bluuebunny/crossref_metadata_2025 huggingface dataset:
Conductivities of Titan's Dusty Ionosphere
Authors: Shebanits O. , Wahlund J.‐E. , Waite J. H. , Dougherty M. K.
Published: January 2022

Titan's ionosphere hosts a globally distributed non‐trivial dusty ion‐ion plasma, providing an environment for studies of dusty ionospheres that is in many aspects unique in our solar system. Thanks to the Cassini mission, Titan's ionosphere also features one of the largest dusty plasma data sets from 126 flybys of the moon over 13 years, from 2004 to 2017. Recent studies have shown that negatively charged dust dramatically alters the electric properties of plasmas, in particular planetary ionospheres. Utilizing the full plasma content of the moon's ionosphere (electrons, positive ions, and negative ions/dust grains), we derive the electric conductivities and define the conductive dynamo region. Our results show that using the full plasma content increases the Pedersen conductivities at ∼1,100–1,200 km altitude by up to 35% compared to the estimates using only electron densities. The Hall conductivities are in general not affected but several cases indicate a reverse Hall effect at ∼900 km altitude (closest approach) and below. The dayside conductivities are shown to be factor ∼7–9 larger than on the nightside, owing to higher dayside plasma densities.
Ongoing Asthenospheric Upwelling and Delamination‐Style Down‐Welling Beneath Northeast China: Evidence From High‐Resolution Magnetotelluric Profiles
Authors: Ye Gaofeng , Xia Zhiheng , Unsworth Martyn , Wei Wenbo , Jin Sheng , Liu Zhilong
Published: January 2022

Northeast China was formed during the progressive closure of the Paleo‐Asian Ocean before the Early Mesozoic, and was then later affected by the westward subduction of the Paleo‐Pacific Plate and the west‐to‐east closure of the Mongolia‐Okhotsk Ocean. Huge volumes of granites were emplaced across this region during the Mesozoic, and widespread Cenozoic volcanism is still active in the Quaternary. To study past and present magmatic processes in this region, two parallel high‐resolution magnetotelluric profiles were collected to produce lithospheric resistivity models. Northwest of the Greater Xing'an Range, the lithosphere has a relatively low resistivity. The resistivity of the upper mantle low‐resistivity anomaly (C2) is consistent with the presence of a few percent of basaltic melt. This feature connects with a shallower low‐resistivity zone (C1) that extends into the crust. Its properties are consistent with 5–10% shoshonitic melt. The lithosphere in the southeast part is highly resistive. The upper mantle high‐resistivity zones (R1 and R2) are interpreted as regions of thickened lithosphere that may be undergoing delamination. The lower crust exhibits localized low‐resistivity zones (C3, C4, and C5), and they are interpreted as partial melt which may have originated in the ongoing upwelling. The overall pattern of magmatism appears to be driven by asthenosphere upwelling which might have been triggered by the Paleo‐Pacific Plate retreat, but the upper mantle low‐resistivity zone originates and rises from the northwest. Down‐welling in the southeast might be the combined effect of the subduction and retreat of the Paleo‐Pacific Plate and the instability of thickened lithosphere.
Evaluation of a Reanalysis‐Driven Configuration of WRF4 Over the Western United States From 1980 to 2020
Authors: Rahimi Stefan , Krantz Will , Lin Yen‐Heng , Bass Benjamin , Goldenson Naomi , Hall Alex , Lebo Zachary J. , Norris Jesse
Published: January 2022

Dynamical downscaling remains a powerful tool for studying regional climate processes, and the genesis of high‐resolution historical and future climate data. This technique is particularly important over areas of complex terrain, such as the western United States (WUS), where global models are especially limited in representing regional climate. After identifying a suite of WRF options that best simulate snow and precipitation for an average water year (2010) over the WUS, we evaluate the performance of the dynamically downscaled European Centre for Medium‐range Weather Forecasting's fifth Reanalysis (ERA5) from 1980 to 2020 on 45‐km, 9‐km, and two 3‐km grids. We find that by decreasing the horizontal grid spacing within WRF, improvements to Sierra Nevada and Northern Rocky Mountain snow, Santa Ana and Diablo winds, and coastal meteorology occur. For landfalling atmospheric rivers (ARs), the downscaled reanalysis simulates greater upstream integrated vapor transport (IVT) than ERA5. However, WRF skillfully simulates the positioning of the IVT and the timing and magnitude of AR precipitation. This potential IVT bias, in conjunction with increasing resolution, leads to a wet precipitation bias across the Sierra Nevada in the 3‐km experiment. This conclusion is supported by streamflow analysis, although we note that the bias in the 3‐km experiment can also be explained by in situ undercatch issues. Meanwhile, the 9‐km experiment is more biased than the 3‐km experiment across the Northern Rocky Mountains compared to in situ measured SWE and precipitation, indicating a geographic sensitivity to biases.
A New Standalone Tool for DC‐Equivalent Network Generation and GIC Calculation in Power Grids With Multiple Voltage Levels
Authors: Marsal S. , Torta J. M. , Canillas‐Pérez V. , Curto J. J.
Published: January 2022

