Towards in vivo photomediated delivery of anticancer peptides: Insights from pharmacokinetic and -dynamic data

An in vivo study of a photoswitchable cytotoxic peptide LMB040 has been undertaken on a chemically induced hepatocellular carcinoma model in immunocompetent rats. We analysed the pharmacokinetic profile of the less toxic photoform (“ring-closed” dithienylethene) of the compound in tumors, plasma, and healthy liver. Accordingly, the peptide can reach a tumor concentration sufficiently high to exert a cytotoxic effect upon photoconversion into the more active (“ring-open”) photoform. Tissue morphology, histology, redox state of the liver, and hepatic biochemical parameters in blood serum were analysed upon treatment with (i) the less active photoform, (ii) the in vivo light-activated alternative photoform, and (iii) compared with a reference chemotherapeutic 5-fluorouracil. We found that application of the less toxic form followed by a delayed in vivo photoconversion into the more toxic ring-open form of LMB040 led to a higher overall survival of the animals, and signs of enhanced immune response were observed compared to the untreated animals

О верификации измерений скорости поверхностных течений когерентным радаром СВЧ-диапазона с помощью дрифтеров

Introduction. Conventional contact measurements of hydrographic parameters frequently fail to provide the necessary accuracy of data in the field of water area monitoring. This problem can be solved using coherent radars enabling direct measurements of surface current velocities.Aim. To establish the accuracy of surface current velocities measured by a Doppler radar using drifter data.Materials and methods. In June 2022, coastal operational oceanography studies were conducted at the hydrophysical test site of the Institute of Oceanology of the Russian Academy of Sciences in the Black Sea near Gelendzhik. Measurements were carried out using a coherent X-band radar installed on the Ashamba research vessel simultaneously with drifter experiments using Lagrangian drifters of the near-surface layer with an underwater 0.5 m sail. Coordinates were transmitted via mobile communication. The drifter data on the current velocity and direction were used to verify radar measurements. Measurements were taken onboard of the research vessel at a low speed and different distances from the shore, near the drifters. The tracks of the vessel and drifters were recorded simultaneously. Processing of the radar data involved obtaining Doppler spectra of signals to estimate the dynamic processes on the sea surface, including the current velocity.Results. Radial components of the near-surface current velocity were calculated. Then, the current velocity values obtained based on the drifter and radar data were compared.Conclusion. The present work makes a contribution to the advancement of methods for measuring surface currents from the board of a moving ship by Doppler radars. The obtained results confirm the suitability of the radar hardware and software and signal processing algorithms for measuring currents. The radar measurement data were found agree well with drifter data in the velocity range from 15 cm/s.Введение. Традиционные контактные средства измерений гидрографических параметров зачастую не обеспечивают необходимую оперативность получаемых данных для решения задач мониторинга акваторий. Перспективным направлением является применение когерентных радаров, позволяющих непосредственно измерять скорости поверхностных течений.Цель работы. Оценка достоверности результатов измерений приповерхностной скорости течения доплеровским радаром сравнением с данными дрифтеров.Материалы и методы. В июне 2022 г. был проведен эксперимент по прибрежной оперативной океанографии в Черном море на акватории гидрофизического полигона "Геленджик" Южного отделения Института океанологии РАН с использованием доплеровского радара. Скорость течения измерялась когерентизированным навигационным радиолокатором сантиметрового диапазона с цифровой обработкой, установленным на научноисследовательском судне "Ашамба", одновременно с дрифтерными экспериментами с использованием лагранжевых дрифтеров приповерхностного слоя с подводным парусом высотой 0.5 м, с передачей координат по мобильной связи. Данные дрифтеров о скорости и направлении течения использовались для верификации радарных измерений. Измерения проводились с борта научно-исследовательского судна на малом ходу на различном расстоянии от берега, вблизи дрифтеров. В процессе измерений осуществлялась запись треков судна и дрифтеров. Обработка данных радиолокатора основана на исследовании спектральных характеристик отраженного сигнала, позволяющих оценивать динамические процессы на морской поверхности.Результаты. По результатам обработки доплеровских спектров были получены радиальные составляющие скорости приповерхностных течений, далее было выполнено сопоставление скорости течений по данным дрифтеров и данным радиолокации.Заключение. Настоящая работа является определенным шагом в усовершенствовании методов измерений поверхностных течений с борта движущегося судна доплеровским радаром. Результаты верификации подтверждают пригодность аппаратно-программной части радара и алгоритмов обработки сигнала для измерения течений. Данные радиолокационных измерений хорошо согласуются с данными дрифтеров в диапазоне скоростей от 15 см/с

Flocking factors' assessment in case of destructive impact on swarm robotic systems

This paper dwells on exposures' analysis of open-environment operated swarm robotic systems. Flocking algorithms for swarm robotics, which use alignment and averaging of direction in local communication radius (after C. Reynolds' model) are considered. The problem where a small group of informed robots has to guide the swarm along a desired direction is also considered. Couzin I. D. et al. (2005) showed that even a minority of informed individuals is able to move the group toward the target Hereafter great number of swarm robotics' flocking algorithms were developed in order to increase swarm system's handiness. Several implicit leadership algorithms for distributed robotic systems were proposed. The idea of this paper is to study and simulate the operation of such kind of above mentioned algorithms in the situation when there are saboteurs which destructively impact swarm system. Specially developed by authors simulation software allows to vary the parameters of system operation, which can be rather the number of agents or their interaction features or etc. On the basis of the experimental data the authors produce the analysis of features in order to determine their relevance to the algorithm

