Demographic and Clinical Characteristics of Mucinous Epithelial Ovarian Cancer, and Survival Following a Mucinous Epithelial Ovarian Cancer Diagnosis

Alternative & renewable energy sources & technolog

X-ray Properties of NGC 253's Starburst-Driven Outflow

We analyze image and spectral data from $\approx$365~ks of observations from the {\it Chandra} X-ray Observatory of the nearby, edge-on starburst galaxy NGC~253 to constrain properties of the hot phase of the outflow. We focus our analysis on the $-$1.1 to $+$0.63 kpc region of the outflow and define several regions for spectral extraction where we determine best-fit temperatures and metal abundances. We find that the temperatures and electron densities peak in the central $\sim$250 pc region of the outflow and decrease with distance. These temperature and density profiles are in disagreement with an adiabatic spherically expanding starburst wind model and suggest the presence of additional physics such as mass loading and non-spherical outflow geometry. Our derived temperatures and densities yield few-Myr cooling times in the nuclear region, which may imply that the hot gas can undergo bulk radiative cooling as it escapes along the minor axis. Our metal abundances of O, Ne, Mg, Si, S, and Fe all peak in the central region and decrease with distance along the outflow, with the exception of Ne which maintains a flat distribution. The metal abundances indicate significant dilution outside of the starburst region. We also find estimates on the mass outflow rates which are $2.8\:M_{\odot}/\rm{yr}$ in the northern outflow and $3.2\:M_{\odot}/\rm{yr}$ in the southern outflow. Additionally, we detect emission from charge exchange and find it has a significant contribution ($20-42$\%) to the total broad-band ($0.5-7$~keV) X-ray emission in the central and southern regions of the outflow.Comment: 15 pages, 9 figure

Fragment screening reveals salicylic hydroxamic acid as an inhibitor of <em>Trypanosoma brucei</em> GPI GlcNAc-PI de-N-acetylase

The zinc-metalloenzyme GlcNAc-PI de-N-acetylase is essential for the biosynthesis of mature GPI anchors and has been genetically validated in the bloodstream form of Trypanosoma brucei, which causes African sleeping sickness. We screened a focused library of zinc-binding fragments and identified salicylic hydroxamic acid as a GlcNAc-PI de-N-acetylase inhibitor with high ligand efficiency. This is the first small molecule inhibitor reported for the trypanosome GPI pathway. Investigating the structure activity relationship revealed that hydroxamic acid and 2-OH are essential for potency, and that substitution is tolerated at the 4- and 5-positions

Aqueous Processes and Microbial Habitability of Gale Crater Sediments from the Blunts Point to the Glenn Torridon Clay Unit

A driving factor for sending the Mars Science Laboratory, Curiosity rover to Gale Crater was the orbital detection of clay minerals in the Glen Torridon (GT) clay unit. Clay mineral detections in GT suggested a past aqueous environment that was habitable, and could contain organic evidence of past microbiology. The mission of the Sample Analysis at Mars (SAM) instrument onboard Curiosity was to detect organic evidence of past microbiology and to detect volatile bearing mineralogy that can inform on whether past geochemical conditions would have supported microbiological activity. The objective of this work was to 1) evaluate the depositional/alteration conditions of Blunts Point (BP) to GT sediments 2) search for evidence of organics, and 3) evaluate microbial habitability in the BP, Vera Rubin Ridge (VRR), and GT sedimentary rock

Leaf litter nutrient uptake in an intermittent blackwater river : influence of tree species and associated biotic and abiotic drivers

Author Posting. © The Author(s), 2014. This is the author's version of the work. It is posted here by permission of British Ecological Society for personal use, not for redistribution. The definitive version was published in Functional Ecology 29 (2015): 849-860, doi:10.1111/1365-2435.12399.Organic matter may sequester nutrients as it decomposes, increasing in total N and P mass via multiple uptake pathways. During leaf litter decomposition, microbial biomass and accumulated inorganic materials immobilize and retain nutrients, and therefore both biotic and abiotic drivers may influence detrital nutrient content. We examined the relative importance of these types of nutrient immobilization and compared patterns of nutrient retention in recalcitrant and labile leaf litter. Leaf packs of water oak (Quercus nigra), red maple (Acer rubrum) and Ogeechee tupelo (Nyssa ogeche) were incubated for 431 days in an intermittent blackwater stream and periodically analyzed for mass loss, nutrient and metal content, and microbial biomass. These data informed regression models explaining temporal changes in detrital nutrient content. Informal exploratory models compared estimated biologically-associated nutrient stocks (fungal, bacterial, leaf tissue) to observed total detrital nutrient stocks. We predicted that (1) labile and recalcitrant leaf litter would act as sinks at different points in the breakdown process, (2) plant and microbial biomass would not account for the entire mass of retained nutrients, and (3) total N content would be more closely approximated than total P content solely from nutrients stored in leaf tissue and microbial biomass, due to stronger binding of P to inorganic matter. Labile litter had higher nutrient concentrations throughout the study. However, lower mass loss of recalcitrant litter facilitated greater nutrient retention over longer incubations, suggesting that it may be an important long-term sink. N and P content were significantly related to both microbial biomass and metal content, with slightly stronger correlation to metal content over longer incubations.This work was funded by the USDA-CSREES Integrated Research, Education, and Extension Competitive Grants Program’s National Integrated Water Quality Program (Award No. 2004-5113002224), Hatch & State funds allocated to the Georgia Agricultural Experiment Stations, USDA-ARS CRIS project funds, and a Student Research Grant awarded to Andrew Mehring from the Odum School of Ecology, University of Georgia.2016-01-2

