bluuebunny/crossref_metadata_2025_split huggingface dataset:
The DNA‐dependent protease AtWSS1A suppresses persistent double strand break formation during replication
Authors: Hacker Leonie , Capdeville Niklas , Feller Laura , Enderle‐Kukla Janina , Dorn Annika , Puchta Holger 
Published: November 2021

Summary

The protease WSS1A is an important factor in the repair of DNA‐protein crosslinks in plants.

Here we show that the loss of WSS1A leads to a reduction of 45S rDNA repeats and chromosomal fragmentation in Arabidopsis. Moreover, in the absence of any factor of the RTR (RECQ4A/TOP3α/RMI1/2) complex, which is involved in the dissolution of DNA replication intermediates, WSS1A becomes essential for viability.

If WSS1A loss is combined with loss of the classical (c) or alternative (a) nonhomologous end joining (NHEJ) pathways of double‐strand break (DSB) repair, the resulting mutants show proliferation defects and enhanced chromosome fragmentation, which is especially aggravated in the absence of aNHEJ. This indicates that WSS1A is involved either in the suppression of DSB formation or in DSB repair itself. To test the latter we induced DSB by CRISPR/Cas9 at different loci in wild‐type and mutant cells and analyzed their repair by deep sequencing. However, no change in the quality of the repair events and only a slight increase in their quantity was found.

Thus, by removing complex DNA‐protein structures, WSS1A seems to be required for the repair of replication intermediates which would otherwise be resolved into persistent DSB leading to genome instability.
MoErv29 promotes apoplastic effector secretion contributing to virulence of the rice blast fungus Magnaporthe oryzae
Authors: Qian Bin , Su Xiaotong , Ye Ziyuan , Liu Xinyu , Liu Muxing , Shen Danyu , Chen Han , Zhang Haifeng , Wang Ping , Zhang Zhengguang 
Published: November 2021

Summary

During plant‐pathogenic fungi and host plants interactions, numerous pathogen‐derived proteins are secreted resulting in the activation of the unfolded protein response (UPR) pathway. For efficient trafficking of secretory proteins, including those important in disease progression, the cytoplasmic coat protein complex II (COPII) exhibits a multifunctional role whose elucidation remains limited.

Here, we discovered that the COPII cargo receptor MoErv29 functions as a target of MoHac1, a previously identified transcription factor of the UPR pathway. In Magnaporthe oryzae, deletion of MoERV29 severely affected the vegetative growth, conidiation and biotrophic invasion of the fungus in susceptible rice hosts.

We demonstrated that MoErv29 is required for the delivery of secreted proteins through recognition and binding of the amino‐terminal tripeptide motifs following the signal peptide. By using bioinformatics analysis, we predicted a cargo spectrum of MoErv29 and found that MoErv29 is required for the secretion of many proteins, including extracellular laccases and apoplastic effectors. This secretion is mediated through the conventional endoplasmic reticulum–Golgi secretion pathway and is important for conferring host recognition and disease resistance.

Taken together, our results revealed how MoErv29 operates on effector secretion, and our findings provided a critical link between COPII vesicle trafficking and the UPR pathway.
Type 1 diabetes affects the brain functional connectivity underlying working memory processing
Authors: Gallardo‐Moreno Geisa B. , Alvarado‐Rodríguez Francisco J. , Romo‐Vázquez Rebeca , Vélez‐Pérez Hugo , González‐Garrido Andrés A. 
Published: November 2021

