bluuebunny/crossref_metadata_2025 huggingface dataset:
Robust Subsurface Biological Response During the Decaying Stage of an Extreme Indian Ocean Dipole in 2019
Authors: Li Hongliang , Zhang Jingjing , Wang Xinyang , Zhu Yuanli , Liu Lin , Wang Baodong , Zhang Xuelei , Wei Qinsheng , Ding Ruibin , Xuan Jiliang , Shou Lu , Zhou Feng , Chen Jianfang
Published: August 2022

The Indian Ocean Dipole (IOD) is the predominant interannual climate mode and is critical in regulating the biogeochemical cycles of the equatorial Indian Ocean (EIO). However, the dynamics of nutrient supply and the magnitude of biological responses are less understood. Here, by comparing the biophysical in situ observations across the eastern EIO during the decaying period of a positive IOD in 2019 and neutral condition in 2017, we identify that the shoaling thermocline, initiated by reinforced easterly wind, lifts the nutricline into the euphotic layer under positive IOD condition. Coincidently, the strong turbulent mixing induced by the shear instability between the opposite‐flowing surface current and subsurface Equatorial Undercurrent increases the upward turbulent nutrient flux into the euphotic zone. Their combined effect triggers a vigorous subsurface biological response over the eastern EIO, with approximately twofold higher integrated chlorophyll‐a contents in the water column during a positive IOD than under neutral condition.
Significantly Increased Lightning Activity Over the Tibetan Plateau and Its Relation to Thunderstorm Genesis
Authors: Qie Xiushu , Qie Kai , Wei Lei , Zhu Kexin , Sun Zhuling , Yuan Shanfeng , Jiang Rubin , Zhang Hongbo , Xu Chen
Published: August 2022

Under the context of global warming, we identified a significant increase in lightning activity in the last two decades over the Tibetan Plateau (TP), the highest plateau on earth, based on two data sets. The largest rise of lightning activity was found over the region with high lightning density represented by the eastern TP at a rate of 0.072 ± 0.069 fl km−2 yr−1 during 1996–2013 from Optical Transient Detector/Lightning Imaging Sensor. World Wide Lightning Location Network data also showed a remarkable increase in lightning strokes during 2010–2019 in the maximum lightning density region, while the change was insignificant in the low lightning density region. Further investigations revealed that most of the TP region experienced a significant increase in thunderstorm frequency, which was responsible for the increase in lightning activity, rather than an increase in thunderstorm intensity. Increased lightning activity implies a potential risk to human beings and the fragile ecosystem over the TP in a warmer climate.
On the Kinetic Theory of Subauroral Arcs
Authors: Mishin Evgeny , Streltsov Anatoly
Published: August 2022

We report on a novel scenario of subauroral arcs within strong subauroral ion drifts (SAID)‐STEVE and Picket Fence. Their explanation requires a local source of low‐energy, ε < 18.75 eV, suprathermal electrons, and N2 vibrational and electronic excitation below ∼270 km. We show that the ionospheric feedback instability in strong SAID flows with depleted density troughs generates intense, small‐scale field‐aligned currents and parallel electric fields below the F2 peak. With these fields, we employed a rigorous numerical solution of the Boltzmann kinetic equation for the distribution of ionospheric electrons and determined the power going to excitation and ionization of neutral gas (the energy balance). The obtained suprathermal electron population and energy balance at altitudes of ∼130–140 km are just what is necessary for Picket Fence. Concerning STEVE, the kinetic theory predictions are in a good qualitative agreement with its basic features, such as the enhanced continuum emissions. Besides, the theory predicts that subauroral arcs might have the transient phase with typical aurora‐like emissions that fade out afterward.
Three‐Dimensional Configuration of Induced Magnetic Fields Around Mars
Authors: Zhang Chi , Rong Zhaojin , Klinger Lucy , Nilsson Hans , Shi Zhen , He Fei , Gao Jiawei , Li Xinzhou , Futaana Yoshifumi , Ramstad Robin , Wang Xiaodong , Holmström Mats , Barabash Stas , Fan Kai , Wei Yong
Published: August 2022

Using over 6 years of magnetic field data (October 2014–December 2020) collected by the Mars Atmosphere and Volatile EvolutioN, we conduct a statistical study on the three‐dimensional average magnetic field structure around Mars. We find that this magnetic field structure conforms to the pattern typical of an induced magnetosphere, that is, the interplanetary magnetic field (IMF) which is carried by the solar wind and which drapes, piles up, slips around the planet, and eventually forms a tail in the wake. The draped field lines from both hemispheres along the direction of the solar wind electric field (E) are directed toward the nightside magnetic equatorial plane, indicating that they are “sinking” toward the wake. These “sinking” field lines from the +E‐hemisphere (E pointing away from the plane) are more flared and dominant in the tail, while the field lines from the –E‐hemisphere (E pointing toward) are more stretched and “pinched” toward the plasma sheet. Such highly “pinched” field lines even form a loop over the pole of the –E‐hemisphere. The tail current sheet also shows an E‐asymmetry: the sheet is thicker with a stronger tailward force at +E‐flank, but much thinner and with a weaker (even turns sunward) at –E‐flank. Additionally, we find that IMF Bx can induce a kink‐like field structure at the boundary layer; the field strength is globally enhanced and the field lines flare less during high dynamic pressure.
Synthesis and Stability of an Eight‐Coordinated Fe3O4 High‐Pressure Phase: Implications for the Mantle Structure of Super‐Earths
Authors: Zurkowski C. C. , Yang J. , Chariton S. , Prakapenka V. B. , Fei Y.
Published: August 2022

