bluuebunny/crossref_metadata_2025 huggingface dataset:
Borehole‐Based Characterization of Deep Mixed‐Mode Crevasses at a Greenlandic Outlet Glacier
Authors: Hubbard Bryn , Christoffersen Poul , Doyle Samuel H. , Chudley Thomas R. , Schoonman Charlotte M. , Law Robert , Bougamont Marion
Published: June 2021

Optical televiewer borehole logging within a crevassed region of fast‐moving Store Glacier, Greenland, revealed the presence of 35 high‐angle planes that cut across the background primary stratification. These planes were composed of a bubble‐free layer of refrozen ice, most of which hosted thin laminae of bubble‐rich “last frozen” ice, consistent with the planes being the traces of former open crevasses. Several such last‐frozen laminae were observed in four traces, suggesting multiple episodes of crevasse reactivation. The frequency of crevasse traces generally decreased with depth, with the deepest detectable trace being 265 m below the surface. This is consistent with the extent of the warmer‐than‐modeled englacial ice layer in the area, which extends from the surface to a depth of ∼400 m. Crevasse trace orientation was strongly clustered around a dip of 63° and a strike that was offset by 71° from orthogonal to the local direction of principal extending strain. The traces’ antecedent crevasses were therefore interpreted to have originated upglacier, probably ∼8 km distant involving mixed‐mode (I and III) formation. We conclude that deep crevassing is pervasive across Store Glacier, and therefore also at all dynamically similar outlet glaciers. Once healed, their traces represent planes of weakness subject to reactivation during subsequent advection through the glacier. Given their depth, it is highly likely that such traces—particularly those formed downglacier—survive surface ablation to reach the glacier terminus, where they may represent foci for fracture and iceberg calving.
A Positive Cloud‐to‐Ground Flash Caused by a Sequence of Bidirectional Leaders that Served to Form a Ground‐Reaching Branch of a Pre‐Existing Horizontal Channel
Authors: Wu Bin , Lyu Weitao , Qi Qi , Ma Ying , Chen Lyuwen , Jiang Ruijiao , Zhu Yanan , Rakov Vladimir A.
Published: June 2021

High‐speed video and electric field change data were used to analyze the initiation and propagation of four predominantly vertical bidirectional leaders making connection to a predominantly horizontal channel previously formed aloft. The four bidirectional leaders sequentially developed along the same path and served to form a positive branch of the horizontal in‐cloud channel, which became a downward positive leader producing a 135‐kA positive cloud‐to‐ground (+CG) return stroke. The positive (lower) end of each bidirectional leader elongated abruptly at the time of connection of the negative (upper) end to the pre‐existing channel aloft. Thirty‐six negative streamer‐like filaments (resembling recently reported “needles”) extended sideways over ∼110 to 740 m from the pre‐existing horizontal channel at speeds of ∼0.5 to 1.9 × 107 m/s, in response to the injection of negative charge associated with the +CG.
Impacts of Ionospheric Ions on Magnetic Reconnection and Earth's Magnetosphere Dynamics
Authors: Toledo‐Redondo S. , André M. , Aunai N. , Chappell C. R. , Dargent J. , Fuselier S. A. , Glocer A. , Graham D. B. , Haaland S. , Hesse M. , Kistler L. M. , Lavraud B. , Li W. , Moore T. E. , Tenfjord P. , Vines S. K.
Published: June 2021

Ionospheric ions (mainly H+, He+, and O+) escape from the ionosphere and populate the Earth's magnetosphere. Their thermal energies are usually low when they first escape the ionosphere, typically a few electron volt to tens of electron volt, but they are energized in their journey through the magnetosphere. The ionospheric population is variable, and it makes significant contributions to the magnetospheric mass density in key regions where magnetic reconnection is at work. Solar wind—magnetosphere coupling occurs primarily via magnetic reconnection, a key plasma process that enables transfer of mass and energy into the near‐Earth space environment. Reconnection leads to the triggering of magnetospheric storms, auroras, energetic particle precipitation and a host of other magnetospheric phenomena. Several works in the last decades have attempted to statistically quantify the amount of ionospheric plasma supplied to the magnetosphere, including the two key regions where magnetic reconnection occurs: the dayside magnetopause and the magnetotail. Recent in situ observations by the Magnetospheric Multiscale spacecraft and associated modeling have advanced our current understanding of how ionospheric ions alter the magnetic reconnection process, including its onset and efficiency. This article compiles the current understanding of the ionospheric plasma supply to the magnetosphere. It reviews both the quantification of these sources and their effects on the process of magnetic reconnection. It also provides a global description of how the ionospheric ion contribution modifies the way the solar wind couples to the Earth's magnetosphere and how these ions modify the global dynamics of the near‐Earth space environment.
Light and Shadow in Mapping Alpine Snowpack With Unmanned Aerial Vehicles in the Absence of Ground Control Points
Authors: Revuelto Jesús , López‐Moreno Juan Ignacio , Alonso‐González Esteban
Published: June 2021

