bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cities and COVID-19: navigating the new normal
Authors: Khan Iman , Iftikhar Muhammad Naveed , Ali Saleem H. , Khalid Shua 
Published: March 2021

Non-technical summary
Urban density is erroneously regarded as the main factor in the spread of COVID-19 in cities. A review of extant literature and findings from our case study of Karachi, Pakistan indicate that inequalities in income, healthcare, and living conditions play a key role in the spread of contagions along with government responsiveness to the pandemic. Moving forward, urban policies need to address these inequalities through changes in housing policies and decentralized governance systems. Cities must adapt to sustainable modes of travel, reduce digital inequalities, and encourage people friendly urban planning to become resilient in the face of pandemics.

Technical summary
COVID-19 has changed how urban residents relate to their cities. Urban centers have become epicenters of disease, which has raised questions about the long-term sustainability of high-density settlements and public transport usage. However, the spread of COVID-19 in cities is incorrectly attributed to urban density.
Using the case study of Karachi, Pakistan, we find that inequality of income, healthcare, and living conditions is a major contributing factor to the spread of COVID-19. Data on positive COVID-19 cases, density, and socioeconomic status were obtained at the Union Council level from administrative districts of Karachi, Pakistan between March 2020, and July 2020. Despite low population densities, low-to-middle income neighborhoods in Karachi had a higher proportion of positive cases. Further, the experience of dense cities such as Hanoi in Vietnam and New York in the US differs regarding the spread of COVID-19. Hence, the government's response to the pandemic is also a major factor in containing the outbreak.
Our findings suggest that a crisis in a city is exacerbated by its inability to take advantage of its density, inequality in the distribution of resources, lack of inclusiveness, and centralized governance mechanisms that make it difficult to respond quickly to situations. Thus, urban planning scholarship and practice should take an interdisciplinary approach to make cities equitable, inclusive, and adaptive.

Social media summary
Cities in the developing world have an opportunity for more resilient renewal in the post-COVID world.
Optimizing Precipitation Forecasts for Hydrological Catchments in Ethiopia Using Statistical Bias Correction and Multi‐Modeling
Authors: Stellingwerf Sippora , Riddle Emily , Hopson Thomas M. , Knievel Jason C. , Brown Barbara , Gebremichael Mekonnen 
Published: March 2021

AbstractAccurate rainfall forecasts on timescales ranging from a few hours to several weeks are needed for many hydrological applications. This study examines bias, skill and reliability of four ensemble forecast systems (from Canada, UK, Europe, and the United States) and a multi‐model ensemble as applied to Ethiopian catchments. By verifying these forecasts on hydrological catchments, we focus on spatial scales that are relevant to many actual water forecasting applications, such as flood forecasting and reservoir optimization. By most verification metrics tested, the bias corrected European model is the best individual model at predicting daily rainfall variations, while the Canadian model shows the most realistic ensemble spread and thus the most reliable forecast probabilities, including those of extreme events. The skill of the multi‐model ensemble outperforms individual models by most metrics, and is skillful up to 9 days ahead. Skill is higher for the 0–5 day model accumulation than for the first 24 h, suggesting that timing errors strongly penalize the skill of forecasts with shorter accumulation periods. Due to seasonality in the model biases, bias correction is best applied to each month individually. Forecasting extreme rainfall is a challenge for Ethiopia, especially over mountainous regions where positive skill is only reached after bias correction. Compared to individual models, the multi‐model ensemble has a higher probability of detecting extreme rainfall and a lower false alarm rate, with usable skill at 24 h lead times.
Constraints on the Depth, Thickness, and Strength of the G Discontinuity in the Central Pacific From S Receiver Functions
Authors: Mark H. F. , Collins J. A. , Lizarralde D. , Hirth G. , Gaherty J. B. , Evans R. L. , Behn M. D. 
Published: March 2021

