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Abstract Background In order to support the ongoing research across Europe to facilitate access to novel radionuclides, the PRISMAP consortium (European medical radionuclides programme) was established to offer the broadest catalog of non-conventional radionuclides for medical and translational research. The aim of this article is to introduce readers with current status of novel radionuclides in Europe. Main body A consortium questionnaire was disseminated through the PRISMAP consortium and user community, professional associations and preclinical/clinical end users in Europe and the current status of clinical end-users in nuclear medicine were identified. A total of 40 preclinical/clinical users institutions took part in the survey. Clinical end users currently use the following radionuclides in their studies: 177Lu, 68 Ga, 111In, 90Y, other alpha emitters, 225Ac, 64Cu and Terbium isotopes. Radionuclides that would be of interest for users within the next 2–5 years are 64Cu, Terbium radionuclide “family” and alpha emitters, such as 225Ac. Conclusions Thanks to a questionnaire distributed by the PRISMAP consortium, the current status and needs of clinical end-users in nuclear medicine were identified.

Abstract Genomes exhibit large regions with segmental copy number variation, many of which include entire genes and are multiallelic. We have developed a computational method GeneToCN that counts the frequencies of gene-specific k-mers in FASTQ files and uses this information to infer copy number of the gene. We validated the copy number predictions for amylase genes (AMY1, AMY2A, AMY2B) using experimental data from digital droplet PCR (ddPCR) on 39 individuals and observed a strong correlation (R = 0.99) between GeneToCN predictions and experimentally determined copy numbers. An additional validation on FCGR3 genes showed a higher concordance for FCGR3A compared to two other methods, but reduced accuracy for FCGR3B. We further tested the method on three different genomic regions (SMN, NPY4R, and LPA Kringle IV-2 domain). Predicted copy number distributions of these genes in a set of 500 individuals from the Estonian Biobank were in good agreement with the previously published studies. In addition, we investigated the possibility to use GeneToCN on sequencing data generated by different technologies by comparing copy number predictions from Illumina, PacBio, and Oxford Nanopore data of the same sample. Despite the differences in variability of k-mer frequencies, all three sequencing technologies give similar predictions with GeneToCN.

The radionuclides 43Sc, 44g/mSc, and 47Sc can be produced cost-effectively in sufficient yield for medical research and applications by irradiating natTi and natV target materials with protons. Maximizing the production yield of the therapeutic 47Sc in the highest cross section energy range of 24–70 MeV results in the co-production of long-lived, high-γ-ray-energy 46Sc and 48Sc contaminants if one does not use enriched target materials. Mass separation can be used to obtain high molar activity and isotopically pure Sc radionuclides from natural target materials; however, suitable operational conditions to obtain relevant activity released from irradiated natTi and natV have not yet been established at CERN-MEDICIS and ISOLDE. The objective of this work was to develop target units for the production, release, and purification of Sc radionuclides by mass separation as well as to investigate target materials for the mass separation that are compatible with high-yield Sc radionuclide production in the 9–70 MeV proton energy range. In this study, the in-target production yield obtained at MEDICIS with 1.4 GeV protons is compared with the production yield that can be reached with commercially available cyclotrons. The thick-target materials were irradiated at MEDICIS and comprised of metallic natTi, natV metallic foils, and natTiC pellets. The produced radionuclides were subsequently released, ionized, and extracted from various target and ion source units and mass separated. Mono-atomic Sc laser and molecule ionization with forced-electron-beam-induced arc-discharge ion sources were investigated. Sc radionuclide production in thick natTi and natV targets at MEDICIS is equivalent to low- to medium-energy cyclotron-irradiated targets at medically relevant yields, furthermore benefiting from the mass separation possibility. A two-step laser resonance ionization scheme was used to obtain mono-atomic Sc ion beams. Sc radionuclide release from irradiated target units most effectively could be promoted by volatile scandium fluoride formation. Thus, isotopically pure 44g/mSc, 46Sc, and 47Sc were obtained as mono-atomic and molecular ScF 2+ ion beams and collected for the first time at CERN-MEDICIS. Among all the investigated target materials, natTiC is the most suitable target material for Sc mass separation as molecular halide beams, due to high possible operating temperatures and sustained release.

