bluuebunny/crossref_metadata_2025 huggingface dataset:
On-chip deterministic operation of quantum dots in dual-mode waveguides for a plug-and-play single-photon source
Authors: Uppu Ravitej , Eriksen Hans T. , Thyrrestrup Henri , Uğurlu Aslı D. , Wang Ying , Scholz Sven , Wieck Andreas D. , Ludwig Arne , Löbl Matthias C. , Warburton Richard J. , Lodahl Peter , Midolo Leonardo
Published: July 2020

A deterministic source of coherent single photons is an enabling device for quantum information processing. Quantum dots in nanophotonic structures have been employed as excellent sources of single photons with the promise of scaling up towards multiple photons and emitters. It remains a challenge to implement deterministic resonant optical excitation of the quantum dot required for generating coherent single photons, since residual light from the excitation laser should be suppressed without compromising source efficiency and scalability. Here, we present a planar nanophotonic circuit that enables deterministic pulsed resonant excitation of quantum dots using two orthogonal waveguide modes for separating the laser and the emitted photons. We report a coherent and stable single-photon source that simultaneously achieves high-purity (g(2)(0) = 0.020 ± 0.005), high-indistinguishability (V = 96 ± 2%), and >80% coupling efficiency into the waveguide. Such ‘plug-and-play’ single-photon source can be integrated with on-chip optical networks implementing photonic quantum processors.
Machine-learning approach expands the repertoire of anti-CRISPR protein families
Authors: Gussow Ayal B. , Park Allyson E. , Borges Adair L. , Shmakov Sergey A. , Makarova Kira S. , Wolf Yuri I. , Bondy-Denomy Joseph , Koonin Eugene V.
Published: July 2020

The CRISPR-Cas are adaptive bacterial and archaeal immunity systems that have been harnessed for the development of powerful genome editing and engineering tools. In the incessant host-parasite arms race, viruses evolved multiple anti-defense mechanisms including diverse anti-CRISPR proteins (Acrs) that specifically inhibit CRISPR-Cas and therefore have enormous potential for application as modulators of genome editing tools. Most Acrs are small and highly variable proteins which makes their bioinformatic prediction a formidable task. We present a machine-learning approach for comprehensive Acr prediction. The model shows high predictive power when tested against an unseen test set and was employed to predict 2,500 candidate Acr families. Experimental validation of top candidates revealed two unknown Acrs (AcrIC9, IC10) and three other top candidates were coincidentally identified and found to possess anti-CRISPR activity. These results substantially expand the repertoire of predicted Acrs and provide a resource for experimental Acr discovery.
Random forest machine learning models for interpretable X-ray absorption near-edge structure spectrum-property relationships
Authors: Torrisi Steven B. , Carbone Matthew R. , Rohr Brian A. , Montoya Joseph H. , Ha Yang , Yano Junko , Suram Santosh K. , Hung Linda
Published: July 2020

X-ray absorption spectroscopy (XAS) produces a wealth of information about the local structure of materials, but interpretation of spectra often relies on easily accessible trends and prior assumptions about the structure. Recently, researchers have demonstrated that machine learning models can automate this process to predict the coordinating environments of absorbing atoms from their XAS spectra. However, machine learning models are often difficult to interpret, making it challenging to determine when they are valid and whether they are consistent with physical theories. In this work, we present three main advances to the data-driven analysis of XAS spectra: we demonstrate the efficacy of random forests in solving two new property determination tasks (predicting Bader charge and mean nearest neighbor distance), we address how choices in data representation affect model interpretability and accuracy, and we show that multiscale featurization can elucidate the regions and trends in spectra that encode various local properties. The multiscale featurization transforms the spectrum into a vector of polynomial-fit features, and is contrasted with the commonly-used “pointwise” featurization that directly uses the entire spectrum as input. We find that across thousands of transition metal oxide spectra, the relative importance of features describing the curvature of the spectrum can be localized to individual energy ranges, and we can separate the importance of constant, linear, quadratic, and cubic trends, as well as the white line energy. This work has the potential to assist rigorous theoretical interpretations, expedite experimental data collection, and automate analysis of XAS spectra, thus accelerating the discovery of new functional materials.
Quantifying defects in thin films using machine vision
Authors: Taherimakhsousi Nina , MacLeod Benjamin P. , Parlane Fraser G. L. , Morrissey Thomas D. , Booker Edward P. , Dettelbach Kevan E. , Berlinguette Curtis P.
Published: July 2020

The sensitivity of thin-film materials and devices to defects motivates extensive research into the optimization of film morphology. This research could be accelerated by automated experiments that characterize the response of film morphology to synthesis conditions. Optical imaging can resolve morphological defects in thin films and is readily integrated into automated experiments but the large volumes of images produced by such systems require automated analysis. Existing approaches to automatically analyzing film morphologies in optical images require application-specific customization by software experts and are not robust to changes in image content or imaging conditions. Here, we present a versatile convolutional neural network (CNN) for thin-film image analysis which can identify and quantify the extent of a variety of defects and is applicable to multiple materials and imaging conditions. This CNN is readily adapted to new thin-film image analysis tasks and will facilitate the use of imaging in automated thin-film research systems.
Occupancy maps of 208 chromatin-associated proteins in one human cell type
Authors: Partridge E. Christopher , Chhetri Surya B. , Prokop Jeremy W. , Ramaker Ryne C. , Jansen Camden S. , Goh Say-Tar , Mackiewicz Mark , Newberry Kimberly M. , Brandsmeier Laurel A. , Meadows Sarah K. , Messer C. Luke , Hardigan Andrew A. , Coppola Candice J. , Dean Emma C. , Jiang Shan , Savic Daniel , Mortazavi Ali , Wold Barbara J. , Myers Richard M. , Mendenhall Eric M.
Published: July 2020

