bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-assembly of tessellated tissue sheets by expansion and collision
Authors: Heinrich Matthew A. , Alert Ricard , Wolf Abraham E. , Košmrlj Andrej , Cohen Daniel J. 
Published: July 2022

AbstractTissues do not exist in isolation—they interact with other tissues within and across organs. While cell-cell interactions have been intensely investigated, less is known about tissue-tissue interactions. Here, we studied collisions between monolayer tissues with different geometries, cell densities, and cell types. First, we determine rules for tissue shape changes during binary collisions and describe complex cell migration at tri-tissue boundaries. Next, we propose that genetically identical tissues displace each other based on pressure gradients, which are directly linked to gradients in cell density. We present a physical model of tissue interactions that allows us to estimate the bulk modulus of the tissues from collision dynamics. Finally, we introduce TissEllate, a design tool for self-assembling complex tessellations from arrays of many tissues, and we use cell sheet engineering techniques to transfer these composite tissues like cellular films. Overall, our work provides insight into the mechanics of tissue collisions, harnessing them to engineer tissue composites as designable living materials.
Electrical resistance of the current collector controls lithium morphology
Authors: Oyakhire Solomon T. , Zhang Wenbo , Shin Andrew , Xu Rong , Boyle David T. , Yu Zhiao , Ye Yusheng , Yang Yufei , Raiford James A. , Huang William , Schneider Joel R. , Cui Yi , Bent Stacey F. 
Published: July 2022

AbstractThe electrodeposition of low surface area lithium is critical to successful adoption of lithium metal batteries. Here, we discover the dependence of lithium metal morphology on electrical resistance of substrates, enabling us to design an alternative strategy for controlling lithium morphology and improving electrochemical performance. By modifying the current collector with atomic layer deposited conductive (ZnO, SnO2) and resistive (Al2O3) nanofilms, we show that conductive films promote the formation of high surface area lithium deposits, whereas highly resistive films promote the formation of lithium clusters of low surface area. We reveal an electrodeposition mechanism in which radial diffusion of electroactive species is promoted on resistive substrates, resulting in lateral growth of large (150 µm in diameter) planar lithium deposits. Using resistive substrates, similar lithium morphologies are formed in three distinct classes of electrolytes, resulting in up to ten-fold improvement in battery performance. Ultimately, we report anode-free pouch cells using the Al2O3-modified copper that maintain 60 % of their initial discharge capacity after 100 cycles, displaying the benefits of resistive substrates for controlling lithium electrodeposition.
An LNA-amide modification that enhances the cell uptake and activity of phosphorothioate exon-skipping oligonucleotides
Authors: Baker Ysobel R. , Thorpe Cameron , Chen Jinfeng , Poller Laura M. , Cox Lina , Kumar Pawan , Lim Wooi F. , Lie Lillian , McClorey Graham , Epple Sven , Singleton Daniel , McDonough Michael A. , Hardwick Jack S. , Christensen Kirsten E. , Wood Matthew J. A. , Hall James P. , El-Sagheer Afaf H. , Brown Tom 
Published: July 2022

AbstractOligonucleotides that target mRNA have great promise as therapeutic agents for life-threatening conditions but suffer from poor bioavailability, hence high cost. As currently untreatable diseases come within the reach of oligonucleotide therapies, new analogues are urgently needed to address this. With this in mind we describe reduced-charge oligonucleotides containing artificial LNA-amide linkages with improved gymnotic cell uptake, RNA affinity, stability and potency. To construct such oligonucleotides, five LNA-amide monomers (A, T, C, 5mC and G), where the 3′-OH is replaced by an ethanoic acid group, are synthesised in good yield and used in solid-phase oligonucleotide synthesis to form amide linkages with high efficiency. The artificial backbone causes minimal structural deviation to the DNA:RNA duplex. These studies indicate that splice-switching oligonucleotides containing LNA-amide linkages and phosphorothioates display improved activity relative to oligonucleotides lacking amides, highlighting the therapeutic potential of this technology.
Deciphering polymorphism in 61,157 Escherichia coli genomes via epistatic sequence landscapes
Authors: Vigué Lucile , Croce Giancarlo , Petitjean Marie , Ruppé Etienne , Tenaillon Olivier , Weigt Martin 
Published: July 2022