AbstractVisuospatial working memory (VSWM) deficits have been demonstrated to occur during the development of type‐1‐diabetes (T1D). Despite confirming the early appearance of distinct task‐related brain activation patterns in T1D patients compared to healthy controls, the effect of VSWM load on functional brain connectivity during task performance is still unknown. Using electroencephalographic methods, the present study evaluated this topic in clinically well‐controlled T1D young patients and healthy individuals, while they performed a VSWM task with different memory load levels during two main VSWM processing phases: encoding and maintenance. The results showed a significantly lower number of correct responses and longer reaction times in T1D while performing the task. Besides, higher and progressively increasing functional connectivity indices were found for T1D patients in response to cumulative degrees of VSWM load, from the beginning of the VSWM encoding phase, without notably affecting the VSWM maintenance phase. In contrast, healthy controls managed to solve the task, showing lower functional brain connectivity during the initial VSWM processing steps with more gradual task‐related adjustments. Present results suggest that T1D patients anticipate high VSWM load demands by early recruiting supplementary processing resources as the probable expression of a more inefficient, though paradoxically better adjusted to task demands cognitive strategy.
Correlating genotype with phenotype using CFTR‐mediated whole‐cell Cl− currents in human nasal epithelial cells
Authors: Noel Sabrina , Servel Nathalie , Hatton Aurélie , Golec Anita , Rodrat Mayuree , Ng Demi R. S. , Li Hongyu , Pranke Iwona , Hinzpeter Alexandre , Edelman Aleksander , Sheppard David N. , Sermet‐Gaudelus Isabelle 
Published: November 2021

AbstractDysfunction of the epithelial anion channel cystic fibrosis transmembrane conductance regulator (CFTR) causes a wide spectrum of disease, including cystic fibrosis (CF) and CFTR‐related diseases (CFTR‐RDs). Here, we investigate genotype–phenotype–CFTR function relationships using human nasal epithelial (hNE) cells from a small cohort of non‐CF subjects and individuals with CF and CFTR‐RDs and genotypes associated with either residual or minimal CFTR function using electrophysiological techniques. Collected hNE cells were either studied directly with the whole‐cell patch‐clamp technique or grown as primary cultures at an air–liquid interface after conditional reprogramming. The properties of cAMP‐activated whole‐cell Cl− currents in freshly isolated hNE cells identified them as CFTR‐mediated. Their magnitude varied between hNE cells from individuals within the same genotype and decreased in the rank order: non‐CF > CFTR residual function > CFTR minimal function. CFTR‐mediated whole‐cell Cl− currents in hNE cells isolated from fully differentiated primary cultures were identical to those in freshly isolated hNE cells in both magnitude and behaviour, demonstrating that conditional reprogramming culture is without effect on CFTR expression and function. For the cohort of subjects studied, CFTR‐mediated whole‐cell Cl− currents in hNE cells correlated well with CFTR‐mediated transepithelial Cl− currents measured in vitro with the Ussing chamber technique, but not with those determined in vivo with the nasal potential difference assay. Nevertheless, they did correlate with the sweat Cl− concentration of study subjects. Thus, this study highlights the complexity of genotype–phenotype–CFTR function relationships, but emphasises the value of conditionally reprogrammed hNE cells in CFTR research and therapeutic testing.
imageKey points
The genetic disease cystic fibrosis is caused by pathogenic variants in the cystic fibrosis transmembrane conductance regulator (CFTR), an ion channel, which controls anion flow across epithelia lining ducts and tubes in the body.
This study investigated CFTR function in nasal epithelial cells from people with cystic fibrosis and CFTR variants with a range of disease severity.
CFTR function varied widely in nasal epithelial cells depending on the identity of CFTR variants, but was unaffected by conditional reprogramming culture, a cell culture technique used to grow large numbers of patient‐derived cells.
Assessment of CFTR function in vitro in nasal epithelial cells and epithelia, and in vivo in the nasal epithelium and sweat gland highlights the complexity of genotype–phenotype–CFTR function relationships.
Conventional rigid 2D substrates cause complex contractile signals in monolayers of human induced pluripotent stem cell‐derived cardiomyocytes
Authors: Huethorst Eline , Mortensen Peter , Simitev Radostin D. , Gao Hao , Pohjolainen Lotta , Talman Virpi , Ruskoaho Heikki , Burton Francis L. , Gadegaard Nikolaj , Smith Godfrey L. 
Published: November 2021

