bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclical variations of fluid sources and stress state in a shallow megathrust-zone mélange
Authors: Cerchiari Anna , Remitti Francesca , Mittempergher Silvia , Festa Andrea , Lugli Federico , Cipriani Anna
Published: February 2020

Differences in REE patterns of calcite from extensional and shear veins of the Sestola Vidiciatico Tectonic Unit in the Northern Apennines suggest variations in fluid source during the seismic cycle in an ancient analogue of a shallow megathrust (
T
max
c
. 100–150°C). In shear veins, a positive Eu anomaly suggests an exotic fluid source, probably hotter than the fault environment. Small-scale extensional veins were derived instead from a local fluid in equilibrium with the fault rocks. Mutually crosscutting relations between two extensional vein sets, parallel and perpendicular to the megathrust, suggest repeated shifting of the
σ
1
and
σ
3
stresses during the seismic cycle. This is consistent with: (1) a seismic phase, with brittle failure along the thrust, crystallization of shear veins from an exotic fluid, stress drop and stress rotation; (2) a post-seismic phase, with fault-normal compaction and formation of fault-normal extensional veins fed by local fluids; (3) a reloading phase, where shear stress and pore pressure are gradually restored and fault-parallel extensional veins form, until the thrust fails again. The combination of geochemical and structural analyses in veins from exhumed megathrust analogues represents a promising tool to better understand the interplay between stress state and fluids in modern subduction zones.

Supplementary material:
Cathodoluminescence microphotographs, methodological details of the microstructural analysis, microphotographs of the location of analysed spots and a geochemical data table are available at
https://doi.org/10.6084/m9.figshare.c.4842165

Thematic collection:
This article is part of the Polygenetic mélanges collection available at:
https://www.lyellcollection.org/cc/polygenetic-melanges
Structural evolution and medium-temperature thermochronology of central Madagascar: implications for Gondwana amalgamation
Authors: Armistead Sheree E. , Collins Alan S. , Redaa Ahmad , Jepson Gilby , Gillespie Jack , Gilbert Sarah , Blades Morgan L. , Foden John D. , Razakamanana Théodore
Published: February 2020

Madagascar occupied an important place in the amalgamation of Gondwana and preserves a record of several Neoproterozoic events that are linked to orogenesis of the East African Orogen. In this study, we integrate remote sensing, field data and thermochronology to unravel complex deformation in the Ikalamavony and Itremo domains of central Madagascar. The deformation sequence comprises a gneissic foliation (S
1
), followed by south- to SW-directed, tight to isoclinal, recumbent folding (D
2
). These are overprinted by north-trending upright folds that formed during an approximately east–west shortening event (D
3
). Together these produced type 1 and type 2 fold interference patterns throughout the Itremo and Ikalamavony domains. We show that the Itremo and Ikalamavony domains were deformed together in the same orogenic system, which we interpret as the
c
. 630 Ma collision of Azania with Africa along the Vohibory Suture in southwestern Madagascar. In eastern Madagascar, deformation is syn- to post-550 Ma, and probably formed in response to final closure of the Mozambique Ocean along the Betsimisaraka Suture that amalgamated Madagascar with the Dharwar Craton of India. Apatite U–Pb and novel laser ablation triple quadrupole inductively coupled plasma mass spectrometry (LA-QQQ-ICP-MS) muscovite and biotite Rb–Sr thermochronology indicates that much of central Madagascar cooled through
c
. 500°C at
c
. 500 Ma.

Supplementary material:
A detailed geological map of central Madagascar (Supplementary A), detailed methods and geo- and thermochronology results (Supplementary B), isotopic data for geo- and thermochronology (Supplementary C) and Landsat images and structural interpretation examples (Supplementary D) are available at
https://doi.org/10.6084/m9.figshare.c.4840575
Risk Quantification in Stochastic Simulation under Input Uncertainty
Authors: Zhu Helin , Liu Tianyi , Zhou Enlu
Published: February 2020

When simulating a complex stochastic system, the behavior of output response depends on input parameters estimated from finite real-world data, and the finiteness of data brings input uncertainty into the system. The quantification of the impact of input uncertainty on output response has been extensively studied. Most of the existing literature focuses on providing inferences on the mean response at the true but unknown input parameter, including point estimation and confidence interval construction. Risk quantification of mean response under input uncertainty often plays an important role in system evaluation and control, because it provides inferences on extreme scenarios of mean response in all possible input models. To the best of our knowledge, it has rarely been systematically studied in the literature. In this article, first we introduce risk measures of mean response under input uncertainty and propose a nested Monte Carlo simulation approach to estimate them. Then we develop asymptotical properties such as consistency and asymptotic normality for the proposed nested risk estimators. We further study the associated budget allocation problem for efficient nested risk simulation and finally use a sharing economy example to illustrate the importance of accessing and controlling risk due to input uncertainty.
Extending Explicitly Modelled Simulation Debugging Environments with Dynamic Structure
Authors: Mierlo Simon Van , Vangheluwe Hans , Breslav Simon , Goldstein Rhys , Khan Azam
Published: February 2020

