bluuebunny/crossref_metadata_2025 huggingface dataset:
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

Neurons 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

Layered 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

Pangenomic 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

Lysophosphatidic 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

Nanocapsules 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

Mitochondrial 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

Hypoxia 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

Quantum 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

Mesenchymal 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

In 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

The 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

Saltmarshes 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

Interaction 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

Utilizing 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

This 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.
Magneto-transport and Thermal properties of TiH diatomic molecule under the influence of magnetic and Aharonov-Bohm (AB) fields
Authors: Edet C. O. , Khordad R. , Ettah E. B. , Aljunid S. A. , Endut R. , Ali N. , Asjad M. , Ushie P. O. , Ikot A. N.
Published: September 2022

In this study, the effects of Aharonov-Bohm (AB) and magnetic fields on the thermodynamic and magneto-transport properties of TiH diatomic molecule using the Deng-Fan potential as a model are investigated. The functional analysis approach (FAA) is used to solve the Schrodinger equation in the presence of magnetic and AB fields with Deng-Fan potential. The energy equation, as well as the wave function, have been derived. The analytic expressions for the thermo-magnetic and transport properties of the Deng-Fan potential are derived using the energy equation and the partition function. These properties obtained are thoroughly analysed utilising graphical representations. Our analysis shows that the magnetic susceptibility of the TiH exhibits a diamagnetic behaviour, and the specific heat capacity behaviour agrees with the famous Dulong-Petit law when the system is subjected to AB field variations and a fixed magnetic field. Albeit, a slight anomaly is observed in the behaviour of the specific heat capacity. Our findings will be valuable in various fields of physics, including chemical and molecular physics and condensed matter physics, where the derived models could be applied to study other diatomic molecules and quantum dots, respectively.
Antimicrobial potential of a ponericin-like peptide isolated from Bombyx mori L. hemolymph in response to Pseudomonas aeruginosa infection
Authors: Nesa Jannatun , Jana Swapan Kumar , Sadat Abdul , Biswas Kinkar , Kati Ahmet , Kaya Ozge , Mondal Rittick , Dam Paulami , Thakur Mintu , Kumar Anoop , Hossain Maidul , Lima Lucas R. , Rezende Samilla B. , Bhattacharjya Debjoy , Gangopadhyay Debnirmalya , Ghorai Suvankar , Altuntas Sevde , Panda Amiya Kumar , Chakrabarti Pinak , Swarnakar Shambhu , Chakraborty Joydeep , Yilmaz Berfin , Macedo Maria L. R. , Franco Octávio L. , Cardoso Marlon H. , Mandal Amit Kumar
Published: September 2022

The main effectors in the innate immune system of Bombyx mori L. are antimicrobial peptides (AMPs). Here, we infected B. mori with varied inoculum sizes of Pseudomonas aeruginosa ATCC 25668 cells to investigate changes in morpho-anatomical responses, physiological processes and AMP production. Ultraviolet–visible spectra revealed a sharp change in λmax from 278 to 285 nm (bathochromic shift) in the hemolymph of infected B. mori incubated for 24 h. Further, Fourier Transform InfraRed studies on the hemolymph extracted from the infected B. mori showed a peak at 1550 cm−1, indicating the presence of α-helical peptides. The peptide fraction was obtained through methanol, acetic acid and water mixture (90:1:9) extraction, followed by peptide purification using Reverse Phase High Performance Liquid Chromatography. The fraction exhibiting antibacterial properties was collected and characterized by Matrix-Assisted Laser Desorption/Ionization-Time of Flight. A linear α-helical peptide with flexible termini (LLKELWTKMKGAGKAVLGKIKGLL) was found, corresponding to a previously described peptide from ant venom and here denominated as Bm-ponericin-L1. The antibacterial activity of Bm-ponericin-L1 was determined against ESKAPE pathogens. Scanning electron microscopy confirmed the membrane disruption potential of Bm-ponericin-L1. Moreover, this peptide also showed promising antibiofilm activity. Finally, cell viability and hemolytic assays revealed that Bm-ponericin-L1 is non-toxic toward primary fibroblasts cell lines and red blood cells, respectively. This study opens up new perspectives toward an alternative approach to overcoming multiple-antibiotic-resistance by means of AMPs through invertebrates’ infection with human pathogenic bacteria.
PARP3 supervises G9a-mediated repression of adhesion and hypoxia-responsive genes in glioblastoma cells
Authors: Nguekeu-Zebaze Leonel , Hanini Najat , Noll Aurélia , Wadier Nadège , Amé Jean-Christophe , Roegel Lisa , Dantzer Françoise
Published: September 2022

