bluuebunny/crossref_metadata_2025 huggingface dataset:
Deciphering the fine nucleotide diversity of full HLA class I and class II genes in a well‐documented population from sub‐Saharan Africa
Authors: Goeury T. , Creary L. E. , Brunet L. , Galan M. , Pasquier M. , Kervaire B. , Langaney A. , Tiercy J.‐M. , Fernández‐Viña M. A. , Nunes J. M. , Sanchez‐Mazas A.
Published: November 2017

With the aim to understand how next‐generation sequencing (NGS) improves both our assessment of genetic variation within populations and our knowledge on HLA molecular evolution, we sequenced and analysed 8 HLA loci in a well‐documented population from sub‐Saharan Africa (Mandenka). The results of full‐gene NGS‐MiSeq sequencing compared with those obtained by traditional typing techniques or limited sequencing strategies showed that segregating sites located outside exon 2 are crucial to describe not only class I but also class II population diversity. A comprehensive analysis of exons 2, 3, 4 and 5 nucleotide diversity at the 8 HLA loci revealed remarkable differences among these gene regions, notably a greater variation concentrated in the antigen recognition sites of class I exons 3 and some class II exons 2, likely associated with their peptide‐presentation function, a lower diversity of HLA‐C exon 3, possibly related to its role as a KIR ligand, and a peculiar molecular diversity of HLA‐A exon 2, revealing demographic signals. Based on full‐length HLA sequences, we also propose that the most frequent DRB1 allele in the studied population,DRB1*13:04, emerged from an allelic conversion involving 3 potential alleles as donors andDRB1*11:02:01as recipient. Finally, our analysis revealed a high occurrence of theDRB1*13:04‐DQA1*05:05:01‐DQB1*03:19haplotype, possibly resulting from a selective sweep due to protection toOnchorcerca volvulus, a prevalent pathogen in West Africa. This study unveils highly relevant information on the molecular evolution of HLA genes in relation to their immune function, calling for similar analyses in other populations living in contrasting environments.
Low sensitivity and frequent cross‐reactions in commercially available antibody detection ELISA assays for Taenia solium cysticercosis
Authors: Garcia Hector H. , Castillo Yesenia , Gonzales Isidro , Bustos Javier A. , Saavedra Herbert , Jacob Louis , Del Brutto Oscar H. , Wilkins Patricia P. , Gonzalez Armando E. , Gilman Robert H. ,   the Cysticercosis Working Group in Peru
Published: November 2017

Objective

To evaluate the diagnostic performance of two commercially available ELISA kits, Novalisa® and Ridascreen®, for the detection of antibodies to Taenia solium, compared to serological diagnosis of neurocysticercosis (NCC) by LLGP‐EITB (electro‐immunotransfer blot assay using lentil‐lectin purified glycoprotein antigens).

Methods

Archive serum samples from patients with viable NCC (n = 45) or resolved, calcified NCC (n = 45), as well as sera from patients with other cestode parasites (hymenolepiasis, n = 45 and cystic hydatid disease, n = 45), were evaluated for cysticercosis antibody detection using two ELISA kits, Novalisa® and Ridascreen®. All NCC samples had previously tested positive, and all samples from heterologous infections were negative on LLGP‐EITB for cysticercosis. Positive rates were calculated by kit and sample group and compared between the two kits.

Results

Compared to LLGP‐EITB, the sensitivity of both ELISA assays to detect specific antibodies in patients with viable NCC was low (44.4% and 22.2%), and for calcified NCC, it was only 6.7% and 4.5%. Sera from patients with cystic hydatid disease were highly cross‐reactive in both ELISA assays (38/45, 84.4%; and 25/45, 55.6%). Sera from patients with hymenolepiasis cross‐reacted in five cases in one of the assays (11.1%) and in only one sample with the second assay (2.2%).

Conclusions

The performance of Novalisa® and Ridascreen® was poor. Antibody ELISA detection cannot be recommended for the diagnosis of neurocysticercosis.
The Sorghum bicolor reference genome: improved assembly, gene annotations, a transcriptome atlas, and signatures of genome organization
Authors: McCormick Ryan F. , Truong Sandra K. , Sreedasyam Avinash , Jenkins Jerry , Shu Shengqiang , Sims David , Kennedy Megan , Amirebrahimi Mojgan , Weers Brock D. , McKinley Brian , Mattison Ashley , Morishige Daryl T. , Grimwood Jane , Schmutz Jeremy , Mullet John E.
Published: November 2017

Sorghum bicolor is a drought tolerant C4 grass used for the production of grain, forage, sugar, and lignocellulosic biomass and a genetic model for C4 grasses due to its relatively small genome (approximately 800 Mbp), diploid genetics, diverse germplasm, and colinearity with other C4 grass genomes. In this study, deep sequencing, genetic linkage analysis, and transcriptome data were used to produce and annotate a high‐quality reference genome sequence. Reference genome sequence order was improved, 29.6 Mbp of additional sequence was incorporated, the number of genes annotated increased 24% to 34 211, average gene length and N50 increased, and error frequency was reduced 10‐fold to 1 per 100 kbp. Subtelomeric repeats with characteristics of Tandem Repeats in Miniature (TRIM) elements were identified at the termini of most chromosomes. Nucleosome occupancy predictions identified nucleosomes positioned immediately downstream of transcription start sites and at different densities across chromosomes. Alignment of more than 50 resequenced genomes from diverse sorghum genotypes to the reference genome identified approximately 7.4 M single nucleotide polymorphisms (SNPs) and 1.9 M indels. Large‐scale variant features in euchromatin were identified with periodicities of approximately 25 kbp. A transcriptome atlas of gene expression was constructed from 47 RNA‐seq profiles of growing and developed tissues of the major plant organs (roots, leaves, stems, panicles, and seed) collected during the juvenile, vegetative and reproductive phases. Analysis of the transcriptome data indicated that tissue type and protein kinase expression had large influences on transcriptional profile clustering. The updated assembly, annotation, and transcriptome data represent a resource for C4 grass research and crop improvement.
Journey to the centre of the cell: Virtual reality immersion into scientific data
Authors: Johnston Angus P.R. , Rae James , Ariotti Nicholas , Bailey Benjamin , Lilja Andrew , Webb Robyn , Ferguson Charles , Maher Sheryl , Davis Thomas P. , Webb Richard I. , McGhee John , Parton Robert G.
Published: November 2017

