Effects of inhomogeneous broadening on reflection spectra of Bragg multiple quantum well structures with a defect

The reflection spectrum of a multiple quantum well structure with an inserted defect well is considered. The defect is characterized by the exciton frequency different from that of the host's wells. It is shown that for relatively short structures, the defect produces significant modifications of the reflection spectrum, which can be useful for optoelectronic applications. Inhomogeneous broadening is shown to affect the spectrum in a non-trivial way, which cannot be described by the standard linear dispersion theory. A method of measuring parameters of both homogeneous and inhomogeneous broadenings of the defect well from a single CW reflection spectrum is suggested.Comment: 27 pages, 6 eps figures; RevTe

ГЕОДИНАМИЧЕСКАЯ МОДЕЛЬ ВЗАИМОДЕЙСТВИЯ ЗОНЫ СУБДУКЦИИ С КОНТИНЕНТАЛЬНОЙ ЛИТОСФЕРОЙ В ОБЛАСТИ ПЕРЕХОДА ОТ ТИХОГО ОКЕАНА К ВОСТОЧНОЙ АЗИИ

East Asia is the vast region of Asia which is characterized by a complex geological structure and high activity of seismic and tectonic processes. Satellite geodetic data, reflecting the recent crustal movements in the region, demonstrate a considerable variability in magnitude and direction of motions both along the strike of island-arc margins and deep into the continent. To explain the anomalies in the Earth's surface displacement field, the paper proposes a geodynamic model of East Asia which involves the mechanism of interaction between the continental lithosphere of the region and the continent-to-ocean transition area along the Kuril-Kamchatka and Japanese island arcs. The proposed concept includes the model of the upper-mantle convective cell, developing beneath the continental lithosphere, in combination with the keyboard-block model explaining the regularities of seismic cycle in the island-arc margins. It has been shown that the consideration of interaction between the lithosphere and upper mantle in the continent-to-ocean transition area in the framework of the model of non-stationary convective cell allows us to explain the recent crustal movements observed up to a distance of 2000 km and the seismic tomography data without involving additional lithospheric blocks. The model contributes to the development of the physically grounded geodynamic approach to the analysis of recent tectonics and eliminates the inconsistencies between the observed data and classical plate tectonics in East Asia.Регион Восточной Азии характеризуется сложным геологическим строением и высокой сейсмической и тектонической активностью. Данные спутниковой геодезии, отражающие современные движения земной поверхности региона, демонстрируют существенную изменчивость по величине и направлению как вдоль простирания островодужных окраин, так и в глубь континента. В работе для объяснения аномалий поля смещений земной поверхности предлагается геодинамическая модель Восточной Азии, учитывающая механизм взаимодействия континентальной литосферы региона и переходной зоны континент – океан вдоль Курило-Камчатской и Японской островных дуг. Представленная концепция включает в себя модель верхнемантийной конвективной ячейки, развивающейся под континентальной литосферой, в сочетании с клавишно-блоковой моделью, объясняющей закономерности сейсмического цикла в островодужных окраинах. Показано, что учет взаимодействия литосферы и верхней мантии в зоне перехода континент – океан позволяет в рамках модели нестационарной конвективной ячейки объяснить наблюдающиеся на удалении до 2000 км современные движения земной поверхности и данные сейсмической томографии без привлечения дополнительных литосферных блоков. Модель способствует развитию физически обоснованного геодинамического подхода к анализу современной тектоники и позволяет устранить противоречия между наблюдаемыми данными и классической тектоникой плит в регионе Восточной Азии

Microsatellite Instability in Pediatric High Grade Glioma Is Associated with Genomic Profile and Differential Target Gene Inactivation

High grade gliomas (HGG) are one of the leading causes of cancer-related deaths in children, and there is increasing evidence that pediatric HGG may harbor distinct molecular characteristics compared to adult tumors. We have sought to clarify the role of microsatellite instability (MSI) in pediatric versus adult HGG. MSI status was determined in 144 patients (71 pediatric and 73 adults) using a well established panel of five quasimonomorphic mononucleotide repeat markers. Expression of MLH1, MSH2, MSH6 and PMS2 was determined by immunohistochemistry, MLH1 was assessed for mutations by direct sequencing and promoter methylation using MS-PCR. DNA copy number profiles were derived using array CGH, and mutations in eighteen MSI target genes studied by multiplex PCR and genotyping. MSI was found in 14/71 (19.7%) pediatric cases, significantly more than observed in adults (5/73, 6.8%; p = 0.02, Chi-square test). MLH1 expression was downregulated in 10/13 cases, however no mutations or promoter methylation were found. MSH6 was absent in one pediatric MSI-High tumor, consistent with an inherited mismatch repair deficiency associated with germline MSH6 mutation. MSI was classed as Type A, and associated with a remarkably stable genomic profile. Of the eighteen classic MSI target genes, we identified mutations only in MSH6 and DNAPKcs and described a polymorphism in MRE11 without apparent functional consequences in DNA double strand break detection and repair. This study thus provides evidence for a potential novel molecular pathway in a proportion of gliomas associated with the presence of MSI

