bluuebunny/crossref_metadata_2025 huggingface dataset:
Multidimensional Scaling and Relatedness Research
Authors: Graffelman Jan , Femenía Iván Galván , de Cid Rafael , Barceló-i-Vidal Carles
Published: April 2018

Multidimensional scaling is a well-known multivariate technique, that is often used in genetics for studying population substructure. In this paper we show that multidimensional scaling of marker data is of relevance for relatedness research. Relatedness is usually investigated by estimating and plotting identity-by-state and identity-by-descent allele-sharing statistics. We show that outlying individuals in a map obtained by multidimensional scaling of genetic variables do not necessarily stem from a different human population, but can be the consequence of relatedness. We propose a method for classifying pairs of individuals into the standard relationship categories that combines genetic bootstrapping, multidimensional scaling and discriminant analysis. We validate our method with simulation studies. Given the variant filtering procedures, our method classifies relationships up to and including the fourth degree with high accuracy (96-97%), using only identity by state. The usefulness of the method is illustrated with data from the 1,000 genomes and the GCAT projects.
A high-throughput technique to quantify pathogens’ virulence on the insect model Galleria mellonella
Authors: Parthuisot Nathalie , Rouquette Jacques , Ferdy Jean-Baptiste
Published: April 2018

We combined spectrophotometry and an original statistical approach to infer bacteria virulence, using the lepidoptera Galleria mellonella as a host model. With this method, it is possible to use a microplate reader to automatize data collection on both pathogens multiplication and host survival on batches of 96 samples.
Functional Quantitative Trait Loci (QTL) analysis for adaptive traits in a three-generation Scots pine pedigree
Authors: Calleja-Rodriguez A , Li Z , Hallingbäck H R , Sillanpää M J , Wu H X , Abrahamsson S , García-Gil MR
Published: April 2018

In forest tree breeding, QTL identification aims to accelerate the breeding cycle and increase the genetic gain of traits with economical and ecological value. In our study, both phenotypic data and predicted breeding values were used in the identification QTL linked to the adaptive value in a three-generation pedigree population, for the first time in a conifer species (Pinus sylvestrisL.). A total of 11 470 open pollinated F2-progeny trees established at three different locations, were measured for growth and adaptive traits. Breeding values were predicted for their 360 mothers, originating from a single cross of two parents. A multilevel LASSO association analysis was conducted to detect QTL using genotypes of the mothers with the corresponding phenotypes and estimated breeding values (EBVs). Different levels of genotype-by-environment (G×E) effects among sites and ages were detected for survival and height. Moderate-to-low narrow sense heritabilities and EBVs accuracies were found for all traits and all sites. We identified 18 AFLPs and 12 SNPs to be associated with QTL for one or more traits. 62 QTL were significant with percentages of variance explained ranging from 1.7 to 18.9%, mostly for traits based on phenotypic data. Two SNP-QTL showed pleiotropic effects for traits related with survival, seed and flower production. Furthermore, we detected several QTL with significant effects across multiple ages, which could be considered as strong candidate loci for early selection. The lack of reproducibility of some QTL detected across sites may be due to environmental heterogeneity and QTL-by-environment effects.
CD4+ T cell fate decisions are stochastic, precede cell division, depend on GITR co-stimulation, and are associated with uropodium development
Authors: Cobbold Stephen P. , Adams Elizabeth , Howie Duncan , Waldmann Herman
Published: April 2018

During an immune response, naïve CD4+ T cells proliferate and generate a range of effector, memory and regulatory T cell subsets, but how these processes are co-ordinated remains unclear. A traditional model suggests that memory cells use mitochondrial respiration and are survivors from a pool of previously proliferating and glycolytic, but short-lived effector cells. A more recent model proposes a binary commitment to either a memory or effector cell lineage during a first, asymmetric cell division, with each lineage able to undergo subsequent proliferation and differentiation. We used improved fixation and staining methods with imaging flow cytometry in an optimised in vitro system that indicates a third model. We found that cell fates result from stochastic decisions that depend on GITR co-stimulation and which take place before any cell division. Effector cell commitment is associated with mTORC2 signalling leading to uropodium development, while developing memory cells lose mitochondria, have a nuclear localization of NFκB and depend on TGFβ for their survival. Induced, T helper subsets and foxp3+ regulatory T cells were found in both the effector and memory cell lineages. This in vitro model of T cell differentiation is well suited to testing how manipulation of cytokine, nutrient other components of the microenvironment might be exploited for therapeutic purposes.
Mitochondria promote neuropeptide secretion inCaenorhabditis elegansby preventing activation of hypoxia inducible factor
Authors: Zhao Tongtong , Kaplan Joshua M
Published: April 2018

Neurons are highly dependent on mitochondrial function, and mitochondrial damage has been implicated in many neurological and neurodegenerative diseases. Relatively little is known about how mitochondria regulate neuronal function. Here we show that axonal mitochondria are necessary for neuropeptide secretion inCaenorhabditis elegans, and that oxidative phosphorylation, but not mitochondrial calcium uptake, is required for secretion. Oxidative phosphorylation produces cellular ATP, reactive oxygen species, and consumes oxygen. Disrupting any of these functions could inhibit neuropeptide secretion. We show that blocking mitochondria transport into axons inhibits neuropeptide secretion through activation of the hypoxia inducible factor HIF-1. Our results suggest that axonal mitochondria modulate neuropeptide secretion by regulating transcriptional responses induced by metabolic stress.
Effect of selection on bias and accuracy in genomic prediction of breeding values
Authors: Gowane G. R. , Lee Sang Hong , Clark Sam , Moghaddar Nasir , Al-Mamun Hawlader A , van der Werf Julius H. J.
Published: April 2018

