bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two-dimensional ferroelectric channel transistors integrating ultra-fast memory and neural computing
Authors: Wang Shuiyuan , Liu Lan , Gan Lurong , Chen Huawei , Hou Xiang , Ding Yi , Ma Shunli , Zhang David Wei , Zhou Peng 
Published: January 2021

AbstractWith the advent of the big data era, applications are more data-centric and energy efficiency issues caused by frequent data interactions, due to the physical separation of memory and computing, will become increasingly severe. Emerging technologies have been proposed to perform analog computing with memory to address the dilemma. Ferroelectric memory has become a promising technology due to field-driven fast switching and non-destructive readout, but endurance and miniaturization are limited. Here, we demonstrate the α-In2Se3 ferroelectric semiconductor channel device that integrates non-volatile memory and neural computation functions. Remarkable performance includes ultra-fast write speed of 40 ns, improved endurance through the internal electric field, flexible adjustment of neural plasticity, ultra-low energy consumption of 234/40 fJ per event for excitation/inhibition, and thermally modulated 94.74% high-precision iris recognition classification simulation. This prototypical demonstration lays the foundation for an integrated memory computing system with high density and energy efficiency.
Engineering fluorinated-cation containing inverted perovskite solar cells with an efficiency of >21% and improved stability towards humidity
Authors: Wang Xiao , Rakstys Kasparas , Jack Kevin , Jin Hui , Lai Jonathan , Li Hui , Ranasinghe Chandana Sampath Kumara , Saghaei Jaber , Zhang Guanran , Burn Paul L. , Gentle Ian R. , Shaw Paul E. 
Published: January 2021

AbstractEfficient and stable perovskite solar cells with a simple active layer are desirable for manufacturing. Three-dimensional perovskite solar cells are most efficient but need to have improved environmental stability. Inclusion of larger ammonium salts has led to a trade-off between improved stability and efficiency, which is attributed to the perovskite films containing a two-dimensional component. Here, we show that addition of 0.3 mole percent of a fluorinated lead salt into the three-dimensional methylammonium lead iodide perovskite enables low temperature fabrication of simple inverted solar cells with a maximum power conversion efficiency of 21.1%. The perovskite layer has no detectable two-dimensional component at salt concentrations of up to 5 mole percent. The high concentration of fluorinated material found at the film-air interface provides greater hydrophobicity, increased size and orientation of the surface perovskite crystals, and unencapsulated devices with increased stability to high humidity.
Machine learning enables design automation of microfluidic flow-focusing droplet generation
Authors: Lashkaripour Ali , Rodriguez Christopher , Mehdipour Noushin , Mardian Rizki , McIntyre David , Ortiz Luis , Campbell Joshua , Densmore Douglas 
Published: January 2021

AbstractDroplet-based microfluidic devices hold immense potential in becoming inexpensive alternatives to existing screening platforms across life science applications, such as enzyme discovery and early cancer detection. However, the lack of a predictive understanding of droplet generation makes engineering a droplet-based platform an iterative and resource-intensive process. We present a web-based tool, DAFD, that predicts the performance and enables design automation of flow-focusing droplet generators. We capitalize on machine learning algorithms to predict the droplet diameter and rate with a mean absolute error of less than 10 μm and 20 Hz. This tool delivers a user-specified performance within 4.2% and 11.5% of the desired diameter and rate. We demonstrate that DAFD can be extended by the community to support additional fluid combinations, without requiring extensive machine learning knowledge or large-scale data-sets. This tool will reduce the need for microfluidic expertise and design iterations and facilitate adoption of microfluidics in life sciences.
Hepatocyte-specific IL11 cis-signaling drives lipotoxicity and underlies the transition from NAFLD to NASH
Authors: Dong Jinrui , Viswanathan Sivakumar , Adami Eleonora , Singh Brijesh K. , Chothani Sonia P. , Ng Benjamin , Lim Wei Wen , Zhou Jin , Tripathi Madhulika , Ko Nicole S. J. , Shekeran Shamini G. , Tan Jessie , Lim Sze Yun , Wang Mao , Lio Pei Min , Yen Paul M. , Schafer Sebastian , Cook Stuart A. , Widjaja Anissa A. 
Published: January 2021

