bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting fault slip via transfer learning
Authors: Wang Kun , Johnson Christopher W. , Bennett Kane C. , Johnson Paul A. 
Published: December 2021

AbstractData-driven machine-learning for predicting instantaneous and future fault-slip in laboratory experiments has recently progressed markedly, primarily due to large training data sets. In Earth however, earthquake interevent times range from 10’s-100’s of years and geophysical data typically exist for only a portion of an earthquake cycle. Sparse data presents a serious challenge to training machine learning models for predicting fault slip in Earth. Here we describe a transfer learning approach using numerical simulations to train a convolutional encoder-decoder that predicts fault-slip behavior in laboratory experiments. The model learns a mapping between acoustic emission and fault friction histories from numerical simulations, and generalizes to produce accurate predictions of laboratory fault friction. Notably, the predictions improve by further training the model latent space using only a portion of data from a single laboratory earthquake-cycle. The transfer learning results elucidate the potential of using models trained on numerical simulations and fine-tuned with small geophysical data sets for potential applications to faults in Earth.
Bedform segregation and locking increase storage of natural and synthetic particles in rivers
Authors: Dallmann J. , Phillips C. B. , Teitelbaum Y. , Saavedra Cifuentes Edwin Y. , Sund N. , Schumer R. , Arnon S. , Packman A. I. 
Published: December 2021

AbstractWhile the ecological significance of hyporheic exchange and fine particle transport in rivers is well established, these processes are generally considered irrelevant to riverbed morphodynamics. We show that coupling between hyporheic exchange, suspended sediment deposition, and sand bedform motion strongly modulates morphodynamics and sorts bed sediments. Hyporheic exchange focuses fine-particle deposition within and below mobile bedforms, which suppresses bed mobility. However, deposited fines are also remobilized by bedform motion, providing a mechanism for segregating coarse and fine particles in the bed. Surprisingly, two distinct end states emerge from the competing interplay of bed stabilization and remobilization: a locked state in which fine particle deposition completely stabilizes the bed, and a dynamic equilibrium in which frequent remobilization sorts the bed and restores mobility. These findings demonstrate the significance of hyporheic exchange to riverbed morphodynamics and clarify how dynamic interactions between coarse and fine particles produce sedimentary patterns commonly found in rivers.
Single dose of chimeric dengue-2/Zika vaccine candidate protects mice and non-human primates against Zika virus
Authors: Baldwin Whitney R. , Giebler Holli A. , Stovall Janae L. , Young Ginger , Bohning Kelly J. , Dean Hansi J. , Livengood Jill A. , Huang Claire Y.-H. 
Published: December 2021

AbstractThe development of a safe and effective Zika virus (ZIKV) vaccine has become a global health priority since the widespread epidemic in 2015-2016. Based on previous experience in using the well-characterized and clinically proven dengue virus serotype-2 (DENV-2) PDK-53 vaccine backbone for live-attenuated chimeric flavivirus vaccine development, we developed chimeric DENV-2/ZIKV vaccine candidates optimized for growth and genetic stability in Vero cells. These vaccine candidates retain all previously characterized attenuation phenotypes of the PDK-53 vaccine virus, including attenuation of neurovirulence for 1-day-old CD-1 mice, absence of virulence in interferon receptor-deficient mice, and lack of transmissibility in the main mosquito vectors. A single DENV-2/ZIKV dose provides protection against ZIKV challenge in mice and rhesus macaques. Overall, these data indicate that the ZIKV live-attenuated vaccine candidates are safe, immunogenic and effective at preventing ZIKV infection in multiple animal models, warranting continued development.
Mechanisms of SARS-CoV-2 neutralization by shark variable new antigen receptors elucidated through X-ray crystallography
Authors: Ubah Obinna C. , Lake Eric W. , Gunaratne Gihan S. , Gallant Joseph P. , Fernie Marie , Robertson Austin J. , Marchant Jonathan S. , Bold Tyler D. , Langlois Ryan A. , Matchett William E. , Thiede Joshua M. , Shi Ke , Yin Lulu , Moeller Nicholas H. , Banerjee Surajit , Ferguson Laura , Kovaleva Marina , Porter Andrew J. , Aihara Hideki , LeBeau Aaron M. , Barelle Caroline J. 
Published: December 2021

