SCUBA-2 is a 10 000-bolometer submillimetre camera on the James Clerk Maxwell Telescope. The instrument commissioning was completed in 2011 September, and full science operations began in 2011 ...October. To harness the full potential of this powerful new astronomical tool, the instrument calibration must be accurate and well understood. To this end, the algorithms for calculating the line-of-sight opacity have been improved, and the derived atmospheric extinction relationships at both wavebands of the SCUBA-2 instrument are presented. The results from over 500 primary and secondary calibrator observations have allowed accurate determination of the flux conversion factors (FCF) for the 850 and 450 μm arrays. Descriptions of the instrument beam shape and photometry methods are presented. The calibration factors are well determined, with relative calibration accuracy better than 5 per cent at 850 μm and 10 per cent at 450 μm, reflecting the success of the derived opacity relations as well as the stability of the performance of the instrument over several months. The sample size of the calibration observations and accurate FCFs have allowed the determination of the 850 and 450 μm fluxes of several well-known submillimetre sources, and these results are compared with previous measurements from SCUBA.
Context.
The Galactic plane has been observed extensively by a large number of Galactic plane surveys from infrared to radio wavelengths at an angular resolution below 40′′. However, a 21 cm line and ...continuum survey with comparable spatial resolution is lacking.
Aims.
The first half of THOR data (
l
= 14.0°−37.9°, and
l
= 47.1°−51.2°, |
b
|≤ 1.25°) has been published in our data release 1 paper. With this data release 2 paper, we publish all the remaining spectral line data and Stokes I continuum data with high angular resolution (10′′–40′′), including a new H
I
dataset for the whole THOR survey region (
l
= 14.0−67.4° and |
b
|≤ 1.25°). As we published the results of OH lines and continuum emission elsewhere, we concentrate on the H
I
analysis in this paper.
Methods.
With the
Karl G. Jansky
Very Large Array (VLA) in C-configuration, we observed a large portion of the first Galactic quadrant, achieving an angular resolution of ≤40′′. At
L
Band, the WIDAR correlator at the VLA was set to cover the 21 cm H
I
line, four OH transitions, a series of H
nα
radio recombination lines (RRLs;
n
= 151 to 186), and eight 128 MHz-wide continuum spectral windows, simultaneously.
Results.
We publish all OH and RRL data from the C-configuration observations, and a new H
I
dataset combining VLA C+D+GBT (VLA D-configuration and GBT data are from the VLA Galactic Plane Survey) for the whole survey. The H
I
emission shows clear filamentary substructures at negative velocities with low velocity crowding. The emission at positive velocities is more smeared-out, likely due to higher spatial and velocity crowding of structures at the positive velocities. Compared to the spiral arm model of the Milky Way, the atomic gas follows the Sagittarius and Perseus Arm well, but with significant material in the inter-arm regions. With the C-configuration-only H
I
+continuum data, we produce an H
I
optical depth map of the THOR areal coverage from 228 absorption spectra with the nearest-neighbor method. With this
τ
map, we corrected the H
I
emission for optical depth, and the derived column density is 38% higher than the column density with optically thin assumption. The total H
I
mass with optical depth correction in the survey region is 4.7 × 10
8
M
⊙
, 31% more than the mass derived assuming the emission is optically thin. If we applied this 31% correction to the whole Milky Way, the total atomic gas mass would be 9.4–10.5 × 10
9
M
⊙
. Comparing the H
I
with existing CO data, we find a significant increase in the atomic-to-molecular gas ratio from the spiral arms to the inter-arm regions.
Conclusions.
The high-sensitivity and resolution THOR H
I
dataset provides an important new window on the physical and kinematic properties of gas in the inner Galaxy. Although the optical depth we derive is a lower limit, our study shows that the optical depth correction issignificant for H
I
column density and mass estimation. Together with the OH, RRL and continuum emission from the THOR survey, these new H
I
data provide the basis for high-angular-resolution studies of the interstellar medium in different phases.
