Abstract: The bulk properties of elementary metals and copper based binary alloys have been investigated using automated first-principles simulations to evaluate their potential to replace copper and tungsten as interconnecting wires in the coming CMOS technology nodes. The intrinsic properties of the screened candidates based on their cohesive energy and on their electronic properties have been used as a metrics to reflect their resistivity and their sensitivity to electromigration. Using these values, the 'performances' of the alloys have been benchmarked with respect to the Cu and W ones. It turns out that for some systems, alloying Cu with another element leads to a reduced tendency to electromigration. This is however done at the expense of a decrease of the conductivity of the alloy with respect to the bulk metal. (C) 2014 The Electrochemical Society. All rights reserved.

Abstract: In the present work, a novel graphene (GN) and gelatin (GTN) composite was prepared and used as an immobilization matrix for hemoglobin (Hb). Compared with Hb immobilized on a bare, GN or GTN modified glassy carbon electrode (GCE), a stable and pair of well-defined quasi redox couple was observed at an Hb modified GN/GTN composite GCE at a formal potential of −0.306 V versus Ag|AgCl. The direct electrochemical behavior of Hb was greatly enhanced by the presence of both GTN and GN. A heterogeneous electron transfer rate constant (Ks) was calculated as 3.82 s−1 for Hb immobilized at GN/GTN modified GCE, which indicates the fast direct electron transfer of Hb toward the electrode surface. The biosensor shows a stable and wide linear response for H2O2 in the linear response range from 0.1 μM to 786.6 μM with an analytical sensitivity and limit of detection of 0.48 μAμM−1 cm−2 and 0.04 μM, respectively. The fabricated biosensor holds its high selectivity in the presence of potentially active interfering species and metal ions. The biosensor shows its satisfactory practical ability in the commercial contact lens solution and human serum samples.

Abstract: Nanocrystalline ZnO:Al nanoparticles are suitable building blocks for transparent conductive layers. As the concentration of substitutional tetrahedral Al is an important factor for improving conductivity, here we aim to increase the fraction of substitutional Al. To this end, synthesis parameters of a solvothermal reaction yielding ZnO:Al nanorods were varied. A unique set of complementary techniques was combined to reveal the exact position of the aluminium ions in the ZnO lattice and demonstrated its importance in order to evaluate the potential of ZnO:Al nanocrystals as optimal building blocks for solution deposited transparent conductive oxide layers. Both an extension of the solvothermal reaction time and stirring during solvothermal treatment result in a higher total tetrahedral aluminium content in the ZnO lattice. However, only the longer solvothermal treatment effectively results in an increase of the substitutional positions aimed for.

Abstract: Aquaporins (AQPs) are transmembrane proteins that conduct not only water molecules across the cell membrane but also other solutes, such as reactive oxygen and nitrogen species (RONS), produced (among others) by cold atmospheric plasma (CAP). These RONS may induce oxidative stress in the cell interior, which plays a role in cancer treatment. The underlying mechanisms of the transport of RONS across AQPs, however, still remain obscure. We apply molecular dynamics simulations to investigate the permeation of both hydrophilic (H₂O₂and OH) and hydrophobic (NO₂and NO) RONS through AQP1. Our simulations show that these RONS can all penetrate across the pores of AQP1. The permeation free energy barrier of OH and NO is lower than that of H₂O₂and NO₂, indicating that these radicals may have easier access to the pore interior and interact with the amino acid residues of AQP1. We also study the effect of RONS-induced oxidation of both the phospholipids and AQP1 (i.e., sulfenylation of Cys₁₉₁) on the transport of the above-mentioned RONS across AQP1. Both lipid and protein oxidation seem to slightly increase the free energy barrier for H₂O₂and NO₂permeation, while for OH and NO, we do not observe a strong effect of oxidation. The simulation results help to gain insight in the underlying mechanisms of the noticeable rise of CAP-induced RONS in cancer cells, thereby improving our understanding on the role of AQPs in the selective anticancer capacity of CAP.

