The quasi-geostrophic approximation for the rotating stratified Boussinesq equations

We prove that the solution of the 3D inviscid Boussinesq equations converges to the solution of the quasi-geostrophic (QG) equations in an asymptotic regime where the intensities of rotation and stratification increase to infinity while the rotation-stratification ratio tends to any positive number other than one. Despite the non-uniformity of the generic convergence rates near the region where the ratio is one, we further show that such quasi-geostrophic approximation continues to be valid even when the ratio goes to one as long as both intensities increase to infinity fast enough. In contrast, we prove non-convergence when such intensities grow sufficiently slow to infinity with the ratio tending to one. Our proof of the non-convergence result contains the first mathematical proof of the Devil's staircase paradox that was originally cast in Theoret. Comput. Fluid Dynamics 9, 223-251 (1997). Combining both results for convergence and non-convergence, we give a lower bound for the growth of the convergence rates when the ratio tends to one. Independently of the aforementioned results proved with respect to the mixed norm for $L^q(0,T;W^{1,\infty})$ which is spatially a type of $L^\infty$, we investigate as well whether spatially $L^2$ type spaces are appropriate for analyzing the quasi-geostrophic approximation or not. We verify that non-convergence actually takes place for any fixed positive rotation-stratification ratio with respect to the $H^s$ norm with any integer $s\geq 3$. Nevertheless, in view of the projections onto the eigenspaces of the linear propagator, we specify a particular class of initial data which ensures convergence even in such $H^s$ regardless of the ratio

SSumM: Sparse Summarization of Massive Graphs

Given a graph G and the desired size k in bits, how can we summarize G within k bits, while minimizing the information loss? Large-scale graphs have become omnipresent, posing considerable computational challenges. Analyzing such large graphs can be fast and easy if they are compressed sufficiently to fit in main memory or even cache. Graph summarization, which yields a coarse-grained summary graph with merged nodes, stands out with several advantages among graph compression techniques. Thus, a number of algorithms have been developed for obtaining a concise summary graph with little information loss or equivalently small reconstruction error. However, the existing methods focus solely on reducing the number of nodes, and they often yield dense summary graphs, failing to achieve better compression rates. Moreover, due to their limited scalability, they can be applied only to moderate-size graphs. In this work, we propose SSumM, a scalable and effective graph-summarization algorithm that yields a sparse summary graph. SSumM not only merges nodes together but also sparsifies the summary graph, and the two strategies are carefully balanced based on the minimum description length principle. Compared with state-of-the-art competitors, SSumM is (a) Concise: yields up to 11.2X smaller summary graphs with similar reconstruction error, (b) Accurate: achieves up to 4.2X smaller reconstruction error with similarly concise outputs, and (c) Scalable: summarizes 26X larger graphs while exhibiting linear scalability. We validate these advantages through extensive experiments on 10 real-world graphs.Comment: to be published in the 26th ACM SIGKDD International Conference on Knowledge Discovery and Data Mining (KDD '20

Caspase-3 Activation via Mitochondria Is Required for Long-Term Depression and AMPA Receptor Internalization

NMDA receptor-dependent synaptic modifications, such as long-term potentiation (LTP) and long-term depression (LTD), are essential for brain development and function. LTD occurs mainly by the removal of AMPA receptors from the postsynaptic membrane, but the underlying molecular mechanisms remain unclear. Here, we show that activation of caspase-3 via mitochondria is required for LTD and AMPA receptor internalization in hippocampal neurons. LTD and AMPA receptor internalization are blocked by peptide inhibitors of caspase-3 and -9. In hippocampal slices from caspase-3 knockout mice, LTD is abolished whereas LTP remains normal. LTD is also prevented by overexpression of the anti-apoptotic proteins XIAP or Bcl-xL, and by a mutant Akt1 protein that is resistant to caspase-3 proteolysis. NMDA receptor stimulation that induces LTD transiently activates caspase-3 in dendrites, without causing cell death. These data indicate an unexpected causal link between the molecular mechanisms of apoptosis and LTD.National Institutes of Health (U.S.) (Fellowship F32-NS046126)National Institutes of Health (U.S.). Intramural Research ProgramNational Institute of Mental Health (U.S.