Recent developments in unmanned aerial vehicles (UAV) and structure from motion (SfM) algorithms have shown reliable results for retrieving snow depth distribution. However, their ability to obtain accurate results usually relies on deploying and measuring the exact position of ground control points (GCP) for georeferencing the information. Commercial UAVs can now provide real time kinematic (RTK) positioning of the images with centimetric accuracy. Nonetheless, their operational applicability for observing snow distribution in highly heterogeneous mountain areas has not been evaluated. This study presents a complete assessment of the reliability of snow depth observations from a fixed‐wing UAV working in RTK mode with an RGB camera. During the 2018–2019 season, seven field campaigns (13 UAV flights) were undertaken covering 0.48 km2 in complex alpine terrain in the Pyrenees. The UAV observations obtained under different light conditions and flight block configurations (altitude and image overlaps) in the same day were evaluated with terrestrial laser scanner acquisitions. Two SfM processing options of the UAV images were also compared. When the study area received direct solar light, the results were comparable to previous studies that had used GCPs, with an average root mean squared error of 0.19 m and an average absolute snow volume discrepancy lower than 4%. However, when large areas were under shadow from the terrain, or solar light was affected by clouds, the estimated error tripled. The quality of the snow depth maps was little affected by the snow covered area and the flight mission configurations.
Innovative Study of Resistor Shunt‐Based Bridged‐T Topology With Bandpass Negative Group Delay Behavior
Authors: Xu Zhifei , Nebhen Jamel , Chan George , Rahajandraibe Wenceslas , Ravelo Blaise
Published: June 2021

In this paper, new bridged‐T network operating with bandpass (BP) negative group delay (NGD) function is introduced. The circuit design is innovatively based on an inductorless passive RC‐network. The innovative bridged‐T topology is implemented with a R‐shunt configuration. The analytical transfer function of voltages and equivalent impedance‐matrix are carefully calculated. The BP NGD analysis and design of the bridged‐T topology is developed. The BP NGD properties and specifications are analytically investigated. A proof of concept of R‐shunt bridged‐T prototype with a surface‐mounted device printed circuit board is designed, fabricated, and measured to verify the BP NGD behavior from theoretical equations and simulations. As expected, the theoretical, simulation, and measurements results are in very good agreement. From measurement results, the fabricated BP NGD C‐shunt bridged‐T reaches a delay of about −45 ns and a center frequency of about 0.5 MHz over a −3 dB attenuation.
Demonstration of epitaxial growth of strain-relaxed GaN films on graphene/SiC substrates for long wavelength light-emitting diodes
Authors: Yu Ye , Wang Tao , Chen Xiufang , Zhang Lidong , Wang Yang , Niu Yunfei , Yu Jiaqi , Ma Haotian , Li Xiaomeng , Liu Fang , Deng Gaoqiang , Shi Zhifeng , Zhang Baolin , Wang Xinqiang , Zhang Yuantao
Published: June 2021

Strain modulation is crucial for heteroepitaxy such as GaN on foreign substrates. Here, the epitaxy of strain-relaxed GaN films on graphene/SiC substrates by metal-organic chemical vapor deposition is demonstrated. Graphene was directly prepared on SiC substrates by thermal decomposition. Its pre-treatment with nitrogen-plasma can introduce C–N dangling bonds, which provides nucleation sites for subsequent epitaxial growth. The scanning transmission electron microscopy measurements confirm that part of graphene surface was etched by nitrogen-plasma. We study the growth behavior on different areas of graphene surface after pre-treatment, and propose a growth model to explain the epitaxial growth mechanism of GaN films on graphene. Significantly, graphene is found to be effective to reduce the biaxial stress in GaN films and the strain relaxation improves indium-atom incorporation in InGaN/GaN multiple quantum wells (MQWs) active region, which results in the obvious red-shift of light-emitting wavelength of InGaN/GaN MQWs. This work opens up a new way for the fabrication of GaN-based long wavelength light-emitting diodes.
Acute myeloid leukemia with IDH1 and IDH2 mutations: 2021 treatment algorithm
Authors: Issa Ghayas C. , DiNardo Courtney D.
Published: June 2021

Acute myeloid leukemia is a genetically heterogeneous hematologic malignancy; approximately 20% of AML harbors a mutation in the isocitrate dehydrogenase (IDH) genes, IDH1 or IDH2. These recurrent mutations in key metabolic enzymes lead to the production of the oncometabolite 2-hydroxyglutarate, which promotes leukemogenesis through a block in normal myeloid differentiation. Since this discovery, selective oral inhibitors of mutant IDH1 and IDH2 have subsequently been developed and are now approved as single agent therapy, based on clinical efficacy observed within the original first-in-human trials. The investigation of IDH inhibitors in combination with standard therapies such as azacytidine, with intensive chemotherapy, and with other small molecule targeted therapies in rational combinations are currently under evaluation to further improve upon clinical efficacy.
Minimal residual disease assessment by multiparameter flow cytometry in transplant-eligible myeloma in the EMN02/HOVON 95 MM trial
Authors: Oliva Stefania , Bruinink Davine Hofste op , Rihova Lucie , D’Agostino Mattia , Pantani Lucia , Capra Andrea , van der Holt Bronno , Troia Rossella , Petrucci Maria Teresa , Villanova Tania , Vsianska Pavla , Jugooa Romana , Brandt-Hagens Claudia , Gilestro Milena , Offidani Massimo , Ribolla Rossella , Galli Monica , Hajek Roman , Gay Francesca , Cavo Michele , Omedé Paola , van der Velden Vincent H. J. , Boccadoro Mario , Sonneveld Pieter
Published: June 2021

