bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zebrafish imaging reveals TP53 mutation switching oncogene-induced senescence from suppressor to driver in primary tumorigenesis
Authors: Haraoka Yukinari , Akieda Yuki , Nagai Yuri , Mogi Chihiro , Ishitani Tohru 
Published: March 2022

AbstractMost tumours are thought to arise through oncogenic cell generation followed by additional mutations. How a new oncogenic cell primes tumorigenesis by acquiring additional mutations remains unclear. We show that an additional TP53 mutation stimulates primary tumorigenesis by switching oncogene-induced senescence from a tumour suppressor to a driver. Zebrafish imaging reveals that a newly emerged oncogenic cell with the RasG12V mutation becomes senescent and is eliminated from the epithelia, which is prevented by adding a TP53 gain-of-function mutation (TP53R175H) into RasG12V cells. Surviving RasG12V-TP53R175H double-mutant cells senesce and secrete senescence-associated secretory phenotype (SASP)-related inflammatory molecules that convert neighbouring normal cells into SASP factor-secreting senescent cells, generating a heterogeneous tumour-like cell mass. We identify oncogenic cell behaviours that may control the initial human tumorigenesis step. Ras and TP53 mutations and cellular senescence are frequently detected in human tumours; similar switching may occur during the initial step of human tumorigenesis.
Evolutionary transition from a single RNA replicator to a multiple replicator network
Authors: Mizuuchi Ryo , Furubayashi Taro , Ichihashi Norikazu 
Published: March 2022

AbstractIn prebiotic evolution, self-replicating molecules are believed to have evolved into complex living systems by expanding their information and functions open-endedly. Theoretically, such evolutionary complexification could occur through successive appearance of novel replicators that interact with one another to form replication networks. Here we perform long-term evolution experiments of RNA that replicates using a self-encoded RNA replicase. The RNA diversifies into multiple coexisting host and parasite lineages, whose frequencies in the population initially fluctuate and gradually stabilize. The final population, comprising five RNA lineages, forms a replicator network with diverse interactions, including cooperation to help the replication of all other members. These results support the capability of molecular replicators to spontaneously develop complexity through Darwinian evolution, a critical step for the emergence of life.
DNA-based platform for efficient and precisely targeted bioorthogonal catalysis in living systems
Authors: You Yawen , Deng Qingqing , Wang Yibo , Sang Yanjuan , Li Guangming , Pu Fang , Ren Jinsong , Qu Xiaogang 
Published: March 2022

AbstractAs one of the typical bioorthogonal reactions, copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction holds great potential in organic synthesis, bioconjugation, and surface functionalization. However, the toxicity of Cu(I), inefficient catalytic activity, and the lack of cell specific targeting of the existing catalysts hampered their practical applications in living systems. Herein, we design and construct a DNA-based platform as a biocompatible, highly efficient, and precisely targeted bioorthogonal nanocatalyst. The nanocatalyst presents excellent catalytic efficiency in vitro, which is one order of magnitude higher than the commonly used catalyst CuSO4/sodium ascorbate. The theoretical calculation further supports the contribution of DNA structure and its interaction with substrates to the superior catalytic activity. More importantly, the system can achieve efficient prodrug activation in cancer cells through cell type-specific recognition and produce a 40-fold enhancement of transformation compared to the non-targeting nanocatalyst, resulting in enhanced antitumor efficacy and reduced adverse effects. In vivo tumor therapy demonstrates the safety and efficacy of the system in mammals.
Extra kinetic dimensions for label discrimination
Authors: Chouket Raja , Pellissier-Tanon Agnès , Lahlou Aliénor , Zhang Ruikang , Kim Diana , Plamont Marie-Aude , Zhang Mingshu , Zhang Xi , Xu Pingyong , Desprat Nicolas , Bourgeois Dominique , Espagne Agathe , Lemarchand Annie , Saux Thomas Le , Jullien Ludovic 
Published: March 2022

