J.

    2013-12-01

    The Mid-Cayman Rise (MCR) is Earth's deepest and slowest spreading mid-ocean ridge located in the western Caribbean. With an axial rift valley floor at a depth of ~4200-6500 m, it represents one of the deepest sections of ridge crest worldwide. In 2009, the world's deepest hydrothermal vents (Piccard at 4960 m) and an ultramafic-influenced system only 20 km away on top of an oceanic core complex (Von Damm at 2350 m) were discovered along the MCR. Each site is hosted in a distinct geologic setting with different thermal and chemical regimes. The Von Damm site is a particularly interesting location to examine chemolithoautotrophic subseafloor microbial communities due to the abundant hydrogen, methane, and organic compounds in the venting fluids. Here, we used a combination of stable isotope tracing, next-generation sequencing, and single cell techniques to determine the identity, activity, and genomic repertoire of subseafloor anaerobic archaea involved in methane cycling in hydrothermal fluids venting at the Von Damm site. Molecular sequencing of phylogenetic marker genes revealed the presence of diverse archaea that both generate and consume methane across a geochemical and thermal spectrum of vents. Stable isotope tracing experiments were used to detect biological utilization of formate and dissolved inorganic carbon, and methane generation at 70 °C under anaerobic conditions. Results indicate that methanogenesis with formate as a substrate is occurring at 70 °C at two Von Damm sites, Ginger Castle and the Main Orifice. The results are consistent with thermodynamic predictions for carbon speciation at the temperatures encountered at the ultramafic-hosted Von Damm, where formate is predicted to be thermodynamically stable, and may thus serve as a an important source of carbon. Diverse thermophilic methanogenic archaea belonging to the genera Methanothermococcus were detected at all vent sites with both 16S rRNA tag sequencing and single cell sorting. Other

  15. Sinus Tumors

    MedlinePlus

    ... Tumors Nasal Deformities Choanal Atresia Epiphora (Excessive Tearing) Disclosure Statement Printer Friendly Sinus Tumors Abtin Tabaee, MD Introduction Tumors of the nose and paranasal sinuses are rare, accounting for fewer than 1% of all tumors. These ...

  16. Vascular-Associated Muc4/Vwf Co-Localization in Human Conjunctival Malignant Melanoma Specimens-Tumor Metastasis by Migration?

    PubMed

    Kakkassery, Vinodh; Winterhalter, Sibylle; Nick, Ann-Christin; Joachim, Stephanie C; Joussen, Antonia M; Kociok, Norbert

    2017-10-01

    To investigate whether vascular differentiation marker von Willebrand factor (vWf) and proliferation marker KI67 expression correlate with MUC4 localization around stromal tumor vascularization in human conjunctival malignant melanoma (CMM). For the purposes of this study, we analyzed samples from human CMMs (n = 4), conjunctival compound nevi (n = 7), and samples from healthy conjunctiva (n = 7) for MUC1, 4, and 16 by immunohistochemistry. To test CMM vessel association of MUC4, we investigated the co-localization of MUC4 with vWf or KI67 in human CMM specimens (n = 10) by immunohistochemistry. Also, we investigated the MUC4 localization around vessels of healthy conjunctiva (n = 10). The immunohistochemical analysis demonstrated membrane-associated mucin expression in epithelia of CMM, nevi and healthy conjunctiva, whereas only MUC4 was localized perivascular in CMM tissue in this preliminary analysis. Co-staining analysis with vWf and KI67 demonstrated MUC4 localization around stromal vessels in human CMM specimens. In contrast, no MUC4 localization has been seen around healthy conjunctiva stroma vessels. MUC4 was detected around vWf/KI67-positive CMM stromal vascular tissue, but not around healthy conjunctival stroma vessels. Therefore, we assume that MUC4 might play a role in tumor cell migration toward vessels inducing metastasis.

  17. Captopril improves tumor nanomedicine delivery by increasing tumor blood perfusion and enlarging endothelial gaps in tumor blood vessels.

    PubMed

    Zhang, Bo; Jiang, Ting; Tuo, Yanyan; Jin, Kai; Luo, Zimiao; Shi, Wei; Mei, Heng; Hu, Yu; Pang, Zhiqing; Jiang, Xinguo

    2017-12-01

    Poor tumor perfusion and unfavorable vessel permeability compromise nanomedicine drug delivery to tumors. Captopril dilates blood vessels, reducing blood pressure clinically and bradykinin, as the downstream signaling moiety of captopril, is capable of dilating blood vessels and effectively increasing vessel permeability. The hypothesis behind this study was that captopril can dilate tumor blood vessels, improving tumor perfusion and simultaneously enlarge the endothelial gaps of tumor vessels, therefore enhancing nanomedicine drug delivery for tumor therapy. Using the U87 tumor xenograft with abundant blood vessels as the tumor model, tumor perfusion experiments were carried out using laser Doppler imaging and lectin-labeling experiments. A single treatment of captopril at a dose of 100 mg/kg significantly increased the percentage of functional vessels in tumor tissues and improved tumor blood perfusion. Scanning electron microscopy of tumor vessels also indicated that the endothelial gaps of tumor vessels were enlarged after captopril treatment. Immunofluorescence-staining of tumor slices demonstrated that captopril significantly increased bradykinin expression, possibly explaining tumor perfusion improvements and endothelial gap enlargement. Additionally, imaging in vivo, imaging ex vivo and nanoparticle distribution in tumor slices indicated that after a single treatment with captopril, the accumulation of 115-nm nanoparticles in tumors had increased 2.81-fold with a more homogeneous distribution pattern in comparison to non-captopril treated controls. Finally, pharmacodynamics experiments demonstrated that captopril combined with paclitaxel-loaded nanoparticles resulted in the greatest tumor shrinkage and the most extensive necrosis in tumor tissues among all treatment groups. Taken together, the data from the present study suggest a novel strategy for improving tumor perfusion and enlarging blood vessel permeability simultaneously in order to improve

  18. Clinical features and natural history of von Hippel-Lindau disease.

    PubMed

    Maher, E R; Yates, J R; Harries, R; Benjamin, C; Harris, R; Moore, A T; Ferguson-Smith, M A

    1990-11-01

    The clinical features, age at onset and survival of 152 patients with von Hippel-Lindau disease were studied. Mean age at onset was 26.3 years and 97 per cent of patients had presented by aged 60 years. Retinal angioma was the first manifestation in 65 patients (43 per cent), followed by cerebellar haemangioblastoma (n = 60, 39 per cent) and renal cell carcinoma (n = 15, 10 per cent). Overall, 89 patients (59 per cent) developed a cerebellar haemangioblastoma, 89 (59 per cent) a retinal angioma, 43 (28 per cent) renal cell carcinoma, 20 (13 per cent) spinal haemangioblastoma and 11 (7 per cent) a phaeochromocytoma. Renal, pancreatic and epididymal cysts were frequent findings but their exact incidence was not accurately assessed. Mean age at diagnosis of renal cell carcinoma (44.0 +/- 10.9 years) was significantly older than that for cerebellar haemangioblastoma (29.0 +/- 10.0 years) and retinal angioma (25.4 +/- 12.7 years). The probability of a patient with von Hippel-Lindan disease developing a cerebellar haemangioblastoma, retinal angioma or renal cell carcinoma by age 60 years was 0.84, 0.7 and 0.69, respectively. A comprehensive screening protocol for affected patients and at-risk relatives is presented, based on detailed analysis of age at onset data for each of the major complications. Median actuarial survival was 49 years, with renal cell carcinoma the leading cause of death.

  19. Mutations in the von Hippel-Lindau (VHL) tumor suppressor gene and VHL-haplotype analysis in patients with presumable congenital erythrocytosis.

    PubMed

    Cario, Holger; Schwarz, Klaus; Jorch, Norbert; Kyank, Ulrike; Petrides, Petro E; Schneider, Dominik T; Uhle, Renate; Debatin, Klaus-Michael; Kohne, Elisabeth

    2005-01-01

    Congenital erythrocytoses or polycythemias are rare and heterogeneous. A homozygous mutation (C598T->Arg200Trp) in the von Hippel-Lindau (VHL) gene was originally identified as the cause of the endemic Chuvash polycythemia. Subsequently this and other mutations in the VHL gene were also detected in several patients of different ethnic origin. Haplotype analyses of the VHL gene suggested a common origin for the Chuvash-type mutation. Thirty-four patients with presumable congenital erythrocytosis due to an unknown underlying disorder were examined for VHL gene mutations and VHL region haplotypes. Four patients were homozygous and one patient heterozygous for the Chuvash-type mutation. One additional patient presented a previously not described heterozygous mutation G311->T VHL in exon 1. The haplotype analyses were in agreement with recently published data for three of the four patients with homozygous mutations as well as for the patient with a heterozygous Chuvash-type mutation. One patient of Turkish origin with homozygous Chuvash-type mutation had a haplotype not previously found in individuals with Chuvash-type mutation. These results confirm that mutations in the VHL gene are responsible for a substantial proportion of patients with congenital erythrocytoses. Erythrocytoses due to a C598->T mutation of the VHL gene are not geographically restricted. The majority of patients with Chuvash polycythemia share a common VHL gene haplotype. The different haplotype in one of the patients with Chuvash-type mutation indicates that this mutation was not spread only from a single founder but developed independently in other individuals.

  20. Dr. von Braun In Front of a Display of Missiles

    NASA Technical Reports Server (NTRS)

    1960-01-01

    In this photo, Director of the US Army Ballistic Missile Agency (ABMA) Development Operations Division, Dr. Wernher von Braun, is standing before a display of Army missiles celebrating ABMA's Fourth Open House. The missiles in the background include (left to right) a satellite on a Juno II shroud with a Nike Ajax pointing left in front of a Jupiter missile. The Lacrosse is in front of the Juno II. The Nike Hercules points skyward in front of the Juno II and the Redstone.

  1. Modulating the Tumor Microenvironment to Enhance Tumor Nanomedicine Delivery

    PubMed Central

    Zhang, Bo; Hu, Yu; Pang, Zhiqing

    2017-01-01

    Nanomedicines including liposomes, micelles, and nanoparticles based on the enhanced permeability and retention (EPR) effect have become the mainstream for tumor treatment owing to their superiority over conventional anticancer agents. Advanced design of nanomedicine including active targeting nanomedicine, tumor-responsive nanomedicine, and optimization of physicochemical properties to enable highly effective delivery of nanomedicine to tumors has further improved their therapeutic benefits. However, these strategies still could not conquer the delivery barriers of a tumor microenvironment such as heterogeneous blood flow, dense extracellular matrix, abundant stroma cells, and high interstitial fluid pressure, which severely impaired vascular transport of nanomedicines, hindered their effective extravasation, and impeded their interstitial transport to realize uniform distribution inside tumors. Therefore, modulation of tumor microenvironment has now emerged as an important strategy to improve nanomedicine delivery to tumors. Here, we review the existing strategies and approaches for tumor microenvironment modulation to improve tumor perfusion for helping more nanomedicines to reach the tumor site, to facilitate nanomedicine extravasation for enhancing transvascular transport, and to improve interstitial transport for optimizing the distribution of nanomedicines. These strategies may provide an avenue for the development of new combination chemotherapeutic regimens and reassessment of previously suboptimal agents. PMID:29311946

  2. Transfusion medicine management for reconstructive spinal repair in a patient with von Willebrand's disease and a history of heavy surgical bleeding.

    PubMed

    Bolan, C D; Rick, M E; Polly, D W

    2001-12-01

    A case report of a multidisciplinary approach to a second reconstructive back surgery in a patient with von Willebrand's disease, flatback syndrome, and a history of heavy surgical bleeding is presented. To review the perioperative planning and assessment of hemostasis and transfusion medicine management, including administration of Humate P, a Factor VIII preparation with high von Willebrand factor content. Reconstructive spinal procedures may require significant transfusion support even in patients with normal preoperative hemostasis. In addition to the hemostatic problem caused by von Willebrand's disease, the reported patient requested minimal exposure to allogeneic blood products because of hepatitis C infection acquired from previous transfusions. The multidisciplinary team included the patient, hematologist, blood bank medical director, anesthesiologist, and operating surgeon. Preoperative assessment showed a Type 2A von Willebrand's disease variant. A careful planning process included a test infusion of desmopressin and extensive autologous donations of red cells, plasma, and platelets, which were collected before the procedure. Anterior and posterior spine fusions were performed during a 14-hour procedure. Hemostasis and clinical response were excellent. Humate P was administered perioperatively as assessed by the baseline Factor VIII and von Willebrand's disease levels, the plasma volume, the half-life of infused Humate P, and the anticipated risk and tolerance for bleeding. The estimated blood loss was 5 L. Replacement included 9 units of autologous red cells, 6 units of autologous plasma, 2 autologous plateletpheresis collections, a single allogeneic plateletpheresis product, and 17,000 units of Humate P administered over the perioperative period. Using a careful multidisciplinary approach, excellent hemostasis can be achieved with minimal exposure to untreated allogeneic blood products during aggressive spinal surgery in a patient with a clinically

  3. Diagnosis and management of von Willebrand disease: a developing country perspective.

    PubMed

    Nair, Sukesh Chandran; Viswabandya, Auro; Srivastava, Alok

    2011-07-01

    Special challenges exist in the management of patients with von Willebrand disease (VWD) because of limitations in diagnostic facilities and therapeutic options. However, even within these limitations, it is possible to establish comprehensive services for this condition. Our data show that among 202 patients with VWD, 107 were type 3, 62 were type 1, and the others different categories of type 2. Basic tests such as bleeding time and activated partial thromboplastin time with factor (F)VIII coagulant are able to diagnose most of those with severe disease. We have been able to adapt the specific tests such as von Willebrand factor (VWF) ristocetin cofactor and VWF antigen from the tedious batched manual methods to cost-effective automated methods on advanced coagulometers. Discriminatory tests such as VWF collagen binding, VWF:FVIIIB, ristocetin-induced platelet agglutination (RIPA) are done in batches. Therapeutic options and for the treatment of bleeding include desmopressin, cryoprecipitate, and intermediate purity VWF-containing clotting factor concentrates. Tranexamic acid is also widely used as well as hormonal therapy for menorrhagia. We have also shown that modest doses of intermediate purity FVIII (Koate DVI; Talecris Biotherapeutics, Raleigh, NC, USA) at 35 IU/kg preoperatively and 10 to 20 IU/kg after that are sufficient for surgical hemostasis in these patients. © Thieme Medical Publishers.

  4. Constitutional von Hippel-Lindau (VHL) gene deletions detected in VHL families by fluorescence in situ hybridization.

    PubMed

    Pack, S D; Zbar, B; Pak, E; Ault, D O; Humphrey, J S; Pham, T; Hurley, K; Weil, R J; Park, W S; Kuzmin, I; Stolle, C; Glenn, G; Liotta, L A; Lerman, M I; Klausner, R D; Linehan, W M; Zhuang, Z

    1999-11-01

    von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited cancer syndrome predisposing to a variety of tumor types that include retinal hemangioblastomas, hemangioblastomas of the central nervous system, renal cell carcinomas, pancreatic cysts and tumors, pheochromocytomas, endolymphatic sac tumors, and epididymal cystadenomas [W. M. Linehan et al., J. Am. Med. Assoc., 273: 564-570, 1995; E. A. Maher and W. G. Kaelin, Jr., Medicine (Baltimore), 76: 381-391, 1997; W. M. Linehan and R. D. Klausner, In: B. Vogelstein and K. Kinzler (eds.), The Genetic Basis of Human Cancer, pp. 455-473, McGraw-Hill, 1998]. The VHL gene was localized to chromosome 3p25-26 and cloned [F. Latif et al., Science (Washington DC), 260: 1317-1320, 1993]. Germline mutations in the VHL gene have been detected in the majority of VHL kindreds. The reported frequency of detection of VHL germline mutations has varied from 39 to 80% (J. M. Whaley et al., Am. J. Hum. Genet., 55: 1092-1102, 1994; Clinical Research Group for Japan, Hum. Mol. Genet., 4: 2233-2237, 1995; F. Chen et al., Hum. Mutat., 5: 66-75, 1995; E. R. Maher et al., J. Med. Genet., 33: 328-332, 1996; B. Zbar, Cancer Surv., 25: 219-232, 1995). Recently a quantitative Southern blotting procedure was found to improve this frequency (C. Stolle et al., Hum. Mutat., 12: 417-423, 1998). In the present study, we report the use of fluorescence in situ hybridization (FISH) as a method to detect and characterize VHL germline deletions. We reexamined a group of VHL patients shown previously by single-strand conformation and sequencing analysis not to harbor point mutations in the VHL locus. We found constitutional deletions in 29 of 30 VHL patients in this group using cosmid and P1 probes that cover the VHL locus. We then tested six phenotypically normal offspring from four of these VHL families: two were found to carry the deletion and the other four were deletion-free. In addition, germline mosaicism of the VHL gene was identified in

  5. Wernher von Braun

    NASA Image and Video Library

    1969-07-01

    This photograph depicts Dr. von Braun (at right, showing his back) and other NASA officials surveying the deep-sea research submarine "Ben Franklin." Named for American patriot and inventor Ben Franklin, who discovered the Gulf Steam, the 50-foot Ben Franklin was built between 1966 and 1968 in Switzerland for deep-ocean explorer Jacques Piccard and the Grumman Aircraft Engineering Corporation. The submersible made a famous 30-day drift dive off the East Coast of the United States and Canada in 1969 mapping the Gulf Stream's currents and sea life, and also made space exploration history by studying the behavior of aquanauts in a sealed, self-contained, self-sufficient capsule for NASA. On July 14, 1969, the Ben Franklin was towed to the high-velocity center of the Stream off the coast of Palm Beach, Florida. With a NASA observer on board, the sub descended to 1,000 feet off of Riviera Beach, Florida and drifted 1,400 miles north with the current for more than four weeks, reemerging near Maine. During the course of the dive, NASA conducted exhaustive analyses of virtually every aspect of onboard life. They measured sleep quality and patterns, sense of humor and behavioral shifts, physical reflexes, and the effects of a long-term routine on the crew. The submarine's record-shattering dive influenced the design of Apollo and Skylab missions and continued to guide NASA scientists as they devised future marned space-flight missions.

  6. Wernher von Braun

    NASA Image and Video Library

    1969-07-01

    This photograph depicts Dr. von Braun (fourth from far right) and other NASA officials surveying the deep-sea research submarine "Ben Franklin." Named for American patriot and inventor Ben Franklin, who discovered the Gulf Steam, the 50-foot Ben Franklin was built between 1966 and 1968 in Switzerland for deep-ocean explorer Jacques Piccard and the Grumman Aircraft Engineering Corporation. The submersible made a famous 30-day drift dive off the East Coast of the United States and Canada in 1969 mapping the Gulf Stream's currents and sea life, and also made space exploration history by studying the behavior of aquanauts in a sealed, self-contained, self-sufficient capsule for NASA. On July 14, 1969, the Ben Franklin was towed to the high-velocity center of the Stream off the coast of Palm Beach, Florida. With a NASA observer on board, the sub descended to 1,000 feet off of Riviera Beach, Florida and drifted 1,400 miles north with the current for more than four weeks, reemerging near Maine. During the course of the dive, NASA conducted exhaustive analyses of virtually every aspect of onboard life. They measured sleep quality and patterns, sense of humor and behavioral shifts, physical reflexes, and the effects of a long-term routine on the crew. The submarine's record-shattering dive influenced the design of Apollo and Skylab missions and continued to guide NASA scientists as they devised future marned space-flight missions.

  7. Molecular and clinical profile of von Willebrand disease in Spain (PCM-EVW-ES): comprehensive genetic analysis by next-generation sequencing of 480 patients

    PubMed Central

    Borràs, Nina; Batlle, Javier; Pérez-Rodríguez, Almudena; López-Fernández, María Fernanda; Rodríguez-Trillo, Ángela; Lourés, Esther; Cid, Ana Rosa; Bonanad, Santiago; Cabrera, Noelia; Moret, Andrés; Parra, Rafael; Mingot-Castellano, María Eva; Balda, Ignacia; Altisent, Carme; Pérez-Montes, Rocío; Fisac, Rosa María; Iruín, Gemma; Herrero, Sonia; Soto, Inmaculada; de Rueda, Beatriz; Jiménez-Yuste, Víctor; Alonso, Nieves; Vilariño, Dolores; Arija, Olga; Campos, Rosa; Paloma, María José; Bermejo, Nuria; Berrueco, Rubén; Mateo, José; Arribalzaga, Karmele; Marco, Pascual; Palomo, Ángeles; Sarmiento, Lizheidy; Iñigo, Belén; Nieto, María del Mar; Vidal, Rosa; Martínez, María Paz; Aguinaco, Reyes; César, Jesús María; Ferreiro, María; García-Frade, Javier; Rodríguez-Huerta, Ana María; Cuesta, Jorge; Rodríguez-González, Ramón; García-Candel, Faustino; Cornudella, Rosa; Aguilar, Carlos; Vidal, Francisco; Corrales, Irene

    2017-01-01

    Molecular diagnosis of patients with von Willebrand disease is pending in most populations due to the complexity and high cost of conventional molecular analyses. The need for molecular and clinical characterization of von Willebrand disease in Spain prompted the creation of a multicenter project (PCM-EVW-ES) that resulted in the largest prospective cohort study of patients with all types of von Willebrand disease. Molecular analysis of relevant regions of the VWF, including intronic and promoter regions, was achieved in the 556 individuals recruited via the development of a simple, innovative, relatively low-cost protocol based on microfluidic technology and next-generation sequencing. A total of 704 variants (237 different) were identified along VWF, 155 of which had not been previously recorded in the international mutation database. The potential pathogenic effect of these variants was assessed by in silico analysis. Furthermore, four short tandem repeats were analyzed in order to evaluate the ancestral origin of recurrent mutations. The outcome of genetic analysis allowed for the reclassification of 110 patients, identification of 37 asymptomatic carriers (important for genetic counseling) and re-inclusion of 43 patients previously excluded by phenotyping results. In total, 480 patients were definitively diagnosed. Candidate mutations were identified in all patients except 13 type 1 von Willebrand disease, yielding a high genotype-phenotype correlation. Our data reinforce the capital importance and usefulness of genetics in von Willebrand disease diagnostics. The progressive implementation of molecular study as the first-line test for routine diagnosis of this condition will lead to increasingly more personalized and effective care for this patient population. PMID:28971901

  8. ["As we're not willing to hang and behead and not able to deport...". On Emil Kraepelin's influence on Franz von Liszt].

    PubMed

    Schmidt-Recla, A; Steinberg, H

    2008-03-01

    Emil Kraepelin started his scientific career with a pamphlet demanding complete restructure of German penal law. It is well known that Kraepelin was a recipient of Cesare Lombroso's theses on degeneration and atavism. Therefore his demand for a correctional law completely replacing penal law is easily understood. Still undiscussed however is the question of whether Kraepelin's brochure had a decisive effect on German criminal law, especially on the so-called Marburg Program of Franz von Liszt, still viewed as the first emergence of modern criminal law and policies in Germany. Examination of this shows that despite major theoretical faults, Kraepelin came to conclusions that correspond remarkably with von Liszt's. Special focus should be directed on the psychologist Wilhelm Wundt, who criticised Kraepelin's juridical attempt in a very kind yet fundamental way, and on the relationship that existed between Kraepelin and von Liszt.

  9. Remission of recurrent gastrointestinal bleeding after septal reduction therapy in patients with hypertrophic obstructive cardiomyopathy-associated acquired von Willebrand syndrome.

    PubMed

    Blackshear, J L; Stark, M E; Agnew, R C; Moussa, I D; Safford, R E; Shapiro, B P; Waldo, O A; Chen, D

    2015-02-01

    Gastrointestinal hemorrhage is considered to be a severe complication of von Willebrand disease. The optimal therapy for acquired von Willebrand syndrome and severe gastrointestinal bleeding with hypertrophic cardiomyopathy is undefined. Seventy-seven patients (median age, 67 years; interquartile range [IQR], 56-75 years; 49% women) with hypertrophic cardiomyopathy underwent von Willebrand factor multimer testing and acquisition of bleeding history. Bleeding was detected in 27 (36%) (median age, 74 years; IQR 66-76 years; 74% women), 20 with gastrointestinal bleeding, including 11 women with transfusion dependence. In these 11 women, the median duration of transfusion dependency was 36 months (IQR 18-44 months), and the median number of transfusions required was 25 (IQR 20-38). Two patients had undergone bowel resection for bleeding, one of them twice. Seven patients showed angiodysplasia, and the remainder had no endoscopic lesion. Bleeding recurred after bowel surgery or endoscopic intervention and medical therapy for hypertrophic cardiomyopathy in 10 of 11 patients. Two patients had septal myectomy, and six patients underwent alcohol septal ablation. With the exception of one patient in whom a significant gradient persisted after septal ablation, after the periprocedural period, patients after septal reduction therapy remained free of recurrent bleeding and need for transfusions. Acquired von Willebrand syndrome is common in hypertrophic cardiomyopathy. Gastrointestinal bleeding often recurs after endoscopic therapy, but may be relieved by structural cardiac repair. © 2014 International Society on Thrombosis and Haemostasis.

  10. Nonlocal modeling and buckling features of cracked nanobeams with von Karman nonlinearity

    NASA Astrophysics Data System (ADS)

    Akbarzadeh Khorshidi, Majid; Shaat, Mohamed; Abdelkefi, Abdessattar; Shariati, Mahmoud

    2017-01-01

    Buckling and postbuckling behaviors of cracked nanobeams made of single-crystalline nanomaterials are investigated. The nonlocal elasticity theory is used to model the nonlocal interatomic effects on the beam's performance accounting for the beam's axial stretching via von Karman nonlinear theory. The crack is then represented as torsional spring where the crack severity factor is derived accounting for the nonlocal features of the beam. By converting the beam into an equivalent infinite long plate with an edge crack subjected to a tensile stress at the far field, the crack energy release rate, intensity factor, and severity factor are derived according to the nonlocal elasticity theory. An analytical solution for the buckling and the postbuckling responses of cracked nonlocal nanobeams accounting for the beam axial stretching according to von Karman nonlinear theory of kinematics is derived. The impacts of the nonlocal parameter on the critical buckling loads and the static nonlinear postbuckling responses of cracked nonlocal nanobeams are studied. The results indicate that the buckling and postbuckling behaviors of cracked nanobeams are strongly affected by the crack location, crack depth, nonlocal parameter, and length-to-thickness ratio.