AbstractSingle-domain Variable New Antigen Receptors (VNARs) from the immune system of sharks are the smallest naturally occurring binding domains found in nature. Possessing flexible paratopes that can recognize protein motifs inaccessible to classical antibodies, VNARs have yet to be exploited for the development of SARS-CoV-2 therapeutics. Here, we detail the identification of a series of VNARs from a VNAR phage display library screened against the SARS-CoV-2 receptor binding domain (RBD). The ability of the VNARs to neutralize pseudotype and authentic live SARS-CoV-2 virus rivalled or exceeded that of full-length immunoglobulins and other single-domain antibodies. Crystallographic analysis of two VNARs found that they recognized separate epitopes on the RBD and had distinctly different mechanisms of virus neutralization unique to VNARs. Structural and biochemical data suggest that VNARs would be effective therapeutic agents against emerging SARS-CoV-2 mutants, including the Delta variant, and coronaviruses across multiple phylogenetic lineages. This study highlights the utility of VNARs as effective therapeutics against coronaviruses and may serve as a critical milestone for nearing a paradigm shift of the greater biologic landscape.
Stochastic fluctuations of bosonic dark matter
Authors: Centers Gary P. , Blanchard John W. , Conrad Jan , Figueroa Nataniel L. , Garcon Antoine , Gramolin Alexander V. , Kimball Derek F. Jackson , Lawson Matthew , Pelssers Bart , Smiga Joseph A. , Sushkov Alexander O. , Wickenbrock Arne , Budker Dmitry , Derevianko Andrei 
Published: December 2021

AbstractNumerous theories extending beyond the standard model of particle physics predict the existence of bosons that could constitute dark matter. In the standard halo model of galactic dark matter, the velocity distribution of the bosonic dark matter field defines a characteristic coherence timeτc. Until recently, laboratory experiments searching for bosonic dark matter fields have been in the regime where the measurement timeTsignificantly exceedsτc, so null results have been interpreted by assuming a bosonic field amplitude Φ0fixed by the average local dark matter density. Here we show that experiments operating in theT ≪ τcregime do not sample the full distribution of bosonic dark matter field amplitudes and therefore it is incorrect to assume a fixed value of Φ0when inferring constraints. Instead, in order to interpret laboratory measurements (even in the event of a discovery), it is necessary to account for the stochastic nature of such a virialized ultralight field. The constraints inferred from several previous null experiments searching for ultralight bosonic dark matter were overestimated by factors ranging from 3 to 10 depending on experimental details, model assumptions, and choice of inference framework.
The long non-coding RNA landscape of Candida yeast pathogens
Authors: Hovhannisyan Hrant , Gabaldón Toni 
Published: December 2021

AbstractLong non-coding RNAs (lncRNAs) constitute a poorly studied class of transcripts with emerging roles in key cellular processes. Despite efforts to characterize lncRNAs across a wide range of species, these molecules remain largely unexplored in most eukaryotic microbes, including yeast pathogens of the Candida clade. Here, we analyze thousands of publicly available sequencing datasets to infer and characterize the lncRNA repertoires of five major Candida pathogens: Candida albicans, Candida tropicalis, Candida parapsilosis, Candida auris and Candida glabrata. Our results indicate that genomes of these species encode hundreds of lncRNAs that show levels of evolutionary constraint intermediate between those of intergenic genomic regions and protein-coding genes. Despite their low sequence conservation across the studied species, some lncRNAs are syntenic and are enriched in shared sequence motifs. We find co-expression of lncRNAs with certain protein-coding transcripts, hinting at potential functional associations. Finally, we identify lncRNAs that are differentially expressed during infection of human epithelial cells for four of the studied species. Our comprehensive bioinformatic analyses of Candida lncRNAs pave the way for future functional characterization of these transcripts.
Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza
Authors: Chivukula Sudha , Plitnik Timothy , Tibbitts Timothy , Karve Shrirang , Dias Anusha , Zhang Donghui , Goldman Rebecca , Gopani Hardip , Khanmohammed Asad , Sarode Ashish , Cooper Dustin , Yoon Heesik , Kim Younghoon , Yan Yanhua , Mundle Sophia T. , Groppo Rachel , Beauvais Adrien , Zhang Jinrong , Anosova Natalie G. , Lai Charles , Li Lu , Ulinski Gregory , Piepenhagen Peter , DiNapoli Joshua , Kalnin Kirill V. , Landolfi Victoria , Swearingen Ron , Fu Tong-Ming , DeRosa Frank , Casimiro Danilo 
Published: December 2021

