bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring contact area in a sliding human finger‐pad contact
Authors: Liu X. , Carré M. J. , Zhang Q. , Lu Z. , Matcher S. J. , Lewis R.
Published: June 2017

Background/Purpose

The work outlined in this paper was aimed at achieving further understanding of skin frictional behaviour by investigating the contact area between human finger‐pads and flat surfaces.

Methods

Both the static and the dynamic contact areas (in macro‐ and micro‐scales) were measured using various techniques, including ink printing, optical coherence tomography (OCT) and Digital Image Correlation (DIC).

Results

In the studies of the static measurements using ink printing, the experimental results showed that the apparent and the real contact area increased with load following a piecewise linear correlation function for a finger‐pad in contact with paper sheets. Comparisons indicated that the OCT method is a reliable and effective method to investigate the real contact area of a finger‐pad and allow micro‐scale analysis. The apparent contact area (from the DIC measurements) was found to reduce with time in the transition from the static phase to the dynamic phase while the real area of contact (from OCT) increased.

Conclusions

The results from this study enable the interaction between finger‐pads and contact object surface to be better analysed, and hence improve the understanding of skin friction.
Making students part of the dataset: a model for statistical enquiry in social issues
Authors: Brown Mark
Published: June 2017

This article reviews a flexible model for engaging students in statistical enquiry. Data from a student survey are first used to stimulate interest and introduce statistical concepts, while easing the transition to working with larger ‘real world’ secondary data.
Demotivating Intentional Mentalism
Authors: Lipski Joachim
Published: June 2017

Intentional Mentalism is the view that mental intentionality is primary to non‐mental intentionality and that the latter is derived from the former. In this article I examine three views which have been taken to motivate Intentional Mentalism: conventionalism as invoked by Searle, Gricean pragmatism, and the language of thought hypothesis. I argue that none of these views motivates Intentional Mentalism, and that, in fact, the former two imply its rejection.
A study of optimum aeration efficiency of a lab‐scale air‐diffused system
Authors: Al Ba'ba'a Hasan B. , Amano Ryoichi S.
Published: June 2017

Up to now, tremendous efforts have been devoted to modelling the oxygen transfer coefficient (kLa) for diffused aeration systems, while not considering the corresponding energy consumption. Enhancing kLa is favorable for an exemplary oxygenation process, but may come at the cost of greater energy withdrawal, an unwelcome tradeoff. Assessing the aeration efficiency (the rate of oxygen delivered per unit energy) reflects the overall effectiveness of an aeration process and guarantees a superior system performance. Presented here is a lab‐scale study that investigates the effect of the orifice diameter, the airflow rate and the water column on the aeration efficiency. Various combinations of the studied parameters were tested using a cylindrical tank with a single orifice for air injection. An optimal performance of the aeration efficiency was observed at an orifice diameter of 0.3 mm when tested under 0.91 m water column and an airflow rate of 0.05 SLPM. Furthermore, a new empirical formula of aeration efficiency was established with a high correlation index (R2 = 0.97) to allow preliminary prediction of aeration efficiency.
Macroeconomic Switching Regimes and Monetary Policy in Canada
Authors: Lange Ronald Henry
Published: June 2017

This study examines the behaviour of monetary policy in Canada over the last 40 years using a Markov-switching VAR model of the macroeconomy. The Markov-switching estimates capture three continuous regimes that are interpreted as the ‘surprise’ regime from 1972Q1 to 1982Q2, the ‘recovery’ regime from 1982Q3 to 1991Q3 and the ‘target’ regime from 1991Q4 to 2014Q4. Monetary policy multipliers for the output gap are greater than one for all three regimes, suggesting that the central bank does not accommodate any expected changes in inflation over the long-run due to the domestic relationship between the output gap and future inflation. The long-run multipliers for inflation are equal to one in the surprise and recovery regimes, indicating that monetary policy also responds to offset inflation shocks. Overall, the policy multipliers and impulse response functions indicate a proactive central bank that responds systematically to movements in the output gap in order to control expected future inflation and to inflation surprises in the three regimes. The regime-dependent behaviour of monetary policy indicates a central bank pursuing an implicit form of inflation targeting as a means of achieving a nominal anchor for policy. The implicit inflation tar­gets are consistent with historical episodes of inflation in Canada over the past 40 years.
Lysozyme orientation and conformation on MoS2 surface: Insights from molecular simulations
Authors: Fan Hongjie , Zhao Daohui , Li Yingtu , Zhou Jian
Published: June 2017

Two-dimensional molybdenum disulfide (MoS2) has attracted intense interest owing to its unique properties and promising biosensor applications. To develop effective biocompatible platforms, it is crucial to understand the interactions between MoS2 and biological molecules such as proteins, but little knowledge exists on the orientation and conformation of proteins on the MoS2 surface at the molecular level. In this work, the lysozyme adsorption on the MoS2 surface was studied by molecular dynamics simulations, wherein six different orientations were selected based on the different faces of lysozyme. Simulation results showed that lysozyme tends to adsorb on the MoS2 surface in an “end-on” orientation, indicating that orientations within this range are favorable for stable adsorption. The end-on orientation could be further categorized into “bottom end-on” and “top end-on” orientations. The driving forces responsible for the adsorption were dominated by van der Waals interactions and supplemented by electrostatic interactions. Further, the conformations of the lysozyme adsorbed on the MoS2 surface were basically preserved. This simulation study promotes the fundamental understanding of interactions between MoS2 and proteins and can guide the development of future biomedical applications of MoS2.
Draft Genome Sequences of Mycobacterium kansasii Clinical Strains
Authors: Borówka Paulina , Lach Jakub , Bakuła Zofia , van Ingen Jakko , Safianowska Aleksandra , Brzostek Anna , Dziadek Jarosław , Strapagiel Dominik , Jagielski Tomasz
Published: June 2017

