bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design automation of microfluidic single and double emulsion droplets with machine learning
Authors: Lashkaripour Ali , McIntyre David P. , Calhoun Suzanne G. K. , Krauth Karl , Densmore Douglas M. , Fordyce Polly M. 
Published: January 2024

AbstractDroplet microfluidics enables kHz screening of picoliter samples at a fraction of the cost of other high-throughput approaches. However, generating stable droplets with desired characteristics typically requires labor-intensive empirical optimization of device designs and flow conditions that limit adoption to specialist labs. Here, we compile a comprehensive droplet dataset and use it to train machine learning models capable of accurately predicting device geometries and flow conditions required to generate stable aqueous-in-oil and oil-in-aqueous single and double emulsions from 15 to 250 μm at rates up to 12000 Hz for different fluids commonly used in life sciences. Blind predictions by our models for as-yet-unseen fluids, geometries, and device materials yield accurate results, establishing their generalizability. Finally, we generate an easy-to-use design automation tool that yield droplets within 3 μm (<8%) of the desired diameter, facilitating tailored droplet-based platforms and accelerating their utility in life sciences.
Parity-conserving Cooper-pair transport and ideal superconducting diode in planar germanium
Authors: Valentini Marco , Sagi Oliver , Baghumyan Levon , de Gijsel Thijs , Jung Jason , Calcaterra Stefano , Ballabio Andrea , Aguilera Servin Juan , Aggarwal Kushagra , Janik Marian , Adletzberger Thomas , Seoane Souto Rubén , Leijnse Martin , Danon Jeroen , Schrade Constantin , Bakkers Erik , Chrastina Daniel , Isella Giovanni , Katsaros Georgios 
Published: January 2024

AbstractSuperconductor/semiconductor hybrid devices have attracted increasing interest in the past years. Superconducting electronics aims to complement semiconductor technology, while hybrid architectures are at the forefront of new ideas such as topological superconductivity and protected qubits. In this work, we engineer the induced superconductivity in two-dimensional germanium hole gas by varying the distance between the quantum well and the aluminum. We demonstrate a hard superconducting gap and realize an electrically and flux tunable superconducting diode using a superconducting quantum interference device (SQUID). This allows to tune the current phase relation (CPR), to a regime where single Cooper pair tunneling is suppressed, creating a$$\sin \left(2\varphi \right)$$sin2φCPR. Shapiro experiments complement this interpretation and the microwave drive allows to create a diode with ≈ 100% efficiency. The reported results open up the path towards integration of spin qubit devices, microwave resonators and (protected) superconducting qubits on the same silicon technology compatible platform.
Programmable high-dimensional Hamiltonian in a photonic waveguide array
Authors: Yang Yang , Chapman Robert J. , Haylock Ben , Lenzini Francesco , Joglekar Yogesh N. , Lobino Mirko , Peruzzo Alberto 
Published: January 2024

AbstractWaveguide lattices offer a compact and stable platform for a range of applications, including quantum walks, condensed matter system simulation, and classical and quantum information processing. However, to date, waveguide lattice devices have been static and designed for specific applications. We present a programmable waveguide array in which the Hamiltonian terms can be individually electro-optically tuned to implement various Hamiltonian continuous-time evolutions on a single device. We used a single array with 11 waveguides in lithium niobate, controlled via 22 electrodes, to perform a range of experiments that realized the Su-Schriffer-Heeger model, the Aubrey-Andre model, and Anderson localization, which is equivalent to over 2500 static devices. Our architecture’s micron-scale local electric fields overcome the cross-talk limitations of thermo-optic phase shifters in other platforms such as silicon, silicon-nitride, and silica. Electro-optic control allows for ultra-fast and more precise reconfigurability with lower power consumption, and with quantum input states, our platform can enable the study of multiple condensed matter quantum dynamics with a single device.
MAPS: pathologist-level cell type annotation from tissue images through machine learning
Authors: Shaban Muhammad , Bai Yunhao , Qiu Huaying , Mao Shulin , Yeung Jason , Yeo Yao Yu , Shanmugam Vignesh , Chen Han , Zhu Bokai , Weirather Jason L. , Nolan Garry P. , Shipp Margaret A. , Rodig Scott J. , Jiang Sizun , Mahmood Faisal 
Published: January 2024