Gentamicin is an essential broad-spectrum aminoglycoside antibiotic that is used in over 40 clinical conditions and has shown activity against a wide range of nosocomial, biofilm-forming, multi-drug resistant bacteria. Nevertheless, the low cellular penetration and serious side effects of gentamicin, as well as the fear of the development of antibacterial resistance, has led to a search for ways to circumvent these obstacles. This review provides an overview of the chemical and pharmacological properties of gentamicin and offers six different strategies (the isolation of specific types of gentamicin, encapsulation in polymeric nanoparticles, hydrophobization of the gentamicin molecule, and combinations of gentamicin with other antibiotics, polyphenols, and natural products) that aim to enhance the drug delivery and antibacterial activity of gentamicin. In addition, factors influencing the synthesis of gentamicin-loaded polymeric (poly (lactic-co-glycolic acid) (PLGA) and chitosan) nanoparticles and the methods used in drug release studies are discussed. Potential research directions and future perspectives for gentamicin-loaded drug delivery systems are given.

This study focuses on neutron-irradiated beryllium interactions with air of differing humidity, simulating water cooled fusion reactor malfunction.Beryllium in the form of ∼ 1 mm ∅ pebbles has been used in the study. Both non-irradiated and neutron-irradiated pebbles were thermally treated and studied using thermogravimetric/differential thermal analysis in dry airflow with relative humidity (RH) 90% RH.Surface structure and composition was investigated with scanning electron microscopy (SEM) and energy dispersion X-ray spectrometry (EDX). Tritium release was monitored using a tritium monitor.Results show that elevated RH coupled with neutron irradiation damage on beryllium yields the largest mass increase of 180% (in relation to the initial mass) compared to non-irradiated Be treated in RH

In this study, a tritium enrichment system in the water phase has been developed based on the combination of a proton exchange membrane (PEM) electrolysis cell and a fuel cell. As the PEM, Nafion ^TM and laboratory-synthesized sulfonated poly(ether ether ketone) membranes modified with an additional graphene layer in order to enhance the tritium separation factor were used. Both differences in the kinetics of the hydrogen evolution reaction and transport through the graphene layer of different isotopes are the driving factors expected to affect the separation of hydrogen isotopes. The separation factor was measured both during the electrolysis and fuel cell stage using different membranes. The facilitating effect of the graphene on the separation efficiency was determined during the study. The separation factor obtained by the proposed method was evidently higher than that obtained by other conventional methods.

In 2021 JET exploited its unique capabilities to operate with T and D–T fuel with an ITER-like Be/W wall (JET-ILW). This second major JET D–T campaign (DTE2), after DTE1 in 1997, represented the culmination of a series of JET enhancements—new fusion diagnostics, new T injection capabilities, refurbishment of the T plant, increased auxiliary heating, in-vessel calibration of 14 MeV neutron yield monitors—as well as significant advances in plasma theory and modelling in the fusion community. DTE2 was complemented by a sequence of isotope physics campaigns encompassing operation in pure tritium at high T-NBI power. Carefully conducted for safe operation with tritium, the new T and D–T experiments used 1 kg of T (vs 100 g in DTE1), yielding the most fusion reactor relevant D–T plasmas to date and expanding our understanding of isotopes and D–T mixture physics. Furthermore, since the JET T and DTE2 campaigns occurred almost 25 years after the last major D–T tokamak experiment, it was also a strategic goal of the European fusion programme to refresh operational experience of a nuclear tokamak to prepare staff for ITER operation. The key physics results of the JET T and DTE2 experiments, carried out within the EUROfusion JET1 work package, are reported in this paper. Progress in the technological exploitation of JET D–T operations, development and validation of nuclear codes, neutronic tools and techniques for ITER operations carried out by EUROfusion (started within the Horizon 2020 Framework Programme and continuing under the Horizon Europe FP) are reported in (Litaudon et al Nucl. Fusion accepted), while JET experience on T and D–T operations is presented in (King et al Nucl. Fusion submitted).