AbstractIL11 is important for fibrosis in non-alcoholic steatohepatitis (NASH) but its role beyond the stroma in liver disease is unclear. Here, we investigate the role of IL11 in hepatocyte lipotoxicity. Hepatocytes highly express IL11RA and secrete IL11 in response to lipid loading. Autocrine IL11 activity causes hepatocyte death through NOX4-derived ROS, activation of ERK, JNK and caspase-3, impaired mitochondrial function and reduced fatty acid oxidation. Paracrine IL11 activity stimulates hepatic stellate cells and causes fibrosis. In mouse models of NASH, hepatocyte-specific deletion of Il11ra1 protects against liver steatosis, fibrosis and inflammation while reducing serum glucose, cholesterol and triglyceride levels and limiting obesity. In mice deleted for Il11ra1, restoration of IL11 cis-signaling in hepatocytes reconstitutes steatosis and inflammation but not fibrosis. We found no evidence for the existence of IL6 or IL11 trans-signaling in hepatocytes or NASH. These data show that IL11 modulates hepatocyte metabolism and suggests a mechanism for NAFLD to NASH transition.
The role of water in host-guest interaction
Authors: Rizzi Valerio , Bonati Luigi , Ansari Narjes , Parrinello Michele 
Published: January 2021

AbstractOne of the main applications of atomistic computer simulations is the calculation of ligand binding free energies. The accuracy of these calculations depends on the force field quality and on the thoroughness of configuration sampling. Sampling is an obstacle in simulations due to the frequent appearance of kinetic bottlenecks in the free energy landscape. Very often this difficulty is circumvented by enhanced sampling techniques. Typically, these techniques depend on the introduction of appropriate collective variables that are meant to capture the system’s degrees of freedom. In ligand binding, water has long been known to play a key role, but its complex behaviour has proven difficult to fully capture. In this paper we combine machine learning with physical intuition to build a non-local and highly efficient water-describing collective variable. We use it to study a set of host-guest systems from the SAMPL5 challenge. We obtain highly accurate binding free energies and good agreement with experiments. The role of water during the binding process is then analysed in some detail.
Improvement of obesity-associated disorders by a small-molecule drug targeting mitochondria of adipose tissue macrophages
Authors: Wang Yawei , Tang Binlin , Long Lei , Luo Peng , Xiang Wei , Li Xueru , Wang Huilan , Jiang Qingzhi , Tan Xu , Luo Shenglin , Li Huijuan , Wang Ziwen , Chen Zelin , Leng Yu , Jiang Zhongyong , Wang Yang , Ma Le , Wang Rui , Zeng Chunyu , Liu Zujuan , Wang Yu , Miao Hongming , Shi Chunmeng 
Published: January 2021

AbstractPro-inflammatory activation of adipose tissue macrophages (ATMs) is causally linked to obesity and obesity-associated disorders. A number of studies have demonstrated the crucial role of mitochondrial metabolism in macrophage activation. However, there is a lack of pharmaceutical agents to target the mitochondrial metabolism of ATMs for the treatment of obesity-related diseases. Here, we characterize a near-infrared fluorophore (IR-61) that preferentially accumulates in the mitochondria of ATMs and has a therapeutic effect on diet-induced obesity as well as obesity-associated insulin resistance and fatty liver. IR-61 inhibits the classical activation of ATMs by increasing mitochondrial complex levels and oxidative phosphorylation via the ROS/Akt/Acly pathway. Taken together, our findings indicate that specific enhancement of ATMs oxidative phosphorylation improves chronic inflammation and obesity-related disorders. IR-61 might be an anti-inflammatory agent useful for the treatment of obesity-related diseases by targeting the mitochondria of ATMs.
Transcriptional and morphological profiling of parvalbumin interneuron subpopulations in the mouse hippocampus
Authors: Que Lin , Lukacsovich David , Luo Wenshu , Földy Csaba 
Published: January 2021

AbstractThe diversity reflected by >100 different neural cell types fundamentally contributes to brain function and a central idea is that neuronal identity can be inferred from genetic information. Recent large-scale transcriptomic assays seem to confirm this hypothesis, but a lack of morphological information has limited the identification of several known cell types. In this study, we used single-cell RNA-seq in morphologically identified parvalbumin interneurons (PV-INs), and studied their transcriptomic states in the morphological, physiological, and developmental domains. Overall, we find high transcriptomic similarity among PV-INs, with few genes showing divergent expression between morphologically different types. Furthermore, PV-INs show a uniform synaptic cell adhesion molecule (CAM) profile, suggesting that CAM expression in mature PV cells does not reflect wiring specificity after development. Together, our results suggest that while PV-INs differ in anatomy and in vivo activity, their continuous transcriptomic and homogenous biophysical landscapes are not predictive of these distinct identities.
Atomically thin photoanode of InSe/graphene heterostructure
Authors: Zheng Haihong , Lu Yizhen , Ye Kai-Hang , Hu Jinyuan , Liu Shuai , Yan Jiawei , Ye Yu , Guo Yuxi , Lin Zhan , Cheng Jun , Cao Yang 
Published: January 2021

