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Using the novel $JWST$/NIRCam observations in the Abell 2744 field, we present a first spatially resolved overview of an $HST$-dark galaxy, spectroscopically confirmed at $z=2.58$ with magnification $\mu\approx1.9$. While being largely invisible at $\sim$1 $\mu$m with NIRCam, except for sparse clumpy sub-structures, the object is well-detected and resolved in the long-wavelength bands with a spiral shape clearly visible in F277W. By combining ancillary ALMA and $Herschel$ data, we infer that this object is an edge-on dusty spiral with an intrinsic stellar mass log$(M_*/M_\odot)\sim11.3$ and a dust-obscured SFR$\sim 300~M_\odot$~yr$^{-1}$. A massive quiescent galaxy (log$(M_*/M_\odot)\sim10.8$) with tidal features lies 2\farcs{0} away ($r$$\sim$9 kpc), at a consistent redshift as inferred by $JWST$ photometry, indicating a potential major merger. The dusty spiral lies on the main-sequence of star formation, and shows high dust attenuation in the optical ($34$ would be only detectable in F356W and F444W in UNCOVER-like survey, and become totally $JWST$-dark at $z\sim6$. This suggests that detecting highly attenuated galaxies in the Epoch of Reionization might be a challenging task for $JWST$., Comment: 15 pages, 5 figures, 1 table. Accepted to ApJL

Summary Background The PROUD-PV and CONTINUATION-PV trials aimed to compare the novel monopegylated interferon ropeginterferon alfa-2b with hydroxyurea, the standard therapy for patients with polycythaemia vera, over 3 years of treatment. Methods PROUD-PV and its extension study, CONTINUATION-PV, were phase 3, randomised, controlled, open-label, trials done in 48 clinics in Europe. Patients were eligible if 18 years or older with early stage polycythaemia vera (no history of cytoreductive treatment or less than 3 years of previous hydroxyurea treatment) diagnosed by WHO's 2008 criteria. Patients were randomly assigned 1:1 to ropeginterferon alfa-2b (subcutaneously every 2 weeks, starting at 100 μg) or hydroxyurea (orally starting at 500 mg/day). After 1 year, patients could opt to enter the extension part of the trial, CONTINUATION-PV. The primary endpoint in PROUD-PV was non-inferiority of ropeginterferon alfa-2b versus hydroxyurea regarding complete haematological response with normal spleen size (longitudinal diameter of ≤12 cm for women and ≤13 cm for men) at 12 months; in CONTINUATION-PV, the coprimary endpoints were complete haematological response with normalisation of spleen size and with improved disease burden (ie, splenomegaly, microvascular disturbances, pruritus, and headache). We present the final results of PROUD-PV and an interim analysis at 36 months of the CONTINUATION-PV study (per statistical analysis plan). Analyses for safety and efficacy were per-protocol. The trials were registered on EudraCT, 2012-005259-18 (PROUD-PV) and 2014-001357-17 (CONTINUATION-PV, which is ongoing). Findings Patients were recruited from Sept 17, 2013 to March 13, 2015 with 306 enrolled. 257 patients were randomly assigned, 127 were treated in each group (three patients withdrew consent in the hydroxyurea group), and 171 rolled over to the CONTINUATION-PV trial. Median follow-up was 182·1 weeks (IQR 166·3–201·7) in the ropeginterferon alfa-2b and 164·5 weeks (144·4–169·3) in the standard therapy group. In PROUD-PV, 26 (21%) of 122 patients in the ropeginterferon alfa-2b group and 34 (28%) of 123 patients in the standard therapy group met the composite primary endpoint of complete haematological response with normal spleen size. In CONTINUATION-PV, complete haematological response with improved disease burden was met in 50 (53%) of 95 patients in the ropeginterferon alfa-2b group versus 28 (38%) of 74 patients in the hydroxyurea group, p=0·044 at 36 months. Complete haematological response without the spleen criterion in the ropeginterferon alfa-2b group versus standard therapy group were: 53 (43%) of 123 patients versus 57 (46%) of 125 patients, p=0·63 at 12 months (PROUD-PV), and 67 (71%) of 95 patients versus 38 (51%) of 74 patients, p=0·012 at 36 months (CONTINUATION-PV). The most frequently reported grade 3 and grade 4 treatment-related adverse events were increased γ-glutamyltransferase (seven [6%] of 127 patients) and increased alanine aminotransferase (four [3%] of 127 patients) in the ropeginterferon alfa-2b group, and leucopenia (six [5%] of 127 patients) and thrombocytopenia (five [4%] of 127 patients) in the standard therapy group. Treatment-related serious adverse events occurred in three (2%) of 127 patients in the ropeginterferon alfa-2b group and five (4%) of 127 patients in the hydroxyurea group. One treatment-related death was reported in the standard therapy group (acute leukaemia). Interpretation In patients with early polycythaemia vera, who predominantly presented without splenomegaly, ropeginterferon alfa-2b was effective in inducing haematological responses; non-inferiority to hydroxyurea regarding haematological response and normal spleen size was not shown at 12 months. However, response to ropeginterferon alfa-2b continued to increase over time with improved responses compared with hydroxyurea at 36 months. Considering the high and durable haematological and molecular responses and its good tolerability, ropeginterferon alfa-2b offers a valuable and safe long-term treatment option with features distinct from hydroxyurea. Funding AOP Orphan Pharmaceuticals AG.

