bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aedes aegypti Argonaute 2 controls arbovirus infection and host mortality
Authors: Dong Shengzhang , Dimopoulos George 
Published: September 2023

AbstractAe. aegypti mosquitoes transmit some of the most important human viral diseases that are responsible for a significant public health burden worldwide. The small interfering RNA (siRNA) pathway is considered the major antiviral defense system in insects. Here we show that siRNA pathway disruption by CRISPR/Cas9-based Ago2 knockout impaired the mosquitoes’ ability to degrade arbovirus RNA leading to hyper-infection accompanied by cell lysis and tissue damage. Ago2 disruption impaired DNA repair mechanisms and the autophagy pathway by altering histone abundance. This compromised DNA repair and removal of damaged cellular organelles and dysfunctional aggregates promoted mosquito death. We also report that hyper-infection of Ago2 knockout mosquitoes stimulated a broad-spectrum antiviral immunity, including apoptosis, which may counteract infection. Taken together, our studies reveal novel roles for Ago2 in protecting mosquitoes from arbovirus infection and associated death.
Pharmacological inhibition of TBK1/IKKε blunts immunopathology in a murine model of SARS-CoV-2 infection
Authors: Ullah Tomalika R. , Johansen Matt D. , Balka Katherine R. , Ambrose Rebecca L. , Gearing Linden J. , Roest James , Vivian Julian P. , Sapkota Sunil , Jayasekara W. Samantha N. , Wenholz Daniel S. , Aldilla Vina R. , Zeng Jun , Miemczyk Stefan , Nguyen Duc H. , Hansbro Nicole G. , Venkatraman Rajan , Kang Jung Hee , Pang Ee Shan , Thomas Belinda J. , Alharbi Arwaf S. , Rezwan Refaya , O’Keeffe Meredith , Donald William A. , Ellyard Julia I. , Wong Wilson , Kumar Naresh , Kile Benjamin T. , Vinuesa Carola G. , Kelly Graham E. , Laczka Olivier F. , Hansbro Philip M. , De Nardo Dominic , Gantier Michael P. 
Published: September 2023

AbstractTANK-binding kinase 1 (TBK1) is a key signalling component in the production of type-I interferons, which have essential antiviral activities, including against SARS-CoV-2. TBK1, and its homologue IκB kinase-ε (IKKε), can also induce pro-inflammatory responses that contribute to pathogen clearance. While initially protective, sustained engagement of type-I interferons is associated with damaging hyper-inflammation found in severe COVID-19 patients. The contribution of TBK1/IKKε signalling to these responses is unknown. Here we find that the small molecule idronoxil inhibits TBK1/IKKε signalling through destabilisation of TBK1/IKKε protein complexes. Treatment with idronoxil, or the small molecule inhibitor MRT67307, suppresses TBK1/IKKε signalling and attenuates cellular and molecular lung inflammation in SARS-CoV-2-challenged mice. Our findings additionally demonstrate that engagement of STING is not the major driver of these inflammatory responses and establish a critical role for TBK1/IKKε signalling in SARS-CoV-2 hyper-inflammation.
Light-enhanced molecular polarity enabling multispectral color-cognitive memristor for neuromorphic visual system
Authors: Lee Jongmin , Jeong Bum Ho , Kamaraj Eswaran , Kim Dohyung , Kim Hakjun , Park Sanghyuk , Park Hui Joon 
Published: September 2023

AbstractAn optoelectronic synapse having a multispectral color-discriminating ability is an essential prerequisite to emulate the human retina for realizing a neuromorphic visual system. Several studies based on the three-terminal transistor architecture have shown its feasibility; however, its implementation with a two-terminal memristor architecture, advantageous to achieving high integration density as a simple crossbar array for an ultra-high-resolution vision chip, remains a challenge. Furthermore, regardless of the architecture, it requires specific material combinations to exhibit the photo-synaptic functionalities, and thus its integration into various systems is limited. Here, we suggest an approach that can universally introduce a color-discriminating synaptic functionality into a two-terminal memristor irrespective of the kinds of switching medium. This is possible by simply introducing the molecular interlayer with long-lasting photo-enhanced dipoles that can adjust the resistance of the memristor at the light-irradiation. We also propose the molecular design principle that can afford this feature. The optoelectronic synapse array having a color-discriminating functionality is confirmed to improve the inference accuracy of the convolutional neural network for the colorful image recognition tasks through a visual pre-processing. Additionally, the wavelength-dependent optoelectronic synapse can also be leveraged in the design of a light-programmable reservoir computing system.
Whole-genome screens reveal regulators of differentiation state and context-dependent migration in human neutrophils
Authors: Belliveau Nathan M. , Footer Matthew J. , Akdoǧan Emel , van Loon Aaron P. , Collins Sean R. , Theriot Julie A. 
Published: September 2023