Space Weather phenomena pose a major socio‐economic threat due, in part, to the vulnerability of power network transformers to geomagnetically induced currents (GIC). In 1985, Lehtinen and Pirjola (LP) provided a method to calculate GICs in a single‐voltage‐level network. The need to account for lower voltages has caused the proliferation of GIC risk assessments applied to power grids with multiple voltages. We hereby present a tool to systematically generate the direct currents (DC)‐equivalent of a multiple‐voltage‐level network. The LP and Nodal Admittance Matrix methods are the most popular schemes to compute the GIC from the resulting equivalent network by solving the circuit laws for the earthing current or the voltage at each node, respectively. A new scheme is presented here that solves the circuit laws for the current flowing between the bus nodes and the neutral point which, unlike LP, requires no (infinite‐resistance) earth connections for the buses. The number of equations/unknowns of the resulting GIC matrix equation is reduced compared to the traditional methods, thus optimizing the computational cost ‐an advantage that becomes important for large networks‐, while keeping a good condition of the design matrix associated with the inversion. Examples are shown for different test cases and a standalone computationally efficient code is provided.
Cerebellar connectivity maps embody individual adaptive behavior in mice
Authors: Spaeth Ludovic , Bahuguna Jyotika , Gagneux Theo , Dorgans Kevin , Sugihara Izumi , Poulain Bernard , Battaglia Demian , Isope Philippe
Published: January 2022

The cerebellar cortex encodes sensorimotor adaptation during skilled locomotor behaviors, however the precise relationship between synaptic connectivity and behavior is unclear. We studied synaptic connectivity between granule cells (GCs) and Purkinje cells (PCs) in murine acute cerebellar slices using photostimulation of caged glutamate combined with patch-clamp in developing or after mice adapted to different locomotor contexts. By translating individual maps into graph network entities, we found that synaptic maps in juvenile animals undergo critical period characterized by dissolution of their structure followed by the re-establishment of a patchy functional organization in adults. Although, in adapted mice, subdivisions in anatomical microzones do not fully account for the observed spatial map organization in relation to behavior, we can discriminate locomotor contexts with high accuracy. We also demonstrate that the variability observed in connectivity maps directly accounts for motor behavior traits at the individual level. Our findings suggest that, beyond general motor contexts, GC-PC networks also encode internal models underlying individual-specific motor adaptation.
Manipulation of current rectification in van der Waals ferroionic CuInP2S6
Authors: Jiang Xingan , Wang Xueyun , Wang Xiaolei , Zhang Xiangping , Niu Ruirui , Deng Jianming , Xu Sheng , Lun Yingzhuo , Liu Yanyu , Xia Tianlong , Lu Jianming , Hong Jiawang
Published: January 2022

Developing a single-phase self-rectifying memristor with the continuously tunable feature is structurally desirable and functionally adaptive to dynamic environmental stimuli variations, which is the pursuit of further smart memristors and neuromorphic computing. Herein, we report a van der Waals ferroelectric CuInP2S6 as a single memristor with superior continuous modulation of current and self-rectifying to different bias stimuli (sweeping speed, direction, amplitude, etc.) and external mechanical load. The synergetic contribution of controllable Cu+ ions migration and interfacial Schottky barrier is proposed to dynamically control the current flow and device performance. These outstanding sensitive features make this material possible for being superior candidate for future smart memristors with bidirectional operation mode and strong recognition to input faults and variations.
Asymmetric reinforcement learning facilitates human inference of transitive relations
Authors: Ciranka Simon , Linde-Domingo Juan , Padezhki Ivan , Wicharz Clara , Wu Charley M. , Spitzer Bernhard
Published: January 2022

Humans and other animals are capable of inferring never-experienced relations (for example, A > C) from other relational observations (for example, A > B and B > C). The processes behind such transitive inference are subject to intense research. Here we demonstrate a new aspect of relational learning, building on previous evidence that transitive inference can be accomplished through simple reinforcement learning mechanisms. We show in simulations that inference of novel relations benefits from an asymmetric learning policy, where observers update only their belief about the winner (or loser) in a pair. Across four experiments (n = 145), we find substantial empirical support for such asymmetries in inferential learning. The learning policy favoured by our simulations and experiments gives rise to a compression of values that is routinely observed in psychophysics and behavioural economics. In other words, a seemingly biased learning strategy that yields well-known cognitive distortions can be beneficial for transitive inferential judgements.
Equitable access to COVID-19 vaccines makes a life-saving difference to all countries
Authors: Ye Yang , Zhang Qingpeng , Wei Xuan , Cao Zhidong , Yuan Hsiang-Yu , Zeng Daniel Dajun
Published: January 2022

Despite broad agreement on the negative consequences of vaccine inequity, the distribution of COVID-19 vaccines is imbalanced. Access to vaccines in high-income countries (HICs) is far greater than in low- and middle-income countries (LMICs). As a result, there continue to be high rates of COVID-19 infections and deaths in LMICs. In addition, recent mutant COVID-19 outbreaks may counteract advances in epidemic control and economic recovery in HICs. To explore the consequences of vaccine (in)equity in the face of evolving COVID-19 strains, we examine vaccine allocation strategies using a multistrain metapopulation model. Our results show that vaccine inequity provides only limited and short-term benefits to HICs. Sharper disparities in vaccine allocation between HICs and LMICs lead to earlier and larger outbreaks of new waves. Equitable vaccine allocation strategies, in contrast, substantially curb the spread of new strains. For HICs, making immediate and generous vaccine donations to LMICs is a practical pathway to protect everyone.
Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection
Authors: del Rosario Ricardo C. H. , Poschmann Jeremie , Lim Carey , Cheng Catherine Y. , Kumar Pavanish , Riou Catherine , Ong Seow Theng , Gerges Sherif , Hajan Hajira Shreen , Kumar Dilip , Marzuki Mardiana , Lu Xiaohua , Lee Andrea , Wijaya Giovani Claresta , Rayan Nirmala Arul , Zhuang Zhong , Du Bruyn Elsa , Chee Cynthia Bin Eng , Lee Bernett , Lum Josephine , Zolezzi Francesca , Poidinger Michael , Rotzschke Olaf , Khor Chiea Chuen , Wilkinson Robert J. , Wang Yee T. , Chandy George K , De Libero Gennaro , Singhal Amit , Prabhakar Shyam
Published: January 2022

