bluuebunny/crossref_metadata_2025 huggingface dataset:
Variation of leakage current conduction mechanism by heat treatment in Bi-based lead-free piezoelectric ceramics
Authors: Kim Sangwook , Nam Hyunwook , Sapkota Piyush , Khanal Gopal Prasad , Fujii Ichiro , Ueno Shintaro , Wada Satoshi
Published: March 2021

The leakage current mechanism in the as-sintered and quenched 0.75BiFeO3–0.25BaTiO3 (0.75BF–0.25BT) ceramics is evaluated by the space-charge-limited current (SCLC), Poole–Frenkel (P–F) emission, Schottky (ST) emission, and Fowler–Nordheim (F–N) tunneling mechanism. The discrepancy observed in the optical dielectric constant of BF and BT between the reported value and the values calculated from the P–F and ST emission plots suggests that the P–F emission and ST emission mechanisms do not contribute to the leakage current behavior of the 0.75BF–0.25BT ceramics. Subsequently, F–N tunneling is observed under a high electric field in the as-sintered 0.75BF–0.25BT ceramics, whereas the direct tunneling effect is exhibited throughout the measured electric field in the quenched ceramics. The SCLC mechanism is dominant in both the as-sintered and quenched 0.75BF–0.25BT ceramics. A change from Ohmic conduction to trap-filled-limit conduction is observed with an increase in the applied electric field in the as-sintered ceramics, whereas the quenched ceramics only revealed Ohmic conduction over the entire range of the measured electric field. The different behaviors exhibited in the SCLC mechanism between the as-sintered and the quenched ceramics imply that the conduction mechanism can be controlled by heat treatment.
Nonequilibrium thermodynamics of non-ideal chemical reaction networks
Authors: Avanzini Francesco , Penocchio Emanuele , Falasco Gianmaria , Esposito Massimiliano
Published: March 2021

All current formulations of nonequilibrium thermodynamics of open chemical reaction networks rely on the assumption of non-interacting species. We develop a general theory that accounts for interactions between chemical species within a mean-field approach using activity coefficients. Thermodynamic consistency requires that rate equations do not obey standard mass-action kinetics but account for the interactions with concentration dependent kinetic constants. Many features of the ideal formulations are recovered. Crucially, the thermodynamic potential and the forces driving non-ideal chemical systems out of equilibrium are identified. Our theory is general and holds for any mean-field expression of the interactions leading to lower bounded free energies.
Self-interaction correction in water–ion clusters
Authors: Wagle Kamal , Santra Biswajit , Bhattarai Puskar , Shahi Chandra , Pederson Mark R. , Jackson Koblar A. , Perdew John P.
Published: March 2021

We study the importance of self-interaction errors in density functional approximations for various water–ion clusters. We have employed the Fermi–Löwdin orbital self-interaction correction (FLOSIC) method in conjunction with the local spin-density approximation, Perdew–Burke–Ernzerhof (PBE) generalized gradient approximation (GGA), and strongly constrained and appropriately normed (SCAN) meta-GGA to describe binding energies of hydrogen-bonded water–ion clusters, i.e., water–hydronium, water–hydroxide, water–halide, and non-hydrogen-bonded water–alkali clusters. In the hydrogen-bonded water–ion clusters, the building blocks are linked by hydrogen atoms, although the links are much stronger and longer-ranged than the normal hydrogen bonds between water molecules because the monopole on the ion interacts with both permanent and induced dipoles on the water molecules. We find that self-interaction errors overbind the hydrogen-bonded water–ion clusters and that FLOSIC reduces the error and brings the binding energies into closer agreement with higher-level calculations. The non-hydrogen-bonded water–alkali clusters are not significantly affected by self-interaction errors. Self-interaction corrected PBE predicts the lowest mean unsigned error in binding energies (≤50 meV/H2O) for hydrogen-bonded water–ion clusters. Self-interaction errors are also largely dependent on the cluster size, and FLOSIC does not accurately capture the subtle variation in all clusters, indicating the need for further refinement.
Threatened but not conserved: flying-fox roosting and foraging habitat in Australia
Authors: Timmiss Libby A. , Martin John M. , Murray Nicholas J. , Welbergen Justin A. , Westcott David , McKeown Adam , Kingsford Richard T.
Published: March 2021