Transcription factors are DNA-binding proteins that have key roles in gene regulation1,2. Genome-wide occupancy maps of transcriptional regulators are important for understanding gene regulation and its effects on diverse biological processes3–6. However, only a minority of the more than 1,600 transcription factors encoded in the human genome has been assayed. Here we present, as part of the ENCODE (Encyclopedia of DNA Elements) project, data and analyses from chromatin immunoprecipitation followed by high-throughput sequencing (ChIP–seq) experiments using the human HepG2 cell line for 208 chromatin-associated proteins (CAPs). These comprise 171 transcription factors and 37 transcriptional cofactors and chromatin regulator proteins, and represent nearly one-quarter of CAPs expressed in HepG2 cells. The binding profiles of these CAPs form major groups associated predominantly with promoters or enhancers, or with both. We confirm and expand the current catalogue of DNA sequence motifs for transcription factors, and describe motifs that correspond to other transcription factors that are co-enriched with the primary ChIP target. For example, FOX family motifs are enriched in ChIP–seq peaks of 37 other CAPs. We show that motif content and occupancy patterns can distinguish between promoters and enhancers. This catalogue reveals high-occupancy target regions at which many CAPs associate, although each contains motifs for only a minority of the numerous associated transcription factors. These analyses provide a more complete overview of the gene regulatory networks that define this cell type, and demonstrate the usefulness of the large-scale production efforts of the ENCODE Consortium.
A large-scale binding and functional map of human RNA-binding proteins
Authors: Van Nostrand Eric L. , Freese Peter , Pratt Gabriel A. , Wang Xiaofeng , Wei Xintao , Xiao Rui , Blue Steven M. , Chen Jia-Yu , Cody Neal A. L. , Dominguez Daniel , Olson Sara , Sundararaman Balaji , Zhan Lijun , Bazile Cassandra , Bouvrette Louis Philip Benoit , Bergalet Julie , Duff Michael O. , Garcia Keri E. , Gelboin-Burkhart Chelsea , Hochman Myles , Lambert Nicole J. , Li Hairi , McGurk Michael P. , Nguyen Thai B. , Palden Tsultrim , Rabano Ines , Sathe Shashank , Stanton Rebecca , Su Amanda , Wang Ruth , Yee Brian A. , Zhou Bing , Louie Ashley L. , Aigner Stefan , Fu Xiang-Dong , Lécuyer Eric , Burge Christopher B. , Graveley Brenton R. , Yeo Gene W.
Published: July 2020

Many proteins regulate the expression of genes by binding to specific regions encoded in the genome1. Here we introduce a new data set of RNA elements in the human genome that are recognized by RNA-binding proteins (RBPs), generated as part of the Encyclopedia of DNA Elements (ENCODE) project phase III. This class of regulatory elements functions only when transcribed into RNA, as they serve as the binding sites for RBPs that control post-transcriptional processes such as splicing, cleavage and polyadenylation, and the editing, localization, stability and translation of mRNAs. We describe the mapping and characterization of RNA elements recognized by a large collection of human RBPs in K562 and HepG2 cells. Integrative analyses using five assays identify RBP binding sites on RNA and chromatin in vivo, the in vitro binding preferences of RBPs, the function of RBP binding sites and the subcellular localization of RBPs, producing 1,223 replicated data sets for 356 RBPs. We describe the spectrum of RBP binding throughout the transcriptome and the connections between these interactions and various aspects of RNA biology, including RNA stability, splicing regulation and RNA localization. These data expand the catalogue of functional elements encoded in the human genome by the addition of a large set of elements that function at the RNA level by interacting with RBPs.
An atlas of dynamic chromatin landscapes in mouse fetal development
Authors: Gorkin David U. , Barozzi Iros , Zhao Yuan , Zhang Yanxiao , Huang Hui , Lee Ah Young , Li Bin , Chiou Joshua , Wildberg Andre , Ding Bo , Zhang Bo , Wang Mengchi , Strattan J. Seth , Davidson Jean M. , Qiu Yunjiang , Afzal Veena , Akiyama Jennifer A. , Plajzer-Frick Ingrid , Novak Catherine S. , Kato Momoe , Garvin Tyler H. , Pham Quan T. , Harrington Anne N. , Mannion Brandon J. , Lee Elizabeth A. , Fukuda-Yuzawa Yoko , He Yupeng , Preissl Sebastian , Chee Sora , Han Jee Yun , Williams Brian A. , Trout Diane , Amrhein Henry , Yang Hongbo , Cherry J. Michael , Wang Wei , Gaulton Kyle , Ecker Joseph R. , Shen Yin , Dickel Diane E. , Visel Axel , Pennacchio Len A. , Ren Bing
Published: July 2020