AbstractHuman induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CM) in monolayers interact mechanically via cell–cell and cell–substrate adhesion. Spatiotemporal features of contraction were analysed in hiPSC‐CM monolayers (1) attached to glass or plastic (Young's modulus (E) >1 GPa), (2) detached (substrate‐free) and (3) attached to a flexible collagen hydrogel (E = 22 kPa). The effects of isoprenaline on contraction were compared between rigid and flexible substrates. To clarify the underlying mechanisms, further gene expression and computational studies were performed. HiPSC‐CM monolayers exhibited multiphasic contractile profiles on rigid surfaces in contrast to hydrogels, substrate‐free cultures or single cells where only simple twitch‐like time‐courses were observed. Isoprenaline did not change the contraction profile on either surface, but its lusitropic and chronotropic effects were greater in hydrogel compared with glass. There was no significant difference between stiff and flexible substrates in regard to expression of the stress‐activated genes NPPA and NPPB. A computational model of cell clusters demonstrated similar complex contractile interactions on stiff substrates as a consequence of cell‐to‐cell functional heterogeneity. Rigid biomaterial surfaces give rise to unphysiological, multiphasic contractions in hiPSC‐CM monolayers. Flexible substrates are necessary for normal twitch‐like contractility kinetics and interpretation of inotropic interventions.
imageKey points
Spatiotemporal contractility analysis of human induced pluripotent stem cell‐derived cardiomyocyte (hiPSC‐CM) monolayers seeded on conventional, rigid surfaces (glass or plastic) revealed the presence of multiphasic contraction patterns across the monolayer with a high variability, despite action potentials recorded in the same areas being identical.
These multiphasic patterns are not present in single cells, in detached monolayers or in monolayers seeded on soft substrates such as a hydrogel, where only ‘twitch’‐like transients are observed.
HiPSC‐CM monolayers that display a high percentage of regions with multiphasic contraction have significantly increased contractile duration and a decreased lusotropic drug response.
There is no indication that the multiphasic contraction patterns are associated with significant activation of the stress‐activated NPPA or NPPB signalling pathways.
A computational model of cell clusters supports the biological findings that the rigid surface and the differential cell–substrate adhesion underly multiphasic contractile behaviour of hiPSC‐CMs.
Fisher Identifiability Analysis of Longitudinal Vehicle Dynamics
Authors: Kandel Aaron , Wahba Mohamed , Fathy Hosam K. 
Published: November 2021

Abstract
This article investigates the theoretical Cramér-Rao bounds on estimation accuracy of longitudinal vehicle dynamics parameters. This analysis is motivated by the value of parameter estimation in various applications, including chassis model validation and active safety. Relevant literature addresses this demand through algorithms capable of estimating chassis parameters for diverse conditions. While the implementation of such algorithms has been studied, the question of fundamental limits on their accuracy remains largely unexplored. We address this question by presenting two contributions. First, this article presents theoretical findings which reveal the prevailing effects underpinning vehicle chassis parameter identifiability. We then validate these findings with data from on-road experiments. Our results demonstrate, among a variety of effects, the strong relevance of road grade variability in determining parameter identifiability from a drive cycle. These findings can motivate improved experimental designs in the future.
A Study of Crack Growth in Sandwich Composite Beams
Authors: El-Sayed Sami I. , Sridharan Srinivasan 
Published: November 2021

Abstract
The paper proposes models to track the face-core interfacial delamination growth and crack kinking into the sandwich core, respectively. The models consist in interposing a cohesive layer along a pre-existing delamination or an identified plane of crack propagation. The former, designated as CLD (cohesive layer delamination model) is investigated first in detail using an example of a restrained beam specimen. The Influence of the key parameters of the model, viz. the thickness of the cohesive layer and the strength and stiffness of the cohesive layer material, have been studied. It is found that the model is fairly robust and is not sensitive to changes in parameters other than the critical strain energy release rate. The second model is a highly simplified one, but it is nevertheless a comprehensive model which can track the crack path by identifying crack planes in various elements using a maximum tensile stress criterion. This is designated as CLDK model as it deal with delamination and crack kinking — whichever is the preferred mode of fracture. The models are constructed ensuring that the crack opening is controlled by the critical value of strain energy release rate in mode I fracture. Experimental results of two sandwich specimens, viz. bottom restrained beams with 0° and −10° tilt angle respectively were used for comparison. The results indicate that the both the models are able to capture the initiation and track the growth of the interfacial delamination. The CLDK model tracks the crack kinking into the core, and its subsequent return to the facesheet-core interface.
Micromechanical Analysis of Nonlinear Response of Unidirectional Composites: A Fundamental Approach
Authors: Jadhav Virendra R. , Sridharan Srinivasan 
Published: November 2021