Mycobacterium kansasii
is a nontuberculous mycobacterial (NTM) pathogen, frequently isolated from clinical samples and responsible for a large part of NTM infections in the human population. Here, we report the draft genome sequences of 12
M. kansasii
strains isolated from clinical and host-associated sources from the Netherlands, Germany, and Poland.
Draft Genome Sequence of Blood Disease Bacterium A2 HR-MARDI, a Pathogen Causing Banana Bacterial Wilt
Authors: Badrun Rafidah , Abu Bakar Norliza , Laboh Rozeita , Redzuan Rohaiza , Bala Jaganath Indu
Published: June 2017

Blood disease bacterium A2 HR-MARDI was isolated from banana plants infected with banana blood disease and which were planted in Kuala Kangsar, Malaysia. Here, we report a draft genome sequence of blood disease bacterium A2 HR-MARDI, which could provide important information on the virulence mechanism of this pathogen.
Complete Genome Sequences of Two Geographically Distinct Legionella micdadei Clinical Isolates
Authors: Osborne Amy J. , Jose Bethany R. , Perry Jasper , Smeele Zoe , Aitken Jack , Gardner Paul P. , Slow Sandy
Published: June 2017

Legionella
is a highly diverse genus of intracellular bacterial pathogens that cause Legionnaire’s disease (LD), an often severe form of pneumonia. Two
L. micdadei
sp. clinical isolates, obtained from patients hospitalized with LD from geographically distinct areas, were sequenced using PacBio SMRT cell technology, identifying incomplete phage regions, which may impact virulence.
Complete Genome Sequence of Escherichia coli BLR(DE3), a
recA
-Deficient Derivative of E. coli BL21(DE3)
Authors: Goffin Philippe , Dehottay Philippe
Published: June 2017

Escherichia coli
BLR(DE3) is a commercially available
recA
-deficient derivative of BL21(DE3), one of the most widely used strains for recombinant protein expression. Here, we present the full-genome sequence of BLR(DE3) and highlight additional differences with its parent strain BL21(DE3) which were previously unreported but may affect its physiology.
Complete Genome Sequence of a Recombinant Porcine Reproductive and Respiratory Syndrome Virus Strain from Two Genotype 1 Modified Live Virus Vaccine Strains
Authors: Renson Patricia , Touzain Fabrice , Lebret Arnaud , Le Dimna Mireille , Quenault Hélène , Normand Valérie , Claude Jean-Baptiste , Pez Floriane , Rose Nicolas , Blanchard Yannick , Bourry Olivier
Published: June 2017

This paper provides information on the complete genome sequence of a porcine reproductive and respiratory syndrome virus (PRRSV) strain isolated on a French pig farm which was identified as a recombinant strain from two commercial modified live virus vaccine strains of genotype 1 (VP-046BIS and DV strains).
Complete Genome Sequences of Three Salmonella enterica subsp.
enterica
Serovar Saintpaul Isolates Associated with a 2013 Multistate Outbreak in the United States
Authors: Yao Kuan , Muruvanda Tim , Allard Marc W. , Hoffmann Maria
Published: June 2017

In 2013, a multistate outbreak of
Salmonella enterica
subsp.
enterica
serovar Saintpaul from cucumber caused 84 cases of salmonellosis in the United States. In this announcement, we report the complete genome sequences of three clinical
Salmonella
Saintpaul isolates associated with the 2013 outbreak.
Complete Genome Sequence of a Community-Associated Methicillin-Resistant Staphylococcus aureus Hypervirulent Strain, USA300-C2406, Isolated from a Patient with a Lethal Case of Necrotizing Pneumonia
Authors: McClure Jo-Ann , Zhang Kunyan
Published: June 2017

USA300 is a predominant community-associated methicillin-resistant
Staphylococcus aureus
strain causing significant morbidity and mortality. We present here the full annotated genome of a USA300 hypervirulent clinical strain, USA300-C2406, isolated from a patient with a lethal case of necrotizing pneumonia, to gain a better understanding of USA300 hypervirulence.
Draft Genome Sequence of a Strain of
Bacillus intestinalis
sp. nov., a New Member of Sporobiota Isolated from the Small Intestine of a Single Patient with Intestinal Cancer
Authors: Tetz Victor , Tetz George
Published: June 2017

We report here the draft genome sequence of
Bacillus intestinalis
strain 1731, a novel spore-forming bacterium isolated from the small intestine of a patient with intestinal cancer. The genome comprised 4,047,276 bp, with 43.9% G+C content. There were 3,913 predicted protein-coding genes, including those associated with antibiotic resistance and virulence.
Fine-Tuning of the Cpx Envelope Stress Response Is Required for Cell Wall Homeostasis in Escherichia coli
Authors: Delhaye Antoine , Collet Jean-François , Laloux Géraldine
Published: June 2017

