bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of DNA Polymerase and Number of Rounds of Amplification in PCR on 16S rRNA Gene Sequence Data
Authors: Sze Marc A. , Schloss Patrick D.
Published: May 2019

A steep decline in sequencing costs drove an explosion in studies characterizing microbial communities from diverse environments. Although a significant amount of effort has gone into understanding the error profiles of DNA sequencers, little has been done to understand the downstream effects of the PCR amplification protocol. We quantified the effects of the choice of polymerase and number of PCR cycles on the quality of downstream data. We found that these choices can have a profound impact on the way that a microbial community is represented in the sequence data. The effects are relatively small compared to the variation in human stool samples; however, care should be taken to use polymerases with the highest possible fidelity and to minimize the number of rounds of PCR. These results also underscore that it is not possible to directly compare sequence data generated under different PCR conditions.
Neuropilin-1 Regulates the Secondary CD8 T Cell Response to Virus Infection
Authors: Hwang Ji Young , Sun Yanbo , Carroll Christopher R. , Usherwood Edward J.
Published: May 2019

CD8 T cell responses are critical to control both virus infections and tumors. The ability of these cells to persist for long periods of time can result in lifelong immunity, as relatively small populations of cells can expand rapidly to counter reexposure to the same insult. Understanding the molecules necessary for this rapid secondary expansion is critical if we are to develop therapies that can provide lifelong protection. This report shows an important and complex role for the molecule neuropilin-1 in the secondary response. Several cancer therapies targeting neuropilin-1 are in development, and this work will lead to better understanding of the effect these therapies could have upon the protective CD8 T cell response.
Rationale, design and objectives of two phase III, randomised, placebo-controlled studies of GLPG1690, a novel autotaxin inhibitor, in idiopathic pulmonary fibrosis (ISABELA 1 and 2)
Authors: Maher Toby M , Kreuter Michael , Lederer David J , Brown Kevin K , Wuyts Wim , Verbruggen Nadia , Stutvoet Simone , Fieuw Ann , Ford Paul , Abi-Saab Walid , Wijsenbeek Marlies
Published: May 2019

Introduction

While current standard of care (SOC) for idiopathic pulmonary fibrosis (IPF) slows disease progression, prognosis remains poor. Therefore, an unmet need exists for novel, well-tolerated agents that reduce lung function decline and improve quality of life. Here we report the design of two phase III studies of the novel IPF therapy, GLPG1690.

Methods and analysis

Two identically designed, phase III, international, randomised, double-blind, placebo-controlled, parallel-group, multicentre studies (ISABELA 1 and 2) were initiated in November 2018. It is planned that, in each study, 750 subjects with IPF will be randomised 1:1:1 to receive oral GLPG1690 600 mg, GLPG1690 200 mg or placebo, once daily, on top of local SOC, for at least 52 weeks. The primary endpoint is rate of decline of forced vital capacity (FVC) over 52 weeks. Key secondary endpoints are week 52 composite endpoint of disease progression or all-cause mortality (defined as composite endpoint of first occurrence of ≥10% absolute decline in per cent predicted FVC or all-cause mortality at week 52); time to first respiratory-related hospitalisation until end of study; and week 52 change from baseline in the St George’s Respiratory Questionnaire total score (a quality-of-life measure).

Ethics and dissemination

Studies will be conducted in accordance with Good Clinical Practice guidelines, Declaration of Helsinki principles, and local ethical and legal requirements. Results will be reported in a peer-reviewed publication.

Trial registration numbers

NCT03711162;NCT03733444.
How to continually make the case for fundamental science: from the perspective of a protein kinase
Authors: Woodgett James Robert
Published: May 2019

The strength of the scientific process is its immunity from human frailties. The built-in error correction and robustness of principles protect and nurture truth, despite both intended and unintended errors and naivety. What it doesn’t secure is understanding of how the scientific sausage is made. Here, a scientific journey revolving around a single protein that spans nearly 35 years is used to illustrate the twists and turns that can accompany any scientific path. Lessons learned from such exploration speak to the need for story-telling in communicating scientific meaning — and the effectiveness of this will influence future investment and understanding of the scientific endeavor.
A node influence ranking algorithm based on probability walking model
Authors: Song Chen , Huang Guoyan , Zhang Bing , Ren Jiadong , Zhang Xiankun
Published: May 2019

For the limitation that current node influence ranking algorithms can only be applied in a single type of network and the results are inaccurate, an algorithm based on similarity is proposed. When a node is similar to many nodes in the network, it is representative and can be treated as an influential node. Firstly, probability walking model is used to simulate the initiative visit between nodes in different types of networks. Secondly, superposed probabilistic transfer similarity is defined based on the model considering nodes’ inbound and outbound information. Finally, node ranking algorithm is set up using the new similarity measuring method. Experiments show that the algorithm can evaluate different kinds of networks with high accuracy, whether the network is directed or undirected, weighted or unweighted.
Sediment-wear morphology prediction method of hydraulic machine based on differential-quadrature method
Authors: Han Wei , Chen Yu , Li Rennian , Su Min , Peng Guoyi , Wei Sanze
Published: May 2019