Minimal residual disease (MRD) by multiparameter flow cytometry (MFC) is the most effective tool to define a deep response in multiple myeloma (MM). We conducted an MRD correlative study of the EMN02/HO95 MM phase III trial in newly diagnosed MM patients achieving a suspected complete response before maintenance and every 6 months during maintenance. Patients received high-dose melphalan (HDM) versus bortezomib-melphalan-prednisone (VMP) intensification, followed by bortezomib-lenalidomide-dexamethasone (VRd) versus no consolidation, and lenalidomide maintenance. Bone marrow (BM) samples were processed in three European laboratories, applying EuroFlow-based MFC protocols (eight colors, two tubes) with 10−4−10−5 sensitivity. At enrollment in the MRD correlative study, 76% (244/321) of patients were MRD-negative. In the intention-to-treat analysis, after a median follow-up of 75 months, 5-year progression-free survival was 66% in MRD-negative versus 31% in MRD-positive patients (HR 0.39; p < 0.001), 5-year overall survival was 86% versus 69%, respectively (HR 0.41; p < 0.001). MRD negativity was associated with reduced risk of progression or death in all subgroups, including ISS-III (HR 0.37) and high-risk fluorescence in situ hybridization (FISH) patients (HR 0.38;). In the 1-year maintenance MRD population, 42% of MRD-positive patients at pre-maintenance became MRD-negative after lenalidomide exposure. In conclusion, MRD by MFC is a strong prognostic factor. Lenalidomide maintenance further improved MRD-negativity rate.
Nuclear compartmentalization of TERT mRNA and TUG1 lncRNA is driven by intron retention
Authors: Dumbović Gabrijela , Braunschweig Ulrich , Langner Heera K. , Smallegan Michael , Biayna Josep , Hass Evan P. , Jastrzebska Katarzyna , Blencowe Benjamin , Cech Thomas R. , Caruthers Marvin H. , Rinn John L.
Published: June 2021

The spatial partitioning of the transcriptome in the cell is an important form of gene-expression regulation. Here, we address how intron retention influences the spatio-temporal dynamics of transcripts from two clinically relevant genes: TERT (Telomerase Reverse Transcriptase) pre-mRNA and TUG1 (Taurine-Upregulated Gene 1) lncRNA. Single molecule RNA FISH reveals that nuclear TERT transcripts uniformly and robustly retain specific introns. Our data suggest that the splicing of TERT retained introns occurs during mitosis. In contrast, TUG1 has a bimodal distribution of fully spliced cytoplasmic and intron-retained nuclear transcripts. We further test the functionality of intron-retention events using RNA-targeting thiomorpholino antisense oligonucleotides to block intron excision. We show that intron retention is the driving force for the nuclear compartmentalization of these RNAs. For both RNAs, altering this splicing-driven subcellular distribution has significant effects on cell viability. Together, these findings show that stable retention of specific introns can orchestrate spatial compartmentalization of these RNAs within the cell. This process reveals that modulating RNA localization via targeted intron retention can be utilized for RNA-based therapies.
Photocatalyzed cycloaromatization of vinylsilanes with arylsulfonylazides
Authors: Chen Fengjuan , Shao Youxiang , Li Mengke , Yang Can , Su Shi-Jian , Jiang Huanfeng , Ke Zhuofeng , Zeng Wei
Published: June 2021

Sila-molecules have recently attracted attention due to their promising applications in medical and industrial fields. Compared with all-carbon parent compounds, the different covalent radius and electronegativity of silicon from carbon generally endow the corresponding sila-analogs with unique biological activity and physicochemical properties. Vinylsilanes feature both silyl-hyperconjugation effect and versatile reactivities, developing vinylsilane-based Smiles rearrangement will therefore provide an efficient platform to assemble complex silacycles. Here we report a practical Ir(III)-catalyzed cycloaromatization ofortho-alkynylaryl vinylsilanes with arylsulfonyl azides for delivering naphthyl-fused benzosiloles under visible-light photoredox conditions. The combination of experiments and density functional theory (DFT) energy profiles reveals the reaction mechanism involving α-silyl radical Smiles rearrangement.
Perilipin 5 links mitochondrial uncoupled respiration in brown fat to healthy white fat remodeling and systemic glucose tolerance
Authors: Gallardo-Montejano Violeta I. , Yang Chaofeng , Hahner Lisa , McAfee John L. , Johnson Joshua A. , Holland William L. , Fernandez-Valdivia Rodrigo , Bickel Perry E.
Published: June 2021

Exposure of mice or humans to cold promotes significant changes in brown adipose tissue (BAT) with respect to histology, lipid content, gene expression, and mitochondrial mass and function. Herein we report that the lipid droplet coat protein Perilipin 5 (PLIN5) increases markedly in BAT during exposure of mice to cold. To understand the functional significance of cold-induced PLIN5, we created and characterized gain- and loss-of-function mouse models. Enforcing PLIN5 expression in mouse BAT mimics the effects of cold with respect to mitochondrial cristae packing and uncoupled substrate-driven respiration. PLIN5 is necessary for the maintenance of mitochondrial cristae structure and respiratory function during cold stress. We further show that promoting PLIN5 function in BAT is associated with healthy remodeling of subcutaneous white adipose tissue and improvements in systemic glucose tolerance and diet-induced hepatic steatosis. These observations will inform future strategies that seek to exploit thermogenic adipose tissue as a therapeutic target for type 2 diabetes, obesity, and nonalcoholic fatty liver disease.
Saving superconducting quantum processors from decay and correlated errors generated by gamma and cosmic rays
Authors: Martinis John M.
Published: June 2021

