We report here the results of an investigation of W and Nd isotopes in the SNC (Shergottite-Nakhlite-Chassignite (martian)) meteorites. We have determined that epsilon W-182 values in the nakhlites ...are uniform within analytical uncertainties and have an average value of approx. 3. Also, while epsilon W-182 values in the shergottites have a limited range (from 0.3-0.7), their epsilon Nd-142 values vary considerably (from -0.2-0.9). There appears to be no correlation between epsilon W-182 and epsilon Nd-142 in the nakhlites and shergottites. These results shed new light on early differentiation processes on Mars, particularly on the timing and nature of fractionation in silicate reservoirs. Assuming a two-stage model, the metallic core is estimated to have formed at approx. 12 Myr after the beginning of the solar system. Major silicate differentiation established the nakhlite source reservoir before approx. 4542 Ma and the shergottite source reservoirs at 4525 sup +19 sub -21 Ma. These ages imply that, within the uncertainties afforded by the Hf-182-W-182 and Sm-146-Nd-142 chronometers, the silicate differentiation events that established the source reservoirs of the nakhlites and shergottites may have occurred contemporaneously, possibly during crystallization of a global magma ocean. The distinct W-182-Nd-142 isotope systematics in the nakhlites and the shergottites imply the presence of at least three isotopically distinct silicate reservoirs on Mars, two of which are depleted in incompatible lithophile elements relative to chondrites, and the third is enriched. The two depleted silicate reservoirs most likely reside in the Martian mantle, while the enriched reservoir could be either in the crust or the mantle. Therefore, the W-182-Nd-142 isotope systematics indicate that the nakhlites and the shergottites originated from distinct source reservoirs and cannot be petrogenetically related. A further implication is that the source reservoirs of the nakhlites and shergottites on Mars have been isolated since their establishment before approx. 4.5 Ga. Therefore, there has been no giant impact or efficient global mantle convection to thoroughly homogenize the Martian mantle following the establishment of the SNC source reservoirs.
Asuka 881394 is a unique basaltic meteorite that originated in the crust of a differentiated planetesimal in the early Solar System. We present high precision Pb, Mg, and Cr isotopic compositions of ...bulk samples and mineral separates from this achondrite. A
207Pb–
206Pb internal isochron obtained from the radiogenic pyroxene and whole-rock fractions of Asuka 881394 yields an absolute age of 4566.5
±
0.2
Ma, which we consider to be the best estimate for the crystallization age of this basaltic achondrite. The
26Al–
26Mg systematics show some evidence of disturbance, but 5 of the 6 analyzed whole-rock and mineral fractions define an isochron corresponding to a
27Al/
26Al ratio of (1.28
±
0.07)
×
10
−6. Comparison with the
26Al–
26Mg and Pb–Pb systematics in the D’Orbigny achondrite translates to a
26Al–
26Mg age of 4565.4
±
0.2
Ma for Asuka 881394. The
53Mn–
53Cr systematics in whole-rock, silicate and chromite fractions correspond to a
53Mn/
55Mn ratio of (3.85
±
0.23)
×
10
−6. Compared to the most precise
53Mn–
53Cr and Pb–Pb systematics available for the D’Orbigny angrite, this translates to a
53Mn–
53Cr age of 4565.3
±
0.4
Ma; similarly, a comparison with the NWA 4801 angrite yields a
53Mn–
53Cr age of 4565.5
±
0.4
Ma, in agreement with the age obtained relative to D’Orbigny. While the
26Al–
26Mg and
53Mn–
53Cr ages appear to be concordant in Asuka 881394, these ages are ∼1
Ma younger than its
207Pb–
206Pb age. This discordance might have been caused by one or more of several reasons, including differences in the closure temperatures for Pb versus Cr and Mg diffusion in their host minerals combined with slow cooling of the parent body as well as differential resetting of isotopic systems by a process other than volume diffusion, e.g., shock metamorphism. The ancient age of Asuka 881394 suggests that basaltic volcanism on its parent planetesimal occurred within ∼3
Ma of the formation of earliest solids in the Solar System, essentially contemporaneously with chondrule formation. This requires that the Asuka 881394 parent body was fully accreted within ∼500,000
yrs of Solar System formation.