AbstractNeutrophils are the most abundant leukocyte in humans and provide a critical early line of defense as part of our innate immune system. We perform a comprehensive, genome-wide assessment of the molecular factors critical to proliferation, differentiation, and cell migration in a neutrophil-like cell line. Through the development of multiple migration screen strategies, we specifically probe directed (chemotaxis), undirected (chemokinesis), and 3D amoeboid cell migration in these fast-moving cells. We identify a role for mTORC1 signaling in cell differentiation, which influences neutrophil abundance, survival, and migratory behavior. Across our individual migration screens, we identify genes involved in adhesion-dependent and adhesion-independent cell migration, protein trafficking, and regulation of the actomyosin cytoskeleton. This genome-wide screening strategy, therefore, provides an invaluable approach to the study of neutrophils and provides a resource that will inform future studies of cell migration in these and other rapidly migrating cells.
Experimental confirmation of driving pressure boosting and smoothing for hybrid-drive inertial fusion at the 100-kJ laser facility
Authors: Yan Ji , Li Jiwei , He X. T. , Wang Lifeng , Chen Yaohua , Wang Feng , Han Xiaoying , Pan Kaiqiang , Liang Juxi , Li Yulong , Guan Zanyang , Liu Xiangming , Che Xingsen , Chen Zhongjing , Zhang Xing , Xu Yan , Li Bin , He Minqing , Cai Hongbo , Hao Liang , Liu Zhanjun , Zheng Chunyang , Dai Zhensheng , Fan Zhengfeng , Qiao Bin , Li Fuquan , Jiang Shaoen , Yu M. Y. , Zhu Shaoping 
Published: September 2023

AbstractIn laser-driven inertial confinement fusion, driving pressure boosting and smoothing are major challenges. A proposed hybrid-drive (HD) scheme can offer such ideal HD pressure performing stable implosion and nonstagnation ignition. Here we report that in the hemispherical and planar ablator targets installed in the semicylindrical hohlraum scaled down from the spherical hohlraum of the designed ignition target, under indirect-drive (ID) laser energies of ~43–50 kJ, the peak radiation temperature of 200 ± 6 eV is achieved. And using only direct-drive (DD) laser energies of 3.6–4.0 kJ at an intensity of 1.8 × 1015 W/cm2, in the hemispherical and planar targets the boosted HD pressures reach 3.8–4.0 and 3.5–3.6 times the radiation ablation pressure respectively. In all the above experiments, significant HD pressure smoothing and the important phenomenon of how a symmetric strong HD shock suppresses the asymmetric ID shock pre-compressed fuel are demonstrated. The backscattering and hot-electron energy fractions both of which are about one-third of that in the DD scheme are also measured.
Epitaxial growth of metal-organic framework nanosheets into single-crystalline orthogonal arrays
Authors: Zou Yingying , Liu Chao , Zhang Chaoqi , Yuan Ling , Li Jiaxin , Bao Tong , Wei Guangfeng , Zou Jin , Yu Chengzhong 
Published: September 2023

AbstractConstruction of two-dimensional nanosheets into three-dimensional regular structures facilitates the mass transfer and exploits the maximum potential of two-dimensional building blocks in applications such as catalysis. Here, we report the synthesis of metal-organic frameworks with an orthogonal nanosheet array. The assembly involves the epitaxial growth of single crystalline metal-organic framework nanosheets with a naturally non-preferred facet exposure as the shell on a cubic metal-organic framework as the core. The nanosheets, despite of two typical shapes and crystallographic orientations, also form a single crystalline orthogonally arrayed framework. The density and size of nanosheets in the core-shell-structured composite metal-organic frameworks can be well adjusted. Moreover, metal-organic frameworks with a single composition and hollow orthogonal nanosheet array morphology can be obtained. Benefiting from the unusual facet exposure and macroporous structure, the designed structure exhibits improved electrocatalytic oxygen evolution activity compared to conventional nanosheets.
Structure of human drug transporters OATP1B1 and OATP1B3
Authors: Ciută Anca-Denise , Nosol Kamil , Kowal Julia , Mukherjee Somnath , Ramírez Ana S. , Stieger Bruno , Kossiakoff Anthony A. , Locher Kaspar P. 
Published: September 2023

