bluuebunny/crossref_metadata_2025 huggingface dataset:
Latitudinal Dependence of the Kelvin‐Helmholtz Instability and Beta Dependence of Vortex‐Induced High‐Guide Field Magnetic Reconnection
Authors: Vernisse Y. , Lavraud B. , Faganello M. , Fadanelli S. , Sisti M. , Califano F. , Eriksson S. , Gershman D. J. , Dorelli J. , Pollock C. , Giles B. , Avanov L. , Burch J. , Dargent J. , Ergun R. E. , Farrugia C. J. , Génot V. , Hasegawa H. , Jacquey C. , Kacem I. , Kieokaew R. , Kuznetsova M. , Moore T. , Nakamura T. , Paterson W. , Penou E. , Phan T. D. , Russell C. T. , Saito Y. , Sauvaud J.‐A. , Toledo‐Redondo S.
Published: March 2020

We investigate both large‐ and small‐scale properties of a Kelvin‐Helmholtz (KH) event at the dusk flank magnetopause using Magnetospheric Multiscale observations on 8 September 2015. We first use two types of 3‐D simulations (global and local) to demonstrate that Magnetospheric Multiscale is close to the most KH unstable region, and so the occurrence of vortex‐induced reconnection may be expected. Because they produce low‐shear current sheets, KH vortices constitute a perfect laboratory to investigate magnetic reconnection with large guide field and low asymmetry. Recent works suggest that magnetic reconnection may be suppressed when a current sheet combines large guide field and pressure gradient (which induces a diamagnetic drift). We thus perform a statistical analysis of high‐resolution data for the 69 KH‐induced low‐shear magnetic reconnection events observed on that day. We find that the suppression mechanism is not at work for most of the observed reconnecting current sheets, as predicted, but we also find that almost all nonreconnecting current sheets should be reconnecting according to this model. This confirms the fact that the model provides a necessary but not sufficient condition for reconnection to occur. Finally, based on the same data set, we study the latitudinal distribution of these magnetic reconnection events combined with global magnetospheric modeling. We find that reconnection associated with KH vortices occurs over a significant range of latitudes at the flank magnetopause. It is not confined to the plane where the growth rate is maximum, in agreement with recent 3‐D simulations.
Rift Structure and Sediment Infill of Hyperextended Continental Crust: Insights From 3D Seismic and Well Data (Xisha Trough, South China Sea)
Authors: Lei Chao , Alves Tiago M. , Ren Jianye , Tong Chuanxin
Published: March 2020

Three‐dimensional seismic and well data from the deepwater Xisha Trough are used to investigate the rift structure and sediment infill of a region formed adjacently to the initial oceanic ridge of the South China Sea (SCS). The high‐quality data permitted a detailed analysis of features such as (1) detachment faults soling out at the Moho, (2) rotated and thinned continental blocks covered by thick sediment, and (3) changes in the location of basin depocenters resulting from detachment faulting. During the continental rifting phase (Eocene to earliest Oligocene), faulting was broadly distributed in the Xisha Trough and resulted in the generation of isolated grabens/half grabens filled by proximal sediment sources. During continental breakup in the Northwest Ocean Sector of SCS (Oligocene), extension became restricted to a narrow region where highly tilted continental blocks and thin crust were formed. Sediment was, at that time, fed to distal depocenters, which are presently bounded by listric faults rooted in a basal detachment. Later in a second stage (early Miocene), synchronously with continental breakup in the Southwest Ocean Sector of the SCS, the study area was blanketed by thick sediment. During the two continental breakup events, the hyperextended Xisha Trough was affected by closely spaced, small‐scale faults rather than large basement‐related structures. Our study highlights the effect of continental breakup as a way to broaden sediment influx from multiple sources into deepwater basins. As a corollary, this work recognizes two distinct breakup sequences in the Xisha Trough and concludes on their geodynamic significance to the SCS.
Snow Water Equivalent Measurements in Remote Arctic Alaska Watersheds
Authors: Stuefer S. L. , Kane D. L. , Dean K. M.
Published: March 2020

Snow surveys in two Arctic watersheds located in Alaska, USA, provide 32 years of spatially distributed snow water equivalent (SWE) and snow depth observations. Annual snow surveys from the Imnavait Creek (20,036 measurements from 1985 to 2017) and Upper Kuparuk River (5,804 measurements from 1997 to 2017) watersheds were conducted to capture end‐of‐winter snow accumulation. The average end‐of‐winter SWE in the Upper Kuparuk River watershed (102 ± 29 mm) is consistently less than the Imnavait Creek watershed (130 ± 34 mm) during the common period of record (1997–2017). The average end‐of‐winter SWE in both watersheds indicates a positive trend. Comparison of SWE records with cumulative solid precipitation measured at the Imnaviat [sic] SNOTEL site highlights the undercatch of gauge precipitation and difference in long‐term trends. In this paper, we present a historic overview of data collection, discuss data accuracy, and point out advantages and limitations associated with ground‐based snow measurements in remote Arctic locations. As new methods and techniques of measuring SWE and solid precipitation become available, the presented data set will provide a historic perspective for new observations and will quantitatively relate current or future snow conditions to those that have occurred since the late twentieth century.
The circFASN/miR-33a pathway participates in tacrolimus-induced dysregulation of hepatic triglyceride homeostasis
Authors: Zhang Chenzhi , Chen Kangchen , Wei Rongli , Fan Guanghan , Cai Xuechun , Xu Li , Cen Beini , Wang Jianguo , Xie Haiyang , Zheng Shusen , Xu Xiao
Published: March 2020

