Seasonal impact analysis on population due to continuous sulphur emissions from severonikel smelters of the Kola Peninsula

cited By 0This study is devoted to investigation of total deposition and loading patterns for population of the North-West Russia and Scandinavian countries due to continuous emissions (following “mild emission scenario”) of sulphates from the Cu-Ni smelters (Severonikel enterprise, Murmansk region, Russia). The Lagrangian long-range dispersion model (Danish Emergency Response Model for Atmosphere) was run in a long-term mode to simulate atmospheric transport, dispersion and deposition over the Northern Hemispheric’s domain north of 10°N, and results were integrated and analyzed in the GIS environment. Analysis was performed on annual and seasonal scales, including depositions, impact on urban areas and calculating individual and collective loadings on population in selected regions of Russia and Scandinavian countries. It was found that wet deposition dominates, and it is higher in winter. The North-West Russia is more influenced by the Severonikel emissions compared with the Scandinavian countries. Among urban areas, the Russian cities of Murmansk (due to its proximity to the source) and Arkhangelsk (due to dominating atmospheric flows) are under the highest impact. The yearly individual loadings on population are the largest (up to 120 kg/person) for the Murmansk region; lower (15 kg/person) for territories of the northern Norway, and the smallest (less than 5 kg/person) for the eastern Finland, Karelia Republic, and Arkhangelsk region. These loadings have distinct seasonal variability with a largest contribution during winter-spring for Russia, spring – for Norway, and autumn – for Finland and Sweden; and the lowest during summer (i.e. less than 10 and 1 kg/person for the Russia and Scandinavian countries, respectively). The yearly collective loadings for population living on the impacted territories in Russia, Finland, Norway, and Sweden are 2628, 140.4, 13, and 10.7 tonnes, respectively. © 2018, Lomonosov Moscow State University. All rights reserved.Peer reviewe

Application of a split-Cre system for high-capacity adenoviral vector amplification

Background and aims: High-capacity adenoviral vectors (HC-AdV) show extended DNA payload and stability of gene expression in vivo due to the absence of viral coding sequences. However, production requires methods to trans-complement viral proteins, usually through Helper Viruses (HV). The Cre/loxP system is frequently employed to remove the packaging signal in HV genomes, in order to avoid their encapsidation. However, chronic exposure to the Cre recombinase in packaging cells is detrimental. We have applied the dimerizable Cre system to overcome this limitation. Methods and results: Cre was split in two fragments devoid of recombinase function (N-terminal 244 and C-terminal 99 amino-acids). In one version of the system, interaction with both moieties was favored by rapamycin-dependent heterodimerization domains (DiCre). Other version contained only Cre sequences (oCre). We generated packaging cells and HVs expressing the complementary fragments and studied their performance for HC-AdV production. We found that both conformations avoided interference with the growth of packaging cells, and the oCre system was particularly suitable for HC-AdV amplification. Conclusions: The split-Cre system improves the performance of packaging cells and can reduce the time and cost of HC-AdV amplification up to 30% and 15%, respectively. This may contribute to the standardization of HC-AdV production

Transaction processing in consistency-aware user’s applications deployed on NoSQL databases

NoSQL databases are capable of storing and processing big data which is characterized by various properties such as volume, variety and velocity. Such databases are used in a variety of user applications that need large volume of data which is highly available and efficiently accessible. But they do not enforce or require strong data consistency nor do they support transactions. This paper investigates into the transaction processing in consistency-aware applications hosted on MongoDB and Riak which are two representatives of Document and Key-Value NoSQL databases, respectively. It develops new transaction schemes in order to provide NoSQL databases with transactional facilities as well as to analyze the effects of transactions on data consistency and efficiency in user’s applications. The proposed schemes are evaluated using the YCSB + T benchmark which is based on Yahoo! Cloud Services Benchmark (YCSB). Experimental results show that using the proposed schemes, strong consistency can be achieved in MongoDB and Riak without severely affecting their efficiency. We also conduct experiments in order to analyse the level of consistencyof MongoDB and Riak transactional systems

Rhodamine 6G and 800 intermolecular heteroaggregates embedded in PMMA for near-infrared wavelength shifting

