bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optoelectronic frequency-modulated continuous-wave terahertz spectroscopy with 4 THz bandwidth
Authors: Liebermeister Lars , Nellen Simon , Kohlhaas Robert B. , Lauck Sebastian , Deumer Milan , Breuer Steffen , Schell Martin , Globisch Björn 
Published: February 2021

AbstractBroadband terahertz spectroscopy enables many promising applications in science and industry alike. However, the complexity of existing terahertz systems has as yet prevented the breakthrough of this technology. In particular, established terahertz time-domain spectroscopy (TDS) schemes rely on complex femtosecond lasers and optical delay lines. Here, we present a method for optoelectronic, frequency-modulated continuous-wave (FMCW) terahertz sensing, which is a powerful tool for broadband spectroscopy and industrial non-destructive testing. In our method, a frequency-swept optical beat signal generates the terahertz field, which is then coherently detected by photomixing, employing a time-delayed copy of the same beat signal. Consequently, the receiver current is inherently phase-modulated without additional modulator. Owing to this technique, our broadband terahertz spectrometer performs (200 Hz measurement rate, or 4 THz bandwidth and 117 dB peak dynamic range with averaging) comparably to state-of-the-art terahertz-TDS systems, yet with significantly reduced complexity. Thickness measurements of multilayer dielectric samples with layer-thicknesses down to 23 µm show its potential for real-world applications. Within only 0.2 s measurement time, an uncertainty of less than 2 % is achieved, the highest accuracy reported with continuous-wave terahertz spectroscopy. Hence, the optoelectronic FMCW approach paves the way towards broadband and compact terahertz spectrometers that combine fiber optics and photonic integration technologies.
Implications of the 2019–2020 megafires for the biogeography and conservation of Australian vegetation
Authors: Godfree Robert C. , Knerr Nunzio , Encinas-Viso Francisco , Albrecht David , Bush David , Christine Cargill D. , Clements Mark , Gueidan Cécile , Guja Lydia K. , Harwood Tom , Joseph Leo , Lepschi Brendan , Nargar Katharina , Schmidt-Lebuhn Alexander , Broadhurst Linda M. 
Published: February 2021

AbstractAustralia’s 2019–2020 ‘Black Summer’ bushfires burnt more than 8 million hectares of vegetation across the south-east of the continent, an event unprecedented in the last 200 years. Here we report the impacts of these fires on vascular plant species and communities. Using a map of the fires generated from remotely sensed hotspot data we show that, across 11 Australian bioregions, 17 major native vegetation groups were severely burnt, and up to 67–83% of globally significant rainforests and eucalypt forests and woodlands. Based on geocoded species occurrence data we estimate that >50% of known populations or ranges of 816 native vascular plant species were burnt during the fires, including more than 100 species with geographic ranges more than 500 km across. Habitat and fire response data show that most affected species are resilient to fire. However, the massive biogeographic, demographic and taxonomic breadth of impacts of the 2019–2020 fires may leave some ecosystems, particularly relictual Gondwanan rainforests, susceptible to regeneration failure and landscape-scale decline.
Fast acting allosteric phosphofructokinase inhibitors block trypanosome glycolysis and cure acute African trypanosomiasis in mice
Authors: McNae Iain W. , Kinkead James , Malik Divya , Yen Li-Hsuan , Walker Martin K. , Swain Chris , Webster Scott P. , Gray Nick , Fernandes Peter M. , Myburgh Elmarie , Blackburn Elizabeth A. , Ritchie Ryan , Austin Carol , Wear Martin A. , Highton Adrian J. , Keats Andrew J. , Vong Antonio , Dornan Jacqueline , Mottram Jeremy C. , Michels Paul A. M. , Pettit Simon , Walkinshaw Malcolm D. 
Published: February 2021

AbstractThe parasitic protist Trypanosoma brucei is the causative agent of Human African Trypanosomiasis, also known as sleeping sickness. The parasite enters the blood via the bite of the tsetse fly where it is wholly reliant on glycolysis for the production of ATP. Glycolytic enzymes have been regarded as challenging drug targets because of their highly conserved active sites and phosphorylated substrates. We describe the development of novel small molecule allosteric inhibitors of trypanosome phosphofructokinase (PFK) that block the glycolytic pathway resulting in very fast parasite kill times with no inhibition of human PFKs. The compounds cross the blood brain barrier and single day oral dosing cures parasitaemia in a stage 1 animal model of human African trypanosomiasis. This study demonstrates that it is possible to target glycolysis and additionally shows how differences in allosteric mechanisms may allow the development of species-specific inhibitors to tackle a range of proliferative or infectious diseases.
Phenotypic covariance across the entire spectrum of relatedness for 86 billion pairs of individuals
Authors: Kemper Kathryn E. , Yengo Loic , Zheng Zhili , Abdellaoui Abdel , Keller Matthew C. , Goddard Michael E. , Wray Naomi R. , Yang Jian , Visscher Peter M. 
Published: February 2021