Dyslipidemia exhibits a high incidence after liver transplantation, in which tacrolimus, a widely used immunosuppressant, plays a fundamental role. MicroRNAs and related circRNAs represent a class of noncoding RNAs that have been recognized as important regulators of genes associated with lipid metabolism. However, their transcriptional activities and functional mechanisms in tacrolimus-related dyslipidemia remain unclear. In this study, we observed that tacrolimus could induce triglyceride accumulation in hepatocytes by stimulating sterol response element-binding proteins (SREBPs) and miR-33a. Our in silico and experimental analyses identified miR-33a as a direct target of circFASN. Tacrolimus could downregulate circFASN and result in elevated miR-33a in vivo and in vitro. Overexpression of circFASN or silencing of miR-33a decreased the promoting effects of tacrolimus on triglyceride accumulation. Clinically, the incidence of dyslipidemia in liver transplant recipients with elevated serum miR-33a after liver transplantation was higher than that in patients without elevated serum miR-33a (46.3% vs. 18.8% p = 0.012, n = 73). Our results showed that the circFASN/miR-33a regulatory system plays a distinct role in tacrolimus-induced disruption of lipid homeostasis. MiR-33a is likely a risk factor for tacrolimus-related dyslipidemia, providing a potential therapeutic target to combat tacrolimus-induced dyslipidemia after liver transplantation.
The Agpat4/LPA axis in colorectal cancer cells regulates antitumor responses via p38/p65 signaling in macrophages
Authors: Zhang Dapeng , Shi Rongchen , Xiang Wei , Kang Xia , Tang Bo , Li Chuan , Gao Linfeng , Zhang Xuan , Zhang Lili , Dai Rongyang , Miao Hongming
Published: March 2020

Lipid metabolic reprogramming plays an essential role in regulating the progression of colorectal cancer (CRC). However, the effect of lysophosphatidic acid (LPA) metabolism on CRC development is incompletely characterized. Here, we compared the mRNA levels of human CRC tissues to those of paracarcinoma tissues and focused on the notably enriched LPA metabolic pathways. We identified and verified that 1-acylglycerol-3-phosphate O-acyltransferase 4 (Agpat4) was aberrantly expressed in CRC tissues and predicted poor survival in CRC patients. Manipulating Agpat4 expression in CRC cells did not affect the growth or migration of CRC cells in vitro, whereas Agpat4 silencing suppressed CRC cell growth in subcutaneous and peritoneal xenograft models. Mechanistically, Agpat4 silencing-induced LPA release from CRC cells and polarized macrophages to an M1-like phenotype through LPA receptors 1 and 3. This M1 activation, characterized by elevated p38/p65 signaling and increased proinflammatory cytokines, promoted the infiltration and activation of CD4+ and CD8+ T cells in the tumor microenvironment. Modulation of the Agpat4/LPA/p38/p65 axis regulated macrophage polarization, T-cell activity and CRC progression. Notably, combined therapy with LPA and regular chemotherapy drugs synergistically suppressed CRC development. Taken together, our results showed that the Agpat4/LPA axis in CRC cells regulated p38/p65 signaling-dependent macrophage polarization, T-cell activation, and CRC progression. The Agpat4/LPA/p38/p65 axis might represent a potential target for therapy in the clinic.
Targeted assemblies of cas1 suggest CRISPR-Cas’s response to soil warming
Authors: Wu Ruonan , Chai Benli , Cole James R , Gunturu Santosh K , Guo Xue , Tian Renmao , Gu Ji-Dong , Zhou Jizhong , Tiedje James M
Published: March 2020

There is an increasing interest in the clustered regularly interspaced short palindromic repeats CRISPR-associated protein (CRISPR-Cas) system to reveal potential virus–host dynamics. The universal and most conserved Cas protein, cas1 is an ideal marker to elucidate CRISPR-Cas ecology. We constructed eight Hidden Markov Models (HMMs) and assembled cas1 directly from metagenomes by a targeted-gene assembler, Xander, to improve detection capacity and resolve the diverse CRISPR-Cas systems. The eight HMMs were first validated by recovering all 17 cas1 subtypes from the simulated metagenome generated from 91 prokaryotic genomes across 11 phyla. We challenged the targeted method with 48 metagenomes from a tallgrass prairie in Central Oklahoma recovering 3394 cas1. Among those, 88 were near full length, 5 times more than in de-novo assemblies from the Oklahoma metagenomes. To validate the host assignment by cas1, the targeted-assembled cas1 was mapped to the de-novo assembled contigs. All the phylum assignments of those mapped contigs were assigned independent of CRISPR-Cas genes on the same contigs and consistent with the host taxonomies predicted by the mapped cas1. We then investigated whether 8 years of soil warming altered cas1 prevalence within the communities. A shift in microbial abundances was observed during the year with the biggest temperature differential (mean 4.16 °C above ambient). cas1 prevalence increased and even in the phyla with decreased microbial abundances over the next 3 years, suggesting increasing virus–host interactions in response to soil warming. This targeted method provides an alternative means to effectively mine cas1 from metagenomes and uncover the host communities.
Magnetic–acoustic biphysical invisible coats for underwater objects
Authors: Zhou Yi , Chen Jian , Liu Liu , Fan Zheng , Ma Yungui
Published: March 2020

