Ectodomain shedding of the hypoxia-induced carbonic anhydrase IX is a metalloprotease-dependent process regulated by TACE/ADAM17

Carbonic anhydrase IX (CA IX) is a transmembrane protein whose expression is strongly induced by hypoxia in a broad spectrum of human tumours. It is a highly active enzyme functionally involved in both pH control and cell adhesion. Its presence in tumours usually indicates poor prognosis. Ectodomain of CA IX is detectable in the culture medium and body fluids of cancer patients, but the mechanism of its shedding has not been thoroughly investigated. Here, we analysed several cell lines with natural and ectopic expression of CA IX to show that its ectodomain release is sensitive to metalloprotease inhibitor batimastat (BB-94) and that hypoxia maintains the normal rate of basal shedding, thus leading to concomitant increase in cell-associated and extracellular CA IX levels. Using CHO-M2 cells defective in shedding, we demonstrated that the basal CA IX ectodomain release does not require a functional TNFα-converting enzyme (TACE/ADAM17), whereas the activation of CA IX shedding by both phorbol-12-myristate-13-acetate and pervanadate is TACE-dependent. Our results suggest that the cleavage of CA IX ectodomain is a regulated process that responds to physiological factors and signal transduction stimuli and may therefore contribute to adaptive changes in the protein composition of tumour cells and their microenvironment

PPARδ Activation Acts Cooperatively with 3-Phosphoinositide-Dependent Protein Kinase-1 to Enhance Mammary Tumorigenesis

Peroxisome proliferator-activated receptorδ (PPARδ) is a transcription factor that is associated with metabolic gene regulation and inflammation. It has been implicated in tumor promotion and in the regulation of 3-phosphoinositide-dependent kinase-1 (PDK1). PDK1 is a key regulator of the AGC protein kinase family, which includes the proto-oncogene AKT/PKB implicated in several malignancies, including breast cancer. To assess the role of PDK1 in mammary tumorigenesis and its interaction with PPARδ, transgenic mice were generated in which PDK1 was expressed in mammary epithelium under the control of the MMTV enhancer/promoter region. Transgene expression increased pT308AKT and pS9GSK3β, but did not alter phosphorylation of mTOR, 4EBP1, ribosomal protein S6 and PKCα. The transgenic mammary gland also expressed higher levels of PPARδ and a gene expression profile resembling wild-type mice maintained on a diet containing the PPARδ agonist, GW501516. Both wild-type and transgenic mice treated with GW501516 exhibited accelerated rates of tumor formation that were more pronounced in transgenic animals. GW501516 treatment was accompanied by a distinct metabolic gene expression and metabolomic signature that was not present in untreated animals. GW501516-treated transgenic mice expressed higher levels of fatty acid and phospholipid metabolites than treated wild-type mice, suggesting the involvement of PDK1 in enhancing PPARδ-driven energy metabolism. These results reveal that PPARδ activation elicits a distinct metabolic and metabolomic profile in tumors that is in part related to PDK1 and AKT signaling

Analiza parametrów determinujących roczne zapotrzebowanie na ciepło dla budynków jednokondygnacyjnych

The quality of most buildings may be affected during the initial phase of architectural design. Therefore, it is important to optimize input parameters, which significantly influence energy efficiency. In principle, it is possible to speak of a deterministic approach, which considers input parameters to be fixed, or a stochastic approach, which takes a wider set of input parameters into account. A reference building is evaluated in terms of energy performance, where input parameters are changed in order to determine a correlation coefficient. Regressions were written to express the impact architectural design has on energy performance.W pracy przedstawiono analizę wpływu wybranych rozwiązań architektonicznych i materiałowo-konstrukcyjnych na wartość rocznego zapotrzebowania na ciepło do ogrzewania jednokondygnacyjnych budynków mieszkalnych (typu bungalow). Analizie poddano współczynnik kształtu, izolacyjność cieplną przegród - współczynnik przenikania ciepła, orientację w stosunku do stron świata, mostki termiczne, wielkość przeszklenia budynków, zyski ciepła od promieniowania słonecznego. Przedstawiono histogramy oraz współczynniki regresji