Reference populations for genomic selection (GS) usually involve highly selected individuals, which may result in biased prediction of estimated genomic breeding values (GEBV). In the present study, bias and accuracy of GEBV were explored for various genetic models and prediction methods when using selected individuals for a reference. Data were simulated for an animal breeding program to compare Best Linear Unbiased Prediction of breeding values using pedigree based relationships (PBLUP), genomic relationships for genotyped animals only (GBLUP) and a Single Step approach (SSGBLUP), where information on genotyped individuals was used to infer a matrix H with relationships among all available genotyped and non-genotyped individuals that were linked through pedigree. In SSGBLUP, various weights (α=0.95, 0.80, 0.50) for the genomic relationship matrix (G) relative to the numerator relationship matrix (A) were applied to construct H and in another version (SSGBLUP_F), inbreeding was accounted for while computing A-1. With GBLUP, accuracy of GEBV prediction increased linearly with an increase in the number of animals selected in reference. For the scenario with no-selection and random mating (RR) prediction was unbiased. For GBLUP, lower accuracy and bias observed in the scenarios with selection and random mating (SR) or selection and positive assortative mating (SA), in which prediction bias increased when a smaller and highly selected proportion genotyped. Bias disappeared when all individuals were genotyped. SSGBLUP_F showed higher accuracy compared to GBLUP and bias of prediction was negligible even with selective genotyping. However, PBLUP and SSGBLUP showed bias in SA owing to not fully accounting for allele frequency changes because of selection of quantitative trait loci (QTL) with larger effects and also due to high inbreeding rate. In genetic models with fewer QTL but each with larger effect, predictions were less accurate and more biased for selection scenarios. Results suggest that prediction accuracy and bias is affected by the genetic architecture of the trait. Selective genotyping lead to significant bias in GEBV prediction. SSGBLUP with appropriate scaling of A and G matrices can provide accurate and less biased prediction but scaling requires careful consideration in populations under selection and with high levels of inbreeding.
A 3D Topographical Model of Parenchymal Infiltration and Perivascular Invasion in Glioblastoma
Authors: Wolf Kayla J. , Lee Stacey , Kumar Sanjay
Published: April 2018

Glioblastoma (GBM) is the most common and invasive primary brain cancer. GBM tumors are characterized by diffuse infiltration, with tumor cells invading slowly through the hyaluronic acid (HA)-rich parenchyma toward vascular beds and then migrating rapidly along microvasculature. Progress in understanding local infiltration, vascular homing, and perivascular invasion is limited by an absence of culture models that recapitulate these hallmark processes. Here we introduce a platform for GBM invasion consisting of a tumor-like cell reservoir and a parallel open channel “vessel” embedded in 3D HA-RGD matrix. We show that this simple paradigm is sufficient to capture multi-step invasion and transitions in cell morphology and speed reminiscent of those seen in GBM. Specifically, seeded tumor cells grow into multicellular masses that expand and invade the surrounding HA-RGD matrices while extending long (10-100 µm), thin protrusions resembling those observed for GBM in vivo. Upon encountering the channel, cells orient along the channel wall, adopt a 2D-like morphology, and migrate rapidly along the channel. Structured illumination microscopy reveals distinct cytoskeletal architectures for cells invading through the HA matrix versus those migrating along the vascular channel. Substitution of collagen I in place of HA-RGD supports the same sequence of events but with faster local invasion and a more mesenchymal morphology. These results indicate that topographical effects are generalizable across matrix formulations, but that mechanisms underlying invasion are matrix-dependent. We anticipate that our reductionist paradigm should speed the development of mechanistic hypotheses that could be tested in more complex tumor models.
Confounding factors in algal phosphorus limitation experiments
Authors: Beck Whitney S. , Hall Ed K.
Published: April 2018