In breast cancer, Poly(ADP-ribose) polymerase 3 (PARP3) has been identified as a key driver of tumor aggressiveness exemplifying its selective inhibition as a promising surrogate for clinical activity onto difficult-to-treat cancers. Here we explored the role of PARP3 in the oncogenicity of glioblastoma, the most aggressive type of brain cancer. The absence of PARP3 did not alter cell proliferation nor the in vivo tumorigenic potential of glioblastoma cells. We identified a physical and functional interaction of PARP3 with the histone H3 lysine 9 methyltransferase G9a. We show that PARP3 helps to adjust G9a-dependent repression of the adhesion genes Nfasc and Parvb and the hypoxia-responsive genes Hif-2α, Runx3, Mlh1, Ndrg1, Ndrg2 and Ndrg4. Specifically for Nfasc, Parvb and Ndrg4, PARP3/G9a cooperate for an adjusted establishment of the repressive mark H3K9me2. While examining the functional consequence in cell response to hypoxia, we discovered that PARP3 acts to maintain the cytoskeletal microtubule stability. As a result, the absence of PARP3 markedly increases the sensitivity of glioblastoma cells to microtubule-destabilizing agents providing a new therapeutic avenue for PARP3 inhibition in brain cancer therapy.
High gain chopper supplied from PV system to fed synchronous reluctance motor drive for pumping water application
Authors: Elbarbary Z. M. Salem , Cheema Khalid Mehmood , Al-Gahtani Saad F. , El-Sehiemy Ragab A.
Published: September 2022

Power generation for renewable energy sources increased rapidly during last few years. Similarly, the high gain dc–dc boost choppers are taking place of conventional power converters used for photovoltaic (PV) appliances. Researchers are developing different methods in order to provide high voltage gain, low ripple, reduced switch stress, low converter costs, and minimized variations of PV operating points. This study proposes a two-stage converter for a freestanding water pumping motor drive power by solar PV system. According to the proposed system, at first, a high gain (HG) cell and a DC-to-DC boost converter are combined to increase the PV voltage to high levels. Later on, the resulting dc voltage feds a three-phase synchronous reluctance motor drive that operates centrifugal pump load. The perturb and observe approach is utilized to get the maximum power out of the solar PV module. Moreover, indirect field-oriented control is implemented to accomplish smooth starting of synchronous reluctance motor. In order to validate the effectiveness of proposed technique, a MATLAB/Simulink environment-based simulation setup along with an experimental prototype is developed. Additionally, various cases are considered based on different operating conditions and irradiance levels to collect and analyse the results.
Lossy compression of matrices by black box optimisation of mixed integer nonlinear programming
Authors: Kadowaki Tadashi , Ambai Mitsuru
Published: September 2022

In edge computing, suppressing data size is a challenge for machine learning models that perform complex tasks such as autonomous driving, in which computational resources (speed, memory size and power) are limited. Efficient lossy compression of matrix data has been introduced by decomposing it into the product of an integer and real matrices. However, its optimisation is difficult as it requires simultaneous optimisation of an integer and real variables. In this paper, we improve this optimisation by utilising recently developed black-box optimisation (BBO) algorithms with an Ising solver for binary variables. In addition, the algorithm can be used to solve mixed-integer programming problems that are linear and non-linear in terms of real and integer variables, respectively. The differences between the choice of Ising solvers (simulated annealing, quantum annealing and simulated quenching) and the strategies of the BBO algorithms (BOCS, FMQA and their variations) are discussed for further development of the BBO techniques.
A robust spike sorting method based on the joint optimization of linear discrimination analysis and density peaks
Authors: Zhang Yiwei , Han Jiawei , Liu Tengjun , Yang Zelan , Chen Weidong , Zhang Shaomin
Published: September 2022

