bluuebunny/crossref_metadata_2025 huggingface dataset:
Hopeful universalism
Authors: REA MICHAEL
Published: October 2020

This article argues against the rationality of ‘hopeful universalism’, the components of which include theunconditional considered hopethat soteriological universalism is true, and an absence of belief that it is true. Some proponents maintain that there is simply not enough evidence to affirm or deny universalism; others believe that it is probably false but nonetheless hope they are mistaken. This article argues that worshippers of God who maintain unconditional considered hope in the truth of universalism ought either to believe universalism or seek to abandon their hope in its truth, depending (in part) on how their confidence in the considerations that steer them away from universalism measure up against the beliefs that underwrite their hope in its truth. For such people, neither withholding belief in universalism nor believing that it is false while continuing to hope that it is true is a rational option.
Complexity, resources and text borrowing in state legislatures
Authors: Hansen Eric R. , Jansa Joshua M.
Published: October 2020

Do states copy or reinvent language from complex policies as they diffuse, and does this depend on legislative resources? We argue that states will more frequently reinvent more complex policies, but that states with high-resource legislatures will reinvent more than their low-resource counterparts for more complex policies. We test the theory using the bill texts from 18 policies that diffused across the 50 states from 1983 to 2014, measuring reinvention and complexity using text analysis tools. In line with expectations, we find that complex policies are reinvented more than simple policies and that high-resource legislatures reinvent bills more than low-resource legislatures on average. However, we also find that low-resource legislatures reinvent complex policies at about the same rate as high-resource legislatures. The results indicate that even legislatures with limited resources work to adapt complex policies during the diffusion process.
Thin-layer solutions of the Helmholtz equation
Authors: OCKENDON J. R. , TEW R. H.
Published: October 2020

This paper gives a brief overview of some configurations in which high-frequency wave propagation modelled by Helmholtz equation gives rise to solutions that vary rapidly across thin layers. The configurations are grouped according to their mathematical structure and tractability and one of them concerns a famous open problem of mathematical physics.
Rapid right ventricular pacing for balloon aortic valvuloplasty: expanding its routine use in neonates and infants
Authors: Mylonas Konstantinos S. , Kavvouras Charalampos , Karouli Panagiota , Avramidis Dimosthenis , Papagiannis Ioannis , Anderson David , Mitropoulos Fotios , Tzifa Aphrodite
Published: October 2020

Objective:

Rapid right ventricular pacing during balloon aortic valvuloplasty is commonly used to achieve balloon stability in children and adults. There is no consensus for the use of the technique in neonates and infants. We sought to review our institutional experience with rapid right ventricular pacing-assisted balloon aortic valvuloplasty across all age groups and evaluate the safety and effectiveness of the technique in the sub-group of neonates and infants <12months.

Methods:

Retrospective study between February, 2011 and February, 2020.

Results:

A total of 37 patients (Group I: 21 neonates/infants <12months and Group II: 16 children 12 months–16 years) were analysed. Catheter-measured left ventricular to aortic gradient reduced from median of 66 mmHg (with a range from 30 to 125 mmHg) to 14 mmHg (with a range from 5 to 44 mmHg) in Group I and 44 mmHg (with a range from 28 to 93 mmHg) to 18 mmHg (with a range from 2 to 65 mmHg) in Group II (p < 0.001). Procedure and fluoroscopy times were identical in the two groups. Balloon:annulus ratio was 0.94 and 0.88 in Groups I and II, respectively. Freedom from reintervention was 100% for Group I at a median time of 3.2 years and 81% at 2.7 years for Group II. Reinterventions in Group II (3/16 pts) were performed predominantly for complex left ventricular outflow tract stenosis. At follow-up echocardiogram, 45% of patients in Group I had no aortic regurgitation, 30% trace-mild, 20% mild-moderate, and 5% moderate aortic regurgitation, whereas in Group II, 50% of patients had no aortic regurgitation, 32% had mild aortic regurgitation, and 18% mild-moderate aortic regurgitation. Unicuspid valves were only encountered in Group 1 (2/21 pts, 10%) and they were predictive of mild-aortic regurgitation during follow-up (p = 0.003). Ventricular fibrillation occurred in three neonates with suspicion of myocardial ischemia on the pre-procedure echocardiogram. All were successfully defibrillated.

Conclusions:

Rapid right ventricular pacing can be expanded in neonates and infants to potentially decrease the incidence of aortic regurgitation and reintervention rates, hence avoiding high-risk surgical bail-out procedures for severe aortic regurgitation in the first year of life. Myocardial ischemia may predispose to ventricular dysrhythmias during rapid right ventricular pacing.
TRUE NATURALISM, GOODNESS, AND GOD
Authors: Ellis Fiona
Published: October 2020

I defend a form of naturalism which has much in common with Iris Murdoch's ‘true naturalism’, but I argue that it can accommodate God. I consider what it could mean for naturalism to be theistic in this sense, and respond to the charge that it leaves no room for the transcendent.
Deep Tectonics in the Eastern Hellenides Uncovered: The Record of Variscan Continental Amalgamation, Permo‐Triassic Rifting, and Early Alpine Collision in Pre‐Variscan Continental Crust in the W‐Rhodope (Vertiscos‐Ograzden Complex, N‐Greece)
Authors: Mposkos Evripidis , Krohe Alexander , Baziotis Ioannis
Published: October 2020