The Encyclopedia of DNA Elements (ENCODE) project has established a genomic resource for mammalian development, profiling a diverse panel of mouse tissues at 8 developmental stages from 10.5 days after conception until birth, including transcriptomes, methylomes and chromatin states. Here we systematically examined the state and accessibility of chromatin in the developing mouse fetus. In total we performed 1,128 chromatin immunoprecipitation with sequencing (ChIP–seq) assays for histone modifications and 132 assay for transposase-accessible chromatin using sequencing (ATAC–seq) assays for chromatin accessibility across 72 distinct tissue-stages. We used integrative analysis to develop a unified set of chromatin state annotations, infer the identities of dynamic enhancers and key transcriptional regulators, and characterize the relationship between chromatin state and accessibility during developmental gene regulation. We also leveraged these data to link enhancers to putative target genes and demonstrate tissue-specific enrichments of sequence variants associated with disease in humans. The mouse ENCODE data sets provide a compendium of resources for biomedical researchers and achieve, to our knowledge, the most comprehensive view of chromatin dynamics during mammalian fetal development to date.
Landscape of cohesin-mediated chromatin loops in the human genome
Authors: Grubert Fabian , Srivas Rohith , Spacek Damek  V , Kasowski Maya , Ruiz-Velasco Mariana , Sinnott-Armstrong Nasa , Greenside Peyton , Narasimha Anil , Liu Qing , Geller Benjamin , Sanghi Akshay , Kulik Michael , Sa Silin , Rabinovitch Marlene , Kundaje Anshul , Dalton Stephen , Zaugg Judith B. , Snyder Michael
Published: July 2020

Physical interactions between distal regulatory elements have a key role in regulating gene expression, but the extent to which these interactions vary between cell types and contribute to cell-type-specific gene expression remains unclear. Here, to address these questions as part of phase III of the Encyclopedia of DNA Elements (ENCODE), we mapped cohesin-mediated chromatin loops, using chromatin interaction analysis by paired-end tag sequencing (ChIA-PET), and analysed gene expression in 24 diverse human cell types, including core ENCODE cell lines. Twenty-eight per cent of all chromatin loops vary across cell types; these variations modestly correlate with changes in gene expression and are effective at grouping cell types according to their tissue of origin. The connectivity of genes corresponds to different functional classes, with housekeeping genes having few contacts, and dosage-sensitive genes being more connected to enhancer elements. This atlas of chromatin loops complements the diverse maps of regulatory architecture that comprise the ENCODE Encyclopedia, and will help to support emerging analyses of genome structure and function.
The Late Triassic Ischigualasto Formation at Cerro Las Lajas (La Rioja, Argentina): fossil tetrapods, high-resolution chronostratigraphy, and faunal correlations
Authors: Desojo Julia B. , Fiorelli Lucas E. , Ezcurra Martín D. , Martinelli Agustín G. , Ramezani Jahandar , Da Rosa Átila. A. S. , von Baczko M. Belén , Trotteyn M. Jimena , Montefeltro Felipe C. , Ezpeleta Miguel , Langer Max C.
Published: July 2020

Present knowledge of Late Triassic tetrapod evolution, including the rise of dinosaurs, relies heavily on the fossil-rich continental deposits of South America, their precise depositional histories and correlations. We report on an extended succession of the Ischigualasto Formation exposed in the Hoyada del Cerro Las Lajas (La Rioja, Argentina), where more than 100 tetrapod fossils were newly collected, augmented by historical finds such as the ornithosuchidVenaticosuchus rusconiiand the putative ornithischianPisanosaurus mertii. Detailed lithostratigraphy combined with high-precision U–Pb geochronology from three intercalated tuffs are used to construct a robust Bayesian age model for the formation, constraining its deposition between 230.2 ± 1.9 Ma and 221.4 ± 1.2 Ma, and its fossil-bearing interval to 229.20 + 0.11/− 0.15–226.85 + 1.45/− 2.01 Ma. The latter is divided into a lowerHyperodapedonand an upperTeyumbaitabiozones, based on the ranges of the eponymous rhynchosaurs, allowing biostratigraphic correlations to elsewhere in the Ischigualasto-Villa Unión Basin, as well as to the Paraná Basin in Brazil. The temporally calibrated Ischigualasto biostratigraphy suggests the persistence of rhynchosaur-dominated faunas into the earliest Norian. Our ca. 229 Ma age assignment toPi. mertiipartially fills the ghost lineage between younger ornithischian records and the oldest known saurischians at ca. 233 Ma.
Offspring of obese mice display enhanced intake and sensitivity for palatable stimuli, with altered expression of taste signaling elements
Authors: Choo Ezen , Wong Lauren , Chau Patricia , Bushnell Jennifer , Dando Robin
Published: July 2020

Maternal body mass index and gestational weight gain predict future obesity status of the offspring. In studies of both rodents and non-human primates, maternal obesity also predicts a preference for palatable foods in the offspring. In this study, we used C57BL/6J mice to investigate whether an underlying cause for an increase in palatable food consumption in the offspring of obese mice was a change in taste function. Adult female mice were fed a normal chow (NC) or a high fat diet (HFD) for 5 weeks before mating, then also during the gestation (3 weeks) and lactation (3 weeks) periods, with offspring always maintained on a normal chow diet; thus the only experience offspring had with high fat food was via maternal exposure. Offspring exhibited similar weight, blood glucose levels and baseline water and chow intake in adulthood. Taste response was assessed after reaching maturity, using brief-access taste testing, with female offspring of obese dams showing an enhanced response to sucrose, and both sexes consuming more sucrose, sucralose and high fat diet if from obese mothers. Offspring also exhibited increased taste bud expression of mRNA for sweet receptor subunits T1R (Taste receptor type) 2 and 3, as well as other markers associated with taste signaling. Taste morphology in both groups appeared similar. Results indicate that obesity in the mother may lead to unhealthy feeding behavior in the offspring, correlating with altered expression of taste signaling elements, which likely drive increased avidity for palatable foods.
Transcriptome profiling and in silico detection of the antimicrobial peptides of red king crab Paralithodes camtschaticus
Authors: Yakovlev Igor A. , Lysøe Erik , Heldal Inger , Steen Hege , Hagen Snorre B. , Clarke Jihong Liu
Published: July 2020

