bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward a Safe Archaeology Field School
Authors: Emerson Matthew C.
Published: March 2021

Archaeology field schools provide unique opportunities for firsthand exposure, team-based learning, and pre-professional experience. A participant's decision to pursue a career in archaeology may reflect initial fieldwork group experiences and individual interactions with field school leaders and staff. Today, safety, security, and equity policies along with staff and operational procedures that support them are essential for instructing and inspiring all who wish to experience archaeological fieldwork. Drawing on three decades of field school participation and administration, the author describes specific examples of fieldwork learning contexts as well as insights into operating a safe, secure, and welcoming field school. Conclusions include general guidelines that are applicable and desirable for short-term, season-long, or special skills field schools.
Earthquake Preparedness and Knowledge of Recommended Self-Protective Actions: A Survey of Nursing Students
Authors: Longo Bernadette M.
Published: March 2021

Objective:

Nurses are a vital workforce to the disaster response of an earthquake. The aim of this study was to assess preexisting knowledge in baccalaureate nursing students about disaster preparedness and self-protective behavioral responses during an earthquake.

Methods:

A descriptive cross-sectional survey of nursing students from a seismologically active region was conducted. Data were collected prior to earthquake preparedness education and ShakeOut drills designed to enhance personal safety.

Results:

A total of 274 nursing students participated in the survey (response rate – 93%). More than half (57%) of respondents did not feel prepared for an earthquake; 88% were without a household emergency plan and 82% lacked emergency supplies. Self-protective actions of drop, cover, and hold on and stay in bed were accurately identified by 77% and 96% of respondents, respectively. Hazardous actions selected included stand in a doorway (77% of respondents) and go outside into the street (23% of respondents).

Conclusions:

These results demonstrate a lack of personal disaster preparedness in nursing students and several behavioral responses that do not promote self-preservation during seismic activity. Although existing baccalaureate nursing education addresses competencies for disaster care, actions are needed to develop curriculum that emphasizes preparedness and safety to regional environmental hazards.
Entropy, irreversibility and cascades in the inertial range of isotropic turbulence
Authors: Vela-Martín Alberto , Jiménez Javier
Published: March 2021

This paper analyses the turbulent energy cascade from the perspective of statistical mechanics, and relates interscale energy fluxes to statistical irreversibility and information entropy production. The microscopical reversibility of the energy cascade is tested by constructing a reversible three-dimensional turbulent system using a dynamic model for the sub-grid stresses. This system, when reversed in time, develops a sustained inverse cascade towards the large scales, evidencing that the characterisation of the inertial energy cascade must consider the possibility of an inverse regime. This experiment is used to study the origin of statistical irreversibility and the prevalence of direct over inverse energy cascades in isotropic turbulence. Statistical irreversibility, a property of statistical ensembles in phase space related to entropy production, is connected to the dynamics of the energy cascade in physical space by considering the space locality of the energy fluxes and their relation to the local structure of the flow. A mechanism to explain the probabilistic prevalence of direct energy transfer is proposed based on the dynamics of the rate-of-strain tensor, which is identified as the most important source of statistical irreversibility in the energy cascade.
Aesthetic community
Authors: Ronen Ruth
Published: March 2021

Taste, as a faculty of aesthetic appreciation, involves an individual, and yet assumes a community. In this article, a distinctly singular mode of being attuned to objects of taste is shown to be conditioned by the consent of others and by being-with others, thereby constituting what is named here an ‘aesthetic community.’ This idea of an aesthetic community is traced back to Kant's sensus communis and to Heidegger's notion of preservation: for both, it is the presence of a community that conditions aesthetic experience.
Current limitations to high-resolution structure determination by single-particle cryoEM
Authors: D'Imprima Edoardo , Kühlbrandt Werner
Published: March 2021

CryoEM has become the method of choice for determining the structure of large macromolecular complexes in multiple conformations, at resolutions where unambiguous atomic models can be built. Two effects that have limited progress in single-particle cryoEM are (i) beam-induced movement during image acquisition and (ii) protein adsorption and denaturation at the air-water interface during specimen preparation. While beam-induced movement now appears to have been resolved by all-gold specimen support grids with very small holes, surface effects at the air-water interface are a persistent problem. Strategies to overcome these effects include the use of alternative support films and new techniques for specimen deposition. We examine the future potential of recording perfect images of biological samples for routine structure determination at atomic resolution.
Equality for Prospective People: A Novel Statement and Defence
Authors: Voorhoeve Alex
Published: March 2021

A possible person'sconditional expected well-beingis what the quality of their prospects would be if they were to come into existence. This article examines the role that this form of expected well-being should play in distributing benefits among prospective people and in deciding whom to bring into existence. It argues for a novel egalitarian view on which it is important to ensure equality in people's life prospects, not merely between actual individuals, but also between all individuals who, given our choices, have a chance of coming into existence. The article argues that such egalitarianism for prospective people springs from equal concern for each prospective person and has plausible implications. It further shows that it has a rationale in respect for both the unity of the individual and the separateness of persons. Finally, it defends this view against a key objection and shows it is superior to a rival view.
Peripheral insulin sensitivity predicting cognitive function in euthymic bipolar disorder patients
Authors: Chang Hui Hua , Tseng Huai-Hsuan , Chang Wei Hung , Huang Kuan-Chung , Lu Tsung-Hua , Yang Yen Kuang , Chen Po See
Published: March 2021

Objective

High prevalence of insulin resistance (IR) has been reported in bipolar disorder (BD) patients. Importantly, impaired insulin sensitivity could modulate the course and treatment outcome in BD. Here, we hypothesized that insulin sensitivity could be potentially associated with the neurocognitive trajectory in euthymic BD. We aimed to examine differences in insulin sensitivity and executive function between BD patients and controls.

