We unveil the complex shape of a proto-supercluster at z ∼ 2.45 in the COSMOS field exploiting the synergy of both spectroscopic and photometric redshifts. Thanks to the spectroscopic redshifts of ...the VIMOS Ultra-Deep Survey (VUDS), complemented by the zCOSMOS-Deep spectroscopic sample and high-quality photometric redshifts, we compute the three-dimensional (3D) overdensity field in a volume of ∼100 × 100 × 250 comoving Mpc3 in the central region of the COSMOS field, centred at z ∼ 2.45 along the line of sight. The method relies on a two-dimensional (2D) Voronoi tessellation in overlapping redshift slices that is converted into a 3D density field, where the galaxy distribution in each slice is constructed using a statistical treatment of both spectroscopic and photometric redshifts. In this volume, we identify a proto-supercluster, dubbed “Hyperion” for its immense size and mass, which extends over a volume of ∼60 × 60 × 150 comoving Mpc3 and has an estimated total mass of ∼4.8 × 1015 M⊙. This immensely complex structure contains at least seven density peaks within 2.4 ≲ z ≲ 2.5 connected by filaments that exceed the average density of the volume. We estimate the total mass of the individual peaks, Mtot, based on their inferred average matter density, and find a range of masses from ∼0.1 × 1014 M⊙ to ∼2.7 × 1014 M⊙. By using spectroscopic members of each peak, we obtain the velocity dispersion of the galaxies in the peaks, and then their virial mass Mvir (under the strong assumption that they are virialised). The agreement between Mvir and Mtot is surprisingly good, at less than 1−2σ, considering that (almost all) the peaks are probably not yet virialised. According to the spherical collapse model, these peaks have already started or are about to start collapsing, and they are all predicted to be virialised by redshift z ∼ 0.8−1.6. We finally perform a careful comparison with the literature, given that smaller components of this proto-supercluster had previously been identified using either heterogeneous galaxy samples (Lyα emitters, sub-mm starbursting galaxies, CO emitting galaxies) or 3D Lyα forest tomography on a smaller area. With VUDS, we obtain, for the first time across the central ∼1 deg2 of the COSMOS field, a panoramic view of this large structure, that encompasses, connects, and considerably expands in a homogeneous way on all previous detections of the various sub-components. The characteristics of this exceptional proto-supercluster, its redshift, its richness over a large volume, the clear detection of its sub-components, together with the extensive multi-wavelength imaging and spectroscopy granted by the COSMOS field, provide us the unique possibility to study a rich supercluster in formation.
Gliomas are associated with high mortality because of their exceedingly invasive character. As these tumors acquire their invasiveness from low-grade tumors, it is very important to understand the ...detailed molecular mechanisms of invasion onset. Recent evidences suggest the significant role of microRNAs in tumor invasion. Thus, we hypothesized that deregulation of microRNAs may be important for the malignant progression of gliomas. We found that the aberrant expression of miR-21 is responsible for glioma invasion by disrupting the negative feedback circuit of Ras/MAPK signaling, which is mediated by Spry2. Upregulation of miR-21 was triggered by tumor microenvironmental factors such as hyaluronan and growth factors in glioma cells lacking functional phosphatase and tensin homolog (PTEN), but not harboring wild-type PTEN. Consistently with these in vitro results, Spry2 protein levels were significantly decreased in 79.7% of invasive WHO grade II-IV human glioma tissues, but not in non-invasive grade I and normal tissues. The Spry2 protein levels were not correlated with their mRNA levels, but inversely correlated with miR-21 levels. Taken together, these results suggest that the post-transcriptional regulation of Spry2 by miR-21 has an essential role on the malignant progression of human gliomas. Thus, Spry2 may be a novel therapeutic target for treating gliomas.
We report a detection of the baryon acoustic oscillation (BAO) feature in the three-dimensional correlation function of the transmitted flux fraction in the Lyα forest of high-redshift quasars. The ...study uses 48 640 quasars in the redshift range 2.1 ≤ z ≤ 3.5 from the Baryon Oscillation Spectroscopic Survey (BOSS) of the third generation of the Sloan Digital Sky Survey (SDSS-III). At a mean redshift z = 2.3, we measure the monopole and quadrupole components of the correlation function for separations in the range 20 h-1 Mpc < r < 200 h-1 Mpc. A peak in the correlation function is seen at a separation equal to (1.01 ± 0.03) times the distance expected for the BAO peak within a concordance ΛCDM cosmology. This first detection of the BAO peak at high redshift, when the universe was strongly matter dominated, results in constraints on the angular diameter distance DA and the expansion rate H at z = 2.3 that, combined with priors on H0 and the baryon density, require the existence of dark energy. Combined with constraints derived from cosmic microwave background observations, this result implies H(z = 2.3) = (224 ± 8) km s-1 Mpc-1, indicating that the time derivative of the cosmological scale parameter ȧ = H(z = 2.3)/(1 + z) is significantly greater than that measured with BAO at z ~ 0.5. This demonstrates that the expansion was decelerating in the range 0.7 < z < 2.3, as expected from the matter domination during this epoch. Combined with measurements of H0, one sees the pattern of deceleration followed by acceleration characteristic of a dark-energy dominated universe.
Improvements in magnetic resonance imaging (MRI), total mesorectal excision (TME) surgery, and the use of (chemo)radiotherapy (CRT) have improved local control of rectal cancer; however, we have been ...unable to eradicate local recurrence (LR). Even in the face of TME and negative resection margins (R0), a significant proportion of patients with enlarged lateral lymph nodes (LLNs) suffer from lateral LR (LLR). Japanese studies suggest that the addition of an LLN dissection (LLND) could reduce LLR. This multicenter pooled analysis aims to ascertain whether LLNs actually pose a problem and whether LLND results in fewer LLRs.