  11. Extraneuraxial hemangioblastoma: A clinicopathologic study of 10 cases with molecular analysis of the VHL gene.

    PubMed

    Muscarella, Lucia Anna; Bisceglia, Michele; Galliani, Carlos A; Zidar, Nina; Ben-Dor, David Jonathan; Pasquinelli, Gianandrea; la Torre, Annamaria; Sparaneo, Angelo; Fanburg-Smith, Julie C; Lamovec, Janez; Michal, Michal; Bacchi, Carlos E

    2018-05-29

    Less than 250 extraneuraxial hemangioblastomas occurring in paraneuraxial or peripheral sites have been reported to date, sporadically or in the setting of von Hippel-Lindau disease. Seventeen such cases underwent molecular genetic analysis, using either the patient's peripheral blood in 9 cases or paraffin embedded tumor tissue in the rest. VHL gene mutations were documented in 3/9 cases in which DNA from peripheral blood lymphocytes was used, all with clinically manifest von Hippel-Lindau disease; instead, no VHL gene alterations were found in all of the 8 cases with sporadic extraneuraxial hemangioblastoma in which DNA from tumor tissue was analyzed. Our aim is to investigate the molecular genetic profile of the VHL gene in extraneuraxial hemangioblastoma using paraffin embedded tumor tissues. The clinical features, histopathology, and molecular investigations of 10 extraneuraxial hemangioblastomas (7 females, 3 males; median age: 47 years) are presented herein. The histopathologic diagnosis was supported by immunohistochemistry (10/10) and electron microscopy (4/10). Molecular genetic analysis was conducted (10/10) for VHL gene mutations, LOH, and gene promoter methylation. Two of the present cases were already published with only limited or no molecular investigations. Four tumors of the present series were paraneuraxial, and 6 peripheral (2 involved soft tissues, and 4 the kidney). One tumor was von Hippel-Lindau disease-associated, 1 was classified as "hemangioblastoma-only VHLD", 7 were sporadic, and one was unknown. All were histopathologically analogous to their counterpart located inside the central nervous system. Immunophenotypically, all tumors expressed vimentin, S-100, NSE, and alpha-inhibin (10/10). Ultrastructurally, unbound lipid droplets filled the cytoplasms of the stromal cells. Molecular analysis revealed 3 inactivating mutations (1 germline, two somatic) in the coding sequence of the VHL gene in 2 different extraneuraxial hemangioblastomas

  12. Digitale Transformation, aber wie? - Von der Spielwiese zur Umsetzungsplanung

    NASA Astrophysics Data System (ADS)

    Kaiser, Thomas

    Es besteht wohl kaum Anlass zur Annahme, dass die seit Jahrzehnten etablierten Markt- und Technologiestrukturen der Energiewirtschaft sich nicht in einem radikalen Ablöseprozess mit Gewinnern und Verlierern befinden. Aber Vorsicht - vordergründig bereits verloren erscheinende Geschäftsmodelle erfahren im Zuge der Digitalisierung einerseits noch intensiveren Wettbewerbsdruck, können aber andererseits von diesem "technologischen Jungbrunnen" profitieren, um verlorenes Terrain zurückzugewinnen. Im folgenden Kapitel wird ein Managementzyklus aufgezeigt, der in Anlehnung an die bereits erfolgreiche Implementierung digitaler R/Evolutionen anderer Branchen aufzeigt, wie die Geschäftsleitung systematisch kostenbewusst und zielorientiert die Digitalisierung umsetzen kann.

  13. von Willebrand Factor Test

    MedlinePlus

    ... Cancer Therapy Glucose Tests Gonorrhea Testing Gram Stain Growth Hormone Haptoglobin hCG Pregnancy hCG Tumor Marker HDL Cholesterol ... Semen Analysis Serotonin Serum Free Light Chains Sex Hormone Binding Globulin ... Transferrin Receptor Stool Culture Stool Elastase Strep ...

  14. Von Hippel-Lindau Syndrome

    MedlinePlus

    ... examination to look for retinal tumors, beginning around age 2 Yearly physical examination Yearly blood test and/or 24-hour urine test to screen for elevated catecholamines, beginning around age 5 Yearly abdominal ultrasound to look at the ...

  15. Tourismus

    NASA Astrophysics Data System (ADS)

    Matzarakis, Andreas; Lohmann, Martin

    Für den Tourismus haben Klima und Wetter eine große Relevanz: als Treiber des Verhaltens wie auch als Angebotsfaktor. Wetter und Klima sind demnach sowohl Bestandteil des touristischen Angebotes als auch limitierende Faktoren des Tourismus und Steuergrößen für die touristische Nachfrage. Insofern liegt es nahe, dass dieser Sektor vom Klimawandel betroffen sein wird. Der Tourismus ist aber auch ein Faktor, der seinerseits erheblich auf das Klima und den Klimawandel zurückwirkt. Dabei ist der Klimawandel aber nur einer von vielen voneinander abhängig erscheinenden Einflussfaktoren, denen der Sektor "Tourismus" ausgesetzt ist. Das heißt, es handelt sich um ein komplexes Wirkungsgefüge. Das Kapitel widmet sich den Klimawandelfolgen im Tourismus und macht diese beispielhaft an den Regionen "Küsten" sowie "Mittel- und Hochgebirge" fest, um Anpassungsmöglichkeiten anzufügen.

  16. Nebenwirkungen von TNF-alpha-Inhibitoren am Hautorgan.

    PubMed

    Lindhaus, Claudia; Tittelbach, Jörg; Elsner, Peter

    2017-03-01

    TNF-alpha-Inhibitoren werden seit Anfang der 1990er Jahre erfolgreich zur Behandlung diverser immunvermittelter entzündlicher Erkrankungen eingesetzt. Inzwischen gibt es eine umfangreiche Datenlage bezüglich ihrer Sicherheit. Nebenwirkungen sind bezogen auf die Häufigkeit der Anwendung selten und meist nicht schwerwiegend. Zu den Nebenwirkungen am Hautorgan zählen lokale injektionsassoziierte Reaktionen, Infektionen, immunvermittelte Reaktionen sowie Neoplasien. Die häufigsten schwerwiegenden Nebenwirkungen sind infektiöser Natur. Mykobakterielle Infektionen, aber auch non-mykobakterielle Erreger, Viren und Pilze können potenziell letale, systemische Infektionen auslösen. Im Folgenden wird eine Übersicht über das gegenwärtige Wissen bezüglich der Nebenwirkungen von TNFα-Inhibitoren am Hautorgan gegeben. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  17. Study of types of some species of “Filaria” (Nematoda) parasites of small mammals described by von Linstow and Molin

    PubMed Central

    Guerrero, R.; Bain, O.

    2011-01-01

    Parasitic nematodes from the Berlin (ZMB) and Vienna (NMW) Museum collections referred to the genus Filaria Mueller, 1787 by von Linstow or Molin were studied. Three samples were in good condition and the specimens redescribed. Litomosa hepatica (von Linstow, 1897) n. comb., sample ZMB Vermes Entozoa 3368, from the megachiropteran Pteropus neohibernicus, Bismarck Archipelago, resembles L. maki Tibayrenc, Bain & Ramanchandran, 1979, from Pteropus vampyrus, in Malaysia, but the buccal capsule differs. Both species display particular morphological characters which differ from species of Litomosa parasitic in microchiropterans. The remaining material originates from Brazil. The spicule morphology of Litomosoides circularis (von Linstow, 1899) Chandler, 1931, sample ZMB Vermes Entozoa 1059 from Hesperomys spec. (= Holochilus brasiliensis), Porto Alegre, confirms that it belongs to the sigmodontis group; the microfilaria presents characters of the genus Litomosoides, e.g. body attenuated at both extremities and salient cephalic hook. Taxonomic discussions by others confirm that species of Litomosoides belonging to the sigmodontis group and described subsequently are distinct from L. circularis. Litomosoides serpicula (Molin, 1858) Guerrero, Martin, Gardner & Bain, 2002, is redescribed, sample NMW 6323 from the bat Phyllostoma spiculatum (= Sturnira lilium), Ypanema. It is very close to L. brasiliensis Almeida, 1936, type host Moytis sp., but distinguished by a single ring in the buccal capsule, rather than two, supporting previous conclusions that the taxon L. brasiliensis, as generally regarded, may represent a complex of species. Samples NMW 6322 and NMW 6324, from other bats and also identified by Molin (1858) as Filaria serpicula, contain unidentifiable fragments of Litomosoides incertae sedis. Filaria hyalina von Linstow, 1890, sample ZMB Vermes Entozoa Q 3905 from Sorex vulgaris (= Sorex araneus), is incertae sedis because it contains two unidentifiable posterior

  18. Alexander von Humboldt's perceptions of colonial Spanish America.

    PubMed

    Rebok, Sandra

    2009-01-01

    This study presents an in-depth analysis of Alexander von Humboldt's descriptions and critical comments on the colonial society of the different regions he visited during his well-known expedition through the Americas (1799-1804). The criticisms of colonialism that he expressed, reflecting his personal convictions, have already been the focal point of many studies, but Humboldt also was able to offer a more differentiated assessment through comparisons of regional and local traditions and developments. This essay focuses on his personal diaries, which offer many interesting comments on colonial societies. These considerations and impressions made during the expedition are of particular scholarly value since they were not subject to censorship of any kind.

  19. Schönheit und andere Provokationen - Eine neue evolutionsbiologische Theorie der Kunst

    NASA Astrophysics Data System (ADS)

    Junker, Thomas

    Die Evolution hat viele spektakuläre Phänomene hervorgebracht - von der Eleganz des Vogelflugs über die gigantischen Körper der Dinosaurier und die farbenprächtige Vielfalt der Korallenriffe bis hin zu ihrem jüngsten Geniestreich - der menschlichen Kunst. Die schönen Künste - Malerei, Bildhauerei und Architektur, Theater, Tanz, Oper und Filmkunst, Musik und Literatur - Produkte der Evolution? Diese Vorstellung mutet vielen Menschen fremd an, aber wie könnte es anders sein? Denn wenn Charles Darwin recht hat, dann sind nicht nur die körperlichen Merkmale der Menschen als Antworten auf die Erfordernisse des Lebens entstanden, sondern auch ihre geistigen Fähigkeiten und Verhaltensweisen. Im Jahr 1859 hatte er auf den letzten Seiten seines berühmten Buches über die Entstehung der Arten eine kühne Prophezeiung gemacht: Durch die Evolutionstheorie werde es "zu einer bemerkenswerten Revolution in der Naturwissenschaft kommen […]. Die Psychologie wird auf die neue Grundlage gestellt, dass jede geistige Kraft und Fähigkeit notwendigerweise durch graduelle Übergänge erworben wird“ (Darwin 1859, S. 484, 488; Junker 2008).

  20. Treatment Option Overview (Wilms Tumor and Other Childhood Kidney Tumors)

    MedlinePlus

    ... Kidney Cancer Research Wilms Tumor and Other Childhood Kidney Tumors Treatment (PDQ®)–Patient Version General Information About Wilms Tumor and Other Childhood Kidney Tumors Go to Health Professional Version Key Points ...

  1. Symmetries and solutions of the non-autonomous von Bertalanffy equation

    NASA Astrophysics Data System (ADS)

    Edwards, Maureen P.; Anderssen, Robert S.

    2015-05-01

    For growth in a closed environment, which is indicative of the situation in laboratory experiments, autonomous ODE models do not necessarily capture the dynamics under investigation. The importance and impact of a closed environment arise when the question under examination relates, for example, to the number of the surviving microbes, such as in a study of the spoilage and contamination of food, the gene silencing activity of fungi or the production of a chemical compound by bacteria or fungi. Autonomous ODE models are inappropriate as they assume that only the current size of the population controls the growth-decay dynamics. This is reflected in the fact that, asymptotically, their solutions can only grow or decay monotonically or asymptote. Non-autonomous ODE models are not so constrained. A natural strategy for the choice of non-autonomous ODEs is to take appropriate autonomous ones and change them to be non-autonomous through the introduction of relevant non-autonomous terms. This is the approach in this paper with the focus being the von Bertalanffy equation. Since this equation has independent importance in relation to practical applications in growth modelling, it is natural to explore the deeper relationships between the introduced non-autonomous terms through a symmetry analysis, which is the purpose and goal of the current paper. Infinitesimals are derived which allow particular forms of the non-autonomous von Bertalanffy equation to be transformed into autonomous forms for which some new analytic solutions have been found.

  2. Bleeding score in type 1 von Willebrand disease patients using the condensed MCMDM-1 vWD validated questionnaire.

    PubMed

    Pathare, A; Al Hajri, F; Al Omrani, S; Al Obaidani, N; Al Balushi, B; Al Falahi, K

    2018-05-13

    Assessment of the severity of bleeding symptom has led to the evolution of bleeding assessment tools which are now validated. To administer the condensed molecular and clinical markers for the diagnosis and management of type 1 von Willebrand disease VWD (MCMDM-1 vWD) questionnaire to the Omani type 1 vWD patients and correlate it with the laboratory parameters. Patients and controls were personally interviewed and the condensed MCMDM-1 vWD questionnaire administered by a single investigator. Bleeding score (BS) was calculated, based on the presence or absence of the bleeding symptoms according to a standard validated questionnaire in both the patients and the controls. The median age of the patient cohort was 27 (range, 7-49) years with 60.87% of females. The median time to administer condensed MCMDM-1 BS questionnaire was 11 minutes (interquartile range-IQR;7,16). Overall, bleeding from the oral cavity was the most predominant symptom (63%). The median BS was 5 (IQR;1,8) although individual scores ranged between 0 and 29. However, there was no statistically significant difference in BS between genders (males: median 4; IQR 1,6 and females: median 5, IQR 1,10) (P > .05, Kruskal-Wallis test) The Spearman's correlation value of BS was weak with FVIII:C levels and von Willebrand Ristocetin co-factor activity; very weak with von Willebrand Antigen level, and moderate with vonWillebrand Collagen Binding activity being -0.29, -0.28, -0.14 and -0.43, respectively. The BS reflects the severity of bleeding among the vWD patients. Although the BS was abnormal, it did not correlate significantly with the surrogate laboratory parameters [P > .05]. © 2018 John Wiley & Sons Ltd.

  3. The von Hippel-Lindau protein sensitizes renal carcinoma cells to apoptotic stimuli through stabilization of BIM(EL).

    PubMed

    Guo, Y; Schoell, M C; Freeman, R S

    2009-04-23

    von Hippel-Lindau (VHL) disease is caused by germ-line mutations in the VHL tumor suppressor gene and is the most common cause of inherited renal cell carcinoma (RCC). Mutations in the VHL gene also occur in a large majority of sporadic cases of clear-cell RCC, which have high intrinsic resistance to chemotherapy and radiotherapy. Here we show that VHL-deficient RCC cells express lower levels of the proapoptotic Bcl-2 family protein BIM(EL) and are more resistant to etoposide and UV radiation-induced death compared to the same cells stably expressing the wild-type VHL protein (pVHL). Reintroducing pVHL into VHL-null cells increased the half-life of BIM(EL) protein without affecting its mRNA expression, and overexpressing pVHL inhibited BIM(EL) polyubiquitination. Suppressing pVHL expression with RNA interference resulted in a decrease in BIM(EL) protein and a corresponding decrease in the sensitivity of RCC cells to apoptotic stimuli. Directly inhibiting BIM(EL) expression in pVHL-expressing RCC cells caused a similar decrease in cell death. These results demonstrate that pVHL acts to promote BIM(EL) protein stability in RCC cells, and that destabilization of BIM(EL) in the absence of pVHL contributes to the increased resistance of VHL-null RCC cells to certain apoptotic stimuli.

  4. Of von Willebrand factor and platelets.

    PubMed

    Bryckaert, Marijke; Rosa, Jean-Philippe; Denis, Cécile V; Lenting, Peter J

    2015-01-01

    Hemostasis and pathological thrombus formation are dynamic processes that require multiple adhesive receptor-ligand interactions, with blood platelets at the heart of such events. Many studies have contributed to shed light on the importance of von Willebrand factor (VWF) interaction with its platelet receptors, glycoprotein (GP) Ib-IX-V and αIIbβ3 integrin, in promoting primary platelet adhesion and aggregation following vessel injury. This review will recapitulate our current knowledge on the subject from the rheological aspect to the spatio-temporal development of thrombus formation. We will also discuss the signaling events generated by VWF/GPIb-IX-V interaction, leading to platelet activation. Additionally, we will review the growing body of evidence gathered from the recent development of pathological mouse models suggesting that VWF binding to GPIb-IX-V is a promising target in arterial and venous pathological thrombosis. Finally, the pathological aspects of VWF and its impact on platelets will be addressed.

  5. Molecular and clinical profile of von Willebrand disease in Spain (PCM-EVW-ES): comprehensive genetic analysis by next-generation sequencing of 480 patients.

    PubMed

    Borràs, Nina; Batlle, Javier; Pérez-Rodríguez, Almudena; López-Fernández, María Fernanda; Rodríguez-Trillo, Ángela; Lourés, Esther; Cid, Ana Rosa; Bonanad, Santiago; Cabrera, Noelia; Moret, Andrés; Parra, Rafael; Mingot-Castellano, María Eva; Balda, Ignacia; Altisent, Carme; Pérez-Montes, Rocío; Fisac, Rosa María; Iruín, Gemma; Herrero, Sonia; Soto, Inmaculada; de Rueda, Beatriz; Jiménez-Yuste, Víctor; Alonso, Nieves; Vilariño, Dolores; Arija, Olga; Campos, Rosa; Paloma, María José; Bermejo, Nuria; Berrueco, Rubén; Mateo, José; Arribalzaga, Karmele; Marco, Pascual; Palomo, Ángeles; Sarmiento, Lizheidy; Iñigo, Belén; Nieto, María Del Mar; Vidal, Rosa; Martínez, María Paz; Aguinaco, Reyes; César, Jesús María; Ferreiro, María; García-Frade, Javier; Rodríguez-Huerta, Ana María; Cuesta, Jorge; Rodríguez-González, Ramón; García-Candel, Faustino; Cornudella, Rosa; Aguilar, Carlos; Vidal, Francisco; Corrales, Irene

    2017-12-01

    Molecular diagnosis of patients with von Willebrand disease is pending in most populations due to the complexity and high cost of conventional molecular analyses. The need for molecular and clinical characterization of von Willebrand disease in Spain prompted the creation of a multicenter project (PCM-EVW-ES) that resulted in the largest prospective cohort study of patients with all types of von Willebrand disease. Molecular analysis of relevant regions of the VWF , including intronic and promoter regions, was achieved in the 556 individuals recruited via the development of a simple, innovative, relatively low-cost protocol based on microfluidic technology and next-generation sequencing. A total of 704 variants (237 different) were identified along VWF , 155 of which had not been previously recorded in the international mutation database. The potential pathogenic effect of these variants was assessed by in silico analysis. Furthermore, four short tandem repeats were analyzed in order to evaluate the ancestral origin of recurrent mutations. The outcome of genetic analysis allowed for the reclassification of 110 patients, identification of 37 asymptomatic carriers (important for genetic counseling) and re-inclusion of 43 patients previously excluded by phenotyping results. In total, 480 patients were definitively diagnosed. Candidate mutations were identified in all patients except 13 type 1 von Willebrand disease, yielding a high genotype-phenotype correlation. Our data reinforce the capital importance and usefulness of genetics in von Willebrand disease diagnostics. The progressive implementation of molecular study as the first-line test for routine diagnosis of this condition will lead to increasingly more personalized and effective care for this patient population. Copyright© 2017 Ferrata Storti Foundation.

  6. Tumor-Infiltrating Immune Cells Promoting Tumor Invasion and Metastasis: Existing Theories

    PubMed Central

    Man, Yan-gao; Stojadinovic, Alexander; Mason, Jeffrey; Avital, Itzhak; Bilchik, Anton; Bruecher, Bjoern; Protic, Mladjan; Nissan, Aviram; Izadjoo, Mina; Zhang, Xichen; Jewett, Anahid

    2013-01-01

    It is a commonly held belief that infiltration of immune cells into tumor tissues and direct physical contact between tumor cells and infiltrated immune cells is associated with physical destructions of the tumor cells, reduction of the tumor burden, and improved clinical prognosis. An increasing number of studies, however, have suggested that aberrant infiltration of immune cells into tumor or normal tissues may promote tumor progression, invasion, and metastasis. Neither the primary reason for these contradictory observations, nor the mechanism for the reported diverse impact of tumor-infiltrating immune cells has been elucidated, making it difficult to judge the clinical implications of infiltration of immune cells within tumor tissues. This mini-review presents several existing hypotheses and models that favor the promoting impact of tumor-infiltrating immune cells on tumor invasion and metastasis, and also analyzes their strength and weakness. PMID:23386907

  7. Retrospektive Analyse von Zufallsbefunden, die bei Patienten mit kutanem malignen Malignom durch (18) F-Fluordeoxyglucose-PET/CT erhoben wurden.

    PubMed

    Conrad, Franziska; Winkens, Thomas; Kaatz, Martin; Goetze, Steven; Freesmeyer, Martin

    2016-08-01

    Bei der (18) F-Fluordeoxyglucose-Positronenemissionstomographie/Computertomographie (FDG-PET/CT) ergeben sich häufig Zufallsbefunde. In der vorliegenden Studie konzentrierten wir uns auf mittels FDG-PET/CT erhaltene Zufallsbefunde bei Patienten mit kutanem Melanom und überprüften deren Relevanz hinsichtlich weiterer diagnostischer Maßnahmen und Interventionen. Die Krankenakten von 181 konsekutiven Melanom-Patienten wurden retrospektiv ausgewertet, um das Management von Zufallsbefunden zu dokumentieren. Der Schwerpunkt lag dabei auf den histologischen Befunden. Bei 33 von 181 (18 %) Patienten lagen 39 relevante Zufallsbefunde vor, und zwar im Kolorektalbereich (n = 15 Patienten), in der Schilddrüse (n = 8), der Prostata (n = 2), dem Bewegungsapparat (n = 2), in Lymphknoten (n = 2), der Parotis (n = 1), den Mandeln (n = 1), den Nieren (n = 1) und der Gallenblase (n = 1). Bei 25 Patienten schlossen sich weitere diagnostische Verfahren an, wobei in 21 Fällen ein klinisches Korrelat nachgewiesen wurde. Bei 16 von 21 Patienten ergab sich eine Neoplasie, darunter fünf maligne Läsionen (vier Kolonkarzinome und ein Prostatakarzinom). Die Malignome wurden frühzeitig diagnostiziert und in der Mehrzahl der Fälle erfolgreich entfernt. Der Einsatz der FDG-PET/CT als Routine-Diagnostik wird in den Leitlinien empfohlen und ist indiziert bei malignem Melanom ab Stadium IIC. In dieser Studie wurden auf effektive Weise ansonsten nicht erkannte Krebserkrankungen, insbesondere Kolonkarzinome, detektiert. In den meisten Fällen war eine frühe Intervention möglich. Zufallsbefunde durch FDG-PET/CT sollten, unter Berücksichtigung des Zustands und der Wünsche des Patienten, mit den geeigneten diagnostischen Maßnahmen abgeklärt werden. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  8. [Kombinierte Anwendung von Strahlentherapie und adjuvanter Therapie mit einem Mistelextrakt (Viscum album L.) zur Behandlung des oralen malignen Melanoms beim Hund: Eine retrospektive Studie].

    PubMed

    von Bodungen, Uta; Ruess, Katja; Reif, Marcus; Biegel, Ulrike

    2017-01-01

    Hintergrund: Orale maligne Melanome (OMM) des Hundes zeichnen sich durch schnelles Wachstum, lokale Invasion und hohe Metastasierungsraten aus. Extrakte auf Basis von Viscum album L. (VAE) werden zunehmend in der Krebstherapie sowohl in der Human- als auch in der Veterinärmedizin eingesetzt. Ziel unserer Studie war es zu untersuchen, inwieweit die adjuvante Therapie mit VAE eine therapeutische Option zur Behandlung von OMM ist. Besonderes Augenmerk galt dabei der Überlebenszeit und möglichen Nebenwirkungen. Tiere und Methoden: 26 Hunde mit OMM, die in einem der größten veterinäronkologischen Zentren der Schweiz allesamt eine Strahlentherapie erhielten (teilweise nach operativer Tumorresektion) wurden in die retrospektive Studie eingeschlossen: 18 Hunde wurden mit VAE behandelt (1 ml VAE (Iscador®) in ansteigenden Konzentrationen von 0,1 bis 20 mg/ml subkutan 3-mal pro Woche (VAE-Gruppe), 8 erhielten keine adjuvante Behandlung (Vergleichsgruppe). Wir verglichen die Größenentwicklung der OMM sowie die Überlebenszeit. Ergebnisse: Patienten mit Bestrahlung und adjuvanter VAE-Therapie zeigten mit 236 Tagen eine signifikant längere mediane Überlebenszeit im Vergleich zu Patienten mit Bestrahlung, aber ohne adjuvante VAE-Therapie (49 Tage; Log-Rank-Test: p = 0,0047). Die VAE-Therapie verlängerte die Überlebenszeit um mehr als zwei Drittel (Hazard Ratio (HR) = 0,30, 95%-Konfidenzintervall (KI) 0,11-0,86; p = 0,024), während ein höheres Tumorstadium gemäß UICC (Union internationale contre le cancer) einen statistischen Trend zur Verdopplung des Sterberisikos zeigte (UICC-Stadium III/IV vs. I/II: HR = 2,12, 95%-KI 0,88-5,12; p = 0,095). Zwei Patienten zeigten milde Nebenwirkungen während der VAE-Behandlung. Einer der beiden zeigte 1 Tag lang ein selbstlimitiertes Fieber, bei dem anderen Patienten reduzierten wir die Dosis von einem konzentrierteren zu einem weniger konzentrierten VAE (Serie 0) aufgrund von Müdigkeit, die daraufhin verschwand

  9. Expansion of tumor-infiltrating lymphocytes (TIL) from human pancreatic tumors.

    PubMed

    Hall, MacLean; Liu, Hao; Malafa, Mokenge; Centeno, Barbara; Hodul, Pamela J; Pimiento, José; Pilon-Thomas, Shari; Sarnaik, Amod A

    2016-01-01

    We evaluated whether tumor infiltrating lymphocytes (TIL) could be expanded from surgically resected tumors from pancreatic cancer patients. Tumors were resected from pancreatic cancer patients. Tumors were minced into fragments and cultured in media containing high dose interleukin-2 (IL-2) for up to 6 weeks. T cell phenotype, activation markers, and reactivity were measured. TIL expansion was measured in 19 patient samples. The majority of these TIL were CD4 + T cells and were highly activated. Purified CD8 + T cells produced IFN-γ in response to HLA-matched pancreatic tumor targets. PD-1 blockade and 4-1BB stimulation were demonstrated as effective strategies to improve effective TIL yield, including the production of tumor-reactive pancreatic TIL. TIL expanded from pancreatic tumors are functional and able to respond to pancreatic tumor associated antigens. PD-1 blockade, 41BB stimulation, and CD8 + T cell enrichment are effective strategies to improve TIL yield and tumor reactivity. These results support the development of adoptive cell therapy strategies using TIL for the treatment of pancreatic cancer.