The Vertiskos‐Ograzden metamorphic complex (VOC; W‐Rhodope Metamorphic Domain, RMD) is a key area for reconstructing the geodynamic history of the Hellenides. We distinguish four metamorphic events: (1) an (U)HP eclogite facies metamorphism, succeeded by partial melting during decompression, amphibolite facies reequilibration in the kyanite stability field, and injection of muscovite pegmatites; (2) a LP‐HT event, associated with partial melting within the stability field of sillimanite, cordierite, and K‐feldspar (andalusite at subsolidus conditions) and magmatic intrusions; (3) a prograde moderate high‐pressure (MHP) metamorphism within the kyanite stability field increasing to the NE from epidote amphibolite to upper amphibolite facies; and (4) in the easternmost VOC, a LP amphibolite facies event (new cordierite and andalusite). Considering existing geochronological data, the VOC formed part of successive tectonic settings: (1) the “Variscan” collision zone between “East‐Avalonian” and Armorican continental fragments; (2) the Triassic middle crust of a continental rift zone, (leading to formation of oceanic crust, in the eastern VOC); (3) late Jurassic‐early Cretaceous closure of the oceanic basin and accretion of the VOC to southern European margin and northeastward polarity of subduction/collision; (4) late Cretaceous extension and crustal thinning. Then, subduction of the Neo‐Tethys and Apulian plate underneath Europe occurred, and the VOC plus the upper units of the RMD were part of the upper (European) plate. Large‐scale north dipping low‐angle normal detachments exhumed the VOC from the vicinity of a magmatic arc presently situated in the north RMD and Sredna Gora and Strandja zones and drag it into its present position.
Spreadsheet Tools for Quantifying Seepage Flux Across the GW‐SW Interface
Authors: Ford R. G. , Lien B. K. , Acree S. D. , Ross R. R.
Published: October 2020

Identifying the spatial distribution and magnitude of seepage flux across the groundwater‐surface water (GW‐SW) interface is critical for assessing potential impairments and restoration alternatives for water bodies adjacent to sites with groundwater contamination. Measurement of the vertical distribution and time‐varying characteristics of temperature in sediments provides an indirect way to map out spatial and temporal patterns of seepage flux into surface water. Two spreadsheet‐based calculation tools are introduced that implement four one‐dimensional analytical solutions to calculate the magnitude and direction of seepage flux based on measurement of steady‐state vertical temperature profiles or transient diel temperature signals at two depths within sediment. Performance of these calculation tools is demonstrated for a pond receiving contaminated groundwater discharge from an adjacent landfill. Transient versus steady‐state model performance is compared, and limitations of transient models are illustrated for a situation with unfavorable sediment characteristics and inadequate sensor spacing. The availability of a range of analytical solutions implemented within Microsoft Excel® is intended to encourage practitioners to explore use of this seepage flux characterization method and develop greater insight into best practices for model selection and use.
Air Quality Response in China Linked to the 2019 Novel Coronavirus (COVID‐19) Lockdown
Authors: Miyazaki K. , Bowman K. , Sekiya T. , Jiang Z. , Chen X. , Eskes H. , Ru M. , Zhang Y. , Shindell D.
Published: October 2020

Efforts to stem the spread of COVID‐19 in China hinged on severe restrictions to human movement starting 23 January 2020 in Wuhan and subsequently to other provinces. Here, we quantify the ancillary impacts on air pollution and human health using inverse emissions estimates based on multiple satellite observations. We find that Chinese NOx emissions were reduced by 36% from early January to mid‐February, with more than 80% of reductions occurring after their respective lockdown in most provinces. The reduced precursor emissions increased surface ozone by up to 16 ppb over northern China but decreased PM2.5 by up to 23 μg m−3 nationwide. Changes in human exposure are associated with about 2,100 more ozone‐related and at least 60,000 fewer PM2.5‐related morbidity incidences, primarily from asthma cases, thereby augmenting efforts to reduce hospital admissions and alleviate negative impacts from potential delayed treatments.
Continental Interior and Edge Breakup at Convergent Margins Induced by Subduction Direction Reversal: A Numerical Modeling Study Applied to the South China Sea Margin
Authors: Li Fucheng , Sun Zhen , Yang Hongfeng , Lin Jian , Stock Joann M. , Zhao Zhongxian , Xu Hehua , Sun Longtao
Published: October 2020

The dynamics of continental breakup at convergent margins has been described as the results of backarc opening caused by slab rollback or drag force induced by subduction direction reversal. Although the rollback hypothesis has been intensively studied, our understanding of the consequence of subduction direction reversal remains limited. Using thermo‐mechanical modeling based on constraints from the South China Sea (SCS) region, we investigate how subduction direction reversal controls the breakup of convergent margins. The numerical results show that two distinct breakup modes, namely, continental interior and edge breakup (“edge” refers to continent above the plate boundary interface), may develop depending on the “maturity” of the convergent margin and the age of the oceanic lithosphere. For a slab age of ~15 to ~45 Ma, increasing the duration of subduction promotes the continental interior breakup mode, where a large block of the continental material is separated from the overriding plate. In contrast, the continental edge breakup mode develops when the subduction is a short‐duration event, and in this mode, a wide zone of less continuous continental fragments and tearing of the subducted slab occur. These two modes are consistent with the interior (relic late Mesozoic arc) and edge (relic forearc) rifting characteristics in the western and eastern SCS margin, suggesting that variation in the northwest‐directed subduction duration of the Proto‐SCS might be a reason for the differential breakup locus along the strike of the SCS margin. Besides, a two‐segment trench associated with the northwest‐directed subduction is implied in the present‐day SCS region.
Seasonal Temperature Oscillations Drive Contrasting Arsenic and Antimony Mobilization in a Mining‐Impacted River System
Authors: Johnston Scott G. , Karimian Niloofar , Burton Edward D.
Published: October 2020

