131 research outputs found
The Total Synthesis of (â)-Scabrolide A
The first total synthesis of the norcembranoid diterpenoid scabrolide A is disclosed. The route begins with the synthesis of two chiral pool-derived fragments, which undergo a convergent coupling to expediently introduce all 19 carbon atoms of the natural product. An intramolecular DielsâAlder reaction and an enoneâolefin cycloaddition/fragmentation sequence are then employed to construct the fused [5â6â7] linear carbocyclic core of the molecule and complete the total synthesis
The Total Synthesis of (â)-Scabrolide A
The first total synthesis of the norcembranoid diterpenoid scabrolide A is disclosed. The route begins with the synthesis of two chiral pool-derived fragments, which undergo a convergent coupling to expediently introduce all 19 carbon atoms of the natural product. An intramolecular DielsâAlder reaction and an enoneâolefin cycloaddition/fragmentation sequence are then employed to construct the fused [5â6â7] linear carbocyclic core of the molecule and complete the total synthesis
Towards More Precise Survey Photometry for PanSTARRS and LSST: Measuring Directly the Optical Transmission Spectrum of the Atmosphere
Motivated by the recognition that variation in the optical transmission of
the atmosphere is probably the main limitation to the precision of ground-based
CCD measurements of celestial fluxes, we review the physical processes that
attenuate the passage of light through the Earth's atmosphere. The next
generation of astronomical surveys, such as PanSTARRS and LSST, will greatly
benefit from dedicated apparatus to obtain atmospheric transmission data that
can be associated with each survey image. We review and compare various
approaches to this measurement problem, including photometry, spectroscopy, and
LIDAR. In conjunction with careful measurements of instrumental throughput,
atmospheric transmission measurements should allow next-generation imaging
surveys to produce photometry of unprecedented precision. Our primary concerns
are the real-time determination of aerosol scattering and absorption by water
along the line of sight, both of which can vary over the course of a night's
observations.Comment: 41 pages, 14 figures. Accepted PAS
The Enantioselective Synthesis of Eburnamonine, Eucophylline, and 16âČ-epi-Leucophyllidine
A synthetic approach to the heterodimeric bisindole alkaloid leucophyllidine is disclosed herein. An enantioenriched lactam building block, synthesized through palladium-catalyzed asymmetric allylic alkylation, served as the precursor to both hemispheres. The eburnamonine-derived fragment was synthesized through a BischlerâNapieralski/hydrogenation approach, while the eucophylline-derived fragment was synthesized by FriedlĂ€nder quinoline synthesis and two sequential CâH functionalization steps. A convergent Stille coupling and phenol-directed hydrogenation united the two monomeric fragments to afford 16âČ-epi-leucophyllidine in 21 steps from commercial material
L-Cell Expression of Melanocortin-4-Receptor Is Marginal in Most of the Small Intestine in Mice and Humans and Direct Stimulation of Small Intestinal Melanocortin-4-Receptors in Mice and Rats Does Not Affect GLP-1 Secretion.
The molecular sensors underlying nutrient-stimulated GLP-1 secretion are currently being investigated. Peripheral administration of melanocortin-4 receptor (MC4R) agonists have been reported to increase GLP-1 plasma concentrations in mice and humans but it is unknown whether this effect results from a direct effect on the GLP-1 secreting L-cells in the intestine, from other effects in the intestine or from extra-intestinal effects. We investigated L-cell expression of MC4R in mouse and human L-cells by reanalyzing publicly available RNA sequencing databases (mouse and human) and by RT-qPCR (mouse), and assessed whether administration of MC4R agonists to a physiologically relevant gut model, isolated perfused mouse and rat small intestine, would stimulate GLP-1 secretion or potentiate glucose-stimulated secretion. L-cell MC4R expression was low in mouse duodenum and hardly detectable in the ileum and MC4R expression was hardly detectable in human L-cells. In isolated perfused mouse and rat intestine, neither intra-luminal nor intra-arterial administration of NDP-alpha-MSH, a potent MC4R agonist, had any effect on GLP-1 secretion (P â„0.98, n = 5-6) from the upper or lower-half of the small intestine in mice or in the lower half in rats. Furthermore, HS014-an often used MC4R antagonist, which we found to be a partial agonist-did not affect the glucose-induced GLP-1 response in the rat, P = 0.62, n = 6). Studies on transfected COS7-cells confirmed bioactivity of the used compounds and that concentrations employed were well within in the effective range. Our combined data therefore suggest that MC4R-activated GLP-1 secretion in rodents either exclusively occurs in the colon or involves extra-intestinal signaling