Endogenous antimicrobial peptides (AMPs) are evolutionarily ancient factors of innate immunity, which are produced by all multicellular organisms and play a key role in their protection against infection. Red king crab (Paralithodes camtschaticus), also called Kamchatka crab, is widely distributed and the best known species of all king crabs belonging to the family Lithodidae. Despite their economic importance, the genetic resources of king crabs are scarcely known and no full-genome sequences are available to date. Therefore, analysis of the red king crab transcriptome and identification and characterization of its AMPs could potentially contribute to the development of novel antimicrobial drug candidates when antibiotic resistance has become a global health threat. In this study, we sequenced the P. camtschaticus transcriptomes from carapace, tail flap and leg tissues using an Illumina NGS platform. Libraries were systematically analyzed for gene expression profiles along with AMP prediction. By an in silico approach using public databases we defined 49 cDNAs encoding for AMP candidates belonging to diverse families and functional classes, including buforins, crustins, paralithocins, and ALFs (anti-lipopolysaccharide factors). We analyzed expression patterns of 27 AMP genes. The highest expression was found for Paralithocin 1 and Crustin 3, with more than 8,000 reads. Other paralithocins, ALFs, crustins and ubiquicidins were among medium expressed genes. This transcriptome data set and AMPs provide a solid baseline for further functional analysis in P. camtschaticus. Results from the current study contribute also to the future application of red king crab as a bio-resource in addition to its being a known seafood delicacy.
The colours of Rome in the walls of Cástulo (Linares, Spain)
Authors: Tuñón José , Sánchez Alberto , Parras David J. , Amate Pilar , Montejo Manuel , Ceprián Bautista
Published: July 2020

Wall paintings have become one of the most relevant, complex and challenging research subjects in Archaeometry. Minimally- or non-invasive, accurate and multidisciplinary methods are needed to successfully address the problems posed by their physical and chemical properties and by their analysis techniques. Specifically, the analytical method implemented for the study of this type of samples must enable a precise separation of the chemical information from backgrounds and scenes, allowing the identification of pigment’s components in overlapping layers, the detection of minority components and the elucidation of pigment mixtures. Thus, this paper puts forward a multidisciplinary approach towards these goals by means of the combined use of micro Energy Dispersive X-ray Fluorescence (µEDXRF) surface mapping and single-spot micro-Raman spectroscopy and µEDXRF analysis. The samples under research come from the site of Cástulo (Linares, Spain), one of the most important Roman cities in the Iberian Peninsula. It must be emphasized the uniqueness of the walls of Cástulo, their optimal conservation state and the richness and variety of the colour’s palette used in their decoration, which make them an excellent and representative example of Roman wall paintings.
High fractional excretion of glycation adducts is associated with subsequent early decline in renal function in type 1 diabetes
Authors: Perkins Bruce A. , Rabbani Naila , Weston Andrew , Adaikalakoteswari Antonysunil , Lee Justin A. , Lovblom Leif E. , Cardinez Nancy , Thornalley Paul J.
Published: July 2020

Increased protein glycation, oxidation and nitration is linked to the development of diabetic nephropathy. We reported levels of serum protein glycation, oxidation and nitration and related hydrolysis products, glycation, oxidation and nitration free adducts in patients with type 1 diabetes (T1DM) during onset of microalbuminuria (MA) from the First Joslin Kidney Study, a prospective case–control study of patients with T1DM with and without early decline in GFR. Herein we report urinary excretion of the latter analytes and related fractional excretion values, exploring the link to MA and early decline in GFR. We recruited patients with T1DM and normoalbuminuria (NA) (n = 30) or new onset MA with and without early GFR decline (n = 22 and 33, respectively) for this study. We determined urinary protein glycation, oxidation and nitration free adducts by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry (LC–MS/MS) and deduced fractional excretion using reported plasma levels and urinary and plasma creatinine estimates. We found urinary excretion of pentosidine was increased ca. twofold in patients with MA, compared to normoalbuminuria (0.0442 vs 0.0103 nmol/mg creatinine, P < 0.0001), and increased ca. threefold in patients with early decline in GFR, compared to patients with stable GFR (0.0561 vs 0.0176 nmol/mg creatinine, P < 0.01). Urinary excretion of all other analytes was unchanged between the study groups. Remarkably, fractional excretions of 6 lysine and arginine-derived glycation free adducts were higher in patients with early decline in GFR, compared to those with stable GFR. Impaired tubular reuptake of glycation free adducts by lysine and arginine transporter proteins in patients with early GFR decline is likely involved. We conclude that higher fractional excretions of glycation adducts are potential biomarkers for early GFR decline in T1DM and MA. Measurement of these analytes could provide the basis for identifying patients at risk of early decline in renal function to target and intensify renoprotective treatment.
Combining transcriptomics and genetic linkage based information to identify candidate genes associated with Heterobasidion-resistance in Norway spruce
Authors: Chaudhary Rajiv , Lundén Karl , Dalman Kerstin , Dubey Mukesh , Nemesio-Gorriz Miguel , Karlsson Bo , Stenlid Jan , Elfstrand Malin
Published: July 2020

