bluuebunny/crossref_metadata_2025_split huggingface dataset:
A biophysical account of multiplication by a single neuron
Authors: Groschner Lukas N. , Malis Jonatan G. , Zuidinga Birte , Borst Alexander 
Published: February 2022

AbstractNonlinear, multiplication-like operations carried out by individual nerve cells greatly enhance the computational power of a neural system1–3, but our understanding of their biophysical implementation is scant. Here we pursue this problem in the Drosophila melanogaster ON motion vision circuit4,5, in which we record the membrane potentials of direction-selective T4 neurons and of their columnar input elements6,7 in response to visual and pharmacological stimuli in vivo. Our electrophysiological measurements and conductance-based simulations provide evidence for a passive supralinear interaction between two distinct types of synapse on T4 dendrites. We show that this multiplication-like nonlinearity arises from the coincidence of cholinergic excitation and release from glutamatergic inhibition. The latter depends on the expression of the glutamate-gated chloride channel GluClα8,9 in T4 neurons, which sharpens the directional tuning of the cells and shapes the optomotor behaviour of the animals. Interacting pairs of shunting inhibitory and excitatory synapses have long been postulated as an analogue approximation of a multiplication, which is integral to theories of motion detection10,11, sound localization12 and sensorimotor control13.
TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A
Authors: Brown Anna-Leigh , Wilkins Oscar G. , Keuss Matthew J. , Hill Sarah E. , Zanovello Matteo , Lee Weaverly Colleen , Bampton Alexander , Lee Flora C. Y. , Masino Laura , Qi Yue A. , Bryce-Smith Sam , Gatt Ariana , Hallegger Martina , Fagegaltier Delphine , Phatnani Hemali ,   NYGC ALS Consortium, Phatnani Hemali , Kwan Justin , Sareen Dhruv , Broach James R. , Simmons Zachary , Arcila-Londono Ximena , Lee Edward B. , Van Deerlin Vivianna M. , Shneider Neil A. , Fraenkel Ernest , Ostrow Lyle W. , Baas Frank , Zaitlen Noah , Berry James D. , Malaspina Andrea , Fratta Pietro , Cox Gregory A. , Thompson Leslie M. , Finkbeiner Steve , Dardiotis Efthimios , Miller Timothy M. , Chandran Siddharthan , Pal Suvankar , Hornstein Eran , MacGowan Daniel J. , Heiman-Patterson Terry , Hammell Molly G. , Patsopoulos Nikolaos. A. , Butovsky Oleg , Dubnau Joshua , Nath Avindra , Bowser Robert , Harms Matthew , Aronica Eleonora , Poss Mary , Phillips-Cremins Jennifer , Crary John , Atassi Nazem , Lange Dale J. , Adams Darius J. , Stefanis Leonidas , Gotkine Marc , Baloh Robert H. , Babu Suma , Raj Towfique , Paganoni Sabrina , Shalem Ophir , Smith Colin , Zhang Bin , Harris Brent , Broce Iris , Drory Vivian , Ravits John , McMillan Corey , Menon Vilas , Wu Lani , Altschuler Steven , Lerner Yossef , Sattler Rita , Van Keuren-Jensen Kendall , Rozenblatt-Rosen Orit , Lindblad-Toh Kerstin , Nicholson Katharine , Gregersen Peter , Lee Jeong-Ho , Koks Sulev , Muljo Stephen , Newcombe Jia , Gustavsson Emil K. , Seddighi Sahba , Reyes Joel F. , Coon Steven L. , Ramos Daniel , Schiavo Giampietro , Fisher Elizabeth M. C. , Raj Towfique , Secrier Maria , Lashley Tammaryn , Ule Jernej , Buratti Emanuele , Humphrey Jack , Ward Michael E. , Fratta Pietro 
Published: February 2022