Visualization of scientific data is crucial not only for scientific discovery but also to communicate science and medicine to both experts and a general audience. Until recently, we have been limited to visualizing the three‐dimensional (3D) world of biology in 2 dimensions. Renderings of 3D cells are still traditionally displayed using two‐dimensional (2D) media, such as on a computer screen or paper. However, the advent of consumer grade virtual reality (VR) headsets such as Oculus Rift and HTC Vive means it is now possible to visualize and interact with scientific data in a 3D virtual world. In addition, new microscopic methods provide an unprecedented opportunity to obtain new 3D data sets. In this perspective article, we highlight how we have used cutting edge imaging techniques to build a 3D virtual model of a cell from serial block‐face scanning electron microscope (SBEM) imaging data. This model allows scientists, students and members of the public to explore and interact with a “real” cell. Early testing of this immersive environment indicates a significant improvement in students’ understanding of cellular processes and points to a new future of learning and public engagement. In addition, we speculate that VR can become a new tool for researchers studying cellular architecture and processes by populating VR models with molecular data.
Modeling of Glue Penetration Into Natural Fiber Reinforcements by Roller Infusion
Authors: Jiang Lai , Walczyk Daniel F. , Li Bingbing
Published: November 2017

Roller infusion by nip rollers is widely used in the infusion industry with broad applications, which is also adopted as one of the seven steps of a newly developed manufacturing process for making fungal mycelium-based biocomposites. One important technical issue related to infusion textile reinforcements for such biocomposites is how to predict and control the infusion fluid penetration depth, which directly affects the quality and performances of the preformed textile skins. Currently, the analytical relations between the modeling parameters and the final infusion penetration depth are still not well understood. Few studies have been performed on such topic and some of which used oversimplified assumptions. A new analytical model is developed in this paper, and the infusion penetration curves are plotted based on certain input parameters including infusion speed, infusion fluid flow rate, and clamping forces of the two rollers. The model-calculated results are then validated by experiments that are performed with the same parameters. The measured parameters of prepared non-Newtonian starch-based natural glue are used both in the modeling and experiments, and the results are close enough for model validation.
Mistuned Higher-Order Mode Forced Response of an Embedded Compressor Rotor—Part II: Mistuned Forced Response Prediction
Authors: Li Jing , Aye-Addo Nyansafo , Kielb Robert , Key Nicole
Published: November 2017

This paper is the second part of a two-part paper that presents a comprehensive study of the higher-order mode (HOM) mistuned forced response of an embedded rotor blisk in a multistage axial research compressor. The resonant response of the second-stage rotor (R2) in its first chordwise bending (1CWB) mode due to the second harmonic of the periodic passing of its neighboring stators (S1 and S2) is investigated computationally and experimentally at three steady loading conditions in the Purdue three-stage compressor research facility. A nonintrusive stress measurement system (NSMS, or blade tip-timing) is used to measure the blade vibration. Two reduced-order mistuning models of different levels of fidelity are used, namely, the fundamental mistuning model (FMM) and the component mode mistuning (CMM), to predict the response. Although several modes in the 1CWB modal family appear in frequency veering and high modal density regions, they do not heavily participate in the response such that very similar results are produced by the FMM and the CMM models of different sizes. A significant response amplification factor of 1.5–2.0 is both measured and predicted, which is on the same order of magnitude of what was commonly reported for low-frequency modes. In this study, a good agreement between predictions and measurements is achieved for the deterministic analysis. This is complemented by a sensitivity analysis which shows that the mistuned system is highly sensitive to the discrepancies in the experimentally determined blade frequency mistuning.
A Lifetime Prediction Method of Pressured Gas Polyethylene Pipes by Thermal-Oxidative Aging Test and Tensile Test
Authors: Wang Yang , Lan Hui-qing , Meng Tao , Chen Shan , Zuo Jian-dong , Lin Nan
Published: November 2017

Polyethylene (PE) pipes have the advantages of low weight, corrosion resistance, high impact resistance, and superior flexibility, and have been widely used for various urban gas engineering. With the increase of service life, the aging of PE pipes has become a safety issue that needs to be solved. So far, the aging performance of PE pipes are researched at home and abroad, but there are few reports on the aging performance of PE pipes under different pressures which are similar to actual urban gas working condition. Therefore, an accelerated aging test of gas PE pipes under different pressures was carried out by a thermal oxygen aging experimental setups. After that, mechanical properties of the aged PE pipes were tested by a tensile test. Then, based on the tensile test's results, empirical equations of pressured urban gas PE pipes were got by Arrhenius fit of the data, and finally, a life prediction model of pressured urban gas PE pipes was proposed. The results show that tensile strength (TS) of the aged gas PE pipes reduces with the increasing internal pressure. The lives of the PE gas pipes with internal pressure of 0.1 MPa, 0.2 MPa, 0.3 MPa, and 0.4 MPa are 10%, 22.4%, 34.7%, and 44% shorter than those without internal pressure, respectively. This life prediction method is not only suitable for pressured urban gas PE pipes, but also for other plastic pipes in similar environments.
In vitro model of potential metal cation exchanges in biological apatite
Authors: Shi Haishan , Zhang Jing , Ye Xiaoling , Wu Tingting , Ye Jiandong
Published: November 2017