The widespread adoption of Modelling and Simulation (M8S) techniques hinges on the availability of tools supporting each phase in the M8S-based workflow. This includes tasks such as specifying, implementing, experimenting with, as well as debugging, simulation models. We have previously developed a technique where advanced debugging environments are generated from an explicit behavioural model of the user interface and the simulator. These models are extracted from the code of existing modelling environments and simulators and instrumented with debugging operations. This technique can be reused for a large family of modelling formalisms but was not yet considered for dynamic-structure formalisms; debugging models in these formalisms is challenging, as entities can appear and disappear during simulation. In this article, we adapt and apply our approach to accommodate dynamic-structure formalisms. To this end, we present a modular, reusable approach, which includes an architecture and a workflow. We observe that to effectively debug dynamic-structure models, domain-specific visualizations developed by the modeller should be (re)used for debugging tasks. To demonstrate our technique, we use Dynamic-Structure DEVS (a formalism that includes the characteristics of discrete-event and agent-based modelling paradigms) and an implementation of its simulation semantics in the PythonPDEVS tool as a running example. We apply our technique on NetLogo, a popular multi-agent simulation tool, to demonstrate the generality of our approach.
A Deep Learning Architecture for Psychometric Natural Language Processing
Authors: Ahmad Faizan , Abbasi Ahmed , Li Jingjing , Dobolyi David G. , Netemeyer Richard G. , Clifford Gari D. , Chen Hsinchun
Published: February 2020

Psychometric measures reflecting people’s knowledge, ability, attitudes, and personality traits are critical for many real-world applications, such as e-commerce, health care, and cybersecurity. However, traditional methods cannot collect and measure rich psychometric dimensions in a timely and unobtrusive manner. Consequently, despite their importance, psychometric dimensions have received limited attention from the natural language processing and information retrieval communities. In this article, we propose a deep learning architecture, PyNDA, to extract psychometric dimensions from user-generated texts. PyNDA contains a novel representation embedding, a demographic embedding, a structural equation model (SEM) encoder, and a multitask learning mechanism designed to work in unison to address the unique challenges associated with extracting rich, sophisticated, and user-centric psychometric dimensions. Our experiments on three real-world datasets encompassing 11 psychometric dimensions, including trust, anxiety, and literacy, show that PyNDA markedly outperforms traditional feature-based classifiers as well as the state-of-the-art deep learning architectures. Ablation analysis reveals that each component of PyNDA significantly contributes to its overall performance. Collectively, the results demonstrate the efficacy of the proposed architecture for facilitating rich psychometric analysis. Our results have important implications for user-centric information extraction and retrieval systems looking to measure and incorporate psychometric dimensions.
Parallel Data Distribution Management on Shared-memory Multiprocessors
Authors: Marzolla Moreno , D'Angelo Gabriele
Published: February 2020

The problem of identifying intersections between two sets of
d
-dimensional axis-parallel rectangles appears frequently in the context of agent-based simulation studies. For this reason, the High Level Architecture (HLA) specification—a standard framework for interoperability among simulators—includes a Data Distribution Management (DDM) service whose responsibility is to report all intersections between a set of subscription and update regions. The algorithms at the core of the DDM service are CPU-intensive, and could greatly benefit from the large computing power of modern multi-core processors. In this article, we propose two parallel solutions to the DDM problem that can operate effectively on shared-memory multiprocessors. The first solution is based on a data structure (the interval tree) that allows concurrent computation of intersections between subscription and update regions. The second solution is based on a novel parallel extension of the Sort Based Matching algorithm, whose sequential version is considered among the most efficient solutions to the DDM problem. Extensive experimental evaluation of the proposed algorithms confirm their effectiveness on taking advantage of multiple execution units in a shared-memory architecture.
Computational Parquetry
Authors: Iseringhausen Julian , Weinmann Michael , Huang Weizhen , Hullin Matthias B.
Published: February 2020

Parquetry is the art and craft of decorating a surface with a pattern of differently colored veneers of wood, stone, or other materials. Traditionally, the process of designing and making parquetry has been driven by color, using the texture found in real wood only for stylization or as a decorative effect. Here, we introduce a computational pipeline that draws from the rich natural structure of strongly textured real-world veneers as a source of detail to approximate a target image as faithfully as possible using a manageable number of parts. This challenge is closely related to the established problems of patch-based image synthesis and stylization in some ways, but fundamentally different in others. Most importantly, the limited availability of resources (any piece of wood can only be used once) turns the relatively simple problem of finding the right piece for the target location into the combinatorial problem of finding optimal parts while avoiding resource collisions. We introduce an algorithm that efficiently solves an approximation to the problem. It further addresses challenges like gamut mapping, feature characterization, and the search for fabricable cuts. We demonstrate the effectiveness of the system by fabricating a selection of pieces of parquetry from different kinds of unstained wood veneer.
Conceptualization, History, and Future of the Paraphilias
Authors: Moser Charles , Kleinplatz Peggy J.
Published: February 2020

There is no accepted definition of the term paraphilia despite its being listed as an essential feature of a class of mental disorders known as the paraphilic disorders. The origin of the term, history of its inclusion as a diagnosis, and logical flaws inherent in the various definitions are discussed in this review. We examine the basis for pathologizing individuals with paraphilias, consider what paraphilias can tell us about how humans develop their sexual interests, and question the usefulness of dividing sexual interests into paraphilias and normophilias. The construct of the paraphilias appears to be poorly conceived and has outlived its usefulness.
Rapid Analytical Instrumentation for Electrochemical Impedance Spectroscopy Measurements
Authors: Hu Yuan , Brahim Sean , Maat Stefan , Davies Patricia , Kundu Arpan , Fisher Timothy S.
Published: February 2020