Conservation relies upon a primary understanding of changes in a species’ population size, distribution, and habitat use. Bats represent about one in five mammal species in the world, but understanding for most species is poor. For flying-foxes, specifically the 66 Pteropus species globally, 31 are classified as threatened (Vulnerable, Endangered, Critically Endangered) on the IUCN Red List. Flying-foxes typically aggregate in colonies of thousands to hundreds of thousands of individuals at their roost sites, dispersing at sunset to forage on floral resources (pollen, nectar, and fruit) in nearby environments. However, understanding of flying-fox roosting habitat preferences is poor, hindering conservation efforts in many countries. In this study, we used a database of 654 known roost sites of the four flying-fox species that occur across mainland Australia to determine the land-use categories and vegetation types in which roost sites were found. In addition, we determined the land-use categories and vegetation types found within the surrounding 25 km radius of each roost, representing primary foraging habitat. Surprisingly, for the four species most roosts occurred in urban areas (42–59%, n = 4 species) followed by agricultural areas (21–31%). Critically, for the two nationally listed species, only 5.2% of grey-headed and 13.9% of spectacled flying-fox roosts occurred in habitat within protected areas. Roosts have previously been reported to predominantly occur in rainforest, mangrove, wetland, and dry sclerophyll vegetation types. However, we found that only 20–35% of roosts for each of the four species occurred in these habitats. This study shows that flying-fox roosts overwhelmingly occurred within human-modified landscapes across eastern Australia, and that conservation reserves inadequately protect essential habitat of roosting and foraging flying-foxes.
Adaptation of pancreatic cancer cells to nutrient deprivation is reversible and requires glutamine synthetase stabilization by mTORC1
Authors: Tsai Pei-Yun , Lee Min-Sik , Jadhav Unmesh , Naqvi Insia , Madha Shariq , Adler Ashley , Mistry Meeta , Naumenko Sergey , Lewis Caroline A. , Hitchcock Daniel S. , Roberts Frederick R. , DelNero Peter , Hank Thomas , Honselmann Kim C. , Morales Oyarvide Vicente , Mino-Kenudson Mari , Clish Clary B. , Shivdasani Ramesh A. , Kalaany Nada Y.
Published: March 2021

Significance

Pancreatic ductal adenocarcinoma (PDA) is a highly lethal malignancy with no effective therapies. PDA aggressiveness partly stems from its ability to grow within a uniquely dense stroma restricting nutrient access. This study demonstrates that PDA clones that survive chronic nutrient deprivation acquire reversible nongenetic adaptations allowing them to switch between metabolic states optimal for growth under nutrient-replete or nutrient-deprived conditions. One contributing factor to this adaptation is mTORC1 activation, which stabilizes glutamine synthetase (GS) necessary for glutamine generation in nutrient-deprived cancer cells. Our findings imply that although total GS levels may not be a prognostic marker for aggressive disease, GS inhibition is of high therapeutic value, as it targets specific cell clusters adapted to nutrient starvation, thus mitigating tumor growth.
Inhibition of neuroinflammatory nitric oxide signaling suppresses glycation and prevents neuronal dysfunction in mouse prion disease
Authors: Bourgognon Julie-Myrtille , Spiers Jereme G. , Robinson Sue W. , Scheiblich Hannah , Glynn Paul , Ortori Catharine , Bradley Sophie J. , Tobin Andrew B. , Steinert Joern R.
Published: March 2021

Significance

We present evidence that alleviating nitrergic stress during early phases of neurodegeneration reduces neuroinflammatory posttranslational nitric oxide signaling and glycation-assisted dysfunction in the hippocampus of prion-diseased mice, a mechanism which might be applicable to other protein-misfolding neurodegenerative conditions. We confirmed that pharmacological suppression of nitrergic activity reduces the formation of advanced glycation end-products, diminishes prion protein misfolding, and averts neuronal dysfunction. This intervention could present an approach to diminish the detrimental neuroinflammatory effects seen in neurodegeneration and highlights nitrergic stress and glycation signaling as putative targets for disease-modifying treatments. The correlation between protein glycation and prion misfolding—as reported for several other misfolding proteins—links NO signaling to the neuroprotective effects seen following NOS inhibition.
Raf promotes dimerization of the Ras G-domain with increased allosteric connections
Authors: Packer Morgan R. , Parker Jillian A. , Chung Jean K. , Li Zhenlu , Lee Young Kwang , Cookis Trinity , Guterres Hugo , Alvarez Steven , Hossain Md Amin , Donnelly Daniel P. , Agar Jeffrey N. , Makowski Lee , Buck Matthias , Groves Jay T. , Mattos Carla
Published: March 2021

Significance

Ras GTPases, KRas, HRas, and NRas control cell proliferation via the Ras/Raf/MEK/ERK pathway through a process in which Ras dimerization is required but not mechanistically understood. Here, we show that Raf-RBD promotes Ras dimerization resulting in strong allosteric linkages between Galectin-binding residues on Raf-RBD at the two extreme ends of the dimer. This suggests that the dimer of the Ras/Raf–RBD complex couples to Galectin dimers to form a multivalent signaling complex for synchronized activation of Raf kinase, providing a new framework to be tested in the mechanistic understanding of Ras/Raf signaling.
Pericytes regulate vascular immune homeostasis in the CNS
Authors: Török Orsolya , Schreiner Bettina , Schaffenrath Johanna , Tsai Hsing-Chuan , Maheshwari Upasana , Stifter Sebastian A. , Welsh Christina , Amorim Ana , Sridhar Sucheta , Utz Sebastian G. , Mildenberger Wiebke , Nassiri Sina , Delorenzi Mauro , Aguzzi Adriano , Han May H. , Greter Melanie , Becher Burkhard , Keller Annika
Published: March 2021

Significance

The CNS vasculature tightly regulates the passage of circulating molecules and leukocytes into the CNS. In the neuroinflammatory disease multiple sclerosis (MS), these regulatory mechanisms fail, and autoreactive T cells invade the CNS via blood vessels, leading to neurological deficits depending on where the lesions are located. The region-specific mechanisms directing the development of such lesions are not well understood. In this study, we investigated whether pericytes regulate CNS endothelial cell permissiveness toward leukocyte trafficking into the brain parenchyma. By using a pericyte-deficient mouse model, we show that intrinsic changes in the brain vasculature due to absence of pericytes facilitate the neuroinflammatory cascade and can influence the localization of the neuroinflammatory lesions.
Nav1.3 and FGF14 are primary determinants of the TTX-sensitive sodium current in mouse adrenal chromaffin cells
Authors: Martinez-Espinosa Pedro L. , Yang Chengtao , Xia Xiao-Ming , Lingle Christopher J.
Published: March 2021

