An emerging consensus in the evolution, phylogeny, and systematics of marsupials and their fossil relatives (Metatheria)

Marsupials and their fossil relatives, which collectively comprise Metatheria, have been of scientific interest for centuries, with many aspects of their evolution and systematics subject to intense research and debate. Here, we review progress over the last 25 years, which has included the description of many new species (modern and fossil), and major improvements in understanding of their phylogenetic relationships, as well as the overall evolutionary history and biogeography of Marsupialia (crown-clade) and Metatheria (total-clade). Significant advances have included the deployment of increasingly sophisticated molecular, morphological, and total evidence analyses, which have resolved most previously disputed relationships among and within the modern marsupial orders. A broad systematic consensus is now emerging, although several major areas of contention remain, particularly among fossil metatherians. New modern species continue to be described at an impressive rate, with almost 50 named in the last 25 years, and many more await discovery. There has also been an explosion in the discovery and description of fossil marsupials and non-marsupial metatherians (~270 species), principally from Australasia and the Americas but also from Antarctica, Europe, and Asia. Most are represented by dental specimens only, but some consist of complete and well-preserved material, which has led to major improvements in our understanding of the evolution of cranial and postcranial morphology. Improvements in the fossil record and advances in methods for inferring divergence times have helped clarify when and where key events occurred in metatherian evolution, and the patterns of subclade diversification. We also have improved understanding of biogeographical relationships among metatherians on different landmasses. Despite enormous progress, numerous key uncertainties remain due to major gaps in the fossil record (e.g., Antarctica, Late Cretaceous, and early Paleogene of Australia) and a comparative lack of studies that directly combine molecular and fossil data. Future advances will largely depend on improvements in the fossil record and studies that better integrate neontological and paleontological evidence

Demonstrating Additional Law of Relativistic Velocities based on Squeezed Light

Special relativity is foundation of many branches of modern physics, of which theoretical results are far beyond our daily experience and hard to realized in kinematic experiments. However, its outcomes could be demonstrated by making use of convenient substitute, i.e. squeezed light in present paper. Squeezed light is very important in the field of quantum optics and the corresponding transformation can be regarded as the coherent state of SU(1; 1). In this paper, the connection between the squeezed operator and Lorentz boost is built under certain conditions. Furthermore, the additional law of relativistic velocities and the angle of Wigner rotation are deduced as well

Design and Evaluation of Techniques to Utilize Implicit Rating Data in Complex Information Systems.

Research in personalization, including recommender systems, focuses on applications such as in online shopping malls and simple information systems. These systems consider user profile and item information obtained from data explicitly entered by users - where it is possible to classify items involved and to make personalization based on a direct mapping from user or user group to item or item group. However, in complex, dynamic, and professional information systems, such as Digital Libraries, additional capabilities are needed to achieve personalization to support their distinctive features: large numbers of digital objects, dynamic updates, sparse rating data, biased rating data on specific items, and challenges in getting explicit rating data from users. In this report, we present techniques for collecting, storing, processing, and utilizing implicit rating data of Digital Libraries for analysis and decision support. We present our pilot study to find virtual user groups using implicit rating data. We demonstrate the effectiveness of implicit rating data for characterizing users and finding virtual user communities, through statistical hypothesis testing. Further, we describe a visual data mining tool named VUDM (Visual User model Data Mining tool) that utilizes implicit rating data. We provide the results of formative evaluation of VUDM and discuss the problems raised and plans for further studies

The bright optical afterglow of the nearby gamma-ray burst of 29 March 2003

Many past studies of cosmological gamma-ray bursts (GRBs) have been limited because of the large distance to typical GRBs, resulting in faint afterglows. There has long been a recognition that a nearby GRB would shed light on the origin of these mysterious cosmic explosions, as well as the physics of their fireballs. However, GRBs nearer than z=0.2 are extremely rare, with an estimated rate of localisation of one every decade. Here, we report the discovery of bright optical afterglow emission from GRB 030329. Our prompt dissemination and the brilliance of the afterglow resulted in extensive followup (more than 65 telescopes) from radio through X-ray bands, as well as measurement of the redshift, z=0.169. The gamma-ray and afterglow properties of GRB 030329 are similar to those of cosmological GRBs (after accounting for the small distance), making this the nearest known cosmological GRB. Observations have already securely identified the progenitor as a massive star that exploded as a supernova, and we anticipate futher revelations of the GRB phenomenon from studies of this source.Comment: 13 pages, 4 figures. Original tex

Outcomes Associated With Oral Anticoagulants Plus Antiplatelets in Patients With Newly Diagnosed Atrial Fibrillation.

