Flux-Across-Surfaces Theorem for a Dirac Particle

We consider the asymptotic evolution of a relativistic spin-1/2-particle. i.e. a particle whose wavefunction satisfies the Dirac equation with external static potential. We prove that the probability for the particle crossing a (detector) surface converges to the probability, that the direction of the momentum of the particle lies within the solid angle defined by the (detector) surface, as the distance of the surface goes to infinity. This generalizes earlier non relativistic results, known as flux across surfaces theorems, to the relativistic regime

Microtubule inhibition as a proposed mechanism for the anthelmintic effect of phytochemicals isolated from Cicerbita alpina

The alpine plant Cicerbita alpina (L.) Wallr., when grown as a sprout, is known as a bitter-tasting culinary delicacy. Recently it has also been reported to have anthelmintic activity, prompting further investigation into its mechanism of action. Liquid-liquid fractions were prepared from a methanolic extract of the aerial parts and were submitted in parallel to embryo development (ED), worm motility (WMT), and cytotoxicity assays for anthelmintic and toxicity evaluations. The anthelminthic assays revealed the more polar fractions to be most active against Ascaridia galli embryos (BuOH | 68% ED | c = 500 μg/ml and EtOAc | 65% ED | c = 500 μg/ml) and Caenorhabditis elegans adult worms (BuOH | 49% WMT | c = 150 μg/ml and EtOAc | 74% WMT | c = 150 μg/ml) suggesting the fraction's constituents possess dual anthelmintic activity against multiple life-cycle stages (i.e., eggs, worms) of helminths. Additionally, the BuOH fraction was non-cytotoxic to human cell-lines. Subsequent FCC and SEC derived subfractions were submitted to the anthelmintic assay workflow and the enriched subfractions B1 and E3.8, phytochemically assigned as 11-β,13-dihydrolactucin and luteolin, demonstrated bioactivity against the embryo phenotype (B1 | 58% ED | c = 1.8 μM and E3.8 | 46% ED | c = 1.7 μM) within range of the flubendazole control. Furthermore, luteolin was found to inhibit C. elegans egg hatching (luteolin | 65% EH | c = 10 μM | t = 10 h) within the range of the control albendazole. Both identified anthelmintic phytochemicals were found to affect tubulin polymerisation at a concentration of c = 50 μM. Together with in silico virtual screening studies, these results suggest microtubule stabilisation as a possible anthelmintic target and mechanism of action. This work effectively advocates the consideration of C. alpina extracts and fractions for the development of herbal therapeutics against parasitic helminth

Super-resolved compressive demonstrator for Earth Observation applications in the Medium Infrared: instrumental concept, optical design and expected performances

Earth Observation (EO) systems are generating an ever-increasing amount of data to be handled on board yet with limited resources, which sometimes hinders a full exploitation of the information content. In this paper, we present a demonstrator of a super-resolved compressive imager operating in whiskbroom mode in the Visible-Near Infrared (VISNIR) and Medium Infrared (MIR) spectral ranges. The demonstrator, which is under development in the frame of the EU H2020 funded SURPRISE project, is based on the use of a Digital MicroMirror Device (DMD) as a core element of its architecture and it is inspired by a single-pixel camera in order to avoid the use of large focal plane arrays. The demonstrator has 10 channels in the VNIR and two channels in the MIR and it can reach a super-resolution factor from 4 x 4 to 32 x 32, that is the ratio between the number of pixels of the image reconstructed at the end of the process and the number of pixels of the detector. Besides, on the grounds of the results obtained by image reconstruction tests on simulated datasets by using Deep Learning based algorithms, data are expected to be natively compressed with a Compression Ratio up to 50%. The study is expected to provide valuable insight for the future development of a novel class of EO instruments with improved performances in terms of ground sampling distance, native compression and on-board processing capabilities. Additional presentation content can be accessed on the supplemental content page

The SURPRISE demonstrator: a super-resolved compressive instrument in the visible and medium infrared for Earth Observation