Biological apatite is ion-doped and provides an active pool for the exchange with foreign impurity ions. In this work, an in vitro model of hydrated metastable octacalcium phosphate (OCP) crystals was established to mimetically investigate the distinct exchange of trivalent and divalent cations (Fe3+ and Sr2+) with biological apatite. Fe3+ significantly promoted the collapses of OCP crystals and the formation of amorphous sol-like ferric phosphates, while Sr2+ facilitated the epitaxial growth and stability of OCP crystals. The involvement of Ca2+ maintained the crystalline integrity and inhibited the ion exchange within OCP crystals. This in vitro model would lay the foundation for the further investigation of the metabolism of biological apatite.
A transfer learning approach to goodness of pronunciation based automatic mispronunciation detection
Authors: Huang Hao , Xu Haihua , Hu Ying , Zhou Gang
Published: November 2017

Goodness of pronunciation (GOP) is the most widely used method for automatic mispronunciation detection. In this paper, a transfer learning approach to GOP based mispronunciation detection when applying maximum F1-score criterion (MFC) training to deep neural network (DNN)-hidden Markov model based acoustic models is proposed. Rather than train the whole network using MFC, a DNN is used, whose hidden layers are borrowed from native speech recognition with only the softmax layer trained according to the MFC objective function. As a result, significant mispronunciation detection improvement is obtained. In light of this, the two-stage transfer learning based GOP is investigated in depth. The first stage exploits the hidden layer(s) to extract phonetic-discriminating features. The second stage uses a trainable softmax layer to learn the human standard for judgment. The validation is carried out by experimenting with different mispronunciation detection architectures using acoustic models trained by different criteria. It is found that it is preferable to use frame-level cross-entropy to train the hidden layer parameters. Classifier based mispronunciation detection is further experimented with using features computed by transfer learning based GOP and it is shown that it also helps to achieve better results.
A revised metric for calculating acoustic dispersion applied to stop inventories
Authors: Hauser Ivy
Published: November 2017

Dispersion Theory [DT; Liljencrants and Lindblom (1972). Language 12(1), 839–862] claims that acoustically dispersed vowel inventories should be typologically common. Dispersion is often quantified using triangle area between three mean vowel formant points. This approach is problematic; it ignores distributions, which affect speech perception [Clayards, Tanenhaus, Aslin, and Jacobs (2008). Cognition 108, 804–809]. This letter proposes a revised metric for calculating dispersion which incorporates covariance. As a test case, modeled vocal tract articulatory-acoustic data of stop consonants [Schwartz, Boe, Badin, and Sawallis (2012). J. Phonetics 40, 20–36] are examined. Although the revised metric does not recover DT predictions for stop inventories, it changes results, showing that dispersion results depend on metric choice, which is often overlooked. The metric can be used in any acoustic space to include information about within-category variation when calculating dispersion.
Autoimmune diseases surface after cancer treatment
Authors: Couzin-Frankel Jennifer
Published: November 2017

Side effects of new immunotherapy drugs draw scrutiny
Ancient Australian goes home
Authors: Pickrell John
Published: November 2017

Researchers still hope for access to “Mungo Man” bones
The future of plastics recycling
Authors: Garcia Jeannette M. , Robertson Megan L.
Published: November 2017

Chemical advances are increasing the proportion of polymer waste that can be recycled
Evolution of neurovirulent Zika virus
Authors: Screaton Gavin , Mongkolsapaya Juthathip
Published: November 2017

A Zika virus mutation leads to increased neurovirulence
ATP promotes the fast migration of dendritic cells through the activity of pannexin 1 channels and P2X
7
receptors
Authors: Sáez Pablo J. , Vargas Pablo , Shoji Kenji F. , Harcha Paloma A. , Lennon-Duménil Ana-María , Sáez Juan C.
Published: November 2017

Through an autocrine loop involving its receptor P2X
7
and pannexin 1 channels, the danger signal ATP enhances the migration of dendritic cells.
Microtubules tune mechanotransduction through NOX2 and TRPV4 to decrease sclerostin abundance in osteocytes
Authors: Lyons James S. , Joca Humberto C. , Law Robert A. , Williams Katrina M. , Kerr Jaclyn P. , Shi Guoli , Khairallah Ramzi J. , Martin Stuart S. , Konstantopoulos Konstantinos , Ward Christopher W. , Stains Joseph P.
Published: November 2017

Cytoskeleton stiffness, which is affected by the abundance of detyrosinated tubulin, regulates mechanosensitivity in osteocytes.
Papers of note in
Nature

551
(7680)
Authors: VanHook Annalisa M.
Published: November 2017

This week’s articles identify a mechanism by which liver inflammation suppresses antitumor immunity; a bacterial effector protein that targets host defense proteins for degradation; and a signaling mechanism for detecting and repairing a specific type of DNA damage.
New connections: Making dendritic cells go faster
Authors: Foley John F.
Published: November 2017

Danger signals, such as microbial products or ATP, enhance the speed of migrating dendritic cells to lymph nodes to initiate an immune response.
Leading components in forward elastic hadron scattering: Derivative dispersion relations and asymptotic uniqueness
Authors: Fagundes D. A. , Menon M. J. , Silva P. V. R. G.
Published: November 2017