AbstractHighly multiplexed protein imaging is emerging as a potent technique for analyzing protein distribution within cells and tissues in their native context. However, existing cell annotation methods utilizing high-plex spatial proteomics data are resource intensive and necessitate iterative expert input, thereby constraining their scalability and practicality for extensive datasets. We introduce MAPS (Machine learning for Analysis of Proteomics in Spatial biology), a machine learning approach facilitating rapid and precise cell type identification with human-level accuracy from spatial proteomics data. Validated on multiple in-house and publicly available MIBI and CODEX datasets, MAPS outperforms current annotation techniques in terms of speed and accuracy, achieving pathologist-level precision even for typically challenging cell types, including tumor cells of immune origin. By democratizing rapidly deployable and scalable machine learning annotation, MAPS holds significant potential to expedite advances in tissue biology and disease comprehension.
Elastocapillarity-driven 2D nano-switches enable zeptoliter-scale liquid encapsulation
Authors: Ronceray Nathan , Spina Massimo , Chou Vanessa Hui Yin , Lim Chwee Teck , Geim Andre K. , Garaj Slaven 
Published: January 2024

AbstractBiological nanostructures change their shape and function in response to external stimuli, and significant efforts have been made to design artificial biomimicking devices operating on similar principles. In this work we demonstrate a programmable nanofluidic switch, driven by elastocapillarity, and based on nanochannels built from layered two-dimensional nanomaterials possessing atomically smooth surfaces and exceptional mechanical properties. We explore operational modes of the nanoswitch and develop a theoretical framework to explain the phenomenon. By predicting the switching-reversibility phase diagram—based on material, interfacial and wetting properties, as well as the geometry of the nanofluidic circuit—we rationally design switchable nano-capsules capable of enclosing zeptoliter volumes of liquid, as small as the volumes enclosed in viruses. The nanoswitch will find useful application as an active element in integrated nanofluidic circuitry and could be used to explore nanoconfined chemistry and biochemistry, or be incorporated into shape-programmable materials.
Covalent PARylation of DNA base excision repair proteins regulates DNA demethylation
Authors: Schwarz Simon D. , Xu Jianming , Gunasekera Kapila , Schürmann David , Vågbø Cathrine B. , Ferrari Elena , Slupphaug Geir , Hottiger Michael O. , Schär Primo , Steinacher Roland 
Published: January 2024

AbstractThe intracellular ATP-ribosyltransferases PARP1 and PARP2, contribute to DNA base excision repair (BER) and DNA demethylation and have been implicated in epigenetic programming in early mammalian development. Recently, proteomic analyses identified BER proteins to be covalently poly-ADP-ribosylated by PARPs. The role of this posttranslational modification in the BER process is unknown. Here, we show that PARP1 senses AP-sites and SSBs generated during TET-TDG mediated active DNA demethylation and covalently attaches PAR to each BER protein engaged. Covalent PARylation dissociates BER proteins from DNA, which accelerates the completion of the repair process. Consistently, inhibition of PARylation in mESC resulted both in reduced locus-specific TET-TDG-targeted DNA demethylation, and in reduced general repair of random DNA damage. Our findings establish a critical function of covalent protein PARylation in coordinating molecular processes associated with dynamic DNA methylation.
Unlocking regioselective meta-alkylation with epoxides and oxetanes via dynamic kinetic catalyst control
Authors: Bai Peng-Bo , Durie Alastair , Wang Gang-Wei , Larrosa Igor 
Published: January 2024

AbstractRegioselective arene C−H bond alkylation is a powerful tool in synthetic chemistry, yet subject to many challenges. Herein, we report the meta-C−H bond alkylation of aromatics bearing N-directing groups using (hetero)aromatic epoxides as alkylating agents. This method results in complete regioselectivity on both the arene as well as the epoxide coupling partners, cleaving exclusively the benzylic C−O bond. Oxetanes, which are normally unreactive, also participate as alkylating reagents under the reaction conditions. Our mechanistic studies reveal an unexpected reversible epoxide ring opening process undergoing catalyst-controlled regioselection, as key for the observed high regioselectivities.
Effects of plant tissue permeability on invasion and population bottlenecks of a phytopathogen
Authors: Jiang Gaofei , Zhang Yuling , Chen Min , Ramoneda Josep , Han Liangliang , Shi Yu , Peyraud Rémi , Wang Yikui , Shi Xiaojun , Chen Xinping , Ding Wei , Jousset Alexandre , Hikichi Yasufumi , Ohnishi Kouhei , Zhao Fang-Jie , Xu Yangchun , Shen Qirong , Dini-Andreote Francisco , Zhang Yong , Wei Zhong 
Published: January 2024