Assessing algal nutrient limitation is critical for understanding the interaction of primary production and nutrient cycling in streams, and nutrient diffusing substrate (NDS) experiments are often used to determine limiting nutrients such as nitrogen (N) and phosphorus (P). Unexpectedly, many experiments have also shown decreased algal biomass on NDS P treatments compared to controls. To address whether inhibition of algal growth results from direct P toxicity, NDS preparation artifacts, or environmental covariates, we first quantified the frequency of nutrient inhibition in published experiments. We also conducted a meta-analysis to determine whether heterotrophic microbial competition or selective grazing could explain decreases in algal biomass with P additions. We then deployed field experiments to determine whether P-inhibition of algal growth could be explained by P toxicity, differences in phosphate cation (K vs. Na), differences in phosphate form (monobasic vs. dibasic), or production of H2O2during NDS preparation. We found significant inhibition of algal growth in 12.9% of published NDS P experiments as compared to 4.7% and 3.6% of N and NP experiments. The meta-analysis did not show enhanced heterotrophy on NDS P treatments or selective grazing of P-rich algae. Our field experiments did not show inhibition of autotrophic growth with P additions, but we found significantly lower gross primary productivity (GPP) and biomass-specific GPP of benthic algae on monobasic phosphate salts as compared to dibasic phosphate salts, likely because of reduced pH levels. Additionally, we note that past field experiments and meta-analyses support the plausibility of direct P toxicity or phosphate form (monobasic vs. dibasic) leading to inhibition of algal growth, particularly when other resources such as N or light are limiting. Given that multiple mechanisms may be acting simultaneously, we recommend practical, cost-effective steps to minimize the potential for P-inhibition of algal growth as an artifact of NDS experimental design.
Athymic mice reveal a requirement for T-cell–microglia interactions in establishing a microenvironment supportive ofNf1low-grade glioma growth
Authors: Pan Yuan , Xiong Min , Chen Ran , Ma Yu , Corman Courtney , Maricos Meron , Kindler Urs , Semtner Marcus , Chen Yi-Hsien , Dahiya Sonika , Gutmann David H.
Published: April 2018

Pediatric low-grade gliomas (LGGs) frequently do not engraft in immunocompromised mice, limiting their use as an experimental platform. In contrast, murine Neurofibromatosis-1 (Nf1) optic LGG stem cells (o-GSCs) form glioma-like lesions in wild-type, but not athymic, mice following transplantation. Here, we show that the inability of athymic mice to support o-GSC engraftment results from impaired microglia/macrophage function, including reduced expression of Ccr2 and Ccl5, both of which are required for o-GSC engraftment andNf1optic glioma growth. Impaired Ccr2 and Ccl5 expression in athymic microglia/macrophages was restored by T-cell exposure, establishing T-cell–microglia/macrophage interactions as critical stromal determinants that support NF1 LGG growth.
Increased HOXA5 expression provides a selective advantage for gain of whole chromosome 7 in IDH wild-type glioblastoma
Authors: Cimino Patrick J. , Kim Youngmi , Wu Hua-Jun , Alexander Jes , Wirsching Hans-Georg , Szulzewsky Frank , Pitter Ken , Ozawa Tatsuya , Wang Jiguang , Vazquez Julio , Arora Sonali , Rabadan Raul , Levine Ross , Michor Franziska , Holland Eric C.
Published: April 2018

Glioblastoma is the most frequently occurring and invariably fatal primary brain tumor in adults. The vast majority of glioblastomas is characterized by chromosomal copy number alterations, including gain of whole chromosome 7 and loss of whole chromosome 10. Gain of whole chromosome 7 is an early event in gliomagenesis that occurs in proneural-like precursor cells, which give rise to all isocitrate dehydrogenase (IDH) wild-type glioblastoma transcriptional subtypes. Platelet-derived growth factor A (PDGFA) is one gene on chromosome 7 known to drive gliomagenesis, but, given its location near the end of 7p, there are likely several other genes located along chromosome 7 that select for its increased whole-chromosome copy number within glioblastoma cells. To identify other potential genes that could select for gain of whole chromosome 7, we developed an unbiased bioinformatics approach that identified homeobox A5 (HOXA5) as a gene whose expression correlated with gain of chromosome 7 and a more aggressive phenotype of the resulting glioma. High expression of HOXA5 in glioblastoma was associated with a proneural gene expression pattern and decreased overall survival in both human proneural and PDGF-driven mouse glioblastoma. Furthermore, HOXA5 overexpression promoted cellular proliferation and potentiated radioresistance. We also found enrichment of HOXA5 expression in recurrent human and mouse glioblastoma at first recurrence after radiotherapy. Overall, this study implicates HOXA5 as a chromosome 7-associated gene-level locus that promotes selection for gain of whole chromosome 7 and an aggressive phenotype in glioblastoma.
In-depth characterization of the cisplatin mutational signature in human cell lines and in esophageal and liver tumors
Authors: Boot Arnoud , Huang Mi Ni , Ng Alvin W.T. , Ho Szu-Chi , Lim Jing Quan , Kawakami Yoshiiku , Chayama Kazuaki , Teh Bin Tean , Nakagawa Hidewaki , Rozen Steven G.
Published: April 2018

Cisplatin reacts with DNA and thereby likely generates a characteristic pattern of somatic mutations, called a mutational signature. Despite widespread use of cisplatin in cancer treatment and its role in contributing to secondary malignancies, its mutational signature has not been delineated. We hypothesize that cisplatin's mutational signature can serve as a biomarker to identify cisplatin mutagenesis in suspected secondary malignancies. Knowledge of which tissues are at risk of developing cisplatin-induced secondary malignancies could lead to guidelines for noninvasive monitoring for secondary malignancies after cisplatin chemotherapy. We performed whole genome sequencing of 10 independent clones of cisplatin-exposed MCF-10A and HepG2 cells and delineated the patterns of single and dinucleotide mutations in terms of flanking sequence, transcription strand bias, and other characteristics. We used the mSigAct signature presence test and nonnegative matrix factorization to search for cisplatin mutagenesis in hepatocellular carcinomas and esophageal adenocarcinomas. All clones showed highly consistent patterns of single and dinucleotide substitutions. The proportion of dinucleotide substitutions was high: 8.1% of single nucleotide substitutions were part of dinucleotide substitutions, presumably due to cisplatin's propensity to form intra- and interstrand crosslinks between purine bases in DNA. We identified likely cisplatin exposure in nine hepatocellular carcinomas and three esophageal adenocarcinomas. All hepatocellular carcinomas for which clinical data were available and all esophageal cancers indeed had histories of cisplatin treatment. We experimentally delineated the single and dinucleotide mutational signature of cisplatin. This signature enabled us to detect previous cisplatin exposure in human hepatocellular carcinomas and esophageal adenocarcinomas with high confidence.
Timeline of engagement research and future research directions
Authors: Kunte Manjiri , Rungruang Parisa
Published: April 2018