Oxidative stress and proinflammatory cytokines contribute to demyelination and axonal damage in a cerebellar culture model of neuroinflammation

Background: Demyelination and axonal damage are critical processes in the pathogenesis of multiple sclerosis (MS). Oxidative stress and pro-inflammatory cytokines elicited by inflammation mediates tissue damage. Methods/Principal Findings: To monitor the demyelination and axonal injury associated with microglia activation we employed a model using cerebellar organotypic cultures stimulated with lipopolysaccharide (LPS). Microglia activated by LPS released pro-inflammatory cytokines (IL-1β, IL-6 and TNFα), and increased the expression of inducible nitric oxide synthase (iNOS) and production of reactive oxygen species (ROS). This activation was associated with demyelination and axonal damage in cerebellar cultures. Axonal damage, as revealed by the presence of non-phosphorylated neurofilaments, mitochondrial accumulation in axonal spheroids, and axonal transection, was associated with stronger iNOS expression and concomitant increases in ROS. Moreover, we analyzed the contribution of pro-inflammatory cytokines and oxidative stress in demyelination and axonal degeneration using the iNOS inhibitor ethyl pyruvate, a free-scavenger and xanthine oxidase inhibitor allopurinol, as well as via blockage of pro-inflammatory cytokines using a Fc-TNFR1 construct. We found that blocking microglia activation with ethyl pyruvate or allopurinol significantly decreased axonal damage, and to a lesser extent, demyelination. Blocking TNFα significantly decreased demyelination but did not prevented axonal damage. Moreover, the most common therapy for MS, interferon-beta, was used as an example of an immunomodulator compound that can be tested in this model. In vitro, interferon-beta treatment decreased oxidative stress (iNOS and ROS levels) and the release of pro-inflammatory cytokines after LPS stimulation, reducing axonal damage. Conclusion: The model of neuroinflammation using cerebellar culture stimulated with endotoxin mimicked myelin and axonal damage mediated by the combination of oxidative stress and pro-inflammatory cytokines. This model may both facilitate understanding of the events involved in neuroinflammation and aid in the development of neuroprotective therapies for the treatment of MS and other neurodegenerative diseases

Detection of recurrent rearrangement breakpoints from copy number data

<p>Abstract</p> <p>Background</p> <p>Copy number variants (CNVs), including deletions, amplifications, and other rearrangements, are common in human and cancer genomes. Copy number data from array comparative genome hybridization (aCGH) and next-generation DNA sequencing is widely used to measure copy number variants. Comparison of copy number data from multiple individuals reveals recurrent variants. Typically, the interior of a recurrent CNV is examined for genes or other loci associated with a phenotype. However, in some cases, such as gene truncations and fusion genes, the target of variant lies at the boundary of the variant.</p> <p>Results</p> <p>We introduce Neighborhood Breakpoint Conservation (NBC), an algorithm for identifying rearrangement breakpoints that are highly conserved at the same locus in multiple individuals. NBC detects recurrent breakpoints at varying levels of resolution, including breakpoints whose location is exactly conserved and breakpoints whose location varies within a gene. NBC also identifies pairs of recurrent breakpoints such as those that result from fusion genes. We apply NBC to aCGH data from 36 primary prostate tumors and identify 12 novel rearrangements, one of which is the well-known TMPRSS2-ERG fusion gene. We also apply NBC to 227 glioblastoma tumors and predict 93 novel rearrangements which we further classify as gene truncations, germline structural variants, and fusion genes. A number of these variants involve the protein phosphatase PTPN12 suggesting that deregulation of PTPN12, via a variety of rearrangements, is common in glioblastoma.</p> <p>Conclusions</p> <p>We demonstrate that NBC is useful for detection of recurrent breakpoints resulting from copy number variants or other structural variants, and in particular identifies recurrent breakpoints that result in gene truncations or fusion genes. Software is available at <url>http://http.//cs.brown.edu/people/braphael/software.html</url>.</p

