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Revisiting the involvement of tau in complex neural network remodeling: analysis of the extracellular neuronal activity in organotypic brain slice co-cultures
No full textObjective: Tau ablation has a protective effect in epilepsy due to inhibition of the hyperexcitability/hypersynchrony. Protection may also occur in transgenic models of Alzheimer's disease by reducing the epileptic activity and normalizing the excitation/inhibition imbalance. However, it is difficult to determine the exact functions of tau, because tau knockout (tauKO) brain networks exhibit elusive phenotypes. In this study, we aimed to further explore the physiological role of tau using brain network remodeling. Approach: The effect of tau ablation was investigated in hippocampal-entorhinal slice co-cultures during network remodeling. We recorded the spontaneous extracellular neuronal activity over two weeks in single-slice cultures and co-cultures from control and tauKO mice. We compared the burst parameters and applied concepts and analytical tools intended for the analysis of the network synchrony and connectivity. Main results: Comparison of the control and tauKO co-cultures revealed that tau ablation had an anti-synchrony effect on the hippocampal-entorhinal two-slice networks at late stages of culture, in line with the literature. Differences were also found between the single-slice and co-culture conditions, which indicated that tau ablation had differential effects at the sub-network scale. For instance, tau ablation was found to have an anti-synchrony effect on the co-cultured hippocampal slices throughout the culture, possibly due to a reduction in the excitation/inhibition ratio. Conversely, tau ablation led to increased synchrony in the entorhinal slices at early stages of the co-culture, possibly due to homogenization of the connectivity distribution. Significance: The new methodology presented here proved useful for investigating the role of tau in the remodeling of complex brain-derived neural networks. The results confirm previous findings and hypotheses concerning the effects of tau ablation on neural networks. Moreover, the results suggest, for the first time, that tau has multifaceted roles that vary in different brain sub-networks
Analysis of Tidal Accelerations in the Solar System and in Extrasolar Planetary Systems
No full textVolcanism powered by tidal forces inside celestial bodies can provide enough energy to keep important solvents for living systems in the liquid phase. A prerequisite to calculate such tidal interactions and consequences is depending on simulations for tidal accelerations in a multi-body system. Unfortunately, from measurements in many extrasolar planetary systems, only few physical and orbital parameters are well-known enough for investigated celestial bodies. For calculating tidal acceleration vectors under missing most orbital parameter exactly, a simulation method is developed that is only based on a few basic parameters, easily measurable even in extrasolar planetary systems. Such a method as the one presented here allows finding a relation between the tidal acceleration vectors and potential heating inside celestial objects. Using the values and results of our model approach to our solar system as a “gold standard” for feasibility allowed us to classify this heating in relation to different forms of volcanism. This “gold standard” approach gave us a classification measure for the relevance of tidal heating in other extrasolar systems with a reduced availability of exact physical parameters. We help to estimate conditions for the identification of potential candidates for further sophisticated investigations by more complex established methods such as viscoelastic multi-body theories. As a first example, we applied the procedures developed here to the extrasolar planetary system TRAPPIST-1 as an example to check our working hypothesis
Glucose Derivative Induced Vasculopathy in Children on Chronic Peritoneal Dialysis
No full textAbstract
Background and Aims
Patients with chronic kidney disease patients (CKD) have an exceedingly high cardiovascular risk. While vasculopathy is further accelerated during peritoneal dialysis (PD), the pathophysiological role of reactive metabolites such as glucose degradation products (GDP) is uncertain.
Method
Omental and parietal peritoneal tissues from 100 non-CKD individuals, 107 children with CKD5, 60 children treated with neutral pH, low GDP, and 30 children treated with acidic pH, high GDP PD fluids underwent standardized digital histomorphometry. Omental arterioles localized within the fat tissue, protected from direct PD fluid exposure were microdissected for multi-omics analysis. Key regulated pathways were validated by quantitative immunostaining, with localization microscopy in peritoneal tissues of matched cohorts and in vitro in human umbilical vein endothelial cells.
Results
Arterioles from children with CKD5 exhibited reduced lumen to vessel ratio (L/V) and reduced endothelial telomere length compared to non-CKD individuals; gene ontology analysis identified enrichment of arteriolar genes associated with nuclear telomere cap complex and focal adhesion. Pathway analysis of arteriolar cross-omics identified top canonical pathways including telomere extension by telomerase, actin cytoskeleton, integrin and tight junction signalling.
