RIM-Binding Protein 2 organizes Ca2+channel topography and regulates release probability and vesicle replenishment at a fast central synapse

RIM-Binding Protein 2 (RIM-BP2) is a multi-domain protein of the presynaptic active zone (AZ). By binding to Rab-interacting protein (RIM), bassoon and voltage-gated Ca²⁺channels (CaV), it is considered to be a central organizer of the topography of CaVand release sites of synaptic vesicles (SVs) at the AZ. Here, we investigated the role of RIM-BP2 at the endbulb of Held synapse of auditory nerve fibers with bushy cells of the cochlear nucleus, a fast relay of the auditory pathway with high release probability. Disruption of RIM-BP2 lowered release probability altering short-term plasticity and reduced evoked excitatory postsynaptic currents (EPSCs). Analysis of SV pool dynamics during high frequency train stimulation indicated a reduction of SVs with high release probability but an overall normal size of the readily releasable SV pool (RRP). The Ca2+-dependent fast component of SV replenishment after RRP depletion was slowed. Ultrastructural analysis by super-resolution light and electron microscopy revealed an impaired topography of presynaptic CaVand a reduction of docked and membrane-proximal SVs at the AZ. We conclude that RIM-BP2 organizes the topography of CaV, and promotes SV tethering and docking. This way RIM-BP2 is critical for establishing a high initial release probability as required to reliably signal sound onset information that we found to be degraded in bushy cells of RIM-BP2-deficient mice in vivo

The formation of secondary organic aerosol from the isoprene + OH reaction in the absence of NO_x

The reaction of isoprene (C₅H₈) with hydroxyl radicals has been studied in the absence of nitrogen oxides (NO_x) to determine physical and chemical characteristics of the secondary organic aerosol formed. Experiments were conducted using a smog chamber operated in a steady-state mode permitting measurements of moderately low aerosol levels. GC-MS analysis was conducted to measure methyl butenediols in the gas phase and polyols in the aerosol phase. Analyses were made to obtain several bulk aerosol parameters from the reaction including values for the organic mass to organic carbon ratio, the effective enthalpy of vaporization (ΔH_vap^eff), organic peroxide fraction, and the aerosol yield. <br><br> The gas phase analysis showed the presence of methacrolein, methyl vinyl ketone, and four isomers of the methyl butenediols. These gas-phase compounds may serve as precursors for one or more of several compounds detected in the aerosol phase including 2-methylglyceric acid, three 2-methyl alkenetriols, and two 2-methyl tetrols. In contrast to most previous studies, the 2-methyl tetrols (and the 2-methyl alkenetriols) were found to form in the absence of acidic sulfate aerosol. However, reaction conditions did not favor the production of HO₂ radicals, thus allowing RO₂+RO₂ reactions to proceed more readily than if higher HO₂ levels had been generated. <br><br> SOA/SOC (i.e. OM/OC) was found to average 1.9 in the absence of NO_x. The effective enthalpy of vaporization was measured as 38.6 kJ mol^&minus;1, consistent with values used previously in modeling studies. The yields in this work (using an independent technique than used previously) are lower than those of Kroll et al. (2006) for similar aerosol masses. SOC yields reported in this work range from 0.5–1.4% for carbon masses between 17 and 49 μgC m^&minus;3

SOA formation from the atmospheric oxidation of 2-methyl-3-buten-2-ol and its implications for PM_2.5

