bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subglacial precipitates record Antarctic ice sheet response to late Pleistocene millennial climate cycles
Authors: Piccione Gavin , Blackburn Terrence , Tulaczyk Slawek , Rasbury E. Troy , Hain Mathis P. , Ibarra Daniel E. , Methner Katharina , Tinglof Chloe , Cheney Brandon , Northrup Paul , Licht Kathy 
Published: September 2022

AbstractIce cores and offshore sedimentary records demonstrate enhanced ice loss along Antarctic coastal margins during millennial-scale warm intervals within the last glacial termination. However, the distal location and short temporal coverage of these records leads to uncertainty in both the spatial footprint of ice loss, and whether millennial-scale ice response occurs outside of glacial terminations. Here we present a >100kyr archive of periodic transitions in subglacial precipitate mineralogy that are synchronous with Late Pleistocene millennial-scale climate cycles. Geochemical and geochronologic data provide evidence for opal formation during cold periods via cryoconcentration of subglacial brine, and calcite formation during warm periods through the addition of subglacial meltwater originating from the ice sheet interior. These freeze-flush cycles represent cyclic changes in subglacial hydrologic-connectivity driven by ice sheet velocity fluctuations. Our findings imply that oscillating Southern Ocean temperatures drive a dynamic response in the Antarctic ice sheet on millennial timescales, regardless of the background climate state.
Transcriptional dynamics of murine motor neuron maturation in vivo and in vitro
Authors: Patel Tulsi , Hammelman Jennifer , Aziz Siaresh , Jang Sumin , Closser Michael , Michaels Theodore L. , Blum Jacob A. , Gifford David K. , Wichterle Hynek 
Published: September 2022

AbstractNeurons born in the embryo can undergo a protracted period of maturation lasting well into postnatal life. How gene expression changes are regulated during maturation and whether they can be recapitulated in cultured neurons remains poorly understood. Here, we show that mouse motor neurons exhibit pervasive changes in gene expression and accessibility of associated regulatory regions from embryonic till juvenile age. While motifs of selector transcription factors, ISL1 and LHX3, are enriched in nascent regulatory regions, motifs of NFI factors, activity-dependent factors, and hormone receptors become more prominent in maturation-dependent enhancers. Notably, stem cell-derived motor neurons recapitulate ~40% of the maturation expression program in vitro, with neural activity playing only a modest role as a late-stage modulator. Thus, the genetic maturation program consists of a core hardwired subprogram that is correctly executed in vitro and an extrinsically-controlled subprogram that is dependent on the in vivo context of the maturing organism.
Layered feedback control overcomes performance trade-off in synthetic biomolecular networks
Authors: Hu Chelsea Y. , Murray Richard M. 
Published: September 2022

AbstractLayered feedback is an optimization strategy in feedback control designs widely used in engineering. Control theory suggests that layering multiple feedbacks could overcome the robustness-speed performance trade-off limit. In natural biological networks, genes are often regulated in layers to adapt to environmental perturbations. It is hypothesized layering architecture could also overcome the robustness-speed performance trade-off in genetic networks. In this work, we validate this hypothesis with a synthetic biomolecular network in living E. coli cells. We start with system dynamics analysis using models of various complexities to guide the design of a layered control architecture in living cells. Experimentally, we interrogate system dynamics under three groups of perturbations. We consistently observe that the layered control improves system performance in the robustness-speed domain. This work confirms that layered control could be adopted in synthetic biomolecular networks for performance optimization. It also provides insights into understanding genetic feedback control architectures in nature.
Pangenomic analysis of Chinese gastric cancer
Authors: Yu Yingyan , Zhang Zhen , Dong Xiaorui , Yang Ruixin , Duan Zhongqu , Xiang Zhen , Li Jun , Li Guichao , Yan Fazhe , Xue Hongzhang , Jiao Du , Lu Jinyuan , Lu Huimin , Zhang Wenmin , Wei Yangzhen , Fan Shiyu , Li Jing , Jia Jingya , Zhang Jun , Ji Jun , Liu Pixu , Lu Hui , Zhao Hongyu , Chen Saijuan , Wei Chaochun , Chen Hongzhuan , Zhu Zhenggang 
Published: September 2022

