bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prime editing with genuine Cas9 nickases minimizes unwanted indels
Authors: Lee Jaesuk , Lim Kayeong , Kim Annie , Mok Young Geun , Chung Eugene , Cho Sung-Ik , Lee Ji Min , Kim Jin-Soo 
Published: March 2023

AbstractUnlike CRISPR-Cas9 nucleases, which yield DNA double-strand breaks (DSBs), Cas9 nickases (nCas9s), which are created by replacing key catalytic amino-acid residues in one of the two nuclease domains of S. pyogenesis Cas9 (SpCas9), produce nicks or single-strand breaks. Two SpCas9 variants, namely, nCas9 (D10A) and nCas9 (H840A), which cleave target (guide RNA-pairing) and non-target DNA strands, respectively, are widely used for various purposes, including paired nicking, homology-directed repair, base editing, and prime editing. In an effort to define the off-target nicks caused by these nickases, we perform Digenome-seq, a method based on whole genome sequencing of genomic DNA treated with a nuclease or nickase of interest, and find that nCas9 (H840A) but not nCas9 (D10A) can cleave both strands, producing unwanted DSBs, albeit less efficiently than wild-type Cas9. To inactivate the HNH nuclease domain further, we incorporate additional mutations into nCas9 (H840A). Double-mutant nCas9 (H840A + N863A) does not exhibit the DSB-inducing behavior in vitro and, either alone or in fusion with the M-MLV reverse transcriptase (prime editor, PE2 or PE3), induces a lower frequency of unwanted indels, compared to nCas9 (H840A), caused by error-prone repair of DSBs. When incorporated into prime editor and used with engineered pegRNAs (ePE3), we find that the nCas9 variant (H840A + N854A) dramatically increases the frequency of correct edits, but not unwanted indels, yielding the highest purity of editing outcomes compared to nCas9 (H840A).
Widespread natural methane and oil leakage from sub-marine Arctic reservoirs
Authors: Serov Pavel , Mattingsdal Rune , Winsborrow Monica , Patton Henry , Andreassen Karin 
Published: March 2023

AbstractParceling the anthropogenic and natural (geological) sources of fossil methane in the atmosphere remains problematic due to a lack of distinctive chemical markers for their discrimination. In this light, understanding the distribution and contribution of potential geological methane sources is important. Here we present empirical observations of hitherto undocumented, widespread and extensive methane and oil release from geological reservoirs to the Arctic Ocean. Methane fluxes from >7000 seeps significantly deplete in seawater, but nevertheless reach the sea surface and may transfer to the air. Oil slick emission spots and gas ebullition are persistent across multi-year observations and correlate to formerly glaciated geological structures, which have experienced km-scale glacial erosion that has left hydrocarbon reservoirs partially uncapped since the last deglaciation ~15,000 years ago. Such persistent, geologically controlled, natural hydrocarbon release may be characteristic of formerly glaciated hydrocarbon-bearing basins which are common across polar continental shelves, and could represent an underestimated source of natural fossil methane within the global carbon cycle.
Long-range skin Josephson supercurrent across a van der Waals ferromagnet
Authors: Hu Guojing , Wang Changlong , Wang Shasha , Zhang Ying , Feng Yan , Wang Zhi , Niu Qian , Zhang Zhenyu , Xiang Bin 
Published: March 2023

AbstractThe emerging field of superconducting spintronics promises new quantum device architectures without energy dissipation. When entering a ferromagnet, a supercurrent commonly behaves as a spin singlet that decays rapidly; in contrast, a spin-triplet supercurrent can transport over much longer distances, and is therefore more desirable, but so far has been observed much less frequently. Here, by using the van der Waals ferromagnet Fe3GeTe2 (F) and spin-singlet superconductor NbSe2 (S), we construct lateral Josephson junctions of S/F/S with accurate interface control to realize long-range skin supercurrent. The observed supercurrent across the ferromagnet can extend over 300 nm, and exhibits distinct quantum interference patterns in an external magnetic field. Strikingly, the supercurrent displays pronounced skin characteristics, with its density peaked at the surfaces or edges of the ferromagnet. Our central findings shed new light on the convergence of superconductivity and spintronics based on two-dimensional materials.
Unravelling the clinicopathological and functional significance of replication protein A (RPA) heterotrimeric complex in breast cancers
Authors: Algethami Mashael , Toss Michael S. , Woodcock Corinne L. , Jaipal Chandar , Brownlie Juliette , Shoqafi Ahmed , Alblihy Adel , Mesquita Katia A. , Green Andrew R. , Mongan Nigel P. , Jeyapalan Jennie N. , Rakha Emad A. , Madhusudan Srinivasan 
Published: March 2023