Forward amplitude analyses constitute an important approach in the investigation of the energy dependence of the total hadronic cross-section [Formula: see text] and the [Formula: see text] parameter. The standard picture indicates for [Formula: see text] a leading log-squared dependence at the highest c.m. energies, in accordance with the Froissart–Lukaszuk–Martin bound and as predicted by the COMPETE Collaboration in 2002. Beyond this log-squared (L2) leading dependence, other amplitude analyses have considered a log-raised-to-gamma form [Formula: see text], with [Formula: see text] as a real free fit parameter. In this case, analytic connections with [Formula: see text] can be obtained either through dispersion relations (derivative forms), or asymptotic uniqueness (Phragmén–Lindelöff theorems). In this work, we present a detailed discussion on the similarities and mainly the differences between the Derivative Dispersion Relation (DDR) and Asymptotic Uniqueness (AU) approaches and results, with focus on the [Formula: see text] and L2 leading terms. We also develop new Regge–Gribov fits with updated dataset on [Formula: see text] and [Formula: see text] from [Formula: see text] and [Formula: see text] scattering, including all available data in the region 5 GeV–8 TeV. The recent tension between the TOTEM and ATLAS results at 7 TeV and mainly at 8 TeV is discussed and considered in the data reductions. Our main conclusions are the following: (1) all fit results present agreement with the experimental data analyzed and the goodness-of-fit is slightly better in case of the DDR approach; (2) by considering only the TOTEM data at the LHC region, the fits with L[Formula: see text] indicate [Formula: see text] (AU approach) and [Formula: see text] (DDR approach); (3) by including the ATLAS data the fits provide [Formula: see text] (AU) and [Formula: see text] (DDR); (4) in the formal and practical contexts, the DDR approach is more adequate for the energy interval investigated than the AU approach. A pedagogical and detailed review on the analytic results for [Formula: see text] and [Formula: see text] from the Regge–Gribov, DDR and AU approaches is presented. Formal and practical aspects related to forward amplitude analyses are also critically discussed.
Backward Bifurcation in a Cholera Model: A Case Study of Outbreak in Zimbabwe and Haiti
Authors: Sharma Sandeep , Kumari Nitu
Published: November 2017

In this paper, a nonlinear deterministic model is proposed with a saturated treatment function. The expression of the basic reproduction number for the proposed model was obtained. The global dynamics of the proposed model was studied using the basic reproduction number and theory of dynamical systems. It is observed that proposed model exhibits backward bifurcation as multiple endemic equilibrium points exist when [Formula: see text]. The existence of backward bifurcation implies that making [Formula: see text] is not enough for disease eradication. This, in turn, makes it difficult to control the spread of cholera in the community. We also obtain a unique endemic equilibria when [Formula: see text]. The global stability of unique endemic equilibria is performed using the geometric approach. An extensive numerical study is performed to support our analytical results. Finally, we investigate two major cholera outbreaks, Zimbabwe (2008–09) and Haiti (2010), with the help of the present study.
Stability and Bifurcation of a Fishery Model with Crowley–Martin Functional Response
Authors: Maiti Atasi Patra , Dubey B.
Published: November 2017

To understand the dynamics of a fishery system, a nonlinear mathematical model is proposed and analyzed. In an aquatic environment, we considered two populations: one is prey and another is predator. Here both the fish populations grow logistically and interaction between them is of Crowley–Martin type functional response. It is assumed that both the populations are harvested and the harvesting effort is assumed to be dynamical variable and tax is considered as a control variable. The existence of equilibrium points and their local stability are examined. The existence of Hopf-bifurcation, stability and direction of Hopf-bifurcation are also analyzed with the help of Center Manifold theorem and normal form theory. The global stability behavior of the positive equilibrium point is also discussed. In order to find the value of optimal tax, the optimal harvesting policy is used. To verify our analytical findings, an extensive numerical simulation is carried out for this model system.
Stability and Bifurcation Analysis in the Photosensitive CDIMA System with Delayed Feedback Control
Authors: Wei Xin , Wei Junjie
Published: November 2017

A diffusive photosensitive CDIMA system with delayed feedback subject to Neumann boundary conditions is considered. We derive the conditions of the occurrence of Turing instability. We also investigate the influence of delay on the stability of the positive equilibrium of the system, and prove that delay induces the occurrence of Hopf bifurcation. By computing the normal form on the center manifold, we give the formulas determining the properties of the Hopf bifurcation. Finally, we give some numerical simulations to support and strengthen the theoretical results. Our study shows that diffusion and delayed feedback can effect the stability of the equilibrium of the system.
Deformation of the quintom cosmological model and its consequences
Authors: Sadeghi J. , Pourhassan B. , Nekouee Z. , Shokri M.
Published: November 2017

In this paper, we investigate the effects of noncommutative phase-space on the quintom cosmological model. In that case, we discuss about some cosmological parameters and show that they depend on the deformation parameters. We find that the noncommutative parameter plays important role which helps to re-arrange the divergency of cosmological constant. We draw time-dependent scale factor and investigate the effect of noncommutative parameters. Finally, we take advantage from noncommutative phase-space and obtain the deformed Lagrangian for the quintom model. In order to discuss some cosmological phenomena as dark energy and inflation, we employ Noether symmetry.
INVESTIGATING THE EFFECTS OF PASSIVE MECHANICAL ANKLE ON UNILATERAL OSTEOMYOPLASTIC TRANSTIBIAL AMPUTEES
Authors: Garikayi Talon , Van Den Heever Dawie , Matope Stephen
Published: November 2017

