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Background. The development of highly oriented conjugates of quantum dots (QDs) and single-domain antibodies (sdAbs) as innovative fluorescence imaging nanoprobes that specifically recognize tumor biomarkers, in particular, epidermal growth factor receptor (EGFR), is a promising approach to improving immunohistochemical tumor typing.Aim. The study was aimed at developing fluorescent nanoprobes based on QDs and sdAbs that specifically recognize EGFR, as well as evaluating their functional characteristics (size and optical properties) and functional activity.Materials and methods. QDs were obtained using high-temperature organometallic synthesis and transferred into the aqueous phase by means of stepwise replacement of ligands on the QD surface. The QDs and sdAbs were conjugated in an oriented manner using a bifunctional cross-linking agent. Detailed characteristics of the resulting conjugates were analyzed by the dynamic light scattering and immunoassay methods. Functional activity was assessed on the model human epidermoid carcinoma cells line A431.Results. The QD–sdAb conjugates have been standardized in terms of control parameters determining their functional activity, in particular, hydrodynamic diameter and efficiency of binding with target tumor cells. They are characterized by high dispersity, homogeneity, and specific functional activity towards their molecular target.Conclusion. The results demonstrate the potential use of the designed QD–sdAb conjugates for EGRF detection in immunohistochemical typing of tumor.

Introduction. It is known that the agonist of TLR-3 Poly(I:C), used as an adjuvant in a number of models of antitumor vaccines, causes inhibition of melanoma B16 growth, but the immunological aspects involved in this process have not been fully studied.The aim of the study was to evaluate changes of the immunophenotype of the spleen cells of C57BL / 6 mice caused by the tumor load and / or Poly(I:C), which is necessary for better understanding of the processes occurring during Poly(I:C) inhibition of melanoma B16-F10.Materials and methods. The immunophenotype of splenocytes of C57Bl / 6 mice was studied by flow cytometry asfollowing: the group 1 was a control (intact animals), the group 2 was mice with subcutaneously transplanted melanoma B16-F10, the group 3 was mice without a tumor treated with Poly(I:C) and the group 4 – mice with subcutaneously transplanted melanoma B16-F10 treated with Poly(I:C).Results. Median values of parameters such as the CD4 / CD8 immunoregulatory index, the percentage of CD69+ CD4+ and CD8+ T cells, the number of B and NK cells for the group of mice with melanoma treated with Poly(I:C) were between the values in the control group and in the group of mice with B16-F10. when comparing the results, the number of B and NK cells, the percentage of CD69+ on CD4+ and CD8+ T cells, their median in the group of mice with melanoma treated with Poly(I:C) was closer to the control than to the values obtained in the B16-F10 group and in the group of healthy mice receiving Poly(I:C). At the same time, we found that the total number of CD3+ cells, the number of naive CD4+ and CD8+ T cells was higher in the group of mice with melanoma treated with Poly(I:C) compared to all other groups.Conclusion. The analysis revealed the changes of the immunophenotype of murine spleen cells (CD4 / CD8, the percentage of CD69+ CD4+ and CD8+ T cells, the number of B and NK cells), which were affected by the tumor load and / or the administration of Poly adjuvant (I:C). Changes in the immunophenotype of murine splenocytes were associated with the tumor load and its size. It was also found that the splenocyte immunophenotype was affected by the repeated administration of Poly(I:C) during the tumor growth.

An autonomous non-profit organization “Center for Conflict Resolution in Medicine” is an independent forensic expert organization licensed to carry out medical activities and to conduct assessments of the quality of medical care on criminal and civil cases. It is also the clinical base of the Department of Forensic Medicine of the Pirogov Russian National Research Medical University, where the resident physicians are trained. In 2018-2019, the Center for Conflict Resolution in Medicine made 105 forensic examinations of case materials and medical documents. The organization successfully combines forensic examinations and teaching resident physicians.