Asfotase alfa therapy for children with hypophosphatasia

Background. Hypophosphatasia (HPP) is caused by loss-of-function mutation(s) of the gene that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). Consequently, cell-surface deficiency of TNSALP phosphohydrolase activity leads to extracellular accumulation of inorganic pyrophosphate, a natural substrate of TNSALP and inhibitor of mineralization. Children with HPP can manifest rickets, skeletal pain, deformity, fracture, muscle weakness, and premature deciduous tooth loss. Asfotase alfa is a recombinant, bone-targeted, human TNSALP injected s.c. to treat HPP. In 2012, we detailed the 1-year efficacy of asfotase alfa therapy for the life-threatening perinatal and infantile forms of HPP. Methods. Here, we evaluated the efficacy and safety of asfotase alfa treatment administered to children 6–12 years of age at baseline who were substantially impaired by HPP. Two radiographic scales quantitated HPP skeletal disease, including comparisons to serial radiographs from similarly affected historical control patients. Results. Twelve children receiving treatment were studied for 5 years. The 6-month primary endpoint was met, showing significant radiographic improvement. Additional significant improvements included patient growth, strength, motor function, agility, and quality of life, which for most patients meant achieving normal values for age- and sex-matched peers that were sustained at 5 years of treatment. For most, pain and disability resolved. Mild to moderate injection-site reactions were common and were sometimes associated with lipohypertrophy. Low anti–asfotase alfa antibody titers were noted in all patients. No evidence emerged for clinically important ectopic calcification or treatment resistance. Conclusions. Asfotase alfa enzyme replacement therapy has substantial and sustained efficacy with a good safety profile for children suffering from HPP. Trial Registration. ClinicalTrials.gov NCT00952484 (https://clinicaltrials.gov/ct2/show/NCT00952484) and NCT01203826 (https://clinicaltrials.gov/ct2/show/NCT01203826). Funding. Alexion Pharmaceuticals Inc. and Shriners Hospitals for Children

Seismological structure of the 1.8 Ga Trans-Hudson Orogen of North America

Precambrian tectonic processes are debated: what was the nature and scale of orogenic events on the younger, hotter, and more ductile Earth? Northern Hudson Bay records the Paleoproterozoic collision between the Western Churchill and Superior plates—the ∼1.8 Ga Trans-Hudson Orogeny (THO)—and is an ideal locality to study Precambrian tectonic structure. Integrated field, geochronological, and thermobarometric studies suggest that the THO was comparable to the present-day Himalayan-Karakoram-Tibet Orogen (HKTO). However, detailed understanding of the deep crustal architecture of the THO, and how it compares to that of the evolving HKTO, is lacking. The joint inversion of receiver functions and surface wave data provides new Moho depth estimates and shear velocity models for the crust and uppermost mantle of the THO. Most of the Archean crust is relatively thin (∼39 km) and structurally simple, with a sharp Moho; upper-crustal wave speed variations are attributed to postformation events. However, the Quebec-Baffin segment of the THO has a deeper Moho (∼45 km) and a more complex crustal structure. Observations show some similarity to recent models, computed using the same methods, of the HKTO crust. Based on Moho character, present-day crustal thickness, and metamorphic grade, we support the view that southern Baffin Island experienced thickening during the THO of a similar magnitude and width to present-day Tibet. Fast seismic velocities at >10 km below southern Baffin Island may be the result of partial eclogitization of the lower crust during the THO, as is currently thought to be happening in Tibet

Comparison of Marker-based Pairwise Relatedness Estimators on a Pedigreed Plant Population