While Earth Observation (EO) data has become ever more vital to understanding the planet and addressing societal challenges, applications are still limited by revisit time and spatial resolution. Though low Earth orbit missions can achieve resolutions better than 100 m, their revisit time typically stands at several days, limiting capacity to monitor dynamic events. Geostationary (GEO) missions instead typically provide data on an hour-basis but with spatial resolution limited to 1 km, which is insufficient to understand local phenomena. In this paper, we present the SURPRISE project - recently funded in the frame of the H2020 programme – that gathers the expertise from eight partners across Europe to implement a demonstrator of a super-spectral EO payload - working in the visible (VIS) - Near Infrared (NIR) and in the Medium InfraRed (MIR) and conceived to operate from GEO platform -with enhanced performance in terms of at-ground spatial resolution, and featuring innovative on-board data processing and encryption functionalities. This goal will be achieved by using Compressive Sensing (CS) technology implemented via Spatial Light Modulators (SLM). SLM-based CS technology will be used to devise a super-resolution configuration that will be exploited to increase the at-ground spatial resolution of the payload, without increasing the number of detector’s sensing elements at the image plane. The CS approach will offer further advantages for handling large amounts of data, as is the case of superspectral payloads with wide spectral and spatial coverage. It will enable fast on-board processing of acquired data for information extraction, as well as native data encryption on top of native compression. SURPRISE develops two disruptive technologies: Compressive Sensing (CS) and Spatial Light Modulator (SLM). CS optimises data acquisition (e.g. reduced storage and transmission bandwidth requirements) and enables novel onboard processing and encryption functionalities. SLM here implements the CS paradigm and achieves a super-resolution architecture. SLM technology, at the core of the CS architecture, is addressed by: reworking and testing off-the-shelf parts in relevant environment; developing roadmap for a European SLM, micromirror array-type, with electronics suitable for space qualification. By introducing for the first time the concept of a payload with medium spatial resolution (few hundreds of meters) and near continuous revisit (hourly), SURPRISE can lead to a EO major breakthrough and complement existing operational services. CS will address the challenge of large data collection, whilst onboard processing will improve timeliness, shortening time needed to extract information from images and possibly generate alarms. Impact is relevant to industrial competitiveness, with potential for market penetration of the demonstrator and its components

Correction to: Solving patients with rare diseases through programmatic reanalysis of genome-phenome data

In the original publication of the article, consortium author lists were missing in the articl

Serum iron levels and the risk of Parkinson disease: a Mendelian randomization study

BACKGROUND: Although levels of iron are known to be increased in the brains of patients with Parkinson disease (PD), epidemiological evidence on a possible effect of iron blood levels on PD risk is inconclusive, with effects reported in opposite directions. Epidemiological studies suffer from problems of confounding and reverse causation, and mendelian randomization (MR) represents an alternative approach to provide unconfounded estimates of the effects of biomarkers on disease. We performed a MR study where genes known to modify iron levels were used as instruments to estimate the effect of iron on PD risk, based on estimates of the genetic effects on both iron and PD obtained from the largest sample meta-analyzed to date. METHODS AND FINDINGS: We used as instrumental variables three genetic variants influencing iron levels, HFE rs1800562, HFE rs1799945, and TMPRSS6 rs855791. Estimates of their effect on serum iron were based on a recent genome-wide meta-analysis of 21,567 individuals, while estimates of their effect on PD risk were obtained through meta-analysis of genome-wide and candidate gene studies with 20,809 PD cases and 88,892 controls. Separate MR estimates of the effect of iron on PD were obtained for each variant and pooled by meta-analysis. We investigated heterogeneity across the three estimates as an indication of possible pleiotropy and found no evidence of it. The combined MR estimate showed a statistically significant protective effect of iron, with a relative risk reduction for PD of 3% (95% CI 1%-6%; p = 0.001) per 10 microg/dl increase in serum iron. CONCLUSIONS: Our study suggests that increased iron levels are causally associated with a decreased risk of developing PD. Further studies are needed to understand the pathophysiological mechanism of action of serum iron on PD risk before recommendations can be mad

Solving unsolved rare neurological diseases-a Solve-RD viewpoint.

Funder: Durch Princess Beatrix Muscle Fund Durch Speeren voor Spieren Muscle FundFunder: University of Tübingen Medical Faculty PATE programFunder: European Reference Network for Rare Neurological Diseases | 739510Funder: European Joint Program on Rare Diseases (EJP-RD COFUND-EJP) | 44140962

Solving patients with rare diseases through programmatic reanalysis of genome-phenome data.