AbstractThe relative motion of the lithosphere with respect to the asthenosphere implies the existence of a boundary zone that accommodates shear between the rigid plates and flowing mantle. This shear zone is typically referred to as the lithosphere‐asthenosphere boundary (LAB). The width of this zone and the mechanisms accommodating shear across it have important implications for coupling between mantle convection and surface plate motion. Seismic observations have provided evidence for several physical mechanisms that might help enable relative plate motion, but how these mechanisms each contribute to the overall accommodation of shear remains unclear. Here we present receiver function constraints on the discontinuity structure of the oceanic upper mantle at the NoMelt site in the central Pacific, where local constraints on shear velocity, anisotropy, conductivity, and attenuation down to ∼300 km depth provide a comprehensive picture of upper mantle structure. We image a seismic discontinuity with a Vsv decrease of 4.5% or more over a 0–20 km thick gradient layer centered at a depth of ∼65 km. We associate this feature with the Gutenberg discontinuity (G), and interpret our observation of G as resulting from strain localization across a dehydration boundary based on the good agreement between the discontinuity depth and that of the dry solidus. Transitions in Vsv, azimuthal anisotropy, conductivity, and attenuation observed at roughly similar depths suggest that the G discontinuity represents a region of localized strain within a broader zone accommodating shear between the lithosphere and asthenosphere.
Adapting to Changing Labor Productivity as a Result of Intensified Heat Stress in a Changing Climate
Authors: Zhu Jinxin , Wang Shuo , Zhang Boen , Wang Dagang 
Published: March 2021

AbstractThe intensification of heat stress reduces the labor capacity and hence poses a threat to socio‐economic development. The reliable projection of the changing climate and the development of sound adaptation strategies are thus desired for adapting to the decreasing labor productivity under climate change. In this study, an optimization modeling approach coupled with dynamical downscaling is proposed to design the optimal adaptation strategies for improving labor productivity under heat stress in China. The future changes in heat stress represented by the wet‐bulb globe temperature (WBGT) are projected with a spatial resolution of 25 × 25 km by a regional climate model (RCM) through the dynamical downscaling of its driving global climate model (GCM). Uncertain information such as system costs, environmental costs, and subsidies are also incorporated into the optimization process to provide reliable decision alternatives for improving labor productivity. Results indicate that the intensification of WBGT is overestimated by the GCM compared to the RCM. Such an overestimation can lead to more losses in working hours derived from the GCM than those from the RCM regardless of climate scenarios. Nevertheless, the overestimated heat stress does not alter the regional measures taken to adapt to decreasing labor productivity. Compared to inland regions, the monsoon‐affected regions tend to improve labor productivity by applying air conditioning rather than working overtime due to the cost differences. Consequently, decision‐makers need to optimally make a balance between working overtime and air conditioning measures to meet sustainable development goals.
Autocorrelation of the Ground Vibrations Recorded by the SEIS‐InSight Seismometer on Mars
Authors: Compaire N. , Margerin L. , Garcia R. F. , Pinot B. , Calvet M. , Orhand‐Mainsant G. , Kim D. , Lekic V. , Tauzin B. , Schimmel M. , Stutzmann E. , Knapmeyer‐Endrun B. , Lognonné P. , Pike W. T. , Schmerr N. , Gizon L. , Banerdt W. B. 
Published: March 2021

AbstractSince early February 2019, the SEIS (Seismic Experiment for Interior Structure) seismometer deployed at the surface of Mars in the framework of the InSight mission has been continuously recording the ground motion at Elysium Planitia. In this study, we take advantage of this exceptional data set to put constraints on the crustal properties of Mars using seismic interferometry (SI). To carry out this task, we first examine the continuous records from the very broadband seismometer. Several deterministic sources of environmental noise are identified and specific preprocessing strategies are presented to mitigate their influence. Applying the principles of SI to the single‐station configuration of InSight, we compute, for each Sol and each hour of the martian day, the diagonal elements of the time‐domain correlation tensor of random ambient vibrations recorded by SEIS. A similar computation is performed on the diffuse waveforms generated by more than a hundred Marsquakes. A careful signal‐to‐noise ratio analysis and an inter‐comparison between the two datasets suggest that the results from SI are most reliable in a narrow frequency band around 2.4 Hz, where an amplification of both ambient vibrations and seismic events is observed. The average autocorrelation functions (ACFs) contain well identifiable seismic arrivals, that are very consistent between the two datasets. Interpreting the vertical and horizontal ACFs as, respectively, the P‐ and S‐ seismic reflectivity below InSight, we propose a simple stratified velocity model of the crust, which is mostly compatible with previous results from receiver function analysis. Our results are discussed and compared to recent works from the literature.
Time-expanded phase-sensitive optical time-domain reflectometry
Authors: Soriano-Amat Miguel , Martins Hugo F. , Durán Vicente , Costa Luis , Martin-Lopez Sonia , Gonzalez-Herraez Miguel , Fernández-Ruiz María R. 
Published: March 2021

