bluuebunny/crossref_metadata_2025_split huggingface dataset:
Size Polydispersity Tunes Slip Avalanches of Granular Gouge
Authors: Ma Gang , Zou Yuxiong , Gao Ke , Zhao Jidong , Zhou Wei 
Published: November 2020

AbstractGranular materials have frequently been used as representations of natural fault gouges. Although they can reproduce proper avalanche behaviors, the universality of the scaling exponent of avalanche size remains debatable. As a core issue in both amorphous plasticity and geophysics, avalanche universality may help reconcile the avalanche behaviors of earthquake and granular materials into the same universality class. We examine numerically the signatures of stress avalanches emerging from quasi‐static shear of granular materials with different size polydispersity. A persistent serrated plastic flow phenomenon is observed in our models with varying polydispersity. The stress drop is well defined by a truncated power law distribution P(s) ~ s−τexp(−s/smax). The exponent τ and cutoff stress drop smax show a clear dependence on polydispersity, which reflects a tuned criticality. We further calculate the effective temperature from the statistics of energy fluctuations. The effective temperature volatility can be used to explain the tuned critical behaviors of granular gouge.
A Persistent Depletion of Plasma Ions Within Jupiter's Auroral Polar Caps
Authors: Pollock C. J. , Ebert R. W. , Allegrini F. , Bagenal F. , McComas D. J. , Szalay J. R. , Valek P. 
Published: November 2020

AbstractRegions poleward of Jupiter's main auroral ovals are largely devoid of 0.01 to 46 keV/q ions. We report ion measurements from the plasma instrument on the Juno spacecraft in polar orbit around Jupiter that characterize the presence or absence of structured ion fluxes poleward of the main ovals. We approximate geometric centers of published north and south Jovian main ovals and develop a probability metric for observation of plasma ions as a function of angular distance from these centers to the magnetic foot points of the observations, in the north and south separately. Using data from Juno's first 26 perijoves, at Jovicentric distances of 1.06 to 12 RJ, this metric shows a systematic decrease within both north and south main ovals, in the probability of observing plasma ions as the chosen centers are approached. This is consistent with previous reports of large electrostatic potential drops above Jupiter's polar caps.
Inferring Florida Current Volume Transport From Satellite Altimetry
Authors: Volkov Denis L. , Domingues Ricardo , Meinen Christopher S. , Garcia Rigoberto , Baringer Molly , Goni Gustavo , Smith Ryan H. 
Published: November 2020

AbstractThe nearly four‐decades‐long quasi‐continuous daily measurements of the Florida Current (FC) volume transport with a submarine cable at about 27°N represents the longest climate record of a boundary current in existence. Given the extremely high utility of this time series for monitoring the Atlantic meridional overturning circulation, as well as for improving understanding and prediction of the regional weather, climate phenomena, coastal sea‐level, and ecosystem dynamics, efforts are underway to establish a suitable backup observing system in case the cable becomes inoperable in the future. This study explores the utility of along‐track satellite altimetry measurements since 1993 as a potential cable backup by establishing the relationship between the cross‐stream sea surface height gradients and the FC volume transport derived from cable measurements and ship sections. We find that despite the lower temporal resolution, satellite altimetry can indeed serve as a decent but limited backup observing system. The FC transport inferred from satellite altimetry captures about 60% of the variability observed in the concurrent cable estimates, and the estimated error bars for the altimetry‐derived transport are larger than those of the cable transport (2.1 Sv vs. 1.5 Sv). We nevertheless demonstrate that satellite altimetry reproduces the seasonal, intra‐seasonal, and inter‐annual variability of the FC transport fairly well, as well as large transport anomalies during extreme weather events, such as tropical storms and hurricanes. The altimetry‐derived transport can be provided in near‐real time and serve the need to fill in data gaps in the cable record and assess its quality over time.
Magnetotaxis as an Adaptation to Enable Bacterial Shuttling of Microbial Sulfur and Sulfur Cycling Across Aquatic Oxic‐Anoxic Interfaces
Authors: Li Jinhua , Liu Peiyu , Wang Jian , Roberts Andrew P. , Pan Yongxin 
Published: November 2020