AbstractRecent approval of mRNA vaccines for emergency use against COVID-19 is likely to promote rapid development of mRNA-based vaccines targeting a wide range of infectious diseases. Compared to conventional approaches, this vaccine modality promises comparable potency while substantially accelerating the pace of development and deployment of vaccine doses. Already demonstrated successfully for single antigen vaccines such as for COVID-19, this technology could be optimized for complex multi-antigen vaccines. Herein, utilizing multiple influenza antigens, we demonstrated the suitability of the mRNA therapeutic (MRT) platform for such applications. Seasonal influenza vaccines have three or four hemagglutinin (HA) antigens of different viral subtypes. In addition, influenza neuraminidase (NA), a tetrameric membrane protein, is identified as an antigen that has been linked to protective immunity against severe viral disease. We detail the efforts in optimizing formulations of influenza candidates that use unmodified mRNA encoding full-length HA or full-length NA encapsulated in lipid nanoparticles (LNPs). HA and NA mRNA-LNP formulations, either as monovalent or as multivalent vaccines, induced strong functional antibody and cellular responses in non-human primates and such antigen-specific antibody responses were associated with protective efficacy against viral challenge in mice.
A light-fuelled nanoratchet shifts a coupled chemical equilibrium
Authors: Kathan Michael , Crespi Stefano , Thiel Niklas O. , Stares Daniel L. , Morsa Denis , de Boer John , Pacella Gianni , van den Enk Tobias , Kobauri Piermichele , Portale Giuseppe , Schalley Christoph A. , Feringa Ben L. 
Published: December 2021

AbstractBiological molecular machines enable chemical transformations, assembly, replication and motility, but most distinctively drive chemical systems out of-equilibrium to sustain life1,2. In such processes, nanometre-sized machines produce molecular energy carriers by driving endergonic equilibrium reactions. However, transforming the work performed by artificial nanomachines3–5into chemical energy remains highly challenging. Here, we report a light-fuelled small-molecule ratchet capable of driving a coupled chemical equilibrium energetically uphill. By bridging two imine6–9macrocycles with a molecular motor10,11, the machine forms crossings and consequently adopts several distinct topologies by either a thermal (temporary bond-dissociation) or photochemical (unidirectional rotation) pathway. While the former will relax the machine towards the global energetic minimum, the latter increases the number of crossings in the system above the equilibrium value. Our approach provides a blueprint for coupling continuous mechanical motion performed by a molecular machine with a chemical transformation to reach an out-of-equilibrium state.
Dynamic X-ray elastography using a pulsed photocathode source
Authors: Kamezawa Chika , Cramer Avilash , Krull Wolfgang , Yashiro Wataru , Hyodo Kazuyuki , Gupta Rajiv 
Published: December 2021

AbstractX-ray absorption of breast cancers and surrounding healthy tissue can be very similar, a situation that sometimes leads to missed cancers or false-positive diagnoses. To increase the accuracy of mammography and breast tomosynthesis, we describe dynamic X-ray elastography using a novel pulsed X-ray source. This new imaging modality provides both absorption and mechanical properties of the imaged material. We use a small acoustic speaker to vibrate the sample while a synchronously pulsed cold cathode X-ray source images the mechanical deformation. Using these stroboscopic images, we derive two-dimensional stiffness maps of the sample in addition to the conventional X-ray image. In a breast phantom composed of ZrO2 powder embedded in gel, dynamic elastography derived stiffness maps were able to discriminate a hard inclusion from surrounding material with a contrast-to-noise ratio (CNR) of 4.5. The CNR on the corresponding absorption image was 1.1. This demonstrates the feasibility of dynamic X-ray elastography with a synchronously pulsed X-ray source.
Harmonic convergence coordinates swarm mating by enhancing mate detection in the malaria mosquito Anopheles gambiae
Authors: Garcia Castillo Stefano S. , Pritts Kevin S. , Krishnan Raksha S. , Harrington Laura C. , League Garrett P. 
Published: December 2021