Purpose The study presents an investigation of the asymmetries in normal gait associated with the use of prosthetic mechanical passive ankle devices when performing ambulatory-related activities for unilateral osteomyoplastic transtibial amputees. Asymmetries in gait may lead to low-back pain and other long-term effects associated with hip compensation and excessive energy consumption. Methods Unilateral transtibial osteomyoplastic amputees were tasked to perform normal gait. The Vicon Motion system and Myomotion System consisting of electromyography sensors and inertial measurement units were used to collect data. Quantitative gait analysis was used for the analysis of anatomical angles for the ankle, knee, hip and pelvis. The results were compared to normative data. Result It was hypothesized that the unilateral amputees would demonstrate high peaks on the hip, knee and ankle of the intact side so as to compensate for the lack of propulsive force on the passive ankle of the prosthetic limb. All parameters for anatomical angles were found to be significant ([Formula: see text]), hip flexion ([Formula: see text]), knee flexion ([Formula: see text]) and ankle dorsiflexion ([Formula: see text]). Temporal and distance variables were quantitatively analyzed and there was no significant difference. Poor management of range of motion was observed on the ankle and the knee. There was minimum hip extension during the stance phase. There was excessive hip rotation and foot plantarflexion on the intact side of the amputee as hip compensation was being applied during the toe-off period and early swing. Amputees exhibited short stance time duration. Conclusion This study demonstrated that amputees can achieve same distance variables as normal subjects; however, this causes variations in anatomical angles which result in asymmetries in normal gait. Variations in lateral pelvic tilt indicated possible development of lower back pain and changes in posture.
Multibody Dynamics of a Floating Wind Turbine Considering the Flexibility Between Nacelle and Tower
Authors: Jahangiri Vahid , Ettefagh Mir Mohammad
Published: November 2017

Stability and dynamic modeling of the floating wind turbine (FWT) is a crucial challenge in designing of the type of structures. In this paper, the tension leg platform (TLP) type FWT is modeled as a multibody system considering the flexibility between the nacelle and tower. The flexibility of the FWT is modeled as a torsional spring and damper. It has 6 degrees of freedom (DOFs) related to the large-amplitude translation and rotation of the tower and 4 DOFs related to the relative rotation between the rotor-nacelle assembly and the tower. First, the nonlinear equations of motion are derived by the theory of momentum cloud based on the conservation of momentum. Then, the equations of motion are solved and the system is simulated in MATLAB. Moreover, the effect of flexibility between the nacelle and tower is investigated via the dynamic response. The stability of the system in three different environmental conditions is studied. Finally, the spring and damping coefficients for the system response to get near to instability are determined, by which the critical region is defined. The simulation results demonstrate the importance of the flexibility between the nacelle and tower on the overall behavior of the system and its stability.
Nature and Evolution of the Ore-Forming Fluids from Nanmushu Carbonate-Hosted Zn-Pb Deposit in the Mayuan District, Shaanxi Province, Southwest China
Authors: Xiong Suo-Fei , Gong Yong-Jun , Yao Shu-Zhen , Shen Chuan-Bo , Ge Xiang , Jiang Shao-Yong
Published: November 2017

The Nanmushu carbonate-hosted Zn-Pb deposit is located in the Mayuan district of Shaanxi Province, a newly discovered metallogenic district next to the Sichuan Basin, in the northern margin of the Yangtze Block, which is the largest and the only one that is currently mined in this district. The δ34S values of sulfides are characterized by positive values with a peak around +18‰, and the reduced sulfur may have derived from reduction of SO42- from paleoseawater or evaporitic sulfates that have possibly been leached by basinal brines during mineralization stage. Detailed fluid inclusion study shows two types of fluids in the sphalerite, quartz, dolomite, calcite and barite, that is, aqueous-salt dominant inclusions (type I) and hydrocarbon-bearing inclusions (type II). The Laser Raman spectroscopy study shows occurrence of certain amount of CH4, C4H6, and bitumen. The salinities show similar values around 6 to 12 wt% NaCl equivalent but a decreasing temperature from early to late stages (typically 200° to 320°C in stage I, 180° to 260°C in stage II, and 140° to 180°C in stage III). These features may be related to basinal brines mixing between an external higher salinity CaCl2  ±  MgCl2-rich fluid and a local H2O-NaCl methane-rich fluid.
Tomatidine Attenuates Airway Hyperresponsiveness and Inflammation by Suppressing Th2 Cytokines in a Mouse Model of Asthma
Authors: Kuo Chieh-Ying , Huang Wen-Chung , Liou Chian-Jiun , Chen Li-Chen , Shen Jiann-Jong , Kuo Ming-Ling
Published: November 2017

Tomatidine is isolated from the fruits of tomato plants and found to have anti-inflammatory effects in macrophages. In the present study, we investigated whether tomatidine suppresses airway hyperresponsiveness (AHR) and eosinophil infiltration in asthmatic mice. BALB/c mice were sensitized with ovalbumin and treated with tomatidine by intraperitoneal injection. Airway resistance was measured by intubation analysis as an indication of airway responsiveness, and histological studies were performed to evaluate eosinophil infiltration in lung tissue. Tomatidine reduced AHR and decreased eosinophil infiltration in the lungs of asthmatic mice. Tomatidine suppressed Th2 cytokine production in bronchoalveolar lavage fluid. Tomatidine also blocked the expression of inflammatory and Th2 cytokine genes in lung tissue. In vitro, tomatidine inhibited proinflammatory cytokines and CCL11 production in inflammatory BEAS-2B bronchial epithelial cells. These results indicate that tomatidine contributes to the amelioration of AHR and eosinophil infiltration by blocking the inflammatory response and Th2 cell activity in asthmatic mice.
Nontrivial Solution for the Fractional p-Laplacian Equations via Perturbation Methods
Authors: Luo Huxiao , Li Shengjun , Tang Xianhua
Published: November 2017

