bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractNeural 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

AbstractAsparaginyl 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

AbstractControlled 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

AbstractExtracellular 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

AbstractFormaldehyde (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

AbstractThis 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

AbstractThe 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

AbstractAutomated 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

AbstractMinimally 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

AbstractHigh 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

AbstractClostridium 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

AbstractDisturbances 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

AbstractMany 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

AbstractBiofilms 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

AbstractLysosomal 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.