Abstract
Micromechanical models with different representative volume elements have been developed to study their ability to predict nonlinear response of unidirectional composites. A simple, square cells type micro-mechanical model similar to those widely used by other researchers is compared with a more advanced 3-phase finite element based micro-mechanical model. The models utilize the “bulk” properties of the matrix without attempting to “tune” the model to fit with experimental response of laminae. This is a more fundamental approach and constitutes a departure from current practice. The models account for shear softening, matrix cracking and the presence of residual stresses. A smeared cracking approach was used to characterize the micro-cracking in matrix. Experimental studies were performed on laminae, laminates and cylinders made from carbon epoxy composites. Experimental comparisons show that the more accurate micro-mechanical model with proper partial cracking options provides good bounds on experimental response with consistent accuracy. A square cells type model however is not consistent in its predictions, thus raising questions about its applicability in any general micro-mechanics based analysis.
Damage Assessment in Thermal Barrier Coatings Using Thermal Wave Imaging Technique
Authors: Chen X. , Newaz G. , Han X. 
Published: November 2021

Abstract
Thermal wave imaging (TWI) was used to investigate damage processes in electron beam-physical vapor deposited (EB-PVD) ZrO2-8% wt.%Y2O3 thermal barrier coatings (TBCs) during thermal cycling. TWI is a non-destructive and non-contact evaluation method. Small interfacial decohesions from manufacturing were captured by TWI after only two thermal cycles, but the decohesions did not grow with thermal cycling. No delamination was found in TBC specimens until failure, while surface temperature profiles of TWI indicated increases of thermal wave signal amplitude with thermal cycles. Local interfacial damage formed due to high thermal residual stresses during thermal cycling and induced thermal contact resistance in the TBCs, which resulted in the increases of thermal wave signal amplitude. The results of TWI confirmed the progressive damage evolution in TBCs observed by microscopy. The buckling propagation and spallation process were monitored by TWI.
Novel Concept of Advanced Thermal Protection Coating Based on Fullerenes
Authors: Loutfy Raouf O. , Wexler Eugene M. 
Published: November 2021

Abstract
Experimental study has been carried out to investigate thermal protection properties of thin fullerene coatings subjected to external heating. It was shown that due to low thermal conductivity and high emissivity, micron-scale fullerene films were capable of withstanding elevated temperatures (up to 800°C) resulting in over 100°C temperature decrease on the “cold” surface of the underlying substrate. Based on obtained results, practically important recommendations are made.
The Mechanics of Dynamic Fiber Push-Out: Experimental and Numerical Study
Authors: Lambros John , Bi Xiaopeng , Geubelle Philippe H. 
Published: November 2021

Abstract
This paper summarizes our recent progress on the experimental and numerical study of dynamic debonding and frictional push-out in composite systems. A modified split Hopkinson pressure bar system is adopted to perform dynamic fiber push-out experiments on model single fiber composite systems. A cohesive/volumetric finite element scheme is developed to capture the initiation and propagation of the crack along the fiber/matrix interface. Interface properties are extracted by comparison between experimental and numerical results. Effects of loading rate and surface roughness are presented. The results indicate that the combination of the experimental and numerical analysis constitutes a valuable tool to study the failure process in composites under high loading rates.
Stochastic Applications in Crashworthiness
Authors: Koganti Rama P. , Caliskan Ari G. 
Published: November 2021

