Miracle-dz/UniFAR-FTUs huggingface dataset:
Phosphorylation of SAMHD1 Thr592 increases C-terminal domain dynamics, tetramer dissociation and ssDNA binding kinetics

SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) is driven into its activated tetramer form by binding of GTP activator and dNTP activators/substrates. In addition, the inactive monomeric and dimeric forms of the enzyme bind to single-stranded (ss) nucleic acids. During DNA replication SAMHD1 can be phosphorylated by CDK1 and CDK2 at its C-terminal threonine 592 (pSAMHD1), enabling the enzyme to localize to stalled replication forks (RFs) and promote their restart. Since localization of a potent dNTPase at stalled RFs is not harmonious with DNA replication, we used a series of kinetic and thermodynamic measurements to explore a hypothesis where the combined effects of T592 phosphorylation and ssDNA binding serves as a dual switch to turn-off SAMHD1 dNTPase activity. We report that phosphorylation has only a small effect on the dNTPase activity and ssDNA binding affinity of SAMHD1. However, perturbation of the native T592 by phosphorylation decreased the thermal stability of tetrameric SAMHD1 and accelerated tetramer dissociation in the absence and presence of ssDNA (~15-fold). In addition, we found that ssDNA binds competitively with GTP to the A1 site. A full-length SAMHD1 cryo-EM structure revealed substantial baseline dynamics in the C-terminal domain (which contains T592) which may be modulated by phosphorylation. We propose that T592 phosphorylation increases tetramer dynamics and allows invasion of ssDNA into the A1 site and the previously characterized DNA binding surface at the dimer-dimer interface. These features are consistent with rapid and regiospecific inactivation of pSAMHD1 dNTPase at RFs or other sites of free ssDNA in cells.
Systematic classification error profoundly impacts inference in high-depth Whole Genome Shotgun Sequencing datasets

There is little consensus in the literature as to which approach for classification of Whole Genome Shotgun (WGS) sequences is best. In this paper, we examine two of the most popular algorithms, Kraken2 and Metaphlan2 utilizing four publicly available datasets. As expected from previous literature, we found that Kraken2 reports more overall taxa while Metaphlan2 reports fewer taxa while classifying fewer overall reads. To our surprise, however, Kraken 2 reported not only more taxa but many more taxa that were significantly associated with metadata. This implies that either Kraken2 is more sensitive to taxa that are biologically relevant and are simply missed by Metaphlan2, or that Kraken2’s classification errors are generated in such a way to impact inference. To discriminate between these two possibilities, we compared Spearman correlations coefficients of each taxa against each taxa with higher abundance from the same dataset. We found that Kraken2, but not Metaphlan2, showed a consistent pattern of classifying low abundance taxa that generated high correlation coefficients with higher abundance taxa. Neither Metaphlan2, nor 16S sequences that were available for two of our four datasets, showed this pattern. Simple simulations based on a variable Poisson error rate sampled from the uniform distribution with an average error rate of 0.0005 showed strikingly strong concordance with the observed correlation patterns from Kraken2. Our results suggest that Kraken2 consistently misclassifies high abundance taxa into the same erroneous low abundance taxa creating “phantom” taxa have a similar pattern of inference as the high abundance source. Because of the large sequencing depths of modern WGS cohorts, these “phantom” taxa will appear statistically significant in statistical models even with a low overall rate of classification error from Kraken. Our simulations suggest that this can occur with average error rates as low as 1 in 2,000 reads. These data suggest a novel metric for evaluating classifier accuracy and suggest that the pattern of classification errors should be considered in addition to overall classification error rate since consistent classification errors have a more profound impact on inference compared to classification errors that do not always result in assignment to the same erroneous taxa. This work highlights fundamental questions on how classifiers function and interact with large sequencing depth and statistical models that still need to be resolved for WGS, especially if correlation coefficients between taxa are to be used to build covariance networks. Our work also suggests that despite its limitations, 16S rRNA sequencing may still be useful as neither of the two most popular 16S classifiers showed these patterns of inflated correlation coefficients between taxa.
PEP7 is a ligand for receptor kinase SIRK1 to regulate aquaporins and root growth

