Biologische und funktionale Charakterisierung von Tumoren im Gastrointestinaltrakt durch genomweite Genexpressions-Analyse und Identifizierung von potentiellen Tumormarkern

Die Untersuchungen in der vorliegenden Arbeit umfassen mit dem Magenkarzinom, dem kolorektalen Karzinom und dem neuroendokrinen Tumor drei verschiedene Entitäten, die zwar alle im Gastrointestinaltrakt lokalisiert sind, deren Genese und Progression aber unterschiedlich abläuft. 1. Etablierung und Evaluierung eines Serum-Protein-Biochips, der durch die quantitative Bestimmung von neun Biomarkern im Serum von Patienten eine frühestmögliche Diagnose eines vorhandenen kolorektalen Karzinoms ermöglicht. Dazu wurden insgesamt 474 Seren mit der Evidence Investigator™ Biochip Technologie der Firma Randox getestet. 2. Etablierung und Charakterisierung einer gewebebasierten Signatur zur Bestimmung der Lokalisation des Primärtumors bei neuroendokrinen Tumoren (NETs) mit CUP-Syndrom (cancer of unknown primary). Anhand des Expressionslevels dreier Gene (CD302, PPWD1 und ABHD14B) konnte der Entstehungsort des Primärtumors bei knapp 100 NETs mit einer Spezifität von 67-98% bestimmt werden. Der Drei-Gen-Klassifikators wurde patentiert. 3. Erstellung und Auswertung von DNA Aberrations-Profilen sowie Darstellung der fehlregulierten Signalwege an 29 Magenkarzinomen, anhand derer gezeigt werden konnte, dass die Anzahl der individuellen DNA-Aberrationen mit der Überlebenswahrscheinlichkeit der Patienten korreliert und dass es Subgruppen beim Magenkarzinom gibt, die unabhängig von der TNM- und der Laurén-Klassifikation auf verschiedene Chemotherapien ansprechen. Zusammenfassend zeigen die Ergebnisse der drei untersuchten Tumorentitäten des Gastrointestinaltraktes, dass die Vernetzung von globalen, adaptierten Verfahren, wie der Genenexpressions-Analyse mit funktionellen Untersuchungen einzelner Gene, es erlauben biologische und klinische Fragestellungen translational zu untersuchen, um so einerseits molekulargenetische Grundlagen der malignen Progression von Tumoren weiter aufzuklären und andererseits zur Optimierung von Diagnose und individualisierter Therapie beitragen zu können

Derivative chromosome 1 and GLUT1 deficiency syndrome in a sibling pair

<p>Abstract</p> <p>Background</p> <p>Genomic imbalances constitute a major cause of congenital and developmental abnormalities. GLUT1 deficiency syndrome is caused by various de novo mutations in the facilitated human glucose transporter 1 gene (1p34.2) and patients with this syndrome have been diagnosed with hypoglycorrhachia, mental and developmental delay, microcephaly and seizures. Furthermore, 1q terminal deletions have been submitted in the recent reports and the absence of corpus callosum has been related to the deletion between <it>C1orf100 </it>and <it>C1orf121 </it>in 1q44.</p> <p>Results</p> <p>This study reports on a sibling pair with developmental delay, mental retardation, microcephaly, hypotonia, epilepsy, facial dysmorphism, ataxia and impaired speech. Chromosome analysis revealed a derivative chromosome 1 in both patients. FISH and MCB analysis showed two interstitial deletions at 1p34.2 and 1q44. SNP array and array-CGH analysis also determined the sizes of deletions detailed. The deleted region on 1p34.2 encompasses 33 genes, among which is <it>GLUT1 </it>gene (<it>SLC2A1</it>). However, the deleted region on 1q44 includes 59 genes and distal-proximal breakpoints were located in the ZNF672 gene and SMYD3 gene, respectively.</p> <p>Conclusion</p> <p>Haploinsufficiency of <it>GLUT1 </it>leads to GLUT1 deficiency syndrome, consistent with the phenotype in patients of this study. Conversely, in the deleted region on 1q44, none of the genes are related to findings in these patients. Additionally, the results confirm previous reports on that corpus callosal development may depend on the critical gene(s) lying in 1q44 proximal to the <it>SMYD3 </it>gene.</p

The search for the primary tumor in metastasized gastroenteropancreatic neuroendocrine neoplasm.

Gastroenteropancreatic neuroendocrine tumors (NETs) often present as liver metastasis from a carcinoma of unknown primary. We recently showed that primary NETs from the pancreas, small intestine and stomach as well as their respective liver metastases differ from each other by the expression profile of the three genes CD302, PPWD1 and ABHB14B. The gene and protein expression of CD302, PPWD1, and ABHB14B was studied in abdominal NET metastases to identify the site of the respective primary tumors. Cryopreserved tissue from NET metastases collected in different institutions (group A: 29, group B: 50, group C: 132 specimens) were examined by comparative genomic hybridization (Agilent 105 K), gene expression analysis (Agilent 44 K) (groups A and B) and immunohistochemistry (group C). The data were blindly evaluated, i.e. without knowing the site of the primary. Gene expression analysis correctly revealed the primary in the ileum in 94 % of the cases of group A and in 58 % of group B. A pancreatic primary was predicted in 83 % (group A) and 20 % (group B), respectively. The combined sensitivity of group A and B was 75 % for ileal NETs and 38 % for pancreatic NETs. Immunohistochemical analysis of group C revealed an overall sensitivity of 80 %. Gene and protein expression analysis of CD302 and PPWD1 in NET metastases correctly identifies the primary in the pancreas or the ileum in 80 % of the cases, provided that the tissue is well preserved. Immunohistochemical profiling revealed CD302 as the best marker for ileal and PPWD1 for pancreatic detection