Methods

Sixty-two patients with BD receiving mood stabilizer treatment and 62 controls, matching age, sex, and body mass index, were recruited in this study. Insulin sensitivity was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). The Wisconsin card-sorting test (WCST) was applied to test participants’ ability to shift cognitive set. Group differences were measured and multivariate regression analysis was performed to examine relationships among factors.

Results

The results indicated that the HOMA-IR (P = .048) value in the patients with BD were significantly higher than those in controls. With regards to executive function, the BD patients performed significantly poorer than the control subjects (P < .05). Moreover, the interaction effect between BD diagnosis and HOMA-IR value on the WCST-preservation errors was significant (P = .01), and post-hoc analyses showed that the cognitive abilities were worse in the BD patients with a higher IR than in the others groups.

Conclusion

Insulin sensitivity is associated with the neurocognitive performance in euthymic BD patients. Although the underlying mechanisms remain unclear, interventions to improve insulin sensitivity could potentially improve the functional outcome of BD.
Consumption of artificially sweetened soft drinks and risk of gastrointestinal cancer: a meta-analysis of observational studies
Authors: Jatho Alfred , Cambia Jansen Marcos , Myung Seung-Kwon
Published: March 2021

Objective:

There remain inconclusive findings from previous observational epidemiological studies on whether consumption of artificially sweetened soft drinks (ASSD) increases the risk of gastrointestinal (GI) cancer. We investigated the associations between the consumption of ASSD and the risk of GI cancer using a meta-analysis.

Design:

Systematic review and meta-analysis.

Setting:

PubMed and EMBASE were searched using keywords until May 2020 to identify observational epidemiological studies on the association between the consumption of ASSD and the risk of GI cancer.

Subjects:

Twenty-one case–control studies and seventeen cohort studies with 12 397 cancer cases and 2 474 452 controls.

Results:

In the random-effects meta-analysis of all the studies, consumption of ASSD was not significantly associated with the risk of overall GI cancer (OR/relative risk (RR), 1·02; 95 % CI, 0·92, 1·14). There was no significant association between the consumption of ASSD and the risk of overall GI cancer in the subgroup meta-analyses by study design (case–control studies: OR, 0·95; 95 % CI, 0·82, 1·11; cohort studies: RR, 1·14; 95 % CI, 0·97, 1·33). In the subgroup meta-analysis by type of cancer, consumption of ASSD was significantly associated with the increased risk of liver cancer (OR/RR, 1·28; 95 % CI, 1·03, 1·58).

Conclusions:

The current meta-analysis of observational epidemiological studies suggests that overall, there is no significant association between the consumption of ASSD and the risk of GI cancer.
Thermodynamics of the Magnetotail Current Sheet Thinning
Authors: Yushkov E. V. , Petrukovich A. A. , Artemyev A. V. , Nakamura R.
Published: March 2021

Substorm growth phase in the magnetotail is characterized by formation of a thin current sheet (CS) becomes unstable due to external or internal drivers. Such instability results in magnetic field line reconnection, the substorm onset. The CS thinning, as a key process of substorm dynamics, has been included into many global and local simulations of the magnetotail magnetic reconnection. However, recent observations indicate that the evolution of plasma characteristics and magnetic field configuration during the CS thinning can differ from predictions of the classical adiabatic scenario. In this study, we combine two most extensive datasets of the CS evolution, as observed by Cluster and THEMIS missions for 2001–2009 and 2015, respectively. We show that for a wide range of downtail distances and dawn‐dusk direction there are quite similar quantitative characteristics of the thinning: the magnetic field line stretching (north‐south magnetic field decrease), the intensification of the current density, and the evolution of plasma temperatures and densities. We confirm that the process cannot be directly associated with increase of the lobe magnetic pressure. Using advantages of multispacecraft measurements and CS flapping motion, we demonstrate that the thinning is usually result in the equatorial density increase and plasma temperature decrease. We discuss the revealed evolution features in the context of the thermodynamical CS characteristics for contemporary thinning models.
Pitch Angle Phase Shift in Ring Current Ions Interacting With Ultra‐Low‐Frequency Waves: Van Allen Probes Observations
Authors: Li Xing‐Yu , Liu Zhi‐Yang , Zong Qiu‐Gang , Zhou Xu‐Zhi , Hao Yi‐Xin , Rankin Robert , Zhang Xiao‐Xin
Published: March 2021

Drift‐bounce resonance between ultra‐low‐frequency (ULF) waves and ring current ions has been widely studied, because of its important role in ring current acceleration and relevant geomagnetic activities. To identify drift‐bounce resonance in observations, 180° phase shifts across resonant pitch angle have been proposed as diagnostic signatures. This study, however, presents observations that suggest this criterion may be invalid when phase space density (PSD) distributions vary nonmonochromatically with energy. We identified 14 ULF wave‐ion interaction cases from 2‐years Van Allen Probes data. In these cases, 180° phase shifts across pitch angle are observed at particular energies. Near these energies, pitch angle‐dependent PSD bump‐on‐tail distributions were also observed. As a result, at fixed energies, the sign of ion PSD energy gradient changes across pitch angle, which then can result in the observed 180° phase shift. Based on the observations, we suggest 180° phase shifts across pitch angle can also result from pitch angle‐dependent bump‐on‐tail distributions, which should be taken into account in future ULF wave‐ion interaction studies.
Flickering Low Frequency Auroral Hiss
Authors: LaBelle James
Published: March 2021