Purpose

Studies suggest that engagement is related with organizationally desired outcomes, including performance, productivity, profitability, employee retention, organization citizenship behavior and employee well-being. Despite its practical relevance in the workplace, the concept of engagement has been theoretically dispersed. Therefore, this study aims to present a conceptual review of engagement studies leading to the development of a nomological framework and an evolution timeline for the concept.

Design/methodology/approach

The present study is divided into three sections. The first section elicits the nomological framework based on the comparison between engagement, its predecessors and its contemporary concepts such as motivation theories, job design theories, burnout theories and positive psychology. A review of related theories and concepts highlights the similarities and differences vis-a-vis engagement. In the second section, the study depicts the evolution of the engagement concept based on the nomological framework. The evolution is discussed through the decades of before 1990, 1990-2000, 2000-2010 and 2010 onwards. To consolidate the theories and concepts, the authors covered studies that defined engagement as role engagement, personal engagement, work engagement and employee engagement. The third section presents the future research directions based on the framework and evolution.

Findings

The literature review reveals future research directions. These include the addition of new antecedents and theoretical frameworks to enrich the explanatory power and practical relevance of the antecedents of engagement, exploring the context of work with qualitative and mixed method designs, exploring the unit of “role” in engagement studies and the need for more replication studies in this field.

Originality/value

The key contributions of this paper are the nomological framework and the timeline of the evolution of engagement concept.
The association between immunoexpression levels of oxidant and antioxidant enzymes and lip squamous cell carcinoma
Authors: Tseng Hui‐Wen , Tseng Hui‐Hwa , Liou Huei‐Han , Tsai Kuo‐Wang , Ger Luo‐Ping , Shiue Yow‐Ling
Published: April 2018

The aim of this study was to investigate the associations among the immunoexpression levels of manganese superoxide dismutase (Mn‐SOD), glutathione peroxidase (GPx), and myeloperoxidase (MPO) in lip squamous cell carcinoma (LSCC) tissues and the clinicopathological characteristics, and prognostic factors in patients with LSCC. The immunoexpression levels of Mn‐SOD, GPx, and MPO were examined in 76 LSCC tissue samples using immunohistochemical staining on tissue microarray slides, and compared to those in normal lip mucosa adjacent to venous lakes (normal controls), normal tissue adjacent to corresponding tumors (NTACT), and recurrent tumors. Associations between immunoexpression levels and clinicopathological characteristics were analyzed using the Student's t‐test. The prognostic factors were analyzed using Cox regression. The immunoexpression levels of Mn‐SOD, GPx, and MPO were significantly different among the normal controls, NTACTs, tumors, and recurrent tumors (Mn‐SOD: p = 0.001, GPx: p < 0.001, MPO: p < 0.001). Lower lip cancer was associated with higher Mn‐SOD immunoexpression levels (p = 0.04) and probably indicated higher oxidative stress. Lymph node involvement with a lower immunoexpression level of MPO (p = 0.007) indicated compensatory mechanism to attenuate oxidative damage. A low Mn‐SOD immunoexpression level was borderline significantly associated with a worse prognosis for disease‐specific survival, and it was probably related to a lower capacity for coping with oxidative stress.
Labor pain in women with and without severe fear of childbirth: A population‐based, longitudinal study
Authors: Junge Carolin , von Soest Tilmann , Weidner Kerstin , Seidler Andreas , Eberhard‐Gran Malin , Garthus‐Niegel Susan
Published: April 2018

Background

This prospective study aims to investigate whether severe fear of childbirth increases pain perceptions during birth and whether co‐occurring maternal health and birth factors as well as length and weight of the child explain the association.

Methods

The study sample comprised women with a vaginal delivery and was drawn from the Akershus Birth Cohort. Data from the hospital birth's record and questionnaires at weeks 17‐19 and 32 of pregnancy and 8 weeks postpartum were used (n = 1649). Analysis of variance and analysis of covariance were conducted to examine whether ratings of labor pain differed significantly between women with and without severe fear of childbirth and which factors explained the difference.

Results

Women with severe fear of childbirth experienced significantly more labor pain than women without severe fear of childbirth (P < .01). However, when controlling for symptoms of maternal depression and anxiety, use of epidural/spinal anesthetic or nitrous oxide gas, and menstrual pain, this difference was no longer significant (P = .09).