AbstractPathogen genetic diversity varies in response to environmental changes. However, it remains unclear whether plant barriers to invasion could be considered a genetic bottleneck for phytopathogen populations. Here, we implement a barcoding approach to generate a pool of 90 isogenic and individually barcoded Ralstonia solanacearum strains. We used 90 of these strains to inoculate tomato plants with different degrees of physical permeability to invasion (intact roots, wounded roots and xylem inoculation) and quantify the phytopathogen population dynamics during invasion. Our results reveal that the permeability of plant roots impacts the degree of population bottleneck, genetic diversity, and composition of Ralstonia populations. We also find that selection is the main driver structuring pathogen populations when barriers to infection are less permeable, i.e., intact roots, the removal of root physical and immune barriers results in the predominance of stochasticity in population assembly. Taken together, our study suggests that plant root permeability constitutes a bottleneck for phytopathogen invasion and genetic diversity.
Mucosal TLR5 activation controls healthspan and longevity
Authors: Lim Jae Sung , Jeon Eun Jae , Go Hye Sun , Kim Hyung-Jin , Kim Kye Young , Nguyen Thi Quynh Trang , Lee Da Young , Kim Kyu Suk , Pietrocola Federico , Hong Seol Hee , Lee Shee Eun , Kim Kyoung-Shim , Park Tae-Shin , Choi Dong-Hee , Jeong Yu-Jin , Park Jong-Hwan , Kim Hyeon Sik , Min Jung-Joon , Kim Yong Sook , Park Joon Tae , Cho Jae-Ho , Lee Gil-Woo , Lee Ji Hyeon , Choy Hyon E. , Park Sang Chul , Lee Chul-Ho , Rhee Joon Haeng , Serrano Manuel , Cho Kyung A 
Published: January 2024

AbstractAddressing age-related immunological defects through therapeutic interventions is essential for healthy aging, as the immune system plays a crucial role in controlling infections, malignancies, and in supporting tissue homeostasis and repair. In our study, we show that stimulating toll-like receptor 5 (TLR5) via mucosal delivery of a flagellin-containing fusion protein effectively extends the lifespan and enhances the healthspan of mice of both sexes. This enhancement in healthspan is evidenced by diminished hair loss and ocular lens opacity, increased bone mineral density, improved stem cell activity, delayed thymic involution, heightened cognitive capacity, and the prevention of pulmonary lung fibrosis. Additionally, this fusion protein boosts intestinal mucosal integrity by augmenting the surface expression of TLR5 in a certain subset of dendritic cells and increasing interleukin-22 (IL-22) secretion. In this work, we present observations that underscore the benefits of TLR5-dependent stimulation in the mucosal compartment, suggesting a viable strategy for enhancing longevity and healthspan.
Electronic paddle-wheels in a solid-state electrolyte
Authors: Dhattarwal Harender S. , Somni Rahul , Remsing Richard C. 
Published: January 2024

AbstractSolid-state superionic conductors (SSICs) are promising alternatives to liquid electrolytes in batteries and other energy storage technologies. The rational design of SSICs and ultimately their deployment in battery technologies is hindered by the lack of a thorough understanding of their ion conduction mechanisms. In SSICs containing molecular ions, rotational dynamics couple with translational diffusion to create a paddle-wheel effect that facilitates conduction. The paddle-wheel mechanism explains many important features of molecular SSICs, but an explanation for ion conduction and anharmonic lattice dynamics in SSICs composed of monatomic ions is still needed. We predict that ion conduction in the classic SSIC AgI involves electronic paddle-wheels, rotational motion of localized electron pairs that couples to and facilitates ion diffusion. The electronic paddle-wheel mechanism creates a universal perspective for understanding ion conductivity in both monatomic and molecular SSICs that will create design principles for engineering solid-state electrolytes from the electronic level up to the macroscale.
The ALT pathway generates telomere fusions that can be detected in the blood of cancer patients
Authors: Muyas Francesc , Rodriguez Manuel José Gómez , Cascão Rita , Afonso Angela , Sauer Carolin M. , Faria Claudia C. , Cortés-Ciriano Isidro , Flores Ignacio 
Published: January 2024