Impact of Socioeconomic Status on 30-Day and 1-Year Mortalities after Intensive Care Unit Admission in South Korea: A Retrospective Cohort Study

Background Socioeconomic status (SES) is closely associated with health outcomes, including mortality in critically ill patients admitted to intensive care unit (ICU). However, research regarding this issue is lacking, especially in countries where the National Health Insurance System is mainly responsible for health care. This study aimed to investigate how the SES of ICU patients in South Korea is associated with mortality. Methods This was a retrospective observational study of adult patients aged ≥20 years admitted to ICU. Associations between SES-related factors recorded at the time of ICU admission and 30-day and 1-year mortalities were analyzed using univariable and multivariable Cox regression analyses. Results A total of 6,008 patients were included. Of these, 394 (6.6%) died within 30 days of ICU admission, and 1,125 (18.7%) died within 1 year. Multivariable Cox regression analysis found no significant associations between 30-day mortality after ICU admission and SES factors (P>0.05). However, occupation was significantly associated with 1-year mortality after ICU admission. Conclusions Our study shows that 30-day mortality after ICU admission is not associated with SES in the National Health Insurance coverage setting. However, occupation was associated with 1-year mortality after ICU admission

A novel mechanism of hippocampal LTD involving muscarinic receptor-triggered interactions between AMPARs, GRIP and liprin-α

<p>Abstract</p> <p>Background</p> <p>Long-term depression (LTD) in the hippocampus can be induced by activation of different types of G-protein coupled receptors, in particular metabotropic glutamate receptors (mGluRs) and muscarinic acethycholine receptors (mAChRs). Since mGluRs and mAChRs activate the same G-proteins and isoforms of phospholipase C (PLC), it would be expected that these two forms of LTD utilise the same molecular mechanisms. However, we find a distinct mechanism of LTD involving GRIP and liprin-α.</p> <p>Results</p> <p>Whilst both forms of LTD require activation of tyrosine phosphatases and involve internalisation of AMPARs, they use different molecular interactions. Specifically, mAChR-LTD, but not mGluR-LTD, is blocked by peptides that inhibit the binding of GRIP to the AMPA receptor subunit GluA2 and the binding of GRIP to liprin-α. Thus, different receptors that utilise the same G-proteins can regulate AMPAR trafficking and synaptic efficacy via distinct molecular mechanisms.</p> <p>Conclusion</p> <p>Our results suggest that mAChR-LTD selectively involves interactions between GRIP and liprin-α. These data indicate a novel mechanism of synaptic plasticity in which activation of M1 receptors results in AMPAR endocytosis, via a mechanism involving interactions between GluA2, GRIP and liprin-α.</p

Central nervous system superficial siderosis related to spinal lesions

Superficial siderosis is a rare disease of the central nervous system, which is characterized by chronic intrathecal hemorrhage leading to hemosiderin deposition on the leptomeninges and subpial layers of the brain and spinal cord. Patients with the syndrome typically present with sensorineural hearing loss, myelopathy, cerebellar ataxia, pyramidal signs, and cognitive impairment. The most common etiologies of the disease include bleeding of unknown cause, ruptured aneurysms, arteriovenous malformation, and traumatic injury of the brain. Here, we describe two patients diagnosed with superficial siderosis caused by spinal lesions, which is an unusual cause of chronic bleeding due to the presence of the disease

The reemergence of long-term potentiation in aged Alzheimer's disease mouse model

Mouse models of Alzheimer’s disease (AD) have been developed to study the pathophysiology of amyloid β protein (Aβ) toxicity, which is thought to cause severe clinical symptoms such as memory impairment in AD patients. However, inconsistencies exist between studies using these animal models, specifically in terms of the effects on synaptic plasticity, a major cellular model of learning and memory. Whereas some studies find impairments in plasticity in these models, others do not. We show that long-term potentiation (LTP), in the CA1 region of hippocampal slices from this mouse, is impared at Tg2576 adult 6–7 months old. However, LTP is inducible again in slices taken from Tg2576 aged 14–19 months old. In the aged Tg2576, we found that the percentage of parvalbumin (PV)-expressing interneurons in hippocampal CA1-3 region is significantly decreased, and LTP inhibition or reversal mediated by NRG1/ErbB signaling, which requires ErbB4 receptors in PV interneurons, is impaired. Inhibition of ErbB receptor kinase in adult Tg2576 restores LTP but impairs depotentiation as shown in aged Tg2576. Our study suggests that hippocampal LTP reemerges in aged Tg2576. However, this reemerged LTP is an insuppressible form due to impaired NRG1/ErbB signaling, possibly through the loss of PV interneurons

Microtubule-associated protein tau is essential for long-term depression in the hippocampus