Error-corrected quantum computers can only work if errors are small and uncorrelated. Here, I show how cosmic rays or stray background radiation affects superconducting qubits by modeling the phonon to electron/quasiparticle down-conversion physics. For present designs, the model predicts about 57% of the radiation energy breaks Cooper pairs into quasiparticles, which then vigorously suppress the qubit energy relaxation time (T1 ~ 600 ns) over a large area (cm) and for a long time (ms). Such large and correlated decay kills error correction. Using this quantitative model, I show how this energy can be channeled away from the qubit so that this error mechanism can be reduced by many orders of magnitude. I also comment on how this affects other solid-state qubits.
Characteristics of mathematical modeling languages that facilitate model reuse in systems biology: a software engineering perspective
Authors: Schölzel Christopher , Blesius Valeria , Ernst Gernot , Dominik Andreas
Published: June 2021

Reuse of mathematical models becomes increasingly important in systems biology as research moves toward large, multi-scale models composed of heterogeneous subcomponents. Currently, many models are not easily reusable due to inflexible or confusing code, inappropriate languages, or insufficient documentation. Best practice suggestions rarely cover such low-level design aspects. This gap could be filled by software engineering, which addresses those same issues for software reuse. We show that languages can facilitate reusability by being modular, human-readable, hybrid (i.e., supporting multiple formalisms), open, declarative, and by supporting the graphical representation of models. Modelers should not only use such a language, but be aware of the features that make it desirable and know how to apply them effectively. For this reason, we compare existing suitable languages in detail and demonstrate their benefits for a modular model of the human cardiac conduction system written in Modelica.
High FIB4 index is an independent risk factor of diabetic kidney disease in type 2 diabetes
Authors: Saito Haruka , Tanabe Hayato , Kudo Akihiro , Machii Noritaka , Higa Moritake , Yamaguchi Satoshi , Maimaituxun Gulinu , Abe Kazumichi , Takahashi Atsushi , Tanaka Kenichi , Asahi Koichi , Masuzaki Hiroaki , Ohira Hiromasa , Kazama Junichiro J. , Shimabukuro Michio
Published: June 2021

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) may be linked to development of chronic kidney diseases (CKD). The FIB4 index, a noninvasive liver fibrosis score, has been reported to predict CKD in non-diabetic patients, but there are no reports yet in diabetic cases. Therefore, we evaluated the prognostic impact of FIB4 index on the risk of developing diabetic kidney disease (DKD) in Japanese patients with type 2 diabetes in a retrospective cohort study. We assessed patients with type 2 diabetes with an eGFR ≥ 60 mL/min/1.73 m2 and without dipstick positive proteinuria (≥ 1 +) at their first visit to our department. Participants were divided into two groups based on the FIB4 index at their first visit: FIB4 index > 1.3 and FIB4 index ≤ 1.3. The primary endpoint was defined as a decrease in eGFR < 60 mL/min/1.73 m2 or the onset of proteinuria during the course of treatment. The average age of all 584 type 2 diabetic participants (360 [61.6%] men) was 55 ± 11 years. There were 187 patients in the FIB4 index group > 1.3 (32.0%) and the median observation period was 6.0 (3.8–11.0) years. Kaplan–Meier survival analysis indicated that the risks of developing DKD, eGFR < 60 and proteinuria were all higher in FIB4 index > 1.3 patients than in FIB4 ≤ 1.3 patients. In the Cox regression analysis, an FIB4 index > 1.3 was a significant predictor for onset of DKD (HR 1.54, 95% CI 1.15–2.08) and proteinuria (HR 1.55, 95% CI 1.08–2.23), but not for an eGFR < 60 (HR 1.14, 95% CI 0.79–1.99). To the best of our knowledge, this is the first study to demonstrate that an FIB4 index > 1.3 has a prognostic impact on the development of CKD and proteinuria in type 2 diabetic patients. This warrants further investigation of the prognostic impact of the development of DKD or proteinuria.
Responses to chemical cross-talk between the Mycobacterium ulcerans toxin, mycolactone, and Staphylococcus aureus
Authors: Dhungel Laxmi , Burcham Lindsey , Park Joo Youn , Sampathkumar Harshini Devi , Cudjoe Albert , Seo Keun Seok , Jordan Heather
Published: June 2021

Buruli ulcer is a neglected tropical disease caused by the environmental pathogen, Mycobacterium ulcerans whose major virulence factor is mycolactone, a lipid cytotoxic molecule. Buruli ulcer has high morbidity, particularly in rural West Africa where the disease is endemic. Data have shown that infected lesions of Buruli ulcer patients can be colonized by quorum sensing bacteria such as Staphylococcus aureus, S. epidermidis, and Pseudomonas aeruginosa, but without typical pathology associated with those pathogens’ colonization. M. ulcerans pathogenesis may not only be an individual act but may also be dependent on synergistic or antagonistic mechanisms within a polymicrobial network. Furthermore, co-colonization by these pathogens may promote delayed wound healing, especially after the initiation of antibiotic therapy. Hence, it is important to understand the interaction of M. ulcerans with other bacteria encountered during skin infection. We added mycolactone to S. aureus and incubated for 3, 6 and 24 h. At each timepoint, S. aureus growth and hemolytic activity was measured, and RNA was isolated to measure virulence gene expression through qPCR and RNASeq analyses. Results showed that mycolactone reduced S. aureus hemolytic activity, suppressed hla promoter activity, and attenuated virulence genes, but did not affect S. aureus growth. RNASeq data showed mycolactone greatly impacted S. aureus metabolism. These data are relevant and significant as mycolactone and S. aureus sensing and response at the transcriptional, translational and regulation levels will provide insight into biological mechanisms of interspecific interactions that may play a role in regulation of responses such as effects between M. ulcerans, mycolactone, and S. aureus virulence that will be useful for treatment and prevention.
An electrochemical sensor for nanomolar detection of caffeine based on nicotinic acid hydrazide anchored on graphene oxide (NAHGO)
Authors: Jose Jemini , Subramanian Viswanathan , Shaji Sadasivan , Sreeja P. B.
Published: June 2021