A Low Cost Concept for Data Acquisition Systems Applied to Decentralized Renewable Energy Plants

The present paper describes experiences of the use of monitoring and data acquisition systems (DAS) and proposes a new concept of a low cost DAS applied to decentralized renewable energy (RE) plants with an USB interface. The use of such systems contributes to disseminate these plants, recognizing in real time local energy resources, monitoring energy conversion efficiency and sending information concerning failures. These aspects are important, mainly for developing countries, where decentralized power plants based on renewable sources are in some cases the best option for supplying electricity to rural areas. Nevertheless, the cost of commercial DAS is still a barrier for a greater dissemination of such systems in developing countries. The proposed USB based DAS presents a new dual clock operation philosophy, in which the acquisition system contains two clock sources for parallel information processing from different communication protocols. To ensure the low cost of the DAS and to promote the dissemination of this technology in developing countries, the proposed data acquisition firmware and the software for USB microcontrollers programming is a free and open source software, executable in the Linux and Windows® operating systems

Vergleich zwischen berechneter und gemessener Nutzenergieabgabe eines Flachkollektors bei typischen Witterungen

Calorimetric measurements were made to determine the useful energy output of an one cover flat-plate collector with non-selective coating. The metereological data were recorded simultaneously. The data-base consists of instantaneous measurements with a time interval of 25 seconds. The collector perfonnance was studied with respect to the influence of transient solar radiation. Results: In the vincinity of the conversion factor no the collector perfonns as a linear converter of insolation to sensitive heat. A significant impact an the efficiency during transient insolation was not observed if reflexion lasses (Diffuse fraction, angular modifier of the ($\tau \alpha)_{e}$ product for direct solar radiation) and thennal lasses were taken into account. The collector perfonnance for transient global radiation at elevated temperature levels agreed well with the efficiency characteristic derived from quasi steady state measurements, if heat capacity effects were not taken into account. The model used for computing the collector efficiency from the metereological data showed for all operating conditions an accuracy of ± 2% compared with the measured results. Prediction of all-day collector efficiency by using the efficiency curve based on the BSE-Procedure for an air velocity of 5 $\frac{m}{sec}$ showed deviationsof 6% of the measured results, which lead under low efficiency conditions to considerable differences between predicted and measured useful energy output. For metereological conditions of the test site and neighbouring regions the accuracy of the estimations could improve by using an efficiency curve for an average air velocity of 3 $\frac{m}{sec}$, if no other data is available.For predicting the useful energy output more accurately a higher resolution of the efficiency curves with respect to air velocity is necessary, alternatively a method to model the influence of air velocity is adequate. Experimental determination of the collector efficiency is possible for fast transients of radiation if time intervals for data aquisition is properly extended. The results indicate that an integration interval of 30 to 60 minutes is appropriate. The useability of BSE-test-procedures in the climatic conditions of middleEurope could be largely enhanced, if transient conditions were accepted. This implies additional efforts in equipment and instrumentation

Thermisches Verhalten von Energieabsorbern als Wärmequellenanlage in Wärmepumpe-Heizungsanlagen

The useful energy output of absorber plates was measured under the seasonal range of weather conditions over a period of 1 year.The absorber plates were oriented to the south either with thermal insulation on the rear side or elevated from the supporting plane to allow additional heat exchange on the rear side. Calorimetric measurements of the plates were carried out with simultaneousrecording of meteorological data. Comprehensive data were collected in respect of black-painted absorber plates as well as those with selective coating. An elaborate model for simulating the heat transfer on an absorber plate was verified by the measured results. The thermal performance of an absorber roof as heatpump-source was studied by simulation over periods of one year each for a single-family detached house. The calculations were based on hourly meteorological data measured during 1973 in Hamburg and 1979 in Braunschweig. The househeating-systems were simulated with respect to three different heat source devices : - A heatpump evaporator with forced air convection as a reference device. - Absorber roofs with selective or nonselective coatings either as an integrated part of the roof with rear-side insulation or elevated from the roof construction. - An extended heat source device which includes an ice/water latent heal; storage tank besides the absorber roof. The construction parameters of the heatpump-systems were varied in order to investigate the percentage of commercial energy input needed to cover the total heat demand

Wärmeübergänge am Energieabsorber und deren Abhängigkeit von meteorologischen Parametern

The useful energy output of absorber plates was measured under the seasonal range of weather conditions over a period of 1 year. The absorber plates were mounted in an inclined position (60 °) oriented to the south either with thermal insulation on the rear side or elevated from the supporting plane to allow additional heat exchange on the rear side. Calorimetric measurements of the plates at different temperature levels were carried out with simultaneous recording of meteorological data. Comprehensive data were collected in respect of black- painted absorber plates as well as those with selective coating. It has been demonstrated that the stagnation temperature of an absorber plate, which is yielded under no-flow conditions, is a suitable parameter for calculating the useful energy output by simulation. The model describing the thermal performance of absorber plates is based on heat exchanger characteristics and includes the effect of absorption of radiation. The results obtained from the model were verified over the wide range of measured temperature levels

Die Verantwortung der Stadtverordnetenversammlung, ihrer Organe und der Betriebe fuer die Leitung und Planung der sozialistischen Arbeitskultur

UB Potsdam-280-1973/3136 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman