The sensitivity of innovative techniques for measuring low levels of radon in the environment using passive detectors.

In recent years, there has been a significant surge in interest in measuring low radon levels in the environment. These measurements are valuable, particularly for identifying radon priority areas as required by the European Council Directive 2013/59/EURATOM and for research related to climate change. Due to the limited sensitivity of existing radon detectors/monitors in addressing these challenges, substantial efforts have been devoted to developing new designs. This report compares the sensitivity of several innovative designs with that of existing passive radon monitors. These novel designs incorporate alpha track detectors, including large area low background detectors, with activated carbon fabric used as an efficient radon adsorber/radiator. Recent innovative solutions to mitigate the impact of temperature and humidity on detectors using adsorbers are also discussed. The background signal of detectors intended for use in these novel designs is examined, and their sensitivity is evaluated. The findings demonstrate that these novel designs have the potential to significantly enhance the sensitivity of long-term radon measurements, surpassing the detectors currently in widespread use by more than an order of magnitude.

Adcitmer® , a new CD56-targeting monomethyl auristatin E-conjugated antibody, is a potential therapeutic approach in Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive skin cancer, whose tumour cells often express CD56. While immune checkpoint inhibitors constitute a major advance for treating patients with MCC with advanced disease, new therapeutic options are still urgently required. OBJECTIVES: To produce and evaluate the therapeutic performance of a new antibody-drug conjugate (Adcitmer® ) targeting CD56 in preclinical models of MCC. METHODS: CD56 expression was evaluated in a MCC cohort (immunohistochemistry on a tissue microarray of 90 tumour samples) and MCC cell lines. Interaction of an unconjugated CD56-targeting antibody with CD56+ MCC cell lines was investigated by immunohistochemistry and imaging flow cytometry. Adcitmer® product was generated by the bioconjugation of CD56-targeting antibody to a cytotoxic drug (monomethyl auristatin E) using the McSAF Inside® bioconjugation process. The chemical properties and homogeneity of Adcitmer® were characterized by hydrophobic interaction chromatography. Adcitmer® cytotoxicity was evaluated in vitro and in an MCC xenograft mice model. RESULTS: Similar to previous reports, CD56 was expressed by 66% of MCC tumours in our cohort, confirming its relevance as a therapeutic target. Specific binding and internalization of the unconjugated CD56-targeting antibody was validated in MCC cell lines. The high homogeneity of the newly generated Adcitmer® was confirmed by hydrophobic interaction chromatography. The CD56-mediated cytotoxicity of Adcitmer® was demonstrated in vitro in MCC cell lines. Moreover, Adcitmer® significantly reduced tumour growth in a MCC mouse model. CONCLUSIONS: Our study suggests that Adcitmer® should be further assessed as a therapeutic option in patients with MCC, as an alternative therapy or combined with immune checkpoint inhibitors.

Optimization and diagnostic evaluation of monoclonal antibody-based blocking ELISA formats for detection of neutralizing antibodies to Hendra virus in mammalian sera.

Maintenance of Hendra virus (HeV) in pteropid bat populations has been associated with spillover events in horses, humans and dogs. Experimental studies have demonstrated infections for several other species including guinea pigs, cats and ferrets. The criteria of a sensitive and specific serological test that is effective for a range of species, but which does not require use of live virus, has not been satisfactorily addressed by currently available tests. We have evaluated the use of two HeV neutralizing monoclonal antibodies (mAbs) in a blocking format enzyme-linked immunosorbent assay (bELISA) to detect serum antibody against a recombinant expressed HeV G protein (sol G) in several animal species. The human mAb m102.4 neutralises both HeV and the closely related Nipah virus (NiV); the mouse mAb 1.2 neutralises only HeV. Given these functional differences, we have investigated both antibodies using a bELISA format. Diagnostic sensitivity (DSe) and diagnostic specificity (DSp) were optimized using individual thresholds for mAb 1.2 and m102.4. For mAb 1.2 the positive threshold of >33% inhibition yielded DSe and DSp values of 100% (95% CI 95.3-100.0) and 99.5 (95% CI 98.8-99.8) respectively; for mAb m102.4 a positive threshold of >49% inhibition gave DSe and DSp values of 100 (95% CI 95.3-100.0) and 99.8 (95% CI 99.2-100.0) respectively. At these thresholds the DSe was 100% for both tests relative to the virus neutralization test. Importantly, the occurrence of false positive reactions did not overlap across the assays. Therefore, by sequential and selective application of these assays, it is possible to identify false positive reactions and achieve a DSp that approximates 100% in the test population.

Identifying radon priority areas and dwellings with radon exceedances in Bulgaria using stored CD/DVDs.

The implementation of the 2013/59/EURATOM directive in the part related to radon exposure imposes challenges for radon measurement methodology and radon survey design. Among them is the need to have estimates (preferably direct) of the annual average radon concentrations, which can be directly compared to the recommended reference levels. On this basis, the surveys should make possible the identification of dwellings with indoor radon above the reference levels and "radon priority areas" where significant proportion of the dwellings falls in this category. The performance of the CD/DVD method for radon measurements as a tool to address these issues is presented. A recent large scale field study based on the CD/DVD method that was carried out in the suburb area of Sofia, Bulgaria is described. Part of the studied area was affected in the past by the uranium mining and milling industry. In total 462 disks (CDs and DVDs) taken from 335 private dwellings from 10 districts in the region were analyzed. The results revealed the large heterogeneity in radon distribution in the area, with the percentage of dwellings with a 222Rn level above 300 Bq m-3 ranking from about 7% to 74%. The district of Yana, for which this percent was 74, was identified as the area of highest radon priority in the region. The paper also discusses how prompt identification of dwellings with radon above the reference level by CD/DVDs can be incorporated within an integrated approach to the radon problem. Within this approach the radon hazard is identified shortly after the stakeholder's decision to test, which allows fast solution of the problem without waiting the long (and usually demotivating) one-year period needed for direct results by the commonly used prospective methods.

THE CD/DVD METHOD AS A TOOL FOR THE HEALTH PHYSICS SERVICE AND VENTILATION DIAGNOSTICS IN UNDERGROUND MINES.

The CD/DVDs used as radon (222Rn) and thoron (220Rn) detectors can provide a sufficiently sensitive and cost-efficient option for passive radiation monitoring in underground mines. This note presents results of measurements made under real environmental conditions by CD/DVDs. Comparison with conventional diffusion chambers was made and good correspondence was observed. Correlation between 222Rn and 220Rn was studied by CD/DVDs and no signs for any correlation were observed. Dedicated study in a mine gallery showed that CD/DVDs can be successfully used for the purposes of ventilation diagnostics by identifying sources of air contaminated with radon.

COMPARATIVE STUDY OF RADON AND THORON MEASUREMENTS IN FOUR ROMANIAN SHOW CAVES.

Measurements have been carried out using four types of passive detectors in four of the most popular show caves in Romania. Three types of detectors (RSKS, RadTrak and CD) were used for radon measurements and two (Raduet and CD) for thoron measurement. Activity concentrations in air were measured in the same locations for two seasons, autumn and winter. Measured values for the different caves varied between below detection limit (5 Bq m-3) and 4024 Bq m-3 for radon and from below 10 to 583 Bq m-3 for thoron. The results indicate a very good correlation between RSKS and RadTrak detectors (r = 0.96). The most significant difference between radon concentrations measured with different types of detectors (RSKS and CD) was higher than 150%. The study suggests that the activity concentration of radon in caves, measured using track detectors, could not be influenced by the type of detector used if the microclimate factor is acknowledged.

[Determining the level of occurrence of the lipid nucleus of atherosclerotic plaques in the abdominal aorta by means of infrared Fourier spectroscopy].