The Heterobasidion annosum s.l species complex comprises the most damaging forest pathogens to Norway spruce. We revisited previously identified Quantitative Trait Loci (QTLs) related to Heterobasidion-resistance in Norway spruce to identify candidate genes associated with these QTLs. We identified 329 candidate genes associated with the resistance QTLs using a gene-based composite map for Pinaceae. To evaluate the transcriptional responses of these candidate genes to H. parviporum, we inoculated Norway spruce plants and sequenced the transcriptome of the interaction at 3 and 7 days post inoculation. Out of 298 expressed candidate genes 124 were differentially expressed between inoculation and wounding control treatment. Interestingly, PaNAC04 and two of its paralogs in the subgroup III-3 of the NAC family transcription factors were found to be associated with one of the QTLs and was also highly induced in response to H. parviporum. These genes are possibly involved in the regulation of biosynthesis of flavonoid compounds. Furthermore, several of the differentially expressed candidate genes were associated with the phenylpropanoid pathway including a phenylalanine ammonia-lyase, a cinnamoyl-CoA reductase, a caffeoyl-CoA O-methyltransferase and a PgMYB11-like transcription factor gene. Combining transcriptome and genetic linkage analyses can help identifying candidate genes for functional studies and molecular breeding in non-model species.
Evaluation of qPCR reference genes in GH-overexpressing transgenic zebrafish (Danio rerio)
Authors: Rassier Gabriela T. , Silveira Tony L. R. , Remião Mariana H. , Daneluz Larissa O. , Martins Amanda W. S. , Dellagostin Eduardo N. , Ortiz Hadassa G. , Domingues William B. , Komninou Eliza R. , Kütter Mateus T. , Marins Luis F. F. , Campos Vinicius Farias
Published: July 2020

Reference genes (RGs) must have a stable expression in tissues in all experimental conditions to normalize real-time quantitative reverse transcription PCR (qRT-PCR) data. F0104 is a highly studied lineage of zebrafish developed to overexpress the growth hormone (GH). It is assumed that the transgenic process may influence the expression levels of commonly used RGs. The objective of the present study was to make a comprehensive analysis of stability of canditade RGs actb1, actb2, b2m, eif2s2, eef1a1, gapdh, rplp2, rpl7, rpl13α, tuba1, and rps18, in gh-transgenic and non-transgenic zebrafish. Liver, brain, intestine and muscle samples from both groups had qRT-PCR results analyzed by dCt, geNorm, NormFinder, BestKeeper, and RefFinder softwares. Consensus analyses among software concluded that rpl13α, rpl7, and eef1a1 are the most stable genes for zebrafish, considering the studied groups and tissues. Gapdh, rps18, and tuba1 suffered variations in stability among different tissues of both groups, and so, they were listed as the genes with lowest stability. Results from an average pairwise variations test indicated that the use of two RGs would generate reliable results for gene expression analysis in the studied tissues. We conclude that genes that are commonly used in mammals for qRT-PCR assays have low stability in both non-transgenic and gh-transgenic zebrafish reinforcing the importance of using species-specific RGs.
Rituximab-containing therapy for cold agglutinin disease: a retrospective study of 16 patients
Authors: Jia Ming-nan , Qiu Yu , Wu Yan-yan , Cai Hao , Zhou Dao-bin , Cao Xin-xin , Li Jian
Published: July 2020

Cold agglutinin disease (CAD) is a rare form of autoimmune haemolytic anaemia, and because of its rareness, there is no standard treatment for CAD patients. We retrospectively analysed the response to rituximab-containing therapy in CAD patients at our hospital. All patients received rituximab-containing therapy for at least 1 month. A total of 16 patients (11 males and 5 females) were included. The median age at the onset of the disease was 63.5 years (range 41–79). Most patients had manifestations including anaemia (81.3%) or cold-induced circulatory symptoms (75.0%). The median haemoglobin level was 72 g/L (range 29–101), and the median cold agglutinin titre was 1,024 (range 64–2,048). Thirteen of 16 patients (81%) responded to the therapy. Responders achieved a median increase in haemoglobin levels of 45 g/L. Grade 3–4 neutropenia occurred in 3 patients (19%), but only 1 (6%) of them experienced infection. Anaphylaxis related to rituximab occurred in 1 patient. During follow-up, five patients experienced relapse, and two patients died. The estimated median progression-free survival was 36 months, and median overall survival was not yet reached. In conclusion, A rituximab-based therapy in accordance with individual patient characteristics may be a reasonable choice for CAD patients.
Noise suppression beyond the thermal limit with nanotransistor biosensors
Authors: Kutovyi Yurii , Madrid Ignacio , Zadorozhnyi Ihor , Boichuk Nazarii , Kim Soo Hyeon , Fujii Teruo , Jalabert Laurent , Offenhaeusser Andreas , Vitusevich Svetlana , Clément Nicolas
Published: July 2020