The envelope of Gram-negative bacteria is an essential compartment that constitutes a protective and permeability barrier between the cell and its environment. The envelope also hosts the cell wall, a mesh-like structure made of peptidoglycan (PG) that determines cell shape and provides osmotic protection. Since the PG must grow and divide in a cell-cycle-synchronized manner, its synthesis and remodeling are tightly regulated. Here, we discovered that PG homeostasis is intimately linked to the levels of activation of the Cpx system, an envelope stress response system traditionally viewed as being involved in protein quality control in the envelope. We first show that Cpx is activated when PG integrity is challenged and that this activation provides protection to cells exposed to antibiotics inhibiting PG synthesis. By rerouting the outer membrane lipoprotein NlpE, a known Cpx activator, to a different envelope subcompartment, we managed to manipulate Cpx activation levels. We found that Cpx overactivation leads to aberrant cellular morphologies, to an increased sensitivity to β-lactams, and to dramatic division and growth defects, consistent with a loss of PG homeostasis. Remarkably, these phenotypes were largely abrogated by the deletion of
ldtD
, a Cpx-induced gene involved in noncanonical PG cross-linkage, suggesting that this transpeptidase is an important link between PG homeostasis and the Cpx system
.
Altogether our data show that fine-tuning of an envelope quality control system constitutes an important layer of regulation of the highly organized cell wall structure.

IMPORTANCE
The envelope of Gram-negative bacteria is essential for viability. First, it includes the cell wall, a continuous polymer of peptidoglycan (PG) that determines cell morphology and protects against osmotic stress. Moreover, the envelope constitutes a protective barrier between the cell interior and the environment. Therefore, mechanisms called envelope stress response systems (ESRS) exist to monitor and defend envelope integrity against harmful conditions. Cpx is a major ESRS that detects and manages the accumulation of misfolded proteins in the envelope of
Escherichia coli
. We found that this protein quality control system also plays a fundamental role in the regulation of PG assembly. Strikingly, the level of Cpx response is critical, as an excessive activation leads to phenotypes associated with a loss of cell wall integrity. Thus, by contributing to PG homeostasis, the Cpx system lies at the crossroads between key processes of bacterial life, including cell shape, growth, division, and antibiotic resistance.
Host-Primed Ebola Virus GP Exposes a Hydrophobic NPC1 Receptor-Binding Pocket, Revealing a Target for Broadly Neutralizing Antibodies
Authors: Bornholdt Zachary A. , Ndungo Esther , Fusco Marnie L. , Bale Shridhar , Flyak Andrew I. , Crowe James E. , Chandran Kartik , Saphire Erica Ollmann
Published: June 2017

The filovirus surface glycoprotein (GP) mediates viral entry into host cells. Following viral internalization into endosomes, GP is cleaved by host cysteine proteases to expose a receptor-binding site (RBS) that is otherwise hidden from immune surveillance. Here, we present the crystal structure of proteolytically cleaved Ebola virus GP to a resolution of 3.3 Å. We use this structure in conjunction with functional analysis of a large panel of pseudotyped viruses bearing mutant GP proteins to map the Ebola virus GP endosomal RBS at molecular resolution. Our studies indicate that binding of GP to its endosomal receptor Niemann-Pick C1 occurs in two distinct stages: the initial electrostatic interactions are followed by specific interactions with a hydrophobic trough that is exposed on the endosomally cleaved GP
1
subunit. Finally, we demonstrate that monoclonal antibodies targeting the filovirus RBS neutralize all known filovirus GPs, making this conserved pocket a promising target for the development of panfilovirus therapeutics.

IMPORTANCE
Ebola virus uses its glycoprotein (GP) to enter new host cells. During entry, GP must be cleaved by human enzymes in order for receptor binding to occur. Here, we provide the crystal structure of the cleaved form of Ebola virus GP. We demonstrate that cleavage exposes a site at the top of GP and that this site binds the critical domain C of the receptor, termed Niemann-Pick C1 (NPC1). We perform mutagenesis to find parts of the site essential for binding NPC1 and map distinct roles for an upper, charged crest and lower, hydrophobic trough in cleaved GP. We find that this 3-dimensional site is conserved across the filovirus family and that antibody directed against this site is able to bind cleaved GP from every filovirus tested and neutralize viruses bearing those GPs.
Abciximab-induced delayed profound thrombocytopaenia
Authors: Jbara Manar , Bhogal Sukhdeep , Bajaj Kailash , Chhabra Lovely
Published: June 2017

Abciximab, the first approved glycoprotein (GP IIb/IIIa) inhibitor, is being widely used during acute coronary syndromes and offers the promising approach to antithrombotic therapy. We present a case of a young woman who initially received abciximab infusion for undergoing percutaneous coronary intervention of left anterior descending artery and was eventually diagnosed with abciximab-induced delayed thrombocytopaenia. This case outlines the importance of close follow-up of these patients to prevent serious adverse events.
High-grade myxofibrosarcoma of the abdominal wall
Authors: Antbring Richard , Parker Sam G , Lordan Jeffrey T , Windsor Alastair CJ
Published: June 2017

The authors present a case of a 57-year-old man, who presented to the surgical clinic with a mass in the suprapubic region. A CT scan revealed a well-circumscribed lobular, heterogeneous soft tissue mass measuring 12×8.6×7.8 cm. The final histopathological diagnosis from the resection of the lesion was a myxofibrosarcoma (MFS), grade 3. The management of MFS includes surgical and oncological options which are reviewed here. These are aimed at complete excision and reducing the risk of local occurrence.
Estimated total costs from non-fatal and fatal bicycle crashes in the USA: 1997–2013
Authors: Gaither Thomas W , Sanford Thomas A , Awad Mohannad A , Osterberg E Charles , Murphy Gregory P , Lawrence Bruce A , Miller Ted R , Breyer Benjamin N
Published: June 2017

Introduction

Emergency department visits and hospital admissions resulting from adult bicycle trauma have increased dramatically. Annual medical costs and work losses of these incidents last were estimated for 2005 and quality-of-life losses for 2000.

