bluuebunny/crossref_metadata_2025 huggingface dataset:
A trivalent HCV vaccine elicits broad and synergistic polyclonal antibody response in mice and rhesus monkey
Authors: Wang Xuesong , Yan Yu , Gan Tianyu , Yang Xi , Li Dapeng , Zhou Dongming , Sun Qiang , Huang Zhong , Zhong Jin
Published: November 2017

Objective

Despite the development of highly effective direct-acting antivirals, a prophylactic vaccine is needed for eradicating HCV. A major hurdle of HCV vaccine development is to induce immunity against HCV with high genome diversity. We previously demonstrated that a soluble E2 (sE2) expressed from insect cells induces broadly neutralising antibodies (NAbs) and prevents HCV infection. The objective of this study is to develop a multivalent HCV vaccine to increase the antigenic coverage.

Design

We designed a trivalent vaccine containing sE2 from genotype 1a, 1b and 3a. Mice and rhesus macaques were immunised with monovalent or trivalent sE2 vaccine, and sera or purified immunoglobulin were assessed for neutralisation against a panel of cell culture-derived virion (HCVcc) of genotype 1–7 in cell culture. Splenocytes from the vaccinated macaques were assessed for HCV-specific T cell response.

Results

We showed that the trivalent vaccine elicited pangenotypic NAbs in mice, which neutralised HCVcc of all the seven genotypes more potently than the monovalent vaccine. Further analyses demonstrated that each sE2 component of this trivalent vaccine elicited unique spectrum of NAbs which acted synergistically to inhibit HCV infection. Finally, the trivalent vaccine triggered stronger and more uniform multigenotypic neutralising antibody response than the monovalent vaccine in rhesus macaques.

Conclusions

In summary, we developed a trivalent HCV vaccine that induces broad and synergistic-acting neutralising antibodies in mice and non-human primates.
Incidence and serotype characterisation ofStreptococcus agalactiaein a Portuguese hospital
Authors: Pinto Ana Mafalda , Pereira Tamegão Aires , Alves Valquíria , Araújo António , Lage Olga Maria
Published: November 2017

Aims

Streptococcus agalactiae,commonly known as group BStreptococcus(GBS), has been recognised as a worldwide causative pathogenic agent of neonatal sepsis, meningitis and pneumonia. To better understand the behaviour ofS. agalactiaein pregnant women from a hospital from the North of Portugal, retrospective analyses were performed to describe epidemiological, clinical and microbiological characteristics of the isolates obtained.

Methods

Based on laboratorial records and the hospital’s patient files, a 6-year retrospective study was performed to analyseS. agalactiaeisolates from screened pregnant women between 35 and 37 weeks of gestation and hospitalised neonates from pregnant women between 24 and 41 weeks of gestation admitted in Hospital Pedro Hispano. Serotype characterisation was also performed in 67 GBS strains.

Results

In 6692 pregnant women between 35 and 37 weeks of gestation screened between 2011 and 2016, a total of 1377S. agalactiaeisolates (21%) were found. A high percentage (40%) of unknown colonisation status among hospitalised neonates from pregnant women between 24 and 41 weeks of gestations was also found. The incidence of neonatal sepsis was 8.7 (95% CI 7.0 to 10.8) cases per 1000 live births. Regarding serotype characterisation, serotype III (22.4%) was the most frequent, followed by serotype Ia (19.4%) and serotypes Ib and V (both with 17.9%).

Conclusion

High epidemiological values of GBS colonisation and incidence were found in this study. In Portugal studies on the epidemiology and behaviour ofS. agalactiaeremain limited, reinforcing the importance and need forS. agalactiaescreening across the country.
CEBPAmutational analysis in acute myeloid leukaemia by a laboratory-developed next-generation sequencing assay
Authors: Ng Christopher Wai Siong , Kosmo Bustamin , Lee Peak-Ling , Lee Chun Kiat , Guo Jingxue , Chen Zhaojin , Chiu Lily , Lee Hong Kai , Ho Sherry , Zhou Jianbiao , Lin Mingxuan , Tan Karen M L , Ban Kenneth H K , Tan Tin Wee , Chng Wee Joo , Yan Benedict
Published: November 2017

Aim

The presence of biallelicCEBPAmutations is a favourable prognostic feature in acute myeloid leukaemia (AML).CEBPAmutations are currently identified through conventional capillary sequencing (CCS). With the increasing adoption of next-generation sequencing (NGS) platforms, challenges with regard to amplification efficiency ofCEBPAdue to the high GC content may be encountered, potentially resulting in suboptimal coverage. Here, the performance of an amplicon-based NGS method using a laboratory-developedCEBPA-specific Nextera XT (CEBNX) was evaluated.

Methods

Mutational analyses of theCEBPAgene of 137 AML bone marrow or peripheral blood retrospective specimens were performed by the amplification of theCEBPAgene using the Expand Long Range dNTPack and the amplicons processed by CCS and NGS.CEBPA-specific libraries were then constructed using the Nextera XT V.2 kit. All FASTQ files were then processed with the MiSeq Reporter V.2.6.2.3 using the PCR Amplicon workflow via the customisedCEBPA-specific manifest file. The variant calling format files were analysed using the Illumina Variant Studio V.2.2.

Results

A coverage per base of 3631X to 28184X was achieved. 22 samples (16.1%) were found to containCEBPAmutations, with variant allele frequencies (VAF) ranging from 3.8% to 58.2%. Taking CCS as the ‘gold standard’, sensitivity and specificity of 97% and 97% was achieved. For the transactivation domain 2 polymorphism (c.584_589dupACCCGC/p.His195_Pro196dup), the CEBNX achieved 100% sensitivity and 100% specificity relative to CCS.

