139 research outputs found
A smoothed stochastic earthquake rate model considering seismicity and fault moment release for Europe
We present a time-independent gridded earthquake rate forecast for the European region including Turkey. The spatial component of our model is based on kernel density estimation techniques, which we applied to both past earthquake locations and fault moment release on mapped crustal faults and subduction zone interfaces with assigned slip rates. Our forecast relies on the assumption that the locations of past seismicity is a good guide to future seismicity, and that future large-magnitude events occur more likely in the vicinity of known faults. We show that the optimal weighted sum of the corresponding two spatial densities depends on the magnitude range considered. The kernel bandwidths and density weighting function are optimized using retrospective likelihood-based forecast experiments. We computed earthquake activity rates (a- and b-value) of the truncated Gutenberg-Richter distribution separately for crustal and subduction seismicity based on a maximum likelihood approach that considers the spatial and temporal completeness history of the catalogue. The final annual rate of our forecast is purely driven by the maximum likelihood fit of activity rates to the catalogue data, whereas its spatial component incorporates contributions from both earthquake and fault moment-rate densities. Our model constitutes one branch of the earthquake source model logic tree of the 2013 European seismic hazard model released by the EU-FP7 project âSeismic HAzard haRmonization in Europe' (SHARE) and contributes to the assessment of epistemic uncertainties in earthquake activity rates. We performed retrospective and pseudo-prospective likelihood consistency tests to underline the reliability of our model and SHARE's area source model (ASM) using the testing algorithms applied in the collaboratory for the study of earthquake predictability (CSEP). We comparatively tested our model's forecasting skill against the ASM and find a statistically significant better performance for testing periods of 10-20yr. The testing results suggest that our model is a viable candidate model to serve for long-term forecasting on timescales of years to decades for the European regio
The influence of palatal harvesting technique on the donor site vascular injury: A splitâ mouth comparative cadaver study
BackgroundThe aim of this study was to evaluate the influence of two harvesting approaches on the donor site vascular injury.MethodsA splitâ mouth cadaver study was designed on 21 fresh donor heads. Every hemiâ palate was assigned to receive the trapâ door harvesting technique (TDT) or the epithelialized free gingival graft harvesting technique (FGGT). A soft tissue graft was harvested from each side for histology analyses. Betadine solution was used to inject the external carotid artery and a collagen sponge was positioned over the harvested area to compare the amount of â leakage.â ResultsThe mean leakage observed was 16.56Ă Ă¹à3.01 ĂÂľL in the FGGTâ harvested sites, and 69.21Ă Ă¹à7.08 ĂÂľL for the TDT group, a ratio of 4.18 (PĂ <Ă 0.01). Regression analyses demonstrated a trend for more leakage at thinner palatal sites for the FGGT group (PĂ =Ă 0.09), and a statistically significant correlation for the TDTâ harvest sites (PĂ =Ă 0.02). Additionally, a shallow palatal vault height (PVH) was associated with a higher leakage in both harvesting groups (PĂ =Ă 0.02). The histomorphometric analyses revealed that grafts harvested with TDT exhibited a significantly higher mean number of medium (øà=Ă 0.1 to 0.5Ă mm, PĂ =Ă 0.03), and large vessels (ø â ÂĽ 0.5Ă mm, PĂ =Ă 0.02).ConclusionsWithin the limitations of the present research, the TDT resulted in a significantly higher leakage than the FGGT, which was also correlated with the histology analyses where a greater number of medium and large vessels were observed in the harvested grafts.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153658/1/jper10394.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153658/2/jper10394_am.pd
Endothelial cell-derived interleukin-6 regulates tumor growth
Abstract
Background
Endothelial cells play a complex role in the pathobiology of cancer. This role is not limited to the making of blood vessels to allow for influx of oxygen and nutrients required for the high metabolic demands of tumor cells. Indeed, it has been recently shown that tumor-associated endothelial cells secrete molecules that enhance tumor cell survival and cancer stem cell self-renewal. The hypothesis underlying this work is that specific disruption of endothelial cell-initiated signaling inhibits tumor growth.
Methods
Conditioned medium from primary human dermal microvascular endothelial cells (HDMEC) stably transduced with silencing RNA for IL-6 (or controls) was used to evaluate the role of endothelial-derived IL-6 on the activation of key signaling pathways in tumor cells. In addition, these endothelial cells were co-transplanted with tumor cells into immunodefficient mice to determine the impact of endothelial cell-derived IL-6 on tumor growth and angiogenesis.