This work reports a low-cost custom electrochemical instrument capable of performing rapid and accurate electrochemical impedance spectroscopy (EIS) for supercapacitors over a broad frequency band (10 mHz to 2 kHz). Conventionally, EIS is measured via sinusoidal perturbations; however, such an approach suffers from lengthy measurement time. Chirp signals have been shown previously to reduce EIS measurement time for supercapacitors for relative narrow frequency bands (1 Hz to 2 kHz). However, to characterize supercapacitors comprehensively, much broader frequency bands are required. Here, we present a custom instrument with an adaptive measurement algorithm for performing EIS measurements in a wide frequency range of 10 mHz to 2 kHz with low measurement uncertainties. The results obtained using this new technique has been validated here with a commercial instrument on several types of supercapacitors. Furthermore, measurement time on average decreases from 1500 s to less than 400 s. The overall cost of the custom instrument is 90% lower as compared to the commercial instrument. The custom instrument’s accuracy, time efficiency and low cost are expected to benefit electrochemical researchers.
Ab Initio Studies of Discharge Mechanism of MnO2 in Deep-Cycled Rechargeable Zn/MnO2 Batteries
Authors: Magar Birendra Ale , Paudel Nirajan , Lambert Timothy N. , Vasiliev Igor
Published: February 2020

Rechargeable alkaline Zn/MnO2 batteries are an attractive solution for large-scale energy storage applications. Recently, Bi and Cu additives have been used to increase the cycle life and capacity of rechargeable Zn/MnO2 batteries, with an equivalent of the full two-electron capacity realized for many cycles, in the absence of zinc. However, the mechanism of the effect of Bi and Cu on the performance of rechargeable Zn/MnO2 batteries has not been investigated in detail. We apply first-principles density functional computational methods to study the discharge mechanisms of the unmodified and Bi/Cu-modified γ-MnO2 electrodes in rechargeable alkaline Zn/MnO2 batteries. Using the results of our calculations, we analyze the possible redox reaction pathways in the γ-MnO2 electrode and identify the electrochemical processes leading to the formation of irreversible discharge reaction products, such as hausmannite and hetaerolite. Our study demonstrates the possibility of formation of intermediate Bi-Mn and Cu-Mn oxides in deep-cycled Bi/Cu-modified MnO2 electrodes. The formation of intermediate Bi-Mn and Cu-Mn oxides could reduce the rate of accumulation of irreversible reaction products in the MnO2 electrode and improve the rechargeability and cyclability of Zn/MnO2 batteries.
Preventing Cell-to-Cell Propagation of Thermal Runaway in Lithium-Ion Batteries
Authors: Srinivasan Rengaswamy , Thomas M. E. , Airola M. B. , Carkhuff B. G. , Frizzell-Makowski L. J. , Alkandry H. , Reuster J. G. , Oguz H. N. , Green P. W. , La Favors J. , Currano L. J. , Demirev P. A.
Published: February 2020

It is presumed that heat generated from a trigger cell under thermal runaway (TR) in multi-cell Li-ion batteries is transferred to adjacent cells mostly by convection of ejected hot matter (and to a lesser degree by direct contact and radiative heat transfer). Therefore, venting the energized materials (ejecta) from the battery compartment should prevent cell-to-cell TR propagation. However, engineering solutions to vent ejecta from TR of an individual cell fail to prevent TR propagation, subsequently causing battery fires. Real-time in situ FTIR spectroscopy of ejecta from a cell driven into TR demonstrates that large amounts of carbonate esters are already vented from the cell before it goes into TR. The vented hot gases cool down and condense on top of adjacent cells. Subsequently, when the trigger cell reaches TR, this condensate ignites, transferring heat and potentially driving the receiving cells into TR. Computational fluid dynamics and thermal simulations of this pathway support the experimental findings. Numerical results indicate that a fraction of the solvent vented from the trigger cell is sufficient for efficient TR propagation. Our results shed new light on thermal propagation in multi-cell Li-ion batteries and suggest novel methods to prevent TR propagation.
Electrochemical Gas Sensor Integrated with Vanadium Monoxide Nanowires for Monitoring Low Concentrations of Ammonia Emission
Authors: Sekhar Praveen K. , Graf David , Ojelere Olusola , Saha Tonmoy Kumar , Riheen Manjurul Ahsan , Mathur Sanjay
Published: February 2020

An electrochemical sensor for the detection of extremely low concentration of ammonia (1 part per billion, ppb) was fabricated by integrating vanadium monoxide (VOx; x = 0.8–1.2) nanowires on the platinum electrodes. The nanowire-based sensor responds at room temperature non-linearly to a staircase sequence of ammonia from 1 ppb to 100 ppb. The rise and fall time of the nanowire sensor was found to be 10 s and 9 s, respectively. While the immobilization of VO nanowires increased the electrochemical surface area, the defect rich and ionic nature of the VO surface (V2+O2−) facilitated the chemical interaction and adsorption of polar ammonia molecules as evident in the room temperature response of the VO@Pt amperometric electrochemical sensor. The availability of metal centered d-electrons and the semiconductor nature of vanadium monoxide lowered the interfacial resistance of the nanowire-modified sensor enabling the lower detection limit of ammonia. The sensor seems to respond to CH4, H2S and C3H6 as well although the NH3 response is nearly six-fold compared to these common interfering compounds. The results pave the way for a low-cost alternative paper-based sensor to monitor ammonia emissions primarily from confined animal feeding operations (CAFOs).
The physiological modulation by intracellular kinases of hippocampal γ-oscillation in vitro
Authors: Wang JianGang , Gao XiaHuan , Wang YaLi , Wang MengMeng , Ge ChunBo , Liu ZhiHua , Xie Xin-E , Chen ZhengYue , Song JingGui , Lu ChengBiao
Published: February 2020