AbstractCharacterizing the effect of mutations is key to understand the evolution of protein sequences and to separate neutral amino-acid changes from deleterious ones. Epistatic interactions between residues can lead to a context dependence of mutation effects. Context dependence constrains the amino-acid changes that can contribute to polymorphism in the short term, and the ones that can accumulate between species in the long term. We use computational approaches to accurately predict the polymorphisms segregating in a panel of 61,157 Escherichia coli genomes from the analysis of distant homologues. By comparing a context-aware Direct-Coupling Analysis modelling to a non-epistatic approach, we show that the genetic context strongly constrains the tolerable amino acids in 30% to 50% of amino-acid sites. The study of more distant species suggests the gradual build-up of genetic context over long evolutionary timescales by the accumulation of small epistatic contributions.
Single-cell analysis highlights differences in druggable pathways underlying adaptive or fibrotic kidney regeneration
Authors: Balzer Michael S. , Doke Tomohito , Yang Ya-Wen , Aldridge Daniel L. , Hu Hailong , Mai Hung , Mukhi Dhanunjay , Ma Ziyuan , Shrestha Rojesh , Palmer Matthew B. , Hunter Christopher A. , Susztak Katalin 
Published: July 2022

AbstractThe kidney has tremendous capacity to repair after acute injury, however, pathways guiding adaptive and fibrotic repair are poorly understood. We developed a model of adaptive and fibrotic kidney regeneration by titrating ischemic injury dose. We performed detailed biochemical and histological analysis and profiled transcriptomic changes at bulk and single-cell level (> 110,000 cells) over time. Our analysis highlights kidney proximal tubule cells as key susceptible cells to injury. Adaptive proximal tubule repair correlated with fatty acid oxidation and oxidative phosphorylation. We identify a specific maladaptive/profibrotic proximal tubule cluster after long ischemia, which expresses proinflammatory and profibrotic cytokines and myeloid cell chemotactic factors. Druggability analysis highlights pyroptosis/ferroptosis as vulnerable pathways in these profibrotic cells. Pharmacological targeting of pyroptosis/ferroptosis in vivo pushed cells towards adaptive repair and ameliorates fibrosis. In summary, our single-cell analysis defines key differences in adaptive and fibrotic repair and identifies druggable pathways for pharmacological intervention to prevent kidney fibrosis.
Gas permeation through graphdiyne-based nanoporous membranes
Authors: Zhou Zhihua , Tan Yongtao , Yang Qian , Bera Achintya , Xiong Zecheng , Yagmurcukardes Mehmet , Kim Minsoo , Zou Yichao , Wang Guanghua , Mishchenko Artem , Timokhin Ivan , Wang Canbin , Wang Hao , Yang Chongyang , Lu Yizhen , Boya Radha , Liao Honggang , Haigh Sarah , Liu Huibiao , Peeters Francois M. , Li Yuliang , Geim Andre K. , Hu Sheng 
Published: July 2022

AbstractNanoporous membranes based on two dimensional materials are predicted to provide highly selective gas transport in combination with extreme permeance. Here we investigate membranes made from multilayer graphdiyne, a graphene-like crystal with a larger unit cell. Despite being nearly a hundred of nanometers thick, the membranes allow fast, Knudsen-type permeation of light gases such as helium and hydrogen whereas heavy noble gases like xenon exhibit strongly suppressed flows. Using isotope and cryogenic temperature measurements, the seemingly conflicting characteristics are explained by a high density of straight-through holes (direct porosity of ∼0.1%), in which heavy atoms are adsorbed on the walls, partially blocking Knudsen flows. Our work offers important insights into intricate transport mechanisms playing a role at nanoscale.
Ductal keratin 15+ luminal progenitors in normal breast exhibit a basal-like breast cancer transcriptomic signature
Authors: Kohler Katharina Theresa , Goldhammer Nadine , Demharter Samuel , Pfisterer Ulrich , Khodosevich Konstantin , Rønnov-Jessen Lone , Petersen Ole William , Villadsen René , Kim Jiyoung 
Published: July 2022