Adrenal chromaffin cells (CCs) in rodents express rapidly inactivating, tetrodotoxin (TTX)-sensitive sodium channels. The resulting current has generally been attributed to Nav1.7, although a possible role for Nav1.3 has also been suggested. Nav channels in rat CCs rapidly inactivate via two independent pathways which differ in their time course of recovery. One subpopulation recovers with time constants similar to traditional fast inactivation and the other ∼10-fold slower, but both pathways can act within a single homogenous population of channels. Here, we use Nav1.3 KO mice to probe the properties and molecular components of Nav current in CCs. We find that the absence of Nav1.3 abolishes all Nav current in about half of CCs examined, while a small, fast inactivating Nav current is still observed in the rest. To probe possible molecular components underlying slow recovery from inactivation, we used mice null for fibroblast growth factor homology factor 14 (FGF14). In these cells, the slow component of recovery from fast inactivation is completely absent in most CCs, with no change in the time constant of fast recovery. The use dependence of Nav current reduction during trains of stimuli in WT cells is completely abolished in FGF14 KO mice, directly demonstrating a role for slow recovery from inactivation in determining Nav current availability. Our results indicate that FGF14-mediated inactivation is the major determinant defining use-dependent changes in Nav availability in CCs. These results establish that Nav1.3, like other Nav isoforms, can also partner with FGF subunits, strongly regulating Nav channel function.
Role of grain alignment and oxide impurity in thermoelectric properties of textured n-type Bi–Te–Se alloy
Authors: Bose Rapaka S C , K M Dilip , Mele Paolo , Ramesh K
Published: March 2021

A nanostructured n-type Bi2Te2.7Se0.3 (BTS) alloy with a unique microstructure was prepared using a facile melting-rotation-quenching process followed by ball-milling and uniaxial hot-press sintering at 623 K. Anisotropy in the resulting microstructure showed anisotropic electrical and thermal transport properties in two directions normal to the pressing axis. The texture of the nanostructured BTS alloy was analyzed by x-ray diffraction and scanning electron microscopy. Based on the geometric phase analysis of a high resolution transmission electron microscopy images, abundant dislocations, high grain boundary density, and oxide impurity were identified, which act as phonon scattering centers. Higher anisotropy in thermal conductivity combined with oxide impurity resulted in an ultra-low phonon thermal conductivity of ∼0.305 W mK−1 at 423 K in the nanostructured n-type BTS in the direction parallel to the pressing axis. Laser power- and temperature-dependent Raman spectra analyses provided a deeper insight into the anisotropy in thermal transport properties. Optimum power factor and low thermal conductivity, due to the combination of grain alignment and oxide impurity, resulted in a dimensionless figure of merit (zT ) value of ∼0.75 at 423 K. In comparison, the high and opposite temperature dependences of electrical conductivity and thermal conductivity led to a better average zT value of ∼0.68 and a thermoelectric energy conversion efficiency percentage of ∼4.4% in the operating temperature range (300–423 K) in the direction parallel to the pressing axis.
Localization of double spalling on the outer rings of paired ball bearings by time-delay sound analysis
Authors: Bai Xiaotian , Shi Huaitao , Sun Jie , Wang Zinan , Zou Defang
Published: March 2021

Rolling bearings are widely used in spindle systems, and are usually arranged in pairs for higher running accuracy. Spalling often occurs on the outer ring of rolling bearings, and the impact of double spalling located on a single bearing is quite different from that of spalling on both bearings. This paper proposes a method for localizing double spalling based on radiated sound signals. A model of the sound radiation produced by spalling is established, and the sound signals are analyzed in the time and frequency domains. The numerical simulation and experimental results show that double spalling can be detected through the appearance of corresponding frequency components, and the relative spalling positions can be distinguished through the time–delay ratio (TDR) between the impacts in the time-domain signal. When spalling takes place on the same bearing, the distances to the sources of the impact sounds are different, compared to spalling on different bearings, leading to significant differences in the TDRs of the time domain signal. Impacts from different spalling locations can be distinguished from the time domain signal, and the double spalling localization can be realized through TDR matching. The method provides a new approach for accurate fault localization, which is helpful for the operation and maintenance of spindle systems.
A spatial-temporal algorithm for three-dimensional particle tracking velocimetry using two-view systems
Authors: Wu Y , Wang Q , Zhao C Y
Published: March 2021