Data from 1,216 consecutive patients with cT3/T4 rectal cancers up to 8 cm from the anal verge who underwent surgery in a 5-year period were collected. LLND was performed in 142 patients (12%). MRIs were re-evaluated with a standardized protocol to assess LLN features.
On pretreatment MRI, 703 patients (58%) had visible LLN, and 192 (16%) had a short axis of at least 7 mm. One hundred eight patients developed LR (5-year LR rate, 10.0%), of which 59 (54%) were LLRs (5-year LLR rate, 5.5%). After multivariable analyses, LLNs with a short axis of at least 7 mm resulted in a significantly higher risk of LLR (hazard ratio, 2.060; P = .045) compared with LLNs of less than 7 mm. In patients with LLNs at least 7 mm, (C)RT plus TME plus LLND resulted in a 5-year LLR of 5.7%, which was significantly lower than that in patients who underwent (C)RT plus TME (5-year LLR, 19.5%; P = .042).
LLR is still a significant problem after (C)RT plus TME in LLNs with a short axis at least 7 mm on pretreatment MRI. The addition of LLND results in a significantly lower LLR rate.
Aim
To investigate the effects of LY2405319, an analogue of fibroblast growth factor 21 (FGF21), on glucose homeostasis in streptozotocin (STZ)‐induced insulin‐deficient mice (STZ mice).
Methods
...Nine‐week‐old male C57BL/6J mice were administered a single intraperitoneal injection of STZ (150 mg/kg). One week later, after confirmation of hyperglycaemia, saline or LY2405319 (5 mg/kg) was injected subcutaneously daily for 4 weeks. Changes in glucose homeostasis, energy metabolism and brown adipose tissue (BAT) function were assessed.
Results
The STZ mice had elevated blood glucose and reduced plasma FGF21 levels, impaired glucose uptake in the BAT, and BAT mitochondria with absent or swollen cristae and fewer lipid vacuoles. LY2405319 significantly reduced blood glucose levels and this was associated with increased BAT glucose uptake and changes in gene expression and morphology, indicating improved mitochondrial lipid metabolism in the BAT. Importantly, the ability of LY2405319 to lower blood glucose in STZ mice was compromised after removing interscapular BAT.
Conclusions
Our results show that LY2405319 reduces blood glucose levels in insulin‐deficient diabetes by improving BAT metabolism. Additional studies investigating the therapeutic potential of FGF21 for the treatment of type 1 diabetes are warranted.
The endoplasmic reticulum (ER) has a remarkably complex structure, composed of a single bilayer that forms the nuclear envelope, along with a network of sheets and dynamic tubules. Our understanding ...of the biological significance of the complex architecture of the ER has improved dramatically in the last few years. The identification of proteins and forces required for maintaining ER shape, as well as more advanced imaging techniques, has allowed the relationship between ER shape and function to come into focus. These studies have also revealed unexpected new functions of the ER and novel ER domains regulating alterations in ER dynamics. The importance of ER structure has become evident as recent research has identified diseases linked to mutations in ER-shaping proteins. In this review, we discuss what is known about the maintenance of ER architecture, the relationship between ER structure and function, and diseases associated with defects in ER structure.
The ice shelves in the Amundsen Sea are thinning rapidly, and the main reason for their decline appears to be warm ocean currents circulating below the ice shelves and melting these from below. Ocean ...currents transport warm dense water onto the shelf, channeled by bathymetric troughs leading to the deep inner basins. A hydrographic mooring equipped with an upward-looking ADCP has been placed in one of these troughs on the central Amundsen shelf. The two years (2010/11) of mooring data are here used to characterize the inflow of warm deep water to the deep shelf basins. During both years, the warm layer thickness and temperature peaked in austral fall. The along-trough velocity is dominated by strong fluctuations that do not vary in the vertical. These fluctuations are correlated with the local wind, with eastward wind over the shelf and shelf break giving flow toward the ice shelves. In addition, there is a persistent flow of dense lower Circumpolar Deep Water (CDW) toward the ice shelves in the bottom layer. This bottom-intensified flow appears to be driven by buoyancy forces rather than the shelfbreak wind. The years of 2010 and 2011 were characterized by a comparatively stationary Amundsen Sea low, and hence there were no strong eastward winds during winter that could drive an upwelling of warm water along the shelf break. Regardless of this, there was a persistent flow of lower CDW in the bottom layer during the two years. The average heat transport toward the ice shelves in the trough was estimated from the mooring data to be 0.95 TW.
Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the ...potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts’ personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.
Single emitters have been considered as sources of single photons in various contexts, including cryptography, quantum computation, spectroscopy and metrology. The success of these applications will ...crucially rely on the efficient directional emission of photons into well-defined modes. To accomplish high efficiency, researchers have investigated microcavities at cryogenic temperatures, photonic nanowires and near-field coupling to metallic nano-antennas. However, despite impressive progress, the existing realizations substantially fall short of unity collection efficiency. Here, we report on a theoretical and experimental study of a dielectric planar antenna, which uses a layered structure to tailor the angular emission of a single oriented molecule. We demonstrate a collection efficiency of 96% using a microscope objective at room temperature and obtain record detection rates of ∼50 MHz. Our scheme is wavelength-insensitive and can be readily extended to other solid-state emitters such as colour centres and semiconductor quantum dots.
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