When mechanisms of coalescence and sintering at the nanoscale fundamentally differ: Molecular dynamics study.

Employing classical isothermal molecular dynamics, we simulated coalescence of mesoscopic Au nanodroplets, containing from several thousands to several hundred thousands of atoms, and sintering of mesoscopic solid Au nanoparticles. For our atomistic simulations, we used the embedded atom method. The employed open access program large-scale atomic/molecular massively parallel simulator makes it possible to realize parallel graphical processing unit calculations. We have made a conclusion that the regularities and mechanisms of the nanodroplet coalescence (temperature is higher than the nanoparticle melting temperature) and of the solid nanoparticle sintering differ from each other. We have also concluded that the nanodroplet coalescence may be interpreted as a hydrodynamic phenomenon at the nanoscale whereas sintering of solid nanoparticles is a much more complex phenomenon related to different mechanisms, including collective rearrangements of atoms, the surface diffusion, and other types of diffusion. At the same time, collective rearrangements of atoms relate not only to the solid nanoparticle sintering but also to the nanodroplet coalescence. In general, our molecular dynamics results on sintering of Au nanoparticles consisting of 10 000-30 000 atoms agree with the Ferrando-Minnai kinetic trapping concept that was earlier confirmed in molecular dynamics experiments on Au nanoclusters consisting of about 100 atoms.

Two-octave-wide (3-12 µm) subharmonic produced in a minimally dispersive optical parametric oscillator cavity.

We report a subharmonic (frequency-divide-by-2) optical parametric oscillator (OPO) with a continuous wavelength span of 3 to 12 µm (-37dB level) that covers most of the molecular rovibrational "signature" region. The key to obtaining such a wide spectral span is the use of an OPO with a minimal dispersion-through the choice of intracavity elements, the use of all gold-coated mirrors, and a special "injector" mirror. The system delivers up to 245 mW of the average power with the conversion efficiency exceeding 20% from a 2.35 µm Kerr-lens mode-locked pump laser.

[Modern technologies of regenerative rehabilitation in the treatment of patients with abnormal scars]. / Sovremennye tekhnologii regenerativnoi reabilitatsii v lechenii patsientov s patologicheskimi rubtsovymi izmeneniyami.

OBJECTIVE: To evaluate an efficacy of lipoaspirate-based products in pathologic scarring management. MATERIAL AND METHODS: There were 118 patients with external scars. Depending on scar type, localization and need for soft tissue augmentation, three different methods were used for lipoaspirate-based product preparation: 15-minute sedimentation, centrifugation at 1200 g for 3 minutes and emulsification with a channel diameter of 1.2 mm. Results were assessed using the Manchester Scar Scale (MSS) and photographing. RESULTS: According to MSS analysis, the following results were obtained: before treatment - 11.6 (9.3-13.3) scores, 3 months after treatment - 6.5 (5.1-7.2) scores, 6 months after treatment - 5.2 (4.5-6.1) scores. Significant differences were obtained for baseline values and both control points. Stable results were obtained in long-term follow-up period (12-24 months). No major adverse effects were observed. Minor complications were registered in 10.1% of patients. CONCLUSION: Injections of lipoaspirate-based products is an effective option for the treatment of patients with pathologic scarring. This approach is intermediate between conservative and conventional surgical treatment.

[Lumbar microdiscectomy using intraoperative ultrasound]. / Poiasnichnaia mikrodiskéktomiia s primeneniem intraoperatsionnogo ul'trazvukovogo issledovaniia.

OBJECTIVE: To analyze advisability of intraoperative ultrasound during lumbar microdiscectomy. MATERIAL AND METHODS: We used intraoperative ultrasound to identify and localize various tissues and structures of the spinal canal, optimize surgical approach to the herniated disc and assess decompression of neural structures. The study was conducted in 48 patients with herniated discs of the lumbar spine who were operated for the period from 2014 to 2017. We used ultrasound devices BK Medical Pro Focus 2202 and BK Medical Flex Focus 400 with neurosurgical transducer Craniotomy 8862 and Burr-Hole 8863. Examinations were performed before and after flavotomy during neural decompression and after decompression. All patients underwent laboratory, clinical and instrumental survey. We analyzed changes of functional and neurological status and investigated various possibilities of intraoperative ultrasound and its impact on postoperative outcomes. RESULTS: Intraoperative ultrasound is valuable to verify various tissues and structures of the lumbar spine. On-line scanning gives a correct volumetric representation of the various anatomical structures and their spatial relationships that is essential for less traumatic and more radical surgery. CONCLUSION: Intraoperative ultrasound is easy, harmless, inexpensive and widely available method of intraoperative imaging. US data may be comparable with those of intraoperative CT and MRI. Intraoperative ultrasound during lumbar microdiscectomy results better postoperative outcomes.