The formation of secondary organic aerosol (SOA) generated by irradiating 2-methyl-3-buten-2-ol (MBO) in the presence and/or absence of NO_x, H₂O₂, and/or SO₂ was examined. Experiments were conducted in smog chambers operated in either dynamic or static mode. A filter/denuder sampling system was used for simultaneously collecting gas- and particle-phase products. The structural characterization of gas and particulate products was investigated using BSTFA, BSTFA + PFBHA, and DNPH derivatization techniques followed by GC-MS and liquid chromatography analysis. This analysis showed the occurrence of more than 68 oxygenated organic compounds in the gas and particle phases, 28 of which were tentatively identified. The major components observed include 2,3-dihydroxyisopentanol (DHIP), 2-hydroxy-2-oxoisopentanol, 2,3-dihydroxy-3-methylbutanal, 2,3-dihydroxy-2-methylsuccinic acid, 2-hydroxy-2-methylpropanedioic acid, acetone, glyoxal, methylglyoxal, glycolaldehyde, and formaldehyde. Most of these oxygenated compounds were detected for the first time in this study. <br><br> While measurements of the gas-phase photooxidation products have been made, the focus of this work has been an examination of the particle phase. SOA from some experiments was analyzed for the organic mass to organic carbon ratio (OM/OC), the effective enthalpy of vaporization (&Delta;H_vap^eff), and the aerosol yield. Additionally, aerosol size, volume, and number concentrations were measured by a Scanning Mobility Particle Sizer coupled to a Condensation Particle Counter system. The OM/OC ratio was 2.1 in the MBO/H₂O₂ system. The ΔH_vap^eff was 41 kJ mol⁻¹, a value similar to that of isoprene SOA. The laboratory SOA yield measured in this study was 0.7% in MBO/H₂O₂ for an aerosol mass of 33 μg m⁻³. Secondary organic aerosol was found to be negligible under conditions with oxides of nitrogen (NO_x) present. Time profiles and proposed reaction schemes are provided for selected compounds. <br><br> The contribution of SOA products from MBO oxidation to ambient PM_2.5 was investigated by analyzing a series of ambient PM_2.5 samples collected in several places around the United States. In addition to the occurrence of several organic compounds in both field and laboratory samples, DHIP was found to originate only from the oxidation of MBO, and therefore this compound could potentially serve as a tracer for MBO SOA. Initial attempts have been made to quantify the concentrations of DHIP and other compounds based on surrogate compound calibrations. The average concentrations of DHIP in ambient PM_2.5 samples from Duke Forest in North Carolina ranged from zero during cold seasons to approximately 1 ng m⁻³ during warm seasons. This appears to be the first time that DHIP has been detected in ambient PM_2.5 samples. The occurrence of several other compounds in both laboratory and field samples suggests that SOA originating from MBO can contribute under selected ambient conditions to the ambient aerosol mainly in areas where MBO emissions are high

Characterization of polar organosulfates in secondary organic aerosol from the unsaturated aldehydes 2-E-pentenal, 2-E-hexenal, and 3-Z-hexenal

We show in the present study that the unsaturated aldehydes 2-E-pentenal, 2-E-hexenal, and 3-Z-hexenal are biogenic volatile organic compound (BVOC) precursors for polar organosulfates with molecular weights (MWs) 230 and 214, which are also present in ambient fine aerosol from a forested site, i.e., K-puszta, Hungary. These results complement those obtained in a previous study showing that the green leaf aldehyde 3-Z-hexenal serves as a precursor for MW 226 organosulfates. Thus, in addition to isoprene, the green leaf volatiles (GLVs) 2-E-hexenal and 3-Z-hexenal, emitted due to plant stress (mechanical wounding or insect attack), and 2-E-pentenal, a photolysis product of 3-Z-hexenal, should be taken into account for secondary organic aerosol and organosulfate formation. Polar organosulfates are of climatic relevance because of their hydrophilic properties and cloud effects. Extensive use was made of organic mass spectrometry (MS) and detailed interpretation of MS data (i.e., ion trap MS and accurate mass measurements) to elucidate the chemical structures of the MW 230, 214 and 170 organosulfates formed from 2-E-pentenal and indirectly from 2-E-hexenal and 3-Z-hexenal. In addition, quantum chemical calculations were performed to explain the different mass spectral behavior of 2,3-dihydroxypentanoic acid sulfate derivatives, where only the isomer with the sulfate group at C-3 results in the loss of SO3. The MW 214 organosulfates formed from 2-E-pentenal are explained by epoxidation of the double bond in the gas phase and sulfation of the epoxy group with sulfuric acid in the particle phase through the same pathway as that proposed for 3-sulfooxy-2-hydroxy-2-methylpropanoic acid from the isoprene-related alpha,beta-unsaturated aldehyde methacrolein in previous work (Lin et al., 2013). The MW 230 organosulfates formed from 2-E-pentenal are tentatively explained by a novel pathway, which bears features of the latter pathway but introduces an additional hydroxyl group at the C-4 position. Evidence is also presented that the MW 214 positional isomer, 2-sulfooxy-3-hydroxypentanoic acid, is unstable and decarboxylates, giving rise to 1-sulfooxy-2-hydroxybutane, a MW 170 organosulfate. Furthermore, evidence is obtained that lactic acid sulfate is generated from 2-E-pentenal. This chemistry could be important on a regional and local scale where GLV emissions such as from grasses and cereal crops are substantial