Reprocessed X-ray emission in Active Galactic Nuclei (AGN) can provide fundamental information about the circumnuclear environments of supermassive black holes. Recent mid-infrared studies have shown evidence of an extended dusty structure perpendicular to the torus plane. In this work, we build a self-consistent X-ray model for the Circinus Galaxy including the different physical components observed at different wavelengths and needed to reproduce both the morphological and spectral properties of this object in the mid-infrared. The model consists of four components: the accretion disk, the broad line region (BLR), a flared disk in the equatorial plane and a hollow cone in the polar direction. Our final model reproduces well the 3--70 keV Chandra and NuSTAR spectra of Circinus, including the complex Fe K$\alpha$ zone and the spectral curvature, although several additional Gaussian lines, associated to either ionized iron or to broadened Fe K$\alpha$/K$\beta$ lines, are needed. We find that the flared disk is Compton thick ($ N_{\rm H,d}= \rm 1.01^{+0.03}_{-0.24}\times 10^{25}\: cm^{-2}$) and geometrically thick ($CF=0.55^{+0.01}_{-0.05}$), and that the hollow cone has a Compton-thin column density ($ N_{\rm H,c}= \rm 2.18^{+0.47}_{-0.43}\times 10^{23}\: cm^{-2}$), which is consistent with the values inferred by mid-infrared studies. Including also the BLR, the effective line of sight column density is $ N_{\rm H}= \rm 1.47^{+0.03}_{-0.24}\times 10^{25}\: cm^{-2}$. This approach to X-ray modelling, i.e. including all the different reprocessing structures, will be very important to fully exploit data from future X-ray missions., Comment: Accepted for publication in MNRAS. 15 pages, 10 figures, 8 tables

Artificial light at night (ALAN) has the potential to change the day-night activity of marine benthic grazers, and can therefore alter the top-down control they exert on macroalgal communities. In laboratory experiments, we investigated the influence of three realistic ALAN regimes on food consumption and feeding rhythmicity in the sea urchins Arbacia lixula and Paracentrotus lividus as well as in the snail Cerithium spp. from the Adriatic Sea. Food consumption was assessed in assays with algal pellets, while feeding rhythms were documented with 24 h time-lapse photography. Both was done in ALAN-acclimated and in non-acclimated animals. We observed temporary and potential long-term changes in the feeding rhythms of Cerithium spp. and Paracentrotus lividus, respectively, but found no lasting influence of ALAN on consumption rates. Effects were weaker when ALAN was applied only part-night, which suggests a possible mitigation measure to reduce the impact of nighttime lighting on coastal ecosystems.