Host cell chromatin changes are thought to play an important role in the pathogenesis of infectious diseases. Here we describe a histone acetylome-wide association study (HAWAS) of an infectious disease, on the basis of genome-wide H3K27 acetylation profiling of peripheral blood granulocytes and monocytes from persons with active Mycobacterium tuberculosis (Mtb) infection and healthy controls. We detected >2,000 differentially acetylated loci in either cell type in a Singapore Chinese discovery cohort (n = 46), which were validated in a subsequent multi-ethnic Singapore cohort (n = 29), as well as a longitudinal cohort from South Africa (n = 26), thus demonstrating that HAWAS can be independently corroborated. Acetylation changes were correlated with differential gene expression. Differential acetylation was enriched near potassium channel genes, including KCNJ15, which modulates apoptosis and promotes Mtb clearance in vitro. We performed histone acetylation quantitative trait locus (haQTL) analysis on the dataset and identified 69 candidate causal variants for immune phenotypes among granulocyte haQTLs and 83 among monocyte haQTLs. Our study provides proof-of-principle for HAWAS to infer mechanisms of host response to pathogens.
Kinematic characteristics during gait in frail older women identified by principal component analysis
Authors: Tsuchida Wakako , Kobayashi Yoshiyuki , Inoue Koh , Horie Masanori , Yoshihara Kumiko , Ooie Toshihiko
Published: January 2022

Frailty is associated with gait variability in several quantitative parameters, including high stride time variability. However, the associations between joint kinematics during walking and increased gait variability with frailty remain unclear. In the current study, principal component analysis was used to identify the key joint kinematics characteristics of gait related to frailty. We analyzed whole kinematic waveforms during the entire gait cycle obtained from the pelvis and lower limb joint angle in 30 older women (frail/prefrail: 15 participants; non-frail: 15 participants). Principal component analysis was conducted using a 60 × 1224 input matrix constructed from participants’ time-normalized pelvic and lower-limb-joint angles along three axes (each leg of 30 participants, 51 time points, four angles, three axes, and two variables). Statistical analyses revealed that only principal component vectors 6 and 9 were related to frailty. Recombining the joint kinematics corresponding to these principal component vectors revealed that frail older women tended to exhibit greater variability of knee- and ankle-joint angles in the sagittal plane while walking compared with non-frail older women. We concluded that greater variability of knee- and ankle-joint angles in the sagittal plane are joint kinematic characteristics of gait related to frailty.
Solid-state synthesis of CdFe2O4 binary catalyst for potential application in renewable hydrogen fuel generation
Authors: Asiri Abdullah M. , Adeosun Waheed A. , Khan Sher Bahadar , Alamry Khalid A. , Marwani Hadi M. , Zakeeruddin Shaik M. , Grätzel Michael
Published: January 2022

Clean energy is highly needed at this time when the energy requirements are rapidly increasing. The observed increasing energy requirement are largely due to continued industrialization and global population explosion. The current means of energy source is not sustainable because of several reasons, most importantly, environmental pollution and human health deterioration due to burning of fossil fuels. Therefore, this study develops a new catalyst for hydrogen and oxygen evolution by water splitting as a potential energy vector. The binary metal oxide catalyst CdFe2O4 was synthesized by the solventless solid-mechanical alloying method. The as-prepared catalyst was well characterized by several methods including field emission scanning electron microscopy (FESEM), X-ray diffraction spectroscopy (XRD), X-ray photoelectron spectroscopy (XPS), Fourier Transform infrared red spectroscopy (FTIR), energy dispersive X-ray spectroscopy (XEDS). The as-prepared catalyst, CdFe2O4 was successfully applied for water electrolysis at a moderate overpotential (470 mV). Specifically, the onset potential for the oxygen and hydrogen evolution reactions (OER and HER) were 1.6 V/RHE and 0.2 V/RHE respectively (vs. the reversible hydrogen electrode). The electrode potential required to reach 10 mA/cm-2 for OER (in alkaline medium) and HER (in acidic medium) was 1.70 V/RHE (corresponding to overpotential η = 0.47 and − 0.30 V/RHE (η = − 0.30 V) respectively. Similarly, the developed OER and HER catalyst displayed high current and potential stability for a period of 12 h. This approach is seen as the right track of making water electrolysis for hydrogen energy feasible through provision of low-energy requirement for the electrolytic process. Therefore, CdFe2O4 is a potential water splitting catalyst for hydrogen evolution which is a clean fuel and an antidote for world dependence on fossil fuel for energy generation.
Five hypoxia and immunity related genes as potential biomarkers for the prognosis of osteosarcoma
Authors: Liu Dachang , Hu Ziwei , Jiang Jie , Zhang Junlei , Hu Chunlong , Huang Jian , Wei Qingjun
Published: January 2022