Results
We observed that tumor cells adjacent to blood vessels show strong phosphorylation of STAT3, a key mediator of tumor progression. In search for a possible mechanism for the activation of the STAT3 signaling pathway, we observed that silencing interleukin (IL)-6 in tumor-associated endothelial cells inhibited STAT3 phosphorylation in tumor cells. Notably, tumors vascularized with IL-6-silenced endothelial cells showed lower intratumoral microvessel density, lower tumor cell proliferation, and slower growth than tumors vascularized with control endothelial cells.
Conclusions
Collectively, these results demonstrate that IL-6 secreted by endothelial cells enhance tumor growth, and suggest that cancer patients might benefit from targeted approaches that block signaling events initiated by endothelial cells.http://deepblue.lib.umich.edu/bitstream/2027.42/109499/1/12885_2013_Article_4365.pd
Coordinated and Interoperable Seismological Data and Product Services in Europe: the EPOS Thematic Core Service for Seismology
In this article we describe EPOS Seismology, the Thematic Core Service consortium for the seismology domain within the European Plate Observing System infrastructure. EPOS Seismology was developed alongside the build-up of EPOS during the last decade, in close collaboration between the existing pan-European seismological initiatives ORFEUS (Observatories and Research Facilities for European Seismology), EMSC (Euro-Mediterranean Seismological Center) and EFEHR (European Facilities for Earthquake Hazard and Risk) and their respective communities. It provides on one hand a governance framework that allows a well-coordinated interaction of the seismological community services with EPOS and its bodies, and on the other hand it strengthens the coordination among the already existing seismological initiatives with regard to data, products and service provisioning and further development. Within the EPOS Delivery Framework, ORFEUS, EMSC and EFEHR provide a wide range of services that allow open access to a vast amount of seismological data and products, following and implementing the FAIR principles and supporting open science. Services include access to raw seismic waveforms of thousands of stations together with relevant station and data quality information, parametric earthquake information of recent and historical earthquakes together with advanced event-specific products like moment tensors or source models and further ancillary services, and comprehensive seismic hazard and risk information, covering latest European scale models and their underlying data. The services continue to be available on the well-established domain-specific platforms and websites, and are also consecutively integrated with the interoperable central EPOS data infrastructure. EPOS Seismology and its participating organizations provide a consistent framework for the future development of these services and their operation as EPOS services, closely coordinated also with other international seismological initiatives, and is well set to represent the European seismological research infrastructures and their stakeholders withi
RESEARCH ON THE WORKING PROCESS OPTIMIZATION OF A COMBINED INSTALLATION FOR GRAINS CLEANING
This paper presents experimental research of qualitative indexes of impurities separation out of grains seeds for one installation which used combined principles of separation (according to specific mass and aerodynamic properties of seeds). The installation used on the experimental research was composed of a gravity separator and an aspiration installation. Based on data obtained by measurements and regulated qualitative indicators the cleaning process indexes have been determined
Myasthenia Gravis â a beginning with no end
Myasthenia gravis is one of the neurological diseases with a relatively recent history, full of mistakes, in which the British and German neurology schools have attempted to find answers when confronted with the unknown. The paper aims at making a historical account of the disease from its discovery in the 16th century, when the first case of myasthenia gravis was medically diagnosed, to the beginning of the 20th century, when the dawn of modern therapy started to show
Human Very Small Embryonic-Like Cells Generate Skeletal Structures, In Vivo
Human very small embryonic-like (hVSEL) cells are a resident population of multipotent stem cells in the bone marrow involved in the turnover and regeneration of tissues. The levels of VSEL cells in blood are greatly increased in response to injury, and they have been shown to repair injured tissues. Adult hVSEL cells, SSEA-4+/CD133+/CXCR4+/Lin?