bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics of Micafungin in Critically Ill Patients
Authors: Gastine Silke , Lanckohr Christian , Blessou Magalie , Horn Dagmar , Fobker Manfred , Bause Daniela , Hempel Georg , Ellger Björn 
Published: November 2019

AbstractWe investigated covariates of pharmacokinetics of micafungin in critically ill patients. After application of micafungin, plasma samples were collected. Non-linear mixed effects modelling (NONMEM 7.3) was used to develop the pharmacokinetic model. Using this model, the adequacy of a fixed 100 mg dosing regimen was evaluated in the study cohort. A two-compartment model with linear elimination was found to describe the obtained data. SOFA score was identified as a significant covariate on both clearance and central volume of distribution, respectively. Patients in highly critical condition, represented by a SOFA above 10 showed a 30.8% lower central volume of distribution than the less critically ill patients. For patients with bilirubin levels above 4 mg/dl, clearance was decreased by 21.1%. Renal replacement therapy (RRT) did not influence micafungin clearance or the volumes of distribution. In a posthoc evaluation of the modeled population, 100 mg micafungin was suitable when assessing the PKPD targets (AUC/MIC) for C. albicans and C. glabrata, with insufficient target attainment for C. parapsilosis. Micafungin pharmacokinetics appear not to be influenced by the status of RRT. A dose of 100 mg micafungin is suitable for infections with C. albicans and C. glabrata in critically ill patients.
Wild specimens of sand fly phlebotomine Lutzomyia evansi, vector of leishmaniasis, show high abundance of Methylobacterium and natural carriage of Wolbachia and Cardinium types in the midgut microbiome
Authors: Vivero Rafael J. , Villegas-Plazas Marcela , Cadavid-Restrepo Gloria E. , Herrera Claudia Ximena Moreno , Uribe Sandra I. , Junca Howard 
Published: November 2019

AbstractPhlebotomine sand flies are remarkable vectors of several etiologic agents (virus, bacterial, trypanosomatidLeishmania), posing a heavy health burden for human populations mainly located at developing countries. Their intestinal microbiota is involved in a wide range of biological and physiological processes, and could exclude or facilitate such transmission of pathogens. In this study, we investigated the Eubacterial microbiome from digestive tracts ofLu. evansiadults structure using 16S rRNA gene sequence amplicon high throughput sequencing (Illumina MiSeq) obtained from digestive tracts ofLu. evansiadults. The samples were collected at two locations with high incidence of the disease in humans: peri-urban and forest ecosystems from the department of Sucre, Colombia. 289,068 quality-filtered reads of V4 region of 16S rRNA gene were obtained and clustered into 1,762 operational taxonomic units (OTUs) with 97% similarity. Regarding eubacterial diversity, 14 bacterial phyla and 2 new candidate phyla were found to be consistently associated with the gut microbiome content. Proteobacteria, Firmicutes, and Bacteroidetes were the most abundant phyla in all the samples and the core microbiome was particularly dominated byMethylobacteriumgenus.Methylobacteriumspecies, are known to have mutualistic relationships with some plants and are involved in shaping the microbial community in the phyllosphere. As a remarkable feature, OTUs classified asWolbachiaspp. were found abundant on peri-urban ecosystem samples, in adult male (OTUs n = 776) and unfed female (OTUs n = 324). Furthermore, our results provide evidence of OTUs classified asCardiniumendosymbiont in relative abundance, notably higher with respect toWolbachia. The variation in insect gut microbiota may be determined by the environment as also for the type of feeding. Our findings increase the richness of the microbiota associated withLu. evansi. In this study, OTUs ofMethylobacteriumfound inLu. evansiwas higher in engorged females, suggesting that there are interactions between microbes from plant sources, blood nutrients and the parasites they transmit during the blood intake.
Long-term dispersion of river gravel in a canyon in the Atacama Desert, Central Andes, deduced from their 10Be concentrations
Authors: Carretier Sébastien , Regard Vincent , Leanni Laëtitia , Farías Marcelo 
Published: November 2019

