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Authors: Koribalski, Bärbel S.; Staveley-Smith, L.; Westmeier, T.; Serra, P.; Spekkens, K.; Wong, O. I.; Lee-Waddell, K.; Lagos, C. D. P.; Obreschkow, D.; Ryan-Weber, E. V.; Zwaan, M.; Kilborn, V.; Bekiaris, G.; Bekki, K.; Bigiel, F.; Boselli, A.; Bosma, A.; Catinella, B.; Chauhan, G.; Cluver, M. E. Colless, M.; Courtois, H. M.; Crain, R. A.; de Blok, W. J. G.; Dénes, H.; Duffy, A. R.; Elagali, A.; Fluke, C. J.; For, B. -Q.; Heald, G.; Henning, P. A.; Hess, K. M.; Holwerda, B. W.; Howlett, C.; Jarrett, T.; Jones, D. H.; Jones, M. G.; Józsa, G. I. G.; Jurek, R.; Jütte, E.; Kamphuis, P.; Karachentsev, I.; Kerp, J.; Kleiner, D.; Kraan-Korteweg, R. C.; López-Sánchez, Á. R.; Madrid, J.; Meyer, M.; Mould, J.; Murugeshan, C.; Norris, R. P.; Oh, S. -H.; Oosterloo, T. A.; Popping, A.; Putman, M.; Reynolds, T. N.; Rhee, J.; Robotham, A. S. G.; Ryder, S.; Schröder, A. C.; Shao, Li; Stevens, A. R. H.; Taylor, E. N.; van der Hulst, J. M.; Verdes-Montenegro, L.; Wakker, B. P.; Wang, J.; Whiting, M.; Winkel, B.; Wolf, C., The Widefield ASKAP L-band Legacy All-sky Blind surveY (wallaby) is a next-generation survey of neutral hydrogen (H i) in the Local Universe. It uses the widefield, high-resolution capability of the Australian Square Kilometer Array Pathfinder (ASKAP), a radio interferometer consisting of 36 × 12 -m dishes equipped with Phased-Array Feeds (PAFs), located in an extremely radio-quiet zone in Western Australia. wallaby aims to survey three-quarters of the sky (− 90 < δ< + 30 ) to a redshift of z≲ 0.26 , and generate spectral line image cubes at ∼30 arcsec resolution and ∼1.6 mJy beam per 4 km s channel sensitivity. ASKAP’s instantaneous field of view at 1.4 GHz, delivered by the PAF’s 36 beams, is about 30 sq deg. At an integrated signal-to-noise ratio of five, wallaby is expected to detect around half a million galaxies with a mean redshift of z∼ 0.05 (∼200 Mpc). The scientific goals of wallaby include: (a) a census of gas-rich galaxies in the vicinity of the Local Group; (b) a study of the H i properties of galaxies, groups and clusters, in particular the influence of the environment on galaxy evolution; and (c) the refinement of cosmological parameters using the spatial and redshift distribution of low-bias gas-rich galaxies. For context we provide an overview of recent and planned large-scale H i surveys. Combined with existing and new multi-wavelength sky surveys, wallaby will enable an exciting new generation of panchromatic studies of the Local Universe. — First results from the wallaby pilot survey are revealed, with initial data products publicly available in the CSIRO ASKAP Science Data Archive (CASDA). © 2020, Springer Nature B.V., The Australian SKA Pathfinder (ASKAP) is part of the Australia Telescope National Facility (ATNF) which is managed by CSIRO. Operation of ASKAP is funded by the Australian Government with support from the National Collaborative Research Infrastructure Strategy (NCRIS). ASKAP uses the resources of the Pawsey Supercomputing Centre. Establishment of ASKAP, the Murchison Radio-astronomy Observatory (MRO) and the Pawsey Supercomputing Centre are initiatives of the Australian Government, with support from the Government of Western Australia and the Science and Industry Endowment Fund. We acknowledge the Wajarri Yamatji as the traditional owners of the Observatory site. FB and DK acknowledge funding from the European Union's Horizon 2020 research and innovation programme; grant agreement No 726384 (FB) and No 679627 (DK). MEC is a recipient of an Australian Research Council Future Fellowship (project number FT170100273) funded by the Australian Government. RKK acknowledges the South African Research Chairs Initiative of the Department of Science and Innovation. RKK and GIGJ acknowledge the South African National Research Foundation for their support. MGJ and LVM acknowledge support from the grants AYA2015-65973-C3-1-R (MINECO/FEDER, UE) and RTI2018-096228-B-C31 (MICIU/FEDER, EU), as well as from the State Agency for Research of the Spanish MCIU through the "Center of Excellence Severo Ochoa" award for the Instituto de Astrofisica de Andalucia (SEV-20170709). MGJ is supported by a Juan de la Cierva formacion fellowship (FJCI-2016-29685). PK is partially supported by the BMBF project 05A17PC2 for D-MeerKAT. DO is a recipient of an Australian Research Council Future Fellowship (FT190100083) funded by the Australian Government. KS acknowledges support from the Natural Sciences and Engineering Research Council of Canada (NSERC). JMvdH acknowledges support from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement nr. 291531. Parts of this research were supported by the Australian Research Council Centre of Excellence for All Sky Astrophysics in 3 Dimensions (ASTRO 3D), through project number CE170100013.

