Properties and drug release profile of poly(N-isopropylacrylamide) microgels functionalized with maleic anhydride and alginate

This study highlights the advantages of functionalized poly(N-isopropylacrylamide) (PNIPAAm) microgels over pure PNIPAAm microgels in terms of polymer network properties and drug release profiles. PNIPAAm network was modified by addition of maleic anhydride (MA) as a comonomer and by formation of interpenetrating polymer network in the presence of alginate. The functionalized thermosensitive microgels in the size range from 20 to 80 μm and with better performance in comparison with pure PNIPAAm microgels were prepared by inverse suspension polymerization. The impact of MA and alginate on the PNIPAAm microgel structure was evaluated through analysis of microgel size, size distribution, volume phase transition temperature (VPTT), equilibrium swelling ratio as well as morphology of the system. It was shown that the controlled modification of PNIPAAm network could result in microgels of considerably improved swelling capacity with unchanged thermosensitivity and maintained open pore morphology. In addition, drug release behavior of microgels could be markedly altered. Release of procaine hydrochloride from the selected microgels was studied using Franz diffusion cell at temperatures below and above VPTT of the microgels. Temperature-controlled drug release pattern was dependent on the type of functionalization of PNIPAAm network. According to drug loading properties and drug release mechanism, PNIPAAm/MA copolymer microgels demonstrated the optimal performances.     

Laser-induced fluorescence-capillary electrophoresis and fluorescence microplate reader measurement: two methods to quantify the effect of antibiotics

Putative antibiotic drugs have to be classified according to their bactericidal potential. Two new methods by means of fluorescence spectroscopy (FS) using a fluorescence microplate reader (FMR) and laser-induced fluorescence capillary electrophoresis (LIF-CE), respectively, were developed for the assessment of the bactericidal efficiency using the LIVE/DEAD BacLight viability kit composed of the two fluorescent nucleic acid stains, SYTO9 (stains all cells green) and propidium iodide (stains cells with damaged membrane red). By correlation of the ratio of green and red fluorescence with the percentage of live cells by employing FS and LIF-CE, respectively, dose response curves of drug-treated Pseudomonas spp. and Streptococcus spp. samples were calculated, which allowed for the assessment of ED50 values. Both methods led to similar results which were in agreement with the minimum inhibitory concentrations (MICs) obtained by conventional broth microdilution. The application of the BacLight viability kit on drug-treated bacteria cultures presents a rapid method of assessing the antibiotic potency which is of great importance for high throughput screening in the development of new antibiotics. Additionally, the new LIF-CE method, which based on the use of a second unlabeled bacteria injection as a stacking front, allowed drawing conclusions from the electrophoretic profile about the constitution of the bacterial population. Thus, the tendency of bacterial chain formation and alterations in the live/dead ratio of the bacterial composition can be directly observed in the presence of different antibiotics.     

Validation of a vector version of the 6S radiative transfer code for atmospheric correction of satellite data. Part II. Homogeneous Lambertian and anisotropic surfaces

This is the second part of the validation effort of the recently developed vector version of the 6S (Second Simulation of a Satellite Signal in the Solar Spectrum) radiative transfer code (6SV1), primarily used for the calculation of look-up tables in the Moderate Resolution Imaging Spectroradiometer (MODIS) atmospheric correction algorithm. The 6SV1 code was tested against a Monte Carlo code and Coulson's tabulated values for molecular and aerosol atmospheres bounded by different Lambertian and anisotropic surfaces. The code was also tested in scalar mode against the scalar code SHARM to resolve the previous 6S accuracy issues in the case of an anisotropic surface. All test cases were characterized by good agreement between the 6SV1 and the other codes: The overall relative error did not exceed 0.8%. The study also showed that ignoring the effects of radiation polarization in the atmosphere led to large errors in the simulated top-of-atmosphere reflectances: The maximum observed error was approximately 7.2% for both Lambertian and anisotropic surfaces.     

Dichromated pullulan diffraction gratings: influence of environmental conditions and storage time on their properties

Investigations of the environmental stability of diffraction gratings, recorded in dichromated pullulan (DCP), are reported. Profile changes of DCP surface relief gratings, under high humidity conditions, were analyzed using an atomic force microscope. It was found that the profile was not altered, while the diffraction efficiency was preserved. The influence of storage life on the diffraction efficiency and surface profile of DCP gratings were also investigated. It was concluded that DCP gratings offer much better stability compared with the dichromated gelatin.     

Synthetic pores with reactive signal amplifiers as artificial tongues

The sensation of taste is mediated by activation or deactivation of transmembrane pores. Artificial stimulus-responsive pores are enormously appealing as sensor components because changes in their activity are readily detectable in many different ways. However, the detection of multiple components in complex matrices (such as foods) with one pore sensor has so far remained elusive because the specificity necessary for sensing a target compound in complex mixtures is incompatible with the broad applicability needed for the detection of multiple components. Here, we present synthetic pores that, like our tongues, can sense flavours in food and in addition make them visibly detectable. Differential sensing and pattern recognition are solutions based on empirical and biomimetic approaches. They have been explored with synthetic receptor arrays and electronic tongues. In contrast, our approach is non-empirical as it exploits reactive amplifiers that covalently capture elusive analytes after enzymatic signal generation and drag them into synthetic pores for blockage. Reactive amplification proved to be highly sensitive and adaptable to various analytes and pores. Moreover, it can be combined with reactive filtration for minimizing interference. The system was tested on real food samples for detection of sucrose, lactose, lactate, acetate, citrate and glutamate to demonstrate the feasibility of these synthetic pores as universal sensors.     