Damage caused by abrasive wear is a significant problem for hydraulic machinery in rivers with sediments. Traditional prediction methods of abrasive wear morphology with the fixed geometrical boundary are difficult to reflect the physical reality of wear because of the interaction of sediment wear, flow pattern and flow boundary. In this study, a gradual wear method based on the idea of differential-quadrature is established to investigate the asymptotic wear behavior of hydraulic machinery. The average wear rate and depth of voxels on the geometrical boundary can be obtained by the unsteady numerical simulation with RNG [Formula: see text]-[Formula: see text] turbulent model and DPM multiphase flow model. Segmented voxels of geometrical boundary of flow are reconstructed after a calculation period until the end of the total running time. So, the progressive wear morphologies of flow-passage walls can be revealed step by step. The prediction method is used to predict the wear of the clearance flow in the guide vane. The numerical results are in good agreement with the actual wear depth on the wear surfaces at the actual running time, which indicates that the specified prediction method in this paper is applicable and effective.
Tunable gallium nitride-based devices for ultrafast signal processing
Authors: Xie Peng , Wen Yu , Yang Wenqiang , Wan Zishen , Liu Jiarui , Wang Xinyu , Da Siqi , Wang Yishan
Published: May 2019

In this paper, we propose a micro-ring resonator model based on gallium nitride (GaN) and graphene, which exhibits tunable properties of nonlinearity. It provides a great bandwidth covering from visible to telecommunication band. Especially, based on the characteristic of GaN, it has unique advantages in shorter wavelength, which is used for demonstrating the ultrafast signal processing including wavelength conversion, temporal amplification and pulse compression. Moreover, the tunable signal processing is achieved via the method of applying additional bias voltage to graphene without changing the geometric dimension of the device. These results have significant potential applications of nonlinear optics and optical communications.
Speech enhancement based on noise classification and deep neural network
Authors: Wang Wenbo , Liu Houguang , Yang Jianhua , Cao Guohua , Hua Chunli
Published: May 2019

Deep neural network (DNN) has recently been successfully adopted as a regression model in speech enhancement. Nonetheless, training machines to adapt different noise is a challenging task. Because every noise has its own characteristics which can be combined with speech utterance to give huge variation on which the model has to operate on. Thus, a joint framework combining noise classification (NC) and speech enhancement using DNN was proposed. We first determined the noise type of contaminated speech by the voice activity detection (VAD)-DNN and the NC-DNN. Then based on the noise classification results, the corresponding SE-DNN model was applied to enhance the contaminated speech. In addition, in order to make method simpler, the structure of different DNNs was similar and the features were the same. Experimental results show that the proposed method effectively improved the performance of speech enhancement in complex noise environments. Besides, the accuracy of classification had a great influence on speech enhancement.
Interaction solutions of the first BKP equation
Authors: Chen Jing , Yu Jian-Ping , Ma Wen-Xiu , Sun Yong-Li , Khalique Chaudry Masood
Published: May 2019

In this paper, we study the interaction solutions of the first BKP equation by using the Hirota direct method and taking long-wave limit. In order to obtain the interaction solutions, the multi-soliton solutions are firstly derived using the Hirota direct method, then the interaction solutions are successfully constructed by properly choosing appropriate parameters and taking long-wave limit on the soliton solutions. These parameters have great influences on the propagation directions, shapes as well as energy. Moreover, the dynamic properties of these obtained solutions are illustrated vividly by some graphs. The results in this work could be used to solve nonlinear problems in nonlinear optics and engineering field.
Novel localized wave interaction phenomena and dynamics in the generalized discrete Hirota equation via the generalized (2,N − 2)-fold Darboux transformation
Authors: Wang Hao-Tian , Wen Xiao-Yong , Liu Yaqing
Published: May 2019

We investigate the generalized discrete Hirota equation, which is an integrable discrete version of Hirota equation. The generalized [Formula: see text]-fold Darboux transformation (i.e. generalized [Formula: see text]-fold Darboux transformation when [Formula: see text] with two spectral parameters) is presented to derive the novel localized wave interaction solutions. Moreover, some inelastic interaction evolution phenomena of rogue wave and breather are studied graphically. Numerical simulations are used to explore the dynamical behaviors of certain localized wave interaction solutions, which show that their evolutions are stable against a small noise. The results obtained in this paper can be used to find the interaction properties of localized nonlinear waves in nonlinear optics and relevant fields.
State Estimation Based on Ensemble DA–DSVM in Power System
Authors: Wang Shunjiang , Pu Baoming , Li Ming , Ge Weichun , Liu Qianwei , Pei Yujie
Published: May 2019

This paper investigates the state estimation problem of power systems. A novel, fast and accurate state estimation algorithm is presented to solve this problem based on the one-dimensional denoising autoencoder and deep support vector machine (1D DA–DSVM). Besides, for further reducing the computation burden, a partitioning method is presented to divide the power system into several sub-networks and the proposed algorithm can be applied to each sub-network. A hybrid computing architecture of Central Processing Unit (CPU) and Graphics Processing Unit (GPU) is employed in the overall state estimation, in which the GPU is used to estimate each sub-network and the CPU is used to integrate all the calculation results and output the state estimate. Simulation results show that the proposed method can effectively improve the accuracy and computational efficiency of the state estimation of power systems.
Efficiency Improvement of Classification Model Based on Altered K-Means Using PCA and Outlier
Authors: Jung Se-Hoon , Kim Jong-Chan
Published: May 2019