AbstractThe organic anion transporting polypeptides OATP1B1 and OATP1B3 are membrane proteins that mediate uptake of drugs into the liver for subsequent conjugation and biliary excretion, a key step in drug elimination from the human body. Polymorphic variants of these transporters can cause reduced drug clearance and adverse drug effects such as statin-induced rhabdomyolysis, and co-administration of OATP substrates can lead to damaging drug-drug interaction. Despite their clinical relevance in drug disposition and pharmacokinetics, the structure and mechanism of OATPs are unknown. Here we present cryo-EM structures of human OATP1B1 and OATP1B3 bound to synthetic Fab fragments and in functionally distinct states. A single estrone-3-sulfate molecule is bound in a pocket located in the C-terminal half of OATP1B1. The shape and chemical nature of the pocket rationalize the preference for diverse organic anions and allow in silico docking of statins. The structure of OATP1B3 is determined in a drug-free state but reveals a bicarbonate molecule bound to the conserved signature motif and a histidine residue that is prevalent in OATPs exhibiting pH-dependent activity.
A GPU-based computational framework that bridges neuron simulation and artificial intelligence
Authors: Zhang Yichen , He Gan , Ma Lei , Liu Xiaofei , Hjorth J. J. Johannes , Kozlov Alexander , He Yutao , Zhang Shenjian , Kotaleski Jeanette Hellgren , Tian Yonghong , Grillner Sten , Du Kai , Huang Tiejun 
Published: September 2023

AbstractBiophysically detailed multi-compartment models are powerful tools to explore computational principles of the brain and also serve as a theoretical framework to generate algorithms for artificial intelligence (AI) systems. However, the expensive computational cost severely limits the applications in both the neuroscience and AI fields. The major bottleneck during simulating detailed compartment models is the ability of a simulator to solve large systems of linear equations. Here, we present a novel Dendritic Hierarchical Scheduling (DHS) method to markedly accelerate such a process. We theoretically prove that the DHS implementation is computationally optimal and accurate. This GPU-based method performs with 2-3 orders of magnitude higher speed than that of the classic serial Hines method in the conventional CPU platform. We build a DeepDendrite framework, which integrates the DHS method and the GPU computing engine of the NEURON simulator and demonstrate applications of DeepDendrite in neuroscience tasks. We investigate how spatial patterns of spine inputs affect neuronal excitability in a detailed human pyramidal neuron model with 25,000 spines. Furthermore, we provide a brief discussion on the potential of DeepDendrite for AI, specifically highlighting its ability to enable the efficient training of biophysically detailed models in typical image classification tasks.
Bisphosphonate conjugation enhances the bone-specificity of NELL-1-based systemic therapy for spaceflight-induced bone loss in mice
Authors: Ha Pin , Kwak Jin Hee , Zhang Yulong , Shi Jiayu , Tran Luan , Liu Timothy Pan , Pan Hsin-Chuan , Lee Samantha , Kim Jong Kil , Chen Eric , Shirazi-Fard Yasaman , Stodieck Louis S. , Lin Andy , Zheng Zhong , Dong Stella Nuo , Zhang Xinli , Wu Benjamin M. , Ting Kang , Soo Chia 
Published: September 2023

AbstractMicrogravity-induced bone loss results in a 1% bone mineral density loss monthly and can be a mission critical factor in long-duration spaceflight. Biomolecular therapies with dual osteogenic and anti-resorptive functions are promising for treating extreme osteoporosis. We previously confirmed that NELL-like molecule-1 (NELL-1) is crucial for bone density maintenance. We further PEGylated NELL-1 (NELL-polyethylene glycol, or NELL-PEG) to increase systemic delivery half-life from 5.5 to 15.5 h. In this study, we used a bio-inert bisphosphonate (BP) moiety to chemically engineer NELL-PEG into BP-NELL-PEG and specifically target bone tissues. We found conjugation with BP improved hydroxyapatite (HA) binding and protein stability of NELL-PEG while preserving NELL-1’s osteogenicity in vitro. Furthermore, BP-NELL-PEG showed superior in vivo bone specificity without observable pathology in liver, spleen, lungs, brain, heart, muscles, or ovaries of mice. Finally, we tested BP-NELL-PEG through spaceflight exposure onboard the International Space Station (ISS) at maximal animal capacity (n = 40) in a long-term (9 week) osteoporosis therapeutic study and found that BP-NELL-PEG significantly increased bone formation in flight and ground control mice without obvious adverse health effects. Our results highlight BP-NELL-PEG as a promising therapeutic to mitigate extreme bone loss from long-duration microgravity exposure and musculoskeletal degeneration on Earth, especially when resistance training is not possible due to incapacity (e.g., bone fracture, stroke).
Non-adaptive measurement-based quantum computation on IBM Q
Authors: Mackeprang Jelena , Bhatti Daniel , Barz Stefanie 
Published: September 2023