Transistor biosensors are mass-fabrication-compatible devices of interest for point of care diagnosis as well as molecular interaction studies. While the actual transistor gates in processors reach the sub-10 nm range for optimum integration and power consumption, studies on design rules for the signal-to-noise ratio (S/N) optimization in transistor-based biosensors have been so far restricted to 1 µm2 device gate area, a range where the discrete nature of the defects can be neglected. In this study, which combines experiments and theoretical analysis at both numerical and analytical levels, we extend such investigation to the nanometer range and highlight the effect of doping type as well as the noise suppression opportunities offered at this scale. In particular, we show that, when a single trap is active near the conductive channel, the noise can be suppressed even beyond the thermal limit by monitoring the trap occupancy probability in an approach analog to the stochastic resonance effect used in biological systems.
Radiomics feature reproducibility under inter-rater variability in segmentations of CT images
Authors: Haarburger Christoph , Müller-Franzes Gustav , Weninger Leon , Kuhl Christiane , Truhn Daniel , Merhof Dorit
Published: July 2020

Identifying image features that are robust with respect to segmentation variability is a tough challenge in radiomics. So far, this problem has mainly been tackled in test–retest analyses. In this work we analyse radiomics feature reproducibility in two phases: first with manual segmentations provided by four expert readers and second with probabilistic automated segmentations using a recently developed neural network (PHiseg). We test feature reproducibility on three publicly available datasets of lung, kidney and liver lesions. We find consistent results both over manual and automated segmentations in all three datasets and show that there are subsets of radiomic features which are robust against segmentation variability and other radiomic features which are prone to poor reproducibility under differing segmentations. By providing a detailed analysis of robustness of the most common radiomics features across several datasets, we envision that more reliable and reproducible radiomic models can be built in the future based on this work.
The relationship between blood metabolites of the tryptophan pathway and kidney function: a bidirectional Mendelian randomization analysis
Authors: Cheng Yurong , Li Yong , Benkowitz Paula , Lamina Claudia , Köttgen Anna , Sekula Peggy
Published: July 2020

Blood metabolites of the tryptophan pathway were found to be associated with kidney function and disease in observational studies. In order to evaluate causal relationship and direction, we designed a study using a bidirectional Mendelian randomization approach. The analyses were based on published summary statistics with study sizes ranging from 1,960 to 133,413. After correction for multiple testing, results provided no evidence of an effect of metabolites of the tryptophan pathway on estimated glomerular filtration rate (eGFR). Conversely, lower eGFR was related to higher levels of four metabolites: C-glycosyltryptophan (effect estimate = − 0.16, 95% confidence interval [CI] (− 0.22; − 0.1); p = 9.2e−08), kynurenine (effect estimate = − 0.18, 95% CI (− 0.25; − 0.11); p = 1.1e−06), 3-indoxyl sulfate (effect estimate = − 0.25, 95% CI (− 0.4; − 0.11); p = 6.3e−04) and indole-3-lactate (effect estimate = − 0.26, 95% CI (− 0.38; − 0.13); p = 5.4e−05). Our study supports that lower eGFR causes higher blood metabolite levels of the tryptophan pathway including kynurenine, C-glycosyltryptophan, 3-indoxyl sulfate, and indole-3-lactate. These findings aid the notion that metabolites of the tryptophan pathway are a consequence rather than a cause of reduced eGFR. Further research is needed to specifically examine relationships with respect to chronic kidney disease (CKD) progression among patients with existing CKD.
Electronic phase shift measurement for the determination of acoustic wave DOA using single MEMS biomimetic sensor
Authors: Rabelo Renato C. , Alves Fabio D. , Karunasiri Gamani
Published: July 2020

MEMS acoustic sensors have been developed to mimic the highly-accurate sound-locating system of the Ormia ochracea fly, which detects sound wavelengths much larger than its hearing organ. A typical ormia-based MEMS directional sound sensor possesses two coupled wings that vibrate in response to sound according to a superposition of its two main resonant modes, rocking and bending. Vibrations are transduced into electronic signals by interdigitated comb finger capacitors at each wing’s end along with a capacitance measuring circuitry. A sensor designed to exhibit resonant modes closely placed in frequency, enhancing their coupling, was operated with a closed cavity behind the wings. Simultaneous and independent measurements of electronic signals generated at each of the single sensor wings were used to determine incident sound direction of arrival (DOA). DOA was found proportional to the phase shift between them and to the difference over the sum of their amplitudes as well. Single sensor phase shift DOA measurement presented a resolution better than 3° for sound pressure levels of 25 mPa or greater. These results indicate that a single sensor operating in closed-cavity configuration can provide hemispherical unambiguous direction of arrival of sound waves which wavelength is much larger than the sensor size.
Climate change models predict decreases in the range of a microendemic freshwater fish in Honduras
Authors: McMahan Caleb D. , Fuentes-Montejo César E. , Ginger Luke , Carrasco Juan Carlos , Chakrabarty Prosanta , Matamoros Wilfredo A.
Published: July 2020

