Mixed Oxides as Successful Sorption Materials for Some Active Pharmaceutical Ingredients

Mixed oxides based on Mg-Al, Mg-Fe, Zn-Al, and Ni-Mg-Al were prepared, characterized and used as sorption materials for different types of active pharmaceutical ingredients (APIs)– nicotinic acid, salicylic acid, ibuprofen, paracetamol and ascorbic acid. Immobilization of APIs on solid supports was confirmed using X-Ray diffraction and infrared spectroscopy. Overall, the best sorption material for mentioned substances showed to be mixed Mg-Al oxides (>80 % of immobilized substance after 4 h except ascorbic acid). On the other hand, Mg-Fe and Mg-Ni-Al materials did not possess high sorption capacity (max. 59 % after 4 h). From studied substances, the immobilization amount was the lowest in the case of ascorbic acid (max. 44 % immobilized after 4 h), the highest amount was immobilized in the case of salicylic and nicotinic acids (>95 %, 4 h). The discussion regarding the structure of substances and properties of sorption materials is also offered. This work is licensed under a Creative Commons Attribution 4.0 International License

Quantitative insights into the cyanobacterial cell economy

© Zavřel et al. Phototrophic microorganisms are promising resources for green biotechnology. Compared to heterotrophic microorganisms, however, the cellular economy of phototrophic growth is still insufficiently understood. We provide a quantitative analysis of light-limited, light-saturated, and light-inhibited growth of the cyanobacterium Synechocystis sp. PCC 6803 using a reproducible cultivation setup. We report key physiological parameters, including growth rate, cell size, and photosynthetic activity over a wide range of light intensities. Intracellular proteins were quantified to monitor proteome allocation as a function of growth rate. Among other physiological acclimations, we identify an upregulation of the translational machinery and downregulation of light harvesting components with increasing light intensity and growth rate. The resulting growth laws are discussed in the context of a coarse-grained model of phototrophic growth and available data obtained by a comprehensive literature search. Our insights into quantitative aspects of cyanobacterial acclimations to different growth rates have implications to understand and optimize photosynthetic productivity

Effects of a red card on goal-scoring in World Cup football matches

We examine the effect of the sending-off of a player on the goal-scoring rates in FIFA World Cup matches in tournaments from 1998 to 2014. We use a hazard rate framework in which the effect of a red card is modeled as a shift in the goal-scoring rate. A red card may harm the team that receives a red card and may be beneficial for their opponent. Indeed, we find that the goal-scoring rate of the sanctioned team goes down, while the goal-scoring rate of the non-sanctioned team goes up

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

Optimum and standard beam widths for numerical modeling of interface scattering problems

Author Posting. © Acoustical Society of America, 2000. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 107 (2000): 1095-1102, doi:10.1121/1.428399.Gaussian beams provide a useful insonifying field for surface or interface scattering problems such as encountered in electromagnetics, acoustics and seismology. Gaussian beams have these advantages: (i) They give a finite size for the scattering region on the interface. (ii) The incident energy is restricted to a small range of grazing angles. (iii) They do not have side lobes. (iv) They have a convenient mathematical expression. The major disadvantages are: (i) Insonification of an interface is nonuniform. The scattered field will depend on the location of the scatterers within the beam. (ii) The beams spread, so that propagation becomes an integral component of the scattering problem. A standard beam parameterization is proposed which keeps propagation effects uniform among various models so that the effects of scattering only can be compared. In continuous wave problems, for a given angle of incidence and incident amplitude threshold, there will be an optimum Gaussian beam which keeps the insonified area as small as possible. For numerical solutions of pulse beams, these standard parameters provide an estimate of the smallest truncated domain necessary for a physically meaningful result.This work was carried out under Office of Naval Research Grant Nos. N00014-90-I-1493, N00014-96-1-0460, and N00014-95-1-0506 and under a Mellon Independent Study Award from Woods Hole Oceanographic Institution

Electron & Biomass Dynamics of Cyanothece Under Interacting Nitrogen & Carbon Limitations