Peritoneal vasculopathy progressed with PD vintage and was more pronounced with high versus low GDP exposure (p<0.001). Compared to CKD5, low GDP-PD upregulated 145/110 and downregulated 38/34 arteriolar genes/proteins, high GDP-PD upregulated 684/137 and supressed 1560/55 genes/proteins (p<0.01). High GDP milieu induced upregulation of arteriolar genes involved in cell death/apoptosis and suppressed genes related to cell viability/survival, cytoskeleton organization and immune response biofunctions. Vasculopathy associated canonical pathways concordantly regulated on arteriolar gene and protein level with high GDP exposure included cell death/proliferation, apoptosis, cytoskeleton organization, metabolism and detoxification, cell junction signalling, and immune response.
Quantitative validation in PD cohorts with similar PD vintage, dialytic glucose exposure and age (n=15 / group) verified increased proapoptotic activity and cytoskeleton disintegration with high-GDP exposure; single-molecule-localization microscopy demonstrated arteriolar endothelial zonula occludens-1 (ZO-1) disruption. Absolute and relative to endoluminal surface length, arteriolar endothelial cell counts were inversely correlated with GDP exposure, with apoptosis marker caspase-3, TGF-ß induced pSMAD2/3, interleukin-6, ZO-1 protein abundance and the degree of vasculopathy. In vitro, exposure to GDP 3,4-dideoxyglucosone-3-ene dose-dependently reduced nuclear endothelial lamin-A/C and membrane ZO-1 assembly. Transendothelial electrical resistance was decreased. ZO-1 and sealing tight junction claudin-5 protein abundance were decreased in cells after incubation with high GDP compared to low GDP PD fluid and culture media. On nanoscale level GDP reduced junction cluster formation in the membrane area.
Conclusion
Multi-omics analysis of omental arterioles from children without pre-existing vasculopathy and life-style related confounders identified key mechanisms of vascular aging in CKD5 and the major contribution of GDP to accelerated vasculopathy during PD, i.e. disruption of endothelial cell junctions and cytoskeleton and induction of apoptosis
Sentiment Analysis of Cyber-Attack Incident Reports
No full textThis article examines sentiment of 12,821 reports on cyber-attacks on firms around the world from 2011 to mid-year 2019. With theworld wide web (www) and associated technologies connecting opinions worldwide, sentiment in the world wide web is an importantperspective to understanding developments in cyber-attacks and the public opinion thereof, because much of the public debate isshared online. Such sentiment can potentially explain developments in regulation and may be indirectly associated with the buildingof defense mechanisms of cyber-victims. Results show that the quantity of reports on cyber-attacks on firms has been increasing,but the sentiment of reports on cyber-attacks has been decreasing. Both trends reflect the increasing severity of the issue and arelikely contributing to regulatory responses. Results also show that the sentiment is conditional to the source that reports the cyber-attack
Development of low-density coatings for soft x-ray reflectivity enhancement for ATHENA and other missions
No full textMetallic coatings made of precious metals (e.g. Ir, Pt or Au) with high atomic number Z have been traditionally employed at grazing incidence for X-rays reflection and focalization. These materials offer a range of reflection extended to higher energies, but also present a series of absorption edges, which limit the reflectivity in the 2-4 keV band and below. Therefore the search for alternative coatings, able to improve the reflection in the soft energy range, is particularly relevant for the development of future telescopes, like ATHENA (ESA), Lynx (NASA) and eXTP (CAS). Low-Z overcoatings (e.g. carbon or B4C), applied on top of the high-Z metallic layer, can enhance the reflectivity in the softer band (mainly below 2 keV), but conventional deposition methods for these materials are not easily compatible with some of the mainstream technologies for mirror fabrication (notably, the silicon pore optics that will be used for the ATHENA X-ray mission which is being implemented by ESA). In this work we discuss novel solutions (carbon-like overcoatings realized by dip coating or vapor phase deposition), which can be particularly convenient for the application to ATHENA and to future telescopes
PropTech Germany 2021 Studie
No full textPropTech-Charakteristika
Die 185 teilnehmenden PropTechs sind den Reifegrad-Clustern Early Stager (19,5%), Grown Ups (57,8%) und Conquerer (22,7%) zuzuordnen. 48% der Prop-Techs sind sehr junge Unternehmen mit den Gründungsjahren 2018 - 2020. Durchschnittlich liegen 1,6 Jahre zwi-schen Gründung des Unternehmens und Launch des Produktes. Jeweils die Mehrheit der Teilnehmer bedient ausschließlich das B2B-Segment (80,0%), operiert mit weniger als 15 Mitarbeitern (65,4%) und befindet sich im Produkt-Entwicklungsstadium des laufenden Betriebs (70,8%). Die Spanne der von den PropTechs erzielten Umsätze ist weit. Korrespondierend mit dem “jungen” Unternehmensalter erzielten 29,7% der PropTechs nur bis zu 10.000€ Jahresumsatz in 2020. Jedoch geben an-dererseits 16,2% der Befragten einen Jahresumsatz von über 1 Mio. € an. Technologisch überwiegt die Plattformtechnologie in allen Lebenszyklusphasen. Als Einnahmenmodell existieren mehrheitlich Subscription- oder Lizenz-vereinbarungen, und eine laufende monatliche oder jährliche Gebühr wird meist als Preismodell genutzt. Schnittstellen verschiedenen Typs sind bereits bei 73,0% der PropTechs verfügbar.
