A molecular triad composed of a triarylamine donor, a triarylborane acceptor, and a photoisomerizable dithienylethene bridge has been synthesized and explored by cyclic voltammetry, UV–vis, and ...luminescence spectroscopy. The effects of irradiation with UV light and fluoride addition on the electrochemical and optical spectroscopic properties of the donor–bridge–acceptor molecule were investigated. Photoisomerization of the dithienylethene bridge affects the triarylboron reduction potential, but not the triarylamine oxidation potential. UV–vis experiments reveal that the association constant for fluoride binding at the triarylborane site is independent of the isomerization state of the bridge. Irradiation of a THF solution of our donor–bridge–acceptor molecule with UV light, followed by F– addition, leads to a different color of the sample than UV irradiation alone or F– addition alone.
Acid sphingomyelinase deficiency (ASMD) (also known as Niemann-Pick disease types A and B) is a rare and debilitating lysosomal storage disorder. This prospective, multi-center, multinational ...longitudinal study aimed to characterize the clinical features of chronic forms of ASMD and disease burden over time in children and adults.
Fifty-nine patients (31 males/28 females) ranging in age from 7 to 64 years with chronic ASMD types A/B and B and at least two disease symptoms participated from 5 countries. Disease characteristics were assessed at baseline, after 1 year, and at the final visit (ranging from 4.5 to 11 years). Thirty patients (51%) were < 18 years at baseline (median age 12 years), and 29 were adults (median age 32 years). Overall, 32/59 patients completed the final visit, 9 died, 9 discontinued, and 9 were lost to follow up. Common clinical characteristics that tended to worsen gradually with time were splenomegaly, hepatomegaly, interstitial lung disease, lung diffusion capacity (DL
), and dyslipidemia. Spleen volumes ranged from 4 to 29 multiples of normal at baseline, and splenomegaly was moderate or severe in 86%, 83%, and 90% of individuals at baseline, year 1, and final visits, respectively. The proportion of all individuals with interstitial lung disease was 66% (39/59) at baseline and 78% (25/32) at the final visit, while median % predicted DL
decreased by > 10% from baseline to the final visit. Nine patients died (15%), eight of causes related to ASMD (most commonly pneumonia); of these eight patients, five (63%) had symptom onset at or before age 2. Overall, six of the nine deaths occurred before age 50 with three occurring before age 20. Individuals with either severe splenomegaly or prior splenectomy were ten times more likely to have died during the follow-up period than those with smaller or intact spleens (odds ratio 10.29, 95% CI 1.7, 62.7). Most children had growth deficits that persisted into adulthood.
This study provides important information about the natural history of chronic ASMD and provides a longitudinal view of the spectrum of disease manifestations and major morbidities in children and adults and supports the selection of clinically meaningful endpoints in therapeutic trials.
The dwarf planet Ceres (diameter 939 km) is the largest object in the main asteroid belt. Recent investigations suggest that Ceres is a thermally evolved, volatile-rich body with potential geological ...activity, a body which was never completely molten but possibly differentiated into a rocky core, an ice-rich mantle, and which may contain remnant internal liquid water. Thermal alteration and exogenic material infall contribute to producing a (dark) carbonaceous chondritic-like surface containing ammoniated phyllosilicates. Here we report imaging and spectroscopic analyses of Occator crater derived from the Framing Camera and the Visible and Infrared Spectrometer onboard Dawn. We found that the central bright spot (Cerealia Facula) of Occator is ∼30 Myr younger than the crater itself. The central spot is located in a central pit which contains a dome that is spectrally homogenous, exhibiting absorption features that are consistent with carbonates. Multiple radial fractures across the dome indicate an extrusive formation process. Our results lead us to conclude that the floor region was subject to past endogenic activity. Dome and bright material in its vicinity formed likely due to a long-lasting, periodic, or episodic ascent of bright material from a subsurface reservoir rich in carbonates. Originally triggered by an impact event, gases, possibly dissolved from a subsurface water/brine layer, enabled material rich in carbonates to ascend through fractures and be deposited onto the surface.
Ceres is a partially differentiated dwarf planet, as confirmed by NASA's Dawn mission. The Urvara basin (diameter ~170 km) is its third-largest impact feature, enabling insights into the cerean ...crust. Urvara's geology and mineralogy suggest a potential brine layer at the crust-mantle transition. Here we report new findings that help in understanding the structure and composition of the cerean crust. These results were derived by using the highest-resolution Framing Camera images acquired by Dawn at Ceres. Unexpectedly, we found meter-scale concentrated exposures of bright material (salts) along the crater's upper central ridge, which originate from an enormous depth, possibly from a deep-seated brine or salt reservoir. An extended resurfacing modified the southern floor ~100 Myr after crater formation (~250 Myr), long after the dissipation of the impact-generated heat. In this resurfaced area, one floor scarp shows a granular flow pattern of bright material, showing spectra consistent with the presence of organic material, the first such finding on Ceres beyond the vast Ernutet area. Our results strengthen the hypothesis that Ceres is and has been a geologically active world even in recent epochs, with salts and organic-rich material playing a major role in its evolution.