Hippocampal network oscillations at gamma frequency band (γ-oscillation, 20–80 Hz) are synchronized synaptic activities generated by the interactions between the excitatory and inhibitory interneurons and are associated with higher brain function such as learning and memory. Despite extensive studies about the modulation of intracellular kinases on synaptic transmission and plasticity, little is known about the effects of these kinases on γ-oscillations. In this study, we examined the effects of several critical intracellular kinases such as cyclic AMP-dependent protein kinase (PKA), protein kinase B (PKB)/Akt, protein kinase C (PKC), extracellular-regulated protein kinases (ERK) and AMP-activated protein kinase (AMPK), known to regulate synaptic transmission, on hippocampal γ-oscillations in vitro. We found that AMPK inhibitor but not PKA, PKC, or ERK inhibitor, strongly enhanced the power of γ-oscillation (γ-power) and that Akt inhibitor weakly increased γ-power. Western blot analysis confirmed that AMPK inhibitor reduced the expression of p-AMPK but not total AMPK. By using the slice whole cell voltage-clamp technique, we found that AMPK inhibitor increased the frequency but not amplitude of spontaneous inhibitory postsynaptic currents (sIPSC) and had no effect on either frequency or amplitude of spontaneous excitatory postsynaptic currents (sEPSC). Therefore, AMPK activation negatively modulates hippocampal γ-oscillation via modulation of the inhibitory neurons.
Simultaneous isolation of endothelial and alveolar epithelial type I and type II cells during mouse lung development in the absence of a transgenic reporter
Authors: Donati Yves , Blaskovic Sanja , Ruchonnet-Métrailler Isabelle , Lascano Maillard Josefina , Barazzone-Argiroffo Constance
Published: February 2020

Mouse lung developmental maturation and final alveolarization phase begin at birth. During this dynamic process, alveolar cells modify their morphology and anchorage to the extracellular matrix. In particular, alveolar epithelial cell (AEC) type I undergo cytoplasmic flattening and folding to ensure alveoli lining. We developed FACS conditions for simultaneous isolation of alveolar epithelial and endothelial cells in the absence of specific reporters during the early and middle alveolar phase. We evidenced for the first time a pool of extractable epithelial cell populations expressing high levels of podoplanin at postnatal day (pnd)2, and we confirmed by RT-qPCR that these cells are already differentiated but still immature AEC type I. Maturation causes a decrease in isolation yields, reflecting the morphological changes that these cell populations are undergoing. Moreover, we find that major histocompatibility complex II (MHCII), reported as a good marker of AEC type II, is poorly expressed at pnd2 but highly present at pnd8. Combined experiments using LysoTracker and MHCII demonstrate the de novo acquisition of MCHII in AEC type II during lung alveolarization. The lung endothelial populations exhibit FACS signatures from vascular and lymphatic compartments. They can be concomitantly followed throughout alveolar development and were obtained with a noticeable increased yield at the last studied time point (pnd16). Our results provide new insights into early lung alveolar cell isolation feasibility and represent a valuable tool for pure AEC type I preparation as well as further in vitro two- and three-dimensional studies.
Respiratory defects in the CrtapKO mouse model of osteogenesis imperfecta
Authors: Dimori Milena , Heard-Lipsmeyer Melissa E. , Byrum Stephanie D. , Mackintosh Samuel G. , Kurten Richard C. , Carroll John L. , Morello Roy
Published: February 2020

Respiratory disease is a leading cause of mortality in patients with osteogenesis imperfecta (OI), a connective tissue disease that causes severely reduced bone mass and is most commonly caused by dominant mutations in type I collagen genes. Previous studies proposed that impaired respiratory function in OI patients was secondary to skeletal deformities; however, recent evidence suggests the existence of a primary lung defect. Here, we analyzed the lung phenotype of Crtap knockout (KO) mice, a mouse model of recessive OI. While we confirm changes in the lung parenchyma that are reminiscent of emphysema, we show that CrtapKO lung fibroblasts synthesize type I collagen with altered posttranslation modifications consistent with those observed in bone and skin. Unrestrained whole body plethysmography showed a significant decrease in expiratory time, resulting in an increased ratio of inspiratory time over expiratory time and a concomitant increase of the inspiratory duty cycle in CrtapKO compared with WT mice. Closed-chest measurements using the forced oscillation technique showed increased respiratory system elastance, decreased respiratory system compliance, and increased tissue damping and elasticity in CrtapKO mice compared with WT. Pressure-volume curves showed significant differences in lung volumes and in the shape of the curves between CrtapKO mice and WT mice, with and without adjustment for body weight. This is the first evidence that collagen defects in OI cause primary changes in lung parenchyma and several respiratory parameters and thus negatively impact lung function.
The hallmarks of severe pulmonary arterial hypertension: the cancer hypothesis—ten years later
Authors: Cool Carlyne D. , Kuebler Wolfgang M. , Bogaard Harm Jan , Spiekerkoetter Edda , Nicolls Mark R. , Voelkel Norbert F.
Published: February 2020

