A Large-Scale, Open-Domain, Mixed-Interface Dialogue-Based ITS for STEM

We present Korbit, a large-scale, open-domain, mixed-interface, dialogue-based intelligent tutoring system (ITS). Korbit uses machine learning, natural language processing and reinforcement learning to provide interactive, personalized learning online. Korbit has been designed to easily scale to thousands of subjects, by automating, standardizing and simplifying the content creation process. Unlike other ITS, a teacher can develop new learning modules for Korbit in a matter of hours. To facilitate learning across a widerange of STEM subjects, Korbit uses a mixed-interface, which includes videos, interactive dialogue-based exercises, question-answering, conceptual diagrams, mathematical exercises and gamification elements. Korbit has been built to scale to millions of students, by utilizing a state-of-the-art cloud-based micro-service architecture. Korbit launched its first course in 2019 on machine learning, and since then over 7,000 students have enrolled. Although Korbit was designed to be open-domain and highly scalable, A/B testing experiments with real-world students demonstrate that both student learning outcomes and student motivation are substantially improved compared to typical online courses

Phenoloxidase activity acts as a mosquito innate immune response against infection with semliki forest virus

Several components of the mosquito immune system including the RNA interference (RNAi), JAK/STAT, Toll and IMD pathways have previously been implicated in controlling arbovirus infections. In contrast, the role of the phenoloxidase (PO) cascade in mosquito antiviral immunity is unknown. Here we show that conditioned medium from the Aedes albopictus-derived U4.4 cell line contains a functional PO cascade, which is activated by the bacterium Escherichia coli and the arbovirus Semliki Forest virus (SFV) (Togaviridae; Alphavirus). Production of recombinant SFV expressing the PO cascade inhibitor Egf1.0 blocked PO activity in U4.4 cell- conditioned medium, which resulted in enhanced spread of SFV. Infection of adult female Aedes aegypti by feeding mosquitoes a bloodmeal containing Egf1.0-expressing SFV increased virus replication and mosquito mortality. Collectively, these results suggest the PO cascade of mosquitoes plays an important role in immune defence against arboviruses

Silver hake tracks changes in Northwest Atlantic circulation

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Communications 2 (2011): 412, doi:10.1038/ncomms1420.Recent studies documenting shifts in spatial distribution of many organisms in response to a warming climate highlight the need to understand the mechanisms underlying species distribution at large spatial scales. Here we present one noteworthy example of remote oceanographic processes governing the spatial distribution of adult silver hake, Merluccius bilinearis, a commercially important fish in the Northeast US shelf region. Changes in spatial distribution of silver hake over the last 40 years are highly correlated with the position of the Gulf Stream (GS). These changes in distribution are in direct response to local changes in bottom temperature on the continental shelf that are responding to the same large scale circulation change affecting the GS path, namely changes in the Atlantic Meridional Overturning Circulation (AMOC). If AMOC weakens as is suggested by global climate models, silver hake distribution will remain in a poleward position, the extent to which could be forecast at both decadal and multidecadal scales.J.A.N. was supported by the NOAA Fisheries and the Environment program (FATE). T.M.J. and Y.O.K. were supported by the WHOI Ocean Climate Change Institute and Ocean Life Institute

Synthetic Protocells Interact with Viral Nanomachinery and Inactivate Pathogenic Human Virus

We present a new antiviral strategy and research tool that could be applied to a wide range of enveloped viruses that infect human beings via membrane fusion. We test this strategy on two emerging zoonotic henipaviruses that cause fatal encephalitis in humans, Nipah (NiV) and Hendra (HeV) viruses. In the new approach, artificial cell-like particles (protocells) presenting membrane receptors in a biomimetic manner were developed and found to attract and inactivate henipavirus envelope glycoprotein pseudovirus particles, preventing infection. The protocells do not accumulate virus during the inactivation process. The use of protocells that interact with, but do not accumulate, viruses may provide significant advantages over current antiviral drugs, and this general approach may have wide potential for antiviral development

Foreign policy and globalization theory: The case of Israel

Since the early 1990s, international relations has witnessed a stimulating debate on globalization. This debate laid the foundations for globalization theory (GT), providing the tools for an empirical examination of the globalization of multiple activities: from politics and organized violence, to finance, trade and production, through culture and environmental degradation. However, examination of what appear to be the best-known works on globalization reveals that foreign policy has been virtually excluded from GT. In this context, based on what is described here as a synergistic transformationalist approach (STA) to globalization, I provide a critique of GT. The critique is geared towards examining why foreign policy hitherto has been overlooked by contemporary GT. I expose the problems this generates and address them by exploring how STA enables GT to incorporate foreign policy. I use the case of Israel heuristically to elicit how incorporating foreign policy into GT may provide a better understanding of the relationship between foreign policy and globalization. Three themes are highlighted: the role of foreign policy in inducing and reproducing globalization; determining the mutually constitutive relationship between globalization and the state; and shaping the interfacing between international politics and globalization

Actively evolving subglacial conduits and eskers initiate ice shelf channels at an Antarctic grounding line

Ice-shelf channels are long curvilinear tracts of thin ice found on Antarctic ice shelves. Many of them originate near the grounding line, but their formation mechanisms remain poorly understood. Here we use ice-penetrating radar data from Roi Baudouin Ice Shelf, East Antarctica, to infer that the morphology of several ice-shelf channels is seeded upstream of the grounding line by large basal obstacles indenting the ice from below. We interpret each obstacle as an esker ridge formed from sediments deposited by subglacial water conduits, and calculate that the eskers’ size grows towards the grounding line where deposition rates are maximum. Relict features on the shelf indicate that these linked systems of subglacial conduits and ice-shelf channels have been changing over the past few centuries. Because ice-shelf channels are loci where intense melting occurs to thin an ice shelf, these findings expose a novel link between subglacial drainage, sedimentation and ice-shelf stability