In the present study, a novel temporal three-dimensional particle tracking velocimetry (3D PTV) algorithm for flow measurements with only two views is developed and validated with synthetic particles. The spatial information in image and object spaces, as well as the temporal predictions, are strongly coupled to improve the particle tracking accuracy. A well-designed cost function, simultaneously penalizing the reconstruction and tracking processes, is minimized to determine the most reliable traces. The algorithm shows a correctness over 98% up to 0.0273 ppp (particles per pixel) when using ideal synthetic particle positions, which is superior to several artificial intelligence methods. Moreover, an improved particle identification algorithm is proposed to handle overlapped particles and reduce the error introduced into the 3D PTV scheme. The algorithm adopts a particle position shifting process to tackle the correct particle numbers iteratively, which shows better performance than some other methods. A comparative study indicates that particle identification accuracy has a significant effect on the subsequent 3D reconstruction and tracking processes. The 3D PTV and particle identification algorithms show good consistencies under two types of flow conditions: a homogeneous isotropic turbulent flow and a vortex ring flow. Comparing with multiple-view setups, two-view systems are more compact and cost-effective, especially in conditions requiring high-speed cameras. With the newly established algorithms, a two-view system is now able to handle higher particle-seeding densities and thus can resolve higher spatial resolutions, which is significant for applications in turbulent flow and particle motion measurements.
Stacking nuances modulate the mechanical properties of graphene/SnO2 nanocomposites
Authors: Banarouei Seyed Arman , Yu Luxia , Jian Cuiying
Published: March 2021

Due to its superior mechanical properties, graphene is widely used as reinforcement materials in nanocomposites. In this work, a series of indentation simulations was performed, using finite element method, to investigate the mechanical properties of graphene/TiO2 and graphene/SnO2 nanocomposite films. The force–displacement curves obtained from simulations were first compared to analytical results, which demonstrates that with increasing the thicknesses of metal oxide layers, the mechanical responses of nanocomposites exhibit a transition from non-linear behaviors to linear behaviors. Furthermore, consistent with literature works, increasing graphene volume fraction can enhance the Young’s modulus of the corresponding heterostructure. Interestingly, this enhancement can be modulated by nuances in stacking orders, i.e. layer arrangements, of nanocomposites. Through analyzing stress and strain distributions, the underlying mechanisms were proposed. Our results reported here provide comprehensive characterizations and understandings on the reinforcement effects of graphene on graphene/metal oxide nanocomposites.
Design of cylindrical soft vacuum actuator for soft robots
Authors: Cheng Peilin , Ye Yuze , Jia Jiangming , Wu Chuanyu , Xie Qizhi
Published: March 2021

Soft robots have been significantly studied in recent decades, and among their key components are soft actuators. Vacuum is one of the main drivers of soft actuators. In this study, we propose a novel cylindrical soft vacuum actuator (CSVA) consisting of a top layer, bottom layer, and cylindrical internal chamber. Under a vacuum, the bottom layer was concaved into the internal chamber. A simplified analytical model was established to analyze the relationship between the vacuum pressure and the deformation height of the bottom layer. A validation experiment was conducted to verify the effectiveness of the proposed analytical model. The potential applications of the CSVA in the design of soft robots were also explored. A jellyfish-inspired swimming robot, an octopus-inspired suction cup, and a soft–rigid gripper were designed according to the concave deformation of the bottom layer. Then, the swimming speed of the swimming robot, the adsorption force of the suction cup, and the grasping capability of the soft–rigid gripper were investigated. The experimental results show that the maximum swimming speed of the swimming robot is 55.3 mm s−1 at a flapping frequency of 0.6 Hz. The adsorption forces of the suction cup both in air and underwater are 16.8 N and 17.5 N, respectively. The soft–rigid gripper with a pinching-grasping mode can grasp objects of various shapes and sizes in air and underwater. The experimental results demonstrate the feasibility of the soft vacuum actuator in the design of various soft robots.
On the nonlinear Schrödinger equation with a boundary condition involving a time derivative of the field
Authors: Xia Baoqiang
Published: March 2021

We study the nonlinear Schrödinger equation on the half-line with a new boundary condition presented by Zambon. This new boundary involves a time derivative of the field and was already shown by Zambon to be integrable. In this paper we re-establish the integrability of such a boundary both by using the Sklyanin’s formalism and by using the tool of Bäcklund transformations. Moreover, we present a method to derive explicit formulae for multi-soliton solutions of the boundary problem by virtue of the Darboux transformation method in conjunction with a boundary dressing technique.
Generation, reflection and transmission of nonlinear harmonic waves by direct superposition of anharmonic dipoles
Authors: Hardhienata Hendradi
Published: March 2021

It is well known that the linear and nonlinear light reflection and transmission formula can be obtained from the standard macroscopic Maxwell equation. In the past, a microscopic approach based on the Ewald–Oseen extinction theorem to derive the reflection and transmission formula by direct dipole summation has been performed by Fearn et al where they successfully derived the Fresnel formula in linear optics. In this work, we extend their work for the first time to derive the nonlinear reflection and transmission formula by direct summation of anharmonically oscillating dipoles for the case of a normal incidence wave, yielding similar results with coupled-mode-theory (CMT). We demonstrate for a decaying incoming field that dipolar radiation is no longer forbidden inside the bulk of a centrosymmetric material. Using the simplified bond hyperpolarizability model (SBHM), we find that these additional bulk dipole contribution must be accounted along with the surface dipoles and bulk quadrupolar contribution to explain recent rotational anisotropy SHG intensity experimental data of Si(111) with high precision.
Multiple characterization of some glassy-alloys as photon and neutron shields: In-silico Monte Carlo investigation
Authors: Perişanoğlu U , El-Agawany F I , Tekin H O , Kavaz E , Zakaly Hesham M H , Issa Shams A M , Zaid M H M , Sidek H A A , Matori K A , Rammah Y S
Published: March 2021

