bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment with a neutrophil elastase inhibitor and ofloxacin reduces P. aeruginosa burden in a mouse model of chronic suppurative otitis media
Authors: Khomtchouk K. M. , Joseph L. I. , Khomtchouk B. B. , Kouhi A. , Massa S. , Xia A. , Koliesnik I. , Pletzer D. , Bollyky P. L. , Santa Maria P. L. 
Published: April 2021

AbstractChronic suppurative otitis media (CSOM) is a widespread, debilitating problem with poorly understood immunology. Here, we assess the host response to middle ear infection over the course of a month post-infection in a mouse model of CSOM and in human subjects with the disease. Using multiparameter flow cytometry and a binomial generalized linear machine learning model, we identified Ly6G, a surface marker of mature neutrophils, as the most informative factor of host response driving disease in the CSOM mouse model. Consistent with this, neutrophils were the most abundant cell type in infected mice and Ly6G expression tracked with the course of infection. Moreover, neutrophil-specific immunomodulatory treatment using the neutrophil elastase inhibitor GW 311616A significantly reduces bacterial burden relative to ofloxacin-only treated animals in this model. The levels of dsDNA in middle ear effusion samples are elevated in both humans and mice with CSOM and decreased during treatment, suggesting that dsDNA may serve as a molecular biomarker of treatment response. Together these data strongly implicate neutrophils in the ineffective immune response to P. aeruginosa infection in CSOM and suggest that immunomodulatory strategies may benefit drug-tolerant infections for chronic biofilm-mediated disease.
Targeting nucleotide metabolism enhances the efficacy of anthracyclines and anti-metabolites in triple-negative breast cancer
Authors: Davison Craig , Morelli Roisin , Knowlson Catherine , McKechnie Melanie , Carson Robbie , Stachtea Xanthi , McLaughlin Kylie A. , Prise Vivien E. , Savage Kienan , Wilson Richard H. , Mulligan Karl A. , Wilson Peter M. , Ladner Robert D. , LaBonte Melissa J. 
Published: April 2021

AbstractTriple-negative breast cancer (TNBC) remains the most lethal breast cancer subtype with poor response rates to the current chemotherapies and a lack of additional effective treatment options. We have identified deoxyuridine 5′-triphosphate nucleotidohydrolase (dUTPase) as a critical gatekeeper that protects tumour DNA from the genotoxic misincorporation of uracil during treatment with standard chemotherapeutic agents commonly used in the FEC regimen. dUTPase catalyses the hydrolytic dephosphorylation of deoxyuridine triphosphate (dUTP) to deoxyuridine monophosphate (dUMP), providing dUMP for thymidylate synthase as part of the thymidylate biosynthesis pathway and maintaining low intracellular dUTP concentrations. This is crucial as DNA polymerase cannot distinguish between dUTP and deoxythymidylate triphosphate (dTTP), leading to dUTP misincorporation into DNA. Targeting dUTPase and inducing uracil misincorporation during the repair of DNA damage induced by fluoropyrimidines or anthracyclines represents an effective strategy to induce cell lethality. dUTPase inhibition significantly sensitised TNBC cell lines to fluoropyrimidines and anthracyclines through imbalanced nucleotide pools and increased DNA damage leading to decreased proliferation and increased cell death. These results suggest that repair of treatment-mediated DNA damage requires dUTPase to prevent uracil misincorporation and that inhibition of dUTPase is a promising strategy to enhance the efficacy of TNBC chemotherapy.
Ultrasound-triggered herceptin liposomes for breast cancer therapy
Authors: Elamir Amal , Ajith Saniha , Sawaftah Nour Al , Abuwatfa Waad , Mukhopadhyay Debasmita , Paul Vinod , Al-Sayah Mohammad H. , Awad Nahid , Husseini Ghaleb A. 
Published: April 2021

