LaRA 2: parallel and vectorized program for sequence–structure alignment of RNA sequences

Background The function of non-coding RNA sequences is largely determined by their spatial conformation, namely the secondary structure of the molecule, formed by Watson–Crick interactions between nucleotides. Hence, modern RNA alignment algorithms routinely take structural information into account. In order to discover yet unknown RNA families and infer their possible functions, the structural alignment of RNAs is an essential task. This task demands a lot of computational resources, especially for aligning many long sequences, and it therefore requires efficient algorithms that utilize modern hardware when available. A subset of the secondary structures contains overlapping interactions (called pseudoknots), which add additional complexity to the problem and are often ignored in available software. Results We present the SeqAn-based software LaRA 2 that is significantly faster than comparable software for accurate pairwise and multiple alignments of structured RNA sequences. In contrast to other programs our approach can handle arbitrary pseudoknots. As an improved re-implementation of the LaRA tool for structural alignments, LaRA 2 uses multi-threading and vectorization for parallel execution and a new heuristic for computing a lower boundary of the solution. Our algorithmic improvements yield a program that is up to 130 times faster than the previous version. Conclusions With LaRA 2 we provide a tool to analyse large sets of RNA secondary structures in relatively short time, based on structural alignment. The produced alignments can be used to derive structural motifs for the search in genomic databases.

Numerical Flow Modeling of Artificial Ocean Upwelling

Artificial Upwelling (AU) of nutrient-rich Deep Ocean Water (DOW) to the ocean's sunlit surface layer has recently been put forward as a means of increasing marine CO2 sequestration and fish production. AU and its possible benefits have been studied in the context of climate change mitigation as well as food security for a growing human population. However, extensive research still needs to be done into the feasibility, effectiveness and potential risks, and side effects associated with AU to be able to better predict its potential. Fluid dynamic modeling of the AU process and the corresponding inorganic nutrient transport can provide necessary information for a better quantification of the environmental impacts of specific AU devices and represents a valuable tool for their optimization. Yet, appropriate capture of all flow phenomena relevant to the AU process remains a challenging task that only few models are able to accomplish. In this paper, simulation results obtained with a newly developed numerical solution method are presented. The method is based on the open-source modeling environment OpenFOAM. It solves the unsteady Reynolds-Averaged Navier-Stokes (RANS) equations with additional transport equations for energy, salinity, and inorganic nutrients. The method aims to be widely applicable to oceanic flow problems including temperature- and salinity-induced density stratification and passive scalar transport. The studies presented in this paper concentrate on the direct effects of the AU process on nutrient spread and concentration in the ocean's mixed surface layer. Expected flow phenomena are found to be captured well by the new method. While it is a known problem that cold DOW that is upwelled to the surface tends to sink down again due to its high density, the simulations presented in this paper show that the upwelled DOW settles at the lower boundary of the oceans mixed surface layer, thus keeping a considerable portion of the upwelled nutrients available for primary production. Comparative studies of several design variants, with the aim of maximizing the amount of nutrients that is retained inside the mixed surface layer, are also presented and analyzed.

SPACECRAFT RELIABILITY CALCULATIONS USING STATISTICAL REGULARITIES IN OCCURRENCES OF FAILURES IN DEVICES, UNITS AND ASSEMBLIES DURING THEIR OPERATION

The paper addresses reliability analysis of manned spacecraft with the use of statistical regularities in in-flight failures of their devices, units and assemblies. It formulates validity criteria for using a device failure in reliability analysis, proposes a method for analyzing and classifying failures which enables factoring in different types of failures in reliability analyses. It considers a hypothesis of the absence of statistically significant differences in probabilities of individual valid failures and demonstrates the feasibility of its adoption with the use of dispersion analysis. A method is developed for evaluating product reliability using a functional relationship between reliability and the number of failures occurring in flight which makes it possible to significantly simplify reliability analysis for complex products, to establish the number of in-flight failures that is acceptable from the standpoint of the product reliability requirements, to study various product architectures from the standpoint of reliability criteria. It proposes a method for evaluating the lower boundary for the probability of manned spacecraft completing their missions based on the failure modes, effects and criticality analysis, and demonstrates the feasibility of optimizing the product redundancy scheme based on the fault tolerance requirements. Key words: manned spacecraft, flight, failure, fault tolerance, classification of failures, reliability, probability of failure-free operation, statistical analysis, dispersion analysis.