We study the existence of nontrivial solution of the following equation without compactness: (-Δ)pαu+up-2u=f(x,u),  x∈RN, where N,p≥2,  α∈(0,1),  (-Δ)pα is the fractional p-Laplacian, and the subcritical p-superlinear term f∈C(RN×R) is 1-periodic in xi for i=1,2,…,N. Our main difficulty is that the weak limit of (PS) sequence is not always the weak solution of fractional p-Laplacian type equation. To overcome this difficulty, by adding coercive potential term and using mountain pass theorem, we get the weak solution uλ of perturbation equations. And we prove that uλ→u as λ→0. Finally, by using vanishing lemma and periodic condition, we get that u is a nontrivial solution of fractional p-Laplacian equation.
Efficacy of Abiraterone and Enzalutamide in Pre- and Postdocetaxel Castration-Resistant Prostate Cancer: A Trial-Level Meta-Analysis
Authors: Fang Mike , Nakazawa Mary , Antonarakis Emmanuel S. , Li Chun
Published: November 2017

We examined the comparative efficacies of first-line abiraterone and enzalutamide in pre- and postdocetaxel settings in castration-resistant prostate cancer (CRPC) through a trial level meta-analysis. A mixed method approach was applied to 19 unique studies containing 17 median overall survival (OS) estimates and 13 median radiographic progression-free survival (PFS) estimates. We employed a random-effects meta-analysis to compare efficacies of abiraterone and enzalutamide with respect to OS and PFS. In the predocetaxel setting, enzalutamide use was associated with an increase in median OS of 5.9 months (p<0.001), hazard ratio (HR) = 0.81, and an increase in median PFS of 8.3 months (p<0.001), HR = 0.47 compared to abiraterone. The advantage of enzalutamide improved after adjusting for baseline Gleason score to 19.5 months (p<0.001) and 14.6 months (p<0.001) in median OS and PFS, respectively. In the postdocetaxel setting, the advantage of enzalutamide use was nominally significant for median PFS (1.2 months p=0.02 without adjustment and 2.2 months and p=0.0007 after adjustment); there was no significant difference in median OS between the two agents. The results from this comprehensive meta-analysis suggest a survival advantage with the use of first-line enzalutamide over abiraterone in CRPC and highlight the need for prospective clinical trials.
A Novel Rear-End Collision Detection Algorithm Based on GNSS Fusion and ANFIS
Authors: Sun Rui , Xie Fei , Xue Dabin , Zhang Yucheng , Ochieng Washington Yotto
Published: November 2017

Rear-end collisions are one of the most common types of accidents on roads. Global Satellite Navigation Systems (GNSS) have recently become sufficiently flexible and cost-effective in order to have great potential for use in rear-end collision avoidance systems (CAS). Nevertheless, there are two main issues associated with current vehicle rear-end CAS: (1) achieving relative vehicle positioning and dynamic parameters with sufficiently high accuracy and (2) a reliable method to extract the car-following status from such information. This paper introduces a novel integrated algorithm for rear-end collision detection. Access to high accuracy positioning is enabled by GNSS, electronic compass, and lane information fusion with Cubature Kalman Filter (CKF). The judgment of the car-following status is based on the application of the Adaptive Neurofuzzy Inference System (ANFIS). The field test results show that the designed algorithm could effectively detect rear-end collisions with an accuracy of 99.61% and a false alarm rate of 5.26% in the 10 Hz output rate.
Precision Oncology: Between Vaguely Right and Precisely Wrong
Authors: Brock Amy , Huang Sui
Published: November 2017

Precision Oncology seeks to identify and target the mutation that drives a tumor. Despite its straightforward rationale, concerns about its effectiveness are mounting. What is the biological explanation for the "imprecision?" First, Precision Oncology relies on indiscriminate sequencing of genomes in biopsies that barely represent the heterogeneous mix of tumor cells. Second, findings that defy the orthodoxy of oncogenic "driver mutations" are now accumulating: the ubiquitous presence of oncogenic mutations in silent premalignancies or the dynamic switching without mutations between various cell phenotypes that promote progression. Most troublesome is the observation that cancer cells that survive treatment still will have suffered cytotoxic stress and thereby enter a stem cell–like state, the seeds for recurrence. The benefit of “precision targeting” of mutations is inherently limited by this counterproductive effect. These findings confirm that there is no precise linear causal relationship between tumor genotype and phenotype, a reminder of logician Carveth Read's caution that being vaguely right may be preferable to being precisely wrong. An open-minded embrace of the latest inconvenient findings indicating nongenetic and "imprecise" phenotype dynamics of tumors as summarized in this review will be paramount if Precision Oncology is ultimately to lead to clinical benefits. Cancer Res; 77(23); 6473–9. ©2017 AACR.
NKG2D-Dependent Antitumor Effects of Chemotherapy and Radiotherapy against Glioblastoma
Authors: Weiss Tobias , Schneider Hannah , Silginer Manuela , Steinle Alexander , Pruschy Martin , Polić Bojan , Weller Michael , Roth Patrick
Published: November 2017

Purpose: NKG2D is a potent activating immune cell receptor, and glioma cells express the cognate ligands (NKG2DL). These ligands are inducible by cellular stress and temozolomide (TMZ) or irradiation (IR), the standard treatment of glioblastoma, could affect their expression. However, a role of NKG2DL for the efficacy of TMZ and IR has never been addressed.

