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.
Molecular Dynamics Simulation , Databases, Factual
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.
Molecular Dynamics Simulation , Databases, Factual , Monte Carlo Method
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.
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.
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.
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.
Cardiomyopathy, Dilated , Cardiomyopathy, Hypertrophic , Actin Cytoskeleton/genetics , Actins/chemistry , Actins/genetics , Animals , Calcium , Cardiomyopathy, Dilated/genetics , Cardiomyopathy, Hypertrophic/genetics , Cattle , Humans , Hypertrophy , Mutation , Myosins , Tropomyosin/genetics
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.
Neurons , Synapses , Action Potentials/physiology , Dendrites/physiology , Models, Neurological , Neurons/physiology , Pyramidal Cells
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.
Algorithms , Biological Evolution , Computer Simulation , Learning , Machine Learning
The human mutant cardiac α-actins p.A295S or p.R312H and p.E361G, correlated with hypertrophic or dilated cardiomyopathy, respectively, were expressed by the baculovirus/Sf21 insect cell system and purified to homogeneity. The purified cardiac actins maintained their native state but showed differences in Ca2+-sensitivity to stimulate the myosin-subfragment1 ATPase. Here we analyzed the interactions of these c-actins with actin-binding and -modifying proteins implicated in cardiomyocyte differentiation. We demonstrate that Arp2/3 complex and the formin mDia3 stimulated the polymerization rate and extent of the c-actins, albeit to different degrees. In addition, we tested the effect of the MICAL-1 monooxygenase, which modifies the supramolecular actin organization during development and adaptive processes. MICAL-1 oxidized these c-actin variants and induced their de-polymerization, albeit at different rates. Transfection experiments using MDCK cells demonstrated the preferable incorporation of wild type and p.A295S c-actins into their microfilament system but of p.R312H and p.E361G actins into the submembranous actin network. Transduction of neonatal rat cardiomyocytes with adenoviral constructs coding HA-tagged c-actin variants showed their incorporation into microfilaments after one day in culture and thereafter into thin filaments of nascent sarcomeric structures at their plus ends (Z-lines) except the p.E361G mutant, which preferentially incorporated at the minus ends.
BACKGROUND: Availability of patient-specific image data, gathered from preoperatively conducted studies, like computed tomography scans and magnetic resonance imaging studies, during a surgical procedure is a key factor for surgical success and patient safety. Several alternative input methods, including recognition of hand gestures, have been proposed for surgeons to interact with medical image viewers during an operation. Previous studies pointed out the need for usability evaluation of these systems. OBJECTIVES: We describe the accuracy and usability of a novel software system, which integrates gesture recognition via machine learning into an established image viewer. METHODS: This pilot study is a prospective, observational trial, which asked surgeons to interact with software to perform two standardized tasks in a sterile environment, modeled closely to a real-life situation in an operating room. To assess usability, the validated "System Usability Scale" (SUS) was used. On a technical level, we also evaluated the accuracy of the underlying neural network. RESULTS: The neural network reached 98.94% accuracy while predicting the gestures during validation. Eight surgeons with an average of 6.5 years of experience participated in the usability study. The system was rated on average with 80.25 points on the SUS. CONCLUSION: The system showed good overall usability; however, additional areas of potential improvement were identified and further usability studies are needed. Because the system uses standard PC hardware, it made for easy integration into the operating room.
Imaging, Three-Dimensional/instrumentation , Operating Rooms , Humans , Neural Networks, Computer , Reproducibility of Results , Software , Surgeons , Task Performance and Analysis , User-Computer Interface
The heterogeneous hydrolysis of dinitrogen pentoxide (N2O5) plays an important role in regulating NOx. The N2O5 uptake coefficient, γ(N2O5), was determined using an iterative box model that was constrained to observational data obtained in suburban Beijing from February to March 2016. The box model determined 2289 individual γ(N2O5) values that varied from <0.001 to 0.02 with an average value of 0.0046 ± 0.0039 (and a median value of 0.0032). We found the derived winter γ(N2O5) values in Beijing were relatively low as compared to values reported in previous field studies conducted during winter in Hong Kong (average value of 0.014) and the eastern U.S. coast (median value of 0.0143). In our study, field evidence of the suppression of γ(N2O5) values due to pNO3- content, organics and the enhancement by aerosol liquid water content (ALWC) is in line with previous laboratory study results. Low ALWC, high pNO3- content, and particle morphology (inorganic core with an organic shell) accounted for the low γ(N2O5) values in the North China Plain (NCP) during wintertime. The field-derived γ(N2O5) values are well reproduced by a revised parameterization method, which includes the aerosol size distribution, ALWC, nitrate and organic coating, suggesting the feasibility of comprehensive parameterization in the NCP during wintertime.
The massively parallel nature of biological information processing plays an important role due to its superiority in comparison to human-engineered computing devices. In particular, it may hold the key to overcoming the von Neumann bottleneck that limits contemporary computer architectures. Physical-model neuromorphic devices seek to replicate not only this inherent parallelism, but also aspects of its microscopic dynamics in analog circuits emulating neurons and synapses. However, these machines require network models that are not only adept at solving particular tasks, but that can also cope with the inherent imperfections of analog substrates. We present a spiking network model that performs Bayesian inference through sampling on the BrainScaleS neuromorphic platform, where we use it for generative and discriminative computations on visual data. By illustrating its functionality on this platform, we implicitly demonstrate its robustness to various substrate-specific distortive effects, as well as its accelerated capability for computation. These results showcase the advantages of brain-inspired physical computation and provide important building blocks for large-scale neuromorphic applications.
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.