Methods

We estimated costs associated with adult bicycle injuries in the USA using 1997–2013 non-fatal incidence data from the National Electronic Injury Surveillance System with cost estimates from the Consumer Product Safety Commission's Injury Cost Model, and 1999–2013 fatal incidence data from the National Vital Statistics System costed by similar methods.

Results

Approximately 3.8 million non-fatal adult bicycle injuries were reported during the study period and 9839 deaths. In 2010 dollars, estimated adult bicycle injury costs totalled $24.4 billion in 2013. Estimated injury costs per mile bicycled fell from $2.85 in 2001 to $2.35 in 2009. From 1999 to 2013, total estimated costs were $209 billion due to non-fatal bicycle injuries and $28 billion due to fatal injuries. Inflation-free annual costs in the study period increased by 137% for non-fatal injuries and 23% for fatal injuries. The share of non-fatal costs associated with injuries to riders age 45 and older increased by 1.6% (95% CI 1.4% to 1.9%) annually. The proportion of costs due to incidents that occurred on a street or highway steadily increased by 0.8% (95% CI 0.4% to 1.3%) annually.

Conclusions

Inflation-free costs per case associated with non-fatal bicycle injuries are increasing. The growth in costs is especially associated with rising ridership, riders 45 and older, and street/highway crashes.
My week: Greta Manfrin
Authors: Manfrin Greta
Published: June 2017

Greta Manfrin joined Vets Now through its Cutting Edge programme. Here, she describes a recent working week as the principal vet at an out‐of‐hours pet emergency clinic in Gillingham, Kent.
Degenerate ITS7 primer enhances oomycete community coverage and PCR sensitivity to Aphanomyces species, economically important plant pathogens
Authors: Esmaeili Taheri A. , Chatterton S. , Gossen B.D. , McLaren D.L.
Published: June 2017

Metagenomic analysis of oomycetes through deep amplicon sequencing has been conducted primarily using the ITS6–ITS7 primer set that targets the ITS1 region. While this primer set shows a perfect match to most oomycete taxa, ITS7 contains 3 mismatches to the corresponding binding site of plant pathogens within the genus Aphanomyces. Polymerase chain reaction (PCR) efficiency differs for taxa with uneven primer matching characteristics, which may explain why previous studies have detected this genus at low abundance. To overcome the impact of these mismatches on PCR sensitivity, the mismatched nucleotides were replaced with degenerate nucleotides. Oomycete communities from 35 soil samples collected from asymptomatic and root rot diseased sites in pea fields across Alberta were analyzed simultaneously using ITS6–ITS7 and ITS6–ITS7-a.e. (modified version of ITS7) primer sets on 1 Illumina MiSeq run. The number of high-quality reads obtained by ITS6–ITS7-a.e. was more than twice that of ITS6–ITS7. The relative abundance of Pythium spp. was reduced and Aphanomyces spp. increased. Aphanomyces cf. cladogamus and Aphanomyces euteiches were the second and third most abundant species, respectively, in the pea rhizosphere using the ITS7-a.e. primer, but were rare using the ITS7 primer. These results indicate that use of ITS7-a.e. provides a more accurate picture of oomycete communities than ITS7 by enhancing PCR sensitivity to Aphanomyces.
Effective action of in Krein space quantization
Authors: Forghan B. , Razavi S.
Published: June 2017

The appearance of divergence creates computational issues in the process of calculating the one-loop effective action of [Formula: see text] in quantum field theory. In this paper, it is demonstrated that using Krein space quantization with Ford’s method of fluctuated metrics, divergence can be removed and that without using any traditional regularization method, it is possible to arrive at a finite solution for the effective action.
Shock wave occurrence and soliton propagation in polariton condensates
Authors: Belounis A.M. , Kessal S.
Published: June 2017

We study the effects of the gain and the loss of polaritons on the wave propagation in polariton condensates. This system is described by a modified Gross–Pitaevskii equation. In the case of small damping, we use the reductive perturbation method to transform this equation; we get a modified Burgers equation in the dispersionless limit and a damped Korteweg – de Vries equation in a more general case. We demonstrate that the shock wave occurrence depends on the gain and the loss of polaritons in the dispersionless polariton condensate. The resolution of the damped Korteweg – de Vries equation shows that the soliton behaves like a damped wave in the case of a constant damping. Based on an asymptotic solution, the survival time and the distance traveled by this soliton are evaluated. We solve the damped Korteweg – de Vries equation and the modified Gross–Pitaevskii numerically to validate the analytical calculations and discuss especially the soliton propagation in the system.
Black hole solutions in Rastall theory
Authors: Heydarzade Y. , Moradpour H. , Darabi F.
Published: June 2017

The Reissner–Nordström black hole solution in a generic cosmological constant background in the context of Rastall gravity is obtained. It is shown that the cosmological constant arises naturally from the consistency of the non-vacuum field equations of the Rastall theory for a spherical symmetric space–time, rather than its ad hoc introduction in the usual Einstein and Einstein–Maxwell field equations. The usual Reissner–Nordström, Schwarzschild, and Schwarzschild – (anti-)de Sitter black hole solutions in the framework of this theory are also addressed as the special independent subclasses of the obtained general solution.
INSURANCE INCLUSION, TIME PREFERENCE AND STOCK INVESTMENT OF THE CHINESE HOUSEHOLDS
Authors: YANG YINAN , WANG QIAN
Published: June 2017

