504 research outputs found

    Historical biogeography of the squids from the family Loliginidae (Teuthoidea: Myopsida)

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    IndexaciĂłn: Scopus.According to the vicariant hypothesis proposed by Brakoniecki (1986) the closure of the Sea of Tethys and the opening of the Atlantic Ocean would play an important role in the history of squids of the family Loliginidae, which is reflected in its current neritic distribution. Our study evaluated this hypothesis and alternative ideas to understand the historical biogeography of loliginid squids. This work is based on a phylogenetic hypothesis rebuilt with mitochondrial and nuclear sequences that incorporates the estimation of divergence times and ancestral distribution. Our results sustain that the squids of the family Loliginidae would have originated in the Western Pacific during the Late Paleocene about 59 My, following, during their diversification, at least 20 dispersion and 6 vicariant events. The first vicariant event fragments the ancestral distribution, remaining the ancestor of Sepioteuthis in the south and the subfamily Loligininae in the north. Successive events of dispersion, and some of vicariance (unrelated with the movement of tectonic plates and opening of the Atlantic Ocean), modeled it distribution. Our inference suggest a different origin compared to proposed by Brakoniecki (Tethys Sea), consistent with a center of origin that supports the most diversity of the family, with a predominance of dispersion processes over vicariant events, which explain the present distribution pattern.http://www.lajar.cl/pdf/imar/v45n1/Art%C3%ADculo_45_1_11.pd

    Exponential stability of the wave equation with memory and time delay

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    We study the asymptotic behaviour of the wave equation with viscoelastic damping in presence of a time-delayed damping. We prove exponential stability if the amplitude of the time delay term is small enough

    CGRP inhibitors for migraine prophylaxis: a safety review

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    Introduction: Since calcitonin gene-related peptide (CGRP) plays an important role in the pathophysiology of migraine via the activation of the trigeminovascular system, the newest prophylactic treatments directly block CGRP or its receptor. However, the safety of these novel antimigraine drugs is not yet sufficiently established. Areas covered: Based on the blockade of CGRP or its receptor, this review considers: (i) the effects of the novel prophylactic antimigraine drugs (i.e. gepants and monoclonal antibodies) in clinical trials; and (ii) the potentially negative effects of blocking CGRP or its receptor in terms of safety. Expert opinion: In the last decade, clinical trials have demonstrated the efficacy of new drugs for the preventive treatment of migraine which aim to (i) block CGRP or its receptor; (ii) increase tolerability as compared to the currently available prophylactics; and/or (iii) be more effective and safer than other treatments. However, these trials are limited to study the safety on the short term, and a cardiovascular risk with prolonged use cannot be excluded. Clearly, basic science experimental studies and long-term clinical trials (i.e. Phase IV) are required to delineate the safety of the newest prophylactic antimigraine drugs without causing unwanted side effects due to chronic CGRP (receptor) blockade

    Antarctic ice sheet discharge driven by atmosphere-ocean feedbacks at the Last Glacial Termination

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    Reconstructing the dynamic response of the Antarctic ice sheets to warming during the Last Glacial Termination (LGT; 18,000–11,650 yrs ago) allows us to disentangle ice-climate feedbacks that are key to improving future projections. Whilst the sequence of events during this period is reasonably well-known, relatively poor chronological control has precluded precise alignment of ice, atmospheric and marine records, making it difficult to assess relationships between Antarctic ice-sheet (AIS) dynamics, climate change and sea level. Here we present results from a highly-resolved ‘horizontal ice core’ from the Weddell Sea Embayment, which records millennial-scale AIS dynamics across this extensive region. Counterintuitively, we find AIS mass-loss across the full duration of the Antarctic Cold Reversal (ACR; 14,600–12,700 yrs ago), with stabilisation during the subsequent millennia of atmospheric warming. Earth-system and ice-sheet modelling suggests these contrasting trends were likely Antarctic-wide, sustained by feedbacks amplified by the delivery of Circumpolar Deep Water onto the continental shelf. Given the anti-phase relationship between inter-hemispheric climate trends across the LGT our findings demonstrate that Southern Ocean-AIS feedbacks were controlled by global atmospheric teleconnections. With increasing stratification of the Southern Ocean and intensification of mid-latitude westerly winds today, such teleconnections could amplify AIS mass loss and accelerate global sea-level rise

    A Spatially Resolved Study of Cold Dust, Molecular Gas, H ii Regions, and Stars in the z = 2.12 Submillimeter Galaxy ALESS67.1