A simple modified sensor was developed with nicotinic acid hydrazide anchored on graphene oxide (NAHGO), by ultrasonic-assisted chemical route, using hydroxy benzotriazole as a mediator. Structural and morphologies of NAHGO samples were investigated in detail by Fourier-Transform Infrared spectroscopy (FT-IR), Powder X-ray diffraction (P-XRD), Raman spectroscopy, Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and Thermogravimetric analysis (TGA). The detailed morphological examination and electrochemical studies revealed the delaminated sheet with the tube-like structure of NAHGO provided the route for more electroactive surface which influenced the electrooxidation of caffeine with increased current. The electrochemical behaviour of NAHGO on a glassy carbon electrode (GCE) for caffeine detection was demonstrated by employing voltammetric techniques. The influence of scan rate, pH, and concentration on caffeine's peak current was also studied. The NAHGO sensor was employed for the determination of caffeine in imol plus and energy drinks. The detection limit determined was 8.7 × 10–9 M, and the best value was reported so far. The results show that NAHGO modified electrodes are one of the best preferences to establish new, efficient, and reliable analytical tools for the detection of caffeine.
Multi-photon above threshold ionization of multi-electron atoms and molecules using the R-matrix approach
Authors: Benda Jakub , Mašín Zdeněk
Published: June 2021

We formulate a computationally efficient time-independent method based on the multi-electron molecular R-matrix formalism. This method is used to calculate transition matrix elements for the multi-photon ionization of atoms and molecules under the influence of a perturbative field. The method relies on the partitioning of space which allows us to calculate the infinite-range free-free dipole integrals analytically in the outer region, beyond the range of the initial bound wave function. This approach is valid for an arbitrary order, that is, any number of photons absorbed both in the bound and the continuum part of the spectrum (below- and above-threshold ionization). We calculate generalized multi-photon cross sections and angular distributions of different systems (H, He, $$\hbox {H}_{{2}}$$

H
2

, $$\hbox {CO}_{{2}}$$

CO
2

) and validate our approach by comparison with data from the literature.
Robust diagnostic classification via Q-learning
Authors: Ardulov Victor , Martinez Victor R. , Somandepalli Krishna , Zheng Shuting , Salzman Emma , Lord Catherine , Bishop Somer , Narayanan Shrikanth
Published: June 2021

Machine learning (ML) models have demonstrated the power of utilizing clinical instruments to provide tools for domain experts in gaining additional insights toward complex clinical diagnoses. In this context these tools desire two additional properties: interpretability, being able to audit and understand the decision function, and robustness, being able to assign the correct label in spite of missing or noisy inputs. This work formulates diagnostic classification as a decision-making process and utilizes Q-learning to build classifiers that meet the aforementioned desired criteria. As an exemplary task, we simulate the process of differentiating Autism Spectrum Disorder from Attention Deficit-Hyperactivity Disorder in verbal school aged children. This application highlights how reinforcement learning frameworks can be utilized to train more robust classifiers by jointly learning to maximize diagnostic accuracy while minimizing the amount of information required.
Endothelial-derived cardiovascular disease-related microRNAs elevated with prolonged sitting pattern among postmenopausal women
Authors: Chang Ya-Ju , Tuz-Zahra Fatima , Godbole Suneeta , Avitia Yesenia , Bellettiere John , Rock Cheryl L. , Jankowska Marta M. , Allison Matthew A. , Dunstan David W. , Rana Brinda , Natarajan Loki , Sears Dorothy D.
Published: June 2021

Time spent sitting is positively correlated with endothelial dysfunction and cardiovascular disease risk. The underlying molecular mechanisms are unknown. MicroRNAs contained in extracellular vesicles (EVs) reflect cell/tissue status and mediate intercellular communication. We explored the association between sitting patterns and microRNAs isolated from endothelial cell (EC)-derived EVs. Using extant actigraphy based sitting behavior data on a cohort of 518 postmenopausal overweight/obese women, we grouped the woman as Interrupted Sitters (IS; N = 18) or Super Sitters (SS; N = 53) if they were in the shortest or longest sitting pattern quartile, respectively. The cargo microRNA in EC-EVs from the IS and SS women were compared. MicroRNA data were weighted by age, physical functioning, MVPA, device wear days, device wear time, waist circumference, and body mass index. Screening of CVD-related microRNAs demonstrated that miR-199a-5p, let-7d-5p, miR-140-5p, miR-142-3p, miR-133b level were significantly elevated in SS compared to IS groups. Group differences in let-7d-5p, miR-133b, and miR-142-3p were validated in expanded groups. Pathway enrichment analyses show that mucin-type O-glycan biosynthesis and cardiomyocyte adrenergic signaling (P < 0.001) are downstream of the three validated microRNAs. This proof-of-concept study supports the possibility that CVD-related microRNAs in EC-EVs may be molecular transducers of sitting pattern-associated CVD risk in overweight postmenopausal women.
Nitrogen fixation and denitrification activity differ between coral- and algae-dominated Red Sea reefs
Authors: El-Khaled Yusuf C. , Roth Florian , Rädecker Nils , Tilstra Arjen , Karcher Denis B. , Kürten Benjamin , Jones Burton H. , Voolstra Christian R. , Wild Christian
Published: June 2021

