Complete and partial time-delay signature suppression in a laser array.

We model dynamics of a quantum dot based micropillar laser array subject to the time-delayed optical feedback. The global coupling provided by the feedback generates a rich set of various instabilities including chaotic regimes with strong time-delay signature in the autocorrelation function. We demonstrate that the dispersion of the array coupling phases leads to effective suppression of the time-delay signature due to the dispersion of the system's internal timescales. We find that the transition to the complete suppression of the time-delay signature appears via a chimera state where highly correlated and non-correlated laser outputs coexist. The degree of correlation in the chimera state depends on the coupling phase dispersion.

Cytotoxic Activity of Macrophages as a Tumor Malignancy Factor.

An experimental cell-based model was developed to study antibody-independent cytotoxic activity of macrophages that allows selection of derivative tumor cells resistant to this activity and clarification of the mechanisms responsible for this selection. Cytotoxic macrophages showing antibody-independent cytotoxic activity were obtained. Derivatives of PC3 and H1299 cells resistant to cytotoxic macrophage activity were generated. The main characteristics of the obtained derivative cells were studied. The proposed experimental model can be used as a tool for studying the mechanisms of the development of tumor cells resistance to antibody-independent cytotoxic activity of macrophages.

The Mechanism of the Development of Macrophage Tolerance in Tumor Microenvironment.

Bacteria forming the resident microbiome of the tumor are an integral component of its microenvironment. The interaction of the tumor microbiome with the tumor or tumor stromal cells is not well understood. We hypothesized that bacteria in the tumor microenvironment induce macrophage tolerance. Macrophage tolerance is a phenomenon of macrophage inability to respond to a repetitive inflammatory stimulus, which leads to a loss of cytotoxic activity. We studied the development of macrophage tolerance under the influence of bacteria and cytokines of the tumor microenvironment in vitro. It was found that the macrophage tolerance in the tumor stroma can develop in response to bacterial cell wall components and inflammatory factors. The acquired tolerance is inability of macrophages to produce proinflammatory cytokines TNFα, IL-1ß, and MCP-1 and activation of the production of immunosuppressive IL-10.

[Parvovirus B19 infection in HIV-infected patients].

Here we provide a review of the literature and a description of our own clinical case. The patient was a 32-year-old woman who had been infected with HIV for 6 years without antiretroviral therapy. The test results showed CD4 87 cells/l, viral load 3750 copies/ml. Normochromic normocytic anemia and reticulocytopenia developed soon. In the myelogram, all erythroblasts were 0.5%. The viral load of parvovirus B19 DNA according to PCR was more than 9 million IU/ml. Pure red cell aplasia associated with parvovirus B19 was diagnosed. We started antiretroviral therapy with efavirenz, lamevudine and tenofovir. In addition to blood transfusions, we administered intravenous donor immunoglobulin with a dose increase from 5000 mg to 20 000 mg per day. After discontinuing of intravenous immunoglobulins, the laboratory test results were stable over the next 5 months: hemoglobin was more than 115 g/L, reticulocytes more than 3%, in the myelogram all erythroblasts were 21%. However, the elimination of parvovirus B19 wasnt achieved. The maximum decrease in viral load for parvovirus B19 was down to 720 IU/ml. A typical feature of the case was the lack of pure red cell aplasia of the bone marrow with the existing viral load of parvovirus B19. HIV infection progressed: 44 cells/l, viral load not determined. The case ended lethally.

[Pure red cell aplasia of the bone marrow in combination with thymoma. A literature review and own data].

Eight patients were observed with a rare combination of thymoma and pure red cell aplasia of bone marrow (PRCA), of which seven women were between 44 to 68 years old. The diagnosis of PRCA was established before the detection of thymoma in 1 patient, simultaneously in 3, after - in 4. Seven patients underwent timomectomy. The weight of removed thymomas was from 200 to 780 grams. Morphological type A thymoma variant (spindle cell) was installed in 2 patients, type B1 - in 2, type B2 - in 2, type B3 - in 2. Complete remissions were obtained using cyclophosphamide and cyclosporin in 5 patients, lasting from 6 months to 7 years. The results of immunological studies with the identification of non - hemolytic antibodies to the proteolytic antigen (Pr1d) on the erythrocyte membrane in 4 patients are presented. Of these, two studied patients simultaneously detected antibodies to the Pr1d antigen and the interspecific antigen of mammalian erythroblasts (IAME). It is shown that the lifespan of red blood cells are not changed. The direct Coombs test was negative in 5 patients, but with the help of aggregate hemaglutination test and enzyme immunoassay, antibodies were detected on the surface of erythrocytes. The pathogenesis of this combination of diseases remains unclear and needs to be elucidated.

Laboratory time-resolved X-ray diffractometry for investigation of reversible structural changes induced in single crystals by external electric field.

Time-resolved technique of X-ray diffraction curve measurement was implemented at a laboratory X-ray source using a high-speed data acquisition system. The time resolution of up to 100 µs was achieved via this X-ray diffractometry technique in the experiment of rocking curve dynamics measurement in a piezoelectric lanthanum-gallium silicate crystal under the influence of high voltage periodic pulsed electric field with an amplitude of 3.08 kV/mm corresponding to the pre-breakdown state. This perturbation caused a quick angular shift of the rocking curve caused by crystal lattice deformation due to the piezoelectric effect. The absence of the diffraction curve broadening effect was shown as well as the absence of the other significant relaxation-like variations of the curve parameters which are inherent for the migration of charge carriers (ions or vacancies) under the external electric field.

Coinheritance of HbD-Punjab/ß+-thalassemia (IVSI+5 G-C) in patient with Gilbert's syndrome.

