426 research outputs found
Surrogate safety measures and traffic conflict observations.
The chapter primarily focuses on observing traffic conflicts (also known as near-accidents) as a site-based road safety analysis technique. Traffic conflicts are a type of surrogate safety measure. The term surrogate indicates that non-accident-based indicators are used to assess VRU safety instead ofthe more traditional approach focusing on accidents (see chapter 2). The theory underpinning surrogate safety measures is briefly described, followed by a discussion on the characteristics of the traffic conflict technique. Next, guidelines for conducting traffic conflict observations using trained human observers or video cameras are presented. Chapter 4 concludes with examples of the use of the traffic conflict technique in road safety studies focusing on VRUs
Mannose 6-Phosphate Receptor Is Reduced in -Synuclein Overexpressing Models of Parkinsons Disease
Increasing evidence points to defects in autophagy as a common denominator in most neurodegenerative conditions. Progressive functional decline in the autophagy-lysosomal pathway (ALP) occurs with age, and the consequent impairment in protein processing capacity has been associated with a higher risk of neurodegeneration. Defects in cathepsin D (CD) processing and Îą-synuclein degradation causing its accumulation in lysosomes are particularly relevant for the development of Parkinson's disease (PD). However, the mechanism by which alterations in CD maturation and Îą-synuclein degradation leads to autophagy defects in PD neurons is still uncertain. Here we demonstrate that MPR300 shuttling between endosomes and the trans Golgi network is altered in Îą-synuclein overexpressing neurons. Consequently, CD is not correctly trafficked to lysosomes and cannot be processed to generate its mature active form, leading to a reduced CD-mediated Îą-synuclein degradation and Îą-synuclein accumulation in neurons. MPR300 is downregulated in brain from Îą-synuclein overexpressing animal models and in PD patients with early diagnosis. These data indicate MPR300 as crucial player in the autophagy-lysosomal dysfunctions reported in PD and pinpoint MRP300 as a potential biomarker for PD
Cdc42 promotes transendothelial migration of cancer cells through β1 integrin.
Cancer cells interact with endothelial cells during the process of metastatic spreading. Here, we use a small interfering RNA screen targeting Rho GTPases in cancer cells to identify Cdc42 as a critical regulator of cancer cell-endothelial cell interactions and transendothelial migration. We find that Cdc42 regulates β1 integrin expression at the transcriptional level via the transcription factor serum response factor (SRF). β1 integrin is the main target for Cdc42-mediating interaction of cancer cells with endothelial cells and the underlying extracellular matrix, as exogenous β1 integrin expression was sufficient to rescue the Cdc42-silencing phenotype. We show that Cdc42 was required in vivo for cancer cell spreading and protrusion extension along blood vessels and retention in the lungs. Interestingly, transient Cdc42 depletion was sufficient to decrease experimental lung metastases, which suggests that its role in endothelial attachment is important for metastasis. By identifying β1 integrin as a transcriptional target of Cdc42, our results provide new insight into Cdc42 function
Entanglement-enhanced probing of a delicate material system
Quantum metrology uses entanglement and other quantum effects to improve the
sensitivity of demanding measurements. Probing of delicate systems demands high
sensitivity from limited probe energy and has motivated the field's key
benchmark-the standard quantum limit. Here we report the first
entanglement-enhanced measurement of a delicate material system. We
non-destructively probe an atomic spin ensemble by means of near-resonant
Faraday rotation, a measurement that is limited by probe-induced scattering in
quantum-memory and spin-squeezing applications. We use narrowband,
atom-resonant NOON states to beat the standard quantum limit of sensitivity by
more than five standard deviations, both on a per-photon and per-damage basis.
This demonstrates quantum enhancement with fully realistic loss and noise,
including variable-loss effects. The experiment opens the way to ultra-gentle
probing of single atoms, single molecules, quantum gases and living cells.Comment: 7 pages, 8 figures; Nature Photonics, advance online publication, 16
December 201
NuSTAR Hard X-ray Survey of the Galactic Center Region I: Hard X-ray Morphology and Spectroscopy of the Diffuse Emission
We present the first sub-arcminute images of the Galactic Center above 10
keV, obtained with NuSTAR. NuSTAR resolves the hard X-ray source IGR
J17456-2901 into non-thermal X-ray filaments, molecular clouds, point sources
and a previously unknown central component of hard X-ray emission (CHXE).
NuSTAR detects four non-thermal X-ray filaments, extending the detection of
their power-law spectra with - up to ~50 keV. A
morphological and spectral study of the filaments suggests that their origin
may be heterogeneous, where previous studies suggested a common origin in young
pulsar wind nebulae (PWNe). NuSTAR detects non-thermal X-ray continuum emission
spatially correlated with the 6.4 keV Fe K fluorescence line emission
associated with two Sgr A molecular clouds: MC1 and the Bridge. Broad-band
X-ray spectral analysis with a Monte-Carlo based X-ray reflection model
self-consistently determined their intrinsic column density (
cm), primary X-ray spectra (power-laws with ) and set a
lower limit of the X-ray luminosity of Sgr A* flare illuminating the Sgr A
clouds to erg s. Above ~20 keV, hard
X-ray emission in the central 10 pc region around Sgr A* consists of the
candidate PWN G359.95-0.04 and the CHXE, possibly resulting from an unresolved
population of massive CVs with white dwarf masses . Spectral energy distribution analysis suggests that G359.95-0.04 is
likely the hard X-ray counterpart of the ultra-high gamma-ray source HESS
J1745-290, strongly favoring a leptonic origin of the GC TeV emission.Comment: 27 pages. Accepted for publication in the Astrophysical Journa
Optimizing patient care and outcomes through the congenital heart center of the 21st century
Pediatric cardiovascular services are responding to the dynamic changes in the medical environment, including the business of medicine. The opportunity to advance our pediatric cardiology field through collaboration is now realized, permitting us to define meaningful quality metrics and establish national benchmarks through multicenter efforts. In March 2016, the American College of Cardiology hosted the first Adult Congenital/Pediatric Cardiology Section Congenital Heart Community Day. This was an open participation meeting for clinicians, administrators, patients/parents to propose metrics that optimize patient care and outcomes for a stateâ ofâ theâ art congenital heart center of the 21st century. Care center collaboration helps overcome the barrier of relative small volumes at any given program. Patients and families have become active collaborative partners with care centers in the definition of acute and longitudinal outcomes and our quality metrics. Understanding programmatic metrics that create an environment to provide outstanding congenital heart care will allow centers to improve their structure, processes and ultimately outcomes, leading to an increasing number of centers that provide excellent care. This manuscript provides background, as well listing of proposed specialty domain quality metrics for centers, and thus serves as an updated baseline for the ongoing dynamic process of optimizing care and realizing patient value.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143653/1/chd12575_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143653/2/chd12575.pd
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