Super‐Earths ranging up to 10 Earth masses (ME) with Earth‐like density are common among the observed exoplanets thus far, but their measured masses and radii do not uniquely elucidate their internal structure. Exploring the phase transitions in the Mg‐silicates that define the mantle‐structure of super‐Earths is critical to characterizing their interiors, yet the relevant terapascal conditions are experimentally challenging for direct structural analysis. Here we investigated the crystal chemistry of Fe3O4 as a low‐pressure analog to Mg2SiO4 between 45–115 GPa and up to 3000 K using powder and single crystal X‐ray diffraction in the laser‐heated diamond anvil cell. Between 60–115 GPa and above 2000 K, Fe3O4 adopts an 8‐fold coordinated Th3P4‐type structure (I‐43d, Z = 4) with disordered Fe2+ and Fe3+ into one metal site. This Fe‐oxide phase is isostructural with that predicted for Mg2SiO4 above 500 GPa in super‐Earth mantles and suggests that Mg2SiO4 can incorporate both ferric and ferrous iron at these conditions. The pressure‐volume behavior observed in this 8‐fold coordinated Fe3O4 indicates a maximum 4% density increase across the 6‐ to 8‐fold coordination transition in the analog Mg‐silicate. Reassessment of the FeO—Fe3O4 fugacity buffer considering the Fe3O4 phase relationships identified in this study reveals that increasing pressure and temperature to 120 GPa and 3000 K in Earth and planetary mantles drives iron toward oxidation.
Ubap1 knock-in mice reproduced the phenotype of SPG80
Authors: Shimozono Keisuke , Nan Haitian , Hata Takanori , Saito Kozo , Kim Yeon-Jeong , Nagatomo Hiroaki , Ohtsuka Toshihisa , Koizumi Schuichi , Takiyama Yoshihisa
Published: August 2022

SPG80 is a neurodegenerative disorder characterized by a pure type of juvenile-onset hereditary spastic paraplegia and is caused by a heterozygous mutation of the UBAP1 (ubiquitin-associated protein 1) gene. UBAP1 is one of the subunits of the endosomal sorting complex required for transport I and plays a role in endosome sorting by binding to ubiquitin-tagged proteins. In this study, we generated novel Ubap1+/E176Efx23 knock-in mice, in which the SOUBA domain of Ubap1 was completely deleted with the UMA domain being intact, as an animal model of SPG80. The knock-in mice with this heterozygous Ubap1 truncated mutation appeared normal at birth, but they developed progressive hind limb dysfunction several months later. Molecular pathologically, loss of neurons in the spinal cord and accumulation of ubiquitinated proteins were observed in Ubap1+/E176Efx23 knock-in mice. In addition, changes in the distributions of Rab5 and Rab7 in the spinal cord suggest that this mutation in Ubap1 disturbs endosome-mediated vesicular trafficking. This is the first report of a mouse model that reproduces the phenotype of SPG80. Our knock-in mice may provide a clue for understanding the molecular pathogenesis underlying UBAP1-related HSP and screening of therapeutic agents.
Frequency comb-to-comb stabilization over a 1.3-km free-space atmospheric optical link
Authors: Yang Jaewon , IL Lee Dong , Shin Dong-Chel , Lee Jaehyun , Kim Byung Soo , Kang Hyun Jay , Kim Young-Jin , Kim Seung-Woo
Published: August 2022

Stabilizing a frequency comb to an ultra-stable optical frequency reference requires a multitude of optoelectronic peripherals that have to operate under strict ambient control. Meanwhile, the frequency comb-to-comb stabilization aims to synchronize a slave comb to a well-established master comb with a substantial saving in required equipment and efforts. Here, we report an utmost case of frequency comb-to-comb stabilization made through a 1.3 km free-space optical (FSO) link by coherent transfer of two separate comb lines along with a feedback suppression control of atmospheric phase noise. The FSO link offers a transfer stability of 1.7 × 10–15 at 0.1 s averaging, while transporting the master comb’s stability of 1.2 × 10–15 at 1.0 s over the entire spectrum of the slave comb. Our remote comb-to-comb stabilization is intended to expedite diverse long-distance ground-to-ground or ground-to-satellite applications; as demonstrated here for broadband molecular spectroscopy over a 6 THz bandwidth as well as ultra-stable microwaves generation with phase noise of -80 dBc Hz–1 at 1 Hz.
An excellent deep-ultraviolet birefringent material based on [BO2]∞ infinite chains
Authors: Zhang Fangfang , Chen Xinglong , Zhang Min , Jin Wenqi , Han Shujuan , Yang Zhihua , Pan Shilie
Published: August 2022

Birefringent materials play indispensable roles in modulating the polarization of light and are vital in the laser science and technology. Currently, the design of birefringent materials operating in the deep-ultraviolet region (DUV, λ ≤200 nm) is still a great challenge. In this work, we developed a new DUV birefringent crystal LiBO2 based on [BO2]∞ infinite chains in the Li-B-O system, which simultaneously achieves the shortest UV cutoff edge (164 nm) and the largest birefringence (≥0.168 at 266 nm) among all the reported borate-based DUV birefringent materials. Single crystals of LiBO2 with dimensions up to Ø55 × 34 mm3 were grown by the Czochralski method, providing access to large-sized single crystal with low cost. Moreover, it has a high laser damage threshold and stable physicochemical properties. These outstanding characters unambiguously support that LiBO2 can be an excellent birefringent material for DUV application.
Time in schizophrenia: a link between psychopathology, psychophysics and technology
Authors: Amadeo Maria Bianca , Esposito Davide , Escelsior Andrea , Campus Claudio , Inuggi Alberto , Pereira Da Silva Beatriz , Serafini Gianluca , Amore Mario , Gori Monica
Published: August 2022

