bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hallmarks of primate lentiviral immunodeficiency infection recapitulate loss of innate lymphoid cells
Authors: Mudd Joseph C. , Busman-Sahay Kathleen , DiNapoli Sarah R. , Lai Stephen , Sheik Virginia , Lisco Andrea , Deleage Claire , Richardson Brian , Palesch David J. , Paiardini Mirko , Cameron Mark , Sereti Irini , Reeves R. Keith , Estes Jacob D. , Brenchley Jason M. 
Published: September 2018

AbstractInnate lymphoid cells (ILCs) play critical roles in mucosal barrier defense and tissue homeostasis. While ILCs are depleted in HIV-1 infection, this phenomenon is not a generalized feature of all viral infections. Here we show in untreated SIV-infected rhesus macaques (RMs) that ILC3s are lost rapidly in mesenteric lymph nodes (MLNs), yet preserved in SIV+ RMs with pharmacologic or natural control of viremia. In healthy uninfected RMs, experimental depletion of CD4+ T cells in combination with dextran sodium sulfate (DSS) is sufficient to reduce ILC frequencies in the MLN. In this setting and in chronic SIV+ RMs, IL-7Rα chain expression diminishes on ILC3s in contrast to the IL-18Rα chain expression which remains stable. In HIV-uninfected patients with durable CD4+ T cell deficiency (deemed idiopathic CD4+ lymphopenia), similar ILC deficiencies in blood were observed, collectively identifying determinants of ILC homeostasis in primates and potential mechanisms underlying their depletion in HIV/SIV infection.
High-resolution NMR studies of antibiotics in cellular membranes
Authors: Medeiros-Silva João , Jekhmane Shehrazade , Paioni Alessandra Lucini , Gawarecka Katarzyna , Baldus Marc , Swiezewska Ewa , Breukink Eefjan , Weingarth Markus 
Published: September 2018

AbstractThe alarming rise of antimicrobial resistance requires antibiotics with unexploited mechanisms. Ideal templates could be antibiotics that target the peptidoglycan precursor lipid II, known as the bacterial Achilles heel, at an irreplaceable pyrophosphate group. Such antibiotics would kill multidrug-resistant pathogens at nanomolecular concentrations without causing antimicrobial resistance. However, due to the challenge of studying small membrane-embedded drug–receptor complexes in native conditions, the structural correlates of the pharmaceutically relevant binding modes are unknown. Here, using advanced highly sensitive solid-state NMR setups, we present a high-resolution approach to study lipid II-binding antibiotics directly in cell membranes. On the example of nisin, the preeminent lantibiotic, we show that the native antibiotic-binding mode strongly differs from previously published structures, and we demonstrate that functional hotspots correspond to plastic drug domains that are critical for the cellular adaptability of nisin. Thereby, our approach provides a foundation for an improved understanding of powerful antibiotics.
Clopidogrel as a donor probe and thioenol derivatives as flexible promoieties for enabling H2S biomedicine
Authors: Zhu Yaoqiu , Romero Elkin L. , Ren Xiaodong , Sanca Angel J. , Du Congkuo , Liu Cai , Karim Zubair A. , Alshbool Fatima Z. , Khasawneh Fadi T. , Zhou Jiang , Zhong Dafang , Geng Bin 
Published: September 2018

AbstractHydrogen sulfide has emerged as a critical endogenous signaling transmitter and a potentially versatile therapeutic agent. The key challenges in this field include the lack of approved hydrogen sulfide-releasing probes for in human exploration and the lack of controllable hydrogen sulfide promoieties that can be flexibly installed for therapeutics development. Here we report the identification of the widely used antithrombotic drug clopidogrel as a clinical hydrogen sulfide donor. Clopidogrel is metabolized in patients to form a circulating metabolite that contains a thioenol substructure, which is found to undergo spontaneous degradation to release hydrogen sulfide. Model studies demonstrate that thioenol derivatives are a class of controllable promoieties that can be conveniently installed on a minimal structure of ketone with an α-hydrogen. These results can provide chemical tools for advancing hydrogen sulfide biomedical research as well as developing hydrogen sulfide-releasing drugs.
RNA modification landscape of the human mitochondrial tRNALys regulates protein synthesis
Authors: Richter Uwe , Evans Molly E. , Clark Wesley C. , Marttinen Paula , Shoubridge Eric A. , Suomalainen Anu , Wredenberg Anna , Wedell Anna , Pan Tao , Battersby Brendan J. 
Published: September 2018