In the generation and analysis of Big Data following the development of various information devices, the old data processing and management techniques reveal their hardware and software limitations. Their hardware limitations can be overcome by the CPU and GPU advancements, but their software limitations depend on the advancement of hardware. This study thus sets out to address the increasing analysis costs of dense Big Data from a software perspective instead of depending on hardware. An altered [Formula: see text]-means algorithm was proposed with ideal points to address the analysis costs issue of dense Big Data. The proposed algorithm would find an optimal cluster by applying Principal Component Analysis (PCA) in the multi-dimensional structure of dense Big Data and categorize data with the predicted ideal points as the central points of initial clusters. Its clustering validity index and [Formula: see text]-measure results were compared with those of existing algorithms to check its excellence, and it had similar results to them. It was also compared and assessed with some data classification techniques investigated in previous studies and we found that it made a performance improvement of about 3–6% in the analysis costs.
Approximate analytical solution of fractional order biochemical reaction model and its stability analysis
Authors: Dubey Ved Prakash , Kumar Rajnesh , Kumar Devendra
Published: May 2019

Approximate analytical solution of the system of coupled nonlinear Ordinary Differential Equations (ODEs) of a biochemical reaction model is much relevant due to its practical significance to biochemists. In this paper, an effective and powerful mathematical technique, viz. fractional homotopy analysis transform method (FHATM), is employed to get the numerical solutions of biochemical reaction model with time fractional derivatives. The adopted scheme is the beautiful copulation of homotopy analysis technique and Laplace transform algorithm. This paper shows that the adopted scheme is quite easy as well as computationally attractive in the context of a solution procedure. The Caputo-type fractional derivatives are considered in the present paper. Approximate results of the probability density functions of the time fractional biochemical reaction model are computed for miscellaneous fractional Brownian motions as well as for classical motion and are presented graphically. The time fractional biochemical reaction model with respect to stability analysis for various values of fractional order [Formula: see text] is also analyzed. In the context of stability discussion, we have used the fractional Routh–Hurwitz stability criterion to establish the local stability of the biochemical reaction model of fractional order.
Very large convergent multi-fluted glacigenic deposits in the NW Highlands, Scotland
Authors: Davies T. R. H. , Warburton J. , Turnbull J. M.
Published: May 2019

We describe two large convergent multi-fluted glacigenic deposits in the NW Highlands, Scotland, and point out their resemblance to a number of landforms emerging from presently deglaciating areas of Greenland and Antarctica. We suggest that they all result from locally sourced sediment being deposited by local ice-flow, which was laterally confined by the margins of much larger adjacent glaciers or ice-streams. The NW Highlands features thus seem likely to be the result of processes active during the latter part of the Devensian Glaciation. One of these deposits, on the peninsula between Loch Broom and Little Loch Broom, is evidently sourced from the west-facing Coire Dearg of Beinn Ghobhlach, but was emplaced in a WNW direction rather than along the WSW fall-line. This suggests that the ice that emplaced it was confined by the margins of large glaciers then occupying the adjacent valleys of Loch Broom and Little Loch Broom. The second much larger and more prominent deposit, in Applecross, is composed of bouldery Torridonian sandstone till emplaced on to glacially scoured bedrock; the only feasible source location for this material is about 12 km distant, which requires that the deposit was carried by ice across the trough of Strath Maol Chalum and emplaced while active ice-streams confined it laterally to its present-day location. This, in turn, requires that ice lay in the Inner Sound between Applecross and Skye to an elevation 400–500 m above present-day sea-level. The Wester Ross Re-advance of 15–14 ka left a fragment of lateral moraine against the most easterly flute and buried the distal end of the flutes with hummocky moraine. We hypothesize that the fluted deposits reflect the locations of the ice-stream margins that constrained deposition of locally derived ice-transported sediment, rather than the flow-lines of the ice-stream itself.
Garbage collection as a joint venture
Authors: Degenbaev Ulan , Lippautz Michael , Payer Hannes
Published: May 2019

A collaborative approach to reclaiming memory in heterogeneous software systems.
An Exploratory Study on Software-Defined Data Center Hard Disk Drives
Authors: Li Yin , Chen Xubin , Zheng Ning , Hao Jingpeng , Zhang Tong
Published: May 2019

This article presents a design framework aiming to reduce mass data storage cost in data centers. Its underlying principle is simple: Assume one may noticeably reduce the HDD manufacturing cost by significantly (i.e., at least several orders of magnitude) relaxing raw HDD reliability, which ensures the eventual data storage integrity via low-cost system-level redundancy. This is called system-assisted HDD bit cost reduction. To better utilize both capacity and random IOPS of HDDs, it is desirable to mix data with complementary requirements on capacity and random IOPS in each HDD. Nevertheless, different capacity and random IOPS requirements may demand different raw HDD reliability vs. bit cost trade-offs and hence different forms of system-assisted bit cost reduction. This article presents a software-centric design framework to realize data-adaptive system-assisted bit cost reduction for data center HDDs. Implementation is solely handled by the filesystem and demands only minor change of the error correction coding (ECC) module inside HDDs. Hence, it is completely transparent to all the other components in the software stack (e.g., applications, OS kernel, and drivers) and keeps fundamental HDD design practice (e.g., firmware, media, head, and servo) intact. We carried out analysis and experiments to evaluate its implementation feasibility and effectiveness. We integrated the design techniques into
ext4
to further quantitatively measure its impact on system speed performance.
Personal data and the internet of things
Authors: Pasquier Thomas , Eyers David , Bacon Jean
Published: May 2019