AbstractMagnetotactic bacteria (MTB) widely inhabit the oxic‐anoxic interface (OAI) of sediments and water columns, with their motility guided by geomagnetic fields (a behavior known as magnetotaxis). Beside biomineralizing membrane‐enveloped magnetite or greigite nanocrystals called magnetosomes, cells of many MTB groups contain numerous sulfur globules within their cells. Here, by combining transmission electron microscopy and synchrotron‐based scanning transmission X‐ray microscopy, we investigated the cellular structure and chemistry of Candidatus Magnetobacterium casensis (Mcas), a giant rod‐shaped MTB from the Nitrospirae phylum. We find that nitrate‐storing vacuoles and linearly polymeric sulfur globules occur exclusively within some Mcas cells along with magnetosomal magnetite. Genomic prediction indicates that Mcas cells have the potential to oxidize sulfide to sulfate (i.e., S2− → S0 → SO32− → SO42−), to reduce sulfate to sulfide (i.e., SO42− → SO32− → S2−), and to reduce nitrate to NH4+/N2. Together with previous environmental observations, comparative genomic analysis allows us to propose a model for Mcas involving the microbial sulfur cycle across aquatic OAIs based on magnetotaxis. Via directional movement guided by geomagnetic fields, Mcas cells shuttle either upward to upper microoxic zones for sulfur oxidation and nitrate accumulation in the OAI, or downward to deeper anoxic zones for sulfur deposition by coupling sulfide oxidation and nitrate reduction. Development of magnetotaxis makes MTB an efficient bacterial shuttle for C, N, S, and Fe across aquatic OAI environments and likely contributes significantly to their global biogeochemical cycling. It also benefits cell growth and magnetosomal magnetite formation in MTB.
Modeling Geomagnetic Interference on Railway Signaling Track Circuits
Authors: Boteler D. H. 
Published: November 2020

AbstractMisoperation of railway signaling during geomagnetic disturbances has occurred in a number of countries. Railway signals are activated by track circuits that detect the presence of a train in a particular rail section, but geomagnetically induced electric fields can interfere with the track circuit operation, causing the wrong signal to be displayed. This paper develops a new model for track circuit operation that includes the induced geoelectric fields produced by geomagnetic field variations. Rails are modeled as transmission lines with series impedance given by the rail resistance and parallel admittance determined by the current leakage from the rail through the ballast to ground. The transmission line model is then converted into an equivalent‐pi circuit for each rail and these are combined with the track circuit power and relay components to form a nodal admittance network for the track circuit. This is used to examine the effect of induced geoelectric fields on track circuit operation. First, an individual track circuit is examined and it is shown how the length, between insulating rail joints, of the individual rails influences the geomagnetic interference voltage produced across the track circuit relay. Then a series of track circuits is considered: A general solution is developed and then the conditions are identified that allow this to be reduced to a simpler solution considering each track circuit individually. This modeling provides insight into the conditions that produce signaling problems and provides the tools to assess the geomagnetic hazard to railway signaling.
PDK4 promotes vascular calcification by interfering with autophagic activity and metabolic reprogramming
Authors: Ma Wen-Qi , Sun Xue-Jiao , Zhu Yi , Liu Nai-Feng 
Published: November 2020

AbstractPyruvate dehydrogenase kinase 4 (PDK4) is an important mitochondrial matrix enzyme in cellular energy regulation. Previous studies suggested that PDK4 is increased in the calcified vessels of patients with atherosclerosis and is closely associated with mitochondrial function, but the precise regulatory mechanisms remain largely unknown. This study aims to investigate the role of PDK4 in vascular calcification and the molecular mechanisms involved. Using a variety of complementary techniques, we found impaired autophagic activity in the process of vascular smooth muscle cells (VSMCs) calcification, whereas knocking down PDK4 had the opposite effect. PDK4 drives the metabolic reprogramming of VSMCs towards a Warburg effect, and the inhibition of PDK4 abrogates VSMCs calcification. Mechanistically, PDK4 disturbs the integrity of the mitochondria-associated endoplasmic reticulum membrane, concomitantly impairing mitochondrial respiratory capacity, which contributes to a decrease in lysosomal degradation by inhibiting the V-ATPase and lactate dehydrogenase B interaction. PDK4 also inhibits the nuclear translocation of the transcription factor EB, thus inhibiting lysosomal function. These changes result in the interruption of autophagic flux, which accelerates calcium deposition in VSMCs. In addition, glycolysis serves as a metabolic adaptation to improve VSMCs oxidative stress resistance, whereas inhibition of glycolysis by 2-deoxy-D-glucose induces the apoptosis of VSMCs and increases the calcium deposition in VSMCs. Our results suggest that PDK4 plays a key role in vascular calcification through autophagy inhibition and metabolic reprogramming.
DEPDC1B is a tumor promotor in development of bladder cancer through targeting SHC1
Authors: Lai Chin-Hui , Xu Kexin , Zhou Jianhua , Wang Mingrui , Zhang Weiyu , Liu Xianhui , Xiong Jie , Wang Tao , Wang Qi , Wang Huanrui , Xu Tao , Hu Hao 
Published: November 2020