PROCESSING OF HARDENED CYLINDRICAL GEAR WHEELS OF THE CUTTING GEARBOX OF THE COMBINE UKD 200-500

The article discusses the latest developments of unique technological methods of gear milling of cylindrical gears for preliminary blade gear processing of hardened cylindrical gears of the cutting reducer of the UKD200-500 coal mining harvester for the final gear grinding of gear teeth with modulus m = 16 mm, with hardness HRC 56 ... 62. The peculiarity of the design of special hob cutters is that a circle passing through the lower boundary points of the involute is used as the palloid of the machine gearing of the tool and part. Pre-cutting the teeth of hardened wheels with carbide milling cutters allows you to remove the main allowance for the final gear grinding.

Computationally Efficient Direction-of-Arrival Estimation Algorithms for a Cubic Coprime Array

In this paper, we investigate the problem of direction-of-arrival (DOA) estimation for massive multi-input multi-output (MIMO) radar, and propose a total array-based multiple signals classification (TA-MUSIC) algorithm for two-dimensional direction-of-arrival (DOA) estimation with a coprime cubic array (CCA). Unlike the conventional multiple signal classification (MUSIC) algorithm, the TA-MUSIC algorithm employs not only the auto-covariance matrix but also the mutual covariance matrix by stacking the received signals of two sub cubic arrays so that full degrees of freedom (DOFs) can be utilized. We verified that the phase ambiguity problem can be eliminated by employing the coprime property. Moreover, to achieve lower complexity, we explored the estimation of signal parameters via the rotational invariance technique (ESPRIT)-based multiple signal classification (E-MUSIC) algorithm, which uses a successive scheme to be computationally efficient. The Cramer–Rao bound (CRB) was taken as a theoretical benchmark for the lower boundary of the unbiased estimate. Finally, numerical simulations were conducted in order to demonstrate the effectiveness and superiority of the proposed algorithms.

The impact of gravity wave drag modifications on stratospheric pathways of Arctic-midlatitude linkages using deep learning

<p>The global warming has been observed to be more severe in the Arctic compared to the rest of the world. This enhanced warming i.e. Arctic Amplification is not just the result of local feedback processes in the Arctic. The stratospheric pathways of Arctic-midlatitude linkages and large-scale dynamical processes can contribute to the Arctic Amplification. The polar stratospheric dynamics crucially depends on the atmospheric waves at all scales. The winter polar vortex can be disturbed by gravity waves in the middle atmosphere. To investigate the sensitivity of the polar vortex dynamics, large-scale dynamical processes, and the stratospheric pathways of the Arctic-midlatitude linkages to the modification of gravity wave drag, we conduct sensitivity experiments using the global atmospheric model ICON-NWP (ICOsahedral Nonhydrostatic Model for Numerical Weather Prediction). These sensitivity experiments are performed by imposing a repeated annual cycle of the year 1986 for sea surface temperatures and sea ice as lower boundary conditions and for greenhouse gas concentrations as external forcing. This year is selected as both El-Nino Southern Oscillation and Pacific decadal oscillation were in their neutral phase and no explosive volcanic eruption has occurred. Hence, lower boundary and external forcing conditions in this year can serve as a useful proxy for the multi-year mean condition and an estimate of its internal variability. We performed simulations where in the control simulation the sub-grid parameterization scheme for both orographic and non-orographic gravity wave drags are switched on. The other two experiments are identical to the control simulation except that either orographic or non-orographic gravity wave drags are switched off.</p> <p>Recently, deep learning has extraordinarily progressed our ability to recognize complex patterns in big datasets. Deep neural networks have shown great capabilities to capture the dynamical process of the atmosphere. Applying deep learning algorithms on experiments’ results, the impact of gravity wave drag modifications on large-scale mechanisms of the Arctic Amplification will be analyzed. Special emphasis will be put on the effects of gravity wave drag modifications on the polar vortex dynamics.</p>

Characterization of platelet functionality in pediatric patients with kaposiform hemangioendothelioma / Kasabach-Merritt phenomenon

Background. Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor of infancy commonly associated with Kasabach-Merritt phenomenon (KMP) that includes thrombocytopenia and coagulation dysfunction. Platelet receptor CLEC-2 -tumor cell podoplanin interaction is considered the key mechanism of thrombocytopenia in KMP, however, the effect of long-term exposure to podoplanin on platelet function is unknown. Procedure. Here we examined blood samples from six patients with KHE and one KMP. Platelet calcium signaling and functional responses to conventional activation and CLEC-2 stimulation were analyzed by continuous and endpoint live cell flow cytometry. Platelet aggregation in response to ADP or rhodocytin was analyzed by low-angle light scattering approach (LaSca). Additionally, ex vivo thrombus formation on collagen was observed in parallel-plate flow chambers. Results. We demonstrate that in KHE/KMP platelet functional responses to strong stimulation were on the lower boundary of age-matched normal ranges, while calcium mobilization and fibrinogen binding upon stimulation with ADP alone were significantly lower than control values. Platelet di-aggregate formation in response to ADP was also diminished in most of the patients. Formation of platelet aggregates in collagen-coated parallel plate flow chambers was also noticeably lower than in the age-matched control group. Calcium mobilization in response to CLEC-2 stimulation was unaltered in the patients and could be blocked by low-molecular-weight inhibitors, 2CP and HB125. Conclusions. While platelet responsiveness in KHE/KMP is moderately altered, their CLEC-2 receptors remain functional and respond to inhibition. Therefore, our findings suggest that CLEC-2-targeting molecules are new potential agents in therapeutic management of this life-threatening condition.