It has been widely demonstrated that time processing is altered in patients with schizophrenia. This perspective review delves into such temporal deficit and highlights its link to low-level sensory alterations, which are often overlooked in rehabilitation protocols for psychosis. However, if temporal impairment at the sensory level is inherent to the disease, new interventions should focus on this dimension. Beyond more traditional types of intervention, here we review the most recent digital technologies for rehabilitation and the most promising ones for sensory training. The overall aim is to synthesise existing literature on time in schizophrenia linking psychopathology, psychophysics, and technology to help future developments.
miR-596-3p suppresses brain metastasis of non-small cell lung cancer by modulating YAP1 and IL-8
Authors: Li Chenlong , Zheng Hongshan , Xiong Jinsheng , Huang Yuxin , Li Haoyang , Jin Hua , Ai Siqi , Wang Yingjie , Su Tianqi , Sun Guiyin , Xiao Xu , Fu Tianjiao , Wang Yujie , Gao Xin , Liang Peng
Published: August 2022

Brain metastasis (BM) frequently occurs in advanced non-small cell lung cancer (NSCLC) and is associated with poor clinical prognosis. Due to the location of metastatic lesions, the surgical resection is limited and the chemotherapy is ineffective because of the existence of the blood brain barrier (BBB). Therefore, it is essential to enhance our understanding about the underlying mechanisms associated with brain metastasis in NSCLC. In the present study, we explored the RNA-Seq data of brain metastasis cells from the GEO database, and extracted RNA collected from primary NSCLC tumors as well as paired brain metastatic lesions followed by microRNA PCR array. Meanwhile, we improved the in vivo model and constructed a cancer stem cell-derived transplantation model of brain metastasis in mice. Our data indicated that the level of miR-596-3p is high in primary NSCLC tumors, but significantly downregulated in the brain metastatic lesion. The prediction target of microRNA suggested that miR-596-3p was considered to modulate two genes essential in the brain invasion process, YAP1 and IL-8 that restrain the invasion of cancer cells and permeability of BBB, respectively. Moreover, in vivo experiments suggested that our model mimics the clinical aspect of NSCLC and improves the success ratio of brain metastasis model. The results demonstrated that miR-596-3p significantly inhibited the capacity of NSCLC cells to metastasize to the brain. Furthermore, these finding elucidated that miR-596-3p exerts a critical role in brain metastasis of NSCLC by modulating the YAP1-IL8 network, and this miRNA axis may provide a potential therapeutic strategy for brain metastasis.
Identification of a BRAF/PA28γ/MEK1 signaling axis and its role in epithelial-mesenchymal transition in oral submucous fibrosis
Authors: Xie Changqing , Li Zaiye , Hua Yufei , Sun Silu , Zhong Liang , Chen Qian , Feng Hui , Ji Ning , Li Taiwen , Zhou Xikun , Zeng Xin , Tang Zhangui , Sun Chongkui , Li Jing , Chen Qianming
Published: August 2022

Oral submucous fibrosis (OSF) is a chronic and insidious oral potentially malignant disorder associated with a 4–17% risk of oral squamous cell carcinoma (OSCC). Our previous study found that proteasomal activator 28 gamma (PA28γ) is frequently overexpressed in oral squamous cell carcinoma and negatively correlated with poor patient prognosis. However, the role of PA28γ in the occurrence and development of OSF remains unclear. Here, we screened PA28γ-related genes and investigated their function in OSF. We demonstrated that the expression of PA28γ was positively associated with MEK1 and gradually elevated from normal to progressive stages of OSF tissue. Arecoline, a pathogenic component of OSF, could upregulate the protein levels of PA28γ and phosphorylated MEK1 and contribute to epithelial to mesenchymal transition (EMT) in epithelial cells. Notably, PA28γ could interact with MEK1 and upregulate its phosphorylation level. Furthermore, arecoline upregulated BRAF, which can interact with PA28γ and upregulate its protein level. Additionally, BRAF, PA28γ, and MEK1 could form protein complexes and then enhance the MEK1/ERK signaling pathways. The concrete mechanism of the protein stability of PA28γ is that BRAF mediates its degradation by inhibiting its ubiquitination. These findings underscore the instrumental role of PA28γ in the BRAF/MEK1 pathway and enhanced EMT through MEK1/ERK activation in OSF.
CNT-molecule-CNT (1D-0D-1D) van der Waals integration ferroelectric memory with 1-nm2 junction area
Authors: Phan Thanh Luan , Seo Sohyeon , Cho Yunhee , An Vu Quoc , Lee Young Hee , Duong Dinh Loc , Lee Hyoyoung , Yu Woo Jong
Published: August 2022

The device’s integration of molecular electronics is limited regarding the large-scale fabrication of gap electrodes on a molecular scale. The van der Waals integration (vdWI) of a vertically aligned molecular layer (0D) with 2D or 3D electrodes indicates the possibility of device’s integration; however, the active junction area of 0D-2D and 0D-3D vdWIs remains at a microscale size. Here, we introduce the robust fabrication of a vertical 1D-0D-1D vdWI device with the ultra-small junction area of 1 nm2 achieved by cross-stacking top carbon nanotubes (CNTs) on molecularly assembled bottom CNTs. 1D-0D-1D vdWI memories are demonstrated through ferroelectric switching of azobenzene molecules owing to the cis-trans transformation combined with the permanent dipole moment of the end-tail -CF3 group. In this work, our 1D-0D-1D vdWI memory exhibits a retention performance above 2000 s, over 300 cycles with an on/off ratio of approximately 105 and record current density (3.4 × 108 A/cm2), which is 100 times higher than previous study through the smallest junction area achieved in a vdWI. The simple stacking of aligned CNTs (4 × 4) allows integration of memory arrays (16 junctions) with high device operational yield (100%), offering integration guidelines for future molecular electronics.
Direct observation of ideal electromagnetic fluids
Authors: Li Hao , Zhou Ziheng , Sun Wangyu , Lobet Michaël , Engheta Nader , Liberal Iñigo , Li Yue
Published: August 2022

