ALBERT

Description: We use a 0-D photochemical box model and a 3-D global chemistry-climate model, combined with observations from the NOAA Southeast Nexus (SENEX) aircraft campaign, to understand the sources and sinks of glyoxal over the Southeast United States. Box model simulations suggest a large difference in glyoxal production among three isoprene oxidation mechanisms (AM3ST, AM3B, and MCM v3.3.1). These mechanisms are then implemented into a 3-D global chemistry-climate model. Comparison with field observations shows that the average vertical profile of glyoxal is best reproduced by AM3ST with an effective reactive uptake coefficient γ glyx of 2 × 10 -3 , and AM3B without heterogeneous loss of glyoxal. The two mechanisms lead to 0-0.8 µg m -3 secondary organic aerosol (SOA) from glyoxal in the boundary layer of the Southeast U.S. in summer. We consider this to be the lower limit for the contribution of glyoxal to SOA, as other sources of glyoxal other than isoprene are not included in our model. In addition, we find that AM3B shows better agreement on both formaldehyde and the correlation between glyoxal and formaldehyde ( R GF  = [GLYX]/[HCHO]), resulting from the suppression of δ-isoprene peroxy radicals (δ-ISOPO 2 ). We also find that MCM v3.3.1 may underestimate glyoxal production from isoprene oxidation, in part due to an underestimated yield from the reaction of IEPOX peroxy radicals (IEPOXOO) with HO 2 . Our work highlights that the gas-phase production of glyoxal represents a large uncertainty in quantifying its contribution to SOA.

Description: Manganoquadratite, ideally AgMnAsS3, is a new mineral from the Uchucchacua polymetallic deposit, Oyon district, Catajambo, Lima Department, Peru. It occurs as dark gray, anhedral to subhedral grains up 0.5 mm across, closely associated with alabandite, Mn-rich calcite, Mn-rich sphalerite, proustite, pyrite, pyrrhotite, tennantite, argentotennantite, stannite, and other unnamed minerals of the system Pb-Ag-Sb-Mn-As-S. Manganoquadratite is opaque with a metallic luster and possesses a reddish-brown streak. It is brittle, the Vickers microhardness (VHN10) is 81 kg/mm2 (range 75–96) (corresponding Mohs hardness of 2–2½). The calculated density is 4.680 g/cm3 (on the basis of the empirical formula). In plane-polarized reflected light, manganoquadratite is moderately bireflectant and very weakly pleochroic from dark gray to a blue gray. Internal reflections are absent. Between crossed polars, the mineral is anisotropic, without characteristic rotation tints. Reflectance percentages (Rmin and Rmax) for the four standard COM wavelengths are 29.5, 31.8 (471.1 nm), 28.1, 30.5 (548.3 nm), 27.3, 29.3 (586.6 nm), and 26.0, 28.2 (652.3 nm), respectively.Manganoquadratite is tetragonal, space group P4322, with unit-cell parameters: a = 5.4496(5), c = 32.949(1) Å, V = 978.5(1) Å3, c:a = 6.046, Z = 8. The structure, refined to R1 = 0.0863 for 907 reflections with Fo 〉 4σ(Fo), consists of a stacking along [001] of alabandite-like Mn2S2 layers connected to each to other by a couple of AgAsS2 sheets where As3+ forms typical AsS3 groups, whereas Ag+ cations are fivefold coordinated. The six strongest lines in the observed X-ray powder-diffraction pattern [d in Å (I/I0) (hkl)] are: 3.14 (60) (116), 2.739 (50) (0 0 12), 2.710 (100) (200), 1.927(70) (2 0 12 + 220), 1.645 (25) (3 0 16), and 1.573 (20) (22 12).Electron microprobe analyses gave the chemical formula (on the basis of six atoms) (Ag0.95Cu0.05)∑=1.00 (Mn0.96Pb0.04)∑=1.00(As0.87Sb0.14)∑=1.01S2.99, leading to the simplified formula AgMnAsS3.The name was chosen to indicate the close analogy of the formula and unit-cell dimensions with quadratite, Ag(Cd,Pb)(As,Sb)S3. The new mineral and mineral name have been approved by the Commission on New Minerals, Nomenclature and Classification, IMA 2011-008.