Handwritten digit recognition by bio-inspired hierarchical networks

The human brain processes information showing learning and prediction abilities but the underlying neuronal mechanisms still remain unknown. Recently, many studies prove that neuronal networks are able of both generalizations and associations of sensory inputs. In this paper, following a set of neurophysiological evidences, we propose a learning framework with a strong biological plausibility that mimics prominent functions of cortical circuitries. We developed the Inductive Conceptual Network (ICN), that is a hierarchical bio-inspired network, able to learn invariant patterns by Variable-order Markov Models implemented in its nodes. The outputs of the top-most node of ICN hierarchy, representing the highest input generalization, allow for automatic classification of inputs. We found that the ICN clusterized MNIST images with an error of 5.73% and USPS images with an error of 12.56%

Influence of aerosol acidity on the chemical composition of secondary organic aerosol from β-caryophyllene

The secondary organic aerosol (SOA) yield of β-caryophyllene photooxidation is enhanced by aerosol acidity. In the present study, the influence of aerosol acidity on the chemical composition of β-caryophyllene SOA is investigated using ultra performance liquid chromatography/electrospray ionization-time-of-flight mass spectrometry (UPLC/ESI-TOFMS). A number of first-, second- and higher-generation gas-phase products having carbonyl and carboxylic acid functional groups are detected in the particle phase. Particle-phase reaction products formed via hydration and organosulfate formation processes are also detected. Increased acidity leads to different effects on the abundance of individual products; significantly, abundances of organosulfates are correlated with aerosol acidity. To our knowledge, this is the first detection of organosulfates and nitrated organosulfates derived from a sesquiterpene. The increase of certain particle-phase reaction products with increased acidity provides chemical evidence to support the acid-enhanced SOA yields. Based on the agreement between the chromatographic retention times and accurate mass measurements of chamber and field samples, three β-caryophyllene products (i.e., β-nocaryophyllon aldehyde, β-hydroxynocaryophyllon aldehyde, and β-dihydroxynocaryophyllon aldehyde) are suggested as chemical tracers for β-caryophyllene SOA. These compounds are detected in both day and night ambient samples collected in downtown Atlanta, GA and rural Yorkville, GA during the 2008 August Mini-Intensive Gas and Aerosol Study (AMIGAS)

Yields and molecular composition of gas-phase and secondary organic aerosol from the photooxidation of the volatile consumer product benzyl alcohol: formation of highly oxygenated and hydroxy nitro-aromatic compounds

Recently, volatile chemical products (VCPs) have been increasingly recognized as important precursors for secondary organic aerosol (SOA) and ozone in urban areas. However, their atmospheric chemistry, physical transformation, and impact on climate, environment, and human health remain poorly understood. Here, the yields and chemical composition at the molecular level of gas- and particle-phase products originating from the photooxidation of one of these VCPs, benzyl alcohol (BnOH), are reported. The SOA was generated in the presence of seed aerosol from nebulized ammonium sulfate solution in a 14.5 m3 smog chamber operated in flow mode. More than 50 organic compounds containing nitrogen and/or up to seven oxygen atoms were identified by mass spectrometry. While a detailed non-targeted analysis has been made, our primary focus has been to examine highly oxygenated and nitro-aromatic compounds. The major components include ring-opening products with a high oxygen-to-carbon ratio (e.g., malic acid, tartaric acids, arabic acid, trihydroxy-oxo-pentanoic acids, and pentaric acid) and ring-retaining products (e.g., benzaldehyde, benzoic acid, catechol, 3-nitrobenzyl alcohol, 4-nitrocatechol, 2-hydroxy-5-nitrobenzyl alcohol, 2-nitrophloroglucinol, 3,4-dihydroxy-5-nitrobenzyl alcohol). The presence of some of these products in the gas and particle phases simultaneously provides evidence of their gas–particle partitioning. These oxygenated oxidation products made dominant contributions to the SOA particle composition in both low- and high-NOx systems. Yields, organic mass to organic carbon ratio, and proposed reaction schemes for selected compounds are provided. The aerosol yield was 5.2 % for BnOH/H2O2 at an SOA concentration of 52.9 µg m−3 and ranged between 1.7 % and 8.1 % for BnOH / NOx at an SOA concentration of 40.0–119.5 µg m−3.</p