Near-zero-index (NZI) media have been theoretically identified as media where electromagnetic radiations behave like ideal electromagnetic fluids. Within NZI media, the electromagnetic power flow obeys equations similar to those of motion for the velocity field in an ideal fluid, so that optical turbulence is intrinsically inhibited. Here, we experimentally observe the electromagnetic power flow distribution of such an ideal electromagnetic fluid propagating within a cutoff waveguide by a semi-analytical reconstruction technique. This technique provides direct proof of the inhibition of electromagnetic vorticity at the NZI frequency, even in the presence of complex obstacles and topological changes in the waveguide. Phase uniformity and spatially-static field distributions, essential characteristics of NZI materials, are also observed. Measurement of the same structure outside the NZI frequency range reveals existence of vortices in the power flow, as expected for conventional optical systems. Therefore, our results provide an important step forward in the development of ideal electromagnetic fluids, and introduce a tool to explore the subwavelength behavior of NZI media including fully vectorial and phase information.
Dynamic magnetic crossover at the origin of the hidden-order in van der Waals antiferromagnet CrSBr
Authors: López-Paz Sara A. , Guguchia Zurab , Pomjakushin Vladimir Y. , Witteveen Catherine , Cervellino Antonio , Luetkens Hubertus , Casati Nicola , Morpurgo Alberto F. , von Rohr Fabian O.
Published: August 2022

The van-der-Waals material CrSBr stands out as a promising two-dimensional magnet. Here, we report on its detailed magnetic and structural characteristics. We evidence that it undergoes a transition to an A-type antiferromagnetic state below TN ≈ 140 K with a pronounced two-dimensional character, preceded by ferromagnetic correlations within the monolayers. Furthermore, we unravel the low-temperature hidden-order within the long-range magnetically-ordered state. We find that it is associated to a slowing down of the magnetic fluctuations, accompanied by a continuous reorientation of the internal field. These take place upon cooling below Ts ≈ 100 K, until a spin freezing process occurs at T* ≈ 40 K. We argue this complex behavior to reflect a crossover driven by the in-plane uniaxial anisotropy, which is ultimately caused by its mixed-anion character. Our findings reinforce CrSBr as an important candidate for devices in the emergent field of two-dimensional magnetic materials.
Single-atom nanozymes catalytically surpassing naturally occurring enzymes as sustained stitching for brain trauma
Authors: Zhang Shaofang , Li Yonghui , Sun Si , Liu Ling , Mu Xiaoyu , Liu Shuhu , Jiao Menglu , Chen Xinzhu , Chen Ke , Ma Huizhen , Li Tuo , Liu Xiaoyu , Wang Hao , Zhang Jianning , Yang Jiang , Zhang Xiao-Dong
Published: August 2022

Regenerable nanozymes with high catalytic stability and sustainability are promising substitutes for naturally-occurring enzymes but are limited by insufficient and non-selective catalytic activities. Herein, we developed single-atom nanozymes of RhN4, VN4, and Fe-Cu-N6 with catalytic activities surpassing natural enzymes. Notably, Rh/VN4 preferably forms an Rh/V-O-N4 active center to decrease reaction energy barriers and mediates a “two-sided oxygen-linked” reaction path, showing 4 and 5-fold higher affinities in peroxidase-like activity than the FeN4 and natural horseradish peroxidase. Furthermore, RhN4 presents a 20-fold improved affinity in the catalase-like activity compared to the natural catalase; Fe-Cu-N6 displays selectivity towards the superoxide dismutase-like activity; VN4 favors a 7-fold higher glutathione peroxidase-like activity than the natural glutathione peroxidase. Bioactive sutures with Rh/VN4 show recyclable catalytic features without apparent decay in 1 month and accelerate the scalp healing from brain trauma by promoting the vascular endothelial growth factor, regulating the immune cells like macrophages, and diminishing inflammation.
High activity and selectivity of single palladium atom for oxygen hydrogenation to H2O2
Authors: Yu Shiming , Cheng Xing , Wang Yueshuai , Xiao Bo , Xing Yiran , Ren Jun , Lu Yue , Li Hongyi , Zhuang Chunqiang , Chen Ge
Published: August 2022

Nanosized palladium (Pd)-based catalysts are widely used in the direct hydrogen peroxide (H2O2) synthesis from H2 and O2, while its selectivity and yield remain inferior because of the O-O bond cleavage from both the reactant O2 and the produced H2O2, which is assumed to have originated from various O2 adsorption configurations on the Pd nanoparticles. Herein, single Pd atom catalyst with high activity and selectivity is reported. Density functional theory calculations certify that the O-O bond breaking is significantly inhibited on the single Pd atom and the O2 is easier to be activated to form *OOH, which is a key intermediate for H2O2 synthesis; in addition, H2O2 degradation is shut down. Here, we show single Pd atom catalyst displays a remarkable H2O2 yield of 115 mol/gPd/h and H2O2 selectivity higher than 99%; while the concentration of H2O2 reaches 1.07 wt.% in a batch.
Control of non-REM sleep by ventrolateral medulla glutamatergic neurons projecting to the preoptic area
Authors: Teng Sasa , Zhen Fenghua , Wang Li , Schalchli Jose Canovas , Simko Jane , Chen Xinyue , Jin Hao , Makinson Christopher D. , Peng Yueqing
Published: August 2022