Conclusions

Our laboratory-developed CEBNX workflow shows high coverage and thus overcomes the challenges associated with amplification efficiency and low coverage ofCEBPA.Therefore, our assay is suitable for deployment in the clinical laboratory.
Relative heart size and fish foraging ecology in a lake food web
Authors: Edmunds Nicholas B. , McCann Kevin S. , Laberge Frédéric
Published: November 2017

Organisms occupying high trophic positions in food webs are proposed to exert a stabilizing effect on ecosystems under changing conditions. A possible mechanism underlying this phenomenon is higher mobility of large-bodied predators, which allows broad spatial scale foraging across habitats. If top predators foraging flexibly across habitats display an enhanced capacity for mobility, they should have increased blood circulation requirements compared with other organisms in a food web. Blood circulation capacity can be estimated from the relative size of the heart ventricle, the muscle mass that powers the cardiac pump. We sampled wild teleost fish in a freshwater lake food web to investigate the relationship between relative heart ventricle size and individual measures of trophic position, energy channel use (littoral versus pelagic), and foraging flexibility (coupling) estimated from 15N and 13C stable isotope signatures. The results showed that relative ventricle size is associated with increased relative trophic position and decreased use of littoral carbon across species, but not within species, in this system. The foraging flexibility required for coupling was not associated with heart ventricle size.
The multiple local structures in liquid water
Authors: Yang Cheng , Zhou Xin
Published: November 2017

The debate over whether the structure of liquid water is homogeneous or mixed with a variety of structures has been going on for more than one century. With the discovery of different amorphous ices and advances in computer technology, mixture model is gaining more and more attention. In this paper, the latest progress in the experiment and simulation of the local structure of liquid water is introduced firstly. Secondly, the principal component analysis is used to study the water’s Raman spectra and tetrahedral-order distributions. We find that both the spectra and distributions can be obtained by linear superposition of two basic functions, which correspond to the existence of two local structures in liquid water. Finally, we introduce the development of using the binary regular solution theory to explain some thermodynamic properties of liquid water.
InN/GaN quantum dot superlattices: Charge-carrier states and surface electronic structure
Authors: Kanouni F. , Brezini A. , Djenane M. , Zou Q.
Published: November 2017

We have theoretically investigated the electron energy spectra and surface states energy in the three dimensionally ordered quantum dot superlattices (QDSLs) made of InN and GaN semiconductors. The QDSL is assumed in this model to be a matrix of GaN containing cubic dots of InN of the same size and uniformly distributed. For the miniband’s structure calculation, the resolution of the effective mass Schrödinger equation is done by decoupling it in the three directions within the framework of Kronig–Penney model. We found that the electrons minibands in infinite ODSLs are clearly different from those in the conventional quantum-well superlattices. The electrons localization and charge-carrier states are very dependent on the quasicrystallographic directions, the size and the shape of the dots which play a role of the artificial atoms in such QD supracrystal. The energy spectrum of the electron states localized at the surface of InN/GaN QDSL is represented by Kronig–Penney like-model, calculated via direct matching procedure. The calculation results show that the substrate breaks symmetrical shape of QDSL on which some localized electronic surface states can be produced in minigap regions. Furthermore, we have noticed that the surface states degeneracy is achieved in like very thin bands located in the minigaps, identified by different quantum numbers n[Formula: see text], n[Formula: see text], n[Formula: see text]. Moreover, the surface energy bands split due to the reduction of the symmetry of the QDSL in z-direction.
Deriving the average-case performance of bandwidth-like interfaces for tasksets with infinite minimum inter-arrival time, equal task density, uniformly distributed deadlines, and infinite number of tasks
Authors: Andersson Björn , Kim Hyoseung , Lehoczky John , de Niz Dionisio
Published: November 2017

Many solutions for composability and compositionality rely on specifying the interface for a component using bandwidth. Some previous works specify period (P) and budget (Q) as an interface for a component.
Q/P
provides us with a bandwidth (the share of a processor that this component may request);
P
specifies the time granularity of the allocation of this processing capacity. Other works add another parameter,
deadline
, which can help to provide tighter bounds on how this processing capacity is distributed. Yet other works use the parameters α and Δ where α is the bandwidth and Δ specifies how smoothly this bandwidth is distributed. It is known [4] that such bandwidth-like interfaces carry a cost: there are tasksets that could be guaranteed to be schedulable if tasks were scheduled directly on the processor, but with bandwidth-like interfaces, it is impossible to guarantee the taskset to be schedulable. It is known that this penalty can be infinite, i.e., the use of bandwidth-like interfaces may require the use of a processor that has a speed that is
k
times faster, and one can show this for any
k.
This brings the following question: "What is the average-case performance penalty of bandwidth-like interfaces?" A previous paper [5] has partially answered this question by stating an expression on this penalty as a function of taskset parameters and then randomly generated tasksets to obtain a probability distribution of this penalty. In this paper, we answer this question analytically for the case that the taskset has tasks with infinite minimum inter-arrival time, equal task density, uniformly distributed deadlines, and the number of tasks approaches infinity. For this specific case, we derive an expression; if deadlines are uniformly distributed in [0,1], then we find that the penalty is two. We also run experiments to explore systems with these assumptions but for finite number of tasks. From these experiments, we conclude that (i) the larger the number of tasks is, the larger the penalty is, (ii) the larger the number of tasks is, the less skewed the probability distribution is, and (iii) the larger the number of tasks is, the smaller the variance of the penalty is. We are currently working on the case where deadlines follow other distributions.
Reproducibility and representativity
Authors: Maxim C. , Gogonel A. , Asavoae I. , Asavoae M. , Cucu-Grosjean L.
Published: November 2017