AbstractAttributing the similarity between individuals to genetic and non-genetic factors is central to genetic analyses. In this paper we use the genomic relationship ($$\pi$$π) among 417,060 individuals to investigate the phenotypic covariance between pairs of individuals for 32 traits across the spectrum of relatedness, from unrelated pairs through to identical twins. We find linear relationships between phenotypic covariance and$$\pi$$πthat agree with the SNP-based heritability ($$\hat h_{SNP}^2$$ĥSNP2) in unrelated pairs ($$\pi \, < \, 0.02$$π<0.02), and with pedigree-estimated heritability in close relatives ($$\pi \, > \, 0.05$$π>0.05). The covariance increases faster than$$\pi \hat h_{SNP}^2$$πĥSNP2in distant relatives ($$0.02 \, > \, \pi \, > \, 0.05$$0.02>π>0.05), and we attribute this to imperfect linkage disequilibrium between causal variants and the common variants used to construct$$\pi$$π. We also examine the effect of assortative mating on heritability estimates from different experimental designs. We find that full-sib identity-by-descent regression estimates for height (0.66 s.e. 0.07) are consistent with estimates from close relatives (0.82 s.e. 0.04) after accounting for the effect of assortative mating.
A scalable physician-level deep learning algorithm detects universal trauma on pelvic radiographs
Authors: Cheng Chi-Tung , Wang Yirui , Chen Huan-Wu , Hsiao Po-Meng , Yeh Chun-Nan , Hsieh Chi-Hsun , Miao Shun , Xiao Jing , Liao Chien-Hung , Lu Le 
Published: February 2021

AbstractPelvic radiograph (PXR) is essential for detecting proximal femur and pelvis injuries in trauma patients, which is also the key component for trauma survey. None of the currently available algorithms can accurately detect all kinds of trauma-related radiographic findings on PXRs. Here, we show a universal algorithm can detect most types of trauma-related radiographic findings on PXRs. We develop a multiscale deep learning algorithm called PelviXNet trained with 5204 PXRs with weakly supervised point annotation. PelviXNet yields an area under the receiver operating characteristic curve (AUROC) of 0.973 (95% CI, 0.960–0.983) and an area under the precision-recall curve (AUPRC) of 0.963 (95% CI, 0.948–0.974) in the clinical population test set of 1888 PXRs. The accuracy, sensitivity, and specificity at the cutoff value are 0.924 (95% CI, 0.912–0.936), 0.908 (95% CI, 0.885–0.908), and 0.932 (95% CI, 0.919–0.946), respectively. PelviXNet demonstrates comparable performance with radiologists and orthopedics in detecting pelvic and hip fractures.
Auxin-mediated protein depletion for metabolic engineering in terpene-producing yeast
Authors: Lu Zeyu , Peng Bingyin , Ebert Birgitta E. , Dumsday Geoff , Vickers Claudia E. 
Published: February 2021

AbstractIn metabolic engineering, loss-of-function experiments are used to understand and optimise metabolism. A conditional gene inactivation tool is required when gene deletion is lethal or detrimental to growth. Here, we exploit auxin-inducible protein degradation as a metabolic engineering approach in yeast. We demonstrate its effectiveness using terpenoid production. First, we target an essential prenyl-pyrophosphate metabolism protein, farnesyl pyrophosphate synthase (Erg20p). Degradation successfully redirects metabolic flux toward monoterpene (C10) production. Second, depleting hexokinase-2, a key protein in glucose signalling transduction, lifts glucose repression and boosts production of sesquiterpene (C15) nerolidol to 3.5 g L−1 in flask cultivation. Third, depleting acetyl-CoA carboxylase (Acc1p), another essential protein, delivers growth arrest without diminishing production capacity in nerolidol-producing yeast, providing a strategy to decouple growth and production. These studies demonstrate auxin-mediated protein degradation as an advanced tool for metabolic engineering. It also has potential for broader metabolic perturbation studies to better understand metabolism.
Analysis of metagenome-assembled viral genomes from the human gut reveals diverse putative CrAss-like phages with unique genomic features
Authors: Yutin Natalya , Benler Sean , Shmakov Sergei A. , Wolf Yuri I. , Tolstoy Igor , Rayko Mike , Antipov Dmitry , Pevzner Pavel A. , Koonin Eugene V. 
Published: February 2021