AbstractReplication Protein A (RPA), a heterotrimeric complex consisting of RPA1, 2, and 3 subunits, is a single-stranded DNA (ssDNA)-binding protein that is critically involved in replication, checkpoint regulation and DNA repair. Here we have evaluated RPA in 776 pure ductal carcinomas in situ (DCIS), 239 DCIS that co-exist with invasive breast cancer (IBC), 50 normal breast tissue and 4221 IBC. Transcriptomic [METABRIC cohort (n = 1980)] and genomic [TCGA cohort (n = 1090)] evaluations were completed. Preclinically, RPA deficient cells were tested for cisplatin sensitivity and Olaparib induced synthetic lethality. Low RPA linked to aggressive DCIS, aggressive IBC, and shorter survival outcomes. At the transcriptomic level, low RPA tumours overexpress pseudogene/lncRNA as well as genes involved in chemical carcinogenesis, and drug metabolism. Low RPA remains linked with poor outcome. RPA deficient cells are sensitive to cisplatin and Olaparib induced synthetic lethality. We conclude that RPA directed precision oncology strategy is feasible in breast cancers.
High performance flexible Sn-Pb mixed perovskite solar cells enabled by a crosslinking additive
Authors: Li Ya , Yan Suhao , Cao Jiupeng , Chen Haoyu , Liu Bingxu , Xie Jiankai , Shu Yuting , Wang Fangfang , Wang Aifei , Dong Jingjin , Qin Tianshi 
Published: March 2023

AbstractFlexible perovskite solar cells (PSCs) have drawn increasing attention due to their promising applications for wearable electronics and aerospace applications. However, the efficiency and stability of flexible PSCs still lag behind their rigid counterparts. Here, we use N,N-dimethyl acrylamide (DMAA) to in situ synthesize cross-linking polymer for flexible Sn–Pb mixed PSCs. DMAA can gather at grain boundary as a scaffold to regulate the crystallization of perovskite and reduce defects. The rigid and flexible Sn–Pb mixed PSCs showed efficiencies of 16.44% and 15.44%, respectively. In addition, the flexible Sn–Pb mixed PSCs demonstrated excellent bending durability, which retained over 80% of the original efficiency after 5000 bending cycles at a radius of 5 mm.
A dataset of asymptomatic human gait and movements obtained from markers, IMUs, insoles and force plates
Authors: Grouvel Gautier , Carcreff Lena , Moissenet Florent , Armand Stéphane 
Published: March 2023

AbstractHuman motion capture and analysis could be made easier through the use of wearable devices such as inertial sensors and/or pressure insoles. However, many steps are still needed to reach the performance of optoelectronic systems to compute kinematic parameters. The proposed dataset has been established on 10 asymptomatic adults. Participants were asked to walk at different speeds on a 10-meters walkway in a laboratory and to perform different movements such as squats or knee flexion/extension tasks. Three-dimensional trajectories of 69 reflective markers placed according to a conventional full body markerset, acceleration and angular velocity signals of 8 inertial sensors, pressure signals of 2 insoles, 3D ground reaction forces and moments obtained from 3 force plates were simultaneously recorded. Eight calculated virtual markers related to joint centers were also added to the dataset. This dataset contains a total of 337 trials including static and dynamic tasks for each participant. Its purpose is to enable comparisons between various motion capture systems and stimulate the development of new methods for gait analysis.
Age and market capitalization drive large price variations of cryptocurrencies
Authors: Pessa Arthur A. B. , Perc Matjaž , Ribeiro Haroldo V. 
Published: March 2023

