Pulmonary DWCNT Exposure Causes Sustained Local and Low-Level Systemic Inflammatory Changes in Mice

Carbon nanotubes (CNTs) represent promising vectors to facilitate cellular drug delivery and to overcome biological barriers, but some types may also elicit persistent pulmonary inflammation based on their fibre characteristics. Here, we show the pulmonary response to aqueous suspensions of block copolymer dispersed, double-walled carbon nanotubes (DWCNT, length 1–10 lm) in mice by bronchoalveolar lavage (BAL) analysis, and BAL and blood cytokine and lung antioxidant profiling. The intratracheally instilled dose of 50 lg DWCNT caused significant pulmonary inflammation that was not resolved during a 7- day observation period. Light microscopy investigation of the uptake of DWCNT agglomerates revealed no particle ingestion for granulocytes, but only for macrophages. Accumulating macrophage, multinucleated macrophage and lymphocyte numbers in the alveolar region further indicated ineffective resolution with chronification of the inflammation. The local inflammatory impairment of the lung was accompanied by pulmonary antioxidant depletion and haematological signs of systemic inflammation. While the observed inflammation during its acute phase was dominated by neutrophils and neutrophil recruiting cytokines, the contribution of macrophages and lymphocytes with related cytokines became more significant after day 3 of exposure. This study confirms that acute pulmonary toxicity can occur on exposure of high doses of DWCNT agglomerates and offers further insight for improved nanotube design parameters to avoid potential long-term toxicity

Ghajn Klieb, (Rabat, Malta)

Between October and December 1999 a team of local and foreign undergraduates from the University of Malta carried out a survey of the site at Ghajn Klieb outside Rabat. The exercise constituted the practical part of a unit on the Principles of Archaeological Surveying directed by Dr Nicholas Vella of the Department of Classics & Archaeology. For the survey the team was joined by Hanna Stager, a graduate of the same department, who also researched some of the references used in this article. Initial reconnaissance of the site was carried out on 15 October 1999 with Nathaniel Cutajar and Michelle B uhagiar, Curator and Assistant Curator respectively at the National Museum of Archaeology. The scatter of surface ceramics and the existence of previously known and unknown features revealed the extent and potential of the site. It was decided that the locality of Ghajn Klieb warranted systematic study that could be carried out in various stages, with the longterm aim being an assessment of human activity and cultural behaviour at the site. The Museums Department gave the go-ahead for this project, and permission to collect the surface ceramics was granted. This short report is intended to give an outline of the work undertaken to date. Emphasis is placed on the field methods adopted and on the presentation of what we believe to be worth talking about at this stage. An effort is here made by the senior author to unravel the collaborative nature of the exercise by lending weight to individual thoughts and interpretations that arose while work progressed in the field.peer-reviewe

Інформаційне законодавство. Основні нормативні акти

Наведено основні нормативні акти з регулювання інформаційних відносин, зокрема, у сфері інформації, інформаційних агентств, телекомунікації, радіочастотного ресурсу України, інформатизації, телебачення тощо. Розраховано на студентів, які здобувають вищу освіту в галузях знань "Право", "Інформаційна безпека", "Комп'ютерні науки", "Телекомунікації"

Errors in the bisulfite conversion of DNA: modulating inappropriate- and failed-conversion frequencies

Bisulfite treatment can be used to ascertain the methylation states of individual cytosines in DNA. Ideally, bisulfite treatment deaminates unmethylated cytosines to uracils, and leaves 5-methylcytosines unchanged. Two types of bisulfite-conversion error occur: inappropriate conversion of 5-methylcytosine to thymine, and failure to convert unmethylated cytosine to uracil. Conventional bisulfite treatment requires hours of exposure to low-molarity, low-temperature bisulfite (‘LowMT’) and, sometimes, thermal denaturation. An alternate, high-molarity, high-temperature (‘HighMT’) protocol has been reported to accelerate conversion and to reduce inappropriate conversion. We used molecular encoding to obtain validated, individual-molecule data on failed- and inappropriate-conversion frequencies for LowMT and HighMT treatments of both single-stranded and hairpin-linked oligonucleotides. After accounting for bisulfite-independent error, we found that: (i) inappropriate-conversion events accrue predominantly on molecules exposed to bisulfite after they have attained complete or near-complete conversion; (ii) the HighMT treatment is preferable because it yields greater homogeneity among sites and among molecules in conversion rates, and thus yields more reliable data; (iii) different durations of bisulfite treatment will yield data appropriate to address different experimental questions; and (iv) conversion errors can be used to assess the validity of methylation data collected without the benefit of molecular encoding