AbstractIntense storms or earthquakes in mountains can supply large amounts of gravel to rivers. Gravel clasts then travel at different rates, with periods of storage and periods of displacement leading to their downstream dispersion over millennia. The rate of this dispersion controls the long-term downcutting rate in mountainous rivers as well as the grain-size signature of climate and tectonic variations in sedimentary basins. Yet, the millennial dispersion rates of gravel are poorly known. Here, we use 10Be concentrations measured in individual pebbles from a localized source along a 56 km-long canyon in the Central Andes to document the distribution of long-term gravel transit rates. We show that an inverse grain-size velocity relationship previously established from short-term tracer gravel in different rivers worldwide can be extrapolated to the long-term transit rates in the Aroma River, suggesting some universality of this relationship. Gravel are also dispersed by large differences in the mean transport rates independent of gravel size, highlighting that some gravel rest at the river surface over tens of thousands of years. These different transport rates imply a strong spreading of the gravel plumes, providing direct proof for the long-term river buffering of sediment signals between mountainous sources and sedimentary basins. The inferred distribution of residence times suggests the first evidence of anomalous diffusion in gravel transport over long timespans.
Specificity and Efficiency of the Uracil DNA Glycosylase-Mediated Strand Cleavage Surveyed on Large Sequence Libraries
Authors: Hölz Kathrin , Pavlic Angelina , Lietard Jory , Somoza Mark M. 
Published: November 2019

AbstractUracil-DNA glycosylase (UDG) is a critical DNA repair enzyme that is well conserved and ubiquitous in nearly all life forms. UDG protects genomic information integrity by catalyzing the excision from DNA of uracil nucleobases resulting from misincorporation or spontaneous cytosine deamination. UDG-mediated strand cleavage is also an important tool in molecular biotechnology, allowing for controlled and location-specific cleavage of single- and double DNA chemically or enzymatically synthesized with single or multiple incorporations of deoxyuridine. Although the cleavage mechanism is well-understood, detailed knowledge of efficiency and sequence specificity, in both single and double-stranded DNA contexts, has so far remained incomplete. Here we use an experimental approach based on the large-scale photolithographic synthesis of uracil-containing DNA oligonucleotides to comprehensively probe the context-dependent uracil excision efficiency of UDG.
Targeted enhancement of flotillin-dependent endocytosis augments cellular uptake and impact of cytotoxic drugs
Authors: Fekri Farnaz , Abousawan John , Bautista Stephen , Orofiamma Laura , Dayam Roya M. , Antonescu Costin N. , Karshafian Raffi 
Published: November 2019

AbstractCellular uptake is limiting for the efficacy of many cytotoxic drugs used to treat cancer. Identifying endocytic mechanisms that can be modulated with targeted, clinically-relevant interventions is important to enhance the efficacy of various cancer drugs. We identify that flotillin-dependent endocytosis can be targeted and upregulated by ultrasound and microbubble (USMB) treatments to enhance uptake and efficacy of cancer drugs such as cisplatin. USMB involves targeted ultrasound following administration of encapsulated microbubbles, used clinically for enhanced ultrasound image contrast. USMB treatments robustly enhanced internalization of the molecular scaffold protein flotillin, as well as flotillin-dependent fluid-phase internalization, a phenomenon dependent on the protein palmitoyltransferase DHHC5 and the Src-family kinase Fyn. USMB treatment enhanced DNA damage and cell killing elicited by the cytotoxic agent cisplatin in a flotillin-dependent manner. Thus, flotillin-dependent endocytosis can be modulated by clinically-relevant USMB treatments to enhance drug uptake and efficacy, revealing an important new strategy for targeted drug delivery for cancer treatment.
Mechanical properties of the shoulder and pectoralis major in breast cancer patients undergoing breast-conserving surgery with axillary surgery and radiotherapy
Authors: Lipps David B. , Leonardis Joshua M. , Dess Robert T. , McGinnis Gwendolyn J. , Marsh Robin B. , Strauss Jonathan B. , Hayman James A. , Pierce Lori J. , Jagsi Reshma 
Published: November 2019