Magnetic fields and acoustic waves are the two fundamental measures to perceive underwater objects, which, however, have never been simultaneously handled before. In this work, we propose and demonstrate a biphysical submillimeter-thick metamaterial coat that can simultaneously make underwater objects invisible to both magnetic fields and acoustic waves. The conformal coat is a subtle integration of an open-cavity acoustic absorber made of a dissipative acoustic metasurface (AMS) and a bilayer magnetic cloak. Experimentally, a magnetic cloaking effect with a field disturbance ratio of <0.5% is obtained over a broad-frequency range (10–250 kHz), and the compound metamaterial coat can strongly attenuate ultrasonic waves with a near-unity absorptivity. The magnetic subcoat can be freely combined with various AMS layers to achieve a wideband acoustic stealth effect for different spectral regimes. This work may open up a new way to build multifunctional devices for various waterborne applications.
Imaging grain microstructure in a model ceramic energy material with optically generated coherent acoustic phonons
Authors: Wang Yuzhou , Hurley David H. , Hua Zilong , Pezeril Thomas , Raetz Samuel , Gusev Vitalyi E. , Tournat Vincent , Khafizov Marat
Published: March 2020

Characterization of microstructure, chemistry and function of energy materials remains a challenge for instrumentation science. This active area of research is making considerable strides with methodologies that employ bright X-rays, electron microscopy, and optical spectroscopy. However, further development of instruments capable of multimodal measurements, is necessary to reveal complex microstructure evolution in realistic environments. In this regard, laser-based instruments have a unique advantage as multiple methodologies are easily combined into a single instrument. A pump-probe method that uses optically generated acoustic phonons is expanding standard optical characterization by providing depth resolved information. Here we report on an extension of this method to image grain microstructure in ceria. Rich information regarding the orientation of individual crystallites is obtained by noting how the polarization of the probe beam influences the detected signal amplitude. When paired with other optical microscopies, this methodology will provide new perspectives for characterization of ceramic materials.
Modulation of BIN2 kinase activity by HY5 controls hypocotyl elongation in the light
Authors: Li Jian , Terzaghi William , Gong Yanyan , Li Congran , Ling Jun-Jie , Fan Yangyang , Qin Nanxun , Gong Xinqi , Zhu Danmeng , Deng Xing Wang
Published: March 2020

ELONGATED HYPOCOTYL 5 (HY5), a basic domain/leucine zipper (bZIP) transcription factor, acts as a master regulator of transcription to promote photomorphogenesis. At present, it’s unclear whether HY5 uses additional mechanisms to inhibit hypocotyl elongation. Here, we demonstrate that HY5 enhances the activity of GSK3-like kinase BRASSINOSTEROID-INSENSITIVE 2 (BIN2), a key repressor of brassinosteroid signaling, to repress hypocotyl elongation. We show that HY5 physically interacts with and genetically acts through BIN2 to inhibit hypocotyl elongation. The interaction of HY5 with BIN2 enhances its kinase activity possibly by the promotion of BIN2 Tyr200 autophosphorylation, and subsequently represses the accumulation of the transcription factor BRASSINAZOLE-RESISTANT 1 (BZR1). Leu137 of HY5 is found to be important for the HY5-BIN2 interaction and HY5-mediated regulation of BIN2 activity, without affecting the transcriptional activity of HY5. HY5 levels increase with light intensity, which gradually enhances BIN2 activity. Thus, our work reveals an additional way in which HY5 promotes photomorphogenesis, and provides an insight into the regulation of GSK3 activity.
Generalization properties of neural network approximations to frustrated magnet ground states
Authors: Westerhout Tom , Astrakhantsev Nikita , Tikhonov Konstantin S. , Katsnelson Mikhail I. , Bagrov Andrey A.
Published: March 2020

Neural quantum states (NQS) attract a lot of attention due to their potential to serve as a very expressive variational ansatz for quantum many-body systems. Here we study the main factors governing the applicability of NQS to frustrated magnets by training neural networks to approximate ground states of several moderately-sized Hamiltonians using the corresponding wave function structure on a small subset of the Hilbert space basis as training dataset. We notice that generalization quality, i.e. the ability to learn from a limited number of samples and correctly approximate the target state on the rest of the space, drops abruptly when frustration is increased. We also show that learning the sign structure is considerably more difficult than learning amplitudes. Finally, we conclude that the main issue to be addressed at this stage, in order to use the method of NQS for simulating realistic models, is that of generalization rather than expressibility.
A bifunctional asparaginyl endopeptidase efficiently catalyzes both cleavage and cyclization of cyclic trypsin inhibitors
Authors: Du Junqiao , Yap Kuok , Chan Lai Yue , Rehm Fabian B. H. , Looi Fong Yang , Poth Aaron G. , Gilding Edward K. , Kaas Quentin , Durek Thomas , Craik David J.
Published: March 2020