We present a catalogue of galaxies in the northern Zone of Avoidance (ZoA), extracted from the shallow version of the blind HI survey with the Effelsberg 100 m radio telescope, EBHIS, that has a sensitivity of 23 mJy/beam at 10.24 km/s velocity resolution. The catalogue comprises 170 detections in the region Dec >= -5 degrees and |b| < 6 degrees. About a third of the detections (N=67) have not been previously recorded in HI. While 29 detections have no discernible counterpart at any wavelength other than HI, 48 detections (28%) have a counterpart visible on optical or NIR images but are not recorded as such in the literature. New HI detections were found as close as 7.5 Mpc (EZOA J2120+45), and at the edge of the Local Volume, at 10.1 Mpc, we have found two previously unknown dwarf galaxies (EZOA J0506+31 and EZOA J0301+56). Existing large-scale structures crossing the northern ZoA have been established more firmly by the new detections, with the possibility of new filaments. We conclude that the high rate of 39% new HI\detections in the northern ZoA, which has been extensively surveyed with targeted observations in the past, proves the power of blind HI surveys. The full EBHIS survey, which will cover the full northern sky with a sensitivity comparable to the HIPASS survey of the southern sky, is expected to add many new detections and uncover new structures in the northern ZoA., 19 pages, 10 figures, accepted by MNRAS, online material available through MNRAS or by request

We present a homogeneous 2MASS bright galaxy catalogue at low Galactic latitudes ($|b| \le 10.0^{\rm o}$, called Zone of Avoidance) which is complete to a Galactic extinction-corrected magnitude of $K^o_s \le 11.25^{\rm m}$. It also includes galaxies in regions of high foreground extinctions ($E(B-V) > 0.95^{\rm m}$) situated at higher latitudes. This catalogue forms the basis of studies of large-scale structures, flow fields and extinction across the ZoA and complements the ongoing 2MASS Redshift and Tully-Fisher surveys. It comprises 3763 galaxies, 70% of which have at least one radial velocity measurement in the literature. The catalogue is complete up to star density levels of $\log N_*/{\rm deg}^2, 29 pages, 16 figures; accepted for publication in MNRAS; full catalogue available as ancillary file in sourcefile package

Mono ADP-ribosylation is a common characteristic of bacterial toxins resulting to aberrant activation or inactivation of target proteins. The C3 exoenzyme of Clostridium botulinum (C3bot) ADP-ribosylates the small GTPases RhoA, RhoB and RhoC, leading to inactivation of these important regulators and impaired down-stream signaling. Quantification of ADP-ribosylation using gel migration assays, antibodies, and radioactivity-based methods are limited. Therefore a novel LC-MS-based method to specifically determine and quantify ADP-ribosylation of Rho GTPases was established. A heavy labeled protein standard that contained ADP-ribosylation specific peptides in similar amounts in ADP ribosylated and non ADP ribosylated form was used for relative quantification in vivo. In a proof of principle experiment HT22 cells were treated with C3bot and the kinetics of RhoA/B and RhoC ADP-ribosylation were determined in vivo.

We present results of a blind 21cm HI-line imaging survey of a galaxy overdensity located behind the Milky Way at $\ell,b$ $\approx$ 160 deg, 0.5 deg. The overdensity corresponds to a Zone-of-Avoidance crossing of the Perseus-Pisces Supercluster filament. Although it is known that this filament contains an X-ray galaxy cluster (3C129) hosting two strong radio galaxies, little is known about galaxies associated with this potentially rich cluster because of the high Galactic dust extinction. We mapped a sky area of $\sim$9.6 sq.deg using the Westerbork Synthesis Radio Telescope in a hexagonal mosaic of 35 pointings observed for 12 hours each, in the radial velocity range $cz = 2400 - 16600$ km/s. The survey has a sensitivity of 0.36 mJy/beam rms at a velocity resolution of 16.5 km/s. We detected 211 galaxies, 62% of which have a near-infrared counterpart in the UKIDSS Galactic Plane Survey. We present a catalogue of the HI properties and an HI atlas containing total intensity maps, position-velocity diagrams, global HI profiles and UKIDSS counterpart images. For the resolved galaxies we also present HI velocity fields and radial HI surface density profiles. A brief analysis of the structures outlined by these galaxies finds that 87 of them lie at the distance of the Perseus-Pisces Supercluster ($cz \sim 4000 - 8000$ km/s) and seem to form part of the 3C129 cluster. Further 72 detections trace an overdensity at a velocity of $cz \approx$ 10000 km/s and seem to coincide with a structure predicted from mass density reconstructions in the first 2MASS Redshift Survey., 28 pages, 18 figures, 6 Tables, accepted for publication in MNRAS

A blind HI survey of the extragalactic sky behind the southern Milky Way has been conducted with the multibeam receiver on the 64-m Parkes radio telescope. The survey covers the Galactic longitude range 212 < l < 36 and Galactic latitudes |b| < 5, and yields 883 galaxies to a recessional velocity of 12,000 km/s. The survey covers the sky within the HIPASS area to greater sensitivity, finding lower HI-mass galaxies at all distances, and probing more completely the large-scale structures at and beyond the distance of the Great Attractor. Fifty-one percent of the HI detections have an optical/NIR counterpart in the literature. A further 27% have new counterparts found in existing, or newly obtained, optical/NIR images. The counterpart rate drops in regions of high foreground stellar crowding and extinction, and for low-HI mass objects. Only 8% of all counterparts have a previous optical redshift measurement. A notable new galaxy is HIZOA J1353-58, a possible companion to the Circinus galaxy. Merging this catalog with the similarly-conducted northern extension (Donley et al. 2005), large-scale structures are delineated, including those within the Puppis and Great Attractor regions, and the Local Void. Several newly-identified structures are revealed here for the first time. Three new galaxy concentrations (NW1, NW2 and NW3) are key in confirming the diagonal crossing of the Great Attractor Wall between the Norma cluster and the CIZA J1324.7-5736 cluster. Further contributors to the general mass overdensity in that area are two new clusters (CW1 and CW2) in the nearer Centaurus Wall, one of which forms part of the striking 180 deg (100/h Mpc) long filament that dominates the southern sky at velocities of ~3000 km/s, and the suggestion of a further Wall at the Great Attractor distance at slightly higher longitudes., Published in Astronomical Journal 9 February 2016 (accepted 26 September 2015); 42 pages, 7 tables, 18 figures, main figures data tables only available in the on-line version of journal

