Dust in the reionization era: ALMA observations of a zz=8.38 Galaxy

We report on the detailed analysis of a gravitationally-lensed Y-band dropout, A2744_YD4, selected from deep Hubble Space Telescope imaging in the Frontier Field cluster Abell 2744. Band 7 observations with the Atacama Large Millimeter Array (ALMA) indicate the proximate detection of a significant 1mm continuum flux suggesting the presence of dust for a star-forming galaxy with a photometric redshift of $z\simeq8$. Deep X-SHOOTER spectra confirms the high redshift identity of A2744_YD4 via the detection of Lyman $\alpha$ emission at a redshift $z$=8.38. The association with the ALMA detection is confirmed by the presence of [OIII] 88$\mu$m emission at the same redshift. Although both emission features are only significant at the 4 $\sigma$ level, we argue their joint detection and the positional coincidence with a high redshift dropout in the HST images confirms the physical association. Analysis of the available photometric data and the modest gravitational magnification ($\mu\simeq2$) indicates A2744_YD4 has a stellar mass of $\sim$ 2$\times$10$^9$ M$_{\odot}$, a star formation rate of $\sim20$ M$_{\odot}$/yr and a dust mass of $\sim$6$\times$10$^{6}$ M$_{\odot}$. We discuss the implications of the formation of such a dust mass only $\simeq$200 Myr after the onset of cosmic reionisation.Comment: Accepted for publication in ApJ

Developmental Origin of Patchy Axonal Connectivity in the Neocortex: A Computational Model

Injections of neural tracers into many mammalian neocortical areas reveal a common patchy motif of clustered axonal projections. We studied in simulation a mathematical model for neuronal development in order to investigate how this patchy connectivity could arise in layer II/III of the neocortex. In our model, individual neurons of this layer expressed the activator-inhibitor components of a Gierer-Meinhardt reaction-diffusion system. The resultant steady-state reaction-diffusion pattern across the neuronal population was approximately hexagonal. Growth cones at the tips of extending axons used the various morphogens secreted by intrapatch neurons as guidance cues to direct their growth and invoke axonal arborization, so yielding a patchy distribution of arborization across the entire layer II/III. We found that adjustment of a single parameter yields the intriguing linear relationship between average patch diameter and interpatch spacing that has been observed experimentally over many cortical areas and species. We conclude that a simple Gierer-Meinhardt system expressed by the neurons of the developing neocortex is sufficient to explain the patterns of clustered connectivity observed experimentall

Regulatorische Handhabung der selektiven Erstattung von Arzneimitteln in den ausgewählten Ländern England, Niederlande, Frankreich und Schweden

[Einleitung] Im Rahmen des AMNOG wurde die Preisbildung für patentgeschützte Arzneimittel und damit die Erstattung durch die GKV neu geregelt. Seit 2011 wird in einer Verhandlung festgelegt, wie viel die Krankenkassen ab dem 13. Monat nach Marktzugang für neue Arzneimittel bezahlen, während die Preisbildung in den ersten 12 Monaten nach wie vor frei ist (§ 130b SGB V). Die zentrale Entscheidungsgrundlage für die Verhandlung ist eine zuvor durchgeführte Nutzenbewertung (§ 35a SGB V). Insbesondere das vom G-BA im Rahmen der Nutzenbewertung festgestellte Ausmaß des Nutzens bzw. Zusatznutzens stellt ein wichtiges Kriterium für die Höhe des festzusetzenden Preises dar. Der Nutzen bzw. Zusatznutzen eines Arzneimittels kann dabei für Teile der von der arzneimittelrechtlichen Zulassung abgedeckten Populationen deutlich unterschiedlich ausfallen. Der auf dieser Basis festgesetzte Erstattungsbetrag bzw. Preis ist unterdessen für das zugelassene Arzneimittel einheitlich, wird somit ggf. den unterschiedlichen Nutzenniveaus mehr oder weniger gerecht. Vor diesem Hintergrund wird auch von einem „Mischpreis“ gesprochen. Bei Mischpreisen kann es zu Konstellationen kommen, bei denen ein Präparat unter Gegebenheiten verordnet wird, bei dem sein Preis im Einzelfall gemessen am individuellen Nutzen des betreffenden Patienten zu hoch im Sinne der sozialgesetzlich geforderten Wirtschaftlichkeit ist. Sofern die Erstattungsfähigkeit von Arzneimitteln mit unterschiedlichen Nutzenniveaus nicht auf bestimmte Teilpopulationen mit entsprechenden Nutzenniveaus eingeschränkt wird, kommt es in der Praxis zwangsläufig zu Verordnungen, bei denen der Preis nicht „nutzengerecht“ ist. Die sich hieraus ergebende Situation gibt Anlass zur Untersuchung der Frage, ob und wie eine Einschränkung der Erstattungsfähigkeit, d. h. eine selektive Erstattung, zu einer besseren Handhabung der skizzierten Problematik beitragen könnte