AbstractVariants of UNC13A, a critical gene for synapse function, increase the risk of amyotrophic lateral sclerosis and frontotemporal dementia1–3, two related neurodegenerative diseases defined by mislocalization of the RNA-binding protein TDP-434,5. Here we show that TDP-43 depletion induces robust inclusion of a cryptic exon in UNC13A, resulting in nonsense-mediated decay and loss of UNC13A protein. Two common intronic UNC13A polymorphisms strongly associated with amyotrophic lateral sclerosis and frontotemporal dementia risk overlap with TDP-43 binding sites. These polymorphisms potentiate cryptic exon inclusion, both in cultured cells and in brains and spinal cords from patients with these conditions. Our findings, which demonstrate a genetic link between loss of nuclear TDP-43 function and disease, reveal the mechanism by which UNC13A variants exacerbate the effects of decreased TDP-43 function. They further provide a promising therapeutic target for TDP-43 proteinopathies.
Effective drug combinations in breast, colon and pancreatic cancer cells
Authors: Jaaks Patricia , Coker Elizabeth A. , Vis Daniel J. , Edwards Olivia , Carpenter Emma F. , Leto Simonetta M. , Dwane Lisa , Sassi Francesco , Lightfoot Howard , Barthorpe Syd , van der Meer Dieudonne , Yang Wanjuan , Beck Alexandra , Mironenko Tatiana , Hall Caitlin , Hall James , Mali Iman , Richardson Laura , Tolley Charlotte , Morris James , Thomas Frances , Lleshi Ermira , Aben Nanne , Benes Cyril H. , Bertotti Andrea , Trusolino Livio , Wessels Lodewyk , Garnett Mathew J. 
Published: February 2022

AbstractCombinations of anti-cancer drugs can overcome resistance and provide new treatments1,2. The number of possible drug combinations vastly exceeds what could be tested clinically. Efforts to systematically identify active combinations and the tissues and molecular contexts in which they are most effective could accelerate the development of combination treatments. Here we evaluate the potency and efficacy of 2,025 clinically relevant two-drug combinations, generating a dataset encompassing 125 molecularly characterized breast, colorectal and pancreatic cancer cell lines. We show that synergy between drugs is rare and highly context-dependent, and that combinations of targeted agents are most likely to be synergistic. We incorporate multi-omic molecular features to identify combination biomarkers and specify synergistic drug combinations and their active contexts, including in basal-like breast cancer, and microsatellite-stable or KRAS-mutant colon cancer. Our results show that irinotecan and CHEK1 inhibition have synergistic effects in microsatellite-stable or KRAS–TP53 double-mutant colon cancer cells, leading to apoptosis and suppression of tumour xenograft growth. This study identifies clinically relevant effective drug combinations in distinct molecular subpopulations and is a resource to guide rational efforts to develop combinatorial drug treatments.
The bacterial toxin colibactin triggers prophage induction
Authors: Silpe Justin E. , Wong Joel W. H. , Owen Siân V. , Baym Michael , Balskus Emily P. 
Published: February 2022

AbstractColibactin is a chemically unstable small-molecule genotoxin that is produced by several different bacteria, including members of the human gut microbiome1,2. Although the biological activity of colibactin has been extensively investigated in mammalian systems3, little is known about its effects on other microorganisms. Here we show that colibactin targets bacteria that contain prophages, and induces lytic development through the bacterial SOS response. DNA, added exogenously, protects bacteria from colibactin, as does expressing a colibactin resistance protein (ClbS) in non-colibactin-producing cells. The prophage-inducing effects that we observe apply broadly across different phage–bacteria systems and in complex communities. Finally, we identify bacteria that have colibactin resistance genes but lack colibactin biosynthetic genes. Many of these bacteria are infected with predicted prophages, and we show that the expression of their ClbS homologues provides immunity from colibactin-triggered induction. Our study reveals a mechanism by which colibactin production could affect microbiomes and highlights a role for microbial natural products in influencing population-level events such as phage outbreaks.
Lowering the setting value of the esophageal endoscopic submucosal dissection device enabled tissue damage control in vitro porcine model
Authors: Yamaguchi Yukiko , Uesato Masaya , Yonemoto Shohei , Maruyama Tetsuro , Urahama Ryuma , Suito Hiroshi , Kishimoto Takashi , Shiko Yuki , Ozawa Yoshihito , Kawasaki Yohei , Matsubara Hisahiro 
Published: February 2022

