Continuous-flow reactors for the rapid evolution and validation of kinetic motifs

In this paper we apply the concept of a kinetic motif as a simple way to represent all the time-dependent behaviour in a single-step or multi-step reaction system. Small-scale continuous-flow reactors offer the potential to rapidly collect large amounts of data while accessing conventionally challenging experimental conditions. The scope of the approach is demonstrated on reaction case study examples

P,P-Bis[4-(dimethylamino)phenyl]-N,N-bis(propan-2-yl)phosphinic amide

The molecular structure of the title compound, C22H 34N3OP, adopts a distorted tetrahedral geometry at the P atom, with the most noticeable distortion being for the O - P - N angle [117.53 (10)°]. An effective cone angle of 187° was calculated for the compound. In the crystal, weak C - H⋯O interactions create infinite chains along [100], whereas C - H⋯π interactions propagating in [001] generate a herringbone motif

Rac-[2-(Dicyclohexylphosphanyl)phenyl](phenyl)phosphinic diisopropylamide-borane hemihydrate

In the title compound, C30H48BNOP2·0.5H2O, the water molecule is disordered about an inversion centre. Both phosphorus atoms shows distortions in their tetrahedral environments with the cyclohexyl substituents disordered over two orientations in a 0.851 (3):0.149 (3) occupancy ratio. The crystal structure is assembled via O - H⋯O interactions between pairs of phosphininc amide molecules and water molecules, creating hydrogen-bonded dimers with graph-set R 2 4(8) along [001]. Weak C - H⋯O interactions are also observed

Synergy of stereo cloud top height and ORAC optimal estimation cloud retrieval: evaluation and application to AATSR

In this paper we evaluate the retrievals of cloud top height when stereo derived heights are combined with the radiometric cloud top heights retrieved from the ORAC (Optimal Retrieval of Aerosol and Cloud) algorithm. This is performed in a mathematically rigorous way using the ORAC optimal estimation retrieval framework, which includes the facility to use independent a priori information. Key to the use of a priori information is a characterisation of their associated uncertainty. This paper demonstrates the improvements that are possible using this approach and also considers their impact on the microphysical cloud parameters retrieved. The AATSR instrument has two views and three thermal channels so is well placed to demonstrate the synergy of the two techniques. The stereo retrieval is able to improve the accuracy of the retrieved cloud top height when compared to collocated Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO), particularly in the presence of boundary layer inversions and high clouds. The impact on the microphysical properties of the cloud such as optical depth and effective radius was evaluated and found to be very small with the biggest differences occurring over bright land surfaces and for high clouds. Overall the cost of the retrievals increased indicating a poorer radiative fit of radiances to the cloud model, which currently uses a single layer cloud model. Best results and improved fit to the radiances may be obtained in the future if a multi-layer model is used

Future Possibilities for Observing HI at High Redshift

We briefly review the beginnings of HI astronomy, proceed to an assessment of our current capabilities in this area, and continue by considering what will be necessary to push back the frontier to cosmological distances. We then consider how such a leap in performance might be realized.Comment: 8 page LaTeX requires crckapb.sty and psfig.sty, 9 compressed and tarred postscript figures (750kB) available at ftp://ftp.nfra.nl/pub/outgoing/rbraun/futposhi/figs.tar.Z Complete compressed postscript paper (790kB) available at ftp://ftp.nfra.nl/pub/outgoing/rbraun/futposhi/paper.ps.Z To appear in "Cold Gas at High Redshift", Eds. M.Bremer et al. (Kluwer, Dordrecht

Support available for and perceived priorities of people with polymyalgia rheumatica and giant cell arteritis: results of the PMRGCAuk members' survey 2017

Polymyalgia rheumatica and giant cell arteritis are relatively common, but under research inflammatory rheumatological conditions. This survey aimed to ascertain the matters in which patients feel they need support with these conditions and appraise how the Charity PMRGCAuk currently supports these needs and could do so in the future. PMRGCAuk members (n = 910) were invited to complete an on-line survey. The survey requested the respondent's history of PMR and or GCA, their perceived priorities for support for people with PMR and or GCA and views on the services already provided by the Charity. A total of 209 people completed the survey. Less than 24% had heard of either PMR or GCA before their diagnosis. Priorities in supporting people with PMR and or GCA included: being on and tapering off glucocorticoids (76.6%), specifically, length of treatment and the risks versus benefits and managing side effects. Respondents generally reported satisfaction with the services currently provided by PMRGCAuk. The support provided by PMRGCAuk is very helpful to members and fills an important gap in provision for people with PMR and or GCA. The areas in which the greatest proportions of participants requested support do not have an evidence base to underpin them. It is incumbent on the research community to address patients' concerns and provide an evidence base where it is required by those affected

Attenuation of leukocyte sequestration by selective blockade of PECAM-1 or VCAM-1 in murine endotoxemia

