Interpretable classification of Alzheimer's disease pathologies with a convolutional neural network pipeline.

Neuropathologists assess vast brain areas to identify diverse and subtly-differentiated morphologies. Standard semi-quantitative scoring approaches, however, are coarse-grained and lack precise neuroanatomic localization. We report a proof-of-concept deep learning pipeline that identifies specific neuropathologies-amyloid plaques and cerebral amyloid angiopathy-in immunohistochemically-stained archival slides. Using automated segmentation of stained objects and a cloud-based interface, we annotate > 70,000 plaque candidates from 43 whole slide images (WSIs) to train and evaluate convolutional neural networks. Networks achieve strong plaque classification on a 10-WSI hold-out set (0.993 and 0.743 areas under the receiver operating characteristic and precision recall curve, respectively). Prediction confidence maps visualize morphology distributions at high resolution. Resulting network-derived amyloid beta (Aβ)-burden scores correlate well with established semi-quantitative scores on a 30-WSI blinded hold-out. Finally, saliency mapping demonstrates that networks learn patterns agreeing with accepted pathologic features. This scalable means to augment a neuropathologist's ability suggests a route to neuropathologic deep phenotyping

Syntheses of 3-[(Alkylamino)methylene]-6-methyl-1Hpyridine-2,4-diones, Fluorescence Probes 3-Substituted 7-Methyl-6H-pyrano[3,2-c]pyridine-2,5-diones, and Tetrahydro-6H-2,10-dioxa-9-azaanthracen-1-ones

Various condensation and ring-closing reactions were used for the syntheses of 3-[(alkylamino)methylene]-6-methylpyridine-2,4(1H,3H)-diones, bicyclic pyridinones, and tricyclic morpholinopyrones. For instance, 3-[(dialkylamino)methylene]-6-methylpyridine-2,4(1H,3H)-diones were synthesized from the condensation of dialkylamines and 3-formyl-4-hydroxy-6-methylpyridin-2(1H)-one. 3-Formyl-4-hydroxy-6-methylpyridin-2(1H)-one, derived from 3-formyl-4-hydroxy-6-methylpyridin-2(1H)-one, was used to construct a number of bicyclic pyridinones via a one-pot Knoevenagal and intramolecular lactonization reaction. Tricyclic morpholinopyrones were assembled from a dialkylation reaction involving a dinucleophile, 3-amino-4-hydroxy-6-methyl-2H-pyran-2-one, and a dielectrophile, trans-3,6-dibromocyclohexene. Depending on the reaction conditions, isomers of the tricyclic molecules can be selectively produced, and their chemical structures were unequivocally determined using single-crystal X-ray analyses and 2D COSY spectroscopy. The fluorescently active bicyclic pyridinone compounds show longer absorption (368–430 nm; maximum) and emission wavelengths (450–467 nm) than those of 7-amino-4-methylcoumarin (AMC; λ[subscript abs,max] = 350 nm; λ[subscript em] = 430 nm) suggesting these molecules, such as 3-(2-aminoacetyl)-7-methyl-2H-pyrano[3,2-c]pyridine-2,5(6H)-dione, can be employed as fluorescence activity based probes for tracing biological pathways

Mg-induced increase of band gap in Zn1-xMgxO nanorods revealed by x-ray absorption and emission spectroscopy

[[abstract]]X-rayabsorption near-edge structure (XANES) and x-ray emission spectroscopy (XES) measurements were used to investigate the effect of Mgdoping in ZnOnanorods. The intensities of the features in the O K-edge XANES spectra of Zn1−xMgxOnanorods are lower than those of pure ZnOnanorods, suggesting that Mgdoping increases the negative effective charge of O ions. XES and XANES spectra of O 2p states indicate that Mgdoping raises (lowers) the conduction-band-minimum (valence-band-maximum) and increases the band gap. The band gap is found to increase linearly with the Mg content, as revealed by photoluminescence and combined XANES and XES measurements.[[booktype]]紙本[[booktype]]電子版[[countrycodes]]US

Fluorine doped tin oxide as an alternative of indium tin oxide for bottom electrode of semi-transparent organic photovoltaic devices