This review gives a worldwide overview on Power-to-Gas projects producing hydrogen or renewable substitute natural gas focusing projects in central Europe. It deepens and completes the content of previous reviews by including hitherto unreviewed projects and by combining project names with details such as plant location. It is based on data from 153 completed, recent and planned projects since 1988 which were evaluated with regards to plant allocation, installed power development, plant size, shares and amounts of hydrogen or substitute natural gas producing examinations and product utilization phases. Cost development for electrolysis and carbon dioxide methanation was analyzed and a projection until 2030 is given with an outlook to 2050. The results show substantial cost reductions for electrolysis as well as for methanation during the recent years and a further price decline to less than 500 euro per kilowatt electric power input for both technologies until 2050 is estimated if cost projection follows the current trend. Most of the projects examined are located in Germany, Denmark, the United States of America and Canada. Following an exponential global trend to increase installed power, today's Power-to-Gas applications are operated at about 39 megawatt. Hydrogen and substitute natural gas were investigated on equal terms concerning the number of projects.

Overview Purely electrical energy storage technologies are very efficient, however they are also very expensive and have the smallest capacities. Electrochemical-energy storage reaches higher capacities at smaller costs, but at the expense of efficiency. This pattern continues in a similar way for chemical-energy storage. In terms of capacities, the limits of batteries (accumulators) are reached when low-loss long-term storage is of need. Chemical-energy storage and stocking fulfills these requirements completely. The storing itself may be subject to significant efficiency losses, but, from today’s point of view and in combination with the existing gas and fuel infrastructure, it is the only national option with regards to the long-term storage of renewable energies. Chemical-energy storage is the backbone of today’s conventional energy supply. Solid (wood and coal), liquid (mineral oil), and gaseous (natural gas) energy carriers are ‘energy storages’ themselves, and are stored using different technologies. In the course of energy transition, chemical-energy storage will be of significant importance, mainly as long-term storage for the power sector, but also in the form of combustibles and fuels for transport and heat. Not only are conventional storing technologies discussed within this chapter, but a detailed explanation is also given about the storage of renewable energies in the form of gaseous (power-to-gas, PtG) and liquid (power-to-liquid, PtL) energy carriers for electricity, heat, chemicals, and in the form of synthetic fuels.

Overview Chemical-energy storage systems use caverns, porous storage facilities, tanks, and storage rooms to store chemical energy sources. Caverns, caves, and reservoirs can also be used to store gaseous media such as air, liquid media such as water, and solid media such as rock. The principles of mechanical energy storage are based on classical Newtonian mechanics, or in other words on fundamental physics from the eighteenth and nineteenth centuries. As a result, these types of storage are typically divided into two categories; storage of kinetic and potential energy, or storage of ‘pressure energy’. In this chapter, storage media is categorized by its aggregate state, and described by its function and application: first compressed air energy storage and then conventional electricity storage—pumped-storage plants. The chapter continues with a discussion of innovative methods of storing potential energy using water as a medium. These include artificially constructed pumped storage, pumped storage in the open sea, dam storage on rivers, pumped storage on heaps in repurposed mining areas, underfloor or underground pumped storage, and surface mine storage. The chapter concludes with a description of classical and modern flywheel energy storage systems. This age-old technology is then compared with a new concept: mechanical stored energy exploiting both pumped storage and change in the potential energy of rocks or large boulders.

Since the end of the 1980s, the Westbahn line has been undergoing successive upgrading to a modern high-speed line. The aim is to considerably increase the capacity and the travel speed up to 250 km/h. Regarding the infrastructure, this entails the new construction or upgrading of many sections including a number of tunnels due to the extended route and the topographical conditions. The requirements applicable to railway tunnels have changed significantly since the start of tunnel construction activities for the upgrading of the Westbahn. At the same time mechanised tunnelling technology has made great progress. These two developments have led to the situation that mechanised tunnel boring has become increasingly established in Austria as a viable alternative to NATM as a construction method for rail tunnels. The present article describes the procedure at the responsible company of Austrian Railways, OBB-Infrastruktur AG, in connection with these developments and explains the considerations leading to the selection of the tunnelling method. Seit Ende der 1980er Jahre wird die Westbahn sukzessive zu einer modernen Hochleistungsstrecke ausgebaut. Die Ziele sind, die Streckenkapazitat deutlich zu steigern und die Fahrgeschwindigkeit bis auf 250 km/h anzuheben. Infrastrukturseitig sind dafur zahlreiche Neu- und Ausbauabschnitte notwendig, die wegen ihrer gestreckten Linienfuhrung und der gegebenen topografischen Verhaltnisse auch einige Tunnelbauwerke beinhalten. Die Anforderungen an Eisenbahntunnel haben sich seit dem Beginn der Tunnelbauaktivitaten fur den Westbahnausbau wesentlich verandert. Gleichzeitig hat in dieser Zeitspanne die Technologie des maschinellen Tunnelvortriebs grose Fortschritte erzielt. Beide Entwicklungen haben dazu gefuhrt, dass sich der maschinelle Tunnelvortrieb in Osterreich auch beim Bau von Eisenbahntunneln zunehmend als konkurrenzfahige Baumethode zum NOT-Vortrieb etabliert hat. Der vorliegende Beitrag erlautert die Vorgangsweise der OBB-Infrastruktur AG im Zusammenhang mit diesen Entwicklungen und legt dar, welche Uberlegungen bezuglich der Wahl der Tunnelbaumethode angestellt wurden.