Osteosarcoma accounts for a frequently occurring cancer of the primary skeletal system. In osteosarcoma cells, a hypoxic microenvironment is commonly observed that drives tumor growth, progression, and heterogeneity. Hypoxia and tumor-infiltrating immune cells might be closely related to the prognosis of osteosarcoma. In this study, we aimed to determine the biomarkers and therapeutic targets related to hypoxia and immunity through bioinformatics methods to improve the clinical prognosis of patients. We downloaded the gene expression data of osteosarcoma samples and normal samples in the UCSC Xena database and GTEx database, respectively, and downloaded the validation dataset (GSE21257) in the GEO database. Subsequently, we performed GO enrichment analysis and KEGG pathway enrichment analysis on the data of the extracted osteosarcoma hypoxia-related genes. Through univariate COX regression analysis, lasso regression analysis, multivariate COX regression analysis, etc., we established a predictive model for the prognosis of osteosarcoma. Five genes, including ST3GAL4, TRIM8, STC2, TRPS1, and FAM207A, were found by screening. In particular, we analyzed the immune cell composition of each gene based on the five genes through the CIBERSORT algorithm and verified each gene at the cell and tissue level. Our findings are valuable for the clinical diagnosis and treatment of this disease.
Dried blood spot sampling for hepatitis B virus quantification, sequencing and mutation detection
Authors: Bezerra Cristianne Sousa , Portilho Moyra Machado , Barbosa Jakeline Ribeiro , de Azevedo Carolina Pimentel , Mendonça Ana Carolina da Fonseca , da Cruz José Napoleão Monte , Frota Cristiane Cunha , do Lago Bárbara Vieira , Villar Lívia Melo
Published: January 2022

Hepatitis B virus (HBV) diagnosis is performed on serum samples, but the access to this diagnosis is difficult in low-income regions. The use of dried blood spot (DBS) samples does not require special structure for collection, storage or transport. This study evaluates the use of DBS for detection, quantification and sequencing of HBV DNA usingin-housetechniques. Two study groups were included: 92 HBsAg + individuals and 49 negative controls. Serum and DBS samples were submitted to quantitative and qualitativein-housePCR forS/polgenes, sequencing and phylogenetic analyses. Total of 84 serum samples were successfully amplified. Of them, 63 paired DBS were also positive in qualitative PCR. Qualitative PCR in DBS presented a sensitivity of 75% and specificity of 100% (Kappa = 0.689). Quantitative PCR in DBS presented a detection limit of 852.5 copies/mL (250 IU/mL), sensitivity of 77.63% and specificity of 100% (Kappa = 0.731). A total of 63 serum samples and 36 DBS samples were submitted to sequencing, revealing the circulation of genotypes A (65.08%), D (4.8%), E (3.2%) and F (27%) with 100% of correspondence between serum and DBS. All sequenced samples displayed polymorphisms in HBsAg gene. An HIV-coinfected patient presented the rtM204V/I-rtL180M double resistance mutation in serum and DBS. In conclusion, DBS is an alternative to detect, quantify and characterize HBV DNA, being a possibility of increasing diagnosis in low-income settings, closing gaps in HBV control.
Cross-platform analysis of public responses to the 2019 Ridgecrest earthquake sequence on Twitter and Reddit
Authors: Ruan Tao , Kong Qingkai , McBride Sara K. , Sethjiwala Amatullah , Lv Qin
Published: January 2022

Online social networks (OSNs) have become a powerful tool to study collective human responses to extreme events such as earthquakes. Most previous research concentrated on a single platform and utilized users’ behaviors on a single platform to study people’s general responses. In this study, we explore the characteristics of people’s behaviors on different OSNs and conduct a cross-platform analysis of public responses to earthquakes. Our findings support the Uses and Gratification theory that users on Reddit and Twitter are engaging with platforms that they may feel best reflect their sense of self. Using the 2019 Ridgecrest earthquakes as our study cases, we collected 510,579 tweets and 45,770 Reddit posts (including 1437 submissions and 44,333 comments) to answer the following research questions: (1) What were the similarities and differences between public responses on Twitter and Reddit? (2) Considering the different mechanisms of Twitter and Reddit, what unique information of public responses can we learn from Reddit as compared with Twitter? By answering these research questions, we aim to bridge the gap of cross-platform public responses research towards natural hazards. Our study evinces that the users on the two different platforms have both different topics of interest and different sentiments towards the same earthquake, which indicates the necessity of investigating cross-platform OSNs to reveal a more comprehensive picture of people’s general public responses towards certain disasters. Our analysis also finds that r/conspiracy subreddit is one of the major venues where people discuss the 2019 Ridgecrest earthquakes on Reddit and different misinformation/conspiracies spread on Twitter and Reddit platforms (e.g., “Big one is coming” on Twitter and “Nuclear test” on Reddit).
Strategies for COVID-19 vaccination under a shortage scenario: a geo-stochastic modelling approach
Authors: Barreiro N. L. , Ventura C. I. , Govezensky T. , Núñez M. , Bolcatto P. G. , Barrio R. A.
Published: January 2022