Discussion

Although the results show that labor pain is related to multiple physiological and psychological factors in a complex manner, symptoms of maternal depression and anxiety seem to play a central role for the experience of labor pain, and should therefore be focused on by health practitioners.
Enhancer of zeste homolog 2 promotes cisplatin resistance by reducing cellular platinum accumulation
Authors: Sun Si , Zhao Simei , Yang Qiang , Wang Wenwen , Cai E , Wen Yiping , Yu Lili , Wang Zehua , Cai Jing
Published: April 2018

Enhancer of zeste homolog 2 (EZH2), which is overexpressed in a wide range of tumors, contributes to ovarian cancer malignancy in several different ways. We aimed to illustrate the role of EZH2 in ovarian cancer cisplatin resistance and to identify possible underlying mechanisms of this role that may provide a rationale for targeting EZH2 in cancer treatment. Here, we present data indicating that EZH2 overexpression is associated with cisplatin resistance and intracellular platinum drug accumulation. Measurements of EZH2 in 84 ovarian cancer patients suggested that patients with high EZH2 levels tend to have poor responses to cisplatin. The EZH2 level progressively increased in cells receiving repeated cisplatin exposure. Downregulation of EZH2 not only sensitized cellular reactions to cisplatin and increased cellular platinum accumulation when cells were exposed to both cisplatin and BODIPY‐Pt (a fluorescent cisplatin complex) but also protected copper transporter 1, a high‐affinity copper transporter closely related to cisplatin resistance, from cisplatin‐induced proteasomal degradation. Overall, these findings identify a new mechanism that expands the unrecognized role of EZH2 in ovarian cancer cisplatin resistance.
4‐(4‐Hydroxyphenyl)‐2‐butanol (rhododendrol)‐induced melanocyte cytotoxicity is enhanced by UVB exposure through generation of oxidative stress
Authors: Goto Noriko , Tsujimoto Mariko , Nagai Hiroshi , Masaki Taro , Ito Shosuke , Wakamatsu Kazumasa , Nishigori Chikako
Published: April 2018

4‐(4‐Hydroxyphenyl)‐2‐butanol (rhododendrol, RD), a skin‐whitening agent, was reported to cause skin depigmentation in some users, which is attributed to its cytotoxicity to melanocyte. It was reported that cytotoxicity to melanocyte is possibly mediated by oxidative stress in a tyrosinase activity‐dependent manner. We examined the effect of UV radiation (UVR) on RD‐induced melanocyte cytotoxicity as an additional aggravating factor. UVR enhanced RD‐induced cytotoxicity in normal human epidermal melanocytes (NHEMs) via the induction of endoplasmic reticulum (ER) stress. Increased generation of intracellular reactive oxygen species (ROS) was detected. Pretreatment with N‐acetyl cysteine (NAC), antioxidant and precursor of glutathione significantly attenuated ER stress‐induced cytotoxicity in NHEMs treated with RD and UVR. Increase in cysteinyl‐RD‐catechol and RD‐pheomelanin in NHEMs treated with RD and UVR suggested that, after UVR excitation, RD or RD metabolites are potent ROS‐generating substances and that the tendency to produce RD‐pheomelanin during melanogenesis amplifies ROS generation in melanocytes. Our results help to elucidate the development mechanisms of RD‐induced leukoderma and provide information for innovation of safe skin‐whitening compounds.
PR‐10 proteins as potential mediators of melatonin‐cytokinin cross‐talk in plants: crystallographic studies of LlPR‐10.2B isoform from yellow lupine
Authors: Sliwiak Joanna , Sikorski Michal , Jaskolski Mariusz
Published: April 2018

LlPR‐10.2B, a Pathogenesis‐related class 10 (PR‐10) protein from yellow lupine (Lupinus luteus) was crystallized in complex with melatonin, an emerging important plant regulator and antioxidant. The structure reveals two molecules of melatonin bound in the internal cavity of the protein, plus a very well‐defined electron density near the cavity entrance, corresponding to an unknown ligand molecule comprised of two flat rings, which is most likely a product of melatonin transformation. In a separate LlPR‐10.2B co‐crystallization experiment with an equimolar mixture of melatonin and trans‐zeatin, which is a cytokinin phytohormone well recognized as a PR‐10‐binding partner, a quaternary 1 : 1 : 1 : 1 complex was formed, in which one of the melatonin‐binding sites has been substituted with trans‐zeatin, whereas the binding of melatonin at the second binding site and binding of the unknown ligand are undisturbed. This unusual complex, when compared with the previously described PR‐10/trans‐zeatin complexes and with the emerging structural information about melatonin binding by PR‐10 proteins, provides intriguing insights into the role of PR‐10 proteins in phytohormone regulation in plants, especially with the involvement of melatonin, and implicates the PR‐10 proteins as low‐affinity melatonin binders under the conditions of elevated melatonin concentration.