Notch signaling is known to regulate the proliferation and differentiation of intestinal stem and progenitor cells; however, direct cellular targets and specific functions of Notch signals had not ...been identified. We show here in mice that Notch directly targets the crypt base columnar (CBC) cell to maintain stem cell activity. Notch inhibition induced rapid CBC cell loss, with reduced proliferation, apoptotic cell death and reduced efficiency of organoid initiation. Furthermore, expression of the CBC stem cell-specific marker Olfm4 was directly dependent on Notch signaling, with transcription activated through RBP-Jκ binding sites in the promoter. Notch inhibition also led to precocious differentiation of epithelial progenitors into secretory cell types, including large numbers of cells that expressed both Paneth and goblet cell markers. Analysis of Notch function in Atoh1-deficient intestine demonstrated that the cellular changes were dependent on Atoh1, whereas Notch regulation of Olfm4 gene expression was Atoh1 independent. Our findings suggest that Notch targets distinct progenitor cell populations to maintain adult intestinal stem cells and to regulate cell fate choice to control epithelial cell homeostasis.
Global Neurosurgery: The Unmet Need Park, Kee B., M.D; Johnson, Walter D., M.D., FACS; Dempsey, Robert J., M.D., FACS
World neurosurgery,
04/2016, Letnik:
88
Journal Article
Recenzirano
Odprti dostop
Abstract Globally, the lack of access to basic surgical care causes three times as much deaths as HIV/AIDS, Tuberculosis, and Malaria combined. The magnitude of this unmet need has been recently ...described, and the numbers are startling. Major shifts in global health agenda has highlighted access to essential and emergency surgery as high priority. A broad examination of the current global neurosurgical efforts to improve access has revealed some strengths particularly in the realm of training. However, the demand grossly outstrips the supply; most people in low income countries do not have access to basic surgical care– either due to lack of availability or affordability. Projects that help create a robust and resilient health system within LMICs require urgent implementation. In this context, concurrent scale-up of manpower, investments in capacity building, local data collection, and analysis for accurate assessment are essential. Additionally, through process of collaboration and consensus building within the neurosurgical community, a unified voice of neurosurgery is necessary to effectively advocate for all those who need neurosurgical care wherever, whenever.
Joubert syndrome (JS) is a recessive neurodevelopmental disorder characterised by hypotonia, ataxia, cognitive impairment, abnormal eye movements, respiratory control disturbances and a distinctive ...mid-hindbrain malformation. JS demonstrates substantial phenotypic variability and genetic heterogeneity. This study provides a comprehensive view of the current genetic basis, phenotypic range and gene-phenotype associations in JS.
We sequenced 27 JS-associated genes in 440 affected individuals (375 families) from a cohort of 532 individuals (440 families) with JS, using molecular inversion probe-based targeted capture and next-generation sequencing. Variant pathogenicity was defined using the Combined Annotation Dependent Depletion algorithm with an optimised score cut-off.
We identified presumed causal variants in 62% of pedigrees, including the first B9D2 mutations associated with JS. 253 different mutations in 23 genes highlight the extreme genetic heterogeneity of JS. Phenotypic analysis revealed that only 34% of individuals have a 'pure JS' phenotype. Retinal disease is present in 30% of individuals, renal disease in 25%, coloboma in 17%, polydactyly in 15%, liver fibrosis in 14% and encephalocele in 8%. Loss of CEP290 function is associated with retinal dystrophy, while loss of TMEM67 function is associated with liver fibrosis and coloboma, but we observe no clear-cut distinction between JS subtypes.
This work illustrates how combining advanced sequencing techniques with phenotypic data addresses extreme genetic heterogeneity to provide diagnostic and carrier testing, guide medical monitoring for progressive complications, facilitate interpretation of genome-wide sequencing results in individuals with a variety of phenotypes and enable gene-specific treatments in the future.
A disintegrin and metalloproteinases (ADAMs) are a family of cell surface proteases that regulate diverse cellular functions, including cell adhesion, migration, cellular signaling, and proteolysis. ...Proteolytically active ADAMs are responsible for ectodomain shedding of membrane-associated proteins. ADAMs rapidly modulate key cell signaling pathways in response to changes in the extracellular environment (e.g., inflammation) and play a central role in coordinating intercellular communication within the local microenvironment. ADAM10 and ADAM17 are the most studied members of the ADAM family in the gastrointestinal tract. ADAMs regulate many cellular processes associated with intestinal development, cell fate specification, and the maintenance of intestinal stem cell progenitor populations. Several signaling pathway molecules that undergo ectodomain shedding by ADAMs e.g., ligands and receptors from epidermal growth factor receptor (EGFR) ErbB and tumor necrosis factor α (TNFα) receptor (TNFR) families help drive and control intestinal inflammation and injury repair responses. Dysregulation of these processes through aberrant ADAM expression or sustained ADAM activity is linked to chronic inflammation, inflammation-associated cancer, and tumorigenesis.