AbstractOne of the complications of esophageal endoscopic submucosal dissection (ESD) is postoperative stricture formation. Stenosis formation is associated with inflammation and fibrosis in the healing process. We hypothesized that the degree of thermal damage caused by the device is related to stricture formation. We aimed to reveal the relationship between thermal damage and setting value of the device. We energized a resected porcine esophagus using the ESD device (Flush Knife 1.5). We performed 10 energization points for 1 s, 3 s, and 5 s at four setting values of the device. We measured the amount of current flowing to the conducted points and the temperature and evaluated the effects of thermal damage pathologically. As results, the mean highest temperatures for 1 s were I (SWIFT Effect3 Wat20): 61.19 °C, II (SWIFT Effect3 Wat30): 77.28 °C, III (SWIFT Effect4 Wat20): 94.50 °C, and IV (SWIFT Effect4 Wat30): 94.29 °C. The mean heat denaturation areas were I: 0.84 mm2, II: 1.00 mm2, III: 1.91 mm2, and IV: 1.54 mm2. The mean highest temperature and mean heat denaturation area were significantly correlated (P < 0.001). In conclusion, Low-current ESD can suppress the actual temperature and thermal damage in the ESD wound.
Carex pulicaris abundance is positively associated with soil acidity, rainfall and floristic diversity in the eastern distribution range
Authors: Sotek Zofia , Stasińska Małgorzata , Malinowski Ryszard , Gamrat Renata , Gałczyńska Małgorzata , Kull Thea , Mochnacký Sergej , Grzejszczak Grzegorz , Paprota Dariusz , Kolarčik Vladislav 
Published: February 2022

AbstractCarex pulicarisis considered an endangered species, and further losses are forecast under the influence of even moderate climate change. Local studies indicate that temporal declines inC. pulicarisabundance are positively correlated to decreases in precipitation and increases in air temperature. Determining ecological properties on larger scales than local ones can help develop effective protection programs for the species. We hypothesize that the local relationships observed betweenC. pulicarisabundance and precipitation, air temperature and soil properties will be confirmed in a spatially-oriented large-scale study performed in situ. Therefore, the present study takes a novel, large-scale integrated approach to (1) precisely characterize the ecological requirements ofC. pulicariswithin its eastern distribution range, and (2) determine the influence of its community type, soil properties and climatic conditions on its abundance. It was found thatC. pulicarisis not a dominant or codominant species in the studied phytocoenoses in the eastern distribution range. Five natural vegetation groups includingC. pulicaris, with significantly diverse species compositions, were resolved: well supported Estonian, Polish, Slovak and Radecz groups, and a weakly-supported Ambiguous group. The abundance ofC. pulicariswas found to be positively correlated with the composition of the geographically-diversified plant communities and atmospheric precipitation, and to be also negatively associated with latitude and soil pH. Although the species is adapted to a relatively wide range of soil types, such adaptation requires appropriate substrate moisture level and light conditions. The species prefers moist organic and mineral soils and grows on both acid and neutral medium, characterized by a narrow C:N ratio, with various amounts of digestible total P, Mg and N, and low levels of digestible K. Climate change, manifested by reduced rainfall, may be one of the most important predictors negatively affecting the occurrence ofC. pulicaris.
Gate reflectometry of single-electron box arrays using calibrated low temperature matching networks
Authors: Filmer Matthew J. , Huebner Matthew , Zirkle Thomas A. , Jehl Xavier , Sanquer Marc , Chisum Jonathan D. , Orlov Alexei O. , Snider Gregory L. 
Published: February 2022

AbstractSensitive dispersive readouts of single-electron devices (“gate reflectometry”) rely on one-port radio-frequency (RF) reflectometry to read out the state of the sensor. A standard practice in reflectometry measurements is to design an impedance transformer to match the impedance of the load to the characteristic impedance of the transmission line and thus obtain the best sensitivity and signal-to-noise ratio. This is particularly important for measuring large impedances, typical for dispersive readouts of single-electron devices because even a small mismatch will cause a strong signal degradation. When performing RF measurements, a calibration and error correction of the measurement apparatus must be performed in order to remove errors caused by unavoidable non-idealities of the measurement system. Lack of calibration makes optimizing a matching network difficult and ambiguous, and it also prevents a direct quantitative comparison between measurements taken of different devices or on different systems. We propose and demonstrate a simple straightforward method to design and optimize a pi matching network for readouts of devices with large impedance, $$Z \ge 1\hbox {M}\Omega$$

Z
≥
1
M
Ω

. It is based on a single low temperature calibrated measurement of an unadjusted network composed of a single L-section followed by a simple calculation to determine a value of the “balancing” capacitor needed to achieve matching conditions for a pi network. We demonstrate that the proposed calibration/error correction technique can be directly applied at low temperature using inexpensive calibration standards. Using proper modeling of the matching networks adjusted for low temperature operation the measurement system can be easily optimized to achieve the best conditions for energy transfer and targeted bandwidth, and can be used for quantitative measurements of the device impedance. In this work we use gate reflectometry to readout the signal generated by arrays of parallel-connected Al-AlOx single-electron boxes. Such arrays can be used as a fast nanoscale voltage sensor for scanning probe applications. We perform measurements of sensitivity and bandwidth for various settings of the matching network connected to arrays and obtain strong agreement with the simulations.
An analytical study of sound transmission loss of functionally graded sandwich cylindrical nanoshell integrated with piezoelectric layers
Authors: Thongchom Chanachai , Saffari Pouyan Roodgar , Refahati Nima , Saffari Peyman Roudgar , Pourbashash Hossein , Sirimontree Sayan , Keawsawasvong Suraparb 
Published: February 2022