  10. Kompressionstherapie - Versorgungspraxis: Informationsstand von Patienten mit Ulcus cruris venosum.

    PubMed

    Protz, Kerstin; Heyer, Kristina; Dissemond, Joachim; Temme, Barbara; Münter, Karl-Christian; Verheyen-Cronau, Ida; Klose, Katharina; Hampel-Kalthoff, Carsten; Augustin, Matthias

    2016-12-01

    Eine Säule der kausalen Therapie bei Patienten mit Ulcus cruris venosum ist die Kompressionstherapie. Sie unterstützt die Abheilung, reduziert Schmerzen und Rezidive und steigert die Lebensqualität. Bislang existieren kaum wissenschaftliche Daten zu dem Versorgungsstand und fachspezifischem Wissen von Patienten mit Ulcus cruris venosum. Standardisierte Fragebögen wurden bundesweit in 55 Pflegediensten, 32 Arztpraxen, vier Wundzentren und -sprechstunden sowie einem Pflegetherapiestützpunkt von Patienten mit Ulcus cruris venosum bei Erstvorstellung anonym ausgefüllt. Insgesamt nahmen 177 Patienten (Durchschnittsalter 69,4 Jahre; 75,1 % Frauen) teil. Ein florides Ulcus cruris venosum bestand im Mittel 17 Monate. 31,1 % hatten keine Kompressionstherapie, 40,1 % Binden und 28,8 % Strümpfe. Bei der Bestrumpfung hatten 13,7 % Kompressionsklasse III, 64,7 % Kompressionsklasse II und 19,6 % Kompressionsklasse I. 70,6 % legten die Strümpfe nach dem Aufstehen an, 21,1 % trugen sie Tag und Nacht. 39,2 % bereiteten die Strümpfe Beschwerden. Lediglich 11,7 % hatten eine An- und Ausziehhilfe. Die Binden wurden im Mittel 40,7 Wochen getragen und bei 69 % nicht unterpolstert. Bei 2,8 % wurde der Knöchel- und Waden-Umfang zur Erfolgskontrolle gemessen. Venensport machten 45,9 %. Ein Drittel hatte keine Kompressionsversorgung, obwohl diese eine Basismaßnahme der Therapie des Ulcus cruris venosum ist. Zudem ist deren korrekte Auswahl und Anwendung angesichts der langen Bestandsdauer der Ulzerationen zu hinterfragen. Weiterführende Fachkenntnisse bei Anwendern und Verordnern sowie Patientenschulungen sind erforderlich. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  11. AIP1 expression in tumor niche suppresses tumor progression and metastasis

    PubMed Central

    Ji, Weidong; Li, Yonghao; He, Yun; Yin, Mingzhu; Zhou, Huanjiao Jenny; Boggon, Titus J.; Zhang, Haifeng; Min, Wang

    2015-01-01

    Studies from tumor cells suggest that tumor suppressor AIP1 inhibits epithelial-mesenchymal transition (EMT). However, the role of AIP1 in the tumor microenvironment has not been examined. We show that a global or vascular endothelial cell (EC)-specific deletion of the AIP1 gene in mice augments tumor growth and metastasis in melanoma and breast cancer models. AIP1-deficient vascular environment not only enhances tumor neovascularization and increases pre-metastatic niche formation, but also secrets tumor EMT-promoting factors. These effects from AIP1 loss are associated with increased VEGFR2 signaling in the vascular EC and could be abrogated by systemic administration of VEGFR2 kinase inhibitors. Mechanistically, AIP1 blocks VEGFR2-dependent signaling by directly binding to the phosphotyrosine residues within the activation loop of VEGFR2. Our data reveal that AIP1, by inhibiting VEGFR2-dependent signaling in tumor niche, suppresses tumor EMT switch, tumor angiogenesis and tumor pre-metastatic niche formation to limit tumor growth and metastasis. PMID:26139244

  12. General Information about Pancreatic Neuroendocrine Tumors (Islet Cell Tumors)

    MedlinePlus

    ... Islet Cell Tumors) Treatment (PDQ®)–Patient Version General Information About Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Go ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  13. Brain tumor - children

    MedlinePlus

    ... children; Neuroglioma - children; Oligodendroglioma - children; Meningioma - children; Cancer - brain tumor (children) ... The cause of primary brain tumors is unknown. Primary brain tumors may ... (spread to nearby areas) Cancerous (malignant) Brain tumors ...

  14. Brain Tumors

    MedlinePlus

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  15. Sporadic Hemangioblastoma Arising from the Infundibulum.

    PubMed

    Pakdaman, Michael N; Austin, Matthew J; Bannykh, Serguei; Pressman, Barry D

    2017-05-01

    Hemangioblastomas are rare vascular tumors most often found in the posterior fossa and cervical spinal cord and commonly associated with von Hippel-Lindau Disease. We report a case of sporadic hemangioblastoma in a patient without von Hippel-Lindau Disease. Imaging characteristics included a solid, suprasellar mass that was homogeneously enhancing. These findings most resembled a pituicytoma or choroid glioma because of the close association with the infundibulum and the homogeneous avid enhancement. Microscopically, the neoplasm was seen to be composed of vascular channels associated with foamy stromal cells, containing clear cytoplasmic vacuoles. Microscopic and immunohistochemical findings were consistent with hemangioblastoma. Hemangioblastomas are a rare form of vascular tumor most commonly associated with von-Hippel Lindau disease. Our finding of non-cystic hemangioblastoma arising from the infundibulum demonstrates that, while rare, hemangioblastomas should be considered on the differential diagnosis for an avidly enhancing suprasellar mass.

  16. Sporadic Hemangioblastoma Arising from the Infundibulum

    PubMed Central

    Pakdaman, Michael N; Austin, Matthew J; Bannykh, Serguei; Pressman, Barry D

    2017-01-01

    Hemangioblastomas are rare vascular tumors most often found in the posterior fossa and cervical spinal cord and commonly associated with von Hippel-Lindau Disease. We report a case of sporadic hemangioblastoma in a patient without von Hippel-Lindau Disease. Imaging characteristics included a solid, suprasellar mass that was homogeneously enhancing. These findings most resembled a pituicytoma or choroid glioma because of the close association with the infundibulum and the homogeneous avid enhancement. Microscopically, the neoplasm was seen to be composed of vascular channels associated with foamy stromal cells, containing clear cytoplasmic vacuoles. Microscopic and immunohistochemical findings were consistent with hemangioblastoma. Hemangioblastomas are a rare form of vascular tumor most commonly associated with von-Hippel Lindau disease. Our finding of non-cystic hemangioblastoma arising from the infundibulum demonstrates that, while rare, hemangioblastomas should be considered on the differential diagnosis for an avidly enhancing suprasellar mass. PMID:29299088

  17. Urogenital tumors

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

    Weller, R.E.

    An overview is provided for veterinary care of urogenital tumors in companion animals, especially the dog. Neoplasms discussed include tumors of the kidney, urinary bladder, prostate, testis, ovary, vagina, vulva and the canine transmissible venereal tumor. Topics addressed include description, diagnosis and treatment.

  18. [Homocysteine and von Willebrand factor in chronic alcoholism].

    PubMed

    Koriakin, A M; Epifantseva, N N; Dadyka, I V; Gorbatovskiĭ, Ia A

    2010-04-01

    The levels of homocysteine (HC) and von Willebrand factor (VWF) as cardiovascular risk factors were studied in patients with Stage II chronic alcoholism. Forty-one men with Stage II chronic alcoholism without clinical signs of somatic and infectious diseases were examined. Their median age was 37 (range 32-40) years; the alcoholization period was 12 (range 8-17) years. Plasma HC and VWF (amount and activity) levels were determined. In 63.4% of chronic alcoholic patients, HC levels was twice as high as in the controls; in 80.6%, both the content and activity of VWF were increased. There was no correlation between the levels of HC and VWF. Vascular endothelial damage concurrent with hyperhomocysteinemia increases a cardiovascular risk in patients with Stage II chronic alcoholism.

  19. Understanding Brain Tumors

    MedlinePlus

    ... to Know About Brain Tumors . What is a Brain Tumor? A brain tumor is an abnormal growth
 ... Tumors” from Frankly Speaking Frankly Speaking About Cancer: Brain Tumors Download the full book Questions to ask ...

  20. Neurocognitive profile of a young adolescent with DK phocomelia/von Voss phocomelia/von Voss Cherstvoy syndrome.

    PubMed

    Antonini, Tanya N; Van Horn Kerne, Valerie; Axelrad, Marni E; Karaviti, Lefkothea P; Schwartz, David D

    2015-07-01

    DK phocomelia/von Voss Cherstvoy syndrome is a rare condition characterized by upper limb and urogenital abnormalities and various brain anomalies. Previously reported cases have noted significant developmental delays, although no formal testing of cognitive abilities has been reported. In this paper we describe results from a comprehensive neuropsychological evaluation of a 12-year-old male with DK phocomelia syndrome. Test findings indicated mild impairment in intellectual functioning, with more significant impairment in adaptive skills and academic achievement. The neuropsychological profile converged with neurological findings, showing a distinct pattern of strengths and weaknesses that suggests functional compromise of posterior brain regions with relatively well-preserved functioning of more anterior regions. Specifically, impairments were evident in perceptual reasoning, visual perception, and visuomotor integration, whereas normal or near normal functioning was evident in memory, receptive language, social cognition, attention, and most aspects of executive functioning. To our knowledge this is the first report to describe the neurocognitive profile of an individual with DK phocomelia syndrome. © 2015 Wiley Periodicals, Inc.

  1. [Countryside obstetrics--Dr. Franz von Ottenthal and the South Tyrolean Medical Market (1860-1869)].

    PubMed

    Hilber, Marina

    2012-01-01

    The paper focuses on the structure of the obstetric market in a rural region of alpine South Tyrol (today: Italy) throughout the 1860s. Besides midwives and parturient women, also male obstetricians are traceable in the actual research area of the Tauferer Ahrntal. Among them was the general practitioner Dr. Franz von Ottenthal, whose medical records (Historiae Morborum, 1847-1899) are used to reconstruct the participation of physicians in the obstetric market. Special emphasis lies on the evaluation of the predominant hierarchies (midwives/surgeons/physicians) and the position of Franz von Ottenthal in this specialized medical sub-segment. Therefore, the quantitative extent of obstetric intervention as well as the qualitative dimension of treatments (medication, surgeries) is investigated. So far, the relevance of Ottenthals obstetric practice as to the gender ratio has been measured as rather high, considering that he generally treated more female than male patients. An attempt will be made to estimate the significance of the obstetric segment within his practice in order to find an explanatory approach for the higher female medical demand.

  2. PREFACE: EmerQuM 11: Emergent Quantum Mechanics 2011 (Heinz von Foerster Congress)

    NASA Astrophysics Data System (ADS)

    Grössing, Gerhard

    2012-05-01

    These proceedings comprise the plenary lectures and poster contributions of the 'Heinz von Foerster Conference 2011' on Emergent Quantum Mechanics (EmerQuM11), which was held at the University of Vienna, 11-13 November 2011. With the 5th International Heinz von Foerster Conference convened at the occasion of von Foerster's 100th birthday, the organizers opted for a twin conference to take place at the Large and Small Ceremonial Halls of the University's main building, respectively. The overall topic was chosen as 'Self-Organization and Emergence', a topic to which von Foerster was an early contributor. While the first conference ('Self-Organization and Emergence in Nature and Society') addressed a more general audience, the second one ('Emergent Quantum Mechanics') was intended as a specialist meeting with a contemporary topic that could both serve as an illustration of von Foerster's intellectual heritage and, more generally, point towards future directions in physics. We thus intended to bring together many of those physicists who are interested in or are working on attempts to understand quantum mechanics as emerging from a suitable classical (or, more generally, deeper level) physics. EmerQuM11 was organized by the Austrian Institute for Nonlinear Studies (AINS), with essential support from the Wiener Institute for Social Science Documentation and Methodology (WISDOM), the Department of Contemporary History at the University of Vienna, and the Heinz von Foerster-Gesellschaft. There were a number of individuals who contributed to the smooth course of our meeting and whom I would like to sincerely thank: Christian Bischof, Thomas Elze, Marianne Ertl, Gertrud Hafner, Werner Korn, Angelika Krawanja, Florian Krug and his team, Sonja Lang, Albert Müller, Ilse Müller, Irene Müller, Karl Müller, Armin Reautschnig, Marion Schirrmacher, Anton Staudinger, Roman Zlabinger, and, last but not least, my AINS colleagues Siegfried Fussy, Herbert Schwabl and Johannes Mesa

  3. TNF Receptor 2 Makes Tumor Necrosis Factor a Friend of Tumors

    PubMed Central

    Sheng, Yuqiao; Li, Feng; Qin, Zhihai

    2018-01-01

    Tumor necrosis factor (TNF) is widely accepted as a tumor-suppressive cytokine via its ubiquitous receptor TNF receptor 1 (TNFR1). The other receptor, TNFR2, is not only expressed on some tumor cells but also on suppressive immune cells, including regulatory T cells and myeloid-derived suppressor cells. In contrast to TNFR1, TNFR2 diverts the tumor-inhibiting TNF into a tumor-advocating factor. TNFR2 directly promotes the proliferation of some kinds of tumor cells. Also activating immunosuppressive cells, it supports immune escape and tumor development. Hence, TNFR2 may represent a potential target of cancer therapy. Here, we focus on expression and role of TNFR2 in the tumor microenvironment. We summarize the recent progress in understanding how TNFR2-dependent mechanisms promote carcinogenesis and tumor growth and discuss the potential value of TNFR2 in cancer treatment. PMID:29892300

  4. Characterization of the Tumor Secretome from Tumor Interstitial Fluid (TIF).

    PubMed

    Gromov, Pavel; Gromova, Irina

    2016-01-01

    Tumor interstitial fluid (TIF) surrounds and perfuses bodily tumorigenic tissues and cells, and can accumulate by-products of tumors and stromal cells in a relatively local space. Interstitial fluid offers several important advantages for biomarker and therapeutic target discovery, especially for cancer. Here, we describe the most currently accepted method for recovering TIF from tumor and nonmalignant tissues that was initially performed using breast cancer tissue. TIF recovery is achieved by passive extraction of fluid from small, surgically dissected tissue specimens in phosphate-buffered saline. We also present protocols for hematoxylin and eosin (H&E) staining of snap-frozen and formalin-fixed, paraffin-embedded (FFPE) tumor sections and for proteomic profiling of TIF and matched tumor samples by high-resolution two-dimensional gel electrophoresis (2D-PAGE) to enable comparative analysis of tumor secretome and paired tumor tissue.

  5. Brain Tumor Symptoms

    MedlinePlus

    ... Fatigue Other Symptoms Diagnosis Types of Tumors Risk Factors Brain Tumor Statistics Brain Tumor Dictionary Webinars Anytime Learning About Us Our Founders Board of Directors Staff Leadership Strategic Plan Financials News Careers Brain Tumor Information Brain Anatomy Brain ...

  6. Wilhelm von Humboldt and the "Orient": On Edward W. Said's Remarks on Humboldt's Orientalist Studies

    ERIC Educational Resources Information Center

    Messling, Markus

    2008-01-01

    From an epistemological perspective, Wilhelm von Humboldt's studies on the Oriental and East Asian languages and writing systems (Egyptian hieroglyphs, Sanskrit, Chinese, Polynesian) raise the question of his position in the Orientalist discourse of his time. Said [Said, E.W., 1978. "Orientalism. Western Conceptions of the Orient, fourth…

  7. Brain Tumor Risk Factors

    MedlinePlus

    ... Factors Brain Tumor Statistics ABTA Publications Brain Tumor Dictionary Upcoming Webinars Anytime Learning Brain Tumor Educational Presentations ... Factors Brain Tumor Statistics ABTA Publications Brain Tumor Dictionary Upcoming Webinars Anytime Learning Brain Tumor Educational Presentations ...

  8. Identification and characterization of the elusive mutation causing the historical von Willebrand Disease type IIC Miami.

    PubMed

    Obser, T; Ledford-Kraemer, M; Oyen, F; Brehm, M A; Denis, C V; Marschalek, R; Montgomery, R R; Sadler, J E; Schneppenheim, S; Budde, U; Schneppenheim, R

    2016-09-01

    Essentials Von Willebrand disease IIC Miami features high von Willebrand factor (VWF) with reduced function. We aimed to identify and characterize the elusive underlying mutation in the original family. An inframe duplication of VWF exons 9-10 was identified and characterized. The mutation causes a defect in VWF multimerization and decreased VWF clearance from the circulation. Background A variant of von Willebrand disease (VWD) type 2A, phenotype IIC (VWD2AIIC), is characterized by recessive inheritance, low von Willebrand factor antigen (VWF:Ag), lack of VWF high-molecular-weight multimers, absence of VWF proteolytic fragments and mutations in the VWF propeptide. A family with dominantly inherited VWD2AIIC but markedly elevated VWF:Ag of > 2 U L(-1) was described as VWD type IIC Miami (VWD2AIIC-Miami) in 1993; however, the molecular defect remained elusive. Objectives To identify the molecular mechanism underlying the phenotype of the original VWD2AIIC-Miami. Patients and Methods We studied the original family with VWD2AIIC-Miami phenotypically and by genotyping. The identified mutation was recombinantly expressed and characterized by standard techniques, confocal imaging and in a mouse model, respectively. Results By Multiplex ligation-dependent probe amplification we identified an in-frame duplication of VWF exons 9-10 (c.998_1156dup; p.Glu333_385dup) in all patients. Recombinant mutant (rm)VWF only presented as a dimer. Co-expressed with wild-type VWF, the multimer pattern was indistinguishable from patients' plasma VWF. Immunofluorescence studies indicated retention of rmVWF in unusually large intracellular granules in the endoplasmic reticulum. ADAMTS-13 proteolysis of rmVWF under denaturing conditions was normal; however, an aberrant proteolytic fragment was apparent. A decreased ratio of VWF propeptide to VWF:Ag and a 1-desamino-8-d-arginine vasopressin (DDAVP) test in one patient indicated delayed VWF clearance, which was supported by clearance data after

  9. Tumor stem cells: A new approach for tumor therapy (Review)

    PubMed Central

    MENG, MIN; ZHAO, XIN-HAN; NING, QIAN; HOU, LEI; XIN, GUO-HONG; LIU, LI-FENG

    2012-01-01

    Recent studies have demonstrated the existence of a minority of tumor cells possessing the stem cell properties of self-renewal and differentiation in leukemia and several solid tumors. However, these cells do not possess the normal regulatory mechanisms of stem cells. Following transplantation, they are capable of initiating tumorigenesis and are therefore known as ‘tumor stem cells’. Cellular origin analysis of tumor stem cells has resulted in three hypotheses: Embryonal rest hypothesis, anaplasia and maturation arrest. Several signaling pathways which are involved in carcinogenesis, including Wnt/β-catenin, Notch and Oct-4 signaling pathways are crucial in normal stem cell self-renewal decisions, suggesting that breakdown in the regulation of self-renewal may be a key event in the development of tumors. Thus, tumors can be regarded as an abnormal organ in which stem cells have escaped from the normal constraints on self-renewal, thus, leading to abnormally differentiated tumor cells that lose the ability to form tumors. This new model for maligancies has significance for clinical research and treatment. PMID:22844351

  10. Brain Tumor Diagnosis

    MedlinePlus

    ... updates Please leave this field empty Brain Tumor Diagnosis SHARE Home > Brain Tumor Information > Diagnosis Listen In cases where a brain tumor is ... to help the doctor reach a brain tumor diagnosis. These tests may also be able help the ...

  11. Chemotherapeutic tumor microparticles combining low-dose irradiation reprogram tumor-promoting macrophages through a tumor-repopulating cell-curtailing pathway

    PubMed Central

    Sun, Yanling; Zheng, Zu'an; Zhang, Huafeng; Yu, Yuandong; Ma, Jingwei; Tang, Ke; Xu, Pingwei; Ji, Tiantian; Liang, Xiaoyu; Chen, Degao; Jin, Xun; Zhang, Tianzhen; Long, Zhixiong; Liu, Yuying; Huang, Bo

    2017-01-01

    ABSTRACT Stem cell-like tumor-repopulating cells (TRCs) have a critical role in establishing a tumor immunosuppressive microenvironment. However, means to enhance antitumor immunity by disrupting TRCs are absent. Our previous studies have shown that tumor cell-derived microparticles (T-MPs) preferentially abrogate TRCs by delivering antitumor drugs into nuclei of TRCs. Here, we show that low dose irradiation (LDI) enhances the effect of cisplatin-packaging T-MPs (Cis-MPs) on TRCs, leading to inhibiting tumor growth in different tumor models. This antitumor effect is not due to the direct killing of tumor cells but is T cell-dependent and relies on macrophages for their efficacy. The underlying mechanism is involved in therapeutic reprograming macrophages from tumor-promotion to tumor-inhibition by disrupting TRCs and curtailing their vicious education on macrophages. These findings provide a novel strategy to reset macrophage polarization and confer their function more like M1 than M2 types with highly promising potential clinical applications. PMID:28680743

  12. Constraints on hydrocarbon and organic acid abundances in hydrothermal fluids at the Von Damm vent field, Mid-Cayman Rise (Invited)

    NASA Astrophysics Data System (ADS)

    McDermott, J. M.; Seewald, J.; German, C. R.; Sylva, S. P.

    2013-12-01

    The generation of organic compounds in vent fluids has been of interest since the discovery of seafloor hydrothermal systems, due to implications for the sustenance of present-day microbial populations and their potential role in the origin of life on early Earth. Possible sources of organic compounds in hydrothermal systems include microbial production, thermogenic degradation of organic material, and abiotic synthesis. Abiotic organic synthesis reactions may occur during active circulation of seawater-derived fluids through the oceanic crust or within olivine-hosted fluid inclusions containing carbon-rich magmatic volatiles. H2-rich end-member fluids at the Von Damm vent field on the Mid-Cayman Rise, where fluid temperatures reach 226°C, provide an exciting opportunity to examine the extent of abiotic carbon transformations in a highly reducing system. Our results indicate multiple sources of carbon compounds in vent fluids at Von Damm. An ultramafic-influenced hydrothermal system located on the Mount Dent oceanic core complex at 2350 m depth, Von Damm vent fluids contain H2, CH4, and C2+ hydrocarbons in high abundance relative to basalt-hosted vent fields, and in similar abundance to other ultramafic-hosted systems, such as Rainbow and Lost City. The CO2 content and isotopic composition in end-member fluids are virtually identical to bottom seawater, suggesting that seawater DIC is unchanged during hydrothermal circulation of seawater-derived fluids. Accordingly, end-member CH4 that is present in slightly greater abundance than CO2 cannot be generated from reduction of aqueous CO2 during hydrothermal circulation. We postulate that CH4 and C2+ hydrocarbons that are abundantly present in Von Damm vent fluids reflect leaching of fluids from carbon- and H2-rich fluid inclusions hosted in plutonic rocks. Geochemical modeling of carbon speciation in the Von Damm fluids suggests that the relative abundances of CH4, C2+ hydrocarbons, and CO2 are consistent with

  13. What the neurosurgeon should know about hemangioblastoma, both sporadic and in Von Hippel-Lindau disease: A literature review

    PubMed Central

    Bamps, Sven; Calenbergh, Frank Van; Vleeschouwer, Steven De; Loon, Johannes Van; Sciot, Raf; Legius, Eric; Goffin, Jan

    2013-01-01

    Background: Hemangioblastomas are associated with Von Hippel-Lindau disease (VHLD) in 10-40% of cases. Based upon a literature review we state the core features the neurosurgeon should be aware of. Methods: We performed a selective literature (Cochrane and Medline) search for hemangioblastoma, both sporadic and VHL associated. We reviewed general characteristics (epidemiology, symptomatology, diagnosis, and management) and focused on follow-up as well as screening modalities for sporadic and VHL associated lesions. Results: Based upon our literature search, we established guidelines for screening and follow-up in both sporadic and VHL associated hemangioblastoma patients. Conclusions: Screening for retinal angiomas, abdominal masses, and pheochromocytomas as well as genetic analysis is recommended for every patient with a newly diagnosed hemangioblastoma. Follow-up is by magnetic resonance imaging (MRI) of the clinical neuronal region at 6 and at 12-24 months postoperatively. For VHL-associated hemangioblastomas yearly investigation for craniospinal hemangioblastoma by MRI and yearly screening and follow-up for retinal angiomas is recommended. Annual abdominal ultrasound with triennial computed tomography (CT) imaging for abdominal masses is postulated. Annual audiometry is to be performed for possible endolymphatic sac tumor, detailed radiographic imaging of the skull base should be performed upon abnormality in auditory testing. Investigations for cystadenomas of the epidydimis and broad ligament only are mandatory on indication. Annual investigation for pheochromocytoma is recommended. PMID:24340227

  14. Plasma and urinary endothelin-1 titers and plasma von Willebrand activity in Pseudoxanthoma elasticum.

    PubMed

    Amadeo, A; Bertulezzi, G; Civelli, L; Porta, C; Moroni, M

    1998-10-01

    We found high endothelin-1 and von Willebrand factor plasma titers not only in two individuals (daughter and father) affected with Pseudoxanthoma elasticum but also in a young unaffected relative. These findings raise the possibility that these molecules could be the first biochemical fingerprints of this, still not clinically evident, rare inherited disorder of elastic tissue.

  15. 'Rediscovery' revised - the cooperation of Erich and Armin von Tschermak-Seysenegg in the context of the 'rediscovery' of Mendel's laws in 1899-1901.

    PubMed

    Simunek, M; Hossfeld, U; Wissemann, V

    2011-11-01

    The 'rediscovery' of Mendel's laws in 1900 is seen as a turning point in modern research on heredity and genetics. In the first half of the 20th century it was generally held that the 'rediscovery' was made several times, independently, and in a parallel fashion by three European botanists (Carl Correns, Hugo de Vries and Erich von Tschermak-Seysenegg). Since the 1950s, however, serious questions have arisen concerning both the chronology and the specific conceptual contribution of the scientists involved. Not only the independence but also parallelism was analysed in the context of individual research programmes of all three of these scholars. The youngest of them, Austrian botanist Erich von Tschermak-Seysenegg, was excluded from the rank of 'rediscoverers'. It is the aim of this paper to use new archival evidence and add important facts both to the chronology and conceptual framework of Erich von Tschermak-Seysenegg's work. An entirely new aspect is added by identifying his older brother, the physiologist Armin von Tschermak-Seysenegg (1870-1952), as a significant spiritus movens of the events of 1900 and 1901. A selected part of their correspondence, covering the period from 13 March 1898 until 19 November 1901, is made available in transcriptions. © 2011 German Botanical Society and The Royal Botanical Society of the Netherlands.