Asparaginyl endopeptidases (AEPs) catalyze the key backbone cyclization step during the biosynthesis of plant-derived cyclic peptides. Here, we report the identification of two AEPs from Momordica cochinchinensis and biochemically characterize MCoAEP2 that catalyzes the maturation of trypsin inhibitor cyclotides. Recombinantly produced MCoAEP2 catalyzes the backbone cyclization of a linear cyclotide precursor (MCoTI-II-NAL) with a kcat/Km of 620 mM−1 s−1, making it one of the fastest cyclases reported to date. We show that MCoAEP2 can mediate both the N-terminal excision and C-terminal cyclization of cyclotide precursors in vitro. The rate of cyclization/hydrolysis is primarily influenced by varying pH, which could potentially control the succession of AEP-mediated processing events in vivo. Furthermore, MCoAEP2 efficiently catalyzes the backbone cyclization of an engineered MCoTI-II analog with anti-angiogenic activity. MCoAEP2 provides enhanced synthetic access to structures previously inaccessible by direct chemistry approaches and enables the wider application of trypsin inhibitor cyclotides in biotechnology applications.
Rapid and continuous regulating adhesion strength by mechanical micro-vibration
Authors: Shui Langquan , Jia Laibing , Li Hangbo , Guo Jiaojiao , Guo Ziyu , Liu Yilun , Liu Ze , Chen Xi
Published: March 2020

Controlled tuning of interface adhesion is crucial to a broad range of applications, such as space technology, micro-fabrication, flexible electronics, robotics, and bio-integrated devices. Here, we show a robust and predictable method to continuously regulate interface adhesion by exciting the mechanical micro-vibration in the adhesive system perpendicular to the contact plane. An analytic model reveals the underlying mechanism of adhesion hysteresis and dynamic instability. For a typical PDMS-glass adhesion system, the apparent adhesion strength can be enhanced by 77 times or weakened to 0. Notably, the resulting adhesion switching timescale is comparable to that of geckos (15 ms), and such rapid adhesion switching can be repeated for more than 2 × 107 vibration cycles without any noticeable degradation in the adhesion performance. Our method is independent of surface microstructures and does not require a preload, representing a simple and practical way to design and control surface adhesion in relevant applications.
New insights in acetaminophen toxicity: HMGB1 contributes by itself to amplify hepatocyte necrosis in vitro through the TLR4-TRIF-RIPK3 axis
Authors: Minsart Charlotte , Liefferinckx Claire , Lemmers Arnaud , Dressen Cindy , Quertinmont Eric , Leclercq Isabelle , Devière Jacques , Moreau Richard , Gustot Thierry
Published: March 2020

Extracellular release of HMGB1 contributes to acetaminophen-induced liver injury. HMGB1 acts as a danger-associated molecular patterns during this toxic process but the mechanisms of action and targeted cells are incompletely defined. Here we studied, in vitro, the role of HMGB1 in amplifying the acetaminophen-induced hepatocyte necrosis process. Using cultured HepaRG cells, primary human hepatocytes and selective chemical inhibitors we evaluated acetaminophen-induced toxicity. We confirmed that addition of acetaminophen induced HepaRG cell death and HMGB1 release. We showed that inhibition of HMGB1 decreased acetaminophen-induced HepaRG cell death, suggesting a feedforward effect. We provide the first evidence that exposure of HepaRG cells to recombinant human HMGB1 (rhHMGB1) also resulted in cell death. Moreover, we found that both acetaminophen and rhHMGB1 induced programmed HepaRG cell necrosis through a RIPK3-dependent mechanism. By using TLR4 blocking antibody, we demonstrated the reduction of the HepaRG cell death induced by acetaminophen and rhHMGB1. Furthermore, inhibition of TRIF, known to induce a RIPK3-dependent cell death, reduced rhHMGB1-induced HepaRG cell death. Our data support that released HMGB1 from acetaminophen-stressed hepatocytes induced necrosis of neighboring hepatocytes by TLR4-TRIF-RIPK3- pathway. This in vitro study gives new insights in the role of HMGB1 in the amplification of acetaminophen-induced toxicity.
Mitochondrial dysfunction and DNA damage accompany enhanced levels of formaldehyde in cultured primary human fibroblasts
Authors: Nadalutti Cristina A. , Stefanick Donna F. , Zhao Ming-Lang , Horton Julie K. , Prasad Rajendra , Brooks Ashley M. , Griffith Jack D. , Wilson Samuel H.
Published: March 2020

Formaldehyde (FA) is a simple biological aldehyde that is produced inside cells by several processes such as demethylation of DNA and proteins, amino acid metabolism, lipid peroxidation and one carbon metabolism (1-C). Although accumulation of excess FA in cells is known to be cytotoxic, it is unknown if an increase in FA level might be associated with mitochondrial dysfunction. We choose to use primary human fibroblasts cells in culture (foreskin, FSK) as a physiological model to gain insight into whether an increase in the level of FA might affect cellular physiology, especially with regard to the mitochondrial compartment. FSK cells were exposed to increasing concentrations of FA, and different cellular parameters were studied. Elevation in intracellular FA level was achieved and was found to be cytotoxic by virtue of both apoptosis and necrosis and was accompanied by both G2/M arrest and reduction in the time spent in S phase. A gene expression assessment by microarray analysis revealed FA affected FSK cells by altering expression of many genes including genes involved in mitochondrial function and electron transport. We were surprised to observe increased DNA double-strand breaks (DSBs) in mitochondria after exposure to FA, as revealed by accumulation of γH2A.X and 53BP1 at mitochondrial DNA foci. This was associated with mitochondrial structural rearrangements, loss of mitochondrial membrane potential and activation of mitophagy. Collectively, these results indicate that an increase in the cellular level of FA can trigger mitochondrial DNA double-strand breaks and dysfunction.
Dynamic response of the nonlocal strain-stress gradient in laminated polymer composites microtubes
Authors: Oyarhossein Mohammad Amin , Alizadeh As’ad , Habibi Mostafa , Makkiabadi Mahmoud , Daman Mohsen , Safarpour Hamed , Jung Dong Won
Published: March 2020

