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Nuclear spin-induced circular dichroism (NSCD) is a molecular effect of differential absorption of left- and right-circularly polarized light due to nuclear spins in the molecule. In this work, new tools for its calculation are presented. Analytic expressions for the computation of the B_K term of NSCD have been derived and implemented for the second-order coupled cluster singles and doubles (CC2) model. NSCD results obtained thereby for three derivatives of azobenzenes have been compared with results from time-dependent density functional theory (TD-DFT). The complementary information that could be obtained from NSCD measurements compared to NMR for these three species is discussed.

While much effort has been devoted to analyzing long-term changes of temperature and precipitation in mean values and extremes, studies on changes in variability have been rather scarce. Trends in variability are, however, important, among others because their interaction with trends in mean values determines the degree with which extremes would change. The knowledge of long-term changes in temporal variability is essential for assessments of climate change impacts on various sectors, including hydrology (floods and droughts), agriculture, health, and energy demand and production.SPAGETTA is a stochastic spatial daily weather generator (WG), which uses first-order multivariate (dimension = number of variables X number of gridpoints) autoregressive model to represent the spatial and temporal variability of surface weather variables (including precipitation and temperature). We consider the generator to be a suitable tool for assessing changes in the spatial and temporal variability of the weather series because of following reasons: (A) The inter-gridpoint lag-0 and lag-1(day) correlations included in a set of WG parameters may serve as representatives for spatial and temporal variability of input weather variables. (B) Statistical significance of changes in the lag-0 and lag-1 correlations derived from the input series may be easily assessed by comparing the changes with a variability of the lag-0 and lag-1 correlations related to the stochasticity in input weather series (the variability is assessed across a set of multiple realisations of the synthetic series). (C) Separate effects of changes in various statistical characteristics on any climatic characteristic may be easily assessed. Specifically, having analysed changes in the means, variability and inter-gridpoint correlations (e.g. based on RCM simulations of the future climate), we may modify only a selected (possibly only a single one) WG parameter(s) before producing the synthetic series and analysing effect of climate change on the climatic characteristics.In the first part of the contribution, we employ SPAGETTA generator to analyse changes in interdiurnal variability of precipitation and temperature in 8 European regions (defined in Dubrovsky et al 2020, Theor Appl Climatol) using (a) gridded observational (last N years vs. first N years in available E-OBS times series) and (b) RCM-simulated surface weather series (2070-2099 vs 1971-2000; outputs from 19 RCMs available from the CORDEX database are analysed). In doing this, we assess the statistical significance of the detected changes. In the second part, we assess separate effects of changes in the means, variability and lag-0 & lag-1 correlations of temperature and precipitation (the changes based on a set of 19 RCM simulations are used to modify the corresponding WG parameters) on a set of climatic indices - including a set of compound precipitation-temperature characteristics representing spells of days with spatially significant extent of significantly non-normal weather (e.g. hot-dry spells).

Long range forecasts provide information about expected future atmospheric and oceanic conditions averaged over periods of one to three months and are attractive for many sectors. They have made considerable progress in recent years, but seasonal predictability remains a problem in many regions (for example in Europe). Demand is also for long range forecasts, which would predict shorter periods than months (for example 3 decades in each month).This study considers four seasonal forecasting systems available in the Copernicus Climate Change Service (C3S) archive which provide near-surface air temperature and precipitation data at 1°by 1°spatial resolution: European Centre for Medium-range Weather Forecast System SEAS5 (ECMWF), Météo – France System 8 (MF), Deutscher Wetterdienst GCFS 2.1 (DWD) and Centro Euro-Mediterraneo sui Cambiamenti Climatici SPSv3.5 (CMCC). It quantifies their value in predicting temperature and precipitation at monthly and shorter (3 decades in each month) temporal resolution over Europe. There are two starting dates, May 1st, and November 1st, and forecasts at lead times up to 3 months for each year in the period 1993–2016 (the longest period of hindcasts common to all systems).We focus on 2 domains: larger (Europe, latitude 42-55°N, longitude 2-30°E) and smaller (the Czech Republic, latitude 47-52°N, longitude 11-20°E). E-OBS daily gridded observational datasets for precipitation and temperature at 0.25°spatial resolution are used as a reference.Several statistical measures such as mean bias and root mean square error are presented for temperature and precipitation at a monthly and shorter (3 decades in each month) temporal resolution over Europe and for the Czech Republic.

The ECA&D data-set collects over 81000 series of observations for the Essential Climate Variables more than 22400 stations from all countries in Europe. Large number of these series are affected by outliers, repeated values and other issues in the measurements. These quality issues need to be identified prior to further processing of the data into e.g. the production of the gridded E-OBS datasets as these issues may lead to erroneous estimates of climate impact indices and trends. In the context of the Copernicus contract C3S2_311 Lot3, the MetQC method developed at GCRI has been implemented for operational use at ECA&D. This new method combines checks on duplicate series, repetitive values and outliers with an inter-stations comparison. Earlier work compared five different quality check methods (MetQC, MASH, ACMANT, NOAA, C3QC) on four benchmark data-sets covered by ECA&D. This work indicated that the MetQC approach performed well in comparison against the other methods and the new method replaces the more primitive approach at ECA&D in which straightforward stand-alone tests were conducted. A strong aspect of the MetQC method is that it provides an estimate for an alternative value of a suspect value based on values of surrounding stations, with a quantification of the reliability of this alternative. The MetQC method has been further refined and tailored to the application at ECA&D to be capable of handling the vast dataset in a reasonable time. The presentation will focus on the improvement in quality for ECA&D and comparisons in terms of numbers of flagged data and given between the new approach and the approach it replaces.

