Shear effects in lateral piezoresponse force microscopy at 180∘^\circ ferroelectric domain walls

In studies using piezoresponse force microscopy, we observe a non-zero lateral piezoresponse at 180$^\circ$ domain walls in out-of-plane polarized, c-axis-oriented tetragonal ferroelectric Pb(Zr$_{0.2}$Ti$_{0.8}$)O$_3$ epitaxial thin films. We attribute these observations to a shear strain effect linked to the sign change of the $d_{33}$ piezoelectric coefficient through the domain wall, in agreement with theoretical predictions. We show that in monoclinically distorted tetragonal BiFeO$_3$ films, this effect is superimposed on the lateral piezoresponse due to actual in-plane polarization, and has to be taken into account in order to correctly interpret the ferroelectric domain configuration.Comment: 4 pages, 3 figure

The CHK1 inhibitor MU380 significantly increases the sensitivity of human docetaxel-resistant prostate cancer cells to gemcitabine through the induction of mitotic catastrophe.

As treatment options for patients with incurable metastatic castration-resistant prostate cancer (mCRPC) are considerably limited, novel effective therapeutic options are needed. Checkpoint kinase 1 (CHK1) is a highly conserved protein kinase implicated in the DNA damage response (DDR) pathway that prevents the accumulation of DNA damage and controls regular genome duplication. CHK1 has been associated with prostate cancer (PCa) induction, progression, and lethality; hence, CHK1 inhibitors SCH900776 (also known as MK-8776) and the more effective SCH900776 analog MU380 may have clinical applications in the therapy of PCa. Synergistic induction of DNA damage with CHK1 inhibition represents a promising therapeutic approach that has been tested in many types of malignancies, but not in chemoresistant mCRPC. Here, we report that such therapeutic approach may be exploited using the synergistic action of the antimetabolite gemcitabine (GEM) and CHK1 inhibitors SCH900776 and MU380 in docetaxel-resistant (DR) mCRPC. Given the results, both CHK1 inhibitors significantly potentiated the sensitivity to GEM in a panel of chemo-naïve and matched DR PCa cell lines under 2D conditions. MU380 exhibited a stronger synergistic effect with GEM than clinical candidate SCH900776. MU380 alone or in combination with GEM significantly reduced spheroid size and increased apoptosis in all patient-derived xenograft 3D cultures, with a higher impact in DR models. Combined treatment induced premature mitosis from G1 phase resulting in the mitotic catastrophe as a prestage of apoptosis. Finally, treatment by MU380 alone, or in combination with GEM, significantly inhibited tumor growth of both PC339-DOC and PC346C-DOC xenograft models in mice. Taken together, our data suggest that metabolically robust and selective CHK1 inhibitor MU380 can bypass docetaxel resistance and improve the effectiveness of GEM in DR mCRPC models. This approach might allow for dose reduction of GEM and thereby minimize undesired toxicity and may represent a therapeutic option for patients with incurable DR mCRPC

Combining half-metals and multiferroics into epitaxial heterostructures for spintronics

We report on the growth of epitaxial bilayers of the La2/3Sr1/3MnO3 (LSMO) half-metallic ferromagnet and the BiFeO3 (BFO) multiferroic, on SrTiO3(001) by pulsed laser deposition. The growth mode of both layers is two-dimensional, which results in unit-cell smooth surfaces. We show that both materials keep their properties inside the heterostructures, i.e. the LSMO layer (11 nm thick) is ferromagnetic with a Curie temperature of ~330K, while the BFO films shows ferroelectricity down to very low thicknesses (5 nm). Conductive-tip atomic force microscope mappings of BFO/LSMO bilayers for different BFO thicknesses reveal a high and homogeneous resistive state for the BFO film that can thus be used as a ferroelectric tunnel barrier in tunnel junctions based on a half-metal

Observation of flat Γ\Gamma moir\'e bands in twisted bilayer WSe2_2

The recent observation of correlated phases in transition metal dichalcogenide moir\'e systems at integer and fractional filling promises new insight into metal-insulator transitions and the unusual states of matter that can emerge near such transitions. Here, we combine real- and momentum-space mapping techniques to study moir\'e superlattice effects in 57.4$^{\circ}$ twisted WSe$_2$ (tWSe$_2$). Our data reveal a split-off flat band that derives from the monolayer $\Gamma$ states. Using advanced data analysis, we directly quantify the moir\'e potential from our data. We further demonstrate that the global valence band maximum in tWSe$_2$ is close in energy to this flat band but derives from the monolayer K-states which show weaker superlattice effects. These results constrain theoretical models and open the perspective that $\Gamma$-valley flat bands might be involved in the correlated physics of twisted WSe$_2$