Severe forms of pulmonary arterial hypertension (PAH) are most frequently the consequence of a lumen-obliterating angiopathy. One pathobiological model is that the initial pulmonary vascular endothelial cell injury and apoptosis is followed by the evolution of phenotypically altered, apoptosis-resistant, proliferating cells and an inflammatory vascular immune response. Although there may be a vasoconstrictive disease component, the increased pulmonary vascular shear stress in established PAH is caused largely by the vascular wall pathology. In this review, we revisit the “quasi-malignancy concept” of severe PAH and examine to what extent the hallmarks of PAH can be compared with the hallmarks of cancer. The cancer model of severe PAH, based on the growth of abnormal vascular and bone marrow-derived cells, may enable the emergence of novel cell-based PAH treatment strategies.
Adaptation of the hepatic transudation barrier to sinusoidal hypertension
Authors: Dongaonkar Ranjeet M. , Quick Christopher M. , Laine Glen A. , Uray Karen , Cox Charles S. , Stewart Randolph H.
Published: February 2020

The role of the hepatic transudation barrier in determining ascites volume and protein content in chronic liver disease is poorly understood. Therefore, the purpose of the present study was to characterize how chronic sinusoidal hypertension impacts hepatic transudation barrier properties and the transudation rate. The suprahepatic inferior vena cava was surgically constricted, and animals were exposed to either short-term (SVH; 2–3 wk) or long-term venous hypertension (LVH; 5–6 wk). Compared with SVH, LVH resulted in lower peritoneal fluid pressure, ascites volume, and ascites protein concentration. The transudation barrier protein reflection coefficient was significantly higher, and the transudation barrier hydraulic conductivity, transudation rate, and transudate-to-lymph protein concentration ratio were significantly lower in LVH animals compared with SVH animals. The sensitivity of transudation rates to acute changes in interstitial fluid pressures was also significantly lower in LVH animals compared with SVH animals. In contrast, there was no detectable difference in hepatic lymph flow rate or sensitivity of lymph flow to acute changes in interstitial fluid pressures between SVH and LVH animals. Taken together, these data suggest that decreased hepatic transudation barrier permeability to fluid and protein and increased reflection coefficient led to a decrease in the hepatic contribution to ascites volume. The present work, to the best of our knowledge, is the first to quantify an anti-ascites adaptation of the hepatic transudation barrier in response to chronic hepatic sinusoidal hypertension.
Acute impact of changes to hemodynamic load on the left ventricular strain-volume relationship in young and older men
Authors: Hulshof Hugo G. , van Dijk Arie P. , Hopman Maria T. E. , van der Sluijs Chris F. , George Keith P. , Oxborough David L. , Thijssen Dick H. J.
Published: February 2020

Chronic changes in left ventricular (LV) hemodynamics, such as those induced by increased afterload (i.e., hypertension), mediate changes in LV function. This study examined the proof of concept that 1) the LV longitudinal strain (ε)-volume loop is sensitive to detecting an acute increase in afterload, and 2) these effects differ between healthy young versus older men. Thirty-five healthy male volunteers were recruited, including 19 young (24 ± 2 yr) and 16 older participants (67 ± 5 yr). Tests were performed before, during, and after 10-min recovery from acute manipulation of afterload. Real-time hemodynamic data were obtained and LV longitudinal ε-volume loops were calculated from four-chamber images using two-dimensional echocardiography. Inflation of the anti-gravity (anti-G) suit resulted in an immediate increase in heart rate, blood pressure, and systemic vascular resistance and a decrease in stroke volume (all P < 0.05). This was accompanied by a decrease in LV peak ε, slower slope of the ε-volume relationship during early diastole, and an increase in uncoupling (i.e., compared with systole; little change in ε per volume decline during early diastole and large changes in ε per volume decline during late diastole) (all P < 0.05). All values returned to baseline levels after recovery (all P > 0.05). Manipulation of cardiac hemodynamics caused comparable effects in young versus older men (all P > 0.05). Acute increases in afterload immediately change the diastolic phase of the LV longitudinal ε-volume loop in young and older men. This supports the potency of the LV longitudinal ε-volume loop to provide novel insights into dynamic cardiac function in humans in vivo.
Vasodilatory and vascular mitochondrial respiratory function with advancing age: evidence of a free radically mediated link in the human vasculature
Authors: Park Soung Hun , Kwon Oh Sung , Park Song-Young , Weavil Joshua C. , Hydren Jay R. , Reese Van , Andtbacka Robert H. I. , Hyngstrom John R. , Richardson Russell S.
Published: February 2020

Recognizing the age-related decline in skeletal muscle feed artery (SMFA) vasodilatory function, this study examined the link between vasodilatory and mitochondrial respiratory function in the human vasculature. Twenty-four SMFAs were harvested from young (35 ± 6 yr, n = 9) and old (71 ± 9 yr, n = 15) subjects. Vasodilation in SMFAs was assessed, by pressure myography, in response to flow-induced shear stress, acetylcholine (ACh), and sodium nitroprusside (SNP) while mitochondrial respiration was measured, by respirometry, in permeabilized SMFAs. Endothelium-dependent vasodilation was significantly attenuated in the old, induced by both flow (young: 92 ± 3, old: 45 ± 4%) and ACh (young: 92 ± 3, old: 54 ± 5%), with no significant difference in endothelium-independent vasodilation. Complex I and I + II state 3 respiration was significantly lower in the old (CI young: 10.1 ± 0.8, old: 7.0 ± 0.4 pmol·s−1·mg−1; CI + II young: 12.3 ± 0.6, old: 7.6 ± 0.4 pmol·s−1·mg−1). The respiratory control ratio (RCR) was also significantly attenuated in the old (young: 2.2 ± 0.1, old: 1.1 ± 0.1). Furthermore, state 3 (CI + II) and 4 respiration, as well as RCR, were significantly correlated ( r = 0.49–0.86) with endothelium-dependent, but not endothelium-independent, function. Finally, the direct intervention with mitochondrial-targeted antioxidant (MitoQ) significantly improved endothelium-dependent vasodilation in the old but not in the young. Thus, the age-related decline in vasodilatory function is linked to attenuated vascular mitochondrial respiratory function, likely by augmented free radicals.