Understanding the neural mechanisms underlying sleep state transitions is a fundamental goal of neurobiology and important for the development of new treatments for insomnia and other sleep disorders. Yet, brain circuits controlling this process remain poorly understood. Here we identify a population of sleep-active glutamatergic neurons in the ventrolateral medulla (VLM) that project to the preoptic area (POA), a prominent sleep-promoting region, in mice. Microendoscopic calcium imaging demonstrate that these VLM glutamatergic neurons display increased activity during the transitions from wakefulness to Non-Rapid Eye Movement (NREM) sleep. Chemogenetic silencing of POA-projecting VLM neurons suppresses NREM sleep, whereas chemogenetic activation of these neurons promotes NREM sleep. Moreover, we show that optogenetic activation of VLM glutamatergic neurons or their projections in the POA initiates NREM sleep in awake mice. Together, our findings uncover an excitatory brainstem-hypothalamic circuit that controls the wake-sleep transitions.
Excitation energy mediated cross-relaxation for tunable upconversion luminescence from a single lanthanide ion
Authors: Fu Xiao , Fu Shuai , Lu Qi , Zhang Jing , Wan Pingping , Liu Jinliang , Zhang Yong , Chen Chia-Hung , Li Wei , Wang Huadong , Mei Qingsong
Published: August 2022

Precise control of energy migration between sensitizer ions and activator ions in lanthanide-doped upconversion nanoparticles (UCNPs) nowadays has been extensively investigated to achieve efficient photon upconversion. However, these UCNPs generally emit blue, green or red light only under fixed excitation conditions. In this work, regulation of the photon transition process between different energy levels of a single activator ion to obtain tunable upconversion fluorescence under different excitation conditions is achieved by introducing a modulator ion. The cross-relaxation process between modulator ion and activator ion can be controlled to generate tunable luminescence from the same lanthanide activator ion under excitation at different wavelengths or with different laser power density and pulse frequency. This strategy has been tested and proven effective in two different nanocrystal systems and its usefulness has been demonstrated for high-level optical encryption.
Pan-cancer efficacy of pralsetinib in patients with RET fusion–positive solid tumors from the phase 1/2 ARROW trial
Authors: Subbiah Vivek , Cassier Philippe A. , Siena Salvatore , Garralda Elena , Paz-Ares Luis , Garrido Pilar , Nadal Ernest , Vuky Jacqueline , Lopes Gilberto , Kalemkerian Gregory P. , Bowles Daniel W. , Seetharam Mahesh , Chang Jianhua , Zhang Hui , Green Jennifer , Zalutskaya Alena , Schuler Martin , Fan Yun , Curigliano Giuseppe
Published: August 2022

Oncogenic RET fusions occur in diverse cancers. Pralsetinib is a potent, selective inhibitor of RET receptor tyrosine kinase. ARROW (NCT03037385, ongoing) was designed to evaluate pralsetinib efficacy and safety in patients with advanced RET-altered solid tumors. Twenty-nine patients with 12 different RET fusion–positive solid tumor types, excluding non-small-cell lung cancer and thyroid cancer, who had previously received or were not candidates for standard therapies, were enrolled. The most common RET fusion partners in 23 efficacy-evaluable patients were CCDC6 (26%), KIF5B (26%) and NCOA4 (13%). Overall response rate, the primary endpoint, was 57% (95% confidence interval, 35–77) among these patients. Responses were observed regardless of tumor type or RET fusion partner. Median duration of response, progression-free survival and overall survival were 12 months, 7 months and 14 months, respectively. The most common grade ≥3 treatment-related adverse events were neutropenia (31%) and anemia (14%). These data validate RET as a tissue-agnostic target with sensitivity to RET inhibition, indicating pralsetinib’s potential as a well-tolerated treatment option with rapid, robust and durable anti-tumor activity in patients with diverse RET fusion–positive solid tumors.
A novel causative functional mutation in GATA6 gene is responsible for familial dilated cardiomyopathy as supported by in silico functional analysis
Authors: Khazamipour Afrouz , Gholampour-Faroji Nazanin , Zeraati Tina , Vakilian Farveh , Haddad-Mashadrizeh Aliakbar , Ghayour Mobarhan Majid , Pasdar Alireza
Published: August 2022

Dilated cardiomyopathy (DCM), one of the most common types of cardiomyopathies has a heterogeneous nature and can be seen in Mendelian forms. Next Generation Sequencing is a powerful tool for identifying novel variants in monogenic disorders. We used whole-exome sequencing (WES) and Sanger sequencing techniques to identify the causative mutation of DCM in an Iranian pedigree. We found a novel variant in the GATA6 gene, leading to substituting Histidine by Tyrosine at position 329, observed in all affected family members in the pedigree, whereas it was not established in any of the unaffected ones. We hypothesized that the H329Y mutation may be causative for the familial pattern of DCM in this family. The predicted models of GATA6 and H329Y showed the high quality according to PROCHECK and ERRAT. Nonetheless, simulation results revealed that the protein stability decreased after mutation, while the flexibility may have been increased. Hence, the mutation led to the increased compactness of GATA6. Overall, these data indicated that the mutation could affect the protein structure, which may be related to the functional impairment of GATA6 upon H329Y mutation, likewise their involvement in pathologies. Further functional investigations would help elucidating the exact mechanism.
Cortical waste clearance in normal and restricted sleep with potential runaway tau buildup in Alzheimer’s disease
Authors: Tekieh Tahereh , Robinson P. A. , Postnova Svetlana
Published: August 2022

