46,426 research outputs found
Data-driven modelling of neurodegenerative disease progression: thinking outside the black box
No full textData-driven disease progression models are an emerging set of computational tools that reconstruct disease timelines for long-term chronic diseases, providing unique insights into disease processes and their underlying mechanisms. Such methods combine a priori human knowledge and assumptions with large-scale data processing and parameter estimation to infer long-term disease trajectories from short-term data. In contrast to ‘black box’ machine learning tools, data-driven disease progression models typically require fewer data and are inherently interpretable, thereby aiding disease understanding in addition to enabling classification, prediction and stratification. In this Review, we place the current landscape of data-driven disease progression models in a general framework and discuss their enhanced utility for constructing a disease timeline compared with wider machine learning tools that construct static disease profiles. We review the insights they have enabled across multiple neurodegenerative diseases, notably Alzheimer disease, for applications such as determining temporal trajectories of disease biomarkers, testing hypotheses about disease mechanisms and uncovering disease subtypes. We outline key areas for technological development and translation to a broader range of neuroscience and non-neuroscience applications. Finally, we discuss potential pathways and barriers to integrating disease progression models into clinical practice and trial settings
Data-Driven Sequence of Changes to Anatomical Brain Connectivity in Sporadic Alzheimer’s Disease
No full textModel-based investigations of transneuronal spreading mechanisms in neurodegenerative diseases relate the pattern of pathology severity to the brain’s connectivity matrix, which reveals information about how pathology propagates through the connectivity network. Such network models typically use networks based on functional or structural connectivity in young and healthy individuals, and only end-stage patterns of pathology, thereby ignoring/excluding the effects of normal aging and disease progression. Here, we examine the sequence of changes in the elderly brain’s anatomical connectivity over the course of a neurodegenerative disease. We do this in a data-driven manner that is not dependent upon clinical disease stage, by using event-based disease progression modeling. Using data from the Alzheimer’s Disease Neuroimaging Initiative dataset, we sequence the progressive decline of anatomical connectivity, as quantified by graph-theory metrics, in the Alzheimer’s disease brain. Ours is the first single model to contribute to understanding all three of the nature, the location, and the sequence of changes to anatomical connectivity in the human brain due to Alzheimer’s disease. Our experimental results reveal new insights into Alzheimer’s disease: that degeneration of anatomical connectivity in the brain may be a viable, even early, biomarker and should be considered when studying such neurodegenerative diseases
p-n Junction Formation in i-Ge Crystal by Laser Radiation
No full textP-n junction is the main component of many semiconductor devices. Thermodiffusion, ion implantation and molecular beam epitaxy are only a few methods to form a p-n junction. The main drawback for these methods is high cost per p-n junction since the equipment for these methods is expensive. A possibility of p-n junction formation by laser radiation was shown in several p- and n-type semiconductors: p-Si[1,2], p-CdTe[3], p-InSb[4,5], p-InAs[6], p-PbSe[7] and p-Ge[8] due to inversion of conductivity type. Unfortunately, the mechanism of p-n junction formation by laser radiation is not clear until now.
In the present research rectification effect of current-voltage characteristic in pure intrinsic Ge crystal after irradiation by Nd:YAG laser was observed. The effect is characterised by threshold intensity of the laser radiation. Increase of rectification ratio of current-voltage characteristics and barrier height with intensity of the laser radiation, energy of laser radiation quanta and number of pulses was observed in this experiment. The mechanism of this phenomenon is explained by generation and redistribution of intrinsic point defects in temperature gradient field, which causes strongly absorbed laser radiation. The redistribution of defects takes place because interstitial atoms drift towards the irradiated surface, but vacancies drift in the opposite direction – in the bulk of semiconductor according to Thermogradient effect. Since interstitials in Ge crystal are of n-type and vacancies are known to be of p-type, a p-n junction is formed.
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[5] A. Medvid‘ et al. Vacuum, 51, 245 (1998).
[6] L. Kurbatov et al. Reports of Acad. Sc.USSR, 268, 594 (1983)
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Acknowledgments.