Synthesis and in vitro Study of Artemisinin/Synthetic Peroxide-Based Hybrid Compounds against SARS-CoV-2 and Cancer

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause life-threatening diseases in millions of people worldwide, in particular, in patients with cancer, and there is an urgent need for antiviral agents against this infection. While in vitro activities of artemisinins against SARS-CoV-2 and cancer have recently been demonstrated, no study of artemisinin and/or synthetic peroxide-based hybrid compounds active against both cancer and SARS-CoV-2 has been reported yet. However, the hybrid drug's properties (e. g., activity and/or selectivity) can be improved compared to its parent compounds and effective new agents can be obtained by modification/hybridization of existing drugs or bioactive natural products. In this study, a series of new artesunic acid and synthetic peroxide based new hybrids were synthesized and analyzed in vitro for the first time for their inhibitory activity against SARS-CoV-2 and leukemia cell lines. Several artesunic acid-derived hybrids exerted a similar or stronger potency against K562 leukemia cells (81–83 % inhibition values) than the reference drug doxorubicin (78 % inhibition value) and they were also more efficient than their parent compounds artesunic acid (49.2 % inhibition value) and quinoline derivative (5.5 % inhibition value). Interestingly, the same artesunic acid-quinoline hybrids also show inhibitory activity against SARS-CoV-2 in vitro (EC₅₀ 13–19 μm ) and no cytotoxic effects on Vero E6 cells (CC₅₀ up to 110 μM). These results provide a valuable basis for design of further artemisinin-derived hybrids to treat both cancer and SARS-CoV-2 infections.     

Novel allene oxide synthase products formed via Favorskii-type rearrangement: mechanistic implications for 12-oxo-10,15-phytodienoic acid biosynthesis

The allene oxide synthase (AOS) pathway is widespread in plants. Its products, such as cyclopentenone 12-oxo-10,15-phytodienoic acid (12-oxo-PDA) and related jasmonates, play important biological roles in plants. We found that 12-oxo-PDA in some plant tissues co-occur with an unknown minor oxylipin 1. In vitro incubations of AOSs with α-linolenic acid 13(S)-hydroperoxide reliably afforded 1 along with 12-oxo-PDA and α-ketol. A similar oxylipin 3 was formed during the AOS conversions of γ-linolenic acid 9(S)-hydroperoxide. Linoleic acid hydroperoxides formed neither products similar to 1 and 3 nor cyclopentenones. Oxylipins 1 and 3 were purified and identified as the products of Favorskii-type rearrangement, (2'Z,4Z)-2-(2'-pentenyl)-4-tridecene-1,13-dioic acid and (2'Z,4Z)-2-(2'-octenyl)-4-decene-1,10-dioic acid, respectively. Detection of Favorskii products 1 and 3 demonstrates that cyclopropanones are short-lived AOS products along with allene oxides. The observed parallels between the Favorskii product 1 and 12-oxo-PDA formation suggests that cyclopropanone is either a byproduct or a precursor of 12-oxo-PDA.     

The importance of ‘process’ in Rethinking Project Management: The story of a UK Government-funded research network

This paper tells the story of a UK Government-funded research network called Rethinking Project Management, funded by the Engineering and Physical Sciences Research Council between 2004 and 2006. The story is significant because of the considerable attention given to the process of the Network, both the inquiry process of ‘rethinking’ project management, and the broader social process in which the rethinking activity was carried out. In telling this story, the lead organisers explain how the inquiry process was organised as a learning system to enable the Network to ‘learn’ its way to relevant directions for future research, and secondly, how the broader social process was organised and facilitated to create a context for effective interaction between the people involved. A significant challenge in managing the research programme was how to engage the participants in purposeful inquiry, which would serve not only the primary aims of the Network, but would also yield new and interesting insights for the people involved. This paper seeks to explain how the lead organisers addressed this challenge, through a detailed and reflective discussion of how the research programme was organised and facilitated to achieve the Network’s primary aims. In summary, the principal aim in telling this story is to highlight the importance of process in collaborative research activity involving academics and practitioners, in order that other researchers might draw on the experience of this Network.     

Test of the FDTD accuracy in the analysis of the scattering resonances associated with high-Q whispering-gallery modes of a circular cylinder

Our objective is the assessment of the accuracy of a conventional finite-difference time-domain (FDTD) code in the computation of the near- and far-field scattering characteristics of a circular dielectric cylinder. We excite the cylinder with an electric or magnetic line current and demonstrate the failure of the two-dimensional FDTD algorithm to accurately characterize the emission rate and the field patterns near high-Q whispering-gallery-mode resonances. This is proven by comparison with the exact series solutions. The computational errors in the emission rate are then studied at the resonances still detectable with FDTD, i.e., having Q-factors up to 10(3).