AbstractAchieving high-efficiency photoelectrochemical water splitting requires a better understanding of ion kinetics, e.g., diffusion, adsorption and reactions, near the photoelectrode’s surface. However, with macroscopic three-dimensional electrodes, it is often difficult to disentangle the contributions of surface effects to the total photocurrent from that of various factors in the bulk. Here, we report a photoanode made from a InSe crystal monolayer that is encapsulated with monolayer graphene to ensure high stability. We choose InSe among other photoresponsive two-dimensional (2D) materials because of its unique properties of high mobility and strongly suppressing electron–hole pair recombination. Using the atomically thin electrodes, we obtained a photocurrent with a density >10 mA cm−2 at 1.23 V versus reversible hydrogen electrode, which is several orders of magnitude greater than other 2D photoelectrodes. In addition to the outstanding characteristics of InSe, we attribute the enhanced photocurrent to the strong coupling between the hydroxide ions and photo-generated holes near the anode surface. As a result, a persistent current even after illumination ceased was also observed due to the presence of ions trapped holes with suppressed electron-hole recombination. Our results provide atomically thin materials as a platform for investigating ion kinetics at the electrode surface and shed light on developing next-generation photoelectrodes with high efficiency.
Host CDK-1 and formin mediate microvillar effacement induced by enterohemorrhagic Escherichia coli
Authors: Huang Cheng-Rung , Kuo Cheng-Ju , Huang Chih-Wen , Chen Yu-Ting , Liu Bang-Yu , Lee Chung-Ta , Chen Po-Lin , Chang Wen-Tsan , Chen Yun-Wen , Lee Tzer-Min , Hsieh Hui-Chen , Chen Chang-Shi 
Published: January 2021

AbstractEnterohemorrhagic Escherichia coli (EHEC) induces changes to the intestinal cell cytoskeleton and formation of attaching and effacing lesions, characterized by the effacement of microvilli and then formation of actin pedestals to which the bacteria are tightly attached. Here, we use a Caenorhabditis elegans model of EHEC infection to show that microvillar effacement is mediated by a signalling pathway including mitotic cyclin-dependent kinase 1 (CDK1) and diaphanous-related formin 1 (CYK1). Similar observations are also made using EHEC-infected human intestinal cells in vitro. Our results support the use of C. elegans as a host model for studying attaching and effacing lesions in vivo, and reveal that the CDK1-formin signal axis is necessary for EHEC-induced microvillar effacement.
Genetic and pharmacological inhibition of the nuclear receptor RORα regulates TH17 driven inflammatory disorders
Authors: Wang Ran , Campbell Sean , Amir Mohammed , Mosure Sarah A. , Bassette Molly A. , Eliason Amber , Sundrud Mark S. , Kamenecka Theodore M. , Solt Laura A. 
Published: January 2021

AbstractFull development of IL-17 producing CD4+ T helper cells (TH17 cells) requires the transcriptional activity of both orphan nuclear receptors RORα and RORγt. However, RORα is considered functionally redundant to RORγt; therefore, the function and therapeutic value of RORα in TH17 cells is unclear. Here, using mouse models of autoimmune and chronic inflammation, we show that expression of RORα is required for TH17 cell pathogenicity. T-cell-specific deletion of RORα reduces the development of experimental autoimmune encephalomyelitis (EAE) and colitis. Reduced inflammation is associated with decreased TH17 cell development, lower expression of tissue-homing chemokine receptors and integrins, and increased frequencies of Foxp3+ T regulatory cells. Importantly, inhibition of RORα with a selective small molecule antagonist mostly phenocopies our genetic data, showing potent suppression of the in vivo development of both chronic/progressive and relapsing/remitting EAE, but with no effect on overall thymic cellularity. Furthermore, use of the RORα antagonist effectively inhibits human TH17 cell differentiation and memory cytokine secretion. Together, these data suggest that RORα functions independent of RORγt in programming TH17 pathogenicity and identifies RORα as a safer and more selective therapeutic target for the treatment of TH17-mediated autoimmunity.
Electron cascade for distant spin readout
Authors: van Diepen Cornelis J. , Hsiao Tzu-Kan , Mukhopadhyay Uditendu , Reichl Christian , Wegscheider Werner , Vandersypen Lieven M. K. 
Published: January 2021