Several estimators have been proposed that use molecular marker data to infer the degree of relatedness for pairs of individuals. The objective of this study was to evaluate the performance of seven estimators when applied to marker data of a set of 33 key individuals from a large complex apple pedigree. The evaluation considered different scenarios of allele frequencies and different numbers of marker loci. The method of moments estimators were Similarity, Queller-Goodknight, Lynch-Ritland and Wang. The maximum likelihood estimators were Thompson, Anderson-Weir and Jacquard. The pedigree-based coancestry coefficients were taken as the point of reference in calculating correlations and root mean square error (RMSE). The marker data comprised 86 multi-allelic SSR markers on 17 linkage groups, covering 11 Morgans. Additionally, we simulated 10 datasets conditional on the real pedigree to support the results on the real dataset. None of the estimators outperformed the others. Knowledge of allele frequencies appeared to be the most influential, i.e., the highest correlations and lowest RMSE were found when frequencies from the founder population were available. When equal allele frequencies were used, all estimators resulted in very similar, but on average lower, correlations. The use of allele frequencies estimated from the set of 33 individuals gave, on average, the poorest results. The maximum likelihood estimators and the Lynch-Ritland estimator were the most sensitive to allele frequencies. The results from the simulation study fully supported the trends in results of the real dataset. This study indicated that high correlations (up to 0.90) and small RMSE (below 0.03), may be obtained when population allelic frequencies are available. In this scenario, the performances of the various estimators were similar, but seemed to favor the maximum likelihood estimators. In the absence of reliable allele frequencies the method of moments estimators were shown to be more robust. The number of marker loci influenced the average performance of the estimators; however, the ranking was not affected. Correlations up to 0.80 were obtained when two markers per chromosome and appropriate allele frequencies were available. Adding more markers to the current dataset may lead to marginal improvements

Peptidylarginine Deiminase 3 (PAD3) Is Upregulated by Prolactin Stimulation of CID-9 Cells and Expressed in the Lactating Mouse Mammary Gland

Peptidylarginine deiminases (PADs) post-translationally convert arginine into neutral citrulline residues. Our past work shows that PADs are expressed in the canine and murine mammary glands; however, the mechanisms regulating PAD expression and the function of citrullination in the normal mammary gland are unclear. Therefore, the first objective herein was to investigate regulation of PAD expression in mammary epithelial cells. We first examined PAD levels in CID-9 cells, which were derived from the mammary gland of mid-pregnant mice. PAD3 expression is significantly higher than all other PAD isoforms and mediates protein citrullination in CID-9 cells. We next hypothesized that prolactin regulates PAD3 expression. To test this, CID-9 cells were stimulated with 5 mug/mL of prolactin for 48 hours which significantly increases PAD3 mRNA and protein expression. Use of a JAK2 inhibitor and a dominant negative (DN)-STAT5 adenovirus indicate that prolactin stimulation of PAD3 expression is mediated by the JAK2/STAT5 signaling pathway in CID-9 cells. In addition, the human PAD3 gene promoter is prolactin responsive in CID-9 cells. Our second objective was to investigate the expression and activity of PAD3 in the lactating mouse mammary gland. PAD3 expression in the mammary gland is highest on lactation day 9 and coincident with citrullinated proteins such as histones. Use of the PAD3 specific inhibitor, Cl4-amidine, indicates that PAD3, in part, can citrullinate proteins in L9 mammary glands. Collectively, our results show that upregulation of PAD3 is mediated by prolactin induction of the JAK2/STAT5 signaling pathway, and that PAD3 appears to citrullinate proteins during lactation

Physician decision making in selection of second-line treatments in immune thrombocytopenia in children.

Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder which presents with isolated thrombocytopenia and risk of hemorrhage. While most children with ITP promptly recover with or without drug therapy, ITP is persistent or chronic in others. When needed, how to select second-line therapies is not clear. ICON1, conducted within the Pediatric ITP Consortium of North America (ICON), is a prospective, observational, longitudinal cohort study of 120 children from 21 centers starting second-line treatments for ITP which examined treatment decisions. Treating physicians reported reasons for selecting therapies, ranking the top three. In a propensity weighted model, the most important factors were patient/parental preference (53%) and treatment-related factors: side effect profile (58%), long-term toxicity (54%), ease of administration (46%), possibility of remission (45%), and perceived efficacy (30%). Physician, health system, and clinical factors rarely influenced decision-making. Patient/parent preferences were selected as reasons more often in chronic ITP (85.7%) than in newly diagnosed (0%) or persistent ITP (14.3%, P = .003). Splenectomy and rituximab were chosen for the possibility of inducing long-term remission (P < .001). Oral agents, such as eltrombopag and immunosuppressants, were chosen for ease of administration and expected adherence (P < .001). Physicians chose rituximab in patients with lower expected adherence (P = .017). Treatment choice showed some physician and treatment center bias. This study illustrates the complexity and many factors involved in decision-making in selecting second-line ITP treatments, given the absence of comparative trials. It highlights shared decision-making and the need for well-conducted, comparative effectiveness studies to allow for informed discussion between patients and clinicians