Sequence comparison of prefrontal cortical brain transcriptome from a tame and an aggressive silver fox (Vulpes vulpes)

<p>Abstract</p> <p>Background</p> <p>Two strains of the silver fox (<it>Vulpes vulpes</it>), with markedly different behavioral phenotypes, have been developed by long-term selection for behavior. Foxes from the tame strain exhibit friendly behavior towards humans, paralleling the sociability of canine puppies, whereas foxes from the aggressive strain are defensive and exhibit aggression to humans. To understand the genetic differences underlying these behavioral phenotypes fox-specific genomic resources are needed.</p> <p>Results</p> <p>cDNA from mRNA from pre-frontal cortex of a tame and an aggressive fox was sequenced using the Roche 454 FLX Titanium platform (> 2.5 million reads & 0.9 Gbase of tame fox sequence; >3.3 million reads & 1.2 Gbase of aggressive fox sequence). Over 80% of the fox reads were assembled into contigs. Mapping fox reads against the fox transcriptome assembly and the dog genome identified over 30,000 high confidence fox-specific SNPs. Fox transcripts for approximately 14,000 genes were identified using SwissProt and the dog RefSeq databases. An at least 2-fold expression difference between the two samples (p < 0.05) was observed for 335 genes, fewer than 3% of the total number of genes identified in the fox transcriptome.</p> <p>Conclusions</p> <p>Transcriptome sequencing significantly expanded genomic resources available for the fox, a species without a sequenced genome. In a very cost efficient manner this yielded a large number of fox-specific SNP markers for genetic studies and provided significant insights into the gene expression profile of the fox pre-frontal cortex; expression differences between the two fox samples; and a catalogue of potentially important gene-specific sequence variants. This result demonstrates the utility of this approach for developing genomic resources in species with limited genomic information.</p

Tracking CNS and systemic sources of oxidative stress during the course of chronic neuroinflammation

The functional dynamics and cellular sources of oxidative stress are central to understanding MS pathogenesis but remain elusive, due to the lack of appropriate detection methods. Here we employ NAD(P)H fluorescence lifetime imaging to detect functional NADPH oxidases (NOX enzymes) in vivo to identify inflammatory monocytes, activated microglia, and astrocytes expressing NOX1 as major cellular sources of oxidative stress in the central nervous system of mice affected by experimental autoimmune encephalomyelitis (EAE). This directly affects neuronal function in vivo, indicated by sustained elevated neuronal calcium. The systemic involvement of oxidative stress is mirrored by overactivation of NOX enzymes in peripheral CD11b(+) cells in later phases of both MS and EAE. This effect is antagonized by systemic intake of the NOX inhibitor and anti-oxidant epigallocatechin-3-gallate. Together, this persistent hyper-activation of oxidative enzymes suggests an "oxidative stress memory" both in the periphery and CNS compartments, in chronic neuroinflammation

Real-space collapse of a polariton condensate

Microcavity polaritons are two-dimensional bosonic fluids with strong nonlinearities, composed of coupled photonic and electronic excitations. In their condensed form, they display quantum hydrodynamic features similar to atomic Bose–Einstein condensates, such as long-range coherence, superfluidity and quantized vorticity. Here we report the unique phenomenology that is observed when a pulse of light impacts the polariton vacuum: the fluid which is suddenly created does not splash but instead coheres into a very bright spot. The real-space collapse into a sharp peak is at odd with the repulsive interactions of polaritons and their positive mass, suggesting that an unconventional mechanism is at play. Our modelling devises a possible explanation in the self-trapping due to a local heating of the crystal lattice, that can be described as a collective polaron formed by a polariton condensate. These observations hint at the polariton fluid dynamics in conditions of extreme intensities and ultrafast times

Эффективность и безопасность эрибулина при различных подтипах рака молочной железы: данные из реальной клинической практики в России

The article presents a pooled experience of the use of eribulin in the real clinical practice of treatment of metastatic breast cancer in Russian oncological institutions. The effectiveness of the drug in monotherapy with HER2‑negative breast cancer was analyzed, groups of patients with most effective use of eribulin were identified depending on the localization of metastases, the most effective lines of therapy. The effectiveness of the drug in combination with trastuzumab in HER2‑positive breast cancer is described, as well as toxic reactions. В статье представлен обобщенный опыт применения эрибулина в реальной клинической практике онкологических учреждений РФ при метастатическом раке молочной железы. Проанализирована эффективность препарата в монотерапии при HER2-отрицательном раке молочных желез, выделены группы больных в зависимости от локализации метастазов, линии терапии, в которых препарат оказался максимально эффективным. Описана эффективность препарата в комбинации с трастузумабом при HER2-положительном раке молочной железы, а также токсические реакции. 