In the present work, the nuclear radiation shielding proficiency of eight glassy alloys (Gd25RE25Co25Al25 (RE = Tb, Dy and Ho)) containing different amounts of rare earth elements was investigated with MCNPX simulation codes. Mass attenuation coefficients (μ/ρ) of the glassy alloys were simulated in the energy interval of 0.2–20 MeV by exploiting MCNPX codes, and the generated data were found to match with theoretical WinXCOM results. Next, other crucial photon attenuation parameters, effective atomic number (Zeff), Half Value Layer (HVL), and Mean Free Path (MFP), were gotten out using μ/ρ values. It was seen that Er20Tm20 and Er20Tb20 samples replaced with Er by Gd had the highest Zeff and μ/ρ values, whereas HVL and MFP values were the smallest among the other glassy alloys. Geometric progression (GP) procedure was enjoyed to achieve the exposure and energy absorption buildup factors (EBF and EABF) for the glassy alloys proposed. EABFs and EBFs took the largest and lowest values for Gd25Tb25 and Er20Tm20, respectively, to the other samples. Furthermore, the glassy alloys’ neutron reduction abilities were estimated by acquiring fast neutron removal cross-sections (∑R). It was noticed that the ∑R values of the glassy alloys are increased with the rising sample density and seen to be comparable to ∑R values of water and ordinary concrete. The results obtained from this study are important in that they show that glassy alloys can be used as radiation shielding.
Outcome of neoadjuvant treatment for pancreatic cancer in elderly patients: comparative, observational cohort study
Authors: Oba A , Wu Y H A , Lieu C H , Meguid C , Colborn K L , Beaty L , Al-Musawi M H , Davis S L , Leal A D , Purcell T , King G , Wooten E S , Fujiwara Y , Goodman K A , Schefter T , Karam S D , Gleisner A L , Ahrendt S , Leong S , Messersmith W A , Schulick R D , Del Chiaro M
Published: March 2021

Background

Use of neoadjuvant therapy for elderly patients with pancreatic cancer has been debatable. With FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan, oxaliplatin) or gemcitabine plus nab-paclitaxel (GnP) showing tremendous effects in improving the overall survival of patients with borderline resectable and locally advanced pancreatic cancer, there is no definitive consensus regarding the use of this regimen in the elderly.

Methods

This study evaluated the eligibility of elderly patients with borderline resectable or locally advanced pancreatic cancer for neoadjuvant therapy. Patients registered in the database of pancreatic cancer at the University of Colorado Cancer Center, who underwent neoadjuvant treatment between January 2011 and March 2019, were separated into three age groups (less than 70, 70–74, 75 or more years) and respective treatment outcomes were compared.

Results

The study included 246 patients with pancreatic cancer who underwent neoadjuvant treatment, of whom 154 and 71 received chemotherapy with FOLFIRINOX and GnP respectively. Among these 225 patients, 155 were younger than 70 years, 36 were aged 70–74 years, and 34 were aged 75 years or older. Patients under 70 years old received FOLFIRINOX most frequently (124 of 155 versus 18 of 36 aged 70–74 years, and 12 of 34 aged 75 years or more; P < 0.001). Resectability was similar among the three groups (60.0, 58.3, and 55.9 per cent respectively; P = 0.919). Trends towards shorter survival were observed in the elderly (median overall survival time 23.6, 18.0, and 17.6 months for patients aged less than 70, 70–74, and 75 or more years respectively; P = 0.090). After adjusting for co-variables, age was not a significant predictive factor.

Conclusion

The safety and efficacy of multiagent chemotherapy in patients aged 75 years or over were similar to those in younger patients. Modern multiagent regimens could be a safe and viable treatment option for clinically fit patients aged at least 75 years.
Aerosols, airflow, and airspace contamination during laparoscopy
Authors: Hardy N , Dalli J , Khan M F , Nolan K , Cahill R A
Published: March 2021

Lay summary

Laparoscopic surgery has been undermined throughout the COVID-19 pandemic by concerns that it may generate an infectious risk to the operating team through aerosolization of peritoneal particles. There is anyway a need for increased awareness and understanding of the occupational hazard for surgical teams regarding unfiltered escape of pollutants generated by surgical smoke and other microbials. Here, the aerosol-generating nature of this access modality was confirmed through repeatable real-time methodology both qualitatively and quantitively to inform best practice and additional engineering solutions to optimize the operating room environment.
Proteomic differences in the hippocampus and cortex of epilepsy brain tissue
Authors: Pires Geoffrey , Leitner Dominique , Drummond Eleanor , Kanshin Evgeny , Nayak Shruti , Askenazi Manor , Faustin Arline , Friedman Daniel , Debure Ludovic , Ueberheide Beatrix , Wisniewski Thomas , Devinsky Orrin
Published: March 2021