Spike sorting is a fundamental step in extracting single-unit activity from neural ensemble recordings, which play an important role in basic neuroscience and neurotechnologies. A few algorithms have been applied in spike sorting. However, when noise level or waveform similarity becomes relatively high, their robustness still faces a big challenge. In this study, we propose a spike sorting method combining Linear Discriminant Analysis (LDA) and Density Peaks (DP) for feature extraction and clustering. Relying on the joint optimization of LDA and DP: DP provides more accurate classification labels for LDA, LDA extracts more discriminative features to cluster for DP, and the algorithm achieves high performance after iteration. We first compared the proposed LDA-DP algorithm with several algorithms on one publicly available simulated dataset and one real rodent neural dataset with different noise levels. We further demonstrated the performance of the LDA-DP method on a real neural dataset from non-human primates with more complex distribution characteristics. The results show that our LDA-DP algorithm extracts a more discriminative feature subspace and achieves better cluster quality than previously established methods in both simulated and real data. Especially in the neural recordings with high noise levels or waveform similarity, the LDA-DP still yields a robust performance with automatic detection of the number of clusters. The proposed LDA-DP algorithm achieved high sorting accuracy and robustness to noise, which offers a promising tool for spike sorting and facilitates the following analysis of neural population activity.
Disarming of type I-F CRISPR-Cas surveillance complex by anti-CRISPR proteins AcrIF6 and AcrIF9
Authors: Kupcinskaite Egle , Tutkus Marijonas , Kopūstas Aurimas , Ašmontas Simonas , Jankunec Marija , Zaremba Mindaugas , Tamulaitiene Giedre , Sinkunas Tomas
Published: September 2022

CRISPR-Cas systems are prokaryotic adaptive immune systems that protect against phages and other invading nucleic acids. The evolutionary arms race between prokaryotes and phages gave rise to phage anti-CRISPR (Acr) proteins that act as a counter defence against CRISPR-Cas systems by inhibiting the effector complex. Here, we used a combination of bulk biochemical experiments, X-ray crystallography and single-molecule techniques to explore the inhibitory activity of AcrIF6 and AcrIF9 proteins against the type I-F CRISPR-Cas system from Aggregatibacter actinomycetemcomitans (Aa). We showed that AcrIF6 and AcrIF9 proteins hinder Aa-Cascade complex binding to target DNA. We solved a crystal structure of Aa1-AcrIF9 protein, which differ from other known AcrIF9 proteins by an additional structurally important loop presumably involved in the interaction with Cascade. We revealed that AcrIF9 association with Aa-Cascade promotes its binding to off-target DNA sites, which facilitates inhibition of CRISPR-Cas protection.
In silico study on the Hepatitis E virus RNA Helicase and its inhibition by silvestrol, rocaglamide and other flavagline compounds
Authors: Pedroni Lorenzo , Dellafiora Luca , Varrà Maria Olga , Galaverna Gianni , Ghidini Sergio
Published: September 2022

Hepatitis E Virus (HEV) follows waterborne or zoonotic/foodborne transmission. Genotype 3 HEV infections are worldwide spread, especially in swine populations, representing an emerging threat for human health, both for farm workers and pork meat consumers. Unfortunately, HEV in vitro culture and analysis are still difficult, resulting in a poor understanding of its biology and hampering the implementation of counteracting strategies. Indeed, HEV encodes for only one non-structural multifunctional and multidomain protein (ORF1), which might be a good candidate for anti-HEV drugging strategies. In this context, an in silico molecular modelling approach that consisted in homology modelling to derive the 3D model target, docking study to simulate the binding event, and molecular dynamics to check complex stability over time was used. This workflow succeeded to describe ORF1 RNA Helicase domain from a molecular standpoint allowing the identification of potential inhibitory compounds among natural plant-based flavagline-related molecules such as silvestrol, rocaglamide and derivatives thereof. In the context of scouting potential anti-viral compounds and relying on the outcomes presented, further dedicated investigations on silvestrol, rocaglamide and a promising oxidized derivative have been suggested. For the sake of data reproducibility, the 3D model of HEV RNA Helicase has been made publicly available.
Magnetic dynamics of hedgehog in icosahedral quasicrystal
Authors: Watanabe Shinji
Published: September 2022