Abstract: Non-thermal plasma (NTP), an ionized gas generated at ambient pressure and temperature, has been an emerging technology for medical applications. Through controlled delivery of reactive oxygen and nitrogen species (ROS/RNS), NTP can elicit hormetic cellular responses, thus stimulating broad therapeutic effects. To enable clinical translation of the promising preclinical research into NTP therapy, a deeper understanding of NTP interactions with clinical substrates is profoundly needed. Since NTP-generated ROS/RNS will inevitably interact with blood in several clinical contexts, understanding their stability in this system is crucial. In this study, two medically relevant NTP delivery modalities were used to assess the stability of NTP-generated ROS/RNS in three aqueous solutions with increasing organic complexities: phosphate-buffered saline (PBS), blood plasma (BP), and processed whole blood. NTP-generated RNS collectively (NO2−, ONOO−), H2O2, and ONOO− exclusively were analyzed over time. We demonstrated that NTP-generated RNS and H2O2 were stable in PBS but scavenged by different components of the blood. While RNS remained stable in BP after initial scavenging effects, it was completely reduced in processed whole blood. On the other hand, H2O2 was completely scavenged in both liquids over time. Our previously developed luminescent probe europium(III) was used for precision measurement of ONOO− concentration. NTP-generated ONOO− was detected in all three liquids for up to at least 30 seconds, thus highlighting its therapeutic potential. Based on our results, we discussed the necessary considerations to choose the most optimal NTP modality for delivery of ROS/RNS to and via blood in the clinical context.

Abstract: In July 2015, the Council of the International Seabed Authority (ISA) adopted seven priority deliverables for the development of the exploitation code. The first priority was the development of a zero draft of the exploitation regulations. This article focusses on the second priority deliverable, namely the development of a payment mechanism for exploitation activities, following detailed financial and economic models based on proposed business plans. Between 2015 and 2017, five workshops have been organised with 196 active participants from 34 countries. The results so far are synthesised, drawing upon the outcome of these workshops, ISA technical papers, and the scholarly literature.

Abstract: Background: Currently, nanoliposomal irinotecan (nal-IRI) + 5-fluorouracil/folinic acid (5-FU/ LV) is the only approved second-line treatment for patients suffering from metastatic pancreatic ductal adenocarcinoma (mPDAC). However, also other chemotherapeutic regimens are used in this setting and due to the lack of clear real-world data on the efficacy of the different regimens, there is no consensus on the optimal treatment sequence for mPDAC patients. Objectives: To provide information on the safe and efficacious use of nal-IRI + 5-FU/LV in clinical practice in Belgium, which is needed for healthcare professionals to estimate the risk-benefit ratio of the intervention. Methods: Medical data of adult patients with mPDAC who were treated with nal-IRI + 5-FU/ LV in one of the participating Belgian hospitals were retrospectively collected. Kaplan-Meier analysis was performed to obtain survival curves to estimate the median overall survival (OS) and progression-free survival (PFS). All other results were presented descriptively. Results: A total of 56 patients [median age at diagnosis: 69 years (range 43 years), 57.1% male] were included. Patients received a median of 5 (range 49 cycles) nal-IRI + 5-FU/LV cycles, extended over 10 weeks (range 130.8 weeks). The median start dose for nal-IRI was 70 mg/ m(2) (range 49.24 mg/m(2)) and chemotherapy dose reduction and delay occurred in, respectively, 42.8% and 37.5% of the patients. The median OS was 6.8 months (95% CI: 5.6-8.4 months) with a 6-month survival rate of 57.4% and a 1-year survival rate of 27.8% in the overall study population. The median OS for patients treated with nal-IRI as second-line therapy or as laterline treatment was, respectively, 6.8 months (95% CI: 5.9-7.0 months) and 5.6 months (95% CI: 4.2-no upper limit). In the overall study population, a median PFS of 3.1 months (95% CI: 2.4-4.6 months) and a disease control rate of 48.3%, comprising 30.4% stable disease, 16.1% partial and 1.8% complete response, was observed. The median PFS for patients treated with nal-IRI as second-line therapy was 3.9 months (95% CI: 2.8-4.8 months) while this was 2.4 months (95% CI: 1.9-9.1 months) for those that received nal-IRI in a later-line treatment. In terms of safety, gastrointestinal problems occurred most (64.3% of the patients) and from all reported treatment emergent adverse events, 39.2% were grade 3 or 4. Conclusion: Nal-IRI + 5-FU/LV is a valuable, effective, and safe sequential treatment option following gemcitabine-based therapy in patients with mPDAC.

Abstract: We investigate the effect of an external magnetic field on the carrier states that are localized at a potential kink and a kink-antikink in bilayer graphene. These chiral states are localized at the interface between two potential regions with opposite signs.

Abstract: The Robin problem for the Helmholtz equation in normal-polar annuli is addressed by using a suitable Fourier-Hankel series technique. Attention is in particular focused on the wide class of domains whose boundaries are defined by the so-called superformula introduced by Gielis. A dedicated numerical procedure based on the computer algebra system Mathematica© is developed in order to validate the proposed methodology. In this way, highly accurate approximations of the solution, featuring properties similar to the classical ones, are obtained.