Epilepsy is a common neurological disorder affecting over 70 million people worldwide, with a high rate of pharmaco-resistance, diverse comorbidities including progressive cognitive and behavioural disorders, and increased mortality from direct (e.g. sudden unexpected death in epilepsy, accidents, drowning) or indirect effects of seizures and therapies. Extensive research with animal models and human studies provides limited insights into the mechanisms underlying seizures and epileptogenesis, and these have not translated into significant reductions in pharmaco-resistance, morbidities or mortality. To help define changes in molecular signalling networks associated with seizures in epilepsy with a broad range of aetiologies, we examined the proteome of brain samples from epilepsy and control cases. Label-free quantitative mass spectrometry was performed on the hippocampal cornu ammonis 1–3 region (CA1–3), frontal cortex and dentate gyrus microdissected from epilepsy and control cases (n = 14/group). Epilepsy cases had significant differences in the expression of 777 proteins in the hippocampal CA1 − 3 region, 296 proteins in the frontal cortex and 49 proteins in the dentate gyrus in comparison to control cases. Network analysis showed that proteins involved in protein synthesis, mitochondrial function, G-protein signalling and synaptic plasticity were particularly altered in epilepsy. While protein differences were most pronounced in the hippocampus, similar changes were observed in other brain regions indicating broad proteomic abnormalities in epilepsy. Among the most significantly altered proteins, G-protein subunit beta 1 (GNB1) was one of the most significantly decreased proteins in epilepsy in all regions studied, highlighting the importance of G-protein subunit signalling and G-protein-coupled receptors in epilepsy. Our results provide insights into common molecular mechanisms underlying epilepsy across various aetiologies, which may allow for novel targeted therapeutic strategies.
Incremental Language Comprehension Difficulty Predicts Activity in the Language Network but Not the Multiple Demand Network
Authors: Wehbe Leila , Blank Idan Asher , Shain Cory , Futrell Richard , Levy Roger , von der Malsburg Titus , Smith Nathaniel , Gibson Edward , Fedorenko Evelina
Published: March 2021

What role do domain-general executive functions play in human language comprehension? To address this question, we examine the relationship between behavioral measures of comprehension and neural activity in the domain-general “multiple demand” (MD) network, which has been linked to constructs like attention, working memory, inhibitory control, and selection, and implicated in diverse goal-directed behaviors. Specifically, functional magnetic resonance imaging data collected during naturalistic story listening are compared with theory-neutral measures of online comprehension difficulty and incremental processing load (reading times and eye-fixation durations). Critically, to ensure that variance in these measures is driven by features of the linguistic stimulus rather than reflecting participant- or trial-level variability, the neuroimaging and behavioral datasets were collected in nonoverlapping samples. We find no behavioral-neural link in functionally localized MD regions; instead, this link is found in the domain-specific, fronto-temporal “core language network,” in both left-hemispheric areas and their right hemispheric homotopic areas. These results argue against strong involvement of domain-general executive circuits in language comprehension.
Seasonal variations in amplitudes and resonance frequencies of the HVSR amplification peaks linked to groundwater
Authors: Rigo Alexis , Sokos Efthimios , Lefils Valentine , Briole Pierre
Published: March 2021

Following the installation of a temporary seismological network in western Greece north of the Gulf of Patras, we determined the quality of the sites of each of the 10 stations in the network. For this, we used the horizontal-to-vertical spectral ratio (HVSR) method and calculated an average curve over randomly selected days between 0 and 10 Hz. The daily HVSR curve is determined by the HVSR 12-hr calculation (1 hr every two) without distinction between seismic ambient noise and earthquake signal. The HVSR curves obtained can be classified in three categories: flat curves without amplification, curves with a amplification peaks covering a large frequency range, and curves with one or more narrow peaks. In this third category C3, one station has one peak, two have two and one has three. On the contrary of what it is commonly assumed, the amplitudes and the resonance frequencies of these narrow peaks are not stable over time in C3. We determined the maximum of the amplitude of each peak with the corresponding central frequency for each day during 2.5 yr. Except for the station with three peaks, which finally appears stable within the uncertainties, the principal peak exhibits a seasonal variation, with a maximum in winter and a minimum in summer, the observations being more dispersed during winter. The second peak, when it exists, varies in the same way except at one station where it varies oppositely. These variations are clearly correlated with the loading and unloading cycle of the underlying aquifers as shown by the comparison with water level and yield measurements from wells located close to the stations. Moreover, they are also correlated with the vertical surface displacements observed at continuously recording GPS stations. The dispersion of the observed maximum amplitude in winter is probably related to the rainfall and the soil moisture modifying the S-wave velocity as revealed by other studies. From this study, we would like to emphasize that the use the HVSR method to constrain the S-wave velocity and the thickness of the sediment layer over the bedrock in the basin, has to be done with caution. Upon further confirmation of its robustness, the HVSR methodology presented here could be a good and easy-to-use tool for a qualitative survey of the aquifer backdrop and its seasonal behaviour, and of the soil moisture conditions.
The GPS velocity field of the Aegean. New observations, contribution of the earthquakes, crustal blocks model
Authors: Briole Pierre , Ganas Athanassios , Elias Panagiotis , Dimitrov Dimitar
Published: March 2021