Accumulation of waste in cortical tissue and glymphatic waste clearance via extracellular voids partly drives the sleep-wake cycle and modeling has reproduced much of its dynamics. Here, new modeling incorporates higher void volume and clearance in sleep, multiple waste compounds, and clearance obstruction by waste. This model reproduces normal sleep-wake cycles, sleep deprivation effects, and performance decreases under chronic sleep restriction (CSR). Once fitted to calibration data, it successfully predicts dynamics in further experiments on sleep deprivation, intermittent CSR, and recovery after restricted sleep. The results imply a central role for waste products with lifetimes similar to tau protein. Strong tau buildup is predicted if pathologically enhanced production or impaired clearance occur, with runaway buildup above a critical threshold. Predicted tau accumulation has timescales consistent with the development of Alzheimer’s disease. The model unifies a wide sweep of phenomena, clarifying the role of glymphatic clearance and targets for interventions against waste buildup.
Climate change contributions to future atmospheric river flood damages in the western United States
Authors: Corringham Thomas W. , McCarthy James , Shulgina Tamara , Gershunov Alexander , Cayan Daniel R. , Ralph F. Martin
Published: August 2022

Atmospheric rivers (ARs) generate most of the economic losses associated with flooding in the western United States and are projected to increase in intensity with climate change. This is of concern as flood damages have been shown to increase exponentially with AR intensity. To assess how AR-related flood damages are likely to respond to climate change, we constructed county-level damage models for the western 11 conterminous states using 40 years of flood insurance data linked to characteristics of ARs at landfall. Damage functions were applied to 14 CMIP5 global climate models under the RCP4.5 “intermediate emissions” and RCP8.5 “high emissions” scenarios, under the assumption that spatial patterns of exposure, vulnerability, and flood protection remain constant at present day levels. The models predict that annual expected AR-related flood damages in the western United States could increase from $1 billion in the historical period to $2.3 billion in the 2090s under the RCP4.5 scenario or to $3.2 billion under the RCP8.5 scenario. County-level projections were developed to identify counties at greatest risk, allowing policymakers to target efforts to increase resilience to climate change.
Distance and similarity measures for normal wiggly dual hesitant fuzzy sets and their application in medical diagnosis
Authors: Ali Jawad , Naeem Muhammad
Published: August 2022

The normal wiggly dual hesitant fuzzy set (NWDHFS) is a modern mathematical tool that can be used to express the deep ideas of membership and non-membership information hidden in the thought-level of decision-makers (DMs). To enhance and expand the applicability of NWDHFSs, this study originates several types of distance and similarity measures between two NWDHFSs. The present paper first revises the basic operational laws of normal wiggly dual hesitant fuzzy elements (NWDHFEs) and then generalizes the rule of length extension for normal wiggly dual hesitant fuzzy setting. Meanwhile, we introduce a variety of distance and similarity measures under the background of NWDHFSs. After that, a family of weighted distance and similarity measures based on NWDHFS is presented and analyzed for discrete and continuous cases. The stated measures are the extension of several existing measures and have the capability to handle uncertain and vague information with a wider range of information. DMs can select the most suitable alternative based on these measures by determining the gap between each alternative and the ideal one. Finally, a practical example concerning disease detection is addressed to demonstrate the applicability and merits of the developed theory and depict the differences between the presented distance and similarity measures.
Development of deep learning chest X-ray model for cardiac dose prediction in left-sided breast cancer radiotherapy
Authors: Koide Yutaro , Aoyama Takahiro , Shimizu Hidetoshi , Kitagawa Tomoki , Miyauchi Risei , Tachibana Hiroyuki , Kodaira Takeshi
Published: August 2022

Deep inspiration breath-hold (DIBH) is widely used to reduce the cardiac dose in left-sided breast cancer radiotherapy. This study aimed to develop a deep learning chest X-ray model for cardiac dose prediction to select patients with a potentially high risk of cardiac irradiation and need for DIBH radiotherapy. We used 103 pairs of anteroposterior and lateral chest X-ray data of left-sided breast cancer patients (training cohort: n = 59, validation cohort: n = 19, test cohort: n = 25). All patients underwent breast-conserving surgery followed by DIBH radiotherapy: the treatment plan consisted of three-dimensional, two opposing tangential radiation fields. The prescription dose of the planning target volume was 42.56 Gy in 16 fractions. A convolutional neural network-based regression model was developed to predict the mean heart dose (∆MHD) reduction between free-breathing (MHDFB) and DIBH. The model performance is evaluated as a binary classifier by setting the cutoff value of ∆MHD > 1 Gy. The patient characteristics were as follows: the median (IQR) age was 52 (47–61) years, MHDFB was 1.75 (1.14–2.47) Gy, and ∆MHD was 1.00 (0.52–1.64) Gy. The classification performance of the developed model showed a sensitivity of 85.7%, specificity of 90.9%, a positive predictive value of 92.3%, a negative predictive value of 83.3%, and a diagnostic accuracy of 88.0%. The AUC value of the ROC curve was 0.864. The proposed model could predict ∆MHD in breast radiotherapy, suggesting the potential of a classifier in which patients are more desirable for DIBH.
Coupled power generators require stability buffers in addition to inertia
Authors: Raman Gurupraanesh , Raman Gururaghav , Peng Jimmy Chih-Hsien
Published: August 2022