Abstract: Background The use of neostigmine after neuromuscular blockade (NMB) has been associated with postoperative respiratory complications. In previous studies, we found lower diaphragmatic activity after neostigmine reversal of NMB, compared to sugammadex. It is still unclear whether the adequate use of neostigmine guarantees normal respiratory muscle function after NMB. In this study, we wanted to assess the effect of commonly used degrees of NMB and their possible reversal strategies on respiratory muscle activity after the return of normal neuromuscular transmission. Methods This is a randomized, controlled, parallel-group, single-centre, double-blind study in patients scheduled for intracranial surgery at a tertiary academic hospital in Belgium. All participants received target controlled propofol/remifentanil anesthesia and were randomized into one of five groups, receiving either a shallow NMB with no reversal (shallow/saline), a shallow NMB with sugammadex reversal (shallow/sugammadex), a moderate NMB with neostigmine reversal (moderate/neostigmine), a moderate NMB with sugammadex reversal (moderate/sugammadex), or a deep NMB with sugammadex reversal (deep/sugammadex). Primary and secondary outcome parameters were diaphragm and intercostal electromyographic (EMG) activity at the moment of resumed spontaneous breathing activity, defined as a maximal interval of 10 min after the first spontaneous breath. Results For the five groups, a total of 55 patients could be included in the final analysis. Median time of spontaneous breathing analyzed was 5 min (IQR 3-9.5 min). Both the moderate/sugammadex and the moderate/neostigmine groups had lower levels of diaphragm EMG compared to the shallow/sugammadex group. The moderate/neostigmine group had lower levels of intercostal EMG activity compared to the shallow/saline group. Conclusions In this study, the depth of neuromuscular blockade and type of reversal strategy impacts respiratory muscle activity at the moment of resumed spontaneous breathing and recovery of neuromuscular blockade. Both groups that received moderate NMB had lower levels of diaphragm EMG, compared to the shallow NMB group with sugammadex reversal. Compared to the shallow NMB group with no reversal, the moderate NMB with neostigmine reversal group had lower intercostal EMG activity.

Abstract: Background Breast cancer (BC) is the most common cancer in women in the developed world. In order to find developing cancers in an early stage, BC screening is commonly used. In Flanders, screening is performed in and outside an organized breast cancer screening program (BCSP). However, the determinants of BC screening coverage for both screening strategies are yet unknown. Objective To assess the determinants of BC screening coverage in Flanders. Methods Reimbursement data were used to attribute a screening status to each woman in the target population for the years 2008-2016. Yearly coverage data were categorized as screening inside or outside BCSP or no screening. Data were clustered by municipality level. A generalized linear equation model was used to assess the determinants of screening type. Results Over all years and municipalities, the median screening coverage rate inside and outside BCSP was 48.40% (IQR: 41.50-54.40%) and 14.10% (IQR: 9.80-19.80%) respectively. A higher coverage rate outside BSCP was statistically significantly (P < 0.001) associated with more crowded households (OR: 3.797, 95% CI: 3.199-4.508), younger age, higher population densities (OR: 2.528, 95% CI: 2.455-2.606), a lower proportion of unemployed job seekers (OR: 0.641, 95% CI: 0.624-0.658) and lower use of dental care (OR: 0.969, 95% CI: 0.967-0.972). Conclusion Coverage rate of BC screening is not optimal in Flanders. Women with low SES that are characterized by younger age, living in a high population density area, living in crowded households, or having low dental care are less likely to be screened for BC in Flanders. If screened, they are more likely to be screened outside the BCSP.

Abstract: Background The diagnosis of active Toxocara canis infections in humans is challenging. Larval stages of T. canis do not replicate in human tissues and disease may result from infection with a single T. canis larva. Recently, we developed a nanobody-based electrochemical magnetosensor assay with superior sensitivity to detect T. canis excretory-secretory (TES) antigens. Here, we evaluate the performance of the assay in children from an Ecuadorian birth cohort that followed children to five years of age. Methods Samples were selected based on the presence of peripheral blood eosinophilia and relative eosinophil counts. The samples were analyzed by the nanobody-based electrochemical magnetosensor assay, which utilizes a bivalent biotinylated nanobody as capturing agent on the surface of streptavidin pre-coated paramagnetic beads. Detection was performed by a different nanobody chemically labelled with horseradish peroxidase. Results Of 87 samples tested, 33 (38%) scored positive for TES antigen recognition by the electrochemical magnetosensor assay. The average concentration of TES antigen in serum was 2.1 ng/ml (SD = 1.1). The positive result in the electrochemical assay was associated with eosinophilia > 19% (P = 0.001). Parasitological data were available for 57 samples. There was no significant association between positivity by the electrochemical assay and the presence of other soil-transmitted helminth infections. Conclusions Our nanobody-based electrochemical assay provides highly sensitive quantification of TES antigens in serum and has potential as a valuable tool for the diagnosis of active human toxocariasis.