Thalassemia and qualitative hemoglobinopathy are hereditary disorders of Hb synthesis that lead to change in the Hb conformation or a decrease in the synthesis of structurally normal Hb, and consequently, to erythron pathology. Many variants of Hb are unstable or have altered affinity for oxygen, and, in heterozygous form can be associated with clinical and hematological manifestations (hemolytic anemia, hypochromic microcytic anemia, erythrocytosis). HbD-Punjab [ß121 (GH4) Glu → Gln; HBB: C.364G> C] is variant of Hb carrying the amino acid substitution in the 121 position of ß-globin chain. In all cases reported so far, patients with HbD-Punjab/ß+-thalassemia (IVSI+5 G-C) combination experienced typical thalassemia with hypochromic microcytosis. HbD-Punjab was detected by electrophoresis from 37 to 94% of total Hb. The article describes rare clinical case of the cohabitation of HbD-Punjab/ß+-thalassemia (IVSI+5 G-C) in a patient with homozygous variant of Gilbert's syndrome observed in AS Loginov Moscow Clinical Scientific Center.

Cervical intraepithelial neoplasia: Telomerase activity and splice pattern of hTERT mRNA.

Cervical cancers are characterized by the persistence of human papilloma virus (HPV) genome that is found in tissue samples starting from the early stages of tumor progression. Just like in other tumors, the activation of telomerase was observed in cervical carcinomas, but information about its expression was controversial. The aim of this study is to find possible correlations between the presence of HPV sequences, activity of telomerase and expression of different spliced forms of hTERT RNA in cervical intraepithelial neoplasias (CIN). The results show that HPV DNA is present in 60% of normal tissue adjacent to CIN lesions and up to 84% in CIN samples. Telomerase activity was found in 28% of adjacent normal tissue and in 68% of CIN II-III. hTERT RNA that encodes an active enzyme was present almost in all CIN samples. Variations in levels of telomerase activity are possibly not regulated by the splicing forms of hTERT mRNA with deletions.

[Telomerase level versus spliced hTERT-specific RNA forms in cervical carcinoma].

An attempt was made to identify molecular markers of different clinical stages of cervical carcinoma caused by papilloma virus (HPV). Presence of viral genome, telomerase level and expression of a gene, which coded the catalytic activity of that enzyme (hTERT), were assayed in 89 patients. HPV (type 16) genome harboring tumors were detected in 73% which was in conformity with the literature and our own data. Telomerase was identified (TRAP) in all tumors and tumor cells cultured in vitro. hTERT-specific RNA was found in all tumor samples, however, increase in its expression was insignificant. As far as the three markers are concerned, no significant differences between clinical stages of tumor were reported.

STAT1 gene expression in cervical carcinomas.

Expression of the STAT1 gene belonging to the group of interferon-regulated genes was analyzed in cervical tumors and cell lines harboring the genome of human papilloma viruses (HPV) of so-called high risk group. Expression of this gene in invasive carcinomas was maintained on a definite level that was not significantly distinct from that in adjacent normal (control) tissue. Tumors from different patients differ from each other by expression level of the STAT1 gene. These variations can be attributed to the heterogeneity of tumor cell population and different ratio between normal and tumor cells, as well as to putative persistence of intra-individual variability of STAT1 expression in normal cell population. It was demonstrated that viral genome status (episomal or integrative) did not influence STAT1 gene transcription. In conclusion, these data demonstrate that the STAT1 gene is expressed in an individual and specific manner both in HPV-positive cervical tumors and cell lines harboring transforming genes of these viruses.

Downregulation of genes encoding for subunits of adaptor complex-3 in cervical carcinomas.

We explored the expression of four genes encoding for subunits of AP-3 in cervical tumors and cancer cell lines. Using RT-PCR we demonstrated more than twofold decrease in the levels of mRNA of AP3D1, AP3B1, AP3M1, and AP3S1 in 32, 28, 23, and 26% tumors in comparison with normal tissues of uterine cervix, respectively. The level of mRNA of at least one subunit was decreased in 28 out of 47 (60%) of tumors and in four out of five cancer cell lines in comparison to tissues adjacent to tumors. The suppression of expression of any of the subunits was revealed in 15 out of 28 cases (54%). The expression of two and more subunits was decreased simultaneously in different combinations in 13 cases (46%). This fact testifies to the lack of a common mechanism of downregulation of four subunits in tumors. There is a tendency to more frequent suppression of AP-3A expression in tumors associated with lymphatic node metastases as compared with tumors without metastases (P = 0.034). Thus, here we demonstrate for the first time the decrease in expression of genes encoding for AP-3A subunits in tumors.

[Molecular markers of the cervical cancer]. / Molekuliarnye markery raka sheiki matki.

The genome of human papilloma viruses from a high-risk group (HPV types 16 and 18) has been detected in 90% of cervical tumors and, in some cases, in the adjacent normal tissues. The presence of viral DNA is the main molecular marker of this neoplasia. HPV genome may persist in the tumors as episomal and integrative forms at early and late stages of tumor progression. The status of viral DNA and the pattern of its expression are similar in all cells of this tumor cell population and seem to be a marker of tumor cell monoclonality. Antibodies to the products of viral oncogenes E6 and E7 were found only in 35% of the patients with tumor where HPV genome is present. Thus, this criteria cannot be used for diagnostic and prognostic purposes. On chromosome 6 in the cervical tumors, the specific marker of heterozygocity on loci 6p21.3 was found. The marker appears at the precancer stage and may be regarded as a marker of tumor monoclonality. Heterozygocity loss in the specific locus in the region 6q16-21 correlates with tumor progression and suggests that there are potential tumor-suppressor genes in this region of chromosome 6. A group of HPV positive tumors with a hypermethylator phenotype is described. These tumors are characterized by the simultaneous methylation and inactivation of multiple genes, including tumor suppressor genes.