AbstractPost-transcriptional RNA modifications play a critical role in the pathogenesis of human mitochondrial disorders, but the mechanisms by which specific modifications affect mitochondrial protein synthesis remain poorly understood. Here we used a quantitative RNA sequencing approach to investigate, at nucleotide resolution, the stoichiometry and methyl modifications of the entire mitochondrial tRNA pool, and establish the relevance to human disease. We discovered that a N1-methyladenosine (m1A) modification is missing at position 58 in the mitochondrial tRNALys of patients with the mitochondrial DNA mutation m.8344 A > G associated with MERRF (myoclonus epilepsy, ragged-red fibers). By restoring the modification on the mitochondrial tRNALys, we demonstrated the importance of the m1A58 to translation elongation and the stability of selected nascent chains. Our data indicates regulation of post-transcriptional modifications on mitochondrial tRNAs is finely tuned for the control of mitochondrial gene expression. Collectively, our findings provide novel insight into the regulation of mitochondrial tRNAs and reveal greater complexity to the molecular pathogenesis of MERRF.
Clinical cancer genomic profiling by three-platform sequencing of whole genome, whole exome and transcriptome
Authors: Rusch Michael , Nakitandwe Joy , Shurtleff Sheila , Newman Scott , Zhang Zhaojie , Edmonson Michael N. , Parker Matthew , Jiao Yuannian , Ma Xiaotu , Liu Yanling , Gu Jiali , Walsh Michael F. , Becksfort Jared , Thrasher Andrew , Li Yongjin , McMurry James , Hedlund Erin , Patel Aman , Easton John , Yergeau Donald , Vadodaria Bhavin , Tatevossian Ruth G. , Raimondi Susana , Hedges Dale , Chen Xiang , Hagiwara Kohei , McGee Rose , Robinson Giles W. , Klco Jeffery M. , Gruber Tanja A. , Ellison David W. , Downing James R , Zhang Jinghui 
Published: September 2018

AbstractTo evaluate the potential of an integrated clinical test to detect diverse classes of somatic and germline mutations relevant to pediatric oncology, we performed three-platform whole-genome (WGS), whole exome (WES) and transcriptome (RNA-Seq) sequencing of tumors and normal tissue from 78 pediatric cancer patients in a CLIA-certified, CAP-accredited laboratory. Our analysis pipeline achieves high accuracy by cross-validating variants between sequencing types, thereby removing the need for confirmatory testing, and facilitates comprehensive reporting in a clinically-relevant timeframe. Three-platform sequencing has a positive predictive value of 97–99, 99, and 91% for somatic SNVs, indels and structural variations, respectively, based on independent experimental verification of 15,225 variants. We report 240 pathogenic variants across all cases, including 84 of 86 known from previous diagnostic testing (98% sensitivity). Combined WES and RNA-Seq, the current standard for precision oncology, achieved only 78% sensitivity. These results emphasize the critical need for incorporating WGS in pediatric oncology testing.
Frequency-dependent effects of subthalamic deep brain stimulation on motor symptoms in Parkinson’s disease: a meta-analysis of controlled trials
Authors: Su Dongning , Chen Huimin , Hu Wanli , Liu Yuye , Wang Zhan , Wang Xuemei , Liu Genliang , Ma Huizi , Zhou Junhong , Feng Tao 
Published: September 2018

AbstractThis study aims to investigate how the frequency settings of deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) influence the motor symptoms of Parkinson’s disease (PD). Stimulation with frequencies less than 100 Hz (mostly 60 or 80 Hz) is considered low-frequency stimulation (LFS) and with frequencies greater than 100 Hz (mostly 130 or 150 Hz) is considered high-frequency stimulation (HFS). We conducted a comprehensive literature review and meta-analysis with a random-effect model. Ten studies with 132 patients were included in our analysis. The pooled results showed no significant difference in the total Unified Parkinson Disease Rating Scale part III (UPDRS-III) scores (mean effect, −1.50; p = 0.19) or the rigidity subscore between HFS and LFS. Compared to LFS, HFS induced greater reduction in the tremor subscore within the medication-off condition (mean effect, 1.01; p = 0.002), while no significance was shown within the medication-on condition (mean effect, 0.01; p = 0.92). LFS induced greater reduction in akinesia subscore (mean effect, −1.68, p = 0.003), the time to complete the stand-walk-sit (SWS) test (mean effect, −4.84; p < 0.00001), and the number of freezing of gait (FOG) (mean effect, −1.71; p = 0.03). These results suggest that two types of frequency settings may have different effects, that is, HFS induces better responses for tremor and LFS induces greater response for akinesia, gait, and FOG, respectively, which are worthwhile to be confirmed in future study, and will ultimately inform the clinical practice in the management of PD using STN-DBS.
Printable all-dielectric water-based absorber
Authors: Bradley Patrick J. , Torrico Max O. Munoz , Brennan Conor , Hao Yang 
Published: September 2018

