bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and implementation of a scalable and versatile test for COVID-19 diagnostics in rural communities
Authors: Ceci A. , Muñoz-Ballester C. , Tegge A. N. , Brown K. L. , Umans R. A. , Michel F. M. , Patel D. , Tewari B. , Martin J. , Alcoreza O. , Maynard T. , Martinez-Martinez D. , Bordwine P. , Bissell N. , Friedlander M. J. , Sontheimer H. , Finkielstein C. V. 
Published: July 2021

AbstractRapid and widespread testing of severe acute respiratory coronavirus 2 (SARS-CoV-2) is essential for an effective public health response aimed at containing and mitigating the coronavirus disease 2019 (COVID-19) pandemic. Successful health policy implementation relies on early identification of infected individuals and extensive contact tracing. However, rural communities, where resources for testing are sparse or simply absent, face distinctive challenges to achieving this success. Accordingly, we report the development of an academic, public land grant University laboratory-based detection assay for the identification of SARS-CoV-2 in samples from various clinical specimens that can be readily deployed in areas where access to testing is limited. The test, which is a quantitative reverse transcription polymerase chain reaction (RT-qPCR)-based procedure, was validated on samples provided by the state laboratory and submitted for FDA Emergency Use Authorization. Our test exhibits comparable sensitivity and exceeds specificity and inclusivity values compared to other molecular assays. Additionally, this test can be re-configured to meet supply chain shortages, modified for scale up demands, and is amenable to several clinical specimens. Test development also involved 3D engineering critical supplies and formulating a stable collection media that allowed samples to be transported for hours over a dispersed rural region without the need for a cold-chain. These two elements that were critical when shortages impacted testing and when personnel needed to reach areas that were geographically isolated from the testing center. Overall, using a robust, easy-to-adapt methodology, we show that an academic laboratory can supplement COVID-19 testing needs and help local health departments assess and manage outbreaks. This additional testing capacity is particularly germane for smaller cities and rural regions that would otherwise be unable to meet the testing demand.
Fully automated fast-flow synthesis of antisense phosphorodiamidate morpholino oligomers
Authors: Li Chengxi , Callahan Alex J. , Simon Mark D. , Totaro Kyle A. , Mijalis Alexander J. , Phadke Kruttika-Suhas , Zhang Genwei , Hartrampf Nina , Schissel Carly K. , Zhou Ming , Zong Hong , Hanson Gunnar J. , Loas Andrei , Pohl Nicola L. B. , Verhoeven David E. , Pentelute Bradley L. 
Published: July 2021

AbstractRapid development of antisense therapies can enable on-demand responses to new viral pathogens and make personalized medicine for genetic diseases practical. Antisense phosphorodiamidate morpholino oligomers (PMOs) are promising candidates to fill such a role, but their challenging synthesis limits their widespread application. To rapidly prototype potential PMO drug candidates, we report a fully automated flow-based oligonucleotide synthesizer. Our optimized synthesis platform reduces coupling times by up to 22-fold compared to previously reported methods. We demonstrate the power of our automated technology with the synthesis of milligram quantities of three candidate therapeutic PMO sequences for an unserved class of Duchenne muscular dystrophy (DMD). To further test our platform, we synthesize a PMO that targets the genomic mRNA of SARS-CoV-2 and demonstrate its antiviral effects. This platform could find broad application not only in designing new SARS-CoV-2 and DMD antisense therapeutics, but also for rapid development of PMO candidates to treat new and emerging diseases.
A low-noise photonic heterodyne synthesizer and its application to millimeter-wave radar
Authors: Kittlaus Eric A. , Eliyahu Danny , Ganji Setareh , Williams Skip , Matsko Andrey B. , Cooper Ken B. , Forouhar Siamak 
Published: July 2021