The article deals with the problem of diagnosis of atherosclerotic alterations in abdominal aorta wall in order to reduce atherosclerosis-related mortality. Targeted treatment requires determining the exact mechanism of development of atherosclerosis. Infrared Fourier spectroscopy is suggested as the most rapid and accurate method of diagnosis and analysis of the content of various organic compounds playing a particular role in the development of the atherosclerotic process. Presented herein are the results of studying various types of fluctuations, whose absorption bands correspond to such organic compounds as collagen, elastin and cholesterol esters. A peculiar feature of this technique consists in a new method of the preparation of the material, including preparation of samples to be studied, with no stage of fixation. Analysed herein is one of the pathogenetic mechanisms of the development of the atherosclerotic process, consisting in accumulation in the vascular intima of low and very low density lipoproteins which are detected at a frequency of 1745 cm(-1), corresponding to stretching vibrations of the C=O bond. These organic compounds saturate from the inside the vascular wall, thus leading to formation of a lipid nucleus of an atherosclerotic plaque, whose centre is located at a certain depth. The authors present the results of studying the level of the centre of the lipid nucleus of an atherosclerotic plaque in abdominal aorta in perished 70-74-year-old people. It was determined that for this age group the level of the lipid nucleus is concentrated at a depth of 200-240 µm. Besides, presented are the results obtained while studying the abdominal aorta in 23-26-year-old deceased people whose vessels were not affected by atherosclerosis. Obtained are comparative results on the shift in bandwidth of amid I and amid II in studying the intima of the healthy aorta and atherosclerosis-affected aorta. This peculiarity may later on become an identifier of the degree of the development of atherosclerosis in man. The results of such studies provide possibility to influence namely the centre of the lipid nucleus as one of the initial stages of the development of atherosclerosis in order to slow down the progression of the disease concerned.

High-affinity FRß-specific CAR T cells eradicate AML and normal myeloid lineage without HSC toxicity.

Acute myeloid leukemia (AML) is an aggressive malignancy, and development of new treatments to prolong remissions is warranted. Chimeric antigen receptor (CAR) T-cell therapies appear promising but on-target, off-tumor recognition of antigen in healthy tissues remains a concern. Here we isolated a high-affinity (HA) folate receptor beta (FRß)-specific single-chain variable fragment (2.48 nm KD) for optimization of FRß-redirected CAR T-cell therapy for AML. T cells stably expressing the HA-FRß CAR exhibited greatly enhanced antitumor activity against FRß(+) AML in vitro and in vivo compared with a low-affinity FRß CAR (54.3 nm KD). Using the HA-FRß immunoglobulin G, FRß expression was detectable in myeloid-lineage hematopoietic cells; however, expression in CD34(+) hematopoietic stem cells (HSCs) was nearly undetectable. Accordingly, HA-FRß CAR T cells lysed mature CD14(+) monocytes, while HSC colony formation was unaffected. Because of the potential for elimination of mature myeloid lineage, mRNA CAR electroporation for transient CAR expression was evaluated. mRNA-electroporated HA-FRß CAR T cells retained effective antitumor activity in vitro and in vivo. Together, our results highlight the importance of antibody affinity in target protein detection and CAR development and suggest that transient delivery of potent HA-FRß CAR T cells is highly effective against AML and reduces the risk for long-term myeloid toxicity.

Micro-Raman and infrared studies of multiferroic TbMn2O5.

We have studied the Raman and infrared spectral response of TbMn2O5 under an applied magnetic field parallel to the easy magnetic a-axis at 4.2 K. Strong spin-lattice coupling in TbMn2O5 is evidenced by a frequency shift of Raman and infrared phonons as a function of magnetic field compared to the phonon response of BiMn2O5 that remains unaffected. The magnetic field behavior of the highest frequency phonons retraces the polarization switching in TbMn2O5 and shows an important frequency softening below 3 T that is modulated by the J 3 and J 4 exchange parameters. The role of the Tb(3+) spin alignment with H is interpreted in terms of a local lattice striction and the contribution of the charge transfer mechanism to the magnetoelectric process is evaluated.