Increasing the inertia is widely considered to be the solution to resolving unstable interactions between coupled oscillators. In power grids, Virtual Synchronous Generators (VSGs) are proposed to compensate for reducing inertia as rotating fossil-fuel-based generators are being phased out. Yet, modeling how VSGs and rotating generators simultaneously contribute energy and inertia, we surprisingly find that instabilities of a small-signal nature could arise despite fairly high system inertia if the generators’ controls are not coordinated at the system level. Importantly, we show there exist both an optimal and a maximum number of such VSGs that can be safely supported, a previously unknown result directly useful for power utilities in long-term planning and prosumer contracting. Meanwhile, to resolve instabilities in the short term until system-level coordination can be achieved, we argue that the new market should include another commodity that we call stability storage, whereby—analogous to energy storage buffering energy imbalances—VSGs act as decentralized stability buffers. While demonstrating the effectiveness of this concept for a wide range of energy futures, we provide policymakers and utilities with a roadmap towards achieving a 100% renewable grid.
Controlling the uncontrolled variation in the diet induced obese mouse by microbiomic characterization
Authors: Bondarenko Valeriia , Løkke Cecillie Reynolds , Dobrowolski Peter , Mentzel Caroline Junker , Castro-Mejía Josué L. , Hansen Camilla Hartmann Friis , Sørensen Dorte Bratbo , Nielsen Dennis Sandris , Krych Lukasz , Hansen Axel Kornerup
Published: August 2022

Group sizes in an animal study are calculated from estimates on variation, effect, power and significance level. Much of the variation in glucose related parameters of the diet-induced obese (DIO) mouse model is due to inter-individual variation in gut microbiota composition. In addition, standard tandem repeats (STRs) in the non-coding DNA shows that inbred mice are not always homogenic. C57BL/6NTac (B6NTac) mice from Taconic and C57BL/6NRj (B6NRj) mice from Janvier Labs were fed a high calorie diet and treated with liraglutide. The fecal microbiota was sequenced before high-calorie feeding (time 1) and after diet-induced obesity instantly before liraglutide treatment (time 2) and mice were divided into clusters on the basis of their microbiota. Although liraglutide in both sub-strains alleviated glucose intolerance and reduced body weight, in a one-way ANOVA a borderline reduction in glycosylated hemoglobin (HbA1c) could only be shown in B6NTac mice. However, if the microbiota clusters from time 1 or time 2 were incorporated in a two-way ANOVA, the HbA1c effect was significant in B6NTac mice in both analyses, while this did not change anything in B6NRj mice. In a one-way ANOVA the estimated group size needed for a significant HbA1c effect in B6NTac mice was 42, but in two-way ANOVAs based upon microbiota clusters of time 1 or time 2 it was reduced to 21 or 12, respectively. The lowering impact on glucose tolerance was also powered by incorporation of microbiota clusters of both times in both sub-strains. B6NRj had up to six, while B6NTac had maximum three alleles in some of their STRs. In B6NRj mice in 28.8% of the STRs the most prevalent allele had a gene frequency less than 90%, while this was only 6.6% in the B6NTac mice. However, incorporation of the STRs with the highest number of alleles or the most even distribution of frequencies in two-way ANOVAs only had little impact on the outcome of data evaluation. It is concluded that the inclusion of microbiota clusters in a two-way ANOVA in the evaluation of the glucose related effects of an intervention in the DIO mouse model might be an efficient tool for increasing power and reducing group sizes in mouse sub-strains, if these have a microbiota, which influences these parameters.
Global transcriptional and circadian regulation in a halotolerant cyanobacterium Halothece sp. PCC7418
Authors: Waditee-Sirisattha Rungaroon , Ito Hiroshi , Kageyama Hakuto
Published: August 2022

Substantial evidence has been accumulated about the molecular basis underlying halotolerance; however, insights into the regulatory networks for relevant genes and mechanisms of their interplay remain elusive. Here, we present a comprehensive transcriptome investigation, using RNA sequencing, of specific metabolic pathways and networks in a halotolerant cyanobacterium, Halothece sp. PCC7418, including the circadian rhythm profile. Dissecting the transcriptome presented the intracellular regulation of gene expressions, which was linked with ion homeostasis, protein homeostasis, biosynthesis of compatible solutes, and signal transduction, for adaptations to high-salinity environments. The efficient production and distribution of energy were also implicated in this acclimation process. Furthermore, we found that high-salinity environments had a dramatic effect on the global transcriptional expression regulated by the circadian clock. Our findings can provide a comprehensive transcriptome for elucidating the molecular mechanisms underlying halotolerance in cyanobacteria.
On the randomness and correlation in the trajectories of alpha particle emitted from 241Am: statistical inference based on information entropy
Authors: El Ghazaly M. , Elmaghraby Elsayed K. , Al-Sayed A. , Mohamed Amal , Dawood Mahmoud S.
Published: August 2022