Arsenic (As) and antimony (Sb) speciation and mobility in river systems can be influenced by the redox conditions of benthic and hyporheic zone sediments. However, our understanding of how temperature fluctuations influence riverine As and Sb mobility over diel and seasonal time frames, via moderation of sediment redox conditions, is poorly constrained. Here we compare diel and seasonal water quality data from a river system contaminated with As and Sb with results from sediment‐water incubations conducted at temperatures spanning 8°C to 32°C under low‐dissolved oxygen conditions. Higher incubation temperatures caused faster microbial respiration, lower redox potential, and greater Asaq concentrations, coincident with reduction of As(V), Mn (III/IV), Fe (III), and SO42−. Initial rates of As3+aq formation increased exponentially with temperature (Q10 = 3.3 ± 0.5) and were positively correlated with microbial respiration (r2 = 0.99, P < 0.01). In contrast, Sbaq displayed an initially negative and comparatively weak overall temperature dependence during incubations. In river waters, diel mobilization of reduced species (As3+aq and Fe2+aq) and contrasting attenuation of Sb was coincident with lower redox potential during nightly respiration cycles. Distinct seasonal oscillations in river water Asaq were exponentially correlated with temperature (r2 = 0.68, P < 0.01), whereas Sbaq was not. These characteristics reflect the fundamental role of anaerobic metabolism (as influenced by temperature) within benthic and hyporheic zone sediments as a key driver of contrasting riverine As and Sb mobility. The findings imply that riverine As mobility may be enhanced, while Sb mobility possibly attenuated, by eutrophication or by elevated stream temperatures due to a warming climate.
Incoherent excess noise spectrally encodes broadband light sources
Authors: Kho Aaron M. , Zhang Tingwei , Zhu Jun , Merkle Conrad W. , Srinivasan Vivek J.
Published: October 2020

Across optics and photonics, excess intensity noise is often considered a liability. Here, we show that excess noise in broadband supercontinuum and superluminescent diode light sources encodes each spectral channel with unique intensity fluctuations, which actually serve a useful purpose. Specifically, we report that excess noise correlations can both characterize the spectral resolution of spectrometers and enable cross-calibration of their wavelengths across a broad bandwidth. Relative to previous methods that use broadband interferometry and narrow linewidth lasers to characterize and calibrate spectrometers, our approach is simple, comprehensive, and rapid enough to be deployed during spectrometer alignment. First, we employ this approach to aid alignment and reduce the depth-dependent degradation of the sensitivity and axial resolution in a spectrometer-based optical coherence tomography (OCT) system, revealing a new outer retinal band. Second, we achieve a pixel-to-pixel correspondence between two otherwise disparate spectrometers, enabling a robust comparison of their respective measurements. Thus, excess intensity noise has useful applications in optics and photonics.
The efficacy assessment of convalescent plasma therapy for COVID-19 patients: a multi-center case series
Authors: Zeng Hao , Wang Dongfang , Nie Jingmin , Liang Haoyu , Gu Jiang , Zhao Anne , Xu Lixin , Lang Chunhui , Cui Xiaoping , Guo Xiaolan , Zhou Changlong , Li Haibo , Guo Bin , Zhang Jinyong , Wang Qiang , Fang Li , Liu Wen , Huang Yishan , Mao Wei , Chen Yaokai , Zou Quanming
Published: October 2020

Convalescent plasma (CP) transfusion has been indicated as a promising therapy in the treatment for other emerging viral infections. However, the quality control of CP and individual variation in patients in different studies make it rather difficult to evaluate the efficacy and risk of CP therapy for coronavirus disease 2019 (COVID-19). We aimed to explore the potential efficacy of CP therapy, and to assess the possible factors associated with its efficacy. We enrolled eight critical or severe COVID-19 patients from four centers. Each patient was transfused with 200–400 mL of CP from seven recovered donors. The primary indicators for clinical efficacy assessment were the changes of clinical symptoms, laboratory parameters, and radiological image after CP transfusion. CP donors had a wide range of antibody levels measured by serology tests which were to some degree correlated with the neutralizing antibody (NAb) level. No adverse events were observed during and after CP transfusion. Following CP transfusion, six out of eight patients showed improved oxygen support status; chest CT indicated varying degrees of absorption of pulmonary lesions in six patients within 8 days; the viral load was decreased to a negative level in five patients who had the previous viremia; other laboratory parameters also tended to improve, including increased lymphocyte counts, decreased C-reactive protein, procalcitonin, and indicators for liver function. The clinical efficacy might be associated with CP transfusion time, transfused dose, and the NAb levels of CP. This study indicated that CP might be a potential therapy for severe patients with COVID-19.
Axial MRI biomarkers of spinal cord damage to predict future walking and motor function: a retrospective study
Authors: Smith Andrew C. , Albin Stephanie R. , O’Dell Denise R. , Berliner Jeffrey C. , Dungan David , Sevigny Mitch , Draganich Christina , Elliott James M. , Weber II Kenneth A.
Published: October 2020

Study design

Retrospective.

Objectives

Primary: to assess if axial damage ratios are predictors of future walking after spinal cord injury (SCI), and if they add any predictive value if initial neurological impairment grades are available. Secondary: to determine if lateral spinal cord regions are predictors of future lower extremity motor scores (LEMS).

Setting

University/hospital.

Methods

Axial T2-weighted MRIs were used. Axial damage ratios and non-damaged lateral cord volumes were calculated. Each participant answered at 1 year after SCI, “Are you able to walk for 150 feet? (45.72 meters)” For the secondary aim, right and left LEMS were used.