  16. Hormone profiling, WHO 2010 grading, and AJCC/UICC staging in pancreatic neuroendocrine tumor behavior

    PubMed Central

    Morin, Emilie; Cheng, Sonia; Mete, Ozgur; Serra, Stefano; Araujo, Paula B; Temple, Sara; Cleary, Sean; Gallinger, Steven; Greig, Paul D; McGilvray, Ian; Wei, Alice; Asa, Sylvia L; Ezzat, Shereen

    2013-01-01

    Pancreatic neuroendocrine tumors (pNETs) are the second most common pancreatic neoplasms, exhibiting a complex spectrum of clinical behaviors. To examine the clinico-pathological characteristics associated with long-term prognosis we reviewed 119 patients with pNETs treated in a tertiary referral center using the WHO 2010 grading and the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging systems, with a median follow-up of 38 months. Tumor size, immunohistochemistry (IHC) profiling and patient characteristics-determining stage were analyzed. Primary clinical outcomes were disease progression or death. The mean age at presentation was 52 years; 55% were female patients, 11% were associated with MEN1 (multiple endocrine neoplasia 1) or VHL (Von Hippel–Lindau); mean tumor diameter was 3.3 cm (standard deviation, SD) (2.92). The clinical presentation was incidental in 39% with endocrine hypersecretion syndromes in only 24% of cases. Nevertheless, endocrine hormone tissue immunoreactivity was identified in 67 (56.3%) cases. According to WHO 2010 grading, 50 (42%), 38 (31.9%), and 3 (2.5%) of tumors were low grade (G1), intermediate grade (G2), and high grade (G3), respectively. Disease progression occurred more frequently in higher WHO grades (G1: 6%, G2: 10.5%, G3: 67%, P = 0.026) and in more advanced AJCC stages (I: 2%, IV: 63%, P = 0.033). Shorter progression free survival (PFS) was noted in higher grades (G3 vs. G2; 21 vs. 144 months; P = 0.015) and in more advanced AJCC stages (stage I: 218 months, IV: 24 months, P < 0.001). Liver involvement (20 vs. 173 months, P < 0.001) or histologically positive lymph nodes (33 vs. 208 months, P < 0.001) were independently associated with shorter PFS. Conversely, tissue endocrine hormone immunoreactivity, independent of circulating levels was significantly associated with less aggressive disease. Age, gender, number of primary tumors, and heredity were not

  17. Modeling of a Von Platen-Munters diffusion absorption refrigeration cycle

    NASA Astrophysics Data System (ADS)

    Agostini, Bruno; Agostini, Francesco; Habert, Mathieu

    2016-09-01

    This article presents a thermodynamical model of a Von-Platen diffusion absorption refrigeration cycle for power electronics applications. It is first validated by comparison with data available in the literature for the classical water-ammonia-helium cycle for commercial absorption fridges. Then new operating conditions corresponding to specific ABB applications, namely high ambient temperature and new organic fluids combinations compatible with aluminium are simulated and discussed. The target application is to cool power electronics converters in harsh environments with high ambient temperature by providing refrigeration without compressor, for passive components losses of about 500 W, with a compact and low cost solution.

  18. Contiguity and Entire Separability of States on von Neumann Algebras

    NASA Astrophysics Data System (ADS)

    Haliullin, Samigulla

    2017-12-01

    We introduce the notions of the contiguity and entirely separability for two sequences of states on von Neumann algebras. The ultraproducts technique allows us to reduce the study of the contiguity to investigation of the equivalence for two states. Here we apply the Ocneanu ultraproduct and the Groh-Raynaud ultraproduct (see Ocneanu (1985), Groh (J. Operator Theory, 11, 2, 395-404 1984), Raynaud (J. Operator Theory, 48, 1, 41-68, 2002), Ando and Haagerup (J. Funct. Anal., 266, 12, 6842-6913, 2014)), as well as the technique developed in Mushtari and Haliullin (Lobachevskii J. Math., 35, 2, 138-146, 2014).

  19. Linking contemporary high resolution magnetic resonance imaging to the von Economo legacy: A study on the comparison of MRI cortical thickness and histological measurements of cortical structure.

    PubMed

    Scholtens, Lianne H; de Reus, Marcel A; van den Heuvel, Martijn P

    2015-08-01

    The cerebral cortex is a distinctive part of the mammalian nervous system, displaying a spatial variety in cyto-, chemico-, and myelinoarchitecture. As part of a rich history of histological findings, pioneering anatomists von Economo and Koskinas provided detailed mappings on the cellular structure of the human cortex, reporting on quantitative aspects of cytoarchitecture of cortical areas. Current day investigations into the structure of human cortex have embraced technological advances in Magnetic Resonance Imaging (MRI) to assess macroscale thickness and organization of the cortical mantle in vivo. However, direct comparisons between current day MRI estimates and the quantitative measurements of early anatomists have been limited. Here, we report on a simple, but nevertheless important cross-analysis between the histological reports of von Economo and Koskinas on variation in thickness of the cortical mantle and MRI derived measurements of cortical thickness. We translated the von Economo cortical atlas to a subdivision of the commonly used Desikan-Killiany atlas (as part of the FreeSurfer Software package and a commonly used parcellation atlas in studies examining MRI cortical thickness). Next, values of "width of the cortical mantle" as provided by the measurements of von Economo and Koskinas were correlated to cortical thickness measurements derived from high-resolution anatomical MRI T1 data of 200+ subjects of the Human Connectome Project (HCP). Cross-correlation revealed a significant association between group-averaged MRI measurements of cortical thickness and histological recordings (r = 0.54, P < 0.001). Further validating such a correlation, we manually segmented the von Economo parcellation atlas on the standardized Colin27 brain dataset and applied the obtained three-dimensional von Economo segmentation atlas to the T1 data of each of the HCP subjects. Highly consistent with our findings for the mapping to the Desikan-Killiany regions, cross

  20. Context-invariant quasi hidden variable (qHV) modelling of all joint von Neumann measurements for an arbitrary Hilbert space

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

    Loubenets, Elena R.

    We prove the existence for each Hilbert space of the two new quasi hidden variable (qHV) models, statistically noncontextual and context-invariant, reproducing all the von Neumann joint probabilities via non-negative values of real-valued measures and all the quantum product expectations—via the qHV (classical-like) average of the product of the corresponding random variables. In a context-invariant model, a quantum observable X can be represented by a variety of random variables satisfying the functional condition required in quantum foundations but each of these random variables equivalently models X under all joint von Neumann measurements, regardless of their contexts. The proved existence ofmore » this model negates the general opinion that, in terms of random variables, the Hilbert space description of all the joint von Neumann measurements for dimH≥3 can be reproduced only contextually. The existence of a statistically noncontextual qHV model, in particular, implies that every N-partite quantum state admits a local quasi hidden variable model introduced in Loubenets [J. Math. Phys. 53, 022201 (2012)]. The new results of the present paper point also to the generality of the quasi-classical probability model proposed in Loubenets [J. Phys. A: Math. Theor. 45, 185306 (2012)].« less

  1. John von Neumann and Klaus Fuchs: an Unlikely Collaboration

    NASA Astrophysics Data System (ADS)

    Bernstein, Jeremy

    2010-03-01

    I discuss the origin of the idea of making a fusion (hydrogen) bomb and the physics involved in it, and then turn to the design proposed for one by the unlikely collaborators John von Neumann and Klaus Fuchs in a patent application they filed at Los Alamos in May 1946, which Fuchs passed on to the Russians in March 1948, and which with substantial modifications was tested on the island of Eberiru on the Eniwetok atoll in the South Pacific on May 8, 1951. This test showed that the fusion of deuterium and tritium nuclei could be ignited, but that the ignition would not propagate because the heat produced was rapidly radiated away. Meanwhile, Stanislaw Ulam and C.J. Everett had shown that Edward Teller’s Classical Super could not work, and at the end of December 1950, Ulam had conceived the idea of super compression, using the energy of a fission bomb to compress the fusion fuel to such a high density that it would be opaque to the radiation produced. Once Teller understood this, he invented a greatly improved, new method of compression using radiation, which then became the heart of the Ulam-Teller bomb design, which was tested, also in the South Pacific, on November 1, 1952. The Russians have freely acknowledged that Fuchs gave them the fission bomb, but they have insisted that no one gave them the fusion bomb, which grew out of design involving a fission bomb surrounded by alternating layers of fusion and fission fuels, and which they tested on November 22, 1955. Part of the irony of this story is that neither the American nor the Russian hydrogen-bomb programs made any use of the brilliant design that von Neumann and Fuchs had conceived as early as 1946, which could have changed the entire course of development of both programs.

  2. Einsatz und Wirksamkeit von Systemtherapien bei Erwachsenen mit schwerer Neurodermitis: Erste Ergebnisse des deutschen Neurodermitis-Registers TREATgermany.

    PubMed

    Schmitt, Jochen; Abraham, Susanne; Trautmann, Freya; Stephan, Victoria; Fölster-Holst, Regina; Homey, Bernhard; Bieber, Thomas; Novak, Natalija; Sticherling, Michael; Augustin, Matthias; Kleinheinz, Andreas; Elsner, Peter; Weidinger, Stephan; Werfel, Thomas

    2017-01-01

    Versorgungsregister dienen der Erfassung des Einsatzes und der Wirksamkeit von Therapien unter realen Versorgungsbedingungen und sind als Basis einer evidenzbasierten Gesundheitsversorgung unverzichtbar. Das deutsche Neurodermitis-Register TREATgermany wurde als weltweit erstes Register für Patienten mit schwerer Neurodermitis 2011 initiiert. Erwachsene mit schwerer Neurodermitis (aktuelle/frühere antientzündliche Systemtherapie und/oder objektiver SCORAD ≥ 40) werden über einen Zeitraum von 24 Monaten prospektiv beobachtet. Anhand validierter Erhebungsinstrumente werden die klinische Erkrankungsschwere (EASI, SCORAD), Lebensqualität (DLQI), Symptome, globale Erkrankungsschwere sowie die Patientenzufriedenheit erfasst und die durchgeführten Therapien dokumentiert. Die vorliegende Analyse beschreibt die Charakteristika, Therapiewahl und Wirksamkeit der eingesetzten antiinflammatorischen Systemtherapien der bis Oktober 2014 eingeschlossenen Patienten. An fünf Zentren wurden insgesamt 78 Patienten (Durchschnittsalter 39 Jahre, 61 % männlich) eingeschlossen. Bei den Patienten besteht eine hohe Inanspruchnahme ambulanter und stationärer Leistungen. Ciclosporin war das am häufigsten eingesetzte Systemtherapeutikum und zeigte die höchste klinische Effektivität (EASI-50-Ansprechrate 51 %; EASI-75-Ansprechrate 34 % nach zwölfwöchiger Therapie). Azathioprin, Methotrexat (MTX), Prednisolon oral, Mycophenolat, Alitretinoin und Leflunomid wurden ebenfalls bei einzelnen Patienten eingesetzt. Die vorliegende Registerauswertung gibt wichtige Hinweise zur derzeitigen Versorgung von Erwachsenen mit schwerer Neurodermitis in Deutschland, dokumentiert die hohe Erkrankungslast, den Nutzen vorhandener Therapien und den Bedarf an weiteren, effektiven und in der Langzeitanwendung sicheren Therapieoptionen. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  3. Parameter estimation of the Farquhar-von Caemmerer-Berry biochemical model from photosynthetic carbon dioxide response curves

    USDA-ARS?s Scientific Manuscript database

    The methods of Sharkey and Gu for estimating the eight parameters of the Farquhar-von Caemmerer-Berry (FvBC) model were examined using generated photosynthesis versus intercellular carbon dioxide concentration (A/Ci) datasets. The generated datasets included data with (A) high accuracy, (B) normal ...

  4. Variabilität des Reviergesangs des Buchfinken (Fringilla coelebs) zur Raum-Zeit-Beschreibung von Metapopulationen

    NASA Astrophysics Data System (ADS)

    Nolte, Björn

    2003-10-01

    Der Buchfinkengesang wurde in Potsdam in zwei Hauptpopulationen über drei Jahre aufgenommen. Jedes Individuum wurde eindeutig am individuellen Strophentypenrepertoire identifiziert. Ein weiterer Punkt der die individuelle Wiedererkennung bestätigt ist die hohe Standorttreue der adulten Männchen. Die beschriebene Methode eignet sich für die Untersuchung von gesamten Populationen, um den Wandel des Gesangs von Populationen in Raum und Zeit zu beschreiben. Die Haupterkenntnisse der Arbeit sind: - Die Gesamtanzahl der Grundstrophentypen innerhalb einer Population bleibt über Jahre konstant. - Die relative Häufigkeit jedes einzelnen Strophentyps variiert von Jahr zu Jahr und von Population zu Population. - Gesangslernen erfolgt exakt mit einem Korrektheitsgrad von mindestens 96%. - Das Song-Sharing ist innerhalb der Population hoch. Die diskutierten Mechanismen für das Song-Sharing sind: Die Lebenserwartung, das Zugverhalten, das Lernverhalten, die Etabliertheit von Strophentypen, Weibchenpräferenzen und die Reaktionen der territorialen Männchen. - Weiterhin wurde ein Modell zur kulturellen Evolution des Buchfinkengesangs programmiert, um die Rolle der Einflussfaktoren, wie Fehlerquote, Abwanderungsrate und Laufzeit zu ermitteln. Der Wandel des Dialektes erfolgt graduell in Raum und Zeit. Daher sind keine scharfen Dialektgrenzen anzutreffen. Trotz dieser Tatsache markieren die etablierten Strophentypen die Population. 50 % der Juvenilen siedeln am Geburtsort, auf diese Weise bleibt der Dialekt erhalten und Inzest wird vermieden. -Analysiert man das Repertoire benachbarten Männchen bei isolierten Alleen, so entspricht die Gesangsangleichung in etwa dem Zufall. -Intraindividuelle Vergleiche der quantitativen Parameter des jeweiligen Strophentyps wurden saisonal und annuell durchgeführt. Saisonal konnten für einen Strophentyp ein Trend ermittelt werden. Bei jährlichen Vergleichen konnten intraindividuell ausschließlich nicht signifikante Ergebnisse ermittelt

  5. [Cystic renal neoplasms. New entities and molecular findings].

    PubMed

    Moch, H

    2010-10-01

    Renal neoplasms with dominant cysts represent a broad spectrum of known as well as novel renal tumor entities. Established renal tumors with dominant cysts include cystic nephroma, mixed epithelial and stromal tumor, synovial sarcoma and multilocular cystic renal cancer (WHO classification 2004). Novel tumor types have recently been reported, which are also characterized by marked cyst formation. Examples are tubulocystic renal cancer and renal cancer in end-stage renal disease. These tumors are very likely to be included in a future WHO classification due to their characteristic phenotype and molecular features. Cysts and clear cell renal cell carcinoma frequently coexist in the kidneys of patients with von Hippel-Lindau disease. Cysts are also a component of many sporadic clear cell renal cell carcinomas. Multilocular cystic renal cell carcinoma is composed almost exclusively of cysts and is regarded as a specific subtype of clear cell renal cancer. Recent molecular findings suggest that clear cell renal cancer may develop via a cyst-dependent mechanism in von Hippel-Lindau syndrome as well as via cyst-independent molecular pathways in sporadic clear cell renal cancer.

  6. Stochastic von Bertalanffy models, with applications to fish recruitment.

    PubMed

    Lv, Qiming; Pitchford, Jonathan W

    2007-02-21

    We consider three individual-based models describing growth in stochastic environments. Stochastic differential equations (SDEs) with identical von Bertalanffy deterministic parts are formulated, with a stochastic term which decreases, remains constant, or increases with organism size, respectively. Probability density functions for hitting times are evaluated in the context of fish growth and mortality. Solving the hitting time problem analytically or numerically shows that stochasticity can have a large positive impact on fish recruitment probability. It is also demonstrated that the observed mean growth rate of surviving individuals always exceeds the mean population growth rate, which itself exceeds the growth rate of the equivalent deterministic model. The consequences of these results in more general biological situations are discussed.

  7. Franz von Leydig (1821-1908), pioneer of comparative histology.

    PubMed

    Schneider, Marlon R

    2012-05-01

    Franz von Leydig, a German histologist and zoologist, is known to every student of human or animal anatomy because of the testicular testosterone-producing cells carrying his name. However, he made many contributions to our knowledge of the fine structure of animal tissues, including more than 200 scientific articles and several books. His most important work, the book Lehrbuch der Histologie des Menschen und der Thiere, established him as a pioneer if not the founder of comparative histology. Leydig taught at three different universities (Würzburg, Tübingen and Bonn) and received many honours from scientific organizations worldwide, including the Royal Society. He died in Rothenburg ob der Tauber, the town of his birth, aged 86 years.

  8. Von Glaserfeld`s Radical Constructivism: A Critical Review

    NASA Astrophysics Data System (ADS)

    Hardy, Michael D.

    We explore Ernst von Glaserfelds radical constructivism, its criticisms, and our own thoughts on what it promises for the reform of science and mathematics teaching. Our investigation reveals that many criticisms of radical constructivism are unwarranted; nevertheless, in its current cognitivist form radical constructivism may be insufficient to empower teachers to overcome objectivist cultural traditions. Teachers need to be empowered with rich understandings of philosophies of science and mathematics that endorse relativist epistemologies; for without such they are unlikely to be prepared to reconstruct their pedagogical practices. More importantly, however, is a need for a powerful social epistemology to serve as a referent for regenerating the culture of science education. We recommend blending radical constructivism with Habermas theory of communicative action to provide science teachers with a moral imperative for adopting a constructivist epistemology.

  9. General Information about Wilms Tumor and Other Childhood Kidney Tumors

    MedlinePlus

    ... Childhood Kidney Tumors Treatment (PDQ®)–Patient Version General Information About Wilms Tumor and Other Childhood Kidney Tumors ... the PDQ Pediatric Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  10. Genotype and phenotype correlation in von Hippel-Lindau disease based on alteration of the HIF-α binding site in VHL protein.

    PubMed

    Liu, Sheng-Jie; Wang, Jiang-Yi; Peng, Shuang-He; Li, Teng; Ning, Xiang-Hui; Hong, Bao-An; Liu, Jia-Yuan; Wu, Peng-Jie; Zhou, Bo-Wen; Zhou, Jing-Cheng; Qi, Nie-Nie; Peng, Xiang; Zhang, Jiu-Feng; Ma, Kai-Fang; Cai, Lin; Gong, Kan

    2018-03-29

    PurposeVon Hippel-Lindau (VHL) disease is a rare hereditary cancer syndrome that reduces life expectancy. We aimed to construct a more valuable genotype-phenotype correlation based on alterations in VHL protein (pVHL).MethodsVHL patients (n = 339) were recruited and grouped based on mutation types: HIF-α binding site missense (HM) mutations, non-HIF-α binding site missense (nHM) mutations, and truncating (TR) mutations. Age-related risks of VHL-associated tumors and patient survival were compared.ResultsMissense mutations conferred an increased risk of pheochromocytoma (HR = 1.854, p = 0.047) compared with truncating mutations. The risk of pheochromocytoma was lower in the HM group than in the nHM group (HR = 0.298, p = 0.003) but was similar between HM and TR groups (HR = 0.901, p = 0.810). Patients in the nHM group had a higher risk of pheochromocytoma (HR = 3.447, p < 0.001) and lower risks of central nervous system hemangioblastoma (CHB) (HR = 0.700, p = 0.045), renal cell carcinoma (HR = 0.610, p = 0.024), and pancreatic tumor (HR = 0.382, p < 0.001) than those in the combined HM and TR (HMTR) group. Moreover, nHM mutations were independently associated with better overall survival (HR = 0.345, p = 0.005) and CHB-specific survival (HR = 0.129, p = 0.005) than HMTR mutations.ConclusionThe modified genotype-phenotype correlation links VHL gene mutation, substrate binding site, and phenotypic diversity (penetrance and survival), and provides more accurate information for genetic counseling and pathogenesis studies.Genetics in Medicine advance online publication, 29 March 2018; doi:10.1038/gim.2017.261.

  11. Tumor Macroenvironment and Metabolism

    PubMed Central

    Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S.; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

    2014-01-01

    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. PMID:24787299

  12. Tumor macroenvironment and metabolism.

    PubMed

    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.

  13. Finite element approximation of an optimal control problem for the von Karman equations

    NASA Technical Reports Server (NTRS)

    Hou, L. Steven; Turner, James C.

    1994-01-01

    This paper is concerned with optimal control problems for the von Karman equations with distributed controls. We first show that optimal solutions exist. We then show that Lagrange multipliers may be used to enforce the constraints and derive an optimality system from which optimal states and controls may be deduced. Finally we define finite element approximations of solutions for the optimality system and derive error estimates for the approximations.

  14. Hemophilia and von Willebrand's disease: 1. Diagnosis, comprehensive care and assessment. Association of Hemophilia Clinic Directors of Canada.

    PubMed Central

    1995-01-01

    OBJECTIVE: To present current strategies for the assessment and comprehensive care of patients with hemophilia and von Willebrand's disease. OPTIONS: Hospital care, home care, single-provider care and multidisciplinary care. OUTCOMES: Morbidity and quality of life associated with bleeding and treatment. EVIDENCE: Relevant clinical studies and reports published from 1974 to 1994 were examined. A search was conducted of own reprint files, MEDLINE, citations in the articles reviewed and references provided by colleagues. In the MEDLINE search the following terms were used singly or in combination: "hemophilia," "von Willebrand's disease," "Factor VIII," "Factor IX," "von Willebrand factor," "diagnosis," "management," "home care," "comprehensive care," "inhibitor," "AIDS," "hepatitis," "life expectancy," "complications," "practice guidelines," "consensus statement" and "controlled trial." The in-depth review included only articles written in English from North America and Europe that were relevant to human disease and to a predetermined outline. The availability of treatment products in Canada was also considered. VALUES: Minimizing morbidity and maximizing functional status and quality of life were given a high value. BENEFITS, HARMS AND COSTS: The optimal use of treatment procedures and home care offers patients the advantages of minimized disability, improved survival and financial benefit. It is also cost effective. Potential harm, including the risk of hepatitis B, hepatitis C and HIV infection, has now been minimized through viral inactivation of plasma-derived coagulation-factor concentrates and through the use of recombinant clotting factor concentrates and other non-plasma-derived hemostatic agents. RECOMMENDATIONS: Patients with hemophilia and severe von Willebrand's disease should be followed in comprehensive care centres that offer expertise in the diagnosis, assessment and management of bleeding and complications and that can meet the educational and

  15. A new ODE tumor growth modeling based on tumor population dynamics

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

    Oroji, Amin; Omar, Mohd bin; Yarahmadian, Shantia

    2015-10-22

    In this paper a new mathematical model for the population of tumor growth treated by radiation is proposed. The cells dynamics population in each state and the dynamics of whole tumor population are studied. Furthermore, a new definition of tumor lifespan is presented. Finally, the effects of two main parameters, treatment parameter (q), and repair mechanism parameter (r) on tumor lifespan are probed, and it is showed that the change in treatment parameter (q) highly affects the tumor lifespan.

  16. Zone-specific remodeling of tumor blood vessels affects tumor growth.

    PubMed

    Tilki, Derya; Kilic, Nerbil; Sevinc, Sema; Zywietz, Friedrich; Stief, Christian G; Ergun, Suleyman

    2007-11-15

    Chaotic organization, abnormal leakiness, and structural instability are characteristics of tumor vessels. However, morphologic events of vascular remodeling in relation to tumor growth are not sufficiently studied yet. By using the rat rhabdomyosarcoma tumor model vascular morphogenesis was studied by light and electron microscopy and immunohistochemistry in relation to tumor regions such as tumor surrounding (TSZ), marginal (TMZ), intermediate (TIZ), and center (TCZ) zones. The analyses revealed that blood vessels of TSZ display a regular ultrastructure, whereas blood vessels of TMZ showed a chaotic organization and unstable structure with a diffuse or even lacking basal lamina, and missing or irregular assembled periendothelial cells. In contrast, blood vessels of TIZ and TCZ exhibited a more or less stabilized vessel structure with increased diameter. Correspondingly, normal assembly of alpha-smooth-muscle-actin (alpha-SMA)-positive cells into the vessel wall was observed in blood vessels of TSZ, TIZ, and TCZ. Also, Ang1 immunostaining was strongest in large vessels of TIZ and TCZ, whereas Ang2 staining was prominent in small vessels of TIZ. Tie2 staining was detectable in small and large vessels of all tumor zones. Immunostaining for alpha(v)beta(3)-integrin was strongest in small vessels of TMZ, whereas large vessels of TIZ and TCZ were almost negative. The results indicate a zone-specific remodeling of tumor blood vessels by stabilization of vessels in TIZ and TCZ, whereas small vessels of these zones obviously undergo regression leading to tumor necrosis. Thus, a better understanding of vascular remodeling and stabilization in tumors would enable new strategies in tumor therapy and imaging. (c) 2007 American Cancer Society.

  17. [Tumor and tumor-like benign mesenchymal lesions of the breast].

    PubMed

    Bisceglia, M; Nirchio, V; Carosi, I; Cappucci, U; Decata, A; Paragone, T; Di Mattia, A L

    1995-02-01

    All the spectrum is encompassed of those miscellaneous pathologic entities occurring in the mammary stroma which are on record up to date other than "mixed fibroepithelial" tumors (fibroadenomas and phyllodes tumors) and tumors both "pure" and "mixed" originating from myoepithelium (adenomyoepitheliomas and pleomorphic adenomas). Also they were excluded those dysreactive-autoimmune diseases (sarcoidosis, sclerosing lymphocytic lobulitis, lobular granulomatous mastitis) and those inflammatory-infectious conditions (tuberculosis, actinomycosis, foreign body reactions, Mondor's disease) which can mimick breast tumors clinically or on image analysis, but on the contrary not evoking the idea of a tumor on histology. Specifically, inflammatory pseudotumor, myofibroblastoma, leiomyoma, neurinoma/neurofibroma, benign fibrous histiocytoma, hemangiopericytoma, fibromatosis, nodular fascitis, variants of lipoma, mesenchymoma, amartoma and its variants, hemangiomas, pseudoangiomatous hyperplasia of stroma, amyloid tumor, granular cell tumor, are consecutively described and discussed, with a large list of references enclosed to each rubric. Most of the pictures are taken from personally observed lesions of the breast. Only few pictures referred to are from their analogue lesions which occurred in soft parts of other locations, with specific mention of that when it was the case. Of note after reviewing the literature the fact that no glomus tumor, nor Kaposi's sarcoma either sporadic or in the context of any immunodeficiency, nor myelolipoma has been recorded yet.

