The oncogene AAMDC links PI3K-AKT-mTOR signaling with metabolic reprograming in estrogen receptor-positive breast cancer

Adipogenesis associated Mth938 domain containing (AAMDC) represents an uncharacterized oncogene amplified in aggressive estrogen receptor-positive breast cancers. We uncover that AAMDC regulates the expression of several metabolic enzymes involved in the one-carbon folate and methionine cycles, and lipid metabolism. We show that AAMDC controls PI3K-AKT-mTOR signaling, regulating the translation of ATF4 and MYC and modulating the transcriptional activity of AAMDC-dependent promoters. High AAMDC expression is associated with sensitization to dactolisib and everolimus, and these PI3K-mTOR inhibitors exhibit synergistic interactions with anti-estrogens in IntClust2 models. Ectopic AAMDC expression is sufficient to activate AKT signaling, resulting in estrogen-independent tumor growth. Thus, AAMDC-overexpressing tumors may be sensitive to PI3K-mTORC1 blockers in combination with anti-estrogens. Lastly, we provide evidence that AAMDC can interact with the RabGTPase-activating protein RabGAP1L, and that AAMDC, RabGAP1L, and Rab7a colocalize in endolysosomes. The discovery of the RabGAP1L-AAMDC assembly platform provides insights for the design of selective blockers to target malignancies having the AAMDC amplification

Gołdap – a small border town

Dzieje przygranicznego miasta Gołdap założonego w 1570 roku dokumentują wpływ ostatnich przemian społeczno-politycznych w skali krajowej i międzynarodowej na strukturę przestrzenną miasta. Dotyczyły one różnorodnych relacji pomiędzy graniczącymi państwami, jak np. ich terytorialnych przemieszczeń, dewiacji ustrojowych, prawnych uwarunkowań egzystencjonalnych oraz przesiedleń ludności. Gołdap na przestrzeni wieków zmieniała nie tylko formę zabudowy, cechy funkcjonalne i mieszkańców, ale też kierunki terytorialnej ekspansji, strukturę użytkowania ziemi. Dzisiejsze miasto odsłania tylko nieliczne ślady tej przeszłości, część z nich dokumentują stare mapy i teksty kronikarskie. Po drugiej wojnie światowej miasto długo adaptowało się do nowej sytuacji i powoli budowało swoją społeczną i przestrzenną tożsamość. Współczesne społeczno-gospodarcze tło rozwoju sprawia, że upodabnia się ono do wielu innych małych miast w Polsce. W jego układzie przestrzennym zarysowują się zarówno wady strukturalne, jak i tendencje rozwojowe typowe dla tej grupy miast, co wyraża najdobitniej mapa użytkowania gruntów miejskich. Ukazuje ona charakterystyczny proces wewnętrznej dekoncentracji zagospodarowania miejskiego, połączony z dezurbanizacją struktury miasta. Gołdap jest przykładem słabości polskiego planowania przestrzennego zwłaszcza w konfrontacji ze spontanicznie zachodzącymi procesami w gospodarowaniu przestrzenią, które miały miejsce w ostatnim dwudziestoleciu.The history of the border town of Gołdap founded in 1570 documents the impact on the structure of its urban space brought by the recent socio-political changes on both the home and international scene. In this case, the changes concerned relations of various kind between the bordering countries such as their shifting frontiers, anomalies in their political systems, legal existential conditions, and population transfers. What changed in Gołdap over the centuries was not only the form of its buildings and their functional characteristics as well as its residents, but also the directions of its expansion and land-use structure. Today the town shows few traces of its past, some surviving only in old maps and chronicles. After World War II, the town took a long time to adapt to the new circumstances and was slow to built its social and spatial identity. The contemporary socio-economic background of its development has rendered it similar to many other small towns in Poland. Consequently, both the structural defects and developmental trends typical of this group of towns are visible in its spatial layout: this is most clearly visible on the map of its land use. It reflects the characteristic process of sprawling development coupled with deurbanisation of the town’s structure. Gołdap is an example of the weaknesses of Polish spatial planning, especially when confronted with the spontaneous processes of space management that have occurred in the last two decades