Despite advances in allogeneic stem cell transplantation, BCR-ABL-positive acute lymphoblastic leukaemia (ALL) remains a high-risk disease, necessitating the development of novel treatment strategies. As the known oncomir, miR-17~92, is regulated by BCR-ABL fusion in chronic myeloid leukaemia, we investigated its role in BCR-ABL translocated ALL. miR-17~92-encoded miRNAs were significantly less abundant in BCR-ABL-positive as compared to -negative ALL-cells and overexpression of miR-17~19b triggered apoptosis in a BCR-ABL-dependent manner. Stable isotope labelling of amino acids in culture (SILAC) followed by liquid chromatography and mass spectroscopy (LC-MS) identified several apoptosis-related proteins including Bcl2 as potential targets of miR-17~19b. We validated Bcl2 as a direct target of this miRNA cluster in mice and humans, and, similar to miR-17~19b overexpression, Bcl2-specific RNAi strongly induced apoptosis in BCR-ABL-positive cells. Furthermore, BCR-ABL-positive human ALL cell lines were more sensitive to pharmacological BCL2 inhibition than negative ones. Finally, in a xenograft model using patient-derived leukaemic blasts, real-time, in vivo imaging confirmed pharmacological inhibition of BCL2 as a new therapeutic strategy in BCR-ABL-positive ALL. These data demonstrate the role of miR-17~92 in regulation of apoptosis, and identify BCL2 as a therapeutic target of particular relevance in BCR-ABL-positive ALL.

The knowledge about the etiology and pathophysiology of sensorineural hearing loss (SNHL) is still very limited. This study aims at the improvement of understanding different types of SNHL by proteome analysis of human perilymph. Sampling of perilymph was established during inner ear surgeries (cochlear implantation, vestibular schwannoma surgeries), and safety of the sampling method was determined by checking hearing threshold with pure-tone audiometry postoperatively. An in-depth shot-gun proteomics approach was performed to identify cochlear proteins and the individual proteome in perilymph of patients. This method enables the identification and quantification of protein composition of perilymph. The proteome of 41 collected perilymph samples with volumes of 1-12 μL was analyzed by data-dependent acquisition, resulting in overall 878 detected protein groups. At least 203 protein groups were solely identified in perilymph, not in reference samples (serum, cerebrospinal fluid), displaying a specific protein pattern for perilymph. Samples were grouped by patient's age and surgery type, leading to the identification of some proteins specific to particular subgroups. Proteins with different abundances between different sample groups were subjected to classification by gene ontology annotations. The identified proteins might serve as biomarkers to develop tools for noninvasive inner ear diagnostics and to elucidate molecular profiles of SNHL.

Toxin B (TcdB) of the nosocomial pathogen C. difficile has been reported to exhibit a glucosyltransferase-dependent and -independent effect on treated HEp-2 cells at toxin concentration above 0.3 nM. In order to investigate and further characterize both effects epithelial cells were treated with wild type TcdB and glucosyltransferase-deficient TcdBNXN and their proteomes were analyzed by LC-MS. Triplex SILAC labeling was used for quantification. Identification of 5212 and quantification of 4712 protein groups was achieved. Out of these 257 were affected by TcdB treatment, 92 by TcdBNXN treatment and 49 by both. TcdB mainly led to changes in proteins that are related to "GTPase mediated signaling" and the "cytoskeleton" while "chromatin" and "cell cycle" related proteins were altered by both, TcdB and TcdBNXN . The obtained dataset of HEp-2 cell proteome helps us to better understand glucosyltransferase-dependent and -independent mechanisms of TcdB and TcdBNXN , particularly those involved in pyknotic cell death. All proteomics data have been deposited in the ProteomeXchange with the dataset identifier PXD006658 (https://proteomecentral.proteomexchange.org/dataset/PXD006658).

Acta Ophthalmol. 2010: 88: 885–890 Abstract. Purpose: Prior to phakic intraocular lens implantation, it is important to obtain precise knowledge of the anterior chamber depth (ACD). Accurate topographic evaluation of the iridocorneal angle is helpful in estimating risk for angle-closure glaucoma. This study investigated the use of the Orbscan II system to measure ACD and the iridocorneal angle in healthy subjects and assessed the influences of age, gender and spherical equivalent on these parameters. Methods: The Orbscan II system was used to determine the ACD and iridocorneal angle in eight different positions in 390 healthy White subjects with a mean age of 41 ± 16 years (range 10–80 years). The sample included 242 male and 148 female subjects. The influences of age, gender and spherical equivalent were assessed using multiple regression analysis. Results: Mean ACD was 2.87 ± 0.04 mm in male subjects and 2.81 ± 0.37 mm in female subjects. The explanatory variables relevant to the ACD were age (partial regression coefficient B = − 0.0115, p

In a bench scale trial biological sulfate reduction was applied to convert anglesite (PbSO4) to galena (PbS). Anglesite is a main constituent in waste fractions such as lead paste from spent car batteries or residues from (in)direct leaching processes. The goal of this study was to develop a technology to decrease lead (Pb) emissions by converting PbSO4 from a waste fraction to PbS, which can be recovered using electrochemical processes. The conversion of PbSO4 to PbS is based on the biological reduction of sulfate and the consequent precipitation of PbS. First sulfate is biologically reduced to sulfide. Secondly, the Pb2+ from the PbSO4 reacts chemically with the sulfide resulting from the first reaction. A bench-scale reactor was started up using sulfate-containing influent. The reactor was seeded with biocatalyst from several full-scale reactors. PbSO4-containing residue was added batch-wise when the formation of sulfide started. The residue contained mainly PbSO4 (51.7%), sulfate (SO42−, 19.9%) and elemental sulfur (S0, 15.1%). PbS precipitates in the bioreactor due to the near-neutral pH at which the sulfate reduction process is carried out. From the electron balance and chemical analyses it was concluded that both sulfate and sulfur present in the residue were biologically reduced. The formation of PbS was confirmed by the increased Pb:O ratio in the sludge (1:0.1) relative to the Pb:O ratio in the PbSO4-containing residue (1:3.3). A potential large-scale application is proposed.