Results

In total, 145 participants were selected. Individuals that could walk had smaller ratios than those that were unable. Walking and axial damage ratios were negatively correlated. A 0.374 ratio cut-off showed optimal sensitivity/specificity. When initial neurological grades were used, axial damage ratios did not add predictive value. Forty-two participants had LEMS available and were included for the secondary aim. Right cord regions and right LEMS were positively correlated and left regions and left LEMS, but these variables were also correlated with each other.

Conclusions

Axial damage ratios were significant predictors of walking ability 1 year after SCI. However, this measure did not add predictive value over initial neurological grades. Lateral cord regions correlated with same-side LEMS, but the opposite was also found, calling this biomarker’s specificity into question. Axial damage ratios may be useful in predicting walking after SCI if initial neurological grades are unavailable.

Sponsorship

This research was funded by a National Institutes of Health award, National Institute of Child Health and Development—NIH R03HD094577.
What could we learn from SARS when facing the mental health issues related to the COVID-19 outbreak? A nationwide cohort study in Taiwan
Authors: Tzeng Nian-Sheng , Chung Chi-Hsiang , Chang Chuan-Chia , Chang Hsin-An , Kao Yu-Chen , Chang Shan-Yueh , Chien Wu-Chien
Published: October 2020

There were several studies about the psychiatric and mental health issues related to the severe adult respiratory syndrome (SARS) outbreak in 2003, however, the association between SARS and the overall risk of psychiatric disorders and suicides has, as yet, to be studied in Taiwan. The aim of this study is to examine as to whether SARS is associated with the risk of psychiatric disorders and suicide. A total of 285 patients with SARS and 2850 controls without SARS (1:10) matched for sex, age, insurance premium, comorbidities, residential regions, level of medical care, and index date were selected between February 25 and June 15, 2003 from the Inpatient Database Taiwan’s National Health Insurance Research Database. During the 12-year follow-up, in which 79 in the SARS cohort and 340 in the control group developed psychiatric disorders or suicide (4047.41 vs. 1535.32 per 100,000 person-years). Fine and Gray’s survival analysis revealed that the SARS cohort was associated with an increased risk of psychiatric disorders and suicide, and the adjusted subdistribution HR (sHR) was 2.805 (95% CI: 2.182–3.605, p < 0.001) for psychiatric disorders and suicide. The SARS cohort was associated with anxiety, depression, sleep disorders, posttraumatic stress disorder/acute stress disorder (PTSD/ASD), and suicide. The sensitivity analysis revealed that the SARS group was associated with anxiety, depression, sleep disorders, PTSD/ASD, and suicide after the individuals with a diagnosis of psychiatric disorders and suicide were excluded within the first year, and with anxiety, depression, and sleep disorders, while those in the first five years were excluded. In conclusion, SARS was associated with the increased risk of psychiatric disorders and suicide.
Intracellular amyloid toxicity induces oxytosis/ferroptosis regulated cell death
Authors: Huang Ling , McClatchy Daniel B. , Maher Pamela , Liang Zhibin , Diedrich Jolene K. , Soriano-Castell David , Goldberg Joshua , Shokhirev Maxim , Yates John R. , Schubert David , Currais Antonio
Published: October 2020

Amyloid beta (Aβ) accumulates within neurons in the brains of early stage Alzheimer’s disease (AD) patients. However, the mechanism underlying its toxicity remains unclear. Here, a triple omics approach was used to integrate transcriptomic, proteomic, and metabolomic data collected from a nerve cell model of the toxic intracellular aggregation of Aβ. It was found that intracellular Aβ induces profound changes in the omics landscape of nerve cells that are associated with a pro-inflammatory, metabolic reprogramming that predisposes cells to die via the oxytosis/ferroptosis regulated cell death pathway. Notably, the degenerative process included substantial alterations in glucose metabolism and mitochondrial bioenergetics. Our findings have implications for the understanding of the basic biology of proteotoxicity, aging, and AD as well as for the development of future therapeutic interventions designed to target the oxytosis/ferroptosis regulated cell death pathway in the AD brain.
Parthenolide promotes the repair of spinal cord injury by modulating M1/M2 polarization via the NF-κB and STAT 1/3 signaling pathway
Authors: Gaojian Tao , Dingfei Qian , Linwei Li , Xiaowei Wang , Zheng Zhou , Wei Liu , Tong Zhu , Benxiang Ning , Yanning Qian , Wei Zhou , Jian Chen
Published: October 2020

Spinal cord injury (SCI) is a severe neurological disease; however, there is no effective treatment for spinal cord injury. Neuroinflammation involves the activation of resident microglia and the infiltration of macrophages is the major pathogenesis of SCI secondary injury and considered to be the therapeutic target of SCI. Parthenolide (PN) has been reported to exert anti-inflammatory effects in fever, migraines, arthritis, and superficial inflammation; however, the role of PN in SCI therapeutics has not been clarified. In this study, we showed that PN could improve the functional recovery of spinal cord in mice as revealed by increased BMS scores and decreased cavity of spinal cord injury in vivo. Immunofluorescence staining experiments confirmed that PN could promote axonal regeneration, increase myelin reconstitution, reduce chondroitin sulfate formation, inhibit scar hyperplasia, suppress the activation of A1 neurotoxic reactive astrocytes and facilitate shift from M1 to M2 polarization of microglia/macrophages. To verify how PN exerts its effects on microglia/macrophages polarization, we performed the mechanism study in vitro in microglia cell line BV-2. PN could significantly reduce M1 polarization in BV2 cells and partially rescue the decrease in the expression of M2 phenotype markers of microglia/macrophage induced by LPS, but no significant effect on M2 polarization stimulated with IL-4 was observed. Further study demonstrated PN inhibited NF-κB signal pathway directly or indirectly, and suppressed activation of signal transducer and activator of transcription 1 or 3 (STAT1/3) via reducing the expression of HDAC1 and subsequently increasing the levels of STAT1/3 acetylation. Overall, our study illustrated that PN may be a promising strategy for traumatic SCI.
PAX6 missense variants in two families with isolated foveal hypoplasia and nystagmus: evidence of paternal postzygotic mosaicism
Authors: Lima Cunha Dulce , Owen Nicholas , Tailor Vijay , Corton Marta , Theodorou Maria , Moosajee Mariya
Published: October 2020