AbstractBreast-conserving surgery (BCS) and radiotherapy reduce breast cancer recurrence but can cause functional deficits in breast cancer survivors. A cross-sectional study quantified the long-term pathophysiological impact of these treatments on biomechanical measures of shoulder stiffness and ultrasound shear wave elastography measures of the shear elastic modulus of the pectoralis major (PM). Nine node-positive patients treated with radiotherapy to the breast and regional nodes after BCS and axillary lymph node dissection (Group 1) were compared to nine node-negative patients treated with radiotherapy to the breast alone after BCS and sentinel node biopsy (Group 2) and nine healthy age-matched controls. The mean follow-up for Group 1 and Group 2 patients was 988 days and 754 days, respectively. Shoulder stiffness did not differ between the treatment groups and healthy controls (p = 0.23). The PM shear elastic modulus differed between groups (p = 0.002), with Group 1 patients exhibiting a stiffer PM than Group 2 patients (p < 0.001) and healthy controls (p = 0.027). The mean prescribed radiotherapy dose to the PM was significantly correlated with passive shear elastic modulus (p = 0.018). Breast cancer patients undergoing more extensive axillary surgery and nodal radiotherapy did not experience long-term functional deficits to shoulder integrity but did experience long-term mechanical changes of the PM.
Entropic nonclassicality and quantum non-Gaussianity tests via beam splitting
Authors: Park Jiyong , Lee Jaehak , Nha Hyunchul 
Published: November 2019

AbstractWe propose entropic nonclassicality criteria for quantum states of light that can be readily tested using homodyne detection with beam splitting operation. Our method draws on the fact that the entropy of quadrature distributions for a classical state is non-increasing under an arbitrary loss channel. We show that our test is strictly stronger than the variance-based squeezing condition and that it can also be extended to detect quantum non-Gaussianity in conjunction with phase randomization. Furthermore, we address how our criteria can be used to identify single-mode resource states to generate two-mode states demonstrating EPR paradox, i.e., quantum steering, via beam-splitter setting.
Germline and somatic mutations of homologous recombination-associated genes in Japanese ovarian cancer patients
Authors: Sugino Kentaro , Tamura Ryo , Nakaoka Hirofumi , Yachida Nozomi , Yamaguchi Manako , Mori Yutaro , Yamawaki Kaoru , Suda Kazuaki , Ishiguro Tatsuya , Adachi Sosuke , Isobe Masanori , Yamaguchi Masayuki , Kashima Katsunori , Motoyama Teiichi , Inoue Ituro , Yoshihara Kosuke , Enomoto Takayuki 
Published: November 2019

AbstractWe explored the frequency of germline and somatic mutations in homologous recombination (HR)-associated genes in major histological types of ovarian cancer. We performed targeted sequencing to assess germline and somatic mutations of 16 HR-associated genes and 4 mismatch repair (MMR) genes among 207 ovarian cancer patients (50 high-grade serous carcinomas (HGSC), 99 clear cell carcinomas (CCC), 39 endometrioid carcinomas (EC), 13 mucinous carcinomas (MC), and 6 low-grade serous carcinomas (LGSC)). Germline or somatic mutations of HR-associated genes were detected in 44% of HGSC, 28% of CCC, 23% of EC, 16% of MC, and 17% of LGSC patients. The profile of HR-associated gene mutations was remarkably different among each histological type. Germline BRCA1/2 mutations were frequently detected in HGSC and were rarely observed in CCC, EC, and MC patients. ATM somatic mutation was more frequently detected in CCC (9%) and EC patients (18%) than in HGSC patients (4%). There was a positive correlation between MMR gene mutations and HR-associated gene mutations (p = 0.0072). Our findings might be useful in selection of ovarian cancer patients that should be treated with PARP inhibitors.
Alpha-PET for Prostate Cancer: Preclinical investigation using 149Tb-PSMA-617
Authors: Umbricht Christoph A. , Köster Ulli , Bernhardt Peter , Gracheva Nadezda , Johnston Karl , Schibli Roger , van der Meulen Nicholas P. , Müller Cristina 
Published: November 2019

