Adapting the method used by many libraries in the acquisitions workflow to export OCLC WorldCat bibliographic records into the local online catalog, the Special Collections Department at the ...University of Colorado at Boulder Libraries developed a process employing a graduate student to provide access to two previously hidden special collections until the materials can be fully cataloged. The completion of the project undertaken by the student assistant resulted in the simultaneous benefits of increased efficiency among the catalogers and greater provision of access to enable users to identify important resources for their research and study. By initiating similar procedures to represent not-yet-cataloged materials with online in-process records, other libraries can move their hidden collections into the view of their users.
An animal model of human osteoporosis which adequately meets many of the criteria needed to test new therapeutic agents is currently unavailable. The old ewe may serve this purpose, as changes in ...bone remodeling occur within 3 months, and a difference in bone mass has been indicated 6 months after ovariectomy. In the current study, we have measured longitudinal changes in bone mass and bone-specific alkaline phosphatase (BSAP) for six months in 7-9 year old ovariectomized (OVX) ewes. Thirty ewes were divided into three groups: sham-treated (n = 9), OVX (n = 12) and OVX with estrogen implants (OVXE, n = 9). Bone mineral density (BMD) was determined at 0, 3 and 6 months in the vertebrae (L4-L6/L5-L7), calcaneus (CAL) and distal radius (DR) using dual-energy X-ray absorptiometry (DEXA). Bone-Specific Alkaline Phosphatase (Tandem-R Ostase; Hybritech) was determined at monthly intervals. Body weight did not significantly change in any group during treatment compared to sham, although a trend of increasing body weight at 3 and 6 months was apparent in both OVX groups. Luteinizing hormone increased in all OVX ewes as a function of time as expected, demonstrating successful ovariectomies. Uterine weight was significantly increased (p < 0.01) in the OVXE animals compared to Sham and OVX groups. BMD did not change significantly during the 6-month treatment period in the CAL or DR. BMD in the vertebrae (L4-L6/L5-L7) was significantly lower in the OVX group compared to sham (p < 0.08).
The discovery of heteroaryl-phenyl-substituted pyrazole derivatives as canine selective COX-2 inhibitors is described. Structure–activity relationship (SAR) studies of this class of compounds led to ...the identification of compound
1 which demonstrated a canine whole blood COX-2 inhibitory IC
50 of 12
nM and selectivity ratio of COX-1/COX-2 greater than 4000-fold.
The discovery of heteroaryl-phenyl-substituted pyrazole derivatives as canine selective COX-2 inhibitors is described. Structure–activity relationship (SAR) studies of this class of compounds led to the identification of compound
1 which demonstrated a canine whole blood COX-2 inhibitory IC
50 of 12
nM and selectivity ratio of COX-1/COX-2 greater than 4000-fold.
► Water flow in the Oxfordian and Dogger limestone of the eastern Paris Basin. ► Present-day recharge is mainly restricted to the southern outcrop area. ► The main flow is led by a northerly ...hydraulic gradient in both aquifers. ► The chemistry of Dogger waters is very different from that of the Oxfordian waters. ► The low gradient and transmissivities of the Dogger formation impose a long residence time.
Within its scientific program devoted to the feasibility of a high level radioactive waste facility in the Callovo-Oxfordian argillaceous rock (COx) of the eastern Paris Basin, Andra has conducted an extensive characterization of the Oxfordian and Dogger limestone formations above and below the COx. More than 25 wells were dedicated to the hydrogeological and geochemical characterization of the Oxfordian and Dogger limestones over a 400
km
2 sector. An original strategy was developed to obtain field hydrogeological measurements and representative formation water samples in these wells. An extensive 3D set of field data and water compositions were obtained over 15
years. The geochemical and isotopic data indicate a meteoric origin for the Oxfordian and Dogger limestone waters. The geological observations revealed a clay rich level horizontally dividing the Oxfordian limestones into two parts in the NE zone of the study area. In the lower Oxfordian, water inflows come mainly from the outcrop in the south-eastern part of the study area. Three meteoric water inflows were identified in the upper Oxfordian in the study area: the first one covers the eastern and southeastern part of the area, the second one covers the diffuse fracturation zone (DFZ) south of the area, and the third one is located in the north eastern part of the area. The two first inflows consist of fresh water, while the last one consists of Mg
2+,
SO
4
2
-
and Na
+ rich waters coming from the erosion of the Purbeckian lithological type facies. Fresh waters from the outcrops flow slowly towards the North West. They equilibrate with the limestone dolomite formations and are enriched by a Na
+ and Cl
− diffusive flux coming from the Dogger through the Callovo-Oxfordian argillaceous rock. These waters mix with the water coming from the North East upper Oxfordian. The Dogger limestone is characterized by sodium chloride groundwaters with higher salinity values than the Oxfordian limestone. North–northwest flows in the Dogger limestone are slower than flows in the Oxfordian formation. In both formations, the DFZ must be considered to be an apart hydrological system.