Planning of Autonomous Multi-agent Intersection

In this paper, we propose a traffic management system with agents acting on behalf autonomous vehicle at the crossroads. Alternatively to existing solutions based on usage of semiautonomous control systems with the control unit, proposed in this paper algorithm apply the principles of decentralized multi-agent control. Agents during their collaboration generate intersection plan and determinate the optimal order of road intersection for a given criterion based on the exchange of information about them and their environment. The paper contains optimization criteria for possible routes selection and experiments that perform in order to estimate the proposed model. Experiment results show that this model can significantly reduce traffic density compared to the traditional traffic management systems. Moreover, the proposed algorithm efficiency increases with road traffic density. Furthermore, the availability of control unit in the system significantly reduces the negative impact of possible failures and hacker attacks

Planning of Autonomous Multi-agent Intersection

In this paper, we propose a traffic management system with agents acting on behalf autonomous vehicle at the crossroads. Alternatively to existing solutions based on usage of semiautonomous control systems with the control unit, proposed in this paper algorithm apply the principles of decentralized multi-agent control. Agents during their collaboration generate intersection plan and determinate the optimal order of road intersection for a given criterion based on the exchange of information about them and their environment. The paper contains optimization criteria for possible routes selection and experiments that perform in order to estimate the proposed model. Experiment results show that this model can significantly reduce traffic density compared to the traditional traffic management systems. Moreover, the proposed algorithm efficiency increases with road traffic density. Furthermore, the availability of control unit in the system significantly reduces the negative impact of possible failures and hacker attacks

4-Dialkylamino-2,5-dihydroimidazol-1-oxyls with Functional Groups at the Position 2 and at the Exocyclic Nitrogen: The pH-Sensitive Spin Labels

Local acidity and electrostatic interactions are associated both with catalytic properties and the adsorption activity of various materials, and with the vital functions of biomolecules. The observation of acid–base equilibria in stable free radicals using EPR spectroscopy represents a convenient method for monitoring pH changes and the investigation of surface electrostatics, the advantages of which are especially evident in opaque and turbid samples and in porous materials such as xerogels. Imidazoline nitroxides are the most commonly used pH-sensitive spin probes and labels due to the high sensitivity of the parameters of the EPR spectra to pH changes, their small size, and their well-developed chemistry. In this work, several new derivatives of 4-(N,N-dialkylamino)-2,5-dihydrioimidazol-1-oxyl, with functional groups suitable for specific binding, were synthesized. The dependence of the parameters of their EPR spectra on pH was studied. Several showed a pKa close to 7.4, following the pH changes in a normal physiological range, and some demonstrated a monotonous change of the hyperfine coupling constant by 0.14 mT upon pH variation by four units

Creation of AlSi12 Alloy Coating by Centrifugal Induction Surfacing with the Addition of Low-Melting Metals

This paper investigates the structure and mechanical characteristics of a coating based on an AlSi12 alloy, obtained by centrifugal induction surfacing as an alternative to a bronze sliding bearing. To provide for the adhesion of an aluminum layer to the inner surface of a steel bearing housing, a sublayer of low-melting metals was formed, while the formation of the main layer and the sublayer was done in a single processing cycle. The low-melting metals had higher density, which ensured that the sublayer was created at the interface with the steel bearing housing under the action of centrifugal forces. It is shown that the low-melting sublayer forms a strong bond both with the aluminum alloy and with the steel base. Lead and tin are used as low-melting additives. It has been established that lead or tin used in a sublayer are indirectly involved in the structural formation of boundary layers of steel and aluminum claddings, acting as a medium for diffuse mass transfer. Thus, lead is not included in the composition of the main coating and does not change the chemical composition of the aluminum layer. After the addition of tin, the aluminum develops a dendritic structure, with tin captured in the interdendritic space. In this case, the deposited layer is saturated with iron with the formation of intermetallic (Fe, Al, Si) compounds, both at the interface and in the coating volume. This paper offers an explanation of the mechanism through which Pb and Sn act on the structure formation of the coating, and on the boundary layer of the steel bearing housing. Tribological tests have shown that the resulting materials are a promising option for plain bearings and highly competitive with the CuSn10P bronze

Structure−Activity Relationships of Photoswitchable Diarylethene- Based β‑Hairpin Peptides as Membranolytic Antimicrobial and Anticancer Agents

Five series (28 structures) of photoswitchable β-hairpin peptides were synthesized based on the cyclic scaffold of the natural antibiotic gramicidin S. Cell-type selectivity was compared for all activated (diarylethene “ringopen”) and deactivated (“ring-closed”) forms in terms of antibacterial activity (MIC against Escherichia coli and Bacillus subtilis), anticancer activity (IC50 against HeLa cell line), and hemolytic cytotoxicity (HC50 against human erythrocytes). Correlations between the conformational plasticity of the peptides, their hydrophobicity, and their bioactivity were also analyzed. Considerable improvements in selectivity were achieved compared to the reference compound. We found a dissociation of the anticancer activity from hemolysis. Phototherapeutic indices (PTI), HC50(closed)/MIC(open) and HC50(closed)/IC50(open), were introduced for the peptides as safety criteria. The highest PTI for HeLa-selective toxicity were observed among analogues containing hydroxyleucine on the hydrophobic face. For one compound, high PTIs were demonstrated across a range of different cancer cell lines, including a doxorubicin-resistant on