AbstractMicrowave photonics offers transformative capabilities for ultra-wideband electronic signal processing and frequency synthesis with record-low phase noise levels. Despite the intrinsic bandwidth of optical systems operating at ~200 THz carrier frequencies, many schemes for high-performance photonics-based microwave generation lack broadband tunability, and experience tradeoffs between noise level, complexity, and frequency. An alternative approach uses direct frequency down-mixing of two tunable semiconductor lasers on a fast photodiode. This form of optical heterodyning is frequency-agile, but experimental realizations have been hindered by the relatively high noise of free-running lasers. Here, we demonstrate a heterodyne synthesizer based on ultralow-noise self-injection-locked lasers, enabling highly-coherent, photonics-based microwave and millimeter-wave generation. Continuously-tunable operation is realized from 1-104 GHz, with constant phase noise of -109 dBc/Hz at 100 kHz offset from carrier. To explore its practical utility, we leverage this photonic source as the local oscillator within a 95-GHz frequency-modulated continuous wave (FMCW) radar. Through field testing, we observe dramatic reduction in phase-noise-related Doppler and ranging artifacts as compared to the radar’s existing electronic synthesizer. These results establish strong potential for coherent heterodyne millimeter-wave generation, opening the door to a variety of future applications including high-dynamic range remote sensing, wideband wireless communications, and THz spectroscopy.
A synthetic tubular molecular transport system
Authors: Stömmer Pierre , Kiefer Henrik , Kopperger Enzo , Honemann Maximilian N. , Kube Massimo , Simmel Friedrich C. , Netz Roland R. , Dietz Hendrik 
Published: July 2021

AbstractCreating artificial macromolecular transport systems that can support the movement of molecules along defined routes is a key goal of nanotechnology. Here, we report the bottom-up construction of a macromolecular transport system in which molecular pistons diffusively move through micrometer-long, hollow filaments. The pistons can cover micrometer distances in fractions of seconds. We build the system using multi-layer DNA origami and analyze the structures of the components using transmission electron microscopy. We study the motion of the pistons along the tubes using single-molecule fluorescence microscopy and perform Langevin simulations to reveal details of the free energy surface that directs the motions of the pistons. The tubular transport system achieves diffusivities and displacement ranges known from natural molecular motors and realizes mobility improvements over five orders of magnitude compared to previous artificial random walker designs. Electric fields can also be employed to actively pull the pistons along the filaments, thereby realizing a nanoscale electric rail system. Our system presents a platform for artificial motors that move autonomously driven by chemical fuels and for performing nanotribology studies, and it could form a basis for future molecular transportation networks.
Self-healing polyurethane-elastomer with mechanical tunability for multiple biomedical applications in vivo
Authors: Jiang Chenyu , Zhang Luzhi , Yang Qi , Huang Shixing , Shi Hongpeng , Long Qiang , Qian Bei , Liu Zenghe , Guan Qingbao , Liu Mingjian , Yang Renhao , Zhao Qiang , You Zhengwei , Ye Xiaofeng 
Published: July 2021

AbstractThe unique properties of self-healing materials hold great potential in the field of biomedical engineering. Although previous studies have focused on the design and synthesis of self-healing materials, their application in in vivo settings remains limited. Here, we design a series of biodegradable and biocompatible self-healing elastomers (SHEs) with tunable mechanical properties, and apply them to various disease models in vivo, in order to test their reparative potential in multiple tissues and at physiological conditions. We validate the effectiveness of SHEs as promising therapies for aortic aneurysm, nerve coaptation and bone immobilization in three animal models. The data presented here support the translation potential of SHEs in diverse settings, and pave the way for the development of self-healing materials in clinical contexts.
High-depth spatial transcriptome analysis by photo-isolation chemistry
Authors: Honda Mizuki , Oki Shinya , Kimura Ryuichi , Harada Akihito , Maehara Kazumitsu , Tanaka Kaori , Meno Chikara , Ohkawa Yasuyuki 
Published: July 2021