The increased number of systems consisting of multiple interacting components imposes the evolution of timing analyses towards methods able to estimate the timing behavior of an entire system by aggregating timings bounds of its components. In this paper we propose the first discussion on the properties required by measurement-based timing analyses to ensure such compositionality. We identify the properties of reproducibility and representativity as necessary conditions to ensure the convergence of any measurement protocol allowing a compositional measurement-based timing analysis.
On the efficiency of sporadic servers on ethernet with FTT-SE
Authors: Iqbal Zahid , Almeida Luis , Ashjaei Mohammad , Behnam Moris
Published: November 2017

Ethernet is generating a growing interest as a network for real-time embedded systems such as airplanes and automobiles. In this realm, network reservations appear as important design elements that favor composability in the time domain. One Ethernet protocol that provides such reservations is FTT-SE. In this work-in-progress we make initial steps to assess the efficiency of one particular worst-case network delay analysis for sporadic reservations associated to asynchronous messages using extensive simulation. With over 1000 message sets we found that analytic values match the observations, on average, in 31% of the messages across all generated sets whereas for 85% of the cases, the analysis upper bounds are within 2.85 times the observed values.
Extended recursive analysis for tilera tile64 NoC architectures
Authors: Ayed Hamdi , Scharbarg Jean-luc , Ermont Jérôme , Fraboul Christian
Published: November 2017

A heterogeneous network, where a switched-Ethernet backbone, e.g. AFDX, interconnects several end systems based on Network-on-Chip (NoC), is a promising candidate to build new avionics architectures. When using such a heterogeneous network for real-time applications, a global worst-case traversal time (WCTT) analysis is needed. In this short paper we focus on the intra-NoC communication on a Tilera TILE64-like NoC. First, we extend the Recursive Calculus (RC) to achieve tighter intra-NoC WCTT. Then, we explain how this intra-NoC WCTT analysis could be used in a compositional manner for the end-to-end inter-NoC delay analysis.
Contracting challenges for system design and integration
Authors: Möstl Mischa , Ernst Rolf
Published: November 2017

In this paper we highlight challenges of the applicability of contracting (based on assumptions and guarantees) for cyber-physical systems design. We illustrate in an example the limitations of an entirely composability-centered contracting approach. An alternative approach is subsequently proposed and applied to the presented example to illustrate that it is capable of handling the limitations demonstrated for the composable approach.
Mas-Related G Protein–Coupled Receptors and the Biology of Itch Sensation
Authors: Meixiong James , Dong Xinzhong
Published: November 2017

Chronic, persistent itch is a devastating symptom that causes much suffering. In recent years, there has been great progress made in understanding the molecules, cells, and circuits underlying itch sensation. Once thought to be carried by pain-sensing neurons, itch is now believed to be capable of being transmitted by dedicated sensory labeled lines. Members of the Mas-related G protein–coupled receptor (Mrgpr) family demarcate an itch-specific labeled line in the peripheral nervous system. In the spinal cord, the expression of other proteins identifies additional populations of itch-dedicated sensory neurons. However, as evidence for labeled-line coding has mounted, studies promoting alternative itch-coding strategies have emerged, complicating our understanding of the neural basis of itch. In this review, we cover the molecules, cells, and circuits related to understanding the neural basis of itch, with a focus on the role of Mrgprs in mediating itch sensation.
Efficient Gabor Phase Based Illumination Invariant for Face Recognition
Authors: Fan Chunnian , Wang Shuiping , Zhang Hao
Published: November 2017

This paper presents a novel Gabor phase based illumination invariant extraction method aiming at eliminating the effect of varying illumination on face recognition. Firstly, It normalizes varying illumination on face images, which can reduce the effect of varying illumination to some extent. Secondly, a set of 2D real Gabor wavelet with different directions is used for image transformation, and multiple Gabor coefficients are combined into one whole in considering spectrum and phase. Lastly, the illumination invariant is obtained by extracting the phase feature from the combined coefficients. Experimental results on the Yale B and the CMU PIE face database show that our method obtained a significant improvement over other related methods for face recognition under large illumination variation condition.
Subspace Method Aided Data-Driven Fault Detection Based on Principal Component Analysis
Authors: Ma Lingling , Li Xiangshun
Published: November 2017

The model-based fault detection technique, which needs to identify the system models, has been well established. The objective of this paper is to develop an alternative procedure instead of identifying the system models. In this paper, subspace method aided data-driven fault detection based on principal component analysis (PCA) is proposed. The basic idea is to use PCA to identify the system observability matrices from input and output data and construct residual generators. The advantage of the proposed method is that we just need to identify the parameterized matrices related to residuals rather than the system models, which reduces the computational steps of the system. The proposed approach is illustrated by a simulation study on the Tennessee Eastman process.
Studies on Chemical Composition and Antioxidant Activity of Rudbeckia triloba
Authors: Moldovan Zenovia , Buleandră Mihaela , Oprea Eliza , Mînea Zamfirica
Published: November 2017