In a world being hit by waves of COVID-19, vaccination is a light on the horizon. However, the roll-out of vaccination strategies and their influence on the pandemic are still open questions. In order to compare the effect of various strategies proposed by the World Health Organization and other authorities, a previously developed SEIRS stochastic model of geographical spreading of the virus is extended by adding a compartment for vaccinated people. The parameters of the model were fitted to describe the pandemic evolution in Argentina, Mexico and Spain to analyze the effect of the proposed vaccination strategies. The mobility parameters allow to simulate different social behaviors (e.g. lock-down interventions). Schemes in which vaccines are applied homogeneously in all the country, or limited to the most densely-populated areas, are simulated and compared. The second strategy is found to be more effective. Moreover, under the current global shortage of vaccines, it should be remarked that immunization is enhanced when mobility is reduced. Additionally, repetition of vaccination campaigns should be timed considering the immunity lapse of the vaccinated (and recovered) people. Finally, the model is extended to include the effect of isolation of detected positive cases, shown to be important to reduce infections.
Multiple roles of bamboo as a regulator of cyanobacterial bloom in aquatic systems
Authors: Hao Aimin , Su Mengyao , Kobayashi Sohei , Zhao Min , Iseri Yasushi
Published: January 2022

To understand the potential roles of terrestrial bamboo on controlling cyanobacterial blooms in aquatic systems, growth rates of the cyanobacterium Microcystis aeruginosa and its competitor algae were examined under different concentrations of bamboo extract. In mono-species cultures with unicellular algal strains, 5.0 g L−1 extract treatment suppressed M. aeruginosa growth, while it had little effect on the growth of green alga Scenedesmus obliquus or promoted the growth of diatom Nitzschia palea. In co-species cultures, the extract treatment increased the effect of S. obliquus and N. palea on the growth of M. aeruginosa. Under the extract treatment with a field-collected M. aeruginosa population, its cell density declined and its colony was etiolated and sank, while co-cultured N. palea increased explosively by invading the colony. These results suggest that bamboo forest stands along banks and artificially installed bamboo poles can affect the aquatic environment for phytoplankton community. Enhancing the growth of competitors, especially diatoms that can invade cyanobacterial colonies, by using extracts or by providing substrates for growth, was suggested to be the major way of the bloom control by bamboo.
Uncovering structural diversity in commuting networks: global and local entropy
Authors: Marin Valentina , Molinero Carlos , Arcaute Elsa
Published: January 2022

In this paper we revisit the concept of mobility entropy. Over time, the structure of spatial interactions among urban centres tends to become more complex and evolves from centralised models to more scattered origin and destination patterns. Entropy measures can be used to explore this complexity, and to quantify the degree of structural diversity of in- and out-flows at different scales and across the system. We use toy models of commuting networks to examine global and local measures, allowing the comparison to occur between different parts of the system. We show that entropy at the link and node level give different insights on the characteristics of the systems, enabling us to identify employment hubs and interdependencies between and within different parts of the system. We compute the measures in the commuting networks of the Northern Powerhouse and Greater South East regions in the UK to examine their relevance when studying real systems of cities. Finally we discuss how these can be used to inform planning and policy decisions oriented towards decentralisation and resilience.
A forecast of staple crop production in Burkina Faso to enable early warnings of shortages in domestic food availability
Authors: Laudien Rahel , Schauberger Bernhard , Waid Jillian , Gornott Christoph
Published: January 2022

Almost half of the Burkinabe population is moderately or severely affected by food insecurity. With climate change, domestic food production may become more under pressure, further jeopardizing food security. In this study, we focus on the production of maize, sorghum and millet as staple cereal crops in Burkina Faso to assess food availability as one component of food security. Based on a statistical weather-driven crop model, we provide a within-season forecast of crop production 1 month before the harvest. Hindcast results from 1984 to 2018 produce an r2of 0.95 in case of known harvest areas and an r2of 0.88 when harvest areas are modelled instead. We compare actually supplied calories with those usually consumed from staple crops, allowing us to provide early information on shortages in domestic cereal production on the national level. Despite the—on average—sufficient domestic cereal production from maize, sorghum and millet, a considerable level of food insecurity prevails for large parts of the population. We suggest to consider such forecasts as an early warning signal for shortages in domestic staple crop production and encourage a comprehensive assessment of all dimensions of food security to rapidly develop counteractions for looming food crises.
H84T BanLec has broad spectrum antiviral activity against human herpesviruses in cells, skin, and mice
Authors: Lloyd M. G. , Liu D. , Legendre M. , Markovitz D. M. , Moffat J. F.
Published: January 2022

H84T BanLec is a molecularly engineered lectin cloned from bananas with broad-spectrum antiviral activity against several RNA viruses. H84T BanLec dimers bind glycoproteins containing high-mannose N-glycans on the virion envelope, blocking attachment, entry, uncoating, and spread. It was unknown whether H84T BanLec is effective against human herpesviruses varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and herpes simplex virus 1 (HSV-1), which express high-mannose N-linked glycoproteins on their envelopes. We evaluated H84T BanLec against VZV-ORF57-Luc, TB40/E HCMV-fLuc-eGFP, and HSV-1 R8411 in cells, skin organ culture, and mice. The H84T BanLec EC50 was 0.025 µM for VZV (SI50 = 4000) in human foreskin fibroblasts (HFFs), 0.23 µM for HCMV (SI50 = 441) in HFFs, and 0.33 µM for HSV-1 (SI50 = 308) in Vero cells. Human skin was obtained from reduction mammoplasties and prepared for culture. Skin was infected and cultured up to 14 days. H84T BanLec prevented VZV, HCMV and HSV-1 spread in skin at 10 µM in the culture medium, and also exhibited dose-dependent antiviral effects. Additionally, H84T BanLec arrested virus spread when treatment was delayed. Histopathology of HCMV-infected skin showed no overt toxicity when H84T BanLec was present in the media. In athymic nude mice with human skin xenografts (NuSkin mice), H84T BanLec reduced VZV spread when administered subcutaneously prior to intraxenograft virus inoculation. This is the first demonstration of H84T BanLec effectiveness against DNA viruses. H84T BanLec may have additional unexplored activity against other, clinically relevant, glycosylated viruses.
Sulfotransferase 4A1 activity facilitates sulfate-dependent cellular protection to oxidative stress
Authors: Brettrager Evan J. , Meehan Arthur W. , Falany Charles N. , van Waardenburg Robert C. A. M.
Published: January 2022