We calculate and analyse the coordinate time-series of 282 permanent GPS stations located in Greece and 47 in surrounding countries. The studied period is 2000–2020. The average GPS time-series length is 6.5 yr. The formal velocity uncertainties are rescaled to be consistent with the velocity scatters measured at 110 pairs of stations separated by less 15 km. We remove the effect of the crustal earthquakes of Mw ≥ 5.3. We quantify and model the post-seismic deformations. Two relaxation times are usually needed: one short of some weeks and one long of 1 yr or more. For the large Mw = 6.9 events of Samothraki 2014 and Methoni 2008, the post-seismic deformation equals or exceeds the coseismic one. We detect at three stations a deformation transient in May 2018 that may correspond to a slow earthquake beneath Zakynthos and northwest Peloponnese, with equivalent magnitude 5.8. The density and accuracy of the velocities make it possible to better quantify several characteristics of the deformation in the Aegean, in particular: (i) the transition from the Anatolian domain, located in the southeast, to the European domain through the western end of the North Anatolian fault; (ii) the north–south extension in the western Aegean; (iii) the east–west extension of the western Peloponnese; (iv) the clockwise rotation of the Pindos; (v) the north–south extension in central Macedonia. Large parts of the central Aegean, eastern Peloponnese and western Crete form a wide stable domain with internal deformation below 2 nstrain yr−1. We build a kinematic model comprising 10 crustal blocks corresponding to areas where the velocities present homogeneous gradients. The blocks boundaries are set to fit with known localized deformation zones, for example, the rift of Corinth, the North Anatolian fault and the Katouna fault. When the velocity steps are clear but not localized, for example, through the Peloponnese, the boundary line is arbitrary and represents the transition zone. The model fits the velocities with a root-mean-square deviation of ±0.9 mm yr−1. At the boundaries between blocks we compare the predicted and observed deformations. We find shear rates of 7.4 and 9.0 mm yr−1 along the Movri and Katouna faults, 14.9 and 8.7 mm yr−1 along the North Anatolian fault near Lemnos and near Skopelos respectively, extension of 7.6, 1.5 and 12.6 mm yr−1 across the Gulf of Patras, the Trichonis Lake and the Ambracian Gulf. The compression across western Epirus is 3.7 mm yr−1. There is a dextral transtensional movement of 4.5 mm yr−1 between the Amorgos and Astypalea islands. Only the Ionian Islands region shows evidence of coupling along the subduction interface.
COVID-19 in aged care homes: a comparison of effects initial government policies had in the UK (primarily focussing on England) and Australia during the first wave
Authors: Chan Daniel Kam Yin , Mclaws Mary-Louise , Forsyth Duncan Ronald
Published: March 2021

Background

COVID-19 pandemic has had a major impact globally, with older people living in aged care homes suffering high death rates.

Objectives

We aimed to compare the impact of initial government policies on this vulnerable older population between the UK and Australia during the first wave of attack.

Methods

We searched websites of governments in the UK and Australia and media outlets. We examined the key policies including the national lockdown dates and the distribution of some important resources (personal protective equipment and testing) and the effects of these initial policies on the mortality rates in the aged care homes during the first wave of attack of COVID-19.

Results

We found that both countries had prioritized resources to hospitals over aged care homes during the first wave of attack. Both countries had lower priority for aged care residents in hospitals (e.g. discharging without testing for COVID-19 or discouraging admissions). However, deaths in aged care homes were 270 times higher in the UK than in Australia as on 7 May 2020 (despite UK having a population only 2.5 times larger than Australia). The lower fatality rate in Australia may have been due to the earlier lockdown strategy when the total daily cases were low in Australia (118) compared to the UK (over 1000), as well as the better community viral testing regime in Australia.

Conclusion

In conclusion, the public health policy in Australia aimed towards earlier intervention with earlier national lockdown and more viral testing to prevent new cases. This primary prevention could have resulted in more lives being saved. In contrast, the initial policy in the UK focussed mainly on protecting resources for hospitals, and there was a delay in national lockdown intervention and lower viral testing rate, resulting in more lives lost in the aged care sector.
Backtesting Value-at-Risk and Expected Shortfall in the Presence of Estimation Error
Authors: Barendse Sander , Kole Erik , van Dijk Dick
Published: March 2021

We investigate the effect of estimation error on backtests of expected shortfall (ES) forecasts. These backtests are based on first-order conditions of a recently introduced family of jointly consistent loss functions for value-at-risk (VaR) and ES. For both single and multiperiod horizons, we provide explicit expressions for the additional terms in the asymptotic covariance matrix that result from estimation error, and propose robust tests that account for it. Monte Carlo experiments show that the tests that ignore these terms suffer from size distortions, which are more pronounced for higher ratios of out-of-sample to in-sample observations. Robust versions of the backtests perform well with power against common alternatives. We also introduce a novel standardization of the conditional joint test statistic that removes the need to estimate higher-order moments and significantly improves its performance. In an application to VaR and ES forecasts for daily FTSE 100 index returns as generated by (GJR-)GARCH and HEAVY models, we find that estimation error substantially impacts the outcome of the backtests, and is not bound to particular subperiods such as the credit crisis.
Evolving ultralight scalars into non-linearity with Lagrangian perturbation theory
Authors: Laguë Alex , Bond J Richard , Hložek Renée , Marsh David J E , Söding Laurin
Published: March 2021

Many models of high energy physics suggest that the cosmological dark sector consists of not just one, but a spectrum of ultralight scalar particles with logarithmically distributed masses. To study the potential signatures of low concentrations of ultralight axion (also known as fuzzy) dark matter, we modify Lagrangian perturbation theory (LPT) by distinguishing between trajectories of different dark matter species. We further adapt LPT to include the effects of a quantum potential, which is necessary to generate correct initial conditions for ultralight axion simulations. Based on LPT, our modified scheme is extremely efficient on large scales and it can be extended to an arbitrary number of particle species at very little computational cost. This allows for computation of self-consistent initial conditions in mixed dark matter models. Additionally, we find that shell-crossing is delayed for ultralight particles and that the deformation tensor extracted from LPT can be used to identify the range of redshifts and scales for which the Madelung formalism of fuzzy dark matter can lead to divergences.
DOCK7 protects against replication stress by promoting RPA stability on chromatin
Authors: Gao Ming , Guo Guijie , Huang Jinzhou , Hou Xiaonan , Ham Hyoungjun , Kim Wootae , Zhao Fei , Tu Xinyi , Zhou Qin , Zhang Chao , Zhu Qian , Liu Jiaqi , Yan Yuanliang , Xu Zhijie , Yin Ping , Luo Kuntian , Weroha John , Deng Min , Billadeau Daniel D , Lou Zhenkun
Published: March 2021

