The South Atlantic rift basin evolved as a branch of a large Jurassic-Cretaceous intraplate rift zone between the African and South American plates during the final break-up of western Gondwana. We ...have compiled and assimilated data from these intraplated rifts and constructed a revised plate kinematic model for the prebreak- up evolution of the South Atlantic. Based on structural restoration of the conjugate South Atlantic margins and intracontinental rift basins in Africa and South America, we achieve a tight-fit reconstruction which eliminates the need for previously inferred large intracontinental shear zones, in particular in Patagonian South America. We conclude that such a multi-velocity, multi-directional rift history exerts primary control on the evolution of these conjugate passive-margin systems and can explain the first-order tectonic structures along the South Atlantic and possibly other passive margins.
A marked bend in the Hawaiian-Emperor seamount chain supposedly resulted from a recent major reorganization of the plate-mantle system there 50 million years ago. Although alternative mantle-driven ...and plate-shifting hypotheses have been proposed, no contemporaneous circum-Pacific plate events have been identified. We report reconstructions for Australia and Antarctica that reveal a major plate reorganization between 50 and 53 million years ago. Revised Pacific Ocean sea-floor reconstructions suggest that subduction of the Pacific-Izanagi spreading ridge and subsequent Marianas/Tonga-Kermadec subduction initiation may have been the ultimate causes of these events. Thus, these plate reconstructions solve long-standing continental fit problems and improve constraints on the motion between East and West Antarctica and global plate circuit closure.
Micropatterning of single crystals for technological applications is a complex, multistep process. Nature provides alternative fabrication strategies, when crystals with exquisite micro-ornamentation ...directly develop within preorganized frameworks. We report a bio-inspired approach to growing large micropatterned single crystals. Micropatterned templates organically modified to induce the formation of metastable amorphous calcium carbonate were imprinted with calcite nucleation sites. The template-directed deposition and crystallization of the amorphous phase resulted in the fabrication of millimeter-sized single calcite crystals with sub-10-µm patterns and controlled crystallographic orientation. We suggest that in addition to regulating the shape, micropatterned frameworks act as sites for stress and impurity release during the amorphous-to-crystalline transition. The proposed mechanisms may have direct biological relevance and broad implications in materials synthesis.
Autism is a heritable disorder, with over 250 associated genes identified to date, yet no single gene accounts for >1-2% of cases. The clinical presentation, behavioural symptoms, imaging and ...histopathology findings are strikingly heterogeneous. A more complete understanding of autism can be obtained by examining multiple genetic or behavioural mouse models of autism using magnetic resonance imaging (MRI)-based neuroanatomical phenotyping. Twenty-six different mouse models were examined and the consistently found abnormal brain regions across models were parieto-temporal lobe, cerebellar cortex, frontal lobe, hypothalamus and striatum. These models separated into three distinct clusters, two of which can be linked to the under and over-connectivity found in autism. These clusters also identified previously unknown connections between Nrxn1α, En2 and Fmr1; Nlgn3, BTBR and Slc6A4; and also between X monosomy and Mecp2. With no single treatment for autism found, clustering autism using neuroanatomy and identifying these strong connections may prove to be a crucial step in predicting treatment response.
Immune checkpoint inhibitors have improved survival outcome of advanced non-small-cell lung cancer (NSCLC). However, most patients do not benefit. Therefore, biomarkers are needed that accurately ...predict response. We hypothesized that molecular profiling of exhaled air may capture the inflammatory milieu related to the individual responsiveness to anti-programmed death ligand 1 (PD-1) therapy. This study aimed to determine the accuracy of exhaled breath analysis at baseline for assessing nonresponders versus responders to anti-PD-1 therapy in NSCLC patients.
This was a prospective observational study in patients receiving checkpoint inhibitor therapy using both a training and validation set of NSCLC patients. At baseline, breath profiles were collected in duplicate by a metal oxide semiconductor electronic nose (eNose) positioned at the rear end of a pneumotachograph. Patients received nivolumab or pembrolizumab of which the efficacy was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at 3-month follow-up. Data analysis involved advanced signal-processing and statistics based on independent t-tests followed by linear discriminant and receiver operating characteristic (ROC) analysis.
Exhaled breath data of 143 NSCLC patients (training: 92, validation: 51) were available at baseline. ENose sensors contributed significantly (P < 0.05) at baseline in differentiating between patients with different responses at 3 months of anti-PD-1 treatment. The eNose sensors were combined into a single biomarker with an ROC-area under the curve (AUC) of 0.89 confidence interval (CI) 0.82–0.96. This AUC was confirmed in the validation set: 0.85 (CI 0.75–0.96).
ENose assessment was effective in the noninvasive prediction of individual patient responses to immunotherapy. The predictive accuracy and efficacy of the eNose for discrimination of immunotherapy responder types were replicated in an independent validation set op patients. This finding can potentially avoid application of ineffective treatment in identified probable nonresponders.
In the last two decades we have witnessed sizable progress in defining the role of gastrointestinal signals in the control of glucose and energy homeostasis. Specifically, the molecular basis of the ...huge metabolic benefits in bariatric surgery is emerging while novel incretin-based medicines based on endogenous hormones such as glucagon-like peptide 1 and pancreas-derived amylin are improving diabetes management. These and related developments have fostered the discovery of novel insights into endocrine control of systemic metabolism, and in particular a deeper understanding of the importance of communication across vital organs, and specifically the gut-brain-pancreas-liver network. Paradoxically, the pancreatic peptide glucagon has reemerged in this period among a plethora of newly identified metabolic macromolecules, and new data complement and challenge its historical position as a gut hormone involved in metabolic control. The synthesis of glucagon analogs that are biophysically stable and soluble in aqueous solutions has promoted biological study that has enriched our understanding of glucagon biology and ironically recruited glucagon agonism as a central element to lower body weight in the treatment of metabolic disease. This review summarizes the extensive historical record and the more recent provocative direction that integrates the prominent role of glucagon in glucose elevation with its under-acknowledged effects on lipids, body weight, and vascular health that have implications for the pathophysiology of metabolic diseases, and the emergence of precision medicines to treat metabolic diseases.