The author gratefully acknowledges financial support in part by Europe Project in the Framework of MATERA+ project, European Regional Development Fund within the project “Sol-gel and laser technologies for the development of nanostructures and barrier structures”, the ESF Projects No. 1DP/1.1.1.2.0/09/ APIA/VIAA/142 and «Support for the implementation of doctoral studies at Riga Technical University»
Experimental investigation into the effect of substrate clamping on the piezoelectric behaviour of thick-film PZT elements
No full textThis paper details an experimental investigation of the clamping effect associated with thick-film piezoelectric elements printed on a substrate. The clamping effect reduces the measured piezoelectric coefficient, d33, of the film. This reduction is due to the influence of the d31 component in the film when a deformation of the structure occurs, by either the direct or indirect piezoelectric effect. Theoretical analysis shows a reduction in the measured d33 of 62%, i.e. a standard bulk lead zirconate titanate (PZT)-5H sample with a manufacturer specified d33 of 593pC/N would fall to 227.8pC/N. To confirm this effect, the d33 coefficients of five thin bulk PZT-5H samples of 220µm thickness were measured before and after their attachment to a metallized 96% alumina substrate. The experimental results show a reduction in d33 of 74% from 529pC/N to 139pC/N. The theoretical analysis was then applied to existing University of Southampton thick-film devices. It is estimated that the measured d33 value of 131pC/N of the thick-film devices is the equivalent of an unconstrained d33 of 345pC/N
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
NMN adenylyltransferase and poly (ADP-Ribose) polymerase in bovine tissues and characterization of NMN adenylyltransferase from bull testis
No full textA note on the countable extensions of separable p\sp {\omega+n}-projective abelian -groups
No full textsummary:It is proved that if is a pure -projective subgroup of the separable abelian -group for such that , then is -projective as well. This generalizes results due to Irwin-Snabb-Cutler (CommentṀathU̇nivṠtṖauli, 1986) and the author (Arch. Math. (Brno), 2005)
THE ANOMALOUS FLUORESCENCE OF N,N-DIALKYL-P-CYANOANILINES
No full textPresent address of Omar S. Khalil: School of Chemistry, Rutgers University New Brunswick, New Jersey, 08903.Author Institution: Coates Chemical Laboratories, Louisiana State UniversityAbsorption and luminescence spectra of N,N-dialkyl-p-cyanoanilines in a variety of solvents are reported. Evidences for ``dimer” and ``excimer” formation are provided and the anomalous luminescences of these molecules, which exhibits three distinctly-different fluorescence emissions and two very dissimilar phosphorescence processes, are interpreted
The effects of clobazam and lorazepam on patient's psychomotor performance and anxiety
No full textBibliography: leaf 162-174.Psychomotor performance, drowsiness and anxiety were measured in 70 anxious outpatients in a randomized double-blind, placebo- controlled trial comparing the 1,5 benzodiazepine clobazam (10 mg (two times a day) to lorazepam (1 mg two times a day). Carefully selected tests were administered pre-treatment and at 2 and 9 days after treatment. Compliance was checked by blood assays. There was a significant improvement in anxiety in the clobazam, lorazepam and placebo groups at 2 days and a further improvement at 9 days but only in the clobazam and lorazepam groups. The lorazepam patients had a significantly higher overall drowsiness rating than the clobazam and placebo groups. Both the clobazam and placebo groups showed an improvement over time in choice reaction time, the Digit Symbol Substitution Test, Purdue Pegboard tests and the Inglis paired-associate learning test. There was no change in critical flicker fusion threshold. The lorazepam-treated patients demonstrated exactly the same pattern on psychomotor performance tests except that there was an impairment in two of the Purdue pegboard tests on day 2. On the basis of previous volunteer studies with lorazepam, a far more general and consistent impairment of psychomotor performance was expected with that drug. This indicates that the finding derived from normal volunteers cannot necessarily be extrapolated to anxious patients. The possible reasons for the different responses in volunteers and patients are discussed. The practical implications of the various findings and the recommendations for future research are also considered
A 2 h periodic variation in the low-mass X-ray binary Ser X-1
No full textSpectroscopy of the low-mass X-ray binary Ser X-1 using the Gran Telescopio Canarias have revealed a ?2 h periodic variability that is present in the three strongest emission lines. We tentatively interpret this variability as due to orbital motion, making it the first indication of the orbital period of Ser X-1. Together with the fact that the emission lines are remarkably narrow, but still resolved, we show that a main-sequence K dwarf together with a canonical 1.4 M? neutron star gives a good description of the system. In this scenario, the most likely place for the emission lines to arise is the accretion disc, instead of a localized region in the binary (such as the irradiated surface or the stream-impact point), and their narrowness is due instead to the low inclination (?10°) of Ser X-1
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