2,530 research outputs found
Transient x-ray diffraction used to diagnose shock compressed Si crystals on the Nova laser
Transient x-ray diffraction is used to record time-resolved information about the shock compression of materials. This technique has been applied on Nova shock experiments driven using a hohlraum x-ray drive. Data were recorded from the shock release at the free surface of a Si crystal, as well as from Si at an embedded ablator/Si interface. Modeling has been done to simulate the diffraction data incorporating the strained crystal rocking curves and Bragg diffraction efficiencies. Examples of the data and post-processed simulations are presented
Testing for Evidence of Maternal Effects among Individuals and Populations of White Crappie
For an increasing number of species, maternal characteristics have been correlated
with the characteristics of their eggs or larvae at the individual level. Documenting these maternal effects at the population level, however, is uncommon. For white crappies Pomoxis annularis, we evaluated whether individual maternal effects on eggs existed and then explored whether incorporating maternal effects explained additional variation in recruitment, a population-level response.
Individual egg quality (measured as ovary energy density) increased with maternal length among individuals from seven Ohio reservoirs in 1999 and three in 2000. Among these same individuals, egg quality increased with maternal condition factor (measured as residual wet mass for a given
length) in 1999 but not in 2000. In 2000 we estimated somatic energy density, an improved measure of condition; egg quality increased with somatic energy density, but somatic energy density was also strongly correlated with maternal length. Hence, we could not determine whether maternal
length or condition was the primary factor influencing white crappie egg quality. Across seven populations, the relative population fecundity (i.e., stock size) of the 1999 year-class was unable
to explain the variation in recruitment to age 2 (Ricker model r^2 = 0.04 and Beverton and Holt model r^2 = 0.02). Mean ovary energy density (i.e., egg quality), however, was unable to explain additional recruitment variability in either model. Hence, we documented evidence of maternal
effects on individual ovaries but not on population-level recruitment. Nonetheless, we recommend that future studies seeking to understand white crappie recruitment continue to consider maternal
effects as a potential factor, especially those studies that may have greater sample sizes at the population level and, in turn, a greater probability of documenting a population-level effect.This research was funded by Federal Aid in Sport Fish Restoration Project F-69-P, administered jointly by U.S. Fish and Wildlife Service and Ohio Department
of Natural Resources, Division of Wildlife
and the Department of Evolution, Ecology, and
Organismal Biology at Ohio State University
Inhibition of the Redox Function of APE1/Ref-1 in Myeloid Leukemia Cell Lines Results in a Hypersensitive Response to Retinoic Acid-induced Differentiation and Apoptosis
Objective
The standard of care for promyelocytic leukemia includes use of the differentiating agent all-trans retinoic acid (RA) and chemotherapy. RA induces cell differentiation through retinoic acid receptor (RAR) transcription factors. Because redox mechanisms influence how readily transcription factors bind to DNA response elements (RARE), the impact of small molecule (E3330) inhibition of the redox regulatory protein, apurinic-apyrimidinic endonuclease/redox effector factor (APE1/Ref-1) on RAR DNA binding and function in RA-induced myeloid leukemia cell differentiation and apoptosis was investigated.
Materials and Methods
The redox function of APE1 was studied using the small molecule inhibitor E3330 in HL-60 and PLB acute myeloid leukemia cells. Electrophoretic mobility shift assays were employed to determine effect of inhibitor on APE1/Ref-1 redox signaling function. Trypan blue assays, Annexin-V/propidium iodide and CD11b staining, and real-time polymerase chain reaction analyses were employed to determine survival, apoptosis, and differentiation status of cells in culture.
Results
RARα binds to its RARE in a redox-dependent manner mediated by APE1/Ref-1 redox regulation. Redox-dependent RAR-RARE binding is blocked by E3330, a small molecule redox inhibitor of APE1/Ref-1. Combination treatment of RA + E3330 results in a profound hypersensitivity of myeloid leukemia cells to RA-induced differentiation and apoptosis. Additionally, redox inhibition by E3330 results in enhanced RAR target gene, BLR-1, expression in myeloid leukemia cells.