Abstract
Due to geometrical, and material property variations, response of any structural member varies from the nominal design value. Typically the geometrical and material variations are the resultant of manufacturing variations. In this paper, the effect of these variations about the nominal values on structural response is studied using stochastic or probabilistic methods. Circular aluminum cross-sections are becoming popular in structural energy management applications. Also, significant research has been done to estimate the mean crush load for a circular section using empirical relations. An empirical relation, which is a function of thickness, outer radius, elastic modulus and yield strength, was used to estimate the mean crush load. Based on the measured thickness, outer radius and yield strength, the mean crush load is calculated using the empirical relation. Also, using the empirical relation, the variation in the mean crush load is estimated using linear statistical approach and Monte-Carlo simulation. In both the stochastic methods, actual mean and standard deviations of thickness, outer radius and yield strength are used. Also, using the extreme variations of these factors, mean crush load is predicted using an implicit Finite Element Analysis (FEA) code. The FEA prediction is in good agreement with the results of the testing. However, the designed mean crush load based on the empirical relation overestimates the crush loads by about 11%. The results of the study showed that the tube thickness and yield strength variations significantly affect the crush loads. Based on the Monte-Carlo simulation and FEA values using the extreme values for the geometrical and mechanical properties, one can design crash structures that take into account the inherent variability of components.
Mathematical Model Methodology to Compare Different Occupant Models in Frontal Impact
Authors: Marshall Rob , Altamore Paul F. 
Published: November 2021

Abstract
Restraint system and vehicle design rely heavily on the use of Anthropomorphic Test Devices and mathematical models of ATD’s to provide information about human occupant response in impact conditions. Recent advances in ATD’s take years to get through the prototyping and evaluation stages before they can be widely used. The recent advances in ATD development will not benefit the testing of many vehicles for quite some time.
The development of mathematical models of new ATD’s that are not yet available for widespread use, as well as mathematical models of humans can provide more information about human occupant responses to engineers. This study develops a method to utilize these mathematical models in combination with a highly detailed vehicle model to gain more understanding of how human occupants will behave in a frontal impact.
A Proposed New Brain Injury Tolerance for Minor Traumatic Brain Injury
Authors: Zhang Liying , Yang King H. , King Albert I. 
Published: November 2021

Abstract
Traumatic brain injuries constitute a significant portion of injury resulting from automotive collisions, motorcycle crashes, and sports collisions. Brain injuries not only represent a serious trauma for those involved but also place an enormous burden on society, often exacting a heavy economical, social, and emotional price. Development of intervention strategies to prevent or minimize these injuries requires a complete understanding of injury mechanism, response and tolerance level. In this study, an attempt is made to delineate actual injury causation and establish a meaningful injury criterion through the use of the actual field accident data. Twenty-four actual field head-to-head collisions that occurred in professional football games were duplicated using a validated finite element human head model. The injury predictors and injury levels were analyzed based on resulting brain tissue responses and were correlated with the site and occurrence of MTBI. Prediction indicated that the shear deformation around the brainstem region could be an injury predictor for concussion. Statistical analyses were performed to establish the new brain injury tolerance level and to further reduce brain injury severity.
Conducting Dynamic Impact Tests Using a “Free-Flight” Drop Tower Facility: Part I — Theory
Authors: Browne Alan L. , Johnson Nancy L. 
Published: November 2021

Abstract
“Free-Flight” drop tower facilities provide an inexpensive means for studying the dynamic impact response and energy absorption capabilities of structural elements. They are thus a commonly used tool, especially in the automotive industry, both for validating analytical predictions of dynamic crush and for determining the dynamic crush response itself in those cases where analytical prediction capability does not exist. This paper discusses the theory underlying drop tower impact testing. Specific topics that are discussed include a general development of the governing equations, a corrected interpretation of these equations, and quantification of (and means of correcting for) the effects of aerodynamic drag, cable friction, and “pressurization” of the test specimen.
Wheelchair Attachable System for Stepping UP
Authors: Barrigar Frederick , Johnson Christopher , Sanchez Julie , Wasiloff James 
Published: November 2021

Abstract
A methodology to apply contemporary mechanism design and synthesis tools to the modeling and development of a mechanical device that provides improved wheelchair mobility over vertical obstacles is presented in this paper. An advanced technique in design concept selection, Pugh Analysis, was utilized as a process to formulate, categorize and rank various design alternatives with respect to criteria such as design targets and constraints. An ADAMS model was developed to simulate the kinematics of the mechanism design selected. Simulation modeling confirmed that an initial feasible mechanism design concept that met or exceeded customer expectations had been achieved. Additional design optimization, design reliability and robustness opportunities are presented as potential follow-on efforts.