This study presents the frequency analysis of a size-dependent laminated polymer composite microtube using a nonlocal strain-stress gradient (NSG) model. By applying energy methods (known as Hamilton’s principle), the motion equations of the laminated micro tube composites are developed. The thermodynamic equations of the laminated microtube are based on first-order shear deformation theory (FSDT), and a generalized differential quadrature method (GDQM) is employed to find the model for the natural frequencies. The results show that by considering C-F boundary conditions (BCs) and every even layers’ number in lower value of length scale parameter, the frequency of the structure drops by soaring this parameter. However, this matter is inverse in its higher value. Eventually, the ply angle’s influences, nonlocality as well as length scale element on the vibration of the laminated composite microstructure are investigated.
Action representation in the mouse parieto-frontal network
Authors: Tombaz Tuce , Dunn Benjamin A. , Hovde Karoline , Cubero Ryan John , Mimica Bartul , Mamidanna Pranav , Roudi Yasser , Whitlock Jonathan R.
Published: March 2020

The posterior parietal cortex (PPC) and frontal motor areas comprise a cortical network supporting goal-directed behaviour, with functions including sensorimotor transformations and decision making. In primates, this network links performed and observed actions via mirror neurons, which fire both when individuals perform an action and when they observe the same action performed by a conspecific. Mirror neurons are believed to be important for social learning, but it is not known whether mirror-like neurons occur in similar networks in other social species, such as rodents, or if they can be measured in such models using paradigms where observers passively view a demonstrator. Therefore, we imaged Ca2+ responses in PPC and secondary motor cortex (M2) while mice performed and observed pellet-reaching and wheel-running tasks, and found that cell populations in both areas robustly encoded several naturalistic behaviours. However, neural responses to the same set of observed actions were absent, although we verified that observer mice were attentive to performers and that PPC neurons responded reliably to visual cues. Statistical modelling also indicated that executed actions outperformed observed actions in predicting neural responses. These results raise the possibility that sensorimotor action recognition in rodents could take place outside of the parieto-frontal circuit, and underscore that detecting socially-driven neural coding depends critically on the species and behavioural paradigm used.
Cross-site and cross-platform variability of automated patch clamp assessments of drug effects on human cardiac currents in recombinant cells
Authors: Kramer James , Himmel Herbert M. , Lindqvist Anders , Stoelzle-Feix Sonja , Chaudhary Khuram W. , Li Dingzhou , Bohme Georg Andrees , Bridgland-Taylor Matthew , Hebeisen Simon , Fan Jingsong , Renganathan Muthukrishnan , Imredy John , Humphries Edward S. A. , Brinkwirth Nina , Strassmaier Tim , Ohtsuki Atsushi , Danker Timm , Vanoye Carlos , Polonchuk Liudmila , Fermini Bernard , Pierson Jennifer Beck , Gintant Gary
Published: March 2020

Automated patch clamp (APC) instruments enable efficient evaluation of electrophysiologic effects of drugs on human cardiac currents in heterologous expression systems. Differences in experimental protocols, instruments, and dissimilar site procedures affect the variability of IC50 values characterizing drug block potency. This impacts the utility of APC platforms for assessing a drug’s cardiac safety margin. We determined variability of APC data from multiple sites that measured blocking potency of 12 blinded drugs (with different levels of proarrhythmic risk) against four human cardiac currents (hERG [IKr], hCav1.2 [L-Type ICa], peak hNav1.5, [Peak INa], late hNav1.5 [Late INa]) with recommended protocols (to minimize variance) using five APC platforms across 17 sites. IC50 variability (25/75 percentiles) differed for drugs and currents (e.g., 10.4-fold for dofetilide block of hERG current and 4-fold for mexiletine block of hNav1.5 current). Within-platform variance predominated for 4 of 12 hERG blocking drugs and 4 of 6 hNav1.5 blocking drugs. hERG and hNav1.5 block. Bland-Altman plots depicted varying agreement across APC platforms. A follow-up survey suggested multiple sources of experimental variability that could be further minimized by stricter adherence to standard protocols. Adoption of best practices would ensure less variable APC datasets and improved safety margins and proarrhythmic risk assessments.
Biologically Inspired Catheter for Endovascular Sensing and Navigation
Authors: Sutton Erin E. , Fuerst Bernhard , Ghotbi Reza , Cowan Noah J. , Navab Nassir
Published: March 2020