Host preferences of ornithophilic biting midges of the genus Culicoides in the Eastern Balkans.

Many biting midges of the genus Culicoides Latreille, 1809 (Diptera: Ceratopogonidae) are competent vectors of a diverse number of pathogens. The identification of their feeding behaviour and of vector-host associations is essential for understanding their transmission capacity. By applying two different nested polymerase chain reaction (PCR) assays, of which one targeted the avian cyt b gene and the other targeted the COI gene of a wide range of vertebrates, we identified the blood hosts of six biting midge species including Culicoides circumscriptus, Culicoides festivipennis, Culicoides punctatus, Culicoides pictipennis, Culicoides alazanicus and Culicoides cf. griseidorsum, the latter two of which are reported in Bulgaria for the first time. Bird DNA was found in 50.6% of 95 investigated bloodmeals, whereas mammalian DNA was identified in 13.7%. Two Culicoides species were found to feed on both birds and mammals. There was remarkable diversity in the range of avian hosts: 23 species from four orders were identified in the abdomens of four Culicoides species. The most common bird species identified was the magpie, Pica pica (n = 7), which was registered in all four ornithophilic biting midge species. Six bloodmeals from the great tit, Parus major, were recorded only in C. alazanicus. None of the studied species of Culicoides appeared to be restricted to a single avian host.

Dietary essential oils improve the hepatic antioxidative status of broiler chickens.

1. A total of 200 male Ross 308 chickens were used to evaluate the effects of a standardised combination of essential oils including 5% carvacrol, 3% cinnamaldehyde and 2% capsicum oleoresin (XT 6930; Pancosma S.A., Geneva, Switzerland) on their performance, hepatic antioxidant concentration and caecal tonsils morphometry. 2. Two diets were offered to broiler chickens from d old to 21 d of age. The control diet (C) was slightly lower in metabolisable energy (12.13 MJ/kg ME) and crude protein (215 g/kg CP) than breeders' recommendation. The second diet, made as XT 6930, was added on the top of the control diet at 100 mg/kg. Each diet was offered ad libitum to birds housed in one of 10 floor pens in a randomised complete block design. The birds were housed in 20 floor pens, 10 birds in each pen, and were allocated to 10 replicates of the two dietary treatments. 3. The concentration of antioxidants in the liver of the birds was determined using high-performance liquid chromatography (HPLC) at 21 d of age. Birds fed control diet only had lower weight and converted less efficiently feed to gain compared to birds fed essential oils-supplemented diet. Feed consumption was not affected by dietary treatments. The antioxidant data showed that supplemented essential oils improved the hepatic concentration of carotenoids and coenzyme Q10 when fed to broiler chickens. The morphometry of the caecal tonsils of the birds was not influenced by dietary treatments. 4. It can be concluded that that dietary combination of essential oils, including carvacrol, cinnamaldehyde and capsicum oleoresin, improved growth, feed efficiency and the hepatic concentration of carotenoids and coenzyme Q10 when fed to broiler chickens.

Polymer brushes with nanoinclusions under shear: A molecular dynamics investigation.

We use molecular dynamics simulations with a dissipative particle dynamics thermostat to study the behavior of nanosized inclusions (colloids) in a polymer brush under shear whereby the solvent is explicitly included in the simulation. The brush is described by a bead-spring model for flexible polymer chains, grafted on a solid substrate, while the polymer-soluble nanoparticles in the solution are taken as soft spheres whose diameter is about three times larger than that of the chain segments and the solvent. We find that the brush number density profile, as well as the density profiles of the nanoinclusions and the solvent, remains insensitive to strong shear although the grafted chains tilt in direction of the flow. The thickness of the penetration layer of nanoinclusions, as well as their average concentration in the brush, stays largely unaffected even at the strongest shear. Our result manifests the remarkable robustness of polymer brushes with embedded nanoparticles under high shear which could be of importance for technological applications.

Thermal breakage and self-healing of a polymer chain under tensile stress.