AbstractThe functionalization of liposomes with monoclonal antibodies is a potential strategy to increase the specificity of liposomes and reduce the side-effects associated with chemotherapeutic agents. The active targeting of the Human Epidermal growth factor Receptor 2 (HER2), which is overexpressed in HER2 positive breast cancer cells, can be achieved by coating liposomes with an anti-HER2 monoclonal antibody. In this study, we synthesized calcein and Doxorubicin-loaded immunoliposomes functionalized with the monoclonal antibody Trastuzumab (TRA). Both liposomes were characterized for their size, phospholipid content and antibody conjugation. Exposing the liposomes to low-frequency ultrasound (LFUS) triggered drug release which increased with the increase in power density. Trastuzumab conjugation resulted in enhancing the sensitivity of the liposomes to LFUS. Compared to the control liposomes, TRA-liposomes showed higher cellular toxicity and higher drug uptake by the HER2 + cell line (SKBR3) which was further improved following sonication with LFUS. Combining immunoliposomes with LFUS is a promising technique in the field of targeted drug delivery that can enhance efficiency and reduce the cytotoxicity of antineoplastic drugs.
Rational thermostabilisation of four-helix bundle dimeric de novo proteins
Authors: Irumagawa Shin , Kobayashi Kaito , Saito Yutaka , Miyata Takeshi , Umetsu Mitsuo , Kameda Tomoshi , Arai Ryoichi 
Published: April 2021

AbstractThe stability of proteins is an important factor for industrial and medical applications. Improving protein stability is one of the main subjects in protein engineering. In a previous study, we improved the stability of a four-helix bundle dimeric de novo protein (WA20) by five mutations. The stabilised mutant (H26L/G28S/N34L/V71L/E78L, SUWA) showed an extremely high denaturation midpoint temperature (Tm). Although SUWA is a remarkably hyperstable protein, in protein design and engineering, it is an attractive challenge to rationally explore more stable mutants. In this study, we predicted stabilising mutations of WA20 by in silico saturation mutagenesis and molecular dynamics simulation, and experimentally confirmed three stabilising mutations of WA20 (N22A, N22E, and H86K). The stability of a double mutant (N22A/H86K, rationally optimised WA20, ROWA) was greatly improved compared with WA20 (ΔTm = 10.6 °C). The model structures suggested that N22A enhances the stability of the α-helices and N22E and H86K contribute to salt-bridge formation for protein stabilisation. These mutations were also added to SUWA and improved its Tm. Remarkably, the most stable mutant of SUWA (N22E/H86K, rationally optimised SUWA, ROSA) showed the highest Tm (129.0 °C). These new thermostable mutants will be useful as a component of protein nanobuilding blocks to construct supramolecular protein complexes.
The association of dietary patterns with dietary inflammatory index, systemic inflammation, and insulin resistance, in apparently healthy individuals with obesity
Authors: Saghafi-Asl Maryam , Mirmajidi Susan , Asghari Jafarabadi Mohammad , Vahid Farhad , Shivappa Nitin , Hébert James R. , Ebrahimzadeh Attari Vahideh 
Published: April 2021

AbstractInflammation is considered a key mechanism leading to obesity. Dietary patterns and certain food items influence inflammation. Few studies have investigated the contribution of major dietary patterns to biological measures of inflammation. Therefore, the present study aimed to examine the associations of different dietary patterns with dietary inflammatory index (DII), systemic inflammation, and insulin resistance (IR) in the apparently healthy obese. In this cross-sectional study, 151 abdominally obese subjects were recruited from the Northwest of Iran. Dietary intake, demographic data, anthropometric indices, and physical activity (PA) was assessed. DII scores were calculated based on a validated 168-item food frequency questionnaire (FFQ). Three dietary patterns were identified, using principal component analysis. Basal blood samples were collected to determine biochemical parameters. Linear regression test with adjusted beta estimates was applied for data analysis. Three dietary patterns were extracted as Healthy, Western, and Traditional. Body mass index (BMI) (p < 0.01) and fat mass (p < 0.001) were directly associated with the Western dietary pattern. Conversely, serum lipopolysaccharide-binding protein (LBP) (b = − 0.1, p < 0.04) was negatively associated with Healthy dietary pattern, after controlling for confounders. The Traditional pattern was found to be inversely related to DII (b = − 0.3, p < 0.001). The association was also reveresed between Traditional pattern and IR (Odds Ratio: 0.3 (95% Confidence Interval 0.1–0.9)). The results suggested that the Western dietary pattern was related to higher BMI and fat mass. In addition, the Healthy pattern was associated with decreased levels of LBP. Adherence to the Traditional dietary pattern was inversely related to DII as well as IR.
Modeling biomass allocation strategy of young planted Zelkova serrata trees in Taiwan with component ratio method and seemingly unrelated regressions
Authors: Chen Chieh-Yin , Ko Shu-Hui , Lam Tzeng Yih 
Published: April 2021