Minimally invasive treatment of vascular disease demands dynamic navigation through complex blood vessel pathways and accurate placement of an interventional device, which has resulted in increased reliance on fluoroscopic guidance and commensurate radiation exposure to the patient and staff. Here we introduce a guidance system inspired by electric fish that incorporates measurements from a newly designed electrogenic sensory catheter with preoperative imaging to provide continuous feedback to guide vascular procedures without additional contrast injection, radiation, image registration, or external tracking. Electrodes near the catheter tip simultaneously create a weak electric field and measure the impedance, which changes with the internal geometry of the vessel as the catheter advances through the vasculature. The impedance time series is then mapped to a preoperative vessel model to determine the relative position of the catheter within the vessel tree. We present navigation in a synthetic vessel tree based on our mapping technique. Experiments in a porcine model demonstrated the sensor’s ability to detect cross-sectional area variation in vivo. These initial results demonstrate the capability and potential of this novel bioimpedance-based navigation technology as a non-fluoroscopic technique to augment existing imaging methods.
High serum adiponectin as a biomarker of renal dysfunction: Results from the KNOW-CKD study
Authors: Song Su Hyun , Oh Tae Ryom , Choi Hong Sang , Kim Chang Seong , Ma Seong Kwon , Oh Kook Hwan , Ahn Curie , Kim Soo Wan , Bae Eun Hui
Published: March 2020

High serum adiponectin is noted in several conditions of chronic kidney disease (CKD) and is a predictor for end stage renal disease. However, the relationship between adiponectin level and renal disease progression is not well established. This study aimed to determine the relationship between serum adiponectin levels and CKD progression. This prospective longitudinal study included 2238 patients from the Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease. Patients were divided into quartiles according to their serum adiponectin level. Composite renal outcome was defined as one or more of the following: initiation of dialysis or transplantation, a two-fold increase in baseline serum creatinine levels, or a 50% decline in the estimated glomerular filtration rate (eGFR) during the follow-up period. A cox proportional hazard ratio model was applied to analyze the relationship between composite renal outcome and serum adiponectin levels. Serum adiponectin level was inversely associated with eGFR (p < 0.001) and positively correlated with urine albumin-creatinine ratio. The highest quartile of serum adiponectin was associated with an increased risk of adverse renal outomes (HR, 1.39; 95%CI, 1.05-1.84; p=0.021). On time-dependent receiver operating characteristic curve analysis, predictive ability of adiponectin for renal outcomes disappeared after adjusting for eGFR. Therefore, serum adiponectin may be a biomarker of renal dysfunction rather than a true risk factor in CKD progression.
Aryl-alkyl-lysines: Novel agents for treatment of C. difficile infection
Authors: Ghosh Chandradhish , AbdelKhalek Ahmed , Mohammad Haroon , Seleem Mohamed N. , Haldar Jayanta
Published: March 2020

Clostridium difficile infections (CDIs) are a growing health concern worldwide. The recalcitrance of C. difficile spores to currently available treatments and concomitant virulence of vegetative cells has made it imperative to develop newer modalities of treatment. Aryl-alkyl-lysines have been earlier reported to possess antimicrobial activity against pathogenic bacteria, fungi, and parasites. Their broad spectrum of activity is attributed to their ability to infiltrate microbial membranes. Herein, we report the activity of aryl-alkyl-lysines against C. difficile and associated pathogens. The most active compound NCK-10 displayed activity comparable to the clinically-used antibiotic vancomycin. Indeed, against certain C. difficile strains, NCK-10 was more active than vancomycin in vitro. Additionally, NCK-10 exhibited limited permeation across the intestinal tract as assessed via a Caco-2 bidirectional permeability assay. Overall, the findings suggest aryl-alkyl-lysines warrant further investigation as novel agents to treat CDI.
Responses of soil microarthropod taxon (Hexapoda: Protura) to natural disturbances and management practices in forest-dominated subalpine lake catchment areas
Authors: Sterzyńska Maria , Shrubovych Julia , Tajovský Karel , Čuchta Peter , Starý Josef , Kaňa Jiří , Smykla Jerzy
Published: March 2020

Disturbances are intrinsic drivers of structure and function in ecosystems, hence predicting their effects in forest ecosystems is essential for forest conservation and/or management practices. Yet, knowledge regarding belowground impacts of disturbance events still remains little understood and can greatly vary by taxonomic and functional identity, disturbance type and local environmental conditions. To address this gap in knowledge, we conducted a survey of soil-dwelling Protura, across forests subjected to different disturbance regimes (i.e. windstorms, insect pest outbreaks and clear-cut logging). We expected that the soil proturan assemblages would differ among disturbance regimes. We also hypothesized that these differences would be driven primarily by variation in soil physicochemical properties thus the impacts of forest disturbances would be indirect and related to changes in food resources. To verify that sampling included two geographically distant subalpine glacial lake catchments that differed in underlying geology, each having four different types of forest disturbance, i.e. control, bark beetle outbreak (BB), windthrow + BB (wind + BB) and clear-cut. As expected, forest disturbance had negative effects on proturan diversity and abundance, with multiple disturbances having the greatest impacts. However, differences in edaphic factors constituted a stronger driver of variability in distribution and abundance of proturans assemblages. These results imply that soil biogeochemistry and resource availability can have much stronger effects on proturan assemblages than forest disturbances.
Estimating degree–degree correlation and network cores from the connectivity of high–degree nodes in complex networks
Authors: Mondragón R. J.
Published: March 2020