A low‐ and medium‐frequency (LF/MF) receiving system at South Pole Station, using a wide‐beam dipole antenna, measured continuous fully sampled waveforms of more than 100 LF auroral hiss events between June and October 2019. Spectra of fluctuations of LF auroral hiss intensity at selected frequencies between 110 and 530 kHz showed these are broadband, with spectral power monotonically decreasing to an upper bound typically 20–60 Hz, comparable to frequencies reported for optical flickering aurora. Occasionally intervals of periodic fluctuations in auroral hiss intensity occurred, in most cases lasting only tens of cycles. On September 1, 2019, periodic fluctuations lasted thousands of cycles during two 30‐s intervals, at frequencies 125–145 Hz. Close examination showed these to be dispersed with low frequencies arriving before high frequencies by approximately 4.5 ms per 100 kHz. Ray‐tracing calculations and consideration of the Temerin et al. (1986, 1993) mechanisms of flickering aurora shows that the September 1 flickering auroral hiss observations are consistent with resonant amplification of whistler mode noise by an electron beam accelerated and modulated by electromagnetic proton cyclotron waves originating near 4,500 km, with the wave excitation taking place at 2,000–3,000 km.
Combined Optical and Radio‐Frequency Perspectives on a Hybrid Cloud‐To‐Ground Lightning Flash Observed by the FORTE Satellite
Authors: Peterson Michael , Light Tracy E. L. , Shao Xuan‐Min
Published: March 2021

We use the coincident optical and radio‐frequency (RF) measurements taken by the Fast On‐orbit Recording of Transient Events (FORTE) satellite to shed light on common optical signatures recorded by NASA and NOAA lightning imagers during Cloud‐to‐Ground (CG) lightning. We build flash cluster data for FORTE using the same techniques as the NASA/NOAA instruments to document the optical/RF evolution of an oceanic hybrid ‐CG flash. The flash began with strong Very High Frequency (VHF)‐band emission from a Narrow Bipolar Event (NBE) that initiated a period of normal bilevel intracloud (IC) activity in two vertical layers (8  and 12 km) that lasted for 490 ms. VHF waveforms show step leader activity ahead of the return stroke. All impulsive VHF sources after the stroke come from the lower (8 km) layer. K‐changes are noted following the return stroke, but no subsequent strokes are detected. The optical flash began 136 ms after the NBE RF pulse. Twenty‐two of the 33 optical groups were dim and occurred during the in‐cloud phase of the flash. This activity included both isolated pulses and sustained periods of illumination over tens of milliseconds. Initial cloud pulses accounted for 23% of the total optical radiance from the flash. Illumination during the return stroke contributed 58% of the total radiance, and the K‐changes and cloud pulses after the stroke supplied the remaining 19%. These results highlight the benefit of having RF alongside optical lightning measurements for clarifying signatures in the optical data and providing information on their physical origins.
Watershed and Lake Attributes Dictate Landscape Patterns of Resource Flows in Mountain Lakes
Authors: Smits Adrianne P. , Currinder Bryan , Framsted Nicholas , Loken Luke C. , Lucero Delores , Neal Kelly A. , Parisek Christine A. , Sickman Jim , Sadro Steven
Published: March 2021

The extent to which terrestrial organic matter supports aquatic consumers remains uncertain because factors regulating resource flows are poorly understood. We sampled 12 lakes throughout the Sierra Nevada (California, USA) spanning large gradients in elevation and size to evaluate how watershed attributes and lake morphometry influence resource flows to lake carbon pools and zooplankton. We found that the size and composition of carbon pools in lakes were often more strongly determined by watershed or lake features rather than by elevational position. Using three different tracers of resource origin (δ13C, Δ14C, C:N ratio), we found terrestrial contributions to most lake resource pools (dissolved organic carbon, particulate organic matter (POM), sediments) and pelagic consumers (zooplankton) were more strongly related to local‐scale watershed features such as vegetation cover or watershed area: lake area rather than to elevation. Landscape patterns in multiple tracers indicated consistent contribution of within‐lake C sources to bulk resource pools across elevations (POM, sediments, zooplankton). δ13C‐enrichment of lake C pools and overlap with δ13C of terrestrial resources can arise due to reduced fractionation of 13C by phytoplankton under CO2 limitation, therefore we recommend careful consideration of potential environmental drivers when interpreting among‐lake patterns in δ13C. Our findings emphasize the importance of local‐scale variation in mediating terrestrial contributions to lake food webs.
Observed Decrease in Soil and Atmosphere Temperature Coupling in Recent Decades Over Northern Eurasia
Authors: Chen Liangzhi , Aalto Juha , Luoto Miska
Published: March 2021