AbstractTelomere fusions (TFs) can trigger the accumulation of oncogenic alterations leading to malignant transformation and drug resistance. Despite their relevance in tumour evolution, our understanding of the patterns and consequences of TFs in human cancers remains limited. Here, we characterize the rates and spectrum of somatic TFs across >30 cancer types using whole-genome sequencing data. TFs are pervasive in human tumours with rates varying markedly across and within cancer types. In addition to end-to-end fusions, we find patterns of TFs that we mechanistically link to the activity of the alternative lengthening of telomeres (ALT) pathway. We show that TFs can be detected in the blood of cancer patients, which enables cancer detection with high specificity and sensitivity even for early-stage tumours and cancers of high unmet clinical need. Overall, we report a genomic footprint that enables characterization of the telomere maintenance mechanism of tumours and liquid biopsy analysis.
Non-canonical interplay between glutamatergic NMDA and dopamine receptors shapes synaptogenesis
Authors: Bénac Nathan , Ezequiel Saraceno G. , Butler Corey , Kuga Nahoko , Nishimura Yuya , Yokoi Taiki , Su Ping , Sasaki Takuya , Petit-Pedrol Mar , Galland Rémi , Studer Vincent , Liu Fang , Ikegaya Yuji , Sibarita Jean-Baptiste , Groc Laurent 
Published: January 2024

AbstractDirect interactions between receptors at the neuronal surface have long been proposed to tune signaling cascades and neuronal communication in health and disease. Yet, the lack of direct investigation methods to measure, in live neurons, the interaction between different membrane receptors at the single molecule level has raised unanswered questions on the biophysical properties and biological roles of such receptor interactome. Using a multidimensional spectral single molecule-localization microscopy (MS-SMLM) approach, we monitored the interaction between two membrane receptors, i.e. glutamatergic NMDA (NMDAR) and G protein-coupled dopamine D1 (D1R) receptors. The transient interaction was randomly observed along the dendritic tree of hippocampal neurons. It was higher early in development, promoting the formation of NMDAR-D1R complexes in an mGluR5- and CK1-dependent manner, favoring NMDAR clusters and synaptogenesis in a dopamine receptor signaling-independent manner. Preventing the interaction in the neonate, and not adult, brain alters in vivo spontaneous neuronal network activity pattern in male mice. Thus, a weak and transient interaction between NMDAR and D1R plays a structural and functional role in the developing brain.
Self-assembly of the smallest and tightest molecular trefoil knot
Authors: Li Zhiwen , Zhang Jingjing , Li Gao , Puddephatt Richard J. 
Published: January 2024

AbstractMolecular knots, whose synthesis presents many challenges, can play important roles in protein structure and function as well as in useful molecular materials, whose properties depend on the size of the knotted structure. Here we report the synthesis by self-assembly of molecular trefoil metallaknot with formula [Au6{1,2-C6H4(OCH2CC)2}3{Ph2P(CH2)4PPh2}3], Au6, from three units of each of the components 1,2-C6H4(OCH2CCAu)2 and Ph2P(CH2)4PPh2. Structure determination by X-ray diffraction revealed that the chiral trefoil knot contains only 54 atoms in the backbone, so that Au6 is the smallest and tightest molecular trefoil knot known to date.
Turnkey photonic flywheel in a microresonator-filtered laser
Authors: Nie Mingming , Musgrave Jonathan , Jia Kunpeng , Bartos Jan , Zhu Shining , Xie Zhenda , Huang Shu-Wei 
Published: January 2024

AbstractDissipative Kerr soliton (DKS) microcomb has emerged as an enabling technology that revolutionizes a wide range of applications in both basic science and technological innovation. Reliable turnkey operation with sub-optical-cycle and sub-femtosecond timing jitter is key to the success of many intriguing microcomb applications at the intersection of ultrafast optics and microwave electronics. Here we propose an approach and demonstrate the first turnkey Brillouin-DKS frequency comb to the best of our knowledge. Our microresonator-filtered laser design offers essential benefits, including phase insensitivity, self-healing capability, deterministic selection of the DKS state, and access to the ultralow noise comb state. The demonstrated turnkey Brillouin-DKS frequency comb achieves a fundamental comb linewidth of 100 mHz and DKS timing jitter of 1 femtosecond for averaging times up to 56 μs. The approach is universal and generalizable to various device platforms for user-friendly and field-deployable comb devices.
Chronic oxytocin administration stimulates the oxytocinergic system in children with autism
Authors: Moerkerke Matthijs , Daniels Nicky , Tibermont Laura , Tang Tiffany , Evenepoel Margaux , Van der Donck Stephanie , Debbaut Edward , Prinsen Jellina , Chubar Viktoria , Claes Stephan , Vanaudenaerde Bart , Willems Lynn , Steyaert Jean , Boets Bart , Alaerts Kaat 
Published: January 2024

