643 research outputs found
Transient deformations in the Suez-Sinai area from GPS observations
We analyze data from four GPS campaigns carried out between 1997 and 2002 on
a network of 11 sites in the Suez-Sinai, the area of collision between the
African and the Arabian plates. This is the key area to understand how and in
which way Sinai behaves like a sub-plate of the African plate and the role
played between seismic and geodetic (long term) deformation release. Our
analysis shows that, on average, the Suez-Sinai area motion (in terms of ITRF00
velocities) matches African plate motion (NNR-NUVEL-1A model). However, the
baseline length variations show transient deformations in Sinai and across the
Gulf of Suez, reaching up a maximum value of about 1.5 cm in five years. Since
current geodynamical models do not predict significant tectonic deformation in
this area, we worked under the hypothesis that a contribute may be due to
post-seismic relaxation. Under this hypothesis, we compared the baselines
length variations with the post-seismic relaxation field associated with five
major local earthquakes occurred in the area, testing two different
viscoelastic models. Our results show that the transient deformations are
better modelled for viscosity values of 1018 Pa s in the lower crust and 1020
Pa s in the asthenosphere. However, since the modelled post-seismic effect
results modest and a certain amount of the detected deformation is not
accounted for, we think that an improved modelling should take into account the
lateral heterogeneities of crust and upper mantle structures
Imaging the pulmonary extracellular matrix
The pulmonary extracellular matrix (ECM) plays an important role in the structure and function of the lung. In many respiratory diseases the profile of the ECM reflects pathological changes. The capacity to visualize the ECM and its alterations is of considerable importance to facilitate a better understanding of pulmonary diseases and eventually augment therapeutic solutions. This short review summarizes the current and novel possibilities for imaging the pulmonary ECM by the use of computed tomography (CT), optical coherence tomography (OCT), confocal laser endomicroscopy (CLE) and molecular imaging. While not all these techniques are as yet implemented in standard clinical practice, we address their main features along with the key possibilities for the future
Books
Oral cancer Oral Cancer: Epidemiology, Etiology and Pathology. Ed. by Colin Smith, Jens Pindborg and W. H. Binnie. Pp. ix + 106. Illustrated. R183,30. USA: Hemisphere. 1990.HPV and cervical cancer Human Papillomavirus and Cervical Cancer. Ed. by N. Munoz, F. X. Bosch and O. M. Jensen. Pp. xii + 155. Illustrated. France: International Agency for Research on Cancer. 1989.Child health Child Health in a Multicultural Society. Ed. by John Black. Pp. 75. Illustrated. £7 (including postage). London: BMJ. 1989. (Available also from Libriger Book Distributors).Merck manual of geriatics Merck Manual of Geriatrics. Ed. by William B. Abrams The Andrew J. Fletcher. Pp. xxii + 1267. Illustrated. RI4,50. and I: Merck. 1990. USALiver disease Progress in Liver Diseases. Vol 9. Ed. by Hans Popper and Fenton Schaffner. Pp. xv + 750. Illustrated. RllO. England: Harcourt Brace Jovanovich. 1990.Clinical dietetics and nutrition Clinical Dietetics and Nutrition. 3rd ed. Ed. by F. P. Antia. Pp. xvi +438. Illustrated. Oxford: Oxford University Press. 1989.Atlas of human anatomy Wolf-Heidegger's Atlas of Human Anatomy. Ed. by H. F. Frick, B. Kummer and R. V. Putz. pp. viii + 599. £(j(J. Basel: Karger. 1990.Health system decentralisation Health System Decentralization. Ed. by A. Mills, J. P. Vaughan, D. L. Smith and I. Tabibzadcll. pp. 151. Illustrated. SFr. 26. Geneva: World Health Organisation. 1990.Handbook of occupational medicine Handbook of Occupational Medicine. Ed. by Robert J. McCunney. Pp. xxiii + 510. Illustrated. Boston: Little, Brown. 1988.Leukaemia Leukaemia. 5th ed. Ed. by Edward S. Henderson and T. Andrew Lister. Pp. vii + 821. Illustrated. RHO. Kent: Harcoun Brace Jovanovich. 1990
What is hidden in the darkness? Deep-learning assisted large-scale protein family curation uncovers novel protein families and folds
Driven by the development and upscaling of fast genome sequencing and assembly pipelines, the number of protein-coding sequences deposited in public protein sequence databases is increasing exponentially. Recently, the dramatic success of deep learning-based approaches applied to protein structure prediction has done the same for protein structures. We are now entering a new era in protein sequence and structure annotation, with hundreds of millions of predicted protein structures made available through the AlphaFold database. These models cover most of the catalogued natural proteins, including those difficult to annotate for function or putative biological role based on standard, homology-based approaches. In this work, we quantified how much of such "dark matter" of the natural protein universe was structurally illuminated by AlphaFold2 and modelled this diversity as an interactive sequence similarity network that can be navigated at https://uniprot3d.org/atlas/AFDB90v4 . In the process, we discovered multiple novel protein families by searching for novelties from sequence, structure, and semantic perspectives. We added a number of them to Pfam, and experimentally demonstrate that one of these belongs to a novel superfamily of toxin-antitoxin systems, TumE-TumA. This work highlights the role of large-scale, evolution-driven protein comparison efforts in combination with structural similarities, genomic context conservation, and deep-learning based function prediction tools for the identification of novel protein families, aiding not only annotation and classification efforts but also the curation and prioritisation of target proteins for experimental characterisation