Quasicrystals (QCs) possess a unique lattice structure without translational invariance, which is characterized by the rotational symmetry forbidden in periodic crystals such as the 5-fold rotation. Recent discovery of the ferromagnetic (FM) long-range order in the terbium-based QC has brought about breakthrough but the magnetic structure and dynamics remain unresolved. Here, we reveal the dynamical as well as static structure of the FM hedgehog state in the icosahedral QC. The FM hedgehog is shown to be characterized by the triple-Q state in the reciprocal-lattice $${{\varvec{q}}}$$

q

space. Dynamical structure factor is shown to exhibit highly structured $${{\varvec{q}}}$$

q

and energy dependences. We find a unique magnetic excitation mode along the 5-fold direction exhibiting the streak fine structure in the $${{\varvec{q}}}$$

q

-energy plane, which is characteristic of the hedgehog in the icosahedral QC. Non-reciprocal magnetic excitations are shown to arise from the FM hedgehog order, which emerge in the vast extent of the $${{\varvec{q}}}$$

q

-energy plane.
Development of a new and facile method for determination of chlorpyrifos residues in green tea by dispersive liquid–liquid microextraction
Authors: Tian Hai , Feng Yujie , Yang Xinfeng , Li Shuhuai , Pang Chaohai , Ma Chen
Published: September 2022

In this work a simple, rapid, and environmentally friendly method has been established for the determination of chlorpyrifos residue in green tea by dispersive liquid–liquid microextraction and gas chromatography-flame photometric detection. Some experimental parameters that influence extraction efficiency, such as the kind and volume of disperser solvents and extraction solvents, extraction time, addition of salt and pH, were investigated. And the optimal experimental conditions were obtained, quantitative analysis was carried out using external standard method. The correlation coefficient of the calibration curves was 0.999 with in 0.05 mg/kg to 5 mg/kg. The results showed that under the optimum conditions, the enrichment factors of the chlorpyrifos was about 554.51, the recoveries for standard addition fell in the range from 91.94 to 104.70% and the relative standard deviations was 4.61%. The limit of quantification of chlorpyrifos in green tea was 0.02 μg/mL at the signal/noise ratio of 3.
Moving towards vertically integrated artificial intelligence development
Authors: Zhang Joe , Budhdeo Sanjay , William Wasswa , Cerrato Paul , Shuaib Haris , Sood Harpreet , Ashrafian Hutan , Halamka John , Teo James T.
Published: September 2022

Substantial interest and investment in clinical artificial intelligence (AI) research has not resulted in widespread translation to deployed AI solutions. Current attention has focused on bias and explainability in AI algorithm development, external validity and model generalisability, and lack of equity and representation in existing data. While of great importance, these considerations also reflect a model-centric approach seen in published clinical AI research, which focuses on optimising architecture and performance of an AI model on best available datasets. However, even robustly built models using state-of-the-art algorithms may fail once tested in realistic environments due to unpredictability of real-world conditions, out-of-dataset scenarios, characteristics of deployment infrastructure, and lack of added value to clinical workflows relative to cost and potential clinical risks. In this perspective, we define a vertically integrated approach to AI development that incorporates early, cross-disciplinary, consideration of impact evaluation, data lifecycles, and AI production, and explore its implementation in two contrasting AI development pipelines: a scalable “AI factory” (Mayo Clinic, Rochester, United States), and an end-to-end cervical cancer screening platform for resource poor settings (Paps AI, Mbarara, Uganda). We provide practical recommendations for implementers, and discuss future challenges and novel approaches (including a decentralised federated architecture being developed in the NHS (AI4VBH, London, UK)). Growth in global clinical AI research continues unabated, and introduction of vertically integrated teams and development practices can increase the translational potential of future clinical AI projects.
A modern automated patch-clamp approach for high throughput electrophysiology recordings in native cardiomyocytes
Authors: Seibertz Fitzwilliam , Rapedius Markus , Fakuade Funsho E. , Tomsits Philipp , Liutkute Aiste , Cyganek Lukas , Becker Nadine , Majumder Rupamanjari , Clauß Sebastian , Fertig Niels , Voigt Niels
Published: September 2022