Most particle detectors are based on the hypothesis that particles are emitted randomly upon nuclear decay. In the present work, we tested the hypothesis of the existence of correlation in the random trajectories of alpha particles emitted from$${}^{241}$$241Am source and the null hypothesis of random trajectories. The trajectories were clued through the registration of track in a solid-state nuclear track detector. The experimental parameters were optimized to identify the possible sources of correlation in the track registration and the detector conditions upon exposure and etching to avoid misleading results. The optimization included authentication of linearity in registration efficiency with exposure time to prevent coalescence of registered tracks. The statistical inference processes were based upon adaptive quadrates analysis of the spatial data, and entropy and divergence analysis of the quadrate data together with the null hypothesis of Poisson distribution of random trajectories. The clustering and dispersion analysis were performed with central deviation tendency, empirical K-function, radial distribution analysis, and proximity Analysis. Results showed a pattern of gained information within the registered tracks that may be attributed to the alteration in the alpha particles’ trajectories induced by the strong electric field due to atoms in the source compound and encapsulation film.
Edge artificial intelligence wireless video capsule endoscopy
Authors: Sahafi A. , Wang Y. , Rasmussen C. L. M. , Bollen P. , Baatrup G. , Blanes-Vidal V. , Herp J. , Nadimi E. S.
Published: August 2022

Gastrointestinal (GI) tract diseases are responsible for substantial morbidity and mortality worldwide, including colorectal cancer, which has shown a rising incidence among adults younger than 50. Although this could be alleviated by regular screening, only a small percentage of those at risk are screened comprehensively, due to shortcomings in accuracy and patient acceptance. To address these challenges, we designed an artificial intelligence (AI)-empowered wireless video endoscopic capsule that surpasses the performance of the existing solutions by featuring, among others: (1) real-time image processing using onboard deep neural networks (DNN), (2) enhanced visualization of the mucous layer by deploying both white-light and narrow-band imaging, (3) on-the-go task modification and DNN update using over-the-air-programming and (4) bi-directional communication with patient’s personal electronic devices to report important findings. We tested our solution in an in vivo setting, by administrating our endoscopic capsule to a pig under general anesthesia. All novel features, successfully implemented on a single platform, were validated. Our study lays the groundwork for clinically implementing a new generation of endoscopic capsules, which will significantly improve early diagnosis of upper and lower GI tract diseases.
Evaluating and mitigating clinical samples matrix effects on TX-TL cell-free performance
Authors: Voyvodic Peter L. , Conejero Ismael , Mesmoudi Khouloud , Renard Eric , Courtet Philippe , Cattoni Diego I. , Bonnet Jerome
Published: August 2022

Cell-free biosensors are promising tools for medical diagnostics, yet their performance can be affected by matrix effects arising from the sample itself or from external components. Here we systematically evaluate the performance and robustness of cell-free systems in serum, plasma, urine, and saliva using two reporter systems, sfGFP and luciferase. In all cases, clinical samples have a strong inhibitory effect. Of the different inhibitors, only RNase inhibitor mitigated matrix effects. However, we found that the recovery potential of RNase inhibitor was partially muted by interference from glycerol contained in the commercial buffer. We solved this issue by designing a strain producing an RNase inhibitor protein requiring no additional step in extract preparation. Furthermore, our new extract yielded higher reporter levels than previous conditions and tempered interpatient variability associated with matrix effects. This systematic evaluation and improvements of cell-free system robustness unified across many types of clinical samples is a significant step towards developing cell-free diagnostics for a wide range of conditions.
Association between long-term weight-change trajectory and cardiovascular disease risk by physical activity level
Authors: Lee Hye Ah , Park Hyesook
Published: August 2022

Using data from the Korean Genome and Epidemiology Study, we identified weight-change patterns during midlife using a group-based trajectory model, and evaluated their associations with the incidence of cardiovascular disease (CVD). At baseline, there were 8774 CVD-free participants. Group-based modeling was used to analyze patterns of weight change over about 16 years. Using multiple model, we evaluated the association between weight-change patterns and CVD risk. During the follow-up period, 741 new CVD cases were identified. The weight-change patterns were characterized as ‘gradual weight gain’, ‘stable weight’, ‘slight weight loss’, and ‘gradual weight loss’. The association between weight-change patterns and CVD risk differed depending on the level of physical activity (PA) at baseline (pinteraction < 0.05). Compared with the stable-weight group, the risk of all CVD (HR 2.5, 95% CI 1.5–4.3) and non-fatal CVD (HR 2.8, 95% CI 1.6–4.9) among the gradual-weight-loss group was apparent in the lowest PA quartile. In addition, on average, a decrease in skeletal-muscle-mass (SMM) levels was observed during the follow-up period, but the decrease in SMM in the gradual-weight-loss group was greater than in the gradual-weight-gain group. Our findings show that gradual weight loss was associated with CVD risk, which was dependent on PA levels.
Tapped-inductor bi-directional Cuk converter with high step-up/down conversion ratio and its optimum design
Authors: Chen Hongxing , Lin Wei-ming , Liu Wen-ran , He Wei
Published: August 2022

A bidirectional DC–DC converter is required for an energy storage system. High efficiency and a high step-up and step-down conversion ratio are the development trends. In this research, a series of bidirectional high-gain Cuk circuits was derived by combining tapped inductors and bidirectional Cuk. After analyzing and comparing the characteristics of each circuit, a bidirectional high-gain Cuk circuit with a tapped-inductor (reverse coupling) was proposed. The proposed converter has a simple structure and a high voltage gain in both the step-down (Buck) and step-up (Boost) operation modes. The voltage stress of S2 was low. The voltage stress of S1 was high, however, and this is a disadvantage of the proposed converter. The proposed circuit’s characteristics were thoroughly examined, including the voltage gain characteristics and the design of the main parameters. We established a power loss model of the new topology, and the tapped-inductor turn ratio was optimized for high efficiency. Finally, a 400 W experimental implementation of the converter was shown to achieve efficiencies of 93.5% and 92.4% in the step-up and step-down modes, respectively. These findings verified the validity of the proposed circuit’s theoretical analysis.