Experimental Design: We assessed the effect of TMZ and IR on NKG2DL in vitro and in vivo in a variety of murine and human glioblastoma models, including glioma-initiating cells, and a cohort of paired glioblastoma samples from patients before and after therapy. Functional effects were studied with immune cell assays. The relevance of the NKG2D system for the efficacy of TMZ and IR was assessed in vivo in syngeneic orthotopic glioblastoma models with blocking antibodies and NKG2D knockout mice.

Results: TMZ or IR induced NKG2DL in vitro and in vivo in all glioblastoma models, and glioblastoma patient samples had increased levels of NKG2DL after therapy with TMZ and IR. This enhanced the immunogenicity of glioma cells in a NGK2D-dependent manner, was independent from cytotoxic or growth inhibitory effects, attenuated by O6-methylguanine-DNA-methyltransferase (MGMT), and required the DNA damage response. The survival benefit afforded by TMZ or IR relied on an intact NKG2D system and was decreased upon inhibition of the NKG2D pathway.

Conclusions: The immune system may influence the activity of convential cancer treatments with particular importance of the NKG2D pathway in glioblastoma. Our data provide a rationale to combine NKG2D-based immunotherapies with TMZ and IR. Clin Cancer Res; 24(4); 882–95. ©2017 AACR.
Effects of Black Raspberry on Dibenzo[a,l]Pyrene Diol Epoxide Induced DNA Adducts, Mutagenesis, and Tumorigenesis in the Mouse Oral Cavity
Authors: Chen Kun-Ming , Guttenplan Joseph B. , Sun Yuan-Wan , Cooper Timothy , Shalaby Nora A.E. , Kosinska Wieslawa , Benitez Gabrielle , Aliaga Cesar , Zhu Junjia , Liao Jason , Gowda Krishne , Amin Shantu , Stoner Gary , El-Bayoumy Karam
Published: November 2017

We previously showed that metabolic activation of the environmental and tobacco smoke constituent dibenzo[a,l]pyrene (DB[a,l]P) to its active fjord region diol epoxide (DB[a,l]PDE) is required to induce DNA damage, mutagenesis, and squamous cell carcinoma (SCC) in the mouse oral cavity. In contrast to procarcinogens, which were employed previously to induce SCC, DB[a,l]PDE does not require metabolic activation to exert its biological effects, and thus, this study was initiated to examine, for the first time, whether black raspberry powder (BRB) inhibits postmetabolic processes, such as DNA damage, mutagenesis, and tumorigenesis. Prior to long-term chemoprevention studies, we initially examined the effect of BRB (5% added to AIN-93M diet) on DNA damage in B6C3F1 mice using LC/MS-MS and on mutagenesis in the lacI gene in the mouse oral cavity. We showed that BRB inhibited DB[a,l]PDE-induced DNA damage (P < 0.05) and mutagenesis (P = 0.053) in the oral cavity. Tumor incidence in the oral cavity (oral mucosa and tongue) of mice fed diet containing 5% BRB was significantly (P < 0.05) reduced from 93% to 66%. Specifically, the incidence of benign tumor was significantly (P < 0.001) reduced from 90% to 31% (62% to 28% in the oral cavity and 28% to 2% in the tongue), a nonsignificant reduction of malignant tumors from 52% to 45%. Our preclinical findings demonstrate for the first time that the chemopreventive efficacy of BRB can be extended to direct-acting carcinogens that do not require phase I enzymes and is not just limited to procarcinogens. Cancer Prev Res; 11(3); 157–64. ©2017 AACR.
Konfrontation oder Stabilisierung: Wie planen Verhaltenstherapeuten die Behandlung bei Posttraumatischer Belastungsstörung?
Authors: Equit Monika , Maurer Stefanie , Michael Tanja , Köllner Volker
Published: November 2017

Hintergrund: Gemäß nationaler und internationaler Leitlinien stellen traumafokussierte/traumaadaptierte Psychotherapien wie kognitiv-behaviorale Verfahren oder Eye Movement Desensitization and Reprocessing (EMDR) Methoden der ersten Wahl bei der Behandlung von Patienten mit Posttraumatischer Belastungsstörung (PTBS) dar. In Meta-Analysen weisen diese Verfahren konsistent die höchsten Effektstärken auf. Hieraus ergeben sich klare Implikationen für die Therapie von PTBS-Patienten. Mit der vorliegenden Studie sollte die Planung einer leitlinienkonformen Behandlung der PTBS anhand der Auswertung von Berichten an den Gutachter im Rahmen der Beantragung einer Richtlinientherapie überprüft werden. Patienten und Methoden: Es wurden 1053 Berichte an den Gutachter untersucht, die im Rahmen der Richtlinienpsychotherapie zur Bewilligung einer Verhaltenstherapie eingereicht wurden. In die Studie eingeschlossen wurden 167 Anträge, in denen ein traumatisches Ereignis, die Diagnose PTBS oder eine traumaspezifische Behandlung genannt wurden. Ergebnisse: 74,3% der Behandlungspläne wurden als leitlinienkonform eingestuft (d.h. traumafokussierte Konfrontationsverfahren bei gesicherter PTBS-Diagnose und keine traumafokussierte Konfrontationsverfahren bei Patienten ohne PTBS-Diagnose). In 70,3% der PTBS-Fälle wurde der Einsatz von Konfrontationsverfahren geplant. Hinweise darauf, dass die Diagnose PTBS von den niedergelassenen Therapeuten zu häufig vergeben wurde, fanden sich nicht. Die Validität der Diagnosen war insgesamt hoch. Schlussfolgerung: Bei rund 30% der PTBS-Patienten wurde von den ambulanten Psychotherapeuten keine traumafokussierte Konfrontation als Behandlungsmethode angegeben. Das Verfahren mit der evidenzbasiert höchsten Wirksamkeit wurde also nicht im Behandlungsplan berücksichtigt. Die Ursachen hierfür sollten durch weitere Untersuchungen geklärt werden.
Higher versus Lower Continuous Renal Replacement Therapy Intensity in Critically ill Patients with Liver Dysfunction
Authors: O'Brien Zachary , Cass Alan , Cole Louise , Finfer Simon , Gallagher Martin , McArthur Colin , McGuiness Shay , Myburgh John , Bellomo Rinaldo , Mårtensson Johan ,   on behalf of the RENAL Study Investigators and the Australian and New Zealand Intensive Care Clinical Trials Group
Published: November 2017