Enzymatic, de novo XNA synthesis represents an alternative method for the production of long oligonucleotides containing chemical modifications at distinct locations. While such an approach is currently developed for DNA, controlled enzymatic synthesis of XNA remains at a relative state of infancy. In order to protect the masking groups of 3′-O-modified LNA and DNA nucleotides against removal caused by phosphatase and esterase activities of polymerases, we report the synthesis and biochemical characterization of nucleotides equipped with ether and robust ester moieties. While the resulting ester-modified nucleotides appear to be poor substrates for polymerases, ether-blocked LNA and DNA nucleotides are readily incorporated into DNA. However, removal of the protecting groups and modest incorporation yields represent obstacles for LNA synthesis via this route. On the other hand, we have also shown that the template-independent RNA polymerase PUP represents a valid alternative to the TdT and we have also explored the possibility of using engineered DNA polymerases to increase substrate tolerance for such heavily modified nucleotide analogs.

A set of styrylpyridinium (SP) compounds was synthesised in order to study their spectroscopic and cell labelling properties. The compounds comprised different electron donating parts (julolidine, p-dimethylaminophenyl, p-methoxyphenyl, 3,4,5-trimethoxyphenyl), conjugated linkers (vinyl, divinyl), and an electron-withdrawing N-alkylpyridinium part. Geminal or bis-compounds incorporating two styrylpyridinium (bis-SP) moieties at the 1,3-trimethylene unit were synthesised. Compounds comprising a divinyl linker and powerful electron-donating julolidine donor parts possessed intensive fluorescence in the near-infrared region (maximum at ~760 nm). The compounds had rather high cytotoxicity towards the cancerous cell lines HT-1080 and MH-22A; at the same time, basal cytotoxicity towards the NIH3T3 fibroblast cell line ranged from toxic to harmful. SP compound 6e had IC50 values of 1.0 ± 0.03 µg/mL to the cell line HT-1080 and 0.4 µg/mL to MH-22A; however, the basal toxicity LD50 was 477 mg/kg (harmful). The compounds showed large Stokes’ shifts, including 195 nm for 6a,b, 240 nm for 6e, and 325 and 352 nm for 6d and 6c, respectively. The highest photoluminescence quantum yield (PLQY) values were observed for 6a,b, which were 15.1 and 12.2%, respectively. The PLQY values for the SP derivatives 6d,e (those with a julolidinyl moiety) were 0.5 and 0.7%, respectively. Cell staining with compound 6e revealed a strong fluorescent signal localised in the cell cytoplasm, whereas the cell nuclei were not stained. SP compound 6e possessed self-assembling properties and formed liposomes with an average diameter of 118 nm. The obtained novel data on near-infrared fluorescent probes could be useful for the development of biocompatible dyes for biomedical applications.

A synthesis of a cationic moiety and fluorescent moieties containing amphiphilic 1,4-dihydropyridine (1,4-DHP) derivatives was performed starting with the Hantzsch-type cyclization of dodecyl acetoacetate, phenylaldehyde and ammonium acetate. Bromination of the 2,6-dimethyl groups of a parent 1,4-DHP compound, followed by nucleophilic substitution of bromine with 4-(anthracen-9-yl)pyridine, produced the desired 1,1′-{[3,5-bis((dodecyloxycarbonyl)-4-phenyl-1,4-dihydropyridine-2,6-diyl]bis(methylene)}bis[4-(anthracen-9-yl)pyridin-1-ium] dibromide. The obtained target compound was fully characterized by the IR, 1H NMR, 13C NMR and HRMS data. Studies of the self-assembling properties and characterization of the nanoparticles obtained by the ethanol injection method were performed using dynamic light scattering (DLS) measurements. DLS measurement data showed that 1,1′-{[3,5-bis((dodecyloxycarbonyl)-4-phenyl-1,4-dihydropyridine-2,6-diyl]bis(methylene)}bis[4-(anthracen-9-yl)pyridin-1-ium] dibromide produced liposomes that had average diameters of 200 nm when the samples were freshly prepared, and 140 nm after 7 days or 1 month storage. The PDI values of the samples were approximately 0.50 and their zeta-potential values were approximately 41 mV when the samples were freshly prepared, and 33 mV after storage. The obtained nanoparticles were stored at room temperature for one month and remained stable during that period. The mean molecular area of the cationic 1,4-DHP-anthracene hybrid 4 was 118 Å2, while the mean molecular area of the cationic 1,4-DHP 5 without anthracene substituents was only 83 Å2. The photoluminescence quantum yield (PLQY) value for the EtOH solution of the 1,4-DHP derivative 4 was 10.8%, but for the 1,4-DHP derivative 5 it was only 1.8%. These types of compounds could be used as synthetic lipids in the further development of prospective theranostic delivery systems.

