bluuebunny/crossref_metadata_2025 huggingface dataset:
Medaka (Oryzias latipes) Multigeneration Test with Triclosan
Authors: Mihaich Ellen , Capdevielle Marie , Urbach-Ross Daniella , Gallagher Sean , Wolf Jeffrey
Published: April 2019

The medaka extended one-generation reproduction test (MEOGRT) is a tier-2 study in the US Environmental Protection Agency's Endocrine Disruptor Screening Program and a level-5 study in the Organisation for Economic Co-operation and Development's conceptual framework. Integrating nonspecific apical and endocrine-specific mechanistic endpoints, results of a MEOGRT can be used, with other data, in a weight-of-evidence evaluation to establish a dose–response relationship for risk assessment and identify potential causal relationships between an endocrine mode of action and adverse effects. The MEOGRT test design was used to evaluate the multigenerational effects of the antimicrobial agent triclosan. Japanese medaka were exposed to nominal concentrations of 1.4, 2.8, 5.6, 11, and 23 μg/L triclosan and a dilution water control starting with adult medaka (F0) through hatch in the second generation (F2). No consistent or concentration-related responses occurred in the 182-d test that suggested an endocrine-mediated effect. There were no impacts on hepatic vitellogenin, secondary sex characteristics, or sex ratio that were linked to an adverse reproductive outcome. Histopathological responses were consistent with a toxic or stress effect, particularly when considered in context with observed reductions in growth. The overall population-relevant no-observed-effect concentration was 11 µg/L based on effects on growth. The results of the present study support a previously conducted weight-of-evidence evaluation concluding that triclosan does not act as an agonist or antagonist within estrogen, androgen, thyroid, or steroidogenic pathways. Environ Toxicol Chem 2019;38:1770–1783. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
Mannose Phosphate Isomerase and Mannose Regulate Hepatic Stellate Cell Activation and Fibrosis in Zebrafish and Humans
Authors: DeRossi Charles , Bambino Kathryn , Morrison Joshua , Sakarin Isabel , Villacorta‐Martin Carlos , Zhang Changwen , Ellis Jillian L. , Fiel M. Isabel , Ybanez Maria , Lee Youngmin A. , Huang Kuan‐lin , Yin Chunyue , Sakaguchi Takuya F. , Friedman Scott L. , Villanueva Augusto , Chu Jaime
Published: April 2019

The growing burden of liver fibrosis and lack of effective antifibrotic therapies highlight the need for identification of pathways and complementary model systems of hepatic fibrosis. A rare, monogenic disorder in which children with mutations in mannose phosphate isomerase (MPI) develop liver fibrosis led us to explore the function of MPI and mannose metabolism in liver development and adult liver diseases. Herein, analyses of transcriptomic data from three human liver cohorts demonstrate that MPI gene expression is down‐regulated proportionate to fibrosis in chronic liver diseases, including nonalcoholic fatty liver disease and hepatitis B virus. Depletion of MPI in zebrafish liver in vivo and in human hepatic stellate cell (HSC) lines in culture activates fibrotic responses, indicating that loss of MPI promotes HSC activation. We further demonstrate that mannose supplementation can attenuate HSC activation, leading to reduced fibrogenic activation in zebrafish, culture‐activated HSCs, and in ethanol‐activated HSCs. Conclusion: These data indicate the prospect that modulation of mannose metabolism pathways could reduce HSC activation and improve hepatic fibrosis.
Study of chromatin remodeling genes implicates SMARCA4 as a putative player in oncogenesis in neuroblastoma
Authors: Bellini Angela , Bessoltane‐Bentahar Nadia , Bhalshankar Jaydutt , Clement Nathalie , Raynal Virginie , Baulande Sylvain , Bernard Virginie , Danzon Adrien , Chicard Mathieu , Colmet‐Daage Léo , Pierron Gaelle , Le Roux Laura , Planchon Julien M. , Combaret Valérie , Lapouble Eve , Corradini Nadège , Thebaud Estelle , Gambart Marion , Valteau‐Couanet Dominique , Michon Jean , Louis‐Brennetot Caroline , Janoueix‐Lerosey Isabelle , Defachelles Anne‐Sophie , Bourdeaut Franck , Delattre Olivier , Schleiermacher Gudrun
Published: April 2019

In neuroblastoma (NB), genetic alterations in chromatin remodeling (CRGs) and epigenetic modifier genes (EMGs) have been described. We sought to determine their frequency and clinical impact. Whole exome (WES)/whole genome sequencing (WGS) data and targeted sequencing (TSCA®) of exonic regions of 33 CRGs/EMGs were analyzed in tumor samples from 283 NB patients, with constitutional material available for 55 patients. The frequency of CRG/EMG variations in NB cases was then compared to the Genome Aggregation Database (gnomAD). The sequencing revealed SNVs/small InDels or focal CNAs of CRGs/EMGs in 20% (56/283) of all cases, occurring at a somatic level in 4 (7.2%), at a germline level in 12 (22%) cases, whereas for the remaining cases, only tumor material could be analyzed. The most frequently altered genes were ATRX (5%), SMARCA4 (2.5%), MLL3 (2.5%) and ARID1B (2.5%). Double events (SNVs/small InDels/CNAs associated with LOH) were observed in SMARCA4 (n = 3), ATRX (n = 1) and PBRM1 (n = 1). Among the 60 variations, 24 (8.4%) targeted domains of functional importance for chromatin remodeling or highly conserved domains but of unknown function. Variations in SMARCA4 and ATRX occurred more frequently in the NB as compared to the gnomAD control cohort (OR = 4.49, 95%CI: 1.63–9.97, p = 0.038; OR 3.44, 95%CI: 1.46–6.91, p = 0.043, respectively). Cases with CRG/EMG variations showed a poorer overall survival compared to cases without variations. Genetic variations of CRGs/EMGs with likely functional impact were observed in 8.4% (24/283) of NB. Our case–control approach suggests a role of SMARCA4 as a player of NB oncogenesis.
NK‐ and T‐cell subsets in malignant mesothelioma patients: Baseline pattern and changes in the context of anti‐CTLA‐4 therapy
Authors: Sottile Rosa , Tannazi Milad , Johansson Maria H. , Cristiani Costanza Maria , Calabró Luana , Ventura Valeria , Cutaia Ornella , Chiarucci Carla , Covre Alessia , Garofalo Cinzia , Pontén Victor , Tallerico Rossana , Frumento Paolo , Micke Patrick , Maio Michele , Kärre Klas , Carbone Ennio
Published: April 2019