AbstractPangenomic study might improve the completeness of human reference genome (GRCh38) and promote precision medicine. Here, we use an automated pipeline of human pangenomic analysis to build gastric cancer pan-genome for 185 paired deep sequencing data (370 samples), and characterize the gene presence-absence variations (PAVs) at whole genome level. Genes ACOT1, GSTM1, SIGLEC14 and UGT2B17 are identified as highly absent genes in gastric cancer population. A set of genes from unaligned sequences with GRCh38 are predicted. We successfully locate one of predicted genes GC0643 on chromosome 9q34.2. Overexpression of GC0643 significantly inhibits cell growth, cell migration and invasion, cell cycle progression, and induces cell apoptosis in cancer cells. The tumor suppressor functions can be reversed by shGC0643 knockdown. The GC0643 is approved by NCBI database (GenBank: MW194843.1). Collectively, the robust pan-genome strategy provides a deeper understanding of the gene PAVs in the human cancer genome.
Structure of the active Gi-coupled human lysophosphatidic acid receptor 1 complexed with a potent agonist
Authors: Akasaka Hiroaki , Tanaka Tatsuki , Sano Fumiya K. , Matsuzaki Yuma , Shihoya Wataru , Nureki Osamu 
Published: September 2022

AbstractLysophosphatidic acid receptor 1 (LPA1) is one of the six G protein-coupled receptors activated by the bioactive lipid, lysophosphatidic acid (LPA). LPA1 is a drug target for various diseases, including cancer, inflammation, and neuropathic pain. Notably, LPA1 agonists have potential therapeutic value for obesity and urinary incontinence. Here, we report a cryo-electron microscopy structure of the active human LPA1-Gi complex bound to ONO-0740556, an LPA analog with more potent activity against LPA1. Our structure elucidated the details of the agonist binding mode and receptor activation mechanism mediated by rearrangements of transmembrane segment 7 and the central hydrophobic core. A structural comparison of LPA1 and other phylogenetically-related lipid-sensing GPCRs identified the structural determinants for lipid preference of LPA1. Moreover, we characterized the structural polymorphisms at the receptor-G-protein interface, which potentially reflect the G-protein dissociation process. Our study provides insights into the detailed mechanism of LPA1 binding to agonists and paves the way toward the design of drug-like agonists targeting LPA1.
Reconstitution of microtubule into GTP-responsive nanocapsules
Authors: Uchida Noriyuki , Kohata Ai , Okuro Kou , Cardellini Annalisa , Lionello Chiara , Zizzi Eric A. , Deriu Marco A. , Pavan Giovanni M. , Tomishige Michio , Hikima Takaaki , Aida Takuzo 
Published: September 2022

AbstractNanocapsules that collapse in response to guanosine triphosphate (GTP) have the potential as drug carriers for efficiently curing diseases caused by cancer and RNA viruses because GTP is present at high levels in such diseased cells and tissues. However, known GTP-responsive carriers also respond to adenosine triphosphate (ATP), which is abundant in normal cells as well. Here, we report the elaborate reconstitution of microtubule into a nanocapsule that selectively responds to GTP. When the tubulin monomer from microtubule is incubated at 37 °C with a mixture of GTP (17 mol%) and nonhydrolysable GTP* (83 mol%), a tubulin nanosheet forms. Upon addition of photoreactive molecular glue to the resulting dispersion, the nanosheet is transformed into a nanocapsule. Cell death results when a doxorubicin-containing nanocapsule, after photochemically crosslinked for properly stabilizing its shell, is taken up into cancer cells that overexpress GTP.
Cryptococcal Hsf3 controls intramitochondrial ROS homeostasis by regulating the respiratory process
Authors: Gao Xindi , Fu Yi , Sun Shengyi , Gu Tingyi , Li Yanjian , Sun Tianshu , Li Hailong , Du Wei , Suo Chenhao , Li Chao , Gao Yiru , Meng Yang , Ni Yue , Yang Sheng , Lan Tian , Sai Sixiang , Li Jiayi , Yu Kun , Wang Ping , Ding Chen 
Published: September 2022

AbstractMitochondrial quality control prevents accumulation of intramitochondrial-derived reactive oxygen species (mtROS), thereby protecting cells against DNA damage, genome instability, and programmed cell death. However, underlying mechanisms are incompletely understood, particularly in fungal species. Here, we show that Cryptococcus neoformans heat shock factor 3 (CnHsf3) exhibits an atypical function in regulating mtROS independent of the unfolded protein response. CnHsf3 acts in nuclei and mitochondria, and nuclear- and mitochondrial-targeting signals are required for its organelle-specific functions. It represses the expression of genes involved in the tricarboxylic acid cycle while promoting expression of genes involved in electron transfer chain. In addition, CnHsf3 responds to multiple intramitochondrial stresses; this response is mediated by oxidation of the cysteine residue on its DNA binding domain, which enhances DNA binding. Our results reveal a function of HSF proteins in regulating mtROS homeostasis that is independent of the unfolded protein response.
Spatial interplay of tissue hypoxia and T-cell regulation in ductal carcinoma in situ
Authors: Sobhani Faranak , Muralidhar Sathya , Hamidinekoo Azam , Hall Allison H. , King Lorraine M. , Marks Jeffrey R. , Maley Carlo , Horlings Hugo M. , Hwang E. Shelley , Yuan Yinyin 
Published: September 2022