  18. [On the Awarding of the First Nobel Prize for Physiology or Medicine to Emil von Behring].

    PubMed

    Hansson, Nils; Enke, Ulrike

    2015-12-01

    In his will of 1895, the Swedish inventor Alfred Nobel laid the foundation for prizes in physics, chemistry, physiology or medicine, literature, and peace to those who had "conferred the greatest benefit on mankind" during the last year. The Nobel Prize is today widely considered as the most prestigious international symbol of scientific excellence, but it still is an exciting research question how it gained such prestige. Drawing on files from the Emil von Behring Archive in Marburg, Germany, and the Archive of the Nobel Assembly for Physiology or Medicine in Stockholm this essay aims at shedding light on why the first Nobel Prize for Physiology or Medicine in 1901 was awarded the German immunologist Emil von Behring, and how this decision was viewed at that time. This study is part of a research project that explores mechanisms leading to scientific recognition by using the example of the Nobel Prize for Physiology or Medicine. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Numerical simulation of laminar plasma dynamos in a cylindrical von Karman flow

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

    Khalzov, I. V.; Brown, B. P.; Schnack, D. D.

    2011-03-15

    The results of a numerical study of the magnetic dynamo effect in cylindrical von Karman plasma flow are presented with parameters relevant to the Madison Plasma Couette Experiment. This experiment is designed to investigate a broad class of phenomena in flowing plasmas. In a plasma, the magnetic Prandtl number Pm can be of order unity (i.e., the fluid Reynolds number Re is comparable to the magnetic Reynolds number Rm). This is in contrast to liquid metal experiments, where Pm is small (so, Re>>Rm) and the flows are always turbulent. We explore dynamo action through simulations using the extended magnetohydrodynamic NIMRODmore » code for an isothermal and compressible plasma model. We also study two-fluid effects in simulations by including the Hall term in Ohm's law. We find that the counter-rotating von Karman flow results in sustained dynamo action and the self-generation of magnetic field when the magnetic Reynolds number exceeds a critical value. For the plasma parameters of the experiment, this field saturates at an amplitude corresponding to a new stable equilibrium (a laminar dynamo). We show that compressibility in the plasma results in an increase of the critical magnetic Reynolds number, while inclusion of the Hall term in Ohm's law changes the amplitude of the saturated dynamo field but not the critical value for the onset of dynamo action.« less

  20. Link between von-Karman energy decay and reconnection heating in turbulent plasmas

    NASA Astrophysics Data System (ADS)

    Shay, M. A.; Parashar, T.; Haggerty, C. C.; Matthaeus, W. H.; Phan, T.; Drake, J. F.; Cassak, P.; Wu, P.

    2016-12-01

    Coherent structures such as current sheets are prevalent in many turbulent plasmas and have been shown to be correlated with dissipation and heating in observations of solar wind turbulence and dissipation in kinetic particle-in-cell (PIC) simulations. However, the role that they play in the dissipation of turbulent energy and ultimately the heating of the plasma are still not well understood. A recent study [1] using kinetic PIC simulations of turbulence found that the total heating in the plasma is consistent with a von-Karman scaling of the cascade rate, and that the proton to electron heating ratio was proportional to the total heating rate and linked to the ratio of gyroperiod to nonlinear turnover time at the ion kinetic scales. We review recent findings regarding the rate of heating in outflow jets during laminar reconnection and apply it to kinetic PIC simulations of turbulence, employing some reasonable assumptions to connect the two theories. The goal is to determine if reconnection is a primary heating mechanism or plays less of a role. Conversely, we also apply the new understanding of the von-Karman cascade to isolated reconnection events to determine if a cascade-like process is controlling the heating rate. [1] W. Matthaeus et al., ApJ Letters, 827, L7, 2016, doi:10.3847/2041-8205/827/1/L7

  1. The immunization site of cytokine-secreting tumor cell vaccines influences the trafficking of tumor-specific T lymphocytes and antitumor efficacy against regional tumors.

    PubMed

    Chang, Chun-Jung; Tai, Kuo-Feng; Roffler, Steve; Hwang, Lih-Hwa

    2004-11-15

    Tumor cells engineered to secrete cytokines, referred to as tumor cell vaccines, can often generate systemic antitumor immunity and, in many cases, cause tumor regression. We compared the efficacy of s.c. immunization or intrahepatic immunization of GM-CSF-expressing tumor cell vaccines on the growth of s.c. or orthotopic liver tumors. A chemically transformed hepatic epithelial cell line, GP7TB, derived from Fischer 344 rats, was used to generate tumor models and tumor cell vaccines. Our results demonstrated that two s.c. injections of an irradiated tumor cell vaccine significantly controlled the growth of s.c. tumors, but was completely ineffective against orthotopic liver tumors. Effector cell infiltration in liver tumors was markedly reduced compared with s.c. tumors. Enhanced apoptosis of some effector cells was observed in the liver tumors compared with the s.c. tumors. Furthermore, the T cells induced by s.c. immunization preferentially migrated to s.c. tumor sites, as demonstrated by adoptive transfer experiments. In contrast, intrahepatic immunization, using parental tumor cells admixed with adenoviruses carrying the GM-CSF gene, yielded significantly better therapeutic effects on the liver tumors than on the s.c. tumors. Adoptive transfer experiments further confirmed that the T cells induced by liver immunization preferentially migrated to the liver tumor sites. Our results demonstrate that distinct T cell populations are induced by different immunization routes. Thus, the homing behavior of T cells depends on the route of immunization and is an important factor determining the efficacy of immunotherapy for regional tumors.

  2. The two glycolytic markers GLUT1 and MCT1 correlate with tumor grade and survival in clear-cell renal cell carcinoma

    PubMed Central

    Dadone, Bérengère; Durand, Matthieu; Borchiellini, Delphine; Amiel, Jean; Pouyssegur, Jacques; Rioux-Leclercq, Nathalie; Pages, Gilles; Burel-Vandenbos, Fanny; Mazure, Nathalie M.

    2018-01-01

    Background Clear-cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer. Although ccRCC is characterized by common recurrent genetic abnormalities, including inactivation of the von Hippel-Lindau (vhl) tumor suppressor gene resulting in stabilization of hypoxia-inducible factors (HIFs), the tumor aggressiveness and outcome of ccRCC is variable. New biomarkers are thus required to improve ccRCC diagnosis, prognosis and therapeutic options. This work aims to investigate the expression of HIF and proteins involved in metabolism and pH regulation. Their correlation to histoprognostic parameters and survival was analyzed. Methods ccRCC of 45 patients were analyzed. HIF-1α, HIF-2α, HAF, GLUT1, MCT1, MCT4, CAIX and CAXII expression was assessed by immunohistochemistry in a semi-quantitative and qualitative manner. The GLUT1, MCT1, MCT4, CAIX and CAXII mRNA levels were analyzed in an independent cohort of 43 patients. Results A significant correlation was observed between increased GLUT1, MCT1, CAXII protein expression and a high Fuhrman grade in ccRCC patients. Moreover, while HIF-1α, HIF-2α and HAF expression was heterogenous within tumors, we observed and confirmed that HIF-2α co-localized with HAF. We confirmed, in an independent cohort, that GLUT1, MCT1 and CAXII mRNA levels correlated with the Fuhrman grade. Moreover, we demonstrated that the high mRNA level of both MCT1 and GLUT1 correlated with poor prognosis. Conclusions This study demonstrates for the first time a link between the aggressiveness of high- Fuhrman grade ccRCC and metabolic reprogramming. It also confirms the role of HIF-2α and HAF in tumor invasiveness. Finally, these results demonstrate that MCT1 and GLUT1 are strong prognostic markers and promising therapeutic targets. PMID:29481555

  3. The two glycolytic markers GLUT1 and MCT1 correlate with tumor grade and survival in clear-cell renal cell carcinoma.

    PubMed

    Ambrosetti, Damien; Dufies, Maeva; Dadone, Bérengère; Durand, Matthieu; Borchiellini, Delphine; Amiel, Jean; Pouyssegur, Jacques; Rioux-Leclercq, Nathalie; Pages, Gilles; Burel-Vandenbos, Fanny; Mazure, Nathalie M

    2018-01-01

    Clear-cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer. Although ccRCC is characterized by common recurrent genetic abnormalities, including inactivation of the von Hippel-Lindau (vhl) tumor suppressor gene resulting in stabilization of hypoxia-inducible factors (HIFs), the tumor aggressiveness and outcome of ccRCC is variable. New biomarkers are thus required to improve ccRCC diagnosis, prognosis and therapeutic options. This work aims to investigate the expression of HIF and proteins involved in metabolism and pH regulation. Their correlation to histoprognostic parameters and survival was analyzed. ccRCC of 45 patients were analyzed. HIF-1α, HIF-2α, HAF, GLUT1, MCT1, MCT4, CAIX and CAXII expression was assessed by immunohistochemistry in a semi-quantitative and qualitative manner. The GLUT1, MCT1, MCT4, CAIX and CAXII mRNA levels were analyzed in an independent cohort of 43 patients. A significant correlation was observed between increased GLUT1, MCT1, CAXII protein expression and a high Fuhrman grade in ccRCC patients. Moreover, while HIF-1α, HIF-2α and HAF expression was heterogenous within tumors, we observed and confirmed that HIF-2α co-localized with HAF. We confirmed, in an independent cohort, that GLUT1, MCT1 and CAXII mRNA levels correlated with the Fuhrman grade. Moreover, we demonstrated that the high mRNA level of both MCT1 and GLUT1 correlated with poor prognosis. This study demonstrates for the first time a link between the aggressiveness of high- Fuhrman grade ccRCC and metabolic reprogramming. It also confirms the role of HIF-2α and HAF in tumor invasiveness. Finally, these results demonstrate that MCT1 and GLUT1 are strong prognostic markers and promising therapeutic targets.

  4. Tumor Expression of CD200 Inhibits IL-10 Production by Tumor-Associated Myeloid Cells and Prevents Tumor Immune Evasion of CTL Therapy

    PubMed Central

    Wang, Lixin; Liu, Jin-Qing; Talebian, Fatemeh; El-Omrani, Hani Y.; Khattabi, Mazin; Yu, Li; Bai, Xue-Feng

    2010-01-01

    CD200 is a cell-surface glycoprotein that functions through interaction with the CD200 receptor (CD200R) on myeloid lineage cells to regulate myeloid cell functions. Expression of CD200 has been implicated in multiple types of human cancer, however the impact of tumor expression of CD200 on tumor immunity remains poorly understood. To evaluate this issue, we generated CD200-positive mouse plasmacytoma J558 and mastocytoma P815 cells. We found that established CD200-positive tumors were often completely rejected by adoptively transferred CTL without tumor recurrence; in contrast, CD200-negative tumors were initially rejected by adoptively transferred CTL but the majority of tumors recurred. Tumor expression of CD200 significantly inhibited suppressive activity and IL-10 production by tumor-associated myeloid cells (TAMC), and as a result, more CTL accumulated in the tumor and exhibited a greater capacity to produce IFN-γ in CD200-positive tumors than in CD200-negative tumors. Neutralization of IL-10 significantly inhibited the suppressor activity of TAMC, and IL-10-deficiency allowed TAMC to kill cancer cells and their antigenic variants, which prevented tumor recurrence during CTL therapy. Thus, tumor expression of CD200 prevents tumor recurrence via inhibiting IL-10 production by TAMC. PMID:20662098

  5. Assessment of the clinical relevance of quantitative sensory testing with Von Frey monofilaments in patients with allodynia and neuropathic pain. A pilot study.

    PubMed

    Keizer, D; van Wijhe, M; Post, W J; Uges, D R A; Wierda, J M K H

    2007-08-01

    Allodynia is a common and disabling symptom in many patients with neuropathic pain. Whereas quantification of pain mostly depends on subjective pain reports, allodynia can also be measured objectively with quantitative sensory testing. In this pilot study, we investigated the clinical relevance of quantitative sensory testing with Von Frey monofilaments in patients with allodynia as a consequence of a neuropathic pain syndrome, by means of correlating subjective pain scores with pain thresholds obtained with quantitative sensory testing. During a 4-week trial, we administered a cannabis extract to 17 patients with allodynia. We quantified the severity of the allodynia with Von Frey monofilaments before, during and after the patients finished the trial. We also asked the patients to rate their pain on a numeric rating scale at these three moments. We found that most of the effect of the cannabis occurred in the last 2 weeks of the trial. In this phase, we observed that the pain thresholds, as measured with Von Frey monofilaments, were inversely correlated with a decrease of the perceived pain intensity. These preliminary findings indicate clinical relevance of quantitative sensory testing with Von Frey monofilaments in the quantification of allodynia in patients with neuropathic pain, although confirmation of our data is still required in further studies to position this method of quantitative sensory testing as a valuable tool, for example, in the evaluation of therapeutic interventions for neuropathic pain.

  6. [Pituitary gland tumors].

    PubMed

    Jesser, J; Schlamp, K; Bendszus, M

    2014-10-01

    This article gives an overview of the most common tumors of the pituitary gland and the differential diagnostics with special emphasis on radiological diagnostic criteria. A selective search of the literature in PubMed was carried out. Pituitary adenomas constitute 10-15% of all intracranial tumors and are the most common tumors of the sellar region. Tumors smaller than 1 cm in diameter are called microadenomas while those larger than 1 cm in diameter are called macroadenomas. Approximately 65% of pituitary gland adenomas secrete hormones whereby approximately 50% secrete prolactin, 10% secrete growth hormone (somatotropin) and 6% secrete corticotropin. Other tumors located in the sella turcica can also cause endocrinological symptoms, such as an oversecretion of pituitary hormone or pituitary insufficiency by impinging on the pituitary gland or its stalk. When tumors spread into the space cranial to the sella turcica, they can impinge on the optic chiasm and cause visual disorders. A common differential diagnosis of a sellar tumor is a craniopharyngeoma. In children up to 10% of all intracranial tumors are craniopharyngeomas. Other differential diagnoses for sellar tumors are metastases, meningiomas, epidermoids and in rare cases astrocytomas, germinomas or Rathke cleft cysts As these tumors are located in an anatomically complex region of the skull base and are often very small, a highly focused imaging protocol is required. The currently favored modality is magnetic resonance imaging (MRI) with the administration of a contrast agent. The sellar region should be mapped in thin slices. In cases of suspected microadenoma the imaging protocol should also contain a sequence with dynamic contrast administration in order to assess the specific enhancement characteristics of the tumor and the pituitary gland.

  7. Renin-secreting tumors.

    PubMed

    Roswell, R H

    1990-02-01

    Hypertension resulting from a renin-secreting tumor was first reported in 1967 by Robertson et al. Kihara and coworkers subsequently coined the term juxtaglomerular cell tumor for a similar tumor in a young woman with hyperreninemic hypertension. Since the description of these first two cases, it has become clear that renin-secreting tumors of both renal and nonrenal origin can cause surgically curable hypertension. Primary reninism has been suggested as a more appropriate term for the clinical syndrome associated with renin-secreting tumors, both renal and extrarenal, whether benign or malignant.

  8. Native multimer analysis of plasma and platelet von Willebrand factor compared to denaturing separation: implication for the interpretation of satellite bands.

    PubMed

    Hohenstein, Kurt; Griesmacher, Andrea; Weigel, Günter; Golderer, Georg; Ott, Helmut Werner

    2011-06-01

    Blue native electrophoresis (BNE) was applied to analyze the von Willebrand factor (vWF) multimers in their native state and to present a methodology to perform blue native electrophoresis on human plasma proteins, which has not been done before. The major difference between this method and the commonly used SDS-agarose gel electrophoresis is the lack of satellite bands in the high-resolution native gel. To further analyze this phenomenon, a second dimension was performed under denaturing conditions. Thereby, we obtained a pattern in which each protein sub-unit from the first dimension dissociates into three distinct sub-bands. These bands confirm the triplet structure, which consists of an intermediate band and two satellite bands. By introducing the second dimension, our novel method separates the triplet structure into a higher resolution than the commonly used SDS-agarose gel electrophoresis does. This helps considerably in the classification of ambiguous von Willebrand's disease subtypes. In addition, our method has the additional advantage of being able to resolve the triplet structure of platelet vWF multimers, which has not been identified previously through conventional SDS-agarose electrophoresis multimer analysis. This potential enables us to compare the triplet structure from platelet and plasmatic vWF, and may help to find out whether structural abnormalities concern the vWF molecule in the platelet itself, or whether they are due to the physiological processing of vWF shed into circulation. Owing to its resolution and sensitivity, this native separation technique offers a promising tool for the analysis and detection of von Willebrand disorder, and for the classification of von Willebrand's disease subtypes. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Two tumor models of curative adoptive chemoimmunotherapy using tumor-infiltrated spleen cells with potent antitumor cytotoxicity stimulated by antigen-sharing tumors.

    PubMed

    Laude, M; Russo, K L; Mokyr, M B; Dray, S

    1993-07-01

    Previously we have established curative protocols for adoptive chemoimmunotherapy (ACIT) of mice bearing different plasmacytomas that are known to bear cross-reacting antigens: (a) the cure of mice bearing an early-stage, nonpalpable MOPC-315 tumor by a very low dose of cyclophosphamide (10 mg/kg) and cultured MOPC-315-tumor-infiltrated (TI) spleen cells (25 x 10(6)) and (b) the cure of mice bearing a late-stage, relatively drug-resistant, highly metastatic RPC-5 tumor with cyclophosphamide (100 mg/kg) and cultured RPC-5 TI spleen cells (25 x 10(6) - 50 x 10(6)). In both models, the spleen cells were obtained from mice bearing a late-stage tumor and were cultured for 5 days in the presence of polyethyleneglycol 6000 and autochthonous tumor cells as a source of tumor antigen. Here we show that RPC-5 tumor cells could substitute for MOPC-315 tumor cells in the 5-day culture of MOPC-315 TI spleen cells so that they became curative in ACIT for mice bearing an early-stage MOPC-315 tumor. Similarly, MOPC-315 tumor cells could substitute for RPC-5 tumor cells in the 5-day culture of RPC-5 TI spleen cells so that they became curative in ACIT of mice bearing a late-stage RPC-5 tumor. In addition, RPC-5 TI spleen cells cultured with either MOPC-315 or RPC-5 tumor cells were effective in curing all mice bearing an early-stage MOPC-315 tumor by ACIT. However, MOPC-315 TI spleen cells whether cultured with MOPC-315 or RPC-5 tumor cells, were much less effective than cultured RPC-5 TI spleen cells in curing mice bearing a late-stage RPC-5 tumor by ACIT (although the survival of these mice was extended significantly). Interestingly, whereas RPC-5 TI spleen cells cultured with either MOPC-315 or RPC-5 tumor cells were as effective as MOPC-315 TI spleen cells cultured under the same conditions in lysing MOPC-315 tumor cells in vitro, MOPC-315 TI spleen cells that had been cultured with either MOPC-315 or RPC-5 tumor cells exerted a much weaker in vitro cytotoxic T lymphocyte

  10. Analytical and numerical analysis of the slope of von Mises planar trusses

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

    Kalina, M.; Frantík, P.

    2016-06-08

    In the present paper, there are presented post-critical stress states which will occur at loading by vertical shift of the top joint in the direction downwards. The formation of certain stress states depends on the size of the angle formed by a straight beam of the von Mises planar truss with horizontal plane. Numerical and analytical methods and their problems with finding the angle were described. The numerical solution applies the method of searching for a minimum of potential energy.

  11. Circulating tumor cells in patients with testicular germ cell tumors.

    PubMed

    Nastały, Paulina; Ruf, Christian; Becker, Pascal; Bednarz-Knoll, Natalia; Stoupiec, Małgorzata; Kavsur, Refik; Isbarn, Hendrik; Matthies, Cord; Wagner, Walter; Höppner, Dirk; Fisch, Margit; Bokemeyer, Carsten; Ahyai, Sascha; Honecker, Friedemann; Riethdorf, Sabine; Pantel, Klaus

    2014-07-15

    Germ cell tumors (GCTs) represent the most frequent malignancies among young men, but little is known about circulating tumor cells (CTCs) in these tumors. Considering their heterogeneity, CTCs were investigated using two independent assays targeting germ cell tumor and epithelial cell-specific markers, and results were correlated with disease stage, histology, and serum tumor markers. CTCs were enriched from peripheral blood (n = 143 patients) and testicular vein blood (TVB, n = 19 patients) using Ficoll density gradient centrifugation. For CTC detection, a combination of germ cell tumor (anti-SALL4, anti-OCT3/4) and epithelial cell-specific (anti-keratin, anti-EpCAM) antibodies was used. In parallel, 122 corresponding peripheral blood samples were analyzed using the CellSearch system. In total, CTCs were detected in 25 of 143 (17.5%) peripheral blood samples, whereas only 11.5% of patients were CTC-positive when considering exclusively the CellSearch assay. The presence of CTCs in peripheral blood correlated with clinical stage (P < 0.001) with 41% of CTC positivity in patients with metastasized tumors and 100% in patients with relapsed and chemotherapy-refractory disease. Histologically, CTC-positive patients suffered more frequently from nonseminomatous primary tumors (P < 0.001), with higher percentage of yolk sac (P < 0.001) and teratoma (P = 0.004) components. Furthermore, CTC detection was associated with elevated serum levels of α-fetoprotein (AFP; P = 0.025), β-human chorionic gonadotropin (βHCG; P = 0.002), and lactate dehydrogenase (LDH; P = 0.002). Incidence and numbers of CTCs in TVB were much higher than in peripheral blood. The inclusion of germ cell tumor-specific markers improves CTC detection in GCTs. CTCs occur frequently in patients with more aggressive disease, and there is a gradient of CTCs with decreasing numbers from the tumor-draining vein to the periphery. ©2014 American Association for Cancer Research.

  12. Coats' disease, Turner syndrome, and von Willebrand disease in a patient with Wildtype Norrie disease pseudoglioma.

    PubMed

    Desai, Rajen U; Saffra, Norman A; Krishna, Rati P; Rosenberg, Steven E

    2011-01-01

    The authors describe a girl diagnosed as having Coats' disease, Turner syndrome (45X karyotype), and type 1 von Willebrand disease. She tested negative for the Norrie disease pseudoglioma (NDP) gene located on the X-chromosome, which has been suspected of contributing to Coats' disease. Copyright 2010, SLACK Incorporated.

  13. Genetics of von Willebrand disease type 1.

    PubMed

    Riddel, James P; Aouizerat, Bradley E

    2006-10-01

    The most common form of von Willebrand disease (VWD) is reported to be type 1, accounting for as much as 80% of reported cases. With prevalence estimates as high as 1.6% in the general population, upwards of 4.5 million Americans may be affected. Unfortunately, VWD type 1 is also the most difficult type to diagnose. Despite the continuing progress in defining the genetic lesions responsible for VWD types 2 and 3, identification of the genetic determinants of VWD type 1 remains elusive. Herein the phenomenon known as VWD is summarized, the challenges associated with the diagnosis of type 1 VWD are described, and the role of genetic research in meeting these challenges is explored. The authors identify key gaps in the current genetics literature and suggest new avenues for future research. Lastly, they explore the role of nurses in this research and clinical endeavor. To the authors'knowledge, this review is the first to address these complex issues in nursing research.

  14. The von Mises stress distribution on the surface of UHMWPE with texture-shaped variation in the presence of normal load and dry sliding contact

    NASA Astrophysics Data System (ADS)

    Lestari, W. D.; Jamari, J.; Bayuseno, A. P.

    2017-04-01

    The texture shapes play a key role in the tribological performance of the surface material. This paper presents a study on the use of the 3D finite element method for surface stress analysis on the different texture shape under load and dry sliding contact. The five texture-shaped model was investigated in this work, namely square, circle, ellipse, triangle, and chevron. The result shown that the square shape has the highest value of von Mises resultant stress under static load. In contrast, the dry sliding contact on the triangle shape provided the highest von Mises stress distribution. The lowest value of von Mises stress can be found in the texture pattern of circle, square, and chevron under influence of load for 17 N, 30 N, and 50 N, respectively. Those texture patterns applied to surface of Ultra High Molecular Weight Polyethylene (UHMWPE) may have a strong effect on the reduction of wear rate and enhance tribological performance.

  15. Tissue engineered tumor models.

    PubMed

    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.

  16. Tumor cell culture on collagen-chitosan scaffolds as three-dimensional tumor model: A suitable model for tumor studies.

    PubMed

    Mahmoudzadeh, Aziz; Mohammadpour, Hemn

    2016-07-01

    Tumor cells naturally live in three-dimensional (3D) microenvironments, while common laboratory tests and evaluations are done in two-dimensional (2D) plates. This study examined the impact of cultured 4T1 cancer cells in a 3D collagen-chitosan scaffold compared with 2D plate cultures. Collagen-chitosan scaffolds were provided and passed confirmatory tests. 4T1 tumor cells were cultured on scaffolds and then tumor cells growth rate, resistance to X-ray radiation, and cyclophosphamide as a chemotherapy drug were analyzed. Furthermore, 4T1 cells were extracted from the scaffold model and were injected into the mice. Tumor growth rate, survival rate, and systemic immune responses were evaluated. Our results showed that 4T1 cells infiltrated the scaffolds pores and constructed a 3D microenvironment. Furthermore, 3D cultured tumor cells showed a slower proliferation rate, increased levels of survival to the X-ray irradiation, and enhanced resistance to chemotherapy drugs in comparison with 2D plate cultures. Transfer of extracted cells to the mice caused enhanced tumor volume and decreased life span. This study indicated that collagen-chitosan nanoscaffolds provide a suitable model of tumor that would be appropriate for tumor studies. Copyright © 2016. Published by Elsevier B.V.

  17. Intranasal pericytic tumors (glomus tumor and sinonasal hemangiopericytoma-like tumor): report of two cases with review of the literature.

    PubMed

    Li, Xiao-Qiu; Hisaoka, Masanori; Morio, Takashi; Hashimoto, Hiroshi

    2003-05-01

    An intranasal glomus tumor and a sinonasal hemangiopericytoma-like tumor are reported. Both patients were elderly women suffering from nasal bleeding, and presented with a polypoid mass arising in the nasal septum. Microscopically, the glomus tumor displayed a proliferation of uniform rounded or cuboidal epithelioid cells arranged in sheets and interrupted by a rich vasculature with a characteristic configuration mimicking the normal glomus bodies, while the sinonasal hemangiopericytoma-like tumor featured a perivascular proliferation of spindle- to oval-shaped cells that were arranged in short fascicles. Both tumors shared immunohistochemical features supporting their myoid differentiation by the expression of vimentin, alpha-smooth muscle actin and muscle-specific actin, albeit with no immunoreaction to desmin. Both the intranasal glomus tumor and sinonasal hemangiopericytoma-like tumor are characterized by a perivascular growth pattern and myoid differentiation, having a close relation to the 'perivascular myomas', which was recently designated.