The paper describes the physicochemical studies made on the decorative plant, Rudbeckia triloba (Asteraceae). For this purpose, essential oil, infusion, decoction, and hydroalcoholic macerate obtained from different aerial parts of Rudbeckia triloba were analyzed. The main phytochemical constituents identified by GC-MS analysis were found to be α-pinene (in dried leaves (46.0%) and flowers (40.1%)) and β-phellandrene (in essential oil of dried inflorescences (26.09%)). The Folin–Ciocalteu and quercetin assays revealed different values of total phenolic and flavonoid contents of petals, leaves, and seeds as a function of the solvent used and extraction procedure. The hydroalcoholic macerate of petals was found to present the maximum phenolic and flavonoid contents (130.29 ± 5.58 mg gallic acid equivalent/g dry vegetable material and 30.72 ± 1.35 mg quercetin equivalent/g dry vegetable material, resp.) and also exhibits the lower value of EC50 (0.32% (v/v)), obtained by applying the DPPH⋅ assay. Comparing the extraction methods applied, the maceration was found to be the most effective for phenolic compounds, most likely due to the solvent (70% ethanol). The use of water-alcohol mixture leads to an improvement of the extraction yield of phenolic compounds (including those with higher molecular weights) than by using water as extractive solvent, in the case of infusions and decocts.
Racial/Ethnic Differences in the Modifying Effect of Community Violence on the Association between Paternity Status and Preterm Birth
Authors: Ihongbe Timothy O. , Masho Saba W.
Published: November 2017

Preterm birth (PTB) is a major public health concern in the US. Lack of established paternity has been linked with increased risk of PTB. Community violence (CV) may modify the association, and racial/ethnic differences may exist. Using a geographically defined cohort of women in Richmond, Virginia (N = 27,518), we examined racial/ethnic differences in the modifying effect of CV on the association between paternity status and PTB. Results showed that lack of established paternity was associated with incremental greater odds of PTB across CV quartiles in NH-Whites (quartile-1: AOR = 1.42, 95% CI = 0.95–2.12; quartile-2: AOR = 1.45, 95% CI = 0.57–3.71; quartile-3: AOR = 3.12, 95% CI = 2.67–6.32), NH-Blacks (quartile-1: AOR = 1.16, 95% CI = 0.85–1.58; quartile-2: AOR = 1.32, 95% CI = 0.82–2.12; quartile-3: AOR = 1.64, 95% CI = 1.24–2.16), and Hispanics (quartile-1: AOR = 1.29, 95% CI = 0.65–2.55; quartile-2: AOR = 1.34, 95% CI = 0.67–2.69). Odds of PTB were highest among NH-White women. Public health practitioners should be aware of the negative effect of lack of paternal presence on PTB in women resident in high violence rate communities and racial/ethnic differences that exist.
An Improved Binary Differential Evolution Algorithm to Infer Tumor Phylogenetic Trees
Authors: Liang Ying , Liao Bo , Zhu Wen
Published: November 2017

Tumourigenesis is a mutation accumulation process, which is likely to start with a mutated founder cell. The evolutionary nature of tumor development makes phylogenetic models suitable for inferring tumor evolution through genetic variation data. Copy number variation (CNV) is the major genetic marker of the genome with more genes, disease loci, and functional elements involved. Fluorescence in situ hybridization (FISH) accurately measures multiple gene copy number of hundreds of single cells. We propose an improved binary differential evolution algorithm, BDEP, to infer tumor phylogenetic tree based on FISH platform. The topology analysis of tumor progression tree shows that the pathway of tumor subcell expansion varies greatly during different stages of tumor formation. And the classification experiment shows that tree-based features are better than data-based features in distinguishing tumor. The constructed phylogenetic trees have great performance in characterizing tumor development process, which outperforms other similar algorithms.
Experimental Study on Water Sensitivity Difference Based on Oiliness of Porous Medium Rock
Authors: Li Jie , Li Wei , Li Li
Published: November 2017

This study presents the differences of water sensitivity experiment of porous medium rock between conventional dry core samples and oil-bearing core. The comparison was made to analyze the impact of single-phase fluid and multiphase fluid on the actual sensitivity of rock. The nuclear magnetic resonance (NMR) test was carried out to reveal the distribution of oil in porous medium and the microscopic influence mechanism of oil phase. The study shows that the initial oil in place could isolate the clay from water, and then the expansion and the migration of the clay were prevented to reduce the decrease of degree of damage.
Adaptation and Validation of the Foot Function Index-Revised Short Form into Polish
Authors: Rutkowski Radosław , Gałczyńska-Rusin Małgorzata , Gizińska Małgorzata , Straburzyński-Lupa Marcin , Zdanowska Agata , Romanowski Mateusz Wojciech , Romanowski Wojciech , Budiman-Mak Elly , Straburzyńska-Lupa Anna
Published: November 2017

Purpose. The aim of the present study was to adapt the Foot Function Index-Revised Short Form (FFI-RS) questionnaire into Polish and verify its reliability and validity in a group of patients with rheumatoid arthritis (RA). Methods. The study included 211 patients suffering from RA. The FFI-RS questionnaire underwent standard linguistic adaptation and its psychometric parameters were investigated. The enrolled participants had been recruited for seven months as a convenient sample from the rheumatological hospital in Śrem (Poland). They represented different sociodemographic characteristics and were characterized as rural and city environments residents. Results. The mean age of the patients was 58.9±10.2 years. The majority of patients (85%) were female. The average final FFI-RS score was 62.9±15.3. The internal consistency was achieved at a high level of 0.95 in Cronbach’s alpha test, with an interclass correlation coefficient ranging between 0.78 and 0.84. A strong correlation was observed between the FFI-RS and Health Assessment Questionnaire-Disability Index (HAQ-DI) questionnaires. Conclusion. The Polish version of FFI-RS-PL indicator is an important tool for evaluating the functional condition of patients’ feet and can be applied in the diagnosis and treatment of Polish-speaking patients suffering from RA.
Double Hodge Theory for a Particle on Torus
Authors: Pandey Vipul Kumar , Mandal Bhabani Prasad
Published: November 2017