Plant receptor kinases constitute a large protein family that regulate various aspects of development and responses to external biotic and abiotic cues. Functional characterization of this protein family and particularly the identification of their ligands remains a major challenge in plant biology. Previously, we identified plasma membrane-intrinsic SUCROSE INDUCED RECEPTOR KINASE 1 (SIRK1) and QIAN SHOU KINASE 1 (QSK1) as a receptor / co-receptor pair involved in regulation of aquaporins in response to osmotic conditions induced by sucrose. Here, we identified a member of the Elicitor Peptide (PEP) family, namely PEP7, as the specific ligand of receptor kinase SIRK1. PEP7 binds to the extracellular domain of SIRK1 with a binding constant of 1.44±0.79 µM and is secreted to the apoplasm specifically in response to sucrose treatment. Stabilization of a signaling complex involving SIRK1, QSK1 and aquaporins as substrates is mediated by alterations in the external sucrose concentration or by PEP7 application. Moreover, the presence of PEP7 induces the phosphorylation of aquaporins in vivo and enhance water influx into protoplasts. The loss-of-function mutant of SIRK1 is not responsive to external PEP7 treatment regarding kinase activity, aquaporin phosphorylation and water influx activity. Our data indicate that the PEP7/SIRK1/QSK1 complex represents a crucial perception and response module mediating sucrose-controlled water flux in plants.
The catalytic domain of cellulose synthase (CESA) is involved in vesicle trafficking and protein dynamics

Cellulose, as the main component of the plant cell wall, is synthesized by a multimeric protein complex named the cellulose synthase (CESA) complex or CSC. In plant cells, CSCs are transported through the endomembrane system to the PM, but how catalytic activity or conserved motifs around the catalytic core domain influence vesicle trafficking or protein dynamics is not well understood. Here, we used a functional YFP-tagged AtCESA6 and site-directed mutagenesis to create 18 single amino acid replacement mutants in key motifs of the catalytic domain including DDG, DXD, TED and QXXRW, to comprehensively analyze how catalytic activity affects plant growth, cellulose biosynthesis, as well as CSC dynamics and trafficking. Plant growth and cellulose content were reduced by nearly all mutations. Moreover, mutations in most conserved motifs reduced the velocity of CSC movement in the PM as well as delivery of CSCs to the PM. Interestingly, the abundance of YFP-CESA6 in the Golgi apparatus was increased or reduced by mutations in DDG and QXXRW motifs, respectively. Post-Golgi trafficking of CSCs was also differentially perturbed by these mutations and, based on these phenotypes, the 18 mutants could be divided into two major groups. Group I comprises mutations causing significantly increased Golgi fluorescence intensity with either an increase or no change in the abundance of cortical SmaCCs compared with wild-type. In contrast, Group II represents mutations with significantly decreased Golgi fluorescence intensity and/or reduced SmaCC density. We propose that Group I mutations cause CSC trafficking defects whereas Group II mutations affect normal CSC rosette formation and hence interfere with subsequent CSC trafficking. Collectively, our results demonstrate that the catalytic domain of CESA6 is essential not only for cellulose biosynthesis, but also complex formation, protein folding and dynamics, vesicle trafficking, or all of the above.
Signalling speed along a key white matter 5 tract influences memory recall ability 6 in humans

30 Conduction velocity is the speed at which electrical signals travel along axons and is a crucial 31 determinant of neural communication. Inferences about conduction velocity can now be made 32 in vivo in humans using magnetic resonance (MR) imaging and a measure called the MR g- 33 ratio. Here, in the first application to cognition, we found that increased MR g-ratio, and by 34 inference faster conduction velocity, specifically in the parahippocampal cingulum bundle, 35 which connects the hippocampus with a range of other brain areas, was associated with better 36 memory recall ability in 217 healthy adults. Moreover, two tract features seemed to favour 37 better memory retrieval – large inner axon diameters and coherently organised neurites, both 38 of which facilitate speedy signalling. These results offer a new perspective on drivers of 39 individual differences in memory recall ability. More broadly, they show that MR g-ratio can 40 provide novel insights into how the human brain processes and integrates information. 41
Talin-drug interaction reveals a key molecular determinant for biphasic mechanical effect: studied under single-molecule resolution

Talin as an adhesion protein, exhibits a strong force-dependent structure-function dynamics. Being a mechanosensitive focal adhesion (FA) protein, talin might interact to several FA targeting drugs; however, the molecular mechanism of talin-drug interactions remains elusive. Here we combined magnetic tweezers and molecular dynamics (MD) simulation to explore mechanical stability of talin with three drugs based on their talin specificity. Interestingly, our study revealed that talin displays a bimodal force distribution with a low and high unfolding force population. We observed that talin nonspecific drugs (tamoxifen and letrozole) display biphasic effect: increase talin mechanical stability upto optimum concentration, followed by a decrease in stability with further concentration increase. By contrast, talin-specific cyanidin 3-O-glucoside promotes a steady increase to talin mechanical stability with its concentration. We reconciled our observation from the simulation study: tamoxifen enters into talin hydrophobic core, eventually destabilizing the protein; whereas cyanidin 3-O-glucoside stabilizes the protein core by maintaining the inter-helix distance. Finally, we observed a strong correlation among hydrophobicity and cavity analysis, illustrating a detailed mechanistic analysis of drug effect on the mechanosensitive protein. Overall this study presents a novel perspective for drug designing against mechanosensitive proteins and studying off-target effects of already known drugs.
The Insulin receptor regulates the persistence of mechanical nociceptive sensitization in flies and mice