A synthesis of 3-(3,5-difluoro-3,5-bis((alkoxy)carbonyl)-2,6-dioxoheptan-4-yl)-1-methylpyridin-1-ium iodides with ethyl or nonyl ester groups at positions 3 and 5 was performed. Treatment of the corresponding 2’,6’-dimethyl-1’,4’-dihydro-[3,4’-bipyridine]-3’,5’-dicarboxylates with Selectfluor® followed by quaternization of pyridine moiety in the obtained dialkyl 2,4-diacetyl-2,4-difluoro-3-(pyridin-3-yl)pentanedioates with methyl iodide gave the desired 3-(3,5-difluoro-3,5-bis((alkoxy)carbonyl)-2,6-dioxoheptan-4-yl)-1-methylpyridin-1-ium iodides. This type of compound would be useful as synthetic lipids for further development of the delivery systems. The obtained target compounds were fully characterized by 1H NMR, 19F NMR, 13C NMR, HRMS, IR and UV data. The estimation of self-assembling properties and characterization of the nanoparticles obtained by ethanol solution injection in an aqueous media were performed by dynamic light scattering (DLS) measurements. DLS measurement data showed that 3-(3,5-difluoro-3,5-bis((nonyloxy)carbonyl)-2,6-dioxoheptan-4-yl)-1-methylpyridin-1-ium iodide created liposomes with the average diameter of 300–400 nm and polydispersity index (PDI) value around 0.30–0.40, while 3-(3,5-difluoro-3,5-bis((ethyloxy)carbonyl)-2,6-dioxoheptan-4-yl)-1-methylpyridin-1-ium iodide formed a heterogeneous sample with PDI value 1, which was not prospective for delivery system development.

Synthesis of a double-charged cationic amphiphilic 1,4-dihydropyridine derivative with dodecyl ester groups at positions 3 and 5 of the 1,4-DHP ring was performed starting from Hantzsch type cyclization of dodecyl acetoacetate, 2-naphthaldehyde and ammonium acetate. Bromination of this compound followed by nucleophilic substitution of bromine with (E)-4-(2-(naphthalen-2-yl)vinyl)pyridine gave the desired cationic amphiphilic 1,1′-{[3,5-bis(dodecyloxycarbonyl)-4-(naphthalen-2-yl)-1,4-dihydropyridine-2,6-diyl]bis(methylene)}bis{4-[(E)-2-(naphthalen-2-yl)vinyl]pyridin-1-ium}dibromide. The obtained target compound was fully characterized by IR, UV, 1H-NMR, 13C-NMR, HRMS and microanalysis. The characterization of the cationic 1,4-DHP nanoparticles in an aqueous solution was performed by DLS measurements. The obtained results showed that the compound formed nanoparticles with an average diameter of around 300 nm, a PDI value of around 490 and a zeta-potential of around 20 mV for freshly prepared samples. However, after one week of storage at room temperature, an aggregation of nanoparticles was detected.