AbstractThe multidisciplinary nature of piezoelectric (PZ) structures necessitates precise and efficient methods to express their behavior under different conditions. This article extends the general usage of PZ materials by introducing acoustic and fluid loading effects in a way that an unfilled multilayer cylindrical nanoshell with a functionally graded (FG) material core and PZ layers is subjected to preliminary external electric load, acoustic waves and external flow motion. As the properties of a functionally graded material changes along the shell thickness, a power law model is assumed to be governing such variations of desired characteristics. Evidently, this system includes different types of couplings and a comprehensive approach is required to describe the structural response. To this aim, the first-order shear deformation theory (FSDT) is used to define different displacement components. Next, the coupled size-dependent vibroacoustic equations are derived based on in conjunction with nonlocal strain gradient theory (NSGT) with the aid of Hamilton’s variational principle and fluid/structure compatibility conditions. NSGT is complemented with hardening and softening material effects which can greatly enhance the precision of results. It is expected to use the findings of this paper in the optimization of similar systems by selecting suitable FG index, incident angle of sound waves, flow Mach number, nonlocal and strain gradient parameters, starting electric potential and geometric features. One of the important findings of this study is that increasing the electric voltage can obtain better sound insulation at small frequencies, specially prior to the ring frequency.
Cascaded 3D UNet architecture for segmenting the COVID-19 infection from lung CT volume
Authors: L. Aswathy A. , S. Vinod Chandra S. 
Published: February 2022

AbstractWorld Health Organization (WHO) declared COVID-19 (COronaVIrus Disease 2019) as pandemic on March 11, 2020. Ever since then, the virus is undergoing different mutations, with a high rate of dissemination. The diagnosis and prognosis of COVID-19 are critical in bringing the situation under control. COVID-19 virus replicates in the lungs after entering the upper respiratory system, causing pneumonia and mortality. Deep learning has a significant role in detecting infections from the Computed Tomography (CT). With the help of basic image processing techniques and deep learning, we have developed a two stage cascaded 3D UNet to segment the contaminated area from the lungs. The first 3D UNet extracts the lung parenchyma from the CT volume input after preprocessing and augmentation. Since the CT volume is small, we apply appropriate post-processing to the lung parenchyma and input these volumes into the second 3D UNet. The second 3D UNet extracts the infected 3D volumes. With this method, clinicians can input the complete CT volume of the patient and analyze the contaminated area without having to label the lung parenchyma for each new patient. For lung parenchyma segmentation, the proposed method obtained a sensitivity of 93.47%, specificity of 98.64%, an accuracy of 98.07%, and a dice score of 92.46%. We have achieved a sensitivity of 83.33%, a specificity of 99.84%, an accuracy of 99.20%, and a dice score of 82% for lung infection segmentation.
Large-scale epitaxy of two-dimensional van der Waals room-temperature ferromagnet Fe5GeTe2
Authors: Ribeiro Mário , Gentile Giulio , Marty Alain , Dosenovic Djordje , Okuno Hanako , Vergnaud Céline , Jacquot Jean-François , Jalabert Denis , Longo Danilo , Ohresser Philippe , Hallal Ali , Chshiev Mairbek , Boulle Olivier , Bonell Frédéric , Jamet Matthieu 
Published: February 2022

AbstractIn recent years, two-dimensional van der Waals materials have emerged as an important platform for the observation of long-range ferromagnetic order in atomically thin layers. Although heterostructures of such materials can be conceived to harness and couple a wide range of magneto-optical and magneto-electrical properties, technologically relevant applications require Curie temperatures at or above room temperature and the ability to grow films over large areas. Here we demonstrate the large-area growth of single-crystal ultrathin films of stoichiometric Fe5GeTe2 on an insulating substrate using molecular beam epitaxy. Magnetic measurements show the persistence of soft ferromagnetism up to room temperature in 12 nm-thick films, with a Curie temperature of 293 K, and a weak out-of-plane magnetocrystalline anisotropy. The ferromagnetic order is preserved in bilayer Fe5GeTe2, with Curie temperature decreasing to 229 K. Surface, chemical, and structural characterizations confirm the layer-by-layer growth, 5:1:2 Fe:Ge:Te stoichiometric elementary composition, and single-crystalline character of the films.
Fortilin interacts with TGF-β1 and prevents TGF-β receptor activation
Authors: Pinkaew Decha , Martinez-Hackert Erik , Jia Wei , King Matthew D. , Miao Fei , Enger Nicole R. , Silakit Runglawan , Ramana Kota , Chen Shi-You , Fujise Ken 
Published: February 2022