Malignant mesothelioma (MM) is a highly aggressive form of cancer with limited treatment options. Although the role of NK cells has been studied in many solid tumors, the pattern of NK‐cell subsets and their recognition of mesothelioma cells remain to be explored. We used RNA expression data of MM biopsies derived from the cancer genome atlas to evaluate the immune cell infiltrates. We characterized the phenotype of circulating NK and T cells of 27 MM patients before and after treatment with an anti‐CTLA‐4 antibody (tremelimumab). These immune cell profiles were compared to healthy controls. The RNA expression data of the MM biopsies indicated the presence of NK cells in a subgroup of patients. We demonstrated that NK cells recognize MM cell lines and that IL‐15 stimulation improved NK cell‐mediated lysis in vitro. Using multivariate projection models, we found that MM patients had a perturbed ratio of CD56bright and CD56dim NK subsets and increased serum concentrations of the cytokines IL‐10, IL‐8 and TNF‐α. After tremelimumab treatment, the ratio between the CD56bright and CD56dim subsets shifted back towards physiological levels. Furthermore, the improved overall survival was correlated with low TIM‐3+CD8+ T‐cell frequency, high DNAM‐1+CD56dim NK‐cell frequency and high expression levels of NKp46 on the CD56dim NK cells before and after immune checkpoint blockade. Together, our observations suggest that NK cells infiltrate MM and that they can recognize and kill mesothelioma cells. The disease is associated with distinct lymphocytes patterns, some of which correlate with prognosis or are affected by treatment with tremelimumab.
In Search of Bioactivity – Phyllobilins, an Unexplored Class of Abundant Heterocyclic Plant Metabolites from Breakdown of Chlorophyll
Authors: Moser Simone , Kräutler Bernhard
Published: April 2019

The fate of the green plant pigment chlorophyll (Chl) in de‐greening leaves has long been a fascinating biological puzzle. In the course of the last three decades, various bilin‐type products of Chl breakdown have been identified, named phyllobilins (PBs). Considered ‘mere’ leftovers of a controlled biological Chl detoxification originally, the quest for finding relevant bioactivities of the PBs has become a new paradigm. Indeed, the PBs are abundant in senescent leaves, in ripe fruit and in some vegetables, and they display an exciting array of diverse heterocyclic structures. This review outlines briefly which types of Chl breakdown products occur in higher plants, describes basics of their bio‐relevant structural and chemical properties and gives suggestions as to ‘why’ the plants produce vast amounts of uniquely ‘decorated’ heterocyclic compounds. Clearly, it is worthwhile to consider crucial metabolic roles of PBs in plants, which may have practical consequences in agriculture and horticulture. However, PBs are also part of our plant‐based nutrition and their physiological and pharmacological effects in humans are of interest, as well.
A blueprint to establish a four‐bed obstetric critical care unit in the labor ward of a central hospital
Authors: Langenegger Eduard J. , Theron Gerhard B. , Hall David R. , Bello Camilo , Escobar Vidarte Maria Fernanda ,   the FIGO Committee for Safe Motherhood and Newborn Health
Published: April 2019

Patients at risk of organ dysfunction or with established organ dysfunction should be referred to central or tertiary‐level hospitals. However, even in central hospitals, intensive care unit (ICU) beds are often unavailable, which may contribute to maternal deaths. One pragmatic solution is to establish obstetric critical care units (OCCUs) in the labor wards of central hospitals; however, specific guidance on how to do this is limited. In addition, globally applicable standards of care are lacking, with uncertainty regarding who should lead obstetric critical care. In this article the specific OCCU infrastructure, equipment and human resources required to establish such units in central hospitals in low‐ and middle‐income countries are described in sufficient detail for easy replication. Admission and discharge guidelines and operational recommendations that include quality indicators are also provided.
Observing home‐visiting quality at scale with the home visit rating scales and a supervisor checklist in Peru
Authors: Rubio‐Codina Marta , Dormal Marta , Araujo M. Caridad
Published: April 2019

As home‐visiting programs expand, there is a need to develop cost‐effective tools to monitor their quality at scale. We compare the Home Visit Rating Scales (HOVRS), an instrument to measure home‐visit process quality widely used in the United States, to a checklist designed for the Peruvian national home‐visiting program, Cuna Mas. Both instruments were administered to a sample of 554 home visits and an equal number of mother–child dyads by their 176 home visitors. While the HOVRS was scored on video recordings of the visits by trained coders, the checklist was scored live by Cuna Mas supervisors. We assessed the validity of both measures in their first application in rural Peru, compared their performance, and selected a subset of items in the checklist to propose a simplified, shorter, and more cost‐efficient instrument. To this end, we reorganized checklist items into constructs that best mapped those covered by the HOVRS and selected the highest performing according to predefined criteria. We found that both the HOVRS and the checklist had high reliability and acceptable levels of validity. We argue that the simplified checklist could prove useful for quality monitoring of service delivery of at‐scale home‐visiting programs and as a tool to support in‐service training.
From High School Curriculum to Literacy Network: Transforming High School English Teaching in California
Authors: Brynelson Nancy , Fletcher Jennifer , Graff Nelson
Published: April 2019