AbstractWe test the quantumness of IBM’s quantum computer IBM Quantum System One in Ehningen, Germany. We generate generalised n-qubit GHZ states and measure Bell inequalities to investigate the n-party entanglement of the GHZ states. The implemented Bell inequalities are derived from non-adaptive measurement-based quantum computation (NMQC), a type of quantum computing that links the successful computation of a non-linear function to the violation of a multipartite Bell-inequality. The goal is to compute a multivariate Boolean function that clearly differentiates non-local correlations from local hidden variables (LHVs). Since it has been shown that LHVs can only compute linear functions, whereas quantum correlations are capable of outputting every possible Boolean function it thus serves as an indicator of multipartite entanglement. Here, we compute various non-linear functions with NMQC on IBM’s quantum computer IBM Quantum System One and thereby demonstrate that the presented method can be used to characterize quantum devices. We find a violation for a maximum of seven qubits and compare our results to an existing implementation of NMQC using photons.
Pollinator-dependent crops significantly contribute to diets and reduce household nutrient deficiencies in sub-Saharan Africa
Authors: Mulungu Kelvin , Tekelewold Hailemariam , Abro Zewdu , Sevgan Subramanian , Muriithi Beatrice , Ecuru Julius , Beesigamukama Dennis , Kassie Menale 
Published: September 2023

AbstractRecent literature highlights the potential of animal pollinator-dependent (PD) crops in enhancing food and nutrition security, although there is a lack of detailed household-level estimates. In this study, we investigate the nutrient composition, productivity, and contribution of PD and pollinator-independent (PI) crops to household nutrition in four sub-Saharan African (SSA) countries. We also evaluate the impact of reallocating resources from PI crops to PD crops on nutrient deficiencies, utilizing nationally representative panel data from three waves and over 30,000 household-year observations. Our findings reveal that PD crops exhibit higher micronutrient content per unit, albeit with lower macronutrient content compared to PI crops. PI crops have higher yield of calories per hectare while PD crops have higher vitamin A yield per hectare. However, protein and iron yield for PD and PI crops varies across countries. PI crops predominantly contribute to macronutrients and iron, while PD crops significantly contribute to vitamin A production. Our econometric results demonstrate that increasing the cultivation of PD crops relative to PI crops reduces the prevalence of nutrient deficiencies and increases crop income without compromising macronutrients production. This suggests that greater investment in PD crop production can be an integral approach to achieving nutrition security in SSA.
Floquet space exploration for the dual-dressing of a qubit
Authors: Fregosi Alessandro , Marinelli Carmela , Gabbanini Carlo , Bevilacqua Giuseppe , Biancalana Valerio , Arimondo Ennio , Fioretti Andrea 
Published: September 2023

AbstractThe application of a periodic nonresonant drive to a system allows the Floquet engineering of effective fields described by a broad class of quantum simulated Hamiltonians. The Floquet evolution is based on two different elements. The first one is a time-independent or stroboscopic evolution with an effective Hamiltonian corresponding to the quantum simulation target. The second element is the time evolution at the frequencies of the nonresonant driving and of its harmonics, denoted as micromotion. We examine experimentally and theoretically the harmonic dual-dressing Floquet engineering of a cold atomic two-level sample. Our focus is the dressing operation with small bare energies and large Rabi frequencies, where frequencies and amplitudes of the stroboscopic/micromotion time evolutions are comparable. At the kHz range of our dressed atom oscillations, we probe directly both the stroboscopic and micromotion components of the qubit global time evolution. We develop ad-hoc monitoring tools of the Floquet space evolution. The direct record of the time evolution following a pulsed excitation demonstrates the interplay between the two components of the spin precession in the Floquet space. From the resonant pumping of the dressed system at its evolution frequencies, Floquet eigenenergy spectra up to the fifth order harmonic of the dressing frequency are precisely measured as function of dressing parameters. Dirac points of the Floquet eigenenergies are identified and, correspondingly, a jump in the dynamical phase shift is measured. The stroboscopic Hamiltonian eigenfrequencies are measured also from the probe of the micromotion sidebands.These monitoring tools are appropriate for quantum simulation/computation investigations. Our results evidence that the stroboscopic phase shift of the qubit wavefunction contains an additional information that opens new simulation directions.
Real world evidence reveals improved survival outcomes in biliary tract cancer through molecular matched targeted treatment
Authors: Doleschal Bernhard , Taghizadeh Hossein , Webersinke Gerald , Piringer Gudrun , Schreil Georg , Decker Jörn , Aichberger Karl J. , Kirchweger Patrick , Thaler Josef , Petzer Andreas , Schmitt Clemens A. , Prager Gerald W. , Rumpold Holger 
Published: September 2023