AbstractTrees accumulate biomass by sequestrating atmospheric carbon and allocate it to different tree components. A biomass component ratio is the ratio of biomass in a tree component to total tree biomass. Modeling the ratios for Zelkova serrata, an important native reforestation tree species in Taiwan, helps in understanding its biomass allocation strategy to design effective silvicultural treatments. In this study, we applied Component Ratio Method (CRM) to relate biomass component ratios of main stem, large branch, twig, and foliage to tree attributes of Z. serrata from a 9-year-old plantation. Nonlinear and linear CRM models were fitted with Seemingly Unrelated Regression to account for model correlations. Linear CRM models with dbh as the predictor had the best fit with model correlations as high as 80%. About 46% and 40% of total tree biomass was allocated to main stem and large branch, respectively. However, main stem biomass decreased by 1.9% with every 1-cm increase in dbh, but large branch biomass increased by 2.2% instead. Results suggest that dominant Z. serrata trees tend to branch and fork, while smaller trees invest in larger main stem. An early pruning treatment should focus on dominant trees to maintain crown ratio and ensure wood quality.
Distinct SARS-CoV-2 antibody reactivity patterns in coronavirus convalescent plasma revealed by a coronavirus antigen microarray
Authors: Assis Rafael , Jain Aarti , Nakajima Rie , Jasinskas Algis , Khan Saahir , Davies Huw , Corash Laurence , Dumont Larry J. , Kelly Kathleen , Simmons Graham , Stone Mars , Di Germanio Clara , Busch Michael , Felgner Philip L. 
Published: April 2021

AbstractA coronavirus antigen microarray (COVAM) was constructed containing 11 SARS-CoV-2, 5 SARS-1, 5 MERS, and 12 seasonal coronavirus recombinant proteins. The array is designed to measure immunoglobulin isotype and subtype levels in serum or plasma samples against each of the individual antigens printed on the array. We probed the COVAM with COVID-19 convalescent plasma (CCP) collected from 99 donors who recovered from a PCR+ confirmed SARS-CoV-2 infection. The results were analyzed using two computational approaches, a generalized linear model (glm) and random forest (RF) prediction model, to classify individual specimens as either Reactive or non-reactive against the SARS-CoV-2 antigens. A training set of 88 pre-COVID-19 specimens (PreCoV) collected in August 2019 and102 positive specimens from SARS-CoV-2 PCR+ confirmed COVID-19 cases was used for these analyses. Results compared with an FDA emergency use authorized (EUA) SARS-CoV2 S1-based total Ig chemiluminescence immunoassay (Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 Total, CoV2T) and with a SARS-CoV-2 S1-S2 spike-based pseudovirus micro neutralization assay (SARS-CoV-2 reporter viral particle neutralization titration (RVPNT) showed high concordance between the three assays. Three CCP specimens that were negative by the VITROS CoV2T immunoassay were also negative by both COVAM and the RVPNT assay. Concordance between VITROS CoV2T and COVAM was 96%, VITROS CoV2T and RVPNT 93%, and RVPNT and COVAM 91%. The discordances were all weakly reactive samples near the cutoff threshold of the VITROS CoV2T immunoassay. The multiplex COVAM allows CCP to be grouped according to antibody reactivity patterns against 11 SARS-CoV-2 antigens. Unsupervised K-means analysis, via the gap statistics, as well as hierarchical clustering analysis revealed three main clusters with distinct reactivity intensities and patterns. These patterns were not recapitulated by adjusting the VITROS CoV2T or RVPNT assay thresholds. Plasma classified by COVAM reactivity patterns offers potential to improve CCP therapeutic efficacy CoV2T alone. The use of a SARS-CoV-2 antigen array can qualify CCP for administration as a treatment for acute COVID-19, and interrogate vaccine immunogenicity and performance in preclinical, clinical studies, and routine vaccination to identify antibody responses predictive of protection from infection and disease.
Skin bacteria of rainbow trout antagonistic to the fish pathogen Flavobacterium psychrophilum
Authors: Takeuchi Mio , Fujiwara-Nagata Erina , Katayama Taiki , Suetake Hiroaki 
Published: April 2021