PURPOSE This study was carried out to investigate the impact of high concentrations of Clostridium difficile toxin A (TcdA) on the proteome of human cells. It should also be examined whether a catalytically deficient mutant (TcdANXN ) has an effect on target cells. EXPERIMENTAL DESIGN Proteome changes were investigated after treatment of HEp-2 cells with 20 nM TcdA for 8 h using a triplex SILAC labeling method and shotgun proteomics. Proteins from differently labeled and treated cells were combined for analysis using an HPLC coupled to an Orbitrap mass spectrometer. RESULTS Nearly 4000 proteins were identified in each replicate and 3500 could be quantified by SILAC triplicate analysis. 51 proteins exhibited an altered abundance with 29 up-regulated and 22 down-regulated proteins. In contrast, TcdANXN had no provable impact on the protein profile of HEp-2 cells. Data analysis of regulated proteins revealed that mainly plasma membrane, cell death, cell proliferation and actin cytoskeleton proteins were affected by TcdA treatment. CONCLUSIONS AND CLINICAL RELEVANCE This proteome analysis showed novel insights of TcdA impact onepithelial cells. Comparison with long-term treatment studies reveals distinctions in affected cellular processes that will improve the understanding of TcdA functions and might help to find new tools for diagnosis and treatment of CDI.

C3bot from Clostridium botulinum is a bacterial mono-ADP-ribosylating enzyme, which transfers an ADP-ribose moiety onto the small GTPases Rho A/B/C. C3bot and the catalytic inactive mutant (C3E174Q) cause axonal and dendritic growth as well as branching in primary hippocampal neurons. In cultured murine hippocampal HT22 cells, protein abundances were analyzed in response to C3bot or C3E174Q treatment using a shotgun proteomics approach. Proteome analyses were performed at four time points over 6 days. More than 4000 protein groups were identified at each time point and quantified in triplicate analyses. On day one, 46 proteins showed an altered abundance, and after 6 days, more than 700 proteins responded to C3bot with an up- or down-regulation. In contrast, C3E174Q had no provable impact on protein abundance. Protein quantification was verified for several proteins by multiple reaction monitoring. Data analysis of altered proteins revealed different cellular processes that were affected by C3bot. They are particularly involved in mitochondrial and lysosomal processes, adhesion, carbohydrate and glucose metabolism, signal transduction, and nuclear proteins of translation and ribosome biogenesis. The results of this study gain novel insights into the function of C3bot in hippocampal cells.

The results obtained in colour vision tests can be influenced by many factors. It is possible that a learning effect disguises the fact that an acquired colour vision disturbance has progressively either deteriorated or been successfully treated. Therefore, the primary object of this study was to examine whether a possible learning effect occurred if screening by the colour vision test Roth 28-hue (E) desaturated was repeated several times, and if this learning effect was age dependent. Sixty-five ocularly and generally healthy subjects participated in the study and were divided into two age groups: group A: 20–39 years, n = 35; group B: 40–59 years, n = 30. Besides their ophthalmological status (visual acuity, refraction, intraocular pressure, cup/disk ratio, central fundus), the cap-sorting test Roth 28-hue (E) desaturated was performed under standardized test conditions. The measurements were repeated after 5 ± 1.72 days (T1), 15 ± 3.53 days (T2), 32 ± 6.97 days (T3), and 189 ± 16.85 days (T4). The ophthalmological parameters of all subjects were inconspicuous. The individual evaluation of the error scores in the cap-sorting test Roth 28-hue (E) desaturated showed large-scale variations. For both age groups there was no statistically significant difference between the right and left eye at any time. The mean values of the younger group remained relatively constant after the first measurement. This age group showed a quick, clearly visible learning effect that persisted over the whole test period. With regard to the older age group the average values deteriorated, remained solid for one month increasing again after 6 months. The results showed an age-related learning effect. Therefore, it is important to repeat the colour vision test within 5 days for the age group 20–39 years. This second test result will then serve as a stable basis for further comparative examinations within a period of 6 months. The subjects of the age group 40–59 years ought to repeat a first colour vision test after 5 and again after 15 days. The result of the second repetition will then offer stable basic values for subsequent tests. © 2006 Wiley Periodicals, Inc. Col Res Appl, 32, 16–21, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/col.20282

By condensation of N,N ′-persubstituted bis-(2-aminophenyl)ketones 4 , bis-(2-amino-5-thienyl)ketones 16 , 2-amino-5-thienyl-(2-amino-5-thiazolyl)ketones 17 , and bis-(2-amino-5-thiazolyl)ketones 18 as well as of N -disubstituted derivaties of alkyl 2-aminothiophene-5-carboxylates 12 , alkyl 2-aminothiazole-5-carboxylates 15 and 2-amino-5-thienyl(2-thienyl)ketones 29 with N -disubstituted anilines 1 , 2-aminothiophenes 2 , 2-aminothiazoles 3 , and 2-methylmercaptothiophenes 34 or their lithiated derivatives a series hitherto unknown heterocyclic Crystal Violet analogues 6–8 , 19–25 , and 40–48 have been prepared and characterised spectroscopically.

Background. Plasminogen activator inhibitor-1 (PAI-1) is a main regulator of the fibrinolytic system. PAI-1 inhibits tissue plasminogen activator and urokinase-type plasminogen activator, resulting in reduced plasminogen activity and attenuated fibrinolysis and proteolysis. The present study was performed to determine the gene expression encoding for PAI-1 in cultured pigmented ciliary epithelial cells of the porcine eye and to detect PAI-1 activity in cell culture supernatants. Methods. Total mRNA of respective confluent primary cultures of porcine ciliary epithelial cells, porcine liver cells and porcine kidney cells was isolated. Reverse transcribed PAI-1 mRNA was measured by real-time polymerase chain reaction (TaqMan PCR) with PAI-1 primers and probes deduced from the human PAI-1 gene. PAI-1 activity in supernatants of the cell cultures was determined by a specific chromogenic test (Coatest PAI). Results. PAI-1 mRNA was localized in all samples of primary cultures of porcine pigmented ciliary epithelial cells. As a negative control we analyzed total mRNA of porcine kidney cells. PAI-1 mRNA was not detectable in these cells. On the other hand, we established PAI-1 mRNA in porcine liver cells as a positive control. High levels of PAI-1 activity were found in all samples of cell culture supernatants. Conclusions. Our results indicate that PAI-1 is produced and secreted by the porcine ciliary epithelium. We suggest that PAI-1 together with components of the fibrin/fibrinolytic system may be involved in aqueous humor outflow. Overproduction of PAI-1 may induce less fibrinolysis and extracellular proteolysis in aqueous humor and trabecular meshwork, which could result in an elevated intraocular pressure by increasing the outflow obstruction. Therefore stimulation of PAI-1 production may perhaps contribute to the pathogenesis of primary open-angle glaucoma.