A new selp-learning control algorithm is presented, designed for plants with unknown cyclic or state-dependem distur-bances. Exemplified by the compensation of pulse converter non-linearities the c...

Different subpopulations of mast cells are characterized by their abundant contents of either tryptase or in addition chymase. These two neutral proteases are found in mast cells and may thus hold a key to the understanding of mast cell dependent reactions. Such studies are however hampered by the lack of readily available supplies of chymase. We have therefore studied the simultaneous purification of both proteases from hairless moro hr/hr mouse skin, using a sequence of salt extractions and chromatographic separations. After three steps of extraction, a 13-fold purification with an 82% yield was obtained for tryptase and a 15-fold purification with a 90% yield for chymase. Further one step purification on conventional sephadex, sephacryl and octyl sepharose columns was unsatisfactory because of further protein contamination of the fractions. Heparin affinity chromatography caused a high loss of tryptase and residual protein contamination. Gradient elution on a benzamidine sepharose 6B column resulted however in a single, low yield (17.9%) tryptase peak and a broader, high yield (>90%) chymase peak, and a 34% yield high purity fraction. The proteases thus purified exhibited their typical inhibitor profile. On Western blot analysis and on autoradiography in the presence of the serine protease inhibitor diisopropylfluorophosphate (DFP), only one 28 kD molecule with chymase activity was identified, whereas a broad 32-38 kD band of tryptase monomers was noted. Taken together, these data show that, after salt extraction and a single benzamidine affinity chromatography step, both mast cell chymase and tryptase can be separated and in case of chymase also highly purified, allowing thus for the study of biological activities of this molecule.

The response of a cylindrical liquid column consisting of an incompressible and frictionless liquid has been investigated for a pitching bridge bottom. The response of the free surface and velocity distribution has been determined and numerically evaluated. In addition, the transient behavior of the column has been treated. Since for nonviscous liquid the response exhibits at the resonances singularity, a semi-empirical damping was introduced in the resonance terms. Its magnitude has to be determined by experiments.

The response of a cylindrical liquid column consisting of incompressible and non-viscous liquid has been investigated for a rotational harmonic excitation of its bottom and top. Free surface displacement and velocity response have been determined and numerically evaluated. In addition, the transient behavior of the liquid column has been treated for a rotational bottom and top excitation which has suddenly been changed to another forcing frequency and excitation angular amplitude. Since the liquid is treated as frictionless, this response exhibits singularities at the resonance frequencies. To circumvent this problem damping has been introduced in a semi-empirical way in the resonance terms, which first limits the response amplitude and has to be measured in experiments. The results are of value for the efficient planning and evaluation of the “LICORE” (Liquid Column Resonances) experiments to be performed during the second German Spacelab Mission D-2.

A finite cylindrical liquid bridge consisting of incompressible and non-viscous liquid is subjected to a harmonic counter-rotational excitation of the top and bottom walls. The response of the free liquid surface and the velocity distribution has been determined and numerically evaluated. Since for a frictionless liquid the response exhibits singularities at the resonances, a semi-empirical damping was introduced in the resonance terms, of which the damping factor has to be determined by experiments.