PAX6 is considered the master regulator of eye development, the majority of variants affecting this gene cause the pan-ocular developmental eye disorder aniridia. Although no genotype-phenotype correlations are clearly established, missense variants affecting the DNA-binding paired domain of PAX6 are usually associated with non-aniridia phenotypes like microphthalmia, coloboma or isolated foveal hypoplasia. In this study, we report two missense heterozygous variants in the paired domain of PAX6 resulting in isolated foveal hypoplasia with nystagmus in two independent families: c.112 C > G; p.(Arg38Gly) and c.214 G > C; p.(Gly72Arg) in exons 5 and 6, respectively. Furthermore, we provide evidence that paternal postzygotic mosaicism is the cause of inheritance, with clinically unaffected fathers and reduced affected allele fraction. This work contributes to increase the phenotypic spectrum caused by PAX6 variants, and to our knowledge, is the first report to describe the presence of postzygotic parental mosaicism causing isolated foveal hypoplasia with nystagmus. These results support the growing evidence that suggest an overestimation of sporadic cases with PAX6 variants, which has strong implications for both genetic counselling and family planning.
Magnesium in subaqueous speleothems as a potential palaeotemperature proxy
Authors: Drysdale Russell , Couchoud Isabelle , Zanchetta Giovanni , Isola Ilaria , Regattieri Eleonora , Hellstrom John , Govin Aline , Tzedakis Polychronis C. , Ireland Trevor , Corrick Ellen , Greig Alan , Wong Henri , Piccini Leonardo , Holden Peter , Woodhead Jon
Published: October 2020

Few palaeoclimate archives beyond the polar regions preserve continuous and datable palaeotemperature proxy time series over multiple glacial-interglacial cycles. This hampers efforts to develop a more coherent picture of global patterns of past temperatures. Here we show that Mg concentrations in a subaqueous speleothem from an Italian cave track regional sea-surface temperatures over the last 350,000 years. The Mg shows higher values during warm climate intervals and converse patterns during cold climate stages. In contrast to previous studies, this implicates temperature, not rainfall, as the principal driver of Mg variability. The depositional setting of the speleothem gives rise to Mg partition coefficients that are more temperature dependent than other calcites, enabling the effect of temperature change on Mg partitioning to greatly exceed the effects of changes in source-water Mg/Ca. Subaqueous speleothems from similar deep-cave environments should be capable of providing palaeotemperature information over multiple glacial-interglacial cycles.
Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study)
Authors: Zhang Yifei , Gu Yanyun , Ren Huahui , Wang Shujie , Zhong Huanzi , Zhao Xinjie , Ma Jing , Gu Xuejiang , Xue Yaoming , Huang Shan , Yang Jialin , Chen Li , Chen Gang , Qu Shen , Liang Jun , Qin Li , Huang Qin , Peng Yongde , Li Qi , Wang Xiaolin , Kong Ping , Hou Guixue , Gao Mengyu , Shi Zhun , Li Xuelin , Qiu Yixuan , Zou Yuanqiang , Yang Huanming , Wang Jian , Xu Guowang , Lai Shenghan , Li Junhua , Ning Guang , Wang Weiqing
Published: October 2020

Human gut microbiome is a promising target for managing type 2 diabetes (T2D). Measures altering gut microbiota like oral intake of probiotics or berberine (BBR), a bacteriostatic agent, merit metabolic homoeostasis. We hence conducted a randomized, double-blind, placebo-controlled trial with newly diagnosed T2D patients from 20 centres in China. Four-hundred-nine eligible participants were enroled, randomly assigned (1:1:1:1) and completed a 12-week treatment of either BBR-alone, probiotics+BBR, probiotics-alone, or placebo, after a one-week run-in of gentamycin pretreatment. The changes in glycated haemoglobin, as the primary outcome, in the probiotics+BBR (least-squares mean [95% CI], −1.04[−1.19, −0.89]%) and BBR-alone group (−0.99[−1.16, −0.83]%) were significantly greater than that in the placebo and probiotics-alone groups (−0.59[−0.75, −0.44]%, −0.53[−0.68, −0.37]%, P < 0.001). BBR treatment induced more gastrointestinal side effects. Further metagenomics and metabolomic studies found that the hypoglycaemic effect of BBR is mediated by the inhibition of DCA biotransformation by Ruminococcus bromii. Therefore, our study reports a human microbial related mechanism underlying the antidiabetic effect of BBR on T2D. (Clinicaltrial.gov Identifier: NCT02861261).
High-latitude biomes and rock weathering mediate climate–carbon cycle feedbacks on eccentricity timescales
Authors: De Vleeschouwer David , Drury Anna Joy , Vahlenkamp Maximilian , Rochholz Fiona , Liebrand Diederik , Pälike Heiko
Published: October 2020