AbstractPhase-sensitive optical time-domain reflectometry (ΦOTDR) is a well-established technique that provides spatio-temporal measurements of an environmental variable in real time. This unique capability is being leveraged in an ever-increasing number of applications, from energy transportation or civil security to seismology. To date, a wide number of different approaches have been implemented, providing a plethora of options in terms of performance (resolution, acquisition bandwidth, sensitivity or range). However, to achieve high spatial resolutions, detection bandwidths in the GHz range are typically required, substantially increasing the system cost and complexity. Here, we present a novel ΦOTDR approach that allows a customized time expansion of the received optical traces. Hence, the presented technique reaches cm-scale spatial resolutions over 1 km while requiring a remarkably low detection bandwidth in the MHz regime. This approach relies on the use of dual-comb spectrometry to interrogate the fibre and sample the backscattered light. Random phase-spectral coding is applied to the employed combs to maximize the signal-to-noise ratio of the sensing scheme. A comparison of the proposed method with alternative approaches aimed at similar operation features is provided, along with a thorough analysis of the new trade-offs. Our results demonstrate a radically novel high-resolution ΦOTDR scheme, which could promote new applications in metrology, borehole monitoring or aerospace.
Orphan nuclear receptors as regulators of intratumoral androgen biosynthesis in castration-resistant prostate cancer
Authors: Zhou Jianfu , Wang Yuliang , Wu Dinglan , Wang Shusheng , Chen Zhiqiang , Xiang Songtao , Chan Franky Leung 
Published: March 2021

AbstractCastration-resistant prostate cancer (CRPC) almost invariably occurs after androgen-deprivation therapy (ADT) for the advanced metastatic disease. It is generally believed that among multiple mechanisms and signaling pathways, CRPC is significantly driven by the reactivation of androgen receptor (AR) signaling in ADT-treated patients with castrate levels of androgen, partially at least mediated by the androgen biosynthesis within the tumor, also known as intratumoral or intraprostatic androgen biosynthesis. Steroidogenic enzymes, such as CYP11A1, CYP17A1, HSD3B1, AKR1C3 and SRD5A, are essential to catalyze the conversion of the initial substrate cholesterol into potent androgens that confers the CRPC progression. Accumulating evidences indicate that many steroidogenic enzymes are upregulated in the progression setting; however, little is known about the dysregulation of these enzymes in CRPC. Orphan nuclear receptors (ONRs) are members of the nuclear receptor superfamily, of which endogenous physiological ligands are unknown and which are constitutively active independent of any physiological ligands. Studies have validated that besides AR, ONRs could be the potential therapeutic targets for prostate cancer, particularly the lethal CRPC progression. Early studies reveal that ONRs play crucial roles in the transcriptional regulation of steroidogenic enzyme genes. Notably, we and others show that three distinct ONRs, including liver receptor homolog-1 (LRH-1, NR5A2), steroidogenic factor 1 (SF-1, AD4BP, NR5A1) and estrogen-related receptor α (ERRα, NR3B1), can contribute to the CRPC progression by promotion of the intratumoral androgen synthesis via their direct transcriptional regulation on multiple steroidogenic enzymes. This review presents an overview of the current understanding on the intratumoral androgen biosynthesis in CRPC, with a special focus on the emerging roles of ONRs in this process.
A self-organized synthetic morphogenic liposome responds with shape changes to local light cues
Authors: Gavriljuk Konstantin , Scocozza Bruno , Ghasemalizadeh Farid , Seidel Hans , Nandan Akhilesh P. , Campos-Medina Manuel , Schmick Malte , Koseska Aneta , Bastiaens Philippe I. H. 
Published: March 2021