The synthesis of defined triphilic terpolymers with hydrophilic, lyophilic, and fluorophilic blocks is an important challenge as a basis for the development of multicompartment self-assembled structures with potential for, e.g., cascade catalysis and multidrug loading. The synthesis of fluorophilic poly(2-oxazoline)s generally suffers from a very low reactivity of fluorinated 2-oxazoline monomers in cationic ring-opening polymerization (CROP). We report a systematic study on overcoming the extremely low reactivity of 2-perfluoroalkyl-2-oxazolines in CROP by the insertion of methyl and ethyl hydrocarbon spacers between the 2-oxazoline ring and the trifluoromethyl group. The kinetic studies showed the gradual increase of the rate of polymerization with increasing of the hydrocarbon spacer length. The monomer with an ethyl spacer was found to have similar reactivity as 2-alkyl-2-oxazolines and allowed the synthesis of defined triphilic triblock copolymers.

Stochastic weather generators (WGs) are tools for producing weather series, mimicking statistical properties of their real-world counterparts. They are often used in climate change impact experiments as a source of the data representing the present and/or future climates (alternative to RCMs and GCMs). Development of our SPAGETTA generator started in 2016 (Dubrovsky et al 2020; https://doi.org/10.1007/s00704-019-03027-z). The presentation will focus on (A) Basic details. (B) Functionalities of the generator. (C) Results obtained with the generator by now. (D) Most critical problems, which were met (and not yet satisfactorily solved) while making the generator fully operational.A. SPAGETTA is a multivariate multisite parametric generator, which is based on autoregressive modeling (following the D. Wilks’ papers). It is designed mainly (but not solely) for use in agricultural and hydrological modeling. It may produce time series of up to 8 variables for as many as (approx.) 200 stations or grid points. Typically, it produces time series of temperature, precipitation, solar radiation, humidity and wind speed. It usually runs with a daily time step.B. The main functionalities include: (1) It may produce arbitrarily long time series representing the climate defined by the data used for calibrating the generator (might be observational data or, for example, RCM outputs). (2) Having modified the WG parameters by the climate change scenario (typically derived from GCM or RCM simulations), SPAGETTA may produce weather series representing the future climate. In this case, one may study sensitivity of selected climatic indices to changes in various statistics (e.g. means and standard deviations of weather variables, and characteristics of temporal and spatial structure of the time series). (3) SPAGETTA may be interpolated so that it can produce weather series for sites with no observational data. (4) It can be linked with the circulation generator so that WG may better represent larger-scale (both in space and time) weather variability.C. The results obtained with the generator by now include: (a) Validation of the generator in terms of WG parameters, various climatic indices, and outputs of hydrological model fed by the synthetic series produced by SPAGETTA. (b) Impacts of the forthcoming climate change on various climatic characteristics (RCM-based climate change scenarios were used here). Focus was put on spatial temperature-precipitation compound characteristics. (c) Validation of the interpolated generator. (d) Validation of the generator driven by the larger scale circulation generator.D. Problems to be solved: (i) Under some circumstances (especially when a large number of the stations is used, or while interpolating the generator), matrices of the AR model imply unstable AR process which diverges to unrealistic values of weather variables. (ii) The generator underestimates the low frequency variability. Development of the larger scale circulation generator, which would eliminate this drawback, is still under development.Only examples of the previous points will be shown in the presentation.

Geodesy Observatory Pecný (GOP) analysis center is one of the International DORIS Service (IDS) analysis centers. GOP fully contributed to the IDS combination of the ITRF2020, reaching various improvements in comparison to the ITRF2014 reprocessing. GOP also participates in the IDS operational solutions. A major progress has been reached in the data preprocessing strategy, South Atlantic Anomaly mitigation and satellite orbit & attitude modeling. improvements in the internal strategy together with an updating of external models to the recent standards resulted in the significant improvement in the station positioning including of the stability of the transformation parameter time series. Also the pole coordinates estimation accuracy has been increased. This improvement is illustrated comparing the statistics of GOP contributions to the IDS combination for the ITRF2014 and ITRF2020. Important improvement in the GOP processing capability is the adaption of the software tools to the RINEX data processing, getting closer to raw DORIS measurement. In addition, we present initial results of the data processing and a modeling verification for the post-ITRF2020 data from the DORIS satellites Sentinel-6A, HY-2C and HY-2D.

The static and dynamic properties of a range of molecular weights (2 × 104 to 1.6 × 105 g/mol) of poly(benzyl methacrylate) have been assessed in four different imidazolium- and pyrrolidinium-based...

The unavailability of housing in the Czech and Slovak Republics is a fundamental problem, which is a consequence of many social, economic, political, and behavioural or historical aspects. The housing affordability deficit has the character of a systemic market failure, which is - paradoxically - linked to the growth of prosperity and resulting from the dual nature of the object (housing) in question - it is both an investment product and a de facto mandatory social need. It is an indicated market failure that justifies state intervention and public support. The housing problem no longer affects only the socially disadvantaged and the middle-income groups. Unfortunately, the deficit of housing affordability has a fatal impact on the competitiveness of cities and regions and its social cohesion and environmental and economic sustainability.

