ABSTRACT We present results of a stellar occultation by the Jupiter Trojan asteroid Patroclus and its nearly equal size moon, Menoetius. The geocentric mid-time of the event was 2013 October 21 ...06:43:02 UT. Eleven sites out of 36 successfully recorded an occultation. Seven chords across Patroclus yielded an elliptical limb fit of 124.6 by 98.2 km. There were six chords across Menoetius that yielded an elliptical limb fit of 117.2 by 93.0 km. There were three sites that got chords on both objects. At the time of the occultation we measured a separation of 664.6 km (0.247 arcsec) and a position angle for Menoetius of 265 7 measured eastward from J2000 north. Combining this occultation data with previous light curve data, the axial ratios of both objects are 1.3 : 1.21 : 1, indicative of a mostly oblate ellipsoid with a slight asymmetry in its equatorial projection. The oblate shape is not an equilibrium shape for the current rotation period, but would be if it were rotating with an ∼8 h period. This faster period is consistent with a pre-evolved state of the system with an orbital separation that is 50% smaller. Our best estimate of the system density is 0.88 g cm−3.
•First attempt to constrain the residence time of spring water in the TMG Aquifer.•Residence times between 17.6 and 41.6yrs indicated by noble gas and tritium data.•Changing modern precipitation ...patterns will impact spring sustainability.
Large scale groundwater abstraction is increasingly being used to support large urban centres especially in areas of low rainfall but presents particular challenges in the management and sustainability of the groundwater system. The Table Mountain Group (TMG) Aquifer is one of the largest and most important aquifer systems in South Africa and is currently being considered as an alternative source of potable water for the City of Cape Town, a metropolis of over four million people. The TMG aquifer is a fractured rock aquifer hosted primarily in super mature sandstones, quartzites and quartz arenites. The groundwater naturally emanates from numerous springs throughout the cape region. One set of springs were examined to assess the source and residence time of the spring water. Oxygen and hydrogen isotopes indicate that the spring water has not been subject to evaporation and in combination with Na/Cl ratios implies that recharge to the spring systems is via coastal precipitation. Although rainfall in the Cape is usually modelled on orographic rainfall, δ18O and δ2H values of some rainfall samples are strongly positive indicating a stratiform component as well. Comparing the spring water δ18O and δ2H values with that of local rainfall, indicates that the springs are likely derived from continuous bulk recharge over the immediate hinterland to the springs and not through large and/or heavy downpours. Noble gas concentrations, combined with tritium and radiocarbon activities indicate that the residence time of the TMG groundwater in this area is decadal in age with a probable maximum upper limit of ∼40years. This residence time is probably a reflection of the slow flow rate through the fractured rock aquifer and hence indicates that the interconnectedness of the fractures is the most important factor controlling groundwater flow. The short residence time of the groundwater suggest that recharge to the springs and the Table Mountain Group Aquifer as a whole is vulnerable to climate change and reductions in regional precipitation. Any plans for large scale abstraction to supplement the City of Cape Town water supply would need to factor this into models of maximum sustainable yield.
P450s (cytochrome P450 mono-oxygenases) are a superfamily of haem-containing mono-oxygenase enzymes that participate in a wide range of biochemical pathways in different organisms from all of the ...domains of life. To facilitate their activity, P450s require sequential delivery of two electrons passed from one or more redox partner enzymes. Although the P450 enzymes themselves show remarkable similarity in overall structure, it is increasingly apparent that there is enormous diversity in the redox partner systems that drive the P450 enzymes. This paper examines some of the recent advances in our understanding of the biodiversity of the P450 redox apparatus, with a particular emphasis on the redox systems in the pathogen Mycobacterium tuberculosis.
Acute kidney injury (AKI) is a common and serious condition with no specific treatment. An episode of AKI may affect organs distant from the kidney, further increasing the morbidity associated with ...AKI. The mechanism of organ cross talk after AKI is unclear. The renal and immune systems of pigs and humans are alike. Using a preclinical animal (porcine) model, we tested the hypothesis that early effects of AKI on distant organs is by immune cell infiltration, leading to inflammatory cytokine production, extravasation, and edema. In 29 pigs exposed to either sham surgery or renal ischemia-reperfusion (control, n = 12; AKI, n = 17), we assessed remote organ (liver, lung, brain) effects in the short (from 2- to 48-h reperfusion) and longer term (5 wk later) using immunofluorescence (for leukocyte infiltration, apoptosis), a cytokine array, tissue elemental analysis (e.g., electrolytes), blood hematology and chemistry (e.g., liver enzymes), and PCR (for inflammatory markers). AKI elicited significant, short-term (∼24 h) increments in enzymes indicative of acute liver damage (e.g. , AST: ALT ratio; P = 0.02) and influenced tissue biochemistry in some remote organs (e.g., lung tissue Ca(2+) increased; P = 0.04). These effects largely resolved after 48 h, and no further histopathology, edema, apoptosis, or immune cell infiltration was noted in the liver, lung, or hippocampus in the short and longer term. AKI has subtle biochemical effects on remote organs in the short term, including a transient increment in markers of acute liver damage. These effects resolved by 48 h, and no further remote organ histopathology, apoptosis, edema, or immune cell infiltration was noted.
