A computationally and cognitively plausible model of supervised and unsupervised learning

Author version made available in accordance with the publisher's policy. "The final publication is available at link.springer.com”The issue of chance correction has been discussed for many decades in the context of statistics, psychology and machine learning, with multiple measures being shown to have desirable properties, including various definitions of Kappa or Correlation, and the psychologically validated ΔP measures. In this paper, we discuss the relationships between these measures, showing that they form part of a single family of measures, and that using an appropriate measure can positively impact learning

Fluid-membrane tethers: minimal surfaces and elastic boundary layers

Thin cylindrical tethers are common lipid bilayer membrane structures, arising in situations ranging from micromanipulation experiments on artificial vesicles to the dynamic structure of the Golgi apparatus. We study the shape and formation of a tether in terms of the classical soap-film problem, which is applied to the case of a membrane disk under tension subject to a point force. A tether forms from the elastic boundary layer near the point of application of the force, for sufficiently large displacement. Analytic results for various aspects of the membrane shape are given.Comment: 12 page

A New Composite Restorative Based on a Hydrophobic Matrix

A hydrophobic restorative composite based on a fluorocarbon analog of an alkyl methacrylate and a bisphenol adduct was formulated into a one-paste system, which polymerized in the presence of blue light. Physical, mechanical, and water-related properties were determined. High contact angles and low water sorption were shown by the experimental composite. Capillary penetration of oral fluids around restorations, therefore, could be prevented in the presence of this highly hydrophobic surface. The physical and mechanical properties of the experimental composite were either comparable to or somewhat less favorable than commercial Bis-GMA composites.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67042/2/10.1177_00220345790580100401.pd

Trisomy 21 activates the kynurenine pathway via increased dosage of interferon receptors

Altres ajuts: This work has also been supported by a "Marató TV3" grant (20141210 to J.F. and 044412 to R.B.).Trisomy 21 (T21) causes Down syndrome (DS), affecting immune and neurological function by ill-defined mechanisms. Here we report a large metabolomics study of plasma and cerebrospinal fluid, showing in independent cohorts that people with DS produce elevated levels of kynurenine and quinolinic acid, two tryptophan catabolites with potent immunosuppressive and neurotoxic properties, respectively. Immune cells of people with DS overexpress IDO1, the rate-limiting enzyme in the kynurenine pathway (KP) and a known interferon (IFN)-stimulated gene. Furthermore, the levels of IFN-inducible cytokines positively correlate with KP dysregulation. Using metabolic tracing assays, we show that overexpression of IFN receptors encoded on chromosome 21 contribute to enhanced IFN stimulation, thereby causing IDO1 overexpression and kynurenine overproduction in cells with T21. Finally, a mouse model of DS carrying triplication of IFN receptors exhibits KP dysregulation. Together, our results reveal a mechanism by which T21 could drive immunosuppression and neurotoxicity in DS

Estuarine clay mineral distribution:Modern analogue for ancient sandstone reservoir quality prediction

The spatial distribution of clay minerals in sandstones, which may both enhance or degrade reservoir quality, is poorly understood. To address this, clay mineral distribution patterns and host‐sediment properties (grain size, sorting, clay fraction abundance and bioturbation intensity) have, for the first time, been determined and mapped at an unprecedentedly high‐resolution in a modern estuarine setting (Ravenglass Estuary, UK). Results show that the estuary sediment is dominated by illite with subordinate chlorite and kaolinite, although the rivers supply sediment with less illite and significantly more chlorite than found in the estuary. Fluvial‐supplied sediment has been locally diluted by sediment derived from glaciogenic drift deposits on the margins of the estuary. Detailed clay mineral maps and statistical analyses reveal that the estuary has a heterogeneous distribution of illite, chlorite and kaolinite. Chlorite is relatively most abundant on the northern foreshore and backshore and is concentrated in coarse‐grained inner estuary dunes and tidal bars. Illite is relatively most abundant (as well as most crystalline and most Fe–Mg‐rich) in fine‐grained inner estuary and central basin mud and mixed flats. Kaolinite has the highest abundance in fluvial sediment and is relatively homogenous in tidally‐influenced environments. Clay mineral distribution patterns in the Ravenglass Estuary have been strongly influenced by sediment supply (residence time) and subsequently modified by hydrodynamic processes. There is no relationship between macro‐faunal bioturbation intensity and the abundance of chlorite, illite or kaolinite. Based on this modern‐analogue study, outer estuarine sediments are likely to be heavily quartz cemented in deeply‐buried (burial temperatures exceeding 80 to 100°C) sandstone reservoirs due to a paucity of clay grade material (<0·5%) to form complete grain coats. In contrast, chlorite‐enriched tidal bars and dunes in the inner estuary, with their well‐developed detrital clay coats, are likely to have quartz cement inhibiting authigenic clay coats in deeply‐buried sandstones