AbstractThe spin of a single electron in a semiconductor quantum dot provides a well-controlled and long-lived qubit implementation. The electron charge in turn allows control of the position of individual electrons in a quantum dot array, and enables charge sensors to probe the charge configuration. Here we show that the Coulomb repulsion allows an initial charge transition to induce subsequent charge transitions, inducing a cascade of electron hops, like toppling dominoes. A cascade can transmit information along a quantum dot array over a distance that extends by far the effect of the direct Coulomb repulsion. We demonstrate that a cascade of electrons can be combined with Pauli spin blockade to read out distant spins and show results with potential for high fidelity using a remote charge sensor in a quadruple quantum dot device. We implement and analyse several operating modes for cascades and analyse their scaling behaviour. We also discuss the application of cascade-based spin readout to densely-packed two-dimensional quantum dot arrays with charge sensors placed at the periphery. The high connectivity of such arrays greatly improves the capabilities of quantum dot systems for quantum computation and simulation.
Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer
Authors: Schettini Francesco , Chic Nuria , Brasó-Maristany Fara , Paré Laia , Pascual Tomás , Conte Benedetta , Martínez-Sáez Olga , Adamo Barbara , Vidal Maria , Barnadas Esther , Fernández-Martinez Aranzazu , González-Farre Blanca , Sanfeliu Esther , Cejalvo Juan Miguel , Perrone Giuseppe , Sabarese Giovanna , Zalfa Francesca , Peg Vicente , Fasani Roberta , Villagrasa Patricia , Gavilá Joaquín , Barrios Carlos H. , Lluch Ana , Martín Miguel , Locci Mariavittoria , De Placido Sabino , Prat Aleix 
Published: January 2021

AbstractNovel antibody-drug conjugates against HER2 are showing high activity in HER2-negative breast cancer (BC) with low HER2 expression (i.e., 1+ or 2+ and lack of ERBB2 amplification). However, the clinical and molecular features of HER2-low BC are yet to be elucidated. Here, we collected retrospective clinicopathological and PAM50 data from 3,689 patients with HER2-negative disease and made the following observations. First, the proportion of HER2-low was higher in HR-positive disease (65.4%) than triple-negative BC (TNBC, 36.6%). Second, within HR-positive disease, ERBB2 and luminal-related genes were more expressed in HER2-low than HER2 0. In contrast, no gene was found differentially expressed in TNBC according to HER2 expression. Third, within HER2-low, ERBB2 levels were higher in HR-positive disease than TNBC. Fourth, HER2-low was not associated with overall survival in HR-positive disease and TNBC. Finally, the reproducibility of HER2-low among pathologists was suboptimal. This study emphasizes the large biological heterogeneity of HER2-low BC, and the need to implement reproducible and sensitive assays to measure low HER2 expression.
Epicutaneous immunization with modified vaccinia Ankara viral vectors generates superior T cell immunity against a respiratory viral challenge
Authors: Pan Youdong , Liu Luzheng , Tian Tian , Zhao Jingxia , Park Chang Ook , Lofftus Serena Y. , Stingley Claire A. , Yan Yu , Mei Shenglin , Liu Xing , Kupper Thomas S. 
Published: January 2021

AbstractModified Vaccinia Ankara (MVA) was recently approved as a smallpox vaccine. Variola is transmitted by respiratory droplets and MVA immunization by skin scarification (s.s.) protected mice far more effectively against lethal respiratory challenge with vaccinia virus (VACV) than any other route of delivery, and at lower doses. Comparisons of s.s. with intradermal, subcutaneous, or intramuscular routes showed that MVAOVA s.s.-generated T cells were both more abundant and transcriptionally unique. MVAOVA s.s. produced greater numbers of lung Ova-specific CD8+ TRM and was superior in protecting mice against lethal VACVOVA respiratory challenge. Nearly as many lung TRM were generated with MVAOVA s.s. immunization compared to intra-tracheal immunization with MVAOVA and both routes vaccination protected mice against lethal pulmonary challenge with VACVOVA. Strikingly, MVAOVA s.s.-generated effector T cells exhibited overlapping gene transcriptional profiles to those generated via intra-tracheal immunization. Overall, our data suggest that heterologous MVA vectors immunized via s.s. are uniquely well-suited as vaccine vectors for respiratory pathogens, which may be relevant to COVID-19. In addition, MVA delivered via s.s. could represent a more effective dose-sparing smallpox vaccine.
The influence of water–rock interactions on household well water in an area of high prevalence chronic kidney disease of unknown aetiology (CKDu)
Authors: McDonough Liza K. , Meredith Karina T. , Nikagolla Chandima , Banati Richard B. 
Published: January 2021