Importance: Patients with nonvalvular atrial fibrillation at risk of stroke should receive oral anticoagulants (OAC). However, approximately 1 in 8 patients in the Global Anticoagulant Registry in the Field (GARFIELD-AF) registry are treated with antiplatelet (AP) drugs in addition to OAC, with or without documented vascular disease or other indications for AP therapy. Objective: To investigate baseline characteristics and outcomes of patients who were prescribed OAC plus AP therapy vs OAC alone. Design, Setting, and Participants: Prospective cohort study of the GARFIELD-AF registry, an international, multicenter, observational study of adults aged 18 years and older with recently diagnosed nonvalvular atrial fibrillation and at least 1 risk factor for stroke enrolled between March 2010 and August 2016. Data were extracted for analysis in October 2017 and analyzed from April 2018 to June 2019. Exposure: Participants received either OAC plus AP or OAC alone. Main Outcomes and Measures: Clinical outcomes were measured over 3 and 12 months. Outcomes were adjusted for 40 covariates, including baseline conditions and medications. Results: A total of 24 436 patients (13 438 [55.0%] male; median [interquartile range] age, 71 [64-78] years) were analyzed. Among eligible patients, those receiving OAC plus AP therapy had a greater prevalence of cardiovascular indications for AP, including acute coronary syndromes (22.0% vs 4.3%), coronary artery disease (39.1% vs 9.8%), and carotid occlusive disease (4.8% vs 2.0%). Over 1 year, patients treated with OAC plus AP had significantly higher incidence rates of stroke (adjusted hazard ratio [aHR], 1.49; 95% CI, 1.01-2.20) and any bleeding event (aHR, 1.41; 95% CI, 1.17-1.70) than those treated with OAC alone. These patients did not show evidence of reduced all-cause mortality (aHR, 1.22; 95% CI, 0.98-1.51). Risk of acute coronary syndrome was not reduced in patients taking OAC plus AP compared with OAC alone (aHR, 1.16; 95% CI, 0.70-1.94). Patients treated with OAC plus AP also had higher rates of all clinical outcomes than those treated with OAC alone over the short term (3 months). Conclusions and Relevance: This study challenges the practice of coprescribing OAC plus AP unless there is a clear indication for adding AP to OAC therapy in newly diagnosed atrial fibrillation

Downregulation of Mcl-1 has anti-inflammatory pro-resolution effects and enhances bacterial clearance from the lung

Phagocytes not only coordinate acute inflammation and host defense at mucosal sites, but also contribute to tissue damage. Respiratory infection causes a globally significant disease burden and frequently progresses to acute respiratory distress syndrome, a devastating inflammatory condition characterized by neutrophil recruitment and accumulation of protein-rich edema fluid causing impaired lung function. We hypothesized that targeting the intracellular protein myeloid cell leukemia 1 (Mcl-1) by a cyclin-dependent kinase inhibitor (AT7519) or a flavone (wogonin) would accelerate neutrophil apoptosis and resolution of established inflammation, but without detriment to bacterial clearance. Mcl-1 loss induced human neutrophil apoptosis, but did not induce macrophage apoptosis nor impair phagocytosis of apoptotic neutrophils. Neutrophil-dominant inflammation was modelled in mice by either endotoxin or bacteria (Escherichia coli). Downregulating inflammatory cell Mcl-1 had anti-inflammatory, pro-resolution effects, shortening the resolution interval (R(i)) from 19 to 7 h and improved organ dysfunction with enhanced alveolar–capillary barrier integrity. Conversely, attenuating drug-induced Mcl-1 downregulation inhibited neutrophil apoptosis and delayed resolution of endotoxin-mediated lung inflammation. Importantly, manipulating lung inflammatory cell Mcl-1 also accelerated resolution of bacterial infection (R(i); 50 to 16 h) concurrent with enhanced bacterial clearance. Therefore, manipulating inflammatory cell Mcl-1 accelerates inflammation resolution without detriment to host defense against bacteria, and represents a target for treating infection-associated inflammation