NEW & NOTEWORTHY In human skeletal muscle feed arteries, the well-recognized age-related fall in endothelium-dependent vasodilatory function is strongly linked to a concomitant fall in vascular mitochondrial respiratory function. The direct intervention with the mitochondrial-targeted antioxidant restored vasodilatory function in the old but not in the young, supporting the concept that exacerbated mitochondrial-derived free radical production is linked to age-related vasodilatory dysfunction. Age-related vasodilatory dysfunction in humans is linked to attenuated vascular mitochondrial respiratory function, likely a consequence of augmented free radical production.
Differential effects of the mode of touch, active and passive, on experience-driven plasticity in the S1 cutaneous digit representation of adult macaque monkeys
Authors: Cybulska-Klosowicz Anita , Tremblay François , Jiang Wan , Bourgeon Stéphanie , Meftah El-Mehdi , Chapman C. Elaine
Published: February 2020

This study compared the receptive field (RF) properties and firing rates of neurons in the cutaneous hand representation of primary somatosensory cortex (areas 3b, 1, and 2) of 9 awake, adult macaques that were intensively trained in a texture discrimination task using active touch (fingertips scanned over the surfaces using a single voluntary movement), passive touch (surfaces displaced under the immobile fingertips), or both active and passive touch. Two control monkeys received passive exposure to the same textures in the context of a visual discrimination task. Training and recording extended over 1–2 yr per animal. All neurons had a cutaneous receptive field (RF) that included the tips of the stimulated digits (D3 and/or D4). In area 3b, RFs were largest in monkeys trained with active touch, smallest in those trained with passive touch, and intermediate in those trained with both; i.e., the mode of touch differentially modified the cortical representation of the stimulated fingers. The same trends were seen in areas 1 and 2, but the changes were not significant, possibly because a second experience-driven influence was seen in areas 1 and 2, but not in area 3b: smaller RFs with passive exposure to irrelevant tactile inputs compared with recordings from one naive hemisphere. We suggest that added feedback during active touch and higher cortical firing rates were responsible for the larger RFs with behavioral training; this influence was tempered by periods of more restricted sensory feedback during passive touch training in the active + passive monkeys.

NEW & NOTEWORTHY We studied experience-dependent sensory cortical plasticity in relation to tactile discrimination of texture using active and/or passive touch. We showed that neuronal receptive fields in primary somatosensory cortex, especially area 3b, are largest in monkeys trained with active touch, smallest in those trained with passive touch, and intermediate in those trained using both modes of touch. Prolonged, irrelevant tactile input had the opposite influence in areas 1 and 2, favoring smaller receptive fields.
Divisive gain modulation enables flexible and rapid entrainment in a neocortical microcircuit model
Authors: Papasavvas Christoforos A. , Trevelyan Andrew J. , Kaiser Marcus , Wang Yujiang
Published: February 2020

We introduce a computational neocortical microcircuit model that features two inhibitory neural populations, with one providing subtractive and the other divisive inhibition to the excitatory population. We demonstrate that divisive inhibition widens the range of input frequencies to which the microcircuit can become entrained and diminishes the time needed to reach full entrainment. We suggest that divisive inhibition enables more adaptive oscillatory activity, with important implications for both normal and pathological brain function.
Statistical Characteristics of the First Passage Time Analysis for the Gene Regulatory Circuit in Bacillus subtilis by Cell Mapping Method
Authors: Wang Liang , Yuan Minjuan , Ma Shichao , Yue Xiaole , Zhang Ying
Published: February 2020

In this paper, we will explore the stochastic exit problem for the gene regulatory circuit in B. subtilis affected by colored noise. The stochastic exit problem studies the state transition in B. subtilis (from competent state to vegetative state in this case) through three different quantities: the probability density function of the first passage time, the mean of first passage time, and the reliability function. To satisfy the Markov nature, we convert the colored noise system into the equivalent white noise system. Then, the stochastic generalized cell mapping method can be used to explore the stochastic exit problem. The results indicate that the intensity of noise and system parameters have the effect on the transition from competent to vegetative state in B. subtilis. In addition, the effectiveness of the stochastic generalized cell mapping method is verified by Monte Carlo simulation.
Cytokeratin-Positive Osteosarcoma Simulating Sarcomatoid Metastatic Carcinoma
Authors: Murtaza Hamza , Arain Abdul Rehman , Anoushiravani Afshin , Thadani Sean , de la Roza Gustavo , Naous Rana , Damron Timothy A.
Published: February 2020