Indium tin oxide (ITO) is commonly used as the transparent bottom electrode for organic solar cells. However, it is known that the cost of the ITO is quite high due to the indium element, and in some studies ITO coated glass substrate is found to be the most expensive component of device fabrication. Moreover, indium migration from ITO can cause stability issues in organic solar cells. Nevertheless, the use of ITO as the bottom electrode is still dominating in the field. Here, we explore the possibility of using fluorine doped tin oxide (FTO) as an alternative to ITO for the bottom electrode of organic solar cells particularly on semi-transparent cells. We present side-by-side comparisons on their optical, morphological and device properties and suggest that FTO could be more suitable than ITO as the bottom electrode for glass substrate based organic photovoltaic devices

Hot Streaks in Artistic, Cultural, and Scientific Careers

The hot streak, loosely defined as winning begets more winnings, highlights a specific period during which an individual's performance is substantially higher than her typical performance. While widely debated in sports, gambling, and financial markets over the past several decades, little is known if hot streaks apply to individual careers. Here, building on rich literature on lifecycle of creativity, we collected large-scale career histories of individual artists, movie directors and scientists, tracing the artworks, movies, and scientific publications they produced. We find that, across all three domains, hit works within a career show a high degree of temporal regularity, each career being characterized by bursts of high-impact works occurring in sequence. We demonstrate that these observations can be explained by a simple hot-streak model we developed, allowing us to probe quantitatively the hot streak phenomenon governing individual careers, which we find to be remarkably universal across diverse domains we analyzed: The hot streaks are ubiquitous yet unique across different careers. While the vast majority of individuals have at least one hot streak, hot streaks are most likely to occur only once. The hot streak emerges randomly within an individual's sequence of works, is temporally localized, and is unassociated with any detectable change in productivity. We show that, since works produced during hot streaks garner significantly more impact, the uncovered hot streaks fundamentally drives the collective impact of an individual, ignoring which leads us to systematically over- or under-estimate the future impact of a career. These results not only deepen our quantitative understanding of patterns governing individual ingenuity and success, they may also have implications for decisions and policies involving predicting and nurturing individuals with lasting impact

Neuropathologic features in the hippocampus and cerebellum of three older men with fragile X syndrome

<p>Abstract</p> <p>Background</p> <p>Fragile X syndrome (FXS) is the most common inherited form of intellectual disability, and is the most common single-gene disorder known to be associated with autism. Despite recent advances in functional neuroimaging and our understanding of the molecular pathogenesis, only limited neuropathologic information on FXS is available.</p> <p>Methods</p> <p>Neuropathologic examinations were performed on post-mortem brain tissue from three older men (aged 57, 64 and 78 years) who had received a clinical or genetic diagnosis of FXS. In each case, physical and cognitive features were typical of FXS, and one man was also diagnosed with autism. Guided by reports of clinical and neuroimaging abnormalities of the limbic system and cerebellum of individuals with FXS, the current analysis focused on neuropathologic features present in the hippocampus and the cerebellar vermis.</p> <p>Results</p> <p>Histologic and immunologic staining revealed abnormalities in both the hippocampus and cerebellar vermis. Focal thickening of hippocampal CA1 and irregularities in the appearance of the dentate gyrus were identified. All lobules of the cerebellar vermis and the lateral cortex of the posterior lobe of the cerebellum had decreased numbers of Purkinje cells, which were occasionally misplaced, and often lacked proper orientation. There were mild, albeit excessive, undulations of the internal granular cell layer, with patchy foliar white matter axonal and astrocytic abnormalities. Quantitative analysis documented panfoliar atrophy of both the anterior and posterior lobes of the vermis, with preferential atrophy of the posterior lobule (VI to VII) compared with age-matched normal controls.</p> <p>Conclusions</p> <p>Significant morphologic changes in the hippocampus and cerebellum in three adult men with FXS were identified. This pattern of pathologic features supports the idea that primary defects in neuronal migration, neurogenesis and aging may underlie the neuropathology reported in FXS.</p

Baseline parameters for rotational thromboelastometry (ROTEM®) in healthy women undergoing elective caesarean delivery: A prospective observational study in Australia