Early phase diabetes is often accompanied by pain sensitization. In the fruit fly Drosophila, the insulin receptor (InR) regulates the persistence of injury-induced thermal nociceptive sensitization. Whether Drosophila InR also regulates the persistence of mechanical nociceptive sensitization remains unclear. Mice with a sensory neuron deletion of the gene encoding the Insulin receptor (Insr) show normal nociceptive baselines, however, it is not known whether deletion of Insr in nociceptive sensory neurons leads to persistent nociceptive hypersensitivity in an inflammatory pain paradigm. In this study, we used fly and mouse nociceptive sensitization models to address these questions. In flies, InR mutants and larvae with sensory neuron-specific expression of RNAi transgenes targeting InR exhibited persistent mechanical hypersensitivity, as previously observed for the thermal sensory modality. Mice with a specific deletion of the Insr gene in NaV1.8+ nociceptive sensory neurons showed normal nociceptive thermal and mechanical baselines similar to controls. In an inflammatory paradigm, however, these mutant mice showed persistent mechanical (but not thermal) hypersensitivity, particularly in female mice. Mice with the NaV1.8+ sensory neuron specific deletion of Insr did not show metabolic abnormalities that would be typical of a systemic defect in insulin signaling. Our results show that some aspects of the regulation of nociceptive hypersensitivity by the Insulin receptor are shared between flies and mice and that this regulation is likely independent of metabolic effects.
BPMN in the Wild: A Reprise

The Business Process Model and Notation (BPMN) language is the de facto standard for business process modeling and automation. While there exists a number of public model collections, there is still a need for ample datasets for empirical analysis on the usage and practice of BPMN. In this paper, we present our repository mining approach for generating a corpus of open source BPMN models by systematically analyzing software projects on GitHub.com . In contrast to our previous work, where we have limited the analysis to a 10% sample of GitHub.com , including 6.1 million projects, we here report the results for our new analysis of the whole 82.8 million projects hosted on GitHub.com at the time of conducting the research. We describe the resulting dataset, containing 79,713 distinct BPMN models from 18,534 open source projects.
The power available to tidal turbines in an open channel flow

Linear momentum actuator disc theory is extended to address the power available to a tidal turbine array spanning the cross-section of an open channel flow. A generalised formulation is presented, which relaxes constraints in previous models on the Froude number of the flow and the geometry of the turbine array, and also considers the effects of far-wake mixing on the overall power removed from the flow. In the limiting case of no free surface deformation, the rigid lid model is recovered. Blockage, the ratio of turbine frontal area to the cross-sectional area of the surrounding flow passage, has the greatest effect on available power, with the peak power coefficient increasing by 55% from 0·60 to 0·93 as the blockage ratio increases from 0·05 to 0·20. A further 3% increase in peak power coefficient is achieved as the Froude number increases from 0·05 to 0·20. The efficiency of energy extraction may be determined relative to the total power extracted from the flow, comprising the power available to the tu.
Process Mining on Video Data

Disciplines like life and natural sciences could gain high benefits from process mining in terms of identifying anomalies in the process or supporting predictive analytics in what is being measured. These disciplines, however, mostly work with data at a much lower level of abstraction and the data does not directly relate to high-level business process concepts as required for process mining. This paper discusses an approach for process mining on video data. As a use case, we applied our approach on video surveillance data of pigpens. Although, our process analytics pipeline from raw video data to a discovered process model has not yet been fully implemented, we are convinced that our approach is an essential contribution towards a (semi)automatic technique aiming to replace manual work.
Preserving Data Consistency in Process Choreographies by Design (short paper)

Data is essential for the execution of business processes. As today’s organizations increasingly collaborate in process choreographies, data relevant to process execution is typically shared among participants. To avoid conflicts in the execution of process choreographies, the preservation of data consistency must be considered in the design of a choreography. However, current choreography modeling languages provide limited data modeling capabilities, thus potential conflicts arising from data inconsistencies at runtime may remain undetected during design time. Therefore, this paper motivates a framework allowing the design of data consistency-aware process choreographies.
Pore Characteristics and Their Effects on the Material Properties of Foamed Concrete Evaluated Using Micro-CT Images and Numerical Approaches

Foamed concrete contains numerous pores inside the material, and these pores are a significant factor determining the material characteristics. In particular, the pore distribution characteristics of foamed concrete significantly affect its thermal and mechanical properties. Therefore, an appropriate investigation is necessary for a more detailed understanding of foamed concrete. Here, a set of foamed concrete samples with different densities is used in order to investigate the density effects on the pore characteristics, as well as the physical properties of the materials. The pore distribution characteristics of these samples are investigated using an X-ray micro-computed tomography (micro-CT) imaging technique with probabilistic and quantitative methods. Using these methods, the anisotropy, the pore circularity factor and the relative density of cell thickness are examined. The thermal (thermal conductivity) and mechanical (directional modulus and strength) properties of each foamed specimen are computed using numerical simulations and compared with experimental results. From the obtained results, the effects of the pore sizes and shapes on the local and global properties of the foamed concrete are examined for developing advanced foamed concrete with lower thermal conductivity by minimizing the strength reduction.
Wake vortex encounters in a flight simulator