Many of the structural characteristics of a network depend on the connectivity with and within the hubs. These dependencies can be related to the degree of a node and the number of links that a node shares with nodes of higher degree. In here we revise and present new results showing how to construct network ensembles which give a good approximation to the degree–degree correlations, and hence to the projections of this correlation like the assortativity coefficient or the average neighbours degree. We present a new bound for the structural cut–off degree based on the connectivity within the hubs. Also we show that the connections with and within the hubs can be used to define different networks cores. Two of these cores are related to the spectral properties and walks of length one and two which contain at least on hub node, and they are related to the eigenvector centrality. We introduce a new centrality measured based on the connectivity with the hubs. In addition, as the ensembles and cores are related by the connectivity of the hubs, we show several examples how changes in the hubs linkage effects the degree–degree correlations and core properties.
Extending the minimal model of metabolic oscillations in Bacillus subtilis biofilms
Authors: Garde Ravindra , Ibrahim Bashar , Schuster Stefan
Published: March 2020

Biofilms are composed of microorganisms attached to a solid surface or floating on top of a liquid surface. They pose challenges in the field of medicine but can also have useful applications in industry. Regulation of biofilm growth is complex and still largely elusive. Oscillations are thought to be advantageous for biofilms to cope with nutrient starvation and chemical attacks. Recently, a minimal mathematical model has been employed to describe the oscillations in Bacillus subtilis biofilms. In this paper, we investigate four different modifications to that minimal model in order to better understand the oscillations in biofilms. Our first modification is towards making a gradient of metabolites from the center of the biofilm to the periphery. We find that it does not improve the model and is therefore, unnecessary. We then use realistic Michaelis-Menten kinetics to replace the highly simple mass-action kinetics for one of the reactions. Further, we use reversible reactions to mimic the diffusion in biofilms. As the final modification, we check the combined effect of using Michaelis-Menten kinetics and reversible reactions on the model behavior. We find that these two modifications alone or in combination improve the description of the biological scenario.
Changes in plasma arylsulfatase A level as a compensatory biomarker of early Parkinson’s disease
Authors: Yoo Han Soo , Lee Jun Sung , Chung Seok Jong , Ye Byoung Seok , Sohn Young H. , Lee Seung-Jae , Lee Phil Hyu
Published: March 2020

Lysosomal dysfunction has been associated with Parkinson’s disease (PD). However, the activity of lysosomal enzymes is heterogeneously observed in PD. We investigated whether arylsulfatase A (ARSA) level can be used as a fluid biomarker of PD and can reflect disease progression. Plasma ARSA level was measured in 55 patients with early and drug-naïve PD, 13 patients with late PD, and 14 healthy controls. We compared the plasma ARSA level among the groups and assessed its correlation to clinical parameters and striatal dopamine transporter (DAT) activity. Plasma ARSA level was not correlated with age. The early PD group had higher plasma ARSA level than the control and late PD groups. In a generalized additive model including all patients with PD, the plasma ARSA level showed an inverted U-shape according to disease duration, peaking at 2.19 years. In patients with early PD, plasma ARSA level was positively correlated to parkinsonian motor score and negatively to striatal DAT activity. In summary, plasma ARSA level was elevated in early stage of PD, and elevated plasma ARSA level was correlated to the clinical and imaging markers of nigrostriatal degeneration. These results suggest that ARSA level is a potential biomarker of compensation in early PD.
Variable transformation of singular cylindrical vector beams using anisotropic crystals
Authors: Khonina Svetlana N. , Porfirev Alexey P. , Kazanskiy Nikolay L.
Published: March 2020

We demonstrated and investigated, both theoretically and experimentally, the transformation of cylindrical vector beams with an embedded phase singularity under the condition of focusing perpendicularly to the axis of the anisotropic calcite crystal. Theoretical and numerical analysis, performed on the basis of decomposing the light field into a set of plane waves for an anisotropic medium, allowed us to study the dependence of the structural transformation of the initial laser beam on the polarisation and phase state in detail. The proposed approach allows one to perform the visual recognition of cylindrically-polarised vector beams of various orders and can be used for the demultiplexing of information channels in the case of polarisation-division multiplexing. The experimentally-obtained results agree with the theoretical findings and demonstrate the reliability of the approach.
All-optically phase-induced polarization modulation by means of holographic method
Authors: Lyu Ziyao , Wang Changshun
Published: March 2020

Phase-induced polarization modulation has been achieved experimentally by means of the all-optical holographic method. An extra spiral phase is added to a Gaussian beam and then a holographic grating is recorded through the interference of a Gaussian beam and the phase-vortex beam with the same linear polarization state in an azobenzene liquid-crystalline film. We report here that the polarization state of the diffraction light from the recorded grating is different from that of the incident light, while no polarization variation occurs for the holographic grating recorded by two Gaussian beams. The phase-induced polarization modulation is mainly attributed to the formation of birefringence in the film generated by phase vortex, which is investigated through the ripple patterns resulting from the competition between photoinduced torques and analysed by the Jones matrix. The experimental results could enrich the connotation between optical parameters and offer a method to realize polarization modulation through phase control.
Water-based slurries for high-energy LiFePO4 batteries using embroidered current collectors
Authors: Aguiló-Aguayo Noemí , Hubmann Dominic , Khan Fahad Ullah , Arzbacher Stefan , Bechtold Thomas
Published: March 2020