This department focuses on literacy leaders, including school and instructional leaders, teachers, and external partners, who are working to improve outcomes for adolescent and adult learners in a wide range of education settings. Columns investigate the challenges and complexities inherent in such work and share lessons learned, impactful strategies and approaches, and promising pathways forward.
Moving Forward: Sustaining Multilingual Literacies
Authors: Guerra Juan C.
Published: April 2019

This department explores how teachers can sustain students’ multilingual literacies and reimagine literacy learning across multiple contexts in conversation with researchers, practitioners, and communities.
Polyglycolic acid‐collagen tube combined with collagen‐binding basic fibroblast growth factor accelerates gait recovery in a rat sciatic nerve critical‐size defect model
Authors: Fujimaki Hisako , Uchida Kentaro , Inoue Gen , Matsushita Osamu , Nemoto Noriko , Miyagi Masayuki , Inage Kazuhide , Takano Shotaro , Orita Sumihisa , Ohtori Seiji , Tanaka Keisuke , Sekiguchi Hiroyuki , Takaso Masashi
Published: April 2019

Several nerve conduits have been investigated for their potential as alternative sources of autografts for bridging neural gaps. However, autologous nerve transplants remain the most effective for nerve repair. We examined clinically approved nerve conduits containing collagen and polyglycolic acid (PGA‐c) combined with collagen‐binding basic fibroblast growth factor (bFGF) containing a polycystic kidney disease (PKD) domain and collagen binding domain (CBD) (bFGF‐PKD‐CBD) in a rat 15‐mm sciatic nerve critical‐size defect model. The treatment groups were: PGA‐c immersed in phosphate‐buffered saline (PBS) (PGA‐c/PBS group), bFGF (PGA‐c/bFGF group), or bFGF‐PKD‐CBD (PGA‐c/bFGF‐PKD‐CBD group), and no treatment (Defect group). Gait and histological analyses were performed. Four weeks after treatment, the recovery rate of the paw print area was significantly greater in the PGA‐c/bFGFPKD‐CBD group than the PGA‐c/PBS and PGA‐c/bFGF groups. Mean intensity of paw prints was significantly greater in the PGA‐c/bFGF‐PKD‐CBD group than the PGA‐c/PBS and Defect groups. Swing time was significantly greater in the PGA‐c/PBS, PGA‐c/bFGF, and PGA‐c/bFGF‐PKD‐CBD groups than the Defect group. At 8 weeks, all three parameters were significantly greater in the PGA‐c/PBS, PGA‐c/bFGF, and PGA‐c/bFGF‐PKD‐CBD groups than the Defect group. Regenerated myelinated fibers were observed in 7/8 (87.5%) rats in the PGA‐c/bFGF‐PKD‐CBD group after 8 weeks, and in 1/8 (12.5%) and 3/8 (37.5%) rats in the PGA‐c/PBS and PGA‐c/bFGF groups, respectively. PGA‐c/bFGF‐PKD‐CBD composites may be promising biomaterials for promoting functional recovery of long‐distance peripheral nerve defects in clinical practice.
Gene polymorphisms of SFTPB rs7316, rs9752 and PAOX rs1046175 affect the diagnostic value of plasma Pro‐SFTPB and DAS in Chinese Han non–small‐cell lung cancer patients
Authors: Wang Kun , Huang Qiubo , Zhao Guangqiang , Yang Jiapeng , Yang Kaiyun , Huang Yunchao
Published: April 2019

Plasma pro‐surfactant protein B (pro‐SFTPB) and N1,N12‐diacetylspermine (DAS) can be used as markers for the diagnosis of non–small‐cell lung carcinoma (NSCLC). Whether the genetic diversity affects the application value of Pro‐SFTPB and DAS as a diagnostic marker for NSCLC is still unknown. This study aims to explore the relationship between SFTPB rs7316, rs9752 and PAOX rs1046175 gene polymorphisms and the diagnostic value of plasma Pro‐SFTPB and DAS in patients with Chinese Han lung cancer. SFTPB rs7316, rs9752 and PAOX rs1046175 genotypes were analyzed by direct sequencing in 425 patients with NSCLC and 425 controls, and the levels of Pro‐SFTPB and DAS in plasma were determined by enzyme‐linked immunosorbent assay (ELISA). The area under the curve (AUC) of the SFTPB rs7316 locus TT genotype for the diagnosis of NSCLC was 0.758, and the AUC of the TC/CC genotype for the diagnosis of NSCLC was 0.872. The AUC of the SFTPB rs9752 locus GG genotype for the diagnosis of NSCLC was 0.935, and the AUC of the GC/CC genotype for the diagnosis of NSCLC was 0.648. The AUC of the PAOX rs1046175 locus GG for the diagnosis of NSCLC was 0.669, and the AUC of the GC/CC genotype for the diagnosis of NSCLC was 0.749. In conclusion, SFTPB rs7316, rs9752, and PAOX rs1046175 gene polymorphisms affect the diagnostic value of plasma Pro‐SFTPB and DAS in patients with Chinese Han NSCLC.
MicroRNA‐203 reinforces stemness properties in melanoma and augments tumorigenesis in vivo
Authors: Sahranavardfard Parisa , Firouzi Javad , Azimi Masoumeh , Khosravani Pardis , Heydari Raheleh , Emami Razavi Amirnader , Dorraj Mahshad , Keighobadi Faezeh , Ebrahimi Marzieh
Published: April 2019