AbstractThe mosquitoAnopheles gambiaeis a major African malaria vector, transmitting parasites responsible for significant mortality and disease burden. Although flight acoustics are essential to mosquito mating and present promising alternatives to insecticide-based vector control strategies, there is limited data on mosquito flight tones during swarming. Here, for the first time, we present detailed analyses of free-flying male and femaleAn. gambiaeflight tones and their harmonization (harmonic convergence) over a complete swarm sequence. Audio analysis of single-sex swarms showed synchronized elevation of male and female flight tones during swarming. Analysis of mixed-sex swarms revealed additional 50 Hz increases in male and female flight tones due to mating activity. Furthermore, harmonic differences between male and female swarm tones in mixed-sex swarms and in single-sex male swarms with artificial female swarm audio playback indicate that frequency differences of approximately 50 Hz or less at the male second and female third harmonics (M2:F3) are maintained both before and during mating interactions. This harmonization likely coordinates male scramble competition by maintaining ideal acoustic recognition within mating pairs while acoustically masking phonotactic responses of nearby swarming males to mating females. These findings advance our knowledge of mosquito swarm acoustics and provide vital information for reproductive control strategies.
The effect of levosimendan on right ventricular function in patients with heart dysfunction: a systematic review and meta-analysis
Authors: Hu Yaoshi , Wei Zhe , Zhang Chaoyong , Lu Chuanghong , Zeng Zhiyu 
Published: December 2021

AbstractLevosimendan exerts positive inotropic and vasodilatory effects. Currently, its effects on right heart function remain uncertain. This systematic review and meta-analysis is intended to illustrate the impacts of levosimendan on systolic function of the right heart in patients with heart dysfunction. We systematically searched electronic databases (PubMed, the Cochrane Library, Embase and Web of Science) up to November 30, 2020, and filtered eligible studies that reported the impacts of levosimendan on right heart function. Of these, only studies whose patients suffered from heart dysfunction or pulmonary hypertension were included. Additionally, patients were divided into two groups (given levosimendan or not) in the initial research. Then, RevMan5.3 was used to conduct further analysis. A total of 8 studies comprising 390 patients were included. The results showed that after 24 h of levosimendan, patients’ right ventricular fractional area change [3.17, 95% CI (2.03, 4.32), P < 0.00001], tricuspid annular plane systolic excursion [1.26, 95% CI (0.35, 2.16), P = 0.007] and tricuspid annular peak systolic velocity [0.86, 95% CI (0.41, 1.32), P = 0.0002] were significantly increased compared to the control group. And there is an increasing trend of cardiac output in levosimendan group [1.06, 95% CI (− 0.16, 2.29), P = 0.09 ] .Furthermore, patients’ systolic pulmonary arterial pressure [− 5.57, 95% CI (− 7.60, − 3.54), P < 0.00001] and mean pulmonary arterial pressure [− 1.01, 95% CI (− 1.64, − 0.37), P = 0.002] were both significantly decreased, whereas changes in pulmonary vascular resistance [− 55.88, 95% CI (− 206.57, 94.82), P = 0.47] were not significant. Our study shows that in patients with heart dysfunction, levosimendan improves systolic function of the right heart and decreases the pressure of the pulmonary artery.
Direct pesticide exposure of insects in nature conservation areas in Germany
Authors: Brühl Carsten A. , Bakanov Nikita , Köthe Sebastian , Eichler Lisa , Sorg Martin , Hörren Thomas , Mühlethaler Roland , Meinel Gotthard , Lehmann Gerlind U. C. 
Published: December 2021

AbstractIn Germany, the decline of insect biomass was observed in nature conservation areas in agricultural landscapes. One of the main causal factors discussed is the use of synthetic pesticides in conventional agriculture. In a Germany-wide field study, we collected flying insects using Malaise traps in nature conservation areas adjacent to agricultural land. We used a multi-component chemical trace element analysis to detect 92 common agricultural pesticides in ethanol from insect traps sampled in May and August 2020. In total, residues of 47 current use pesticides were detected, and insect samples were on average contaminated with 16.7 pesticides. Residues of the herbicides metolachlor-S, prosulfocarb and terbuthylazine, and the fungicides azoxystrobin and fluopyram were recorded at all sites. The neonicotinoid thiacloprid was detected in 16 of 21 nature conservation areas, most likely due to final use before an EU-wide ban. A change in residue mixture composition was noticeable due to higher herbicide use in spring and increasing fungicide applications in summer. The number of substances of recorded residues is related to the proportion of agricultural production area in a radius of 2000 m. Therefore, a drastic pesticide reduction in large buffers around nature conservation areas is necessary to avoid contamination of their insect fauna.
Smoking cessation reduces systemic inflammation and circulating endothelin-1
Authors: Derella Cassandra C. , Tingen Martha S. , Blanks Anson , Sojourner Samantha J. , Tucker Matthew A. , Thomas Jeffrey , Harris Ryan A. 
Published: December 2021