AbstractBladder cancer is one of the most commonly diagnosed malignant tumors in the urinary system and causes a massive cancer-related death. DEPDC1B is a DEP domain-containing protein that has been found to be associated with a variety of human cancers. This study aimed to explore the role and mechanism of DEPDC1B in the development of bladder cancer. The analysis of clinical specimens revealed the upregulated expression of DEPDC1B in bladder cancer, which was positively related to tumor grade. In vitro and in vivo studies showed that DEPDC1B knockdown could inhibit the growth of bladder cancer cells or xenografts in mice. The suppression of bladder cancer by DEPDC1B was executed through inhibiting cell proliferation, cell migration, and promoting cell apoptosis. Moreover, a mechanistic study found that SHC1 may be an important route through which DEPDC1B regulates the development of bladder cancer. Knockdown of SHC1 in DEPDC1B-overexpressed cancer cells could abolish the promotion effects induced by DEPDC1B. In conclusion, DEPDC1B was identified as a key regulator in the development of bladder cancer, which may be used as a potential therapeutic target in the treatment of bladder cancer.
Uncovering the multifaceted roles played by neutrophils in allogeneic hematopoietic stem cell transplantation
Authors: Tecchio Cristina , Cassatella Marco Antonio 
Published: November 2020

AbstractAllogeneic hematopoietic stem cell transplantation (alloHSCT) is a life-saving procedure used for the treatment of selected hematological malignancies, inborn errors of metabolism, and bone marrow failures. The role of neutrophils in alloHSCT has been traditionally evaluated only in the context of their ability to act as a first line of defense against infection. However, recent evidence has highlighted neutrophils as key effectors of innate and adaptive immune responses through a wide array of newly discovered functions. Accordingly, neutrophils are emerging as highly versatile cells that are able to acquire different, often opposite, functional capacities depending on the microenvironment and their differentiation status. Herein, we review the current knowledge on the multiple functions that neutrophils exhibit through the different stages of alloHSCT, from the hematopoietic stem cell (HSC) mobilization in the donor to the immunological reconstitution that occurs in the recipient following HSC infusion. We also discuss the influence exerted on neutrophils by the immunosuppressive drugs delivered in the course of alloHSCT as part of graft-versus-host disease (GVHD) prophylaxis. Finally, the potential involvement of neutrophils in alloHSCT-related complications, such as transplant-associated thrombotic microangiopathy (TA-TMA), acute and chronic GVHD, and cytomegalovirus (CMV) reactivation, is also discussed. Based on the data reviewed herein, the role played by neutrophils in alloHSCT is far greater than a simple antimicrobial role. However, much remains to be investigated in terms of the potential functions that neutrophils might exert during a highly complex procedure such as alloHSCT.
Protein identification by 3D OrbiSIMS to facilitate in situ imaging and depth profiling
Authors: Kotowska Anna M. , Trindade Gustavo F. , Mendes Paula M. , Williams Philip M. , Aylott Jonathan W. , Shard Alexander G. , Alexander Morgan R. , Scurr David J. 
Published: November 2020