The opto-electronic properties of small-molecules and functional dyes usually differ when incorporated into solid matrices with respect to their isolated form due to an aggregation phenomenon that alters their optical and fluorescent properties. These spectroscopic modifications are studied in the framework of the exciton theory of aggregates, which has been extensively applied in the literature for the study of molecular aggregates of the same type of molecules (homoaggregation). Despite the demonstrated potential of the control of the heteroaggregation process (aggregation of different types of molecules), most of the reported works are devoted to intramolecular aggregates, complex molecules formed by several chromophores attached by organic linkers. The intramolecular aggregates are specifically designed to hold a certain molecular structure that, on the basis of the exciton theory, modifies their optical and fluorescent properties with respect to the isolated chromophores that form the molecule. The present article describes in detail the incorporation of Rhodamine 6G (Rh6G) and 800 (Rh800) into polymeric matrices of poly-(methyl methacrylate), PMMA. The simultaneous incorporation of both dyes results in an enhanced fluorescent emission in the near-infrared (NIR), originating from the formation of ground-state Rh6G–Rh800 intermolecular heteroaggregates. The systematic control of the concentration of both rhodamines provides a model system for the elucidation of the heteroaggregate formation. The efficient energy transfer between Rh6G and Rh800 molecules can be used as wavelength shifters to convert effectively the light from visible to NIR, a very convenient wavelength range for many practical applications which make use of inexpensive commercial detectors and systems

Analytical sensitivity of current best-in-class malaria rapid diagnostic tests

BACKGROUND: Rapid diagnostic tests (RDTs) are today the most widely used method for malaria diagnosis and are recommended, alongside microscopy, for the confirmation of suspected cases before the administration of anti-malarial treatment. The diagnostic performance of RDTs, as compared to microscopy or PCR is well described but the actual analytical sensitivity of current best-in-class tests is poorly documented. This value is however a key performance indicator and a benchmark value needed to developed new RDTs of improved sensitivity. METHODS: Thirteen RDTs detecting either the Plasmodium falciparum histidine rich protein 2 (HRP2) or the plasmodial lactate dehydrogenase (pLDH) antigens were selected from the best performing RDTs according to the WHO-FIND product testing programme. The analytical sensitivity of these products was evaluated using a range of reference materials including P. falciparum and Plasmodium vivax whole parasite samples as well as recombinant proteins. RESULTS: The best performing HRP2-based RDTs could detect all P. falciparum cultured samples at concentrations as low as 0.8 ng/mL of HRP2. The limit of detection of the best performing pLDH-based RDT specifically detecting P. vivax was 25 ng/mL of pLDH. CONCLUSION: The analytical sensitivity of P. vivax and Pan pLDH-based RDTs appears to vary considerably from product to product, and improvement of the limit-of-detection for P. vivax detecting RDTs is needed to match the performance of HRP2 and Pf pLDH-based RDTs for P. falciparum. Different assays using different reference materials produce different values for antigen concentration in a given specimen, highlighting the need to establish universal reference assays

Oxaliplatin in combination with liver-specific expression of interleukin 12 reduces the immunosuppressive microenvironment of tumours and eradicates metastatic colorectal cancer in mice

BACKGROUND AND AIMS: New options are needed for the management and prevention of colorectal cancer liver metastases. Interleukin 12 (IL-12) is an immunostimulatory cytokine with proven antitumour effect in animal models. Despite evidence indicating its biological effect in humans, neither the recombinant protein nor gene therapy vectors expressing IL-12 have shown a relevant benefit in patients with cancer. OBJECTIVE: To develop a new approach to overcome the difficulties in obtaining a suitable expression pattern and the immunosuppressive milieu in the tumours which contribute to this poor performance. METHODS: A high-capacity ('gutless') adenoviral vector carrying a liver-specific, mifepristone (Mif)-inducible system for the expression of IL-12 (HC-Ad/RUmIL-12) was used in combination with chemotherapy. Tumours were established in the liver of C57BL/6 mice by inoculation of MC38 colon cancer cells. RESULTS: Intrahepatic injection of HC-Ad/RUmIL-12 and tailored induction regimens allowed the maintenance of safe and efficient levels of IL-12 in vivo. An individualised, stepwise increase in the dose of Mif (125-4000 μg/kg) was needed to compensate for the progressive but transient downregulation of the inducible system. Repeated cycles of Mif induction (every 24 h for 10 days) were needed for optimal tumour eradication. However, complete protection against tumour rechallenge was seen in < 25% of the animals. The administration of oxaliplatin (5 mg/kg intraperitoneally) 3 days before starting the induction regimen achieved efficient elimination of liver metastases with a single cycle of IL-12 induction, and improved protection against tumour rechallenge. This was associated with a shift in the tumour microenvironment towards a more pro-immunogenic phenotype, with an increase in the CD8+/T regulatory cell ratio and a reduction in myeloid-derived suppressor cells. These effects were not seen with 5-fluorouracil, irinotecan or gemcitabine