One of the challenges encountered in microRNA (miRNA) studies is to observe their dual role in different conditions and cells. This leads to a tougher prediction of their behavior as gene expression regulators. miR‐203 has been identified to play a negative role in the progression of malignant melanoma; however, it has been reported, with dual effect, as both an oncomiR and tumor suppressor miRNA in some malignancies, such as breast cancer, meanwhile, the role of miR‐203 in melanoma stem cells or even metastatic cells is unclear. In the present study, after observation of upregulation of miR‐203 in melanoma patient's serum and also melanospheres as cancer stem cells model, we examined its overexpression on the stemness potential and migration ability of melanoma cells. Our data demonstrated that the increased miR‐203 level was significantly associated with significant increase in the ability of proliferation, colony and spheres formation, migration, and tumorigenesis in A375 and NA8 cells. All of these changes were associated with enhancement of BRAF, several epithelial to mesenchymal transition factors, and stemness genes. In conclusion, our results clearly determined that miR‐203 could be down‐regulateddownregulated in melanoma tissues but be overexpressed in melanoma stem cells. It has an important role as oncomiR and promote repopulation, tumorigenicity, self‐renewal, and migration. Therefore, we suggested overexpression of miR‐203 as biomarker for early detection of metastasis. However, more studies are needed to validate our data.
Exosomal microRNA‐155‐5p from PDLSCs regulated Th17/Treg balance by targeting sirtuin‐1 in chronic periodontitis
Authors: Zheng Ya , Dong Chen , Yang Junling , Jin Yi , Zheng Wenjie , Zhou Qiao , Liang Yi , Bao Liuliu , Feng Guijuan , Ji Juan , Feng Xingmei , Gu Zhifeng
Published: April 2019

The mechanism of local inflammation and systemic injury in chronic periodontitis is complicated, in which and exosomes play an important role. In our study, we found that T helper cell 17 (Th17)/regulatory T cell (Treg) balance is destabilized in the peripheral blood of patients with periodontitis, with upregulated Th17 or downregulated Treg, respectively. Porphyromonas gingivalis lipopolysaccharide (LPS) was used to simulate the inflammatory microenvironment of chronic periodontitis. The exosomes were extracted from periodontal ligament stem cells (PDLSCs) in LPS‐induced periodontitis environment, which inversely effected on CD4+ T cells under normal and inflammatory conditions. Furthermore, compared with exosomes from normal PDLSCs, lower expression of microRNA‐155‐5p (miR‐155‐5p) and higher expression of Sirtuin‐1 (SIRT1) were observed in exosomes from LPS‐stimulated PDLSCs. Exosomes from PDLSCs alleviated inflammatory microenvironment through Th17/Treg/miR‐155‐5p/SIRT1 regulatory network. This study aimed to find the “switching” factors that affected the further deterioration of periodontitis to maximally control the multiple downstream damage signal factors to further understand periodontitis and find new targets for its treatment.
Chandipura virus changes cellular miRNome in human microglial cells
Authors: Agrawal Meghna , Rastogi Meghana , Dogra Smriti , Pandey Neha , Basu Anirban , Singh Sunit K.
Published: April 2019

Chandipura virus (CHPV) is a neurotropic virus, known to cause encephalitis in humans. The microRNAs (miRNA/miR) play an important role in the pathogenesis of viral infection. The present study is focused on the role of miRNAs during CHPV (strain 1653514) infection in human microglial cells. The deep sequencing of CHPV‐infected human microglial cells identified a total of 12 differentially expressed miRNA (DEMs). To elucidate the role of DEMs, the target gene prediction, Gene Ontology term (GO Term), pathway enrichment analysis, and miRNA‐messenger RNA (mRNA) interaction network analysis was performed. The GO terms and pathway enrichment analysis provided 146 enriched genes; which were involved in interferon response, cytokine and chemokine signaling. Further, the WGCNA (weighted gene coexpression network analysis) of the enriched genes were discretely categorized into three modules (blue, brown, and turquoise). The hub genes in the blue module may correlate to CHPV induced neuroinflammation. Altogether, the miRNA‐mRNA interaction network and WGCNA study revealed the following pairs, hsa‐miR‐542‐3p and FAF1, hsa‐miR‐92a‐1‐5p and MYD88, and hsa‐miR‐3187‐3p and TNFRSF21, which may contribute to neuroinflammation during CHPV infection in human microglial cells.
The 30–60‐day northward‐propagating intraseasonal oscillation over South China Sea during pre‐monsoon period in a coupled model
Authors: Zheng Bin , Huang Yanyan , Li Chunhui
Published: April 2019

The 50‐year pentad mean simulation outputs of an atmosphere–ocean coupled general circulation model, the Scale INTeraction EXperiment (SINTEX)‐the Frontier Research Center for Global Change (FRCGC) model (SINTEX‐F model), are used to understand processes of the northward‐propagation of intraseasonal oscillations (ISOs) over the South China Sea (SCS) during the pre‐monsoon season. A quite different mean state is found in the SCS before the monsoon onset relative to that of summertime, which is consistent with the observations. Then, 18‐year SCS ISOs, with a relatively larger strength and significant northward component, are selected, and the composite and lead–lag correlation analyses are conducted to explore a possible mechanism for the northward propagation of ISOs in the pre‐monsoon period. Two mechanisms contribute to the northward propagation of the SCS ISOs. One is the vorticity advection by the barotropic southerly mean flow. First, a barotropic vorticity is induced by vertical advection inside the convection centre. During the pre‐monsoon period, the west sides of the upper tropospheric high and the western Pacific subtropical high cover the SCS, thus, there are southerly flows both in the upper and lower troposphere over the SCS. Then the barotropic vorticity induced inside the convection centre shifts to the north because of the advection by the barotropic southerly mean flow. The other is the planetary boundary layer (PBL) moisture advection by the mean flow that lead to a meridional phase leading of the ISO humidity. The northward shift of the PBL moisture promotes a convective instability ahead of the convection centre and leads to the northward propagation of ISOs over the SCS.
More realistic land‐use and vegetation parameters in a regional climate model reduce model biases over China
Authors: Gou Jiaojiao , Wang Fei , Jin Kai , Mu Xingmin , Chen Deliang
Published: April 2019