AbstractReconstituting artificial proto-cells capable of transducing extracellular signals into cytoskeletal changes can reveal fundamental principles of how non-equilibrium phenomena in cellular signal transduction affect morphogenesis. Here, we generated a Synthetic Morphogenic Membrane System (SynMMS) by encapsulating a dynamic microtubule (MT) aster and a light-inducible signaling system driven by GTP/ATP chemical potential into cell-sized liposomes. Responding to light cues in analogy to morphogens, this biomimetic design embodies basic principles of localized Rho-GTPase signal transduction that generate an intracellular MT-regulator signaling gradient. Light-induced signaling promotes membrane-deforming growth of MT-filaments by dynamically elevating the membrane-proximal tubulin concentration. The resulting membrane deformations enable recursive coupling of the MT-aster with the signaling system, which generates global self-organized morphologies that reorganize towards local external cues in dependence on prior shape. SynMMS thereby signifies a step towards bio-inspired engineering of self-organized cellular morphogenesis.
Graded recruitment of pupil-linked neuromodulation by parametric stimulation of the vagus nerve
Authors: Mridha Zakir , de Gee Jan Willem , Shi Yanchen , Alkashgari Rayan , Williams Justin , Suminski Aaron , Ward Matthew P. , Zhang Wenhao , McGinley Matthew James 
Published: March 2021

AbstractVagus nerve stimulation (VNS) is thought to affect neural activity by recruiting brain-wide release of neuromodulators. VNS is used in treatment-resistant epilepsy, and is increasingly being explored for other disorders, such as depression, and as a cognitive enhancer. However, the promise of VNS is only partially fulfilled due to a lack of mechanistic understanding of the transfer function between stimulation parameters and neuromodulatory response, together with a lack of biosensors for assaying stimulation efficacy in real time. We here develop an approach to VNS in head-fixed mice on a treadmill and show that pupil dilation is a reliable and convenient biosensor for VNS-evoked cortical neuromodulation. In an ‘optimal’ zone of stimulation parameters, current leakage and off-target effects are minimized and the extent of pupil dilation tracks VNS-evoked basal-forebrain cholinergic axon activity in neocortex. Thus, pupil dilation is a sensitive readout of the moment-by-moment, titratable effects of VNS on brain state.
The impact of contact tracing and household bubbles on deconfinement strategies for COVID-19
Authors: Willem Lander , Abrams Steven , Libin Pieter J. K. , Coletti Pietro , Kuylen Elise , Petrof Oana , Møgelmose Signe , Wambua James , Herzog Sereina A. , Faes Christel , Beutels Philippe , Hens Niel 
Published: March 2021

AbstractThe COVID-19 pandemic caused many governments to impose policies restricting social interactions. A controlled and persistent release of lockdown measures covers many potential strategies and is subject to extensive scenario analyses. Here, we use an individual-based model (STRIDE) to simulate interactions between 11 million inhabitants of Belgium at different levels including extended household settings, i.e., “household bubbles”. The burden of COVID-19 is impacted by both the intensity and frequency of physical contacts, and therefore, household bubbles have the potential to reduce hospital admissions by 90%. In addition, we find that it is crucial to complete contact tracing 4 days after symptom onset. Assumptions on the susceptibility of children affect the impact of school reopening, though we find that business and leisure-related social mixing patterns have more impact on COVID-19 associated disease burden. An optimal deployment of the mitigation policies under study require timely compliance to physical distancing, testing and self-isolation.
Comprehensive single-cell sequencing reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of nasopharyngeal carcinoma
Authors: Gong Lanqi , Kwong Dora Lai-Wan , Dai Wei , Wu Pingan , Li Shanshan , Yan Qian , Zhang Yu , Zhang Baifeng , Fang Xiaona , Liu Li , Luo Min , Liu Beilei , Chow Larry Ka-Yue , Chen Qingyun , Huang Jinlin , Lee Victor Ho-Fun , Lam Ka-On , Lo Anthony Wing-Ip , Chen Zhiwei , Wang Yan , Lee Anne Wing-Mui , Guan Xin-Yuan 
Published: March 2021