A heteroleptic iron(II) complex Fe(dcpp)(ddpd)2+ with a strongly electron‐withdrawing ligand (dcpp, 2,6‐bis(2‐carboxypyridyl)pyridine) and a strongly electron‐donating tridentate tripyridine ligand ...(ddpd, N,N′‐dimethyl‐N,N′‐dipyridine‐2‐yl‐pyridine‐2,6‐diamine) is reported. Both ligands form six‐membered chelate rings with the iron center, inducing a strong ligand field. This results in a high‐energy, high‐spin state (5T2, (t2g)4(eg*)2) and a low‐spin ground state (1A1, (t2g)6(eg*)0). The intermediate triplet spin state (3T1, (t2g)5(eg*)1) is suggested to be between these states on the basis of the rapid dynamics after photoexcitation. The low‐energy π* orbitals of dcpp allow low‐energy MLCT absorption plus additional low‐energy LL′CT absorptions from ddpd to dcpp. The directional charge‐transfer character is probed by electrochemical and optical analyses, Mößbauer spectroscopy, and EPR spectroscopy of the adjacent redox states Fe(dcpp)(ddpd)3+ and Fe(dcpp)(ddpd)+, augmented by density functional calculations. The combined effect of push–pull substitution and the strong ligand field paves the way for long‐lived charge‐transfer states in iron(II) complexes.
Iron blue dyes: The novel photostable low‐spin FeII complex 22+ (see figure) with two push–pull substituted oligopyridine ligands features highly directional MLCT and LL′CT absorptions extending into the near‐infrared region. Electrochemistry, EPR, and Mößbauer spectroscopy, as well as DFT calculations, confirm iron‐based oxidation and ligand‐centered reduction processes. Relaxation to the ground state after CT excitation seems to circumvent the usual path of FeII complexes via the high‐spin state.
This post hoc subanalysis examined outcomes in adult patients with Morquio A (mucopolysaccharidosis IVA) who received enzyme replacement therapy (ERT) with elosulfase alfa over a 120-weeks period. ...Patients ≥18 years of age evaluated in an open-label, long-term extension study of elosulfase alfa (modified per protocol MPP, n = 32; intent-to-treat ITT, n = 37; MOR-005; NCT01415427) were compared with the ≥18-year-old untreated population with 2-years follow-up from a Morquio A natural history study (n = 10; MorCAP; NCT00787995). The MOR-005 MPP population excluded patients who underwent orthopedic surgical procedures or were noncompliant with study protocol (defined as missing ≥20% of ERT infusions). No MorCAP patients underwent orthopedic surgical procedures during the relevant time period. Endurance was assessed by the 6-min walk test (6MWT) and 3-min stair climb test (3MSCT). Activities of daily living (ADLs) were assessed by the MPS Health Assessment Questionnaire (MPS HAQ).
Least squares (LS) mean (SE) 6MWT distances increased by 34.9 (11.7) m (MPP) and 30.5 (10.8) m (ITT) by week 120; LS mean (SE) change in 3MSCT at week 120 was 6.7 (1.8) stairs/min (MPP) and 5.9 (1.7) stairs/min (ITT). MorCAP patients showed no improvement in 6MWT distance or 3MSCT over a similar period of time. Pulmonary function measures remained unchanged in both MOR-005 and MorCAP adults. All MPS HAQ domain scores improved in MOR-005 adults, whereas MorCAP adults had unchanged caregiver assistance and mobility outcomes and worsened self-care outcomes.
Long-term ERT in adult patients with Morquio A was associated with increased endurance and improvement in performance of ADLs.
Trial Registration NCT01415427 . Name of registry: Long-Term Efficacy and Safety Extension Study of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome). Registered 8 August 2011, retrospectively registered.