Deep purple: By the transformation of readily available N,N-disubstituted 2-aminothiophenes and 2-aminothiazoles into heterocyclic analogues of Crystal Violet, such as, tris(2-dimethylamino-5-thienyl)methinium prechlorate (cation shown), the series of dyes derived from these heterocyclic structural units as the important chromophoric component is significantly extended and a gap in the class of heteroanalogous triphenylmethane dyes has been closed.

By reaction of N, N′-persubstituted bis(2-amino-5-thieny1)ketones 10 and their thiazole analogues 11 and 12 with P2S5 hitherto unknown 2-aminothienyl- or 2-aminothiazolyl-substituted thioketones 13–15 have been prepared and characterized as strongly solvatochromic compounds their sensitivity towards the polarity or solvents is significantly higher than the one of their corresponding ketone precursors 10–12.

The reaction of 2,2-dicyanoethenyl- and 1,2,2-tricyanoethenyl-substituted bromoalkanes, bromomethyl benzenes, thiophenes, and furans 19-22 with 3-aminothioacrylamides and their 2-azaanalogues 23 and 24 gives a series of 5-dicyanoethenyl- and 5-tricyanoethenyl-substituted 2-aminothiophenes, 2-aminothiazoles and their (hetero)benzologous analogues 25-32. The solvatochromism, which is a characteristic feature of these donor-acceptor substituted heterocyclic compounds, was studied in detail and correlated with the Kamlet-Taft solvent parameters.

We report on a blind neutral hydrogen survey for galaxies using the 21 cm multibeam receiver on the Parkes 64 m telescope. The surveyed region covers |b| ≤ 5° in the zone of avoidance (ZOA) from Galactic longitude 308° to 332°. The survey represents the first phase of a blind H I survey covering the southern ZOA (l = 212° to 36°). We have detected H I in 42 galaxies above a 3 σ limit of 60 mJy. The galaxies detected in this survey have velocities out to 6000 km s-1 and H I masses in the range 4 × 107 to 3 × 1010M⊙ (h). Only eight of the 42 galaxies have velocities previously measured. A further nine galaxies appear to have optical counterparts in the Woudt's 1998 catalog. In total, 16 of the galaxies appear to be associated with IRAS sources, although only three of these are without optical counterparts. The estimated median extinction for the 20 galaxies with optical or IR counterparts is AB = 3.8 mag. For the 22 galaxies with no counterparts, the estimated median extinction is AB = 5.6 mag. The distribution of galaxies is suggestive of a connection between the Centaurus supercluster above the Galactic plane and the Pavo-Indus supercluster beneath the plane. No previously hidden concentrations of galaxies were found.

Starting from 2-morpholinothiazoles 6 and 2-morpholinothiophenes 7 and following known routes several 5-dicyanovinyl and 5-tricyanovinyl-substituted derivatives 10–13 have been prepared and their solvatochromic properties estimated.

The envisioned clinical and industrial use of human pluripotent stem cells and their derivatives has given major momentum to the establishment of suspension culture protocols that enable the mass production of cells. Understanding molecular changes accompanying the transfer from adherent to suspension culture is of utmost importance because this information can have a direct effect on the development of optimized culture conditions. In this study we assessed the gene expression of human embryonic stem cells and induced pluripotent stem cells grown in surface-adherent culture (two-dimensional) versus free-floating suspension culture spheroids (three-dimensional). We combined a quantitative proteomic approach based on stable isotope labeling by amino acids in cell culture with deep-sequencing-based transcriptomics. Cells in three-dimensional culture showed reduced expression of proteins forming structural components of cell–cell and cell–extracellular matrix junctions. However, fully unexpected, we found up-regulation of secreted inhibitors of the canonical Wnt signaling pathway and, concomitantly, a reduction in the level of active β-catenin and in the expression of Wnt target genes. In Western blot analyses the cysteine protease calpain was shown to cleave E-cadherin and β-catenin under three-dimensional culture conditions. Our data allowed the development of a model in which calpain cleavage of E-cadherin induces the disintegration of focal cell contacts and generates a 100-kDa E-cadherin fragment required for the formation of three-dimensional cell–cell contacts in spheroids. The parallel release of β-catenin and its potential activation by calpain cleavage are counterbalanced by the overexpression of soluble Wnt pathway inhibitors. According to this model, calpain has a key function in the interplay between E-cadherin and β-catenin-mediated intercellular adhesion and the canonical Wnt signaling pathway. Supporting this model, we show that pharmacological modulation of calpain activity prevents spheroid formation and causes disassembly of preexisting spheroids into single cells, thereby providing novel strategies for improving suspension culture conditions for human pluripotent stem cells in the future.

The corneal horizontal diameter (white-to-white) is abnormal in diseases like microcornea, relative anterior microphthalmos, and corneal dystrophies. Because normal values are described imprecisely in the literature, the purpose of this study was to reevaluate the horizontal corneal diameter as a scientific parameter.The horizontal corneal diameter was measured with the Orbscan II system in 370 right eyes and 373 left eyes of 390 healthy white subjects aged 10-80 years. There were 148 female subjects and 242 male subjects. Each measurement was repeated twice. Differences in gender, between right and left eyes, and age-related alterations were analyzed statistically.The average corneal diameter was 11.71 +/- 0.42 mm. The average corneal diameter was 11.77 +/- 0.37 mm in males compared with 11.64 +/- 0.47 mm in females. The resulting normal ranges were 11.04 to 12.50 for males and 10.70 to 12.58 mm for females. Differences in gender were not significant in the t test for independent samples (P = 0.071). There were no statistically significant differences between right and left eyes in the t test for dependent samples (P = 0.16). Corneal diameters decreased slightly with age.With the obtained normal values, more precise determination of microcornea and macrocornea will be possible in the future. The horizontal corneal diameter was not significantly greater in males than in females. Further studies are needed to show the reasons for the age-related decrease in measurements.