Using the China Household Finance Survey data in 2011, the estimation results of structural equation modeling demonstrate that the respondents with higher time preference rate have a significant higher probability of investing in stocks, which implies that the short-term households will prefer stock investment. The social insurance programs and insurance policies held by the family will have a significantly direct positive effect in promoting stock investment and also a significantly direct positive effect on the respondent’s time preference, which could further indirectly increase the family’s stock investment. These results show that the safety-net built by the Chinese government, including the social security and commercial insurance, is very likely to attract more short-term investors into the stock market. These empirical results provide new evidences to explain the extreme volatility of Chinese stock market and also testify the policy effect of building an environment for people to possess property income in China.
THERMODYNAMIC STUDY OF BINARY ALLOY SYSTEM (Co–Cr) USING CALPHAD METHOD
Authors: SHAH WASEEM ULLAH , SHAH SYED MEHMOOD , KHAN MATIULLAH , KHAN DIL FARAZ , MAMALIS ATHANASIOS G. , YIN HAIQING
Published: June 2017

This paper reports the thermodynamic analysis of (Co–Cr) system using THERMO-calc package (basis for CALPHAD) and PBIN database. Calculations involve binary phase diagram, Gibb’s energy curve and activity curve at three different elevated temperatures 2125[Formula: see text]K, 2150[Formula: see text]K and 2175[Formula: see text]K. Induced miscibility gap is observed at particular concentration. Binary phase diagram shows variation in phases in prescribed alloy with increasing temperature and mole fraction concentration of [Formula: see text]. The total Gibbs energy decreases with increasing temperature showing the stability of Co–Cr system. Activity showed thorough fluctuation resulting in negative deviation from Raoult’s law ideal curve.
Hybrid Grey Wolf Optimizer Using Elite Opposition-Based Learning Strategy and Simplex Method
Authors: Zhang Sen , Luo Qifang , Zhou Yongquan
Published: June 2017

To overcome the poor population diversity and slow convergence rate of grey wolf optimizer (GWO), this paper introduces the elite opposition-based learning strategy and simplex method into GWO, and proposes a hybrid grey optimizer using elite opposition (EOGWO). The diversity of grey wolf population is increased and exploration ability is improved. The experiment results of 13 standard benchmark functions indicate that the proposed algorithm has strong global and local search ability, quick convergence rate and high accuracy. EOGWO is also effective and feasible in both low-dimensional and high-dimensional case. Compared to particle swarm optimization with chaotic search (CLSPSO), gravitational search algorithm (GSA), flower pollination algorithm (FPA), cuckoo search (CS) and bat algorithm (BA), the proposed algorithm shows a better optimization performance and robustness.
An Improved Pigeon-Inspired Optimization for Clustering Analysis Problems
Authors: Li Haiyun , Li Haifeng , Chen Xin , Wei Kaibin
Published: June 2017

Clustering is an important technology in data mining, which attempts to partition a set of objects into clusters based on the values of their attributes. [Formula: see text]-means is a simple and efficient data clustering algorithm. However, it highly depends on the initial solution and is extremely easy to be trapped in local optima. In contrast, meta-heuristic algorithms show good performance to break through the local optima obstacle. In this paper, we propose an improved pigeon-inspired optimization (IPIO) algorithm towards resolving this problem. The algorithm uses an object-based initialization method to generate the initial population and introduces a parametric control strategy to navigate the flying direction. Meanwhile, the climb process of monkey algorithm (MA) with dimension by dimension improvement is adopted to strengthen the local search ability. In this paper, experiments over six real datasets are conducted to validate the effectiveness of IPIO. The experimental results show that IPIO is an efficient alternative in resolving the clustering analysis problem.
Two Types of Immunoassay Based on Nile Blue Labeling Polydopamine Nanospheres
Authors: Li Li , Lu Wenbo , Liu Chang , Wang Ying , Dong Jian , Qian Weiping
Published: June 2017

The sandwich-type immunoassays have been developed by using electrochemical and surface-enhanced Raman scattering (SERS) techniques for the detection of carcinoembryonic antigen (CEA). Nile blue as a kind of Raman dye has been decorated on nanospheres with polydopamine resin (PDR) via [Formula: see text]-stacking interaction. The Nile blue displays the strong SERS signals as well as a characteristic electrochemical reduction peak at [Formula: see text]0.33[Formula: see text]V (versus Ag/AgCl). The implementation of the PDR nanospheres mixing with Au nanoparticles (AuNPs/PDR) exhibits a better electrical conductivity and large SERS enhancement. The immunoassays based on Nile blue-labeled AuNPs/PDR nanospheres have been fabricated by using electrochemical and SERS techniques for the detection of CEA. The proposed immunoassay shows higher sensitivity, high selectivity, lower detection limit and long-term stability. The performances of the electrochemical immunoassay are better than that of SERS immunoassay. For the electrochemical immunoassay, the linear range occurs from 1[Formula: see text]pg/mL to 100[Formula: see text]ng/mL ([Formula: see text]) with a detection limit of 0.68[Formula: see text]pg/mL and signal-to-noise ratio of 3 in the detection of CEA. The data for the analysis of human serum samples by using the electrochemical method are acceptably consistent with those obtained from the enzyme-linked immunosorbent assay (ELISA). The proposed immunoassay exhibits a promising potential for application in clinical diagnosis.
Generalized wavelet collocation method for solving fractional relaxation–oscillation equation arising in fluid mechanics
Authors: Shah Firdous A. , Abass R.
Published: June 2017