It is time to care about digital provenance.
Lifelong learning in artificial neural networks
Authors: Anthes Gary
Published: May 2019

New methods enable systems to rapidly, continuously adapt.
Ethics in technology jobs
Authors: Kirkpatrick Keith
Published: May 2019

Employees are increasingly challenging technology companies on their ethical choices.
Reaching new heights with artificial neural networks
Authors: Hoffmann Leah
Published: May 2019

ACM A.M. Turing Award recipients Yoshua Bengio, Geoffrey Hinton, and Yann LeCun on the promise of neural networks, the need for new paradigms, and the concept of making technology accessible to all.
Global data justice
Authors: Taylor Linnet
Published: May 2019

A new research challenge for computer science.
Through computer architecture, darkly
Authors: Markettos A. T. , Watson R. N. M. , Moore S. W. , Sewell P. , Neumann P. G.
Published: May 2019

Total-system hardware and microarchitectural issues are becoming increasingly critical.
Chiral Plasmonic Nanostructures Enabled by Bottom-Up Approaches
Authors: Urban Maximilian J. , Shen Chenqi , Kong Xiang-Tian , Zhu Chenggan , Govorov Alexander O. , Wang Qiangbin , Hentschel Mario , Liu Na
Published: May 2019

We present a comprehensive review of recent developments in the field of chiral plasmonics. Significant advances have been made recently in understanding the working principles of chiral plasmonic structures. With advances in micro- and nanofabrication techniques, a variety of chiral plasmonic nanostructures have been experimentally realized; these tailored chiroptical properties vastly outperform those of their molecular counterparts. We focus on chiral plasmonic nanostructures created using bottom-up approaches, which not only allow for rational design and fabrication but most intriguingly in many cases also enable dynamic manipulation and tuning of chiroptical responses. We first discuss plasmon-induced chirality, resulting from the interaction of chiral molecules with plasmonic excitations. Subsequently, we discuss intrinsically chiral colloids, which give rise to optical chirality owing to their chiral shapes. Finally, we discuss plasmonic chirality, achieved by arranging achiral plasmonic particles into handed configurations on static or active templates. Chiral plasmonic nanostructures are very promising candidates for real-life applications owing to their significantly larger optical chirality than natural molecules. In addition, chiral plasmonic nanostructures offer engineerable and dynamic chiroptical responses, which are formidable to achieve in molecular systems. We thus anticipate that the field of chiral plasmonics will attract further widespread attention in applications ranging from enantioselective analysis to chiral sensing, structural determination, and in situ ultrasensitive detection of multiple disease biomarkers, as well as optical monitoring of transmembrane transport and intracellular metabolism.
Impacts of Hosting Forced Migrants in Poor Countries
Authors: Maystadt Jean-François , Hirvonen Kalle , Mabiso Athur , Vandercasteelen Joachim
Published: May 2019

Most of the world's displaced people are hosted in low-income countries. Focusing on evidence from poor countries, we review the literature on the economic consequences of hosting refugees or internally displaced people. In the short run, violence, environmental degradation, and disease propagation are major risks to the host populations. In the long run, infrastructure, trade, and labor markets are key channels that determine the impacts on host communities. These impacts can be positive or negative and often unequally distributed among different hosts. We discuss policy options for building resilience in the light of this evidence. Investments in road infrastructure and deepening trade with refugees’ countries of origin are strategies worth exploring for enhancing resilience and transitioning from humanitarian assistance toward development. Finally, we identify key knowledge gaps in this literature and formulate a research agenda for the near future.
Growth and Annealing Properties of Carbon Nanofibers on Carbon Black by Using Chemical Vapour Deposition
Authors: Jedeok  , Todhiyuki  , Nakao Hidenobu
Published: May 2019

Carbon nanofibers (CNFs) were grown as tip growths on carbon black (CB; XC-72R) (CNF-CB) by using chemical vapour deposition (CVD) with Ni catalysts. The as-grown CNF-CB composites were annealed at different temperatures. The crystallinity and thermal properties of the CNF-CB composite increased with an increase in the annealing temperature. The micropore and mesopore areas of the CNF-CB composites decreased and increased, respectively, as compared to those of CB only. The CNF-CB composite annealed at 1600 °C had a higher current density than only CB did, as determined by using cyclic voltammetry (CV). The CNF-CB composites should be extremely useful in various energy applications, such as fuel cells, capacitors, and batteries.
Comparison of Magnetic Auriculotherapy, Laser Auriculotherapy and Their Combination for Treatment of Insomnia in the Elderly: A Double-Blinded Randomised Trial
Authors: Suen Lorna K. P. , Molassiotis A. , Yueng S. K. W. , Yeh C. H.
Published: May 2019