Aims: To study the association between higher versus lower continuous renal replacement therapy (CRRT) intensity and mortality in critically ill patients with combined acute kidney injury and liver dysfunction. Methods: Post-hoc analysis of patients with liver dysfunction (Sequential Organ Failure Assessment liver score ≥2 or diagnosis of liver failure/transplant) included in the Randomized Evaluation of Normal versus Augmented Level renal replacement therapy (RENAL) trial. Results: Of 444 patients, 210 (47.3%) were randomized to higher intensity (effluent flow 40 mL/kg/h) and 234 (52.7%) to lower intensity (effluent flow 25 mL/kg/h) therapy. Overall, 79 and 86% of prescribed effluent flow was delivered in the higher-intensity and lower-intensity groups, respectively (p < 0.001). In total, 113 (54.1%) and 120 (51.3%) patients died in each group. On multivariable Cox regression analysis, we found no independent association between higher CRRT intensity and mortality (HR 0.93, 95% CI 0.70-1.24; p = 0.642). Conclusions: In RENAL patients with liver dysfunction, higher CRRT intensity was not associated with reduced mortality.
Expression Profile of NOTCH3 in Mouse Spermatogonia
Authors: Okada Ryu , Fujimagari Megumi , Koya Eri , Hirose Yoshikazu , Sato Tomomi , Nishina Yukio
Published: November 2017

Stable and sustainable spermatogenesis is supported by the strict regulation of self-renewal and differentiation of spermatogonial stem cells (SSC), which are a rare population of undifferentiated spermatogonia. It has been revealed that some signaling factors regulate the self-renewal of SSC; however, the molecular mechanism of SSC maintenance is still not completely understood. Notch signaling is an evolutionarily conserved juxtacrine signaling that plays important roles in the cell fate determination of various tissue stem cells. Recently, analyses of loss- and gain-of-function suggested that Notch signaling was necessary for normal spermatogenesis. However, the expression of Notch signal components in spermatogonia is still unclear. Here, we analyzed the distribution of NOTCH3-expressing spermatogonia and the target genes. Double immunostaining with differentiation markers revealed that NOTCH3 was expressed in some undifferentiated and differentiated spermatogonia in mouse testes. To define the target gene of Notch3 signaling in spermatogonia, we analyzed the mRNA expression pattern of Hes and Hey family genes during testis development. Hes1 abundance was decreased during testis development, suggesting that spermatogonia may express Hes1. Immunohistochemical analysis showed that HES1 was expressed in prepubertal spermatogonia, whereas it was expressed predominantly in adult Sertoli cells and weakly in adult spermatogonia. Furthermore, NOTCH3-HES1 double-positive spermatogonia were in pup and adult testes. These results suggest that Notch3 signaling in spermatogonia could promote Hes1 expression.
Immunohistochemical Localization of DARPP-32 in the Brain of Two Lungfishes: Further Assessment of Its Relationship with the Dopaminergic System
Authors: López Jesús M. , Morona Ruth , González Agustín
Published: November 2017

The distribution of DARPP-32 (a phosphoprotein related to the dopamine D1 receptor) has been widely used as a means to clarify the brain regions with dopaminoceptive cells, primarily in representative species of tetrapods. The relationship between dopaminergic and dopaminoceptive elements is frequently analyzed using the catecholamine marker tyrosine hydroxylase (TH). In the present study, by means of combined immunohistochemistry, we have analyzed these relationships in lungfishes, the only group of sarcopterygian fishes represented by 6 extant species that are the phylogenetically closest living relatives of tetrapods. We used the Australian lungfish Neoceratodus forsteri and the African lungfish Protopterus dolloi. The DARPP-32 antibody yields a distinct and consistent pattern of neuronal staining in brain areas that, in general, coincide with areas that are densely innervated by TH-immunoreactive fibers. The striatum, thalamus, optic tectum, and torus semicircularis contain intensely DARPP-32-immunoreactive cell bodies and fibers. Cells are also located in the olfactory bulbs, amygdaloid complex, lateral septum, pallidum, preoptic area, suprachiasmatic nucleus, tuberal hypothalamic region, rostral rhombencephalic reticular formation, superior raphe nucleus, octavolateral area, solitary tract nucleus, and spinal cord. Remarkably, DARPP-32-immunoreactive fibers originating in the striatum reach the region of the dopaminergic cells in the mesencephalic tegmentum and represent a well-established striatonigral pathway in lungfishes. Double immunolabeling reveals that DARPP-32 is present in neurons that most likely receive TH input, but it is absent from the catecholaminergic neurons themselves, with the only exception of a few cells in the suprachiasmatic nucleus of Neoceratodus and the solitary tract nucleus of Protopterus. In addition, some species differences exist in the localization of DARPP-32 cells in the pallium, lateral amygdala, thalamus, prethalamus, and octavolateral area. In general, the present study demonstrates that the distribution pattern of DARPP-32, and its relationship with TH, is largely comparable to those reported for tetrapods, highlighting a shared situation among all sarcopterygians.