Coupling of soil‐air temperature is fundamentally relevant to various biophysical and biogeochemical functions near the land surface. However, coupling at an interannual scale is less addressed than at finer timescales, such as diurnal and seasonal scales. Here, we show that interannual variability of soil‐air temperature coupling decreased significantly during 1984–2013 across 196 stations in northern Eurasia. Coupling at a depth of 0.2 m remained significant in only 53% of stations during 1999–2013, while it was significant in 80% of stations during 1984–1998. Decreased coupling is mainly attributable to air temperature change in the snow‐free season and snow cover retreat. Moreover, change in the extreme snow cover frequency also contributes to the decline, while other climate extremes are less influential. The findings can help us to understand long‐term land‐climate thermal interactions and to evaluate soil temperature profiles simulated by land surface models.
Morphotype and Crust Effects on the Geochemistry of Globorotalia inflata
Authors: Jonkers Lukas , Gopalakrishnan Akshat , Weßel Lea , Chiessi Cristiano M. , Groeneveld Jeroen , Monien Patrick , Lessa Douglas , Morard Raphaël
Published: March 2021

Sedimentary specimens of the planktonic foraminifera Globorotalia inflata can provide information on subsurface conditions of past oceans. However, interpretation of their geochemical signal is complicated by possible effects of cryptic diversity and encrustation. Here we address these issues using plankton tow and sediment samples from the western South Atlantic, where two genotypes of G. inflata occur. To separate the genotypes, we analyzed shells from the extreme ends of the morphospace of G. inflata. The δ18O and δ13C of encrusted specimens from both morphotypes are indistinguishable. However, we do find a large influence of encrustation on δ18O and Mg/Ca. Whereas crust Mg/Ca ratios are at all locations lower than lamellar calcite, the crust effect on δ18O is less consistent in space. Plankton tows show that encrusted specimens occur at any depth and that even close to the surface crust Mg/Ca ratios are lower than in lamellar calcite. This is inconsistent with formation of the crust at lower temperature at greater depth. Instead we suggest that the difference between the crust and lamellar calcite Mg/Ca ratio is temperature‐independent and due to the presence of high Mg/Ca bands only in the lamellar calcite. The variable crust effect on δ18O is more difficult to explain, but the higher incidence of crust‐free specimens in warmer waters and the observation that a crust effect is clearest in the confluence zone, hint at the possibility that the difference reflects advective mixing of specimens from warmer and colder areas, rather than vertical migration.
Caribbean plate tilted and actively dragged eastwards by low-viscosity asthenospheric flow
Authors: Chen Yi-Wei , Colli Lorenzo , Bird Dale E. , Wu Jonny , Zhu Hejun
Published: March 2021

The importance of a low-viscosity asthenosphere underlying mobile plates has been highlighted since the earliest days of the plate tectonics revolution. However, absolute asthenospheric viscosities are still poorly constrained, with estimates spanning up to 3 orders of magnitude. Here we follow a new approach using analytic solutions for Poiseuille-Couette channel flow to compute asthenospheric viscosities under the Caribbean. We estimate Caribbean dynamic topography and the associated pressure gradient, which, combined with flow velocities estimated from geologic markers and tomographic structure, yield our best-estimate asthenospheric viscosity of (3.0 ± 1.5)*1018 Pa s. This value is consistent with independent estimates for non-cratonic and oceanic regions, and challenges the hypothesis that higher-viscosity asthenosphere inferred from postglacial rebound is globally-representative. The active flow driven by Galapagos plume overpressure shown here contradicts the traditional view that the asthenosphere is only a passive lubricating layer for Earth’s tectonic plates.
Warming from tropical deforestation reduces worker productivity in rural communities
Authors: Masuda Yuta J. , Garg Teevrat , Anggraeni Ike , Ebi Kristie , Krenz Jennifer , Game Edward T. , Wolff Nicholas H. , Spector June T.
Published: March 2021

The accelerating loss of tropical forests in the 21st century has eliminated cooling services provided by trees in low latitude countries. Cooling services can protect rural communities and outdoor workers with little adaptive capacity from adverse heat exposure, which is expected to increase with climate change. Yet little is still known about whether cooling services can mitigate negative impacts of heat on labor productivity among rural outdoor workers. Through a field experiment in Indonesia, we show that worker productivity was 8.22% lower in deforested relative to forested settings, where wet bulb globe temperatures were, on average, 2.84 °C higher in deforested settings. We demonstrate that productivity losses are driven by behavioral adaptations in the form of increased number of work breaks, and provide evidence that suggests breaks are in part driven by awareness of heat effects on work. Our results indicate that the cooling services from forests have the potential for increasing resilience and adaptive capacity to local warming.
Joint profiling of DNA and proteins in single cells to dissect genotype-phenotype associations in leukemia
Authors: Demaree Benjamin , Delley Cyrille L. , Vasudevan Harish N. , Peretz Cheryl A. C. , Ruff David , Smith Catherine C. , Abate Adam R.
Published: March 2021

Studies of acute myeloid leukemia rely on DNA sequencing and immunophenotyping by flow cytometry as primary tools for disease characterization. However, leukemia tumor heterogeneity complicates integration of DNA variants and immunophenotypes from separate measurements. Here we introduce DAb-seq, a technology for simultaneous capture of DNA genotype and cell surface phenotype from single cells at high throughput, enabling direct profiling of proteogenomic states in tens of thousands of cells. To demonstrate the approach, we analyze the disease of three patients with leukemia over multiple treatment timepoints and disease recurrences. We observe complex genotype-phenotype dynamics that illustrate the subtlety of the disease process and the degree of incongruity between blast cell genotype and phenotype in different clinical scenarios. Our results highlight the importance of combined single-cell DNA and protein measurements to fully characterize the heterogeneity of leukemia.
mTORC1 couples cyst(e)ine availability with GPX4 protein synthesis and ferroptosis regulation
Authors: Zhang Yilei , Swanda Robert V. , Nie Litong , Liu Xiaoguang , Wang Chao , Lee Hyemin , Lei Guang , Mao Chao , Koppula Pranavi , Cheng Weijie , Zhang Jie , Xiao Zhenna , Zhuang Li , Fang Bingliang , Chen Junjie , Qian Shu-Bing , Gan Boyi
Published: March 2021