We consider the thermal breakage of a tethered polymer chain of discrete segments coupled by Morse potentials under constant tensile stress. The chain dynamics at the onset of fracture is studied analytically by Kramers-Langer multidimensional theory and by extensive molecular dynamics simulations in one dimension (1D) and three dimension (3D) space. Comparison with simulation data in one and three dimensions demonstrates that the Kramers-Langer theory provides good qualitative description of the process of bond scission as caused by a collective unstable mode. We derive distributions of the probability for scission over the successive bonds along the chain which reveal the influence of chain ends on rupture in good agreement with theory. The breakage time distribution of an individual bond is found to follow an exponential law as predicted by theory. Special attention is focused on the recombination (self-healing) of broken bonds. Theoretically derived expressions for the recombination time and distance distributions comply with MD observations and indicate that the energy barrier position crossing is not a good criterion for true rupture. It is shown that the fraction of self-healing bonds increases with rising temperature and friction.

Method for wettability characterization based on contact line pinning.

We demonstrate an efficient and reliable method for wettability characterization by determining the contact angle theta which a liquid-vapor interface makes with a solid wall. The purpose is to overcome the difficulties, related to the curvature of the liquid-vapor interface, which make measurements of theta rather uncertain, especially on the micro- and nanoscale. The method employs a specially designed slitlike channel in contact with a reservoir whereby the wettability of one of the slit walls is to be examined whereas the other (auxiliary) wall is separated by half into a lyophilic and a lyophobic part so as to pin the incoming fluid and fix the one end of the liquid-vapor interface. In the present work, the physical background of the method is elucidated theoretically while the method's applicability is demonstrated by molecular-dynamics simulation of a typical Lennard-Jones fluid, in contact with an atomistic wall. The wettability of the latter, as described by the corresponding contact angle theta, is accurately determined by variation of the liquid-wall interaction in a very broad interval.

Capillary filling in microchannels with wall corrugations: a comparative study of the Concus-Finn criterion by continuum, kinetic, and atomistic approaches.

We study the impact of wall corrugations in microchannels on the process of capillary filling by means of three broadly used methods: computational fluid dynamics (CFD), lattice Boltzmann equations (LBE), and molecular dynamics (MD). The numerical results of these approaches are compared and tested against the Concus-Finn (CF) criterion, which predicts pinning of the contact line at rectangular ridges perpendicular to flow for contact angles of theta > 45 degrees . Whereas for theta = 30, 40 (no flow), and 60 degrees (flow) all methods are found to produce data consistent with the CF criterion, at theta = 50 degrees the numerical experiments provide different results. Whereas the pinning of the liquid front is observed both in the LB and CFD simulations, MD simulations show that molecular fluctuations allow front propagation even above the critical value predicted by the deterministic CF criterion, thereby introducing a sensitivity to the obstacle height.

Capillary rise in nanotubes coated with polymer brushes.

The spontaneous rise of a fluid in a brush-coated nanocapillary is studied by molecular dynamics simulation of a coarse-grained model. The cases of changing wettability of both the capillary walls and the brush were examined. We also investigated the impact of polymer chain length on the transport of fluid along the nanotube. We found that capillary filling takes place in both lyophilic and lyophobic tubes, provided that the polymer brush coating is wetted by the fluid. In all the cases studied, capillary rise proceeds by a time-square law, but the mechanisms behind them (Lucas-Washburn or diffusive propagation) differ, depending on the chain length N. For a wettable wall, the speed of fluid imbibition decreases steadily with growing N, whereas the meniscus speed goes through a minimum at intermediate chain lengths. The polymer brush coating reorganizes into "channels" parallel to the tube axis and forms a dense plug of monomers in the vicinity of the meniscus, which moves with the meniscus along the nanotube. For lyophobic capillary walls (covered with a wettable polymer brush), depending on the chain length N, one finds three regimes: (1) short chains--one observes no meniscus motion, but an influx of fluid through the wet brush; (2) intermediate chain lengths--the fluid creates "fluid walls" inside the brush by diffusive spreading, whereby a meniscus is formed and moves up within the fluid walls; and (3) long chains--a "negative curvature" meniscus rises up the capillary by means of diffusive propagation.