Iron and copper are essential micronutrients needed for the proper function of every cell. However, in excessive amounts, these elements are toxic, as they may cause oxidative stress, resulting in damage to the liver and other organs. This may happen due to poisoning, as a side effect of thalassemia infusion therapy or due to hereditary diseases hemochromatosis or Wilson’s disease. The current golden standard of therapy of iron and copper overload is the use of low-molecular-weight chelators of these elements. However, these agents suffer from severe side effects, are often expensive and possess unfavorable pharmacokinetics, thus limiting the usability of such therapy. The emerging concepts are polymer-supported iron- and copper-chelating therapeutics, either for parenteral or oral use, which shows vivid potential to keep the therapeutic efficacy of low-molecular-weight agents, while avoiding their drawbacks, especially their side effects. Critical evaluation of this new perspective polymer approach is the purpose of this review article.

Stochastic weather generators (WGs) are tools for producing weather series, which are statistically similar to the real world weather series. The synthetic series may represent both present and changed (not only the future) climate. In the latter case, WG parameters derived from the observed weather series are modified with climate change scenario, which is typically based on RCM or GCM simulations. As the GCM/RCM simulations are very demanding on computer resources, the numbers of simulations made for individual possible emission scenarios are limited, especially for some (mostly the less probable ones) emission scenarios (e.g. RCP 2.6). Still, many climate change impact studies try to give projections of the CC impacts assuming uncertainties coming from all possible sources, including the modeling uncertainty and uncertainties in emissions & climate sensitivity. To allow generation of weather series fitting the projection of any GCM forced by any emission scenario, we use a pattern scaling approach, in which the standardized climate change scenario (consisting of changes in climatic characteristic related to 1ºC change in global mean temperature) derived from a given GCM is multiplied by a change in global mean temperature (dTg) projected (for a selected emission scenario and climate sensitivity) by a simple climate model MAGICC.In our contribution, we will demonstrate the use of the generator (using SPAGETTA WG, which is our multi-site multi-variate parametric daily WG) in probabilistic projection of future changes in selected climatic characteristics of temperature (T) and precipitation (P); we will focus on spatial hot/cold/dry/wet/hot-dry/hot-wet/cold-dry/cold-wet spells). Standardized climate change scenarios will be derived from multiple GCMs (taken from CMIP5 database) and scaled by dTg projected by MAGICC. Effects of the three above-named sources of uncertainty, as well as the effects of changes in individual statistical characteristics (the means & the site-specific variabilities & the characteristics of the temporal and spatial variability of both T and P) will be assessed.Acknowledgements: Projects GRIMASA (Czech Science Foundation, project no. 18-15958S) and SustES (European Structural and Investment Funds, project no. CZ.02.1.01/0.0/0.0/16_019/0000797).

The PannEx is a GEWEX-initiated, community driven research network in the Pannonian Basin. One of the main scientific issues to address in PannEx is the investigation of precipitation extremes. Meteorological Services in the PannEx area collected the hourly precipitation data and commonly used a computer program, which was developed in the INTENSE project, to produce a set of global hydro-climatic indices. Calculations are carried out on data aggregated 1-, 3- and 6-h intervals. Selected indices are analyzed in this paper to assess the general climatology of the short-term precipitation in the Pannonian basin. The following indices are illustrated on maps and graphs: the annual mean and maxima of 1-h, 3-h and 6-h sums, the count of 3-hr periods greater than 20 mm thresholds, the maximum length of wet hours, the timing of wettest hour and the 1-h precipitation intensity. The seasonal trends of the 1-h precipitation intensity were tested from 1998 to 2019. Analysis of sub-daily precipitation has been limited by the availability of data on a global or a regional scale. The international effort made in this work through collaboration in the PannEx initiative contributes to enlarging the data availability for regional and global analysis of sub-daily precipitation extremes.

We report the controlled synthesis of polymer-stabilized silver nanoparticles (AgNPs) by using microfluidic devices. The microfluidic-based method enabled the preparation of sub-50 nm AgNPs which are much more homogenous compared to those produced in batch reactors where the control over flow and mixing conditions was not performed. The concentration of the silver precursor (silver nitrate - AgNO₃) can be tuned to reach smaller or larger nanoparticles, although within a fairly narrow range. Regardless of the polymeric shell, the reducing agent concentration influences the size and polydispersity of the manufactured silver colloids, and relatively lower amounts allow for the manufacturing of more homogeneous nanoparticles. Notably, the use of the block copolymer PEO-b-P2VP as stabilizing agent leads to larger nanoparticles (23–51 nm) compared to those stabilized by PVP (7–14 nm) as possibly linked to different arrangements of the polymer chains at the interface between the precursor solutions. The produced AgNPs are highly uniform, with size distribution width influenced by the polymer concentration (FWHM < 100 nm were determined at higher concentrations), although this variable does not have a distinguished effect on the final size of the manufactured colloids. Overall, we provide relevant new knowledge within the framework of polymer-stabilized AgNPs since a variety of other polymer chains can be probed, possibly with different outcomes regarding the final particle size. The reported findings can thus guide to significant advances towards the manufacturing of highly homogeneous polymer-coated metallic colloids, particularly when a target size is required.