Effects of Gamma-Radiation on DNA Damage in Onion (Allium cepa L.) Seedlings.

The effect of γ-radiation on the level of nuclear DNA damage in onion seedlings (Allium-test) was studied using the comet assay. DNA breaks were first found in cells of onion seedlings exposed to low-dose radiation (≤ 0.1 Gy). Dose dependence of DNA damage parameters showed nonlinear behavior: a linear section in the low-dose region (below 0.1 Gy) and a dose-independent plateau in the dose range between 1 and 5 Gy. Thus, the comet assay can be used to estimate the biological effects of low-dose γ-radiation on Allium cepa seedlings.

Cr:ZnS laser-pumped subharmonic GaAs optical parametric oscillator with the spectrum spanning 3.6-5.6 µm.

Using a subharmonic optical parametric oscillator (OPO) based on orientation-patterned GaAs, we produced a broadband instantaneous output that spans 3.6-5.6 µm at 50-dB level (4.4-5.2 µm at 3 dB level), has 110 mW of average power, and is suitable for producing wideband-frequency combs in the mid-infrared. The OPO was synchronously pumped by a compact Kerr-lens mode-locked femtosecond Cr:ZnS oscillator with the central wavelength 2.38 µm and pulse repetition frequency 175 MHz.

53BP1 foci as a marker of tumor cell radiosensitivity.

Predicting tumor radiosensitivity has yet to be routinely integrated into radiotherapy. We analyzed the possibility to assess radiosensitivity of tumor cells based on endogenous and radiation-induced 53BP1 foci which are molecular markers of DNA double strand breaks (DSB). In eleven tumor cell lines of different origin, radiosensitivity was assessed by surviving cell fraction following irradiation with 2 Gy (SF2). 53BP1 foci were measured at 4 and 12 h post-irradiation by confocal laser microscopy and dedicated software. The correlation of 53BP1 foci and their post-irradiation kinetics with SF2 was assessed using Spearman rank test. The SF2 correlated with both excess of radiation-induced 53BP1 foci per cell at 4 h after irradiation and decay in number of 53BP1 foci from 4 to 12 h post-irradiation. The fraction of cells with multiple endogenous 53BP1 foci also correlated with SF2 of tumor cells. We conclude that the radiosensitivity of tumor cells can be predicted by kinetics of formation and decay of 53BP1 foci after irradiation. For the first time we report that the fraction of cells with multiple endogenous 53BP1 foci can be used as a marker of tumor cell radiosensitivity.

[Background Level of γH2AX Foci in Human Cells as a Factor of Individual Radiosensitivity].

The paper analyzes the effects of spontaneous level of yH2AX and 53BP1 foci on a frequency of radiation-induced centromere-negative and centromere-positive micronuclei in peripheral blood lymphocytes of 54 healthy individuals after exposure to 2 Gy of ionizing radiation in vitro. An inverse correlation was found between the level of spontaneous yH2AX foci and the frequency of centromere-negative micronuclei after irradiation. The corresponding correlations between the spontaneous level of protein 53BP1 foci and the frequency of centromere-negative micronuclei were not statistically significant. In addition, cells of the individuals with a high frequency of radiation-induced micronuclei were also characterized by a low proliferative activity. It was suggested that DNA double strand break repair works less efficiently in cells of the individuals with low levels of spontaneous yH2AX foci, and a greater number of DNA double strand breaks after exposure to ionizing radiation remains unrepaired, thus leading to a cell cycle block and an increase of the frequency of centromere-negative micronuclei.

[SKEWED X-CHROMOSOME INACTIVATION IN HUMAN MISCARRIAGES].

Sex ratio in first trimester of pregnancy is skewed due to preferential elimination of female embryos. It could be resulted from aberrant X-chromosome inactivation. X-chromosome inactivation was analyzed in extraembryonic tissues of miscarriages and induced abortions with 46, XX karyotype. In chorion cytotrophoblast of both miscarriages and induced abortions observed either random or skewed X-chromosome inactivation. In extraembryonic mesoderm of the control group, random inactivation was observed, whereas 15% of miscarriages had skewed X-chromosome inactivation. The highest frequency of skewed inactivation of one of the parental homologues was observed in the groups of blighted ovum pregnancy and embryos from women with recurrent pregnancy loss. It was suggested that in these cases compartmentalization of cells in the blastocyst probably leads to predominance of cell with mutant active X-chromosome among the cells of inner cell mass carrying the aberrations that are incompatible with normal embryonic development.