Several novel 15-membered-ring macrolide agents (azalide 1, triamilides 2 and 3, and the azalide 3, 6-ketal 4) were identified as potential antibacterial agents against Mannheimia (formerly named as ...Pasteurella) haemolytica, Pasteurella multocida, Haemophilus somnus and Actinobacillus pleuropneumoniae, important etiological agents of bovine and porcine respiratory disease. Compound 3 is the major component of the antibiotic tulathromycin. Antibacterial activity against tilmicosin-resistant P. multocida field isolates was also tested. In vitro MIC 50/90 analysis revealed that the four newly synthesized compounds were more potent than tilmicosin against M. haemolytica (4-8×), P. multocida (8-16×), A. pleuropneumoniae (4×), H. somnus (2× and 16×), and tilmicosin-resistant P. multocida (32×). In time-kill kinetic studies, all four novel compounds and tilmicosin showed bactericidal activity against M. haemolytica, P. multocida and A. pleuropneumoniae at both 4× and 8× MIC. A functional assay using genetically defined mutants revealed that all four novel compounds were poorer substrates for the efflux pump, AcrA/B system, than tilmicosin. A pH study using LPS mutants indicated that the enhanced in vitro potency of the triamilides, particularly compound 3 was mainly due to better penetration of the molecule through the outer membrane. The third amine group at the C-4" position of the triamilde molecules contributed to this increased membrane penetration by increasing overall basicity. These studies indicate that the four novel compounds have potential as antibacterial agents against bovine and porcine respiratory disease.
O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate (VX) is an extremely toxic organophosphate nerve agent that has been weaponized and stockpiled in a number of different countries, and it ...has been used in recent terrorist events. It differs from other well-known organophosphate nerve agents in that its primary use is as a contact poison rather than as an inhalation hazard. For this reason, we examined the effects of application site and skin decontamination on VX toxicity in anesthetized domestic swine after topical application. VX applied to the surface of the ear rapidly resulted in signs of toxicity consistent with the development of cholinergic crisis, including apnea and death. VX on the epigastrium resulted in a marked delayed development of toxic signs, reduced toxicity, and reduction in the rate of cholinesterase depression compared with animals exposed on the ear. Skin decontamination (15 minutes post-VX on the ear) arrested the development of clinical signs and prevented further cholinesterase inhibition and death. These results confirm earlier work that demonstrates the importance of exposure site on the resultant toxicity of this agent and they also show that decontamination postexposure has the potential to be an integral and extremely important component of medical countermeasures against this agent.
Abstract
Dark matter is a key piece of the current cosmological scenario, with weakly interacting massive particles (WIMPs) a leading dark matter candidate. WIMPs have not been detected in their ...conventional parameter space (100 GeV ≲
M
χ
≲ 100 TeV), a mass range accessible with current Imaging Atmospheric Cherenkov Telescopes. As ultraheavy dark matter (UHDM;
M
χ
≳ 100 TeV) has been suggested as an underexplored alternative to the WIMP paradigm, we search for an indirect dark matter annihilation signal in a higher mass range (up to 30 PeV) with the VERITAS
γ
-ray observatory. With 216 hr of observations of four dwarf spheroidal galaxies, we perform an unbinned likelihood analysis. We find no evidence of a
γ
-ray signal from UHDM annihilation above the background fluctuation for any individual dwarf galaxy nor for a joint-fit analysis, and consequently constrain the velocity-weighted annihilation cross section of UHDM for dark matter particle masses between 1 TeV and 30 PeV. We additionally set constraints on the allowed radius of a composite UHDM particle.
Abstract
Superluminous supernovae (SLSNe) are a rare class of stellar explosions with luminosities ∼ 10–100 times greater than ordinary core-collapse supernovae. One popular model to explain the ...enhanced optical output of hydrogen-poor (Type I) SLSNe invokes energy injection from a rapidly spinning magnetar. A prediction in this case is that high-energy gamma-rays, generated in the wind nebula of the magnetar, could escape through the expanding supernova ejecta at late times (months or more after optical peak). This paper presents a search for gamma-ray emission in the broad energy band from 100 MeV to 30 TeV from two Type I SLSNe, SN2015bn, and SN2017egm, using observations from Fermi-LAT and VERITAS. Although no gamma-ray emission was detected from either source, the derived upper limits approach the putative magnetar’s spin-down luminosity. Prospects are explored for detecting very-high-energy (VHE; 100 GeV–100 TeV) emission from SLSNe-I with existing and planned facilities such as VERITAS and CTA.
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