/CD45?, express the pluripotency markers (Oct-4 and Nanog) and may be able to differentiate into cells from all 3 germ lineages. hVSEL cells isolated from blood by apheresis following granulocyte?colony-stimulating factor mobilization were fractionated and enriched by elutriation and fluorescence activated cell sorting. Collagen sponge scaffolds containing 2,000?30,000 hVSEL cells were implanted into cranial defects generated in SCID mice. Analysis by microcomputed tomography showed that a cell population containing VSEL cells produced mineralized tissue within the cranial defects compared with controls at 3 months. Histologic studies showed significant bone formation and cellular organization within the defects compared with cellular or scaffold controls alone. Antibodies to human leukocyte antigens demonstrated that the newly generated tissues were of human origin. Moreover, human osteocalcin was identified circulating in the peripheral blood. There was evidence that some level of hVSEL cells migrated away from the defect site, using quantitative real-time polymerase chain reaction to detect for human-specific Alu sequences. This study demonstrates that hVSEL cells are able to generate human bone tissue in a mouse model of skeletal repair. These studies lay the foundation for future cell-based regenerative therapies for osseous and connective tissue disorders, including trauma and degenerative conditions, such as osteoporosis, fracture repair, and neoplastic repair.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140198/1/scd.2012.0327.pd
Phosphorylation controls autoinhibition of cytoplasmic linker protein-170
Author Posting. Š American Society for Cell Biology, 2010. This article is posted here by permission of American Society for Cell Biology for personal use, not for redistribution. The definitive version was published in Molecular Biology of the Cell 21 (2010): 2661-2673, doi:10.1091/mbc.E09-12-1036.Cytoplasmic linker protein (CLIP)-170 is a microtubule (MT) plus-end-tracking protein that regulates MT dynamics and links MT plus ends to different intracellular structures. We have shown previously that intramolecular association between the N and C termini results in autoinhibition of CLIP-170, thus altering its binding to MTs and the dynactin subunit p150Glued (J. Cell Biol. 2004: 166, 1003â1014). In this study, we demonstrate that conformational changes in CLIP-170 are regulated by phosphorylation that enhances the affinity between the N- and C-terminal domains. By using site-directed mutagenesis and phosphoproteomic analysis, we mapped the phosphorylation sites in the third serine-rich region of CLIP-170. A phosphorylation-deficient mutant of CLIP-170 displays an "open" conformation and a higher binding affinity for growing MT ends and p150Glued as compared with nonmutated protein, whereas a phosphomimetic mutant confined to the "folded back" conformation shows decreased MT association and does not interact with p150Glued. We conclude that phosphorylation regulates CLIP-170 conformational changes resulting in its autoinhibition.This work was supported by National
Institutes of Health grant GM-25062 (to G.G.B.); Netherlands Organization for
Scientific Research grants (to A. A. and N. G.); a Cancer Genomics Centre
grant (to J.v.H.); and Presidential Program of Russian Academy of Sciences
and RFBP grant 05-04-4915 (to E.S.N.)
TESTING THE RESISTANCE STRUCTURES OF TRACTORS AND AGRICULTURAL MACHINERY UNDER SIMULATED AND ACCELERATED REGIME
The need for an increased quality of products, the reduction of the production entry time and the restrictions imposed by the service period of products are the essential reasons which impose the necessity of using the simulated and accelerated regime tests. An accelerated test is necessary to produce the same content of wear deterioration as that one supported by the product (machine, gear, subsystem or component) on its lifetime in normal functioning conditions. Although a test in accelerated regime doesn`t have to produce big loads, unrealistic, which could alter the defecting mechanism? The paper presents the principal methods of test acceleration and exemplifies the test in accelerated and simulated regime by a test of endurance effectuated on the structure of a two plough body, on the Hydropulse stand inside of Testing Department from INMA Bucharest. Also, the paper present photos that were taken during the years from tests in simulated and accelerated regime, on the Hydropulse stand, of different machines and agricultural gears
Monitoraggio in area sismica di beni monumentali: tecniche NDT e procedure di verifica
Negli ultimi anni il concetto di vulnerabilità sismica è tristemente entrato a far parte delle
conoscenze anche dei non addetti ai lavori. Infatti, gli eventi sismici che hanno interessato dagli
inizi del â900 il territorio Italiano, hanno sistematicamente messo in risalto lâelevata vulnerabilitĂ
sismica del nostro patrimonio edilizio, ivi compresi i beni monumentali, nonchĂŠ, lâinesistenza di
qualsiasi attivitĂ di programmazione della manutenzione periodica ordinaria e straordinaria delle
strutture sismo-resistenti, che garantiscono nel tempo la conservazione delle loro capacitĂ di
risposta alle perturbazioni esterne.Il progetto PON sul Monitoraggio in Area Sismica di SIstemi MOnumentali nasce con la
prerogativa di produrre uno strumento dedicato alla tutela di strutture a valenza storico â artistica,
attraverso un percorso di catalogazione, di analisi del bene inteso come elemento costituito da
elementi resistenti e da materiali, di studio del sito dove la struttura è ubicata e di attività di
monitoraggio
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