Despite their incredible diversity, relatively little work has been done to assess impacts of climate change on tropical freshwater organisms. Chortiheros wesseli is a species of Neotropical cichlid (Cichlidae: Cichlinae) restricted to only a few river drainages in the Caribbean-slope of Honduras. Little is known about this species and few specimens had been collected until recently; however, our work with this species in the wild has led to a better understanding of its ecology and habitat preferences making it an excellent model for how freshwater fishes can be affected by climate change. This study assesses the distribution and habitats of Chortiheros wesseli using a combination of field data and species distribution modeling. Results indicate this species is largely limited to its current range, with no realistic suitable habitat nearby. Empirical habitat data show that this species is limited to narrow and shallow flowing waters with rapids and boulders. This habitat type is highly influenced by precipitation, which contributed the greatest influence on the models of present and future habitat suitability. Although several localities are within boundaries of national protected areas, species distribution models all predict a reduction in the range of this freshwater fish based on climate change scenarios. The likelihood of a reduced range for this species will be intensified by adverse changes to its preferred habitats.
Author Correction: Detection of Neorickettsia risticii, the agent of Potomac horse fever, in horses from Rio de Janeiro, Brazil
Authors: Paulino Patrícia Gonzaga , Almosny Nádia , Oliveira Renata , Viscardi Vanessa , Müller Ananda , Guimarães Andresa , Baldani Cristiane , da Silva Claudia , Peckle Maristela , Massard Carlos , Santos Huarrisson
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Role of HSP70 in response to (thermo)radiotherapy: analysis of gene expression in canine osteosarcoma cells by RNA-seq
Authors: Nytko Katarzyna J. , Thumser-Henner Pauline , Russo Giancarlo , Weyland Mathias S. , Rohrer Bley Carla
Published: July 2020

Pre-treatment of tumors with hyperthermia is often used to increase the efficacy of radiotherapy. One of the main proteins induced in response to hyperthermia is heat shock protein 70 (HSP70). The aim of our study was to investigate up- and down-regulated genes in response to (thermo)radiotherapy in HSP70 proficient and deficient canine osteosarcoma cell line (Abrams), and functional role of HSP70 in the mechanism of thermoradiosensitization. Cells were transfected with negative control siRNA or siRNA targeting HSP70 and treated with hyperthermia (HT), radiotherapy (RT), and thermoradiotherapy (HTRT). RNA sequencing was used to analyze gene expression. Hyperthermia and thermoradiotherapy, but not radiotherapy alone, induced differential gene expression. We identified genes differentially expressed only in HSP70 knockdown (thus HSP70-dependent) cells in response to hyperthermia and thermoradiotherapy. Interestingly, cell proliferation but not clonogenicity and apoptosis/necrosis was affected by the HSP70 knockdown in response to thermoradiotherapy. The results suggest that HSP70 regulates expression of specific genes in response to hyperthermia and thermoradiotherapy. Further investigations into the role of specific genes regulated in a HSP70-dependent manner in response to thermoradiotherapy could pave a way into new, combinatorial treatment options for (canine) osteosarcoma and other cancer types.
Running towards amblyopia recovery
Authors: Sansevero Gabriele , Torelli Claudia , Mazziotti Raffaele , Consorti Alan , Pizzorusso Tommaso , Berardi Nicoletta , Sale Alessandro
Published: July 2020

Amblyopia is a neurodevelopmental disorder of the visual cortex arising from abnormal visual experience early in life which is a major cause of impaired vision in infants and young children (prevalence around 3.5%). Current treatments such as eye patching are ineffective in a large number of patients, especially when applied after the juvenile critical period. Physical exercise has been recently shown to enhance adult visual cortical plasticity and to promote visual acuity recovery. With the aim to understand the potentialities for translational applications, we investigated the effects of voluntary physical activity on recovery of depth perception in adult amblyopic rats with unrestricted binocular vision; visual acuity recovery was also assessed. We report that three weeks of voluntary physical activity (free running) induced a marked and long-lasting recovery of both depth perception and visual acuity. In the primary visual cortex, ocular dominance recovered both for excitatory and inhibitory cells and was linked to activation of a specific intracortical GABAergic circuit.
Disturbances in primary dental enamel in Polish autistic children
Authors: Kurek Marta , Borowska Beata , Lubowiedzka-Gontarek Beata , Rosset Iwona , Żądzińska Elżbieta
Published: July 2020

Dental enamel is a structure that is formed as a result of the regular functioning of ameloblasts. The knowledge of the patterns of enamel secretion allows an analysis of their disruptions manifested in pronounced additional accentuated lines. These lines represent a physiological response to stress experienced during enamel development. The aim of this study was to assess the occurrence of accentuated lines in the tooth enamel of autistic boys. The width of the neonatal line and the periodicity of the striae of Retzius were also assessed. The study material consisted of longitudinal ground sections of 56 primary teeth (incisors and molars): 22 teeth from autistic children and 34 teeth from the control group. The Mann–Whitney U test indicates that the accentuated lines were found significantly more often in autistic children (Z = 3.03; p = 0.002). No differentiation in the rate of enamel formation and in the rate of regaining homeostasis after childbirth were found. The obtained results may indicate a higher sensitivity of autistic children to stress factors, manifested in more frequent disturbances in the functioning of ameloblasts or may be a reflection of differences in the occurrence of stress factors in the first years of life in both analyzed groups.
Estimation of pure quantum states in high dimension at the limit of quantum accuracy through complex optimization and statistical inference
Authors: Zambrano Leonardo , Pereira Luciano , Niklitschek Sebastián , Delgado Aldo
Published: July 2020