Glutathione peroxidase 4 (GPX4) utilizes glutathione (GSH) to detoxify lipid peroxidation and plays an essential role in inhibiting ferroptosis. As a selenoprotein, GPX4 protein synthesis is highly inefficient and energetically costly. How cells coordinate GPX4 synthesis with nutrient availability remains unclear. In this study, we perform integrated proteomic and functional analyses to reveal that SLC7A11-mediated cystine uptake promotes not only GSH synthesis, but also GPX4 protein synthesis. Mechanistically, we find that cyst(e)ine activates mechanistic/mammalian target of rapamycin complex 1 (mTORC1) and promotes GPX4 protein synthesis at least partly through the Rag-mTORC1-4EBP signaling axis. We show that pharmacologic inhibition of mTORC1 decreases GPX4 protein levels, sensitizes cancer cells to ferroptosis, and synergizes with ferroptosis inducers to suppress patient-derived xenograft tumor growth in vivo. Together, our results reveal a regulatory mechanism to coordinate GPX4 protein synthesis with cyst(e)ine availability and suggest using combinatorial therapy of mTORC1 inhibitors and ferroptosis inducers in cancer treatment.
Hepatitis B virus cccDNA is formed through distinct repair processes of each strand
Authors: Wei Lei , Ploss Alexander
Published: March 2021

Hepatitis B virus (HBV) is a highly contagious pathogen that afflicts over a third of the world’s population, resulting in close to a million deaths annually. The formation and persistence of the HBV covalently closed circular DNA (cccDNA) is the root cause of HBV chronicity. However, the detailed molecular mechanism of cccDNA formation from relaxed circular DNA (rcDNA) remains opaque. Here we show that the minus and plus-strand lesions of HBV rcDNA require different sets of human repair factors in biochemical repair systems. We demonstrate that the plus-strand repair resembles DNA lagging strand synthesis, and requires proliferating cell nuclear antigen (PCNA), the replication factor C (RFC) complex, DNA polymerase delta (POLδ), flap endonuclease 1 (FEN-1), and DNA ligase 1 (LIG1). Only FEN-1 and LIG1 are required for the repair of the minus strand. Our findings provide a detailed mechanistic view of how HBV rcDNA is repaired to form cccDNA in biochemical repair systems.
A randomised controlled trial to reduce highest priority critically important antimicrobial prescription in companion animals
Authors: Singleton David A. , Rayner Angela , Brant Bethaney , Smyth Steven , Noble Peter-John M. , Radford Alan D. , Pinchbeck Gina L.
Published: March 2021

Robust evidence supporting strategies for companion animal antimicrobial stewardship is limited, despite frequent prescription of highest priority critically important antimicrobials (HPCIA). Here we describe a randomised controlled trial where electronic prescription data were utilised (August 2018–January 2019) to identify above average HPCIA-prescribing practices (n = 60), which were randomly assigned into a control group (CG) and two intervention groups. In March 2019, the light intervention group (LIG) and heavy intervention group (HIG) were notified of their above average status, and were provided with educational material (LIG, HIG), in-depth benchmarking (HIG), and follow-up meetings (HIG). Following notification, follow-up monitoring lasted for eight months (April–November 2019; post-intervention period) for all intervention groups, though HIG practices were able to access further support (i.e., follow-up meetings) for the first six of these months if requested. Post-intervention, in the HIG a 23.5% and 39.0% reduction in canine (0.5% of total consultations, 95% confidence interval, 0.4-0.6, P = 0.04) and feline (4.4%, 3.4-5.3, P < 0.001) HPCIA-prescribing consultations was observed, compared to the CG (dogs: 0.6%, 0.5-0.8; cats: 7.4%, 6.0-8.7). The LIG was associated with a 16.7% reduction in feline HPCIA prescription (6.1% of total consultations, 5.3-7.0, P = 0.03). Therefore, in this trial we have demonstrated effective strategies for reducing veterinary HPCIA prescription.
DeepTCR is a deep learning framework for revealing sequence concepts within T-cell repertoires
Authors: Sidhom John-William , Larman H. Benjamin , Pardoll Drew M. , Baras Alexander S.
Published: March 2021

Deep learning algorithms have been utilized to achieve enhanced performance in pattern-recognition tasks. The ability to learn complex patterns in data has tremendous implications in immunogenomics. T-cell receptor (TCR) sequencing assesses the diversity of the adaptive immune system and allows for modeling its sequence determinants of antigenicity. We present DeepTCR, a suite of unsupervised and supervised deep learning methods able to model highly complex TCR sequencing data by learning a joint representation of a TCR by its CDR3 sequences and V/D/J gene usage. We demonstrate the utility of deep learning to provide an improved ‘featurization’ of the TCR across multiple human and murine datasets, including improved classification of antigen-specific TCRs and extraction of antigen-specific TCRs from noisy single-cell RNA-Seq and T-cell culture-based assays. Our results highlight the flexibility and capacity for deep neural networks to extract meaningful information from complex immunogenomic data for both descriptive and predictive purposes.
Novel evolutionary dynamics of small populations in breast cancer adjuvant and neoadjuvant therapy
Authors: Artzy-Randrup Yael , Epstein Tamir , Brown Joel S. , Costa Ricardo L. B. , Czerniecki Brian J. , Gatenby Robert A.
Published: March 2021