Abstract A real-time model of a wake vortex has been developed for an engineering flight simulator, which enables studies to be undertaken into the effects of wake vortex encounters with civil transport aircraft. A brief summary of the methods used to create a vortex model and integrate it with a real-time flight simulator is presented. Tools have been developed to determine the structural loads on an aircraft during a simulated wake vortex encounter and to visualise the airframe loads. Four wake vortex encounters were flown with different pilot recovery strategies and automatic flight controls. It is clear from analysis of these results that it is difficult for a pilot to appreciate the margin of tail loading during an encounter and a prototype training display is outlined to enable pilots to fully understand the effects of rudder inputs in recovery from these events.
A Study of One-handed Interaction of Large Smartphones: GUI Changes for Better Ergonomics

People tend to use their smartphones one-handed, which is unergonomic for the human musculoskeletal system. Stretching the thumb to reach certain touch keys is uncomfortable. Especially now that smartphones have large screens, normally ranging from 4.5” and above. Exaggerated use of smartphones can lead to repetitive strain injury (RSI), which is caused by static, repetitive movements over an extended time. This master thesis investigates how different touch key locations and touch key sizes affect the ergonomics of user interfaces on large smartphones. Moreover, it examines if the principles of the functional area improve the ergonomics of mobile user interfaces. The functional area is the surface of the touchscreen that is reachable by the thumb. Expert interviews were used to collect data to make hypotheses regarding improving the ergonomics of mobile user interfaces for one-handed interaction. An electromyography (EMG) test was conducted to investigate the hypotheses. EMG is a technology used to measure muscle contractions. The results show a significant correlation between a user interface that applies the functional area and a decline in muscle contraction. However, the decline in muscle contraction only occurs if the functional area is designed specifically for the user’s dominant hand. There were no significant differences between the touch key sizes and the extent of muscle contraction. The findings from this master thesis support the idea that the functional area and changes in the user interface design affect the ergonomics of smartphone interaction.
Enhancing the Draft Assembly with Minhash

In this thesis, we report on the use of minhash techniques to improve the draft assembly of a genome mapping. More specifically, we use minhash to compare the scaffolds of sea urchin and sea cucumber genomes. One of the main contributions of this thesis is the implementation of minhash with the Message Passing Interface (MPI) utilizing Intel Phi co-processors. It is shown that our implementation significantly reduces the processing time for identification of k-mer similarities.
On-line Calculation Method Based on Artificial Neutral Network for Equivalent Stresses in Steam Turbine Rotors

An on-line calculation method based on artificial neural network,for the equivalent stresses in steam turbine rotors was recommended.Formulas calculating the equivalent stresses in rotors using iso-diametric solid cylinder as a model as well as the finite element numerical calculation method were described.Methods and steps for on-line calculating rotors equivalent stresses applying the artifical neural network technology were given with a practical example-calculation of high-pressure(HP) and intermediate pressure(IP) rotors equivalent stresses in a 600 MW steam turbine.Results show that by application the artificial neural network technology in on-line monitoring equivalent stresses of turbine rotors,the calculation speed and accuracy are increased and a basis for turbine rotor equivalent stresses on-line monitoring and life consumption management is provided.
Response characterisation of nanostructures subjected to uncertain loading and material conditions by convex modelling.

Nanostructures are fast becoming the material of choice consequentially opening a new research frontier. Classical continuum computational techniques have proven insufficient in modelling the mechanical behaviour of these structures. The surface and nonlocal effects contributes to the size dependence of nanomaterial mechanical properties. Convex modelling techniques are employed in dealing with uncertainties associated with the lack of accurate measurements of nanostructures, molecular defects, and manufacturing anomalies. Numerical results are produced relating the level of uncertainty to maximum deflection for the nonlocal nanobeam, as well as determining the lowest buckling load subject to the effects of material uncertainty for nanoplates.
Testing of End-of-life Crankshaft Based on Eddy current & Magnetic Memory Method

In order to evaluate the residual fatigue life of end-of-life crankshaft,this paper proposed a new testing method based on eddy current and magnetic memory method.Also,On the basis of dynamic simulation and finite element analysis,which the fillets and oil holes were confirmed as the testing points.Facing the special structure of crankshaft,a testing device was developed.The testing results showed that crankshaft can be measured quickly and expediently by the device and the signals were continuous and exact.So it can provide the basic data for evaluating residual fatigue life of end-of-life crankshaft.