856 research outputs found
FTC Not Required to Rely on Extrinsic Evidence to Determine Fraudulent Implied Claims in Advertising
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Hyperpolarized 13C-pyruvate MRI detects real-time metabolic flux in prostate cancer metastases to bone and liver: a clinical feasibility study.
BackgroundHyperpolarized (HP) 13C-pyruvate MRI is a stable-isotope molecular imaging modality that provides real-time assessment of the rate of metabolism through glycolytic pathways in human prostate cancer. Heretofore this imaging modality has been successfully utilized in prostate cancer only in localized disease. This pilot clinical study investigated the feasibility and imaging performance of HP 13C-pyruvate MR metabolic imaging in prostate cancer patients with metastases to the bone and/or viscera.MethodsSix patients who had metastatic castration-resistant prostate cancer were recruited. Carbon-13 MR examination were conducted on a clinical 3T MRI following injection of 250 mM hyperpolarized 13C-pyruvate, where pyruvate-to-lactate conversion rate (kPL) was calculated. Paired metastatic tumor biopsy was performed with histopathological and RNA-seq analyses.ResultsWe observed a high rate of glycolytic metabolism in prostate cancer metastases, with a mean kPL value of 0.020 ± 0.006 (s-1) and 0.026 ± 0.000 (s-1) in bone (N = 4) and liver (N = 2) metastases, respectively. Overall, high kPL showed concordance with biopsy-confirmed high-grade prostate cancer including neuroendocrine differentiation in one case. Interval decrease of kPL from 0.026 at baseline to 0.015 (s-1) was observed in a liver metastasis 2 months after the initiation of taxane plus platinum chemotherapy. RNA-seq found higher levels of the lactate dehydrogenase isoform A (Ldha,15.7 ± 0.7) expression relative to the dominant isoform of pyruvate dehydrogenase (Pdha1, 12.8 ± 0.9).ConclusionsHP 13C-pyruvate MRI can detect real-time glycolytic metabolism within prostate cancer metastases, and can measure changes in quantitative kPL values following treatment response at early time points. This first feasibility study supports future clinical studies of HP 13C-pyruvate MRI in the setting of advanced prostate cancer
A formal asymmetric synthesis of both enantiomers of the Erythrina Alkaloid 3-Demethoxyerythratidinone
A formal asymmetric synthesis of both enantiomers of the Erythrina alkaloid 3-
demethoxyerythratidinone is reported through the application of a highly functionalised lactam template as
an N-acyliminium precursor
SeaWiFS technical report series. Volume 27: Case studies for SeaWiFS calibration and validation, part 3
This document provides brief reports, or case studies, on a number of investigations sponsored by the Calibration and Validation Team (CVT) within the Sea-viewing Wide Field-of-view Sensor (SeaWiFS) Project. Chapter I describes a comparison of the irradiance immersion coefficients determined for several different marine environmental radiometers (MERs). Chapter 2 presents an analysis of how light absorption by atmospheric oxygen will influence the radiance measurements in band 7 of the SeaWiFS instrument. Chapter 3 gives the results of the second ground-based solar calibration of the instrument, which was undertaken after the sensor was modified to reduce the effects of internal stray light. (The first ground-based solar calibration of SeaWiFS is described in Volume 19 in the SeaWiFS Technical Report Series.) Chapter 4 evaluates the effects of ship shadow on subsurface irradiance and radiance measurements deployed from the deck of the R/V Weatherbird 11 in the Atlantic Ocean near Bermuda. Chapter 5 illustrates the various ways in which a single data day of SeaWiFS observations can be defined, and why the spatial definition is superior to the temporal definition for operational usage
Current Methods for Hyperpolarized [1-13C]pyruvate MRI Human Studies
MRI with hyperpolarized (HP) 13C agents, also known as HP 13C MRI, can
measure processes such as localized metabolism that is altered in numerous
cancers, liver, heart, kidney diseases, and more. It has been translated into
human studies during the past 10 years, with recent rapid growth in studies
largely based on increasing availability of hyperpolarized agent preparation
methods suitable for use in humans. This paper aims to capture the current
successful practices for HP MRI human studies with [1-13C]pyruvate - by far the
most commonly used agent, which sits at a key metabolic junction in glycolysis.
