Chelyabinsk meteorite explains unusual spectral properties of Baptistina Asteroid Family

We investigated the spectral and compositional properties of Chelyabinsk meteorite to identify its possible parent body in the main asteroid belt. Our analysis shows that the meteorite contains two spectrally distinct but compositionally indistinguishable components of LL5 chondrite and shock blackened/impact melt material. Our X-ray diffraction analysis confirms that the two lithologies of the Chelyabinsk meteorite are extremely similar in modal mineralogy. The meteorite is compositionally similar to LL chondrite and its most probable parent asteroid in the main belt is a member of the Flora family. Intimate mixture of LL5 chondrite and shock blackened/impact melt material from Chelyabinsk provides a spectral match with (8) Flora, the largest asteroid in the Flora family. The Baptistina family and Flora family overlap each other in dynamical space. Mineralogical analysis of (298) Baptistina and 9 small family members shows that their surface compositions are similar to LL chondrites, although their absorption bands are subdued and albedos lower when compared to typical S-type asteroids. A range of intimate mixtures of LL5 chondrite and shock blackened/impact melt material from Chelyabinsk provides spectral matches for all these BAF members. We suggest that the presence of a significant shock/impact melt component in the surface regolith of BAF members could be the cause of lower albedo and subdued absorption bands. The parent asteroid of BAF was either a member of the Flora family or had the same basic composition as the Floras (LL Chondrite). The shock pressures produced during the impact event generated enough impact melt or shock blackening to alter the spectral properties of BAF, but keep the BAF composition largely unchanged.Comment: 48 pages, 11 figures, 7 table

Current Performance and On-Going Improvements of the 8.2 m Subaru Telescope

An overview of the current status of the 8.2 m Subaru Telescope constructed and operated at Mauna Kea, Hawaii, by the National Astronomical Observatory of Japan is presented. The basic design concept and the verified performance of the telescope system are described. Also given are the status of the instrument package offered to the astronomical community, the status of operation, and some of the future plans. The status of the telescope reported in a number of SPIE papers as of the summer of 2002 are incorporated with some updates included as of 2004 February. However, readers are encouraged to check the most updated status of the telescope through the home page, http://subarutelescope.org/index.html, and/or the direct contact with the observatory staff.Comment: 18 pages (17 pages in published version), 29 figures (GIF format), This is the version before the galley proo