MYCN-targeting miRNAs are predominantly downregulated during MYCN-driven neuroblastoma tumor formation
MYCN is a transcription factor that plays key roles in both normal development and cancer. In neuroblastoma, MYCN acts as a major oncogenic driver through pleiotropic effects controlled by multiple protein encoding genes as well as microRNAs (miRNAs). MYCN activity is tightly regulated at the level of transcription and protein stability through various mechanisms. Like most genes, MYCN is further controlled by miRNAs, but the full complement of all miRNAs implicated in this process has not been determined through an unbiased approach. To elucidate the role of miRNAs in regulation of MYCN, we thus explored the MYCN-miRNA interactome to establish miRNAs controlling MYCN expression levels. We combined results from an unbiased and genome-wide high-throughput miRNA target reporter screen with miRNA and mRNA expression data from patients and a murine neuroblastoma progression model. We identified 29 miRNAs targeting MYCN, of which 12 miRNAs are inversely correlated with MYCN expression or activity in neuroblastoma tumor tissue. The majority of MYCN-targeting miRNAs in neuroblastoma showed a decrease in expression during murine MYCN-driven neuroblastoma tumor development. Therefore, we provide evidence that MYCN-targeting miRNAs are preferentially downregulated in MYCN-driven neuroblastoma, suggesting that MYCN negatively controls the expression of these miRNAs, to safeguard its expression
The effect of cardiac resynchronization without a defibrillator on morbidity and mortality: an individual patient data meta-analysis of COMPANION and CARE-HF
AIMS: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality for patients with heart failure, reduced left ventricular ejection fraction, QRS duration >130 ms and in sinus rhythm. The aim of this study was to identify patient characteristics that predict the effect, specifically, of CRT pacemakers (CRT-P) on all-cause mortality or the composite of hospitalization for heart failure or all-cause mortality. METHODS AND RESULTS: We conducted an individual patient data meta-analysis of the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) and Cardiac Resynchronization-Heart Failure (CARE-HF) trials. Only patients assigned to CRT-P or control (n = 1738) were included in order to avoid confounding from concomitant defibrillator therapy. The influence of baseline characteristics on treatment effects was investigated. Median age was 67 (59-73) years, most patients were men (70%), 68% had a QRS duration of 150-199 ms and 80% had left bundle branch block. Patients assigned to CRT-P had lower rates for all-cause mortality (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.56-0.81; p < 0.0001) and the composite outcome (HR 0.67, 95% CI 0.58-0.78; p < 0.0001). No pre-specified characteristic, including sex, aetiology of ventricular dysfunction, QRS duration (within the studied range) or morphology or PR interval significantly influenced the effect of CRT-P on all-cause mortality or the composite outcome. However, CRT-P had a greater effect on the composite outcome for patients with lower body surface area and those prescribed beta-blockers. CONCLUSIONS: Cardiac resynchronization therapy-pacemaker reduces morbidity and mortality in appropriately selected patients with heart failure. Benefits may be greater in smaller patients and in those receiving beta-blockers. Neither QRS duration nor morphology independently predicted the benefit of CRT-P. CLINICAL TRIAL REGISTRATION: COMPANION, NCT00180258; CARE-HF, NCT00170300
A Multi-Modal Public Transport Solution For Male, Maldives
Male, the island capital of the Maldives, an archipelago of over 1000 islands in the Indian Ocean faces chronic traffic congestion. This 2 sq km island is home to over 100,000 people. There is a taxi service comprising of around 450 vehicles and a dhoni (ferry) service amounting to over 100 vessels to neighbouring islands. Male, which is fast becoming a small urban centre faces typical peak period traffic issues. The vehicle fleet is dominated by motor cycles which still contribute to traffic congestion in narrow streets. The taxi system which comprises of individually owned taxis registered with a ‘call centre’, provide limited services but fails during peak demand periods especially on rainy days. There is very little coordination between the ferry and taxi services. The paper is based on the results of a detailed urban transport planning study carried out in Male Urban Area which included passenger interviews, vehicle counts and travel time surveys covering all modes of motorized and non-motorized travel. This paper investigates the introduction of a mini-bus transport system that would provide easy transfers between ferries and major traffic generators and attractors. The contribution of a mini-bus service in the long-term is also discussed with respect to implementation of traffic demand management measures. This paper discuses the most appropriate type of vehicle that could be used and the potential framework for ownership and management of such a system taking in to consideration the multi-modal connectivity and also the service parameters for the operation of a successful minibus service. The paper also analyses the present operation of the ferry services and investigates its ownership and operation parameters for efficiency and cost effectiveness. The paper reports reasons for the varied efficiencies seen on the different routes and the impact the informal and loosely regulated service providers have on the key performance indicators of these services. It also compares cost between different ferry services and studies the relationship between the ownership structure, technology levels, productivity and fare.Institute of Transport and Logistics Studies. Faculty of Economics and Business. The University of Sydne
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