Coral reefs experience phase shifts from coral- to algae-dominated benthic communities, which could affect the interplay between processes introducing and removing bioavailable nitrogen. However, the magnitude of such processes, i.e., dinitrogen (N2) fixation and denitrification levels, and their responses to phase shifts remain unknown in coral reefs. We assessed both processes for the dominant species of six benthic categories (hard corals, soft corals, turf algae, coral rubble, biogenic rock, and reef sands) accounting for > 98% of the benthic cover of a central Red Sea coral reef. Rates were extrapolated to the relative benthic cover of the studied organisms in co-occurring coral- and algae-dominated areas of the same reef. In general, benthic categories with high N2fixation exhibited low denitrification activity. Extrapolated to the respective reef area, turf algae and coral rubble accounted for > 90% of overall N2fixation, whereas corals contributed to more than half of reef denitrification. Total N2fixation was twice as high in algae- compared to coral-dominated areas, whereas denitrification levels were similar. We conclude that algae-dominated reefs promote new nitrogen input through enhanced N2fixation and comparatively low denitrification. The subsequent increased nitrogen availability could support net productivity, resulting in a positive feedback loop that increases the competitive advantage of algae over corals in reefs that experienced a phase shift.
Temporal coherency of mechanical stimuli modulates tactile form perception
Authors: Nakatani Masashi , Kobayashi Yasuaki , Ohno Kota , Uesaka Masaaki , Mogami Sayako , Zhao Zixia , Sushida Takamichi , Kitahata Hiroyuki , Nagayama Masaharu
Published: June 2021

The human hand can detect both form and texture information of a contact surface. The detection of skin displacement (sustained stimulus) and changes in skin displacement (transient stimulus) are thought to be mediated in different tactile channels; however, tactile form perception may use both types of information. Here, we studied whether both the temporal frequency and the temporal coherency information of tactile stimuli encoded in sensory neurons could be used to recognize the form of contact surfaces. We used the fishbone tactile illusion (FTI), a known tactile phenomenon, as a probe for tactile form perception in humans. This illusion typically occurs with a surface geometry that has a smooth bar and coarse textures in its adjacent areas. When stroking the central bar back and forth with a fingertip, a human observer perceives a hollow surface geometry even though the bar is physically flat. We used a passive high-density pin matrix to extract only the vertical information of the contact surface, suppressing tangential displacement from surface rubbing. Participants in the psychological experiment reported indented surface geometry by tracing over the FTI textures with pin matrices of the different spatial densities (1.0 and 2.0 mm pin intervals). Human participants reported that the relative magnitude of perceived surface indentation steeply decreased when pins in the adjacent areas vibrated in synchrony. To address possible mechanisms for tactile form perception in the FTI, we developed a computational model of sensory neurons to estimate temporal patterns of action potentials from tactile receptive fields. Our computational data suggest that (1) the temporal asynchrony of sensory neuron responses is correlated with the relative magnitude of perceived surface indentation and (2) the spatiotemporal change of displacements in tactile stimuli are correlated with the asynchrony of simulated sensory neuron responses for the fishbone surface patterns. Based on these results, we propose that both the frequency and the asynchrony of temporal activity in sensory neurons could produce tactile form perception.
Ensemble machine learning of factors influencing COVID-19 across US counties
Authors: McCoy David , Mgbara Whitney , Horvitz Nir , Getz Wayne M. , Hubbard Alan
Published: June 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the causal agent for COVID-19, is a communicable disease spread through close contact. It is known to disproportionately impact certain communities due to both biological susceptibility and inequitable exposure. In this study, we investigate the most important health, social, and environmental factors impacting the early phases (before July, 2020) of per capita COVID-19 transmission and per capita all-cause mortality in US counties. We aggregate county-level physical and mental health, environmental pollution, access to health care, demographic characteristics, vulnerable population scores, and other epidemiological data to create a large feature set to analyze per capita COVID-19 outcomes. Because of the high-dimensionality, multicollinearity, and unknown interactions of the data, we use ensemble machine learning and marginal prediction methods to identify the most salient factors associated with several COVID-19 outbreak measure. Our variable importance results show that measures of ethnicity, public transportation and preventable diseases are the strongest predictors for both per capita COVID-19 incidence and mortality. Specifically, the CDC measures for minority populations, CDC measures for limited English, and proportion of Black- and/or African-American individuals in a county were the most important features for per capita COVID-19 cases within a month after the pandemic started in a county and also at the latest date examined. For per capita all-cause mortality at day 100 and total to date, we find that public transportation use and proportion of Black- and/or African-American individuals in a county are the strongest predictors. The methods predict that, keeping all other factors fixed, a 10% increase in public transportation use, all other factors remaining fixed at the observed values, is associated with increases mortality at day 100 of 2012 individuals (95% CI [1972, 2356]) and likewise a 10% increase in the proportion of Black- and/or African-American individuals in a county is associated with increases total deaths at end of study of 2067 (95% CI [1189, 2654]). Using data until the end of study, the same metric suggests ethnicity has double the association as the next most important factors, which are location, disease prevalence, and transit factors. Our findings shed light on societal patterns that have been reported and experienced in the U.S. by using robust methods to understand the features most responsible for transmission and sectors of society most vulnerable to infection and mortality. In particular, our results provide evidence of the disproportionate impact of the COVID-19 pandemic on minority populations. Our results suggest that mitigation measures, including how vaccines are distributed, could have the greatest impact if they are given with priority to the highest risk communities.
Micro-mechanical insights into the dynamics of crack propagation in snow fracture experiments
Authors: Bobillier Grégoire , Bergfeld Bastian , Dual Jürg , Gaume Johan , van Herwijnen Alec , Schweizer Jürg
Published: June 2021