Quantum tomography has become a key tool for the assessment of quantum states, processes, and devices. This drives the search for tomographic methods that achieve greater accuracy. In the case of mixed states of a single 2-dimensional quantum system adaptive methods have been recently introduced that achieve the theoretical accuracy limit deduced by Hayashi and Gill and Massar. However, accurate estimation of higher-dimensional quantum states remains poorly understood. This is mainly due to the existence of incompatible observables, which makes multiparameter estimation difficult. Here we present an adaptive tomographic method and show through numerical simulations that, after a few iterations, it is asymptotically approaching the fundamental Gill–Massar lower bound for the estimation accuracy of pure quantum states in high dimension. The method is based on a combination of stochastic optimization on the field of the complex numbers and statistical inference, exceeds the accuracy of any mixed-state tomographic method, and can be demonstrated with current experimental capabilities. The proposed method may lead to new developments in quantum metrology.
Summary of discordant results between rapid diagnosis tests, microscopy, and polymerase chain reaction for detecting Plasmodium mixed infection: a systematic review and meta-analysis
Authors: Kotepui Manas , Kotepui Kwuntida Uthaisar , De Jesus Milanez Giovanni , Masangkay Frederick Ramirez
Published: July 2020

Malaria rapid diagnostic tests (RDTs) are widely used to detect malaria parasites among patients who suspected malaria infections in malaria-endemic areas where microscopy is unavailable. Nevertheless, little is known about the performance of RDTs in detecting Plasmodium mixed infections. The present study aimed to evaluate the discordant results between RDTs and microscopy/polymerase chain reaction (PCR) in detecting Plasmodium mixed infections. The PubMed (MEDLINE), Web of Science, and Scopus databases were systematically reviewed to identify related studies that reported the performance of RDTs in detecting Plasmodium mixed infections. Studies were grouped according to the different RDT types including RDT type 2 (pf-HRP2/pan-aldolase), RDT type 3 (pf-HRP2/pan-pLDH), RDT type 4 (Pf-LDH/pan-pLDH), RDT type 5 (Pf/Pv-pLDH), and RDT type 6 (pf-HRP2/Pv-pLDH) for subgroup analysis. The estimates of the different proportions in each analysis group that were visually summarized in a forest plot showed the odds ratio (OR) and 95% confidence interval (CI). Plots were drawn using RevMan (version 5.3; Cochrane Community). Twenty-eight studies were included in the present study. Overall, the meta-analysis showed that RDTs could detect a significantly higher proportion of Plasmodium mixed infections than microscopy (p = 0.0007, OR = 3.33, 95% CI 1.66–6.68). Subgroup analysis demonstrated that only RDTs targeting Pf-specific histidine-rich protein 2 (HRP2)/pan-specific lactate dehydrogenase (LDH) could detect a significantly higher proportion of Plasmodium mixed infections than microscopy (p = 0.004, OR = 8.46, 95% CI 2.75–26.1). The subgroup analysis between RDTs and PCR methods demonstrated that RDTs targeting Pf-specific HRP2/Pv-specific LDH could detect a significantly lower proportion of Plasmodium mixed infections than PCR methods (p = 0.0005, OR = 0.42, 95% CI 0.26–0.68). This is the first study to summarize the discordant results between RDTs and microscopy/PCR in detecting Plasmodium mixed infections. Malaria RDTs targeting Pf-HRP2/pan-pLDH could detect a higher proportion of Plasmodium mixed infections than microscopy, while RDTs targeting Pf-HRP2/Pv-specific LDH could detect a lower proportion of Plasmodium mixed infections than PCR methods. The results of this study will support the selection and careful interpretations of RDTs for a better diagnosis of Plasmodium mixed-species infections and appropriate treatment of malaria patients in endemic and non-endemic settings.
Characterization of pressure fluctuations within a controlled-diffusion blade boundary layer using the equilibrium wall-modelled LES
Authors: Boukharfane Radouan , Parsani Matteo , Bodart Julien
Published: July 2020

In this study, the generation of airfoil trailing edge broadband noise that arises from the interaction of turbulent boundary layer with the airfoil trailing edge is investigated. The primary objectives of this work are: (i) to apply a wall-modelled large-eddy simulation (WMLES) approach to predict the flow of air passing a controlled-diffusion blade, and (ii) to study the blade broadband noise that is generated from the interaction of a turbulent boundary layer with a lifting surface trailing edge. This study is carried out for two values of the Mach number, $${{\rm Ma}}_{\infty } = 0.3$$Ma∞=0.3 and 0.5, two values of the chord Reynolds number, $${{\rm Re}}=8.30 \times 10^5$$Re=8.30×105 and $$2.29 \times 10^6$$2.29×106, and two angles of attack, AoA $$=4^\circ$$=4∘ and $$5^\circ$$5∘. To examine the influence of the grid resolution on aerodynamic and aeroacoustic quantities, we compare our results with experimental data available in the literature. We also compare our results with two in-house numerical solutions generated from two wall-resolved LES (WRLES) calculations, one of which has a DNS-like resolution. We show that WMLES accurately predicts the mean pressure coefficient distribution, velocity statistics (including the mean velocity), and the traces of Reynolds tensor components. Furthermore, we observe that the instantaneous flow structures computed by the WMLES resemble those found in the reference WMLES database, except near the leading edge region. Some of the differences observed in these structures are associated with tripping and the transition to a turbulence mechanism near the leading edge, which are significantly affected by the grid resolution. The aeroacoustic noise calculations indicate that the power spectral density profiles obtained using the WMLES compare well with the experimental data.