Accurate vegetation cover data are important for realistic simulation of regional climate. The default vegetation parameters from Global Land Cover 2000, currently incorporated into global climate models and used in regional climate model RegCM, are not realistic for China, which may have contributed to serious bias in surface climate simulation. In this study, a new set of vegetation parameters considering the Plant Functional Type (PFT) fractions and the corresponding monthly leaf area index (PFT_LAI), were developed based on the land cover and MODIS LAI data sets. The regional climate model RegCM4.5 coupled with the land surface model CLM4.5 were utilized to test the performance of the new vegetation parameters by comparing simulations with observations using different surface parameters. The surface energy balance was analysed to examine the effects of changed vegetation parameters on regional climate. The results showed that the new parameters were more accurate than the GLC2000 parameters when describing the distribution of crops, grassland, and forests over China. The improved vegetation parameters reduced model biases for winter air temperature and precipitation over southern China by 0.9°C and 8%, respectively, and reduced the winter temperature and summer precipitation biases over northeastern China by approximately 0.7°C and 8%, respectively. More accurate surface albedo are the main reasons for reductions in model bias. However, certain biases, such as the cold and dry bias over the Tibetan Plateau, still remained in the simulation results using our new vegetation data.
Ten micrometer pixel, quantum dots color conversion layer for high resolution and full color active matrix micro‐LED display
Authors: Kim Hyo‐Min , Ryu Misun , Cha James H.J. , Kim Hyun Soo , Jeong Tak , Jang Jin
Published: April 2019

A fine patternable quantum dots (QDs) color conversion layer (CCL) for high resolution and full color active matrix (AM) micro‐LED (μ‐LED) display is demonstrated. QDs CCL could be patterned until 10 μm using photolithography process. It is found that multicoatings with red and green QDs (R‐ and G‐QDs) CCLs on LED array can provide full color AM display.
Effect of UDP‐glucuronosyltransferase 1A1 activity on risk for developing Gilbert's syndrome
Authors: Huang May‐Jen , Chen Yi‐Chun , Huang Yang‐Yang , Yang Sien‐Sing , Chen Pei‐Lain , Huang Ching‐Shan
Published: April 2019

Variations at the six nucleotides −3279 (T > G), −53 (A[TA]6TAA > A[TA]7TAA), 211 (G > A), 686 (C > A), 1091 (C > T), and 1456 (T > G) in the UDP‐glucuronosyltransferase 1A1 (UGT1A1) gene were determined in 178 Taiwanese patients with Gilbert's syndrome and in 200 healthy adults. Every subject was classified as a genotype depending on variation status of the six nucleotides in the UGT1A1 gene. The UGT1A1 activity for each genotype was calculated and then those genotypes were divided into 10 subgroups (Q1~Q10) according to their UGT1A1 activities, by using 10% as an interval. There were 24 genotypes observed, with UGT1A1 activity ranged 9%~100% of normal. There were two and six subjects with Gilbert's syndrome and none of healthy controls carrying genotypes in the Q1 and Q2 subgroups, respectively. The odds of developing Gilbert's syndrome were significantly higher for subjects carrying genotypes in the Q3, Q4, and Q5 subgroups than for those with genotype in the Q10 subgroup (odds ratios: 240.22, 59.80, and 14.67, respectively, P < .001 for each). Among the 178 patients of Gilbert's syndrome, serum bilirubin value was inversely correlated with UGT1A1 activity (r = −.306, P < .001). The sensitivity was 72.0% and the specificity was 90.5% by using UGT1A1 activity ≦40% of normal as the cut‐off point to distinguish between healthy subjects and patients of Gilbert's syndrome. Our results demonstrate that UGT1A1 activity is certainly a determinate for serum bilirubin value and UGT1A1 activity ≦40% of normal is a proper risk factor for the development of Gilbert's syndrome.
Phase transitions in (C7H12N2)2[SnCl6]Cl2·1.5H2O crystal, studied by NMR and infrared spectroscopy
Authors: Hajji Rachid , Hlel Faouzi
Published: April 2019

The (C7H12N2)2[SnCl6]Cl2·1.5H2O complex is a new member of the family of hybrid organic–inorganic perovskite compounds. It exhibits two order–disorder phase transitions with changes in the conformation of aromatic cations at the two transition temperatures 360 and 412 K. Differential scanning calorimetry, nuclear magnetic resonance (NMR), and Fourier‐transform infrared (FT‐IR) spectroscopy were used to investigate these phase transitions. These transition mechanisms were investigated in terms of the spin–lattice relaxation times T1 for 1H static NMR and the chemical shifts for 13C CP–MAS. The temperature dependence of T1(1H) and 13C chemical shifts are changed near TC1 and TC2. Furthermore, the splitting for 13C NMR signals in Phases (II) and (III) indicated a ferroelastic characteristic of the compound. In addition, FT‐IR results indicate that the ordered conformational structure of aromatic cations undergoes a remarkable disorder with increasing temperature. The NMR and FT‐IR studies suggest that the phase transition mechanisms are related to the reorientational motion of [C7H12N2]2+ cations as a whole. Phase transition was examined in light of the interesting optical properties of this material.
A Heaviside function‐based density representation algorithm for truss‐like buckling‐induced mechanism design
Authors: Deng Hao
Published: April 2019