Greater specific energy densities in lithium-ion batteries can be achieved by using three-dimensional (3D) porous current collectors, which allow for greater areal mass loadings of the electroactive material. In this paper, we present the use of embroidered current collectors for the preparation of thick, pouch-type Li-ion batteries. Experiments were performed on LiFePO4 (LFP) water-based slurries using styrene-butadiene rubber (SBR) as binder and sodium carboxymethyl cellulose (CMC) as thickener, and formulations of different rheological characteristics were investigated. The electrochemical performance (cyclic voltammetry, rate capability) and morphological characteristics of the LFP half-pouch cells (X-ray micro computed tomography and scanning electron microscopy) were compared between the formulations. An optimum electrode formulation was identified, and a mechanism is proposed to explain differences between the formulations. With the optimum electrode formulation, 350 µm casted electrodes with high mechanical stability were achieved. Electrodes exhibited 4–6 times greater areal mass loadings (4–6 mAh cm−2) and 50% greater electroactive material weight than with foils. In tests of half- and full-pouch embroidered cells, a 50% capacity utilization at 1C-rate and 11% at 2C-rate were observed, with a full recovery at C/5-rate. The cycling stability was also maintained over 55 cycles.
Metabolic and Addiction Indices in Patients on Opioid Agonist Medication-Assisted Treatment: A Comparison of Buprenorphine and Methadone
Authors: Elman Igor , Howard Margaret , Borodovsky Jacob T. , Mysels David , Rott David , Borsook David , Albanese Mark
Published: March 2020

Metabolic hormones stabilize brain reward and motivational circuits, whereas excessive opioid consumption counteracts this effect and may impair metabolic function. Here we addressed the role of metabolic processes in the course of the agonist medication-assisted treatment for opioid use disorder (OUD) with buprenorphine or methadone. Plasma lipids, hemoglobin A1C, body composition, the oral glucose tolerance test (oGTT) and the Sweet Taste Test (STT) were measured in buprenorphine- (n = 26) or methadone (n = 32)- treated subjects with OUD. On the whole, the subjects in both groups were overweight or obese and insulin resistant; they displayed similar oGTT and STT performance. As compared to methadone-treated subjects, those on buprenorphine had significantly lower rates of metabolic syndrome (MetS) along with better values of the high-density lipoproteins (HDL). Subjects with- vs. without MetS tended to have greater addiction severity. Correlative analyses revealed that more buprenorphine exposure duration was associated with better HDL and opioid craving values. In contrast, more methadone exposure duration was associated with worse triglycerides-, HDL-, blood pressure-, fasting glucose- and hemoglobin A1C values. Buprenorphine appears to produce beneficial HDL- and craving effects and, contrary to methadone, its role in the metabolic derangements is not obvious. Our data call for further research aimed at understanding the distinctive features of buprenorphine metabolic effects vis-à-vis those of methadone and their potential role in these drugs’ unique therapeutic profiles.
Small gauge vitrectomy for vitreous amyloidosis and subsequent management of secondary glaucoma in patients with hereditary transthyretin amyloidosis
Authors: Kakihara Shinji , Hirano Takao , Imai Akira , Miyahara Teruyoshi , Murata Toshinori
Published: March 2020

We conducted a retrospective observational study including 31 eyes of 20 patients in order to investigate the efficacy of 25-gauge vitrectomy for vitreous opacity with minimal conjunctival invasion and subsequent management of intraocular pressure (IOP) secondary to hereditary transthyretin amyloidosis. We followed up these patients for an average of 44.7 ± 32.6 months. The primary outcome was best corrected visual acuity (BCVA) at 1 month after surgery and at the final follow-up visit, with management of subsequent IOP elevation. Secondary outcomes included the post-vitrectomy IOP survival rate, to determine the frequency of IOP elevation requiring glaucoma surgery. Mean age at vitrectomy was 55.4 ± 9.1 years. Logarithm of the Minimum Angle of Resolution (LogMAR) BCVA showed immediate improvement from 0.73 ± 0.62 to 0.00 ± 0.22 at 1 month (p = 4.1 × 10−7), an improvement that was maintained up to the final follow-up visit, when IOP was maintained at 13.1 ± 5.2 mmHg. The survival rate of post-vitrectomy IOP control was 0.51, 0.38, and 0.23 at 12, 24, and 60 months, respectively. A poor post-vitrectomy IOP survival rate suggests that removing vitreous amyloid via 25-gauge vitrectomy is not sufficient to guarantee good visual function; subsequent careful follow-up and proper glaucoma management is also required in order to achieve this goal.
Stability testing of resveratrol and viniferin obtained from Vitis vinifera L. by various extraction methods considering the industrial viewpoint
Authors: Kosović Ema , Topiař Martin , Cuřínová Petra , Sajfrtová Marie
Published: March 2020

Solid by-products generated in the winemaking process, can comprise valuable bioactive substances such as resveratrol and viniferin, which can be used in whole range of sectors including medicine, pharmacy, cosmetic industry etc. The changes in content of those stilbenes in extracts obtained by maceration and Soxhlet extraction were monitored using newly modified and validated high-performance liquid chromatography-mass spectrometry method which was proved to be accurate, reproducible, and efficient for their determination. The yields of individual bioactive compounds isolated from winery by-products are crucially dependent on the conditions of used extraction techniques. From this point of view, stability testing including light exposure, elevated temperature, and storage for longer time periods in the solution, represents the basis for optimizing conditions of extraction methods of resveratrol and trans-ε-viniferin. High temperature is beneficial for better release of thermally more stable stilbenes such as trans-resveratrol and trans-ε-viniferin but its application for prolonged time periods can be destructive. Light stress conditions cause the formation of otherwise unavailable cis-ε-viniferin by dimerization and photoisomerization of trans- stilbenes.