Aberrant methylation of placental development genes in chorionic villi of spontaneous abortions with trisomy 16.

In humans, aneuploidy is incompatible with the birth of healthy children and mainly leads to the death of embryos in the early stages of development in the first trimester of pregnancy. Trisomy 16 is the most common aneuploidy among spontaneous abortions of the first trimester of pregnancy. However, the mechanisms leading to the death of embryos with trisomy 16 remain insufficiently investigated. One of these potential mechanisms is abnormal placental development, including aberrant remodeling of spiral arteries. Spiral artery remodeling involves the migration of trophoblast cells into the maternal spiral arteries, replacing their endothelium and remodeling to ensure a stable embryonic nutrition and oxygen supply. This is a complex process which depends on many factors from both the embryo and the mother. We analyzed the methylation level of seven genes (ADORA2B, NPR3, PRDM1, PSG2, PHTLH, SV2C, and TICAM2) involved in placental development in the chorionic villi of spontaneous abortions with trisomy 16 (n = 14), compared with spontaneous abortions with a normal karyotype (n = 31) and the control group of induced abortions (n = 10). To obtain sequencing libraries, targeted amplification of individual gene regions using designed oligonucleotide primers for bisulfite-converted DNA was used. The analysis was carried out using targeted bisulfite massive parallel sequencing. In the group of spontaneous abortions with trisomy 16, the level of methylation of the PRDM1 and PSG2 genes was significantly increased compared to induced abortions (p = 0.0004 and p = 0.0015, respectively). In the group of spontaneous abortions, there was no increase in the level of methylation of the PRDM1 and PSG2 genes, but the level of methylation of the ADORA2B gene was significantly increased compared to the induced abortions (p = 0.032). The results obtained indicate the potential mechanisms of the pathogenetic effect of trisomy 16 on the placental development with the participation of the studied genes.

Robust frequency stabilization of multiple spectroscopy lasers with large and tunable offset frequencies.

We have demonstrated a compact, robust device for simultaneous absolute frequency stabilization of three diode lasers whose carrier frequencies can be chosen freely relative to the reference. A rigid ULE multicavity block is employed, and, for each laser, the sideband locking technique is applied. A small lock error, computer control of frequency offset, wide range of frequency offset, simple construction, and robust operation are the useful features of the system. One concrete application is as a stabilization unit for the cooling and trapping lasers of a neutral-atom lattice clock. The device significantly supports and improves the clock's operation. The laser with the most stringent requirements imposed by this application is stabilized to a line width of 70 Hz, and a residual frequency drift less than 0.5 Hz/s. The carrier optical frequency can be tuned over 350 MHz while in lock.

Interconnected Evolution of Epidemic and Public Vaccination Opinion.

A new model of interconnected coevolving SIRS epidemic and public vaccination opinion pattern is presented. The underlying two-layer network contains strata corresponding to physical interactions in real space and social communications. The layer corresponding to physical interactions is constructed based on data on a real network representing communications between high school students. The evolution of people vaccination attitude is described using an Ising-type model. The model describes a non-trivial dependence of resulting epidemic dynamics on (1) noise amplitude, (2) initial opinion pattern and (3) influence of external information.

Comparative cytogenetics of anembryonic pregnancies and missed abortions in human.

Miscarriage is an important problem in human reproduction, affecting 10-15 % of clinically recognized pregnancies. The cases of embryonic death can be divided into missed abortion (MA), for which the ultrasound sign of the embryo death is the absence of cardiac activity, and anembryonic pregnancy (AP) without an embryo in the gestational sac. The aim of this study was to compare the frequency of chromosomal abnormalities in extraembryonic tissues detected by conventional cytogenetic analysis of spontaneous abortions depending on the presence or absence of an embryo. This is a retrospective study of 1551 spontaneous abortions analyzed using GTG-banding from 1990 to 2022 (266 cases of AP and 1285 cases of MA). A comparative analysis of the frequency of chromosomal abnormalities and the distribution of karyotype frequencies depending on the presence of an embryo in the gestational sac was carried out. Statistical analysis was performed using a chi-square test with a p <0.05 significance level. The total frequency of chromosomal abnormalities in the study was 53.6 % (832/1551). The proportion of abnormal karyotypes in the AP and MA groups did not differ significantly and amounted to 57.1 % (152/266) and 52.9 % (680/1285) for AP and MA, respectively (p = 0.209). Sex chromosome aneuploidies and triploidies were significantly less common in the AP group than in the MA group (2.3 % (6/266) vs 6.8 % (88/1285), p = 0.005 and 4.9 % (13/266) vs 8.9 % (114/1285), p = 0.031, respectively). Tetraploidies were registered more frequently in AP compared to MA (12.4 % (33/266) vs. 8.2 % (106/1285), p = 0.031). The sex ratio among abortions with a normal karyotype was 0.54 and 0.74 for AP and MA, respectively. Thus, although the frequencies of some types of chromosomal pathology differ between AP and MA, the total frequency of chromosomal abnormalities in AP is not increased compared to MA, which indicates the need to search for the causes of AP at other levels of the genome organization, including microstructural chromosomal rearrangements, monogenic mutations, imprinting disorders, and epigenetic abnormalities.