AbstractThe phase interplay between overlapping electric and magnetic dipoles of equal amplitude generated by exclusively alldielectric structures presents an intriguing paradigm in the manipulation of electromagnetic energy. Here, we offer a holistic implementation by proposing an additive manufacturing route and associated design principles that enable the programming and fabrication of synthetic multi-material microstructures. In turn, we compose, manufacture and experimentally validate the first demonstrable 3d printed all-dielectric electromagnetic broadband absorbers that point the way to circumventing the technical limitations of conventional metal-dielectric absorber configurations. One of the key innovations is to judicially distribute a dispersive soft matter with a high-dielectric constant, such as water, in a low-dielectric matrix to enhance wave absorption at a reduced length scale. In part, these results extend the promise of additive manufacturing and illustrate the power of topology optimisation to create carefully crafted magnetic and electric responses that are sure to find new applications across the electromagnetic spectrum.
Critical analysis of (Quasi-)Surprise for community detection in complex networks
Authors: Xiang Ju , Li Hui-Jia , Bu Zhan , Wang Zhen , Bao Mei-Hua , Tang Liang , Li Jian-Ming 
Published: September 2018

AbstractModule or community structures widely exist in complex networks, and optimizing statistical measures is one of the most popular approaches for revealing and identifying such structures in real-world applications. In this paper, we focus on critical behaviors of (Quasi-)Surprise, a type of statistical measure of interest for community structure, accompanied by a series of comparisons with other measures. Specially, the effect of various network parameters on the measures is thoroughly investigated. The critical number of dense subgraphs in partition transition is derived, and a kind of phase diagrams is provided to display and compare the phase transitions of the measures. The effect of “potential well” for (Quasi-)Surprise is revealed, which may be difficult to get across by general greedy (agglomerative or divisive) algorithms. Finally, an extension of Quasi-Surprise is introduced for the study of multi-scale structures. Experimental results are of help for understanding the critical behaviors of (Quasi-)Surprise, and may provide useful insight for the design of effective tools for community detection.
Maintenance DFMO Increases Survival in High Risk Neuroblastoma
Authors: Sholler Giselle L. Saulnier , Ferguson William , Bergendahl Genevieve , Bond Jeffrey P. , Neville Kathleen , Eslin Don , Brown Valerie , Roberts William , Wada Randal K. , Oesterheld Javier , Mitchell Deanna , Foley Jessica , Parikh Nehal S. , Eshun Francis , Zage Peter , Rawwas Jawhar , Sencer Susan , Pankiewicz Debra , Quinn Monique , Rich Maria , Junewick Joseph , Kraveka Jacqueline M. 
Published: September 2018

AbstractHigh risk neuroblastoma (HRNB) accounts for 15% of all pediatric cancer deaths. Despite aggressive therapy approximately half of patients will relapse, typically with only transient responses to second-line therapy. This study evaluated the ornithine decarboxylase inhibitor difluoromethylornithine (DFMO) as maintenance therapy to prevent relapse following completion of standard therapy (Stratum 1) or after salvage therapy for relapsed/refractory disease (Stratum 2). This Phase II single agent, single arm multicenter study enrolled from June 2012 to February 2016. Subjects received 2 years of oral DFMO (750 ± 250 mg/m2 twice daily). Event free survival (EFS) and overall survival (OS) were determined on an intention-to-treat (ITT) basis. 101 subjects enrolled on Stratum 1 and 100 were eligible for ITT analysis; two-year EFS was 84% (±4%) and OS 97% (±2%). 39 subjects enrolled on Stratum 2, with a two-year EFS of 54% (±8%) and OS 84% (±6%). DFMO was well tolerated. The median survival time is not yet defined for either stratum. DFMO maintenance therapy for HRNB in remission is safe and associated with high EFS and OS. Targeting ODC represents a novel therapeutic mechanism that may provide a new strategy for preventing relapse in children with HRNB.
Minority and Majority Charge Carrier Mobility in Cu2ZnSnSe4 revealed by Terahertz Spectroscopy
Authors: Hempel Hannes , Hages Charles J. , Eichberger Rainer , Repins Ingrid , Unold Thomas 
Published: September 2018