AbstractIn this study, it was aimed to investigate 149Tb-PSMA-617 for targeted α-therapy (TAT) using a mouse model of prostate-specific membrane antigen (PSMA)-expressing prostate cancer. 149Tb-PSMA-617 was prepared with >98% radiochemical purity (6 MBq/nmol) for the treatment of mice with PSMA-positive PC-3 PIP tumors. 149Tb-PSMA-617 was applied at 1 × 6 MBq (Day 0) or 2 × 3 MBq (Day 0 & Day 1 or Day 0 & Day 3) and the mice were monitored over time until they had reached a pre-defined endpoint which required euthanasia. The tumor growth was significantly delayed in mice of the treated groups as compared to untreated controls (p < 0.05). TAT was most effective in mice injected with 2 × 3 MBq (Day 0 & 1) resulting in a median lifetime of 36 days, whereas in untreated mice, the median lifetime was only 20 days. Due to the β+-emission of 149Tb, tumor localization was feasible using PET/CT after injection of 149Tb-PSMA-617 (5 MBq). The PET images confirmed the selective accumulation of 149Tb-PSMA-617 in PC-3 PIP tumor xenografts. The unique characteristics of 149Tb for TAT make this radionuclide of particular interest for future clinical translation, thereby, potentially enabling PET-based imaging to monitor the radioligand’s tissue distribution.
Apple B-box factors regulate light-responsive anthocyanin biosynthesis genes
Authors: Plunkett Blue J. , Henry-Kirk Rebecca , Friend Adam , Diack Robert , Helbig Susanne , Mouhu Katriina , Tomes Sumathi , Dare Andrew P. , Espley Richard V. , Putterill Joanna , Allan Andrew C. 
Published: November 2019

AbstractEnvironmentally-responsive genes can affect fruit red colour via the activation of MYB transcription factors. The apple B-box (BBX) gene, BBX33/CONSTANS-like 11 (COL11) has been reported to influence apple red-skin colour in a light- and temperature-dependent manner. To further understand the role of apple BBX genes, other members of the BBX family were examined for effects on colour regulation. Expression of 23 BBX genes in apple skin was analysed during fruit development. We investigated the diurnal rhythm of expression of the BBX genes, the anthocyanin biosynthetic genes and a MYB activator, MYB10. Transactivation assays on the MYB10 promoter, showed that BBX proteins 1, 17, 15, 35, 51, and 54 were able to directly function as activators. Using truncated versions of the MYB10 promoter, a key region was identified for activation by BBX1. BBX1 enhanced the activation of MYB10 and MdbHLH3 on the promoter of the anthocyanin biosynthetic gene DFR. In transformed apple lines, over-expression of BBX1 reduced internal ethylene content and altered both cyanidin concentration and associated gene expression. We propose that, along with environmental signals, the control of MYB10 expression by BBXs in ‘Royal Gala’ fruit involves the integration of the expression of multiple BBXs to regulate fruit colour.
Boron-doped Nanodiamond as an Electrode Material for Aqueous
Electric Double-layer Capacitors
Authors: Miyashita Kenjo , Kondo Takeshi , Sugai Seiya , Tei Takahiro , Nishikawa Masahiro , Tojo Toshifumi , Yuasa Makoto 
Published: November 2019

AbstractHerein, a conductive boron-doped nanodiamond (BDND) particle is
prepared as an electrode material for an aqueous electric double-layer capacitor
with high power and energy densities. The BDND is obtained by depositing a
boron-doped diamond (BDD) on a nanodiamond particle substrate with a primary
particle size of 4.7 nm via microwave plasma-assisted chemical vapor deposition,
followed by heat treatment in air. The BDND comprises BDD and
sp2 carbon components, and exhibits a conductivity
above 1 S cm−1 and a specific surface area of
650 m2 g−1.
Cyclic voltammetry measurements recorded in 1 M
H2SO4 at a BDND electrode in a
two-electrode system shows a capacitance of 15.1 F g−1
and a wide potential window (cell voltage) of 1.8 V, which is much larger than that
obtained at an activated carbon electrode, i.e., 0.8 V. Furthermore, the cell
voltage of the BDND electrode reaches 2.8 V when using saturated
NaClO4 as electrolyte. The energy and power densities per
unit weight of the BDND for charging–discharging in 1 M
H2SO4 at the BDND electrode cell are
10 Wh kg−1 and
104 W kg−1, respectively,
and the energy and power densities per unit volume of the BDND layer are 3–4 mWh
cm−3 and 10 W cm−3,
respectively. Therefore, the BDND is a promising candidate for the development of a
compact aqueous EDLC device with high energy and power densities.
Spike-shape dependence of the spike-timing dependent synaptic plasticity in ferroelectric-tunnel-junction synapses
Authors: Stoliar P. , Yamada H. , Toyosaki Y. , Sawa A. 
Published: November 2019