The sub-energetic GRB 031203 as a cosmic analogue to GRB 980425

Over the six years since the discovery of the gamma-ray burst GRB 980425, associated with the nearby (distance, ~40 Mpc) supernova 1998bw, astronomers have fiercely debated the nature of this event. Relative to bursts located at cosmological distances, (redshift, z~1), GRB 980425 was under-luminous in gamma-rays by three orders of magnitude. Radio calorimetry showed the explosion was sub-energetic by a factor of 10. Here, we report observations of the radio and X-ray afterglow of the recent z=0.105 GRB 031203 and demonstrate that it too is sub-energetic. Our result, when taken together with the low gamma-ray luminosity, suggest that GRB 031203 is the first cosmic analogue to GRB 980425. We find no evidence that this event was a highly collimated explosion viewed off-axis. Like GRB 980425, GRB 031203 appears to be an intrinsically sub-energetic gamma-ray burst. Such sub-energetic events have faint afterglows. Intensive follow-up of faint bursts with smooth gamma-ray light curves (common to both GRBs 031203 and 980425) may enable us to reveal their expected large population.Comment: To Appear in Nature, August 5, 200

Multiphase Gas In Galaxy Halos: The OVI Lyman-limit System toward J1009+0713

We have serendipitously detected a strong O VI-bearing Lyman limit system at z_abs = 0.3558 toward the QSO J1009+0713 (z_em = 0.456) in our survey of low-redshift galaxy halos with the Hubble Space Telescope's Cosmic Origins Spectrograph. Its rest-frame equivalent width of W_r = 835 +/- 49 mA is the highest for an intervening absorber yet detected in any low-redshift QSO sightline, with absorption spanning 400 km s^-1 in its rest frame. HST/WFC3 images of the galaxy field show that the absorber is associated with two galaxies lying at 14 and 46 kpc from the QSO line of sight. The bulk of the absorbing gas traced by H I resides in two strong, blended component groups that possess a total logN(HI) = 18 - 18.8. The ion ratios and column densities of C, N, O, Mg, Si, S, and Fe, except the O VI, can be accommodated into a simple photoionization model in which diffuse, low-metallicity halo gas is exposed to a photoionizing field from stars in the nearby galaxies that propagates into the halo at 10% efficiency. We constrain the metallicity firmly within the range 0.1 - 1 Zsun, and photoionization modeling indirectly indicates a subsolar metallicity of 0.05 - 0.5 Zsun. The appearance of strong O VI and nine Mg II components and our review of similar systems in the literature support the "interface" picture of high-velocity O VI: the total strength of the O VI shows a positive correlation with the number of detected components in the low-ionization gas, however the total O VI column densities still far exceed the values expected from interface models for the number of detected clouds.Comment: 20 pages, 11 figures, accepted for publication in Ap

Tissue Localization and Extracellular Matrix Degradation by PI, PII and PIII Snake Venom Metalloproteinases: Clues on the Mechanisms of Venom-Induced Hemorrhage

20 páginas, 4 figuras, 3 tablas y 7 tablas en material suplementario.Snake venom hemorrhagic metalloproteinases (SVMPs) of the PI, PII and PIII classes were compared in terms of tissue localization and their ability to hydrolyze basement membrane components in vivo, as well as by a proteomics analysis of exudates collected in tissue injected with these enzymes. Immunohistochemical analyses of co-localization of these SVMPs with type IV collagen revealed that PII and PIII enzymes co-localized with type IV collagen in capillaries, arterioles and post-capillary venules to a higher extent than PI SVMP, which showed a more widespread distribution in the tissue. The patterns of hydrolysis by these three SVMPs of laminin, type VI collagen and nidogen in vivo greatly differ, whereas the three enzymes showed a similar pattern of degradation of type IV collagen, supporting the concept that hydrolysis of this component is critical for the destabilization of microvessel structure leading to hemorrhage. Proteomic analysis of wound exudate revealed similarities and differences between the action of the three SVMPs. Higher extent of proteolysis was observed for the PI enzyme regarding several extracellular matrix components and fibrinogen, whereas exudates from mice injected with PII and PIII SVMPs had higher amounts of some intracellular proteins. Our results provide novel clues for understanding the mechanisms by which SVMPs induce damage to the microvasculature and generate hemorrhage.This work was performed in partial fulfillment of the requirements for the PhD degree for Cristina Herrera at Universidad de Costa Rica.Peer reviewe