AbstractDue to its sensitivity and versatility, fluorescence is widely used to detect specifically labeled biomolecules. However, fluorescence is currently limited by label discrimination, which suffers from the broad full width of the absorption/emission bands and the narrow lifetime distribution of the bright fluorophores. We overcome this limitation by introducing extra kinetic dimensions through illuminations of reversibly photoswitchable fluorophores (RSFs) at different light intensities. In this expanded space, each RSF is characterized by a chromatic aberration-free kinetic fingerprint of photochemical reactivity, which can be recovered with limited hardware, excellent photon budget, and minimal data processing. This fingerprint was used to identify and discriminate up to 20 among 22 spectrally similar reversibly photoswitchable fluorescent proteins (RSFPs) in less than 1s. This strategy opens promising perspectives for expanding the multiplexing capabilities of fluorescence imaging.
Silicon-photonics acoustic detector for optoacoustic micro-tomography
Authors: Hazan Yoav , Levi Ahiad , Nagli Michael , Rosenthal Amir 
Published: March 2022

AbstractMedical ultrasound and optoacoustic (photoacoustic) imaging commonly rely on the concepts of beam-forming and tomography for image formation, enabled by piezoelectric array transducers whose element size is comparable to the desired resolution. However, the tomographic measurement of acoustic signals becomes increasingly impractical for resolutions beyond 100 µm due to the reduced efficiency of piezoelectric elements upon miniaturization. For higher resolutions, a microscopy approach is preferred, in which a single focused ultrasound transducer images the object point-by-point, but the bulky apparatus and long acquisition time of this approach limit clinical applications. In this work, we demonstrate a miniaturized acoustic detector capable of tomographic imaging with spread functions whose width is below 20 µm. The detector is based on an optical resonator fabricated in a silicon-photonics platform coated by a sensitivity-enhancing elastomer, which also effectively eliminates the parasitic effect of surface acoustic waves. The detector is demonstrated in vivo in high-resolution optoacoustic tomography.
Noncontact human-machine interaction based on hand-responsive infrared structural color
Authors: An Shun , Zhu Hanrui , Guo Chunzhi , Fu Benwei , Song Chengyi , Tao Peng , Shang Wen , Deng Tao 
Published: March 2022

AbstractNoncontact human-machine interaction provides a hygienic and intelligent approach for the communication between human and robots. Current noncontact human-machine interactions are generally limited by the interaction distance or conditions, such as in the dark. Here we explore the utilization of hand as an infrared light source for noncontact human-machine interaction. Metallic gratings are used as the human-machine interface to respond to infrared radiation from hand and the generated signals are visualized as different infrared structural colors. We demonstrate the applications of the infrared structural color-based human-machine interaction for user-interactive touchless display and real-time control of a robot vehicle. The interaction is flexible to the hand-interface distance ranging from a few centimeters to tens of centimeters and can be used in low lighting condition or in the dark. The findings in this work provide an alternative and complementary approach to traditional noncontact human-machine interactions, which may further broaden the potential applications of human-machine interaction.
Coarse-grained molecular dynamics integrated with convolutional neural network for comparing shapes of temperature sensitive bottlebrushes
Authors: Joshi Soumil Y. , Singh Samrendra , Deshmukh Sanket A. 
Published: March 2022

AbstractQuantification of shape changes in nature-inspired soft material architectures of stimuli-sensitive polymers is critical for controlling their properties but is challenging due to their softness and flexibility. Here, we have computationally designed uniquely shaped bottlebrushes of a thermosensitive polymer, poly(N-isopropylacrylamide) (PNIPAM), by controlling the length of side chains along the backbone. Coarse-grained molecular dynamics simulations of solvated bottlebrushes were performed below and above the lower critical solution temperature of PNIPAM. Conventional analyses (free volume, asphericity, etc.) show that lengths of side chains and their immediate environments dictate the compactness and bending in these architectures. We further developed 100 unique convolutional neural network models that captured molecular-level features and generated a statistically significant quantification of the similarity between different shapes. Thus, our study provides insights into the shapes of complex architectures as well as a general method to analyze them. The shapes presented here may inspire the synthesis of new bottlebrushes.
VHL mosaicism: the added value of multi-tissue analysis
Authors: Oldfield Leslie E. , Grzybowski Jessica , Grenier Sylvie , Chao Elizabeth , Downs Gregory S. , Farncombe Kirsten M. , Stockley Tracy L. , Mete Ozgur , Kim Raymond H. 
Published: March 2022