Sulfotransferase 4A1 (SULT4A1) is an orphan member of the cytosolic SULT superfamily that contains enzymes that catalyze the sulfonation of hydrophobic drugs and hormones. SULT4A1 has been assessed through all classical SULT approaches yet no SULT activity has been reported. To ascertain SULT4A1 function and activity, we utilized Saccharomyces cerevisiae as a model system, which exhibits no endogenous SULT activity nor possesses SULT-related genes. We observed that ectopic SULT4A1 expression in yeast displays similar subcellular localization as reported in mouse neurons and observed that SULT4A1 is associated with the outer mitochondria membrane. SULT4A1 expression stimulates colony formation and protects these cells from hydrogen peroxide and metabolism-associated oxidative stress. These SULT4A1-mediated phenotypes are dependent on extracellular sulfate that is converted in yeast to PAPS, the universal sulfonate donor for SULT activity. Thus, heterologous SULT4A1 expression in yeast is correctly distributed and functional, and SULT4A1 antioxidant activity is sulfate dependent supporting the concept that SULT4A1 has sulfate-associated activity.
Multiple phases of human occupation in Southeast Arabia between 210,000 and 120,000 years ago
Authors: Bretzke K. , Preusser F. , Jasim S. , Miller C. , Preston G. , Raith K. , Underdown S. J. , Parton A. , Parker A. G.
Published: January 2022

Changing climatic conditions are thought to be a major control of human presence in Arabia during the Paleolithic. Whilst the Pleistocene archaeological record shows that periods of increased monsoon rainfall attracted human occupation and led to increased population densities, the impact of arid conditions on human populations in Arabia remains largely speculative. Here, we present data from Jebel Faya in Southeast (SE) Arabia, which document four periods of human occupation between c. 210,000 and 120,000 years ago. The Jebel Faya record indicates that human occupation of SE Arabia was more regular and not exclusively linked to major humid periods. Our data show that brief phases of increased rainfall additionally enabled human settlement in the Faya region. These results imply that the mosaic environments in SE Arabia have likely formed a population refugia at the end of the Middle and the beginning of the Late Pleistocene.
Differential release of extracellular vesicle tRNA from oxidative stressed renal cells and ischemic kidneys
Authors: Lee Hee Kyung , Lee Byung Rho , Lee Tae Jin , Lee Chang Min , Li Chenglong , O’Connor Paul M. , Dong Zheng , Kwon Sang-Ho
Published: January 2022

While urine-based liquid biopsy has expanded to the analyses of extracellular nucleic acids, the potential of transfer RNA (tRNA) encapsulated within extracellular vesicles has not been explored as a new class of urine biomarkers for kidney injury. Using rat kidney and mouse tubular cell injury models, we tested if extracellular vesicle-loaded tRNA and their m1A (N1-methyladenosine) modification reflect oxidative stress of kidney injury and determined the mechanism of tRNA packaging into extracellular vesicles. We determined a set of extracellular vesicle-loaded, isoaccepting tRNAs differentially released after ischemia–reperfusion injury and oxidative stress. Next, we found that m1A modification of extracellular vesicle tRNAs, despite an increase of the methylated tRNAs in intracellular vesicles, showed little or no change under oxidative stress. Mechanistically, oxidative stress decreases tRNA loading into intracellular vesicles while the tRNA-loaded vesicles are accumulated due to decreased release of the vesicles from the cell surface. Furthermore, Maf1-mediated transcriptional repression of the tRNAs decreases the cargo availability for extracellular vesicle release in response to oxidative stress. Taken together, our data support that release of extracellular vesicle tRNAs reflects oxidative stress of kidney tubules which might be useful to detect ischemic kidney injury and could lead to rebalance protein translation under oxidative stress.
Endothelial Notch signaling directly regulates the small GTPase RND1 to facilitate Notch suppression of endothelial migration
Authors: Swaminathan Bhairavi , Youn Seock-Won , Naiche L. A. , Du Jing , Villa Stephanie R. , Metz Jordan B. , Feng Huijuan , Zhang Chaolin , Kopan Raphael , Sims Peter A. , Kitajewski Jan K.
Published: January 2022