AbstractHypoxia promotes aggressive tumor phenotypes and mediates the recruitment of suppressive T cells in invasive breast carcinomas. We investigated the role of hypoxia in relation to T-cell regulation in ductal carcinoma in situ (DCIS). We designed a deep learning system tailored for the tissue architecture complexity of DCIS, and compared pure DCIS cases with the synchronous DCIS and invasive components within invasive ductal carcinoma cases. Single-cell classification was applied in tandem with a new method for DCIS ductal segmentation in dual-stained CA9 and FOXP3, whole-tumor section digital pathology images. Pure DCIS typically has an intermediate level of colocalization of FOXP3+ and CA9+ cells, but in invasive carcinoma cases, the FOXP3+ (T-regulatory) cells may have relocated from the DCIS and into the invasive parts of the tumor, leading to high levels of colocalization in the invasive parts but low levels in the synchronous DCIS component. This may be due to invasive, hypoxic tumors evolving to recruit T-regulatory cells in order to evade immune predation. Our data support the notion that hypoxia promotes immune tolerance through recruitment of T-regulatory cells, and furthermore indicate a spatial pattern of relocalization of T-regulatory cells from DCIS to hypoxic tumor cells. Spatial colocalization of hypoxic and T-regulatory cells may be a key event and useful marker of DCIS progression.
Quantum Fredkin and Toffoli gates on a versatile programmable silicon photonic chip
Authors: Li Yuan , Wan Lingxiao , Zhang Hui , Zhu Huihui , Shi Yuzhi , Chin Lip Ket , Zhou Xiaoqi , Kwek Leong Chuan , Liu Ai Qun 
Published: September 2022

AbstractQuantum logic gates are backbones of quantum information processing (QIP), wherein the typical three-qubit Fredkin and Toffoli gates are essential in quantum computation and communication. So far, the quantum Fredkin gate has only been demonstrated with pre-entangled input states in free-space optics, which limits its usage for independent input photons. Here, we put forward an exquisite scheme and experimentally perform a proof-of-principle demonstration of three-qubit Fredkin and Toffoli gates on a programmable quantum photonic chip. Our scheme can also be used to realize a series of other two-qubit quantum gates. Our work sheds light on the merits of quantum photonic chip in implementing quantum logic gates, and paves the way for advanced quantum chip processors.
Induction of functional xeno-free MSCs from human iPSCs via a neural crest cell lineage
Authors: Kamiya Daisuke , Takenaka-Ninagawa Nana , Motoike Souta , Kajiya Mikihito , Akaboshi Teppei , Zhao Chengzhu , Shibata Mitsuaki , Senda Sho , Toyooka Yayoi , Sakurai Hidetoshi , Kurihara Hidemi , Ikeya Makoto 
Published: September 2022

AbstractMesenchymal stem/stromal cells (MSCs) are adult multipotent stem cells. Here, we induced MSCs from human induced pluripotent stem cells (iPSCs) via a neural crest cell (NCC) lineage under xeno-free conditions and evaluated their in vivo functions. We modified a previous MSC induction method to work under xeno-free conditions. Bovine serum albumin-containing NCC induction medium and fetal bovine serum-containing MSC induction medium were replaced with xeno-free medium. Through our optimized method, iPSCs differentiated into MSCs with high efficiency. To evaluate their in vivo activities, we transplanted the xeno-free-induced MSCs (XF-iMSCs) into mouse models for bone and skeletal muscle regeneration and confirmed their regenerative potency. These XF-iMSCs mainly promoted the regeneration of surrounding host cells, suggesting that they secrete soluble factors into affected regions. We also found that the peroxidasin and IGF2 secreted by the XF-iMSCs partially contributed to myotube differentiation. These results suggest that XF-iMSCs are important for future applications in regenerative medicine.
Expert-level detection of pathologies from unannotated chest X-ray images via self-supervised learning
Authors: Tiu Ekin , Talius Ellie , Patel Pujan , Langlotz Curtis P. , Ng Andrew Y. , Rajpurkar Pranav 
Published: September 2022