The paper is divided into four major topic areas: (1) HP 13C-pyruvate
preparation, (2) MRI system setup and calibrations, (3) data acquisition and
image reconstruction, and (4) data analysis and quantification. In each area,
we identified the key components for a successful study, summarized both
published studies and current practices, and discuss evidence gaps, strengths,
and limitations. This paper is the output of the HP 13C MRI Consensus Group as
well as the ISMRM Hyperpolarized Media MR and Hyperpolarized Methods &
Equipment study groups. It further aims to provide a comprehensive reference
for future consensus building as the field continues to advance human studies
with this metabolic imaging modality
Strong signature of natural selection within an FHIT intron implicated in prostate cancer risk
Previously, a candidate gene linkage approach on brother pairs affected with prostate cancer identified a locus of prostate cancer susceptibility at D3S1234 within the fragile histidine triad gene (FHIT), a tumor suppressor that induces apoptosis. Subsequent association tests on 16 SNPs spanning approximately 381 kb surrounding D3S1234 in Americans of European descent revealed significant evidence of association for a single SNP within intron 5 of FHIT. In the current study, resequencing and genotyping within a 28.5 kb region surrounding this SNP further delineated the association with prostate cancer risk to a 15 kb region. Multiple SNPs in sequences under evolutionary constraint within intron 5 of FHIT defined several related haplotypes with an increased risk of prostate cancer in European-Americans. Strong associations were detected for a risk haplotype defined by SNPs 138543, 142413, and 152494 in all cases (Pearson's χ2 = 12.34, df 1, P = 0.00045) and for the homozygous risk haplotype defined by SNPs 144716, 142413, and 148444 in cases that shared 2 alleles identical by descent with their affected brothers (Pearson's χ2 = 11.50, df 1, P = 0.00070). In addition to highly conserved sequences encompassing SNPs 148444 and 152413, population studies revealed strong signatures of natural selection for a 1 kb window covering the SNP 144716 in two human populations, the European American (π = 0.0072, Tajima's D= 3.31, 14 SNPs) and the Japanese (π = 0.0049, Fay & Wu's H = 8.05, 14 SNPs), as well as in chimpanzees (Fay & Wu's H = 8.62, 12 SNPs). These results strongly support the involvement of the FHIT intronic region in an increased risk of prostate cancer. © 2008 Ding et al
Polymers of Intrinsic Microporosity derived from a carbocyclic analogue of Tröger's base
Tröger's base (TB) is often used as a building block for the synthesis of Polymers of Intrinsic Microporosity (PIMs) due to its rigid bicyclic V-shaped structure. In this study the TB component in the structure of a PIM is replaced by 2,3:6,7-dibenzobicyclo[3.3.1]nonane, a purely carbocyclic analogue of TB. This modification results in only a slightly reduced amount of microporosity as determined using nitrogen adsorption. Further comparisons with previously reported PIMs indicate that this building unit (and therefore TB) is significantly less effective for the generation of intrinsic microporosity than spirobisindane, a commonly used structural unit for PIM synthesis. It appears that the V-shape of the 2,3:6,7-dibenzobicyclo[3.3.1]nonane and TB units allows closer contact between polymer chains thereby enhancing packing efficiency
Cavity BPM System Tests for the ILC Spectrometer
The main physics programme of the International Linear Collider (ILC)
requires a measurement of the beam energy at the interaction point with an
accuracy of or better. To achieve this goal a magnetic spectrometer
using high resolution beam position monitors (BPMs) has been proposed. This
paper reports on the cavity BPM system that was deployed to test this proposal.
We demonstrate sub-micron resolution and micron level stability over 20 hours
for a 1\m long BPM triplet. We find micron-level stability over 1 hour for 3
BPM stations distributed over a 30\m long baseline. The understanding of the
behaviour and response of the BPMs gained from this work has allowed full
spectrometer tests to be carried out.Comment: Paper submitted to Nuclear Instruments and Methods. 35 pages, 23
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