AbstractClinical efficacy of intranasal administration of oxytocin is increasingly explored in autism spectrum disorder, but to date, the biological effects of chronic administration regimes on endogenous oxytocinergic function are largely unknown. Here exploratory biological assessments from a completed randomized, placebo-controlled trial showed that children with autism (n = 79, 16 females) receiving intranasal oxytocin for four weeks (12 IU, twice daily) displayed significantly higher salivary oxytocin levels 24 hours after the last oxytocin nasal spray administration, but no longer at a four-week follow up session. Regarding salivary oxytocin receptor gene (OXTR)epigenetics (DNA-methylation), oxytocin-induced reductions inOXTRDNA-methylation were observed, suggesting a facilitation of oxytocin receptor expression in the oxytocin compared to the placebo group. Notably, heightened oxytocin levels post-treatment were significantly associated with reducedOXTRDNA-methylation and improved feelings of secure attachment. These findings indicate that four weeks of chronic oxytocin administration stimulated the endogenous oxytocinergic system in children with autism.
Microbiome homeostasis on rice leaves is regulated by a precursor molecule of lignin biosynthesis
Authors: Su Pin , Kang Houxiang , Peng Qianze , Wicaksono Wisnu Adi , Berg Gabriele , Liu Zhuoxin , Ma Jiejia , Zhang Deyong , Cernava Tomislav , Liu Yong 
Published: January 2024

AbstractIn terrestrial ecosystems, plant leaves provide the largest biological habitat for highly diverse microbial communities, known as the phyllosphere microbiota. However, the underlying mechanisms of host-driven assembly of these ubiquitous communities remain largely elusive. Here, we conduct a large-scale and in-depth assessment of the rice phyllosphere microbiome aimed at identifying specific host-microbe links. A genome-wide association study reveals a strong association between the plant genotype and members of four bacterial orders, Pseudomonadales, Burkholderiales, Enterobacterales and Xanthomonadales. Some of the associations are specific to a distinct host genomic locus, pathway or even gene. The compound 4-hydroxycinnamic acid (4-HCA) is identified as the main driver for enrichment of bacteria belonging to Pseudomonadales. 4-HCA can be synthesized by the host plant’s OsPAL02 from the phenylpropanoid biosynthesis pathway. A knockout mutant of OsPAL02 results in reduced Pseudomonadales abundance, dysbiosis of the phyllosphere microbiota and consequently higher susceptibility of rice plants to disease. Our study provides a direct link between a specific plant metabolite and rice phyllosphere homeostasis opening possibilities for new breeding strategies.
STYXL1 regulates CCT complex assembly and flagellar tubulin folding in sperm formation
Authors: Chen Yu , Luo Mengjiao , Tu Haixia , Qi Yaling , Guo Yueshuai , Zhang Xiangzheng , Cui Yiqiang , Gao Mengmeng , Zhou Xin , Zhu Tianyu , Zhu Hui , Situ Chenghao , Li Yan , Guo Xuejiang 
Published: January 2024

AbstractTubulin-based microtubule is a core component of flagella axoneme and essential for sperm motility and male fertility. Structural components of the axoneme have been well explored. However, how tubulin folding is regulated in sperm flagella formation is still largely unknown. Here, we report a germ cell-specific co-factor of CCT complex, STYXL1. Deletion of Styxl1 results in male infertility and microtubule defects of sperm flagella. Proteomic analysis of Styxl1-/- sperm reveals abnormal downregulation of flagella-related proteins including tubulins. The N-terminal rhodanese-like domain of STYXL1 is important for its interactions with CCT complex subunits, CCT1, CCT6 and CCT7. Styxl1 deletion leads to defects in CCT complex assembly and tubulin polymerization. Collectively, our findings reveal the vital roles of germ cell-specific STYXL1 in CCT-facilitated tubulin folding and sperm flagella development.