Background. Insomnia is common amongst the elderly. With the adverse effects of prolonged use of hypnotics, the exploration of noninvasive and nonpharmacological complementary methods for insomnia is warranted. Auriculotherapy (AT) is a therapeutic approach where specific points on the auricle are stimulated to manage various physiological disorders. The purpose of this study is to determine the desirable treatment modality using AT to improve the sleep conditions of the elderly. Methods. A three-arm double-blinded randomised trial was conducted on 145 eligible subjects. This study investigated three minimally invasive procedures, namely, laser auriculotherapy (LAT), magneto-auriculotherapy (MAT), and their combination. Seven auricular points were used. Treatment was performed three times a week, for six weeks. Subjects were assessed at baseline, six weeks, and follow-up after six weeks, three months, and six months. Generalised estimating equations were used to evaluate interactions amongst the groups over time based on the Pittsburgh Sleep Quality Index (PSQI), sleep parameters using actigraphic monitoring, health-related quality of life (HRQOL) using SF-12, and PHQ-9 for depression status. Results. The treatment effects of the three procedures were comparable. Significant improvements were found in all of the subjective measures (PSQI, HRQOL, and PHQ-9) for individual groups over time. Improvements in the objective sleep parameters using actigraphic monitoring were detected in subjects who received MAT procedures but not in those who received LAT. The combined MAT and LAT approach did not show any advantage over MAT. Conclusions. The treatment effects of the three procedures were comparable in subjective parameters but not by objective measures using actigraphic monitoring. Longer therapeutic course and more frequent administration of LAT may be considered in future trials to achieve the optimal treatment effect. Trial Registration. This trial is registered with ClinicalTrials.gov: NCT02970695, registered May 2016.
Robustness and Resilience of Structures under Extreme Loads
Authors: Stochino Flavio , Bedon Chiara , Sagaseta Juan , Honfi Daniel
Published: May 2019

Many of modern life activities involve the risk of fire, explosions, and impacts. In addition, natural extreme events are becoming more and more common. Thus, robustness, the ability to avoid disproportionate collapse due to an initial damage, and resilience, the ability to adapt to and recover from the effects of changing external conditions, represent two important characteristics of current structures and infrastructures. Their definitions are reviewed in this paper with the aim of sorting and describing the different approaches proposed in the literature and in the international standards. A simple example is also analysed in order to compare different methods.
Characterization of Microbiota in Endometrial Fluid and Vaginal Secretions in Infertile Women with Repeated Implantation Failure
Authors: Kitaya Kotaro , Nagai Yoko , Arai Wataru , Sakuraba Yoshiyuki , Ishikawa Tomomoto
Published: May 2019

Studies suggest that persisting intrauterine bacterial infectious conditions such as chronic endometritis potentially impair the embryo implantation process. The microbial environment in the female reproductive tract, however, remains largely undetermined in infertile patients with a history of repeated implantation failure (RIF). Using next-generation sequencing, we aimed to characterize the microbiota in the endometrial fluid (EF) and vaginal secretions (VS) in women with RIF. Twenty-eight infertile women with a history of RIF and eighteen infertile women undergoing the first in vitro fertilization-embryo transfer attempt (the control group) were enrolled in the study. On days 6-8 in the luteal phase of the natural, oocyte-pickup, or hormone replacement cycle, the paired EF and VS samples were obtained separately. Extracted genomic DNA was pyrosequenced for the V4 region of 16S ribosomal RNA using a next-generation sequencer. The EF microbiota had higher α-diversity and broader bacterial species than the VS microbiota both in the RIF and control groups. The analysis of the UniFrac distance matrices between EF and VS also revealed significantly different clustering. Additionally, the EF microbiota, but not the VS microbiota, showed significant variation in community composition between the RIF group and the control group. Burkholderia species were not detected in the EF microbiota of any samples in the control group but were detectable in a quarter of the RIF group. To our best knowledge, this is the first study investigating the microbiota in the paired EF and VS samples in infertile women with RIF.
Dynamic Behaviors Analysis of a Chaotic Circuit Based on a Novel Fractional‐Order Generalized Memristor
Authors: Yang Ningning , Cheng Shucan , Wu Chaojun , Jia Rong , Liu Chongxin
Published: May 2019

In this paper, a fractional‐order chaotic circuit based on a novel fractional‐order generalized memristor is proposed. It is proved that the circuit based on the diode bridge cascaded with fractional‐order inductor has volt‐ampere characteristics of pinched hysteresis loop. Then the mathematical model of the fractional‐order memristor chaotic circuit is obtained. The impact of the order and system parameters on the dynamic behaviors of the chaotic circuit is studied by phase trajectory, Poincaré Section, and bifurcation diagram method. The order, as an important parameter, can increase the degree of freedom of the system. With the change of the order and parameters, the circuit will exhibit abundant dynamic behaviors such as coexisting upper and lower limit cycle, single scroll chaotic attractors, and double scroll chaotic attractors under different initial conditions. And the system exhibits antimonotonic behavior of antiperiodic bifurcation with the change of system parameters. The equivalent circuit simulations are designed to verify the results of the theoretical analysis and numerical simulation.
Noise-Robust Heart Rate Estimation Algorithm from Photoplethysmography Signal with Low Computational Complexity
Authors: Shin JaeWook , Cho Jaegeol
Published: May 2019

This paper introduces a noise-robust HR estimation algorithm using wrist-type PPG signals that consist of preprocessing block, motion artifact reduction block, and frequency tracking block. The proposed algorithm has not only robustness for motion noise but also low computational complexity. The proposed algorithm was tested on a data set of 12 subjects and recorded during treadmill exercise in order to verify and compare with other existing algorithms.
Awareness and Malaria Prevention Practices in a Rural Community in the Ho Municipality, Ghana
Authors: Diema Konlan Kennedy , Amu Hubert , Konlan Kennedy Dodam , Japiong Milipaak
Published: May 2019