Energetyczny i środowiskowy profil budynku o niskim zapotrzebowaniu na energię – studium przypadku

Integrated building design should take into account environmental, social and economic dimensions of sustainability. Building design from energy performance ranges from architectural design to the application of technologies for energy conservation. Many applications are focused on insulation of facades, roofs and floors to those that are used systems for renewable energy sources. The aim of the innovations is not only energy saving but also reduces costs and preserves natural resources. One key element of low-energy building design is using the basic form and enclosure of a building to save energy while enhancing occupant comfort. Besides energy need for building operation the significant part of the total energy is energy used in the extraction, processing and transportation of materials used in buildings. This study is aimed to analyze the building materials and structures in terms of embodied environmental impacts and monitoring of physical factors of indoor environment. The paper deals with evaluation of environmental and energy indicators in selected low-energy family house and its optimization in order to reduction of environmental impacts.Zintegrowany projekt budowlany powinien uwzględniać środowiskowe, społeczne i ekonomiczne aspekty zrównoważonego rozwoju. Projektowanie budynków w zakresie efektywności energetycznej obejmuje różne aspekty, począwszy od projektu architektonicznego aż po wykorzystanie technologii związanych z oszczędzaniem energii. Wiele uwagi przywiązuje się do prawidłowej izolacji ścian, dachów i podłóg aż po zastosowanie systemów wykorzystujących odnawialne źródła energii. Celem innowacji jest nie tylko oszczędzanie energii, ale również obniżenie kosztów i ochrona zasobów naturalnych. Niniejsze opracowanie koncentruje się na analizie materiałów budowlanych i konstrukcji w odniesieniu ich do oddziaływania na środowisko oraz na monitorowaniu fizycznych parametrów środowiska wewnętrznego. W pracy przedstawiono ocenę wskaźników energetycznych i środowiskowych w wybranym budynku o niskim zapotrzebowaniu na energię i ich optymalizację w celu zmniejszenia oddziaływania na środowisko

Moznosti rozvoje mobility pracovni sily.

Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Analysis of noise and non-linearity of I-V characteristics of positive temperature coefficient chip thermistors

Noise spectroscopy and I-V characteristic non-linearity measurement were applied as diagnostic tools in order to characterize the volume and contact quality of positive temperature coefficient (PTC) chip sensors and to predict possible contact failure. Correctly made and stable contacts are crucial for proper sensing. I-V characteristics and time dependences of resistance were measured for studied sensors and, besides the samples with stable resistance value, spike type resistance fluctuation was observed for some samples. These spikes often disappear after about 24 hours of voltage application. Linear I-V characteristics were measured for the samples with stable resistance. The resistance fluctuation of burst noise type was observed for some samples showing the I-V characteristic dependent on the electric field orientation. We have found that the thermistors with high quality contacts had a linear I-V characteristic, the noise spectral density is of 1/f type and the third harmonic index is lower than 60 dB. The samples with poor quality contacts show non-linear I-V characteristics and excess noise is given by superposition of g-r and 1/fn type noises, and the third harmonic index is higher than 60 dB

Ultrasonic spectroscopy of silicon single crystal

Specimens of Si single crystals with different crystal orientation [100] and [110] were studied by Electro-Ultrasonic Spectroscopy (EUS) and Resonant Ultrasonic Spectroscopy (RUS). A silicon single crystal is an anisotropic crystal, so its properties are different in different directions in the material relative to the crystal orientation. EUS is based on interaction of two signals: an electric AC signal and an ultrasonic signal, which are working on different frequencies. The ultrasonic wave affects the charge carriers' transport in the structures and the intermodulation electrical signal which is created due to the interaction between the ultrasonic wave and charge carriers, is proportional to the density of structural defects. RUS enables to measure natural frequencies of free elastic vibrations of a simply shaped specimen by scanning a selected frequency range including the appropriate resonances of the measured specimens