Air Pollutants , Ozone , Beijing , New York , Photochemistry , Smog
Inversely tapered silicon photonic resonators on silicon substrates were shown to host multiple high-Q whispering gallery modes and constitute versatile building blocks for CMOS compatible solid state lighting, optical sensing and modulator devices. So far, numerical analyses by the finite difference time domain method have been used to predict the height distribution of whispering gallery modes in such resonators. In this study, we provide an experimental evidence of this mode distribution along the resonator height by selectively exciting whispering gallery modes using cathodoluminescence spectroscopy. Further we derive analytical functions that permit to relate the height distribution of modes with a defined polarization, symmetry and effective refractive index to the geometrical shape of the inversely tapered resonators.
In this study, we analyzed the functional role of the formin Drosophila Homologue of Diaphanous2 (Diaph2) in colorectal cancer cells. We show that stable down-regulation of Diaph2 expression in HT29 cells decreased chromosome alignment and the velocity of chromosome movement during M-phase, thus reducing the proliferation rate and colony formation. In interphase cells, Diaph2 was diffusely distributed in the cytosol, while in metaphase cells the protein was located to spindle microtubules (MTs). Diaph2-depletion increased the concentration of stable spindle MTs, showing that the formin is required to control spindle MT-dynamics. Our cellular data indicate that Diaph2-controls spindle MT-dynamics independent of Cdc42 activity and our in vitro results reveal that bacterially produced full-length (FL) Diaph2 strongly altered MT-dynamics in absence of Cdc42, where its actin-nucleating activity is auto-inhibited. FL-Diaph2 mediates a 10-fold increase in MT-polymerization compared to the Diaph2-FH2-domain. Interestingly, a Diaph2-mutant lacking the FH2-domain (ΔFH2) increased MT-polymerization to a similar extent as the FH2-domain, indicating the existence of a second MT-binding domain. However, in contrast to FL-Diaph2 and the FH2-domain, ΔFH2 did not alter the density of taxol-stabilized MTs. Thus, the FH2-domain and the second Diaph2-binding domain appear to control MT-dynamics by different mechanisms. In summary, our data indicate that Diaph2 controls M-phase progression under basal conditions by regulating spindle MT-dynamics. In addition, a region outside of the canonical MT-regulating FH2-domain is involved in Diaph2-mediated control of MT-dynamics.
Colorectal Neoplasms/metabolism , Formins/metabolism , Microtubules/metabolism , Protein Interaction Domains and Motifs , Animals , Apoptosis/genetics , Biomarkers , Cell Line, Tumor , Cell Proliferation , Colorectal Neoplasms/etiology , Formins/chemistry , Gene Deletion , Gene Expression , Humans , Karyotyping , Protein Multimerization , Spindle Apparatus/metabolism
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).
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.
Dendritic Cells/metabolism , Interferon Regulatory Factor-7/metabolism , Interferon-alpha/metabolism , Suppressor of Cytokine Signaling 1 Protein/metabolism , Suppressor of Cytokine Signaling 3 Protein/metabolism , Toll-Like Receptor 7/metabolism , Cells, Cultured , HEK293 Cells , Humans , Leukocytes, Mononuclear/metabolism , Signal Transduction/physiology
Investigations into brain function and disease depend on the precise classification of neural cell types. Cells of the oligodendrocyte lineage differ greatly in their morphology, but accurate identification has thus far only been possible for oligodendrocyte progenitor cells and mature oligodendrocytes in humans. We find that breast carcinoma amplified sequence 1 (BCAS1) expression identifies an oligodendroglial subpopulation in the mouse and human brain. These cells are newly formed, myelinating oligodendrocytes that segregate from oligodendrocyte progenitor cells and mature oligodendrocytes and mark regions of active myelin formation in development and in the adult. We find that BCAS1+ oligodendrocytes are restricted to the fetal and early postnatal human white matter but remain in the cortical gray matter until old age. BCAS1+ oligodendrocytes are reformed after experimental demyelination and found in a proportion of chronic white matter lesions of patients with multiple sclerosis (MS) even in a subset of patients with advanced disease. Our work identifies a means to map ongoing myelin formation in health and disease and presents a potential cellular target for remyelination therapies in MS.
Multiple Sclerosis/metabolism , Neoplasm Proteins/metabolism , Oligodendroglia/metabolism , Animals , Demyelinating Diseases , Humans , Mice , Multiple Sclerosis/pathology , Myelin Sheath/metabolism
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.
Acromioclavicular Joint/injuries , Arthroscopy/methods , Athletic Injuries/surgery , Clavicle/injuries , Fractures, Bone/surgery , Joint Instability/surgery , Sternoclavicular Joint/injuries , Acromioclavicular Joint/diagnostic imaging , Acromioclavicular Joint/surgery , Athletic Injuries/diagnostic imaging , Chronic Disease , Clavicle/diagnostic imaging , Clavicle/surgery , Comorbidity , Fracture Fixation, Internal , Fractures, Bone/diagnosis , Fractures, Bone/diagnostic imaging , Humans , Joint Instability/diagnosis , Joint Instability/diagnostic imaging , Male , Middle Aged , Postoperative Complications/physiopathology , Range of Motion, Articular/physiology , Reoperation , Skiing/injuries , Sternoclavicular Joint/diagnostic imaging , Sternoclavicular Joint/surgery , Tendons/transplantation , Tomography, X-Ray Computed
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.
Filtration/methods , Food Analysis/methods , Food Contamination/analysis , Membranes, Artificial , Plastics/analysis , Spectrum Analysis, Raman/methods , Aluminum/chemistry , Cellulose/analogs & derivatives , Filtration/instrumentation , Food Analysis/instrumentation , Gold/chemistry , Particle Size , Plastics/isolation & purification , Polycarboxylate Cement/chemistry , Silver/chemistry , Spectrum Analysis, Raman/instrumentation