  18. Verknüpfung von DQ-Indikatoren mit KPIs und Auswirkungen auf das Return on Investment

    NASA Astrophysics Data System (ADS)

    Block, Frank

    Häufig ist nicht klar, welche Beziehungen zwischen Datenqualitätsindikatoren (DQI, Definition folgt weiter unten) und Key Performance Indicators (KPI, s. Abschnitt 1.3 für weitere Details) eines Unternehmens oder einer Organisation bestehen. Dies ist insbesondere deshalb von Bedeutung, da die Kenntnis dieser Beziehungen maßgeblich die Ausprägung eines Datenqualitätsprojekts beeinflusst.

  19. Childhood Brain Tumors

    MedlinePlus

    Brain tumors are abnormal growths inside the skull. They are among the most common types of childhood ... still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches and ...

  20. Neuroendocrine Tumor: Statistics

    MedlinePlus

    ... Tumor > Neuroendocrine Tumor: Statistics Request Permissions Neuroendocrine Tumor: Statistics Approved by the Cancer.Net Editorial Board , 01/ ... the body. It is important to remember that statistics on the survival rates for people with a ...

  1. Intra-Tumor Genetic Heterogeneity in Wilms Tumor: Clonal Evolution and Clinical Implications.

    PubMed

    Cresswell, George D; Apps, John R; Chagtai, Tasnim; Mifsud, Borbala; Bentley, Christopher C; Maschietto, Mariana; Popov, Sergey D; Weeks, Mark E; Olsen, Øystein E; Sebire, Neil J; Pritchard-Jones, Kathy; Luscombe, Nicholas M; Williams, Richard D; Mifsud, William

    2016-07-01

    The evolution of pediatric solid tumors is poorly understood. There is conflicting evidence of intra-tumor genetic homogeneity vs. heterogeneity (ITGH) in a small number of studies in pediatric solid tumors. A number of copy number aberrations (CNA) are proposed as prognostic biomarkers to stratify patients, for example 1q+ in Wilms tumor (WT); current clinical trials use only one sample per tumor to profile this genetic biomarker. We multisampled 20 WT cases and assessed genome-wide allele-specific CNA and loss of heterozygosity, and inferred tumor evolution, using Illumina CytoSNP12v2.1 arrays, a custom analysis pipeline, and the MEDICC algorithm. We found remarkable diversity of ITGH and evolutionary trajectories in WT. 1q+ is heterogeneous in the majority of tumors with this change, with variable evolutionary timing. We estimate that at least three samples per tumor are needed to detect >95% of cases with 1q+. In contrast, somatic 11p15 LOH is uniformly an early event in WT development. We find evidence of two separate tumor origins in unilateral disease with divergent histology, and in bilateral WT. We also show subclonal changes related to differential response to chemotherapy. Rational trial design to include biomarkers in risk stratification requires tumor multisampling and reliable delineation of ITGH and tumor evolution. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  2. A differential diagnosis of inherited endocrine tumors and their tumor counterparts

    PubMed Central

    Toledo, Sergio P. A.; Lourenço, Delmar M.; Toledo, Rodrigo A.

    2013-01-01

    Inherited endocrine tumors have been increasingly recognized in clinical practice, although some difficulties still exist in differentiating these conditions from their sporadic endocrine tumor counterparts. Here, we list the 12 main topics that could add helpful information and clues for performing an early differential diagnosis to distinguish between these conditions. The early diagnosis of patients with inherited endocrine tumors may be performed either clinically or by mutation analysis in at-risk individuals. Early detection usually has a large impact in tumor management, allowing preventive clinical or surgical therapy in most cases. Advice for the clinical and surgical management of inherited endocrine tumors is also discussed. In addition, recent clinical and genetic advances for 17 different forms of inherited endocrine tumors are briefly reviewed. PMID:23917672

  3. Analytic approximations of Von Kármán plate under arbitrary uniform pressure—equations in integral form

    NASA Astrophysics Data System (ADS)

    Zhong, XiaoXu; Liao, ShiJun

    2018-01-01

    Analytic approximations of the Von Kármán's plate equations in integral form for a circular plate under external uniform pressure to arbitrary magnitude are successfully obtained by means of the homotopy analysis method (HAM), an analytic approximation technique for highly nonlinear problems. Two HAM-based approaches are proposed for either a given external uniform pressure Q or a given central deflection, respectively. Both of them are valid for uniform pressure to arbitrary magnitude by choosing proper values of the so-called convergence-control parameters c 1 and c 2 in the frame of the HAM. Besides, it is found that the HAM-based iteration approaches generally converge much faster than the interpolation iterative method. Furthermore, we prove that the interpolation iterative method is a special case of the first-order HAM iteration approach for a given external uniform pressure Q when c 1 = - θ and c 2 = -1, where θ denotes the interpolation iterative parameter. Therefore, according to the convergence theorem of Zheng and Zhou about the interpolation iterative method, the HAM-based approaches are valid for uniform pressure to arbitrary magnitude at least in the special case c 1 = - θ and c 2 = -1. In addition, we prove that the HAM approach for the Von Kármán's plate equations in differential form is just a special case of the HAM for the Von Kármán's plate equations in integral form mentioned in this paper. All of these illustrate the validity and great potential of the HAM for highly nonlinear problems, and its superiority over perturbation techniques.

  4. Depleting tumor-specific Tregs at a single site eradicates disseminated tumors

    PubMed Central

    Marabelle, Aurélien; Kohrt, Holbrook; Sagiv-Barfi, Idit; Ajami, Bahareh; Axtell, Robert C.; Zhou, Gang; Rajapaksa, Ranjani; Green, Michael R.; Torchia, James; Brody, Joshua; Luong, Richard; Rosenblum, Michael D.; Steinman, Lawrence; Levitsky, Hyam I.; Tse, Victor; Levy, Ronald

    2013-01-01

    Activation of TLR9 by direct injection of unmethylated CpG nucleotides into a tumor can induce a therapeutic immune response; however, Tregs eventually inhibit the antitumor immune response and thereby limit the power of cancer immunotherapies. In tumor-bearing mice, we found that Tregs within the tumor preferentially express the cell surface markers CTLA-4 and OX40. We show that intratumoral coinjection of anti–CTLA-4 and anti-OX40 together with CpG depleted tumor-infiltrating Tregs. This in situ immunomodulation, which was performed with low doses of antibodies in a single tumor, generated a systemic antitumor immune response that eradicated disseminated disease in mice. Further, this treatment modality was effective against established CNS lymphoma with leptomeningeal metastases, sites that are usually considered to be tumor cell sanctuaries in the context of conventional systemic therapy. These results demonstrate that antitumor immune effectors elicited by local immunomodulation can eradicate tumor cells at distant sites. We propose that, rather than using mAbs to target cancer cells systemically, mAbs could be used to target the tumor infiltrative immune cells locally, thereby eliciting a systemic immune response. PMID:23728179

  5. Brain tumor - primary - adults

    MedlinePlus

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  6. Profile of von Willebrand factor antigen and von Willebrand factor propeptide in an overall TIA and ischaemic stroke population and amongst subtypes.

    PubMed

    Tobin, W O; Kinsella, J A; Kavanagh, G F; O'Donnell, J S; McGrath, R T; Tierney, S; Egan, B; Feeley, T M; Coughlan, T; Collins, D R; O'Neill, D; Murphy, Sjx; Lim, S J; Murphy, R P; McCabe, Djh

    2017-04-15

    Von Willebrand factor propeptide (VWF:Ag II) is proposed to be a more sensitive marker of acute endothelial activation than von Willebrand factor antigen (VWF:Ag). Simultaneous data on VWF:Ag and VWF:Ag II profiles are very limited following TIA and ischaemic stroke. In this prospective, observational, case-control study, plasma VWF:Ag and VWF:Ag II levels were quantified in 164 patients≤4weeks of TIA or ischaemic stroke (baseline), and then ≥14days (14d) and ≥90days (90d) later, and compared with those from 27 healthy controls. TIA and stroke subtyping was performed according to the TOAST classification. The relationship between VWF:Ag and VWF:Ag II levels and platelet activation status was assessed. 'Unadjusted' VWF:Ag and VWF:Ag II levels were higher in patients at baseline, 14d and 90d than in controls (p≤0.03). VWF:Ag levels remained higher in patients than controls at baseline (p≤0.03), but not at 14d or 90d after controlling for differences in age or hypertension, and were higher in patients at baseline and 90d after controlling for smoking status (p≤0.04). 'Adjusted' VWF:Ag II levels were not higher in patients than controls after controlling for age, hypertension or smoking (p≥0.1). Patients with symptomatic carotid stenosis (N=46) had higher VWF:Ag and VWF:Ag II levels than controls at all time-points (p≤0.002). There was no significant correlation between platelet activation status and VWF:Ag or VWF:Ag II levels. VWF:Ag and VWF:Ag II levels are increased in an overall TIA and ischaemic stroke population, especially in patients with recently symptomatic carotid stenosis. VWF:Ag II was not superior to VWF:Ag at detecting acute endothelial activation in this cohort and might reflect timing of blood sampling in our study. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Tumors and Pregnancy

    MedlinePlus

    Tumors during pregnancy are rare, but they can happen. Tumors can be either benign or malignant. Benign tumors aren't cancer. Malignant ones are. The most common cancers in pregnancy are breast cancer, cervical cancer, lymphoma, and melanoma. ...

  8. Emergency department care for patients with hemophilia and von Willebrand disease.

    PubMed

    Singleton, Tammuella; Kruse-Jarres, Rebecca; Leissinger, Cindy

    2010-08-01

    Patients with bleeding disorders such as hemophilia A, hemophilia B, and von Willebrand disease (VWD) are routinely treated at home, with their care managed in specialized centers. In emergency situations, these patients often present to their local emergency department (ED), where their management can represent a challenge to the emergency physicians and staff who rarely encounter them. Delays in diagnosis and administration of replacement therapy are the factors most commonly identified as predictive of death. Patients and family members are often very well educated in the disease and its management, which can significantly reduce morbidity and mortality. Children with bleeding disorders confer different challenges to the emergency physician and staff: they may present with no obvious signs of trauma or they may present with bruises consistent with non-accidental injury. All possible causes of bruising/bleeding should be investigated, although treatment should be administered promptly. The initial presentation of a bleeding disorder in the pediatric population is often made in the ED. Treatment of hemophilia A and B requires rapid replacement of the deficient clotting factor, with the desired factor level and dosage dependent on the product used and the hemorrhagic situation encountered. In patients with VWD, the main treatments are desmopressin or intravenous infusion of plasma-derived concentrates containing factor VIII and von Willebrand factor. The aim of this review is to outline some of the issues facing emergency physicians and the options available for the treatment of patients with hemophilia A, hemophilia B, and VWD. Copyright 2010. Published by Elsevier Inc.

  9. Tumor Endothelial Cells

    PubMed Central

    Dudley, Andrew C.

    2012-01-01

    The vascular endothelium is a dynamic cellular “organ” that controls passage of nutrients into tissues, maintains the flow of blood, and regulates the trafficking of leukocytes. In tumors, factors such as hypoxia and chronic growth factor stimulation result in endothelial dysfunction. For example, tumor blood vessels have irregular diameters; they are fragile, leaky, and blood flow is abnormal. There is now good evidence that these abnormalities in the tumor endothelium contribute to tumor growth and metastasis. Thus, determining the biological basis underlying these abnormalities is critical for understanding the pathophysiology of tumor progression and facilitating the design and delivery of effective antiangiogenic therapies. PMID:22393533

  10. Simultaneous targeting of tumor antigens and the tumor vasculature using T lymphocyte transfer synergize to induce regression of established tumors in mice.

    PubMed

    Chinnasamy, Dhanalakshmi; Tran, Eric; Yu, Zhiya; Morgan, Richard A; Restifo, Nicholas P; Rosenberg, Steven A

    2013-06-01

    Most systemic cancer therapies target tumor cells directly, although there is increasing interest in targeting the tumor stroma that can comprise a substantial portion of the tumor mass. We report here a synergy between two T-cell therapies, one directed against the stromal tumor vasculature and the other directed against antigens expressed on the tumor cell. Simultaneous transfer of genetically engineered syngeneic T cells expressing a chimeric antigen receptor targeting the VEGF receptor-2 (VEGFR2; KDR) that is overexpressed on tumor vasculature and T-cells specific for the tumor antigens gp100 (PMEL), TRP-1 (TYRP1), or TRP-2 (DCT) synergistically eradicated established B16 melanoma tumors in mice and dramatically increased the tumor-free survival of mice compared with treatment with either cell type alone or T cells coexpressing these two targeting molecules. Host lymphodepletion before cell transfer was required to mediate the antitumor effect. The synergistic antitumor response was accompanied by a significant increase in the infiltration and expansion and/or persistence of the adoptively transferred tumor antigen-specific T cells in the tumor microenvironment and thus enhanced their antitumor potency. The data presented here emphasize the possible beneficial effects of combining antiangiogenic with tumor-specific immunotherapeutic approaches for the treatment of patients with cancer. ©2013 AACR.

  11. Adrenal Gland Tumors: Statistics

    MedlinePlus

    ... Gland Tumor: Statistics Request Permissions Adrenal Gland Tumor: Statistics Approved by the Cancer.Net Editorial Board , 03/ ... primary adrenal gland tumor is very uncommon. Exact statistics are not available for this type of tumor ...

  12. Wilms tumor

    MedlinePlus

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

  13. Insights into the regulation of tumor dormancy by angiogenesis in experimental tumors.

    PubMed

    Indraccolo, Stefano

    2013-01-01

    While it is well established that an angiogenic switch marks escape from tumor dormancy in xenograft models, the molecular pathways involved in the control of tumor cell proliferation or survival by angiogenesis remain substantially uncharted. We recently demonstrated that signals stemming from angiogenic endothelial cells (EC) regulate the behavior of dormant cancer cells. Specifically, we observed that the Notch ligand Dll4, induced by angiogenic factors in EC, triggers Notch3 activation in neighboring tumor cells and promotes a tumorigenic phenotype. Evidence that Notch signaling is involved in tumor dormancy was further strengthened by the observation that MKP-1 levels-a broadly expressed phosphatase-are controlled by Notch3 by regulation of protein ubiquitination and stability. Notch3 and MKP-1 levels are consistently low in dormant tumors, and this is accompanied by relatively high levels of phosphorylated p38, a canonical MKP-1 target previously associated with maintenance of tumor dormancy. These results elucidate a novel angiogenesis-driven mechanism involving the Notch and MAPK pathways that controls tumor dormancy. More in general, angiogenic EC could form part of the vascular niche, a specialized microenvironment which appears to regulate metastatic outgrowth and future studies are needed to clarify the contribution of EC in the regulation of cancer stem cell behavior in the niche.The notion that EC could communicate signals to tumor cells raises questions about the possibility of achieving tumor dormancy by counteracting angiogenesis. In experimental tumors, anti-VEGF drugs typically prune the newly formed vasculature, thus reducing microvessel density, blood flow, and perfusion. These drugs eventually increase hypoxia and cause tumor necrosis but dormancy is rarely observed. Our group recently reported that anti-VEGF therapy causes a dramatic depletion of glucose and an exhaustion of ATP levels in tumors. Moreover, we found that the central metabolic

  14. Double-Targeting Explosible Nanofirework for Tumor Ignition to Guide Tumor-Depth Photothermal Therapy.

    PubMed

    Zhang, Ming-Kang; Wang, Xiao-Gang; Zhu, Jing-Yi; Liu, Miao-Deng; Li, Chu-Xin; Feng, Jun; Zhang, Xian-Zheng

    2018-04-17

    This study reports a double-targeting "nanofirework" for tumor-ignited imaging to guide effective tumor-depth photothermal therapy (PTT). Typically, ≈30 nm upconversion nanoparticles (UCNP) are enveloped with a hybrid corona composed of ≈4 nm CuS tethered hyaluronic acid (CuS-HA). The HA corona provides active tumor-targeted functionality together with excellent stability and improved biocompatibility. The dimension of UCNP@CuS-HA is specifically set within the optimal size window for passive tumor-targeting effect, demonstrating significant contributions to both the in vivo prolonged circulation duration and the enhanced size-dependent tumor accumulation compared with ultrasmall CuS nanoparticles. The tumors featuring hyaluronidase (HAase) overexpression could induce the escape of CuS away from UCNP@CuS-HA due to HAase-catalyzed HA degradation, in turn activating the recovery of initially CuS-quenched luminescence of UCNP and also driving the tumor-depth infiltration of ultrasmall CuS for effective PTT. This in vivo transition has proven to be highly dependent on tumor occurrence like a tumor-ignited explosible firework. Together with the double-targeting functionality, the pathology-selective tumor ignition permits precise tumor detection and imaging-guided spatiotemporal control over PTT operation, leading to complete tumor ablation under near infrared (NIR) irradiation. This study offers a new paradigm of utilizing pathological characteristics to design nanotheranostics for precise detection and personalized therapy of tumors. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Solid tumors.

    PubMed

    Richardson, R C

    1985-05-01

    Soft-tissue tumors are similar in their behavior. Benign tumors can be easily resected in most cases, whereas malignant tumors are relentless in their locally invasive characteristics. A clear understanding of the constraints of the pathologist in reaching a confirmed diagnosis and a logical plan utilizing surgery as the major modality of therapy are necessary for successful management of these tumors. It appears that radiation combined with hyperthermia is beginning to play a significant role in the local control of soft-tissue sarcomas and that single or multi-agent chemotherapy may be of benefit in treatment of nonresectable or metastatic soft-tissue sarcomas. For the immediate future, surgery remains the only nonexperimental modality of therapy, but the rapid advances in the other therapy methods are encouraging.

  16. Calibration and characterization of a highly efficient spectrometer in von Hamos geometry for 7-10 keV x-rays

    DOE PAGES

    Jarrott, L. C.; Wei, M. S.; McGuffey, C.; ...

    2017-04-27

    Here, we have built an absolutely calibrated, highly efficient, Bragg crystal spectrometer in von Hamos geometry. This zinc von Hamos spectrometer uses a crystal made from highly oriented pyrolytic graphite that is cylindrically bent along the non-dispersive axis. It is tuned to measure x-ray spectra in the 7–10 keV range and has been designed to be used on a Ten Inch Manipulator for the Omega and OmegaEP target chambers at the Laboratory for Laser Energetics in Rochester, USA. Significant shielding strategies and fluorescence mitigation have been implemented in addition to an imaging plate detector making it well suited for experimentsmore » in high-intensity environments. Here we present the design and absolute calibration as well as mosaicity and integrated reflectivity measurements.« less

  17. The Oncolytic Activity of Newcastle Disease Virus in Clear Cell Renal Carcinoma Cells in Normoxic and Hypoxic Conditions: The Interplay Between von Hippel-Lindau and Interferon-β Signaling

    PubMed Central

    Ch'ng, Wei-Choong; Stanbridge, Eric J.; Yusoff, Khatijah

    2013-01-01

    Viral-mediated oncolysis is a promising cancer therapeutic approach offering an increased efficacy with less toxicity than the current therapies. The complexity of solid tumor microenvironments includes regions of hypoxia. In these regions, the transcription factor, hypoxia inducible factor (HIF), is active and regulates expression of many genes that contribute to aggressive malignancy, radio-, and chemo-resistance. To investigate the oncolytic efficacy of a highly virulent (velogenic) Newcastle disease virus (NDV) in the presence or absence of HIF-2α, renal cell carcinoma (RCC) cell lines with defective or reconstituted wild-type (wt) von Hippel-Lindau (VHL) activity were used. We show that these RCC cells responded to NDV by producing only interferon (IFN)-β, but not IFN-α, and are associated with increased STAT1 phosphorylation. Restoration of wt VHL expression enhanced NDV-induced IFN-β production, leading to prolonged STAT1 phosphorylation and increased cell death. Hypoxia augmented NDV oncolytic activity regardless of the cells' HIF-2α levels. These results highlight the potential of oncolytic NDV as a potent therapeutic agent in the killing of hypoxic cancer cells. PMID:23506478

  18. Childhood Brain Tumor Epidemiology: A Brain Tumor Epidemiology Consortium Review

    PubMed Central

    Johnson, Kimberly J.; Cullen, Jennifer; Barnholtz-Sloan, Jill S.; Ostrom, Quinn T.; Langer, Chelsea E.; Turner, Michelle C.; McKean-Cowdin, Roberta; Fisher, James L.; Lupo, Philip J.; Partap, Sonia; Schwartzbaum, Judith A.; Scheurer, Michael E.

    2014-01-01

    Childhood brain tumors are the most common pediatric solid tumor and include several histological subtypes. Although progress has been made in improving survival rates for some subtypes, understanding of risk factors for childhood brain tumors remains limited to a few genetic syndromes and ionizing radiation to the head and neck. In this report, we review descriptive and analytical epidemiology childhood brain tumor studies from the past decade and highlight priority areas for future epidemiology investigations and methodological work that is needed to advance our understanding of childhood brain tumor causes. Specifically, we summarize the results of a review of studies published since 2004 that have analyzed incidence and survival in different international regions and that have examined potential genetic, immune system, developmental and birth characteristics, and environmental risk factors. PMID:25192704

  19. 21. Increased FDG uptake in Childhood CNS Tumors is Associated with Tumor Malignancy.

    PubMed

    Borgwardt; Carstensen; Schmiegelow; Højgaard

    2000-07-01

    Background: In adults PET scanning of CNS tumors with the tracer FDG (18F-flourodeoxyglucose) can provide information about the degree of malignancy, tumor extent, and dissemination. FDG PET can also be able to assess tumor response to therapy and to differentiate recurrence from necrosis. Although CNS tumors are the most common solid tumor in childhood, so far only few PET-studies have been reported. Pre-operative assessment of malignancy would facilitate surgical planning and the use of pre-operative chemotherapy.Materials and Methods: 21 children with CNS tumors were referred to clinical FDG PET prior to therapy (M/F = 12/9, median age: 9 (range 0-16)), (4 PNET/medulloblastomas; 1 gr. III ependymoma, 16 benign tumors)). Image processing included co-registration with MRI and image fusion. The FDG uptake in the tumors was ranked 0-5 by a hotspot/cortex-ratio by two observers independently. The FDG uptake in grey and white matter was used as reference for the grading system with FDG uptakes defined as 4 and 2 respectively.Results: 15 of 16 patients with tumors WHO gr. I-II had FDG-uptake of 1-2, and all 5 patients with tumors WHO gr. III-IV had FDG-uptake of 3-4. A WHO gr. I papilloma, known to have a high metabolism caused by high mitochondrial activity, had FDG uptake of 5. Except for this tumor, the FDG uptake was positively correlated with tumor malignancy. MRI/PET co-registration and image fusion increased the specificity of tumor location, as well as of tumor extent, and of heterogeneity (e.g., areas of necrosis).Conclusion: FDG PET with MRI/PET co-registration and image fusion could be an important adjunct in the diagnostic work up of pediatric CNS tumors, and could help define patients eligible for pre-operative chemotherapy.

  20. VON and Its Use in NASA's International Space Station Science Operation

    NASA Technical Reports Server (NTRS)

    Bradford, Robert N.; Chamberlain, Jim

    1999-01-01

    This presentation will provide a brief overview of a International Space Station (ISS) remote user (scientist/experimenter) operation. Specifically, the presentation will show how Voice over IP (VoIP) is integrated into the ISS science payload operation and in the mission voice system. Included will be the details on how a scientist, using VON, will talk to the ISS onboard crew and ground based cadre from a scientist's home location (lab, office or garage) over tile public Internet and science nets. Benefit(s) to tile ISS Program (and taxpayer) and of VoIP versus other implementations also will be presented.

  1. A Splice Variant of the Human Ion Channel TRPM2 Modulates Neuroblastoma Tumor Growth through Hypoxia-inducible Factor (HIF)-1/2α*

    PubMed Central

    Chen, Shu-jen; Hoffman, Nicholas E.; Shanmughapriya, Santhanam; Bao, Lei; Keefer, Kerry; Conrad, Kathleen; Merali, Salim; Takahashi, Yoshinori; Abraham, Thomas; Hirschler-Laszkiewicz, Iwona; Wang, JuFang; Zhang, Xue-Qian; Song, Jianliang; Barrero, Carlos; Shi, Yuguang; Kawasawa, Yuka Imamura; Bayerl, Michael; Sun, Tianyu; Barbour, Mustafa; Wang, Hong-Gang; Madesh, Muniswamy; Cheung, Joseph Y.; Miller, Barbara A.