AbstractNormal breast luminal epithelial progenitors have been implicated as cell of origin in basal-like breast cancer, but their anatomical localization remains understudied. Here, we combine collection under the microscope of organoids from reduction mammoplasties and single-cell mRNA sequencing (scRNA-seq) of FACS-sorted luminal epithelial cells with multicolor imaging to profile ducts and terminal duct lobular units (TDLUs) and compare them with breast cancer subtypes. Unsupervised clustering reveals eleven distinct clusters and a differentiation trajectory starting with keratin 15+ (K15+) progenitors enriched in ducts. Spatial mapping of luminal progenitors is confirmed at the protein level by staining with critical duct markers. Comparison of the gene expression profiles of normal luminal cells with those of breast cancer subtypes suggests a strong correlation between normal breast ductal progenitors and basal-like breast cancer. We propose that K15+ basal-like breast cancers originate in ductal progenitors, which emphasizes the importance of not only lineages but also cellular position within the ductal-lobular tree.
Classifying handedness in chiral nanomaterials using label error robust deep learning
Authors: Groschner C. K. , Pattison Alexander J. , Ben-Moshe Assaf , Alivisatos A. Paul , Theis Wolfgang , Scott M. C. 
Published: July 2022

AbstractHigh-throughput scanning electron microscopy (SEM) coupled with classification using neural networks is an ideal method to determine the morphological handedness of large populations of chiral nanoparticles. Automated labeling removes the time-consuming manual labeling of training data, but introduces label error, and subsequently classification error in the trained neural network. Here, we evaluate methods to minimize classification error when training from automated labels of SEM datasets of chiral Tellurium nanoparticles. Using the mirror relationship between images of opposite handed particles, we artificially create populations of varying label error. We analyze the impact of label error rate and training method on the classification error of neural networks on an ideal dataset and on a practical dataset. Of the three training methods considered, we find that a pretraining approach yields the most accurate results across label error rates on ideal datasets, where size and other morphological variables are held constant, but that a co-teaching approach performs the best in practical application.
A geospatial inventory of regulatory information for wine protected designations of origin in Europe
Authors: Candiago Sebastian , Tscholl Simon , Bassani Leonardo , Fraga Helder , Egarter Vigl Lukas 
Published: July 2022

AbstractThe Wine Protected Designation of Origin (PDO) label is a European quality scheme that protects high quality wines by linking them to legally defined geographic areas and a set of specific production practices. Because of the tight relation between PDO wines and the specifications defined in the official regulatory documents, these products are highly susceptible to changes in climatic, environmental, or socioeconomic conditions. However, the content of these regulatory documents has never been systematically analysed and summarized in a single dataset. Here, we present the first geospatial inventory that organizes regulatory information about the 1177 wine PDO in Europe based on the documents from the official EU geographical indication register. It includes essential legal information that defines the wine PDO such as the geographic boundaries, authorized cultivars and maximum yields. This inventory opens new possibilities for researchers to accurately assess, compare and map the regulatory information in each wine region at an unprecedented level of detail, supporting decision makers in developing adaptation strategies for the preservation of PDO wine regions.
Data-driven discovery of the governing equations of dynamical systems via moving horizon optimization
Authors: Lejarza Fernando , Baldea Michael 
Published: July 2022

AbstractDiscovering the governing laws underpinning physical and chemical phenomena entirely from data is a key step towards understanding and ultimately controlling systems in science and engineering. Noisy measurements and complex, highly nonlinear underlying dynamics hinder the identification of such governing laws. In this work, we introduce a machine learning framework rooted in moving horizon nonlinear optimization for identifying governing equations in the form of ordinary differential equations from noisy experimental data sets. Our approach evaluates sequential subsets of measurement data, and exploits statistical arguments to learn truly parsimonious governing equations from a large dictionary of basis functions. The proposed framework reduces gradient approximation errors by implicitly embedding an advanced numerical discretization scheme, which improves robustness to noise as well as to model stiffness. Canonical nonlinear dynamical system examples are used to demonstrate that our approach can accurately recover parsimonious governing laws under increasing levels of measurement noise, and outperform state of the art frameworks in the literature. Further, we consider a non-isothermal chemical reactor example to demonstrate that the proposed framework can cope with basis functions that have nonlinear (unknown) parameterizations.
Stochastic model of ERK-mediated progesterone receptor translocation, clustering and transcriptional activity
Authors: Marquez-Lago Tatiana T. , Steinberg Stanly 
Published: July 2022