Background. Malaria is no doubt a burden on both the financial and human resources of Ghana. In this study, we examined the awareness of malaria prevention practices among indigenes of Godokpe, a rural community in the Ho Municipality of Ghana. Methods. This descriptive cross-sectional survey that used a self-developed questionnaire recruited 246 residents of Godokpe who were aged 18 years and above using a systematic sampling technique. The Statistical Package for Social Sciences (SPSS) was used to analyze data into descriptive and analytical statistics. The descriptive statistics comprised frequency, percentage, and means. Also, analytical statistics of cross tabulation was conducted considering a p<0.05 at a 95% Confidence Interval to be statistically significant. Findings. About 54% and 20% of the respondents, respectively, had satisfactory and good levels of knowledge on malaria prevention. The methods used in malaria prevention included mosquito coils (72%), cleaning and prevention of water stagnation (62%), mosquito spray (54%), and mosquito net (59%). Also, malaria treatment methods mostly used were quinine (70%) and chloroquine (50.4%). The major sources of information on malaria were television (74%), health professionals (66%), schools (62%), family/friends (60%), and the Internet (51%). Conclusion. School children showed good understanding of malaria and its vectors. There is, therefore, the need to increase the empowerment of teachers with appropriate health information including malaria so that they can continue to deliver malaria information to the pupils.
RNA Sequencing of the NCI-60: Integration into CellMiner and CellMiner CDB
Authors: Reinhold William C. , Varma Sudhir , Sunshine Margot , Elloumi Fathi , Ofori-Atta Kwabena , Lee Sunmin , Trepel Jane B. , Meltzer Paul S. , Doroshow James H. , Pommier Yves
Published: May 2019

CellMiner (http://discover.nci.nih.gov/cellminer) and CellMinerCDB (https://discover.nci.nih.gov/cellminercdb/) are web-based applications for mining publicly available genomic, molecular, and pharmacologic datasets of human cancer cell lines including the NCI-60, Cancer Cell Line Encyclopedia, Genomics of Drug Sensitivity in Cancer, Cancer Therapeutics Response Portal, NCI/DTP small cell lung cancer, and NCI Almanac cell line sets. Here, we introduce our RNA sequencing (RNA-seq) data for the NCI-60 and their access and integration with the other databases. Correlation to transcript microarray expression levels for identical genes and identical cell lines across CellMinerCDB demonstrates the high quality of these new RNA-seq data. We provide composite and isoform transcript expression data and demonstrate diversity in isoform composition for individual cancer- and pharmacologically relevant genes, including HRAS, PTEN, EGFR, RAD51, ALKBH2, BRCA1, ERBB2, TP53, FGFR2, and CTNND1. We reveal cell-specific differences in the overall levels of isoforms and show their linkage to expression of RNA processing and splicing genes as well as resultant alterations in cancer and pharmacologic gene sets. Gene–drug pairings linked by pathways or functions show specific correlations to isoforms compared with composite gene expression, including ALKBH2-benzaldehyde, AKT3-vandetanib, BCR-imatinib, CDK1 and 20-palbociclib, CASP1-imexon, and FGFR3-pazopanib. Loss of MUC1 20 amino acid variable number tandem repeats, which is used to elicit immune response, and the presence of the androgen receptor AR-V4 and -V7 isoforms in all NCI-60 tissue of origin types demonstrate translational relevance. In summary, we introduce RNA-seq data to our CellMiner and CellMinerCDB web applications, allowing their exploration for both research and translational purposes.

Significance:

The current study provides RNA sequencing data for the NCI-60 cell lines made accessible through both CellMiner and CellMinerCDB and is an important pharmacogenomics resource for the field.
Overall Survival in Malignant Glioma Is Significantly Prolonged by Neurosurgical Delivery of Etoposide and Temozolomide from a Thermo-Responsive Biodegradable Paste
Authors: Smith Stuart J. , Tyler Betty M. , Gould Toby , Veal Gareth J. , Gorelick Noah , Rowlinson Jonathan , Serra Riccardo , Ritchie Alison , Berry Phillip , Otto Annette , Choi John , Skuli Nicolas , Estevez-Cebrero Maria , Shakesheff Kevin M. , Brem Henry , Grundy Richard G. , Rahman Ruman
Published: May 2019

Purpose:

High-grade glioma (HGG) treatment is limited by the inability of otherwise potentially efficacious drugs to penetrate the blood–brain barrier. We evaluate the unique intracavity delivery mode and translational potential of a blend of poly(DL-lactic acid-co-glycolic acid; PLGA) and poly(ethylene glycol; PEG) paste combining temozolomide and etoposide to treat surgically resected HGG.

Experimental Design:

To prolong stability of temozolomide prodrug, combined in vitro drug release was quantitatively assessed from low pH–based PLGA/PEG using advanced analytic methods. In vitro cytotoxicity was measured against a panel of HGG cell lines and patient-derived cultures using metabolic assays. In vivo safety and efficacy was evaluated using orthotopic 9L gliosarcoma allografts, previously utilized preclinically to develop Gliadel.

Results:

Combined etoposide and temozolomide in vitro release (22 and 7 days, respectively) was achieved from a lactic acid–based PLGA/PEG paste, used to enhance stability of temozolomide prodrug. HGG cells from central-enhanced regions were more sensitive to each compound relative to primary lines derived from the HGG-invasive margin. Both drugs retained cytotoxic capability upon release from PLGA/PEG. In vivo studies revealed a significant overall survival benefit in postsurgery 9L orthotopic gliosarcomas, treated with intracavity delivered PLGA/PEG/temozolomide/etoposide and enhanced with adjuvant radiotherapy. Long-term survivorship was observed in over half the animals with histologic confirmation of disease-free brain.