    2014-01-01

    The calcium-permeable ion channel TRPM2 is highly expressed in a number of cancers. In neuroblastoma, full-length TRPM2 (TRPM2-L) protected cells from moderate oxidative stress through increased levels of forkhead box transcription factor 3a (FOXO3a) and superoxide dismutase 2. Cells expressing the dominant negative short isoform (TRPM2-S) had reduced FOXO3a and superoxide dismutase 2 levels, reduced calcium influx in response to oxidative stress, and enhanced reactive oxygen species, leading to decreased cell viability. Here, in xenografts generated with SH-SY5Y neuroblastoma cells stably expressing TRPM2 isoforms, growth of tumors expressing TRPM2-S was significantly reduced compared with tumors expressing TRPM2-L. Expression of hypoxia-inducible factor (HIF)-1/2α was significantly reduced in TRPM2-S-expressing tumor cells as was expression of target proteins regulated by HIF-1/2α including those involved in glycolysis (lactate dehydrogenase A and enolase 2), oxidant stress (FOXO3a), angiogenesis (VEGF), mitophagy and mitochondrial function (BNIP3 and NDUFA4L2), and mitochondrial electron transport chain activity (cytochrome oxidase 4.1/4.2 in complex IV). The reduction in HIF-1/2α was mediated through both significantly reduced HIF-1/2α mRNA levels and increased levels of von Hippel-Lindau E3 ligase in TRPM2-S-expressing cells. Inhibition of TRPM2-L by pretreatment with clotrimazole or expression of TRPM2-S significantly increased sensitivity of cells to doxorubicin. Reduced survival of TRPM2-S-expressing cells after doxorubicin treatment was rescued by gain of HIF-1 or -2α function. These data suggest that TRPM2 activity is important for tumor growth and for cell viability and survival following doxorubicin treatment and that interference with TRPM2-L function may be a novel approach to reduce tumor growth through modulation of HIF-1/2α, mitochondrial function, and mitophagy. PMID:25391657

  2. Automatic detection of new tumors and tumor burden evaluation in longitudinal liver CT scan studies.

    PubMed

    Vivanti, R; Szeskin, A; Lev-Cohain, N; Sosna, J; Joskowicz, L

    2017-11-01

    Radiological longitudinal follow-up of liver tumors in CT scans is the standard of care for disease progression assessment and for liver tumor therapy. Finding new tumors in the follow-up scan is essential to determine malignancy, to evaluate the total tumor burden, and to determine treatment efficacy. Since new tumors are typically small, they may be missed by examining radiologists. We describe a new method for the automatic detection and segmentation of new tumors in longitudinal liver CT studies and for liver tumors burden quantification. Its inputs are the baseline and follow-up CT scans, the baseline tumors delineation, and a tumor appearance prior model. Its outputs are the new tumors segmentations in the follow-up scan, the tumor burden quantification in both scans, and the tumor burden change. Our method is the first comprehensive method that is explicitly designed to find new liver tumors. It integrates information from the scans, the baseline known tumors delineations, and a tumor appearance prior model in the form of a global convolutional neural network classifier. Unlike other deep learning-based methods, it does not require large tagged training sets. Our experimental results on 246 tumors, of which 97 were new tumors, from 37 longitudinal liver CT studies with radiologist approved ground-truth segmentations, yields a true positive new tumors detection rate of 86 versus 72% with stand-alone detection, and a tumor burden volume overlap error of 16%. New tumors detection and tumor burden volumetry are important for diagnosis and treatment. Our new method enables a simplified radiologist-friendly workflow that is potentially more accurate and reliable than the existing one by automatically and accurately following known tumors and detecting new tumors in the follow-up scan.

  3. Tumor abolition and antitumor immunostimulation by physico-chemical tumor ablation.

    PubMed

    Keisari, Yona

    2017-01-01

    Tumor ablation by thermal, chemical and radiological sources has received substantial attention for the treatment of many localized malignancies. The primary goal of most ablation procedures is to eradicate all viable malignant cells within a designated target volume through the application of energy or chemicals. Methods such as radiotherapy, chemical and biological ablation, photodynamic therapy, cryoablation, high-temperature ablation (radiofrequency, microwave, laser, and ultrasound), and electric-based ablation have been developed for focal malignancies. In recent years a large volume of data emerged on the effect of in situ tumor destruction (ablation) on inflammatory and immune components resulting in systemic anti-tumor reactions. It is evident that in situ tumor ablation can involve tumor antigen release, cross presentation and the release of DAMPS and make the tumor its own cellular vaccine. Tumor tissue destruction by in situ ablation may stimulate antigen-specific cellular immunity engendered by an inflammatory milieu. Dendritic cells (DCs) attracted to this microenvironment, will undergo maturation after internalizing cellular debris containing tumor antigens and will be exposed to damage associated molecular pattern (DAMP). Mature DCs can mediate antigen-specific cellular immunity via presentation of processed antigens to T cells. The immunomodulatory properties, exhibited by in situ ablation could portend a future collaboration with immunotherapeutic measures. In this review are summarized and discuss the preclinical and clinical studies pertinent to the phenomena of stimulation of specific anti-tumor immunity by various ablation modalities and the immunology related measures used to boost this response.

  4. Antibody treatment of human tumor xenografts elicits active anti-tumor immunity in nude mice

    PubMed Central

    Liebman, Meredith A.; Roche, Marly I.; Williams, Brent R.; Kim, Jae; Pageau, Steven C.; Sharon, Jacqueline

    2007-01-01

    Athymic nude mice bearing subcutaneous tumor xenografts of the human anti-colorectal cancer cell line SW480 were used as a preclinical model to explore anti-tumor immunotherapies. Intratumor or systemic treatment of the mice with murine anti-SW480 serum, recombinant anti-SW480 polyclonal antibodies, or the anti-colorectal cancer monoclonal antibody CO17-1A, caused retardation or regression of SW480 tumor xenografts. Interestingly, when mice that had regressed their tumors were re-challenged with SW480 cells, these mice regressed the new tumors without further antibody treatment. Adoptive transfer of spleen cells from mice that had regressed their tumors conferred anti-tumor immunity to naïve nude mice. Pilot experiments suggest that the transferred anti-tumor immunity is mediated by T cells of both γδ and αβ lineages. These results demonstrate that passive anti-tumor immunotherapy can elicit active immunity and support a role for extra-thymic γδ and αβ T cells in tumor rejection. Implications for potential immunotherapies include injection of tumor nodules in cancer patients with anti-tumor antibodies to induce anti-tumor T cell immunity. PMID:17920694

  5. M-HIFU Inhibits Tumor Growth, Suppresses STAT3 Activity and Enhances Tumor Specific Immunity in a Transplant Tumor Model of Prostate Cancer

    PubMed Central

    Huang, Xiaoyi; Yuan, Fang; Liang, Meihua; Lo, Hui-Wen; Shinohara, Mari L.; Robertson, Cary; Zhong, Pei

    2012-01-01

    Objective In this study, we explored the use of mechanical high intensity focused ultrasound (M-HIFU) as a neo-adjuvant therapy prior to surgical resection of the primary tumor. We also investigated the role of signal transducer and activator of transcription 3 (STAT3) in M-HIFU elicited anti-tumor immune response using a transplant tumor model of prostate cancer. Methods RM-9, a mouse prostate cancer cell line with constitutively activated STAT3, was inoculated subcutaneously in C57BL/6J mice. The tumor-bearing mice (with a maximum tumor diameter of 5∼6 mm) were treated by M-HIFU or sham exposure two days before surgical resection of the primary tumor. Following recovery, if no tumor recurrence was observed in 30 days, tumor rechallenge was performed. The growth of the rechallenged tumor, survival rate and anti-tumor immune response of the animal were evaluated. Results No tumor recurrence and distant metastasis were observed in both treatment groups employing M-HIFU + surgery and surgery alone. However, compared to surgery alone, M-HIFU combined with surgery were found to significantly inhibit the growth of rechallenged tumors, down-regulate intra-tumoral STAT3 activities, increase cytotoxic T cells in spleens and tumor draining lymph nodes (TDLNs), and improve the host survival. Furthermore, M-HIFU combined with surgery was found to significantly decrease the level of immunosuppression with concomitantly increased number and activities of dendritic cells, compared to surgery alone. Conclusion Our results demonstrate that M-HIFU can inhibit STAT3 activities, and when combined synergistically with surgery, may provide a novel and promising strategy for the treatment of prostate cancers. PMID:22911830

  6. Disorder of Endothelia Vessels' Functional State with Malignant Tumors in Patients Exposed Anthropogenic Radiation.

    PubMed

    Pak, Laura; Noso, Yoshihiro; Chaizhunusova, Nailya; Anambaeva, Zukhra; Adylkhanov, Tasbolat; Takeichi, Nobuo; Lzhaev, Sayakhat; Aldyngurov, Daniyar; Tuleutayeva, Raikhan; Argynbekova, Ainur; Tanysheva, Gulyash; Zhazykbayeva, Lashyn; Baissalbayeva, Ainur; Rakhypbekov, Tolebay

    2016-01-01

    The aim of this research is to determine the characteristics of endothelial factors and the hemostatic system conditions with malignant neoplasms patients, which were exposed to ionizing radiation. Total number of examined people is 223, 153 of them are patients with gastrointestinal tract oncopathology. The article presents the results of the analysis of numerical indicators of endothelial condition and platelet hemostasis of patients, who had cancer. They lived in the regions of Kazakhstan, subjected to contamination of radionuclides as a result of nuclear weapons tests, which took place in this region from 1949 to 1989. These results then were compared to cancer patients and healthy individuals with no radiation risk. The study revealed the presence of higher levels of endothelial dysfunction and following trigger of the hemostatic system in patients with malignant tumors of the gastrointestinal tract. In particular, the defined high degree of endothelial dysfunction include endothelium- dependent vasodilation, content desquamated endothelial cells in peripheral blood and von Willebrand factor. These indicators have a clear correlation with the degree of disorder of studied parameters of the hemostasis, which can cause the development of thrombotic complications.

  7. Dynamics of Diffusion Flames in von Karman Swirling Flows Studied

    NASA Technical Reports Server (NTRS)

    Nayagam, Vedha; Williams, Forman A.

    2002-01-01

    Von Karman swirling flow is generated by the viscous pumping action of a solid disk spinning in a quiescent fluid media. When this spinning disk is ignited in an oxidizing environment, a flat diffusion flame is established adjacent to the disk, embedded in the boundary layer (see the preceding illustration). For this geometry, the conservation equations reduce to a system of ordinary differential equations, enabling researchers to carry out detailed theoretical models to study the effects of varying strain on the dynamics of diffusion flames. Experimentally, the spinning disk burner provides an ideal configuration to precisely control the strain rates over a wide range. Our original motivation at the NASA Glenn Research Center to study these flames arose from a need to understand the flammability characteristics of solid fuels in microgravity where slow, subbuoyant flows can exist, producing very small strain rates. In a recent work (ref. 1), we showed that the flammability boundaries are wider and the minimum oxygen index (below which flames cannot be sustained) is lower for the von Karman flow configuration in comparison to a stagnation-point flow. Adding a small forced convection to the swirling flow pushes the flame into regions of higher strain and, thereby, decreases the range of flammable strain rates. Experiments using downward facing, polymethylmethacrylate (PMMA) disks spinning in air revealed that, close to the extinction boundaries, the flat diffusion flame breaks up into rotating spiral flames (refs. 2 and 3). Remarkably, the dynamics of these spiral flame edges exhibit a number of similarities to spirals observed in biological systems, such as the electric pulses in cardiac muscles and the aggregation of slime-mold amoeba. The tail of the spiral rotates rigidly while the tip executes a compound, meandering motion sometimes observed in Belousov-Zhabotinskii reactions.

  8. Expression of pigment epithelium-derived factor and tumor necrosis factor-α is correlated in bladder tumor and is related to tumor angiogenesis.

    PubMed

    Feng, Chen-Chen; Wang, Pao-Hsun; Ding, Qiang; Guan, Ming; Zhang, Yuan-Fang; Jiang, Hao-Wen; Wen, Hui; Wu, Zhong

    2013-02-01

    Angiogenesis is a pivotal process on which solid tumor growth is substantially dependent. Pigment epithelium-derived factor (PEDF) is the most potent natural anti-angiogenic factor, which has seldom been studied in bladder tumor, and whose functioning pathway remains unclear. We have thus investigated PEDF expression in relation to tumor necrosis factor-α (TNF-α) and microvessel density (MVD) with immunohistochemistry. Antibodies of PEDF and TNF-α were examined by Western blotting before immunohistochemistry. Sixty-four urothelial tumor sections and 23 normal controls were stained and expression of PEDF, TNF-α, and MVD were studied. Decreased PEDF expression and increased TNF-α expression was noticed in tumorous tissue compared with healthy urothelium. Lower PEDF expression was related to higher tumor grade but stage. Increased TNF-α expression was noticed in recurrent, larger tumors as well as in tumors with progression in grade and stage. Expression of PEDF and TNF-α was correlated in bladder tumor. PEDF or TNF-α was correlated with MVD negatively or positively, respectively, in cancerous tissue and tumorous grouping without correlation in papillary urothelial neoplasm of low malignant potential. Expressional change of PEDF and TNF-α is in relation to angiogenesis of bladder tumor, especially in bladder cancer development. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Targeting Tumor Oct4 to Deplete Prostate Tumor and Metastasis Initiating Cells

    DTIC Science & Technology

    2016-10-01

    Award Number: W81XWH-13-1-0461 TITLE: Targeting Tumor Oct4 to Deplete Prostate Tumor- and Metastasis-Initiating Cells PRINCIPAL INVESTIGATOR: Daotai...29 2016 4. TITLE AND SUBTILE Targeting Tumor Oct4 to Deplete Prostate Tumor- and Metastasis-Initiating Cells 5a. CONTRACT NUMBER 5b. GRANT NUMBER...the c-MYC oncogene. POU5F1B is a pseudogene of embryonic Oct4 (POU5F1). A recent study found that tumor Oct4 found in prostate cancer cells is due

  10. Entwicklung von Landnutzungsszenarien für landschaftsökologische Fragestellungen

    NASA Astrophysics Data System (ADS)

    Fritsch, Uta

    2002-04-01

    Die Landschaften Mitteleuropas sind das Resultat einer langwierigen Geschichte menschlicher Landnutzung mit ihren unterschiedlichen, z.T. konkurrierenden Nutzungsansprüchen. Durch eine überwiegend intensive Beanspruchung haben die direkten und indirekten Auswirkungen der Landnutzung in vielen Fällen zu Umweltproblemen geführt. Die Disziplin der Landschaftsökologie hat es sich zur Aufgabe gemacht, Konzepte für eine nachhaltige Nutzung der Landschaft zu entwickeln. Eine wichtige Fragestellung stellt dabei die Abschätzung der möglichen Folgen von Landnutzungsänderungen dar. Für die Analyse der relevanten Prozesse in der Landschaft werden häufig mathematische Modelle eingesetzt, welche es erlauben die Landschaft unter aktuellen Verhältnissen oder hinsichtlich veränderter Rahmenbedingungen zu untersuchen. Die hypothetische Änderung der Landnutzung, die als Landnutzungsszenario bezeichnet wird, verkörpert eine wesentliche Modifikation der Rahmenbedingungen, weil Landnutzung mageblich Einfluss auf die natürlichen Prozesse der Landschaft nimmt. Während die Antriebskräfte einer solchen Änderung überwiegend von sozio-ökonomischen und politischen Entscheidungen gesteuert werden, orientiert sich die exakte Verortung der Landnutzungsänderungen an den naturräumlichen Bedingungen und folgt z.T. erkennbaren Regeln. Anhand dieser Vorgaben ist es möglich, räumlich explizite Landnutzungsszenarien zu entwickeln, die als Eingangsdaten für die Modellierung verschiedener landschaftsökologischer Fragestellungen wie z.B. für die Untersuchung des Einflusses der Landnutzung auf den Wasserhaushalt, die Erosionsgefahr oder die Habitatqualität dienen können. Im Rahmen dieser Dissertation wurde das rasterbasierte deterministische Allokationsmodell luck (Land Use Change Scenario Kit) für die explizite Verortung der Landnutzungsänderungen entwickelt. Es basiert auf den in der Landschaftsökologie üblichen räumlichen Daten wie Landnutzung, Boden sowie Topographie

  11. Tumor microenvironment is multifaceted.

    PubMed

    Sautès-Fridman, Catherine; Cherfils-Vicini, Julien; Damotte, Diane; Fisson, Sylvain; Fridman, Wolf Hervé; Cremer, Isabelle; Dieu-Nosjean, Marie-Caroline

    2011-03-01

    Cancer initiation, progression, and invasion occur in a complex and dynamic microenvironment which depends on the hosts and sites where tumors develop. Tumors arising in mucosal tissues may progress in an inflammatory context linked to local viral and/or bacterial infections. At the opposite, tumors developing in immunoprivileged sites are protected from microorganisms and grow in an immunosuppressive environment. In the present review, we summarize and present our recent data on the influence of infectious context and immune cell infiltration organization in human Non-Small Cell Lung Cancers (NSCLC) progression. We show that stimulation of tumor cells by TLR for viral ssRNA, such as TLR7/8, or bacteria, such as TLR4, promotes cell survival and induces chemoresistance. On the opposite, stimulation by TLR3, receptor for double-stranded viral RNA, decreases tumor cell viability and induces chemosensitivity in some lung tumor cell lines. Since fresh lung tumor cells exhibit a gene expression profile characteristic of TLR-stimulated lung tumor cell lines, we suspect that viral and bacterial influence may not only act on the host immune system but also directly on tumor growth and sensitivity to chemotherapy. The stroma of NSCLC contains tertiary lymphoid structures (or Tumor-induced Bronchus-Associated Lymphoid Tissues (Ti-BALT)) with mature DC, follicular DC, and T and B cells. Two subsets of immature DC, Langerhans cells (LC) and interstitial DC (intDC), were detected in the tumor nests and the stroma, respectively. Here, we show that the densities of the three DC subsets, mature DC, LC, and intDC, are highly predictive of disease-specific survival in a series of 74 early-stage NSCLC patients. We hypothesize that the mature DC may derive from local activation and migration of the immature DC--and especially LC which contact the tumor cells--to the tertiary lymphoid structures, after sampling and processing of the tumor antigens. In view of the prominent role of DC in

  12. Glial tumors with neuronal differentiation.

    PubMed

    Park, Chul-Kee; Phi, Ji Hoon; Park, Sung-Hye

    2015-01-01

    Immunohistochemical studies for neuronal differentiation in glial tumors revealed subsets of tumors having both characteristics of glial and neuronal lineages. Glial tumors with neuronal differentiation can be observed with diverse phenotypes and histologic grades. The rosette-forming glioneuronal tumor of the fourth ventricle and papillary glioneuronal tumor have been newly classified as distinct disease entities. There are other candidates for classification, such as the glioneuronal tumor without pseudopapillary architecture, glioneuronal tumor with neuropil-like islands, and the malignant glioneuronal tumor. The clinical significance of these previously unclassified tumors should be confirmed. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Risk of borderline ovarian tumors among women with benign ovarian tumors: A cohort study.

    PubMed

    Guleria, Sonia; Jensen, Allan; Kjær, Susanne K

    2018-01-01

    A growing number of studies suggest that some ovarian cancers can arise from benign and borderline ovarian tumors. However, studies on the association between benign and borderline ovarian tumors are lacking. We studied the overall- and histotype-specific risk of borderline ovarian tumors among women with a benign ovarian tumor. This nationwide cohort study included all Danish women diagnosed with a benign ovarian tumor (n=139,466) during 1978-2012. The cohort was linked to the Danish Pathology Data Bank and standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated. Women with benign ovarian tumors had increased risks for subsequent borderline ovarian tumors (SIR 1.62, 95% CI 1.43-1.82), and this applied to both serous (SIR 1.69, 95% CI 1.39-2.03) and mucinous (SIR 1.75, 95% CI 1.45-2.10) histotypes of borderline ovarian tumors. The risk for borderline ovarian tumors was primarily increased for women diagnosed with a benign ovarian tumor before 40years of age. The risk remained increased up to 9years after a benign ovarian tumor diagnosis. Finally, the associations did not change markedly when analyzed for the different histotypes of benign (solid and cystic tumors) and borderline (serous and mucinous tumors) ovarian tumors. Women with benign ovarian tumors have a long-term increased risk for borderline ovarian tumors. However, as all associations in this study were only adjusted for age and calendar period of diagnosis, more studies that are able to adjust for additional potential confounding variables are required to further understand these associations. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Technical note: comparing von Luschan skin color tiles and modern spectrophotometry for measuring human skin pigmentation.

    PubMed

    Swiatoniowski, Anna K; Quillen, Ellen E; Shriver, Mark D; Jablonski, Nina G

    2013-06-01

    Prior to the introduction of reflectance spectrophotometry into anthropological field research during the 1950s, human skin color was most commonly classified by visual skin color matching using the von Luschan tiles, a set of 36 standardized, opaque glass tiles arranged in a chromatic scale. Our goal was to establish a conversion formula between the tile-based color matching method and modern reflectance spectrophotometry to make historical and contemporary data comparable. Skin pigmentation measurements were taken on the forehead, inner upper arms, and backs of the hands using both the tiles and a spectrophotometer on 246 participants showing a broad range of skin pigmentation. From these data, a second-order polynomial conversion formula was derived by jackknife analysis to estimate melanin index (M-index) based on tile values. This conversion formula provides a means for comparing modern data to von Luschan tile measurements recorded in historical reports. This is particularly important for populations now extinct, extirpated, or admixed for which tile-based measures of skin pigmentation are the only data available. Copyright © 2013 Wiley Periodicals, Inc.

  15. [Victor von Hacker (1852-1933)--recollections of the life and works of an important Billroth student].

    PubMed

    Stanger, O

    2000-04-01

    The year of 1999 marks the 75th anniversary of Viktor von Hacker's retirement as chairman of the Department of Surgery at Karl-Franzens University School of Medicine in Graz. He was a favored pupil of Theodor Billroth (1829-1894). When he took his professorship at Graz in 1903, the present hospital, then as now one of the largest in Europe, was still in planning, and he immediately involved himself in all the subsequent developmental stages. Now we are again living through a stage of major reconstruction and expansion within the context of the "LKH 2000" project which also encompasses the surgical department and wards, most of which have generally remained unchanged since Hacker's time. During his 21 years as chairman of the department, Hacker made major contributions in the fields of gastro-intestinal surgery, esophageal surgery and especially esophagoscopy, as well as plastic surgery. Towards the end of his career, 70 years ago, Viktor von Hacker was named an honorary member of the German Society of Surgery. For these reasons, the man and his work should be recalled.

  16. Combined shape and topology optimization for minimization of maximal von Mises stress

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

    Lian, Haojie; Christiansen, Asger N.; Tortorelli, Daniel A.

    Here, this work shows that a combined shape and topology optimization method can produce optimal 2D designs with minimal stress subject to a volume constraint. The method represents the surface explicitly and discretizes the domain into a simplicial complex which adapts both structural shape and topology. By performing repeated topology and shape optimizations and adaptive mesh updates, we can minimize the maximum von Mises stress using the p-norm stress measure with p-values as high as 30, provided that the stress is calculated with sufficient accuracy.

  17. Combined shape and topology optimization for minimization of maximal von Mises stress

    DOE PAGES

    Lian, Haojie; Christiansen, Asger N.; Tortorelli, Daniel A.; ...

    2017-01-27

    Here, this work shows that a combined shape and topology optimization method can produce optimal 2D designs with minimal stress subject to a volume constraint. The method represents the surface explicitly and discretizes the domain into a simplicial complex which adapts both structural shape and topology. By performing repeated topology and shape optimizations and adaptive mesh updates, we can minimize the maximum von Mises stress using the p-norm stress measure with p-values as high as 30, provided that the stress is calculated with sufficient accuracy.

  18. Zum Ausgleich von generativer und energetischer Sprachbetrachtung (A Comparison of the "Generative" and "Energetic" Views of Language)

    ERIC Educational Resources Information Center

    Weisgerber, Leo

    1972-01-01

    Discussion of two basic conceptions: Wilhelm von Humboldt's idea of language as energeia'' existing within and without man, and Noam Chomsky's idea of language generated by the speaker according to an innate apparatus. Revised version of lectures presented at the University of Bonn, West Germany in August 1971. (RS)

  19. Multi-agent simulation of the von Thunen model formation mechanism

    NASA Astrophysics Data System (ADS)

    Tao, Haiyan; Li, Xia; Chen, Xiaoxiang; Deng, Chengbin

    2008-10-01

    This research tries to explain the internal driving forces of circular structure formation in urban geography via the simulation of interaction between individual behavior and market. On the premise of single city center, unchanged scale merit and complete competition, enterprise migration theory as well, an R-D algorithm, that has agents searched the best behavior rules in some given locations, is introduced with agent-based modeling technique. The experiment conducts a simulation on Swarm platform, whose result reflects and replays the formation process of Von Thünen circular structure. Introducing and considering some heterogeneous factors, such as traffic roads, the research verifies several landuse models and discusses the self-adjustment function of price mechanism.

  20. Towards personalised therapy for von Willebrand disease: a future role for recombinant products.

    PubMed

    Favaloro, Emmanuel J

    2016-05-01

    von Willebrand disease (VWD) is reportedly the most common bleeding disorder and is caused by deficiencies and/or defects in the adhesive plasma protein von Willebrand factor (VWF). Functionally, normal VWF prevents bleeding by promoting both primary and secondary haemostasis. In respect to primary haemostasis, VWF binds to both platelets and sub-endothelial matrix components, especially collagen, to anchor platelets to damaged vascular tissue and promote thrombus formation. VWF also stabilises and protects factor VIII in the circulation, delivering FVIII to the site of injury, which then facilitates secondary haemostasis and fibrin formation/thrombus stabilisation. As a result of this, patients with VWD suffer a bleeding diathesis reflective of a primary defect caused by defective/deficient VWF, which in some patients is compounded by a reduction in FVIII. Management of VWD, therefore, chiefly entails replacement of VWF, and sometimes also FVIII, to protect against bleeding. The current report principally focuses on the future potential for "personalised" management of VWD, given the emerging options in recombinant therapies. Recombinant VWF has been developed and is undergoing clinical trials, and this promising therapy may soon change the way in which VWD is managed. In particular, we can envisage a personalised treatment approach using recombinant VWF, with or without recombinant FVIII, depending on the type of VWD, the extent of deficiencies, and the period and duration of treatment.

  1. Osthole promotes anti-tumor immune responses in tumor-bearing mice with hepatocellular carcinoma.

    PubMed

    Zhang, Lurong; Jiang, Guorong; Yao, Fei; Liang, Guoqiang; Wang, Fei; Xu, Heng; Wu, Yan; Yu, Xiao; Liu, Haiyan

    2015-06-01

    Osthole, a natural coumarin derivative, has been shown to have anti-tumor and anti-inflammatory activity. However, the effect of osthole on anti-tumor immune responses in tumor-bearing mice has not yet been reported. In the present study, osthole treatment did not affect the weight and the coefficient of thymus and spleen in tumor-bearing mice with hepatocellular carcinoma (HCC). However, osthole administration significantly elevated the proportion and number of the splenic CD8(+) T cells, the proportion of CD4(+) T and CD8(+) T cells in tumor tissues, and the levels of IL-2 and TNF-α in the serum of HCC tumor-bearing mice. Our results suggested that osthole could promote the activation of the tumor-infiltrating CD4(+) T and CD8(+) T cells, and elevate the proportion of CD4(+) and CD8(+) effector T cells. Osthole treatment also significantly decreased the proportion of CD4(+)CD25(+)Foxp3(+) regulatory T cells in the spleen. Taken together, osthole could enhance the T cell mediated anti-tumor immune responses in the tumor-bearing mice with HCC.