AbstractIn multicellular organisms, expression profiling in spatially defined regions is crucial to elucidate cell interactions and functions. Here, we establish a transcriptome profiling method coupled with photo-isolation chemistry (PIC) that allows the determination of expression profiles specifically from photo-irradiated regions of interest. PIC uses photo-caged oligodeoxynucleotides for in situ reverse transcription. PIC transcriptome analysis detects genes specifically expressed in small distinct areas of the mouse embryo. Photo-irradiation of single cells demonstrated that approximately 8,000 genes were detected with 7 × 104 unique read counts. Furthermore, PIC transcriptome analysis is applicable to the subcellular and subnuclear microstructures (stress granules and nuclear speckles, respectively), where hundreds of genes can be detected as being specifically localised. The spatial density of the read counts is higher than 100 per square micrometre. Thus, PIC enables high-depth transcriptome profiles to be determined from limited regions up to subcellular and subnuclear resolutions.
Fundamental limitations on distillation of quantum channel resources
Authors: Regula Bartosz , Takagi Ryuji 
Published: July 2021

AbstractQuantum channels underlie the dynamics of quantum systems, but in many practical settings it is the channels themselves that require processing. We establish universal limitations on the processing of both quantum states and channels, expressed in the form of no-go theorems and quantitative bounds for the manipulation of general quantum channel resources under the most general transformation protocols. Focusing on the class of distillation tasks — which can be understood either as the purification of noisy channels into unitary ones, or the extraction of state-based resources from channels — we develop fundamental restrictions on the error incurred in such transformations, and comprehensive lower bounds for the overhead of any distillation protocol. In the asymptotic setting, our results yield broadly applicable bounds for rates of distillation. We demonstrate our results through applications to fault-tolerant quantum computation, where we obtain state-of-the-art lower bounds for the overhead cost of magic state distillation, as well as to quantum communication, where we recover a number of strong converse bounds for quantum channel capacity.
TEM8 marks neovasculogenic tumor-initiating cells in triple-negative breast cancer
Authors: Xu Jiahui , Yang Xiaoli , Deng Qiaodan , Yang Cong , Wang Dong , Jiang Guojuan , Yao Xiaohong , He Xueyan , Ding Jiajun , Qiang Jiankun , Tu Juchuanli , zhang Rui , Lei Qun-Ying , Shao Zhi-min , Bian Xiuwu , Hu Ronggui , Zhang Lixing , Liu Suling 
Published: July 2021

AbstractEnhanced neovasculogenesis, especially vasculogenic mimicry (VM), contributes to the development of triple-negative breast cancer (TNBC). Breast tumor-initiating cells (BTICs) are involved in forming VM; however, the specific VM-forming BTIC population and the regulatory mechanisms remain undefined. We find that tumor endothelial marker 8 (TEM8) is abundantly expressed in TNBC and serves as a marker for VM-forming BTICs. Mechanistically, TEM8 increases active RhoC level and induces ROCK1-mediated phosphorylation of SMAD5, in a cascade essential for promoting stemness and VM capacity of breast cancer cells. ASB10, an estrogen receptor ERα trans-activated E3 ligase, ubiquitylates TEM8 for degradation, and its deficiency in TNBC resulted in a high homeostatic level of TEM8. In this work, we identify TEM8 as a functional marker for VM-forming BTICs in TNBC, providing a target for the development of effective therapies against TNBC targeting both BTIC self-renewal and neovasculogenesis simultaneously.
Appropriate sampling methods and statistics can tell apart fraud from pesticide drift in organic farming
Authors: Benzing Albrecht , Piepho Hans-Peter , Malik Waqas Ahmed , Finckh Maria R. , Mittelhammer Manuel , Strempel Dominic , Jaschik Johannes , Neuendorff Jochen , Guamán Liliana , Mancheno José , Melo Luis , Pavón Omar , Cangahuamín Roberto , Ullauri Juan-Carlos 
Published: July 2021