BACKGROUND. In previous studies, alemtuzumab demonstrated considerable activity in patients with previously treated B-cell chronic lymphocytic leukemia (CLL), including fludarabine-refractory disease. In this retrospective study, the authors evaluated the benefit of alemtuzumab monotherapy in unselected patients with advanced, previously treated CLL who received treatment in the routine clinical setting. METHODS. Data were collected from 115 consecutive patients who received alemtuzumab therapy at 25 participating centers in Austria. Patients received a median of 3 prior lines of therapy (range, 1–11 prior lines of therapy), and 59% had fludarabine-refractory disease. Alemtuzumab was administered intravenously or subcutaneously with a planned schedule of 30 mg 3 times per week for up to 12 weeks. Patients received valacyclovir and trimethoprim/sulfamethoxazole for antiinfective prophylaxis. RESULTS. The overall response rate was 23%, with complete responses achieved in 5% of patients. Stable disease (SD) was achieved in 36% of patients. After a median follow-up of 17.5 months, the median overall survival (OS) was 20.2 months for all patients. A multivariate Cox regression analysis that included pretreatment baseline characteristics, response to therapy, and cumulative dose of alemtuzumab indicated that bulky lymphadenopathy, the administration of ≥3 previous therapies, and lack of response to alemtuzumab remained significant independent risk factors for inferior OS. The median OS had not been reached for responding patients. The median OS was 29.5 months for patients with SD and 10.8 months for patients with progressive disease. CONCLUSIONS. The broad use of alemtuzumab in the routine clinical practice setting is feasible and active in unselected patients with pretreated CLL, and the current results confirmed the activity and safety of this agent, as reported in previously published clinical studies. Cancer 2006. © 2006 American Cancer Society.

Thrombin has recently been shown not only to exert procoagulant activities, but also to induce mito - genic responses of different cell types involved in wound healing via binding to and cleavage of the thrombin re- ceptor. In order to further explore these aspects of thrombin function, human keratinocytes (HaCaT cell line) were examined for their potential mitogenic re- sponsiveness to thrombin and for the dependency of this process on the expression of the high-affinity thrombin receptor. Quiescent keratinocytes were stim- ulated in the mitogenic assay with α-thrombin and the thrombin receptor activating peptides TRAP 42-55 (SFLLRNPNDKYEPY) and TRAP 42-46 (SFLLR). A strong induction of cell proliferation was noted with α- thrombin, TRAP 42-55 and TRAP 42-46 , but not with the "scrambled" peptide (FSLLR). These findings confirm that keratinocytes express the thrombin receptor and that the sequence of the first two amino acids of the generated neo-N-terminus are important for the ac- tivation of the receptor. Using cDNA fragments of the 5' coding sequence of the receptor, Northern blot analysis confirmed that HaCaT keratinocytes express the thrombin receptor. Expression of the receptor was also detected on normal human keratinocytes by im- munohistochemistry and in situ hybridization. These data demonstrate the expression and biologic function of the human thrombin receptor on human keratino- cytes, suggesting that thrombin, among other media- tors, plays an important part in the orchestration of epidermal growth and repair processes.

In order to shed further light on the potential role of mast cells during tissue turnover, we have investigated the number of mast cells containing only tryptase and those storing both tryptase and chymase by enzyme histochemistry in normal versus healing skin. Furthermore, we have studied the in vitro effect of these enzymes on the mitogenesis of subconfluent quiescent fibroblast and HaCaT keratinocyte cultures, using flowcytometric DNA analysis. Chymase-containing mast cell numbers were markedly decreased in scars (P