AbstractThe mobilities of electrons and holes determine the applicability of any semiconductor, but their individual measurement remains a major challenge. Here, we show that time-resolved terahertz spectroscopy (TRTS) can distinguish the mobilities of minority and majority charge carriers independently of the doping-type and without electrical contacts. To this end, we combine the well-established determination of the sum of electron and hole mobilities from photo-induced THz absorption spectra with mobility-dependent ambipolar modeling of TRTS transients. The method is demonstrated on a polycrystalline Cu2ZnSnSe4 thin film and reveals a minority (electron) mobility of 128 cm2/V-s and a majority (hole) carrier mobility of 7 cm2/V-s in the vertical transport direction relevant for light emitting, photovoltaic and solar water splitting devices. Additionally, the TRTS analysis yields an effective bulk carrier lifetime of 4.4 ns, a surface recombination velocity of 6 * 104 cm/s and a doping concentration of ca. 1016 cm−3, thus offering the potential for contactless screen novel optoelectronic materials.
A one-step procedure to probe the viscoelastic properties of cells by Atomic Force Microscopy
Authors: Chim Ya Hua , Mason Louise M. , Rath Nicola , Olson Michael F. , Tassieri Manlio , Yin Huabing 
Published: September 2018

AbstractThe increasingly recognised importance of viscoelastic properties of cells in pathological conditions requires rapid development of advanced cell microrheology technologies. Here, we present a novel Atomic Force Microscopy (AFM)-microrheology (AFM2) method for measuring the viscoelastic properties in living cells, over a wide range of continuous frequencies (0.005 Hz ~ 200 Hz), from a simple stress-relaxation nanoindentation. Experimental data were directly analysed without the need for pre-conceived viscoelastic models. We show the method had an excellent agreement with conventional oscillatory bulk-rheology measurements in gels, opening a new avenue for viscoelastic characterisation of soft matter using minute quantity of materials (or cells). Using this capability, we investigate the viscoelastic responses of cells in association with cancer cell invasive activity modulated by two important molecular regulators (i.e. mutation of the p53 gene and Rho kinase activity). The analysis of elastic (G′(ω)) and viscous (G″(ω)) moduli of living cells has led to the discovery of a characteristic transitions of the loss tangent (G″(ω)/G′(ω)) in the low frequency range (0.005 Hz ~ 0.1 Hz) that is indicative of the capability for cell restructuring of F-actin network. Our method is ready to be implemented in conventional AFMs, providing a simple yet powerful tool for measuring the viscoelastic properties of living cells.
Prognostic Value of Tumor Heterogeneity on 18F-FDG PET/CT in HR+HER2− Metastatic Breast Cancer Patients receiving 500 mg Fulvestrant: a retrospective study
Authors: Zhao Yannan , Liu Cheng , Zhang Yingjian , Gong Chengcheng , Li Yi , Xie Yizhao , Wu Bingrui , Yang Zhongyi , Wang Biyun 
Published: September 2018

AbstractHeterogeneity has been demonstrated to be a predictor of treatment failure and drug resistance. Our study aimed to investigate imaging parameters, including tumor heterogeneity, as prognostic factors of response to 500 mg fulvestrant using 18F-FDG PET/CT. Twenty-seven estrogen receptor (HR)-positive/HER2-negative metastatic breast cancer patients who received 500 mg fulvestrant and underwent 18F-FDG PET/CT before treatment were retrospectively included. In PET/CT scans, conventional parameters (maximum and mean standardized uptake value, metabolic tumor volume [MTV], total lesion glycolysis [TLG]) and heterogeneity parameters (intra-tumor heterogeneity index [HI] and inter-tumor heterogeneity coefficient of variation [COV]) were analyzed. Progression-free survival (PFS) was mainly assessed for efficacy. The survival analyses were performed using the Kaplan–Meier method. Univariate and multivariate analysis were performed using the Cox proportional hazard model. Univariate analysis indicated that a high SUVmax and a high tumor HI at baseline were associated with longer PFS of fulvestrant (P = 0.036 and P = 0.033, respectively). Liver metastasis, SUVmax and HI were statistically significant in multivariate analysis (P values of 0.017, 0.025 and 0.043, respectively). 18F-FDG based intra-tumor heterogeneity appears to be a potential predicator of efficacy of fulvestrant among HR+HER2− metastatic breast cancer patients.
Fasting-dependent Vascular Permeability Enhancement in Brown Adipose Tissues Evidenced by Using Carbon Nanotubes as Fluorescent Probes
Authors: Yudasaka Masako , Yomogida Yohei , Zhang Minfang , Nakahara Masako , Kobayashi Norihiko , Tanaka Takeshi , Okamatsu-Ogura Yuko , Saeki Kumiko , Kataura Hiromichi 
Published: September 2018