Disseminated cancer cells (DCCs) are detected in the circulation and bone marrow of up to 40% of breast cancer (BC) patients with clinically localized disease. The formation of metastases is governed by eco-evolutionary interactions of DCCs with the tissue during the transition from microscopic populations to macroscopic disease. Here, we view BC adjuvant and neoadjuvant treatments in the context of small population extinction dynamics observed in the Anthropocene era. Specifically, the unique eco-evolutionary dynamics of small asexually reproducing cancer populations render them highly vulnerable to: (1) environmental and demographic fluctuations, (2) Allee effects, (3) genetic drift and (4) population fragmentation. Furthermore, these typically interact, producing self-reinforcing, destructive dynamics—termed the Extinction Vortex—eradicating the population even when none of the perturbations is individually capable of causing extinction. We propose that developing BC adjuvant and neoadjuvant protocols may exploit these dynamics to prevent recovery and proliferation of small cancer populations during and after treatment—termed “Eco-evolutionary rescue” in natural extinctions. We hypothesize more strategic application of currently available agents based on the extinction vulnerabilities of small populations could improve clinical outcomes.
Automated design of superconducting circuits and its application to 4-local couplers
Authors: Menke Tim , Häse Florian , Gustavsson Simon , Kerman Andrew J. , Oliver William D. , Aspuru-Guzik Alán
Published: March 2021

Superconducting circuits have emerged as a promising platform to build quantum processors. The challenge of designing a circuit is to compromise between realizing a set of performance metrics and reducing circuit complexity and noise sensitivity. At the same time, one needs to explore a large design space, and computational approaches often yield long simulation times. Here, we automate the circuit design task using SCILLA. The software SCILLA performs a parallelized, closed-loop optimization to design superconducting circuit diagrams that match predefined properties, such as spectral features and noise sensitivities. We employ it to design 4-local couplers for superconducting flux qubits and identify a circuit that outperforms an existing proposal with a similar circuit structure in terms of coupling strength and noise resilience for experimentally accessible parameters. This work demonstrates how automated design can facilitate the development of complex circuit architectures for quantum information processing.
Nanoscale programming of cellular and physiological phenotypes: inorganic meets organic programming
Authors: Dokholyan Nikolay V.
Published: March 2021

The advent of protein design in recent years has brought us within reach of developing a “nanoscale programing language,” in which molecules serve as operands with their conformational states functioning as logic gates. Combining these operands into a set of operations will result in a functional program, which is executed using nanoscale computing agents (NCAs). These agents would respond to any given input and return the desired output signal. The ability to utilize natural evolutionary processes would allow code to “evolve” in the course of computation, thus enabling radically new algorithmic developments. NCAs will revolutionize the studies of biological systems, enable a deeper understanding of human biology and disease, and facilitate the development of in situ precision therapeutics. Since NCAs can be extended to novel reactions and processes not seen in biological systems, the growth of this field will spark the growth of biotechnological applications with wide-ranging impacts, including fields not typically considered relevant to biology. Unlike traditional approaches in synthetic biology that are based on the rewiring of signaling pathways in cells, NCAs are autonomous vehicles based on single-chain proteins. In this perspective, I will introduce and discuss this new field of biological computing, as well as challenges and the future of the NCA. Addressing these challenges will provide a significant leap in technology for programming living cells.
Microbicidal actives with virucidal efficacy against SARS-CoV-2 and other beta- and alpha-coronaviruses and implications for future emerging coronaviruses and other enveloped viruses
Authors: Ijaz M. Khalid , Nims Raymond W. , Zhou Sifang Steve , Whitehead Kelly , Srinivasan Vanita , Kapes Tanya , Fanuel Semhar , Epstein Jonathan H. , Daszak Peter , Rubino Joseph R. , McKinney Julie
Published: March 2021

Mitigating the risk of acquiring coronaviruses including SARS-CoV-2 requires awareness of the survival of virus on high-touch environmental surfaces (HITES) and skin, and frequent use of targeted microbicides with demonstrated efficacy. The data on stability of infectious SARS-CoV-2 on surfaces and in suspension have been put into perspective, as these inform the need for hygiene. We evaluated the efficacies of formulated microbicidal actives against alpha- and beta-coronaviruses, including SARS-CoV-2. The coronaviruses SARS-CoV, SARS-CoV-2, human coronavirus 229E, murine hepatitis virus-1, or MERS-CoV were deposited on prototypic HITES or spiked into liquid matrices along with organic soil loads. Alcohol-, quaternary ammonium compound-, hydrochloric acid-, organic acid-, p-chloro-m-xylenol-, and sodium hypochlorite-based microbicidal formulations were evaluated per ASTM International and EN standard methodologies. All evaluated formulated microbicides inactivated SARS-CoV-2 and other coronaviruses in suspension or on prototypic HITES. Virucidal efficacies (≥ 3 to ≥ 6 log10 reduction) were displayed within 30 s to 5 min. The virucidal efficacy of a variety of commercially available formulated microbicides against SARS-CoV-2 and other coronaviruses was confirmed. These microbicides should be useful for targeted surface and hand hygiene and disinfection of liquids, as part of infection prevention and control for SARS-CoV-2 and emerging mutational variants, and other emerging enveloped viruses.
Causal effects in microbiomes using interventional calculus
Authors: Sazal Musfiqur , Stebliankin Vitalii , Mathee Kalai , Yoo Changwon , Narasimhan Giri
Published: March 2021

