Rapid selection of BRCA1-proficient tumor cells during neoadjuvant therapy for ovarian cancer in BRCA1 mutation carriers

Ovarian carcinomas (OC) often demonstrate rapid tumor shrinkage upon neoadjuvant chemotherapy (NACT). However, complete pathologic responses are very rare and the mechanisms underlying the emergence of residual tumor disease remain elusive. We hypothesized that the change of somatic BRCA1 status may contribute to this process. The loss-of-heterozygosity (LOH) at the BRCA1 locus was determined for 23 paired tumor samples obtained from BRCA1 germ-line mutation carriers before and after NACT. We observed a somatic loss of the wild-type BRCAI allele in 74% (17/23) of OCs before NACT. However, a retention of the wild-type BRCA1 copy resulting in a reversion of LOH status was detected in 65% (11/17) of those patients after NACT. Furthermore, we tested 3 of these reversion samples for LOH at intragenic BRCA1single nucleotide polymorphisms (SNPs) and confirmed a complete restoration of the SNP heterozygosity in all instances. The neoadjuvant chemotherapy for BRCA1-associated OC is accompanied by a rapid expansion of pre-existing BRCA1-proficient tumor clones suggesting that continuation of the same therapy after NACT and surgery may not be justified even in patients initially experiencing a rapid tumor regression. (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe

High genetic diversity of measles virus, World Health Organization European region, 2005-2006

During 2005-2006, nine measles virus (MV) genotypes were identified throughout the World Health Organization European Region. All major epidemics were associated with genotypes D4, D6, and B3. Other genotypes (B2, D5, D8, D9, G2, and H1) were only found in limited numbers of cases after importation from other continents. The genetic diversity of endemic D6 strains was low; genotypes C2 and D7, circulating in Europe until recent years, were no longer identified. The transmission chains of several indigenous MV strains may thus have been interrupted by enhanced vaccination. However, multiple importations from Africa and Asia and virus introduction into highly mobile and unvaccinated communities caused a massive spread of D4 and B3 strains throughout much of the region. Thus, despite the reduction of endemic MV circulation, importation of MV from other continents caused prolonged circulation and large outbreaks after their introduction into unvaccinated and highly mobile communities

Analysis of a waveguide T-junction with a 2D scatterer in the interaction region via Green's theorem approach

A rigorous method for solving 2D scattering by a PEC obstacle of arbitrary cross-section shape within an interaction region of waveguide T-junction is presented. The method extends the conventional Green's theorem approach by using the weight functions, which satisfy not only the wave equation but also the boundary conditions on the scatterer's boundary. Sample results for a rectangular metal insert are presented. The procedure developed is useful for the optimization of waveguide joints

High genetic diversity of measles virus, World Health Organization European Region, 2005-2006

During 2005-2006, nine measles virus (MV) genotypes were identified throughout the World Health Organization European Region. All major epidemics were associated with genotypes D4, D6, and B3. Other genotypes (B2, D5, D8, D9, G2, and H1) were only found in limited numbers of cases after importation from other continents. The genetic diversity of endemic D6 strains was low; genotypes C2 and D7, circulating in Europe until recent years, were no longer identified. The transmission chains of several indigenous MV strains may thus have been interrupted by enhanced vaccination. However, multiple importations from Africa and Asia and virus introduction into highly mobile and unvaccinated communities caused a massive spread of D4 and B3 strains throughout much of the region. Thus, despite the reduction of endemic MV circulation, importation of MV from other continents caused prolonged circulation and large outbreaks after their introduction into unvaccinated and highly mobile communities

Обнаружение и маскирование вредоносных подсхем в последовательностных схемах

Inserting malicious sub-circuits that may destroy a logical circuit or provide leakage of confidential information from a system containing the logical circuit demands detection of such sub-circuits followed their masking if possible. We suggest a method of finding a set of sequential circuit nodes in which Trojan Circuits (TC) may be inserted. After simulating the sequential circuit on the proper input sequences we may find TC if it is present and mask it by the special sub-circuit. The method is based on applying the precise (not heuristic) random estimations of internal nodes control-lability and observability calculated with using a structural description of the combinational part of the sequential cir-cuit. These estimations are computed with applying a State Transition Graph (STG) description, if we suppose that TC may be inserted out of the working area (out of the specification) of the sequential circuit. In addition the algorithms of transfer sequence detection for a set of internal states are used. Reduced Ordered Binary Decision Diagrams (ROBDDs) for the combinational part and its fragments are applied for getting both the estimations and transfer se-quences by means of operations on ROBDDs. It is known that these operations have a polynomial complexity. Note that if TCs are inserted out of the working area, they cannot be detected both under verification and testing in the working area. Techniques of masking TCs are proposed. The experimental results on ISCAS and MCNC benchmarks show applicability of the approach. Masking sub-circuits overhead is appreciated