AbstractCrAssphage is the most abundant human-associated virus and the founding member of a large group of bacteriophages, discovered in animal-associated and environmental metagenomes, that infect bacteria of the phylum Bacteroidetes. We analyze 4907 Circular Metagenome Assembled Genomes (cMAGs) of putative viruses from human gut microbiomes and identify nearly 600 genomes of crAss-like phages that account for nearly 87% of the DNA reads mapped to these cMAGs. Phylogenetic analysis of conserved genes demonstrates the monophyly of crAss-like phages, a putative virus order, and of 5 branches, potential families within that order, two of which have not been identified previously. The phage genomes in one of these families are almost twofold larger than the crAssphage genome (145-192 kilobases), with high density of self-splicing introns and inteins. Many crAss-like phages encode suppressor tRNAs that enable read-through of UGA or UAG stop-codons, mostly, in late phage genes. A distinct feature of the crAss-like phages is the recurrent switch of the phage DNA polymerase type between A and B families. Thus, comparative genomic analysis of the expanded assemblage of crAss-like phages reveals aspects of genome architecture and expression as well as phage biology that were not apparent from the previous work on phage genomics.
Observed Antarctic sea ice expansion reproduced in a climate model after correcting biases in sea ice drift velocity
Authors: Sun Shantong , Eisenman Ian 
Published: February 2021

AbstractThe Antarctic sea ice area expanded significantly during 1979–2015. This is at odds with state-of-the-art climate models, which typically simulate a receding Antarctic sea ice cover in response to increasing greenhouse forcing. Here, we investigate the hypothesis that this discrepancy between models and observations occurs due to simulation biases in the sea ice drift velocity. As a control we use the Community Earth System Model (CESM) Large Ensemble, which has 40 realizations of past and future climate change that all undergo Antarctic sea ice retreat during recent decades. We modify CESM to replace the simulated sea ice velocity field with a satellite-derived estimate of the observed sea ice motion, and we simulate 3 realizations of recent climate change. We find that the Antarctic sea ice expands in all 3 of these realizations, with the simulated spatial structure of the expansion bearing resemblance to observations. The results suggest that the reason CESM has failed to capture the observed Antarctic sea ice expansion is due to simulation biases in the sea ice drift velocity, implying that an improved representation of sea ice motion is crucial for more accurate sea ice projections.
“Hot cross bun” is a potential imaging marker for the severity of cerebellar ataxia in MSA-C
Authors: Zhu Shuzhen , Deng Bin , Huang Zifeng , Chang Zihan , Li Hualin , Liu Hui , Huang Yanjun , Pan Ying , Wang Yanping , Chao Yin-Xia , Chan Ling-Ling , Wu Yih-Ru , Tan Eng-King , Wang Qing 
Published: February 2021

AbstractTo evaluate the correlation between “hot cross bun” sign (HCBs) and disease severity in multiple system atrophy (MSA). We recruited patients with probable and possible MSA with parkinsonism (MSA-P) or the cerebellar ataxia (MSA-C) subtypes. Clinical and imaging characteristics were collected and comparison was performed between MSA-C and MSA-P cases. Spearman test was used to evaluate the correlation between HCBs and other variables. Curve estimate and general linear regression was performed to evaluate the relationship between HCBs and the Scale for Assessment and Rating of Ataxia (SARA). Unified Multiple System Atrophy Rating Scale (UMSARS) IV was used to assess the severity of disease. Multinomial ordered logistic regression was used to confirm the increased likelihood of disability for the disease. Eighty-one MSA with HCBs comprising of 50 MSA-C and 31 MSA-P were recruited. We demonstrated that the severity of HCBs showed a positive linear correlation with SARA scores in MSA-C. Multinomial ordered logistic regression test revealed that the increase in the HCBs grade may be associated with an increased likelihood of disability for the disease severity in MSA, especially in those with cerebellar ataxia subtype. We demonstrated that HCBs is a potential imaging marker for the severity of cerebellar ataxia. The increase in the HCBs grade may be associated with an increased likelihood of disability in MSA-C, but not MSA-P cases, suggesting that it may be a useful imaging indicator for disease progression in Chinese patients with MSA-C.
Anneal-path correction in flux qubits
Authors: Khezri Mostafa , Grover Jeffrey A. , Basham James I. , Disseler Steven M. , Chen Huo , Novikov Sergey , Zick Kenneth M. , Lidar Daniel A. 
Published: February 2021

