Splicing Programs and Cancer

Numerous studies report splicing alterations in a multitude of cancers by using gene-by-gene analysis. However, understanding of the role of alternative splicing in cancer is now reaching a new level, thanks to the use of novel technologies allowing the analysis of splicing at a large-scale level. Genome-wide analyses of alternative splicing indicate that splicing alterations can affect the products of gene networks involved in key cellular programs. In addition, many splicing variants identified as being misregulated in cancer are expressed in normal tissues. These observations suggest that splicing programs contribute to specific cellular programs that are altered during cancer initiation and progression. Supporting this model, recent studies have identified splicing factors controlling cancer-associated splicing programs. The characterization of splicing programs and their regulation by splicing factors will allow a better understanding of the genetic mechanisms involved in cancer initiation and progression and the development of new therapeutic targets

Angiogenesis in tissue engineering : Breathing life into constructed tissue substitutes

Long-term function of three-dimensional (3D) tissue constructs depends on adequate vascularization after implantation. Accordingly, research in tissue engineering has focused on the analysis of angiogenesis. For this purpose, 2 sophisticated in vivo models (the chorioallantoic membrane and the dorsal skinfold chamber) have recently been introduced in tissue engineering research, allowing a more detailed analysis of angiogenic dysfunction and engraftment failure. To achieve vascularization of tissue constructs, several approaches are currently under investigation. These include the modification of biomaterial properties of scaffolds and the stimulation of blood vessel development and maturation by different growth factors using slow-release devices through pre-encapsulated microspheres. Moreover, new microvascular networks in tissue substitutes can be engineered by using endothelial cells and stem cells or by creating arteriovenous shunt loops. Nonetheless, the currently used techniques are not sufficient to induce the rapid vascularization necessary for an adequate cellular oxygen supply. Thus, future directions of research should focus on the creation of microvascular networks within 3D tissue constructs in vitro before implantation or by co-stimulation of angiogenesis and parenchymal cell proliferation to engineer the vascularized tissue substitute in situ

Drone-based photogrammetry combined with deep-learning to estimate hail size distributions and melting of hail on the ground

Hail is a major threat associated with severe thunderstorms and an estimation of the hail size is important for issuing warnings to the public. Operational radar products exist that estimate the size of the expected hail. For the verification of such products, ground based observations are necessary. Automatic hail sensors, as for example within the Swiss hail network, record the kinetic energy of hailstones and can estimate with this the hail diameters. However, due to the small size of the observational area of these sensors (0.2 m2) the estimation of the hail size distribution (HSD) can have large uncertainties. To overcome this issue, we combine drone-based aerial photogrammetry with a state-of-the-art custom trained deep-learning object detection model to identify hailstones in the images and estimate the HSD in a final step. This approach is applied to photogrammetric image data of hail on the ground from a supercell storm, that crossed central Switzerland from southwest to northeast in the afternoon of June 20, 2021. The hail swath of this intense right-moving supercell was intercepted a few minutes after the passage at a soccer field near Entlebuch (Canton Lucerne, Switzerland) and aerial images of the hail on the ground were taken by a commercial DJI drone, equipped with a 50 megapixels full frame camera system. The average ground sampling distance (GSD) that could be reached was 1.5 mm per pixel, which is set by the mounted camera objective with a focal length of 35 mm and a flight altitude of 12 m above ground. A 2D orthomosaic model of the survey area (750 m2) is created based on 116 captured images during the first drone mapping flight. Hail is then detected by using a region-based Convolutional Neural Network (Mask R-CNN). We first characterize the hail sizes based on the individual hail segmentation masks resulting from the model detections and investigate the performance by using manual hail annotations by experts to generate validation and test data sets. The final HSD, composed of 18209 hailstones, is compared with nearby automatic hail sensor observations, the operational weather radar based hail product MESHS (Maximum Expected Severe Hail Size) and some crowdsourced hail reports. Based on the retrieved drone hail data set, a statistical assessment of sampling errors of hail sensors is carried out. Furthermore, five repetitions of the drone-based photogrammetry mission within about 18 min give the unique opportunity to investigate the hail melting process on the ground for this specific supercell hailstorm and location

Shock-induced plasticity in nanocrystalline iron: Large-scale molecular dynamics simulations

Large-scale nonequilibrium molecular dynamics (MD) simulations of shock waves in nanocrystalline iron show evidence of plasticity before the polymorphic transformation takes place. The atomistic structure in the shock direction shows an elastic precursor, plastic deformation, and shock-induced phase transformation from bcc to hcp iron. In this Rapid Communication, large-scale MD models show that the shock response of iron is highly related to the ramp time of the applied shocks. For long ramp times we observe significant plastic relaxation and formation of microstructure defects. Pressure-induced phase transformations in iron are accompanied by stress relaxation achieving almost fully relaxed three-dimensional hydrostatic final states. The evolution of the stress relaxation is in agreement with theory and experiments. Analysis of the x-ray diffraction patterns calculated from the atomistic structure using the Debye equation revealed pronounced anisotropy of the line broadening that is caused by stacking faults in hcp Fe and by dislocations in bcc Fe.Fil: Luu, Hoang Thien. Clausthal University of Applied Technology; AlemaniaFil: Ravelo, Ramón. University of Texas at El Paso; Estados UnidosFil: Rudolph, Martin. TU Bergakademie Freiberg; AlemaniaFil: Bringa, Eduardo Marcial. Universidad de Mendoza; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Germann, Timothy C.. Los Alamos National High Magnetic Field Laboratory; Estados UnidosFil: Rafaja, David. TU Bergakademie Freiberg; AlemaniaFil: Gunkelmann, Nina. Clausthal University of Applied Technology; Alemani