Агрегирование и обработка текстовой информации с нефиксированной структурой

Данный документ посвящен исследованию агрегирования и анализа текстов на предмет формирования тем всех документов в целом. Целью работы является исследование возможности агрегирования и анализа текстов при помощи решения задачи тематического моделирования через построение иерархической модели методами индуктивного обучения, а также реализация низкоуровневого компонента иерархической системы. Актуальность работы заключается в возможностях исследования и использования нового метода анализа текстов, базирующегося на иерархическом подходе к анализу. В работе рассматривались следующие вопросы: - Обзор предметной области - Проектирование решения - Реализация низкоуровневого компонента В результате была спроектирована система для агрегирования текстов, и реализована ее низкоуровневый компонент.This document focuses on the study of the aggregation and analysis of texts in order to form the themes of all documents in general. The purpose of this work is to study the possibility of aggregation and analysis of texts by solving the problem of topic modeling with hierarchical model using inductive learning methods, and implementation of a low-level component of a hierarchical system. The relevance of the work lies in the possibilities of research and the use of a new text analysis method based on a hierarchical approach to analysis. The work addressed the following questions: - Overview of the subject area - Software design - Implementation of the low-level component As a result, a system was designed for aggregation of the texts, and its low-level component is implemented

In situ methods to localize transgenes and transcripts in interphase nuclei: a tool for transgenic plant research

Genetic engineering of commercially important crops has become routine in many laboratories. However, the inability to predict where a transgene will integrate and to efficiently select plants with stable levels of transgenic expression remains a limitation of this technology. Fluorescence in situ hybridization (FISH) is a powerful technique that can be used to visualize transgene integration sites and provide a better understanding of transgene behavior. Studies using FISH to characterize transgene integration have focused primarily on metaphase chromosomes, because the number and position of integration sites on the chromosomes are more easily determined at this stage. However gene (and transgene) expression occurs mainly during interphase. In order to accurately predict the activity of a transgene, it is critical to understand its location and dynamics in the three-dimensional interphase nucleus. We and others have developed in situ methods to visualize transgenes (including single copy genes) and their transcripts during interphase from different tissues and plant species. These techniques reduce the time necessary for characterization of transgene integration by eliminating the need for time-consuming segregation analysis, and extend characterization to the interphase nucleus, thus increasing the likelihood of accurate prediction of transgene activity. Furthermore, this approach is useful for studying nuclear organization and the dynamics of genes and chromatin

Analysis of the modes of energy consumption of the complex of an incoherent scattering of the institute of ionosphere of national academy of sciences and the ministry of education and science of Ukraine

У даній статті представлені результати аналізу режимів енергоспоживання комплексу некогерентного розсіяння Інституту іоносфери НАН і МОН України з метою вирішення проблеми підвищення енергоефективності науково-дослідного комплексу та створення енергоефективної системи електропостачання, яка забезпечить стійку роботу наукового обладнання для виконання дослідницьких програм НАН України. Описана система електроживлення комплексу та режими енергоспоживання комплексу. Описано пристрої радарної системи, а також найбільш потужні споживачі електроенергії, які споживають електроенергію на експериментальні і господарські потреби. Проаналізовано енергоспоживання комплексу некогерентного розсіяння за 2013 р. Отримано і представлено графіки середньої споживаної потужності (середньодобовий показник) і середньої споживаної потужності в режимі вимірювань. Описана доцільність проведення робіт з оптимізації енергопостачання науково-дослідного комплексу Інституту іоносфери. Запропоновано можливі заходи для зниження економічної вартості проведення експериментів з дослідження іоносфери науково-дослідного комплексу некогерентного розсіяння. Проведено аналіз робіт сучасних авторів з метою показати, що підвищення ефективності функціонування систем електропостачання є актуальною проблемою сучасних досліджень.This article presents the results of the analysis of the energy consumption modes of the incoherent scattering complex of the Institute of Ionosphere of the National Academy of Sciences and the Ministry of Education and Science of Ukraine to solve the problem of increasing the energy efficiency of a research complex and creating an energy efficient power supply system that will ensure the sustainability of scientific equipment for research programs of the National Academy of Sciences of Ukraine. The system of power supply of the complex and modes of power consumption of the complex are described. The devices of the radar system are described, as well as the most powerful consumers of electricity, which consume electricity for experimental and economic needs. The energy consumption of the incoherent scattering complex in 2013 is analyzed. Graphs of the average power consumption (daily average) and average power consumption in measurement modes were obtained and presented. The feasibility of work to optimize the energy supply of the research complex of the institute of the ionosphere is described. Possible measures are proposed to reduce the economic cost of conducting experiments on the study of the ionosphere of an incoherent scattering research complex. The analysis of the works of modern authors i s carried out in order to show that increasing the efficiency of the power supply systems is an actual problem of modern research

Coronary artery calcification as a marker for coronary artery stenosis: comparing kidney failure to the general population