ABSTRACT
We present the results of a large multiwavelength follow-up campaign of the tidal disruption event (TDE) AT 2019dsg, focusing on low to high resolution optical spectroscopy, X-ray, and radio ...observations. The galaxy hosts a super massive black hole of mass $\rm (5.4\pm 3.2)\times 10^6\, M_\odot$ and careful analysis finds no evidence for the presence of an active galactic nucleus, instead the TDE host galaxy shows narrow optical emission lines that likely arise from star formation activity. The transient is luminous in the X-rays, radio, UV, and optical. The X-ray emission becomes undetected after ∼100 d, and the radio luminosity density starts to decay at frequencies above 5.4 GHz by ∼160 d. Optical emission line signatures of the TDE are present up to ∼200 d after the light-curve peak. The medium to high resolution spectra show traces of absorption lines that we propose originate in the self-gravitating debris streams. At late times, after ∼200 d, narrow Fe lines appear in the spectra. The TDE was previously classified as N-strong, but after careful subtraction of the host galaxy’s stellar contribution, we find no evidence for these N lines in the TDE spectrum, even though O Bowen lines are detected. The observed properties of the X-ray emission are fully consistent with the detection of the inner regions of a cooling accretion disc. The optical and radio properties are consistent with this central engine seen at a low inclination (i.e. seen from the poles).
A brain-computer interface (BCI) is a system that allows its users to control external devices with brain activity. Although the proof-of-concept was given decades ago, the reliable translation of ...user intent into device control commands is still a major challenge. Success requires the effective interaction of two adaptive controllers: the user's brain, which produces brain activity that encodes intent, and the BCI system, which translates that activity into device control commands. In order to facilitate this interaction, many laboratories are exploring a variety of signal analysis techniques to improve the adaptation of the BCI system to the user. In the literature, many machine learning and pattern classification algorithms have been reported to give impressive results when applied to BCI data in offline analyses. However, it is more difficult to evaluate their relative value for actual online use. BCI data competitions have been organized to provide objective formal evaluations of alternative methods. Prompted by the great interest in the first two BCI Competitions, we organized the third BCI Competition to address several of the most difficult and important analysis problems in BCI research. The paper describes the data sets that were provided to the competitors and gives an overview of the results.
Tectonic reconstructions of Southeast Asia have given rise to numerous controversies that include the accretionary history of Sundaland and the enigmatic tectonic origin of the proto-South China Sea. ...We assimilate a diversity of geological and geophysical observations into a new regional plate model, coupled to a global model, to address these debates. Our approach takes into account terrane suturing and accretion histories, the location of subducted slabs imaged in mantle tomography in order to constrain the evolution of regional subduction zones, as well as plausible absolute and relative plate velocities and tectonic driving mechanisms. We propose a scenario of rifting from northern Gondwana in the latest Jurassic, driven by northward slab pull from north-dipping subduction of Tethyan crust beneath Eurasia, to detach East Java, Mangkalihat, southeast Borneo and West Sulawesi blocks that collided with a Tethyan intra-oceanic subduction zone in the mid-Cretaceous and subsequently accreted to the Sunda margin (i.e., southwest Borneo core) in the Late Cretaceous. In accounting for the evolution of plate boundaries, we propose that the Philippine Sea plate originated on the periphery of Tethyan crust forming this northward conveyor. We implement a revised model for the Tethyan intra-oceanic subduction zones to reconcile convergence rates, changes in volcanism and the obduction of ophiolites. In our model the northward margin of Greater India collides with the Kohistan-Ladakh intra-oceanic arc at ∼53 Ma, followed by continent-continent collision closing the Shyok and Indus-Tsangpo suture zones between ∼42 and 34 Ma. We also account for the back-arc opening of the proto-South China Sea from ∼65 Ma, consistent with extension along east Asia and the formation of supra-subduction zone ophiolites presently found on the island of Mindoro. The related rifting likely detached the Semitau continental fragment from South China, which accreted to northern Borneo in the mid-Eocene, to account for the Sarawak Orogeny. Rifting then re-initiated along southeast China by 37 Ma to open the South China Sea, resulting in the complete consumption of proto-South China Sea by ∼17 Ma when the collision of the Dangerous Grounds and northern Palawan blocks with northern Borneo choked the subduction zone to result in the Sabah Orogeny and the obduction of ophiolites in Palawan and Mindoro. We conclude that the counterclockwise rotation of Borneo was accommodated by oroclinal bending consistent with paleomagnetic constraints, the curved lithospheric lineaments observed in gravity anomalies of the Java Sea and the curvature of the Cretaceous Natuna paleo-subduction zone. We complete our model by constructing a time-dependent network of topological plate boundaries and gridded paleo-ages of oceanic basins, allowing us to compare our plate model evolution to seismic tomography. In particular, slabs observed at depths shallower than ∼1000 km beneath northern Borneo and the South China Sea are likely to be remnants of the proto-South China Sea basin.
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