To control sprouting angiogenesis, endothelial Notch signaling suppresses tip cell formation, migration, and proliferation while promoting barrier formation. Each of these responses may be regulated by distinct Notch-regulated effectors. Notch activity is highly dynamic in sprouting endothelial cells, while constitutive Notch signaling drives homeostatic endothelial polarization, indicating the need for both rapid and constitutive Notch targets. In contrast to previous screens that focus on genes regulated by constitutively active Notch, we characterized the dynamic response to Notch. We examined transcriptional changes from 1.5 to 6 h after Notch signal activation via ligand-specific or EGTA induction in cultured primary human endothelial cells and neonatal mouse brain. In each combination of endothelial type and Notch manipulation, transcriptomic analysis identified distinct but overlapping sets of rapidly regulated genes and revealed many novel Notch target genes. Among the novel Notch-regulated signaling pathways identified were effectors in GPCR signaling, notably, the constitutively active GTPase RND1. In endothelial cells, RND1 was shown to be a novel direct Notch transcriptional target and required for Notch control of sprouting angiogenesis, endothelial migration, and Ras activity. We conclude that RND1 is directly regulated by endothelial Notch signaling in a rapid fashion in order to suppress endothelial migration.
Preprocedural transthoracic Doppler echocardiography to identify stenosis associated with increased coronary flow after revascularisation
Authors: Yamaguchi Masao , Hoshino Masahiro , Sugiyama Tomoyo , Kanaji Yoshihisa , Nogami Kai , Nagamine Tatsuhiro , Misawa Toru , Hada Masahiro , Araki Makoto , Hamaya Rikuta , Usui Eisuke , Murai Tadashi , Lee Tetsumin , Yonetsu Taishi , Sasano Tetsuo , Kakuta Tsunekazu
Published: January 2022

The benefit of percutaneous coronary intervention (PCI) has been reported to be associated with functional stenosis severity defined by fractional flow reserve (FFR). This study aimed to investigate the predictive ability of preprocedural transthoracic Doppler echocardiography (TDE) for increased coronary flow. A total of 50 left anterior descending arteries (LAD) that underwent TDE examinations were analysed. Hyperaemic LAD diastolic peak velocity (hDPV) was used as a surrogate of volumetric coronary flow. The increase in coronary flow was evaluated by the metric of % hDPV-increase defined by 100× (post-PCI hDPV-pre-PCI hDPV)/pre-PCI hDPV. The two groups divided by the median value of % hDPV-increase were compared, and the determinants of a significant coronary flow increase defined as more than the median % hDPV-increase were explored. After PCI, FFR values improved in all cases. hDPV significantly increased from 53.0 to 76.0 mm/s (P < 0.01) and the median % hDPV-increase was 45%, while hDPV decreased in 10 patients. On multivariable analysis, pre-PCI FFR and hDPV were independent predictors of a significant coronary flow increase. Preprocedural TDE-derived hDPV provided significant improvement of identification of lesions that benefit from revascularisation with respect to significant coronary flow increase.
Dynamic increase of M2 macrophages is associated with disease progression of colorectal cancers following cetuximab-based treatment
Authors: Kim Hyung-Don , Kim Sun Young , Kim Jihun , Kim Jeong Eun , Hong Yong Sang , Han Buhm , Tak Eunyoung , Ryu Yeon-Mi , Kim Sang-Yeob , Kim Tae Won
Published: January 2022

We aimed to investigate the dynamic changes of gene expression profiles and immune microenvironment linked to resistance to cetuximab-based treatments in patients with metastatic colorectal cancer (mCRC). A total of 106 patients with RAS-wild type mCRC who were treated with cetuximab-based treatments were included as the study population. RNA-sequencing and multiplexed immunohistochemistry were performed using paired or unpaired pre-treatment and post-treatment tumor tissues. Differentially expressed gene analysis of paired pre-treatment and post-treatment tumor tissues that develop acquired resistance (AR) identified the AR signature. Gene ontology analysis of the AR signature indicated enrichment of immune-related pathway genes. Among the immune subsets whose abundance was estimated by CIBERSORT, M2 macrophages showed the most prominent positive correlation with the expression of the AR signature. Among the post-treatment samples, progressive disease (PD) tumors showed a significantly higher abundance of M2 macrophages compared to non-PD tumors. These findings were validated by multiplexed immunohistochemistry analysis: the density of CD68+CD206+ M2 macrophages significantly increased at the time of PD following cetuximab-based treatment, whereas it did not consistently change in the tumor pairs of non-PD. In conclusion, a dynamic increase of M2 macrophages is associated with disease progression during cetuximab-based treatment of mCRCs. Targeting M2 macrophages is a promising immunotherapeutic strategy in this clinical context.
Recycling of zinc ions in disc-donut column considering forward mixing mass transfer, and effects of pulsed and non-pulsed condition
Authors: Asadollahzadeh Mehdi , Torkaman Rezvan , Torab-Mostaedi Meisam , Saremi Mojtaba
Published: January 2022

The current study focuses on the recovery of zinc ions by solvent extraction in the pulsed contactor. The Zn(II) ions from chloride solution were extracted into the organic phase containing di-(2-ethylhexyl) phosphoric acid (D2EHPA) extractant. The resulting data were characterized for the relative amount of (a) pulsed and no-pulsed condition; and (b) flow rate of both phases. Based on the mass balance equations for the column performance description, numerical computations of mass transfer in a disc-donut column were conducted and validated the experimental data for zinc extraction. Four different models, such as plug flow, backflow, axial dispersion, and forward mixing were evaluated in this study. The results showed that the intensification of the process with the pulsed condition increased and achieved higher mass transfer rates. The forward mixing model findings based on the curve fitting approach validated well with the experimental data. The results showed that an increase in pulsation intensity, as well as the phase flow rates, have a positive impact on the performance of the extractor. In contrast, the enhancement of flow rate led to the reduction of the described model parameters for the adverse phase.
Creation of unexplored tunnel junction by heterogeneous integration of InGaAs nanowires on germanium
Authors: Yoshida Akinobu , Gamo Hironori , Motohisa Junichi , Tomioka Katsuhiro
Published: January 2022