AbstractVon Hippel-Lindau disease (VHL) is an autosomal dominant, inherited syndrome with variants in the VHL gene causing predisposition to multi-organ benign and malignant neoplasms. A germline VHL variant is identified in 95–100% of individuals with a clinical diagnosis of VHL. Here, we present the case of an individual with a clinical diagnosis of VHL disease where peripheral blood DNA analysis did not detect a VHL variant. Sequencing of four tumor tissues (ccRCC, pheochromocytoma, lung via sputum, liver) revealed a VHL c.593 T > C (p.Leu198Pro) variant at varying allele fractions (range: 10–55%) in all tissues. Re-examination of the peripheral blood sequencing data identified this variant at 6% allele fraction. Tumor analysis revealed characteristic cytomorphological, immunohistochemical reactivity for alpha-inhibin, and CAIX, and reduced pVHL reactivity supported VHL-related pseudohypoxia. This report of a rare case of VHL mosaicism highlights the value of tissue testing in VHL variant negative cases.
Solution processed low power organic field-effect transistor bio-chemical sensor of high transconductance efficiency
Authors: Tang Wei , Fu Ying , Huang Yukun , Li Yuanzhe , Song Yawen , Xi Xin , Yu Yude , Su Yuezeng , Yan Feng , Guo Xiaojun 
Published: March 2022

AbstractDeveloping organic field-effect transistor (OFET) biosensors for customizable detection of biomarkers for many diseases would provide a low-cost and convenient tool for both biological studies and clinical diagnosis. In this work, design principles of the OFET transducer for biosensors were derived to relate the signal-to-noise ratio (SNR) to the device-performance parameters. Steep subthreshold swing (SS), proper threshold voltage (Vth), good-enough bias-stress stability, and mechanical durability are shown to be the key prerequisites for realizing OFET bio-sensors of high transconductance efficiency (gm/ID) for large SNR. Combining a low trap-density channel and a high-k/low-k gate dielectric layer, low-temperature (<100 °C) solution-processed flexible OFETs can meet the performance requirements to maximize the gm/ID. An extended gate-structure OFET biosensor was further implemented for label-free detection of miR-21, achieving a detection limit below 10 pM with high selectivity at a low operation voltage (<1 V).
Separator threads in yarn-shaped supercapacitors to avoid short-circuiting upon length
Authors: He Nanfei , Song Junhua , Liao Jinyun , Zhao Feng , Gao Wei 
Published: March 2022

AbstractYarn-shaped supercapacitors (YSCs) are becoming promising energy-supply units with decent mechanical flexibility to be integrated into e-textiles in various shapes and locations. However, a robust YSC configuration that can provide long-term and reliable power output, especially after rigorous weaving and knitting processes, as well as all kinds of end uses, is yet to be established. Most YSCs today still suffer from short-circuiting upon length, primarily due to the structure failure of gel electrolyte that also works as the separator. Herein, we report the incorporation of separator threads in a twisted YSC, to withstand repetitive mechanical deformations. Separator threads are wrapped outside of yarn electrodes as a scaffold to accommodate gel electrolyte, while chemistry and wrapping density of these threads are investigated. With processing parameters optimized, we present an YSC configuration that can bear mechanical deformations along almost all directions, leading to reliable power units in woven or knit fabrics.
Nonclassicality detection from few Fock-state probabilities
Authors: Innocenti Luca , Lachman Lukáš , Filip Radim 
Published: March 2022

AbstractExperimentally certifying the nonclassicality of quantum states in a reliable and efficient way is a challenge that remains both fundamental and daunting. Despite decades of topical research, techniques that can exploit optimally the information available in a given experimental setup are lacking. Here, we introduce a different paradigm to tackle these challenges, that is both directly applicable to experimental realities, and extendible to a wide variety of circumstances. We demonstrate that Klyshko’s criteria, which remained a primary approach to tackle nonclassicality for the past 20 years, is a special case of a much more general class of nonclassicality criteria. We provide both analytical results and numerical evidence for the optimality of our approach in several different scenarios of interest for trapped-ion, superconducting circuits, optical and optomechanical experiments with photon-number resolving detectors. This work represents a significant milestone towards a complete characterisation of the nonclassicality detectable from the limited knowledge scenarios faced in experimental implementations.
Nanoscale studies of electric field effects on monolayer 1T′-WTe2
Authors: Maximenko Yulia , Chang Yueqing , Chen Guannan , Hirsbrunner Mark R. , Swiech Waclaw , Hughes Taylor L. , Wagner Lucas K. , Madhavan Vidya 
Published: March 2022