The first serious competitor to the known solvatochromic pyridiniumphenolate betaines has been uncovered with the 5-dimethylamino-5'-nitro-2,2'-bithiophene 1 a (X=Z=S, Y=CH, R=CH(3)), which has the added benefit of being notably sensitive to solvent in acidic media. By simple heterocyclization further compounds of the general type 1 have been synthesized, and their suitability as solvent indicators was investigated. In this way a new record was set with the selenophene analogue of 1 a.

Purpose The thickness of corneal tissue is an important parameter in refractive surgery, Goldmann applanation tonometry, and corneal diseases. The purpose of the study was to record system-specific normal values with the Orbscan II system and to investigate the influence of sex and age on central and peripheral corneal thickness to characterize more precisely the anatomy of the cornea. Methods The Orbscan II topography system is a computer-assisted slit-beam scanning technology that can map the anterior section of the eye. It was used to take 2 measurements at 10-minute intervals on 777 eyes of 390 normal white subjects ranging in age between 10 and 80 years. Two hundred forty-two participants were men and 148 were women. The central corneal thickness and the nasal, superior, inferior, and temporal peripheral corneal thickness at a distance of 3 mm from the center were analyzed. No correction factor was used. Using nonparametric test methods, we carried out a statistical analysis of the parameters of sex and age. Results The mean central corneal thickness of all 777 eyes was 595 +/- 41 microm. No sex-specific central difference was identifiable (P = 0.33), there was no significant difference between the sides (P = 0.23), and no significant difference was found between the first and second measurement. The group of 10- to 39-year-olds had a mean central corneal thickness of 591 +/- 41 microm, whereas that of 40- to 80-year-olds was 600 +/- 39 microm, which was a significant difference (P = 0.03). The mean peripheral corneal thickness was 689 +/- 46 microm nasally, 688 +/- 42 microm superiorly, 667 +/- 40 microm inferiorly, and 655 +/- 42 microm temporally. Nasally and superiorly, we found a significant negative correlation with age (Spearman rank correlation, P = 0.02). Conclusions The normal values presented here are a suitable reference basis for future studies in whites. Peripheral corneal thickness is asymmetric and seems to undergo age-related anatomic changes. This information should be considered when planning penetrating keratoplasty and refractive surgery.

Ukrain is advertised by the manufacturer as a drug for alternative cancer cures with high activity against progressive Ewing tumors. Using the MTT assay, we compared the cytotoxicity of Ukrain with the cytotoxicity of N,N',N''-triethylenethiophosphoramide (thioTEPA), Chelidonium majus L. alkaloids, doxorubicin, cyclophosphamide and etoposide against four human Ewing tumor cell lines. In addition, we studied the cytotoxicity of thioTEPA combined with C. majus L. alkaloids after 48, 72 and 96 h. All compounds reduced the growth of Ewing tumor cell lines in a dose-dependent manner. The concentrations that reduced cell growth by 50% ranged between 6.2 and 31.1 micromol/l for Ukrain, 1.9 and 26.1 micromol/l for C. majus L. extract, and 1.7 and 448 micromol/l for thioTEPA. The sensitivity profile of Ukrain was comparable to that of the C. majus L. alkaloids, and different from that of thioTEPA, cyclophosphamide, etoposide and doxorubicin. Overall, doxorubicin was the most cytotoxic drug followed by cyclophosphamide. Ukrain and the C. majus L. alkaloids were slightly more cytotoxic than etoposide, while thioTEPA showed the lowest cytotoxicity. Co-exposure of thioTEPA with C. majus L. alkaloids resulted in additive but not in synergistic cytotoxicity. The in-vitro results indicate that the cytotoxicity of Ukrain against Ewing tumors is comparable to that of etoposide. While the latter can be used on the basis of broad clinical experience and known risk-benefit ratio, Ukrain for the present might be considered as a candidate for subsequent drug development by xenograft studies followed by systematic clinical trials.

Udder defence mechanisms are not completely explained by current mastitis research. The anatomical construction of the udder implies that infection of one udder quarter does not influence the immune status of neighbouring quarters. To test this hypothesis, we compared the immune reactions of individual udder quarters in response to microbial attacks. In the course of immune reactions, polymorphonuclear leucocytes (PMN) release oxygen radicals, which can be determined by chemiluminescence (CL). Milk from 140 udder quarters of 36 cows was analysed for somatic cell count (SCC), differential cell count, viability and CL activity. Quarters with an SCC P=0·0012) lower in group A (72·6%) than in healthy quarters of group C (84·0%). Lowering the SCC limit of healthy quarters to (2929 CL units/million PMN) was markedly lower than that of the other groups (5616 in group A and 6445 CL units/million PMN in group C). These results allow the conclusion that the infection of one udder quarter influences the cell activity of neighbouring quarters. When the SCC threshold for healthy quarters was reduced to 50000 cells/ml, greater differences in cell activities were detected between healthy udders and healthy quarters of infected udders.

The data of 1692 susceptibility tests acquired from April 2003 through March 2004 in the mastitis laboratory of the Institute for Food Quality and Safety were summarized in order to help veterinarians confronted with acute mastitis in choosing the appropriate antibiotic. Two thirds of the milk samples were infected with gram-positive cocci. One third of these were identified as Streptococcus (S.) uberis, one fourth as Staphylococcus (S.) aureus. All isolates (100%) of S. uberis, S. dysgalactiae, S. agalactiae and Arcanobacterium pyogenes were susceptible to Penicillin and Ampicillin. Concering S. aureus, nearly 100% of the isolates were susceptible to Oxacillin, Cephalothin, Cefacetril, Cefquinom and Neomycin, but only 88% of the isolates were sensitive to Penicillin, Ampicillin and Cefoperazon. The gram-negative rods (Escherichia (E.) coli, Klebsiella spp. and Pseudomonas spp.) displayed an irregular resistance pattern. More than 93% of all examined isolates including Pseudomonas spp. were susceptible to Colistin. The sensitivity of E. coli and Klebsiella spp.to Marbofloxacin, Enrofloxacin and Cefquinom exceeded 96%. Thus, the susceptibility of gram-positive mastitis pathogens to common antibiotics is favourable. Because the highly effective Colistin is no longer approved for local therapy, the situation for gram-negative bacteria is more difficult.