ЭФФЕКТИВНОСТЬ ПОДДЕРЖИВАЮЩЕЙ ТЕРАПИИ ПОСЛЕ ОКОНЧАНИЯ ПЕРВОЙ ЛИНИИ ЛЕЧЕНИЯ БОЛЬНЫХ МЕТАСТАТИЧЕСКИМ РАКОМ ТОЛСТОЙ КИШКИ – РЕЗУЛЬТАТЫ ПОПУЛЯЦИОННОГО ИССЛЕДОВАНИЯ

Aim. To evaluate the effectiveness of different regimens of maintenance chemotherapy after the first line of treatment for patients with metastatic colorectal cancer.Materials and methods. We performed retrospective analyses of the data from 432 patients from 17 clinics in 14 regions of the Russian Federation who started systemic therapy for metastatic cancer in 2013. The main inclusion criterion was objective response or stabilization after the first 16 weeks of first-line therapy. Four groups of patients were compared, depending on the nature of maintenance therapy: those receiving fluoropyrimidines, a combination of fluoropyrimidines with bevacizumab, monotherapy of bevacizumab and monotherapy of anti-EGFR antibodies. The main criteria for assesment of the effectiveness of treatment were progression-free survival and overall survival. The statistical analysis was performed with the SPSS 20.0 sof tware package.Results. Maintenance therapy after completion of the first 16 weeks of the 1st line of chemotherapy was administered in 126 patients, most of them were treated with fluoropyrimidines (53.1 %). The median overall survival in the maintenance group was 27 versus 21 months in the observation group, p=0.01, HR=0.78 (95 % CI 0.6–1.02) Median progression-free survival in the maintenance group was 11 vs 7 months in the observation group (p&lt;0.001, HR=0.6, 95 % CI 0.5–0.8). The worst results of progression-free survival were observed in the group with monotherapy of bevacizumab – median was 10 months versus 12 months in the fluoropyrimidine monotherapy group, 10 months for the combination of fluoropyrimidine with bevacizumab and 14 months for monotherapy of the anti-EGFR (p=0,9, HR=1.0, 95 % CI 0.9–1.2).Conclusions. There were no statistical differences in survival with different regimens of maintenance therapy. Monotherapy of bevacizumab in maintenance treatment was associated with the worst sur vival rates.Цель. Оценить эффективность различных режимов поддерживающей терапии после окончания первой линии лечения больных метастатическим раком толстой кишки.Материалы и методы. Проведен анализ индивидуальных карт 432 пациентов 17 клиник 14 регионов РФ, которые начали терапию по поводу метастатического рака в 2013 г. Основным критерием отбора в исследование являлось отсутствие прогрессирования в течение первых 16 нед. терапии первой линии. Проведено сравнение четырех групп пациентов в зависимости от характера поддерживающей терапии: получавших фторпиримидины, комбинацию фторпиримидинов с бевацизумабом, бевацизумаб в монорежиме и анти-EGFR антитела. Основными критериями оценки эффективности лечения считались выживаемость без прогрессирования и общая выживаемость. Статистический анализ проводился в пакете программ SPSS 20.0.Результаты. Поддерживающая терапия после завершения первой линии лечения была назначена 126 пациентам, большинству проводилась терапия фторпиримидинами (53,1 %). Медиана продолжительности жизни в группе поддерживающей терапии составила 27 мес. против 21 мес. в группе наблюдения (р=0,01, ОР=0,78, 95 % ДИ 0,6–1,02). Медиана выживаемости без прогрессирования – 11 против 7 мес. (p&lt;0,001, ОР=0,6, 95 % ДИ 0,5–0,8). Наихудшие результаты выживаемости без прогрессирования наблюдались в группе поддерживающего лечения мототерапии бевацизумабом: медиана 10 мес. против 12 мес. в группе монотерапии фторпиримидинами, 10 мес. в группе комбинации фторпиримидинов с бевацизумабом и 14 мес. в группе монотерапии анти-EGFR антителами (р=0,9, ОР=1,0, 95 % ДИ 0,9–1,2).Выводы. Не получено статистических различий в выживаемости при применении различных режимов поддерживающей терапии. Монотерапия бевацизумабом в поддерживающем лечении была ассоциирована с наименьшими показателями выживаемости пациентов