The CHK1 inhibitor MU380 significantly increases the sensitivity of human docetaxel-resistant prostate cancer cells to gemcitabine through the induction of mitotic catastrophe

As treatment options for patients with incurable metastatic castration-resistant prostate cancer (mCRPC) are considerably limited, novel effective therapeutic options are needed. Checkpoint kinase 1 (CHK1) is a highly conserved protein kinase implicated in the DNA damage response (DDR) pathway that prevents the accumulation of DNA damage and controls regular genome duplication. CHK1 has been associated with prostate cancer (PCa) induction, progression, and lethality; hence, CHK1 inhibitors SCH900776 (also known as MK-8776) and the more effective SCH900776 analog MU380 may have clinical applications in the therapy of PCa. Synergistic induction of DNA damage with CHK1 inhibition represents a promising therapeutic approach that has been tested in many types of malignancies, but not in chemoresistant mCRPC. Here, we report that such therapeutic approach may be exploited using the synergistic action of the antimetabolite gemcitabine (GEM) and CHK1 inhibitors SCH900776 and MU380 in docetaxel-resistant (DR) mCRPC. Given the results, both CHK1 inhibitors significantly potentiated the sensitivity to GEM in a panel of chemo-naïve and matched DR PCa cell lines under 2D conditions. MU380 exhibited a stronger synergistic effect with GEM than clinical candidate SCH900776. MU380 alone or in combination with GEM significantly reduced spheroid size and increased apoptosis in all patient-derived xenograft 3D cultures, with a higher impact in DR models. Combined treatment induced premature mitosis from G1 phase resulting in the mitotic catastrophe as a prestage of apoptosis. Finally, treatment by MU380 alone, or in combination with GEM, significantly inhibited tumor growth of both PC339-DOC and PC346C-DOC xenograft models in mice. Taken together, our data suggest that metabolically robust and selective CHK1 inhibitor MU380 can bypass docetaxel resistance and improve the effectiveness of GEM in DR mCRPC models. This approach might allow for dose reduction of GEM and thereby minimize undesired toxicity and may represent a therapeutic o

In silico design of novel probes for the atypical opioid receptor MRGPRX2

The primate-exclusive MRGPRX2 G protein-coupled receptor (GPCR) has been suggested to modulate pain and itch. Despite putative peptide and small molecule MRGPRX2 agonists, selective nanomolar potency probes have not yet been reported. To identify a MRGPRX2 probe, we first screened 5,695 small molecules and found many opioid compounds activated MRGPRX2, including (−)- and (+)-morphine, hydrocodone, sinomenine, dextromethorphan and the prodynorphin-derived peptides, dynorphin A, dynorphin B, and α- and β-neoendorphin. We used these to select for mutagenesis-validated homology models and docked almost 4 million small molecules. From this docking, we predicted ZINC-3573, which represents a potent MRGPRX2-selective agonist, showing little activity against 315 other GPCRs and 97 representative kinases, and an essentially inactive enantiomer. ZINC-3573 activates endogenous MRGPRX2 in a human mast cell line inducing degranulation and calcium release. MRGPRX2 is a unique atypical opioid-like receptor important for modulating mast cell degranulation, which can now be specifically modulated with ZINC-3573