AbstractMonolayer 1 T′-WTe2 is a quantum spin Hall insulator with a gapped 2D-bulk and gapless helical edge states persisting to temperatures ~100 K. Despite the far-ranging interest, the magnitude of the bulk gap, the effect of gating on the 2D-band structure, as well the role interactions are not established. In this work we use STM spectroscopy to measure the intrinsic bulk gap of monolayer 1 T′-WTe2 and show that gate induced electric fields cause large changes of the gap magnitude. Our first-principles DFT-derived tight-binding model reveal that a combination of spatial localization of the conduction and valance bands and Rashba-like spin-orbit coupling leads to a gating induced spin-splitting of the 2D-bulk bands in the tens of meV, thereby reducing the band gap. Our work explains the large sensitivity of the band structure to electric fields and suggests a new avenue for realizing proximity induced non-trivial superconductivity in monolayer 1 T′-WTe2.
Possible star-of-David pattern charge density wave with additional modulation in the kagome superconductor CsV3Sb5
Authors: Luo J. , Zhao Z. , Zhou Y. Z. , Yang J. , Fang A. F. , Yang H. T. , Gao H. J. , Zhou R. , Zheng Guo-qing 
Published: March 2022

AbstractAV3Sb5 (A = K, Rb, Cs) is a novel kagome superconductor coexisting with the charge density wave (CDW) order. Identifying the structure of the CDW order is crucial for understanding the exotic normal state and superconductivity in this system. Here, we report 51V nuclear magnetic resonance (NMR) and 121/123Sb nuclear quadrupole resonance (NQR) studies on kagome-metal CsV3Sb5. Below the CDW transition temperature TCDW ~ 98 K, an abrupt change of spectra was observed, indicating that the transition is of the first order. By further analyzing the spectra, we find that the CDW order is commensurate. And most remarkably, the obtained experimental results suggest that the charge modulation of the CDW order is of star-of-David pattern and accompanied by an additional charge modulation in bulk below T* ~ 40 K. Our results revealing the unconventional CDW order provide new insights into AV3Sb5.
Nonsymmorphic symmetry-protected band crossings in a square-net metal PtPb4
Authors: Wu Han , Hallas Alannah M. , Cai Xiaochan , Huang Jianwei , Oh Ji Seop , Loganathan Vaideesh , Weiland Ashley , McCandless Gregory T. , Chan Julia Y. , Mo Sung-Kwan , Lu Donghui , Hashimoto Makoto , Denlinger Jonathan , Birgeneau Robert J. , Nevidomskyy Andriy H. , Li Gang , Morosan Emilia , Yi Ming 
Published: March 2022

AbstractTopological semimetals with symmetry-protected band crossings have emerged as a rich landscape to explore intriguing electronic phenomena. Nonsymmorphic symmetries in particular have been shown to play an important role in protecting the crossings along a line (rather than a point) in momentum space. Here we report experimental and theoretical evidence for Dirac nodal line crossings along the Brillouin zone boundaries in PtPb4, arising from the nonsymmorphic symmetry of its crystal structure. Interestingly, while the nodal lines would remain gapless in the absence of spin–orbit coupling (SOC), the SOC, in this case, plays a detrimental role to topology by lifting the band degeneracy everywhere except at a set of isolated points. Nevertheless, the nodal line is observed to have a bandwidth much smaller than that found in density functional theory (DFT). Our findings reveal PtPb4 to be a material system with narrow crossings approximately protected by nonsymmorphic crystalline symmetries.
Thought disorder is correlated with atypical spoken binomial orderings
Authors: Murphy Michael , Öngür Dost 
Published: March 2022

AbstractThought disorder may be associated with subtle language abnormalities. Binomials are pairs of words of the same grammatical type that are joined by a conjunction that often have a preferred order (for example, “up and down” is more common than “down and up”). We analyzed speech transcripts from patients with first-episode psychosis and found that atypical ordering of binomial pairs was associated with thought disorder but not with other psychosis symptoms. These results illustrate the potential to generate objective, quantifiable measures of disorganized speech.
Experimental and theoretical study on the corrosion inhibition of mild steel by nonanedioic acid derivative in hydrochloric acid solution
Authors: Al-Amiery Ahmed A. , Mohamad Abu Bakar , Kadhum Abdul Amir H. , Shaker Lina M. , Isahak Wan Nor Roslam Wan , Takriff Mohd S. 
Published: March 2022