Summary
Background
Patients with Crohn's disease (CD) have serologic responses to various microbial antigens. Serologic markers are associated with aggressive forms of disease and can be detected ...before onset of symptoms. Their utility in pre‐clinical disease or prediction of complicated disease course before diagnosis is unclear.
Aim
To evaluate the pattern of serologic anti‐microbial antibodies long prior to diagnosis and the subsequent risk of complicated Crohn's disease at diagnosis.
Methods
Sera from 100 US military personnel with Crohn's disease were obtained from the Department of Defense Serum Repository. For each patient, four samples were obtained at different time points before and around diagnosis, and were tested for 6 microbiota‐directed antibodies (ASCA‐IgA, ASCA‐IgG, anti‐OmpC, anti‐CBir1, anti‐A4‐Fla2 and anti‐FlaX). Associations between the presence and accumulation of Crohn's disease anti‐microbial antibodies before diagnosis and with the later development of complications were evaluated.
Results
Overall, 65 patients were positive for at least one Crohn's disease associated anti‐microbial antibody in the earliest available sample, at a median of 6 years before Crohn's disease diagnosis (interquartile range, 5.6–8.2). The number of positive anti‐microbial antibodies increased up to the time of Crohn's disease diagnosis. Complicated disease developed around the time of diagnosis in 24 patients. The proportion of positive antimicrobial antibodies before diagnosis was higher in patients with complicated vs. noncomplicated Crohn's disease. There was an inverse relationship between the time to first complication and the magnitude of serologic response before diagnosis.
Conclusion
The presence and accumulation of circulating anti‐microbial antibodies years before Crohn's disease diagnosis was associated with complicated Crohn's disease at or shortly after diagnosis.
The Cu hydroxy mineral, atacamite, is commonly associated with saline environments and is generally thought to dissolve rapidly in the presence of fresh water. A Cu contaminated soil from the arid ...Namaqualand region, South Africa, shows atacamite as the dominant Cu containing mineral. The stability of the Cu phase in this soil was determined through equilibrium and leaching studies using both deionised water (DI) and a concentrated (0.5 M) NaCl solution. Initially a high concentration of exchangeable Cu was released from the soils leached with NaCl. Continued leaching with NaCl resulted in a substantial decrease in Cu release as atacamite equilibria started to control dissolved Cu. This suggests that an initial spike of Cu laden water will leach from the soils at the onset of a large rainfall event. Further additions of water will result in a lower but sustained release of Cu from the soil. The Cu contaminated soils are exposed to acidic sulphate leachate thus the dissolution kinetics of synthetic atacamite in the acidic range (pH 5.5–4.0) was determined in both NaCl and DI solutions. The kinetic data showed that atacamite dissolution rates are significantly higher in DI than in NaCl but the rates converge at pH 4. In comparison to common acid soluble minerals, atacamite displays a moderate dissolution rate (10−9.55–10−7.14 mol m−2 s−1) within the acid range (pH 5.5–4.0). The atacamite dissolution reaction order with respect to pH is 1.3 and 1.6 in DI and NaCl solutions, respectively, suggesting that dissolution rates of atacamite are highly pH dependent in the acid range. The type of acid used to lower the pH had no effect on the reaction kinetics, with HNO3 and H2SO4 resulting in comparable dissolution rates of atacamite at pH 4.5.
•Copper release from atacamite rich soils is higher in pure water than in a NaCl solution.•Atacamite shows a moderate dissolution rate in the acidic range (pH 4–5.5).•Atacamite dissolution rate is higher in pure water than in NaCl solution.•Acid type does not influence dissolution rate of atacamite.