The International Ocean Discovery Programme (IODP) and its predecessors generated a treasure trove of Cenozoic climate and carbon cycle dynamics. Yet, it remains unclear how climate and carbon cycle interacted under changing geologic boundary conditions. Here, we present the carbon isotope (δ13C) megasplice, documenting deep-ocean δ13C evolution since 35 million years ago (Ma). We juxtapose the δ13C megasplice with its δ18O counterpart and determine their phase-difference on ~100-kyr eccentricity timescales. This analysis reveals that 2.4-Myr eccentricity cycles modulate the δ13C-δ18O phase relationship throughout the Oligo-Miocene (34-6 Ma), potentially through changes in continental weathering. At 6 Ma, a striking switch from in-phase to anti-phase behaviour occurs, signalling a reorganization of the climate-carbon cycle system. We hypothesize that this transition is consistent with Arctic cooling: Prior to 6 Ma, low-latitude continental carbon reservoirs expanded during astronomically-forced cool spells. After 6 Ma, however, continental carbon reservoirs contract rather than expand during cold periods due to competing effects between Arctic biomes (ice, tundra, taiga). We conclude that, on geologic timescales, System Earth experienced state-dependent modes of climate–carbon cycle interaction.
Mechanism and evolution of the Zn-fingernail required for interaction of VARP with VPS29
Authors: Crawley-Snowdon Harriet , Yang Ji-Chun , Zaccai Nathan R. , Davis Luther J. , Wartosch Lena , Herman Emily K. , Bright Nicholas A. , Swarbrick James S. , Collins Brett M. , Jackson Lauren P. , Seaman Matthew N. J. , Luzio J. Paul , Dacks Joel B. , Neuhaus David , Owen David J.
Published: October 2020

VARP and TBC1D5 are accessory/regulatory proteins of retromer-mediated retrograde trafficking from endosomes. Using an NMR/X-ray approach, we determined the structure of the complex between retromer subunit VPS29 and a 12 residue, four-cysteine/Zn++ microdomain, which we term a Zn-fingernail, two of which are present in VARP. Mutations that abolish VPS29:VARP binding inhibit trafficking from endosomes to the cell surface. We show that VARP and TBC1D5 bind the same site on VPS29 and can compete for binding VPS29 in vivo. The relative disposition of VPS29s in hetero-hexameric, membrane-attached, retromer arches indicates that VARP will prefer binding to assembled retromer coats through simultaneous binding of two VPS29s. The TBC1D5:VPS29 interaction is over one billion years old but the Zn-fingernail appears only in VARP homologues in the lineage directly giving rise to animals at which point the retromer/VARP/TBC1D5 regulatory network became fully established.
Temperature variability implies greater economic damages from climate change
Authors: Calel Raphael , Chapman Sandra C. , Stainforth David A. , Watkins Nicholas W.
Published: October 2020

A number of influential assessments of the economic cost of climate change rely on just a small number of coupled climate–economy models. A central feature of these assessments is their accounting of the economic cost of epistemic uncertainty—that part of our uncertainty stemming from our inability to precisely estimate key model parameters, such as the Equilibrium Climate Sensitivity. However, these models fail to account for the cost of aleatory uncertainty—the irreducible uncertainty that remains even when the true parameter values are known. We show how to account for this second source of uncertainty in a physically well-founded and tractable way, and we demonstrate that even modest variability implies trillions of dollars of previously unaccounted for economic damages.
Millisecond dynamics of an unlabeled amino acid transporter
Authors: Matin Tina R. , Heath George R. , Huysmans Gerard H. M. , Boudker Olga , Scheuring Simon
Published: October 2020

Excitatory amino acid transporters (EAATs) are important in many physiological processes and crucial for the removal of excitatory amino acids from the synaptic cleft. Here, we develop and apply high-speed atomic force microscopy line-scanning (HS-AFM-LS) combined with automated state assignment and transition analysis for the determination of transport dynamics of unlabeled membrane-reconstituted GltPh, a prokaryotic EAAT homologue, with millisecond temporal resolution. We find that GltPh transporters can operate much faster than previously reported, with state dwell-times in the 50 ms range, and report the kinetics of an intermediate transport state with height between the outward- and inward-facing states. Transport domains stochastically probe transmembrane motion, and reversible unsuccessful excursions to the intermediate state occur. The presented approach and analysis methodology are generally applicable to study transporter kinetics at system-relevant temporal resolution.
A system-level approach identifies HIF-2α as a critical regulator of chondrosarcoma progression
Authors: Kim Hyeonkyeong , Cho Yongsik , Kim Hyeon-Seop , Kang Donghyun , Cheon Donghyeon , Kim Yi-Jun , Chang Moon Jong , Lee Kyoung Min , Chang Chong Bum , Kang Seung-Baik , Kang Hyun Guy , Kim Jin-Hong
Published: October 2020

Chondrosarcomas, malignant cartilaginous neoplasms, are capable of transitioning to highly aggressive, metastatic, and treatment-refractory states, resulting in significant patient mortality. Here, we aim to uncover the transcriptional program directing such tumor progression in chondrosarcomas. We conduct weighted correlation network analysis to extract a characteristic gene module underlying chondrosarcoma malignancy. Hypoxia-inducible factor-2α (HIF-2α, encoded by EPAS1) is identified as an upstream regulator that governs the malignancy gene module. HIF-2α is upregulated in high-grade chondrosarcoma biopsies and EPAS1 gene amplification is associated with poor prognosis in chondrosarcoma patients. Using tumor xenograft mouse models, we demonstrate that HIF-2α confers chondrosarcomas the capacities required for tumor growth, local invasion, and metastasis. Meanwhile, pharmacological inhibition of HIF-2α, in conjunction with the chemotherapy agents, synergistically enhances chondrosarcoma cell apoptosis and abolishes malignant signatures of chondrosarcoma in mice. We expect that our insights into the pathogenesis of chondrosarcoma will provide guidelines for the development of molecular targeted therapeutics for chondrosarcoma.
Protease circuits for processing biological information
Authors: Holt Brandon Alexander , Kwong Gabriel A.
Published: October 2020