Обнаружение и маскирование вредоносных подсхем в последовательностных схемах

Inserting malicious sub-circuits that may destroy a logical circuit or provide leakage of confidential information from a system containing the logical circuit demands detection of such sub-circuits followed their masking if possible. We suggest a method of finding a set of sequential circuit nodes in which Trojan Circuits (TC) may be inserted. After simulating the sequential circuit on the proper input sequences we may find TC if it is present and mask it by the special sub-circuit. The method is based on applying the precise (not heuristic) random estimations of internal nodes control-lability and observability calculated with using a structural description of the combinational part of the sequential cir-cuit. These estimations are computed with applying a State Transition Graph (STG) description, if we suppose that TC may be inserted out of the working area (out of the specification) of the sequential circuit. In addition the algorithms of transfer sequence detection for a set of internal states are used. Reduced Ordered Binary Decision Diagrams (ROBDDs) for the combinational part and its fragments are applied for getting both the estimations and transfer se-quences by means of operations on ROBDDs. It is known that these operations have a polynomial complexity. Note that if TCs are inserted out of the working area, they cannot be detected both under verification and testing in the working area. Techniques of masking TCs are proposed. The experimental results on ISCAS and MCNC benchmarks show applicability of the approach. Masking sub-circuits overhead is appreciated

Appearance of a novel measles G3 strain in multiple European countries within a two month period, 2010

During late 2010, a previously unrecognised strain of measles genotype G3 virus was identified in five different European countries by the World Health Organization Measles and Rubella Laboratory Network. Apart from one, none had a travel history to south-east Asia, the usual source of G3 viruses, although epidemiological links could be established between some of the cases. This case series illustrates the value of genotyping and sequencing in tracking measles infections, and identifying otherwise unrecognised chains of transmission

Synergistic Effect of the Combination of the Recombinant Toxin DARPin-LoPE and PDT against HER2-Positive Breast Cancer In Vitro

A promising strategy to enhance the therapeutic effectiveness for the treatment of oncological diseases involves the development of combined therapeutic schemes. In our work, we showed the therapeutic potential of the combined action of the anticancer targeted toxin and PDT against HER2-positive breast cancer in vitro. Photodynamic treatment led to photoinduced cell death with IC50 0.64 µM, and after incubation with the toxin for 48 h, IC50 was 2.8 pM. When using two therapeutic agents at IC50 doses, significant increases in the effectiveness were observed; the viability of the combination-treated cell culture did not exceed 10%. The calculated combination index was 0.07, indicating a significant synergistic effect caused by the agents

Different Approaches to Produce Transgenic Virus B Resistant Chrysanthemum

Chrysanthemum is a vegetative propagated culture in which viral transmission with planting material is important for its production. Chrysanthemum virus B (CVB) belongs to the viruses that strike this plant culture. Chrysanthemum virus B is found everywhere where chrysanthemum is cultivated. Damage to plants by CVB often leads to a complete loss of floral yield. Chrysanthemum (Chrysanthemum morifolium Ramat cv. White Snowdon) was transformed via Agrobacterium-mediated DNA delivery with the aim of improving resistance to CVB infection. Transformation vectors contain the nucleotide sequence of CVB coat proteins (CP) in sense, antisense, and double sense orientation. The transformative vectors also invert repeats of CVB coat protein gene fragments for the induction of RNA-interference. The transgenic chrysanthemum plants were successfully obtained. The integration of the target sequences in plant genomes was confirmed by polymerase chain reaction (PCR) and Southern blot analyses. Chrysanthemum lines were transformed with antisense, sense, and double sense CVB CP sequences, as well as with hairpin RNA-interference constructs that were assayed for resistance to CVB. Infection of transgenic plants by CVB through the grafting of infected scions shows resistance only among plants with carried double sense (16.7%) and hairpin (12.5%) constructs. The plants transformed by sense and double sense sequences were observed and classified as tolerant

Mechanical and Water Absorption Properties of Waterborne Polyurethane/Graphene Oxide Composites

Nanocomposites based on waterborne polyurethane (WPU) and graphene oxide (GO) have been synthesized and characterized. It was found that after the incorporation of GO, WPU films became mechanically more rigid, and the Young’s modulus increased by almost six times. It is shown that the lateral size of GO sheets influences the mechanical properties of WPU/GO composites. In particular, composites with larger lateral size of GO sheets have higher values of Young’s modulus. Additionally, if the mechanical properties are improved with the addition of GO additive, then water absorption decreases for WPU modified with small GO sheets whereas it increases for WPU modified with large GO sheets. Possible reasons for this behavior are discussed