Conclusions:

The significant survival benefit of intracavity chemotherapy demonstrates clinical applicability of PLGA/PEG paste-mediated delivery of temozolomide and etoposide adjuvant to radiotherapy. PLGA/PEG paste offers a future platform for combination delivery of molecular targeted compounds.
Tumor Characteristics Associated with Benefit from Pembrolizumab in Advanced Non–Small Cell Lung Cancer
Authors: Hu-Lieskovan Siwen , Lisberg Aaron , Zaretsky Jesse M. , Grogan Tristan R. , Rizvi Hira , Wells Daniel K. , Carroll James , Cummings Amy , Madrigal John , Jones Benjamin , Gukasyan Jacklin , Shintaku I. Peter , Slamon Dennis , Dubinett Steven , Goldman Jonathan W. , Elashoff David , Hellmann Matthew D. , Ribas Antoni , Garon Edward B.
Published: May 2019

Purpose:

Several biomarkers have been individually associated with response to PD-1 blockade, including PD-L1 and tumor mutational burden (TMB) in non–small cell lung cancer (NSCLC), and CD8 cells in melanoma. We sought to examine the relationship between these distinct variables with response to PD-1 blockade and long-term benefit.

Experimental Design:

We assessed the association between baseline tumor characteristics (TMB, PD-L1, CD4, and CD8) and clinical features and outcome in 38 patients with advanced NSCLC treated with pembrolizumab (median follow-up of 4.5 years, range 3.8–5.5 years).

Results:

PD-L1 expression and CD8 infiltration correlated with each other and each significantly associated with objective response rate (ORR) and progression-free survival (PFS). TMB was independent of PD-L1 and CD8 expression, and trended towards association with ORR and PFS. There was no association between CD4 infiltration and outcomes. Only PD-L1 expression was correlated with overall survival (OS). Among 5 patients with long-term survival >3 years with no additional systemic therapy, PD-L1 expression was the only discriminating feature. The increased predictive value for PFS and OS of composite biomarker inclusive of PD-L1, CD8, CD4, and TMB was limited.

Conclusions:

In patients with NSCLC treated with PD-1 blockade with long-term follow up, TMB, PD-L1, and CD8 were each associated with benefit from PD-1 blockade. Pretreatment PD-L1 expression was correlated with T lymphocyte infiltration and OS, whereas models incorporating TMB and infiltrating CD4 and CD8 lymphocytes did not substantially add to the predictive value of PD-L1 alone for OS.
Insulinoma-Associated-1: From Neuroendocrine Tumor Marker to Cancer Therapeutics
Authors: Chen Chiachen , Notkins Abner L. , Lan Michael S.
Published: May 2019

Insulinoma-associated-1 (IA-1 or INSM1) encodes a zinc-finger transcription factor, which was isolated from a human insulinoma subtraction library, with specific expression patterns, predominantly in developing neuroendocrine tissues and tumors. INSM1 is key in early pancreatic endocrine, sympatho-adrenal lineage, and pan-neurogenic precursor development. Insm1 gene ablation results in impairment of pancreatic β cells, catecholamine biosynthesis, and basal progenitor development during mammalian neocortex maturation. Recently, INSM1 has emerged as a superior, sensitive, and specific biomarker for neuroendocrine tumors. INSM1 regulates downstream target genes and exhibits extranuclear activities associated with multiple signaling pathways, including Sonic Hedgehog, PI3K/AKT, MEK/ERK1/2, ADK, p53, Wnt, histone acetylation, LSD1, cyclin D1, Ascl1, and N-myc. Novel strategies targeting INSM1-associated signaling pathways facilitate the suppression of neuroendocrine tumor growth. In addition, INSM1 promoter–driven reporter assay and/or suicide gene therapy are promising effective therapeutic approaches for targeted specific neuroendocrine tumor therapy. In this review, the current knowledge of the biological role of INSM1 as a neuroendocrine tumor biomarker is summarized, and novel strategies targeting multiple signaling pathways in the context of INSM1 expression in neuroendocrine tumors are further explored.

Implications:

Neuroendocrine transcription factor (INSM1) may serve as a neuroendocrine biomarker for the development of novel cancer therapeutics against neuroendocrine tumors.
Serial C-Reactive Protein Measurements in Newborn Infants without Evidence of Early-Onset Infection
Authors: Macallister Kathryn , Smith-Collins Adam , Gillet Helen , Hamilton Linze , Davis Jonathan
Published: May 2019