Expression of the NUP153 and YWHAB genes from their canonical promoters and alternative promoters of the LINE-1 retrotransposon in the placenta of the first trimester of pregnancy.

The placenta has a unique hypomethylated genome. Due to this feature of the placenta, there is a potential possibility of using regulatory elements derived from retroviruses and retrotransposons, which are suppressed by DNA methylation in the adult body. In addition, there is an abnormal increase in the level of methylation of the LINE-1 retrotransposon in the chorionic trophoblast in spontaneous abortions with both normal karyotype and aneuploidy on different chromosomes, which may be associated with impaired gene transcription using LINE-1 regulatory elements. To date, 988 genes that can be expressed from alternative LINE-1 promoters have been identified. Using the STRING tool, genes (NUP153 and YWHAB) were selected, the products of which have significant functional relationships with proteins highly expressed in the placenta and involved in trophoblast differentiation. This study aimed to analyze the expression of the NUP153 and YWHAB genes, highly active in the placenta, from canonical and alternative LINE-1 promoters in the germinal part of the placenta of spontaneous and induced abortions. Gene expression analysis was performed using real-time PCR in chorionic villi and extraembryonic mesoderm of induced abortions (n = 10), adult lymphocytes (n = 10), spontaneous abortions with normal karyotype (n = 10), and with the most frequent aneuploidies in the first trimester of pregnancy (trisomy 16 (n = 8) and monosomy X (n = 6)). The LINE-1 methylation index was assessed in the chorionic villi of spontaneous abortions using targeted bisulfite massive parallel sequencing. The level of expression of both genes from canonical promoters was higher in blood lymphocytes than in placental tissues (p < 0.05). However, the expression level of the NUP153 gene from the alternative LINE-1 promoter was 17 times higher in chorionic villi and 23 times higher in extraembryonic mesoderm than in lymphocytes (p < 0.05). The expression level of NUP153 and YWHAB from canonical promoters was higher in the group of spontaneous abortions with monosomy X compared to all other groups (p <0.05). The LINE-1 methylation index negatively correlated with the level of gene expression from both canonical (NUP153 - R = -0.59, YWHAB - R = -0.52, p < 0.05) and alternative LINE-1 promoters (NUP153 - R = -0.46, YWHAB - R = -0.66, p < 0.05). Thus, the observed increase in the LINE-1 methylation index in the placenta of spontaneous abortions is associated with the level of expression of the NUP153 and YWHAB genes not only from alternative but also from canonical promoters, which can subsequently lead to negative consequences for normal embryogenesis.

[Immune system disorders and their correction in critically ill patients with toxic and hypoxic encephalopathy].

In this article there are materials, which were received in the process of treatment of 69 patients with azaleptin (leponeks) acute severe poisonings. The immunologic research has shown that the first phase of acute poisonings in patients with toxicohypoxic encephalopathy is accompanied by severe immune alterations. The alterations of proinflammation and antiinflammation cytokines have been investigated and its increase has not been revealed. It was shown, that the employment of citoflavin in intensive therapy of acute poisonings leads to decrease of the level of immunosupression.

[Use of cytoflavin into the complex intensive therapy of acute cerebral insufficiency caused by poisoning].

In the result of treatment of 147 patients with toxic acute brain insufficiency were revealed that the employment of citoflavin (20 ml with 400 ml 5% glucosae twice a day) in 7 days intensive therapy of acute brain insufficiency leaded to decrease of hypoxic brain damages and intensity of brain depression, what was revealed in improvement of brain bioelectric activity. Rehabilitation of central nervous system regulation function and life-support systems leaded to quick rehabilitation of respiratory part of oxygen transport. These changes in acute period leaded to quick reparation of cognitive-mnestic functions and social adaptation. The employment of citoflavin leaded to improvement of clinic of toxicohypoxic encephalopathy and to decrease of secondary lung complications (decrease of coma-period from 45,3 ± 8,2 to 27,7 ± 6,9 hours; decrease of secondary lung complications from 72,7% to 35,9%).