Cellular and humoral immune responses to SARS-CoV-2 vaccination in patients after CD19.CAR-T cell therapy
Differential limit on the extremely-high-energy cosmic neutrino flux in the presence of astrophysical background from nine years of IceCube data
We report a quasi-differential upper limit on the extremely-high-energy (EHE)
neutrino flux above GeV based on an analysis of nine years of
IceCube data. The astrophysical neutrino flux measured by IceCube extends to
PeV energies, and it is a background flux when searching for an independent
signal flux at higher energies, such as the cosmogenic neutrino signal. We have
developed a new method to place robust limits on the EHE neutrino flux in the
presence of an astrophysical background, whose spectrum has yet to be
understood with high precision at PeV energies. A distinct event with a
deposited energy above GeV was found in the new two-year sample, in
addition to the one event previously found in the seven-year EHE neutrino
search. These two events represent a neutrino flux that is incompatible with
predictions for a cosmogenic neutrino flux and are considered to be an
astrophysical background in the current study. The obtained limit is the most
stringent to date in the energy range between and GeV. This result constrains neutrino models predicting a three-flavor
neutrino flux of $E_\nu^2\phi_{\nu_e+\nu_\mu+\nu_\tau}\simeq2\times 10^{-8}\
{\rm GeV}/{\rm cm}^2\ \sec\ {\rm sr}10^9\ {\rm GeV}$. A significant part
of the parameter-space for EHE neutrino production scenarios assuming a
proton-dominated composition of ultra-high-energy cosmic rays is excluded.Comment: The version accepted for publication in Physical Review
Observation of High-Energy Astrophysical Neutrinos in Three Years of IceCube Data
A search for high-energy neutrinos interacting within the IceCube detector
between 2010 and 2012 provided the first evidence for a high-energy neutrino
flux of extraterrestrial origin. Results from an analysis using the same
methods with a third year (2012-2013) of data from the complete IceCube
detector are consistent with the previously reported astrophysical flux in the
100 TeV - PeV range at the level of per flavor and reject a
purely atmospheric explanation for the combined 3-year data at .
The data are consistent with expectations for equal fluxes of all three
neutrino flavors and with isotropic arrival directions, suggesting either
numerous or spatially extended sources. The three-year dataset, with a livetime
of 988 days, contains a total of 37 neutrino candidate events with deposited
energies ranging from 30 to 2000 TeV. The 2000 TeV event is the highest-energy
neutrino interaction ever observed.Comment: 8 pages, 5 figures. Accepted by PRL. The event catalog, event
displays, and other data tables are included after the final page of the
article. Changed from the initial submission to reflect referee comments,
expanding the section on atmospheric backgrounds, and fixes offsets of up to
0.9 seconds in reported event times. Address correspondence to: J. Feintzeig,
C. Kopper, N. Whitehor
Immune cell subsets and their gene expression profiles from human PBMC isolated by Vacutainer Cell Preparation Tube (CPTâą) and standard density gradient
Investigation of two Fermi-LAT gamma-ray blazars coincident with high-energy neutrinos detected by IceCube
After the identification of the gamma-ray blazar TXS 0506+056 as the first
compelling IceCube neutrino source candidate, we perform a systematic analysis
of all high-energy neutrino events satisfying the IceCube realtime trigger
criteria. We find one additional known gamma-ray source, the blazar GB6
J1040+0617, in spatial coincidence with a neutrino in this sample. The chance
probability of this coincidence is 30% after trial correction. For the first
time, we present a systematic study of the gamma-ray flux, spectral and optical
variability, and multi-wavelength behavior of GB6 J1040+0617 and compare it to
TXS 0506+056. We find that TXS 0506+056 shows strong flux variability in the
Fermi-LAT gamma-ray band, being in an active state around the arrival of
IceCube-170922A, but in a low state during the archival IceCube neutrino flare
in 2014/15. In both cases the spectral shape is statistically compatible () with the average spectrum showing no indication of a significant
relative increase of a high-energy component. While the association of GB6
J1040+0617 with the neutrino is consistent with background expectations, the
source appears to be a plausible neutrino source candidate based on its
energetics and multi-wavelength features, namely a bright optical flare and
modestly increased gamma-ray activity. Finding one or two neutrinos originating
from gamma-ray blazars in the given sample of high-energy neutrinos is
consistent with previously derived limits of neutrino emission from gamma-ray
blazars, indicating the sources of the majority of cosmic high-energy neutrinos
remain unknown.Comment: 22 pages, 11 figures, 2 Table
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