AbstractCryptocurrencies are considered the latest innovation in finance with considerable impact across social, technological, and economic dimensions. This new class of financial assets has also motivated a myriad of scientific investigations focused on understanding their statistical properties, such as the distribution of price returns. However, research so far has only considered Bitcoin or at most a few cryptocurrencies, whilst ignoring that price returns might depend on cryptocurrency age or be influenced by market capitalization. Here, we therefore present a comprehensive investigation of large price variations for more than seven thousand digital currencies and explore whether price returns change with the coming-of-age and growth of the cryptocurrency market. We find that tail distributions of price returns follow power-law functions over the entire history of the considered cryptocurrency portfolio, with typical exponents implying the absence of characteristic scales for price variations in about half of them. Moreover, these tail distributions are asymmetric as positive returns more often display smaller exponents, indicating that large positive price variations are more likely than negative ones. Our results further reveal that changes in the tail exponents are very often simultaneously related to cryptocurrency age and market capitalization or only to age, with only a minority of cryptoassets being affected just by market capitalization or neither of the two quantities. Lastly, we find that the trends in power-law exponents usually point to mixed directions, and that large price variations are likely to become less frequent only in about 28% of the cryptocurrencies as they age and grow in market capitalization.
Effect of hetero-atom doping on the electrocatalytic properties of graphene quantum dots for oxygen reduction reaction
Authors: Goswami Mrigaraj , Mandal Sneha , Pillai Vijayamohanan K. 
Published: March 2023

AbstractOxygen reduction is an important reaction involved in a diverse variety of energy storage devices and also in many chemical and biological processes. However, the high cost of suitable catalysts like platinum, rhodium, and iridium proves to be a major obstacle for its commercialization. Consequently, many new materials have emerged in recent years such as various forms of carbon, carbides, nitrides, core–shell particles, Mxenes, and transition metal complexes as alternatives to platinum and other noble metals for oxygen reduction reaction (ORR). Among these, Graphene Quantum Dots (GQDs) as metal-free alternatives have captured universal attention, since electrocatalytic properties can be tuned not only by size and functionalization but by heteroatom doping also. We discuss electrocatalytic properties of GQDs (approximate size 3–5 nm) with specific dopants such as N and S focusing on their synergistic effects of co-doping, prepared by solvothermal routes. Cyclic Voltammetry shows benefits of doping as lowering of the onset potentials while steady-state Galvanostatic Tafel polarization measurements show a clear difference in the apparent Tafel slope, along with enhanced exchange current densities, suggesting higher rate constants.
An evaluation framework for operational interventions on urban mass public transport during a pandemic
Authors: Singh Ramandeep , Hörcher Daniel , Graham Daniel J. 
Published: March 2023

AbstractDecision making in a rapidly changing context, such as the development and progression of a pandemic, requires a dynamic assessment of multiple variable and competing factors. Seemingly beneficial courses of action can rapidly fail to deliver a positive outcome as the context changes. In this paper, we present a flexible data-driven agent-based simulation framework that considers multiple outcome criteria to increase opportunities for safe mobility and economic interactions on urban transit networks while reducing the potential for Covid-19 contagion in a dynamic setting. Using a case study of the Victoria line on the London Underground, we model a number of operational interventions with varied demand levels and social distancing constraints including: alterations to train headways, dwell times, signalling schemes, and train paths. Our model demonstrates that substantial performance gains ranging from 12.3–195.7% can be achieved in metro service provision when comparing the best performing operational scheme and headway with those realised on the Victoria line during the pandemic.
Phylogenetic and functional characterization of water bears (Tardigrada) tubulins
Authors: Novotná Floriančičová Kamila , Baltzis Athanasios , Smejkal Jiří , Czerneková Michaela , Kaczmarek Łukasz , Malý Jan , Notredame Cedric , Vinopal Stanislav 
Published: March 2023