In this data file the characterisation of nanoformulations obtained from calix[4]arene/1,4-dihydropyridine (1,4-DHP) compositions in the various component ratio in an aqueous medium was performed by dynamic light scattering (DLS) technique. The hydrodynamic diameters of nanoparticle main population, polydispersity index and stability of nanoformulation were determined. In this article provided data are directly related to the previously published research articles – “Gene delivery agents possessing antiradical activity: Self-assembling cationic amphiphilic 1,4-dihydropyridine derivatives” [1], and “Studies of the physicochemical and structural properties of self-assembling cationic pyridine derivatives as gene delivery agents” [2] where was described synthesis, transfection activity of 1,1′-((3,5-bis((dodecyloxy)carbonyl)-4-phenyl-1,4-dihydropyridine-2,6-diyl)bis(methylene))bis(pyridin-1-ium) dibromide presented in this data file; and with articles “Cationic amphiphilic calixarenes to compact DNA into small nanoparticles for gene delivery” [3] and “Self-aggregation in aqueous solution of amphiphilic cationic calix[4]arenes. Potential use as vectors and nanocarriers” [4] where was described synthesis and ability to condense DNA for also mentioned calix[4]arenes – 5,11,17,23-tetra-(3-methylimidazolium)-methylene-25,26,27,28-etradodecyloxycalix[4]arene tetrachloride, 5,11,17,23-tetra(N,N-dimethyl-N-hydroxyethylammonium)-methylene-25,26,27,28-tetradodecyloxycalix[4]arene tetrachloride and 5,11,17,23-tetra(N,N-dimethyl-N-hydroxyethylammonium)-methylene-25,26,27,28-tetrahexadecyloxycalix[4]arene tetrachloride. Information provided in this data file can be used in medicinal chemistry for development of novel synthetic lipid nanoformulations.

In the present work, construction of double-charged cationic amphiphilic 1,1′-{[3,5-bis(dodecyl¬oxy-carbonyl)-4-(thiophen-3-yl)-1,4-dihydropyridine-2,6-diyl]bis-(methylene)}bis(pyridin-1-ium) dibromide (7) was performed in four steps. Dodecyl 3-oxobutanoate (1) was condensed with thiophene-3-carbaldehyde (2) which was necessary for Hantzsch cyclisation dodecyl (E/Z)-3-oxo-2-(thiophen-3-ylmethylene)butanoate (3). Two-component Hantzsch type cyclisation of dodecyl (E/Z)-3-aminobut-2-enoate (4) and dodecyl (E/Z)-3-oxo-2-(thiophen-3-ylmethylene)butanoate (3) gave 3,5-bis(dodecyloxycarbonyl)-2,6-dimethyl-4-(thiophen-3-yl)-1,4-dihydropyridine (5). Bromination of compound 5 followed by nucleophilic substitution of bromine with pyridine gave the desired cationic amphiphilic 1,4-dihydropyridine 7. The obtained target compound 7 and new intermediates 3, 5 and 6 were fully characterised by IR, UV, 1H NMR, 13C NMR, HRMS or microanalysis. Characterisation of nanoparticles formed by the cationic 1,4-dihydropyridine 7 in an aqueous solution was performed by DLS measurements.

This work was carried out to identify sources of errors, uncertainties and discrepancies in studies of fuel retention in wall components from the JET tokamak using methods based on thermal desorption. Parallel aims were to establish good practices in measurements and to unify procedures in data handling. A comprehensive program designed for deuterium quantification comprised the definition and preparation of two types of materials (samples of JET limiter Be tiles and deuterium-containing targets produced in the laboratory by magnetron-assisted deposition), their pre-characterization, quantitative analyses of the desorption products in three different thermal desorption spectroscopy systems and a detailed critical comparison of the results. Tritium levels were also determined by several techniques in samples from JET and in tritiated targets manufactured specifically for this research program. Facilities available for studies of Be- and tritium-contaminated materials from JET are presented. Apparatus development, future research options and challenges are discussed.