Nanoparticles (NPs) represent an emerging platform for diagnosis and treatment of various diseases such as cancer, where they can take advantage of enhanced permeability and retention (EPR) effect for solid tumor accumulation. To improve their colloidal stability, prolong their blood circulation time and avoid premature entrapment into reticuloendothelial system, coating with hydrophilic biocompatible polymers is often essential. Most studies, however, employ just one type of coating polymer. The main purpose of this study is to head-to-head compare biological behavior of three leading polymers commonly used as &ldquo, stealth&rdquo, coating materials for biocompatibilization of NPs poly(ethylene oxide), poly(2-ethyl-2-oxazoline) and poly[N-(2-hydroxypropyl)methacrylamide] in an in vivo animal solid tumor model. We used radiolabeled biodegradable hydroxyapatite NPs as a model nanoparticle core within this study and we anchored the polymers to the NPs core by hydroxybisphosphonate end groups. The general suitability of polymers for coating of NPs intended for solid tumor accumulation is that poly(2-ethyl-2-oxazoline) and poly(ethylene oxide) gave comparably similar very good results, while poly[N-(2-hydroxypropyl)methacrylamide] was significantly worse. We did not observe a strong effect of molecular weight of the coating polymers on tumor and organ accumulation, blood circulation time, biodistribution and biodegradation of the NPs.

This C3S service provides various observational surface in-situ datasets for Europe. Its core builds on the European Climate Assessment and Dataset (ECA&D) and the gridded E-OBS daily datasets for Europe. The pan-European E-OBS datasets for temperature, precipitation and sea level pressure are now available as ensemble datasets. Additional gridded datasets for other Essential Climate Variables are developed, like global radiation, wind speed and relative humidity. Next to the pan-European datasets, regional datasets for the Nordic, Alpine and Carphatian regions are available.Climate monitoring products such as the indices defined by the Expert Team on Climate Change Detection and Indices (ETCCDI) areavailable. Within this service, uncertainty estimates are provided as well for the pan-European datasets and indices.All the information from these datasets and indices will flow into monthly State of the Climate reports which are available around the25th of the next month from the dedicated portal for this service. The annual State of the Climate reports are created more centrally withinC3S and this service provides input for that report as well.

A unique architecture of Sentinel-3A and Sentinel-3B satellites includes the shared ultra stable oscillator (USO) by DORIS and GPS receiver. This concept enables to apply GPS estimates of onboard clocks in DORIS processing and to substitute DORIS polynomial clock model by GPS epochwise model. Such an approach is particularly profitable for the mitigation of South Atlantic Anomaly effect (SAA), affecting the short-term frequency stability of USO oscillator in South America and South Atlantic region. GPS clock modeling precisely maps the SAA effect and enables us to demonstrate a difference between Sentinel-3A and Sentinel-3B USO sensitivity to SAA. Moreover, we present an impact on 3Dpositioning, where SAA-related bias reaches in extreme cases a decimeter level. We also determine an effect of the precise clock modeling on the Earth rotation parameters estimation. Elimination of SAA effect also gives us an opportunity to get an SAA free DORIS solution of Sentinel-3A and Sentinel-3Bsatellites. Using this solution as a reference, we estimate an SAA effect on the DORIS positioning by satellites Jason-2, Jason-3, Sentinel, Cryosat-2 and Hy-2A and the efficiency of SAA mitigation strategies for these satellites.

The lack of cellular and tissue specificities in conventional chemotherapies along with the generation of a complex tumor microenvironment (TME) limits the dosage of active agents that reaches tumor sites, thereby resulting in ineffective responses and side effects. Therefore, the development of selective TME-responsive nanomedicines is of due relevance toward successful chemotherapies, albeit challenging. In this framework, we have synthesized novel, ready-to-use ROS-responsive amphiphilic block copolymers (BCs) with two different spacer chemistry designs to connect a hydrophobic boronic ester-based ROS sensor to the polymer backbone. Hydrodynamic flow focusing nanoprecipitation microfluidics (MF) was used in the preparation of well-defined ROS-responsive PSs; these were further characterized by a combination of techniques [

This paper aims to determine the effect of various test configurations on the bond behaviour of sand-coated GFRP (Glass Fibre Reinforced Polymers) reinforcement embedded in concrete. The bond strength was tested using ordinary centric pull-out tests (by ACI 440.3), modified pull-out tests with eccentrically placed bars, and beam tests (following RILEM). The obtained results confirmed the effectiveness of the tested sand-coated surface treatment. However, a significant effect of the test configuration on the bond stress was observed. The thickness of the concrete cover layer also had a significant effect on bond strength.