AbstractPoor drinking water quality in household wells is hypothesised as being a potential contributor to the high prevalence of chronic kidney disease of uncertain aetiology (CKDu) among the farming communities of the Medawachchiya area, Anuradhapura, Sri Lanka. One of the natural processes that can affect water quality is the dissolution of minerals contained within an aquifer by water–rock interactions (WRIs). Here we present a comprehensive assessment of WRIs and their influence on the water chemistry in household wells and spring waters in the Medawachchiya area by combining measurements of environmental isotopes, such as strontium, lithium and stable carbon isotopes and inorganic chemistry parameters, and modelling geochemical mass balance reactions between rainfall and groundwater samples. Our results reveal the presence of strontium, dissolved from both silicate and carbonate minerals, with high isotopic (87Sr/86Sr) ratios of up to 0.7316. Geochemical mass balance modelling and prior 87Sr/86Sr studies on the Wanni Complex bedrock suggest these strontium values may be the result of biotite dissolution. We also identify lithium and uranium contributed from the dissolution of silicates, albeit at concentrations too low to constitute a known health risk. In contrast, the levels of magnesium and calcium in our samples are high and demonstrate that, despite the felsic bedrock, well water chemistry in the Medawachchiya area is dominated by carbonate dissolution.
Quantitative image analysis of microbial communities with BiofilmQ
Authors: Hartmann Raimo , Jeckel Hannah , Jelli Eric , Singh Praveen K. , Vaidya Sanika , Bayer Miriam , Rode Daniel K. H. , Vidakovic Lucia , Díaz-Pascual Francisco , Fong Jiunn C. N. , Dragoš Anna , Lamprecht Olga , Thöming Janne G. , Netter Niklas , Häussler Susanne , Nadell Carey D. , Sourjik Victor , Kovács Ákos T. , Yildiz Fitnat H. , Drescher Knut 
Published: January 2021

AbstractBiofilms are microbial communities that represent a highly abundant form of microbial life on Earth. Inside biofilms, phenotypic and genotypic variations occur in three-dimensional space and time; microscopy and quantitative image analysis are therefore crucial for elucidating their functions. Here, we present BiofilmQ—a comprehensive image cytometry software tool for the automated and high-throughput quantification, analysis and visualization of numerous biofilm-internal and whole-biofilm properties in three-dimensional space and time.
The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on fermented foods
Authors: Marco Maria L. , Sanders Mary Ellen , Gänzle Michael , Arrieta Marie Claire , Cotter Paul D. , De Vuyst Luc , Hill Colin , Holzapfel Wilhelm , Lebeer Sarah , Merenstein Dan , Reid Gregor , Wolfe Benjamin E. , Hutkins Robert 
Published: January 2021

AbstractAn expert panel was convened in September 2019 by The International Scientific Association for Probiotics and Prebiotics (ISAPP) to develop a definition for fermented foods and to describe their role in the human diet. Although these foods have been consumed for thousands of years, they are receiving increased attention among biologists, nutritionists, technologists, clinicians and consumers. Despite this interest, inconsistencies related to the use of the term ‘fermented’ led the panel to define fermented foods and beverages as “foods made through desired microbial growth and enzymatic conversions of food components”. This definition, encompassing the many varieties of fermented foods, is intended to clarify what is (and is not) a fermented food. The distinction between fermented foods and probiotics is further clarified. The panel also addressed the current state of knowledge on the safety, risks and health benefits, including an assessment of the nutritional attributes and a mechanistic rationale for how fermented foods could improve gastrointestinal and general health. The latest advancements in our understanding of the microbial ecology and systems biology of these foods were discussed. Finally, the panel reviewed how fermented foods are regulated and discussed efforts to include them as a separate category in national dietary guidelines.