AbstractQuantum annealers require accurate control and optimized operation schemes to reduce noise levels, in order to eventually demonstrate a computational advantage over classical algorithms. We study a high coherence four-junction capacitively shunted flux qubit (CSFQ), using dispersive measurements to extract system parameters and model the device. Josephson junction asymmetry inherent to the device causes a deleterious nonlinear cross-talk when annealing the qubit. We implement a nonlinear annealing path to correct the asymmetry in situ, resulting in a substantial increase in the probability of the qubit being in the correct state given an applied flux bias. We also confirm the multi-level structure of our CSFQ circuit model by annealing it through small spectral gaps and observing quantum signatures of energy level crossings. Our results demonstrate an anneal-path correction scheme designed and implemented to improve control accuracy for high-coherence and high-control quantum annealers, which leads to an enhancement of success probability in annealing protocols.
Mapping drug-target interactions and synergy in multi-molecular therapeutics for pressure-overload cardiac hypertrophy
Authors: Rai Aparna , Kumar Vikas , Jerath Gaurav , Kartha C. C. , Ramakrishnan Vibin 
Published: February 2021

AbstractAdvancements in systems biology have resulted in the development of network pharmacology, leading to a paradigm shift from “one-target, one-drug” to “target-network, multi-component therapeutics”. We employ a chimeric approach involving in-vivo assays, gene expression analysis, cheminformatics, and network biology to deduce the regulatory actions of a multi-constituent Ayurvedic concoction, Amalaki Rasayana (AR) in animal models for its effect in pressure-overload cardiac hypertrophy. The proteomics analysis of in-vivo assays for Aorta Constricted and Biologically Aged rat models identify proteins expressed under each condition. Network analysis mapping protein–protein interactions and synergistic actions of AR using multi-component networks reveal drug targets such as ACADM, COX4I1, COX6B1, HBB, MYH14, and SLC25A4, as potential pharmacological co-targets for cardiac hypertrophy. Further, five out of eighteen AR constituents potentially target these proteins. We propose a distinct prospective strategy for the discovery of network pharmacological therapies and repositioning of existing drug molecules for treating pressure-overload cardiac hypertrophy.
Data centre water consumption
Authors: Mytton David 
Published: February 2021

AbstractThe information communication technology sector will experience huge growth over the coming years, with 29.3 billion devices expected online by 2030, up from 18.4 billion in 2018. To reliably support the online services used by these billions of users, data centres have been built around the world to provide the millions of servers they contain with access to power, cooling and internet connectivity. Whilst the energy consumption of these facilities regularly receives mainstream and academic coverage, analysis of their water consumption is scarce. Data centres consume water directly for cooling, in some cases 57% sourced from potable water, and indirectly through the water requirements of non-renewable electricity generation. Although in the USA, data centre water consumption (1.7 billion litres/day) is small compared to total water consumption (1218 billion litres/day), there are issues of transparency with less than a third of data centre operators measuring water consumption. This paper examines the water consumption of data centres, the measurement of that consumption, highlights the lack of data available to assess water efficiency, and discusses and where the industry is going in attempts to reduce future consumption.
Monitoring socio-climatic interactions to prioritise drinking water interventions in rural Africa
Authors: Armstrong Andrew , Hope Robert , Munday Callum 
Published: February 2021

AbstractRainfall variability and socioeconomic shocks pose a revenue risk for drinking water services in rural Africa. We examine the year-on-year and seasonal relationship between rainfall and remotely monitored water usage from rural piped schemes in four sub-Saharan countries to identify patterns that warn of a threat to operational sustainability. Continuous monitoring of socio-climatic interactions can reveal distributions and magnitudes of risk and guide policy action to safeguard rural water services.
Total Ortholog Median Matrix as an alternative unsupervised approach for phylogenomics based on evolutionary distance between protein coding genes
Authors: Maruyama Sandra Regina , Rogerio Luana Aparecida , Freitas Patricia Domingues , Teixeira Marta Maria Geraldes , Ribeiro José Marcos Chaves 
Published: February 2021