We report composition-dependent matrix effects in the in-situ measurement of Mg and Si isotope ratios by laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) in natural and ...synthetic silicate glasses. These were determined using two 193nm wavelength excimer laser ablation-multicollector ICPMS systems, one employing a double-focusing mass spectrometer (ThermoFinnigan Neptune) and one employing a single-focusing mass spectrometer with a hexapole/collision cell (GV Instruments IsoProbe). Observed matrix effects in isotopic measurements by LA-ICPMS range from subtle (i.e., less than ≈0.7‰ per amu for Si isotope measurements in natural and synthetic glasses in all instrumental configurations) to significant but mass-dependent (i.e., less than 1.2‰ per amu for Mg isotope measurements performed using the Neptune) to large and significantly non-mass-dependent (i.e., up to 6‰ mass dependent/3‰ non-mass dependent for Mg isotope measurements of natural glasses made with the IsoProbe). Composition-dependent differences in the magnitude and direction of within-run isotopic fractionation (particularly for Mg isotope measurements) suggest that isotopic fractionation at the site of ablation is the main source of matrix effects in measurements employing the double-focusing mass spectrometer. However, the large and significantly non-mass dependent (but systematic and reproducible) matrix effects affecting LA-ICPMS Mg isotope data obtained using the single-focusing IsoProbe appear to be largely due to non-linear scattering processes occurring in the hexapole/collision cell as Mg becomes increasingly diluted by matrix elements.
► Mg and Si isotopes measured by LA-MC-ICPMS in glasses show matrix effects. ► Composition-dependent effects are larger for Mg than for Si isotope measurements. ► Largest Mg isotope matrix effects in measurements using single-focusing MC-ICPMS.
We report on the petrology and geochemistry of the Northwest Africa 2737 (NWA 2737) meteorite that was recovered from the Morrocan Sahara in 2000. It is the second member of the chassignite subclass ...of the SNC (Shergotitte-Nakhlite-Chassignite) group of meteorites that are thought to have originated on Mars. It consists of black olivine- and spinel-cumulate crystals (89.7 and 4.6
wt%, respectively), with intercumulus pyroxenes (augite 3.1
wt% and pigeonite–orthopyroxene 1.0
wt%), analbite glass (1.6
wt%) and apatite (0.2
wt%). Unlike Chassigny, plagioclase has not been observed in NWA 2737. Olivine crystals are rich in Mg, and highly equilibrated (
Fo
=
78.7
±
0.5
mol%). The black color of olivine grains may be related to the strong shock experienced by the meteorite as revealed by the deformation features observed on the macroscopic to the atomic scale. Chromite is zoned from core to rim from Cr
83.4Uv
3.6Sp
13.0 to Cr
72.0Uv
6.9Sp
21.1. Pyroxene compositional trends are similar to those described for Chassigny except that they are richer in Mg. Compositions range from En
78.5Wo
2.7Fs
18.8 to En
76.6Wo
3.2Fs
20.2 for the orthopyroxene, from En
73.5Wo
8.0Fs
18.5 to En
64.0Wo
22.1Fs
13.9for pigeonite, and from En
54.6Wo
32.8Fs
12.6 to En
46.7Wo
44.1Fs
9.2 for augite. Bulk rock oxygen isotope compositions confirm that NWA 2737 is a new member of the martian meteorite clan (Δ
17O
=
0.305
±
0.02‰,
n
=
2). REE abundances measured in NWA 2737 mineral phases are similar to those in Chassigny and suggest a genetic relationship between these two rocks. However, the parent melt of NWA 2737 was less evolved and had a lower Al abundance.
Human type I interferon products have been approved for the treatment of several diseases, though neutralising antibodies against them may develop and reduce therapeutic efficacy. Traditionally, ...potencies of human interferons (IFNs) and of neutralising antibodies (NAbs) against them are quantified by antiviral assays. These are being increasingly replaced by less cumbersome and faster bioassay methods. Since IFNs exert their biological effects by binding to receptors on target cells and stimulating the expression of IFN-inducible genes, measurement of transcribed mRNAs can form the basis of functional bioassays. In this study we have used two approaches, quantitative reverse transcription-polymerase chain reaction (qPCR) and branched DNA (bDNA), to develop efficient, sensitive and robust non-viral assays to quantify type I IFNs
per se and NAbs in sera from patients treated with either IFNβ or IFNα2a. We show the rapid (4
h) induction of the type I IFN-inducible 6-16 mRNA in A549 lung carcinoma cells is sensitively and reproducibly concentration-dependent for both IFNβ and IFNα2a stimulation, is quantifiable by either approach, and is readily adaptable for the detection and measurement of NAbs against type I IFNs. Quantitative neutralisation of IFN-stimulated 6-16 mRNA expression was achieved in both assays when sera from patients receiving IFNβ or IFNα2a therapy known to contain NAbs against these IFNs were tested. Their rapid and potentially automatable performance strongly suggests these assays could be used in a clinical setting to monitor the development of neutralising antibodies in patients receiving IFN therapy.