AbstractBiliary tract cancers are rare cancers with poor prognosis due to a lack of therapeutic options, especially after the failure of first-line systemic treatment. Targeted treatments for this clinical situation are promising and have entered clinical practice. We aimed to describe the overall survival of matched targeted treatment after first-line treatment in patients with biliary tract cancers in an Austrian real-world multicenter cohort. We performed a multicenter retrospective chart review of patients with biliary tract cancer between September 2015 and January 2022. Data, including comprehensive molecular characteristics—next generation sequencing (NGS) and immunohistochemistry (IHC), clinical history, surgical procedures, ablative treatments, patient history, and systemic chemotherapy, were extracted from the records of the participating institutions. Targeted treatment was matched according to the ESMO scale for the clinical actionability of molecular targets (ESCAT). We identified 159 patients with the available molecular characteristics. A total of 79 patients underwent second-line treatment. Of these, 36 patients received matched targeted treatment beyond the first-line and were compared with 43 patients treated with cytotoxic chemotherapy in terms of efficacy outcomes. For Tier I/II alterations, we observed a progression free survival ratio (PFStargeted/PFSpre-chemotherapy) of 1.86, p = 0.059. The overall survival for patients receiving at least two lines of systemic treatment significantly favored the targeted approach, with an overall survival of 22.3 months (95% CI 14.7–29.3) vs. 17.5 months (95% CI 1.7–19.8; p = 0.048). Our results underscore the value of targeted treatment approaches based on extended molecular characterization of biliary tract cancer to improve clinical outcomes.
Simple dihydropyridine-based colorimetric chemosensors for heavy metal ion detection, biological evaluation, molecular docking, and ADMET profiling
Authors: Hamada Wafaa M. , El-Nahass Marwa N. , Noser Ahmed A. , Fayed Tarek A. , El-Kemary Maged , Salem Maha M. , Bakr Eman A. 
Published: September 2023

AbstractIn this study, two novel chemosensors containing dihydropyridine fragment namely; (2E, 2Eʹ)-1,1ʹ-(2,6-dimethyl-1,4-dihydropyridine-3,5-diyl)bis(3-(4-(dimethylamino)phenyl)prop-2-en-1-one) (1), (2E,2E',4E,4E')-1,1ʹ -(2,6-dimethyl-1,4-dihydropyridine-3,5-diyl)bis(5-(4-(dimethylamino)phenyl)penta-2,4-dien-1-one) (2) have been synthesized and characterized. The solvatochromic behavior was explored in different solvents of various polarities. The visual detection, as well as UV–Vis and fluorescence measurements were carried out to explore the colorimetric and optical sensing properties of the investigated chemosensors towards various metal ions such as Al3+, Cr3+, Mn2+, Fe3+, Co2+, Ni2+, Cu2+, Mg2+, Hg2+ and Zn2+. The chemosensors 1 and 2 have strong detecting abilities, with excellent sensitivity and selectivity for Cu2+ and Fe3+, respectively, over the other metal ions. The chemosensors were totally reversible upon addition of EDTA to the formed complexes and displayed a turn on–off-on fluorescence response based on an effect of chelation-quenching fluorescence. The antioxidant activities of the investigated chemosensors were assessed. They were examined in-silico for their capacity to block the Akt signaling pathway, which is involved in cancer proliferation with interpreting their pharmacokinetics aspects. Furthermore, in-vitro antitumor evaluation against a panel of cancer cell lines for the investigated chemosensors has been examined. Conclusively, chemosensor 1 was more effective at scavenging free radicals and as an anticancer agent and could be exploited as a therapeutic candidate for cancer therapy than chemosensor 2 due to its potential inhibition of Akt protein.