Funder: EC | EC Seventh Framework Programm | FP7 Health (FP7-HEALTH - Specific Programme "Cooperation": Health); doi: https://doi.org/10.13039/100011272; Grant(s): 305444, 305444Funder: Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness); doi: https://doi.org/10.13039/501100003329Funder: Generalitat de Catalunya (Government of Catalonia); doi: https://doi.org/10.13039/501100002809Funder: EC | European Regional Development Fund (Europski Fond za Regionalni Razvoj); doi: https://doi.org/10.13039/501100008530Funder: Instituto Nacional de Bioinformática ELIXIR Implementation Studies Centro de Excelencia Severo OchoaFunder: EC | EC Seventh Framework Programm | FP7 Health (FP7-HEALTH - Specific Programme "Cooperation": Health)Reanalysis of inconclusive exome/genome sequencing data increases the diagnosis yield of patients with rare diseases. However, the cost and efforts required for reanalysis prevent its routine implementation in research and clinical environments. The Solve-RD project aims to reveal the molecular causes underlying undiagnosed rare diseases. One of the goals is to implement innovative approaches to reanalyse the exomes and genomes from thousands of well-studied undiagnosed cases. The raw genomic data is submitted to Solve-RD through the RD-Connect Genome-Phenome Analysis Platform (GPAP) together with standardised phenotypic and pedigree data. We have developed a programmatic workflow to reanalyse genome-phenome data. It uses the RD-Connect GPAP's Application Programming Interface (API) and relies on the big-data technologies upon which the system is built. We have applied the workflow to prioritise rare known pathogenic variants from 4411 undiagnosed cases. The queries returned an average of 1.45 variants per case, which first were evaluated in bulk by a panel of disease experts and afterwards specifically by the submitter of each case. A total of 120 index cases (21.2% of prioritised cases, 2.7% of all exome/genome-negative samples) have already been solved, with others being under investigation. The implementation of solutions as the one described here provide the technical framework to enable periodic case-level data re-evaluation in clinical settings, as recommended by the American College of Medical Genetics

Électrocatalyseurs potentiels pour l'électrolyse de l'eau - Challenges et opportunités de différentes familles de catalyseurs