Host range, transmissibility and antigenicity of a pangolin coronavirus

The pathogenic and cross-species transmission potential of SARS-CoV-2-related coronaviruses (CoVs) remain poorly characterized. Here we recovered a wild-type pangolin (Pg) CoV GD strain including derivatives encoding reporter genes using reverse genetics. In primary human cells, PgCoV replicated efficiently but with reduced fitness and showed less efficient transmission via airborne route compared with SARS-CoV-2 in hamsters. PgCoV was potently inhibited by US Food and Drug Administration approved drugs, and neutralized by COVID-19 patient sera and SARS-CoV-2 therapeutic antibodies in vitro. A pan-Sarbecovirus antibody and SARS-CoV-2 S2P recombinant protein vaccine protected BALB/c mice from PgCoV infection. In K18-hACE2 mice, PgCoV infection caused severe clinical disease, but mice were protected by a SARS-CoV-2 human antibody. Efficient PgCoV replication in primary human cells and hACE2 mice, coupled with a capacity for airborne spread, highlights an emergence potential. However, low competitive fitness, pre-immune humans and the benefit of COVID-19 countermeasures should impede its ability to spread globally in human populations

Counterpoint. Early intervention for psychosis risk syndromes: Minimizing risk and maximizing benefit

Background: Malhi et al. in this issue critique the clinical high risk (CHR) syndrome for psychosis. Method: Response to points of critique. Results: We agree that inconsistency in CHR nomenclature should be minimized. We respectfully disagree on other points. In our view: a) individuals with CHR and their families need help, using existing interventions, even though we do not yet fully understand disease mechanisms; b) substantial progress has been made in identification of biomarkers; c) symptoms used to identify CHR are specific to psychotic illnesses; d) CHR diagnosis is not “extremely difficult”; e) the pattern of progression, although heterogenous, is discernible; f) “psychosis-like symptoms” are common but are not used to identify CHR; and g) on the point described as ‘the real risk,’ CHR diagnosis does not frequently cause harmful stigma. Discussion: Malhi et al.'s arguments do not fairly characterize progress in the CHR field nor efforts to minimize stigma. That said, much work remains in areas of consistent nomenclature, mechanisms of disease, dissecting heterogeneity, and biomarkers. With regard to what the authors term the “real risk” of stigma associated with a CHR “label,” however, our view is that avoiding words like “risk” and “psychosis” reinforces the stigma that both they and we mean to oppose. Moreover, patients and their families benefit from being given a term that describes what is happening to them

A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers

We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks. Pathway analysis identified subtypes with high leukocyte infiltration, raising potential implications for immunotherapy. Using 16 key molecular features, we identified five prognostic subtypes and developed a decision tree that classified patients into the subtypes based on just six features that are assessable in clinical laboratories. By performing molecular analyses of 2,579 TCGA gynecological (OV, UCEC, CESC, and UCS) and breast tumors, Berger et al. identify five prognostic subtypes using 16 key molecular features and propose a decision tree based on six clinically assessable features that classifies patients into the subtypes