Dry-snow slab avalanches result from crack propagation in a highly porous weak layer buried within a stratified and metastable snowpack. While our understanding of slab avalanche mechanisms improved with recent experimental and numerical advances, fundamental micro-mechanical processes remain poorly understood due to a lack of non-invasive monitoring techniques. Using a novel discrete micro-mechanical model, we reproduced crack propagation dynamics observed in field experiments, which employ the propagation saw test. The detailed microscopic analysis of weak layer stresses and bond breaking allowed us to define the crack tip location of closing crack faces, analyze its spatio-temporal characteristics and monitor the evolution of stress concentrations and the fracture process zone both in transient and steady-state regimes. Results highlight the occurrence of a steady state in crack speed and stress conditions for sufficiently long crack propagation distances (> 4 m). Crack propagation without external driving force except gravity is possible due to the local mixed-mode shear-compression stress nature at the crack tip induced by slab bending and weak layer volumetric collapse. Our result shed light into the microscopic origin of dynamic crack propagation in snow slab avalanche release that eventually will improve the evaluation of avalanche release sizes and thus hazard management and forecasting in mountainous regions.
Composition and function of the C1b/C1f region in the ciliary central apparatus
Authors: Joachimiak Ewa , Osinka Anna , Farahat Hanan , Świderska Bianka , Sitkiewicz Ewa , Poprzeczko Martyna , Fabczak Hanna , Wloga Dorota
Published: June 2021

Motile cilia are ultrastructurally complex cell organelles with the ability to actively move. The highly conserved central apparatus of motile 9 × 2 + 2 cilia is composed of two microtubules and several large microtubule-bound projections, including the C1b/C1f supercomplex. The composition and function of C1b/C1f subunits has only recently started to emerge. We show that in the model ciliate Tetrahymena thermophila, C1b/C1f contains several evolutionarily conserved proteins: Spef2A, Cfap69, Cfap246/LRGUK, Adgb/androglobin, and a ciliate-specific protein Tt170/TTHERM_00205170. Deletion of genes encoding either Spef2A or Cfap69 led to a loss of the entire C1b projection and resulted in an abnormal vortex motion of cilia. Loss of either Cfap246 or Adgb caused only minor alterations in ciliary motility. Comparative analyses of wild-type and C1b-deficient mutant ciliomes revealed that the levels of subunits forming the adjacent C2b projection but not C1d projection are greatly reduced, indicating that C1b stabilizes C2b. Moreover, the levels of several IFT and BBS proteins, HSP70, and enzymes that catalyze the final steps of the glycolytic pathway: enolase ENO1 and pyruvate kinase PYK1, are also reduced in the C1b-less mutants.
Anticancer drug discovery from Iranian Chrysanthemum cultivars through system pharmacology exploration and experimental validation
Authors: Hodaei Mahboobeh , Rahimmalek Mehdi , Behbahani Mandana
Published: June 2021

Breast cancer is the most common carcinoma in women, and natural products would be effective preventing some side effects of cancer treatment. In the present study, cytotoxic activities of different Iranian Chrysanthemum morifolium cultivars were evaluated in human breast cancer cell lines (MCF-7) and human lymphocytes. A systems pharmacology approach was employed between major compounds of these cultivars (chlorogenic acid, luteolin, quercetin, rutin, ferulic acid, and apigenin) and known breast cancer drugs (tucatinib, methotrexate, tamoxifen, and mitomycin) with 22 breast cancer-related targets to analyze the mechanism through which Chrysanthemum cultivars act on breast cancer. Target validation was performed by the molecular docking method. The results indicated that Chrysanthemum extracts inhibited the proliferation of MCF7 cells in a dose- and cultivar-dependent manner. In all studied cultivars, the most effective extract concentration with the lowest viability of MCF-7 cells, was as much as 312 µg ml−1. Also, higher concentrations of the extracts (> 1000 µg ml−1) reduced the lymphocyte cell viability, demonstrating that these doses were toxic. The gene ontology analysis revealed the therapeutic effects of Chrysanthemum’s active compounds on breast cancer by regulating the biological processes of their protein targets. Moreover, it has been documented that rutin, owing to its anticancer effects and several other health benefits, is a promising multi-targeted herbal ingredient. Finally, the present study compared different Iranian Chrysanthemum cultivars to provide new insights into useful pharmaceutical applications.
The intimate relationship between structural relaxation and the energy landscape of monatomic liquid metals
Authors: Demmel Franz , Hennet Louis , Jakse Noel
Published: June 2021