AbstractRainbow trout fry syndrome (RTFS) and bacterial coldwater disease (BCWD) is a globally distributed freshwater fish disease caused by Flavobacterium psychrophilum. In spite of its importance, an effective vaccine is not still available. Manipulation of the microbiome of skin, which is a primary infection gate for pathogens, could be a novel countermeasure. For example, increasing the abundance of specific antagonistic bacteria against pathogens in fish skin might be effective to prevent fish disease. Here, we combined cultivation with 16S rRNA gene amplicon sequencing to obtain insight into the skin microbiome of the rainbow trout (Oncorhynchus mykiss) and searched for skin bacteria antagonistic to F. psychrophilum. By using multiple culture media, we obtained 174 isolates spanning 18 genera. Among them, Bosea sp. OX14 and Flavobacterium sp. GL7 respectively inhibited the growth of F. psychrophilum KU190628-78 and NCIMB 1947T, and produced antagonistic compounds of < 3 kDa in size. Sequences related to our isolates comprised 4.95% of skin microbial communities, and those related to strains OX14 and GL7 respectively comprised 1.60% and 0.17% of the skin microbiome. Comparisons with previously published microbiome data detected sequences related to strains OX14 and GL7 in skin of other rainbow trout and Atlantic salmon.
Nucleobases thin films deposited on nanostructured transparent conductive electrodes for optoelectronic applications
Authors: Breazu C. , Socol M. , Preda N. , Rasoga O. , Costas A. , Socol G. , Petre G. , Stanculescu A. 
Published: April 2021

AbstractEnvironmentally-friendly bio-organic materials have become the centre of recent developments in organic electronics, while a suitable interfacial modification is a prerequisite for future applications. In the context of researches on low cost and biodegradable resource for optoelectronics applications, the influence of a 2D nanostructured transparent conductive electrode on the morphological, structural, optical and electrical properties of nucleobases (adenine, guanine, cytosine, thymine and uracil) thin films obtained by thermal evaporation was analysed. The 2D array of nanostructures has been developed in a polymeric layer on glass substrate using a high throughput and low cost technique, UV-Nanoimprint Lithography. The indium tin oxide electrode was grown on both nanostructured and flat substrate and the properties of the heterostructures built on these two types of electrodes were analysed by comparison. We report that the organic-electrode interface modification by nano-patterning affects both the optical (transmission and emission) properties by multiple reflections on the walls of nanostructures and the electrical properties by the effect on the organic/electrode contact area and charge carrier pathway through electrodes. These results encourage the potential application of the nucleobases thin films deposited on nanostructured conductive electrode in green optoelectronic devices.
Graphomotor memory in Exner’s area enhances word learning in the blind
Authors: Mizuochi-Endo Tomomi , Itou Kazuyuki , Makuuchi Michiru , Kato Baku , Ikeda Kazuhisa , Nakamura Kimihiro 
Published: April 2021

AbstractHandwriting is thought to impede vocabulary learning in sighted adults because the motor execution of writing interferes with efficient audiovisual processing during encoding. However, the motor memory of writing may facilitate adult word learning when visual sensory inputs are severely restricted. Using functional MRI, we show that late-blind participants, but not sighted participants, learned novel words by recruiting the left dorsal premotor cortex known as Exner’s writing area and its functional coupling with the left hippocampus. During later recall, the phonological and semantic contents of these words are represented in the activation patterns of the left hippocampus as well as in those of left frontotemporal language areas. These findings suggest that motor codes of handwriting help blind participants maintain word-form representations during learning and retrieval. We propose that such reliance on the motor system reflects a broad architecture of the cerebral language network which encompasses the limb motor system as a hardwired component.
A field programmable gate array controlled high‐current pulsed source for airborne transient electromagnetic system
Authors: Liu Wei , Hu Xuquan , Liao Xian , Liu Longhuan , Fu Zhihong 
Published: April 2021

AbstractA high‐current pulsed source with high charging efficiency, high stability and low current ripple is proposed for airborne transient electromagnetic method application. The high voltage capacitor bank is employed to provide and store energy for generating current pulses in the inductive load. An N‐channel interleaved boost module is designed to replenish the capacitor energy gap so that current pulses can be repeated in a short time. The operation principles of the proposed topology are explained and the theoretical analysis is provided. In addition, a convenient and effective control strategy to raise efficiency of the charging circuit is introduced. The concise closed‐loop control method directed at the characteristics of load variations is available for changing the steady operation and control the output current. Logic input and output modules based on field programmable gate array are designed for the controller. A laboratory prototype with the maximum peak current 400 A is built for the load coil of 2.1 mH and 150 mΩ to verify the effectiveness of the proposed topology and control method.
An improved asymmetrical multi‐level inverter topology with boosted output voltage and reduced components count
Authors: Arif M Saad Bin , Mustafa Uvais , Siddique Marif Daula , Ahmad Shahbaz , Iqbal Atif , Ashique Ratil Hasnat , Ayob Shahrin bin 
Published: April 2021