In this paper, a generalized wavelet collocation operational matrix method based on Haar wavelets is proposed to solve fractional relaxation–oscillation equation arising in fluid mechanics. Contrary to wavelet operational methods accessible in the literature, we derive an explicit form for the Haar wavelet operational matrices of fractional order integration without using the block pulse functions. The properties of the Haar wavelet expansions together with operational matrix of integration are utilized to convert the problems into systems of algebraic equations with unknown coefficients. The performance of the numerical scheme is assessed and tested on specific test problems and the comparisons are given with other methods existing in the recent literature. The numerical outcomes indicate that the method yields highly accurate results and is computationally more efficient than the existing ones.
The Role of CtBP1 in Oncogenic Processes and Its Potential as a Therapeutic Target
Authors: Blevins Melanie A. , Huang Mingxia , Zhao Rui
Published: June 2017

Transcriptional corepressor proteins have emerged as an important facet of cancer etiology. These corepressor proteins are often altered by loss- or gain-of-function mutations, leading to transcriptional imbalance. Thus, research directed at expanding our current understanding of transcriptional corepressors could impact the future development of new cancer diagnostics, prognostics, and therapies. In this review, our current understanding of the CtBP corepressors, and their role in both development and disease, is discussed in detail. Importantly, the role of CtBP1 overexpression in adult tissues in promoting the progression of multiple cancer types through their ability to modulate the transcription of developmental genes ectopically is explored. CtBP1 overexpression is known to be protumorigenic and affects the regulation of gene networks associated with “cancer hallmarks” and malignant behavior, including increased cell survival, proliferation, migration, invasion, and the epithelial–mesenchymal transition. As a transcriptional regulator of broad developmental processes capable of promoting malignant growth in adult tissues, therapeutically targeting the CtBP1 corepressor has the potential to be an effective method for the treatment of diverse tumor types. Although efforts to develop CtBP1 inhibitors are still in the early stages, the current progress and the future perspectives of therapeutically targeting this transcriptional corepressor are also discussed. Mol Cancer Ther; 16(6); 981–90. ©2017 AACR.
Colony-Stimulating Factor 1 Receptor Blockade Inhibits Tumor Growth by Altering the Polarization of Tumor-Associated Macrophages in Hepatocellular Carcinoma
Authors: Ao Jian-Yang , Zhu Xiao-Dong , Chai Zong-Tao , Cai Hao , Zhang Yuan-Yuan , Zhang Ke-Zhi , Kong Ling-Qun , Zhang Ning , Ye Bo-Gen , Ma De-Ning , Sun Hui-Chuan
Published: June 2017

Colony-stimulating factor-1 (CSF-1) and its receptor, CSF-1R, regulate the differentiation and function of macrophages and play an important role in macrophage infiltration in the context of hepatocellular carcinoma. The therapeutic effects of CSF-1R blockade in hepatocellular carcinoma remain unclear. In this study, we found that CSF-1R blockade by PLX3397, a competitive inhibitor with high specificity for CSF-1R tyrosine kinase, significantly delayed tumor growth in mouse models. PLX3397 inhibited the proliferation of macrophages in vitro, but intratumoral macrophage infiltration was not decreased by PLX3397 in vivo. Gene expression profiling of tumor-associated macrophages (TAM) showed that TAMs from the PLX3397-treated tumors were polarized toward an M1-like phenotype compared with those from vehicle-treated tumors. In addition, PLX3397 treatment increased CD8+ T-cell infiltration, whereas CD4+ T-cell infiltration was decreased. Further study revealed that tumor cell–derived CSF-2 protected TAMs from being depleted by PLX3397. In conclusion, CSF-1R blockade delayed tumor growth by shifting the polarization rather than the depletion of TAMs. CSF-1R blockade warrants further investigation in the treatment of hepatocellular carcinoma. Mol Cancer Ther; 16(8); 1544–54. ©2017 AACR.
FLT3 Inhibitors in Acute Myeloid Leukemia: Current Status and Future Directions
Authors: Larrosa-Garcia Maria , Baer Maria R.
Published: June 2017

The receptor tyrosine kinase fms-like tyrosine kinase 3 (FLT3), involved in regulating survival, proliferation, and differentiation of hematopoietic stem/progenitor cells, is expressed on acute myeloid leukemia (AML) cells in most patients. Mutations of FLT3 resulting in constitutive signaling are common in AML, including internal tandem duplication (ITD) in the juxtamembrane domain in 25% of patients and point mutations in the tyrosine kinase domain in 5%. Patients with AML with FLT3-ITD have a high relapse rate and short relapse-free and overall survival after chemotherapy and after transplant. A number of inhibitors of FLT3 signaling have been identified and are in clinical trials, both alone and with chemotherapy, with the goal of improving clinical outcomes in patients with AML with FLT3 mutations. While inhibitor monotherapy produces clinical responses, they are usually incomplete and transient, and resistance develops rapidly. Diverse combination therapies have been suggested to potentiate the efficacy of FLT3 inhibitors and to prevent development of resistance or overcome resistance. Combinations with epigenetic therapies, proteasome inhibitors, downstream kinase inhibitors, phosphatase activators, and other drugs that alter signaling are being explored. This review summarizes the current status of translational and clinical research on FLT3 inhibitors in AML, and discusses novel combination approaches. Mol Cancer Ther; 16(6); 991–1001. ©2017 AACR.
Preclinical Efficacy and Molecular Mechanism of Targeting CDK7-Dependent Transcriptional Addiction in Ovarian Cancer
Authors: Zhang Zhenfeng , Peng Huixin , Wang Xiaojie , Yin Xia , Ma Pengfei , Jing Ying , Cai Mei-Chun , Liu Jin , Zhang Meiying , Zhang Shengzhe , Shi Kaixuan , Gao Wei-Qiang , Di Wen , Zhuang Guanglei
Published: June 2017