Ce travail porte sur la synthèse et la caractérisation de différentes classes de catalyseurs et de leur intégration comme électrodes de travail pour une cellule d'électrolyse. Les électrodes à base de complexes moléculaires de ruthénium fabriquées par sérigraphie (Article 2) présentent des activités et des stabilités élevées, à pH neutre, vis-à-vis de l'oxydation de l'eau. Les catalyseurs sous forme d'oligomères montrent des performances supérieures. La conductivité électronique de l'électrode est le facteur limitant de l'activité catalytique d'une telle anode moléculaire. De plus, le faible chargement en catalyseur impose des limitations supplémentaires pour atteindre des densités de courant élevées. L'étude de matériaux catalytiques, composés d'un Métal de transition, d'Azote et de Carbone (Article 3) montre que celui contenant du cobalt a la plus grande activité pour la production d'hydrogène en milieu acide tout en montrant une certaine stabilité. Cette dernière s'explique par la présence de sites atomiques uniques, au détriment de la formation de nanoparticules, obtenus par une méthode de synthèse sans solvant. Ce procédé présente donc une stratégie intéressante pour la synthèse à grande échelle. Cependant, l'augmentation du nombre de site catalytiques dans le matériau reste une difficulté à surmonter. Une méthode (Brevet I) de fabrication des assemblages membrane-électrode a aussi été mise en place. Elle permet le remplacement des membranes coûteuses couramment utilisées. Deux structures de Molybdate de Nickel ont été synthétisées (Article 1) pour fabriquer, après électro-activation, des nanoparticules de γ-NiOOH actif envers la production d'oxygène en pH alcalin. L'élimination du molybdène conduit à une surface électrochimique élevée avec un grand nombre de sites de nickel exposé et explique l'origine de l'activité catalytique élevée. La présence de Molybdène sert donc ici d'agent structurant et porogène. L'étude par spectroscopie Raman montre que le dépôt en forme de bâtonnets (mis en évidence par microscopie électronique) fabriqué sur une mousse de Nickel comporte aussi le signal de la structure en feuille après l'éviction du molybdène. La présence de cette structure s'explique par une couche intermédiaire entre l'électrode en mousse et les bâtonnets visibles par microscopie électronique. Cependant, les résultats semblent indiquer une activité plus élevée pour la structure en bâtonnets. Un résultat essentiel de cette étude est que lors de la synthèse d'une structure en bâtonnets de Molybdate de Nickel sur une électrode, l'absence de la structure en feuille doit être vérifiée. Les différences fondamentales (Article 4) entre les nanostructures ont été caractérisées plus en détail à l'aide de diverses techniques : MEB, DRX et Spectroscopie Raman. Bien que les structures cristallines des deux nanostructures ne soient pas encore totalement résolues, les analyses montrent clairement qu'il s'agit de deux matériaux différents avec leurs propriétés. En effet la structure hydratée en feuille présente une activité supérieure à celle déshydratée pour la production d'hydrogène en milieu alcalin. Il est clair qu'une étape de réduction préliminaire est nécessaire pour accéder à l'activité catalytique exceptionnelle rapportée. Parmi les différentes classes de catalyseurs étudiés, les catalyseurs à nanoparticules semblent être les plus prometteurs pour une intégration réussie dans une cellule d'électrolyse à grande échelle. L'utilisation généralisée de ce type de matériau pourra être envisagée une fois que la stabilité des catalyseurs et de la membrane échangeuse d'anions sera résolue.In this thesis work, different classes of catalysts and their suitability for integration into an electrolyzer cell has been investigated. Ruthenium-based molecular catalysts in Paper II have shown high activities and stabilities towards water oxidation in neutral pH. Especially the oligomeric catalysts exhibited a superior performance. The electrical conductivity of the electrode was discovered as limiting factor on the catalytic activity of such a molecular anode. In addition, the low loading of catalyst might impose limitations on reaching high current densities at reasonable potentials. Among the tested transition metal single atom catalysts synthesized by pyrolyzing transition metal doped ZIF-8 structures in Paper III, cobalt has shown the highest activity towards hydrogen evolution and a stable behaviour in acidic pH. The enhanced stability of single atomic sites compared to the corresponding nanoparticles was proposed. Only a low number of nanoparticles was suggested to have been formed during the solvent free synthesis. Hence, this process might present an interesting strategy for the large-scale synthesis of single atom hydrogen evolution catalysts. However, also for this class of catalyst, the low number of active sites seems to present a difficulty, which has to be overcome. With the novel method presented in Patent I to fabricate a membrane electrode assembly, the usage of commonly used expensive membranes could possibly be avoided. Both as-prepared nickel molybdate hydrate nanoparticle shapes - sheets and rods - have been proposed in Paper I to transform in an electrochemical activation step into γ-NiOOH as active phase for the oxygen evolution reaction in alkaline pH. With the removal of molybdenum a large electrochemical surface area with an increased number of exposed nickel sites was indicated to be the origin behind the high catalytic activity of the nanoparticles. Molybdenum was suggested to only act as structure and pore forming agent. Even for the sample on nickel foam with only rods initially visible by electron microscopy, Raman bands of the sheet structure was observed after selective molybdenum leaching and could be traced back to the intermediate layer between the foam electrode and the nanorods. However, preliminary results indicate a higher activity for the rod structure. The nanosheet layer between the rods and the foam might be an interesting observation for further works concerning nanorods on the electrode and the attribution of the catalytic activity. An essential outcome and proposal of Paper I is that when synthesizing especially a nickel molybdate rod structure on an electrode, the absence of the sheet structure should be verified, which could be done by either selective molybdenum leaching combined with Raman spectroscopy or XRD, or by investigating the volume between rods and the electrode with SEM. With Paper IV the fundamental differences between the nanostructures were characterized with various techniques, indicating strongly that those are two different materials. For the hydrogen evolution reaction in alkaline media, the hydrate sheet structure exhibited a higher activity compared to the anhydrate, but clearly a reduction step is necessary to access the outstanding catalytic activity reported. Among all the investigated catalysts of different classes, the nanoparticle catalysts seem to be the most promising for a successful integration in a large scale electrolyzer cell for widespread use, especially, once the stability of the catalysts and the anion exchange membrane is resolved