Description: In this study, physical and chemical properties of ultrafine aerosol particles are investigated at an urban site in Bakersfield, California, during the CalNex 2010 (California Research at the Nexus of Air Quality and Climate Change) campaign in May and June. Ultrafine particle measurements include particle number size distributions by a scanning Differential Mobility Analyzer (DMA) and size resolved aerosol chemical composition determined with a High-Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS). Growth events of ultrafine particles were observed on most days and had a very regular pattern. A nucleation mode centered at ∼20 nm appeared in the morning and grew to 40–100 nm throughout the day. Microphysical modeling and size-resolved HR-ToF-AMS concentrations showed that organic components provided most of the particle growth in the ultrafine mode, and sulfate provided on most days only a minor contribution to the mass of this mode. The ultrafine particle mass was largely dominated by organics (77%), and was at maximum during the afternoon. Elemental carbon (EC) and the AMS tracer C4H9+ for hydrocarbon-like organic aerosol (HOA) peaked in the early morning during rush hour, indicative of primary emissions. The fact that the particle number concentration peaked in the afternoon, when EC was at minimum, indicates that the midday increase in number concentration was likely due to new particle formation. The potential importance of solar radiation, the condensation sink of vapor on existing particles, concentrations of OH, O3, SO2, NH3, and VOCs for both condensational growth and new particle formation is evaluated based on the covariation of these parameters with ultrafine mass. The results suggest that the ultrafine particles are from secondary sources that are co-emitted or co-produced with glyoxal and formaldehyde.

Description: Menchettiite, ideally AgPb2.40Mn1.60Sb3As2S12, is a new mineral from the Uchucchacua polymetallic deposit, Oyon district, Catajambo, Lima Department, Peru. It occurs as black, anhedral to subhedral grains up to 200 µm across, closely associated with orpiment, tennantite/tetrahedrite, other unnamed minerals of the system Pb-Ag-Sb-Mn-As-S, and calcite. Menchettiite is opaque with a metallic luster and possesses a black streak. It is brittle, with uneven fracture; the Vickers microhardness (VHN100) is 128 kg/mm2 (range 119–136) (corresponding to a Mohs hardness of 2½–3). The calculated density is 5.146 g/cm3 (on the basis of the empirical formula). In plane-polarized incident light, menchettiite is weakly to moderately bireflectant and weakly pleochroic from dark gray to a dark green. Internal reflections are absent. Between crossed polarizers, the mineral is anisotropic, without characteristic rotation tints. Reflectance percentages (Rmin and Rmax) for the four standard COM wavelengths are 33.1, 39.8 (471.1 nm), 31.8, 38.0 (548.3 nm), 30.9, 37.3 (586.6 nm), and 29.0, 35.8 (652.3 nm), respectively.Menchettiite is monoclinic, space group P21/n, with unit-cell parameters: a = 19.233(2), b = 12.633(3), c = 8.476(2) Å, ß = 90.08(2)°, V = 2059.4(8) Å3, a: b: c 1.522:1:0.671, Z = 2, and it is twinned on {100}. The crystal structure was refined to R = 0.0903 for 2365 reflections with Fo 〉 4s(Fo) and it resulted to be topologically identical to those of ramdohrite, uchucchacuaite, and fizélyite. The six strongest X-ray powder-diffraction lines [d in Å (I/I0) (hkl)] are: 3.4066 (39) (3¯12), 3.4025 (39) (312), 3.2853 (100) (520), 2.8535 (50) (2¯32), 2.8519 (47) (232), and 2.1190 (33) (004). Electron-microprobe analyses gave the chemical formula Ag1.95Cu0.01Pb4.81Mn3.20Fe0.02Zn0.01Sb6.09As3.94Bi0.01S23.95Se0.01, on the basis of 44 atoms and according to the structure refinement results. Menchettiite can be classified among the Sb-rich members of the lillianite homeotypic series, which are described with the general formula AgxPb3-2xSb2+xS6. Besides the heterovalent substitution 2Pb2+ ? Ag+ + Sb3+ taken into consideration by the above formula, two isovalent substitutions relate menchettiite to the other lillianite homeotypes, i.e., Mn2+ ? Pb2+ and As3+ ? Sb3+. The name is after Silvio Menchetti (1937–), Professor of Mineralogy and Crystallography at the University of Florence. The new mineral and mineral name have been approved by the Commission on New Minerals, Nomenclature and Classification, IMA (2011–009).

Description: Since the discovery of slow slip events, many methods have been successfully applied to model obvious transient events in geodetic time series, such as the widely used network strain filter. Independent seismological observations of tremors or low frequency earthquakes and repeating earthquakes provide evidence of low amplitude slow deformation but do not always coincide with clear occurrences of transient signals in geodetic time series. Here, we aim to extract the signal corresponding to slow slips hidden in the noise of GPS time series, without using information from independent datasets. We first build a library of synthetic slow slip event templates by assembling a source function with Green's functions for a discretized fault. We then correlate the templates with post-processed GPS time series. Once the events have been detected in time, we estimate their duration T and magnitude M w by modelling a weighted stack of GPS time series. An analysis of synthetic time series shows that this method is able to resolve the correct timing, location, T and M w of events larger than M w 6 in the context of the Mexico subduction zone. Applied on a real data set of 29 GPS time series in the Guerrero area from 2005 to 2014, this technique allows us to detect 28 transient events from M w 6.3 to 7.2 with durations that range from 3 to 39 days. These events have a dominant recurrence time of 40 days and are mainly located at the down dip edges of the M w 〉 7.5 SSEs.