Motivated by key advances in manufacturing techniques, the tailoring of materials to achieve novel properties such as energy dissipation properties has been the focus of active research in engineering and materials science over the past decade. The goal of material design is to determine the optimal spatial layout to achieve a desired macroscopic constitutive response. However, the manufacturing abilities are the key factors to constrain the feasible design space, eg, minimum length and geometry complexity. Traditional density‐based method, where each element works as a variable, always results in complicated geometry with large number of small intricate features. To address the aforementioned challenges, a new density field representation technique, named, Heaviside function‐based geometric representation algorithm, is proposed in this paper, where density field is represented by truss‐like components. Truss‐like components have less control parameters and easier to handle for sensitivities derivation, especially for distance sensitivities. Using bar components to explicitly represent density field can explore design space effectively and generate simple structures without any intricate small features at borders. Furthermore, this density representation method is mesh independent and design variables are reduced significantly so that optimization problem can be solved efficiently using small‐scale optimization algorithm, eg, sequential quadratic programming. However, finding a reasonable initial component distribution is critical to avoid optimization failure. To overcome this difficulty, a jump‐start method is proposed by solving inverse subproblem. The overall optimization progress is divided into three stages, ie, the first stage is obtaining coarse snap‐through material configuration based on traditional density‐based method; the second stage is an inverse optimization problem to fit the geometry component to the solution obtained in stage I; and the stage III is maximizing the energy dissipation capacity. To demonstrate the powerful ability in design buckling‐induced mechanism of the proposed density representation algorithm, buckling‐induced energy dissipation mechanism with snap‐through behavior to achieve the desired energy dissipation capacity considering failure constraint is demonstrated through four numerical examples.
Aromatic Nucleophilic Substitution via Chlorinated Nitrated Benzene Derivatives: Four Energetic Ring‐substituted Furazans
Authors: Feng Zhicun , Zhang Yu , Li Jing , Li Yanan , Zhao Fengqi , Xu Kangzhen
Published: April 2019

According to an energetic molecule integration strategy, four energetic ring‐substituted furazans, 3‐amino‐4‐(2,4‐dinitroanilino)furazan (5), 3‐amino‐4‐picrylaminofurazan (6), 3,4‐bis(picrylamino)furazan (7) and 4‐(4‐aminofurazanamino)‐7‐nitro‐2,1,3‐benzoxadiazole (8), were synthesized through a similar aromatic nucleophilic substitution system. Crystal structures of 5–7 as well as that of a raw material 3,4‐diaminofurazan (1) for comparison are first reported and analyzed in detail. Thermal behavior, detonation properties and impact sensitivities of compounds 5–8 are discussed. Compounds 6–8 possess good potential to be used as energetic materials (EMs). Furthermore, compound 7, as the most promising high‐energy compound with high thermal stability and low sensitivity among the four ring‐substituted furazans, has the lowest impact sensitivity (>23.5 J) comparable to that of 1,1‐diamino‐2,2‐dinitroethylene (FOX‐7), the highest thermal stability [peak temperatures (Tp)=293.63 °C] close to that of cyclotetramethylene tetranitramine (HMX) and 2,4,6‐trinitrotoluene (TNT) and the best detonation performance [detonation pressure (P)=28.4 GPa and detonation velocity (vD)=7878 m s−1] superior to that of 1,3,5‐triamino‐2,4,6‐trinitrobenzene (TATB).
A bypass mechanism of abiraterone‐resistant prostate cancer: Accumulating CYP17A1 substrates activate androgen receptor signaling
Authors: Moll Jan M. , Kumagai Jinpei , van Royen Martin E. , Teubel Wilma J. , van Soest Robert J. , French Pim J. , Homma Yukio , Jenster Guido , de Wit Ronald , van Weerden Wytske M.
Published: April 2019

Background

Intratumoral steroidogenesis and its potential relevance in castration‐resistant prostate cancer (CRPC) and in cytochrome P450, family 17, subfamily A, polypeptide 1 (CYP17A1)‐inhibitor treated hormone‐naïve and patients with CRPC are not well established. In this study, we tested if substrates for de novo steroidogenesis accumulating during CYP17A1 inhibition may drive cell growth in relevant preclinical models.

Methods

PCa cell lines and their respective CRPC sublines were used to model CRPC in vitro. Precursor steroids pregnenolone (Preg) and progesterone (Prog) served as substrate for de novo steroid synthesis. TAK700 (orteronel), abiraterone, and small interfering RNA (siRNA) against CYP17A1 were used to block CYP17A1 enzyme activity. The antiandrogen RD162 was used to assess androgen receptor (AR) involvement. Cell growth was measured by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. AR‐target gene expression was quantified by reverse transcription polymerase chain reaction (RT‐PCR). Nuclear import studies using cells with green fluorescent protein (GFP)‐tagged AR were performed to assess the potential of precursor steroids to directly activate AR.

Results

Preg and Prog stimulated cell proliferation and AR target gene expression in VCaP, DuCaP, LNCaP, and their respective CRPC sublines. The antiandrogen RD162, but not CYP17A1 inhibition with TAK700, abiraterone or siRNA, was able to block Preg‐ and Prog‐induced proliferation. In contrast to TAK700, abiraterone also affected dihydrotestosterone‐induced cell growth, indicating direct AR binding. Furthermore, Prog‐induced AR translocation was not affected by treatment with TAK700 or abiraterone, while it was effectively blocked by the AR antagonist enzalutamide, further demonstrating the direct AR activation by Prog.

Conclusion

Activation of the AR by clinically relevant levels of Preg and Prog accumulating in abiraterone‐treated patients may act as a driver for CRPC. These data provide a scientific rationale for combining CYP17A1 inhibitors with antiandrogens, particularly in patients with overexpressed or mutated‐AR.
Tabletop extreme ultraviolet time‐of‐flight spectrometry for trace analysis of high ionization energy samples
Authors: Arbelo Yunieski , Bleiner Davide
Published: April 2019

Rationale

Species with ionization energies beyond what is accessible using state‐of‐the‐art lab sources are affected by poor detection limits in ordinary mass spectrometry setups, whose throughput is also often limited. Extreme ultraviolet (XUV) photoionization mass spectrometry, in combination with linear time‐of‐flight (TOF), is necessary for the sensitive detection of high ionization energy compounds at trace level. XUV photoionization is available at beamlines, although with limited access. A tabletop setup may fill such a gap.