We investigate all possible nilpotent symmetries for a particle on torus. We explicitly construct four independent nilpotent BRST symmetries for such systems and derive the algebra between the generators of such symmetries. We show that such a system has rich mathematical properties and behaves as double Hodge theory. We further construct the finite field dependent BRST transformation for such systems by integrating the infinitesimal BRST transformation systematically. Such a finite transformation is useful in realizing the various theories with toric geometry.
The Evaluation of Toxicity Induced by Psoraleae Fructus in Rats Using Untargeted Metabonomic Method Based on UPLC‐Q‐TOF/MS
Authors: Xu Yanyan , Zhao Yiwei , Xie Jiabin , Sheng Xue , Li Yubo , Zhang Yanjun
Published: November 2017

Psoraleae Fructus is the dry and mature fruit of leguminous plant Psoralea corylifolia L., with the activity of warming kidney and enhancing yang, warming spleen, and other effects. However, large doses can cause liver and kidney toxicity. Therefore, it is necessary to evaluate the toxicity of Psoraleae Fructus systematically. Although traditional biochemical indicators and pathological tests have been used to evaluate the safety of drug, these methods lack sensitivity and specificity, so a fast and sensitive analytical method is urgently needed. In this study, an ultraperformance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry (UPLC‐Q‐TOF/MS) method was used to analyze the metabolic profiles of rat plasma. The changes of metabolites in plasma samples were detected by partial least squares‐discriminant analysis (PLS‐DA). Compared with the control group, after 7 days of administration, the pathological sections showed liver and kidney toxicity, and the metabolic trend was changed. Finally, 13 potential biomarkers related to the toxicity of Psoraleae Fructus were screened. The metabolic pathways involved were glycerol phospholipids metabolism, amino acid metabolism, energy metabolism, and so forth. The discovery of these biomarkers laid a foundation for better explaining the hepatotoxicity and nephrotoxicity of Psoraleae Fructus and provided a guarantee for its safety evaluation.
Adolescent Trajectories of Aerobic Fitness and Adiposity as Markers of Cardiometabolic Risk in Adulthood
Authors: Jackowski S. A. , Eisenmann J. C. , Sherar L. B. , Bailey D. A. , Baxter-Jones A. D. G.
Published: November 2017

Purpose. The aim of this study was to investigate whether adolescent growth trajectories of aerobic fitness and adiposity were associated with mid-adulthood cardiometabolic risk (CMR).Methods. Participants were drawn from the Saskatchewan Growth and Development Study (1963–1973). Adolescent growth trajectories for maximal aerobic capacity (absolute VO2(AbsVO2)), skinfolds (SF), representing total body (Sum6SF) and central adiposity (TrunkSF), and body mass index (BMI) were determined from 7 to 17 years of age. In mid-adulthood (40 to 50 years of age), 61 individuals (23 females) returned for follow-ups. A CMR score was calculated to group participants as displaying either high or a low CMR. Multilevel hierarchical models were constructed, comparing the adolescent growth trajectories of AbsVO2,Sum6SF, TrunkSF, and BMI between CMR groupings.Results. There were no significant differences in the adolescent development of AbsVO2,Sum6SF, TrunkSF, and BMI between adult CMR groupings (p>0.05). Individuals with high CMR accrued 62% greater adjusted total body fat percentage from adolescence to adulthood (p=0.03).Conclusions. Growth trajectories of adolescent aerobic fitness and adiposity do not appear to be associated with mid-adulthood CMR. Individuals should be encouraged to participate in behaviours that promote healthy aerobic fitness and adiposity levels throughout life to reduce lifelong CMR.
Lannea acida A. Rich. (Anacardiaceae) Ethanol Extract Exhibits Estrogenic Effects and Prevents Bone Loss in an Ovariectomized Rat Model of Osteoporosis
Authors: Oumarou Mouchili Riepouo , Zingue Stéphane , Bakam Berlise Yengwa , Ateba Sylvin Benjamin , Foyet Simplice Harquin , Mbakop Fritz Teddy Tchaptchet , Njamen Dieudonné
Published: November 2017

Phytoestrogens have been shown to prevent postmenopausal osteoporosis. Lannea acida is a medicinal plant traditionally used in Cameroon to treat infertility, gynaecological complaints, and rheumatism. These uses prompted us to evaluate estrogenic activity of Lannea acida bark ethanolic extract and its antiosteoporotic potential in ovariectomized Wistar rats. In vitro, the E‐screen assay was used to assess the ability of L. acida extract to induce MCF‐7 cells proliferation. In vivo, a 3‐day uterotrophic assay and a 12‐week oral treatment in ovariectomized adult rats were carried out to evaluate the ability of L. acida extract to prevent bone mass loss. L. acida extract induced MCF‐7 cell proliferation. In vivo, it significantly increased the uterine wet weight, uterine and vaginal epithelial heights, and mammary glands differentiation. At 200 mg/kg, a long‐term treatment with the extract prevented body weight gain (p < 0.05) and loss of bone mass and/or density (p < 0.05) induced by ovariectomy. Also, a significant (p < 0.001) decrease of alkaline phosphatase activity was observed with 50 mg/kg. L. acida extract improved bone microarchitecture and could restore normal bone mineralization by increasing the inorganic phosphorus and calcium level in bone. These findings provide evidence that Lannea acida is a potential alternative for the prevention of postmenopausal osteoporosis.
Hibiscus syriacusExtract from an Established Cell Culture Stimulates Skin Wound Healing
Authors: di Martino O. , Tito A. , De Lucia A. , Cimmino A. , Cicotti F. , Apone F. , Colucci G. , Calabrò V.
Published: November 2017