Differential cell count of milk is a traditional parameter for the evaluation of udder health. The literature shows great variation in differential cell counts of the milk of healthy mammary glands: macrophages range from 0% to 80%, lymphocytes from 1·5% to 79·5%, polymorphonuclear neutrophils from 3% to 95%, and epithelial cells from 1% to 19%. We conducted three studies to seek explanations for such variation. In the first, we evaluated the impact of polyethylene and glass sampling bottles. The aim of the second study was to compare the results of differential cell counts performed by three different technicians. The third study evaluated two methods of smear preparation. When polyethylene plastic bottles were used, the macrophage population was minimized but lymphocytes remained unaffected. This was shown by an exemplary flow cytometric analysis using four monoclonal antibodies against three lymphocyte surface structures. There were significant differences in the differential cell counts of 40 smears made by three technicians despite identical operating procedures. For the sediment smear, milk was centrifuged once and the sediment spread by eye on a glass slide. For the “coffee grinder” smear method, the sample was subjected to four centrifugations and then placed on a cover glass in order to spread the sediment using centrifugal force. The coffee grinder procedure led to a reduction of lymphocytes and an enrichment of polymorphonuclear neutrophils without affecting the macrophage population. Both methods made it possible to distinguish different udder health classes. It can be concluded that differential cell counts are a useful tool for comparing and monitoring udder health only if: samples are taken in a glass bottle; smears are prepared with the identical technique; and the differential cell counts are performed by a single person.

The aim of this study was to investigate the quantitative changes of visual field in patients with arterial hypertension using standard white-on-white perimetry.Sixty-two patients (f : m = 33 : 29) with arterial hypertension without damage in end-organs were included and divided into three groups: Group 1: systolic/diastolic blood pressure: 120 - 139/80 - 89 mm Hg (n = 18, f : m = 14 : 4, mean age 55 +/- 13 years), group 2: systolic/diastolic blood pressure: 140 - 159/90 - 99 mm Hg (n = 24; f : m = 9 : 15, mean age 55 +/- 12 years), group 3: systolic/diastolic blood pressure: 160 - 179/100 - 109 mm Hg (n = 20; f : m = 10 : 10, mean age 55 +/- 12 years). We compared these patients with an ophthalmological and healthy control group (systolic/diastolic blood pressure120/80 mm Hg, n = 20, f:m = 12 : 8, mean age 55 +/- 9 years). Beside the ophthalmological examinations (visual acuity, refraction, intraocular pressure, slit lamp and fundus examination) quantitative analysis of visual field by Octopus 1-2-3 perimeter was performed. Different parameters (mean deviation (MD), mean sensitivity (MS), loss variance (LV), pattern standard deviation (PSD) and the test-duration) were statistically compared using the Mann-Whitney-U test and the Wilcoxon test.Hypertensive retinopathy grade I - II was found in 10 patients with arterial hypertension. Statistic analysis showed no significant difference of MD, MS, LV, PSD and test duration between the patients with arterial hypertension and the control group (Mann-Whitney-U test: p0.05). There was also no significant difference between the three hypertonic groups (Mann-Whitney-U test: p0.05).The examination of visual field using standard achromatic automated perimetry based on investigation of the parvocellular system. Arterial hypertension, however, does not damage this parvocellular system enough to assess disturbances in the white-on-white perimetry. Further studies are necessary to clarify the value of Frequency Doubling Perimetry, which is based on the detection of early damage of the magnocellular system.

[reaction: see text] A series of alpha,alpha'-bisdiarylamino-capped oligothiophenes C(n) were prepared by the palladium-catalyzed reaction of the dibromo compounds A(i) with diarylamines, N,N-diarylamino-substituted thiophenes or 2,2'-bithiophenes BX(j). These easily oxidizable compounds exhibit a high tendency to form amorphous glasses and characteristic electrochemical and spectroscopic properties that depend significantly on the number of their thiophene moieties.

This chapter examines colour vision in patients with an early stage of arterial hypertension without end-organ damage. A significantly higher median error score in Roth's 28-hue (E) desaturated colour-arrangement test was observed for patients with arterial hypertension than for the control group. These results should be taken into account in colour-vision testing to avoid diagnostic interference between specifically ocular diseases (e.g. glaucoma) and arterial hypertension.

Several animal models demonstrated that NMDA-receptor antagonists like memantine inhibit the excitotoxic action of glutamate in glaucoma. Furthermore, this also enables to slow down the degeneration of retinal ganglion cells. In the following case report we investigated the use and tolerability of memantine in a glaucoma patient.We report on a 73-year old male with progressive glaucoma damage. Treatment with memantine à 20 mg/d lasted for 6 months and was preceded by one week à 10 mg/d. Follow-ups with perimetry and VEP were performed at beginning and 2, 4, 6 and 12 months after.The first control showed an improvement of perimetry. The following examinations demonstrated a stabilization of perimetry and VEP. Because of side-effects there was no tolerability of a higher dose of memantine à 30 mg/d or continuation of the therapy after 6 months.Memantine seems to be neuroprotective in glaucoma patients. At present a multicentric study is under way. More results may be expected shortly.