The use of liposomes as drug delivery systems today is a recognized approach to improving the effectiveness of treatment. Compared with other nanosized carriers, liposomes are highly biocompatible. However, in the literature, there are a number of data on the immunogenicity of some liposomal drugs. Hypersensitivity reactions of moderate to severe severity were noted in some patients with intravenous administration of liposomes Doxil®, Ambisome®, DaunoХome®. The technology of production of liposomes is a laborious process and obtaining liposomal forms on an industrial scale is problematic for researchers and manufacturers around the world. In connection with this, studies on the scaling up of technology for obtaining liposomes and studying the specific toxicity of liposomal preparations are relevant. Objective – evaluation of the quality of prototypes of liposomal dosage form based on tetra-3-phenylthiophthalocyanine hydroxyaluminum obtained by scaled technology in comparison with samples produced in laboratory conditions, as well as studying their mutagenic and immunotoxic properties. Object of the study – tetra-3-phenylthiophthalocyanine hydroxyaluminum liposomal, lyophilizate for the preparation of injection for injection of 1,5 mg, in bottles with a capacity of 20 ml (LLF). Materials and methods. Bengem’s method, extrusion, sterilizing filtration, lyophilization, intercellular contact integrity test (for promoter activity), Ames bacterial test, cytogenetic study of chromosomal aberrations, DNA damage test (DNA comet test), Erne method; hypersensitivity reaction of delayed type, determination of mass and cellness of central and peripheral immunity organs, evaluation of phagocytic activity of peritoneal macrophages. Results. Based on the results of the research, the LLF production technology is scaled, which allows obtaining up to 400 LLF flasks per production cycle. It has been established that LLF at doses of 6 and 24 mg/kg does not cause an increase in the number of chromosomal abnormalities in mice and does not cause DNA damage, in doses of 1,1–22,0 μg/dish LLF does not show mutagenic activity in the Ames bacterial test, in the range concentrations of 0,062–3,1 μg in the test for promoter activity does not separate intercellular contacts. It is determined that in doses of 6 and 12 mg/kg, LLF does not affect humoral and cellular immunity, does not change the mass and cellularity of the central and peripheral organs of the immune system. LLF, 24 hours after administration at doses of 6 and 12 mg/kg, dose-dependently decreases the phagocytic activity of peritoneal macrophages, which is restored after 7 days. Conclusion. The technology of LLF production is scaled. In the doses studied, it was found that LLF does not have the ability to promote the process of carcinogenesis and the lack of influence on the humoral and cellular immune response.

The light-current characteristic (LCC) of semiconductor quantum well lasers is theoretically studied. It is discussed here that, due to internal optical absorption loss, which depends on the electron and hole densities in the optical confinement layer, (i) roll-over of the LCC occurs with increasing injection current, and, (ii) depending on the parameters of laser structures, the LCC can have two branches, i.e. the optical emission at two different output powers will be possible within a certain range of injection currents.

Multiplexed suspension systems of anew generation are capable to provide precise quantitative profiling of mul- tipledisease-specific markers in human body fluids. We have developed suspension microarrays based on microbeads encoded with fluorescent nanociystals, that show undeniable advantages overavailable analogues in terms of improved multiplexing capabilities, physical and optical properties, low cost and simplicity of analysisperformance. We have adapted QD-encoded suspension microarrays for the simultaneous detection of two forms of prostate-specific antigen (PSA) in human serum by means of classical flow cytometiy. In the present study, we describe in detail the designed system properties including evaluation the microarray for quantitative analysis of serum markers in comparison to standard clinical approach ELISA, as well asestimation of the most important analytical characteristics, such as analytic sensitivity (limit of detection), reproducibility, reliability and accuracy of the analysis, the linear rangesfor detectable- marker concentrations. Experimental data suggested that the developed diagnostic system quantifies two forms of PSA in blood serum samples of patients with high accuracy, precision and reliability.