Illuminating milling mechanochemistry by tandem real-time fluorescence emission and Raman spectroscopy monitoring

In pursuit of accessible and interpretable methods for direct and real-time observation of mechanochemical reactions, we demonstrate a tandem spectroscopic method for monitoring of ball-milling transformations combining fluorescence emission and Raman spectroscopy, accompanied by high-level molecular and periodic density-functional theory (DFT) calculations, including periodic time-dependent (TD-DFT) modelling of solid-state fluorescence spectra. This proof-of-principle report presents this readily accessible dual-spectroscopy technique as capable of observing changes to the supramolecular structure of the model pharmaceutical system indometacin during mechanochemical polymorph transformation and cocrystallisation. The observed time-resolved in situ spectroscopic and kinetic data are supported by ex situ X-ray diffraction and solid-state nuclear magnetic resonance spectroscopy measurements. The application of first principles (ab initio) calculations enabled the elucidation of how changes in crystalline environment, that result from mechanochemical reactions, affect vibrational and electronic excited states of molecules. The herein explored interpretation of both real-time and ex situ spectroscopic data through ab initio calculations provides an entry into developing a detailed mechanistic understanding of mechanochemical milling processes and highlights the challenges of using real-time spectroscopy

Bestandsaufnahme der bestehenden Forschungsprojekte in Sachen Verding- und Heimkinder : Bericht zuhanden des Bundesamts für Justiz EJPD

Ehemalige Verdingkinder sowie weitere Betroffene von fürsorgerischen Zwangsmassnahmen (administrativ Versorgte, Zwangssterilisierte, Heimkinder und so weiter) machen seit einiger Zeit verstärkt auf ihr Schicksal aufmerksam. Sie fordern die Durchführung eines Gedenkanlasses. Daneben stehen aber auch weitere Forderungen wie die historische Aufarbeitung, die Errichtung von Anlaufstellen und Härtefallfonds, die Behandlung von finanziellen Forderungen, die Rückgabe von beschlagnahmtem Eigentum, die Akteneinsicht und -sicherung im Raum. Am 27. September 2012 beauftragte das Bundesamt für Justiz Prof. Dr. Martin Lengwiler (Departement Geschichte, Universität Basel), eine Bestandesaufnahme über die bestehenden Forschungsprojekte i. S. Verding- und Heimkinder zu machen. Diese soll als Grundlage für eine spätere historische Aufarbeitung dienen, unabhängig davon, in welcher Form und durch welche Träger diese erfolgen wird. Dieser Bericht liefert die gewünschte Bestandesaufnahme. Er wurde von einem Autorenteam verfasst, zu dem Prof. Dr. Martin Lengwiler (Universität Basel), Prof. Dr. Gisela Hauss (FHNW), Prof. Dr. Thomas Gabriel (ZHAW), Prof. Dr. Anne-Françoise Praz (Universität Fribourg) und Dr. Urs Germann (Bern) gehören. Ziel des Berichts ist es, den aktuellen Forschungsstand möglichst breit zu erfassen und eine Auslegeordnung der relevanten Aspekte, Fragestellungen und Probleme zu machen. Dazu gehört zunächst eine Eingrenzung des Untersuchungsgegenstands (Kapitel 3, S. 9). Anschliessend präsentiert der Bericht eine Bestandesaufnahme über laufende und abgeschlossene historische Forschungsarbeiten im In- und Ausland (Kapitel 4, S. 17 und Kapitel 5, S. 22). Schliesslich skizziert er Optionen für eine historische Aufarbeitung der Fremdplatzierungsproblematik (Kapitel 6, S. 53). Die hier referierten Forschungsarbeiten decken primär die Entwicklungen im 20. Jahrhundert ab. Untersuchungen zum 19. Jahrhundert werden referiert, soweit sie für das Verständnis der Materie und Problematik relevant sind. Der Schwerpunkt des vorliegenden Forschungsstandes liegt allerdings auf der ersten Hälfte des 20. Jahrhunderts, insbesondere auf der Zwischenkriegszeit, so dass dieser Zeitabschnitt im Folgenden ein vergleichsweise grosses Gewicht bekommt. Nur wenige Untersuchungen haben sich bisher mit der zweiten Hälfte des 20. Jahrhunderts beschäftigt. Diesen Umstand gilt es bei der Diskussion der Optionen für weitere Aufarbeitungsanstrengungen im Auge zu behalten (Kapitel 6, S. 53)

Seventh International Joint Conference on Electronic Voting

This volume contains papers presented at E-Vote-ID 2022, the Seventh International JointConference on Electronic Voting, held during October 4–7, 2022. This was the first in-personconference following the COVID-19 pandemic, and, as such, it was a very special event forthe community since we returned to the traditional venue in Bregenz, Austria. The E-Vote-IDconference resulted from merging EVOTE and Vote-ID, and 18 years have now elapsed sincethe first EVOTE conference in Austria.Since that conference in 2004, over 1500 experts have attended the venue, including scholars,practitioners, authorities, electoral managers, vendors, and PhD students. E-Vote-ID collectsthe most relevant debates on the development of electronic voting, from aspects relating tosecurity and usability through to practical experiences and applications of voting systems, alsoincluding legal, social, or political aspects, amongst others, turning out to be an importantglobal referent on these issues