AbstractThe corrosion performance of mild steel (MS) in 1M HCl solution was examined by weight loss (WL), potentiodynamic polarization (PDP), electrochemical impedance spectroscopy (EIS), electrochemical frequency modulation (EFM), and open circuit potential (OCP) measurements in the absence and presence of nonanedihydrazide. PDP measurements indicated that nonanedihydrazide acts as a mixed inhibitor due to its adsorption on the MS surface, exhibiting an inhibition efficiency of more than 97%. The surface morphology investigation of the protective layer on the MS surface confirmed that adsorption of nonanedihydrazide molecules occurred via chemical adsorption following Langmuir’s isotherm model. The effect of temperature on the corrosion performance in the presence of nonanedihydrazide was investigated in the range of 303–333 K, showing that the inhibition efficiency increased with an increase in the inhibitor concentration and decreased with an increase in temperature. A new green corrosion inhibitor was synthesised and theoretical computations were conducted to completely understand the inhibition mechanism. Nonanedihydrazide molecules were investigated by DFT (density functional theory) using the B3LYP functional to evaluate the relationship of corrosion inhibition performance and the molecular structure. The computed theoretical parameters presented significant support for understanding the inhibitive mechanism revealed by the inhibitory molecules and are in good agreement with WL, PDP, EIS, (EFM), and OCP results.
Clinical associations of ESR2 (estrogen receptor beta) expression across thousands of primary breast tumors
Authors: Dalal Hina , Dahlgren Malin , Gladchuk Sergii , Brueffer Christian , Gruvberger-Saal Sofia K. , Saal Lao H. 
Published: March 2022

AbstractEstrogen receptor alpha (ERα, encoded byESR1) is a well-characterized transcription factor expressed in more than 75% of breast tumors and is the key biomarker to direct endocrine therapies. On the other hand, much less is known about estrogen receptor beta (ERβ, encoded byESR2) and its importance in cancer. Previous studies had some disagreement, however most reports suggested a more favorable prognosis for patients with highESR2expression. To add further clarity toESR2in breast cancer, we interrogated a large population-based cohort of primary breast tumors (n = 3207) from the SCAN-B study. RNA-seq showsESR2is expressed at low levels overall with a slight inverse correlation toESR1expression (Spearman R = −0.18, p = 2.2e−16), and highestESR2expression in the basal- and normal-like PAM50 subtypes.ESR2-high tumors had favorable overall survival (p = 0.006), particularly in subgroups receiving endocrine therapy (p = 0.03) and in triple-negative breast cancer (p = 0.01). These results were generally robust in multivariable analyses accounting for patient age, tumor size, node status, and grade. Gene modules consistent with immune response were associated toESR2-high tumors. Taken together, our results indicate thatESR2is generally expressed at low levels in breast cancer but associated with improved overall survival and may be related to immune response modulation.
Determinants of IGF-II influencing stability, receptor binding and activation
Authors: Blyth Andrew , Ortiz Michael , Merriman Allanah , Delaine Carlie , Forbes Briony 
Published: March 2022

AbstractInsulin like growth factor II (IGF-II) is involved in metabolic and mitogenic signalling in mammalian cells and plays important roles in normal fetal development and postnatal growth. It is structurally similar to insulin and binds not only with high affinity to the type 1 insulin-like growth factor receptor (IGF-1R) but also to the insulin receptor isoform A (IR-A). As IGF-II expression is commonly upregulated in cancer and its signalling promotes cancer cell survival, an antagonist that blocks IGF-II action without perturbing insulin signalling would be invaluable. The high degree of structural homology between the IR and IGF-1R makes selectively targeting either receptor in the treatment of IGF-II-dependent cancers very challenging. However, there are sequence differences between insulin and IGF-II that convey receptor selectivity and influence binding affinity and signalling outcome. Insulin residue YB16 is a key residue involved in maintaining insulin stability, dimer formation and IR binding. Mutation of this residue to glutamine (as found in IGF-II) results in reduced binding affinity. In this study we sought to determine if the equivalent residue Q18 in IGF-II plays a similar role. We show through site-directed mutagenesis of Q18 that this residue contributes to IGF-II structural integrity, selectivity of IGF-1R/IR binding, but surprisingly does not influence IR-A signalling activation. These findings provide insights into a unique IGF-II residue that can influence receptor binding specificity whilst having little influence on signalling outcome.