AbstractFortilin is a 172-amino acid multifunctional protein present in both intra- and extracellular spaces. Although fortilin binds and regulates various cellular proteins, the biological role of extracellular fortilin remains unknown. Here we report that fortilin specifically interacts with TGF-β1 and prevents it from activating the TGF-β1 signaling pathway. In a standard immunoprecipitation-western blot assay, fortilin co-immunoprecipitates TGF-β1 and its isoforms. The modified ELISA assay shows that TGF-β1 remains complexed with fortilin in human serum. Both bio-layer interferometry and surface plasmon resonance (SPR) reveal that fortilin directly bind TGF-β1. The SPR analysis also reveals that fortilin and the TGF-β receptor II (TGFβRII) compete for TGF-β1. Both luciferase and secreted alkaline phosphatase reporter assays show that fortilin prevents TGF-β1 from activating Smad3 binding to Smad-binding element. Fortilin inhibits the phosphorylation of Smad3 in both quantitative western blot assays and ELISA. Finally, fortilin inhibits TGFβ-1-induced differentiation of C3H10T1/2 mesenchymal progenitor cells to smooth muscle cells. A computer-assisted virtual docking reveals that fortilin occupies the pocket of TGF-β1 that is normally occupied by TGFβRII and that TGF-β1 can bind either fortilin or TGFβRII at any given time. These data support the role of extracellular fortilin as a negative regulator of the TGF-β1 signaling pathway.
Autonomous self-optimizing defects by refining energy levels through hydrogenation in CeO2–x polymorphism: a walking mobility of oxygen vacancy with enhanced adsorption capabilities and photocatalytic stability
Authors: Verma Ranjana , Singh Jay , Samdarshi Sanjoy Kumar , Srivastava Anchal 
Published: February 2022

The proposed work on ceria photocatalyst shows facile reactivity of oxygen anions with hydrogen molecules, turning inefficient highly disordered CeO2−x into optimized disordered H-CeO2−x which sustains optimized oxygen vacancies and Ce3+ defects.
Study on discharge characteristics and improving surface hydrophobicity of epoxy resin by nanosecond pulse excited argon/hexamethyldisiloxane jet array
Authors: Liu Zhiyan , Xu Jingang , Zhu Xi , Liu Feng , Fang Zhi 
Published: February 2022

AbstractSurface flashover of insulating materials induced by pollution and moisture environment is one of the main reasons for the damage of power system and electrical equipment. The improvement of the insulating materials surface hydrophobicity is key important, which can prevent the pollutants and water attachment, and enhance the insulating performance. In this paper, the super‐hydrophobic film is formed on the surface of epoxy resin by a one‐dimensional (1D) argon (Ar) jet array driven by nanosecond pulse power supply with hexamethyldisiloxane (HMDSO) addition. The influences of the processing time and HMDSO content on the epoxy resin surface hydrophobicity are investigated. It shows that with 0.04 % HMDSO, the jet array achieves a best hydrophobic treatment effect on the epoxy resin surface. After 60 s treatment, the apparent contact angle (ACA) of the epoxy resin surface increases from 60.3° of the untreated surface to 150.0°. The wettability of epoxy resin surface does not change too much as the treatment time beyond 60 s. The maximum ACA value 153.4° appears at 120 s processing time, which is just slightly higher than that of 60 s treatment time. The epoxy resin surface morphology and chemical feature before and after plasma processing are characteristics by the scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier transform infra‐red spectroscopy and X‐ray photoelectron spectroscopy. It shows that the treated epoxy resin surface is covered with dense coral like particles in nanoscales, the original C=O、C‐H and other organic functional groups are replaced by Si‐(CH3), Si‐O‐Si and other silicon containing groups, and the Si content increases from 0.4% to 28.0%. The experimental results provide important references to develop jet array as an efficient tool to enhance the surface hydrophobicity and insulating performance of insulating materials.