AbstractProgesterone receptor (PR) transcriptional activity is a key factor in the differentiation of the uterine endometrium. By consequence, progestin has been identified as an important treatment modality for endometrial cancer. PR transcriptional activity is controlled by extracellular-signal-regulated kinase (ERK) mediated phosphorylation, downstream of growth factor receptors such as EGFR. However, phosphorylation of PR also targets it for ubiquitination and destruction in the proteasome. Quantitative studies of these opposing roles are much needed toward validation of potential new progestin-based therapeutics. In this work, we propose a spatial stochastic model to study the effects of the opposing roles for PR phosphorylation on the levels of active transcription factor. Our numerical simulations confirm earlier in vitro experiments in endometrial cancer cell lines, identifying clustering as a mechanism that amplifies the ability of progesterone receptors to influence gene transcription. We additionally show the usefulness of a statistical method we developed to quantify and control variations in stochastic simulations in general biochemical systems, assisting modelers in defining minimal but meaningful numbers of simulations while guaranteeing outputs remain within a pre-defined confidence level.
Intrauterine growth restriction and its impact on intestinal morphophysiology throughout postnatal development in pigs
Authors: Santos Thaís Garcia , Fernandes Saffir Dominique , de Oliveira Araújo Stefany Bruna , Felicioni Fernando , de Mérici Domingues e Paula Thaís , Caldeira-Brant André Lucas , Ferreira Soraia Viana , de Paula Naves Luciana , de Souza Stefânia Priscilla , Campos Paulo Henrique Reis Furtado , Chiarini-Garcia Hélio , Dias Ana Luísa Neves Alvarenga , de Almeida Fernanda Radicchi Campos Lobato 
Published: July 2022

AbstractIntrauterine growth restriction (IUGR) compromises fetal development, leading to low birth weight, and predisposes to gastrointestinal disorders. Pigs that suffered IUGR present poor postnatal development, resulting in great economic losses to the industry. The small intestine may be involved with impaired development, but studies investigating this issue are still limited. Thus, the present study aimed to investigate small intestine morphofunctional alterations in IUGR pigs throughout the production phases (birth to 150 days). IUGR pigs presented lower body weight from birth to the finishing phase (P < 0.05). Although histomorphometrical parameters were not affected during the pre-weaning period, their commitment was observed specifically in the duodenum of the IUGR group at older ages (P < 0.05). The most detrimental effects on the small intestine, such as deeper duodenum crypts’ depth, lower villus height:crypt depth ratio and absorptive area, increased apoptosis and lower proliferation of the duodenum epithelium were noticed at 70 days of age (P < 0.05). Additionally, IUGR pigs presented the lowest chymotrypsin and amylase activities at 70 and 150 days of age, respectively (P < 0.05). These findings may contribute to the elucidation of morphofunctional disorders of the small intestine in IUGR pigs throughout the different production phases, suggesting that poor postnatal development may be due to intestinal damage.
On the mechanism of marine fouling-prevention performance of oil-containing silicone elastomers
Authors: Kolle Stefan , Ahanotu Onyemaechi , Meeks Amos , Stafslien Shane , Kreder Michael , Vanderwal Lyndsi , Cohen Lucas , Waltz Grant , Lim Chin Sing , Slocum Dave , Greene Elisa Maldonado , Hunsucker Kelli , Swain Geoffrey , Wendt Dean , Teo Serena Lay-Ming , Aizenberg Joanna 
Published: July 2022

