3,960 research outputs found

    Landform identification: Lunar radar images

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    Three sets of polarized radar-echo images of the Moon were examined to establish the relation between radar resolution and landform-identification resolution. After comparison with lunar maps and photographs, real and apparent landforms on the radar images were grouped into one of seven classes. Results show strong relations between radar resolution and diameter or relief of landforms that are clearly identified and those that would probably be correctly identified (class 1 and class 2). Landforms are not detected (class 5) at all diameters and reliefs, but the percentage of undetected landforms decreases with increasing mean diameter and mean relief. Landforms are simply detected (class 4) at most mean diameters and reliefs. Ambiguous arrays (class 6) portrayed by the radar constitute up to about 16, 22, and 15% of the landforms at various diameters and relief values for the 3.8 cm, 70 cm high resolution, and 70 cm low resolution images, respectively. Only a few percent of the landforms portrayed by the radar images at various diameters and relief values are fictitious (class 7)

    Southward expansion: The myth of the West in the promotion of Florida, 1876–1900

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    This article examines the ways in which promoters and developers of Florida, in the decades after Reconstruction, engaged with a popular myth of the West as a means of recasting and selling their state to prospective settlers in the North and Midwest. The myth envisaged a cherished region to the west where worthy Americans could migrate and achieve social and economic independence away from the crowded confines of the East, or Europe. According to state immigration agents, land-promoters and other booster writers, Florida, although a Southern ex-Confederate state, offered precisely these 'western' opportunities for those hard-working Northerners seeking land and an opening for agrarian prosperity. However, the myth, which posited that, in the west, an individual's labour and thrift were rewarded with social and economic improvement, meshed awkwardly with the contemporary emergence of Florida as a popular winter destination for wealthy tourists and invalids seeking leisure and healthfulness away from the North. Yet it also reflected and reinforced promotional notions of racial improvement which would occur with an influx of enterprising Anglo-Americans, who would effectively displace the state's large African American population. In Florida, the myth of the West supported the linked post-Reconstruction processes of state development and racial subjugation

    HAPTEN-SANDWICH LABELING : I. A GENERAL PROCEDURE FOR SIMULTANEOUS LABELING OF MULTIPLE CELL SURFACE ANTIGENS FOR FLUORESCENCE AND ELECTRON MICROSCOPY

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    A hapten-sandwich procedure has been developed for specific labeling of cell surface antigens for fluorescence or electron microscopy. Haptens are azo-coupled to immunoglobulins specific for a cell surface antigen; the hapten-modified cell-bound antibodies can then be visualized by adding fluorescent antihapten antibody, or by adding antihapten antibody followed by hapten-modified markers for electron microscopy. Virus or high molecular weight protein markers are lightly cross-linked before conjugation with hapten to prevent their disruption. Such stable hapten-modified markers, and the accessibility of many different purified anti-azophenyl-hapten antibodies, make it feasible to distinguish more than one membrane antigen in a given labeling experiment. When mouse lymphoid cell populations are labeled with separate markers for Ig and for thymus-associated antigens, many cells exhibit the Ig marker exclusively or the thymic marker predominantly, and some cells are completely free of label

    Type I interferon signaling is required for activation of the inflammasome during Francisella infection

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    Francisella tularensis is a pathogenic bacterium whose virulence is linked to its ability to replicate within the host cell cytosol. Entry into the macrophage cytosol activates a host-protective multimolecular complex called the inflammasome to release the proinflammatory cytokines interleukin (IL)-1β and -18 and trigger caspase-1–dependent cell death. In this study, we show that cytosolic F. tularensis subspecies novicida (F. novicida) induces a type I interferon (IFN) response that is essential for caspase-1 activation, inflammasome-mediated cell death, and release of IL-1β and -18. Extensive type I IFN–dependent cell death resulting in macrophage depletion occurs in vivo during F. novicida infection. Type I IFN is also necessary for inflammasome activation in response to cytosolic Listeria monocytogenes but not vacuole-localized Salmonella enterica serovar Typhimurium or extracellular adenosine triphosphate. These results show the specific connection between type I IFN signaling and inflammasome activation, which are two sequential events triggered by the recognition of cytosolic bacteria. To our knowledge, this is the first example of the positive regulation of inflammasome activation. This connection underscores the importance of the cytosolic recognition of pathogens and highlights how multiple innate immunity pathways interact before commitment to critical host responses

    Bismuth coordination networks containing deferiprone: synthesis, characterisation, stability and antibacterial activity

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    A series of bismuth–dicarboxylate–deferiprone coordination networks have been prepared and structurally characterised. The new compounds have been demonstrated to release the iron overload drug deferiprone on treatment with PBS and have also been shown to have antibacterial activity against H. pylori

    A Hydrogen Bond in Loop A Is Critical for the Binding and Function of the 5-HT3 Receptor†