Databases

Atomic coordinates and processed structure factors corresponding to the final models of the LlPR‐10.2B/melatonin and LlPR‐10.2B/melatonin + trans‐zeatin complexes have been deposited with the Protein Data Bank (PDB) under the accession codes 5MXB and 5MXW. The corresponding raw X‐ray diffraction images have been deposited in the RepOD Repository at the Interdisciplinary Centre for Mathematical and Computational Modelling (ICM) of the University of Warsaw, Poland, and are available for download with the following Digital Object Identifiers (DOI): https://doi.org/10.18150/repod.9923638 and https://doi.org/10.18150/repod.6621013.
Preventing neurodegeneration by adrenergic astroglial excitation
Authors: Zorec Robert , Parpura Vladimir , Verkhratsky Alexei
Published: April 2018

Impairment of the main noradrenergic nucleus of the human brain, the locus coeruleus (LC), which has been discovered in 1784, represents one of defining factors of neurodegenerative diseases progression. Projections of LC neurons release noradrenaline/norepinephrine (NA), which stimulates astrocytes, homeostatic neuroglial cells enriched with adrenergic receptors. There is a direct correlation between the reduction in noradrenergic innervations and cognitive decline associated with ageing and neurodegenerative diseases. It is, therefore, hypothesized that the resilience of LC neurons to degeneration influences the neural reserve that in turn determines cognitive decline. Deficits in the noradrenergic innervation of the brain might be reversed or restrained by increasing the activity of existing LC neurons, transplanting noradrenergic neurons, and/or using drugs that mimic the activity of NA on astroglia. Here, these strategies are discussed with the aim to understand how astrocytes integrate neuronal network activity in the brain information processing in health and disease.
Comparison of hyperspectral classification methods for the analysis of cerium oxide nanoparticles in histological and aqueous samples
Authors: IDELCHIK M.P.S. , DILLON J. , ABARIUTE L. , GUTTENBERG M.A. , SEGARCEANU A. , NEU‐BAKER N.M. , BRENNER S.A.
Published: April 2018

Hyperspectral imaging (HSI) and classification are established methods that are being applied in new ways to the analysis of nanoscale materials in a variety of matrices. Typically, enhanced darkfield microscopy (EDFM)‐based HSI data (also known as image datacubes) are collected in the wavelength range of 400–1000 nm for each pixel in a datacube. Utilising different spectral library (SL) creation methods, spectra from pixels in the datacube corresponding to known materials can be collected into reference spectral libraries (RSLs), which can be used to classify materials in datacubes of experimental samples using existing classification algorithms. In this study, EDFM‐HSI was used to visualise and analyse industrial cerium oxide (CeO2; ceria) nanoparticles (NPs) in rat lung tissues and in aqueous suspension. Rats were exposed to ceria NPs via inhalation, mimicking potential real‐world occupational exposures. The lung tissues were histologically prepared: some tissues were stained with hematoxylin and eosin (H&E) and some were left unstained. The goal of this study was to determine how HSI and classification results for ceria NPs were influenced by (1) the use of different RSL creation and classification methods and (2) the application of those methods to samples in different matrices (stained tissue, unstained tissue, or aqueous solution). Three different RSL creation methods – particle filtering (PF), manual selection, and spectral hourglass wizard (SHW) – were utilised to create the RSLs of known materials in unstained and stained tissue, and aqueous suspensions, which were then used to classify the NPs in the different matrices. Two classification algorithms – spectral angle mapper (SAM) and spectral feature fitting (SFF) – were utilised to determine the presence or absence of ceria NPs in each sample. The results from the classification algorithms were compared to determine how each influenced the classification results for samples in different matrices. The results showed that sample matrix and sample preparation significantly influenced the NP classification thresholds in the complex matrices. Moreover, considerable differences were observed in the classification results when utilising each RSL creation and classification method for each type of sample. Results from this study illustrate the importance of appropriately selecting HSI algorithms based on specific material and matrix characteristics in order to obtain optimal classification results. As HSI is increasingly utilised for NP characterisation for clinical, environmental and health and safety applications, this investigation is important for further refining HSI protocols while ensuring appropriate data collection and analysis.
Clinical evaluation of efficacy, tolerability and pharmacokinetics of yimitasvir phosphate in patients infected with hepatitis C virus
Authors: Zhang Hong , Zhu Xiaoxue , Li Qingmei , Lou Jinfeng , Sun Jixuan , Shen Zhenwei , Chen Hong , Li Xiaojiao , Wu Min , Li Cuiyun , Liu Jingrui , Liu Chengjiao , Hu Yue , Wang Jing , Chen Guiling , Ding Yanhua , Niu Junqi
Published: April 2018

Objective

Yimitasvir phosphate, an inhibitor of nonstructural protein 5A (NS5A) replication complex of hepatitis C virus (HCV), was evaluated in a double-blind, placebo-controlled, parallel, multiple-dose study.

Methods

Twenty-four patients with chronic HCV genotype 1 infection were randomized to receive a 7-day course of yimitasvir phosphate at daily doses of 30, 100 or 200 mg or placebo. Antiviral efficacy, resistance profile, pharmacokinetics (PK), safety and tolerability were assessed.

Key findings

The maximal reduction in HCV RNA from baseline was 5.17 log10 IU/ml. However, most patients experienced viral rebound on or before day 3 after yimitasvir treatment was initiated. The PK profile revealed median peak plasma concentrations at 4–12 h postdose and a mean terminal half-life of 14.47–17.09 h, the basis for daily dosing. Steady drug state was achieved following 5 days of daily dosing. The accumulation rate was low (1.29–1.73). There were no significant alterations in vital signs and laboratory findings among all participants.