In this data file the synthetic procedures for preparation of the original 4-pyridinium-1,4-dihydropyridines (4-Py-1,4-DHP) and their parent compounds – dialkyl 2,6-dimethyl-4-(3-pyridyl)-1,4-dihydropyridine-3,5-dicarboxylates were described. In total, 5 unpublished compounds were obtained and characterised. All the structures of original compounds were confirmed by Nuclear Magnetic Resonance (NMR, including 1H NMR and 13C NMR) and low resolution mass spectra (MS) data. Additionally, the cytotoxic properties of four 4-Py-1,4-DHPs were evaluated on 3 cell lines – normal NIH3T3 (mouse embryonic fibroblast), cancerous HT-1080 (human lung fibrosarcoma) and MH-22A (mouse hepatoma) and self-assembling properties were studied and characterisation of formed nanoparticles were performed using dynamic light scattering technique. In this article provided data are directly related to the previously published research articles – “Novel cationic amphiphilic 1,4-dihydropyridine derivatives for DNA delivery” [1] where compound 5 was tested as gene delivery agent without full physico-chemical characterisation and “Synthesis and studies of calcium channel blocking and antioxidant activities of novel 4-pyridinium and/or N-propargyl substituted 1,4-dihydropyridine derivatives” [2] where synthesis and physico-chemical characterisation as well as calcium channel blocking and antioxidant activities were described for compound 6. Synthesis of other compounds – parent 1,4-DHPs 1 and 2, and 4-Py-1,4-DHPs 3–5, their characterisation, estimation of cytotoxicity and self-assembling properties for all 4-Py-1,4-DHPs 3–6 are reported herein for the first time. Information provided in this data file can be used in medicinal chemistry by other scientists to estimate structure-activity relationships for the analysis and construction of various cationic 1,4-dihydropyridine derivatives and related heterocycles.

This data file describes the synthetic protocol for preparation of the original 2,6-di(bromomethyl)-3,5-bis(alkoxycarbonyl)-4-aryl-1,4-dihydropyridines. In total, 6 unpublished compounds were obtained and characterised. The 2,6-di(bromomethyl)-1,4-dihydropyridines are mainly used as intermediates for synthesis of various lipid-like compounds based on 1,4-dihydropyridine cycle. All the structures of 2,6-di(bromomethyl)-1,4-dihydropyridines were confirmed by Nuclear Magnetic Resonance (NMR, including 1H NMR and 13C NMR) data. The data provided herein are directly related to the previously published research article – “Novel cationic amphiphilic 1,4-dihydropyridine derivatives for DNA delivery” [1] where three derivatives (2,6-di(bromomethyl)-4-phenyl-1,4-dihydropyridines 2a-c) from six presented in this data file were used as starting materials in synthesis of amphiphilic 1,4-dihydropyridines without any purification and characterisation. Synthesis of other three 2,6-di(bromomethyl)-3,5-bis(alkoxycarbonyl)-4-aryl-1,4-dihydropyridines 2d-f and their characterisation are reported herein at the first time. Information provided in this data file can be used in organic synthesis by other chemists to develop synthetic strategies for the construction of various cationic 1,4-dihydropyridine derivatives and related heterocycles.

We examine U.S. dual- and single-class firms from 1980 to 2019 and document their valuation differences over their corporate life cycle. At the IPO, dual-class firms have higher mean valuations than do single-class firms, and some evidence indicates that this premium may emanate from dual-class firm founders' unique vision and leadership skills. As firms age, the valuation premium of dual-class firms tends to dissipate, possibly because dual-class agency problems increase due to a gradual widening of the wedge (the difference between insider voting and cash flow rights) in the post-IPO years. (JEL G32, G34) [ABSTRACT FROM AUTHOR]