Preliminary results of a study on the orp type sewage treatment plant

W pracy przedstawiono wyniki badań składu wód gruntowych pod oczyszczalnią glebowo-roślinną z płytkim, zasilanym okresowo, drenażem rozsączającym w fazie rozruchu technologicznego i w jej pobliżu. Stwierdzono brak negatywnego wpływu eksploatacji obiektu na skład wód gruntowych, mimo że zalegały one stosunkowo płytko. Nastąpiło znaczne zwiększenie przewodnictwa właściwego, co może być wynikiem zasilania warstwy wodonośnej mineralnymi formami zanieczyszczeń, np. siarczanami. Przeprowadzone badania potwierdzają celowość cyklicznego zasilania drenażu, co znacznie poprawia warunki tlenowe i umożliwia wysoki stopień oczyszczania ścieków, a tym samym zminimalizowanie zagrożenia dla wód gruntowych pod obiektem i w jego otoczeniu.This work presents the results of analyses of ground waters under and near the plant-soil sewage treatment facility with shallow, periodically fed infiltration drainage in its technological start phase. No negative influence was found of the object exploitation on the composition of ground waters though the latter were relatively shallow. Considerable increase of specific conductance found in waters could result from feeding the water-bearing layer with mineral pollutants like e.g. sulphates. Performed studies confirm the purposefulness of periodical drainage feeding which markedly improved aeration and enhanced the efficiency of sewage purification and thus minimized the risk for ground waters under and near the object

Sklad chemiczny wod gruntowych na obiektach nawadnianych sciekami przemyslowymi

W pracy przedstawiono wyniki badań składu chemicznego wód gruntowych na obiektach nawadnianych ściekami z cukrowni i drożdżowni. Ścieki z cukrowni, po podczyszczeniu w zbiorniku akumulacyjnym, rozdeszczowywane były na użytkach zielonych. Ścieki z drożdżowni, po rozcieńczeniu wodą, rozdeszczowywane były na gruntach ornych. Oba obiekty nawadniane ściekami pełnią funkcję naturalnych oczyszczalni glebowo-roślinnych. Stan czystości badanych wód gruntowych porównany był z jakością wód spoza terenów oczyszczania ścieków (tła obiektów) oraz z wartościami nieformalnej klasyfikacji jakości wód podziemnych. Z porównania wynika, że oczyszczanie ścieków w warunkach naturalnych nie stwarza zagrożenia zanieczyszczenia wód gruntowych związkami biogennymi. Istotnie wyższe wartości w stosunku do wód w tle wykazywał tylko N-NO₃, jednak jego ilości odpowiadały umownym wartościom z Ib i II klasy jakości wód podziemnych. Wpływ eksploatacji obu obiektów na stan czystości wód gruntowych odzwierciedlały jedynie stężenia potasu, które istotnie wyższe były w wodach na obiektach niż w tle i w obu przypadkach przekraczały umowne wartości z klasyfikacji jakości wód podziemnych.Paper presents the results of investigations on chemical composition of ground waters on the objects irrigated with wastewater from sugar and yeast factories. Wastewater from sugar factory was pre-treated in a storage tank before it was sprinkle-irrigated on the grassland. Wastewater from the yeast factory was diluted with water before it was sprinkle-irrigated on the arable land. Both objects irrigated with the wastewater functioned as natural soil-vegetation waste-water treatment plants. The purity of tested ground water was compared with the quality of water from outside of wastewater treatment areas (objects’ background) as well as with the values of informal underground water quality classification. The comparison showed that the treatment of wastewater in natural environment did not cause any risk of ground water pollution with biogenic compounds. The significantly higher, in relation to waters in the background, was only N-NO₃ concentration, however, these values corresponded with conventional values for lb and II ground water quality classes. An impact of both treatment objects on the purity of ground waters showed only potassium concentrations - significantly higher than in the background and exceeding in both cases the conventional classification values of underground water quality

Odplyw zanieczyszczen z mikrozlewni rolniczej polozonej na Przedgorzu Sudeckim

Zastosowanie systematycznego drenowania w warunkach górskich w znaczący sposób zwiększa ilość wody odprowadzanej z mikrozlewni rolniczej. Ze względu na znaczne stężenia azotu i fosforu w wodach odprowadzanych z tej zlewni istnieje niebezpieczeństwo okresowego (luty - marzec) pogorszenia jakości wody w ciekach. W celu ograniczenia odpływu zanieczyszczeń należy rozważyć możliwość retencjonowania wody odprowadzanej z górnej części, bądź ograniczenia intensywności odwodnienia poprzez zastosowanie drenowania niesystematycznego.An application of systematic pipe drainage in the mountain regions increases the runoffs from agricultural catchment. There is danger of periodic water quality deterioration (February - March) in watercourses owing to high nitrogen and phosphorus concentrations in these runoffs. It should be considered the possibility of runoff water retention from the upper part of catchment or limitation of the drainage rate by use of unsystematic piping arrangement in order to reduce the pollution runoff