Ovarian cancer remains a significant cause of gynecologic cancer mortality, and novel therapeutic strategies are urgently needed in clinic as new treatment options. We previously showed that BET bromodomain inhibitors displayed promising efficacy for the treatment of epithelial ovarian cancer by downregulating pivot transcription factors. However, the potential antitumor activities and molecular mechanisms of other epigenetic or transcriptional therapies have not been systematically determined. Here, by performing an unbiased high-throughput drug screen to identify candidate compounds with antineoplastic effects, we identified THZ1, a recently developed covalent CDK7 inhibitor, as a new transcription-targeting compound that exerted broad cytotoxicity against ovarian tumors. Mechanistically, CDK7 represented a previously unappreciated actionable vulnerability in ovarian cancer, and CDK7 inhibition led to a pronounced dysregulation of gene transcription, with a preferential repression of E2F-regulated genes and transcripts associated with super-enhancers. Our findings revealed the molecular underpinnings of THZ1 potency and established pharmaceutically targeting transcriptional addiction as a promising therapeutic strategy in aggressive ovarian cancer. Mol Cancer Ther; 16(9); 1739–50. ©2017 AACR.
Eppikajutsuto Protects against Food Allergy Induced by Ovalbumin in a Murine Model
Authors: Matsui Teruaki , Yamashita Hirotaka , Mori Mikito , Tanaka Hiroyuki , Inagaki Naoki
Published: June 2017

Background: Currently, there are no efficient medications available for the prevention and treatment of food allergy (FA). Herbal medicines, including traditional Japanese Kampo medicines (TJKMs), are promising therapeutic drugs. Methods: We screened 18 TJKMs for treatment of FA symptoms in a mouse FA model induced by ovalbumin (OVA). BALB/c mice were sensitized intraperitoneally by an OVA/aluminum hydroxide gel mixture followed by 4 booster doses of oral OVA and FA symptom induction by 50 mg of OVA. TJKMs were orally administered for 28 days from the day of sensitization to the day before FA symptom induction. Evaluated FA symptoms included a decrease in body temperature and allergic diarrhea. Allergic sensitization was determined by plasma OVA-specific IgE levels. Cytokine mRNA levels in mesenteric lymph nodes, plasma mouse mast cell protease-1, and the number of mast cells in the small and large intestines were analyzed. Additionally, the therapeutic effect of the TJKM eppikajutsuto (EJT) on mast cell degranulation was determined in active anaphylaxis and passive cutaneous anaphylaxis models. Results: EJT effectively prevented FA symptoms. Although OVA-specific IgE levels and the intestinal mast cell numbers were not different between the EJT-treated and untreated FA mice, plasma mMcpt1 and IL-4 levels were lower in EJT-treated FA mice than untreated FA mice. EJT could alleviate symptoms in both active and passive anaphylaxis models. Conclusion: EJT prevented OVA-induced FA symptoms in a mouse model, suggesting that EJT might exert its therapeutic activity via IL-4 suppression and the inhibition of mucosal mast cell degranulation.
A New Approach to Developing Birth Weight Reference Charts: A Retrospective Observational Study
Authors: Joseph Farmey A. , Hyett Jon A. , McGeechan Kevin , Schluter Philip J. , Gordon Adrienne , McLennan Andrew , De Vries Bradley S.
Published: June 2017

Introduction: Birth weight reference charts based on historical infant birth weights have significant bias at preterm gestations because many preterm births are associated with abnormal growth. This study aims to determine whether more accurate birth weight charts can be constructed using data only from births that follow spontaneous onset of labour. Materials and Methods: This study was a single-centre retrospective observational study of 115,712 singleton live births. Births were classified as spontaneous or iatrogenic. Quantile regression was used to model the relationship between gestational age, sex, labour onset, and birth weight. Comparison was made of birth weights in the spontaneous and iatrogenic cohorts by gestation, and to existing ultrasound-based charts. Results: Birth weights of spontaneous and iatrogenic births were significantly different for gestational age at the median and 10th centiles. Iatrogenic preterm infants weighed less than their spontaneous preterm counterparts. Median and 10th centile birth weights derived from the spontaneous birth cohort closely approximate previous ultrasound-based curves. Discussion: Iatrogenic births are more likely to be associated with pre-existing growth disturbance. Inclusion of these data has significant impact on centile charts. Birth weight charts derived from only spontaneous births may offer a more accurate reference for clinicians.
Ex utero Intrapartum Treatment to Ventricular Pacing: A Novel Delivery Strategy for Complete Atrioventricular Block with Severe Bradycardia
Authors: Cuneo Bettina F. , Mitchell Max B. , Marwan Ahmed I. , Green Matthew , von Alvensleben Johannes C. , Reynolds Regina , Crombleholme Timothy M. , Galan Henry L.
Published: June 2017