Heteroepitaxy has inherent concerns regarding crystal defects originated from differences in lattice constant, thermal expansion coefficient, and crystal structure. The selection of III–V materials on group IV materials that can avoid these issues has however been limited for applications such as photonics, electronics, and photovoltaics. Here, we studied nanometer-scale direct integration of InGaAs nanowires (NWs) on Ge in terms of heterogenous integration and creation of functional materials with an as yet unexplored heterostructure. We revealed that changing the initial Ge into a (111)B-polar surce anabled vertical InGaAs NWs to be integrated for all In compositions examined. Moreover, the growth naturally formed a tunnel junction across the InGaAs/Ge interface that showed a rectification property with a huge current density of several kAcm−2 and negative differential resistance with a peak-to-valley current ratio of 2.8. The described approach expands the range of material combinations for high-performance transistors, tandem solar cells, and three-dimensional integrations.
Investigating the human jejunal microbiota
Authors: Villmones Heidi Cecilie , Svanevik Marius , Ulvestad Elling , Stenstad Tore , Anthonisen Inger Lill , Nygaard Randi Monsen , Dyrhovden Ruben , Kommedal Øyvind
Published: January 2022

Descriptions of the small intestinal microbiota are deficient and conflicting. We aimed to get a reliable description of the jejunal bacterial microbiota by investigating samples from two separate jejunal segments collected from the luminal mucosa during surgery. Sixty patients with morbid obesity selected for elective gastric bypass surgery were included in this survey. Samples collected by rubbing a swab against the mucosa of proximal and mid jejunal segments were characterized both quantitatively and qualitatively using a combination of microbial culture, a universal quantitative PCR and 16S deep sequencing. Within the inherent limitations of partial 16S sequencing, bacteria were assigned to the species level. By microbial culture, 53 patients (88.3%) had an estimated bacterial density of < 1600 cfu/ml in both segments whereof 31 (51.7%) were culture negative in both segments corresponding to a bacterial density below 160 cfu/ml. By quantitative PCR, 46 patients (76.7%) had less than 104 bacterial genomes/ml in both segments. The most abundant and frequently identified species by 16S deep sequencing were associated with the oral cavity, most often from the Streptococcus mitis group, the Streptococcus sanguinis group, Granulicatella adiacens/para-adiacens, the Schaalia odontolytica complex and Gemella haemolysans/taiwanensis. In general, few bacterial species were identified per sample and there was a low consistency both between the two investigated segments in each patient and between patients. The jejunal mucosa of fasting obese patients contains relatively few microorganisms and a core microbiota could not be established. The identified microbes are likely representatives of a transient microbiota and there is a high degree of overlap between the most frequently identified species in the jejunum and the recently described ileum core microbiota.
Biomarkers associated with rhythm status after cardioversion in patients with atrial fibrillation
Authors: Meyre Pascal B. , Aeschbacher Stefanie , Blum Steffen , Voellmin Gian , Kastner Peter M. , Hennings Elisa , Kaufmann Beat A. , Kühne Michael , Osswald Stefan , Conen David
Published: January 2022

Biomarkers may help to improve our knowledge about the complex pathophysiology of atrial fibrillation (AF). In this study we sought to identify significant changes in biomarkers and clinical measures in patients with and without AF recurrence after electrical cardioversion. We measured 21 conventional and new biomarkers before and 30 days after electrical cardioversion and assessed the associations of changes in biomarker levels with rhythm status at follow-up. Significant between-group changes were observed for bone morphogenetic protein 10 (BMP10), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and total bilirubin. Their respective changes were − 10.4%, − 62.0% and − 25.6% in patients with sinus rhythm, and 3.1%, 1.1% and − 9.4% in patients with recurrent AF, for a between-group difference of − 13.5% (95% confidence interval [CI] − 19.3% to − 7.6%; P < 0.001), − 63.1% (95% CI − 76.6% to − 49.6%; P < 0.001) and − 16.3% (95% CI − 27.9% to − 4.7%; P = 0.007). In multivariable models, the reductions of BMP10 and NT-proBNP were significantly associated with follow-up rhythm status (β coefficient per 1 − SD decrease, − 3.85; 95% CI − 6.34 to − 1.35; P = 0.003 for BMP10 and − 5.84; 95% CI − 10.22 to − 1.47; P = 0.009 for NT-proBNP. In conclusion, changes in BMP10 und NT-proBNP levels were independently associated with rhythm status after cardioversion, suggesting that these markers may be dependent on the actual heart rhythm.
The Role of Clinical Medicine
Authors: Wyse Richard K. , Cooper Antony A. , Stott Simon R. W.
Published: January 2022

This chapter outlines the interface between specific, therapeutic-area focussed, drug repurposing objectives to decisions, and various approaches, surrounding the subsequent configuration and conduct of clinical trials. Ideally, these clinical trials will provide definitive proof of concept, safety, tolerability and efficacy in patient studies that lead to regulatory approval. We have never come across a how-to guide that helps with establishing and running a major drug repurposing clinical trial programme, so we have had to learn by experience alone. We therefore attempt here to offer suggestions about how such objectives can be achieved and share details of ways of solving some of the various expected and unexpected topics that are often encountered and necessitate solving in order to maintain forward momentum. To provide this practical experience we turn to, and share, what we have learned during our decade-long, global drug repurposing programme, now involving >20 repurposed drugs, and which focuses on neuroprotective clinical trials of 1–2 years duration in patients with Parkinson's disease. We concentrate on ensuring the maintenance of high quality in all aspects of our repurposing initiative as this helps it grow much faster with the active help of clinicians, non-clinical academics, patients, pharmaceutical companies and governments.