Formal reference ranges for rotational thromboelastometry (ROTEM®) in pregnancy have not been obtained in the recommended minimum sample size of 120. This prospective observational study aimed to establish baseline parameters in an Australian population of women undergoing elective caesarean delivery. The secondary aim was to compare these reference ranges with those from prior studies and the manufacturer.Women undergoing elective caesarean delivery at term were included if they were at term, with normal body mass index and had no conditions affecting coagulation. ROTEM® reference ranges were derived by calculating the 2.5 and 97.5 percentiles for INTEM/EXTEM/FIBTEM amplitude at 5 minutes (A5), amplitude at 15 minutes (A15), coagulation time (CT), maximum clot firmness (MCF), and clot formation time (CFT).Of 202 women screened, 132 met the inclusion criteria, having a mean age of 32.7 ± 5.0 years and median body mass index of 23.8 kg/m (interquartile range 21.5-26.4). The reference ranges for selected ROTEM® parameters were as follows: FIBTEM A5 (13-28 mm), FIBTEM CT (40-74 s), FIBTEM MCF (16-34 mm), EXTEM A5 (39-66 mm), EXTEM CT (43-69 s), INTEM A5 (38-63 mm).ROTEM® reference ranges for women with uncomplicated term pregnancies were reported as per the International Federation of Clinical Chemistry. The FIBTEM MCF and FIBTEM/EXTEM/INTEM amplitudes were higher in comparison to the manufacturer's reference ranges for the non-obstetric population. The EXTEM CT was shorter than the non-obstetric reference ranges. These ranges show an increase in coagulability during normal pregnancy compared to the non-pregnant reference ranges

Touching a Teddy Bear Mitigates the Negative Effects of Social Exclusion

There is little empirical research to date that looks at how the deleterious effects of social exclusion can be mitigated. We examined how touching an inanimate object—a teddy bear— might impact the effect of social exclusion on prosocial behavior. Across two studies, we found that socially excluded individuals who touched a teddy bear acted more prosocially as compared to socially excluded individuals who just viewed the teddy bear from a distance. This effect was only observed for socially excluded participants and not for socially included (or control) participants. Overall, the findings suggest that touching a teddy bear mitigates the negative effects of social exclusion to increase prosocial behavior. In Study 2, positiv

Pilot-aided estimation and equalisation of a Radio-over-Fibre system in Wideband Code Division Multiple Access

In this study, the impact of a Radio-over-Fibre (RoF) subsystem on the capacity performance of wideband code division multiple access is evaluated. This study investigates the use of pilot-aided channel estimation to compensate for the optical subsystem non-linearities for different channel conditions, estimation intervals and coding schemes. The results show that pilot-aided channel estimation is an effective method for compensating the composite impairments of the optical subsystem and the radio frequency (RF) channel. It is found that there is always a suitable pilot power level which maximises the system capacity performance regardless of coding scheme and channel condition. Also, the peak capacity is only slightly affected by a decrease in the estimation interval

Merging history of three bimodal clusters

We present a combined X-ray and optical analysis of three bimodal galaxy clusters selected as merging candidates at z ~ 0.1. These targets are part of MUSIC (MUlti--Wavelength Sample of Interacting Clusters), which is a general project designed to study the physics of merging clusters by means of multi-wavelength observations. Observations include spectro-imaging with XMM-Newton EPIC camera, multi-object spectroscopy (260 new redshifts), and wide-field imaging at the ESO 3.6m and 2.2m telescopes. We build a global picture of these clusters using X-ray luminosity and temperature maps together with galaxy density and velocity distributions. Idealized numerical simulations were used to constrain the merging scenario for each system. We show that A2933 is very likely an equal-mass advanced pre-merger ~ 200 Myr before the core collapse, while A2440 and A2384 are post-merger systems ~ 450 Myr and ~1.5 Gyr after core collapse, respectively). In the case of A2384, we detect a spectacular filament of galaxies and gas spreading over more than 1 h^{-1} Mpc, which we infer to have been stripped during the previous collision. The analysis of the MUSIC sample allows us to outline some general properties of merging clusters: a strong luminosity segregation of galaxies in recent post-mergers; the existence of preferential axes --corresponding to the merging directions-- along which the BCGs and structures on various scales are aligned; the concomitance, in most major merger cases, of secondary merging or accretion events, with groups infalling onto the main cluster, and in some cases the evidence of previous merging episodes in one of the main components. These results are in good agreement with the hierarchical scenario of structure formation, in which clusters are expected to form by successive merging events, and matter is accreted along large--scale filaments