Osteosarcoma, the most common primary malignant bone tumor, rarely stains positive for epithelial markers such as cytokeratin on immunohistochemical analysis. We describe a 52-year-old man with a destructive distal femoral metaphyseal lesion who was initially treated for metastatic sarcomatoid carcinoma based on extensive radiographic and histopathologic evaluation. Ultimately, wide resection of the distal femur was performed, revealing high-grade conventional osteosarcoma with intense and diffuse cytokeratin positivity. Such immunohistochemical staining in osteosarcoma is rare, making it difficult to distinguish cytokeratin-positive osteosarcoma from metastatic carcinoma. The presence of a cytokeratin-positive bone neoplasm with malignant osteoid formation on histological studies as well as integration with clinical and radiologic data can help confirm osteosarcoma as the ultimate diagnosis.
Identification of Genes Associated with the Metastasis of Pheochromocytoma/Paraganglioma Based on Weighted Gene Coexpression Network Analysis
Authors: Su Qisheng , Ding Qinpei , Zhang Zunni , Yang Zheng , Qiu Yuling , Li Xiaohong , Mo Wuning
Published: February 2020

Background. Pheochromocytoma/paraganglioma (PCPG) is a benign neuroendocrine neoplasm in most cases, but metastasis and other malignant behaviors can be observed in this tumor. The aim of this study was to identify genes associated with the metastasis of PCPG. Methods. The Cancer Genome Atlas (TCGA) expression profile data and clinical information were downloaded from the cbioportal, and the weighted gene coexpression network analysis (WGCNA) was conducted. The gene coexpression modules were extracted from the network through the WGCNA package of R software. We further extracted metastasis‐related modules of PCPG. Enrichment analysis of Biological Process of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes was carried out for important modules, and survival analysis of hub genes in the modules was performed. Results. A total of 168 PCPG samples were included in this study. The weighted gene coexpression network was constructed with 5125 genes of the top 25% variance among the 20501 genes obtained from the database. We identified 11 coexpression modules, among which the salmon module was associated with the age of PCPG patients at diagnosis, metastasis, and malignancy of the tumors. Conclusion. WGCNA was performed to identify the gene coexpression modules and hub genes in the metastasis‐related gene module of PCPG. The findings in this study provide a new clue for further study of the mechanisms underlying the PCPG metastasis.
Minireview on the Relations between Gut Microflora and Parkinson’s Disease: Further Biochemical (Oxidative Stress), Inflammatory, and Neurological Particularities
Authors: Ilie Ovidiu-Dumitru , Ciobica Alin , McKenna Jack , Doroftei Bogdan , Mavroudis Ioannis
Published: February 2020

The aetiology of Parkinson’s disease (PD) is a highly debated topic. Despite the progressive increase in the number of patients diagnosed with PD over the last couple of decades, the causes remain largely unknown. This report is aimed at highlighting the main features of the microbial communities which have been termed “the second brain” that may be a major participant in the etiopathophysiology of PD. It is possible that dysbiosis could be caused by an overactivity of proinflammatory cytokines which act on the gastrointestinal tract as well as infections. The majority of patients who are diagnosed with PD display gastrointestinal symptoms as one of the earliest features. In addition, an unbalanced cycle of oxidative stress caused by dysbacteriosis may have the effect of gradually promoting PD’s specific phenotype. Thus, it seems that bacteria possess the ability to manipulate the brain by initiating specific responses, defining their capability to configure the human body, with oxidative stress playing a pivotal role in preventing infections but also in activating related signalling pathways.
Effect of Clogging on the Permeability of Porous Asphalt Pavement
Authors: Ma Yaolu , Chen Xianhua , Geng Yanfen , Zhang Xinlan
Published: February 2020

The purpose of this paper is to report on the drainage of porous asphalt pavement evaluation method suited for use in analyzing clogging effect. To preliminarily reveal the decrease in permeability caused by clogging of permeable asphalt pavement, an innovative device was proposed to evaluate the anisotropy of permeability influenced by clogging, and the maximum drainage capacity without surface ponding can be obtained when the supplied water was controlled. Then, finite element models for asphalt pavements with hydromechanical coupling were proposed based on porous media theory and Biot’s theory. The variation in pore water pressure was simulated by considering the decrease in voids and the increase in clogging grains. The results indicate that the internally retained water should not be ignored because the semiconnected voids were filled with water rapidly at the beginning of permeability tests. To avoid surface ponding, the drainage capacity coefficient (DCC) can be used to evaluate the maximum drainage capacity (MDC) influenced by clogging. Moreover, the pore water pressure increased due to the reduction in voids and a high level of clogging. In addition, the peak value of pore water pressure is also affected by the upper‐layer height of the pavement. Under the action of clogging and driving load, a reasonable thickness of the upper layer and a drainage evaluation should be considered to improve road safety.
Payload Parameter Identification of a Flexible Space Manipulator System via Complex Eigenvalue Estimation
Authors: Ni Zhiyu , Wu Shunan , Zhang Yewei , Wu Zhigang
Published: February 2020

Manipulator systems are widely used in payload capture and movement in the ground/space operation due to their dexterous manipulation capability. In this study, a method for identifying the payload parameters of a flexible space manipulator using the estimated system of complex eigenvalue matrix is proposed. The original nonlinear dynamic model of the manipulator is linearized at a selected working point. Subsequently, the system state-space model and corresponding complex eigenvalue parameters are determined by the observer/Kalman filter identification algorithm using the torque input signal of the motor and the vibration output signals of the link. Therefore, the inertia parameters of the payload, that is, the mass and the moment of inertia, can be derived from the identified complex eigenvalue system and mode shapes by solving a least-squares problem. In numerical simulations, the proposed parameter identification method is implemented and compared with the classical recursive least-squares and affine projection sign algorithms. Numerical results demonstrate that the proposed method can effectively estimate the payload parameters with satisfactory accuracy.
Aloe Emodin Reduces Cardiac Inflammation Induced by a High-Fat Diet through the TLR4 Signaling Pathway
Authors: Chen Yingfu , Feng Burong , Yuan Ye , Hu Juan , Zhao Wei , Jiang Huiwei , Li Wen , Fan Ziyi , Du Zhimin
Published: February 2020