Conclusions

This study shows that yimitasvir phosphate was well tolerated, and the PK profile supported daily dosing regimens. A 1-week (7-day) treatment course led to a quick and significant reduction in HCV RNA level in this cohort with HCV GT-1 infection.
Analysis of the first‐time pass rate of the American College of Veterinary Emergency and Critical Care certifying examination (2010–2015)
Authors: Jandrey Karl E. , Goggs Robert , Kerl Marie , Guillaumin Julien , Kent Michael S.
Published: April 2018

Objectives

To disseminate information regarding the annual pass rates for the American College of Veterinary Emergency and Critical Care (ACVECC) certifying examination. To compare the first‐time pass rates (FTPR) of ACVECC residents trained in academic and private practice settings.

Design

Retrospective study.

Setting

ACVECC examination.

Animals

None.

Interventions

None.

Measurements and Main Results

Anonymized ACVECC examination performance data from 2010–2015 inclusive were analyzed. Overall pass rates and FTPR were calculated for all candidates and categorized by type of residency training program. The overall pass rate for all candidates was 64.3%. The median pass rate for the 6‐year period was 63.8% [IQR 59.3–67.3%]. The FTPR for residents trained in academic programs was significantly higher than for residents trained in private practice (77.1% vs 47.2%,P< 0.0001). When residents were subdivided by species‐focus of training program, there was no significant difference between academic versus private practice training programs for large‐animal candidates (P= 0.2), but there remained a significant difference between residency training programs for small‐animal candidates (P< 0.0001).

Conclusions

Between 2010 and 2015 residents trained in academic training programs were significantly more likely to pass the ACVECC certifying examination compared to those trained in private practice training programs. The causes of this difference are uncertain, are likely multifactorial and warrant further investigation.
Alternative pathway to brominate 2,13-benzothiadiazole: Preparation of 4,7-dibromobenzo[c]-1,2,5-thiadiazole via N-bromosuccinimide
Authors: Tan Shu Er , Sarjadi Mohd. Sani
Published: April 2018

This present work reports an alternative pathway to brominate the 2,1,3-benzothiadiazole (BT). The conventional method to brominate a phenyl/benzene ring is to use the bromine solution (Br2) together with hydrobromic acid (HBr). This is because the phenyl/benzene rings exhibit high stability due to the delocalized -conjugation, which the substitution of bromines into the rings can only be done through a strong bromination source, e.g. the Br2/HBr. Besides that, there is another bromine source, known as N-bromosuccinimide (NBS), which is normally used for bromination of thiophene rings but not the phenyl/benzene ring. The bromination ability of NBS is relatively mild than the Br2/HBr. Herein, this research shows that bromination of benzene/phenyl ring through NBS is possible under a drastic condition that involved the usage of 96% concentrated sulphuric acid and chloroform at room temperature. This alternative pathway can be used when there is limit access to the Br2 and bromination through NBS is relatively less dangerous than the Br2/HBr.
A combination of Broyden-Fletcher-Goldfarb-Shanno (BFGS) and n-th section method for solving small-scale unconstrained optimization
Authors: Ramli Atikah , Jusoh Ibrahim , Mohd Ali Mohd Rivaie
Published: April 2018

In this research, a new inexact line search method known as n-th section method is used to obtain the step size in BFGS method. The n-th section method is the modification of the original bisection method. As in bisection method, this simple n-th section method divides each interval section with an even number of interval which is greater than two. This new proposed algorithm is compared with the original bisection, newton and secant method in terms of number of iteration. Numerical results is obtained based on small scale functions .This research shows that the algorithm is more efficient than using the ordinary line search methods. Besides, this proposed algorithm also possessed global convergence properties.
Effects of diversification of assets in optimizing risk of portfolio
Authors: Jayeola Dare , Ismail Zulhaimy , Firdaus Sufahani Suliadi
Published: April 2018

Diversification is a strategic option that investors use to optimize their portfolio. Diversification is investing in many assets for the purpose of minimizing risk or maximizing return of portfolio. It is an opportunity by which investors improve from his micro-firm into macro-firm. The investors’ aim is to make an optimal choice that leads to minimization of risk and maximization of return, but the platform that achieves these objectives is not at the finger tips. The purpose of this study is to propose procedures for constructing optimal portfolio for rational investors. Also, the study demonstrates the benefits of diversification of each asset in portfolio. The assets allocations divulge by Black Litterman model are used to estimate risk of both portfolios and assets. We explore DataStream (Yahoo finance) of Gold, Oil, Silver and Platinum. It is observed that diversifying in Gold minimizes higher risk and achieve more benefits than other assets in the portfolio, which made portfolio1 to be optimal portfolio. In view of these facts, it means diversifying in gold acts as hedge/safe haven for investors during economic recession.
Estimating relative risk for dengue disease in Peninsular Malaysia using INLA
Authors: Abd Naeeim Nurul Syafiah , Abdul Rahman Nuzlinda
Published: April 2018