The microtubule-associated protein tau is a principal component of neurofibrillary tangles, and has been identified as a key molecule in Alzheimer's disease and other tauopathies. However, it is unknown how a protein that is primarily located in axons is involved in a disease that is believed to have a synaptic origin. To investigate a possible synaptic function of tau, we studied synaptic plasticity in the hippocampus and found a selective deficit in long-term depression (LTD) in tau knockout mice in vivo and in vitro, an effect that was replicated by RNAi knockdown of tau in vitro. We found that the induction of LTD is associated with the glycogen synthase kinase-3-mediated phosphorylation of tau. These observations demonstrate that tau has a critical physiological function in LTD.A.T. was supported by the research funding for longevity sciences (23-39) from National Center for Geriatrics and Gerontology, and the Strategic Research Programme for Brain Science ('Integrated Research on Neuropsychiatric Disorders') and Grant in Aid for Scientific Research on Innovative Areas ('Brain Environment') from the Ministry of Education, Science, Sports and Culture of Japan. K.C., D.J.W. and G.L.C. were supported by UK Wellcome Trust-MRC Neurodegenerative Disease Initiative Programme. K.C. was supported by the Korea-UK Alzheimer's Disease Research Consortium programme from the Ministry of Health and Welfare (Korea). G.L.C. was supported by the WCU Programme (Korea). I.S. was supported by the British Council. The collaboration between K.C. and A.T. was supported by a Sasakawa Foundation grant awarded to K.C. K.C. was supported by the Wolfson Research Merit Award and the Royal Society, London

Early Detection of Cerebral Infarction With Middle Cerebral Artery Occlusion With Functional Near-Infrared Spectroscopy: A Pilot Study

Background: NIRSIT, a functional near-infrared spectroscopy (fNIRS) device with 204 channels, can measure oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR) in non-pulsatile blood flow non-invasively using the absorption difference between HbO2 and HbR at a wavelength of 700–1,000 nm and can display the perfusion status in real time.Objective: We applied NIRSIT to patients with stroke to evaluate the usefulness of NIRSIT as an fNIRS device for the early detection of stroke.Methods: We performed a prospective pilot study in an emergency department (ED). Adult patients who had suspected symptoms and signs of stroke within 12 h of the first abnormal time and who underwent intravenous thrombolysis (IVT) or intra-arterial thrombectomy with acute middle cerebral artery (MCA) or internal carotid artery (ICA) infarction were enrolled. NIRSIT was applied to the patients before the imaging study, and the perfusion status of the brain was displayed in real time at the bedside. We compared the NIRSIT results with the mean transit time (MTT) map from perfusion computed tomography (PCT) and the time-to-peak (TTP) map from perfusion-weighted magnetic resonance imaging (PWI).Results: Six male and three female patients were enrolled, and the median age was 74 years. The most common symptom was unilateral extremity weakness (77.8%), followed by dysarthria (33.3%) and aphasia (11.1%). The median National Institutes of Health Stroke Scale (NIHSS) score was 17. All cases of MCA infarction showed different cerebral oxygen saturation values between bilateral lobes of the brain in fNIRS imaging, and these values matched the PCT and PWI results.Conclusions: The brain hemisphere with low oxygen saturation on fNIRS showed hypoperfusion on PCT or PWI. The fNIRS device could be useful in assessing the perfusion status of the brain and detecting MCA or ICA infarction in real time at the bedside

Intracellular oligomeric amyloid-beta rapidly regulates GluA1 subunit of AMPA receptor in the hippocampus

The acute neurotoxicity of oligomeric forms of amyloid-beta 1-42 (Abeta) is implicated in the pathogenesis of Alzheimer's disease (AD). However, how these oligomers might first impair neuronal function at the onset of pathology is poorly understood. Here we have examined the underlying toxic effects caused by an increase in levels of intracellular Abeta, an event that could be important during the early stages of the disease. We show that oligomerised Abeta induces a rapid enhancement of AMPA receptor-mediated synaptic transmission (EPSCA) when applied intracellularly. This effect is dependent on postsynaptic Ca(2+) and PKA. Knockdown of GluA1, but not GluA2, prevents the effect, as does expression of a S845-phosphomutant of GluA1. Significantly, an inhibitor of Ca(2+)-permeable AMPARs (CP-AMPARs), IEM 1460, reverses the increase in the amplitude of EPSCA. These results suggest that a primary neuronal response to intracellular Abeta oligomers is the rapid synaptic insertion of CP-AMPARs