This work focuses on the synthesis and self-assembly of triphilic poly(2-oxazoline) triblock copolymers with high fluorine content toward our future aim of developing poly(2-oxazoline) magnetic resonance imaging (MRI) contrast agents. A highly fluorinated 2-substituted-2-oxazoline monomer, namely 2-(1H,1H,2H,2H-perfluorooctyl)-2-oxazoline, was synthesized using the Grignard reaction. The polymerization kinetics of the synthesized monomer was studied, and it was used for the preparation of triblock copolymers with hydrophilic 2-methyl-2-oxazoline, hydrophobic 2-octyl-2-oxazoline, and fluorophilic blocks by cationic ring-opening polymerization yielding polymers with low relatively dispersity (1.21.4). The presence of the blocks with the different nature in one copolymer structure facilitated self-assembly of the copolymers in water and dimethyl sulfoxide as observed by dynamic light scattering, cryo-transmission electron microscopy, and small-angle neutron scattering. The nanoparticle morphology is strongly influenced by the order and length of each block and the nature of solvent, leading to nanoparticles with coreshell structure as confirmed by small-angle neutron scattering. The reported poly(2-oxazoline) block copolymers with high fluorine content have high potential for future development of MRI contrast agents.

The article deals with the two current problems of determining long-term strength of non-metallic reinforcement in concrete structures: degradation of GFRP reinforcement caused by alkaline environment and cyclic loading. The alkaline environment of concrete with a pH higher than 12.0 affects the glass fibres degradative, whereas this degradation presents by reduction of their mechanical characteristics, resulting in a decrease in the tensile strength of the whole composite. An experimental results of cyclic loading on fatigue life of GFRP bars are presented. The specimens of bare bars and bars encased in concrete were tested. At the tested stress levels, the concrete has a positive effect on the fatigue life of FRP due to confinement, which prevents the fibers from a broom-like failure mode. Two different S-N curves for bare and encased bars are described. At the tested stress levels, considerable matrix or matrix/fiber interface damage occurs at the beginning of the cyclic loading, whereas the fibres are likely to remain intact. Obtained results will allow to define the reliability coefficients for long term behavior of GFRP reinforcement more precisely. It will help to optimal design of GFRP reinforced concrete structures.

We show that mannan-based conjugates possess exceptional features for multimodal imaging because of their biocompatibility, biodegradability and self-targeting properties. Two new mannan conjugates, containing a gadolinium complex and a fluorescent probe, one based only on polysaccharide and the other one comprising polysaccharide with poly(2-methyl-2-oxazoline) grafts, were prepared and simultaneously visualized in vitro and in vivo by magnetic resonance and fluorescence imaging. The synthesis of these mannan-based complexes was based on alkylation with allyl bromide or grafting with poly(2-methyl-2-oxazoline) chains, followed by a thiol-ene click reaction with cysteamine to introduce primary amino groups into their structure. Finally, the obtained conjugates were functionalized with contrast labels using the corresponding N-hydroxysuccinimide esters. When used to detect lymph nodes, the polymers showed better imaging properties than a commercially available contrast agent.

The growth response of trees to changing climate is frequently discussed as increasing temperatures and more severe droughts become major risks for forest ecosystems. However, the ability of trees to cope with the changing climate and the effects of other environmental factors on climate-growth relationships are still poorly understood. There is thus an increasing need to understand the ability of individual trees to cope with changing climate in various environments. To improve the current understanding, a large tree-ring network covering the whole area of the Czech Republic (in 7 × 7 km grids) was utilized to investigate how the climate-growth relationships of Norway spruce are affected by 1) various geographical variables, 2) changing levels of acidic deposition, 3) soil characteristics and 4) age, tree diameter and neighbourhood competition. The period from 1930 to 2013 was divided into four, 21-year long intervals of differing levels of acidic deposition, which peaked in the 1972–1993 period. Our individual-based, spatiotemporal, multivariate analyses revealed that spruce growth was mostly affected by drought and warm summers. Drought plays the most important negative role at lower altitudes, while the positive effect of higher temperature was identified for trees at higher altitudes. Increased levels of acidic deposition, together with geographical variables, were identified as the most important factors affecting climate-growth association. Tree age, tree size and soil characteristics also significantly modulate climate-growth relationships. The importance of all environmental variables on climate-growth relationships was suppressed by acidic deposition during periods when this was at a high level; growth was significantly more enhanced by spring and summer temperatures during these periods. Our results suggest that spruce will undergo significant growth reduction under the predicted climate changes, especially at the lower altitudes which lie outside of its natural range.

Paper describes a testing procedure for the determination of tensile strength of the composite reinforcing bars subjected to elevated temperatures. Experimentally obtained results on GFRP bars with different diameter are presented and discussed. Moreover, a brief comparison with an analytical approach was included. Almost identical temperature reduction rate of tensile strength was observed for all tested specimens, regardless diameter of the bar. Therefore, it can be expected, that different bar diameter should not significantly affect the results especially if steady state conditions were assumed.

A series of well-defined methoxy-poly(ethylene glycol)-block-polylactic acid (mPEG-b-PLA) diblock copolymers were successfully synthesized, characterized and used for the construction of anticancer nanoparticle delivery system. Nanoparticles (NPs) based on these polymers were prepared by employing the nanoprecipitation method, and they were non-covalently loaded with curcumin, curcumin-bortezomib model or curcumin-bortezomib complex (curc-BTZ). Both curcumin and bortezomib are rather hydrophobic and poorly water-soluble potent anticancer drugs with synergic effects forming together a pH-sensitive complex, stable at pH of blood plasma, yet hydrolytically labile at mildly acidic milieu typical for endosomes and interstitial space in solid tumors. PEG-Curcumin-loaded and curc-BTZ-loaded NPs with 100–150 nm size showed the maximum cellular uptake by HeLa, MCF-7 and MDA-MB 231 cells after 3 h. The NPs were located in the cytoplasm of the cells but not inside the nucleus. Bare NPs did not induce any cytotoxicity in the same cell lines in in vitro experiments, even at very high concentrations (up to 800 µg/mL). NPs containing curcumin were cytotoxic with an IC50 of 25 µg/mL, which corresponds to 2.5 µg/mL of loaded curcumin. These results show that the efficacy of curcumin is significantly enhanced when using the NPs as carriers. The efficiency was further augmented through the complexation of BTZ with curcumin. When using free curc-BTZ-complex, MCF-7 cells were more sensitive to the free complex 18.8 nM (IC50) than MDA-MB-231 cells 122.4 nM (IC50). Nanoparticle formulations with these drugs caused significant cytotoxicity with 7.5 nM (IC50) and 59.2 nM (IC50) after 24 h of the treatment.