AbstractSmoking increases systemic inflammation and circulating endothelin-1 (ET-1), both of which contribute to an elevated risk of cardiovascular disease (CVD). The present study sought to test the hypothesis that a 12-week smoking cessation intervention would contribute to a long-term reduction in circulating ET-1, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). 30 individuals participated in a 12-week evidence-based smoking cessation program at Augusta University. Serum cotinine, plasma inflammatory cytokines, and plasma ET-1 were determined at baseline, immediately after the 12-week cessation program (end of treatment, EOT), and 12-months (12M) following the cessation program. Serum cotinine was significantly reduced (p < 0.001) at EOT and 12M following the smoking cessation program. Compared to BL (7.0 ± 1.6 pg/mL), TNF-α was significantly reduced at EOT (6.3 ± 1.5 pg/mL, p = 0.001) and 12M (5.2 ± 2.7 pg/mL, p < 0.001). ET-1 was significantly lower at EOT (1.9 ± 0.6 pg/mL, p = 0.013) and at 12M (2.0 ± 0.8 pg/mL, p = 0.091) following smoking cessation compared with BL (2.3 ± 0.6 pg/mL). BL concentrations of cotinine were significantly associated with basal ET-1 (r = 0.449, p = 0.013) and the change in cotinine at 12M following smoking cessation was significantly associated with the change in plasma ET-1 at 12M (r = 0.457, p = 0.011). Findings from the present pilot investigation demonstrate that a 12-week smoking cessation program reduces circulating concentrations of ET-1 and TNF-α for at least a year. The reduction in serum cotinine was associated with the decrease in circulating ET-1. The attenuation in ET-1 and inflammation may in part, contribute to the lower risk of CVD that is observed with smoking cessation.
Detachable dissolvable microneedles: intra-epidermal and intradermal diffusion, effect on skin surface, and application in hyperpigmentation treatment
Authors: Sawutdeechaikul Pritsana , Kanokrungsee Silada , Sahaspot Thanyapat , Thadvibun Kamonwan , Banlunara Wijit , Limcharoen Benchaphorn , Sansureerungsikul Titiporn , Rutwaree Teeranut , Oungeun Miranda , Wanichwecharungruang Supason 
Published: December 2021

AbstractDelivering bioactive compounds into skin tissue has long been a challenge. Using ex vivo porcine and rat skins, here we demonstrate that a detachable dissolvable microneedle (DDMN) array, a special dissolvable microneedle that allows needle detachment from the base within 2 min post administration, can effectively embed a model compound into epidermis and dermis. Diffusion of the compound from the needle embedding sites to the nearby skin tissue is demonstrated at various post administration periods. The relationship between the time that a conventional dissolvable microneedle array is left on skin without needle detachment from the base and the degree of skin surface abrasion at each microneedle penetration spot is also demonstrated on skin of human volunteers. Co-loading glutathione with vitamin C (vitC) can stabilize vitC in the DDMN. DDMN loaded with vitC and glutathione can help erasing post-acne-hyperpigmentation spots.
Role of eccentricity in early Holocene African and Asian summer monsoons
Authors: Wu Chi-Hua , Lee Shih-Yu , Tsai Pei-Chia 
Published: December 2021

AbstractThe effect of precession on paleoclimate changes depends on eccentricity. However, whether and to what degree eccentricity relates to millennial-scale monsoonal changes remain unclear. By investigating climate simulations with a fixed precession condition of 9 ka before the present, we explored the potential influence of eccentricity on early-Holocene changes in the Afro–Asian summer monsoons. Compared with the lower eccentricity of the present day, higher eccentricity in the early Holocene strengthened the continental summer monsoons, Pacific anticyclone, and Hadley circulation, particularly over the ocean. Over Africa, the eccentricity-induced “dry-gets-wetter” condition could be related to the Green Sahara, suggesting a superimposed effect of precession. Over the western Pacific, the tropical response to eccentricity may have been competitive in terms of what an extremely high obliquity may have caused. A downscaled modulation of eccentricity in relation to precession and obliquity cannot be ignored when paleomonsoon records are studied. Regarding early-Holocene monsoonal changes in South Asia, however, a high eccentricity may have had only a secondary effect on enhancing the monsoonal precipitation in the southern edge of the Tibetan Plateau, exhibiting the weak power of candle-like heating. This suggested that sizable monsoonal changes over the northern Indian Ocean and India–Pakistan region are unrelated to early-Holocene eccentricity.