A series of anchor‐functionalized cyclometalated bis(tridentate) ruthenium(II) triarylamine hybrids Ru(dbp‐X)(tctpy)2− 2 a2−–2 c2− (H3tctpy=2,2′;6′,2′′‐terpyridine‐4,4′,4′′‐tricarboxylic acid; ...dpbH=1,3‐dipyridylbenzene; X=N(4‐C6H4OMe)2 (2 a2−), NPh2 (2 b2−), N‐carbazolyl 2 c2−) was synthesized and characterized. All complexes show broad absorption bands in the range 300–700 nm with a maximum at about 545 nm. Methyl esters Ru(Me3tctpy)(dpb‐X)+ 1 a+–1 c+ are oxidized to the strongly coupled mixed‐valent species 1 a2+–1 c2+ and the RuIII(aminium) complexes 1 a3+–1 c3+ at comparably low oxidation potentials. Theoretical calculations suggest an increasing spin delocalization between the metal center and the triarylamine unit in the order 1 a2+<1 b2+<1 c2+. Solar cells were prepared with the saponified complexes 2 a2−–2 c2− and the reference dye N719 as sensitizers using the I3−/I− couple and Co(bpy)33+/2+ and Co(ddpd)23+/2+ couples as B(C6F5)4− salts as electrolytes (bpy=2,2′‐bipyridine; ddpd=N,N′‐dimethyl‐N,N′‐dipyridin‐2‐yl‐pyridine‐2,6‐diamine). Cells with 2 c2− and I3−/I− electrolyte perform similarly to cells with N719. In the presence of cobalt electrolytes, all efficiencies are reduced, yet under these conditions 2 c2− outperforms N719.
Anchor‐functionalized cyclometalated bis(tridentate) ruthenium(II) triarylamine hybrids featuring mixed‐valent states of varying resonance stabilization were employed in dye‐sensitized solar cells (DSSCs) in combination with different electrolytes. Together with cobalt‐based electrolytes, the N‐carbazole substituted dye surpasses the N719 dye.
The dwarf planet (1) Ceres, the largest object in the main asteroid belt with a mean diameter of about 950 kilometres, is located at a mean distance from the Sun of about 2.8 astronomical units (one ...astronomical unit is the Earth-Sun distance). Thermal evolution models suggest that it is a differentiated body with potential geological activity. Unlike on the icy satellites of Jupiter and Saturn, where tidal forces are responsible for spewing briny water into space, no tidal forces are acting on Ceres. In the absence of such forces, most objects in the main asteroid belt are expected to be geologically inert. The recent discovery of water vapour absorption near Ceres and previous detection of bound water and OH near and on Ceres (refs 5-7) have raised interest in the possible presence of surface ice. Here we report the presence of localized bright areas on Ceres from an orbiting imager. These unusual areas are consistent with hydrated magnesium sulfates mixed with dark background material, although other compositions are possible. Of particular interest is a bright pit on the floor of crater Occator that exhibits probable sublimation of water ice, producing haze clouds inside the crater that appear and disappear with a diurnal rhythm. Slow-moving condensed-ice or dust particles may explain this haze. We conclude that Ceres must have accreted material from beyond the 'snow line', which is the distance from the Sun at which water molecules condense.
Variations and spatial distributions of bright and dark material on dwarf planet Ceres play a key role in understanding the processes that have led to its present surface composition. We define ...limits for “bright” and “dark” material in order to distinguish them consistently, based on the reflectance of the average surface using Dawn Framing Camera data. A systematic classification of four types of bright material is presented based on their spectral properties, composition, spatial distribution, and association with specific geomorphological features. We found obvious correlations of reflectance with spectral shape (slopes) and age; however, this is not unique throughout the bright spots. Although impact features show generally more extreme reflectance variations, several areas can only be understood in terms of inhomogeneous distribution of composition as inferred from Dawn Visible and Infrared Spectrometer data. Additional material with anomalous composition and spectral properties are rare. The identification of the composition and origin of the dark, particularly the darkest material, remains to be explored. The spectral properties and the morphology of the dark sites suggest an endogenic origin, but it is not clear whether they are more or less primitive surficial exposures or excavated subsurface but localized material. The reflectance, spectral properties, inferred composition, and geologic context collectively suggest that the bright and dark material tends to gradually change toward the average surface over time. This could be because of multiple processes, i.e., impact gardening/space weathering, and lateral mixing, including thermal and aqueous alteration, accompanied by changes in composition and physical properties such as grain size, surface temperature, and porosity (compaction).
Dwarf planet Ceres ( ∼ 940 km) is the largest object in the main asteroid belt. Investigations suggest that Ceres is a thermally evolved, volatile-rich body with potential geological activity, a body ...that was never completely molten, but one that possibly partially differentiated into a rocky core and an ice-rich mantle, and may contain remnant internal liquid water. Thermal alteration and the infall of exogenic material contribute to producing a (dark) carbonaceous chondritic-like surface containing ammoniated phyllosilicates. Here we report imaging and spectroscopic analyses of data on the bright Oxo crater derived from the Framing Camera and the Visible and Infrared Spectrometer on board the Dawn spacecraft. We confirm that the transitional complex crater Oxo ( ∼ 9 km) exhibits exposed surface water-ice. We show that this water-ice-rich material is associated exclusively with two lobate deposits at pole-facing scarps, deposits that also contain carbonates and admixed phyllosilicates. Due to Oxo's location at −4802 m below the cerean reference ellipsoid and its very young age of only 190 ka (1 : +100 ka, −70 ka), Oxo is predestined for ongoing water-ice sublimation.
PDF