AbstractIn tasks involving the interpretation of medical images, suitably trained machine-learning models often exceed the performance of medical experts. Yet such a high-level of performance typically requires that the models be trained with relevant datasets that have been painstakingly annotated by experts. Here we show that a self-supervised model trained on chest X-ray images that lack explicit annotations performs pathology-classification tasks with accuracies comparable to those of radiologists. On an external validation dataset of chest X-rays, the self-supervised model outperformed a fully supervised model in the detection of three pathologies (out of eight), and the performance generalized to pathologies that were not explicitly annotated for model training, to multiple image-interpretation tasks and to datasets from multiple institutions.
A digital mask to safeguard patient privacy
Authors: Yang Yahan , Lyu Junfeng , Wang Ruixin , Wen Quan , Zhao Lanqin , Chen Wenben , Bi Shaowei , Meng Jie , Mao Keli , Xiao Yu , Liang Yingying , Zeng Danqi , Du Zijing , Wu Yuxuan , Cui Tingxin , Liu Lixue , Iao Wai Cheng , Li Xiaoyan , Cheung Carol Y. , Zhou Jianhua , Hu Youjin , Wei Lai , Lai Iat Fan , Yu Xinping , Chen Jingchang , Wang Zhonghao , Mao Zhen , Ye Huijing , Xiao Wei , Yang Huasheng , Huang Danping , Lin Xiaoming , Zheng Wei-shi , Wang Ruixuan , Yu-Wai-Man Patrick , Xu Feng , Dai Qionghai , Lin Haotian 
Published: September 2022

AbstractThe storage of facial images in medical records poses privacy risks due to the sensitive nature of the personal biometric information that can be extracted from such images. To minimize these risks, we developed a new technology, called the digital mask (DM), which is based on three-dimensional reconstruction and deep-learning algorithms to irreversibly erase identifiable features, while retaining disease-relevant features needed for diagnosis. In a prospective clinical study to evaluate the technology for diagnosis of ocular conditions, we found very high diagnostic consistency between the use of original and reconstructed facial videos (κ ≥ 0.845 for strabismus, ptosis and nystagmus, and κ = 0.801 for thyroid-associated orbitopathy) and comparable diagnostic accuracy (P ≥ 0.131 for all ocular conditions tested) was observed. Identity removal validation using multiple-choice questions showed that compared to image cropping, the DM could much more effectively remove identity attributes from facial images. We further confirmed the ability of the DM to evade recognition systems using artificial intelligence-powered re-identification algorithms. Moreover, use of the DM increased the willingness of patients with ocular conditions to provide their facial images as health information during medical treatment. These results indicate the potential of the DM algorithm to protect the privacy of patients’ facial images in an era of rapid adoption of digital health technologies.
Role of saltmarsh systems in estuarine trapping of microplastics
Authors: Ogbuagu Chiedozie C. , Kassem Hachem , Udiba Udiba U. , Stead Jessica L. , Cundy Andrew B. 
Published: September 2022

AbstractSaltmarshes are important natural ecosystems along many temperate (and other) coastlines. They stabilize sediments and act as biofilters for a range of industrial pollutants and, potentially, microplastics. Accumulation of microplastics along estuarine coastlines may be enhanced by the presence of saltmarsh species, as they offer better particle trapping efficiency than adjacent intertidal mudflats under prevailing flood and ebb tidal currents. However, the trapping efficiency of entire saltmarsh systems under varying flow conditions has not been widely assessed. While the effects of saltmarsh systems on water flow, and on sediment transport and trapping, have been relatively well studied, little is known about the contributions of saltmarsh halophytes, resident organisms and the associated saltmarsh sediments to the trapping of microplastics. To address this, a series of flume experiments were undertaken to examine transport and accumulation of Bakelite particles (~ 500 µm) and PVC nurdles (~ 5 mm) as model plastics in sub-sampled saltmarsh and intertidal mudflat monoliths. The results showed that saltmarsh systems influenced the hydrodynamics within and above the canopy, enhancing turbulence and shear stresses. With increasing flow velocities (≤ 0.51 m s−1), negligible quantities (2$$\times$$×10−4 mg L−1) of sediments and Bakelite particles were eroded and resuspended. The algal biogenic roughness from the mudflat, and the vegetative roughness from theSpartinaplants on the saltmarsh, inhibited the transportation of the microplastics within the tested systems. Resident burrowing crabs (Carcinus maenas) promoted the burial, release and transport of microplastics. The results of this study provide evidence of the contributory roles of saltmarsh systems in the sequestration of microplastics and sediment stabilization. Estuarine saltmarsh systems can act as sinks for microplastics with enhanced burial from burrowing crabs under favourable flow conditions.
IoT malware detection architecture using a novel channel boosted and squeezed CNN
Authors: Asam Muhammad , Khan Saddam Hussain , Akbar Altaf , Bibi Sameena , Jamal Tauseef , Khan Asifullah , Ghafoor Usman , Bhutta Muhammad Raheel 
Published: September 2022