Background: C-reactive protein (CRP) is used to assist the diagnosis and monitoring of newborn infection. Little is known about CRP activity after birth in the absence of infection. Objective: The aim of this work was to describe postnatal CRP responses in the first days of life in asymptomatic infants with a negative blood culture. Methods: Data were collected from infants who had a blood culture taken at <72 h of age in a UK maternity hospital. All CRP values and their time from birth were recorded. Infants with signs of infection, positive blood culture, or major congenital anomalies were excluded. Infants were analysed by gestation (greater or less than 37 weeks). Normalised CRP curves were generated by linear interpolation and centile curves were derived. Comparisons of median CRP values between groups were made by Mann-Whitney U test at 24, 36, and 48 h. Results: During the study period a total of 219 babies were screened. After exclusions, 73 infants (58 term, 15 preterm) were analysed. In asymptomatic term neonates the CRP (mg/L) peaked at 9.4 after 34.6 h. In preterm babies the CRP peak was 1.75 at 43 h. The median (IQR) values were higher in the term group at 24 and 36 h: 2.5 (1–10.5) versus 0 (0–2.2; p = 0.02) and 3 (0–8.6) versus 0 (0–2.8; p = 0.031). Conclusions: A CRP rise was demonstrated in term and preterm infants without evidence of infection. This rise was greatest in term infants. CRP values must be interpreted in the context of an infant’s clinical condition and not used alone to guide clinical decision making.
Levofloxacin for NIH Category II Chronic Bacterial Prostatitis: A Real-Life Study
Authors: Magri Vittorio , Perletti Gianpaolo , Cai Tommaso , Stamatiou Konstantinos , Trinchieri Alberto , Montanari Emanuele
Published: May 2019

Background: Mounting worldwide resistance trends make the use of fluoroquinolone (FQ) antibacterial agents increasingly difficult. This is felt more acutely in the case of urogenital infections, which are mainly caused by Gram-negative pathogens. For years, levofloxacin and other FQs have been the first-line drugs for treating National Institutes of Health (NIH) category II chronic bacteria prostatitis (CBP). Eradication rates achieved by levofloxacin in the frame of randomized trials vary greatly, ranging between 71 and 86%. Objectives: This was a retrospective observational study to investigate the efficacy of levofloxacin against CBP in a real-life setting (urological outpatient wards). Methods: A database including the clinical records of >2,500 CBP patients was reviewed. Patients were selected based on strict inclusion criteria. They were treated for 4 weeks with 500 mg levofloxacin per day, alone or combined with other antibacterials. Besides standard urological procedures including the 4-glass test for pathogen isolation, international symptom questionnaires (the NIH Chronic Prostatitis Symptom Index [NIH-CPSI] and International Prostate Symptom Score [IPSS]) were administered. Results: Pathogen eradication was achieved in 79% of the cases treated with levofloxacin as a single agent and 87.8% of patients who received a combination of levofloxacin and azithromycin. The 11% increase in the eradication rate in the latter group is statistically significant. In addition, the levofloxacin-azithromycin combination caused a significant decrease in prostate volume and significantly increased the bladder-voided volume. IPSS and NIH-CPSI values and the urinary peak flow rate decreased to a similar extent in both treatment groups. No adverse effects were reported by patients belonging to either treatment group. Conclusion: Levofloxacin retained its therapeutic efficacy in patients assessed in a real-life setting, and high eradication rates were attained when it was administered as a single agent. A combination of an FQ with azithromycin induced a significant improvement of eradication rates. This strategy may be an interesting option in both first-referral and relapsing cases, although caution should be exercised when patients are at risk of developing arrhythmias, tendinitis, or other adverse effects.
Psychosocial Impact of Dysarthria: The Patient-Reported Outcome as Part of the Clinical Management
Authors: Atkinson-Clement Cyril , Letanneux Alban , Baille Guillaume , Cuartero Marie-Charlotte , Véron-Delor Lauriane , Robieux Camille , Berthelot Manon , Robert Danièle , Azulay Jean-Philippe , Defebvre Luc , Ferreira Joaquim , Eusebio Alexandre , Moreau Caroline , Pinto Serge
Published: May 2019

Background: Dysarthria in neurological disorders can have psychosocial consequences. The dysarthric speaker’s perspective towards the disorder’s psychosocial impact is essential in its global assessment and management. For such purposes, assessment tools such as the Dysarthria Impact Profile (DIP) are indispensable. Objective: We aimed to confirm the relevance of using the DIP to quantify the psychosocial consequences of dysarthria in neurological diseases. Methods: We studied 120 participants, 15 healthy controls and 105 patients with different kinds of dysarthria induced by several neurological disorders (Parkinson’s disease [PD], Huntington’s disease, dystonia, cerebellar ataxia, progressive supranuclear palsy [PSP], multiple system atrophy, lateral amyotrophic sclerosis). All participants underwent a cognitive evaluation and a speech intelligibility assessment and completed three self-reported questionnaires: the 36-Item Short Form Health Survey, the Voice Handicap Index (VHI), and the DIP. Results: The psychometric properties of the DIP were confirmed, including internal consistency (α = 0.93), concurrent validity (correlation with the VHI: r = –0.77), and discriminant validity (accuracy = 0.93). Psychosocial impact of dysarthria was revealed by the DIP for all patients. Intelligibility loss was found strongly correlated with the psychosocial impact of dysarthria: for a similar level of intelligibility impairment, the DIP total score was similar regardless of the pathological group. However, our findings suggest that the psychosocial impact measured by the DIP could be partially independent from the severity of dysarthria (indirectly addressed here via speech intelligibility): the DIP was able to detect patients without any intelligibility impairment, but with a psychosocial impact. Conclusions: All patients reported a communication complaint, attested by the DIP scores, despite the fact that not all patients, notably PD, ataxic, and PSP patients, had an intelligibility deficit. The DIP should be used in clinical practice to contribute to a holistic evaluation and management of functional communication in patients with dysarthria.