AbstractPesticide residues are much lower in organic than in conventional food. The article summarizes the available residue data from the EU and the U.S. organic market. Differences between samples from several sources suggest that organic products are declared conventional, when they have residues—but the origin of the residues is not always investigated. A large number of samples are being tested by organic certifiers, but the sampling methods often do not allow to determine if such residues stem from prohibited pesticide use by organic farmers, from mixing organic with conventional products, from short-range spray-drift from neighbour farms, from the ubiquitous presence of such substances due to long-distance drift, or from other sources of contamination. Eight case studies from different crops and countries are used to demonstrate that sampling at different distances from possible sources of short-distance drift in most cases allows differentiating deliberate pesticide application by the organic farmer from drift. Datasets from 67 banana farms in Ecuador, where aerial fungicide spraying leads to a heavy drift problem, were subjected to statistical analysis. A linear discriminant function including four variables was identified for distinguishing under these conditions application from drift, with an accuracy of 93.3%.
Noise reduction in X-ray photon correlation spectroscopy with convolutional neural networks encoder–decoder models
Authors: Konstantinova Tatiana , Wiegart Lutz , Rakitin Maksim , DeGennaro Anthony M. , Barbour Andi M. 
Published: July 2021

AbstractLike other experimental techniques, X-ray photon correlation spectroscopy is subject to various kinds of noise. Random and correlated fluctuations and heterogeneities can be present in a two-time correlation function and obscure the information about the intrinsic dynamics of a sample. Simultaneously addressing the disparate origins of noise in the experimental data is challenging. We propose a computational approach for improving the signal-to-noise ratio in two-time correlation functions that is based on convolutional neural network encoder–decoder (CNN-ED) models. Such models extract features from an image via convolutional layers, project them to a low dimensional space and then reconstruct a clean image from this reduced representation via transposed convolutional layers. Not only are ED models a general tool for random noise removal, but their application to low signal-to-noise data can enhance the data’s quantitative usage since they are able to learn the functional form of the signal. We demonstrate that the CNN-ED models trained on real-world experimental data help to effectively extract equilibrium dynamics’ parameters from two-time correlation functions, containing statistical noise and dynamic heterogeneities. Strategies for optimizing the models’ performance and their applicability limits are discussed.
Development and validation of HPLC-MS2 methodology for the accurate determination of C4–C8 B-type flavanols and procyanidins
Authors: Bussy Ugo , Olanrewaju Yusuf , Crozier Alan , Ottaviani Javier , Kwik-Uribe Catherine 
Published: July 2021

AbstractCocoa flavanols and procyanidins (CFs), natural dietary bioactives, have been studied extensively over the past two decades for their potential health benefits. Research on their safety and efficacy is critically dependent upon on the ability to reliably characeterize the research materials that are utilized, and with growing consumer availability of CF-based products, reliable methods for the detection of potential adulteration are of increasing importance. This research focused on the development of a high performance liquid chromatography-tandem mass spectrometry method (HPLC-MS2) using primary standards and 13C-labelled procyanidins as internal standards. The ability of MS2 detection to discriminate A- and B-type procyanidins was demonstrated. Method performances were validated for degrees of polymerization up to four in seven model food matrices. Accuracy ranged from 90.9 to 125.4% and precision was < 10% at lower concentrations. Finally, the method was applied to cocoa-based samples and compared to the AOAC 2020.05 analytical protocol, supporting the use of NIST 8403 as reference material for HPLC-MS2 analysis.
Multi-omics integration of methyltransferase-like protein family reveals clinical outcomes and functional signatures in human cancer
Authors: Campeanu Ion John , Jiang Yuanyuan , Liu Lanxin , Pilecki Maksymilian , Najor Alvina , Cobani Era , Manning Morenci , Zhang Xiaohong Mary , Yang Zeng-Quan 
Published: July 2021