Background. Aloe emodin (AE) is a lipid-lowering agent, which could be used to treat hyperlipidemia, thereby reducing the risk of cardiovascular disease. Recent evidence suggests that hyperlipidemia is associated with many cardiac pathological alterations and might worsen myocardial damages. Purpose. The purpose of this study is to evaluate the potential roles and mechanisms of AE in hyperlipidemia-induced oxidative stress and inflammation in the heart. Study Design. We established a hyperlipidemia-induced cardiac inflammation model in rats and cells then administered AE and observed its effect on hyperlipidemia-induced cardiac inflammation. Methods. We used a mouse model of hyperlipidemia caused by a high-fat diet (HFD) for 10 weeks and cell culture experimental models of inflammation in the heart stimulated by PA for 14 h. Inflammatory markers were detected by qRT-PCR, WB, and immunofluorescence. Results. We demonstrated that the expression levels of proinflammatory cytokines IL-1β, IL-6, and TNF-α were increased in the HFD group compared to the normal diet (ND) group, whereas AE treatment significantly reduced their levels in the myocardium. In addition, vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecule 1 (ICAM-1) protein expressions were also inhibited by AE. Our in vitro study showed AE treatment dose-dependently decreased the expression of IL-1β, IL-6, and TNF-α in PA-treated H9C2 cells. Further experiments revealed that AE inhibited PA-induced cell death and promoted the production of intracellular reactive oxygen species (ROS). Mechanically, AE significantly suppressed the upregulation in protein levels of TLR4, IκB, and p-P65l in vivo and in vitro. Conclusion. Taken together, our findings disclose that AE could alleviate HFD/PA-induced cardiac inflammation via inhibition of the TLR4/NF-κB signaling pathway. Thus, AE may be a promising therapeutic strategy for preventing hyperlipidemia-induced myocardial injury.
Relevance of Fatty Acids to Sperm Maturation and Quality
Authors: Collodel Giulia , Castellini Cesare , Lee Jetty Chung-Yung , Signorini Cinzia
Published: February 2020

Almost 50% of infertility cases are associated with human male infertility. The sperm membrane is a key structure influencing sperm morphology and function in normal and pathological conditions. The fatty acid profile determines the performance not only of sperm motility but also of acrosomal reaction and sperm-oocyte fusion. This review presents available knowledge on the role of fatty acid composition in human sperm and spermatogenesis and discusses the influence of dietary fatty acids on the sperm fatty acid profile. Recent studies in biological sciences and clinical researches in this field are also reported. The topic object of this review has potential application in medicine by identifying potential causes of infertility.
Selective and Potent CDK8/19 Inhibitors Enhance NK-Cell Activity and Promote Tumor Surveillance
Authors: Hofmann Marco H. , Mani Rajeswaran , Engelhardt Harald , Impagnatiello Maria A. , Carotta Sebastian , Kerenyi Marc , Lorenzo-Herrero Seila , Böttcher Jark , Scharn Dirk , Arnhof Heribert , Zoephel Andreas , Schnitzer Renate , Gerstberger Thomas , Sanderson Michael P. , Rajgolikar Girish , Goswami Swagata , Vasu Sumithira , Ettmayer Peter , Gonzalez Segundo , Pearson Mark , McConnell Darryl B. , Kraut Norbert , Muthusamy Natarajan , Moll Jürgen
Published: February 2020

Natural killer (NK) cells play a pivotal role in controlling cancer. Multiple extracellular receptors and internal signaling nodes tightly regulate NK activation. Cyclin-dependent kinases of the mediator complex (CDK8 and CDK19) were described as a signaling intermediates in NK cells. Here, we report for the first time the development and use of CDK8/19 inhibitors to suppress phosphorylation of STAT1S727 in NK cells and to augment the production of the cytolytic molecules perforin and granzyme B (GZMB). Functionally, this resulted in enhanced NK-cell–mediated lysis of primary leukemia cells. Treatment with the CDK8/19 inhibitor BI-1347 increased the response rate and survival of mice bearing melanoma and breast cancer xenografts. In addition, CDK8/19 inhibition augmented the antitumoral activity of anti–PD-1 antibody and SMAC mimetic therapy, both agents that promote T-cell–mediated antitumor immunity. Treatment with the SMAC mimetic compound BI-8382 resulted in an increased number of NK cells infiltrating EMT6 tumors. Combination of the CDK8/19 inhibitor BI-1347, which augments the amount of degranulation enzymes, with the SMAC mimetic BI-8382 resulted in increased survival of mice carrying the EMT6 breast cancer model. The observed survival benefit was dependent on an intermittent treatment schedule of BI-1347, suggesting the importance of circumventing a hyporesponsive state of NK cells. These results suggest that CDK8/19 inhibitors can be combined with modulators of the adaptive immune system to inhibit the growth of solid tumors, independent of their activity on cancer cells, but rather through promoting NK-cell function.