PropTechs im Immobilien-Lebenszyklus
In der Immobilienwertschöpfungskette bedient das Gros der Teilnehmer den Betrieb die Bewirtschaftung von Immo-bilien, wobei jedoch im Durchschnitt 3,2 Lebenszyklusphasen von den Prop-Techs bedient werden. Somit bewegen sie sich tendenziell nicht in den tradierten Grenzen und Prozessen der Immo-bilienwirtschaft. Die meisten PropTechs mit hohen Umsätzen sind in der Be-wirtschaftung oder Vermarktung von Immobilien aktiv. Als Assetklasse dominiert klar Wohnen, gefolgt von Büro und Mixed-Use, wobei aber ein Prop-Tech durchschnittlich 4,3 Assetklassen bedient. Im Wohnsegment dominieren jedoch die PropTechs mit noch sehr geringen Umsätzen. Hier herrscht auch der höchste B2C Anteil der Assetklassen vor. Nur 20,5% der PropTechs legen sich auf eine Assetklasse fest.
Aktuelle Lage des deutschen PropTech-Marktes
Für das Jahr 2020 empfinden die Prop-Techs die Auftragslage als äußerst posi-tiv, und auch der mittelfristigen Entwicklung der Jahre bis Ende 2023 blickt eine überwältigende Mehrheit positiv entgegen. So verzeichneten in 2020 70,8% der PropTechs mehr Neugeschäft, davon 35,9% deutlich mehr Neugeschäft. Für 2021 bis 2023 erwarten 52,4% der PropTechs deutlich mehr Neugeschäft und insgesamt über 91,4% sehen positive Vorzeichen für die Marktentwicklung. Hinsichtlich des Corona-Effekts konn-ten die Unternehmen mehrheitlich eher von der Pandemie profitieren; für die Zukunft ergibt sich ein aus ihrer Sicht noch positiveres Bild. Ganze 66,5% erwarten zukünftig eine Zunahme ihres Geschäftes durch Corona und weitere 26,0% sehen keine Auswirkungen. Lediglich 7,6% erwarten pandemiebedingt eine Abnahme des eigenen Geschäfts. Nach eigenen Einschätzungen gehören PropTechs also mehrheitlich zu den Gewinnern der Pandemie.
Herausforderungen für PropTechs im deutschen Immobilienmarkt
In der Studie wurden drei Phasen des proptechseitigen Vermarktungsprozesses untersucht: Aufbau des Geschäftsmodells, Produktverkauf und Implemen-tierung. Die Phase des Produktverkaufs ist für 53% der PropTechs die hürden-reichste Phase deutlich vor dem Aufbau des Geschäftsmodells und Implementierung beim Kunden. Die wesentlichen Herausforderungen beim Aufbau des Geschäftsmodells sind für alle Prop-Tech-Cluster die Entscheidungsstrukturen beim Kunden, gefolgt von dem geringen Druck zur Digitalisierung in der Immobilienbranche und Produktentwicklungskosten sowie der Zugang zu Daten, wobei dieser für Early Stager am schwierigsten erscheint. In der Phase des Produktverkaufs zeigt sich, dass die größte Hürde in der geringen Risikobereitschaft des Establishments, in Technologien von PropTechs zu investieren, liegt - gepaart mit mangelndem Vertrauen und einem mangelnden Verständnis in Bezug auf die Technologie sowie das Potenzial der Produkte. Weiterhin liegt im schwierigen Zugang zum richtigen Ansprechpartner eine wesentliche Verkaufshürde.