Magneto‐structural studies of paramagnetic metal cages

A central concern within the field of molecular magnetism has been the elucidation of magneto-structural correlations. This thesis describes a variety of systems and endeavours to study the relationship between structure and magnetic properties in these systems. The first body of work (chapters 2 and 3) studies CrIII dimers, with the metal centres displaying a dialkoxo bridging moiety and latterly an additional carboxylate bridge to direct the synthesis of ferromagnetic analogues. The second section of work (chapters 4‐6) moves forward to the study of larger, heterometallic 3d‐3d compounds, through the synthesis of a large family of Anderson type MIII 2MII 5 wheels and a subsequent family of (VIVO)2MII 5 wheels. Chapter 2 describes a series of di‐alkoxo bridged Cr(III) dimers, synthesised using the pyridine alcohol ligands 2‐pyridinemethanol (hmpH) and 2‐pyridineethanol (hepH) as well as 2‐picolinic acid (picH). The structures fall into four general categories and are of formula: [Cr2(OMe)2(pic)4], [Cr2(hmp)2(pic)2X2] (where X = Cl, Br), [Cr2(L)2Cl4(A)2] (where L = hmp, A = H2O; L = hmp, A = pyridine; L = hmp, A = 4‐picoline; L = hep, A = H2O), and [Cr(hmp)(hmpH)Cl2. Magnetic studies show relatively weak antiferromagnetic exchange interactions between the Cr(III) centres and DFT calculations are used to develop magneto‐structural correlations, showing that the magnitude and sign of the J value is strongly dependent upon the orientation of the dihedral angle formed between the bridging Cr2O2 plane and the O–R vector of the bridging group, and the Cr–O–Cr–O dihedral angle. Chapter 3 builds on the work from the previous chapter with discussion of a large family of chromium(III) dimers, synthesised using a combination of carboxylate and diethanolamine type ligands. The compounds have the general formula [Cr2(R1‐deaH)2(O2CR2)Cl2]Cl where R1 = Me and R2 = H, Me, CMe3, Ph, 3,5‐(Cl)2Ph, (Me)5Ph, R1 = Et and R2 = H, Ph. The compound [Cr2(Me‐deaH)2Cl4] was also synthesised in order to study the effect of removing/adding the carboxylate bridge to the observed magnetic behaviour. Magnetic studies reveal ferromagnetic exchange interactions between the Cr(III) centres in the carboxylate bridged family with coupling constants in the range +0.37 < J < +8.02 cm‐1. Removal of the carboxylate to produce the dialkoxide‐bridged compound results in antiferromagnetic exchange between the Cr(III) ions. DFT calculations to further develop the magneto-structural correlations reveal the ferromagnetic exchange is the result of an orbital counter-complementarity effect occurring upon introduction of the bridging carboxylate. Chapter 4 reports a family of heterometallic Anderson‐type ‘wheels’ of general formula [MIII 2MII 5(hmp)12](ClO4)4 (where MIII = Cr or Al and MII = Ni or Zn giving [Cr2Ni5], [Cr2Zn5], [Al2Ni5] and [Al2Zn5]; hmpH = 2‐pyridinemethanol) synthesised solvothermally. The metallic skeleton describes a centred hexagon with the MIII sites disordered around the outer wheel. The structural disorder is characterised via single crystal X‐ray crystallography, 1‐3D 1H and 13C solution‐state NMR spectroscopy of the diamagnetic analogue, and solid‐state 27Al MAS NMR spectroscopy of the Al containing analogues. Alongside ESI mass spectrometry, these techniques show that structure is retained in solution, and that the disorder is present in both the solution and solid‐state. Solid‐state dc susceptibility and magnetisation measurements on [Cr2Zn5] and [Al2Ni5] reveal the Cr‐Cr and Ni‐Ni exchange interactions to be JCr‐Cr = ‐1 cm‐1 and JNi‐Ni,r = ‐5 cm‐1, JNi‐Ni,c = 10 cm‐1. Fixing these values allows us to extract JCr‐Ni,r = ‐1.2 cm‐1, JCr‐Ni,c = 2.6 cm‐1, the exchange between adjacent Ni and Cr ions on the ring is antiferromagnetic and between Cr ions on the ring and the central Ni ion is ferromagnetic. Chapter 5 focusses on planar molecules, espanding the family of heterometallic Anderson‐type ‘wheels’ discussed in chapter 4 to include MIII = Cr, Al and MII = Co, Fe, Mn, Cu, affording five new species of formulae [Cr2Co5(hmp)12](ClO4)4, [Cr2Fe5(hmp)12](ClO4)4, [Cr2Mn5(hmp)12](ClO4)4, [Cr2Cu5(hmp)12](ClO4)2(NO3)2 and [Al2Co5(hmp)12](ClO4)4. As per previous family members, the two MIII sites are disordered around the outer wheel, with the exception of [Cr2Cu5] where the the CuII sites are localised. A structurally related, but enlarged planar disc possessing a [MIII 6MII] hexagon capped on each edge by a CuII ion is also reported, which is formed only when MIII = Al and MII = Cu. In [AlIII 6CuII 7(OH)12(hmp)12](ClO4)6(NO3)2 the Anderson moiety contains a central, (symmetry‐imposed) octahedral CuII ion surrounded by a wheel of AlIII ions. Solid‐state dc susceptibility and magnetisation measurements reveal the presence of competing exchange interactions in the Anderson wheels family, and weak antiferromagnetic exchange between the CuII ions in [Al6Cu7]. Chapter 6 describes two heterometallic wheels of formula [(VIVO)2MII 5(hmp)10Cl2](ClO4)2∙2MeOH (where MII = Ni or Co) displaying the same Anderson‐type structure as seen in chapters 4 and 5, however the use of the vanadyl moiety has the effect of removing the disorder, with the two vanadyl ions sitting on opposing sides of the ring. The magnetic properties of both show competing antiferroand ferromagnetic interactions