AbstractTardigrades are microscopic ecdysozoans that can withstand extreme environmental conditions. Several tardigrade species undergo reversible morphological transformations and enter into cryptobiosis, which helps them to survive periods of unfavorable environmental conditions. However, the underlying molecular mechanisms of cryptobiosis are mostly unknown. Tubulins are evolutionarily conserved components of the microtubule cytoskeleton that are crucial in many cellular processes. We hypothesize that microtubules are necessary for the morphological changes associated with successful cryptobiosis. The molecular composition of the microtubule cytoskeleton in tardigrades is unknown. Therefore, we analyzed and characterized tardigrade tubulins and identified 79 tardigrade tubulin sequences in eight taxa. We found three α-, seven β-, one γ-, and one ε-tubulin isoform. To verify in silico identified tardigrade tubulins, we also isolated and sequenced nine out of ten predictedHypsibius exemplaristubulins. All tardigrade tubulins were localized as expected when overexpressed in mammalian cultured cells: to the microtubules or to the centrosomes. The presence of a functional ε-tubulin, clearly localized to centrioles, is attractive from a phylogenetic point of view. Although the phylogenetically close Nematoda lost their δ- and ε-tubulins, some groups of Arthropoda still possess them. Thus, our data support the current placement of tardigrades into the Panarthropoda clade.
Process development for an effective COVID-19 vaccine candidate harboring recombinant SARS-CoV-2 delta plus receptor binding domain produced by Pichia pastoris
Authors: Kalyoncu Sibel , Yilmaz Semiramis , Kuyucu Ayca Zeybek , Sayili Dogu , Mert Olcay , Soyturk Hakan , Gullu Seyda , Akinturk Huseyin , Citak Erhan , Arslan Merve , Taskinarda Melda Guray , Tarman Ibrahim Oguzhan , Altun Gizem Yilmazer , Ozer Ceren , Orkut Ridvan , Demirtas Aysegul , Tilmensagir Idil , Keles Umur , Ulker Ceren , Aralan Gizem , Mercan Yavuz , Ozkan Muge , Caglar Hasan Onur , Arik Gizem , Ucar Mehmet Can , Yildirim Muzaffer , Yildirim Tugce Canavar , Karadag Dilara , Bal Erhan , Erdogan Aybike , Senturk Serif , Uzar Serdar , Enul Hakan , Adiay Cumhur , Sarac Fahriye , Ekiz Arzu Tas , Abaci Irem , Aksoy Ozge , Polat Hivda Ulbegi , Tekin Saban , Dimitrov Stefan , Ozkul Aykut , Wingender Gerhard , Gursel Ihsan , Ozturk Mehmet , Inan Mehmet 
Published: March 2023

AbstractRecombinant protein-based SARS-CoV-2 vaccines are needed to fill the vaccine equity gap. Because protein-subunit based vaccines are easier and cheaper to produce and do not require special storage/transportation conditions, they are suitable for low-/middle-income countries. Here, we report our vaccine development studies with the receptor binding domain of the SARS-CoV-2 Delta Plus strain (RBD-DP) which caused increased hospitalizations compared to other variants. First, we expressed RBD-DP in thePichia pastorisyeast system and upscaled it to a 5-L fermenter for production. After three-step purification, we obtained RBD-DP with > 95% purity from a protein yield of > 1 g/L of supernatant. Several biophysical and biochemical characterizations were performed to confirm its identity, stability, and functionality. Then, it was formulated in different contents with Alum and CpG for mice immunization. After three doses of immunization, IgG titers from sera reached to > 106and most importantly it showed high T-cell responses which are required for an effective vaccine to prevent severe COVID-19 disease. A live neutralization test was performed with both the Wuhan strain (B.1.1.7) and Delta strain (B.1.617.2) and it showed high neutralization antibody content for both strains. A challenge study with SARS-CoV-2 infected K18-hACE2 transgenic mice showed good immunoprotective activity with no viruses in the lungs and no lung inflammation for all immunized mice.
Hybrid high-concentration photovoltaic system designed for different weather conditions
Authors: Sun Chi , Wu Chi-Shou , Lin Yong-Sheng , Kao Tsung Sheng , Fang Shuo-Ting , Chiu Yao-Hsuan , Sun Ching-Cherng 
Published: March 2023

AbstractIn this study, we propose a novel high-concentration photovoltaic (HCPV) cell by considering both the light leakage characteristics of the Fresnel-lens-based solar cell modules and the performance issues arising from cloud shading in practical use. We use our self-constructed systems to conduct field measurements for up to half a year under various environmental conditions. According to the acquired results, it was surprising to know that in the area other than the focusing area, the so-called light leakage region, there always bears illuminance of about 20,000–40,000 lx whether it is a sunny day or a cloudy day with different cloud conditions. Such an interesting result is caused by the light scattering of the clouds and the inherent leakage characteristic of a Fresnel lens. To prove this important finding, we simulated the illuminance of the Fresnel lens structure used in the measurement with apertures of different sizes to determine the detected area. In the laboratory, the diffuse plates were used to mimic the situation of varying cloud layer thicknesses. The trend of calculated and measured results fitted well with the field measurements. Also, the experimental and simulation results show that the round angle and draft facet of the Fresnel lens were responsible for light leakage. This finding prompted us to propose a hybrid high-concentration solar module in which more cost-effective polycrystalline silicon solar cells are placed around the high-efficiency wafer of HCPV to capture the dissipated light leakage and convert it into usable electricity.
Label-free macrophage phenotype classification using machine learning methods
Authors: Hourani Tetiana , Perez-Gonzalez Alexis , Khoshmanesh Khashayar , Luwor Rodney , Achuthan Adrian A. , Baratchi Sara , O’Brien-Simpson Neil M. , Al-Hourani Akram 
Published: March 2023