AbstractThis paper presents an improved Multi‐level Inverter topology utilizing the concept of boosting‐capacitor and two DC sources with reduced switches count for generating 17‐level output. The topology employs 10 unidirectional switches including one bidirectional switch. Comparison with other recent topologies shows that the proposed topology employs a reduced number of devices and better performance. The topology combines the modularity of H‐Bridge with the boosting capacity of the switched capacitor topology. Special care is taken while designing the switching strategy for voltage balancing of the capacitors. The authors also have generalized the topology to produce ‘n’ level output. Relevant expressions are also formed and reported. Experimental validation, as well as simulation, is performed, and results are verified. Nearest level control is used as the modulation technique.
A two‐stage tunable detector with enhanced rejection capabilities
Authors: Xu Da , Hao Chengpeng , Hou Chaohuan 
Published: April 2021

AbstractThis paper focuses on the method of an adaptive detector which works against Gaussian background with unknown parameters, such as covariance matrix. The authors design a tunable detector for point‐like targets by mixing the Kelly's generalized likelihood ratio test and the enhanced Rao test. The analytical expression of the false alarm probability and detection probability of the proposed detector are derived. The performances of the new scheme are assessed, and analysed in comparison with its natural counterparts. The results show that it can provide enhanced rejection capabilities of mismatched signals, at the price of a limited detection loss for matched signals.
Determination of spectroscopic parameters for 313 M dwarf stars from their APOGEE Data Release 16 H-band spectra
Authors: Sarmento Pedro , Rojas-Ayala Bárbara , Delgado Mena Elisa , Blanco-Cuaresma Sergi 
Published: April 2021

Context. Interest has been growing among the scientific community with respect to the stellar parameters of M dwarfs in recent years, with potential applications ranging from galactic characterization to exoplanet detection.
Aims. The main motivation for this work is to develop an alternative and objective method for deriving stellar parameters for M dwarfs using the H-band spectra provided by the Apache Point Observatory Galactic Evolution Experiment (APOGEE).
Methods. We took synthetic spectra generated with iSpec, Turbospectrum, MARCS model atmospheres, along with a custom line list that includes over 1 000 000 water lines, and we compared the data to APOGEE observations, with parameters that were determined through χ2 minimization.
Results. We present spectroscopic parameters (Teff, [M/H], log g, vmic) for a sample of 313 M dwarfs obtained from their APOGEE H-band spectra. The generated synthetic spectra reproduce observed spectra to a high level of accuracy. The impact of the spectra normalization on the results are analyzed as well.
Conclusions. We compared our output parameters with those obtained with the APOGEE Stellar Parameter and Chemical Abundances Pipeline for the same stellar spectrum and we find that the values agree within the expected uncertainties. Comparisons with other previous near-infrared and optical data from the literature are also available, with median differences within our estimated uncertainties found in most cases. Here, we explore possible reasons for these differences. The full H-band line list, the line selection for the synthesis, and the synthesized spectra are available for download, along with the calculated stellar parameters.
Prävention bei Frauen ab 50 – Ernährung und Hormone im Alter
Authors: Kleine-Gunk Bernd 
Published: April 2021

ZusammenfassungHormonmangel bei Frauen in der Postmenopause beschleunigt Alterungsprozesse und ist damit neben der biologischen Alterung ein Risikofaktor für die häufigsten tödlichen Krankheiten. Eine Hormonersatztherapie mit Östrogenen schützt jüngere, gefäßgesunde Frauen vor späteren kardiovaskulären Erkrankungen und nach neueren Studien auch vor Demenz. Die Häufigkeit von Oberschenkelhalsfrakturen kann ebenfalls durch Hormongaben reduziert werden. Daneben beeinflussen auch Lebensstil und Ernährung Morbidität und Mortalität. Normalgewicht und eine ausreichende Zufuhr von ω-3-Fettsäuren sowie antioxidativen und antiinflammatorischen Substanzen aus Obst und Gemüse haben protektive Wirkungen. Kalzium, Vitamin D und Muskeltraining schützen vor Osteoporose.