Abstract: Vincent van Gogh's still lifes Irises and Roses were investigated to shed light onto the degree to which the paintings had changed, both individually and in relation to each other since they were painted, particularly in regard to the fading of the red lakes. Non-invasive techniques, including macroscopic X-ray fluorescence mapping, reflectance imaging spectroscopy, and X-radiography, were combined with microanalytical techniques in a select number of samples. The in-depth microchemical analysis was necessary to overcome the complications that arise when evaluating by non-invasive methods alone the compositions of passages with complex layering and mixing of paints. The results obtained by these two approaches were complemented by color measurements performed on paint cross-sections and on protected edges, and with historical information provided by the artist's own descriptions, early reviews and reproductions, and the data was used to carry out digital color simulations that provided, to a certain extent, a visualization of how the paintings may have originally appeared.

Abstract: This paper reports on how the application of macro X-ray fluorescence (MA-XRF) imaging, in combination with the re-examination of existing paint cross-sections, has led to the discovery of a new pigment in Rembrandt's palette: artificial orpiment. In the NWO Science4Arts 'ReVisRembrandt' project, novel chemical imaging techniques are being developed and applied to the study of Rembrandt's late paintings in order to help resolve outstanding questions and to gain a better understanding of his late enigmatic painting technique. One of the selected case studies is the Portrait of a Couple as Isaac and Rebecca, known as 'The Jewish Bride', dated c. 1665 and on view in the Rijksmuseum. During the re-installation of the Rijksmuseum in 2013, the picture was scanned using the Bruker M6 Jetstream MAXRF scanner. The resulting elemental distribution maps made it possible to distinguish many features in the painting, such as bone black remains of the original hat (P, Ca maps), and the now discolored smalt-rich background (Co, Ni, As, K maps). The arsenic (As) map also revealed areas of high-intensity in Isaac's sleeve and Rebecca's dress where it could be established that it was not related with the pigment smalt that also contains arsenic. This pointed to the presence of a yellow or orange arsenic-containing pigment, such as realgar or orpiment that is not associated with the artist's palette. Subsequent examination of existing paint cross-sections from these locations taken by Karin Groen in the 1990s identified isolated, almost perfectly round particles of arsenic sulfide. The round shape corresponds with published findings on a purified form of artificial orpiment glass obtained by dry processing, a sublimation reaction. In bright field, the particles characteristically exhibit a dark cross in the middle caused by internal light reflections. The results of additional non-invasive techniques (portable XRD and portable Raman) are discussed, as well as the implications of this finding and how it fits with Rembrandt's late experimental painting technique.

Abstract: Prior studies have shown the improved ability to identify artists' pigments by combining results from X-ray fluorescence (XRF), which provides elemental information, with reflectance spectroscopy in the visible to near infrared (400-1000 nm) that provides information on electronic transitions. Extending the spectral range of reflectance spectroscopy into the UV, 350-400 nm, allows identification of several white pigments since their electronic transitions occur in this region (e.g., zinc white and rutile and anatase forms of titanium white). Extending the range further into the infrared, out to 2500 nm, provides information on vibrational transitions of various functional groups, such as hydroxyl, carbonate, and methyl groups. This allows better identification of mineral-based pigments and some paint binders. The combination of elemental information with electronic and vibrational transitions provides a more robust method to identify artists' materials in situ. The collection of both sets of spectral information across works of art, such as paintings and works on paper, allows generating a more complete map of artists' materials. Here, we describe a 2-D scanner that simultaneously collects XRF spectra and reflectance spectra from 350 to 2500 nm across the surfaces of works of art. The scanner consists of a stationary, single pixel XRF spectrometer and fiber optic reflectance spectrometer along with a 2-D position-controlled easel that moves the artwork in front of the two detection systems. The dual-mode scanner has been tested on a variety of works of art from illuminated manuscripts (0.1 x 0.1 m(2)) to paintings as large as 1.7 x 1.9 m(2). The scanner is described and two sets of results are presented. The first is the XRF scanning of a large warped panel painting by Andrea del Sarto titled Charity. The second is a combined XRF and reflectance scan of Georges Seurat's painting titled Haymakers at Montfermeil. The XRF was collected at 1 mm spatial sampling and the reflectance spectral data at 3 mm. Combining the results from the data sets was found to enhance the identification of pigments as well as yield distribution maps, in spite of the relatively low reflectance spatial sampling. The elemental and reflectance maps allowed the identification and mapping of lead white, cobalt blue, viridian, ochres, and likely chrome yellow. The maps also provide information on the mixing of pigments. While the reflectance image cube has 10-20x larger spatial samples than desired, the elimination of having to use two hyperspectral cameras to cover the range from 400 to 2500 nm makes for a low cost dual modality scanner.