We report on the synthesis and solution properties of novel fluorine-containing copolymers. Our synthetic approach provides an easy way to attach a CnF2n+1 perfluorinated terminal chain to a poly(2-methyl-2-oxazoline)–block–poly(2-octyl-2-oxazoline) copolymer and to combine hydrophilic, hydrophobic and fluorophilic moieties into one segmented polymer. A series of such quasi-triblock copolymers was prepared with variation of the length of the fluorinated chain end. Using a variety of experimental methods including dynamic light scattering and transmission cryo-electron microscopy, we prove that all of the synthesized copolymers self-assemble into nanostructures in aqueous milieu. The structures and shapes of the nanostructures are controlled by the length of the perfluoroalkyl chain. Single-layer and multi-layer vesicles as well as rod-like micelles are observed in aqueous solutions. The supramolecular structures described represent a potential platform for 19F magnetic resonance imaging contrast agents.

The aim of this study was to develop biocompatible polyplex nanoparticles with physicochemical properties suitable for the delivery of photosensitizer temoporfin. We prepared, characterized, and compared the two types of polyplex nanoformulations consisting of sodium alginate in combination with chitosan polymer or chitosan oligomer lactate. We obtained the polyplex system by multiple electrostatic interactions between cationic chitosan and anionic alginate and identified key process parameters. Particle size distribution, dispersity, and zeta potential were determined by dynamic light scattering (DLS), and the diameter and the morphology of the individual particles were visualized by a transmission electron microscopy (TEM). It was found that size distribution of the polyplex nanoparticles depends on the concentrations of chitosan and alginate stock solutions and the order and ratio of addition of stock solutions as well as on the pH of the resulting mixture. It appears that the nanoparticles are homogeneous, although micrographs indicate some (vague, indistinct) core-shell structure. The nanoparticles are stable at pH 7.4 (pH of blood plasma) and show only very little drug leak in experiment modeling conditions of blood pool transport to target tissues.

Carbon nanospecies (CNPs) are of high interest in current research due to their many unique properties. They may be created by common processes, such as burning. Therefore, they can become potential contaminants and may have a negative impact on human health and the biosphere. Moreover, they may also catalyze protein misfolding and subsequent amyloid formation, which is extremely hard to treat. We investigated the influence of single-walled carbon nanotubes (SWNTs), fullerene (C60), carbon quantum dots (CDs) and nanodiamonds (NDs) on amyloid formation. This research utilized the hen egg-white lysozyme (HEWL) as a model system. Fibrils were detected by fluorescence of thioflavin-T (ThT) or Nile red (NR) and the results were confirmed by transmission electron microscopy (TEM). We have found that NDs promoted amyloid fibril formation at all concentrations. The highest concentration of C60 (250 μg ml−1) accelerated the process of fibrillation, while smaller concentrations (16 and 80 μg ml−1) prolonged the lag phase and were comparable to the control. SWNTs prolonged the lag phase of amyloid formation at all concentrations. CDs efficiently terminated the growth of amyloid fibrils. When we compared the amyloidogenicity of all four types of CNPs, the following trend was apparent: NDs > control > C60 > CDs > SWNTs.