Description: Secondary aerosols formed from anthropogenic pollutants and natural emissions have substantial impacts on human health, air quality and the Earth's climate. New particle formation (NPF) contributes up to 70% of the global production of cloud condensation nuclei, but the effects of biogenic volatile organic compounds (BVOCs) and their oxidation products on NPF processes in forests are poorly understood. Observations show that isoprene, the most abundant BVOC, suppresses NPF in forests. But the previously proposed chemical mechanism underlying this suppression process contradicts atmospheric observations. By reviewing observations made in other forests, it is clear that NPF rarely takes place during the summer when emissions of isoprene are high, even though there are sufficient concentrations of monoterpenes. But at present it is not clear how isoprene and its oxidation products may change the oxidation chemistry of terpenes and how NO x and other atmospheric key species affect NPF in forest environments. Future laboratory experiments with chemical speciation of gas phase nucleation precursors and clusters and chemical composition of particles smaller than 10 nm are required to understand the role of isoprene in NPF. Our results show that climate models can overpredict aerosol's first indirect effect when not considering the absence of NPF in the southeastern U.S. forests during the summer using the current nucleation algorithm that includes only sulfuric acid and total concentrations of low volatility organic compounds. This highlights the importance of understanding NPF processes as function of temperature, RH and BVOC compositions to make valid predictions of NPF and CCN at a wide range of atmospheric conditions.

Description: Organosulfates are important secondary organic aerosol (SOA) components and good tracers for aerosol heterogeneous reactions. However, the knowledge of their spatial distribution, formation conditions, and environmental impact is limited. In this study, we report two organosulfates, an isoprene-derived IEPOX (2,3-epoxy-2-methyl-1,4-butanediol) sulfate and a glycolic acid (GA) sulfate, measured using the NOAA Particle Analysis Laser Mass Spectrometer (PALMS) onboard the NASA DC8 aircraft over the continental US during the DC3 and SEAC4RS campaigns. During these campaigns, IEPOX sulfate was estimated to account for 1.4% of submicron aerosol mass (or 2.2% of organic aerosol mass) on average near the ground in the southeast US, with lower concentrations in the western US (0.2-0.4%) and at high altitudes (〈0.2%). Compared to IEPOX sulfate, GA sulfate was more uniformly distributed, accounting for about 0.5% aerosol mass on average, and may be more abundant globally. A number of other organosulfates were detected; none were as abundant as these two. Ambient measurements confirmed that IEPOX sulfate is formed from isoprene oxidation and is a tracer for isoprene SOA formation. The organic precursors of GA sulfate may include glycolic acid and likely have both biogenic and anthropogenic sources. Higher aerosol acidity as measured by PALMS and relative humidity tend to promote IEPOX sulfate formation, and aerosol acidity largely drives in situ GA sulfate formation at high altitudes. This study suggests the formation of aerosol organosulfates depends not only on the appropriate organic precursors but also on emissions of anthropogenic sulfur dioxide (SO 2 ), which contributes to aerosol acidity.