Towards increased reliability of resistance welded joints for aircraft assembly

This study focuses on the opportunities and challenges of applying the static resistance welding process to a full scale upper shell fuselage demonstrator. An adapted resistance welding setup and process which produces high quality welds over the whole welding surface with a defined weld seam is described. The effects of scaling and the challenges that arise during the welding of the demonstrator are discussed. Approaches to solutions are presented to meet the required reliability of resistance welded joints in application

Sputtering and Characterization ofMAX-Phase Forming Cr Al C and Ti Al C Coatings and Their Application on γ-Based Titanium Aluminides

MAX-phases are of increasing interest as coating material for high temperatureapplications due to their unique metallic as well as ceramic properties. Herein,the deposition of Cr2AlC and Ti3AlC2or Ti2AlC MAX-phase forming coatings bymagnetron sputtering is demonstrated. Using pure elemental targets, themanufacturing with a coating thickness of above 7 m is established. TheMAX-phase forming coatings are characterized by high-temperature X-ray dif-fraction (HT-XRD) measurements and provide a good oxidation behavior due tothe development of protective thermally grown oxide layers. The performance ofthe MAX-phases is strongly depended on the substrate material and theaccompanying interdiffusion processes. Therefore, the Ti–Al–C coating is favoredfor TiAl alloys due to the thermodynamic stability of the Ti2AlC MAX phase inparticular in the presence of the γ-TiAl phase. An excellent oxidation behavior isconrmed up to 300 h at 850C due to the development of an alumina layerabove a homogenous Ti2AlC phase coating. The Cr2AlC MAX-phase coatingdegrades after 100 h at 800C due to interdiffusion processes between coatingand substrate and the accompanying development of carbides and nitridephases. Nevertheless, the oxidation resistance of the Cr–Al– C-coated TiAl alloy isgiven by the formation of the Ti2AlC MAX-phase

Liquid–liquid phase separation of the Golgi matrix protein GM130

Golgins are an abundant class of peripheral membrane proteins of the Golgi. These very long (50–400 nm) rod-like proteins initially capture cognate transport vesicles, thus enabling subsequent SNARE-mediated membrane fusion. Here, we explore the hypothesis that in addition to serving as vesicle tethers, Golgins may also possess the capacity to phase separate and, thereby, contribute to the internal organization of the Golgi. GM130 is the most abundant Golgin at the cis Golgi. Remarkably, overexpressed GM130 forms liquid droplets in cells analogous to those described for numerous intrinsically disordered proteins with low complexity sequences, even though GM130 is neither low in complexity nor intrinsically disordered. Virtually pure recombinant GM130 also phase-separates into dynamic, liquid-like droplets in close to physiological buffers and at concentrations similar to its estimated local concentration at the cis Golgi

Exciton Mediated Superconductivity in PrOs4Sb12

The most important character of the exotic superconductor PrOs4Sb12 is the existence of low-lying excitations (excitons) with a finite energy gap and it appears as the magnetic field-induced order above 4.5 T. We focus on the a_u conduction band, which hybridizes with a Pr 4f^2 state strongly, coupled to the excitons. It results in an attractive interaction between the conduction electrons. The symmetry of the superconducting order parameter is determined by dispersion relation of the exciton. For the bcc system PrOs4Sb12, a d-wave state [kx ky + omega ky kz + omega^2 kz kx, omega=exp(pm i 2 pi/3)] is stabilized with broken time reversal symmetry.Comment: 4 page

Interrogating the CD27:CD70 axis in αCD40-dependent control of pancreatic adenocarcinoma

Immune checkpoint blockade immunotherapy has radically changed patient outcomes in multiple cancer types. Pancreatic cancer is one of the notable exceptions, being protected from immunotherapy by a variety of mechanisms, including the presence of a dense stroma and immunosuppressive myeloid cells. Previous studies have demonstrated that CD40 stimulation can remodel the tumor microenvironment in a manner that promotes effector immune cell responses and can cooperate with immune checkpoint inhibition for durable tumor control mediated by T cells. Here we confirm the capability of this combination therapy to dramatically, and durably, control pancreatic cancer growth in an orthotopic model and that the immune memory to this cancer is primarily a function of CD4+ T cells. We extend this understanding by demonstrating that recruitment of recently primed T cells from the draining lymph nodes is not necessary for the observed control, suggesting that the pre-existing intra-tumoral cells respond to the combination therapy. Further, we find that the efficacy of CD40 stimulation is not dependent upon CD70, which is commonly induced on dendritic cells in response to CD40 agonism. Finally, we find that directly targeting the receptor for CD70, CD27, in combination with the TLR3 agonist polyIC, provides some protection despite failing to increase the frequency of interferon gamma-secreting T cells