The color arrangement test can be applied for early diagnosis of diabetic retinopathy, even small confusion of colors influence clinical diagnosis. It is therefore necessary to be aware of influential factors.Forty-four patients with color-experience (VW-Werk Wolfsburg) were included and devided in two groups: group 1: non-smokers without ophthalmological and systemic diseases (n = 27, 42+/-9 years), group 2: smokers without ophthalmological and systemic diseases (n = 17; 43+/-8 years). The control group 3 (n = 30; 42+/-4 years) included non-smokers and the control group 4 (n = 10; 42+/-8 years) smokers, both groups without color-experience, ophthalmological and systemic diseases. Besides the ophthalmological examinations (visual acuity, refraction, intraocular pressure, slit lamp and fundus examination) the color-vision was tested by the color-arrangement-test Roth 28-hue (E) desaturated monocularly under standard conditions: The background used was black cardboard, illuminated by two Osram fluorescent lamps (L36W/12LDL Daylight) providing 2000 lux at the test table.Ophthalmological examination in all subjects was without pathological findings. The mean error score in the non-smokers with color-experience (median+/-mean absolute deviation: 48+/-47) was lower than in the non-smokers without color experience (72+/-45; Mann-Withney-U-Test: p = 0.02). The mean error score in the smokers with color-experience (60+/-60) was lower than in the smokers without color-experience (156+/-65; p = 0.0014). No statistically significant difference was found between the measurements of the right and left eye (Wilcoxon-Test: group 1: p = 0.89; group 2: p = 0.9; group 3: p = 0.77; group 4: p = 0.87).Color experience improves the results in color-arrangement-tests like the Roth 28-hue (E) desaturated and should be considered in quantitative evaluation.

Despite advances in both targeted therapies with ABL-specific tyrosine kinase inhibitors and in allogeneic stem cell transplantation, BCR-ABL positive acute lymphoblastic leukemia (ALL) remains a very high-risk disease, necessitating the development of novel treatment strategies. miRNAs are small non-coding RNAs which regulate gene expression posttranscriptionally in a sequence-specific manner. miRNAs usually repress the expression of many target genes. We hypothesized that miRNAs may help to identify potential therapeutic targets if (i) they are expressed in a disease-specific manner and if (ii) modulating their expression induces a desired phenotype, such as apoptosis of tumour cells, in appropriate experimental models. Based on our observation that miR∼17-92-encoded miRNAs are significantly less abundant in primary BCR-ABL-positive as compared to negative ALL-cells, we studied the expression and function of miRNAs encoded by the miR∼17-92 derivative miR∼17-19b in a murine pro-B-cell line with inducible BCR-ABL-expression (TonB). Induction of BCR-ABL expression in TonB cells reduced endogenous miR-17, miR-18a, and miR-19 by 2 to 3.5-fold, confirming that expression of the miR∼17-92 cluster is controlled by BCR-ABL. Interestingly, over-expression of miR∼17-19b by lentiviral gene transfer led to a substantial induction of apoptosis in TonB cells in a BCR-ABL-dependent manner. To identify potential miRNA targets, we used a proteomic approach based on stable isotope labeling of amino acids in cell culture (SILAC) followed by liquid chromatography and mass spectroscopy (LC-MS) in miR∼17-19b transgenic TonB cells. Several apoptosis-related proteins were differentially expressed including Bcl2, an established inhibitor of mitochondrial pro-apoptotic pathways. The miRNA target prediction program RNA22 predicted several miR∼17-19b miRNA-binding sites within both murine and human Bcl2 mRNA, and we demonstrated direct miRNA binding to Bcl2 mRNA by luciferase reporter and anti-AGO2 RIP chip analyses. As with miR∼17-19b over-expression, Bcl2 specific RNAi strongly induced apoptosis in murine TonB and the human BCR-ABL-positive cell lines BV-173, Tom1 and SupB15. BCR-ABL positive human ALL-cell lines were also more sensitive than negative ones to pharmacological BCL2 inhibition with the BH3 mimetic ABT 737. In addition, inhibition of BCL2 by ABT 737 and BCR-ABL kinase activity by Imatinib exert different anti-leukemic effects with differential impact on miR∼17-92 miRNA-expression. To assess the therapeutic potential of BCL2 inhibition we used a xenotransplantation assay with real time in vivo monitoring of drug therapies by bioluminescent imaging. ABT-737 treatment substantially inhibited expansion of luciferase-expressing human primary BCR-ABL-positive ALL xenografts in NOD/LtSz-scid IL-2Rγ null (NSG) mice and significantly lengthened their median survival. Taken together, our data identify BCL2 as a therapeutic target of particular relevance in BCR-ABL-positive ALL and indicate involvement of miR∼17-92-encoded miRNAs in regulation of apoptosis in these cells. The validity of this miRNA-based approach to identify potential drug targets is demonstrated by the efficacy of the BCL2 inhibitor ABT-737 in an in vivo model of human BCR-ABL positive ALL, suggesting that BCL2 inhibition should be considered for early phase clinical testing as a strategy to improve disease outcomes. Disclosures: No relevant conflicts of interest to declare.

MHONGOOSE is a deep survey of the neutral hydrogen distribution in a representative sample of 30 nearby disk and dwarf galaxies with HI masses from 10^6 to ~10^{11} M_sun, and luminosities from M_R ~ -12 to M_R ~ -22. The sample is selected to uniformly cover the available range in log(M_HI). Our extremely deep observations, down to HI column density limits of well below 10^{18} cm^{-2} - or a few hundred times fainter than the typical HI disks in galaxies - will directly detect the effects of cold accretion from the intergalactic medium and the links with the cosmic web. These observations will be the first ever to probe the very low-column density neutral gas in galaxies at these high resolutions. Combination with data at other wavelengths, most of it already available, will enable accurate modelling of the properties and evolution of the mass components in these galaxies and link these with the effects of environment, dark matter distribution, and other fundamental properties such as halo mass and angular momentum. MHONGOOSE can already start addressing some of the SKA-1 science goals and will provide a comprehensive inventory of the processes driving the transformation and evolution of galaxies in the nearby universe at high resolution and over 5 orders of magnitude in column density. It will be a Nearby Galaxies Legacy Survey that will be unsurpassed until the advent of the SKA, and can serve as a highly visible, lasting statement of MeerKAT's capabilities., To be published in "MeerKAT Science: On the Pathway to the SKA". Proceedings of Science. Workshop held 25-27 May, 2016 Stellenbosch, South Africa