Crucial conventional patch-clamp approaches to investigate cellular electrophysiology suffer from low-throughput and require considerable experimenter expertise. Automated patch-clamp (APC) approaches are more experimenter independent and offer high-throughput, but by design are predominantly limited to assays containing small, homogenous cells. In order to enable high-throughput APC assays on larger cells such as native cardiomyocytes isolated from mammalian hearts, we employed a fixed-well APC plate format. A broad range of detailed electrophysiological parameters including action potential, L-type calcium current and basal inward rectifier current were reliably acquired from isolated swine atrial and ventricular cardiomyocytes using APC. Effective pharmacological modulation also indicated that this technique is applicable for drug screening using native cardiomyocyte material. Furthermore, sequential acquisition of multiple parameters from a single cell was successful in a high throughput format, substantially increasing data richness and quantity per experimental run. When appropriately expanded, these protocols will provide a foundation for effective mechanistic and phenotyping studies of human cardiac electrophysiology. Utilizing scarce biopsy samples, regular high throughput characterization of primary cardiomyocytes using APC will facilitate drug development initiatives and personalized treatment strategies for a multitude of cardiac diseases.
Multicomponent Raman spectral regression using complete and incomplete models and convolutional neural networks
Authors: Boateng Derrick , Hu Chuanzhen , Dai Yichuan , Chu Kaiqin , Du Jun , Smith Zachary J.
Published: September 2022

A critical study of CNN networks for Raman regression problems is presented. In evaluating performance on models where spectral information is missing, CNN performs as well as state-of-the-art methods,withoutthe need for spectral pre-processing.
Chronocoulometric signalling of BNP using a novel quantum dot aptasensor
Authors: Oranzie Marlon , Douman Samantha F. , Uhuo Onyinyechi V. , Mokwebo Kefilwe V. , Sanga Nelia , Iwuoha Emmanuel I.
Published: September 2022

This study is a first-time report of the development of a quantum dot based aptasensor for brain natriuretic peptide (BNP) detection using chronocoulometry for real-time analysis.
Phytic acid determination in food products using the extract of rice sprout and SBA@DABCO nanoparticle-modified filter paper as a novel electrochemical biosensor
Authors: Rahimi-Mohseni Mohadeseh , Raoof Jahan Bakhsh , Aghajanzadeh Tahereh A. , Ojani Reza
Published: September 2022

An electrochemical phytic acid (PA) biosensor was developed using phytase enzyme and SBA@DABCO nanoparticles. The biosensor showed excellent selectivity and sensitivity for the determination of PA in real samples such as biscuit and flour.
Carbon dot-functionalized macroporous adsorption resin for bifunctional ultra-sensitive detection and fast removal of iron(iii) ions
Authors: Huang Chao , Wang Hongwei , Xu Yunjia , Ma Shujuan , Gong Bolin , Ou Junjie
Published: September 2022

Heavy metal pollution has spread around the world with the development of industry, posing a major threat to human health.
Abilities of the BRICHOS domain to prevent neurotoxicity and fibril formation are dependent on a highly conserved Asp residue
Authors: Chen Gefei , Andrade-Talavera Yuniesky , Zhong Xueying , Hassan Sameer , Biverstål Henrik , Poska Helen , Abelein Axel , Leppert Axel , Kronqvist Nina , Rising Anna , Hebert Hans , Koeck Philip J. B. , Fisahn André , Johansson Jan
Published: September 2022

Activities of the BRICHOS domain against amyloid fibril formation and amyloid-induced neurotoxicity are affected by pH.
Crystalline chalcogenidometalate-based compounds from uncommon reaction media
Authors: Wu Zhou , Stuhrmann Gina , Dehnen Stefanie
Published: September 2022

The synthesis of crystalline chalcogenidometalate-based compounds obtained in uncommon reaction media—in particular ionic liquids, surfactants, or hydrazine—allows access to unusual architectures and functional chemical as well as physical properties.
New semi-ladder polymers for ambipolar organic light-emitting transistors
Authors: Du Yachu , Yuan Dafei , Awais Mohammad A. , Yu Luping
Published: September 2022

