Optical Propagation and Communication

Contains an introduction and reports on four research project.Maryland Procurement Office Contract MDA 904-90-C-5070Charles S. Draper Laboratories Contract DL-H-441698National Institute of Standards and Technology Grant 60-NANBOD-1052U.S. Army Research Office Grant DAAL03-90-G-0128U.S. Navy - Office of Naval Research Grant N00014-89-J-1163U.S. Air Force - Office of Scientific Research Contract F49620-90-C-003

DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology

Differential Impact of Tetratricopeptide Repeat Proteins on the Steroid Hormone Receptors

Tetratricopeptide repeat (TPR) motif containing co-chaperones of the chaperone Hsp90 are considered control modules that govern activity and specificity of this central folding platform. Steroid receptors are paradigm clients of Hsp90. The influence of some TPR proteins on selected receptors has been described, but a comprehensive analysis of the effects of TPR proteins on all steroid receptors has not been accomplished yet.We compared the influence of the TPR proteins FK506 binding proteins 51 and 52, protein phosphatase-5, C-terminus of Hsp70 interacting protein, cyclophillin 40, hepatitis-virus-B X-associated protein-2, and tetratricopeptide repeat protein-2 on all six steroid hormone receptors in a homogeneous mammalian cell system. To be able to assess each cofactor's effect on the transcriptional activity of on each steroid receptor we employed transient transfection in a reporter gene assay. In addition, we evaluated the interactions of the TPR proteins with the receptors and components of the Hsp90 chaperone heterocomplex by coimmunoprecipitation. In the functional assays, corticosteroid and progesterone receptors displayed the most sensitive and distinct reaction to the TPR proteins. Androgen receptor's activity was moderately impaired by most cofactors, whereas the Estrogen receptors' activity was impaired by most cofactors only to a minor degree. Second, interaction studies revealed that the strongly receptor-interacting co-chaperones were all among the inhibitory proteins. Intriguingly, the TPR-proteins also differentially co-precipitated the heterochaperone complex components Hsp90, Hsp70, and p23, pointing to differences in their modes of action.The results of this comprehensive study provide important insight into chaperoning of diverse client proteins via the combinatorial action of (co)-chaperones. The differential effects of the TPR proteins on steroid receptors bear on all physiological processes related to steroid hormone activity

DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology

Long-term changes and regional differences in temperature and precipitation in the metropolitan area of Hamburg

Climate changes and the urban climate of the 'green city' Hamburg and its metropolitan region are analyzed using observational data for temperature and precipitation. Values for Hamburg's synoptic site HH-Fuhlsbuttel start in 1891 and are used to determine climate changes. Additional data from up to 45 climate stations are used to analyze the different aspects of the regional climate and urban effects on the temperature [urban heat island (UHI)] and precipitation [urban precipitation impact (UPI)]. The analysis of the long-term data shows that the climate has already changed. Annual precipitation significantly increases similar to 0.8 mm/year when focusing on years 1891-2007 and similar to 1.3 mm/year for 1948-2007. Precipitation increases are largest in November through March and March as well as June for 1978-2007. For April and July of this period, a precipitation decrease is found. The precipitation distribution shows that moderate daily precipitation amounts (10 mm/day have increased by 20% in the same period. Average temperatures significantly increase by 0.07 K/decade (1891-2007), 0.19 K/decade (1948-2007). 0.6 K/decade (1978-2007) with largest significant increases in fall. For the UHI, it is found that the average temperature is higher up to 1.1 K in the densely build-up city area than outside. Values are about halved for more green urban areas but also depend on more local impacts. The minimum temperatures are up to 3 K higher and maximum temperatures slightly lower in the inner city than in the rural during summer. The winter temperatures are higher throughout the urban area. The UHI differences depend on wind speed; this dependence is best described by using the inverse square root of the wind speed. Classification using different wind directions shows that the precipitation is significantly higher (5-20%) for downwind of urban areas compared with the upwind side. Copyright (C) 2009 Royal Meteorological Societ