Zróżnicowanie podstawowych zmiennych makroekonomicznych w województwach

The aim of the present study is descriptive analysis of the spatial variation of basic macroeconomic variables in the provinces. Variables whose variation is considered here are: GDP per capita gross value of fixed assets per capita, investment per capita, wages and the unemployment rate. Work carried out in the discussion, because of the availability of relevant statistics for the CSO ww.stat.gov.pl in August 2012, concern the years 2002–2009 (GDP per capita and gross fixed assets per capita), 2002–2010 (investment per capita), or 2002–2011 (wages and unemployment rate). Summarizes the development of taxonomic analysis of complex economic indicators of macroeconomic variables previously considered

Quaternary exhumation of the Carpathians: a record from the Orava-Nowy Targ intramontane basin, Western Carpathians, Polish Galicia and Slovakia

Quaternary exhumation of the Carpathians: a record from the Orava-Nowy Targ Intramontane Basin, Western Carpathians (Poland and Slovakia)The Neogene-Quaternary infill of the Orava-Nowy Targ Intramontane Basin comprises two tiers showing contrasting lithologies. The Neogene tier is largely composed of claystones and siltstones, whereas the Quaternary tier is dominated by gravels. The two sequences are separated by an erosional surface underlain by a regolith. Deposition of the Neogene sequence took place during subsidence of the basin. No prominent relief existed in the area of the present-day mountains actually surrounding the basin at that time. The regolith started to form at the onset of basin inversion. Still, no prominent relief existed in the present-day mountains. The onset of deposition of Quaternary gravels in the basin corresponds to acceleration of uplift of the surrounding mountains, which has been continuing until now. The Pieniny Klippen Belt has been subject to erosion, at least locally, from the deposition of the basal part of the Neogene sequence filling the Orava-Nowy Targ Basin until present times. In contrast, the Paleogene cover of the Tatra Mts was removed only during the Quaternary.</jats:p

The BSUIN project

Baltic Sea Underground Innovation Network (BSUIN) is an European Union funded project that extends capabilities of underground laboratories. The aim of the project is to join efforts in making the underground laboratories in the Baltic Sea Region’s more accessible for innovation, business development and science by improving the availability of information about the underground facilities, service offerings, user experience, safety and marketing.The development of standards for the characterization of underground laboratories will allow to compared them with each other. This will help you choose the best places for physical measurements such as neutrino physics or searching for dark matter. The project concerns laboratories where so far no measurements have been made, and even undergrounds where there are no organized laboratories yet.The description of the BSUIN project and the first results of characterization of natural radioactive background in underground laboratories will be presented ˙ The BSUIN Project is funded by Interreg Baltic Sea funding cooperation [2]

BCR and its mutants, the reciprocal t(9;22)-associated ABL/BCR fusion proteins, differentially regulate the cytoskeleton and cell motility

BACKGROUND: The reciprocal (9;22) translocation fuses the bcr (breakpoint cluster region) gene on chromosome 22 to the abl (Abelson-leukemia-virus) gene on chromosome 9. Depending on the breakpoint on chromosome 22 (the Philadelphia chromosome – Ph+) the derivative 9+ encodes either the p40((ABL/BCR) )fusion transcript, detectable in about 65% patients suffering from chronic myeloid leukemia, or the p96((ABL/BCR) )fusion transcript, detectable in 100% of Ph+ acute lymphatic leukemia patients. The ABL/BCRs are N-terminally truncated BCR mutants. The fact that BCR contains Rho-GEF and Rac-GAP functions strongly suggest an important role in cytoskeleton modeling by regulating the activity of Rho-like GTPases, such as Rho, Rac and cdc42. We, therefore, compared the function of the ABL/BCR proteins with that of wild-type BCR. METHODS: We investigated the effects of BCR and ABL/BCRs i.) on the activation status of Rho, Rac and cdc42 in GTPase-activation assays; ii.) on the actin cytoskeleton by direct immunofluorescence; and iii) on cell motility by studying migration into a three-dimensional stroma spheroid model, adhesion on an endothelial cell layer under shear stress in a flow chamber model, and chemotaxis and endothelial transmigration in a transwell model with an SDF-1α gradient. RESULTS: Here we show that both ABL/BCRs lost fundamental functional features of BCR regarding the regulation of small Rho-like GTPases with negative consequences on cell motility, in particular on the capacity to adhere to endothelial cells. CONCLUSION: Our data presented here describe for the first time an analysis of the biological function of the reciprocal t(9;22) ABL/BCR fusion proteins in comparison to their physiological counterpart BCR

