Secondary organic aerosol reduced by mixture of atmospheric vapours.

Secondary organic aerosol contributes to the atmospheric particle burden with implications for air quality and climate. Biogenic volatile organic compounds such as terpenoids emitted from plants are important secondary organic aerosol precursors with isoprene dominating the emissions of biogenic volatile organic compounds globally. However, the particle mass from isoprene oxidation is generally modest compared to that of other terpenoids. Here we show that isoprene, carbon monoxide and methane can each suppress the instantaneous mass and the overall mass yield derived from monoterpenes in mixtures of atmospheric vapours. We find that isoprene 'scavenges' hydroxyl radicals, preventing their reaction with monoterpenes, and the resulting isoprene peroxy radicals scavenge highly oxygenated monoterpene products. These effects reduce the yield of low-volatility products that would otherwise form secondary organic aerosol. Global model calculations indicate that oxidant and product scavenging can operate effectively in the real atmosphere. Thus highly reactive compounds (such as isoprene) that produce a modest amount of aerosol are not necessarily net producers of secondary organic particle mass and their oxidation in mixtures of atmospheric vapours can suppress both particle number and mass of secondary organic aerosol. We suggest that formation mechanisms of secondary organic aerosol in the atmosphere need to be considered more realistically, accounting for mechanistic interactions between the products of oxidizing precursor molecules (as is recognized to be necessary when modelling ozone production).

Extension of the MolMod Database to Transferable Force Fields.

MolMod, a web-based database for classical force fields for molecular simulations of fluids [Mol. Sim. 45, 10 (2019), 806-814], was extended to transferable force fields. Eight transferable force fields, including all-atom and united-atom type force fields, were implemented in the MolMod database: OPLS-UA, OPLS-AA, COMPASS, CHARMM, GROMOS, TraPPE, Potoff, and TAMie. These transferable force fields cover a large variety of chemical substance classes. The system is designed such that new transferable force fields can be readily integrated. A graphical user interface was implemented that enables the construction of molecules. The MolMod database compiles the force field for the specified component and force field type and provides the corresponding data and meta data as well as ready-to-use input files for the molecule for different simulation engines. This helps the user to flexibly choose molecular models and integrate them swiftly in their individual workflows, reducing risks of input errors in molecular simulations.

Quantum annealing for industry applications: introduction and review.

Quantum annealing (QA) is a heuristic quantum optimization algorithm that can be used to solve combinatorial optimization problems. In recent years, advances in quantum technologies have enabled the development of small- and intermediate-scale quantum processors that implement the QA algorithm for programmable use. Specifically, QA processors produced by D-Wave systems have been studied and tested extensively in both research and industrial settings across different disciplines. In this paper we provide a literature review of the theoretical motivations for QA as a heuristic quantum optimization algorithm, the software and hardware that is required to use such quantum processors, and the state-of-the-art applications and proofs-of-concepts that have been demonstrated using them. The goal of our review is to provide a centralized and condensed source regarding applications of QA technology. We identify the advantages, limitations, and potential of QA for both researchers and practitioners from various fields.

Functional Characterization of Cardiac Actin Mutants Causing Hypertrophic (p.A295S) and Dilated Cardiomyopathy (p.R312H and p.E361G).

Human wild type (wt) cardiac α-actin and its mutants p.A295S or p.R312H and p.E361G correlated with hypertrophic or dilated cardiomyopathy, respectively, were expressed by using the baculovirus/Sf21 insect cell system. The c-actin variants inhibited DNase I, indicating maintenance of their native state. Electron microscopy showed the formation of normal appearing actin filaments though they showed mutant specific differences in length and straightness correlating with their polymerization rates. TRITC-phalloidin staining showed that p.A295S and p.R312H exhibited reduced and the p.E361G mutant increased lengths of their formed filaments. Decoration of c-actins with cardiac tropomyosin (cTm) and troponin (cTn) conveyed Ca2+-sensitivity of the myosin-S1 ATPase stimulation, which was higher for the HCM p.A295S mutant and lower for the DCM p.R312H and p.E361G mutants than for wt c-actin. The lower Ca2+-sensitivity of myosin-S1 stimulation by both DCM actin mutants was corrected by the addition of levosimendan. Ca2+-dependency of the movement of pyrene-labeled cTm along polymerized c-actin variants decorated with cTn corresponded to the relations observed for the myosin-S1 ATPase stimulation though shifted to lower Ca2+-concentrations. The N-terminal C0C2 domain of cardiac myosin-binding protein-C increased the Ca2+-sensitivity of the pyrene-cTM movement of bovine, recombinant wt, p.A295S, and p.E361G c-actins, but not of the p.R312H mutant, suggesting decreased affinity to cTm.