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    The binding sites of Cys-loop receptors are formed from at least six loops (A−F). Here we have used mutagenesis, radioligand binding, voltage clamp electrophysiology, and homology modeling to probe the role of two residues in loop A of the 5-HT_3 receptor: Asn128 and Glu129. The data show that substitution of Asn128, with a range of alternative natural and unnatural amino acids, changed the EC_(50) (from ∼10-fold more potent to ∼10-fold less potent than that of the wild type), increased the maximal peak current for mCPBG compared to 5-HT (R_(max)) 2−19-fold, and decreased n_H, indicating this residue is involved in receptor gating; we propose Asn128 faces away from the binding pocket and plays a role in facilitating transitions between conformational states. Substitutions of Glu129 resulted in functional receptors only when the residue could accept a hydrogen bond, but with both these and other substitutions, no [^3H]granisetron binding could be detected, indicating a role in ligand binding. We propose that Glu129 faces into the binding pocket, where, through its ability to hydrogen bond, it plays a critical role in ligand binding. Thus, the data support a modified model of the 5-HT_3 receptor binding site and show that loop A plays a critical role in both the ligand binding and function of this receptor

    Ketones Prevent Oxidative Impairment of Hippocampal Synaptic Integrity through K\u3csub\u3eATP\u3c/sub\u3e Channels

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    Dietary and metabolic therapies are increasingly being considered for a variety of neurological disorders, based in part on growing evidence for the neuroprotective properties of the ketogenic diet (KD) and ketones. Earlier, we demonstrated that ketones afford hippocampal synaptic protection against exogenous oxidative stress, but the mechanisms underlying these actions remain unclear. Recent studies have shown that ketones may modulate neuronal firing through interactions with ATP-sensitive potassium (KATP) channels. Here, we used a combination of electrophysiological, pharmacological, and biochemical assays to determine whether hippocampal synaptic protection by ketones is a consequence of KATP channel activation. Ketones dose-dependently reversed oxidative impairment of hippocampal synaptic integrity, neuronal viability, and bioenergetic capacity, and this action was mirrored by the KATP channel activator diazoxide. Inhibition of KATP channels reversed ketone-evoked hippocampal protection, and genetic ablation of the inwardly rectifying K+ channel subunit Kir6.2, a critical component of KATP channels, partially negated the synaptic protection afforded by ketones. This partial protection was completely reversed by co-application of the KATP blocker, 5-hydoxydecanoate (5HD). We conclude that, under conditions of oxidative injury, ketones induce synaptic protection in part through activation of KATP channels

    The structural basis of function in Cys-loop receptors

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    Cys-loop receptors are membrane-spanning neurotransmitter-gated ion channels that are responsible for fast excitatory and inhibitory transmission in the peripheral and central nervous systems. The best studied members of the Cys-loop family are nACh, 5-HT_3, GABA_A and glycine receptors. All these receptors share a common structure of five subunits, pseudo-symmetrically arranged to form a rosette with a central ion-conducting pore. Some are cation selective (e.g. nACh and 5-HT_3) and some are anion selective (e.g. GABA_A and glycine). Each receptor has an extracellular domain (ECD) that contains the ligand-binding sites, a transmembrane domain (TMD) that allows ions to pass across the membrane, and an intracellular domain (ICD) that plays a role in channel conductance and receptor modulation. Cys-loop receptors are the targets for many currently used clinically relevant drugs (e.g. benzodiazepines and anaesthetics). Understanding the molecular mechanisms of these receptors could therefore provide the catalyst for further development in this field, as well as promoting the development of experimental techniques for other areas of neuroscience. In this review, we present our current understanding of Cys-loop receptor structure and function. The ECD has been extensively studied. Research in this area has been stimulated in recent years by the publication of high-resolution structures of nACh receptors and related proteins, which have permitted the creation of many Cys loop receptor homology models of this region. Here, using the 5-HT_3 receptor as a typical member of the family, we describe how homology modelling and ligand docking can provide useful but not definitive information about ligand interactions. We briefly consider some of the many Cys-loop receptors modulators. We discuss the current understanding of the structure of the TMD, and how this links to the ECD to allow channel gating, and consider the roles of the ICD, whose structure is poorly understood. We also describe some of the current methods that are beginning to reveal the differences between different receptor states, and may ultimately show structural details of transitions between them

    Experimental investigation of hysteresis in the break-up of liquid curtains

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    Findings from an experimental investigation of the break-up of liquid curtains are reported, with the overall aim of examining stability windows for multi-layer liquid curtains composed of Newtonian fluids, where the properties of each layer can be kept constant or varied. For a single-layer curtain it is known that the minimum flow rate required for initial stability can be violated by carefully reducing the flow rate below this point, which defines a hysteresis region. However, when two or three layers are used to form a composite curtain, the hysteresis window can be considerably reduced depending on the experimental procedure used. Extensive quantitative measurements of this hysteresis region are provided alongside an examination of the influence of physical properties such as viscosity and surface tension. The origins of curtain break-up for two different geometries are analysed; first where the curtain width remains constant, pinned by straight edge guides; and second where the curtain is tapered by angled edge guides. For both cases, the rupture speed is measured, which appears to be consistent with the Taylor-Culick velocity. Observations of the typical linearly spaced jets which form after the break-up has transpired and the periodicity of these jets are compared to the Rayleigh-Taylor wavelength and previous experimental measurements. Furthermore, the curtain stability criterion originally developed by Brown (1961), summarised in terms of a Weber number, has recently been extended to multi-layer curtains by Dyson et al. (2009); thus this report provides the first experimental measurements which puts this to the test. Ultimately, it is found that only the most viscous and polymer-based liquids violate this criterion
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