Nanoinclusions in polymer brushes with explicit solvent--a molecular dynamics investigation.

We use molecular dynamics simulations with a dissipative particle dynamics (DPD) thermostat to study the behavior of nanosized inclusions (colloids) in a polymer brush which is in contact with an explicit solvent in the NPT ensemble. The brush is described by a bead-spring model for flexible polymer chains, grafted on a solid substrate, while the polymer-soluble nanoparticles in the solution are taken as hard spheres. By varying the chain length N, the grafting density of the brush, sigma(g), and the size of the nanoparticles b, we determine the equilibrium particle penetration depth delta and the average concentration of nanoinclusions phi(nano) in the penetration layer delta at constant pressure. In agreement with a recent theoretical prediction, we demonstrate that for nanoinclusions of size bb(*) the thickness of this layer delta is proportional to h(b(*)/b)(3) where h is brush height and b(*) is proportional to sigma(g)(-2/3) is a typical size below which smaller particles are uniformly distributed in the brush. We also observe that particles, larger than some threshold value b(max) do not mix with the brush. The mean density of nanoinclusions is found to scale as phi(nano) is proportional to (b(*)/b)(3) within the whole range of parameter variation. The diffusivity of nanoparticles, embedded in the polymer brush, in direction perpendicular to the grafting plane is found to be up to 20% higher than parallel to the plane. The variation of the respective diffusion coefficients D(perpendicular)(nano) and D(parallel)(nano) changes with growing volume fraction of the nanoparticles in agreement with theoretical predictions.

The escape transition of a polymer: a unique case of non-equivalence between statistical ensembles.

A flexible polymer chain under good solvent conditions, end-grafted on a flat repulsive substrate surface and compressed by a piston of circular cross-section with radius L may undergo the so-called "escape transition" when the height of the piston D above the substrate and the chain length N are in a suitable range. In this transition, the chain conformation changes from a quasi-two-dimensional self-avoiding walk of "blobs" of diameter D to an inhomogeneous "flower" state, consisting of a "stem" (stretched string of blobs extending from the grafting site to the piston border) and a "crown" outside of the confining piston. The theory of this transition is developed using a Landau free-energy approach, based on a suitably defined (global) order parameter and taking also effects due to the finite chain length N into account. The parameters of the theory are determined in terms of known properties of limiting cases (unconfined mushroom, chain confined between infinite parallel walls). Due to the non-existence of a local order parameter density, the transition has very unconventional properties (negative compressibility in equilibrium, non-equivalence between statistical ensembles in the thermodynamic limit, etc.). The reasons for this very unusual behavior are discussed in detail. Using Molecular Dynamics (MD) simulation for a simple bead-spring model, with N in the range 50

Dynamics of a stretched nonlinear polymer chain.

We study the relaxation dynamics of a coarse-grained polymer chain at different degrees of stretching by both analytical means and numerical simulations. The macromolecule is modeled as a string of beads, connected by anharmonic springs, subject to a tensile force applied at the end monomer of the chain while the other end is fixed at the origin of coordinates. The impact of bond nonlinearity on the relaxation dynamics of the polymer at different degrees of stretching is treated analytically within the Gaussian self-consistent (GSC) approach and then compared to simulation results derived from two different methods: Monte Carlo (MC) and Molecular Dynamics (MD). At low and medium degrees of chain elongation we find good agreement between GSC predictions and the MC simulations. However, for strongly stretched chains, the MD method, which takes into account inertial effects, reveals two important aspects of the nonlinear interaction between monomers: (i) a coupling and energy transfer between the damped, oscillatory normal modes of the chain and (ii) the appearance of nonvanishing contributions of a continuum of frequencies around the characteristic modes in the power spectrum of the normal mode correlation functions.