AbstractBrown adipose tissue (BAT), which is composed of thermogenic brown adipocytes (BA) and non-parenchymal components including vasculatures and extracellular matrix, contribute to the maintenance of body temperature. BAT distribution is detected by positron emission tomography-computed tomography (PET/CT) using 18F-fluorodeoxy glucose (18F-FDG) or single-photon-emission computed tomography-computed tomography (SPECT/CT) using [123/125I]-beta-methyl-p-iodophenyl-pentadecanoic acid. Although sympathetic nerve activity and thermogenic capacity of BA is downregulated under fasting conditions in mice, fasting-dependent structural changes and fluid kinetics of BAT remain unknown. Here we show that the fasting induces fine and reversible structural changes in the non-parenchymal region in murine BAT with widened intercellular spaces and deformed collagen bands as revealed by electron microscopy. Interestingly, a newly introduced near infrared fluorescent probe of single-walled carbon nanotubes (CNTs) coated with phospholipid polyethylene glycol (PLPEG) easily demonstrated enhanced vascular permeability in BAT by the fasting. PLPEG-CNTs extravasated and remained in intercellular spaces or further redistributed in parenchymal cells in fasted mice, which is a previously unknown phenomenon. Thus, PLPEG-CNTs provide a powerful tool to trace fluid kinetics in sub-tissue levels.
Modeling the production of belly button lint
Authors: Deepu P. 
Published: September 2018

AbstractWe show that respiratory cycle provides a periodic traction force for the production of belly button lint or navel fluff. The relative motion induced between clothing and skin, during breathing, transports the clothing fibers over the abdominal skin via an asymmetric sliding mechanism effected by the specific orientation of the cuticle scales of body hair. The source of these fibers can be the piece of clothing worn adjacent the navel area or the drying towel used after shower. The ratchet like topology of hair surface ensures a net unidirectional transport of these fibers. Since the predominant direction of growth of hair in the abdomen is toward the navel, this unidirectional transport leads to a perpetual accumulation of fibers in the navel over the course of the day. By analyzing the force balance on a moving fiber and the transport dynamics of its number density distribution, we develop a mathematical model to describe the accretion rate of lint fibers in the navel.
Enhanced flame retardancy of polyethylene/magnesium hydroxide with polycarbosilane
Authors: Wang Chunfeng , Wang Yongliang , Han Zhidong 
Published: September 2018

AbstractPolycarbosilane (PCS) was used for surface modification of magnesium hydroxide (MNH) to enhance the flame retardant effectiveness by forming cohesive binding between MgO particles with ceramic adhesive. Chemical interaction and ceramic reaction were revealed between PCS and MNH, which made for a compact, thermal stable and ceramic-like barrier during the combustion of polyethylene (PE). The flame retardancy of PE/MNH/PCS composites was greatly enhanced and a limiting oxygen index (LOI) of 35.0 was achieved at the PCS/MNH ratio of 4/26 in the composite with 30 wt.% PCS modified MNH. Such results were superior in terms of high LOI value at low global content of MNH. Thanks to the better shielding effect of the integrated and self-supporting ceramic char, the peak heat release rate (p-HRR) and the total heat release (THR) of PE/MNH/PCS composites with 50 wt.% PCS modified MNH were remarkably decreased by 36% and 25% in comparison with PE/MNH with 50 wt.% MNH, respectively. The ceramic reaction between PCS and MNH, the superior thermal stability due to crosslinked PCS and the good barrier function of cohesive ceramic layer play important roles in the effective flame retardant mechanism.
Exploring photosensitization as an efficient antifungal method
Authors: Espinoza César , González Miriam C. Rodríguez , Mendoza Guillermo , Creus Alberto Hernández , Trigos Ángel , Fernández José J. 
Published: September 2018

AbstractLipid bilayers containing ergosterol show signs of destruction when they are treated with singlet oxygen, due to the conversion of ergosterol into its peroxy derivative. Applying this previous knowledge, an antifungal method was explored using Candida tropicalis as model, and membrane permeation under photosensitization conditions became evident. These data were complemented through AFM images of artificial lipid bilayers, using cholesterol or ergosterol as structural sterols, showing their corresponding morphologies at the nanoscale. Based on these results, an antifungal method was developed, which shows evidence of the extent of membrane permeation during photosensitization. Such photosensitization offers an effective alternative treatment, especially in membranes with a high ergosterol content, suggesting that this procedure constitutes an easy and efficient antifungal method.