Causal inference in biomedical research allows us to shift the paradigm from investigating associational relationships to causal ones. Inferring causal relationships can help in understanding the inner workings of biological processes. Association patterns can be coincidental and may lead to wrong conclusions about causality in complex systems. Microbiomes are highly complex, diverse, and dynamic environments. Microbes are key players in human health and disease. Hence knowledge of critical causal relationships among the entities in a microbiome, and the impact of internal and external factors on microbial abundance and their interactions are essential for understanding disease mechanisms and making appropriate treatment recommendations. In this paper, we employ causal inference techniques to understand causal relationships between various entities in a microbiome, and to use the resulting causal network to make useful computations. We introduce a novel pipeline for microbiome analysis, which includes adding an outcome or “disease” variable, and then computing the causal network, referred to as a “disease network”, with the goal of identifying disease-relevant causal factors from the microbiome. Internventional techniques are then applied to the resulting network, allowing us to compute a measure called the causal effect of one or more microbial taxa on the outcome variable or the condition of interest. Finally, we propose a measure called causal influence that quantifies the total influence exerted by a microbial taxon on the rest of the microiome. Our pipeline is robust, sensitive, different from traditional approaches, and able to predict interventional effects without any controlled experiments. The pipeline can be used to identify potential eubiotic and dysbiotic microbial taxa in a microbiome. We validate our results using synthetic data sets and using results on real data sets that were previously published.
The unique mean seasonal cycle in the Indian Ocean anchors its various air-sea coupled modes across the basin
Authors: Xu Xinqiang , Wang Lei , Yu Weidong
Published: March 2021

The interannual variability of the sea surface temperature (SST) in the Indian Ocean is complex and characterized by various air-sea coupled modes, which occur around El Niño/La Niña's peak phase (i.e. December–January–February, DJF). Indian Ocean Dipole Mode (IODM) develops over the tropical Indian Ocean and peaks in September–October–November (SON), while Ningaloo Niño, Subtropical Indian Ocean Dipole (SIOD) and Indian Ocean Basin Mode (IOBM) occur respectively over northwest off Australia, subtropical and tropical Indian Ocean, during boreal winter to spring. The apparent contrast between their divergent regionality and convergent seasonality around DJF triggers the present study to examine the interaction between the local mean monsoonal cycle and the anomalous forcing from El Niño/La Niña. The diagnosis confirms that the Indian Ocean’s unique complexity, including the monsoonal circulation over the tropics and the trade wind over the subtropical southern Indian Ocean, plays the fundamental role in anchoring the various regional air-sea coupled modes across the basin. The SST anomalies can be readily explained by the wind-evaporation-SST (WES) mechanism, which works together with other more regional-dependent dynamic and thermodynamic mechanisms. This implies that El Niño/La Niña brings much predictability for the Indian Ocean variations.
First isolation and analysis of caesium-bearing microparticles from marine samples in the Pacific coastal area near Fukushima Prefecture
Authors: Miura Hikaru , Ishimaru Takashi , Ito Yukari , Kurihara Yuichi , Otosaka Shigeyoshi , Sakaguchi Aya , Misumi Kazuhiro , Tsumune Daisuke , Kubo Atsushi , Higaki Shogo , Kanda Jota , Takahashi Yoshio
Published: March 2021

A part of the radiocaesium from the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident was emitted as glassy, water-resistant caesium-bearing microparticles (CsMPs). Here, we isolated and investigated seven CsMPs from marine particulate matter and sediment. From the elemental composition, the 134Cs/137Cs activity ratio, and the 137Cs activity per unit volume results, we inferred that the five CsMPs collected from particulate matter were emitted from Unit 2 of the FDNPP, whereas the two CsMPs collected from marine sediment were possibly emitted from Unit 3, as suggested by (i) the presence of calcium and absence of zinc and (ii) the direction of the atmospheric plume during the radionuclide emission event from Unit 3. The presence of CsMPs can cause overestimation of the solid–water distribution coefficient of Cs in marine sediments and particulate matter and a high apparent radiocaesium concentration factor for marine biota. CsMPs emitted from Unit 2, which were collected from the estuary of a river that flowed through a highly contaminated area, may have been deposited on land and then transported by the river. By contrast, CsMPs emitted from Unit 3 were possibly transported eastward by the wind and deposited directly onto the ocean surface.
Digital biomarker of mental fatigue
Authors: Tseng Vincent Wen-Sheng , Valliappan Nachiappan , Ramachandran Venky , Choudhury Tanzeem , Navalpakkam Vidhya
Published: March 2021

Mental fatigue is an important aspect of alertness and wellbeing. Existing fatigue tests are subjective and/or time-consuming. Here, we show that smartphone-based gaze is significantly impaired with mental fatigue, and tracks the onset and progression of fatigue. A simple model predicts mental fatigue reliably using just a few minutes of gaze data. These results suggest that smartphone-based gaze could provide a scalable, digital biomarker of mental fatigue.
Development of a potent embryonic chick lens model for studying congenital cataracts in vivo
Authors: Li Zhen , Gu Sumin , Quan Yumeng , Varadaraj Kulandaiappan , Jiang Jean X.
Published: March 2021