Study in spatio-temporal disease mapping models give a great worth in epidemiology, in describing the pattern of disease incidence across geographical space and time. This paper studies generalized linear mixed models (GLMM) for the analysis of spatial and temporal variability of dengue disease rates. For spatio-temporal study, the models accommodate spatially correlated random effects as well as temporal effects together with the space time interaction. The space time interaction is used to capture any additional effects that are not explained by the main factors of space and time. However, as study including time dimension is quite complex for disease mapping, the temporal effects that only relate to structured and unstructured time pattern are considered in these models as initial screening in studying disease pattern and time trend. The models are fitted within a hierarchical Bayesian framework using Integrated Nested Laplace Approximation (INLA) methodology. For this study, there are three main objectives. First, to choose the best model that represent the disease phenomenon. Second, to estimate the relative risk of disease based on the model selected and lastly, to visualize the risk spatial pattern and temporal trend using graphical representation. The models are applied to monthly dengue fever data in Peninsular Malaysia reported to Ministry of Health Malaysia for year 2015 by district level.
The n-th section method: A modification of Bisection
Authors: Mohd Ali Mohd Rivaie , Fakhri Muhammad Imza , Hayati Nujma , Ramli Nurul Atikah , Jusoh Ibrahim
Published: April 2018

Bisection method is the easiest method to find the root of a function. This method is based on the existence of a root on a specified interval. This interval is then halved or divided into two parts. The root is known to be laying in either one of these interval. The iterative sequence is continued until a desired stopping criterion is reached. In this research, a new modification of bisection method namely fourth section and sixth section methods are introduced. These methods are tested for several selected functions by using Maple software. The results are then analyzed based on the number of iterations and the CPU times. Based on the results, it is shown that when the interval increases, the CPU will also increase. However, the number of iterations is reduced significantly.
Structural and luminescent characteristic of Sm3+ doped magnesium sulfide borate red phosphor for white LED
Authors: Dalhatu Saddiq Abubakar , Hussin Rosli , Deraman Karim , Ibrahim Bulus , Abdullahi Yamusa , Mohammed Aliyu
Published: April 2018

Polycrystalline compositions based on MgO, SO3 and B2O3 have both scientific and technological importance because of their useful applications. Doping with rare earth elements not only due to a rearrangement in the structure, but also to variation in the luminescence properties. Magnesium sulfide borate doped samarium oxide (MgSBO3:Sm3+) phosphors were prepared by solid state reaction and their structural and luminescence characteristic were studied and reported. IR and Raman spectral studies have been made to explore the presence of functional groups and various structural units in the prepared Polycrystalline. The formation of SO4, BO4, BO3, B-O-B and S-O-B structural units have been investigated. The emission and excitation properties were studied. And the results show that the emission and excitation spectra of these phosphors can be excited by ultraviolet (UV) 341, 370 and 409 nm light, and emit green, yellow and red light with intense peak at 601 nm, which are nicely in accordance with the widely applied near- UV LED chip. The emission intensities of these phosphors were increased with increases doping concentration. Therefore, these phosphors are the promising luminescent material towards white red LED applications.
The independence polynomial of conjugate graph and noncommuting graph of groups of small order.
Authors: Najmuddin Nabilah , Sarmin Nor Haniza , Erfanian Ahmad
Published: April 2018

An independent set of a graph is a set of pairwise non-adjacent vertices. The independence polynomial of a graph is defined as a polynomial in which the coefficient is the number of the independent set in the graph.  Meanwhile, a graph of a group G is called conjugate graph if the vertices are non-central elements of G and two distinct vertices are adjacent if they are conjugate. The noncommuting graph is defined as a graph whose vertex set is non-central elements in which two vertices are adjacent if and only if they do not commute. In this research, the independence polynomial of the conjugate graph and noncommuting graph are found for three nonabelian groups of order at most eight.
A comparison of method for treating missing daily rainfall data in Peninsular Malaysia
Authors: Kamaruzaman Izzat Fakharuddin , Wan Zin Wan Zawiah , Mohd Ariff Noratiqah
Published: April 2018

This study modified a method for treating missing values in daily rainfall data from 104 selected rainfall stations. The daily rainfall data were obtained from the Department of Irrigation and Drainage Malaysia (DID) for the periods of 1965 to 2015. The missing values throughout the 51 years period were estimated using the various types of weighting methods. In determining the best imputation method, three test for evaluating model performance has been used. The findings of this study indicate that the proposed method is more efficient than the traditional method. The homogeneity of the data series was checked using the homogeneity tests recommended by the existing literatures. The results indicated that more than 40% of the rainfall stations were homogenous based on the proposed method.
The determinants of electricity consumption for ASEAN countries
Authors: Ismail Mohd Tahir , Mahmud Nadhilah , Abdul Rahman Rosmanjawati
Published: April 2018

The present study investigates the causal relationship between ASEAN seven member countries electricity consumption (EC) and some determinants such as gross domestic product (GDP), exports (EXP) and carbon dioxide emission (CO2) using vector autoregressive (VAR) framework via vector error correction (VEC) model for the period from 1980-2015. The findings show that the effect of the chosen determinants is different among the seven countries. Within the sample period, by utilizing Granger causality test, out of the seven countries, only four revealed either unidirectional or bidirectional causality running from EC to the three determinants, GDP, EXP and CO2. Whereas, thru forecast error variance decomposition (FEVD), forecasting beyond the sample period uncovered a shock to EC will also spread to GDP, EXP and CO2. The present study suggests that ASEAN should take note in designing their electricity policy, since electricity affect and be affected by other factors. In addition, ASEAN also should find solutions on how to control CO2 emission through EC.