Characterization of platelet functionality in pediatric patients with kaposiform hemangioendothelioma / Kasabach-Merritt phenomenon

Background. Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor of infancy commonly associated with Kasabach-Merritt phenomenon (KMP) that includes thrombocytopenia and coagulation dysfunction. Platelet receptor CLEC-2 -tumor cell podoplanin interaction is considered the key mechanism of thrombocytopenia in KMP, however, the effect of long-term exposure to podoplanin on platelet function is unknown. Procedure. Here we examined blood samples from 7 patients with KHE/KMP. Platelet calcium signaling and functional responses to conventional activation and CLEC-2 stimulation were analyzed by continuous and endpoint live cell flow cytometry. Platelet aggregation in response to ADP or rhodocytin was analyzed by low-angle light scattering approach (LaSca). Additionally, ex vivo thrombus formation on collagen was observed in parallel-plate flow chambers. Results. We demonstrate that in KHE/KMP platelet functional responses to strong stimulation were on the lower boundary of age-matched normal ranges, while calcium mobilization and fibrinogen binding upon stimulation with ADP alone were significantly lower than control values. Platelet di-aggregate formation in response to ADP was also diminished in most of the patients. Formation of platelet aggregates in collagen-coated parallel plate flow chambers was also noticeably lower than in the age-matched control group. Calcium mobilization in response to CLEC-2 stimulation was unaltered in the patients and could be blocked by low-molecular-weight inhibitors, 2CP and HB125. Conclusions. While platelet responsiveness in KHE/KMP is moderately altered, platelet CLEC-2 receptors remain functional and respond to inhibition. Therefore, our findings suggest that CLEC-2-targeting molecules are new potential agents in therapeutic management of this life-threatening condition.

I-mode pedestal relaxation events in the Alcator C-Mod and ASDEX Upgrade tokamaks

In some conditions, I-mode plasmas can feature pedestal relaxation events (PREs) that transiently enhance the energy reaching the divertor target plates. To shed light on their appearance, characteristics and energy reaching the divertor targets, a comparative study between two tokamaks – Alcator C-Mod and ASDEX Upgrade – is carried out. It is found that PREs appear only in a subset of I-mode discharges, mainly when the plasma is close to the H-mode transition. Also, a growing oscillating precursor before the PRE onset is observed in the region close to the separatrix in both devices, and a discussion on a possible triggering mechanism is outlined. The PRE relative energy loss from the confined region is found to increase with decreasing pedestal top collisionality ν* ped. Similarly, also the relative electron temperature drop at the pedestal top, which is related to the conductive energy loss, rises with decreasing ν* ped. Based on these relations, the PRE relative energy loss in future devices such as DEMO and ARC is estimated. Finally, the divertor peak energy fluence due to the PRE is measured on each device. Those values are then compared to the model introduced in [1] for type-I ELMs. The model is shown to provide an upper boundary for PRE energy fluence data, while a lower boundary is found by dividing the model by three. These two boundaries are used to make projections of the PRE divertor energy fluence to DEMO and ARC.

Rayleigh–Bénard Instability of an Ellis Fluid Saturated Porous Channel with an Isoflux Boundary

The onset of the thermal instability is investigated in a porous channel with plane parallel boundaries saturated by a non–Newtonian shear–thinning fluid and subject to a horizontal throughflow. The Ellis model is adopted to describe the fluid rheology. Both horizontal boundaries are assumed to be impermeable. A uniform heat flux is supplied through the lower boundary, while the upper boundary is kept at a uniform temperature. Such an asymmetric setup of the thermal boundary conditions is analysed via a numerical solution of the linear stability eigenvalue problem. The linear stability analysis is developed for three–dimensional normal modes of perturbation showing that the transverse modes are the most unstable. The destabilising effect of the non–Newtonian shear–thinning character of the fluid is also demonstrated as compared to the behaviour displayed, for the same flow configuration, by a Newtonian fluid.