Marine diazotrophs are a diverse group with key roles in biogeochemical fluxes linked to primary productivity. The unicellular, diazotrophic cyanobacterium Cyanothece is widely found in coastal, subtropical oceans. We analyze the consequences of diazotrophy on growth efficiency, compared to NO3–-supported growth in Cyanothece, to understand how cells cope with N2-fixation when they also have to face carbon limitation, which may transiently affect populations in coastal environments or during blooms of phytoplankton communities. When grown in obligate diazotrophy, cells face the double burden of a more ATP-demanding N-acquisition mode and additional metabolic losses imposed by the transient storage of reducing potential as carbohydrate, compared to a hypothetical N2 assimilation directly driven by photosynthetic electron transport. Further, this energetic burden imposed by N2-fixation could not be alleviated, despite the high irradiance level within the cultures, because photosynthesis was limited by the availability of dissolved inorganic carbon (DIC), and possibly by a constrained capacity for carbon storage. DIC limitation exacerbates the costs on growth imposed by nitrogen fixation. Therefore, the competitive efficiency of diazotrophs could be hindered in areas with insufficient renewal of dissolved gases and/or with intense phytoplankton biomass that both decrease available light energy and draw the DIC level down

Human disturbance is the most limiting factor driving habitat selection of a large carnivore throughout Continental Europe

Habitat selection is a multi-scale process driven by trade-offs between benefits, such as resource abundance, and disadvantages, such as the avoidance of risk. The latter includes human disturbances, to which large carnivores, with their large spatial requirements, are especially sensitive. We investigated the ecological processes underlying multi-scale habitat selection of a large carnivore, namely Eurasian lynx, across European landscapes characterized by different levels of human modification. Using a unique dataset of 125 lynx from 9 study sites across Europe, we compared used and available locations within landscape and home-range scales using a novel Mixed Effect randomForest approach, while considering environmental predictors as proxies for human disturbances and environmental resources. At the landscape scale, lynx avoided roads and human settlements, while at the home-range scale natural landscape features associated with shelter and prey abundance were more important. The results showed sex was of relatively low variable importance for lynx's general habitat selection behaviour. We found increasingly homogeneous responses across study sites with finer selection scales, suggesting that study site differences determined coarse selection, while utilization of resources at the finer selection scale was broadly universal. Thereby describing lynx's requirement, if not preference, for heterogeneous forests and shelter from human disturbances and implying that regional differences in coarse-scale selection are driven by availability rather than preference. These results provide crucial information for conserving this species in human-dominated landscapes, as well as for the first time, to our knowledge, generalising habitat selection behaviour of a large carnivore species at a continental scale.acceptedVersio

Increasing Incidence of Geomyces destructans Fungus in Bats from the Czech Republic and Slovakia

BACKGROUND: White-nose syndrome is a disease of hibernating insectivorous bats associated with the fungus Geomyces destructans. It first appeared in North America in 2006, where over a million bats died since then. In Europe, G. destructans was first identified in France in 2009. Its distribution, infection dynamics, and effects on hibernating bats in Europe are largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: We screened hibernacula in the Czech Republic and Slovakia for the presence of the fungus during the winter seasons of 2008/2009 and 2009/2010. In winter 2009/2010, we found infected bats in 76 out of 98 surveyed sites, in which the majority had been previously negative. A photographic record of over 6000 hibernating bats, taken since 1994, revealed bats with fungal growths since 1995; however, the incidence of such bats increased in Myotis myotis from 2% in 2007 to 14% by 2010. Microscopic, cultivation and molecular genetic evaluations confirmed the identity of the recently sampled fungus as G. destructans, and demonstrated its continuous distribution in the studied area. At the end of the hibernation season we recorded pathologic changes in the skin of the affected bats, from which the fungus was isolated. We registered no mass mortality caused by the fungus, and the recorded population decline in the last two years of the most affected species, M. myotis, is within the population trend prediction interval. CONCLUSIONS/SIGNIFICANCE: G. destructans was found to be widespread in the Czech Republic and Slovakia, with an epizootic incidence in bats during the most recent years. Further development of the situation urgently requires a detailed pan-European monitoring scheme

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