368 research outputs found
A Novel Azeotropic Mixture for Solvent Extraction of Edible Oils
Rosana G. Moreira, Editor-in-Chief; Texas A&M UniversityThis is a paper from International Commission of Agricultural Engineering (CIGR, Commission Internationale du Genie Rural) E-Journal Volume 8 (2006): A Novel Azeotropic Mixture for Solvent Extraction of Edible Oils. Manuscript FP 06 005. Vol. VIII. April, 2006
FRET Dyes Significantly Affect SAXS Intensities of Proteins
Structural analyses in biophysics aim at revealing a relationship between a molecule's dynamic structure and its physiological function. Förster resonance energy transfer (FRET) and small‐angle X‐ray scattering (SAXS) are complementary experimental approaches to this. Their concomitant application in combined studies has recently opened a lively debate on how to interpret FRET measurements in the light of SAXS data with the popular example of the radius of gyration, commonly derived from both FRET and SAXS. There still is a lack of understanding in how to mutually relate and interpret quantities equally obtained from FRET or SAXS, and to what extent FRET dyes affect SAXS intensities in combined applications. In the present work, we examine the interplay of FRET and SAXS from a computational simulation perspective. Molecular simulations are a valuable complement to experimental approaches and supply instructive information on dynamics. As FRET depends not only on the mutual separation but also on the relative orientations, the dynamics, and therefore also the shapes of the dyes, we utilize a novel method for simulating FRET‐dye‐labeled proteins to investigate these aspects in atomic detail. We perform structure‐based simulations of four different proteins with and without dyes in both folded and unfolded conformations. In‐silico derived radii of gyration are different with and without dyes and depend on the chosen dye pair. The dyes apparently influence the dynamics of unfolded systems. We find that FRET dyes attached to a protein have a significant impact on theoretical SAXS intensities calculated from simulated structures, especially for small proteins. Radii of gyration from FRET and SAXS deviate systematically, which points to further underlying mechanisms beyond prevalent explanation approaches
Progression and mortality in patients with CKD attending outpatient nephrology clinics across Europe: A novel analytic approach
The incidence of renal replacement therapy (RRT) varies across countries. Yet, little is known about the epidemiology of chronic kidney disease (CKD) outcomes. Our aim was to describe progression and mortality risk in CKD patients not on RRT attending outpatient nephrology clinics across Europe.
We used individual data from nine CKD cohorts participating in the European CKD Burden Consortium. A joint model was used to estimate mean eGFR change and mortality risk simultaneously, thereby accounting for mortality risk when estimating eGFR decline and vice versa, while also correcting for the measurement error in eGFR. Results were adjusted for important risk factors (baseline eGFR, age, sex, albuminuria, primary renal disease, diabetes, hypertension, obesity and smoking).
27,771 patients from five countries were included. The adjusted mean annual eGFR decline varied from 0.77 (95%CI 0.45,1.08) ml/min/1.73m2 in the Belgium cohort to 2.43 (95%CI 2.11,2.75) ml/min/1.73m2 in the Spanish cohort. As compared to the Italian PIRP cohort, the adjusted mortality hazard ratio varied from 0.22 (95%CI 0.11,0.43) in the London LACKABO cohort to 1.30 (95%CI 1.13,1.49) in the English CRISIS cohort.
Outcomes in CKD patients attending outpatient nephrology clinics varied markedly across European regions. Although eGFR decline showed minor variation, the most variation was observed in CKD mortality. Our results suggest that different healthcare organization systems are potentially associated with differences in outcome of CKD patients within Europe. These results can be used by policy makers to plan resources on a regional, national and European level
Diamond Detectors for the TOTEM Timing Upgrade
This paper describes the design and the performance of the timing detector
developed by the TOTEM Collaboration for the Roman Pots (RPs) to measure the
Time-Of-Flight (TOF) of the protons produced in central diffractive
interactions at the LHC. The measurement of the TOF of the protons allows the
determination of the longitudinal position of the proton interaction vertex and
its association with one of the vertices reconstructed by the CMS detectors.
The TOF detector is based on single crystal Chemical Vapor Deposition (scCVD)
diamond plates and is designed to measure the protons TOF with about 50 ps time
precision. This upgrade to the TOTEM apparatus will be used in the LHC run 2
and will tag the central diffractive events up to an interaction pileup of
about 1. A dedicated fast and low noise electronics for the signal
amplification has been developed. The digitization of the diamond signal is
performed by sampling the waveform. After introducing the physics studies that
will most profit from the addition of these new detectors, we discuss in detail
the optimization and the performance of the first TOF detector installed in the
LHC in November 2015.Comment: 26 pages, 18 figures, 2 tables, submitted for publication to JINS
KRAS-regulated glutamine metabolism requires UCP2-mediated aspartate transport to support pancreatic cancer growth
The oncogenic KRAS mutation has a critical role in the initiation of human pancreatic ductal adenocarcinoma (PDAC) since it rewires glutamine metabolism to increase reduced nicotinamide adenine dinucleotide phosphate (NADPH) production, balancing cellular redox homeostasis with macromolecular synthesis1,2. Mitochondrial glutamine-derived aspartate must be transported into the cytosol to generate metabolic precursors for NADPH production2. The mitochondrial transporter responsible for this aspartate efflux has remained elusive. Here, we show that mitochondrial uncoupling protein 2 (UCP2) catalyses this transport and promotes tumour growth. UCP2-silenced KRASmut cell lines display decreased glutaminolysis, lower NADPH/NADP+ and glutathione/glutathione disulfide ratios and higher reactive oxygen species levels compared to wild-type counterparts. UCP2 silencing reduces glutaminolysis also in KRASWT PDAC cells but does not affect their redox homeostasis or proliferation rates. In vitro and in vivo, UCP2 silencing strongly suppresses KRASmut PDAC cell growth. Collectively, these results demonstrate that UCP2 plays a vital role in PDAC, since its aspartate transport activity connects the mitochondrial and cytosolic reactions necessary for KRASmut rewired glutamine metabolism2, and thus it should be considered a key metabolic target for the treatment of this refractory tumour
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