Association between B-cell depletion and attack risk in neuromyelitis optica spectrum disorder: An exploratory analysis from N-MOmentum, a double-blind, randomised, placebo-controlled, multicentre phase 2/3 trial

BACKGROUND: Inebilizumab is an anti-CD19 antibody approved for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults with aquaporin-4 autoantibodies. The relationship between B-cell, plasma-cell (PC), and immunoglobulin depletion with longitudinal reductions in NMOSD activity after inebilizumab treatment was characterised post hoc in an exploratory analysis from the N-MOmentum study (NCT02200770). METHODS: Peripheral blood CD20+ B cells, PC gene signature, and immunoglobulin levels were assessed throughout N-MOmentum (follow-up =2.5 years); correlations with clinical metrics and magnetic resonance imaging (MRI) lesion activity were assessed. FINDINGS: Inebilizumab induced durable B-cell and PC depletion within 1 week versus placebo. Although no association was observed between B-cell counts at time of attack and NMOSD activity, depth of B-cell depletion after the first dosing period correlated with clinical outcomes. All participants receiving inebilizumab demonstrated a robust long-term therapeutic response, and participants with =4 cells/µL after the first 6-month dosing interval had persistently deeper B-cell depletion, lower annualised attack rates (estimated rate [95% CI]: 0.034 [0.024–0.04] vs 0.086 [0.056–0.12]; p = 0.045), fewer new/enlarging T2 MRI lesions (0.49 [0.43–0.56] vs 1.36 [1.12–1.61]; p < 0.0001), and a trend towards decreased Expanded Disability Status Scale worsening (0.076 [0.06–0.10] vs 0.14 [0.10–0.18]; p = 0.093). Antibodies to inebilizumab, although present in a proportion of treated participants, did not alter outcomes. INTERPRETATION: This analysis suggests that compared with placebo, inebilizumab can provide specific, rapid, and durable depletion of B cells in participants with NMOSD. Although deep and persistent CD20+ B-cell depletion correlates with long-term clinical stability, early, deep B-cell depletion correlates with improved disease activity metrics in the first 2 years

Serum neurofilament light chain levels at attack predict post-attack disability worsening and are mitigated by inebilizumab: analysis of four potential biomarkers in neuromyelitis optica spectrum disorder.

OBJECTIVE: To investigate relationships between serum neurofilament light chain (sNfL), ubiquitin C-terminal hydrolase L1 (sUCHL1), tau (sTau) and glial fibrillary acidic protein (sGFAP) levels and disease activity/disability in neuromyelitis optica spectrum disorder (NMOSD), and the effects of inebilizumab on these biomarkers in N-MOmentum. METHODS: N-MOmentum randomised participants to receive inebilizumab or placebo with a randomised controlled period (RCP) of 28 weeks and an open-label follow-up period of ≥2 years. The sNfL, sUCHL1, sTau and sGFAP were measured using single-molecule arrays in 1260 scheduled and attack-related samples from N-MOmentum participants (immunoglobulin G (IgG) autoantibodies to aquaporin-4-positive, myelin oligodendrocyte glycoprotein-IgG-positive or double autoantibody-negative) and two control groups (healthy donors and patients with relapsing-remitting multiple sclerosis). RESULTS: The concentration of all four biomarkers increased during NMOSD attacks. At attack, sNfL had the strongest correlation with disability worsening during attacks (Spearman R2=0.40; p=0.01) and prediction of disability worsening after attacks (sNfL cut-off 32 pg/mL; area under the curve 0.71 (95% CI 0.51 to 0.89); p=0.02), but only sGFAP predicted upcoming attacks. At RCP end, fewer inebilizumab-treated than placebo-treated participants had sNfL&gt;16 pg/mL (22% vs 45%; OR 0.36 (95% CI 0.17 to 0.76); p=0.004). CONCLUSIONS: Compared with sGFAP, sTau and sUCHL1, sNfL at attack was the strongest predictor of disability worsening at attack and follow-up, suggesting a role for identifying participants with NMOSD at risk of limited post-relapse recovery. Treatment with inebilizumab was associated with lower levels of sGFAP and sNfL than placebo. TRIAL REGISTRATION NUMBER: NCT02200770