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    We present detailed studies of a z = 2.12 submillimeter galaxy, ALESS67.1, using sub-arcsecond resolution ALMA, adaptive optics-aided VLT/SINFONI, and Hubble Space Telescope (HST)/CANDELS data to investigate the kinematics and spatial distributions of dust emission (870 ÎŒm continuum), 12CO(J = 3–2), strong optical emission lines, and visible stars. Dynamical modeling of the optical emission lines suggests that ALESS67.1 is not a pure rotating disk but a merger, consistent with the apparent tidal features revealed in the HST imaging. Our sub-arcsecond resolution data set allows us to measure half-light radii for all the tracers, and we find a factor of 4–6 smaller sizes in dust continuum compared to all the other tracers, including 12CO; also, ultraviolet (UV) and Hα emission are significantly offset from the dust continuum. The spatial mismatch between the UV continuum and the cold dust and gas reservoir supports the explanation that geometrical effects are responsible for the offset of the dusty galaxy on the IRX–ÎČ diagram. Using a dynamical method we derive an αCO=1.8±1.0{\alpha }_{\mathrm{CO}}=1.8\pm 1.0, consistent with other submillimeter galaxies (SMGs) that also have resolved CO and dust measurements. Assuming a single αCO{\alpha }_{\mathrm{CO}} value we also derive resolved gas and star formation rate surface densities, and find that the core region of the galaxy (â‰Č5\lesssim 5 kpc) follows the trend of mergers on the Schmidt–Kennicutt relationship, whereas the outskirts (≳5\gtrsim 5 kpc) lie on the locus of normal star-forming galaxies, suggesting different star formation efficiencies within one galaxy. Our results caution against using single size or morphology for different tracers of the star formation activity and gas content of galaxies, and therefore argue the need to use spatially resolved, multi-wavelength observations to interpret the properties of SMGs, and perhaps even for z>1z\gt 1 galaxies in general

    Minibeam radiation therapy enhanced tumor delivery of PEGylated liposomal doxorubicin in a triple-negative breast cancer mouse model

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    Background: Minibeam radiation therapy is an experimental radiation therapy utilizing an array of parallel submillimeter planar X-ray beams. In preclinical studies, minibeam radiation therapy has been shown to eradicate tumors and cause significantly less damage to normal tissue compared to equivalent radiation doses delivered by conventional broadbeam radiation therapy, where radiation dose is uniformly distributed. Methods: Expanding on prior studies that suggested minibeam radiation therapy increased perfusion in tumors, we compared a single fraction of minibeam radiation therapy (peak dose:valley dose of 28 Gy:2.1 Gy and 100 Gy:7.5 Gy) and broadbeam radiation therapy (7 Gy) in their ability to enhance tumor delivery of PEGylated liposomal doxorubicin and alter the tumor microenvironment in a murine tumor model. Plasma and tumor pharmacokinetic studies of PEGylated liposomal doxorubicin and tumor microenvironment profiling were performed in a genetically engineered mouse model of claudin-low triple-negative breast cancer (T11). Results: Minibeam radiation therapy (28 Gy) and broadbeam radiation therapy (7 Gy) increased PEGylated liposomal doxorubicin tumor delivery by 7.1-fold and 2.7-fold, respectively, compared to PEGylated liposomal doxorubicin alone, without altering the plasma disposition. The enhanced tumor delivery of PEGylated liposomal doxorubicin by minibeam radiation therapy is consistent after repeated dosing, is associated with changes in tumor macrophages but not collagen or angiogenesis, and nontoxic to local tissues. Our study indicated that the minibeam radiation therapy’s ability to enhance the drug delivery decreases from 28 to 100 Gy peak dose. Discussion: Our studies suggest that low-dose minibeam radiation therapy is a safe and effective method to significantly enhance the tumor delivery of nanoparticle agents

    An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

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    For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

    Changing state of the climate system

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    Chapter 2 assesses observed large-scale changes in climate system drivers, key climate indicators and principal modes of variability. Chapter 3 considers model performance and detection/attribution, and Chapter 4 covers projections for a subset of these same indicators and modes of variability. Collectively, these chapters provide the basis for later chapters, which focus upon processes and regional changes. Within Chapter 2, changes are assessed from in situ and remotely sensed data and products and from indirect evidence of longer-term changes based upon a diverse range of climate proxies. The time-evolving availability of observations and proxy information dictate the periods that can be assessed. Wherever possible, recent changes are assessed for their significance in a longer-term context, including target proxy periods, both in terms of mean state and rates of change

    Bone marrow-derived and resident liver macrophages display unique transcriptomic signatures but similar biological functions

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    Abstract: Background and aims: Kupffer cells (KCs), the resident tissue macrophages of the liver, play a crucial role in the clearance of pathogens and other particulate materials that reach the systemic circulation. Recent studies have identified KCs as a yolk sac-derived resident macrophage population that is replenished independently of monocytes in the steady state. Although it is now established that following local tissue injury, bone-marrow derived monocytes may infiltrate the tissue and differentiate into macrophages, the extent to which newly differentiated macrophages functionally resemble the KCs they have replaced has not been extensively studied. Methods and results: Here we show using intravital microscopy, morphometric analysis and gene expression profiling that bone marrow derived “KCs” accumulating as a result of genotoxic injury resemble, but are not identical to their yolk-sac (YS) counterparts. An ion homeostasis gene signature, including genes associated with scavenger receptor function and extracellular matrix deposition, allows discrimination between these two KC populations. Reflecting the differential expression of scavenger receptors, YS-derived KCs were more effective at accumulating Ac-LDL, whereas surprisingly they were poorer than BM-derived KCs when assessed for uptake of a range of bacterial pathogens. The two KC populations were almost indistinguishable in regard to i) response to LPS challenge, ii) phagocytosis of effete RBCs and iii) their ability to contain infection and direct granuloma formation against Leishmania donovani, a KC-tropic intracellular parasite. Conclusions: BM-derived KCs differentiate locally to resemble YS-derived KC in most but not all respects, with implications for models of infectious diseases, liver injury and bone marrow transplantation. In addition, the gene signature we describe adds to the tools available for distinguishing KC subpopulations based on their ontology
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