Omega-3 fatty acids in high-risk cardiovascular patients: a meta-analysis of randomized controlled trials

<p>Abstract</p> <p>Background</p> <p>Multiple randomized controlled trials (RCTs) have examined the cardiovascular effects of omega-3 fatty acids and have provided unexplained conflicting results. A meta-analysis of these RCTs to estimate efficacy and safety and potential sources of heterogeneity may be helpful.</p> <p>Methods</p> <p>The Cochrane library, MEDLINE, and EMBASE were systematically searched to identify all interventional trials of omega-3 fatty acids compared to placebo or usual diet in high-risk cardiovascular patients. The primary outcome was all-cause mortality and secondary outcomes were coronary restenosis following percutaneous coronary intervention and safety. Meta-analyses were carried out using Bayesian random-effects models, and heterogeneity was examined using meta-regression.</p> <p>Results</p> <p>A total of 29 RCTs (n = 35,144) met our inclusion criteria, with 25 reporting mortality and 14 reporting restenosis. Omega-3 fatty acids were not associated with a statistically significant decreased mortality (relative risk [RR] = 0.88, 95% Credible Interval [CrI] = 0.64, 1.03) or with restenosis prevention (RR = 0.89, 95% CrI = 0.72, 1.06), though the probability of some benefit remains high (0.93 and 0.90, respectively). However in meta-regressions, there was a >90% probability that larger studies and those with longer follow-up were associated with smaller benefits. No serious safety issues were identified.</p> <p>Conclusions</p> <p>Although not reaching conventional statistical significance, the evidence to date suggests that omega-3 fatty acids may result in a modest reduction in mortality and restenosis. However, caution must be exercised in interpreting these benefits as results were attenuated in higher quality studies, suggesting that bias may be at least partially responsible. Additional high quality studies are required to clarify the role of omega-3 fatty acid supplementation for the secondary prevention of cardiovascular disease.</p

Engineering supported membranes for cell biology

Cell membranes exhibit multiple layers of complexity, ranging from their specific molecular content to their emergent mechanical properties and dynamic spatial organization. Both compositional and geometrical organizations of membrane components are known to play important roles in life processes, including signal transduction. Supported membranes, comprised of a bilayer assembly of phospholipids on the solid substrate, have been productively served as model systems to study wide range problems in cell biology. Because lateral mobility of membrane components is readily preserved, supported lipid membranes with signaling molecules can be utilized to effectively trigger various intercellular reactions. The spatial organization and mechanical deformation of supported membranes can also be manipulated by patterning underlying substrates with modern micro- and nano-fabrication techniques. This article focuses on various applications and methods to spatially patterned biomembranes by means of curvature modulations and spatial reorganizations, and utilizing them to interface with live cells. The integration of biological components into synthetic devices provides a unique approach to investigate molecular mechanisms in cell biology

Peroxisomal alterations in Alzheimer’s disease

In Alzheimer’s disease (AD), lipid alterations are present early during disease progression. As some of these alterations point towards a peroxisomal dysfunction, we investigated peroxisomes in human postmortem brains obtained from the cohort-based, longitudinal Vienna-Transdanube Aging (VITA) study. Based on the neuropathological Braak staging for AD on one hemisphere, the patients were grouped into three cohorts of increasing severity (stages I–II, III–IV, and V–VI, respectively). Lipid analyses of cortical regions from the other hemisphere revealed accumulation of C22:0 and very long-chain fatty acids (VLCFA, C24:0 and C26:0), all substrates for peroxisomal β-oxidation, in cases with stages V–VI pathology compared with those modestly affected (stages I–II). Conversely, the level of plasmalogens, which need intact peroxisomes for their biosynthesis, was decreased in severely affected tissues, in agreement with a peroxisomal dysfunction. In addition, the peroxisomal volume density was increased in the soma of neurons in gyrus frontalis at advanced AD stages. Confocal laser microscopy demonstrated a loss of peroxisomes in neuronal processes with abnormally phosphorylated tau protein, implicating impaired trafficking as the cause of altered peroxisomal distribution. Besides the original Braak staging, the study design allowed a direct correlation between the biochemical findings and the amount of neurofibrillary tangles (NFT) and neuritic plaques, quantified in adjacent tissue sections. Interestingly, the decrease in plasmalogens and the increase in VLCFA and peroxisomal volume density in neuronal somata all showed a stronger association with NFT than with neuritic plaques. These results indicate substantial peroxisome-related alterations in AD, which may contribute to the progression of AD pathology

Management of hydrocele in adolescent patients

Hydrocele is defined as an abnormal collection of serous fluid in the potential space between the parietal and visceral layers of the tunica vaginalis. In the majority of affected adolescents, hydrocele is acquired and is idiopathic in origin. The pathogenesis of idiopathic hydrocele is thought to be an imbalance in the normal process of fluid production and reabsorption. The diagnosis is usually clinical. Taking a thorough history is essential to rule out any fluctuation in size, which is an indication of a patent processus vaginalis. Scrotal ultrasonography is mandatory in nonpalpable testicles to rule out a subtending testicular solid mass requiring inguinal exploration. Otherwise, open hydrocelectomy via a scrotal incision is the standard treatment of idiopathic hydroceles. The second most common cause of hydrocele in adolescents is varicocelectomy. The risk of hydrocele formation is higher with non-artery-sparing procedures or those performed without microsurgical aid, and in surgery requiring cord dissection. If hydrocele occurs after varicocelectomy, initial management should include observation with or without hydrocele aspiration. Large persistent hydroceles are best served by open hydrocelectomy