Congenital cataracts are associated with gene mutations, yet the underlying mechanism remains largely unknown. Here we reported an embryonic chick lens model that closely recapitulates the process of cataract formation. We adopted dominant-negative site mutations that cause congenital cataracts, connexin, Cx50E48K, aquaporin 0, AQP0R33C, αA-crystallin, CRYAA R12C and R54C. The recombinant retroviruses containing these mutants were microinjected into the occlusive lumen of chick lenses at early embryonic development. Cx50E48K expression developed cataracts associated with disorganized nuclei and enlarged extracellular spaces. Expression of AQP0R33C resulted in cortical cataracts, enlarged extracellular spaces and distorted fiber cell organization. αA crystallin mutations distorted lens light transmission and increased crystalline protein aggregation. Together, retroviral expression of congenital mutant genes in embryonic chick lenses closely mimics characteristics of human congenital cataracts. This model will provide an effective, reliable in vivo system to investigate the development and underlying mechanism of cataracts and other genetic diseases.
Publisher Correction: Detection of genetic variation and base modifications at base-pair resolution on both DNA and RNA
Authors: Wang Zhen , Maluenda Jérôme , Giraut Laurène , Vieille Thibault , Lefevre Andréas , Salthouse David , Radou Gaël , Moulinas Rémi , Astete Sandra , D’Avezac Pol , Smith Geoff , André Charles , Allemand Jean-François , Bensimon David , Croquette Vincent , Ouellet Jimmy , Hamilton Gordon
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s42003-021-01894-9
Theoretical evidence of water serving as a promoter for lithium superoxide disproportionation in Li–O2 batteries
Authors: Shan Nannan , Redfern Paul C. , Ngo Anh T. , Zapol Peter , Markovic Nenad , Curtiss Larry A.
Published: March 2021

Theoretical calculations confirm that very small amounts of water can promote the lithium superoxide disproportionation reaction in the Li–O2 battery.
Zanthoxylum alkylamides ameliorate protein metabolism in type 2 diabetes mellitus rats by regulating multiple signaling pathways
Authors: Wei Xunyu , Yang Bing , Chen Xuhui , Wen Leyan , Kan Jianquan
Published: March 2021

ZA ameliorated protein anabolism and energy metabolism of T2DM rats by regulating PI3K/Akt/mTOR and AMPK signaling pathways. ZA improved inflammation and protein catabolism in T2DM rats by regulating TNF-α/NF-κB and PI3K/Akt/FoxO signaling pathways.
Room temperature iron catalyzed transfer hydrogenation using n-butanol and poly(methylhydrosiloxane)
Authors: Linford-Wood Thomas G. , Coles Nathan T. , Webster Ruth L.
Published: March 2021

Reduction of carbon–carbon double bonds is reported using a three-coordinate iron(ii) β-diketiminate pre-catalyst, PMHS and nBuOH.
The development of a magnetic iron/nitrogen-doped graphitized carbon composite with boosted microwave attenuation ability as the wideband microwave absorber
Authors: Chen Cong , Chen Wen , Zong Bing , Ding Xiaohai , Dong Haitao
Published: March 2021

Magnetic carbon-based composites have been attractive candidates for electromagnetic (EM) absorption due to their dual magnetic and dielectric loss ability.
Deposition pressure-induced microstructure control and plasmonic property tuning in hybrid ZnO–AgxAu1−x thin films
Authors: Paldi Robynne L. , Sun Xing , Phuah Xin Li , Lu Juanjuan , Zhang Xinghang , Siddiqui Aleem , Wang Haiyan
Published: March 2021

ZnO–AgxAu1−x oxide–nanoalloy vertically aligned nanocomposite thin films have been grown via pulsed laser deposition and the film morphology and optical properties were tuned through oxygen partial pressure.
Dual-triggered biomimetic vehicles enable treatment of glioblastoma through a cancer stem cell therapeutic strategy
Authors: Geng Wenqian , Zou Hao , Wang Hongbo , Dai Yu , Lu Guangzhao , Sun Zhiguo , Lu Ying , Ding Xueying , Yu Yuan
Published: March 2021

Biomimetic nanocarrier structure and schematic illustration of the proposed strategy of promoting the treatment of glioma for cancer stem cell therapy in combination with chemotherapeutics.
The synthesis of triazine–thiophene–thiophene conjugated porous polymers and their composites with carbon as anode materials in lithium-ion batteries
Authors: Xue Xin , Luo Junming , Kong Lingqian , Zhao Jinsheng , Zhang Yan , Du Hongmei , Chen Shuang , Xie Yu
Published: March 2021

Four different kinds of conjugated porous polymers PTTs were synthesized and their composites with carbon material were used as the electrode materials for LIBs.
Radiative sky cooling of solar cells: fundamental modelling and cooling potential of single-junction devices
Authors: Dumoulin Jérémy , Drouard Emmanuel , Amara Mohamed
Published: March 2021

A fundamental modelling framework of solar cells is presented in order to quantify the potential benefit of enhanced radiative sky cooling for different single-junction technologies, according to their basic electrical and thermal properties.
A turn-on homodimer fluorescent probe based on homo-FRET for the sensing of biothiols in lysosome: a trial of a new turn-on strategy
Authors: Tang Ying-Jie , Fang Wen-Le , Ren Kui , Guo Xiao-Feng , Wang Hong
Published: March 2021

Fluorescence resonance energy transfer (FRET) is often applied to construct fluorescent probes for acquiring high selectivity and sensitivity.