Transfer Learning Based Co-Surrogate Assisted Evolutionary Bi-Objective Optimization for Objectives with Non-Uniform Evaluation Times.

Most existing multiobjective evolutionary algorithms (MOEAs) implicitly assume that each objective function can be evaluated within the same period of time. Typically. this is untenable in many real-world optimization scenarios where evaluation of different objectives involves different computer simulations or physical experiments with distinct time complexity. To address this issue, a transfer learning scheme based on surrogate-assisted evolutionary algorithms (SAEAs) is proposed, in which a co-surrogate is adopted to model the functional relationship between the fast and slow objective functions and a transferable instance selection method is introduced to acquire useful knowledge from the search process of the fast objective. Our experimental results on DTLZ and UF test suites demonstrate that the proposed algorithm is competitive for solving bi-objective optimization where objectives have non-uniform evaluation times.

SOCS1 and SOCS3 Target IRF7 Degradation To Suppress TLR7-Mediated Type I IFN Production of Human Plasmacytoid Dendritic Cells.

Type I IFN production of plasmacytoid dendritic cells (pDCs) triggered by TLR-signaling is an essential part of antiviral responses and autoimmune reactions. Although it was well-documented that members of the cytokine signaling (SOCS) family regulate TLR-signaling, the mechanism of how SOCS proteins regulate TLR7-mediated type I IFN production has not been elucidated yet. In this article, we show that TLR7 activation in human pDCs induced the expression of SOCS1 and SOCS3. SOCS1 and SOCS3 strongly suppressed TLR7-mediated type I IFN production. Furthermore, we demonstrated that SOCS1- and SOCS3-bound IFN regulatory factor 7, a pivotal transcription factor of the TLR7 pathway, through the SH2 domain to promote its proteasomal degradation by lysine 48-linked polyubiquitination. Together, our results demonstrate that SOCS1/3-mediated degradation of IFN regulatory factor 7 directly regulates TLR7 signaling and type I IFN production in pDCs. This mechanism might be targeted by therapeutic approaches to either enhance type I IFN production in antiviral treatment or decrease type I IFN production in the treatment of autoimmune diseases.

Fast Photochemistry in Wintertime Haze: Consequences for Pollution Mitigation Strategies.

In contrast to summer smog, the contribution of photochemistry to the formation of winter haze in northern mid-to-high latitude is generally assumed to be minor due to reduced solar UV and water vapor concentrations. Our comprehensive observations of atmospheric radicals and relevant parameters during several haze events in winter 2016 Beijing, however, reveal surprisingly high hydroxyl radical oxidation rates up to 15 ppbv/h, which is comparable to the high values reported in summer photochemical smog and is two to three times larger than those determined in previous observations during winter in Birmingham (Heard et al. Geophys. Res. Lett. 2004, 31, (18)), Tokyo (Kanaya et al. J. Geophys. Res.: Atmos. 2007, 112, (D21)), and New York (Ren et al. Atmos. Environ. 2006, 40, 252-263). The active photochemistry facilitates the production of secondary pollutants. It is mainly initiated by the photolysis of nitrous acid and ozonolysis of olefins and maintained by an extremely efficiently radical cycling process driven by nitric oxide. This boosted radical recycling generates fast photochemical ozone production rates that are again comparable to those during summer photochemical smog. The formation of ozone, however, is currently masked by its efficient chemical removal by nitrogen oxides contributing to the high level of wintertime particles. The future emission regulations, such as the reduction of nitrogen oxide emissions, therefore are facing the challenge of reducing haze and avoiding an increase in ozone pollution at the same time. Efficient control strategies to mitigate winter haze in Beijing may require measures similar as implemented to avoid photochemical smog in summer.

Development of an optimal filter substrate for the identification of small microplastic particles in food by micro-Raman spectroscopy.