The characteristic property of a liquid, discriminating it from a solid, is its fluidity, which can be expressed by a velocity field. The reaction of the velocity field on forces is enshrined in the transport parameter viscosity. In contrast, a solid reacts to forces elastically through a displacement field, the particles are trapped in their potential minimum. The flow in a liquid needs enough thermal energy to overcome the changing potential barriers, which is supported through a continuous rearrangement of surrounding particles. Cooling a liquid will decrease the fluidity of a particle and the mobility of the neighbouring particles, resulting in an increase of the viscosity until the system comes to an arrest. This process with a concomitant slowing down of collective particle rearrangements might already start deep inside the liquid state. The idea of the potential energy landscape provides an attractive picture for these dramatic changes. However, despite the appealing idea there is a scarcity of quantitative assessments, in particular, when it comes to experimental studies. Here we present results on a monatomic liquid metal through a combination of ab initio molecular dynamics, neutron spectroscopy and inelastic x-ray scattering. We investigated the collective dynamics of liquid aluminium to reveal the changes in dynamics when the high temperature liquid is cooled towards solidification. The results demonstrate the main signatures of the energy landscape picture, a reduction in the internal atomic structural energy, a transition to a stretched relaxation process and a deviation from the high-temperature Arrhenius behavior of the relaxation time. All changes occur in the same temperature range at about $$1.4 \cdot T_{melting}$$

1.4
·

T

melting

, which can be regarded as the temperature when the liquid aluminium enters the landscape influenced phase and enters a more viscous liquid state towards solidification. The similarity in dynamics with other monatomic liquid metals suggests a universal dynamic crossover above the melting point.
An alternative domain-swapped structure of the Pyrococcus horikoshii PolII mini-intein
Authors: Williams Jennie E. , Jaramillo Mario V. , Li Zhong , Zhao Jing , Wang Chunyu , Li Hongmin , Mills Kenneth V.
Published: June 2021

Protein splicing is a post-translational process by which an intein catalyzes its own excision from flanking polypeptides, or exteins, concomitant with extein ligation. Many inteins have nested homing endonuclease domains that facilitate their propagation into intein-less alleles, whereas other inteins lack the homing endonuclease (HEN) and are called mini-inteins. The mini-intein that interrupts the DNA PolII of Pyrococcus horikoshii has a linker region in place of the HEN domain that is shorter than the linker in a closely related intein from Pyrococcus abyssi. The P. horikoshii PolII intein requires a higher temperature for catalytic activity and is more stable to digestion by the thermostable protease thermolysin, suggesting that it is more rigid than the P. abyssi intein. We solved a crystal structure of the intein precursor that revealed a domain-swapped dimer. Inteins found as domain swapped dimers have been shown to promote intein-mediated protein alternative splicing, but the solved P. horikoshii PolII intein structure has an active site unlikely to be catalytically competent.
Comprehensive profiling of novel epithelial–mesenchymal transition mediators and their clinical significance in colorectal cancer
Authors: Ishikawa Satoshi , Nishida Naohiro , Fujino Shiki , Ogino Takayuki , Takahashi Hidekazu , Miyoshi Norikatsu , Uemura Mamoru , Satoh Taroh , Yamamoto Hirofumi , Mizushima Tsunekazu , Doki Yuichiro , Eguchi Hidetoshi
Published: June 2021

Epithelial–mesenchymal transition (EMT) is a drastic phenotypic change during cancer metastasis and is one of the most important hallmarks of aggressive cancer. Although the overexpression of some specific transcription factors explains the functional alteration of EMT-induced cells, a complete picture of this biological process is yet to be elucidated. To comprehensively profile EMT-related genes in colorectal cancer, we quantified the EMT induction ability of each gene according to its similarity to the cancer stromal gene signature and termed it “mesenchymal score.” This bioinformatic approach successfully identified 90 candidate EMT mediators, which are strongly predictive of survival in clinical samples. Among these candidates, we discovered that the neuronal gene ARC, possibly originating from the retrotransposon, unexpectedly plays a crucial role in EMT induction. Profiling of novel EMT mediators we demonstrated here may help understand the complexity of the EMT program and open up new avenues for therapeutic intervention in colorectal cancer.
Estimating the heavy metal concentrations in topsoil in the Daxigou mining area, China, using multispectral satellite imagery
Authors: Yang Yun , Cui Qinfang , Jia Peng , Liu Jinbao , Bai Han
Published: June 2021

A precise estimation of the heavy metal concentrations in soils using multispectral remote sensing technology is challenging. Herein, Landsat8 imagery, a digital elevation model, and geochemical data derived from soil samples are integrated to improve the accuracy of estimating the Cu, Pb, and As concentrations in topsoil, using the Daxigou mining area in Shaanxi Province, China, as a case study. The relationships between the three heavy metals and soil environmental factors were investigated. The optimal combination of factors associated with the elevated concentrations of each heavy metal was determined combining correlation analysis with collinearity tests. A back propagation network optimised using a genetic algorithm was trained with 80% of the data for samples and subsequently employed to estimate the heavy metal concentrations in the area. The validation results show that the RMSE of the proposed model is lower than those of the existing linear model and rule-based M5 model tree. From the spatial distribution map of the three metals concentrations using the proposed method, there are findings that high concentrations of the heavy metals studied occur in the mining area, across the slag storage area, on the sides of the road used for transporting ore materials, and along the base of slopes in the area. These findings are consistent with the survey results in the field. The validation and findings validate the effectiveness of the proposed method.