AbstractFor many decades, silicone elastomers with oil incorporated have served as fouling-release coating for marine applications. In a comprehensive study involving a series of laboratory-based marine fouling assays and extensive global field studies of up to 2-year duration, we compare polydimethylsiloxane (PDMS) coatings of the same composition loaded with oil via two different methods. One method used a traditional, one-pot pre-cure oil addition approach (o-PDMS) and another method used a newer post-cure infusion approach (i-PDMS). The latter displays a substantial improvement in biofouling prevention performance that exceeds established commercial silicone-based fouling-release coating standards. We interpret the differences in performance between one-pot and infused PDMS by developing a mechanistic model based on the Flory–Rehner theory of swollen polymer networks. Using this model, we propose that the chemical potential of the incorporated oil is a key consideration for the design of future fouling-release coatings, as the improved performance is driven by the formation and stabilization of an anti-adhesion oil overlayer on the polymer surface.
A human IgM enriched immunoglobulin preparation, Pentaglobin, reverses autoimmune diabetes without immune suppression in NOD mice
Authors: Wilson Christopher S. , Hoopes Emilee M. , Falk Alexander C. , Moore Daniel J. 
Published: July 2022

AbstractThe immune system of healthy individuals is capable of regulating autoimmunity through multiple mechanisms. In Type 1 Diabetes (T1D) we recently discovered natural IgM, although present at normal levels, is unable to perform its normal immunoregulatory function. Treating diabetic mice with IgM from healthy donors led to reversal of disease without immune depletion. To investigate the therapeutic potential of a human preparation of IgM, we administered an IgM-enriched preparation of immunoglobulin called Pentaglobin. Administration of Pentaglobin therapy reversed disease in diabetic NOD mice and boosted CD4 + Foxp3 + Tregs. Importantly, the impact of Pentaglobin on the immune system was limited to inhibiting beta cell destruction but was not immune depleting nor did it inhibit the immunization response to an irrelevant antigen. These findings indicate that inhibition of deleterious autoimmunity in T1D is possible while leaving protective immunity fully intact.
Reduced cerebral vascular fractal dimension among asymptomatic individuals as a potential biomarker for cerebral small vessel disease
Authors: Aminuddin Niferiti , Achuthan Anusha , Ruhaiyem Nur Intan Raihana , Che Mohd Nassir Che Mohd Nasril , Idris Nur Suhaila , Mustapha Muzaimi 
Published: July 2022

AbstractCerebral small vessel disease is a neurological disease frequently found in the elderly and detected on neuroimaging, often as an incidental finding. White matter hyperintensity is one of the most commonly reported neuroimaging markers of CSVD and is linked with an increased risk of future stroke and vascular dementia. Recent attention has focused on the search of CSVD biomarkers. The objective of this study is to explore the potential of fractal dimension as a vascular neuroimaging marker in asymptomatic CSVD with low WMH burden. Df is an index that measures the complexity of a self-similar and irregular structure such as circle of Willis and its tributaries. This exploratory cross-sectional study involved 22 neurologically asymptomatic adult subjects (42 ± 12 years old; 68% female) with low to moderate 10-year cardiovascular disease risk prediction score (QRISK2 score) who underwent magnetic resonance imaging/angiography (MRI/MRA) brain scan. Based on the MRI findings, subjects were divided into two groups: subjects with low WMH burden and no WMH burden, (WMH+; n = 8) and (WMH−; n = 14) respectively. Maximum intensity projection image was constructed from the 3D time-of-flight (TOF) MRA. The complexity of the CoW and its tributaries observed in the MIP image was characterised using Df. The Df of the CoW and its tributaries, i.e., Df (w) was significantly lower in the WMH+ group (1.5172 ± 0.0248) as compared to WMH− (1.5653 ± 0.0304, p = 0.001). There was a significant inverse relationship between the QRISK2 risk score and Df (w), (rs = − .656, p = 0.001). Df (w) is a promising, non-invasive vascular neuroimaging marker for asymptomatic CSVD with WMH. Further study with multi-centre and long-term follow-up is warranted to explore its potential as a biomarker in CSVD and correlation with clinical sequalae of CSVD.