Integrated approach for the development across Europe of user oriented climate indicators for GFCS high-priority sectors: agriculture, disaster risk reduction, energy, health, water and tourism (INDECIS) Joan Ramon Coll (1), Enric Aguilar (1), Gerard van der Schrier (2), Roberto Coscarelli (3), Erik Engström (4), Yolanda Luna (5), Sergio Vicente-Serrano (6), Petr Stepanek (7), Liliana Velea (8), Richard Allan (9), Ricardo Trigo (10), Ali Nadir Arslan (11), Manuel del Jesús (12), Yvan Caballero (13), Patrick Fournet (14), Albert Soret (15), and Hans van de Vijver (16) (1) Centre for Climate Change-Rovira i Virgili University, (2) Royal Netherlands Meteorological Institute, (3) Consiglio Nazionale della Ricerche - Istituto di Ricerca per la Protezione Idrogeologica, (4) Swedish Meteorological and Hydrological Institute, (5) Agencia Estatal de Meteorología, (6) Instituto Pirenaico de Ecología - Consejo Superior de Investigaciones Científicas, (7) Global Change Research Institute - Czech Academy of Sciences, (8) National Meteorological Administration of Romania, (9) University of Reading, (10) Associação para a Investigação e Desenvolvimento de Ciências - Universidade de Lisboa, (11) Finnish Meteorological Institute, (12) Environmental Hydraulics Institute - University of Cantabria, (13) Bureau de Recherches Géologiques et Minières, BRGM / Water Division, (14) Department of the Environment, Community and Local Government (Met Éireann), (15) Barcelona Supercomputing Center, (16) Royal Meteorological Institute of Belgium - Meteorological and Climatological Research The INDECIS project (see www.indecis.eu ) includes 16 institutions from 12 countries and intends to maximize the benefits achievable from the use of observational data across Europe to develop climate indicators and climate services useful to assess the effects of climate variability, including extreme events, and climate change over socioeconomic systems. INDECIS is starting its second year of work and has already produced its first results. The project contributed to the ECA&D dataset by rescuing around 610K meteorological stationbased daily observations from the Balkans and Central Europe for the different essential variables (maximum and minimum temperature, rainfall, sunshine duration and snow depth) along the 20th century at daily scale. (https://doi.pangaea.de/10.1594/PANGAEA.896957). In addition, 339 climate series (rainfall and temperature) were gathered from Italy and a Global Dataset with 311 wind tall mast data was also recovered. Next to DARE activities, the focus moved to ensure data quality and homogeneity. First, three Quality Control (QC) software suites have been created and are available to use as beta versions (http://www.indecis.eu/software.php): the INQC software and the MetQC software, for the quality control of ECA&D daily data; and the QCSS4TT software built specifically for tall masts wind data. INDECIS has also created a set of daily benchmarks for testing quality control and homogenization methods and software. Two benchmarks are available from the project's website (http://www.indecis.eu/benchmarking.php). One of this Benchmark is based on KNMI Climate Regional model (RACMO) and a Real-Data based Benchmark is created by combining close by stations to simulate real relocations. INDECIS has also produced a list of 136 climate indices and a software suite to compute them (http://www.indecis.eu/indices.php). A list of indicators related to circulation variability have been catalogued to inspect their relations with the computed indices and a new software suite for datasets inter-comparison is under development to examine the strengths and weaknesses of different gridded, reanalyzed and modeled datasets. INDECIS is now engaging with potential users to promote a series of workshops to present and co-develop products and services. In the presentation, an overview of INDECIS activities and results are given. The Project INDECIS started in September 2017 and will last 36 months. It is part of ERA4CS, an ERA-NET initiated by JPI Climate, and funded by FORMAS (SE), DLR (DE), BMWFW (AT), IFD (DK), MINECO (ES), ANR (FR) with co-funding by the European Union (Grant 690462).

The poly(2-methyl-2-oxazoline)-b-poly[N-(2,2-difluoroethyl)acrylamide] self-assembled nanoparticles show great potential in biological applications as, e.g., 19F MRI tumour diagnostic agents. As such their internal structure needs to be thoroughly investigated while the results also help to understand temperature-dependent self-assembly behaviour of copolymers comprised of the hydrophilic and thermoresponsive blocks in general. In this paper, we elucidate internal structure of the nanoparticles formed by temperature-driven self-assembly of the abovementioned diblock copolymer by various methods. The majority of our polymers form micelle-like structures above the cloud point temperature (CPT). However, the presence of thermoresponsive homopolymer chains even in amounts below standard detection limits as well as strong hydrogen bonding causes the formation of larger aggregates interconnected by hydrophobic networks and hydrogen bonds, which contain large amounts of solvent. In the case of our particles, we also observe a strong influence of solvent on CPT, particle formation and overall sample behaviour. The ability of nanoparticles to provide usable 19F NMR signal was also confirmed.

Purpose This paper aims to investigate the role of Smart Technologies and Big Data as relevant dimensions in affecting the emerging social and economic dynamics of society with the aim to trace possible guidelines and pathways for decision makers and researchers interested in the governance of the Smart City’s ecosystem. The increasing attention to the domain of technologies and the amazing scenario that is emerging as a consequence of the influence of Smart Technology and Big Data in everyday life require reflection upon the ways in which the world is changing. Design/methodology/approach The paper adopts the interpretative lens provided by the systems thinking to investigate the challenging domain of the Smart City. A qualitative and interpretative approach is adopted to reflect upon the role of technologies in everyday life. Findings The Smart City ecosystem is defined as a multilevel construct useful for understanding how technical and technological dimensions of the Smart City can be managed not only as supportive instruments but also as key pillars to support, facilitate and ensure an effective cognitive alignment among all the involved actors. Originality/value This paper provides a tangible evidence of the systems thinking contribution in analysing, understanding and managing dimensions and paths of social dynamics. A contribution to previous studies is provided with reference to systems thinking, Big Data and Smart City.