Comparison of downdraft and updraft gasification of biomass in a fixed bed reactor

The aim of this study was to compare and analyze the gasification process of beech wood. The experimental investigation was conducted inside a gasifier, which can be operated in downdraft and updraft gasification system. The most important operating parameter studied in this paper was the influence of the amount of supply air on the temperature distribution, biomass consumption and syngas calorific value. The results show that the amount of air significantly influences the temperature in the combustion zone for the downdraft gasification process, where temperature differences reached more than 150 °C. The increased amount of air supplied to the gasifier caused an increase in fuel consumption for both experimental setups. Experimental results regarding equivalence ratio show that for value below 0.2, the updraft gasification is characterized by a higher calorific value of producer gas, while for about 0.22 a similar calorific value (6.5 MJ/Nm3) for both gasification configurations was obtained. Above this value, an increase in equivalence ratio causes a decrease in the calorific value of gas for downdraft and updraft gasifiers

Experimental study of thermal pyrolysis of turkey feathers

The analysis of chemical composition of turkey feathers reveals over 50% mass content of carbon. Unfortunately, the feathers contain also over 13% by weight of nitrogen and over 2.5% of sulfur. The significant presence of nitrogen and sulfur in turkey feathers indicates potential danger to the environment. The experiments of thermal pyrolysis of turkey feathers were done from a perspective of energy production potential out of gaseous products. The products of thermal pyrolysis were mainly gas and liquid. The calorific value of pyrolysed feathers is comparable with the one of hard carbon. It gets higher for higher temperatures. The calorific value of gaseous products of turkey feathers at 850oC was maximum and it equalled 16.7 MJ/Nm3

Characteristic of tar content and syngas composition during beech updraft gasification

This work aims at study the effect of the operating conditions like equivalence ration and temperature on the updraft gasification of beech wood. The main aspects was to analyze the influence of temperature distribution in the reactor and equivalence ratio on the fuel consumption, syngas composition as well as tar formation characteristics during the gasification process. The light tar content and composition were analysed using gas chromatography coupled with mass spectrometry (GC-MS). Experimental results have shown that the amount of air supplied does not affect the parameters of the gasification process linearly. For lower ER value there was high fuel consumption and high bed temperature in the gasifier, which results in high caloric value of syngas. The results showed that tar yield during updraft gasification depends on the temperature and equivalence ratio. With the increase value of ER and the decrease of temperature on the surface of the bed, the total amount of tar yield increased. The highest temperature on the surface of the bed leads to the smallest tar yield, which can be associated with thermal cracking. The results indicate that both light and heavy tar are changing nonlinearly with different operating conditions. In addition, with decreasing temperature and increasing ER values, the amount of phenol and oxidized aliphatic compounds in the tar samples increased while the BTEX amount decreased. The amount of PAHs, in relation to the temperature and ER, was kept low in all cases

Pyrolysis of biomass and refuse-derived fuel performance in laboratory scale batch reactor

The results of pyrolysis of pine chips and refuse derived fuel fractions are presented. The experiments were carried out in a pilot pyrolysis reactor. The feedstock was analyzed by an elemental analyzer and the X-ray fluorescence spectrometer to determine the elemental composition. To find out optimum conditions for pyrolysis and mass loss as a function of temperature the thermogravimetric analysis was applied. Gases from the thermogravimetric analysis were directed to the infrared spectrometer using gas-flow cuvette to online analysis of gas composition. Chemical composition of the produced gas was measured using gas chromatography with a thermal conductivity detector and a flame ionization detector. The product analysis also took into account the mass balance of individual products

Nonlinear index of refraction measurement by SPM-induced phase regression software

This program calculates nonlinear index of refraction via fitting the phase of the ultrashort laser pulse propagated through the sample to its intensity.<br><div>Intensity and phase of the pulse are calculated using Principal Component Generalized Projections algorithm with bootstrap for error estimation from Frequency-Resolved Optical Gating trace.</div><div>There is a .zip package with measured FROG traces and program output files included.<br></div