When analysing microplastics in food, due to toxicological reasons it is important to achieve clear identification of particles down to a size of at least 1 µm. One reliable, optical analytical technique allowing this is micro-Raman spectroscopy. After isolation of particles via filtration, analysis is typically performed directly on the filter surface. In order to obtain high qualitative Raman spectra, the material of the membrane filters should not show any interference in terms of background and Raman signals during spectrum acquisition. To facilitate the usage of automatic particle detection, membrane filters should also show specific optical properties. In this work, beside eight different, commercially available membrane filters, three newly designed metal-coated polycarbonate membrane filters were tested to fulfil these requirements. We found that aluminium-coated polycarbonate membrane filters had ideal characteristics as a substrate for micro-Raman spectroscopy. Its spectrum shows no or minimal interference with particle spectra, depending on the laser wavelength. Furthermore, automatic particle detection can be applied when analysing the filter surface under dark-field illumination. With this new membrane filter, analytics free of interference of microplastics down to a size of 1 µm becomes possible. Thus, an important size class of these contaminants can now be visualized and spectrally identified. Graphical abstract A newly developed aluminium coated polycarbonate membrane filter enables automatic particle detection and generation of high qualitative Raman spectra allowing identification of small microplastics.

[Chronic acromioclavicular joint injury of Rockwood V type with concomitant chronic anterior sternoclavicular instability]. / Chronische Acromioclaviculargelenkverletzung Typ Rockwood V mit gleichzeitiger chronischer anteriorer sternoclavicularer Instabilität.

Bipolar dislocation of the clavicle is rare. In the literature, every reported bipolar dislocation of the clavicle is caused by a traumatic injury with loss of function of the affected shoulder. Currently, there is no recommendation to treat. A conservative treatment can be tried first to achieve adequate shoulder function. If this cannot be achieved, surgical treatment will be indicated. In the literature, many options for surgical treatment are described. This article presents a case of a chronic Rockwood V injury with chronic anterior sternoclavicular joint instability. The special feature of this case was the arthroscopically assisted stabilization of the acromioclavicular joint (ACJ) with the ipsilateral semitendinosus tendon graft and the open stabilization of the sternoclavicular joint (SCJ) with the ipsilateral gracilis tendon graft. A lateral fracture of the clavicle in the course of the postoperative treatment was treated with a plate osteosynthesis. At follow-up after six months, the postoperative shoulder function was restored. The ACJ and the SCJ were stable in clinical and radiographic examination. This case report shows the first surgical treatment using two tendon grafts for combined stabilization of the ACJ and SCJ.

Metabolism and functions of lipids in myelin.

Rapid conduction of nerve impulses requires coating of axons by myelin sheaths, which are lipid-rich and multilamellar membrane stacks. The lipid composition of myelin varies significantly from other biological membranes. Studies in mutant mice targeting various lipid biosynthesis pathways have shown that myelinating glia have a remarkable capacity to compensate the lack of individual lipids. However, compensation fails when it comes to maintaining long-term stability of myelin. Here, we summarize how lipids function in myelin biogenesis, axon-glia communication and in supporting long-term maintenance of myelin. We postulate that change in myelin lipid composition might be relevant for our understanding of aging and demyelinating diseases. This article is part of a Special Issue titled Brain Lipids.

MS transport assays for γ-aminobutyric acid transporters--an efficient alternative for radiometric assays.

Transport assays for neurotransmitters based on radiolabeled substrates are widely spread and often indispensable in basic research and the drug development process, although the use of radioisotopes is inherently coupled to issues concerning radioactive waste and safety precautions. To overcome these disadvantages, we developed mass spectrometry (MS)-based transport assays for γ-aminobutyric acid (GABA), which is the major inhibitory neurotransmitter in the central nervous system (CNS). These "MS Transport Assays" provide all capabilities of [(3)H]GABA transport assays and therefore represent the first substitute for the latter. The performance of our approach is demonstrated for GAT1, the most important GABA transporter (GAT) subtype. As GABA is endogenously present in COS-7 cells employed as hGAT1 expression system, ((2)H6)GABA was used as a substrate to differentiate transported from endogenous GABA. To record transported ((2)H6)GABA, a highly sensitive, short, robust, and reliable HILIC-ESI-MS/MS quantification method using ((2)H2)GABA as an internal standard was developed and validated according to the Center for Drug Evaluation and Research (CDER) guidelines. Based on this LC-MS quantification, a setup to characterize hGAT1 mediated ((2)H6)GABA transport in a 96-well format was established, that enables automated processing and avoids any sample preparation. The K(m) value for ((2)H6)GABA determined for hGAT1 is in excellent agreement with results obtained from [(3)H]GABA uptake assays. In addition, the established assay format enables efficient determination of the inhibitory potency of GAT1 inhibitors, is capable of identifying those inhibitors transported as substrates, and furthermore allows characterization of efflux. The approach described here combines the strengths of LC-MS/MS with the high efficiency of transport assays based on radiolabeled substrates and is applicable to all GABA transporter subtypes.

Control of oligodendroglial cell number by the miR-17-92 cluster.