Conclusions
The redox function of APE1/Ref-1 regulates RAR binding to its DNA RAREs influencing the response of myeloid leukemia cells to RA-induced differentiation. Targeting of APE1/Ref-1 redox function may allow manipulation of the retinoid response with therapeutic implications
Assessing the impact of a national clinical guideline for the management of chronic pain on opioid prescribing rates:a controlled interrupted time series analysis
Background: Opioids can be effective analgesics, but long-term use may be associated with harms. In 2013, the first national, comprehensive, evidence-based pain management guideline was published, from the Scottish Intercollegiate Guideline Network (SIGN 136: Management of Chronic Pain) with key recommendations on analgesic prescribing. This study aimed to examine the potential impact on national opioid prescribing rates in Scotland. Methods: Trends in national and regional community opioid prescribing data for Scotland were analysed from quarter one (Q1) 2005 to Q2 2020. Interrupted time series regression examined the association of SIGN 136 publication with prescribing rates for opioid-containing drugs. Gabapentinoid prescribing was used as a comparison drug. Results: After a positive prescribing trend pre-publication, the timing of SIGN 136 publication was associated with a negative change in the trend of opioid prescribing rates (−2.82 items per 1000 population per quarter [PTPPQ]; P < 0.01). By Q2 2020, the relative reduction in the opioid prescribing rate was −20.67% (95% CI: −23.61, −17.76). This persisted after correcting for gabapentinoid prescribing and was mainly driven by the reduction in weak opioids, whereas strong opioid prescribing rates continued to rise. Gabapentinoid prescribing showed a significant rise in level (8.00 items per 1000 population; P = 0.01) and trend (0.27 items PTPPQ; P = 0.01) following SIGN 136 publication. Conclusions: The publication of SIGN 136 was associated with a reduction in opioid prescribing rates. This suggests that changes in clinical policy through evidence-based national clinical guidelines may affect community opioid prescribing, though this may be partially replaced by gabapentinoids, and other factors may also contribute
Faster linearizability checking via -compositionality
Linearizability is a well-established consistency and correctness criterion
for concurrent data types. An important feature of linearizability is Herlihy
and Wing's locality principle, which says that a concurrent system is
linearizable if and only if all of its constituent parts (so-called objects)
are linearizable. This paper presents -compositionality, which generalizes
the idea behind the locality principle to operations on the same concurrent
data type. We implement -compositionality in a novel linearizability
checker. Our experiments with over nine implementations of concurrent sets,
including Intel's TBB library, show that our linearizability checker is one
order of magnitude faster and/or more space efficient than the state-of-the-art
algorithm.Comment: 15 pages, 2 figure
Influence of Nanoparticle Size and Shape on Oligomer Formation of an Amyloidogenic Peptide
Understanding the influence of macromolecular crowding and nanoparticles on
the formation of in-register -sheets, the primary structural component
of amyloid fibrils, is a first step towards describing \emph{in vivo} protein
aggregation and interactions between synthetic materials and proteins. Using
all atom molecular simulations in implicit solvent we illustrate the effects of
nanoparticle size, shape, and volume fraction on oligomer formation of an
amyloidogenic peptide from the transthyretin protein. Surprisingly, we find
that inert spherical crowding particles destabilize in-register -sheets
formed by dimers while stabilizing -sheets comprised of trimers and
tetramers. As the radius of the nanoparticle increases crowding effects
decrease, implying smaller crowding particles have the largest influence on the
earliest amyloid species. We explain these results using a theory based on the
depletion effect. Finally, we show that spherocylindrical crowders destabilize
the ordered -sheet dimer to a greater extent than spherical crowders,
which underscores the influence of nanoparticle shape on protein aggregation
Impacts of swine manure application and alternative N-management practices on productivity, sustainability and water quality
In the fourth year of this ongoing project, the effects of nine N-management practices under different tillage and cropping systems were evaluated. Forty experimental plots equipped with individual sumps and subsurface drainage metering and monitoring devices were used for the study. Overall results indicate that manure application rates and methods can be successfully managed for corn-soybean systems without damaging the water quality if the appropriate amount of N from swine manure can be applied
Mechanically Stabilized Tetrathiafulvalene Radical Dimers
Two donor−acceptor [3]catenanes—composed of a tetracationic molecular square, cyclobis(paraquat-4,4′-biphenylene), as the π-electron deficient ring and either two tetrathiafulvalene (TTF) and 1,5-dioxynaphthalene (DNP) containing macrocycles or two TTF-butadiyne-containing macrocycles as the π-electron rich components—have been investigated in order to study their ability to form TTF radical dimers. It has been proven that the mechanically interlocked nature of the [3]catenanes facilitates the formation of the TTF radical dimers under redox control, allowing an investigation to be performed on these intermolecular interactions in a so-called “molecular flask” under ambient conditions in considerable detail. In addition, it has also been shown that the stability of the TTF radical-cation dimers can be tuned by varying the secondary binding motifs in the [3]catenanes. By replacing the DNP station with a butadiyne group, the distribution of the TTF radical-cation dimer can be changed from 60% to 100%. These findings have been established by several techniques including cyclic voltammetry, spectroelectrochemistry and UV−vis−NIR and EPR spectroscopies, as well as with X-ray diffraction analysis which has provided a range of solid-state crystal structures. The experimental data are also supported by high-level DFT calculations. The results contribute significantly to our fundamental understanding of the interactions within the TTF radical dimers
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