Methods

A self‐developed tabletop system, based on a plasma discharge with extreme ultraviolet emission (λ = 5‐50 nm) coupled to a TOF mass spectrometer, was used in this study. Simultaneous validation measurements with a reference electron ionization quadrupole mass filter were carried out. An in‐house developed hollow toroidal coil (HTC) induction detector was used for concomitant photoelectron detection.

Results

Straightforward XUV mass spectra without fragmentation, thanks to the single‐photon ionization, were acquired. The measurements with the reference quadrupole were in agreement with the spectra acquired by XUV‐TOF. The resolution obtained for N2 was at least factor of 2 higher than that measured with the reference quadrupole. Initial energy distributions of photoelectrons were retrieved by cross‐correlation that gave access to the photoionization distribution.

Conclusions

The system allows XUV single‐photon ionization of elements and molecules with IE >10 eV that are of fundamental interest e.g. for water splitting and catalysis research. The demonstrated performance is now suitable for a prototype platform.
Endoscopic robot‐assisted simple enucleation of renal tumours: Impact of learning curve and tumour complexity on trifecta outcomes
Authors: Lu Zhaoxiang , Zhou Jun , Yang Cheng , Zhang Li , Tai Sheng , Xiang Rong , Liang Chaozhao
Published: April 2019

Background

In this article, we report the outcomes of endoscopic robot‐assisted tumour enucleation (ERASE) using a trifecta system.

Methods

One hundred eighty‐two patients were treated with ERASE by a single surgeon between October 2014 and February 2017 and were stratified by quartiles of distribution called ERASE eras 1 to 4 and preoperative aspects and dimensions used for an anatomical (PADUA) score risk group categories. The trifecta achievement rates in different ERASE eras and PADUA score risk group categories were analysed.

Results

The overall trifecta achievement rate was 76.4%; this rate progressively increased along the learning curve and reached 87.2% in ERASE era 4 (0.002). PADUA score risk group categories were inversely correlated with the trifecta achievement rate (P < .001). When both variables were simultaneously considered, a trend towards a higher trifecta achievement rate was observed in the recent series regardless of tumour anatomical complexity.

Conclusions

The trifecta achievement rate increased with surgical experience and was inversely correlated with tumour complexity.
Bioinspired Multivalent Peptide Nanotubes for Sialic Acid Targeting and Imaging‐Guided Treatment of Metastatic Melanoma
Authors: Lei Li , Xu Zhiai , Hu Xianli , Lai Yi , Xu Jie , Hou Bo , Wang Ya , Yu Haijun , Tian Yang , Zhang Wen
Published: April 2019

Tumor metastasis is considered a major cause of cancer‐related human mortalities. However, it still remains a formidable challenge in clinics. Herein, a bioinspired multivalent nanoplatform for the highly effective treatment of the metastatic melanoma is reported. The versatile nanoplatform is designed by integrating indocyanine green and a chemotherapeutic drug (7‐ethyl‐10‐hydroxycamptothecin) into phenylboronic acid (PBA)‐functionalized peptide nanotubes (termed as I/S‐PPNTs). I/S‐PPNTs precisely target tumor cells through multivalent interaction between PBA and overexpressed sialic acid on the tumor surface in order to achieve imaging‐guided combination therapy. It is demonstrated that I/S‐PPNTs are efficiently internalized by the B16‐F10 melanoma cells in vitro in a PBA grafting density–dependent manner. It is further shown that I/S‐PPNTs specifically accumulate and deeply penetrate into both the subcutaneous and lung metastatic B16‐F10 melanoma tumors. More importantly, I/S‐PPNT‐mediated combination chemo‐ and photodynamic therapy efficiently eradicates tumor and suppresses the lung metastasis of B16‐F10 melanoma in an immunocompetent C57BL/6 mouse model. The results highlight the promising potential of the multivalent peptide nanotubes for active tumor targeting and imaging‐guided cancer therapy.
Engineering of Oxygen Vacancy and Electric‐Field Effect by Encapsulating Lithium Titanate in Reduced Graphene Oxide for Superior Lithium Ion Storage
Authors: Meng Tao , Li Bo , Hu Lei , Yang Hao , Fan Wenjie , Zhang Shanqing , Liu Peng , Li Mingyang , Gu Feng Long , Tong Yexiang
Published: April 2019

Rational design of nanostructured electrode materials is highly desired for developing high‐performance lithium‐ion batteries (LIBs). Encapsulating electrode materials in reduced graphene oxide (rGO) shows great potential for manipulation of physicochemical properties at the atomic level, promoting remarkable electrochemical properties. Here, a controllable strategy is proposed to synthesize a “pomegranate‐like” 3D rGO encapsulated lithium titanate composite (CT‐rGO@LTO). The experimental results demonstrate the enriched oxygen vacancies in LTO and the electronic interactions at the interface between LTO and rGO. Density functional theory (DFT) calculations confirm the charge redistribution in the CT‐rGO@LTO composite, establishing a strong electric field with oxygen vacancies. Furthermore, the extra active sites in rGO for Li‐ion storage are investigated via in situ Raman tests. Benefiting from the oxygen vacancies and the electric‐field effect, the CT‐rGO@LTO electrode delivers excellent cycling stability with a capacity retention of 87.1% after 1500 cycles at 5 C. Moreover, the CT‐rGO@LTO electrode is adopted to assemble a full cell with a LiCoO2 cathode, which also displays superior rate capability with capacities of 139.4 and 109.7 mA h g−1 at 0.5 and 10 C, respectively. This work provides profound insights of fabricating high‐performance electrode materials for advanced energy storage.
Corporate social responsibility and competitive advantage: A developing country perspective
Authors: Nyuur Richard B. , Ofori Daniel F. , Amponsah Ms Millicent
Published: April 2019