Silicon nitride (Si3N4) in a form of single and multi-layer nanofilms is proposed to be used as a dielectric layer in nanocapacitors for operation in harsh environmental conditions. Characterization of surface morphology, roughness and chemical bonds of the Si3N4 coatings has an important role in production process as the surface morphology affects the contact surface with other components of the produced device. Si3N4 was synthesized by using low pressure chemical vapour deposition method and depositing single and multi-layer (3 – 5 layers) nanofilms on SiO2 and polycrystalline silicon (PolySi). The total thickness of the synthesized nanofilms was 20 – 60 nm. Surface morphology was investigated by means of scanning electron microscopy (SEM) and atomic force microscopy (AFM). Chemical bonds in the layers were identified by means of Fourier transform infrared spectrometry, attenuated total reflection (FTIR-ATR) method. (From the SEM and AFM images it was estimated that both single and multi-layer coatings are deposited homogenously. Si-N breathing and stretching modes are observed in FTIR spectra and the surface morphology is highly dependent on PolySi, therefore suggesting the decrease of the roughness of the bottom electrode for use in the nanocapacitors.

Abstract Background Recently, alignment-free sequence analysis methods have gained popularity in the field of personal genomics. These methods are based on counting frequencies of short k-mer sequences, thus allowing faster and more robust analysis compared to traditional alignment-based methods. Results We have created a fast alignment-free method, AluMine, to analyze polymorphic insertions of Alu elements in the human genome. We tested the method on 2,241 individuals from the Estonian Genome Project and identified 28,962 potential polymorphic Alu element insertions. Each tested individual had on average 1,574 Alu element insertions that were different from those in the reference genome. In addition, we propose an alignment-free genotyping method that uses the frequency of insertion/deletion-specific 32-mer pairs to call the genotype directly from raw sequencing reads. Using this method, the concordance between the predicted and experimentally observed genotypes was 98.7%. The running time of the discovery pipeline is approximately 2 h per individual. The genotyping of potential polymorphic insertions takes between 0.4 and 4 h per individual, depending on the hardware configuration. Conclusions AluMine provides tools that allow discovery of novel Alu element insertions and/or genotyping of known Alu element insertions from personal genomes within few hours.

ITER-Like-Wall (ILW) project has been carried out at Joint European Torus (JET) to test plasma facing materials relevant to International Thermonuclear Experimental Reactor – ITER [1]. Limiters and an upper dump plate of the vacuum vessel are made of bulk beryllium tiles, whereas for the divertor bulk tungsten and tungsten-coated carbon fibre (CFC) composite tiles are used.During the shutdowns in ILW1 (2012), ILW2 (2014) and ILW3 (2016), selected beryllium tiles were removed from the vacuum vessel. In this study, tiles from three positions were analysed, and analysis results were compared regarding both the tile position in the vacuum vessel and differences in the exploitation conditions during the respective three ILW campaigns: ILW1, ILW2, ILW3. Tritium results have been compared to deuterium data published by other authors [2,3].Tritium measurements were performed by two methods - thermal desorption spectroscopy and beryllium chemical etching. Prior to tritium measurements, scanning electron microscopy was used to study structure of the plasma-facing surfaces.Experimental results revealed that tritium content in beryllium samples over all three campaigns is in range of 1.0·1010 to 9.7·1013 tritium atoms per square centimetre of the plasma-facing surface area (atoms/cm2). Highest tritium content was found in the samples from outer wall of the vacuum vessel - up to 4.0·1013 atoms/cm2 in ILW1, 4.2·1013 atoms/cm2 in ILW2 and 9.7·1013 atoms/cm2 in ILW3. Whereas, the lowest - in the upper part of the vacuum vessel: 5.1·1012, 2.8·1012 and 1.0·1010 atoms/cm2 in ILW1, ILW2 and ILW3, respectively. In contrary to the deuterium, in the outer wall tile higher tritium concentrations were found in the central part of the tiles where plasma induced erosion had occurred according to the SEM analysis data. Difference between tritium content in the central part and side part of tile could reach a magnitude of an order - for example, 9.7·1013 and 6.9·1012 atoms/cm2 in the outer wall tile from the ILW3 campaign. Results obtained within this study give possibility to assess tritium retention mechanism and make estimates of its possible inventory in larger machines such as ITER.