  2. Targeting Paclitaxel-Loaded Nanoparticles to Ovarian Cancer

    DTIC Science & Technology

    2011-05-01

    with each other causes the polymer to collapse to form a nanoparticle of ~20 nm in aqueous solutions as determined by dynamic light scattering (2, 8...molecular target in tumor cells and tumor stroma. Cancer Res. 2008;68:7210-8. 19. von Maltzahn G, Ren Y, Park JH, Min DH, Kotamraju VR, Jayakumar J, et

  3. Dr. von Braun Standing by Five F-1 Engines

    NASA Technical Reports Server (NTRS)

    2004-01-01

    A pioneer of America's space program, Dr. von Braun stands by the five F-1 engines of the Saturn V launch vehicle. This Saturn V vehicle is an actual test vehicle which has been displayed at the U.S. Space Rocket Center in Huntsville, Alabama. Designed and developed by Rocketdyne under the direction of the Marshall Space Flight Center, a cluster of five F-1 engines was mounted on the Saturn V S-IC (first) stage. The engines measured 19-feet tall by 12.5-feet at the nozzle exit and burned 15 tons of liquid oxygen and kerosene each second to produce 7,500,000 pounds of thrust. The S-IC stage is the first stage, or booster, of a 364-foot long rocket that ultimately took astronauts to the Moon.

  4. Simulation of Complex Transport of Nanoparticles around a Tumor Using Tumor-Microenvironment-on-Chip

    PubMed Central

    Kwak, Bongseop; Ozcelikkale, Altug; Shin, Crystal S.; Park, Kinam; Han, Bumsoo

    2014-01-01

    Delivery of therapeutic agents selectively to tumor tissue, which is referred as “targeted delivery,” is one of the most ardently pursued goals of cancer therapy. Recent advances in nanotechnology enable numerous types of nanoparticles (NPs) whose properties can be designed for targeted delivery to tumors. In spite of promising early results, the delivery and therapeutic efficacy of the majority of NPs are still quite limited. This is mainly attributed to the limitation of currently available tumor models to test these NPs and systematically study the effects of complex transport and pathophysiological barriers around the tumors. In this study, thus, we developed a new in vitro tumor model to recapitulate the tumor microenvironment determining the transport around tumors. This model, named tumor-microenvironment-on-chip (T-MOC), consists of 3-dimensional microfluidic channels where tumor cells and endothelial cells are cultured within extracellular matrix under perfusion of interstitial fluid. Using this T-MOC platform, the transport of NPs and its variation due to tumor microenvironmental parameters have been studied including cut-off pore size, interstitial fluid pressure, and tumor tissue microstructure. The results suggest that T-MOC is capable of simulating the complex transport around the tumor, and providing detailed information about NP transport behavior. This finding confirms that NPs should be designed considering their dynamic interactions with tumor microenvironment. PMID:25194778

  5. Case of a tumor comprising gastric cancer and duodenal neuroendocrine tumor

    PubMed Central

    Kaneko, Hiroaki; Miyake, Akio; Ishii, Yasuaki; Sue, Soichiro; Miwa, Haruo; Sasaki, Tomohiko; Tamura, Toshihide; Kondo, Masaaki; Maeda, Shin

    2016-01-01

    The present report describes a rare case of a tumor composed of early gastric cancer and a duodenal neuroendocrine tumor (NET). A 78-year-old woman underwent esophagogastroduodenoscopy at a local institution for screening of the upper gastrointestinal tract which revealed a protruded tumor through the pyloric ring from the pyloric antrum. The tumor was too large to treat at the facility; consequently, she was referred to our hospital for further management. Esophagogastroduodenoscopy with tumor biopsy of the lesion revealed the diagnosis of early gastric cancer. Endoscopic submucosal dissection was performed with sufficient free margins in both vertical and horizontal directions. Histopathological findings showed NET confined to the submucosal layer and covered by well-differentiated adenocarcinoma. Immunohistochemical stainings showed that the two lesions existed continuously. While the possibility of a collision cancer was considered, it was suggested that the two lesions existed continuously. Finally, the tumor was diagnosed as gastric cancer composed of duodenal NET G1, with a lymphatic invasion of NET component. PMID:27688667

  6. Cyclical thrombocytosis, acquired von Willebrand syndrome and aggressive non-melanoma skin cancers are common in patients with Philadelphia-negative myeloproliferative neoplasms treated with hydroxyurea.

    PubMed

    Verner, Emma; Forsyth, Cecily; Grigg, Andrew

    2014-05-01

    Abstract Cyclical thrombocytosis, acquired von Willebrand syndrome, aggressive non-melanoma skin cancers and other hydroxyurea complications have been reported in Philadelphia-negative myeloproliferative neoplasms (MPNs), but their incidence and clinical consequences have not been defined in a large cohort of patients. We conducted a retrospective analysis of 188 consecutive patients with MPNs specifically addressing the incidence of these complications. Cyclical thrombocytosis was documented in 29 patients (15%), the majority of whom were receiving hydroxyurea. Acquired von Willebrand syndrome was identified in 17 of the 84 screened patients (20%), but was not associated with any major bleeding complications. Non-melanoma skin cancers were reported in 51 patients (27%). Hydroxyurea-related fever occurred in nine of 149 patients (6%) who received hydroxyurea. Seventy-three patients (39%) experienced a total of 98 major thrombotic events, with the majority of these occurring prior to or within 3 months of the diagnosis. Cyclical thrombocytosis, acquired von Willebrand syndrome, aggressive non-melanoma skin cancers and other hydroxyurea-related complications are not infrequent in MPNs and have important clinical consequences for management.

  7. Tumor Microenvironment Metabolism: A New Checkpoint for Anti-Tumor Immunity

    PubMed Central

    Scharping, Nicole E.; Delgoffe, Greg M.

    2016-01-01

    When a T cell infiltrates a tumor, it is subjected to a variety of immunosuppressive and regulatory signals in the microenvironment. However, it is becoming increasingly clear that due to the proliferative and energetically-deregulated nature of tumor cells, T cells also operate at a metabolic disadvantage. The nutrient dearth of the tumor microenvironment (TME) creates “metabolic checkpoints” upon infiltrating T cells, impacting their ability to survive, proliferate and function effectively. In this review, we summarize the basics of tumor cell and T cell metabolism and discuss recent advances elucidating the individual metabolic checkpoints exerted on T cells that drive their dysfunction in the TME. PMID:27929420

  8. Molecular and clinical profile of von Willebrand disease in Spain (PCM-EVW-ES): Proposal for a new diagnostic paradigm.

    PubMed

    Batlle, Javier; Pérez-Rodríguez, Almudena; Corrales, Irene; López-Fernández, Maria Fernanda; Rodríguez-Trillo, Ángela; Lourés, Esther; Cid, Ana Rosa; Bonanad, Santiago; Cabrera, Noelia; Moret, Andrés; Parra, Rafael; Mingot-Castellano, María Eva; Balda, Ignacia; Altisent, Carmen; Pérez-Montes, Rocío; Fisac, Rosa María; Iruín, Gemma; Herrero, Sonia; Soto, Inmaculada; de Rueda, Beatriz; Jiménez-Yuste, Victor; Alonso, Nieves; Vilariño, Dolores; Arija, Olga; Campos, Rosa; Paloma, María José; Bermejo, Nuria; Toll, Teresa; Mateo, José; Arribalzaga, Karmele; Marco, Pascual; Palomo, Ángeles; Sarmiento, Lizheidy; Iñigo, Belén; Nieto, María del Mar; Vidal, Rosa; Martínez, María Paz; Aguinaco, Reyes; César, Jesús María; Ferreiro, María; García-Frade, Javier; Rodríguez-Huerta, Ana María; Cuesta, Jorge; Rodríguez-González, Ramón; García-Candel, Faustino; Cornudella, Rosa; Aguilar, Carlos; Borràs, Nina; Vidal, Francisco

    2016-01-01

    The diagnosis of von Willebrand disease (VWD) remains difficult in a significant proportion of patients. A Spanish multicentre study investigated a cohort of 556 patients from 330 families who were analysed centrally. VWD was confirmed in 480. Next generation sequencing (NGS) of the whole coding VWF was carried out in all recruited patients, compared with the phenotype, and a final diagnosis established. A total of 238 different VWF mutations were found, 154 were not included in the Leiden Open Variation Database (LOVD). Of the patients, 463 were found to have VWF mutation/s. A good phenotypic/genotypic association was estimated in 96.5% of the patients. One hundred seventy-four patients had two or more mutations. Occasionally a predominant phenotype masked the presence of a second abnormality. One hundred sixteen patients presented with mutations that had previously been associated with increased von Willebrand factor (VWF) clearance. RIPA unavailability, central phenotypic results disagreement and difficult distinction between severe type 1 and type 3 VWD prevented a clear diagnosis in 70 patients. The NGS study facilitated an appropriate classification in 63 of them. The remaining seven patients presented with a VWF novel mutation pending further investigation. In five patients with a type 3 and two with a type 2A or 2B phenotype with no mutation, an acquired von Willebrand syndrome (AVWS) was suspected/confirmed. These data seem to support NGS as a first line efficient and faster paradigm in VWD diagnosis.

  9. Pituitary Tumors

    MedlinePlus

    ... hormones in your body. This can cause endocrine diseases such as Cushing's syndrome and hyperthyroidism. Symptoms of pituitary tumors include Headaches Vision problems Nausea and vomiting Problems caused ... the tumor. Other options include medicines, radiation therapy, and chemotherapy.

  10. Energy as a Service

    NASA Astrophysics Data System (ADS)

    Pell, Wolfgang

    Energie wird zum Gebrauchsgegenstand, zur Commodity und rückt doch in den Blickpunkt der Aufmerksamkeit. Volkswirtschaftliche, politische, gesellschaftliche und betriebswirtschaftliche Ansprüche lassen Services rund um die Energieversorgung (Energy-related Services) entstehen. Convenience Services, die den Ansprüchen der Konsumenten gerecht werden, wie Visualisierung von (dezentraler) Energieerzeugung und -verbrauch auf Basis digitaler Smart Meter, die den analogen Ferraris-Zähler ersetzen, sowie optimierter Energieeinsatz halten in Haushalten als digitalisierten Standorten (Smart Sites) Einzug. Energieoptimierung auf Basis des Paradigmas "Verbrauch folgt Erzeugung" stellt Nachfrageflexibilität industrieller Prozesse (Demand Response) als Energie-Effizienz-Faktor in den Vordergrund und lässt Services wie ihre Vermarktung als Regelenergie zur Stabilisierung der Netzfrequenz entstehen. Ein Innovation Action Plan liefert einen Ausblick, wohin die Integration neuer Technologien, die Steigerung der Kundennähe und die Entwicklung neuer Geschäftsmodelle die Energiewirtschaft führen kann. Mit Eco-Home und Power-Pool werden zwei konkrete Beispiele für Energy as a Service vorgestellt.

  11. Anti-tumor effects of nitrosylcobalamin against spontaneous tumors in dogs.

    PubMed

    Bauer, Joseph A; Frye, Gerald; Bahr, Anne; Gieg, Jennifer; Brofman, Peter

    2010-10-01

    Given the limited options available to treat canine cancers, the use of companion animals for evaluating new drugs may identify better therapies for veterinary and human oncology. The anti-tumor effects of nitrosylcobalamin (NO-Cbl), an apoptosis-inducing, vitamin B12-based carrier of nitric oxide (NO), was evaluated in four dogs with spontaneous cancer. (1) A 13 year-old female spayed Giant Schnauzer with inoperable thyroid carcinoma and hypercalcemia. (2) A 6 year-old male neutered Golden Retriever with a malignant peripheral nerve sheath tumor (MPNST). (3) A ten yr-old neutered male Bichon Frise with apocrine gland anal sac adenocarcinoma (AGACA). (4) A 7 year-old female spayed Labrador mix with spinal meningioma following partial surgical resection. Tumor regression was measured by physical exam and verified using ultrasound (case 1) and MRI (case 2-4). Serum chemistries and hematologic parameters were monitored throughout the studies. (1) The Giant Schnauzer demonstrated a 77% reduction in tumor volume after ten weeks of daily NO-Cbl treatment. (2) The Golden Retriever demonstrated a 53% reduction in tumor volume after 15 months of daily NO-Cbl therapy. (3) The Bichon Frise demonstrated a 43% regression of the primary tumor and a 90% regression of an iliac lymph node measured by MRI after 15 months of treatment. After 61 months, the dog currently has stable disease, normal liver enzymes, CBC analysis, and no evidence of toxicity. (4) The Labrador demonstrated complete regression of the residual tumor after 6 months of treatment. We have shown previously that NO-Cbl is endocytosed by malignant cells, resulting in intra-tumoral NO release. In this study, we have shown that daily long-term use of NO-Cbl induced responses in all dogs without any signs of toxicity. The use of NO-Cbl capitalizes on the tumor-specific properties of the vitamin B12 receptor and represents a promising anti-cancer therapy.

  12. Two distinct forms of Factor VIII coagulant protein in human plasma. Cleavage by thrombin, and differences in coagulant activity and association with von Willebrand factor.

    PubMed Central

    Weinstein, M J; Chute, L E

    1984-01-01

    We have characterized Factor VIII coagulant protein, present in normal human plasma, that reacts with a specific human 125I-labeled anti-human VIII:C antigen Fab antibody fragment. Two major Factor VIII coagulant antigen populations were present. The first, approximately 85% of the total antigen, was bound to von Willebrand factor and when tested in a standard one-stage assay had Factor VIII coagulant activity. The second antigenic population, eluting near fibrinogen when plasma was gel filtered, was not bound to von Willebrand protein, did not have Factor VIII coagulant activity unless activated, but did block anti-VIII:C Fab neutralization of clotting activity. The two antigenic populations were separable by cryoprecipitation and agarose gel electrophoresis. Although the two antigenic populations differed in their Factor VIII coagulant activity and in their binding to von Willebrand factor, the principal member of both populations is of mol wt 2.4 X 10(5). Both antigens, when proteolyzed by thrombin, were quickly converted to a 1 X 10(5)-mol wt form in association with the appearance of VIII:C activity. The 1 X 10(5)-mol wt antigen was further slowly degraded to an 8 X 10(4)-mol wt form while Factor VIII coagulant activity declined. These results demonstrate the presence of an inactive Factor VIII coagulant protein in plasma, not associated with von Willebrand factor, that can react with thrombin to yield Factor VIII coagulant activity. Images PMID:6421875

  13. Toward real-time tumor margin identification in image-guided robotic brain tumor resection

    NASA Astrophysics Data System (ADS)

    Hu, Danying; Jiang, Yang; Belykh, Evgenii; Gong, Yuanzheng; Preul, Mark C.; Hannaford, Blake; Seibel, Eric J.

    2017-03-01

    For patients with malignant brain tumors (glioblastomas), a safe maximal resection of tumor is critical for an increased survival rate. However, complete resection of the cancer is hard to achieve due to the invasive nature of these tumors, where the margins of the tumors become blurred from frank tumor to more normal brain tissue, but in which single cells or clusters of malignant cells may have invaded. Recent developments in fluorescence imaging techniques have shown great potential for improved surgical outcomes by providing surgeons intraoperative contrast-enhanced visual information of tumor in neurosurgery. The current near-infrared (NIR) fluorophores, such as indocyanine green (ICG), cyanine5.5 (Cy5.5), 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX), are showing clinical potential to be useful in targeting and guiding resections of such tumors. Real-time tumor margin identification in NIR imaging could be helpful to both surgeons and patients by reducing the operation time and space required by other imaging modalities such as intraoperative MRI, and has the potential to integrate with robotically assisted surgery. In this paper, a segmentation method based on the Chan-Vese model was developed for identifying the tumor boundaries in an ex-vivo mouse brain from relatively noisy fluorescence images acquired by a multimodal scanning fiber endoscope (mmSFE). Tumor contours were achieved iteratively by minimizing an energy function formed by a level set function and the segmentation model. Quantitative segmentation metrics based on tumor-to-background (T/B) ratio were evaluated. Results demonstrated feasibility in detecting the brain tumor margins at quasi-real-time and has the potential to yield improved precision brain tumor resection techniques or even robotic interventions in the future.

  14. Decoy receptor 3 enhances tumor progression via induction of tumor-associated macrophages.

    PubMed

    Tai, Shyh-Kuan; Chang, Hsin-Chuan; Lan, Keng-Li; Lee, Chun-Ting; Yang, Chih-Ya; Chen, Nien-Jung; Chou, Teh-Ying; Tarng, Der-Cherng; Hsieh, Shie-Liang

    2012-03-01

    Tumor-associated macrophages (TAMs) are the major component of tumor-infiltrating leukocytes. TAMs are heterogeneous, with distinct phenotypes influenced by the microenvironment surrounding tumor tissues. Decoy receptor 3 (DcR3), a member of the TNFR superfamily, is overexpressed in tumor cells and is capable of modulating host immunity as either a neutralizing decoy receptor or an effector molecule. Upregulation of DcR3 has been observed to correlate with a poor prognosis in various cancers. However, the mechanisms underlying the DcR3-mediated tumor-promoting effect remain unclear. We previously demonstrated that DcR3 modulates macrophage activation toward an M2-like phenotype in vitro and that DcR3 downregulates MHC class II expression in TAMs via epigenetic control. To investigate whether DcR3 promotes tumor growth, CT26-DcR3 stable transfectants were established. Compared with the vector control clone, DcR3-transfectants grew faster and resulted in TAM infiltration. We further generated CD68 promoter-driven DcR3 transgenic (Tg) mice to investigate tumor growth in vivo. Compared with wild-type mice, macrophages isolated from DcR3-Tg mice displayed higher levels of IL-10, IL-1ra, Ym1, and arginase activity, whereas the expression of IL-12, TNF-α, IL-6, NO, and MHC class II was downregulated. Significantly enhanced tumor growth and spreading were observed in DcR3-Tg mice, and the enhanced tumor growth was abolished by arginase inhibitor N-ω-hydroxy-l-norarginine and histone deacetylase inhibitor sodium valproate. These results indicated that induction of TAMs is an important mechanism for DcR3-mediated tumor progression. Our findings also suggest that targeting DcR3 might help in the development of novel treatment strategies for tumors with high DcR3 expression.

  15. Theranostic GO-based nanohybrid for tumor induced imaging and potential combinational tumor therapy.

    PubMed

    Qin, Si-Yong; Feng, Jun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Liu, Xiang-Ji; Luo, Guo-Feng; Zhuo, Ren-Xi; Zhang, Xian-Zheng

    2014-02-12

    Graphene oxide (GO)-based theranostic nanohybrid is designed for tumor induced imaging and potential combinational tumor therapy. The anti-tumor drug, Doxorubicin (DOX) is chemically conjugated to the poly(ethylenimine)-co-poly(ethylene glycol) (PEI-PEG) grafted GO via a MMP2-cleavable PLGLAG peptide linkage. The therapeutic efficacy of DOX is chemically locked and its intrinsic fluorescence is quenched by GO under normal physiological condition. Once stimulated by the MMP2 enzyme over-expressed in tumor tissues, the resulting peptide cleavage permits the unloading of DOX for tumor therapy and concurrent fluorescence recovery of DOX for in situ tumor cell imaging. Attractively, this PEI-bearing nanohybrid can mediate efficient DNA transfection and shows great potential for combinational drug/gene therapy. This tumor induced imaging and potential combinational therapy will open a window for tumor treatment by offering a unique theranostic approach through merging the diagnostic capability and pathology-responsive therapeutic function. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Dr. von Braun and Dr. Stuhlinger With a Model of the Nuclear-Electric Vehicles

    NASA Technical Reports Server (NTRS)

    2004-01-01

    In this photo, taken at the Walt Disney Studios in California, Dr. Wernher von Braun and Dr. Ernst Stuhlinger are shown discussing the concepts of nuclear-electric spaceships designed to undertake the mission to the planet Mars. As a part of the Disney 'Tomorrowland' series on the exploration of space, the nuclear-electric vehicles were shown in the last three television films, entitled 'Mars and Beyond,' which first aired in December 1957.

  17. Malignant pineal germ-cell tumors: an analysis of cases from three tumor registries.

    PubMed

    Villano, J Lee; Propp, Jennifer M; Porter, Kimberly R; Stewart, Andrew K; Valyi-Nagy, Tibor; Li, Xinyu; Engelhard, Herbert H; McCarthy, Bridget J

    2008-04-01

    The exact incidence of pineal germ-cell tumors is largely unknown. The tumors are rare, and the number of patients with these tumors, as reported in clinical series, has been limited. The goal of this study was to describe pineal germ-cell tumors in a large number of patients, using data from available brain tumor databases. Three different databases were used: Surveillance, Epidemiology, and End Results (SEER) database (1973-2001); Central Brain Tumor Registry of the United States (CBTRUS; 1997-2001); and National Cancer Data Base (NCDB; 1985-2003). Tumors were identified using the International Classification of Diseases for Oncology, third edition (ICD-O-3), site code C75.3, and categorized according to histology codes 9060-9085. Data were analyzed using SAS/STAT release 8.2, SEER*Stat version 5.2, and SPSS version 13.0 software. A total of 1,467 cases of malignant pineal germ-cell tumors were identified: 1,159 from NCDB, 196 from SEER, and 112 from CBTRUS. All three databases showed a male predominance for pineal germ-cell tumors (>90%), and >72% of patients were Caucasian. The peak number of cases occurred in the 10- to 14-year age group in the CBTRUS data and in the 15- to 19-year age group in the SEER and NCDB data, and declined significantly thereafter. The majority of tumors (73%-86%) were germinomas, and patients with germinomas had the highest survival rate (>79% at 5 years). Most patients were treated with surgical resection and radiation therapy or with radiation therapy alone. The number of patients included in this study exceeds that of any study published to date. The proportions of malignant pineal germ-cell tumors and intracranial germ-cell tumors are in range with previous studies. Survival rates for malignant pineal germ-cell tumors are lower than results from recent treatment trials for intracranial germ-cell tumors, and patients that received radiation therapy in the treatment plan either with surgery or alone survived the longest.

  18. Targeting von Willebrand Factor in Ischaemic Stroke: Focus on Clinical Evidence.

    PubMed

    Buchtele, Nina; Schwameis, Michael; Gilbert, James C; Schörgenhofer, Christian; Jilma, Bernd

    2018-06-01

    Despite great efforts in stroke research, disability and recurrence rates in ischaemic stroke remain unacceptably high. To address this issue, one potential target for novel therapeutics is the glycoprotein von Willebrand factor (vWF), which increases in thrombogenicity especially under high shear rates as it bridges between vascular sub-endothelial collagen and platelets. The rationale for vWF as a potential target in stroke comes from four bodies of evidence. (1) Animal models which recapitulate the pathogenesis of stroke and validate the concept of targeting vWF for stroke prevention and the use of the vWF cleavage enzyme ADAMTS13 in acute stroke treatment. (2) Extensive epidemiologic data establishing the prognostic role of vWF in the clinical setting showing that high vWF levels are associated with an increased risk of first stroke, stroke recurrence or stroke-associated mortality. As such, vWF levels may be a suitable marker for further risk stratification to potentially fine-tune current risk prediction models which are mainly based on clinical and imaging data. (3) Genetic studies showing an association between vWF levels and stroke risk on genomic levels. Finally, (4) studies of patients with primary disorders of excess or deficiency of function in the vWF axis (e.g. thrombotic thrombocytopenic purpura and von Willebrand disease, respectively) which demonstrate the crucial role of vWF in atherothrombosis. Therapeutic inhibition of VWF by novel agents appears particularly promising for secondary prevention of stroke recurrence in specific sub-groups of patients such as those suffering from large artery atherosclerosis, as designated according to the TOAST classification. Schattauer GmbH Stuttgart.

  19. Richard von Volkmann: surgeon and Renaissance man.

    PubMed

    Willy, Christian; Schneider, Peter; Engelhardt, Michael; Hargens, Alan R; Mubarak, Scott J

    2008-02-01

    Richard von Volkmann (1830-1889), one of the most important surgeons of the 19(th) century, is regarded as one of the fathers of orthopaedic surgery. He was a contemporary of Langenbeck, Esmarch, Lister, Billroth, Kocher, and Trendelenburg. He was head of the Department of Surgery at the University of Halle, Germany (1867-1889). His popularity attracted doctors and patients from all over the world. He was the lead physician for the German military during two wars. From this experience, he compared the mortality of civilian and war injuries and investigated the general poor hygienic conditions in civilian hospitals. This led him to introduce the "antiseptic technique" to Germany that was developed by Lister. His powers of observation and creativity led him to findings and achievements that to this day bear his name: Volkmann's contracture and the Hueter-Volkmann law. Additionally, he was a gifted writer; he published not only scientific literature but also books of children's fairy tales and poems under the pen name of Richard Leander, assuring him a permanent place in the world of literature as well as orthopaedics.

  20. Beneficial Effects of High-Density Lipoproteins on Acquired von Willebrand Syndrome in Aortic Valve Stenosis.

    PubMed

    Gebhard, C; Maafi, F; Stähli, B E; Bonnefoy, A; Gebhard, C E; Nachar, W; de Oliveira Moraes, A Benjamim; Mecteau, M; Mihalache-Avram, T; Lavoie, V; Kernaleguen, A E; Shi, Y; Busseuil, D; Chabot-Blanchet, M; Perrault, L P; Rhainds, D; Rhéaume, E; Tardif, J C

    2018-02-01

     Infusions of apolipoprotein A-I (apoA-I), the major protein component of high-density lipoproteins (HDL), result in aortic valve stenosis (AVS) regression in experimental models. Severe AVS can be complicated by acquired von Willebrand syndrome, a haemorrhagic disorder associated with loss of high-molecular-weight von Willebrand factor (vWF) multimers (HMWM), the latter being a consequence of increased shear stress and enhanced vWF-cleaving protease (ADAMTS-13) activity. Although antithrombotic actions of HDL have been described, its effects on ADAMTS-13 and vWF in AVS are unknown.  We assessed ADAMTS-13 activity in plasma derived from a rabbit model of AVS ( n  = 29) as well as in plasma collected from 64 patients with severe AVS (age 65.0 ± 10.4 years, 44 males) undergoing aortic valve replacement (AVR). In both human and rabbit AVS plasma, ADAMTS-13 activity was higher than that in controls ( p  < 0.05). Accordingly, AVS patients had less HMWM than controls (66.3 ± 27.2% vs. 97.2 ± 24.1%, p  < 0.0001). Both ADAMTS-13 activity and HMWM correlated significantly with aortic transvalvular gradients, thereby showing opposing correlations ( r  = 0.3, p  = 0.018 and r  = -0.4, p  = 0.003, respectively). Administration of an apoA-I mimetic peptide reduced ADAMTS-13 activity in AVS rabbits as compared with the placebo group (2.0 ± 0.5 RFU/sec vs. 3.8 ± 0.4 RFU/sec, p  < 0.05). Similarly, a negative correlation was found between ADAMTS-13 activity and HDL cholesterol levels in patients with AVS ( r  = -0.3, p  = 0.045).  Our data indicate that HDL levels are associated with reduced ADAMTS-13 activity and increased HMWM. HDL-based therapies may reduce the haematologic abnormalities of the acquired von Willebrand syndrome in AVS. Schattauer GmbH Stuttgart.