Corporate social responsibility (CSR) has attracted wider research interests over recent decades. While some studies have examined the impact of CSR activities on firm competitive advantage (CA), the findings so far remain contradictory. Moreover, the role of export orientation, firm strategy, and structure on the association between CSR and CA has not been explicitly examined. Thus, the purpose of this study is to examine the moderating role of export orientation, firm strategy, structure, and firm size on the association between CSR and CA. Using a sample of 179 responses from management staff in organizations across five sectors in a developing country context of Ghana, the study found positive effects of CSR on CA. The study contributes to the resource‐based view (RBV) scholarship by confirming the important complementary effect of export orientation and organizational structure as important resources and capabilities on the CSR–competitiveness relationship. However, no evidence of a moderating effect of firm strategy, or firm size on the CSR–CA relationship was found. These findings are instructive, impactful, and enrich the existing literature on CSR and strategy. Implications for theory and practice are also discussed.
Hajj abattoirs in Makkah: risk of zoonotic infections among occupational workers
Authors: Almasri Malak , Ahmed Qanta A. , Turkestani Abdulhafeez , Memish Ziad A.
Published: April 2019

At completion of Hajj, the Islamic pilgrimage to Makkah, pilgrims give thanks for the blessing, and acceptance, of Hajj, marking the end of the pilgrimage by sacrificing an animal and distributing the sacrificial meat to the poor. With over two million Muslims making Hajj, each Hajj, more than 1.2 million heads of cattle: sheep, goats and camels are slaughtered. Over 16 000 abattoir workers work around the clock to sacrifice and process the cattle in keeping with Islamic law and public health guidelines. Because of their proximity to high densities of cattle and cattle meat, Makkah's abattoir workers are at risk of zoonosis. This was a longitudinal study aimed at determining the risk of some zoonotic diseases among male permanent abattoir workers during Hajj. Specifically, seroprevalence of antigens for Brucella, Crimean–Congo haemorrhagic fever (CCHF), Alkhurma haemorrhagic fever (AHF) and Rift Valley Fever (RVF) were determined, among the study participants. An enrolment questionnaire, and a follow‐up questionnaire, with provision of 10 mL blood for testing 2 days before intense Hajj animal exposure, up to 20 days after intense animal exposure and between 30 and 42 days after Hajj butchering exposures. While working with livestock, study participants were interrogated on hand hygiene and personal protection. Eighty male permanent abattoir workers participated in the study. Majority, 96.25% (n = 77) declared washing their hands with soap and water, most 98.75% (n = 79) never used eye protection, few occupational workers dressed in personal protective clothing or footwear. All workers tested negative for CCHF and RVF, one was positive for AHF and six for Brucella. The risk of some zoonotic infections like Brucella and AHF is low among permanent occupational workers in the slaughtering house in Makkah during Hajj 2013. No serological evidence for CCHF and RVF viruses, even though workers showed low compliance with use of personnel protective equipment.
Y‐chromosome short tandem repeats in forensics—Sexing, profiling, and matching male DNA
Authors: Roewer Lutz
Published: April 2019

The analysis of short tandem repeat (STR) markers located on the Y chromosome is an established method in forensic casework analysis. Usually this method is applied in cases of male‐on‐female sexual assault, in which the victim's DNA is in great excess and masked the male contribution. Y‐STR analysis is able to detect the presence of minuscule amounts of male DNA of one or multiple donors and resulting genetic profiles can be compared to known reference samples. The expert has to determine whether the Y‐STR result of a trace is suitable for a biostatistical calculation in case of a match. The Discrete Laplace method which is implemented in the Y chromosome haplotype reference database (YHRD) can be used to estimate haplotype frequencies with a better approximation than other methods namely the counting method. Moreover, Y‐SNPs in combination with Y‐STRs can infer the biogeographical origin of an unknown male person with comparably high precision due to the availability of a robust phylogenetic tree and large reference data collections. Y‐based ancestry prediction and familial searching can, therefore, provide important investigative leads in crime cases without suspect.

This article is categorized under:

Forensic Biology > Haploid Markers

Forensic Biology > Ancestry Determination using DNA Methods

Forensic Biology > DNA Databases and Biometrics

Forensic Biology > Forensic DNA Technologies
Zusammenfassung und Reflexion
Authors: Buß Imke
Published: April 2019

Diese Dissertation ist der Frage nachgegangen, was Studierbarkeit bedeutet, wenn die Studierendenschaft durch ihre Heterogenität unterschiedliche Anforderungen an ein Studium stellt. Es wurde zunächst analysiert, welche Art der Heterogenität die Studierbarkeit besonders beeinflusst. Die Hochschulforschung und das Qualitätsmanagement an Hochschulen prüfen üblicherweise, ob Studierende mit Kindern oder Pflegeaufgaben, Erwerbstätigkeit oder Beeinträchtigungen das Studium erfolgreich meistern können
Supersymmetry and $$ T\overline{T} $$ deformations
Authors: Chang Chih-Kai , Ferko Christian , Sethi Savdeep
Published: April 2019

Abstract

We propose a manifestly supersymmetric generalization of the solvable

$$ T\overline{T} $$

T

T
¯

deformation of two-dimensional field theories. For theories with (1, 1) and (0, 1) supersymmetry, the deformation is defined by adding a term to the superspace Lagrangian built from a superfield containing the supercurrent. We prove that the energy levels of the resulting deformed theory are determined exactly in terms of those of the undeformed theory. This supersymmetric deformation extends to higher dimensions, where we conjecture that it might provide a higher-dimensional analogue of

$$ T\overline{T} $$

T

T
¯

, producing supersymmetric Dirac or Dirac-Born-Infeld actions in special cases.