Rationale & Objective: The presence of calcified plaques in the coronary arteries is associated with cardiovascular mortality and is a hallmark of chronic kidney failure, but it is unclear whether this is associated with the same degree of coronary artery stenosis as in patients without kidney disease. We compared the relationship of coronary artery calcification (CAC) and stenosis between dialysis patients and patients without chronic kidney disease (CKD).Study Design: Observational cohort study.Setting & Participants: 127 dialysis patients and 447 patients without CKD with cardiovascular risk factors underwent cardiac computed tomography (CT), consisting of non-contrast-enhanced CT and CT angiography. CAC score and degree of coronary artery stenosis were assessed by independent readers.Predictor: Dialysis treatment.Outcome: Association between calcification and stenosis.Analytical Approach: Logistic regression to determine the association between CAC score and the presence of stenosis in a matched cohort and, in the full cohort, testing for the interaction of dialysis status with this relationship.Results: 112 patients were matched from each cohort, totaling 224 patients, using propensity scores for dialysis, balancing numerous cardiovascular risk factors. Median CAC score was 210 (IQR, 19-859) in dialysis patients and 58 (IQR, 0254) in patients without CKD; 35% of dialysis patients and 36% of patients without CKD had coronary artery stenosis >= 50%. Per each 100-unit higher CAC score, the matched dialysis cohort had significantly lower ORs for stenosis than the nonCKD cohort, 0.67 (95% CI, 0.52-0.83) for stenosis >= 50% and 0.75 (95% CI, 0.62-0.90) for stenosis >= 70%.Limitations: No comparison with the gold standard fractional flow reserve.Conclusions: Dialysis patients have higher risk for coronary artery stenosis with higher CAC scores, but this risk is comparatively lower than in patients without CKD with similar CAC scores. In dialysis patients, a high CAC score can easily be found without significant stenosis. Our data enable "translation" of degree of calcification to the probability of coronary stenosis in dialysis patients.Cardiovascular Aspects of Radiolog

Role of Ucp1 enhancer methylation and chromatin remodelling in the control of Ucp1 expression in murine adipose tissue

Aims/hypothesis Increasing the expression of the brown adipose tissue-specific gene uncoupling protein-1 (Ucp1) is a potential target for treating obesity. We investigated the role of DNA methylation and histone modification in Ucp1 expression in adipose cell lines and ex vivo murine adipose tissues. Methods Methylation state of the Ucp1 enhancer was studied using bisulphite mapping in murine adipose cell lines, and tissue taken from cold-stressed mice, coupled with functional assays of the effects of methylation and demethylation of the Ucp1 promoter on gene expression and nuclear protein binding. Results We show that demethylation of the Ucp1 promoter by 5-aza-deoxycytidine increases Ucp1 expression while methylation of Ucp1 promoter–reporter constructs decreases expression. Brown adipose tissue-specific Ucp1 expression is associated with decreased CpG dinucleotide methylation of the Ucp1 enhancer. The lowest CpG dinucleotide methylation state was found in two cyclic AMP response elements (CRE3, CRE2) in the Ucp1 promoter and methylation of the CpG in CRE2, but not CRE3 decreased nuclear protein binding. Chromatin immunoprecipitation assays revealed the presence of the silencing DiMethH3K9 modification on the Ucp1 enhancer in white adipose tissue and the appearance of the active TriMethH3K4 mark at the Ucp1 promoter in brown adipose tissue in response to a cold environment. Conclusions/interpretation The results demonstrate that CpG dinucleotide methylation of the Ucp1 enhancer exhibits tissue-specific patterns in murine tissue and cell lines and suggest that adipose tissue-specific Ucp1 expression involves demethylation of CpG dinucleotides found in regulatory CREs in the Ucp1 enhancer, as well as modification of histone tails

Rapid Transient Production in Plants by Replicating and Non-Replicating Vectors Yields High Quality Functional Anti-HIV Antibody

Background: The capacity of plants and plant cells to produce large amounts of recombinant protein has been well established. Due to advantages in terms of speed and yield, attention has recently turned towards the use of transient expression systems, including viral vectors, to produce proteins of pharmaceutical interest in plants. However, the effects of such high level expression from viral vectors and concomitant effects on host cells may affect the quality of the recombinant product. Methodology/Principal Findings: To assess the quality of antibodies transiently expressed to high levels in plants, we have expressed and characterised the human anti-HIV monoclonal antibody, 2G12, using both replicating and non-replicating systems based on deleted versions of Cowpea mosaic virus (CPMV) RNA-2. The highest yield (approximately 100 mg/kg wet weight leaf tissue) of affinity purified 2G12 was obtained when the non-replicating CPMV-HT system was used and the antibody was retained in the endoplasmic reticulum (ER). Glycan analysis by mass-spectrometry showed that the glycosylation pattern was determined exclusively by whether the antibody was retained in the ER and did not depend on whether a replicating or non-replicating system was used. Characterisation of the binding and neutralisation properties of all the purified 2G12 variants from plants showed that these were generally similar to those of the Chinese hamster ovary (CHO) cell-produced 2G12. Conclusions: Overall, the results demonstrate that replicating and non-replicating CPMV-based vectors are able to direct the production of a recombinant IgG similar in activity to the CHO-produced control. Thus, a complex recombinant protein was produced with no apparent effect on its biochemical properties using either high-level expression or viral replication. The speed with which a recombinant pharmaceutical with excellent biochemical characteristics can be produced transiently in plants makes CPMV-based expression vectors an attractive option for biopharmaceutical development and production