The generation of myelinating cells in the central nervous system requires the initiation of specific gene expression programs in oligodendrocytes. We reasoned that microRNAs (miRNAs) could play an important role in this process by regulating crucial developmental genes. Microarray profiling of cultured oligodendrocytes identified the miR-17-92 miRNA cluster as highly enriched in oligodendrocytes. We specifically deleted the miR-17-92 cluster in oligodendrocytes using 2',3'-cyclic nucleotide 3' phosphodiesterase (Cnp)-Cre mice. Absence of miR-17-92 leads to a reduction in oligodendrocyte number in vivo and we find that the expression of these miRNAs in primary cultures of oligodendrocyte precursor cells promotes cell proliferation by influencing Akt signaling. Together, these results suggest that the miRNA pathway is essential in determining oligodendroglial cell number and that the miR-17-92 cluster is crucial in this process.

Broken symmetry approach to density functional calculation of zero field splittings including anisotropic exchange interactions.

The broken symmetry approach to the calculation of zero field splittings (or magnetic anisotropies) of multinuclear transition metal complexes is further developed. A procedure is suggested how to extract spin Hamiltonian parameters for anisotropic exchange from a set of broken symmetry density functional calculations. For isotropic exchange coupling constants Jij, the established procedure is retrieved, and anisotropic (or pseudodipolar) exchange coupling tensors Dij are obtained analogously. This procedure only yields the sum of the individual single-ion zero field splitting tensors Di. Therefore, a procedure based on localized orbitals has been developed to extract the individual single-ion contributions. With spin Hamiltonian parameters at hand, the zero field splittings of the individual spin multiplets are calculated by an exact diagonalization of the isotropic part, followed by a spin projection done numerically. The method is applied to the binuclear cation [LCr(OH)3CrL](3 +) (L = 1,4,7-trimethyl-1,4,7-triazanonane) for which experimental zero field splittings for all low-energy spin states are known, and to the single-molecule magnet [Fe4(CH3C(CH2O)3)2(dpm)6] (Hdpm = 2,2,6,6-tetramethylheptane-3,5-dione). In both these 3d compounds, the single-ion tensors mainly come from the spin-orbit interaction. Anisotropic exchange is dominated by the spin-dipolar interaction only for the chromium compound. Despite the rather small isotropic exchange couplings in the iron compound, spin-orbit and spin-dipolar contributions to anisotropic exchange are of similar size here.

Nanowire arrays in multicrystalline silicon thin films on glass: a promising material for research and applications in nanotechnology.

Silicon nanowires (SiNW) were formed on large grained, electron-beam crystallized silicon (Si) thin films of only ∼6 µm thickness on glass using nanosphere lithography (NSL) in combination with reactive ion etching (RIE). Electron backscatter diffraction (EBSD) and transmission electron microscopy (TEM) studies revealed outstanding structural properties of this nanomaterial. It could be shown that SiNWs with entirely predetermined shapes including lengths, diameters and spacings and straight side walls form independently of their crystalline orientation and arrange in ordered arrays on glass. Furthermore, for the first time grain boundaries could be observed in individual, straightly etched SiNWs. After heat treatment an electronic grade surface quality of the SiNWs could be shown by X-ray photoelectron spectroscopy (XPS). Integrating sphere measurements show that SiNW patterning of the multicrystalline Si (mc-Si) starting thin film on glass substantially increases absorption and reduces reflection, as being desired for an application in thin film photovoltaics (PV). The multicrystalline SiNWs directly mark a starting point for research not only in PV but also in other areas like nanoelectronics, surface functionalization, and nanomechanics.

Data scheme and data format for transferable force fields for molecular simulation.

A generalized data scheme for transferable classical force fields used in molecular simulations, i.e. molecular dynamics and Monte Carlo simulation, is presented. The data scheme is implemented in an SQL-based data format. The data scheme and data format is machine readable, re-usable, and interoperable. A transferable force field is a chemical construction plan specifying intermolecular and intramolecular interactions between different types of atoms or different chemical groups and can be used for building a model for a given component. The data scheme proposed in this work (named TUK-FFDat) formalizes digitally these chemical construction plans, i.e. transferable force fields. It can be applied to all-atom as well as united-atom transferable force fields. The general applicability of the data scheme is demonstrated for different types of force fields (TraPPE, OPLS-AA, and Potoff). Furthermore, conversion tools for translating the data scheme between .xls spread sheet format and the SQL-based data format are provided. The data format can readily be integrated in existing workflows, simulation engines, and force field databases as well as for linking such.