AbstractLabel-free protein characterization at surfaces is commonly achieved using digestion and/or matrix application prior to mass spectrometry. We report the assignment of undigested proteins at surfaces in situ using secondary ion mass spectrometry (SIMS). Ballistic fragmentation of proteins induced by a gas cluster ion beam (GCIB) leads to peptide cleavage producing fragments for subsequent OrbitrapTM analysis. In this work we annotate 16 example proteins (up to 272 kDa) by de novo peptide sequencing and illustrate the advantages of this approach by characterizing a protein monolayer biochip and the depth distribution of proteins in human skin.
Pathologic and molecular responses to neoadjuvant trastuzumab and/or lapatinib from a phase II randomized trial in HER2-positive breast cancer (TRIO-US B07)
Authors: Hurvitz Sara A. , Caswell-Jin Jennifer L. , McNamara Katherine L. , Zoeller Jason J. , Bean Gregory R. , Dichmann Robert , Perez Alejandra , Patel Ravindranath , Zehngebot Lee , Allen Heather , Bosserman Linda , DiCarlo Brian , Kennedy April , Giuliano Armando , Calfa Carmen , Molthrop David , Mani Aruna , Chen Hsiao-Wang , Dering Judy , Adams Brad , Kotler Eran , Press Michael F. , Brugge Joan S. , Curtis Christina , Slamon Dennis J. 
Published: November 2020

AbstractIn this multicenter, open-label, randomized phase II investigator-sponsored neoadjuvant trial with funding provided by Sanofi and GlaxoSmithKline (TRIO-US B07, Clinical Trials NCT00769470), participants with early-stage HER2-positive breast cancer (N = 128) were recruited from 13 United States oncology centers throughout the Translational Research in Oncology network. Participants were randomized to receive trastuzumab (T; N = 34), lapatinib (L; N = 36), or both (TL; N = 58) as HER2-targeted therapy, with each participant given one cycle of this designated anti-HER2 therapy alone followed by six cycles of standard combination chemotherapy with the same anti-HER2 therapy. The primary objective was to estimate the rate of pathologic complete response (pCR) at the time of surgery in each of the three arms. In the intent-to-treat population, we observed similar pCR rates between T (47%, 95% confidence interval [CI] 30–65%) and TL (52%, 95% CI 38–65%), and a lower pCR rate with L (25%, 95% CI 13–43%). In the T arm, 100% of participants completed all protocol-specified treatment prior to surgery, as compared to 69% in the L arm and 74% in the TL arm. Tumor or tumor bed tissue was collected whenever possible pre-treatment (N = 110), after one cycle of HER2-targeted therapy alone (N = 89), and at time of surgery (N = 59). Higher-level amplification of HER2 and hormone receptor (HR)-negative status were associated with a higher pCR rate. Large shifts in the tumor, immune, and stromal gene expression occurred after one cycle of HER2-targeted therapy. In contrast to pCR rates, the L-containing arms exhibited greater proliferation reduction than T at this timepoint. Immune expression signatures increased in all arms after one cycle of HER2-targeted therapy, decreasing again by the time of surgery. Our results inform approaches to early assessment of sensitivity to anti-HER2 therapy and shed light on the role of the immune microenvironment in response to HER2-targeted agents.
Infection fatality rate of SARS-CoV2 in a super-spreading event in Germany
Authors: Streeck Hendrik , Schulte Bianca , Kümmerer Beate M. , Richter Enrico , Höller Tobias , Fuhrmann Christine , Bartok Eva , Dolscheid-Pommerich Ramona , Berger Moritz , Wessendorf Lukas , Eschbach-Bludau Monika , Kellings Angelika , Schwaiger Astrid , Coenen Martin , Hoffmann Per , Stoffel-Wagner Birgit , Nöthen Markus M. , Eis-Hübinger Anna M. , Exner Martin , Schmithausen Ricarda Maria , Schmid Matthias , Hartmann Gunther 
Published: November 2020