In this paper, we present results from the complete set of cosmic microwave background (CMB) radiation temperature anisotropy observations made with the Arcminute Cosmology Bolometer Array Receiver ...(ACBAR) operating at 150 GHz. We include new data from the final 2005 observing season, expanding the number of detector hours by 210% and the sky coverage by 490% over that used for the previous ACBAR release. As a result, the band-power uncertainties have been reduced by more than a factor of two on angular scales encompassing the third to fifth acoustic peaks as well as the damping tail of the CMB power spectrum. The calibration uncertainty has been reduced from 6% to 2.1% in temperature through a direct comparison of the CMB anisotropy measured by ACBAR with that of the dipole-calibrated WMAP5 experiment. The measured power spectrum is consistent with a spatially flat, CDM cosmological model. We include the effects of weak lensing in the power spectrum model computations and find that this significantly improves the fits of the models to the combined ACBAR+WMAP5 power spectrum. The preferred strength of the lensing is consistent with theoretical expectations. On fine angular scales, there is weak evidence (1.1s) for excess power above the level expected from primary anisotropies. We expect any excess power to be dominated by the combination of emission from dusty protogalaxies and the Sunyaev-Zel'dovich effect (SZE). However, the excess observed by ACBAR is significantly smaller than the excess power at >2000 reported by the CBI experiment operating at 30 GHz. Therefore, while it is unlikely that the CBI excess has a primordial origin; the combined ACBAR and CBI results are consistent with the source of the CBI excess being either the SZE or radio source contamination.
Cerebrovascular disease (CVD) is the second most common cause of cognitive impairment and dementia in aged population. CVD presents in a myriad number of clinical ways based on the functional ...location of pathology. While primary clinical emphasis has been placed on motor, speech and visual deficits, vascular cognitive decline is a vastly under recognized and devastating condition afflicting millions of Americans. CVD, a disease of the blood vessels that supply blood to brain involves an integration between small and large vessels. Cerebral large vessel diseases (LVD) are associated with atherosclerosis, artery-to-artery embolism, intracardiac embolism and a large vessel stroke leading to substantial functional disability. Cerebral small vessel disease (SVD) is critically involved in stroke, brain hemorrhages, cognitive decline and functional loss in elderly patients. An evolving understanding of cellular and molecular mechanisms emphasizes that inflammatory vascular changes contribute to systemic pathologic conditions of the central nervous systems (CNS), with specific clinical presentations including, cognitive decline. Advances in an understanding of pathophysiology of disease processes and therapeutic interventions may help improve outcomes. This review will focus on large and small vessels diseases and their relationship to vascular cognitive decline, atherosclerosis, stroke, and inflammatory neurodegeneration. We will also emphasize the molecular and cellular mechanisms, as well as genetic and epigenetic factors associated with LVD and SVD.
•Large vessel and small vessel diseases (LVD and SVDs) coordinately impact cerebro-vascular diseases (CVD).•Vascular and brain hyper-inflammation play a key role in the LVD and SVD.•Cytokines, angiogenic factors, proteases, and adipokines impact these diseases.•Understanding the cellular and molecular mechanisms, is likely to advance therapeutic strategies for a wide range of CVDs.
A disintegrin and metalloprotease (ADAM) is a membrane-anchored metalloprotease implicated in the ectodomain shedding of cell surface proteins, including the ligands for epidermal growth factor (EGF) ...receptors (EGFR)/ErbB. It has been well documented that the transactivation of the EGFR plays critical roles for many cellular functions, such as proliferation and migration mediated through multiple G protein-coupled receptors (GPCRs). Recent accumulating evidence has suggested that ADAMs are the key metalloproteases activated by several GPCR agonists to produce a mature EGFR ligand leading to the EGFR transactivation. In this review, we describe the current knowledge on ADAMs implicated in mediating EGFR transactivation. The major focus of the review will be on the possible upstream mechanisms of ADAM activation by GPCRs as well as downstream signal transduction and the pathophysiological significances of ADAM-dependent EGFR transactivation.
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