Organic light-emitting transistors (OLETs) combine the light-emitting and gate-modulated electrical switching functions in a single device.
Photoswitchable molecular tweezers: isomerization to control substrate binding, and what aboutvice versa?
Authors: Wezenberg Sander J.
Published: September 2022

Functionalization of molecular photoswitches with binding entities offers control of affinity, while isomerization properties can be influenced by bound substrate.
Hydrophobically-enhanced “on water” cycloaddition of CO2to long-chain terminal epoxides
Authors: Jaroonwatana Wimalin , D’Elia Valerio , Crespy Daniel
Published: September 2022

Long-chain cyclic carbonates were prepared in emulsion by exploiting the confinement of the reagents arising from hydrophobic interactions and hydrogen-bonding.
BODIPY-based metal–organic frameworks as efficient electrochemiluminescence emitters for telomerase detection
Authors: Xu Zhiyuan , Wu Fan , Zhu Da , Fu Haomin , Shen Zhen , Lei Jianping
Published: September 2022

A boron dipyrromethene (BODIPY)-based metal–organic framework (MOF) was designed as an efficient electrochemiluminescence (ECL) nanoemitter for telomerase detection.
Preparation of ZIF-8-coated silica hard-shell microcapsule by semi-batch operation
Authors: Kawada Shuei , Otsubo Takumu , Horie Takafumi , Komoda Yoshiyuki , Ohmura Naoto , Asano Hitoshi , Hidema Ruri , Suzuki Hiroshi , Taniya Keita , Ichihashi Yuichi , Nishiyama Satoru
Published: September 2022

The semi-batch operation effectively fabricated the ZIF-8 cover layer on silica hard-shell microcapsules.
Aggregate emission behaviors and reversible mechanofluorochromic properties of α-cyanostilbene functionalized indolo[3,2-b]carbazole derivatives
Authors: Zhang Yuyang , Chen Fuqiang , Zheng Jie , Song Zhongming , Wang Yanping , Mao Yueyuan , Tang Jing , Guo Jiahao , Wang Xuchun
Published: September 2022

Indolo[3,2-b]carbazole derivatives exhibited a reversible mechanochromic characteristic between yellow and orange emission, due to the synergistic effect of intramolecular planarization and intermolecular J-aggregation stacking.
Characterization of LaGPS:Ce scintillation crystals obtained under a reducing atmosphere
Authors: Gerasymov Ia. , Hubenko K. , Viagin O. , Boyarintseva Ya. , Shaposhnyk A. , Baumer V. , Gorbacheva T. , Zelenskaya O. , Galenin E. , Kurtsev D. , Tkachenko S. , Sidletskiy O.
Published: September 2022

Ce-doped lanthanum gadolinium pyrosilicates are among the most efficient oxide scintillation crystals with a light yield of ca. 40 000 ph MeV −1 and a high energy resolution.
A Ca-based nano bio-coordination polymer providing reversible structural conversion with ability to enhance cytotoxicity of curcumin and induce apoptosis in human gastric cancer AGS cells
Authors: Karimi Alavijeh Roya , Akhbari Kamran , White Jonathan M.
Published: September 2022

A new bio-coordination polymer (bio-CP 2) was prepared, which indicated a reversible structural conversion in the presence and absence of water. This bio-CP showed positive effects on the water solubility and anticancer performances of curcumin.
The potential thermoelectric material Tl3XSe4 (X = V, Ta, Nb): a first-principles study
Authors: Li Bingke , Zhang Chenghua , Sun Zhehao , Han Tao , Zhang Xiang , Du Jia , Wang Jiexue , Xiao Xiuchan , Wang Ning
Published: September 2022

Searching for materials with high figure of merit (ZT) has always been the goal of scientific researchers in energy field. In this paper, Tl3XSe4 crystals are found to be potential thermoelectric materials with the ZT values of 6–10 at 700 K.
Trivalent cation-induced phase separation in proteins: ion specific contribution in hydration also counts
Authors: Saha Ria , Mitra Rajib Kumar
Published: September 2022

Trivalent metal ions induce microscopic liquid–liquid phase separation (LLPS) in negatively charged globular proteins. Explicit change in the hydration associated with ion-induced protein rich LLPS droplet formation is probed here using THz spectroscopy.