AbstractInteraction between devices, people, and the Internet has given birth to a new digital communication model, the internet of things (IoT). The integration of smart devices to constitute a network introduces many security challenges. These connected devices have created a security blind spot, where cybercriminals can easily launch attacks to compromise the devices using malware proliferation techniques. Therefore, malware detection is a lifeline for securing IoT devices against cyberattacks. This study addresses the challenge of malware detection in IoT devices by proposing a new CNN-based IoT malware detection architecture (iMDA). The proposed iMDA is modular in design that incorporates multiple feature learning schemes in blocks including (1) edge exploration and smoothing, (2) multi-path dilated convolutional operations, and (3) channel squeezing and boosting in CNN to learn a diverse set of features. The local structural variations within malware classes are learned by Edge and smoothing operations implemented in the split-transform-merge (STM) block. The multi-path dilated convolutional operation is used to recognize the global structure of malware patterns. At the same time, channel squeezing and merging helped to regulate complexity and get diverse feature maps. The performance of the proposed iMDA is evaluated on a benchmark IoT dataset and compared with several state-of-the CNN architectures. The proposed iMDA shows promising malware detection capacity by achieving accuracy: 97.93%, F1-Score: 0.9394, precision: 0.9864, MCC: 0. 8796, recall: 0.8873, AUC-PR: 0.9689 and AUC-ROC: 0.9938. The strong discrimination capacity suggests that iMDA may be extended for the android-based malware detection and IoT Elf files compositely in the future.
Turbulent current sheet frozen in bursty bulk flow: observation and model
Authors: Zhang L. Q. , Wang Chi , Dai L. , Baumjohann W. , Burch James L. , Khotyaintsev Yu. V. , Wang J. Y. 
Published: September 2022

AbstractUtilizing four-point joint observations by Magnetospheric Multiscale Spacecraft (MMS), we investigate the main features of the current sheet frozen in (CSFI) the bursty bulk flow. Typical event on the steady long-lasting BBF on July 23, 2017 shows the enhanced dawn-dusk current (Jy0) in the CSFI (β ~ 10). The magnitude of the Jy0 in the CSFI is about 5.5 nA/m2. The CSFI is highly turbulent, with the ratio of ∆J/J0 of ~ 2 (where ∆J is perturbed J). The turbulent CSFI is characterized by intermittent current coherent structures. The magnitude of the spiky-J at coherent structures is typically above 30 nA/m2. Spectrum analysis exhibits that BBF turbulence follows distinct dissipation laws inside and outside the CSFI. Based on MMS observations, we propose a new model of the BBF in the framework of magnetohydrodynamics. In this model, the BBF is depicted as a closed plasma system with the localized current sheet frozen at the center of the flow (Taylor’s hypothesis). In the light of principle of Helmholtz-decomposition, the BBF motion in the tail plasma sheet is explained. The model also predicts the thermal expansion of the BBF after leaving the reconnection source region.
Formal synthesis of non-fragile state-feedback digital controllers considering performance requirements for step response
Authors: Cavalcante Thiago , Bessa Iury , Lima Filho Eddie B. de , Cordeiro Lucas C. 
Published: September 2022

AbstractThis work describes an approach for synthesizing state-feedback controllers for discrete-time systems, taking into account performance aspects. The proposed methodology is based on counterexample-guided inductive synthesis (CEGIS), producing safe controllers based on step response performance requirements, such as settling time and maximum-overshoot. Controller candidates are generated through constrained optimization based on genetic algorithms. Each iteration that does not satisfy the initial system requirements is learned as a failed result and then used in another attempt. During the verification phase, it is considered the controller fragility to ensure deployable implementations. Such an approach assists the discrete-time control system design since weaknesses occur during implementation on digital platforms, where systems that meet design requirements are employed. The proposed method is implemented in DSVerifier, a tool that uses bounded (and unbounded) model checking based on satisfiability modulo theories. Experimental results showed that our approach is practical and sound regarding the synthesis of discrete state-feedback control systems that present performance requirements. It considers finite word-length effects, unlike other methods that routinely ignore them.