An important aspect of evaluating the safety of therapeutic biologicals is the assessment of the unwanted immunogenicity of such biologicals in recipients. Properly planned immunogenicity studies ...with appropriately devised strategies are critical if valid conclusions concerning the unwanted immunogenicity are to be derived. Such studies need to be conducted using carefully selected and validated procedures. Several techniques are available for detection and measurement of immunogenicity including immunoassays, radioimmunoprecipitation assays (RIPAs), surface plasmon resonance (SPR) and bioassays. A combination of methods for characterization of the induced antibodies is usually necessary for a detailed understanding of the type(s) of antibodies generated against a therapeutic product. This review considers the benefits and limitations of the various techniques available for antibody detection and outlines a strategy for the assessment of unwanted immunogenicity of therapeutic products.
Abstract Objective To demonstrate the diagnostic yield (DY) across cardiac rhythm monitors stratified by monitoring duration for symptomatic patients with suspected cardiac arrhythmias (palpitations, ...dizziness, syncope, presyncope, lightheadedness). Methods PubMed, Embase, and Scopus were searched to identify published randomized and observational studies between January 1, 2000, and November 28th, 2021. DY data were extracted for comparative studies. The DY of cardiac monitors in these patients was reviewed for Any Arrhythmia, Clinically Relevant Arrhythmia, Explained Episodes (symptomatic and clinically relevant), New Onset Atrial Fibrillation, and Symptomatic Events. Clinically Relevant Arrhythmia was defined by the study and included atrial fibrillation, atrial flutter, atrial tachycardia, other SVT, VT, pause, and bradycardia. Patients who had a history of prior stroke or transient ischemic attack were excluded. Network meta-analysis (NMA) was used to pool estimates. Cardiac monitoring duration was categorized into the following 3 timeframes: 3 days or less (≤3 d), greater than 3 days to less than 30 days (>3 d), and 30 days or greater (≥ 30 d). Results Inclusion and exclusion criteria identified a pooled population of 1696 patients in 6 comparative studies, 2 Randomized Controlled Trials (RCTs) and 4 non-RCTs (Figure 1). NMA results for comparative studies show that monitoring durations of >3 d and ≥30 d provided significant better DY than ≤3 d (Table 1). The odds ratio for DY of >3 d as compared to ≤3 d was 5.75 (95% CI 2.05-19.38) in patients with Any Arrhythmias, 5.99 (95% CI 2.10 - 7.79) in patients with Clinically Relevant Arrhythmias, 10.22 (95% CI 0.61 - 4343.00) in patients with Explained Episodes, and 2.74 (95% CI 1.12 - 7.53) in patients with New Onset Atrial Fibrillation. As only a single study provided results on Symptomatic Events, NMA was not possible for this measure. The odds ratio for DY of >3 d as compared to ≥30 d was 0.02 (95% CI 0.00 - 0.15) in patients with Any Arrhythmias, 0.03 (95% CI 0.00 - 0.10) in patients with Clinically Relevant Arrhythmias, 0.04 (95% CI 0.01 - 0.13) in patients with Explained Episodes, and 0.17 (95% CI 0.03 - 0.66) in patients with diagnosis of New Onset Atrial Fibrillation. Conclusion NMA indicates that >3 d and ≥30 d provide significantly better DY than ≤3 d for identifying Any Arrhythmia, Clinically Relevant Arrhythmia, and New Onset AF. Despite favorable odds ratios for ≥30 d over >3 d, these values were associated with uncertainty due to the limited studies available for monitoring durations of ≥30 d. Overall, in patients experiencing symptoms of palpitations, dizziness, syncope, and without prior stroke or transient ischemic arrest, >3 d of monitoring improved DY compared with shorter monitoring durations.Figure 1.Prisma Flow DiagramTable 1.Diagnostic Yield Comparison.