International audience; Polyelectrolyte microcapsules are promising carriers of drugs and diagnostic agents for designing targeted and controlled delivery systems design. The use of quantum dots (QDs) as fluorescent labels in bioimaging is a promising approach to bioimaging tool development. The potential toxicity of QDs makes their applicability as fluorescent labels in vivo questionable. Therefore, the cytotoxicity of polyelectrolyte microcapsules encoded with semiconductor nanocrystals has been investigated.

Semiconductor nanocrystals (quantum dots, QDs) have a wide range of potential application in multiplexed tissue and cell imaging, and for in vivo molecular diagnostics and therapy. Therefore studying of the toxicity of QDs and their influence on various cellular processes in vitro is necessary to understand their interaction with living systems.; The paper presents the results of studies on the evaluation of CdSe/ZnS QD cytotoxicity, as well as the results of studying their interaction with freshly prepared human monocytes in vitro. Keywords: Quantum dots, semiconductor nanocrystals, cytotoxicity, in vitro models, monocytes.

International audience; Multiplexed analysis of cancer markers is crucial for early tumor diagnosis and screening. We have designed lab-on-a-bead microarray for quantitative detection of three breast cancer markers in human serum. Quantum dots were used as bead-bound fluorescent tags for identifying each marker by means of flow cytometry. Antigen-specific beads reliably detected CA 15-3, CEA, and CA 125 in serum samples, providing clear discrimination between the samples with respect to the antigen levels. The novel microarray is advantageous over the routine single-analyte ones due to the simultaneous detection of various markers. Therefore the developed microarray is a promising tool for serum tumor marker profiling.

Results of solar flare observations obtained in the Konus-Wind experiment from November, 1994 to December, 2013 and in the Helicon Coronas-F experiment during its operation from 2001 to 2005, are presented. For the periods indicated Konus-Wind detected in the trigger mode 834 solar flares, and Helicon-Coronas-F detected more than 300 solar flares. A description of the instruments and data processing techniques are given. As an example, the analysis of the spectral evolution of the flares SOL2012-11-08T02:19 (M 1.7) and SOL2002-03-10T01:34 (C5.1) is made with the Konus-Wind data and the flare SOL2003-10-26T06:11 (X1.2) is analyzed in the 2.223 MeV deuterium line with the Helicon-Coronas-F data., Comment: Published version. A list of the Konus-Wind solar flare triggers and figures of their time profiles are available at http://www.ioffe.ru/LEA/Solar/

Control of spectral and spatial parameters of semiconductor lasers is a key element of their development and application. Surface integrated high-order distributed Bragg reflector (DBR) is the way to narrow diode laser spectrum preserving the conventional postgrowth process of laser diodes. On the other hand, high-order DBR has specific optical losses, which reduce optical output power. In this work we analyzed these specific optical losses and present design of laser resonator containing short front DBR, that allow to significantly reduce losses. With this approach, slope efficiency was greatly increased in contrast with conventional rear DBR laser diodes and 4 W optical output power with spectral width of less than 3 A was attained.

The results of gamma-ray burst observations made in the 10 keV - 8 MeV range with Konus-B instrument on Granat spacecraft are presented. 19 gamma-ray bursts and 60 solar flares have been measured altogether in 27 days at a sensitivity level of 5×10−8 - 5×10−7 erg/cm2. The fast spectral variability of bursts and the presence of features in their spectra in the form of absorption and emission lines are confirmed.

A comprehensive analytical model for the operating characteristics of semiconductor lasers with a low-dimensional active region is developed. Particular emphasis is given to the effect of capture delay of both electrons and holes from a bulk optical confinement region into a quantum-confined active region and an extended set of rate equations is used. We derive a closed-form expression for the internal quantum efficiency as an explicit function of the injection current and parameters of a laser structure. Due to either electron or hole capture delay, the internal efficiency decreases with increasing injection current above the lasing threshold thus causing sublinearity of the light-current characteristic of a laser.