Higher plants are the source of a wide array of bioactive compounds that support skin integrity and health.Hibiscus syriacus, family Malvaceae, is a plant of Chinese origin known for its antipyretic, anthelmintic, and antifungal properties. The aim of this study was to assess the healing and hydration properties ofH. syriacusethanolic extract (HSEE). We established a cell culture fromHibiscus syriacusleaves and obtained an ethanol soluble extract from cultured cells. The properties of the extract were tested by gene expression and functional analyses on human fibroblast, keratinocytes, and skin explants. HSEE treatment increased the healing potential of fibroblasts and keratinocytes. Specifically, HSEE significantly stimulated fibronectin and collagen synthesis by 16 and 60%, respectively, while fibroblasts contractility was enhanced by 30%. These results were confirmed on skin explants, where HSEE accelerated the wound healing activity in terms of epithelium formation and fibronectin production. Moreover, HSEE increased the expression of genes involved in skin hydration and homeostasis. Specifically, aquaporin 3 and filaggrin genes were enhanced by 20 and 58%, respectively. Our data show that HSEE contains compounds capable of stimulating expression of biomarkers relevant to skin regeneration and hydration thereby counteracting molecular pathways leading to skin damage and aging.
Early Contextual Fear Memory Deficits in a Double-Transgenic Amyloid-βPrecursor Protein/Presenilin 2 Mouse Model of Alzheimer’s Disease
Authors: Kishimoto Yasushi , Fukumoto Kai , Nagai Mika , Mizuguchi Ayaka , Kobashi Yuiko
Published: November 2017

Presenilin 1 and presenilin 2 (PS1 and PS2) play a critical role inγ-secretase-mediated cleavage of amyloid-βprecursor protein (APP) and the subsequent generation ofβ-amyloid peptides. The purpose of the present study was to test whether PS2 mutation accelerates the onset of contextual fear memory deficits in a mouse model of AD that expresses a mutation (K670N/M671L) of the human APP with the Swedish mutation (Tg2576 mice). In the present study, an APP/PS2 double-transgenic mouse model (PS2Tg2576) was generated by crossbreeding transgenic mice carrying the human mutant PS2 (N141I) with Tg2576 mice. Contextual fear conditioning was tested in PS2Tg2576 mice aged 3, 4, 6, and 10–12 months. PS2Tg2576 mice showed a tendency of lower freezing behavior as early as 3 months of age, but significant memory impairment was observed from the age of 4 months. The cognitive impairment was more prominent at ages of 6 and 10–12 months. In contrast, Tg2576 mice aged 3 and 4 months exhibited successful acquisition of contextual fear learning, but Tg2576 mice aged 6 months or older showed significantly impaired fear memory. These results show that PS2 mutation significantly accelerates the onset of fear memory deficits in the APP AD model mice.
Preparation of Modified Red Mud-Supported Fe Catalysts for Hydrogen Production by Catalytic Methane Decomposition
Authors: Liu Quanrun , Li Haipeng , Fang Xiaoke , Zhang Jingjie , Zhang Chuanxiang , Ma Mingjie , Li Fenghai , Huang Guangxu
Published: November 2017

A modified red mud- (MRM-) supported Fe catalyst (xFe/MRM) was prepared using the homogeneous precipitation method and applied to methane decomposition to produce hydrogen. The TEM and SEM-EDX results suggested that the particle sizes of the xFe/MRM catalysts were much smaller than that of raw red mud (RM), and the active metal Fe was evenly distributed over the catalyst structure. Moreover, BET results indicated that the surface areas and pore volumes of the catalysts were significantly improved, and the pore sizes of xFe/MRM were distributed from 5 to 12 nm, which is typical for a mesoporous material. The activities of those catalysts for the catalytic decomposition of methane were studied at atmospheric pressure at a moderate temperature of 650°C; the results showed that the xFe/MRM catalysts were more active than RM and MRM. The methane conversion curves of xFe/MRM catalysts exhibited similar variation tendencies (three-step) during the reaction despite different Fe contents, and the loading amount of Fe clearly affected the activity of the catalysts.
The Expression of AQP5 and UTs in the Sweat Glands of Uremic Patients
Authors: Xie Liyi , Jin Li , Feng Jie , Lv Jing
Published: November 2017