We describe a new approach to depot drug delivery in which a copolymer poly[N-isopropyl acrylamide-co-N-(3-imidazolylpropyl)methacrylamide] (PNIPAM-co-ImPM) is considered as the main object and matrix for a new formulation strategy that provides the controlled and sustained release of an incorporated drug. The relatively low content of ImPM groups (1.6 mol%) was determined to be sufficient to introduce pH-sensitive behavior to the polymer. Together with NIPAM units, which possess a thermo-sensitive behavior, a dual sensitivity was imparted to the polymer that was investigated by means of turbidimetry and dynamic light scattering. A change in pH from 9 down to 4 was observed to result in the increase of the polymer transition temperature from 32 to 70 °C. The separation process is also accompanied with the formation of ca. 150–300 nm particles while above the transition temperature. The pH value of approximately 6.5 was defined as a boundary value, where certain properties of the system significantly change. This observation assumes a potential attractiveness of the system for biological applications in which injection is possible using a liquid form at pH ca. 5 without the risk of injection needle obstruction. In this way, a depot is formed at the application site upon simultaneously heating to body temperature and increasing the pH to the physiological value of 7.4. An in vivo experiment using the polymer in PBS (pH = 5.0) with paliperidone as a model drug showed excellent results regarding the release of the drug from a depot. The putative mechanism of action for our depot system is thoroughly described in the article.

Background: The archetypal DNA methyltransferase inhibitors, 5-azacytidine (AZA) and 5-aza-2'-deoxycytidine (DAC) are potent antineoplastic agents used in the treatment of mainly, blood malignancies. However, the administration of these drugs is confounded by their hydrolytic lability which decreases plasma circulation time. Here, we describe a new biodegradable, polyanhydride formulation for drug delivery that circumvents this drawback. Methods: Injectable/implantable polymeric microbeads containing dispersed microcrystals of hydrophilic AZA or DAC packed in a dry environment are protected from hydrolysis, until the hydrolytic zone reaches the core. Diclofenac is embedded into the formulation to decrease any local inflammation. The efficacy of the formulations was confirmed by monitoring the induced demethylation, and cytostatic/cytotoxic effects of continuous drug release from the time-course dissolution of the microbeads, using an in vitro developed cell based reporter system. Results: Poly(sebaccic acid-co-1,4-cyclohexanedicarboxylic acid) containing 30 wt. % drug showed zero-order release (R 2 = 0.984 for linear regression), and release rate of 10.0 %/h within the first 5 h, and subsequent slower release of the remaining drug, thus maintaining the level of drugs in the outer environment considerably longer than the typical plasma half-life of free azanucleosides. At lower concentrations, the differences between powder drug formulations and microbeads were very low or negligible, however, at higher concentrations, we discovered equivalent or increasing effects of the drugs loaded in microbeads. Conclusions: The study provides evidence that microbead formulations of the hydrolytically labile azanucleoside drugs could prevent their chemical decomposition in aqueous solution, and effectively increase plasma circulation time.

This contribution describes the formulation of DBSO (deterministic based structural optimization) design of a tunnel lining. The principle by which a solution may be obtained for a problem concerning the dimensional and reinforcement design optimization of a concrete structure is introduced. The target function is defined as the minimum cost of used materials. The range of allowable solutions from the mathematical viewpoint is defined by constraining conditions expressed by relations derived from:equations of equilibrium (the solution of optimization calculations for a structure with a Winkler foundation using the finite element method),the reliability conditions of a reinforced concrete structure and from the continuity of deformations.The method (algorithm) for obtaining a serviceable reinforcement design (via the implementation of reinforcement types) from an optimal solution is described. The algorithm will be applied to the optimization of a tunnel lining design. FRP reinforcing bars will be used as reinforcement. The thickness of the tunnel lining and the areas of top and bottom reinforcement in cross-sections will be optimized. The obtained results will be compared with an optimized design created for the same tunnel structure but made from steel-reinforced concrete.

The paper focuses on strengthening of loadbearing reinforced concrete vertical members by composite materials. These modern materials are used more and more in the last years. Usage of the FRP fabrics as confinement has several advantages, however there are some uncertainties regarding the design (eg. determining the compressive strength of confined concrete and limit strain of confined concrete). An assessment of influence of the confinement on the elements (its load bearing capacity and ductility) is necessary for design. There is a large number of analytical formulas, standardized approaches and regulations, which specify the resulting influence on the confinement. The paper draws attention to the considerable dispersion between those obtained results.The paper presents an analysis of the influence of reinforced concrete columns strengthening, which are confined with FRP fabric. The obtained theoretical results were compared with a real behaviour of several specimens of confined concrete columns. The short reinforced concrete circular columns were used as the test specimens. The height-diameter ratio of the columns was set as 2:1, therefore an influence of slenderness to loadbearing capacity of the column can be neglected. Consequently, the influence of confinement can be maximized and the dispersion of results according to different methodologies can be emphasized.

The paper focuses on interface shear behavior, more precisely on shear resistance of the interface between lightweight and regular concrete layers cast at different times without shear reinforcement crossing the interface. Different approaches according to most of major design codes (Eurocode, ACI and Model Code 2010 among other) are briefly reviewed, with emphasis on difference between variables resp. material and cross-section characteristics, on which interface resistance depends. Furthermore, two sets of experiments were carried out: direct shear test on Z-type specimens and slant shear test slightly modified to enforce adhesive failure. Obtained results are compared with theoretical values.

The article deals with the theme of strengthening of reinforced concrete columns by confining with carbon composite fabric. Further, this article discusses an influence of used design approach on a final efficiency of strengthening. Due to the dispersion of resulting values of characteristic properties of confined concrete it is quite difficult to qualify the accuracy of the proposed solutions by using the available design approaches. The aim of the performed experimental work was to quantify the factors that influence the strengthening efficiency of the confining of centrically loaded elements, as well as to compare the variance of the theoretically obtained results with the experimental values.