Engineered biocircuits designed with biological components have the capacity to expand and augment living functions. Here we demonstrate that proteases can be integrated into digital or analog biocircuits to process biological information. We first construct peptide-caged liposomes that treat protease activity as two-valued (i.e., signal is 0 or 1) operations to construct the biological equivalent of Boolean logic gates, comparators and analog-to-digital converters. We use these modules to assemble a cell-free biocircuit that can combine with bacteria-containing blood, quantify bacteria burden, and then calculate and unlock a selective drug dose. By contrast, we treat protease activity as multi-valued (i.e., signal is between 0 and 1) by controlling the degree to which a pool of enzymes is shared between two target substrates. We perform operations on these analog values by manipulating substrate concentrations and combine these operations to solve the mathematical problem Learning Parity with Noise (LPN). These results show that protease activity can be used to process biological information by binary Boolean logic, or as multi-valued analog signals under conditions where substrate resources are shared.
The Rho-GEF PIX-1 directs assembly or stability of lateral attachment structures between muscle cells
Authors: Moody Jasmine C. , Qadota Hiroshi , Reedy April R. , Okafor C. Denise , Shanmugan Niveda , Matsunaga Yohei , Christian Courtney J. , Ortlund Eric A. , Benian Guy M.
Published: October 2020

PIX proteins are guanine nucleotide exchange factors (GEFs) that activate Rac and Cdc42, and are known to have numerous functions in various cell types. Here, we show that a PIX protein has an important function in muscle. From a genetic screen in C. elegans, we found that pix-1 is required for the assembly of integrin adhesion complexes (IACs) at borders between muscle cells, and is required for locomotion of the animal. A pix-1 null mutant has a reduced level of activated Rac in muscle. PIX-1 localizes to IACs at muscle cell boundaries, M-lines and dense bodies. Mutations in genes encoding proteins at known steps of the PIX signaling pathway show defects at muscle cell boundaries. A missense mutation in a highly conserved residue in the RacGEF domain results in normal levels of PIX-1 protein, but a reduced level of activated Rac in muscle, and abnormal IACs at muscle cell boundaries.
Magic-angle semimetals
Authors: Fu Yixing , König Elio J. , Wilson Justin H. , Chou Yang-Zhi , Pixley Jedediah H.
Published: October 2020

Breakthroughs in two-dimensional van der Waals heterostructures have revealed that twisting creates a moiré pattern that quenches the kinetic energy of electrons, allowing for exotic many-body states. We show that cold atomic, trapped ion, and metamaterial systems can emulate the effects of a twist in many models from one to three dimensions. Further, we demonstrate at larger angles (and argue at smaller angles) that by considering incommensurate effects, the magic-angle effect becomes a single-particle quantum phase transition (including in a model for twisted bilayer graphene in the chiral limit). We call these models “magic-angle semimetals”. Each contains nodes in the band structure and an incommensurate modulation. At magic-angle criticality, we report a nonanalytic density of states, flat bands, multifractal wave functions that Anderson delocalize in momentum space, and an essentially divergent effective interaction scale. As a particular example, we discuss how to observe this effect in an ultracold Fermi gas.
Unexpected differences between surface and bulk spectroscopic and implied Kondo properties of heavy fermion CeRh2Si2
Authors: Poelchen Georg , Schulz Susanne , Mende Max , Güttler Monika , Generalov Alexander , Fedorov Alexander V. , Caroca-Canales Nubia , Geibel Christoph , Kliemt Kristin , Krellner Cornelius , Danzenbächer Steffen , Usachov Dmitry Yu. , Dudin Pavel , Antonov Victor N. , Allen James W. , Laubschat Clemens , Kummer Kurt , Kucherenko Yuri , Vyalikh Denis V.
Published: October 2020