It is often questionable as to whether or not therapeutic benefit documented in prospective studies reflects that which is observed in routine use. Four prospective studies have explored the efficacy of alemtuzumab in heavily pretreated B-CLL patients, reporting response rates (RR) between 33% to 55%, and median survival between 13–28 months. Here, we report clinical outcomes after therapy with alemtuzumab of 106 consecutive, unselected B-CLL patients treated in 25 centers in Austria. Seventy-two patients were male and 34 female, the median age was 66 years (range, 46–88 years). The majority of patients had advanced stage disease, with 58% having Rai stage IV disease. The patients had received a median of 3 prior therapies (range, 1–11). Alemtuzumab was administered according to guidelines, but in the majority of cases, dosing was individualized, according to tolerability, side effects, and economic considerations. Thus, the median duration of therapy was 7 weeks (range, 2–24 weeks), and median dose was only 390 mg (range, 11–1333 mg). Therapeutic response was determined, strictly adhering to the NCI criteria (duration of complete response [CR]/partial response [PR]/stable disease [SD] ≥ 2 months; adequate radiologic studies of all non-palpable manifestation; marrow for CR). CR, PR, and SD were achieved in 5%, 17%, and 34% of patients (RR 22%). Progressive disease occurred in 34%, and responses were not evaluable in 9%, due to early death. In the 59 patients with overall CR/PR/SD, peripheral blood responses were as follows: 63% CR, 25% PR, and 12% SD. Survival times were encouraging and comparable with other studies. The median survival for all patients was 19 months; 15 months for fludarabine-refractory patients (n = 67) and 31 months for fludarabine-sensitive patients (n = 24; P = 0.04). Survival was dependent on response (P = 0.0001), the number of previous therapy lines (0–3 vs >3; P = 0.0001), and the presence of bulky disease (P = 0.005). Route of administration (IV: 49%; IV to SC 38%; upfront SC 13%) did not influence outcome. Toxicities were within the expected range, with grade 3/4 infections in 37% of patients; grade 4 neutropenia and thrombocytopenia in 25% and 23% of patients, CMV reactivation in 14% (CMV disease in 3%) of patients, and early death (

The totality of effects of a particular drug on patients cannot be truly assessed until many patients have taken it. In order to assess the side effects of any drug, many thousands of patients may have to be observed, and the observation may have to extend over decades. Quinacrine hydrochloride (quinacrine) was used as a malarial-suppressive drug by allied soldiers during World War II. The most commonly occurring side effect was a drug eruption. This at times led to permanent sequelae at an early stage. Further observation revealed late sequelae occurring 7 to 17 years after the war. Two of these late sequelae were observed to become malignant, and in most cases the palmar aspect was involved. This is an area which rarely shows malignant change. It has been observed that quinacrine can be instrumental in inducing skin cancers as late as 34 years after its ingestion.

Wetting and mass transfer in film columns. Calculation of mass transfer in film columns requires a fundamental knowledge about the wetting of the materials comprising the packing bodies. Starting from thermodynamic principles for a description of the solid/liquid interface, methods are discussed which permit an exact calculation of the basic parameters of wetting. It is also shown how the goal of ideal wetting can be approached by choice of material, modification of the surface of the packing bodies, and use of additives. Experience gained with regard to the effect of the various measures on the separation performance leads to conclusions concerning the determination of dimensionless equations for prediction of separation performance.

Es wird Uber das neuartige Verfahren des isostatischen Heispressens berichtet. Das Verdichtungsprinzip wird erlautert. Nach einer Literaturschau Uber bisherige Arbeiten auf diesem neuartigen Gebiet der Pulvermetallurgie wird die Karlsruher Anlage — die erste dieser Art in der BRD — beschrieben. Die Technik der richtigen Probenvorbereitung fur diesen Prozes wird anhand der Herstellung von stabformigen Massiv- und Rohrproben erlautert. Als Beispiel wird die Herstellung eines Cermets des Systems Urandioxid-Molybdan beschrieben. Ein interessanter Nebeneffekt beim isostatischen Heispressen stellt das Warmverschweisen des Preslings mit dem Hullrohr dar. Mogliche Anwendungsgebiete des neuen Verfahrens sind die Herstellung von Brennstaben fur schnelle Brutreaktoren, Kathoden und Kollektoren fur thermionische Emitter, temperaturwechselbestandige, metallhaltige Keramiken und Sonderkeramiken und Systeme mit Metall-Keramik-Diffusions-Ubergangen. Auf dem Gebiet der Werkzeuge aus Schnellstahl bzw. Hartmetall mit hoher Standzeit ist diese Verfahrenstechnik im Vordringen. Fabrication of special materials by Isostatic Hot Pressing The process of Isostatic Hot Pressing is described. The principle of compaction is explained. A review of earlier work in the literature is given. The plant in Karlsruhe — the first in the BRD — is described. The technique of right sample preparation is shown by 2 examples. One of those is the compaction of an UO2-Mo-cermet. During Isostatic Hot Pressing a metallurgical bonding between can and fuel is observed. Some applications of the new process are: the fabrication of fuel pins for fast breeder reactors, cathodes and collectors for thermionic emitters, thermal shock resistant ceramics and metal-ceramic diffusion bonds. In the field of high speed steel and hard-metal with improved lifetime, the new process is advancing.