AbstractMacrophages are heterogeneous innate immune cells that are functionally shaped by their surrounding microenvironment. Diverse macrophage populations have multifaceted differences related to their morphology, metabolism, expressed markers, and functions, where the identification of the different phenotypes is of an utmost importance in modelling immune response. While expressed markers are the most used signature to classify phenotypes, multiple reports indicate that macrophage morphology and autofluorescence are also valuable clues that can be used in the identification process. In this work, we investigated macrophage autofluorescence as a distinct feature for classifying six different macrophage phenotypes, namely: M0, M1, M2a, M2b, M2c, and M2d. The identification was based on extracted signals from multi-channel/multi-wavelength flow cytometer. To achieve the identification, we constructed a dataset containing 152,438 cell events each having a response vector of 45 optical signals fingerprint. Based on this dataset, we applied different supervised machine learning methods to detect phenotype specific fingerprint from the response vector, where the fully connected neural network architecture provided the highest classification accuracy of 75.8% for the six phenotypes compared simultaneously. Furthermore, by restricting the number of phenotypes in the experiment, the proposed framework produces higher classification accuracies, averaging 92.0%, 91.9%, 84.2%, and 80.4% for a pool of two, three, four, five phenotypes, respectively. These results indicate the potential of the intrinsic autofluorescence for classifying macrophage phenotypes, with the proposed method being quick, simple, and cost-effective way to accelerate the discovery of macrophage phenotypical diversity.
Diagnostic ability of macular microvasculature with swept-source OCT angiography for highly myopic glaucoma using deep learning
Authors: Lee Yun Jeong , Sun Sukkyu , Kim Young Kook , Jeoung Jin Wook , Park Ki Ho 
Published: March 2023

AbstractMacular OCT angiography (OCTA) measurements have been reported to be useful for glaucoma diagnostics. However, research on highly myopic glaucoma is lacking, and the diagnostic value of macular OCTA measurements versus OCT parameters remains inconclusive. We aimed to evaluate the diagnostic ability of the macular microvasculature assessed with OCTA for highly myopic glaucoma and to compare it with that of macular thickness parameters, using deep learning (DL). A DL model was trained, validated and tested using 260 pairs of macular OCTA and OCT images from 260 eyes (203 eyes with highly myopic glaucoma, 57 eyes with healthy high myopia). The DL model achieved an AUC of 0.946 with the OCTA superficial capillary plexus (SCP) images, which was comparable to that with the OCT GCL+ (ganglion cell layer + inner plexiform layer; AUC, 0.982; P = 0.268) or OCT GCL++ (retinal nerve fiber layer + ganglion cell layer + inner plexiform layer) images (AUC, 0.997; P = 0.101), and significantly superior to that with the OCTA deep capillary plexus images (AUC, 0.779; P = 0.028). The DL model with macular OCTA SCP images demonstrated excellent and comparable diagnostic ability to that with macular OCT images in highly myopic glaucoma, which suggests macular OCTA microvasculature could serve as a potential biomarker for glaucoma diagnosis in high myopia.
A data-driven investigation of human action representations
Authors: Dima Diana C. , Hebart Martin N. , Isik Leyla 
Published: March 2023

AbstractUnderstanding actions performed by others requires us to integrate different types of information about people, scenes, objects, and their interactions. What organizing dimensions does the mind use to make sense of this complex action space? To address this question, we collected intuitive similarity judgments across two large-scale sets of naturalistic videos depicting everyday actions. We used cross-validated sparse non-negative matrix factorization to identify the structure underlying action similarity judgments. A low-dimensional representation, consisting of nine to ten dimensions, was sufficient to accurately reconstruct human similarity judgments. The dimensions were robust to stimulus set perturbations and reproducible in a separate odd-one-out experiment. Human labels mapped these dimensions onto semantic axes relating to food, work, and home life; social axes relating to people and emotions; and one visual axis related to scene setting. While highly interpretable, these dimensions did not share a clear one-to-one correspondence with prior hypotheses of action-relevant dimensions. Together, our results reveal a low-dimensional set of robust and interpretable dimensions that organize intuitive action similarity judgments and highlight the importance of data-driven investigations of behavioral representations.