AbstractThe tumor microenvironment (TME) of nasopharyngeal carcinoma (NPC) harbors a heterogeneous and dynamic stromal population. A comprehensive understanding of this tumor-specific ecosystem is necessary to enhance cancer diagnosis, therapeutics, and prognosis. However, recent advances based on bulk RNA sequencing remain insufficient to construct an in-depth landscape of infiltrating stromal cells in NPC. Here we apply single-cell RNA sequencing to 66,627 cells from 14 patients, integrated with clonotype identification on T and B cells. We identify and characterize five major stromal clusters and 36 distinct subpopulations based on genetic profiling. By comparing with the infiltrating cells in the non-malignant microenvironment, we report highly representative features in the TME, including phenotypic abundance, genetic alternations, immune dynamics, clonal expansion, developmental trajectory, and molecular interactions that profoundly influence patient prognosis and therapeutic outcome. The key findings are further independently validated in two single-cell RNA sequencing cohorts and two bulk RNA-sequencing cohorts. In the present study, we reveal the correlation between NPC-specific characteristics and progression-free survival. Together, these data facilitate the understanding of the stromal landscape and immune dynamics in NPC patients and provides deeper insights into the development of prognostic biomarkers and therapeutic targets in the TME.
Acceleration of western Arctic sea ice loss linked to the Pacific North American pattern
Authors: Liu Zhongfang , Risi Camille , Codron Francis , He Xiaogang , Poulsen Christopher J. , Wei Zhongwang , Chen Dong , Li Sha , Bowen Gabriel J. 
Published: March 2021

AbstractRecent rapid Arctic sea-ice reduction has been well documented in observations, reconstructions and model simulations. However, the rate of sea ice loss is highly variable in both time and space. The western Arctic has seen the fastest sea-ice decline, with substantial interannual and decadal variability, but the underlying mechanism remains unclear. Here we demonstrate, through both observations and model simulations, that the Pacific North American (PNA) pattern is an important driver of western Arctic sea-ice variability, accounting for more than 25% of the interannual variance. Our results suggest that the recent persistent positive PNA pattern has led to increased heat and moisture fluxes from local processes and from advection of North Pacific airmasses into the western Arctic. These changes have increased lower-tropospheric temperature, humidity and downwelling longwave radiation in the western Arctic, accelerating sea-ice decline. Our results indicate that the PNA pattern is important for projections of Arctic climate changes, and that greenhouse warming and the resultant persistent positive PNA trend is likely to increase Arctic sea-ice loss.
Structural resolution of switchable states of a de novo peptide assembly
Authors: Dawson William M. , Lang Eric J. M. , Rhys Guto G. , Shelley Kathryn L. , Williams Christopher , Brady R. Leo , Crump Matthew P. , Mulholland Adrian J. , Woolfson Derek N. 
Published: March 2021

AbstractDe novo protein design is advancing rapidly. However, most designs are for single states. Here we report a de novo designed peptide that forms multiple α-helical-bundle states that are accessible and interconvertible under the same conditions. Usually in such designs amphipathic α helices associate to form compact structures with consolidated hydrophobic cores. However, recent rational and computational designs have delivered open α-helical barrels with functionalisable cavities. By placing glycine judiciously in the helical interfaces of an α-helical barrel, we obtain both open and compact states in a single protein crystal. Molecular dynamics simulations indicate a free-energy landscape with multiple and interconverting states. Together, these findings suggest a frustrated system in which steric interactions that maintain the open barrel and the hydrophobic effect that drives complete collapse are traded-off. Indeed, addition of a hydrophobic co-solvent that can bind within the barrel affects the switch between the states both in silico and experimentally.