Lyman break and UV-selected galaxies at z ~ 1: II. PACS-100um/160um FIR detections

We report the PACS-100um/160um detections of a sample of 42 GALEX-selected and FIR-detected Lyman break galaxies (LBGs) at z ~ 1 located in the COSMOS field and analyze their ultra-violet (UV) to far-infrared (FIR) properties. The detection of these LBGs in the FIR indicates that they have a dust content high enough so that its emission can be directly detected. According to a spectral energy distribution (SED) fitting with stellar population templates to their UV-to-near-IR observed photometry, PACS-detected LBGs tend to be bigger, more massive, dustier, redder in the UV continuum, and UV-brighter than PACS-undetected LBGs. PACS-detected LBGs at z ~ 1 are mostly disk-like galaxies and are located over the green-valley and red sequence of the color-magnitude diagram of galaxies at their redshift. By using their UV and IR emission, we find that PACS-detected LBGs tend to be less dusty and have slightly higher total star-formation rates (SFRs) than other PACS-detected UV-selected galaxies within their same redshift range. As a consequence of the selection effect due to the depth of the FIR observations employed, all our PACS-detected LBGs are LIRGs. However, none of them are in the ULIRG regime, where the FIR observations are complete. The finding of ULIRGs-LBGs at higher redshifts suggests an evolution of the FIR emission of LBGs with cosmic time. In an IRX-$\beta$ diagram, PACS-detected LBGs at z ~ 1 tend to be located around the relation for local starburst similarly to other UV-selected PACS-detected galaxies at their same redshift. Consequently, the dust-correction factors obtained with their UV continuum slope allow to determine their total SFR, unlike at higher redshifts. However, the dust attenuation derived from UV to NIR SED fitting overestimates the total SFR for most of our PACS-detected LBGs in age-dependent way: the overestimation factor is higher in younger galaxies.Comment: Accepted for publication in MNRA

Epilepsy and neuropsychiatric comorbidities in mice carrying a recurrent Dravet syndrome SCN1A missense mutation

Dravet Syndrome (DS) is an encephalopathy with epilepsy associated with multiple neuropsychiatric comorbidities. In up to 90% of cases, it is caused by functional happloinsufficiency of the SCN1A gene, which encodes the alpha subunit of a voltage-dependent sodium channel (Nav1.1). Preclinical development of new targeted therapies requires accessible animal models which recapitulate the disease at the genetic and clinical levels. Here we describe that a C57BL/6 J knock-in mouse strain carrying a heterozygous, clinically relevant SCN1A mutation (A1783V) presents a full spectrum of DS manifestations. This includes 70% mortality rate during the first 8 weeks of age, reduced threshold for heat-induced seizures (4.7 °C lower compared with control littermates), cognitive impairment, motor disturbances, anxiety, hyperactive behavior and defects in the interaction with the environment. In contrast, sociability was relatively preserved. Electrophysiological studies showed spontaneous interictal epileptiform discharges, which increased in a temperature-dependent manner. Seizures were multifocal, with different origins within and across individuals. They showed intra/inter-hemispheric propagation and often resulted in generalized tonic-clonic seizures. 18F-labelled flourodeoxyglucose positron emission tomography (FDG-PET) revealed a global increase in glucose uptake in the brain of Scn1aWT/A1783V mice. We conclude that the Scn1aWT/A1783V model is a robust research platform for the evaluation of new therapies against DS