Purpose. To research the distribution and quantitative changes of UT-A1, UT-B1, and AQP5 in uremic skin tissue.Methods.34 cases of uremic patients (UP) and 11 controls were recruited. Immunohistochemistry, immunofluorescence, RT-PCR, and Western Blot were used to identify the proteins in sweat glands.Results. AQP5, UT-A1, and UT-B1 were expressed and localized in human skin basal lines, skin sweat glands, and sweat ducts, both in UP and controls. Compared to controls, AQP5 mRNA abundance was significantly decreased in UP (P<0.01), and, with the decrease of eGFR, the AQP5 expression was significantly decreased (P<0.05). By contrast, UT-A1 and UT-B1 mRNA abundance was significantly increased in the skin of UP compared with the control (P<0.01), and, with the decrease of eGFR, the AQP5 expression was significantly increased (P<0.05). We found that the gene changes were coincident with the corresponding target proteins. The urea transporter subtypes, UT-A1 and UT-B1, were expressed in the skin basal cell layer and exocrine sweat glands. The abundance of UT-A1 and UT-B1 in uremic sweat glands was significantly increased in UP, while the expression of AQP5 was decreased.Conclusion. Elimination of urea through the skin by producing sweat is a potential therapeutic strategy for renal failure patients.
Smart Device for the Determination of Heart Rate Variability in Real Time
Authors: Naranjo-Hernández David , Roa Laura M. , Reina-Tosina Javier , Barbarov-Rostan Gerardo , Galdámez-Cruz Omar
Published: November 2017

This work presents a first approach to the design, development, and implementation of a smart device for the real-time measurement and detection of alterations in heart rate variability (HRV). The smart device follows a modular design scheme, which consists of an electrocardiogram (ECG) signal acquisition module, a processing module and a wireless communications module. From five-minute ECG signals, the processing module algorithms perform a spectral estimation of the HRV. The experimental results demonstrate the viability of the smart device and the proposed processing algorithms.
Natural Food Additives and Preservatives for Fish-Paste Products: A Review of the Past, Present, and Future States of Research
Authors: Bashir Khawaja Muhammad Imran , Kim Jin-Soo , An Jeong Hyeon , Sohn Jae Hak , Choi Jae-Suk
Published: November 2017

Fish-paste products, also known as fish cakes or surimi-based products, are worldwide favorites. Surimi, a wet protein concentrate of fish muscle, is used as an intermediate raw material to produce surimi seafood. The flavor, texture, taste, shelf-life, and market value of surimi-based products depend on the source of the fish meat, type of applied heat treatment, and additives used to prepare the surimi. While preparing surimi with chemical additives, several problems have been observed, such as a lack of unique characteristics, inferior acceptability, and poor functionality. Various types of fish-paste products have been developed by using different ingredients (e.g., vegetables, seafood, herbs and oriental medicines, grains and roots including carrots, and functional food materials). However, a systematic review of fish-paste products prepared using natural food additives has not yet been performed. Therefore, the quality characteristics of fish-paste products and their functionalities were elucidated in this study. With the increasing demand for surimi seafood products, the functional properties, physiochemical properties, and shelf-life of surimi-based products need to be improved. This review will aid the preparation of new value-added products in the surimi industry.
miR-139-5p Modulates Radiotherapy Resistance in Breast Cancer by Repressing Multiple Gene Networks of DNA Repair and ROS Defense
Authors: Pajic Marina , Froio Danielle , Daly Sheridan , Doculara Louise , Millar Ewan , Graham Peter H. , Drury Alison , Steinmann Angela , de Bock Charles E. , Boulghourjian Alice , Zaratzian Anaiis , Carroll Susan , Toohey Joanne , O’Toole Sandra A. , Harris Adrian L , Buffa Francesca M. , Gee Harriet E. , Hollway Georgina E. , Molloy Timothy J.
Published: November 2017

Radiotherapy is essential to the treatment of most solid tumors and acquired or innate resistance to this therapeutic modality is a major clinical problem. Here we show that miR-139-5p is a potent modulator of radiotherapy response in breast cancer via its regulation of genes involved in multiple DNA repair and reactive oxygen species defense pathways. Treatment of breast cancer cells with a miR-139-5p mimic strongly synergized with radiation both in vitro and in vivo, resulting in significantly increased oxidative stress, accumulation of unrepaired DNA damage, and induction of apoptosis. Several miR-139-5p target genes were also strongly predictive of outcome in radiotherapy-treated patients across multiple independent breast cancer cohorts. These prognostically relevant miR-139-5p target genes were used as companion biomarkers to identify radioresistant breast cancer xenografts highly amenable to sensitization by cotreatment with a miR-139-5p mimetic.

Significance: The microRNA described in this study offers a potentially useful predictive biomarker of radiosensitivity in solid tumors and a generally applicable druggable target for tumor radiosensitization. Cancer Res; 78(2); 501–15. ©2017 AACR.
A Potent, Metabolically Stable Tubulin Inhibitor Targets the Colchicine Binding Site and Overcomes Taxane Resistance
Authors: Arnst Kinsie E. , Wang Yuxi , Hwang Dong-Jin , Xue Yi , Costello Terry , Hamilton David , Chen Qiang , Yang Jinliang , Park Frank , Dalton James T. , Miller Duane D. , Li Wei
Published: November 2017

Antimitotics that target tubulin are among the most useful chemotherapeutic drugs, but their clinical activity is often limited by the development of multidrug resistance. We recently discovered the novel small-molecule DJ101 as a potent and metabolically stable tubulin inhibitor that can circumvent the drug efflux pumps responsible for multidrug resistance of existing tubulin inhibitors. In this study, we determined the mechanism of action of this drug. The basis for its activity was illuminated by solving the crystal structure of DJ101 in complex with tubulin at a resolution of 2.8Å. Investigations of the potency of DJ101 in a panel of human metastatic melanoma cell lines harboring major clinically relevant mutations defined IC50 values of 7–10 nmol/L. In cells, DJ101 disrupted microtubule networks, suppressed anchorage-dependent melanoma colony formation, and impaired cancer cell migration. In melanoma-bearing mice, DJ101 administration inhibited tumor growth and reduced lung metastasis in the absence of observable toxicity. DJ101 also completely inhibited tumor growth in a paclitaxel-resistant xenograft mouse model of human prostate cancer (PC-3/TxR), where paclitaxel was minimally effective. Our findings offer preclinical proof of concept for the continued development of DJ101 as a next-generation tubulin inhibitor for cancer therapy.