Identification of Milk Component in Ancient Food Residue by Proteomics

Proteomic approaches based on mass spectrometry have been recently used in archaeological and art researches, generating promising results for protein identification. Little information is known about eastward spread and eastern limits of prehistoric milking in eastern Eurasia.In this paper, an ancient visible food remain from Subeixi Cemeteries (cal. 500 to 300 years BC) of the Turpan Basin in Xinjiang, China, preliminarily determined containing 0.432 mg/kg cattle casein with ELISA, was analyzed by using an improved method based on liquid chromatography (LC) coupled with MALDI-TOF/TOF-MS to further identify protein origin. The specific sequence of bovine casein and the homology sequence of goat/sheep casein were identified.The existence of milk component in ancient food implies goat/sheep and cattle milking in ancient Subeixi region, the furthest eastern location of prehistoric milking in the Old World up to date. It is envisioned that this work provides a new approach for ancient residue analysis and other archaeometry field

Structural and Spectroscopic Analysis of the Kinase Inhibitor Bosutinib and an Isomer of Bosutinib Binding to the Abl Tyrosine Kinase Domain

Chronic myeloid leukemia (CML) is caused by the kinase activity of the BCR-Abl fusion protein. The Abl inhibitors imatinib, nilotinib and dasatinib are currently used to treat CML, but resistance to these inhibitors is a significant clinical problem. The kinase inhibitor bosutinib has shown efficacy in clinical trials for imatinib-resistant CML, but its binding mode is unknown. We present the 2.4 Å structure of bosutinib bound to the kinase domain of Abl, which explains the inhibitor's activity against several imatinib-resistant mutants, and reveals that similar inhibitors that lack a nitrile moiety could be effective against the common T315I mutant. We also report that two distinct chemical compounds are currently being sold under the name “bosutinib”, and report spectroscopic and structural characterizations of both. We show that the fluorescence properties of these compounds allow inhibitor binding to be measured quantitatively, and that the infrared absorption of the nitrile group reveals a different electrostatic environment in the conserved ATP-binding sites of Abl and Src kinases. Exploiting such differences could lead to inhibitors with improved selectivity

Crystal Structures of ABL-Related Gene (ABL2) in Complex with Imatinib, Tozasertib (VX-680), and a Type I Inhibitor of the Triazole Carbothioamide Class†

ABL2 (also known as ARG (ABL related gene)) is closely related to the well-studied Abelson kinase cABL. ABL2 is involved in human neoplastic diseases and is deregulated in solid tumors. Oncogenic gene translocations occur in acute leukemia. So far no structural information for ABL2 has been reported. To elucidate structural determinants for inhibitor interaction, we determined the cocrystal structure of ABL2 with the oncology drug imatinib. Interestingly, imatinib not only interacted with the ATP binding site of the inactive kinase but was also bound to the regulatory myristate binding site. This structure may therefore serve as a tool for the development of allosteric ABL inhibitors. In addition, we determined the structures of ABL2 in complex with VX-680 and with an ATP-mimetic type I inhibitor, which revealed an interesting position of the DFG motif intermediate between active and inactive conformations, that may also serve as a template for future inhibitor design

P-loop mutations and novel therapeutic approaches for imatinib failures in chronic myeloid leukemia

Imatinib was the first BCR-ABL-targeted agent approved for the treatment of patients with chronic myeloid leukemia (CML) and confers significant benefit for most patients; however, a substantial number of patients are either initially refractory or develop resistance. Point mutations within the ABL kinase domain of the BCR-ABL fusion protein are a major underlying cause of resistance. Of the known imatinib-resistant mutations, the most frequently occurring involve the ATP-binding loop (P-loop). In vitro evidence has suggested that these mutations are more oncogenic with respect to other mutations and wild type BCR-ABL. Dasatinib and nilotinib have been approved for second-line treatment of patients with CML who demonstrate resistance (or intolerance) to imatinib. Both agents have marked activity in patients resistant to imatinib; however, they have differential activity against certain mutations, including those of the P-loop. Data from clinical trials suggest that dasatinib may be more effective vs. nilotinib for treating patients harboring P-loop mutations. Other mutations that are differentially sensitive to the second-line tyrosine kinase inhibitors (TKIs) include F317L and F359I/V, which are more sensitive to nilotinib and dasatinib, respectively. P-loop status in patients with CML and the potency of TKIs against P-loop mutations are key determinants for prognosis and response to treatment. This communication reviews the clinical importance of P-loop mutations and the efficacy of the currently available TKIs against them