Fetuses with anti-SSA-mediated complete atrioventricular block (CAVB) are at high risk for perinatal death if they present at <20 weeks of gestation and develop ventricular rates of <55 beats per minute (bpm), cardiac dysfunction, or hydrops [Izmirly et al.: Circulation 2011;124:1927-1935; Jaeggi et al.: J Am Coll Cardiol 2002;39:130-137; Eliasson et al.: Circulation 2011;124:1919-1926]. After our experience with two such fetuses who died with pulseless electrical activity despite being paced within 30 min of birth, we performed an ex utero intrapartum treatment procedure to ventricular pacing on a 36-week CAVB fetus with cardiac dysfunction, mild hydrops, and a ventricular rate of 46 bpm. While still on placental bypass, temporary epicardial ventricular pacing leads were successfully placed; the infant was delivered and made a successful transition to postnatal life. This approach can improve the 11-fold increase in mortality for the preterm fetus with long-standing CAVB, severe bradycardia, and heart failure.
Erythrocyte Sodium Sensitivity and Eryptosis in Chronic Hemodialysis Patients
Authors: Meyring-Wösten Anna , Kuntsevich Viktoriya , Campos Israel , Williams Schantel , Ma Jie , Patel Samir , Ornillo Chiarra , Thijssen Stephan , Kotanko Peter
Published: June 2017

Background/Aims: In hemodialysis (HD) patients the endothelial and erythrocyte glycocalyx is impaired which in turn correlates with elevated erythrocyte sodium sensitivity (ESS). Additionally, apoptotic erythrocyte death (eryptosis), characterized by phosphatidylserine (PS) exposure on the cell surface, is increased in this population. We aimed to explore the relationship of ESS and eryptosis. Methods: Blood samples were collected from 11 healthy controls and 20 chronic HD patients before and after midweek HD. ESS was quantified by the salt blood test. PS-exposure, intracellular reactive oxygen species (ROS) of erythrocytes and reticulocytes were assessed by flow cytometry. Results: Compared to controls ESS was significantly higher in HD patients preHD and did not change during treatment. The percentage of eryptotic cells did not differ between controls and patients preHD. However, eryptosis decreased during HD. ESS and eryptosis were uncorrelated, while eryptosis was positively correlated with intracellular ROS and percent reticulocytes. Conclusions: Higher ESS levels in HD patients indicate a pathologic glycocalyx. ESS and eryptosis were not correlated. The decreased eryptosis postHD may possibly be related to dialytic uremic toxin removal, but is likely multifactorial. The relationship between eryptosis and intracellular ROS warrants further research.
Association Between Periodontitis and Low-Grade Albuminuria in Non-Diabetic Adults
Authors: Kang Seok Hui , Park Jong Won , Cho Kyu Hyang , Do Jun-Young
Published: June 2017

Background/Aims: The objective of the present study was to evaluate the clinical association between periodontitis and a high urinary albumin/creatinine ratio (UACR) in individuals without diabetes mellitus. Methods: Data from the Korean National Health and Nutrition Examination Survey were used for this analysis. A high UACR was defined as UACR≥3.9 mg/g for men and UACR≥7.5 mg/g for women. The WHO community periodontal index (CPI) was used to define periodontitis and assess its severity. Results: The numbers of participants without and with periodontitis were 3,046 and 8,571, respectively. The UACR values were higher in participants with periodontitis than in those without periodontitis. Logistic regression showed that the OR for a high UACR with the presence of periodontitis was 1.14 (P=0.044) on multivariate analysis. CPI score was positively associated with UACR. Conclusions: Periodontitis was associated with UACR in the non-diabetic participants in this study. Therefore, participants with periodontitis should be closely monitored for UACR, which can function as an early marker for renal injury.
APOL1
Risk Variants and Cardiovascular Disease
Authors: Chen Teresa K. , Appel Lawrence J. , Grams Morgan E. , Tin Adrienne , Choi Michael J. , Lipkowitz Michael S. , Winkler Cheryl A. , Estrella Michelle M.
Published: June 2017

Objective—

Among African Americans, the apolipoprotein L1 (
APOL1
) risk variants have been associated with various types of kidney disease and chronic kidney disease progression. We aimed to determine whether these same risk variants also confer an increased risk for cardiovascular disease.

Approach and Results—

In a cohort of African Americans with hypertension-attributed chronic kidney disease followed for up to 12 years, we used Cox proportional hazards models to estimate the relative hazard of a composite cardiovascular disease outcome (cardiovascular death or hospitalization for myocardial infarction, cardiac revascularization procedure, heart failure, or stroke) for the
APOL1
high- (2 risk variants) versus low-risk (0–1 risk variant) genotypes. We adjusted for age, sex, ancestry, smoking, heart disease history, body mass index, cholesterol, randomized treatment groups, and baseline and longitudinal estimated glomerular filtration rate, systolic blood pressure, and proteinuria. Among 693 participants with
APOL1
genotyping available (23% high risk), the high-risk group had lower mean estimated glomerular filtration rate (44.7 versus 50.1 mL/min per 1.73 m
2
) and greater proteinuria (median 0.19 versus 0.06) compared with the low-risk group at baseline. There was no significant association between
APOL1
genotypes and the composite cardiovascular disease outcome in both unadjusted (hazard ratio=1.23; 95% confidence interval: 0.83–1.81) and fully adjusted (hazard ratio=1.16; 95% confidence interval: 0.77–1.76) models; however, in using an additive model,
APOL1
high-risk variants were associated with increased cardiovascular mortality.

Conclusions—

Among African Americans with hypertension-attributed chronic kidney disease,
APOL1
risk variants were not associated with an overall risk for cardiovascular disease although some signals for cardiovascular mortality were noted.