Significance: These findings offer preclinical proof of concept for the continued development of DJ101 as a next-generation antitubulin drug for cancer therapy. Cancer Res; 78(1); 265–77. ©2017 AACR.
YAP1 and COX2 Coordinately Regulate Urothelial Cancer Stem-like Cells
Authors: Ooki Akira , Del Carmen Rodriguez Pena Maria , Marchionni Luigi , Dinalankara Wikum , Begum Asma , Hahn Noah M. , VandenBussche Christopher J. , Rasheed Zeshaan A. , Mao Shifeng , Netto George J. , Sidransky David , Hoque Mohammad O.
Published: November 2017

Overcoming acquired drug resistance remains a core challenge in the clinical management of human cancer, including in urothelial carcinoma of the bladder (UCB). Cancer stem-like cells (CSC) have been implicated in the emergence of drug resistance but mechanisms and intervention points are not completely understood. Here, we report that the proinflammatory COX2/PGE2 pathway and the YAP1 growth-regulatory pathway cooperate to recruit the stem cell factor SOX2 in expanding and sustaining the accumulation of urothelial CSCs. Mechanistically, COX2/PGE2 signaling induced promoter methylation of let-7, resulting in its downregulation and subsequent SOX2 upregulation. YAP1 induced SOX2 expression more directly by binding its enhancer region. In UCB clinical specimens, positive correlations in the expression of SOX2, COX2, and YAP1 were observed, with coexpression of COX2 and YAP1 particularly commonly observed. Additional investigations suggested that activation of the COX2/PGE2 and YAP1 pathways also promoted acquired resistance to EGFR inhibitors in basal-type UCB. In a mouse xenograft model of UCB, dual inhibition of COX2 and YAP1 elicited a long-lasting therapeutic response by limiting CSC expansion after chemotherapy and EGFR inhibition. Our findings provide a preclinical rationale to target these pathways concurrently with systemic chemotherapy as a strategy to improve the clinical management of UCB.

Significance: These findings offer a preclinical rationale to target the COX2 and YAP1 pathways concurrently with systemic chemotherapy to improve the clinical management of UCB, based on evidence that these two pathways expand cancer stem-like cell populations that mediate resistance to chemotherapy. Cancer Res; 78(1); 168–81. ©2017 AACR.
ERα Binding by Transcription Factors NFIB and YBX1 Enables FGFR2 Signaling to Modulate Estrogen Responsiveness in Breast Cancer
Authors: Campbell Thomas M. , Castro Mauro A. A. , de Oliveira Kelin Gonçalves , Ponder Bruce A. J. , Meyer Kerstin B.
Published: November 2017

Two opposing clusters of transcription factors (TF) have been associated with the differential risks of estrogen receptor positive or negative breast cancers, but the mechanisms underlying the opposing functions of the two clusters are undefined. In this study, we identified NFIB and YBX1 as novel interactors of the estrogen receptor (ESR1). NFIB and YBX1 are both risk TF associated with progression of ESR1-negative disease. Notably, they both interacted with the ESR1-FOXA1 complex and inhibited the transactivational potential of ESR1. Moreover, signaling through FGFR2, a known risk factor in breast cancer development, augmented these interactions and further repressed ESR1 target gene expression. We therefore show that members of two opposing clusters of risk TFs associated with ESR1-positive and -negative breast cancer can physically interact. We postulate that this interaction forms a toggle between two developmental pathways affected by FGFR2 signaling, possibly offering a junction to exploit therapeutically.

Significance: Binding of the transcription factors NFIB and YBX1 to the estrogen receptor can promote an estrogen-independent phenotype that can be reverted by inhibiting FGFR2 signaling. Cancer Res; 78(2); 410–21. ©2017 AACR.
Small-Molecule Inhibition of Axl Targets Tumor Immune Suppression and Enhances Chemotherapy in Pancreatic Cancer
Authors: Ludwig Kathleen F. , Du Wenting , Sorrelle Noah B. , Wnuk-Lipinska Katarzyna , Topalovski Mary , Toombs Jason E. , Cruz Victoria H. , Yabuuchi Shinichi , Rajeshkumar N.V. , Maitra Anirban , Lorens James B. , Brekken Rolf A.
Published: November 2017

Activation of the receptor tyrosine kinase Axl is associated with poor outcomes in pancreatic cancer (PDAC), where it coordinately mediates immune evasion and drug resistance. Here, we demonstrate that the selective Axl kinase inhibitor BGB324 targets the tumor–immune interface to blunt the aggressive traits of PDAC cells in vitro and enhance gemcitibine efficacy in vivo. Axl signaling stimulates the TBK1–NFκB pathway and innate immune suppression in the tumor microenvironment. In tumor cells, BGB324 treatment drove epithelial differentiation, expression of nucleoside transporters affecting gemcitabine response, and an immune stimulatory microenvironment. Our results establish a preclinical mechanistic rationale for the clinical development of Axl inhibitors to improve the treatment of PDAC patients.

Significance: These results establish a preclinical mechanistic rationale for the clinical development of AXL inhibitors to improve the treatment of PDAC patients. Cancer Res; 78(1); 246–55. ©2017 AACR.