1,054 research outputs found
453 NOVEL BIOINFORMATIC APPROACHES FOR IDENTIFYING PUTATIVE OA BIOMARKERS: LABEL-FREE QUANTIFICATION OF PROTEINS IN THE SECRETÓME OF ARTICULAR CARTILAGE
Synthesis and Assembly of Nonspherical Hollow Silica Colloids Under Confinement
Hard peanut-shaped colloids were synthesized and organized into a degenerate crystal (DC), a phase previously observed only in simulations. In this structure, particle lobes tile a triangular lattice while their orientations uniformly populate the three underlying crystalline directions
Switching of a photochromic molecule on gold electrodes: single-molecule measurements
We have studied the electronic changes caused by light-induced isomerization of a photochromic molecule between an open state (that absorbs in the UV to become closed) and a closed state (that absorbs in the visible to become open). Data obtained using a newly developed repetitive break junction method are interpreted in terms of single-molecule resistances of 526 +/- 90 M Omega in the open form and 4 +/- 1 M Omega in the closed form when the molecule is bound between two gold contacts via dithiol linkages. The corresponding ratio of open to closed resistance is in close agreement with the results of ab initio calculations, though the measured resistances are about half of the calculated values. Optical spectroscopy indicates that the photoisomerization occurs in both directions on small gold particles, evaporated thin gold films, and in the break junction experiments
ZnII(atsm) is protective in amyotrophic lateral sclerosis model mice via a copper delivery mechanism
AbstractMutations in the metalloprotein Cu,Zn-superoxide dismutase (SOD1) cause approximately 20% of familial cases of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease for which effective therapeutics do not yet exist. Transgenic rodent models based on over-expression of mutant SOD1 have been developed and these have provided opportunity to test new therapeutic strategies and to study the mechanisms of mutant SOD1 toxicity. Although the mechanisms of mutant SOD1 toxicity are yet to be fully elucidated, incorrect or incomplete metallation of SOD1 confers abnormal folding, aggregation and biochemical properties, and improving the metallation state of SOD1 provides a viable therapeutic option. The therapeutic effects of delivering copper (Cu) to mutant SOD1 have been demonstrated recently. The aim of the current study was to determine if delivery of zinc (Zn) to SOD1 was also therapeutic. To investigate this, SOD1G37R mice were treated with the metal complex diacetyl-bis(4-methylthiosemicarbazonato)zincII [ZnII(atsm)]. Treatment resulted in an improvement in locomotor function and survival of the mice. However, biochemical analysis of spinal cord tissue collected from the mice revealed that the treatment did not increase overall Zn levels in the spinal cord nor the Zn content of SOD1. In contrast, overall levels of Cu in the spinal cord were elevated in the ZnII(atsm)-treated SOD1G37R mice and the Cu content of SOD1 was also elevated. Further experiments demonstrated transmetallation of ZnII(atsm) in the presence of Cu to form the Cu-analogue CuII(atsm), indicating that the observed therapeutic effects for ZnII(atsm) in SOD1G37R mice may in fact be due to in vivo transmetallation and subsequent delivery of Cu
A new P-wave tomographic model (cap22) for North America: implications for the subduction and cratonic metasomatic modification history of western Canada and Alaska
Our understanding of the present-day state and evolution of the Canadian and Alaskan mantle is hindered by a lack of absolute P-wavespeed constraints that provide complementary sensitivity to composition in conjunction with existing S-wavespeed models. Consequently, cratonic modification, orogenic history of western North America and complexities within the Alaskan Proto-Pacific subduction system remain enigmatic. One challenge concerns the difficulties in extracting absolute arrival-time measurements from often-noisy data recorded by temporary seismograph networks required to fill gaps in continental and global databases. Using the Absolute Arrival-time Recovery Method (AARM), we extract >180,000 new absolute arrival-time residuals from seismograph stations across Canada and Alaska and combine these data with USArray and global arrival-time data from the contiguous US and Alaska. We develop a new absolute P-wavespeed tomographic model, CAP22, spanning North America that significantly improves resolution in Canada and Alaska over previous models. Slow wavespeeds below the Canadian Cordillera sharply abut fast wavespeeds of the continental interior at the Rocky Mountain Trench in southwest Canada. Slow wavespeeds below the Mackenzie Mountains continue farther inland in northwest Canada, indicating Proterozoic-Archean metasomatism of the Slave craton. Inherited tectonic lineaments colocated with this north-south wavespeed boundary suggest that both the crust and mantle may control Cordilleran orogenic processes. In Alaska, fast upper mantle wavespeeds below the Wrangell Volcanic Field favor a conventional subduction related mechanism for volcanism. Finally, seismic evidence for the subducted Kula and Yukon slabs indicate tectonic reconstructions of western North America may require revision
Measuring Care and Justice Moral Orientation: Italian validation and revision of the MMO-2 scale
This study presents the Italian adaptation of the Measure of Moral Orientation Second Revision (MMO-2). Based on Carol Gilligan’s theory of the Ethics of Care, the MMO-2 was designed to measure two complementary moral stances, namely Care and Justice. For this study, questionnaire responses from 683 university students were assessed against an Italian-adapted MMO-2 scale. Data were analysed through Exploratory Structural Equation Modelling first as separate scenarios and then as a single model. The final model comprises four intercorrelated pairs of latent variables and shows highly satisfactory goodness of fit indices with moderate construct validity and reliability. Strengths, limitations, and directions for the future developments of the MMO-2 will be discussed