Description: Asparaginase (ASNase) is one of the cornerstones of the multi-drug treatment protocol that is used to treat acute lymphoblastic leukemia (ALL) in pediatric and adult patients. Despite the fact that ASNase has been used in ALL treatment protocols for decades, little is known about the biodistribution and the mechanism of ASNase turnover in vivo. A large inter-individual variation in ASNase pharmacokinetics is observed in patients. While elevated ASNase levels are associated with an increase in adverse events, underexposure, frequently caused by antibody mediated clearance, seriously reduces therapeutic efficacy. To date, it is not possible to predict pharmacokinetics of ASNase in individual patients and therefore current therapeutic protocols are supported by frequent monitoring of ASNase levels and adjustments of administration schemes. We used an in vivo imaging approach to study ASNase biodistribution and pharmacodynamics in a mouse model and provide in vitro and in vivo evidence that identifies the endo-lysosomal protease Cathepsin B in macrophages as a critical component of ASNase degradation. Results/Discussion Mice were injected with 111Indium-labeled ASNase and biodistribution was monitored by quantitative microSPECT/CT scans and ex vivo analysis of organs using a gamma counter. Over time, ASNase accumulated in the liver and particularly the spleen and the bone marrow. We hypothesized that macrophages in these organs, efficiently take up the ASNase, thereby rapidly clearing the active enzyme from the blood. Immunohistochemical analysis confirmed the presence of ASNase in cells positive for the murine macrophage marker F4/80. To confirm the importance of macrophage populations in ASNase clearance, we depleted mice from phagocytic cells by injection of clodronate liposomes, and studied ASNase biodistribution and kinetics. Indeed, clodronate pretreatment significantly diminished the accumulation of ASNase in the liver, spleen and the bone marrow while doubling the circulatory half-life of serum ASNase activity. We conclude from these experiments that macrophages determine the pharmacokinetics of asparaginase, which raises the question whether rapid clearance of the drug by bone marrow resident macrophages will negatively affect the depletion of asparagine in the bone marrow niche. We previously linked a germline mutation in the gene encoding endosomal protease Cathepsin B to strongly diminished asparaginase degradation in a pediatric ALL patient. To connect the macrophage mediated clearance to the proposed role of Cathepsin B in ASNase degradation, we studied the contribution of this protease in macrophage-mediated degradation of asparaginase. We used cell lines to show that Cathepsin B expression is induced during differentiation from monocytes towards macrophages. This is consistent with our finding that macrophages, but not monocytes, are capable of degrading ASNase. Furthermore, we used both chemical inhibition and RNAi mediated knockdown of Cathepsin B to show that this protease is required for ASNase degradation in these macrophages. Finally, by comparing Cathepsin B knockout mice with wildtype littermates, we demonstrated that loss of Cathepsin B activity significantly delayed clearance of serum asparaginase, consistent with a prominent role for this lysosomal protease in ASNase turnover. In conclusion, by using in vivo imaging we showed that asparaginase is efficiently cleared from the circulation by macrophages. In particular, bone marrow resident macrophages may provide a protective environment for leukemic cells by effectively removing the therapeutic protein from the bone marrow niche. However, both the prominent role of macrophages and the importance of the lysosomal protease Cathepsin B in asparaginase clearance, may allow the rational design of a next generation asparaginase. Disclosures Metselaar: Enceladus Pharmaceuticals: Employment, Equity Ownership.

Description: Background Glucocorticoids (GCs) such as prednisolone and dexamethasone are critical components of multi-agent chemotherapy regimens used in the treatment of acute lymphoblastic leukemia (ALL). Children with ALL are stratified into risk groups based on diagnostic features (i.e. age and cytogenetics) and therapy response. It has been established that the initial response to prednisolone is a major prognostic factor. Moreover, at relapse, de novo or acquired resistance to GCs is common and represents an important determinant in treatment failure. Recent studies performed by us and others have identified IKZF1 gene deletions and mutations as an independent prognostic factor that predicts prognosis and treatment outcome of children with B cell precursor ALL (BCP-ALL). These monoallelic IKZF1 gene deletions either affect the whole gene or may result in expression of dominant-negative IKZF1 isoforms due to intragenic deletions. However, it has not been established whether loss of IKZF1 function directly impacts the response to glucocorticoids. Results We examined whether haplodeficiency for Ikzf1 gene expression in mouse lymphocytes affects glucocorticoid-induced apoptosis. Splenocytes from Ikzf1+/- knockout mice were activated with lipopolysaccharide (LPS) and treated with increasing concentrations of either prednisolone or dexamethasone for 48 hours. B-lymphocytes haplodeficient for IKZF1 showed a significantly enhanced survival after treatment with GCs compared to wild type cells, as measured in an MTS assay and by AnnexinV staining. In case of prednisolone, the inhibitory concentration (IC50) was about ∼200-fold higher in the Ikzf1+/- splenocytes as compared to the wild-type cells. Gene expression analysis revealed that Ikzf1+/- splenocytes displayed lower overall expression levels as well as diminished transcriptional activation of several glucocorticoid receptor (GR)-induced target genes (i.e. Sgk1, Irs2, Zfp36L2). Furthermore, in luciferase reporter assays we established that IKZF1 overexpression enhances GR-mediated transcriptional activation in response to prednisolone. Finally, lentivirus-mediated IKZF1-shRNA expression in Nalm6 cell line, which reduces endogenous IKZF1 protein levels to around 50%, inhibits prednisolone and dexamethasone-induced apoptosis, demonstrating that also in human leukemia cells reduced IKZF1 expression levels protect against GC-induced cell death. In conclusion, our data provide evidence that loss of IKZF1 function mediates resistance to glucocorticoid-induced apoptosis, which may contribute to the poor outcome of IKZF1-deleted BCP-ALL. Disclosures: No relevant conflicts of interest to declare.