Hier ergibt sich aus Sicht der PropTechs, dass die operativ verantwortliche Fach-abteilung im Establishment, in der das Produkt angewendet würde, der wesentliche Influencer für die Kaufentscheidung ist. Als relevantester Ent-scheider wird hingegen mehrheitlich der CEO gesehen. Dies kann ein Hinweis darauf sein, dass Digitalisierungsent-scheidungen immer noch auf strategischer Ebene getroffen werden. Prop-Techs, die es bei einem Kunden bis zur Implementierung geschafft haben, sind über den Berg der Hürden und sehen sich fortan nur moderateren Herausforderungen gegenüber. Von diesen sind die mangelnde Priorität des Projektes auf Kundenseite sowie fehlende C-Level-Sponsorship bzgl. der Durchsetzung von Entscheidungen die wesentlichen Herausforderungen. Somit sehen sich PropTechs mit wenig Unerwartetem bei der Implementierung konfrontiert, dürfen aber auch keine Priorität und Unterstützung vom Kunden erwarten.
Kooperationen
Kooperationen zwischen PropTechs sind überwiegend technischer Natur und haben einen hohen Stellenwert; 71,9% der Bef ragten haben bereits horizontale oder vertikale Kooperationen. Ziele sind hier meist Umsatz-, Netzwerk- und Zielgruppenerweiterung. Die Kooperationsbereitschaft nimmt mit steigendem Reifegrad der PropTechs zu; am ausgeprägtesten ist sie bei Conquerers, wo Kooperationen als Vorteil des Markteintritts nach Deutschland interpretiert werden können. Durch vertikale Kooperationen können PropTechs den Kunden ein er-weitertes bzw. kompletteres Lösungs-portfolio sowie teilweise eine deutlich breitere Anzahl an Use Cases anbieten. Damit einhergehend stehen auch die Themen Ökosystem und Plattformen. PropTechs können mittels Partnerschaften / Kooperationen einen größeren Teil der Wertschöpfungskette abbilden, ihre Angebote bündeln und somit „one stop shop” Lösungen für die Kunden anbieten
Tunable Bulk Polymer Planar Bragg Gratings Electrified via Femtosecond Laser Reductive Sintering of CuO Nanoparticles
No full textThis contribution demonstrates and discusses electrically tunable polymer planar Bragg gratings based on bulk cyclic olefin copolymers. A lithographic single-writing-step method and femtosecond laser reductive sintering of copper(II) oxide nanoparticles are subsequently employed in order to generate buried photonic structures and copper conducting paths on top of the polymer substrate. This way, the necessary number of process steps for fabricating a planar polymer-based electro-optical device is greatly reduced. The response of a fully electrified grating structure follows temperature changes, induced by the copper conducting path, with sensitivities up to −31 pm K−1. Dilatometric measurements show that the specimen's behavior is correlated to the situationally reduced thermal expansion of the bulk polymer substrate. In consequence, the tuning response of the photonic platform follows a second order polynomial, whereas a direct current of 30 mA, which correlates to a power consumption of 18.3 mW, leads to a local temperature increase and a residual Bragg wavelength shift of 19.6 K and −547 pm, respectively. Moreover, the outstanding flexibility of the proposed fabrication concept is underlined by demonstrating alternative conducting path geometries, whereas one of the additional designs is adapted to control the spectral width of the Bragg grating's reflection peak
Optical system for multi Bessel beam high power ultrashort pulsed laser processing using a spatial light modulator
No full textWe report on an optical setup for multi Bessel beam processing combining a refractive axicon and a spatial light modulator.
Based on their particular beam profile, Bessel beams exhibit various advantages over conventional Gaussian beams for
ultrashort pulsed laser processing. Especially for micromachining of transparent materials, applications such as micro-hole
drilling or the generation of voids benefit from the increased focal length of the applied Bessel beam. In addition, on
account of the significantly increased average output power of industrial ultrashort pulsed lasers over the last years, there
is a high demand on multi spot applications for using the available laser power in efficient production processes. Our
optical concept combines the dynamic possibilities of beam splitting using spatial light modulator with the benefits of
Bessel beams facilitating multi Bessel beam processing
Optical characterization of reflective coatings for astronomical telescope mirrors
No full textWith ground based optical telescopes astronomers observe celestial objects over a wide spectral range. As usually three or even more reflections at telescope mirrors are involved, good reflection properties of the mirror coatings are important. The aluminum evaporation technique has been - and is still - the standard solution for the reflective coatings of large astronomical mirrors. Such coatings have excellent reflectivity in the ultraviolet and in the visible, but perform poorly in the infrared. Silver is the metal having highest reflectivity for wavelengths longward of 400 nm, but isn´t the best choice for reflectivity in the ultraviolet and for blue light. To avoid degradation by oxidation, durable silver coatings need to be protected by transmitting overcoating layers. In the presented study, different metallic coatings – including unusual ones like sputtered iridium - are characterized to identify a coating that is most suitable for the spectral range from ultraviolet to infrared. Experimental results are compared to simulations based on the complex refractive indices of these materials. Thereby dependence of incidence angle and polarization is also considered.Poste