299 research outputs found
Monongalia area survey, 1981 : citizens\u27 views on industrial development and quality of life
A comparison of uterine contractile responsiveness to arginine vasopressin in oviparous and viviparous lizards
Nonapeptides and their receptors regulate a diverse range of physiological processes. We assessed the contractile responsiveness of uteri from the squamate viviparous-oviparous species pair, Pseudemoia entrecasteauxii and Lampropholis guichenoti, as well as the bimodally reproductive species, Saiphos equalis, to arginine vasopressin (AVP). We assessed the resulting uterine contractility as a function of pregnancy status, species and parity mode. We also measured mRNA abundance for the nonapeptide receptor, oxytocin receptor (oxtr), in uteri from P. entrecasteauxii and L. guichenoti and compared expression across pregnancy status and parity mode. We found that pregnant uteri exhibited a significantly greater contractile response to AVP than non-pregnant uteri in all three lizard species studied. Cross-species comparisons revealed that uteri from viviparous P. entrecasteauxii were significantly more responsive to AVP than uteri from oviparous L. guichenoti during both pregnant and non-pregnant states. Conversely, for non-pregnant S. equalis, uteri from viviparous individuals were significantly less responsive to AVP than uteri from oviparous individuals, while during pregnancy, there was no difference in AVP contractile responsiveness. There was no difference in expression of oxtr between L. guichenoti and P. entrecasteauxii, or between pregnant and non-pregnant individuals within each species. We found no significant correlation between oxtr expression and AVP contractile responsiveness. These findings indicate that there are differences in nonapeptide signalling across parity mode and suggest that in these lizards, labour may be triggered either by an increase in plasma nonapeptide concentration, or by an increase in expression of a different nonapeptide receptor from the vasopressin-like receptor family
Sansanmycin natural product analogues as potent and selective anti-mycobacterials that inhibit lipid I biosynthesis.
Tuberculosis (TB) is responsible for enormous global morbidity and mortality, and current treatment regimens rely on the use of drugs that have been in use for more than 40 years. Owing to widespread resistance to these therapies, new drugs are desperately needed to control the TB disease burden. Herein, we describe the rapid synthesis of analogues of the sansanmycin uridylpeptide natural products that represent promising new TB drug leads. The compounds exhibit potent and selective inhibition of Mycobacterium tuberculosis, the etiological agent of TB, both in vitro and intracellularly. The natural product analogues were also shown to be nanomolar inhibitors of Mtb phospho-MurNAc-pentapeptide translocase, the enzyme responsible for the synthesis of lipid I in mycobacteria. This work lays the foundation for the development of uridylpeptide natural product analogues as new TB drug candidates that operate through the inhibition of peptidoglycan biosynthesis
Synthesis of norbornane bisether antibiotics via silver-mediated alkylation
A small series of norbornane bisether diguanidines have been synthesized and evaluated as antibacterial agents. The key transformation-bisalkylation of norbornane diol 6-was not successful using Williamson methodology but has been accomplished using Ag2O mediated alkylation. Further functionalization to incorporate two guanidinium groups gave rise to a series of structurally rigid cationic amphiphiles; several of which (16d, 16g and 16h) exhibited antibiotic activity. For example, compound 16d was active against a broad range of bacteria including Pseudomonas aeruginosa (MIC = 8 µg/mL), Escherichia coli (MIC = 8 µg/mL) and methicillin-resistant Staphylococcus aureus (MIC = 8 µg/mL)
Measurement of the cosmic ray spectrum above eV using inclined events detected with the Pierre Auger Observatory
A measurement of the cosmic-ray spectrum for energies exceeding
eV is presented, which is based on the analysis of showers
with zenith angles greater than detected with the Pierre Auger
Observatory between 1 January 2004 and 31 December 2013. The measured spectrum
confirms a flux suppression at the highest energies. Above
eV, the "ankle", the flux can be described by a power law with
index followed by
a smooth suppression region. For the energy () at which the
spectral flux has fallen to one-half of its extrapolated value in the absence
of suppression, we find
eV.Comment: Replaced with published version. Added journal reference and DO
Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory
The Auger Engineering Radio Array (AERA) is part of the Pierre Auger
Observatory and is used to detect the radio emission of cosmic-ray air showers.
These observations are compared to the data of the surface detector stations of
the Observatory, which provide well-calibrated information on the cosmic-ray
energies and arrival directions. The response of the radio stations in the 30
to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of
the incoming electric field. For the latter, the energy deposit per area is
determined from the radio pulses at each observer position and is interpolated
using a two-dimensional function that takes into account signal asymmetries due
to interference between the geomagnetic and charge-excess emission components.
The spatial integral over the signal distribution gives a direct measurement of
the energy transferred from the primary cosmic ray into radio emission in the
AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air
shower arriving perpendicularly to the geomagnetic field. This radiation energy
-- corrected for geometrical effects -- is used as a cosmic-ray energy
estimator. Performing an absolute energy calibration against the
surface-detector information, we observe that this radio-energy estimator
scales quadratically with the cosmic-ray energy as expected for coherent
emission. We find an energy resolution of the radio reconstruction of 22% for
the data set and 17% for a high-quality subset containing only events with at
least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO
Decoding the Molecular Universe -- Workshop Report
On August 9-10, 2023, a workshop was convened at the Pacific Northwest
National Laboratory (PNNL) in Richland, WA that brought together a group of
internationally recognized experts in metabolomics, natural products discovery,
chemical ecology, chemical and biological threat assessment, cheminformatics,
computational chemistry, cloud computing, artificial intelligence, and novel
technology development. These experts were invited to assess the value and
feasibility of a grand-scale project to create new technologies that would
allow the identification and quantification of all small molecules, or to
decode the molecular universe. The Decoding the Molecular Universe project
would extend and complement the success of the Human Genome Project by
developing new capabilities and technologies to measure small molecules
(defined as non-protein, non-polymer molecules less than 1500 Daltons) of any
origin and generated in biological systems or produced abiotically. Workshop
attendees 1) explored what new understanding of biological and environmental
systems could be revealed through the lens of small molecules; 2) characterized
the similarities in current needs and technical challenges between each science
or mission area for unambiguous and comprehensive determination of the
composition and quantities of small molecules of any sample; 3) determined the
extent to which technologies or methods currently exist for unambiguously and
comprehensively determining the small molecule composition of any sample and in
a reasonable time; and 4) identified the attributes of the ideal technology or
approach for universal small molecule measurement and identification. The
workshop concluded with a discussion of how a project of this scale could be
undertaken, possible thrusts for the project, early proof-of-principle
applications, and similar efforts upon which the project could be modeled
Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy
We measure the energy emitted by extensive air showers in the form of radio
emission in the frequency range from 30 to 80 MHz. Exploiting the accurate
energy scale of the Pierre Auger Observatory, we obtain a radiation energy of
15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV
arriving perpendicularly to a geomagnetic field of 0.24 G, scaling
quadratically with the cosmic-ray energy. A comparison with predictions from
state-of-the-art first-principle calculations shows agreement with our
measurement. The radiation energy provides direct access to the calorimetric
energy in the electromagnetic cascade of extensive air showers. Comparison with
our result thus allows the direct calibration of any cosmic-ray radio detector
against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI.
Supplemental material in the ancillary file
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