Ultra-violet angle-resolved photoemission spectroscopy (UV-ARPES) was used to explore the temperature dependence of the Ce-4f spectral responses for surface and bulk in the antiferromagnetic Kondo lattice CeRh2Si2. Spectra were taken from Ce- and Si-terminated surfaces in a wide temperature range, and reveal characteristic 4f patterns for weakly (surface) and strongly (bulk) hybridized Ce, respectively. The temperature dependence of the Fermi level peak differs strongly for both cases implying that the effective Kondo temperature at the surface and bulk can be rather distinct. The greatly reduced crystal–electric-field (CEF) splitting at the surface gives reason to believe that the surface may exhibit a larger effective Kondo temperature because of a higher local-moment effective degeneracy. Further, the hybridization processes could strongly affect the 4f peak intensity at the Fermi level. We derived the k-resolved dispersion of the Kondo peak which is also found to be distinct due to different sets of itinerant bands to which the 4f states of surface and bulk Ce are coupled. Overall our study brings into reach the ultimate goal of quantitatively testing many-body theories that link spectroscopy and transport properties, for both the bulk and the surface, separately. It also allows for a direct insight into the broader problem of Kondo lattices with two different local-moment sublattices, providing some understanding of why the cross-talking between the two Kondo effects is weak.
Author Correction: Rapid dose-dependent Natural Killer (NK) cell modulation and cytokine responses following human rVSV-ZEBOV Ebolavirus vaccination
Authors: Pejoski David , de Rham Casimir , Martinez-Murillo Paola , Santoro Francesco , Auderset Floriane , Medaglini Donata , Pozzi Gianni , Vono Maria , Lambert Paul-Henri , Huttner Angela , Haks Mariëlle C. , Ottenhoff Tom H. M. , Villard Jean , Siegrist Claire-Anne ,   the VEBCON Consortium, Addo Marylyn M. , Agnandji Selidji Todagbe , Becker Stephan , Bejon Philip , Brosnahan Jessica S. , Fast Patricia , Huttner Angela , Krähling Verena , Kieny Marie-Paule , Kremsner Peter G. , Krishna Sanjeev , Lapujade Olivier , Moorthy Vasee , Njuguna Patricia , Savarese Barbara , Siegrist Claire-Anne ,   VSV-EBOVAC Consortium, Agnandji Selidji Todagbe , Ahmed Rafi , Anderson Jenna , Auderset Floriane , Bejon Philip , Borgianni Luisa , Brosnahan Jessica S. , Ciabattini Annalisa , Engler Olivier , Haks Mariëlle C. , Harandi Ali M. , Heppner Donald Gray , Gerlini Alice , Huttner Angela , Kremsner Peter G. , Martinez-Murillo Paola , Medaglini Donata , Monath Thomas , Ndungu Francis , Njuguna Patricia , Ottenhoff Tom H. M. , Page Mark , Pejoski David , Pozzi Gianni , Santoro Francesco , Siegrist Claire-Anne ,   VSV-EBOPLUS Consortium, Agnandji Selidji Todagbe , Anderson Jenna , Auderset Floriane , Borgianni Luisa , Ciabattini Annalisa , Dubey Sheri , Engler Olivier , Fernandes José F. , Haks Mariëlle C. , Harandi Ali M. , Gerlini Alice , Huttner Angela , Kremsner Peter G. , Martinez-Murillo Paola , Medaglini Donata , Monath Thomas , Nakaya Helder , O’Rourke Fiona , Ottenhoff Tom H. M. , Pejoski David , Pozzi Gianni , Rothenberger Sylvia , Santoro Francesco , Siegrist Claire-Anne
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A novel speculum-free imaging strategy for visualization of the internal female lower reproductive system
Authors: Asiedu Mercy N. , Agudogo Júlia S. , Dotson Mary E. , Skerrett Erica , Krieger Marlee S. , Lam Christopher T. , Agyei Doris , Amewu Juliet , Asah-Opoku Kwaku , Huchko Megan , Schmitt John W. , Samba Ali , Srofenyoh Emmanuel , Ramanujam Nirmala
Published: October 2020

Fear of the speculum and feelings of vulnerability during the gynecologic exams are two of the biggest barriers to cervical cancer screening for women. To address these barriers, we have developed a novel, low-cost tool called the Callascope to reimagine the gynecological exam, enabling clinician and self-imaging of the cervix without the need for a speculum. The Callascope contains a 2 megapixel camera and contrast agent spray mechanism housed within a form factor designed to eliminate the need for a speculum during contrast agent administration and image capture. Preliminary bench testing for comparison of the Callascope camera to a $20,000 high-end colposcope demonstrated that the Callascope camera meets visual requirements for cervical imaging. Bench testing of the spray mechanism demonstrates that the contrast agent delivery enables satisfactory administration and cervix coverage. Clinical studies performed at Duke University Medical Center, Durham, USA and in Greater Accra Regional Hospital, Accra, Ghana assessed (1) the Callascope’s ability to visualize the cervix compared to the standard-of-care speculum exam, (2) the feasibility and willingness of women to use the Callascope for self-exams, and (3) the feasibility and willingness of clinicians and their patients to use the Callascope for clinician-based examinations. Cervix visualization was comparable between the Callascope and speculum (83% or 44/53 women vs. 100%) when performed by a clinician. Visualization was achieved in 95% (21/22) of women who used the Callascope for self-imaging. Post-exam surveys indicated that participants preferred the Callascope to a speculum-based exam. Our results indicate the Callascope is a viable option for clinician-based and self-exam speculum-free cervical imaging.

Clinical study registration ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/record/ NCT00900575, Pan African Clinical Trial Registry (PACTR) https://www.pactr.org/ PACTR201905806116817.
Spatial and temporal variations of air pollution over 41 cities of India during the COVID-19 lockdown period
Authors: Vadrevu Krishna Prasad , Eaturu Aditya , Biswas Sumalika , Lasko Kristofer , Sahu Saroj , Garg J. K. , Justice Chris
Published: October 2020

In this study, we characterize the impacts of COVID-19 on air pollution using NO2 and Aerosol Optical Depth (AOD) from TROPOMI and MODIS satellite datasets for 41 cities in India. Specifically, our results suggested a 13% NO2 reduction during the lockdown (March 25–May 3rd, 2020) compared to the pre-lockdown (January 1st–March 24th, 2020) period. Also, a 19% reduction in NO2 was observed during the 2020-lockdown as compared to the same period during 2019. The top cities where NO2 reduction occurred were New Delhi (61.74%), Delhi (60.37%), Bangalore (48.25%), Ahmedabad (46.20%), Nagpur (46.13%), Gandhinagar (45.64) and Mumbai (43.08%) with less reduction in coastal cities. The temporal analysis revealed a progressive decrease in NO2 for all seven cities during the 2020 lockdown period. Results also suggested spatial differences, i.e., as the distance from the city center increased, the NO2 levels decreased exponentially. In contrast, to the decreased NO2 observed for most of the cities, we observed an increase in NO2 for cities in Northeast India during the 2020 lockdown period and attribute it to vegetation fires. The NO2 temporal patterns matched the AOD signal; however, the correlations were poor. Overall, our results highlight COVID-19 impacts on NO2, and the results can inform pollution mitigation efforts across different cities of India.