Comparison of Force Fields for the Prediction of Thermophysical Properties of Long Linear and Branched Alkanes.

The prediction of thermophysical properties at extreme conditions is an important application of molecular simulations. The quality of these predictions primarily depends on the quality of the employed force field. In this work, a systematic comparison of classical transferable force fields for the prediction of different thermophysical properties of alkanes at extreme conditions, as they are encountered in tribological applications, was carried out using molecular dynamics simulations. Nine transferable force fields from three different classes were considered (all-atom, united-atom, and coarse-grained force fields). Three linear alkanes (n-decane, n-icosane, and n-triacontane) and two branched alkanes (1-decene trimer and squalane) were studied. Simulations were carried out in a pressure range between 0.1 and 400 MPa at 373.15 K. For each state point, density, viscosity, and self-diffusion coefficient were sampled, and the results were compared to experimental data. The Potoff force field yielded the best results.

Emulating Dendritic Computing Paradigms on Analog Neuromorphic Hardware.

BrainScaleS-2 is an accelerated and highly configurable neuromorphic system with physical models of neurons and synapses. Beyond networks of spiking point neurons, it allows for the implementation of user-defined neuron morphologies. Both passive propagation of electric signals between compartments as well as dendritic spikes and plateau potentials can be emulated. In this paper, three multi-compartment neuron morphologies are chosen to demonstrate passive propagation of postsynaptic potentials, spatio-temporal coincidence detection of synaptic inputs in a dendritic branch, and the replication of the BAC burst firing mechanism found in layer 5 pyramidal neurons of the neocortex.

A Scalable Approach to Modeling on Accelerated Neuromorphic Hardware.

Neuromorphic systems open up opportunities to enlarge the explorative space for computational research. However, it is often challenging to unite efficiency and usability. This work presents the software aspects of this endeavor for the BrainScaleS-2 system, a hybrid accelerated neuromorphic hardware architecture based on physical modeling. We introduce key aspects of the BrainScaleS-2 Operating System: experiment workflow, API layering, software design, and platform operation. We present use cases to discuss and derive requirements for the software and showcase the implementation. The focus lies on novel system and software features such as multi-compartmental neurons, fast re-configuration for hardware-in-the-loop training, applications for the embedded processors, the non-spiking operation mode, interactive platform access, and sustainable hardware/software co-development. Finally, we discuss further developments in terms of hardware scale-up, system usability, and efficiency.

Nonequilibrium Zeeman splitting in quantum transport through nanoscale junctions.

We calculate the differential conductance G(V) through a quantum dot in an applied magnetic field. We use a Keldysh conserving approximation for weakly correlated and the scattering-states numerical renormalization group for the intermediate and strongly correlated regime out of equilibrium. In the weakly correlated regime, the Zeeman splitting observable in G(V) strongly depends on the asymmetry of the device. In contrast, in the strongly correlated regime the position Δ(K) of the Zeeman-split zero-bias anomaly is almost independent of such asymmetries and of the order of the Zeeman energy Δ(0). We find a crossover from the purely spin-fluctuation driven Kondo regime at small magnetic fields with Δ(K)<Δ(0) to a regime at large fields where the contribution of charge fluctuations induces larger splittings with Δ(K)>Δ(0) as it was observed in recent experiments.

Zero-field splittings from density functional calculations: analysis and improvement of known methods.

Several different approaches have been proposed to calculate the zero-field splitting tensor with density functional methods. In this work, our own derivation is presented in some detail, to allow a theoretical analysis and a comparison with other methods [M. R. Pederson and S. N. Khanna, Phys. Rev. B 60, 9566 (1999); F. Neese, J. Am. Chem. Soc. 128, 10213 (2006); J. Chem. Phys. 127, 164112 (2007)]. Pederson's method can be improved by properly taking into account the quantum nature of spin when extracting the zero field splitting tensor from the magnetic anisotropy. A closed-shell molecule at large distance from an open shell complex will have a spurious contribution to the zero-field splitting tensor calculated with Neese's methods. We thus have analyzed his approach in some detail and found that it can be corrected if one properly transforms the equations used in wave function based theory to a sum-over-states type expression before one interprets it as an energy derivative. If improved along these lines, Neese's and Pederson's methods become identical down to the working equations. The theoretical analysis is illustrated by sample calculations on the well-studied Mn(III)-tris-acetylacetonato complex Mn(acac)(3), both as an isolated molecule and with a Pd(II) dichloro diammine complex at large distance as an innocent spectator.