Attack adjudication in neuromyelitis optica spectrum disorder: Substantiation of criteria by magnetic resonance imaging and biomarkers in N-MOmentum

BackgroundThe N-MOmentum trial investigated safety and efficacy of inebilizumab in participants with neuromyelitis optica spectrum disorder (NMOSD).ObjectiveEvaluate the attack identification process and adjudication committee (AC) performance in N-MOmentum.MethodsAdults (n = 230) with NMOSD and Expanded Disability Status Scale score ⩽8 were randomized (3:1) to inebilizumab 300 mg or placebo. The randomized controlled period was 28 weeks or until adjudicated attack. Attacks were adjudicated according to 18 predefined criteria. Magnetic resonance imaging (MRI) and biomarker (serum glial fibrillary acidic protein [sGFAP]) analyses were performed.ResultsA total of 64 participant-reported neurological events occurred; 51 (80%) were investigator-determined to be attacks. The AC confirmed 43 of the investigator-determined attacks (84%). There was high inter- and intra-AC-member agreement. In 25/64 events (39%) and 14/43 AC-adjudicated attacks (33%), MRI was reviewed during adjudication. Retrospective analysis revealed new domain-specific T1 and T2 MRI lesions in 90% of adjudicated attacks. Increased mean sGFAP concentrations (&gt;2-fold change) from baseline were observed in 56% of adjudicated attacks versus 14% of investigator-determined attacks rejected by the AC and 31% of participant-reported events determined not to be attacks.ConclusionAC adjudication of NMOSD attacks according to predefined criteria appears robust. MRI lesion correlates and sGFAP elevations were found in most adjudicated attacks

Disability Outcomes in the N-MOmentum Trial of Inebilizumab in Neuromyelitis Optica Spectrum Disorder.

To assess treatment effects on Expanded Disability Status Scale (EDSS) score worsening and modified Rankin Scale (mRS) scores in the N-MOmentum trial of inebilizumab, a humanized anti-CD19 monoclonal antibody, in participants with neuromyelitis optica spectrum disorder (NMOSD). Adults (N = 230) with aquaporin-4 immunoglobulin G-seropositive NMOSD or -seronegative neuromyelitis optica and an EDSS score ≤8 were randomized (3:1) to receive inebilizumab 300 mg or placebo on days 1 and 15. The randomized controlled period (RCP) was 28 weeks or until adjudicated attack, with an option to enter the inebilizumab open-label period. Three-month EDSS-confirmed disability progression (CDP) was assessed using a Cox proportional hazard model. The effect of baseline subgroups on disability was assessed by interaction tests. mRS scores from the RCP were analyzed by the Wilcoxon-Mann-Whitney odds approach. Compared with placebo, inebilizumab reduced the risk of 3-month CDP (hazard ratio [HR]: 0.375; 95% CI: 0.148-0.952; p = 0.0390). Baseline disability, prestudy attack frequency, and disease duration did not affect the treatment effect observed with inebilizumab (HRs: 0.213-0.503; interaction tests: all p &gt; 0.05, indicating no effect of baseline covariates on outcome). Mean EDSS scores improved with longer-term treatment. Inebilizumab-treated participants were more likely to have a favorable mRS outcome at the end of the RCP (OR: 1.663; 95% CI: 1.195-2.385; p = 0.0023). Disability outcomes were more favorable with inebilizumab vs placebo in participants with NMOSD. This study provides Class II evidence that for patients with NMOSD, inebilizumab reduces the risk of worsening disability. N-MOmentum is registered at ClinicalTrials.gov: NCT02200770