AbstractA SARS-CoV2 super-spreading event occurred during carnival in a small town in Germany. Due to the rapidly imposed lockdown and its relatively closed community, this town was seen as an ideal model to investigate the infection fatality rate (IFR). Here, a 7-day seroepidemiological observational study was performed to collect information and biomaterials from a random, household-based study population. The number of infections was determined by IgG analyses and PCR testing. We found that of the 919 individuals with evaluable infection status, 15.5% (95% CI:[12.3%; 19.0%]) were infected. This is a fivefold higher rate than the reported cases for this community (3.1%). 22.2% of all infected individuals were asymptomatic. The estimated IFR was 0.36% (95% CI:[0.29%; 0.45%]) for the community and 0.35% [0.28%; 0.45%] when age-standardized to the population of the community. Participation in carnival increased both infection rate (21.3% versus 9.5%, p < 0.001) and number of symptoms (estimated relative mean increase 1.6, p = 0.007). While the infection rate here is not representative for Germany, the IFR is useful to estimate the consequences of the pandemic in places with similar healthcare systems and population characteristics. Whether the super-spreading event not only increases the infection rate but also affects the IFR requires further investigation.
Neuronal processes and glial precursors form a scaffold for wiring the developing mouse cochlea
Authors: Druckenbrod N. R. , Hale E. B. , Olukoya O. O. , Shatzer W. E. , Goodrich L. V. 
Published: November 2020

AbstractIn the developing nervous system, axons navigate through complex terrains that change depending on when and where outgrowth begins. For instance, in the developing cochlea, spiral ganglion neurons extend their peripheral processes through a growing and heterogeneous environment en route to their final targets, the hair cells. Although the basic principles of axon guidance are well established, it remains unclear how axons adjust strategies over time and space. Here, we show that neurons with different positions in the spiral ganglion employ different guidance mechanisms, with evidence for both glia-guided growth and fasciculation along a neuronal scaffold. Processes from neurons in the rear of the ganglion are more directed and grow faster than those from neurons at the border of the ganglion. Further, processes at the wavefront grow more efficiently when in contact with glial precursors growing ahead of them. These findings suggest a tiered mechanism for reliable axon guidance.
Frequency-domain ultrafast passive logic: NOT and XNOR gates
Authors: Maram Reza , Howe James van , Kong Deming , Ros Francesco Da , Guan Pengyu , Galili Michael , Morandotti Roberto , Oxenløwe Leif Katsuo , Azaña José 
Published: November 2020

AbstractElectronic Boolean logic gates, the foundation of current computation and digital information processing, are reaching final limits in processing power. The primary obstacle is energy consumption which becomes impractically large, > 0.1 fJ/bit per gate, for signal speeds just over several GHz. Unfortunately, current solutions offer either high-speed operation or low-energy consumption. We propose a design for Boolean logic that can achieve both simultaneously (high speed and low consumption), here demonstrated for NOT and XNOR gates. Our method works by passively modifying the phase relationships among the different frequencies of an input data signal to redistribute its energy into the desired logical output pattern. We experimentally demonstrate a passive NOT gate with an energy dissipation of ~1 fJ/bit at 640 Gb/s and use it as a building block for an XNOR gate. This approach is applicable to any system that can propagate coherent waves, such as electromagnetic, acoustic, plasmonic, mechanical, or quantum.
A ribosome-associated chaperone enables substrate triage in a cotranslational protein targeting complex
Authors: Hsieh Hao-Hsuan , Lee Jae Ho , Chandrasekar Sowmya , Shan Shu-ou 
Published: November 2020

AbstractProtein biogenesis is essential in all cells and initiates when a nascent polypeptide emerges from the ribosome exit tunnel, where multiple ribosome-associated protein biogenesis factors (RPBs) direct nascent proteins to distinct fates. How distinct RPBs spatiotemporally coordinate with one another to affect accurate protein biogenesis is an emerging question. Here, we address this question by studying the role of a cotranslational chaperone, nascent polypeptide-associated complex (NAC), in regulating substrate selection by signal recognition particle (SRP), a universally conserved protein targeting machine. We show that mammalian SRP and SRP receptors (SR) are insufficient to generate the biologically required specificity for protein targeting to the endoplasmic reticulum. NAC co-binds with and remodels the conformational landscape of SRP on the ribosome to regulate its interaction kinetics with SR, thereby reducing the nonspecific targeting of signalless ribosomes and pre-emptive targeting of ribosomes with short nascent chains. Mathematical modeling demonstrates that the NAC-induced regulations of SRP activity are essential for the fidelity of cotranslational protein targeting. Our work establishes a molecular model for how NAC acts as a triage factor to prevent protein mislocalization, and demonstrates how the macromolecular crowding of RPBs at the ribosome exit site enhances the fidelity of substrate selection into individual protein biogenesis pathways.