AbstractHuman methyltransferase-like (METTL) proteins transfer methyl groups to nucleic acids, proteins, lipids, and other small molecules, subsequently playing important roles in various cellular processes. In this study, we performed integrated genomic, transcriptomic, proteomic, and clinicopathological analyses of 34 METTLs in a large cohort of primary tumor and cell line data. We identified a subset of METTL genes, notably METTL1, METTL7B, and NTMT1, with high frequencies of genomic amplification and/or up-regulation at both the mRNA and protein levels in a spectrum of human cancers. Higher METTL1 expression was associated with high-grade tumors and poor disease prognosis. Loss-of-function analysis in tumor cell lines indicated the biological importance of METTL1, an m7G methyltransferase, in cancer cell growth and survival. Furthermore, functional annotation and pathway analysis of METTL1-associated proteins revealed that, in addition to the METTL1 cofactor WDR4, RNA regulators and DNA packaging complexes may be functionally interconnected with METTL1 in human cancer. Finally, we generated a crystal structure model of the METTL1–WDR4 heterodimeric complex that might aid in understanding the key functional residues. Our results provide new information for further functional study of some METTL alterations in human cancer and might lead to the development of small inhibitors that target cancer-promoting METTLs.
Quantification of pedogenic particles masked by geogenic magnetic fraction
Authors: Szuszkiewicz Marcin , Grison Hana , Petrovský Eduard , Szuszkiewicz Maria Magdalena , Gołuchowska Beata , Łukasik Adam 
Published: July 2021

AbstractPedogenic magnetic fraction in soils is attributed to fine-grained particles, i.e. superparamagnetic grains. In the case of a strongly magnetic geogenic fraction, pedogenic magnetic contribution is hard to detect. To the best of our knowledge, detailed research into the masking of pedogenic superparamagnetic grains and quantification of this effect has not yet been carried out. The principal aim of our research is to quantify the influence of coarse-grained ferrimagnetic fraction on the detection of the superparamagnetic grains. In order to describe the masking phenomenon, volume and frequency-dependent magnetic susceptibility were determined on a set of laboratory prepared samples composed of natural substances: a diamagnetic quartz matrix, detrital coarse-grained ferrimagnetic crystals from alkaline and ultra-alkaline igneous rocks, and superparamagnetic soil concretions formed in the Haplic Cambisol. Mineralogy, concentration, type and grain size of the tested material were described by parameters of environmental magnetism. The magnetic parameters distinguish both geogenic multidomain and pedogenic superparamagnetic grains. The magnetic signal of the superparamagnetic grains is gradually masked by the increasing proportion of multidomain grains of magnetite/maghemite. The experiment clearly describes the masking effect and brings new insight to studies dealing with strongly magnetic soils of natural and/or highly contaminated origin as a tool for estimation of superparamagnetic pedogenic contribution.
Probing cerebellar involvement in cognition through a meta-analysis of TMS evidence
Authors: Gatti Daniele , Rinaldi Luca , Cristea Ioana , Vecchi Tomaso 
Published: July 2021

AbstractTraditionally, the cerebellum has been linked to motor coordination, but growing evidence points to its involvement in a wide range of non-motor functions. Though the number of studies using transcranial magnetic stimulation (TMS) to investigate cerebellar involvement in cognitive processes is growing exponentially, these findings have not yet been synthesized in a meta-analysis. Here, we used meta-analysis to estimate the effects of cerebellar TMS on performance in cognitive tasks for healthy participants. Outcomes included participants’ accuracy and response times (RTs) of several non-motor tasks performed either during or after the administration of TMS. We included overall 41 studies, of which 44 single experiments reported effects on accuracy and 41 on response times (RTs). The meta-analyses showed medium effect sizes (for accuracy: d = 0.61 [95% CI = 0.48, .073]; for RTs: d = 0.40 [95% CI = 0.30, 0.49]), with leave-one-out analyses indicating that cumulative effects were robust, and with moderate heterogeneity. For both accuracy and RTs, the effect of TMS was moderated by the stimulation paradigm adopted but not by the cognitive function investigated, while the timing of the stimulation moderated only the effects on RTs. Further analyses on lateralization revealed no moderation effects of the TMS site. Taken together, these findings indicate that TMS administered over the cerebellum is able to modulate cognitive performance, affecting accuracy or RTs, and suggest that the various stimulation paradigms play a key role in determining the efficacy of cerebellar TMS.