Capsid assembly modulators (CAMs) have emerged as a promising class of antiviral agents. We studied the effects of twenty-one newly designed and synthesized CAMs including heteroaryldihydropyrimidine compounds (HAPs), their analogs and standard compounds on hepatitis B virus (HBV) capsid assembly. Cytoplasmic expression of the HBV core (HBc) gene driven by the exogenously delivered recombinant alphavirus RNA replicon was used for high level production of the full-length HBc protein in mammalian cells. HBV capsid assembly was assessed by native agarose gel immunoblot analysis, electron microscopy and inhibition of virion secretion in HepG2.2.15 HBV producing cell line. Induced fit docking simulation was applied for modelling the structural relationships of the synthesized compounds and HBc. The most efficient were the HAP class compounds—dihydropyrimidine 5-carboxylic acid n-alkoxyalkyl esters, which induced the formation of incorrectly assembled capsid products and their accumulation within the cells. HBc product accumulation in the cells was not detected with the reference HAP compound Bay 41-4109, suggesting different modes of action. A significant antiviral effect and substantially reduced toxicity were revealed for two of the synthesized compounds. Two new HAP compounds revealed a significant antiviral effect and a favorable toxicity profile that allows these compounds to be considered promising leads and drug candidates for the treatment of HBV infection. The established alphavirus based HBc expression approach allows for the specific selection of capsid assembly modulators directly in the natural cell environment.

We provide empirical evidence of the relationship between downward wage rigidity and unemployment volatility by comparing wage dynamics and worker mobility during the Great Recession in two countries where wages adjusted very differently: Latvia and Spain. Using a panel of social security administrative data, we find that wages in Spain were rigid even during periods of rising unemployment. In contrast, Latvian wages were reduced and wage cuts affected 60 percent of jobs. At the same time, the elasticity of workers' transition rates into and out of unemployment to productivity shocks was four times higher in Spain than in Latvia, and these responses were more persistent in Spain. This evidence is consistent with theoretical models that show that unemployment volatility is higher when wages are rigid.

Katarzyna Niemirowicz-Laskowska,1 Katarzyna Głuszek,1 Ewelina Piktel,1 Karlis Pajuste,2 Bonita Durnaś,3 Grzegorz Król,3 Agnieszka Z Wilczewska,4 Paul A Janmey,5 Aiva Plotniece,2 Robert Bucki1 1Department of Microbiological and Nanobiomedical Engineering, Medical University of Bialystok, Bialystok, Poland; 2Laboratory of Membrane Active Compounds and β-Diketones, Latvian Institute of Organic Synthesis, Riga, Latvia; 3Department of Microbiology and Immunology, The Faculty of Health Sciences of the Jan Kochanowski University in Kielce, Kielce, 4Institute of Chemistry, University of Bialystok, Białystok, Poland; 5Department of Physiology, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA, USA Background: 1,4-Dihydropyridine (1,4-DHP) and its derivatives are well-known calcium channel blockers with antiarrhythmic and antihypertensive activities. These compounds exhibit pleiotropic effects including antimicrobial activities that rely on their positive charge and amphipathic nature. Use of magnetic nanoparticles (MNPs) as carriers of 1,4-DHP modulates their properties and enables improved formulations with higher efficacy and less toxicity. Methods: In this study, the antimicrobial and immunomodulatory activities of novel 1,4-DHP derivatives in free form and immobilized on MNPs were determined by evaluating pathogen outgrowth and proinflammatory cytokine release in experimental settings that involve incubation of various 1,4-DHPs with clinical isolates of bacteria or fungi as well as mammalian cell culture models. Results: Conventional immobilization of 1,4-DHP on aminosilane-coated MNPs markedly enhances their antimicrobial activity compared to nonimmobilized molecules, in part because of the higher affinity of these nanosystems for bacterial cell wall components in the presence of human body fluids. Conclusion: Optimized nanosystems are characterized by improved biocompatibility and higher anti-inflammatory properties that provide new opportunities for the therapy of infectious diseases. Keywords: magnetic nanoparticles, 1,4-dihydropyridine, antibacterial, antifungal, immunomodulatory properties