AbstractThe increasing number of available genomic data allowed the development of phylogenomic analytical tools. Current methods compile information from single gene phylogenies, whether based on topologies or multiple sequence alignments. Generally, phylogenomic analyses elect gene families or genomic regions to construct phylogenomic trees. Here, we presented an alternative approach for Phylogenomics, named TOMM (Total Ortholog Median Matrix), to construct a representative phylogram composed by amino acid distance measures of all pairwise ortholog protein sequence pairs from desired species inside a group of organisms. The procedure is divided two main steps, (1) ortholog detection and (2) creation of a matrix with the median amino acid distance measures of all pairwise orthologous sequences. We tested this approach within three different group of organisms: Kinetoplastida protozoa, hematophagous Diptera vectors and Primates. Our approach was robust and efficacious to reconstruct the phylogenetic relationships for the three groups. Moreover, novel branch topologies could be achieved, providing insights about some phylogenetic relationships between some taxa.
High throughput error correction in information reconciliation for semiconductor superlattice secure key distribution
Authors: Xie Jianguo , Wu Han , Xia Chao , Ding Peng , Song Helun , Xu Liwei , Chen Xiaoming 
Published: February 2021

AbstractSemiconductor superlattice secure key distribution (SSL-SKD) has been experimentally demonstrated to be a novel scheme to generate and agree on the identical key in unconditional security just by public channel. The error correction in the information reconciliation procedure is introduced to eliminate the inevitable differences of analog systems in SSL-SKD. Nevertheless, the error correction has been proved to be the performance bottleneck of information reconciliation for high computational complexity. Hence, it determines the final secure key throughput of SSL-SKD. In this paper, different frequently-used error correction codes, including BCH codes, LDPC codes, and Polar codes, are optimized separately to raise the performance, making them usable in practice. Firstly, we perform multi-threading to support multi-codeword decoding for BCH codes and Polar codes and updated value calculation for LDPC codes. Additionally, we construct lookup tables to reduce redundant calculations, such as logarithmic table and antilogarithmic table for finite field computation. Our experimental results reveal that our proposed optimization methods can significantly promote the efficiency of SSL-SKD, and three error correction codes can reach the throughput of Mbps and provide a minimum secure key rate of 99%.
The miRNA199a/SIRT1/P300/Yy1/sST2 signaling axis regulates adverse cardiac remodeling following MI
Authors: Asensio-Lopez Maria Carmen , Sassi Yassine , Soler Fernando , Fernandez del Palacio Maria Josefa , Pascual-Figal Domingo , Lax Antonio 
Published: February 2021

AbstractLeft ventricular remodeling following myocardial infarction (MI) is related to adverse outcome. It has been shown that an up-regulation of plasma soluble ST2 (sST2) levels are associated with lower pre-discharge left ventricular (LV) ejection fraction, adverse cardiovascular outcomes and mortality outcome after MI. The mechanisms involved in its modulation are unknown and there is not specific treatment capable of lowering plasma sST2 levels in acute-stage HF. We recently identified Yin-yang 1 (Yy1) as a transcription factor related to circulating soluble ST2 isoform (sST2) expression in infarcted myocardium. However, the underlying mechanisms involved in this process have not been thoroughly elucidated. This study aimed to evaluate the pathophysiological implication of miR-199a-5p in cardiac remodeling and the expression of the soluble ST2 isoform. Myocardial infarction (MI) was induced by permanent ligation of the left anterior coronary artery in C57BL6/J mice that randomly received antimiR199a therapy, antimiR-Ctrl or saline. A model of biomechanical stretching was also used to characterize the underlying mechanisms involved in the activation of Yy1/sST2 axis. Our results show that the significant upregulation of miR-199a-5p after myocardial infarction increases pathological cardiac hypertrophy by upregulating circulating soluble sST2 levels. AntimiR199a therapy up-regulates Sirt1 and inactivates the co-activator P300 protein, thus leading to Yy1 inhibition which decreases both expression and release of circulating sST2 by cardiomyocytes after myocardial infarction. Pharmacological inhibition of miR-199a rescues cardiac hypertrophy and heart failure in mice, offering a potential therapeutic approach for cardiac failure.