The Konus-W experiment to be flown on board the GGS-Wind spacecraft is designed to observe gamma-ray bursts and solar flares with moderate spectral and high time resolution. Two large scintillators are used to provide omnidirectional sensitivity. The primary scientific objectives are the study of the continuum energy spectra and spectral features of these events in the energy range of 10 keV to 10 MeV, as well as their time histories in soft, medium, and hard energy bands, with a time resolution to 2 ms.

The examination of 231 rheumatic patients, 159 patients with reactive arthritis and 117 rheumatoid arthritis patients identified diagnostic titers of polyvalent antibodies to Borrelia in 6.6% of all the examinees with rheumatism, 11.9% with reactive arthritis and in 7.7% with RA. Lyme arthritis was diagnosed in 1.3% of reactive arthritis patients. To diagnose Lyme arthritis accurately, it is recommended to rest upon clinical symptoms which must be associated with high titers of IgG antibodies to Borrelia growing still higher in the follow-up period.

16 W continuous-wave room temperature front facet output optical power and 74% wallplug efficiency were attained in 100 µm-aperture 1.06 µm-emitting laser diodes with 2–3 mm cavity length. The lasers are based on AlGaAs/GaAs/InGaAs quantum well asymmetric heterostructures with 1.7 µm-thick waveguide having 0.34 cm−1 internal optical loss.

Functional activity of lymphocytes, revealed by means of fluorometric study of the physicochemical properties of the membranes (according to the degree of binding with MBD) and nuclei (according to the degree of AO adsorption on chromatin DNA) was different in patients suffering from rheumatoid arthritis with different blood titers of RF determined by Vaaler-Rose's test. The lowered lymphocyte count in blood plasma was coupled with high functional activity of genome in patients with seronegative RA and with low in seropositive RA patients. Changes in the fluorescence of MBD bound with the membrane differed from those in the fluorescence of AO bound with lymphocyte chromatin. The DNA level in blood plasma of patients with seropositive RA was higher as compared with its levels seen in seronegative patients and healthy subjects.

Effect of noretisterone microdoses (300 microgram) on a functional condition of the hypophysio-ovarian system was investigated. Hormonal studies were conducted in the time course of the control menstrual cycle and during 6 months of continuous noretisterone administration. Ovulation persisted in half of the women under study. Gestagen microdoses proved to produce a less pronounced effect on the hypophysio-ovarian system than estrogen-gestagen drugs.

Following local microwave exposure (460 MHz, 120 mW/cm2) of rabbits using fluorescent probes and chemiluminescent analysis, conformational rearrangements in nuclear and cytoplasmic membranes and in thymus cell chromatin of the animals as well as changes in the intensity of the lipid free radical peroxidation were seen. The character of the changes observed depended both on the localization of the exposure and on the number of exposures.

In this work the possibility of using microwaves for immunomodulation in the immunization of animals with thymus-independent antigen was studied. The projection zones of the thymus and adrenal glands of the test animals were subjected to the action of decimeter, or ultrahigh frequency (UHF), waves, while the corresponding zones of the control animals were subjected to imitation UHF irradiation. Vi-antigen was shown to be a thymus-independent antigen for rabbits (according to the results of the evaluation of the functional state of thymocytes, as manifested by the adsorption of acridine orange by the chromatin of thymocyte nuclei and by the content of RNA and DNA in the thymus). The action of UHF waves on the projection zone of the thymus was accompanied by a decrease in the glucocorticoid activity of the adrenal cortex, observed simultaneously with a pronounced immunostimulating effect. The UHF irradiation of the zone of the adrenal glands was accompanied by immunosuppression in combination with enhanced glucocorticoid activity of the adrenal cortex.

Following local microwave exposure (460 MHz, 120 mW/cm2) of rabbits using fluorescent probes and chemiluminescent analysis, conformational rearrangements in nuclear and cytoplasmic membranes and in thymus cell chromatin of the animals as well as changes in the intensity of the lipid free radical peroxidation were seen. The character of the changes observed depended both on the localization of the exposure and on the number of exposures.