Generation of iPS cell line (ICGi040-A) from skin fibroblasts of a patient with ring small supernumerary marker chromosome 4.

Human induced pluripotent stem cell (iPSC) line, ICGi040-A, was obtained from skin fibroblasts derived from a male patient with mosaic ring small supernumerary marker chromosome 4 (sSMS(4)) and infertility. ICGi040-A cells have karyotype 47,XY,+r(4) in 97% of cells and express a set of pluripotent markers, as well as are able to differentiate in vitro into derivatives of all three embryonic germ layers.

Resonant IR multi-photon dissociation spectroscopy of a trapped and sympathetically cooled biomolecular ion species.

In this work we demonstrate vibrational spectroscopy of polyatomic ions that are trapped and sympathetically cooled by laser-cooled atomic ions. We use the protonated dipeptide tryptophan-alanine (HTyrAla(+)) as a model system, cooled by barium ions to less than 800 mK secular temperature. The spectroscopy is performed on the fundamental vibrational transition of a local vibrational mode at 2.74 µm using a continuous-wave optical parametric oscillator (OPO). Resonant IR multi-photon dissociation spectroscopy (R-IRMPD) (without the use of a UV laser) generates charged molecular fragments, which are sympathetically cooled and trapped, and subsequently released from the trap and counted. We measured the cross section for R-IRMPD under conditions of low intensity, and found it to be approximately two orders smaller than the vibrational excitation cross section. The observed rotational bandwidth of the vibrational transition is larger than the one expected from the combined effects of 300 K black-body temperature, conformer-dependent line shifts, and intermolecular vibrational relaxation broadening (J. Stearns et al., J. Chem. Phys., 2007, 127, 154322-154327). This indicates that as the internal energy of the molecule grows, an increase of the rotational temperature of the molecular ions well above room temperature (up to on the order of 1000 K), and/or an appreciable shift of the vibrational transition frequency (approx. 6-8 cm(-1)) occurs.

Complex biology of constitutional ring chromosomes structure and (in)stability revealed by somatic cell reprogramming.

Human ring chromosomes are often unstable during mitosis, and daughter cells can be partially or completely aneuploid. We studied the mitotic stability of four ring chromosomes, 8, 13, 18, and 22, in long-term cultures of skin fibroblasts and induced pluripotent stem cells (iPSCs) by GTG karyotyping and aCGH. Ring chromosome loss and secondary aberrations were observed in all fibroblast cultures except for r(18). We found monosomy, fragmentation, and translocation of indexed chromosomes. In iPSCs, aCGH revealed striking differences in mitotic stability both between iPSC lines with different rings and, in some cases, between cell lines with the same ring chromosome. We registered the spontaneous rescue of karyotype 46,XY,r(8) to 46,XY in all six iPSC lines through ring chromosome loss and intact homologue duplication with isoUPD(8)pat occurrence, as proven by SNP genotype distribution analysis. In iPSCs with other ring chromosomes, karyotype correction was not observed. Our results suggest that spontaneous correction of the karyotype with ring chromosomes in iPSCs is not universal and that pluripotency is compatible with a wide range of derivative karyotypes. We conclude that marked variability in the frequency of secondary rearrangements exists in both fibroblast and iPSC cultures, expanding the clinical significance of the constitutional ring chromosome.

Atomic force microscopy characterization of corneocytes: effect of moisturizer on their topology, rigidity, and friction.

BACKGROUND/PURPOSE: Atomic force microscopy (AFM) is a novel technique for skin characterization. OBJECTIVES: To develop AFM tests for characterization of the outermost epidermis layer, corneocytes. As an example, the effect of moisturizer on the corneocyte properties is studied. METHODS AND MATERIALS: Topology, rigidity, and friction (between individual corneocytes and AFM probe) of the top layer of corneocytes were measured by means of Veeco DM3100 AFM. Quench moisturizing cream was applied daily on the forearm of five volunteers for a period of 9 days. The skin flakes were collected before and after the treatment using Cuderm tape strips. No additional treatment of flakes was performed before the measurements. RESULTS: A protocol for the AFM study of corneocytes is developed. After the treatment, we observed overall smoothening of the corneocyte surface, an increase of friction, and a decrease of rigidity (the Young modulus). CONCLUSION: AFM can be used as a very sensitive tool for early detection of changes in corneocytes.