Acute kidney injury is common, serious with no specific treatment. Ischemia-reperfusion is a common cause of acute kidney injury (AKI). Clinical trials suggest that preoperative erythropoietin (EPO) ...or remote ischemic preconditioning may have a renoprotective effect. Using a porcine model of warm ischemia-reperfusion-induced AKI (40-min bilateral cross-clamping of renal arteries, 48-h reperfusion), we examined the renoprotective efficacy of EPO (1,000 iu/kg iv.) or remote ischemic preconditioning (3 cycles, 5-min inflation/deflation to 200 mmHg of a hindlimb sphygmomanometer cuff). Ischemia-reperfusion induced significant kidney injury at 24 and 48 h (χ(2), 1 degree of freedom, >10 for 6/7 histopathological features). At 2 h, a panel of biomarkers including plasma creatinine, neutrophil gelatinase-associated lipocalin, and IL-1β, and urinary albumin:creatinine could be used to predict histopathological injury. Ischemia-reperfusion increased cell proliferation and apoptosis in the renal cortex but, for pretreated groups, the apoptotic cells were predominantly intratubular rather than interstitial. At 48-h reperfusion, plasma IL-1β and the number of subcapsular cells in G2-M arrest were reduced after preoperative EPO, but not after remote ischemic preconditioning. These data suggest an intrarenal mechanism acting within cortical cells that may underpin a renoprotective function for preoperative EPO and, to a limited extent, remote ischemic preconditioning. Despite equivocal longer-term outcomes in clinical studies investigating EPO as a renoprotective agent in AKI, optimal clinical dosing and administration have not been established. Our data suggest further clinical studies on the potential renoprotective effect of EPO and remote ischemic preconditioning are justified.
Bone morphogenetic proteins (BMPs) delivered on scaffolds can induce ectopic bone formation after subcutaneous injection. Adenoviral vectors (Ad) carrying BMP2, BMP7, and BMP9 cDNAs have been shown ...to produce bone through endochondral ossification. The present study was performed to elucidate the histological events leading to ectopic ossification for two novel first-generation adenoviral constructs encoding BMPs, AdBMP4 and AdBMP6. In vitro, the viral constructs produced and secreted the mature BMP4 and BMP6 proteins. In vivo, the calf muscles of athymic nude rats were injected with AdBMP4, AdBMP6, AdBMP2, or AdlacZ. Rats were sacrificed 3, 6, 9, 16, 21, 60, and 90 days postinjection. Whereas AdBMP4 produced ectopic bone through mechanisms similar to endochondral ossification, AdBMP6 seemed to induce bone by way of mechanisms similar to both intramembranous and endochondral ossification pathways. At the relatively low vector dose used in this study, AdBMP2 caused an initial recruitment of primitive mesenchymal cells, without further development to bone. From computed tomographic analysis, AdBMP6 produced the most rapid tissue calcification. The ultimate density of ectopic bone formed by AdBMP4 and AdBMP6 was comparable. The current study demonstrates that AdBMP4 and AdBMP6 are more potent than the prototypical osteogenic adenoviral vector AdBMP2 and seem to induce ectopic bone by different mechanisms.
Primary central nervous system lymphomas (PCNSLs) and primary testicular lymphomas (PTLs) are extranodal large B-cell lymphomas (LBCLs) with inferior responses to current empiric treatment regimens. ...To identify targetable genetic features of PCNSL and PTL, we characterized their recurrent somatic mutations, chromosomal rearrangements, copy number alterations (CNAs), and associated driver genes, and compared these comprehensive genetic signatures to those of diffuse LBCL and primary mediastinal large B-cell lymphoma (PMBL). These studies identify unique combinations of genetic alterations in discrete LBCL subtypes and subtype-selective bases for targeted therapy. PCNSLs and PTLs frequently exhibit genomic instability, and near-uniform, often biallelic, CDKN2A loss with rare TP53 mutations. PCNSLs and PTLs also use multiple genetic mechanisms to target key genes and pathways and exhibit near-uniform oncogenic Toll-like receptor signaling as a result of MYD88 mutation and/or NFKBIZ amplification, frequent concurrent B-cell receptor pathway activation, and deregulation of BCL6. Of great interest, PCNSLs and PTLs also have frequent 9p24.1/PD-L1/PD-L2 CNAs and additional translocations of these loci, structural bases of immune evasion that are shared with PMBL.
•PCNSLs and PTLs have a defining genetic signature that differs from other LBCLs and suggests rational targeted therapies.•PCNSLs and PTLs frequently exhibit 9p24.1/PD-L1/PD-L2 copy number alterations and translocations, likely genetic bases of immune evasion.
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