RPA is a critical factor for DNA replication and replication stress response. Surprisingly, we found that chromatin RPA stability is tightly regulated. We report that the GDP/GTP exchange factor DOCK7 acts as a critical replication stress regulator to promote RPA stability on chromatin. DOCK7 is phosphorylated by ATR and then recruited by MDC1 to the chromatin and replication fork during replication stress. DOCK7-mediated Rac1/Cdc42 activation leads to the activation of PAK1, which subsequently phosphorylates RPA1 at S135 and T180 to stabilize chromatin-loaded RPA1 and ensure proper replication stress response. Moreover, DOCK7 is overexpressed in ovarian cancer and depleting DOCK7 sensitizes cancer cells to camptothecin. Taken together, our results highlight a novel role for DOCK7 in regulation of the replication stress response and highlight potential therapeutic targets to overcome chemoresistance in cancer.
Long Hours, Uneasy Feelings: Parliamentary Work in Denmark, Finland and Sweden
Authors: Mannevuo Mona , Rinne Jenni M , Vento Isak
Published: March 2021

Politicians’ work pressure is gaining more attention in parliamentary studies. To participate in the discussion about governing under pressure, this article offers an interdisciplinary approach to investigate how representatives navigate within a flexible, limitless work culture. This article presents a new inquiry to re-examine contemporary political agency by combining cultural studies theories with empirical insights in Nordic countries. By analysing 52 semi-structured interviews with MPs in Denmark, Finland and Sweden, the study finds that politics attracts people who want to change the world, but these attributes may initiate a vicious cycle, taking the form of psychological strain.
Assessment of Pain Modulatory and Somatosensory Profiles in Chronic Tension-Type Headache Patients
Authors: Exposto Fernando G , Bendixen Karina H , Ernberg Malin , Bach Flemming W , Svensson Peter
Published: March 2021

Objective

The aim of this study was to thoroughly phenotype a group of chronic tension-type headache (CTTH) patients.

Methods

Fifteen CTTH patients diagnosed according to the International Classification of Headache Disorders–3 and 15 healthy controls were included in this study. Furthermore, 70 healthy controls were included to establish normative values. Quantitative sensory testing (QST), including temporal summation of pain (TSP), conditioned pain modulation (CPM), and psychological and sleep variables, was assessed in a single session. TSP and CPM were then combined to build pain modulation profiles (PMP) for each individual.

Results

No difference was found between groups for PMP, TSP, and CPM. However, 10 CTTH patients showed a pronociceptive PMP, with 8 related to a deficient CPM and 2 to both a deficient CPM and increased TSP. Increased cold detection thresholds were the most common sensory disturbance found in CTTH patients. Significant differences were seen between groups for pain catastrophizing, depression, and sleep quality although not all patient’s scores were above the clinically meaningful cutoffs.

Conclusions

In summary, CTTH patients presented with different PMP. These PMP may be related to increased TSP, deficient CPM, alterations in thermal detection that may be related to autonomic dysregulation, or a combination of all three. Overall, this suggests that due to their heterogeneous pathophysiology, CTTH patients should be managed according to their underlying pathophysiology and not with a one-size-fits-all approach.
Alleviating effects of lupeol on postprandial hyperglycemia in diabetic mice
Authors: Lee Hyun-Ah , Kim Min-Jung , Han Ji-Sook
Published: March 2021

This study aimed to investigate the inhibition activities of lupeol on carbohydrate digesting enzymes and its ability to improve postprandial hyperglycemia in streptozotocin (STZ)-induced diabetic mice. α-Glucosidase and α-amylase inhibitory assays were executed using a chromogenic method. The effect of lupeol on hyperglycemia after a meal was measured by postprandial blood glucose in STZ-induced diabetic and normal mice. The mice were treated orally with soluble starch (2 g/kg BW) alone (control) or with lupeol (10 mg/kg BW) or acarbose (10 mg/kg BW) dissolved in water. Blood samples were taken from tail veins at 0, 30, 60, and 120 min and blood glucose was measured by a glucometer. Lupeol showed noticeable inhibitory activities on α-glucosidase and α-amylase. The half-maximal inhibitory concentrations (IC50) of lupeol on α-glucosidase and α-amylase were 46.23 ± 9.03 and 84.13 ± 6.82 μM, respectively, which were more significantly effective than those of acarbose, which is a positive control. Increase in postprandial blood glucose level was more significantly lowered in the lupeol-administered group than in the control group of both STZ-induced diabetic and normal mice. In addition, the area under the curve was significantly declined with lupeol administration in the STZ-induced diabetic mice. These findings suggest that lupeol can help lower the postprandial hyperglycemia by inhibiting carbohydrate-digesting enzymes.