3,924 research outputs found

    Calcium-sensing receptor activation increases cell-cell adhesion and Ăź-cell function

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    Background/Aims: The extracellular calcium-sensing receptor (CaR) is expressed in pancreatic β-cells where it is thought to facilitate cell-to-cell communication and augment insulin secretion. However, it is unknown how CaR activation improves β-cell function. Methods: Immunocytochemistry and western blotting confirmed the expression of CaR in MIN6 β-cell line. The calcimimetic R568 (1µM) was used to increase the affinity of the CaR and specifically activate the receptor at a physiologically appropriate extracellular calcium concentration. Incorporation of 5-bromo-2’-deoxyuridine (BrdU) was used to measure cell proliferation, whilst changes in non-nutrient-evoked cytosolic calcium were assessed using fura-2-microfluorimetry. AFM-single-cell-force spectroscopy related CaR-evoked changes in epithelial (E)-cadherin expression to improved functional tethering between coupled cells. Results: Activation of the CaR over 48hr doubled the expression of E-cadherin (206±41%) and increased L-type voltage-dependent calcium channel expression by 70% compared to control. These changes produced a 30% increase in cell-cell tethering and elevated the basal-to-peak amplitude of ATP (50µM) and tolbutamide (100µM)-evoked changes in cytosolic calcium. Activation of the receptor also increased PD98059 (1-100µM) and SU1498 (1-100µM)-dependent β-cell proliferation. Conclusion: Our data suggest that activation of the CaR increases E-cadherin mediated functional tethering between β-cells and increases expression of L-type VDCC and secretagogue-evoked changes in [Ca2+]i. These findings could explain how local changes in calcium, co-released with insulin, activate the CaR on neighbouring cells to help ensure efficient and appropriate secretory function

    Opportunity Recognition: Perceptions of Highly Successful Entrpreneurs

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    This study examined  multiple dimensions  of opportunity recognition  (OR) among a group  of exceptionally successful entrepreneurs and a control group of more randomly selected entrepreneurs.  There were few  differences  between the two groups.  Results  indicated that OR stemmed from prior experience, focusing on markets and customers, and responses to specific problems along with several other sources. Furthermore, OR appeared to he a multiple-step process far more frequently than a "eureka" experience. These results support much of the conventional wisdom about OR and indicate that multiple approaches to OR can lead  to success

    Dose-area product measurements during Barium enema radiograph examinations -a Western Cape study

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    The aim of this study was to obtain a direct measurement of the typical dose delivered to an average adult patient during a barium enema examination. Measurement was done on a sample of 50 patients at three departments, using a dose-area product (DAP) meter. The comparison of the results with UK median levels indicates that the doses measured in South Africa are higher (41 Gy cm2 (dose x area) v. 48 Gy cm2 ). Patient protection can be improved by comparing local practice with national reference levels. The values obtained in this study (first quartile 35 Gy cm2, median 48 Gy cm2, third quartile 84 Gy cm2) are recommended as initial reference dose levels for barium enemas in South Africa

    Converging mechanisms of epileptogenesis and their insight in glioblastoma

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    Glioblastoma (GBM) is the most common and advanced form of primary malignant tumor occurring in the adult central nervous system, and it is frequently associated with epilepsy, a debilitating comorbidity. Seizures are observed both pre- and post-surgical resection, indicating that several pathophysiological mechanisms are shared but also prompting questions about how the process of epileptogenesis evolves throughout GBM progression. Molecular mutations commonly seen in primary GBM, i.e., in PTEN and p53, and their associated downstream effects are known to influence seizure likelihood. Similarly, various intratumoral mechanisms, such as GBM-induced blood-brain barrier breakdown and glioma-immune cell interactions within the tumor microenvironment are also cited as contributing to network hyperexcitability. Substantial alterations to peri-tumoral glutamate and chloride transporter expressions, as well as widespread dysregulation of GABAergic signaling are known to confer increased epileptogenicity and excitotoxicity. The abnormal characteristics of GBM alter neuronal network function to result in metabolically vulnerable and hyperexcitable peri-tumoral tissue, properties the tumor then exploits to favor its own growth even post-resection. It is evident that there is a complex, dynamic interplay between GBM and epilepsy that promotes the progression of both pathologies. This interaction is only more complicated by the concomitant presence of spreading depolarization (SD). The spontaneous, high-frequency nature of GBM-associated epileptiform activity and SD-associated direct current (DC) shifts require technologies capable of recording brain signals over a wide bandwidth, presenting major challenges for comprehensive electrophysiological investigations. This review will initially provide a detailed examination of the underlying mechanisms that promote network hyperexcitability in GBM. We will then discuss how an investigation of these pathologies from a network level, and utilization of novel electrophysiological tools, will yield a more-effective, clinically-relevant understanding of GBM-related epileptogenesis. Further to this, we will evaluate the clinical relevance of current preclinical research and consider how future therapeutic advancements may impact the bidirectional relationship between GBM, SDs, and seizures