Background: Molecular mechanisms regulating leukocyte sequestration into the tissue during endotoxemia and/or sepsis are still poorly understood. This in vivo study investigates the biological role of murine PECAM-1 and VCAM-1 for leukocyte sequestration into the lung, liver and striated skin muscle. Methods: Male BALB/c mice were injected intravenously with murine PECAM-1 IgG chimera or monoclonal antibody (mAb) to VCAM-1 ( 3 mg/kg body weight); controls received equivalent doses of IgG2a ( n = 6 per group). Fifteen minutes thereafter, 2 mg/kg body weight of Salmonella abortus equi endotoxin was injected intravenously. At 24 h after the endotoxin challenge, lungs, livers and striated muscle of skin were analyzed for their myeloperoxidase activity. To monitor intravital leukocyte-endothelial cell interactions, fluorescence videomicroscopy was performed in the skin fold chamber model of the BALB/c mouse at 3, 8 and 24 h after injection of endotoxin. Results: Myeloperoxidase activity at 24 h after the endotoxin challenge in lungs (12,171 +/- 2,357 mU/g tissue), livers ( 2,204 +/- 238 mU/g) and striated muscle of the skin ( 1,161 +/- 110 mU/g) was significantly reduced in both treatment groups as compared to controls, with strongest attenuation in the PECAM-1 IgG treatment group. Arteriolar leukocyte sticking at 3 h after endotoxin (230 +/- 46 cells x mm(-2)) was significantly reduced in both treatment groups. Leukocyte sticking in postcapillary venules at 8 h after endotoxin ( 343 +/- 69 cells/mm(2)) was found reduced only in the VCAM-1-mAb-treated animals ( 215 +/- 53 cells/mm(2)), while it was enhanced in animals treated with PECAM-1 IgG ( 572 +/- 126 cells/mm(2)). Conclusion: These data show that both PECAM-1 and VCAM-1 are involved in endotoxin-induced leukocyte sequestration in the lung, liver and muscle, presumably through interference with arteriolar and/or venular leukocyte sticking. Copyright (C) 2004 S. Karger AG, Basel

In vivo imaging and quantitative analysis of leukocyte directional migration and polarization in inflamed tissue

Directional migration of transmigrated leukocytes to the site of injury is a central event in the inflammatory response. Here, we present an in vivo chemotaxis assay enabling the visualization and quantitative analysis of subtype-specific directional motility and polarization of leukocytes in their natural 3D microenvironment. Our technique comprises the combination of i) semi-automated in situ microinjection of chemoattractants or bacteria as local chemotactic stimulus, ii) in vivo near-infrared reflected-light oblique transillumination (RLOT) microscopy for the visualization of leukocyte motility and morphology, and iii) in vivo fluorescence microscopy for the visualization of different leukocyte subpopulations or fluorescence-labeled bacteria. Leukocyte motility parameters are quantified off-line in digitized video sequences using computer-assisted single cell tracking. Here, we show that perivenular microinjection of chemoattractants [macrophage inflammatory protein-1alpha (MIP-1alpha/Ccl3), platelet-activating factor (PAF)] or E. coli into the murine cremaster muscle induces target-oriented intravascular adhesion and transmigration as well as polarization and directional interstitial migration of leukocytes towards the locally administered stimuli. Moreover, we describe a crucial role of Rho kinase for the regulation of directional motility and polarization of transmigrated leukocytes in vivo. Finally, combining in vivo RLOT and fluorescence microscopy in Cx3CR1(gfp/gfp) mice (mice exhibiting green fluorescent protein-labeled monocytes), we are able to demonstrate differences in the migratory behavior of monocytes and neutrophils.Taken together, we propose a novel approach for investigating the mechanisms and spatiotemporal dynamics of subtype-specific motility and polarization of leukocytes during their directional interstitial migration in vivo

Gaseous Galaxy Halos

Galactic halo gas traces inflowing star formation fuel and feedback from a galaxy's disk and is therefore crucial to our understanding of galaxy evolution. In this review, we summarize the multi-wavelength observational properties and origin models of Galactic and low redshift spiral galaxy halo gas. Galactic halos contain multiphase gas flows that are dominated in mass by the ionized component and extend to large radii. The densest, coldest halo gas observed in neutral hydrogen (HI) is generally closest to the disk (< 20 kpc), and absorption line results indicate warm and warm-hot diffuse halo gas is present throughout a galaxy's halo. The hot halo gas detected is not a significant fraction of a galaxy's baryons. The disk-halo interface is where the multiphase flows are integrated into the star forming disk, and there is evidence for both feedback and fueling at this interface from the temperature and kinematic gradient of the gas and HI structures. The origin and fate of halo gas is considered in the context of cosmological and idealized local simulations. Accretion along cosmic filaments occurs in both a hot (> 10^5.5 K) and cold mode in simulations, with the compressed material close to the disk the coldest and densest, in agreement with observations. There is evidence in halo gas observations for radiative and mechanical feedback mechanisms, including escaping photons from the disk, supernova-driven winds, and a galactic fountain. Satellite accretion also leaves behind abundant halo gas. This satellite gas interacts with the existing halo medium, and much of this gas will become part of the diffuse halo before it can reach the disk. The accretion rate from cold and warm halo gas is generally below a galaxy disk's star formation rate, but gas at the disk-halo interface and stellar feedback may be important additional fuel sources.Comment: 50 pages, 9 figures (1 in 3D, view with a current version of Adobe), to appear in ARA&A, 50, 49