Microservice Transition and its Granularity Problem: A Systematic Mapping Study

Microservices have gained wide recognition and acceptance in software industries as an emerging architectural style for autonomic, scalable, and more reliable computing. The transition to microservices has been highly motivated by the need for better alignment of technical design decisions with improving value potentials of architectures. Despite microservices' popularity, research still lacks disciplined understanding of transition and consensus on the principles and activities underlying "micro-ing" architectures. In this paper, we report on a systematic mapping study that consolidates various views, approaches and activities that commonly assist in the transition to microservices. The study aims to provide a better understanding of the transition; it also contributes a working definition of the transition and technical activities underlying it. We term the transition and technical activities leading to microservice architectures as microservitization. We then shed light on a fundamental problem of microservitization: microservice granularity and reasoning about its adaptation as first-class entities. This study reviews state-of-the-art and -practice related to reasoning about microservice granularity; it reviews modelling approaches, aspects considered, guidelines and processes used to reason about microservice granularity. This study identifies opportunities for future research and development related to reasoning about microservice granularity.Comment: 36 pages including references, 6 figures, and 3 table

Chemical composition of isoprene SOA under acidic and non-acidic conditions: effect of relative humidity

The effect of acidity and relative humidity on bulk isoprene aerosol parameters has been investigated in several studies; however, few measurements have been conducted on individual aerosol compounds. The focus of this study has been the examination of the effect of acidity and relative humidity on secondary organic aerosol (SOA) chemical composition from isoprene photooxidation in the presence of nitrogen oxide (NOx). A detailed characterization of SOA at the molecular level was also investigated. Experiments were conducted in a 14.5&thinsp;m3 smog chamber operated in flow mode. Based on a detailed analysis of mass spectra obtained from gas chromatography–mass spectrometry of silylated derivatives in electron impact and chemical ionization modes, ultra-high performance liquid chromatography/electrospray ionization/time-of-flight high-resolution mass spectrometry, and collision-induced dissociation in the negative ionization modes, we characterized not only typical isoprene products but also new oxygenated compounds. A series of nitroxy-organosulfates (NOSs) were tentatively identified on the basis of high-resolution mass spectra. Under acidic conditions, the major identified compounds include 2-methyltetrols (2MT), 2-methylglyceric acid (2mGA), and 2MT-OS. Other products identified include epoxydiols, mono- and dicarboxylic acids, other organic sulfates, and nitroxy- and nitrosoxy-OS. The contribution of SOA products from isoprene oxidation to PM2.5 was investigated by analyzing ambient aerosol collected at rural sites in Poland. Methyltetrols, 2mGA, and several organosulfates and nitroxy-OS were detected in both the field and laboratory samples. The influence of relative humidity on SOA formation was modest in non-acidic-seed experiments and stronger under acidic seed aerosol. Total secondary organic carbon decreased with increasing relative humidity under both acidic and non-acidic conditions. While the yields of some of the specific organic compounds decreased with increasing relative humidity, others varied in an indeterminate manner from changes in the relative humidity.</p

Spatial and temporal evolution of groundwater arsenic contamination in the Red River delta, Vietnam: Interplay of mobilisation and retardation processes

Geogenic arsenic (As) contamination of groundwater poses a major threat to global health, particularly in Asia. To mitigate this exposure, groundwater is increasingly extracted from low-As Pleistocene aquifers. This, however, disturbs groundwater flow and potentially draws high-As groundwater into low-As aquifers. Here we report a detailed characterisation of the Van Phuc aquifer in the Red River Delta region, Vietnam, where high-As groundwater from a Holocene aquifer is being drawn into a low-As Pleistocene aquifer. This study includes data from eight years (2010–2017) of groundwater observations to develop an understanding of the spatial and temporal evolution of the redox status and groundwater hydrochemistry. Arsenic concentrations were highly variable (0.5–510 μg/L) over spatial scales of <200 m. Five hydro(geo)chemical zones (indicated as A to E) were identified in the aquifer, each associated with specific As mobilisation and retardation processes. At the riverbank (zone A), As is mobilised from freshly deposited sediments where Fe(III)-reducing conditions occur. Arsenic is then transported across the Holocene aquifer (zone B), where the vertical intrusion of evaporative water, likely enriched in dissolved organic matter, promotes methanogenic conditions and further release of As (zone C). In the redox transition zone at the boundary of the two aquifers (zone D), groundwater arsenic concentrations decrease by sorption and incorporations onto Fe(II) carbonates and Fe(II)/Fe(III) (oxyhydr)oxides under reducing conditions. The sorption/incorporation of As onto Fe(III) minerals at the redox transition and in the Mn(IV)-reducing Pleistocene aquifer (zone E) has consistently kept As concentrations below 10 μg/L for the studied period of 2010–2017, and the location of the redox transition zone does not appear to have propagated significantly. Yet, the largest temporal hydrochemical changes were found in the Pleistocene aquifer caused by groundwater advection from the Holocene aquifer. This is critical and calls for detailed investigations