The Neuroscience of Sadness: A Multidisciplinary Synthesis and Collaborative Review for the Human Affectome Project
Sadness is typically characterized by raised inner eyebrows, lowered corners of the mouth, reduced walking speed, and slumped posture. Ancient subcortical circuitry provides a neuroanatomical foundation, extending from dorsal periaqueductal grey to subgenual anterior cingulate, the latter of which is now a treatment target in disorders of sadness. Electrophysiological studies further emphasize a role for reduced left relative to right frontal asymmetry in sadness, underpinning interest in the transcranial stimulation of left dorsolateral prefrontal cortex as an antidepressant target. Neuroimaging studies – including meta-analyses – indicate that sadness is associated with reduced cortical activation, which may contribute to reduced parasympathetic inhibitory control over medullary cardioacceleratory circuits. Reduced cardiac control may – in part – contribute to epidemiological reports of reduced life expectancy in affective disorders, effects equivalent to heavy smoking. We suggest that the field may be moving toward a theoretical consensus, in which different models relating to basic emotion theory and psychological constructionism may be considered as complementary, working at different levels of the phylogenetic hierarchy
An Anglo-Saxon execution cemetery at Walkington Wold, Yorkshire
This paper presents a re-evaluation of a cemetery excavated over
30 years ago at Walkington Wold in east Yorkshire. The cemetery is
characterized by careless burial on diverse alignments, and by the fact that
most of the skeletons did not have associated crania. The cemetery has been
variously described as being the result of an early post-Roman massacre, as
providing evidence for a ‘Celtic’ head cult or as an Anglo-Saxon execution
cemetery. In order to resolve the matter, radiocarbon dates were acquired and
a re-examination of the skeletal remains was undertaken. It was confirmed that
the cemetery was an Anglo-Saxon execution cemetery, the only known example
from northern England, and the site is set into its wider context in the paper
Dynamics of trimming the content of face representations for categorization in the brain
To understand visual cognition, it is imperative to determine when, how and with what information the human brain categorizes the visual input. Visual categorization consistently involves at least an early and a late stage: the occipito-temporal N170 event related potential related to stimulus encoding and the parietal P300 involved in perceptual decisions. Here we sought to understand how the brain globally transforms its representations of face categories from their early encoding to the later decision stage over the 400 ms time window encompassing the N170 and P300 brain events. We applied classification image techniques to the behavioral and electroencephalographic data of three observers who categorized seven facial expressions of emotion and report two main findings: (1) Over the 400 ms time course, processing of facial features initially spreads bilaterally across the left and right occipito-temporal regions to dynamically converge onto the centro-parietal region; (2) Concurrently, information processing gradually shifts from encoding common face features across all spatial scales (e.g. the eyes) to representing only the finer scales of the diagnostic features that are richer in useful information for behavior (e.g. the wide opened eyes in 'fear'; the detailed mouth in 'happy'). Our findings suggest that the brain refines its diagnostic representations of visual categories over the first 400 ms of processing by trimming a thorough encoding of features over the N170, to leave only the detailed information important for perceptual decisions over the P300
The association of cold weather and all-cause and cause-specific mortality in the island of Ireland between 1984 and 2007
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This article has been made available through the Brunel Open Access Publishing Fund.Background This study aimed to assess the relationship between cold temperature and daily mortality in the Republic of Ireland (ROI) and Northern Ireland (NI), and to explore any differences in the population responses between the two jurisdictions. Methods A time-stratified case-crossover approach was used to examine this relationship in two adult national populations, between 1984 and 2007. Daily mortality risk was examined in association with exposure to daily maximum temperatures on the same day and up to 6 weeks preceding death, during the winter (December-February) and cold period (October-March), using distributed lag models. Model stratification by age and gender assessed for modification of the cold weather-mortality relationship. Results In the ROI, the impact of cold weather in winter persisted up to 35 days, with a cumulative mortality increase for all-causes of 6.4% (95%CI=4.8%-7.9%) in relation to every 1oC drop in daily maximum temperature, similar increases for cardiovascular disease (CVD) and stroke, and twice as much for respiratory causes. In NI, these associations were less pronounced for CVD causes, and overall extended up to 28 days. Effects of cold weather on mortality increased with age in both jurisdictions, and some suggestive gender differences were observed. Conclusions The study findings indicated strong cold weather-mortality associations in the island of Ireland; these effects were less persistent, and for CVD mortality, smaller in NI than in the ROI. Together with suggestive differences in associations by age and gender between the two Irish jurisdictions, the findings suggest potential contribution of underlying societal differences, and require further exploration. The evidence provided here will hope to contribute to the current efforts to modify fuel policy and reduce winter mortality in Ireland
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