AbstractResistive switching (RS) devices have attracted increasing attention for artificial synapse applications in neural networks because of their nonvolatile and analogue resistance changes. Among the neural networks, a spiking neural network (SNN) based on spike-timing-dependent plasticity (STDP) is highly energy efficient. To implement STDP in resistive switching devices, several types of voltage spikes have been proposed to date, but there have been few reports on the relationship between the STDP characteristics and spike types. Here, we report the STDP characteristics implemented in ferroelectric tunnel junctions (FTJs) by several types of spikes. Based on simulated time evolutions of superimposed spikes and taking the nonlinear current-voltage (I-V) characteristics of FTJs into account, we propose equations for simulating the STDP curve parameters of a magnitude of the conductance change (ΔGmax) and a time window (τC) from the spike parameters of a peak amplitude (Vpeak) and time durations (tp and td) for three spike types: triangle-triangle, rectangular-triangle, and rectangular-rectangular. The power consumption experiments of the STDP revealed that the power consumption under the inactive-synapse condition (spike timing |Δt| > τC) was as large as 50–82% of that under the active-synapse condition (|Δt| < τC). This finding indicates that the power consumption under the inactive-synapse condition should be reduced to minimize the total power consumption of an SNN implemented by using FTJs as synapses.
Geochemistry of Gold Ores Mined During Celtic Times from the North-Western French Massif Central
Authors: Baron Sandrine , Tămaș Călin G. , Rivoal Marion , Cauuet Béatrice , Télouk Philippe , Albarède Francis 
Published: November 2019

AbstractThe Celtic culture of Western Europe left magnificent gold objects, such as jewellery and weapons from nobility graves and hoarded coins, as well as field evidence of pre-Roman gold mining and metallurgical workshops that attest to the mining of local ores. This is the case of Central France where many precious metallic ores have been mined throughout the ages from the Prehistoric times onwards. One of the lingering problems in assessing the provenance of gold artefacts and coins is the lack of relevant data on the isotope geochemistry and mineralogy of ore sources. Forty gold ores samples were collected and studied from Limousin (French Massif Central), a very significant gold mining district from the Celtic times. Their Pb isotope compositions clearly show a local dichotomy i.e. two distinct groups of ores, one of Late Proterozoic to Early Paleozoic Pb model age and another associated to Variscan ages and consistent with field relationships, mineralogy and elemental analyses. The use of Cu and Ag isotopes, and their coupling with Pb isotopes, will refine the tracing of future metal provenance studies, but also highlight some metallurgical practices like deliberate metal additions to gold artefact or debasement of gold coins. The newly acquired Pb, Ag, and Cu isotopic data on gold ores improves our understanding of ore deposits geology and provide clarifications on the provenance of Celtic gold from this area and its economic importance.
Variations in microbial community structure and functional gene expression in bio-treatment processes with odorous pollutants
Authors: Li Weidong , Ni Jianguo , Cai Shaoqin , Liu Ying , Shen Chenjia , Yang Huayun , Chen Yuquan , Tao Jia , Yu Yunfeng , Liu Qi 
Published: November 2019

AbstractEngineered microbial ecosystems in biofilters have been widely applied to treat odorous gases from industrial emissions. Variations in microbial community structure and function associated with the removal of odorous gases by biofilters are largely unknown. This study performed a metagenomic analysis to discover shifts in microbial community structures in a commercial scale biofilter after treating odorous gas. Our study identified 175,675 functional genes assigned into 43 functional KEGG pathways. Based on the unigene sequences, there were significant changes in microbial community structures in the biofilter after treating odorous gas. The dominant genera were Thiobacillus and Oceanicaulis before the treatment, and were Acidithiobacillus and Ferroplasma after the treatment. A clustering analysis showed that the number of down-regulated microbes exceeded the number of up-regulated microbes, suggesting that odorous gas treatment reduced in microbial community structures. A differential expression analysis identified 29,975 up- and 452,599 down-regulated genes. An enrichment analysis showed 17 classic types of xenobiotic biodegradation pathways. The results identified 16 and 15 genes involved in ammonia and sulfite metabolism, respectively; an analysis of their relative abundance identified several up-regulated genes, which may be efficient genes involved in removing odorous gases. The data provided in this study demonstrate the changes in microbial communities and help identify the dominant microflora and genes that play key roles in treating odorous gases.