    Out-Of-Focus Holography at the Green Bank Telescope

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    We describe phase-retrieval holography measurements of the 100-m diameter Green Bank Telescope using astronomical sources and an astronomical receiver operating at a wavelength of 7 mm. We use the technique with parameterization of the aperture in terms of Zernike polynomials and employing a large defocus, as described by Nikolic, Hills & Richer (2006). Individual measurements take around 25 minutes and from the resulting beam maps (which have peak signal to noise ratios of 200:1) we show that it is possible to produce low-resolution maps of the wavefront errors with accuracy around a hundredth of a wavelength. Using such measurements over a wide range of elevations, we have calculated a model for the wavefront-errors due to the uncompensated gravitational deformation of the telescope. This model produces a significant improvement at low elevations, where these errors are expected to be the largest; after applying the model, the aperture efficiency is largely independent of elevation. We have also demonstrated that the technique can be used to measure and largely correct for thermal deformations of the antenna, which often exceed the uncompensated gravitational deformations during daytime observing. We conclude that the aberrations induced by gravity and thermal effects are large-scale and the technique used here is particularly suitable for measuring such deformations in large millimetre wave radio telescopes.Comment: 10 pages, 7 figures (accepted by Astronomy & Astrophysics

    Characterizing the early vocabulary profiles of preverbal and minimally verbal children with autism spectrum disorder

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    Abstract Children with autism spectrum disorder (ASD) often have significant language delays. But do they learn language differently than neurotypical toddlers? We compared the lexical skills of 64 preverbal and minimally verbal children with ASD, to 461 vocabulary-size-matched typically developing (TD) toddlers. We also examined social features of verb knowledge using a novel collection of social ratings. Children with ASD produced proportionally more verbs than TD toddlers. Children with ASD produced proportionally more action and food words, while TD toddlers produced proportionally more animal, people words, and animal sounds and sound effects. Children with ASD also produced “mommy” and “daddy” at lower rates. We discuss how these differences may reflect an association between lexical development and weaknesses in social communication. Lay abstract Although preverbal and minimally verbal (PV-MV) children with autism spectrum disorder (ASD) represent a significant portion of the ASD population, we have a limited understanding of and characterization of them. Though it is a given that their lexical profiles contain fewer words, it is important to determine whether: a) the words PV-MV children with ASD produce are similar to the first words typically developing (TD) children produce, or b) there are unique features of the limited words that PV-MV children with ASD produce. The current study compared the early word profiles of PV-MV children with ASD to vocabulary-matched TD toddlers. Children with ASD produced proportionally more verbs than TD toddlers. Also, children with ASD produced proportionally more action and food words, while TD toddlers produced proportionally more animal words, animal sounds and sound effects, and people words. Children with ASD also produced “mommy” and “daddy” at lower rates. Our findings identified several areas of overlap in early word learning; however, our findings also point to differences that may be connected to core weaknesses in social communication (i.e., people words). The findings highlight words and categories that could serve as useful targets for communication intervention with PV-MV children with ASD

    Interferometric Observations of the Nuclear Region of Arp220 at Submillimeter Wavelengths

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    We report the first submillimeter interferometric observations of an ultraluminous infrared galaxy. We observed Arp220 in the CO J=3-2 line and 342GHz continuum with the single baseline CSO-JCMT interferometer consisting of the Caltech Submillimeter Observatory (CSO) and the James Clerk Maxwell Telescope (JCMT). Models were fit to the measured visibilities to constrain the structure of the source. The morphologies of the CO J=3-2 line and 342GHz continuum emission are similar to those seen in published maps at 230 and 110GHz. We clearly detect a binary source separated by about 1 arcsec in the east-west direction in the 342GHz continuum. The CO J=3-2 visibility amplitudes, however, indicate a more complicated structure, with evidence for a compact binary at some velocities and rather more extended structure at others. Less than 30% of the total CO J=3-2 emission is detected by the interferometer, which implies the presence of significant quantities of extended gas. We also obtained single-dish CO J=2-1, CO J=3-2 and HCN J=4-3 spectra. The HCN J=4-3 spectrum, unlike the CO spectra, is dominated by a single redshifted peak. The HCN J=4-3/CO J=3-2, HCN J=4-3/HCN J=1-0 and CO J=3-2/2-1 line ratios are larger in the redshifted (eastern) source, which suggests that the two sources may have different physical conditions. This result might be explained by the presence of an intense starburst that has begun to deplete or disperse the densest gas in the western source, while the eastern source harbors undispersed high density gas.Comment: 17 pages, 9 figures, 4 Tables. accepted by Ap
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