bluuebunny/crossref_metadata_2025 huggingface dataset:
A Multiplex PCR Approach for Detecting Dual Infections and Recombinants Involving Major HIV Variants
Authors: Cappy Pierre , De Oliveira Fabienne , Gueudin Marie , Alessandri-Gradt Elodie , Plantier Jean-Christophe
Published: February 2016

The cocirculation of different HIV types and groups can lead to dual infections and recombinants, which hinder diagnosis and therapeutic management. We designed two multiplex PCRs (mPCRs) coupled with capillary electrophoresis to facilitate the detection of such infections. The first, M
MO2
, targets three variants (HIV-1/M, HIV-1/O, and HIV-2), and the second, M
MO
, targets HIV-1/M and HIV-1/O. These mPCRs were validated on DNA and RNA extracts from 19 HIV-1/M, 12 HIV-1/O, and 13 HIV-2 cultures and from mixtures simulating dual infections. They were then assessed with DNA and RNA extracts from samples of 47 clinical monoinfections and HIV-1/M+O dual infections or infections with HIV-1/MO recombinants. Both mPCRs had excellent specificity. Sensitivities ranged from 80 to 100% for
in vitro
samples and from 58 to 100% for clinical samples, with the results obtained depending on the material used and the region of the genome concerned. Sensitivity was generally lower for DNA than for RNA and for amplifications of the integrase and matrix regions. In terms of global detection (at least one target gene for each strain), both mPCRs yielded a detection rate of 100% for
in vitro
samples. M
MO2
detected 100% of the clinical strains from DNA and 97% from RNA, whereas M
MO
detected 100% of the strains from both materials. Thus, for
in vitro
and clinical samples, M
MO2
was a useful tool for detecting dual infections with HIV-1 and HIV-2 (referred to as HIV-1+HIV-2) and HIV-1/M+O, and M
MO
was useful for detecting both MO dual infections and MO mosaic patterns.
Mammalian Pathogenesis and Transmission of H7N9 Influenza Viruses from Three Waves, 2013-2015
Authors: Belser Jessica A. , Creager Hannah M. , Sun Xiangjie , Gustin Kortney M. , Jones Tara , Shieh Wun-Ju , Maines Taronna R. , Tumpey Terrence M.
Published: February 2016

Three waves of human infection with H7N9 influenza viruses have concluded to date, but only viruses within the first wave (isolated between March and September 2013) have been extensively studied in mammalian models. While second- and third-wave viruses remain closely linked phylogenetically and antigenically, even subtle molecular changes can impart critical shifts in mammalian virulence. To determine if H7N9 viruses isolated from humans during 2013 to 2015 have maintained the phenotype first identified among 2013 isolates, we assessed the ability of first-, second-, and third-wave H7N9 viruses isolated from humans to cause disease in mice and ferrets and to transmit among ferrets. Similar to first-wave viruses, H7N9 viruses from 2013 to 2015 were highly infectious in mice, with lethality comparable to that of the well-studied A/Anhui/1/2013 virus. Second- and third-wave viruses caused moderate disease in ferrets, transmitted efficiently to cohoused, naive contact animals, and demonstrated limited transmissibility by respiratory droplets. All H7N9 viruses replicated efficiently in human bronchial epithelial cells, with subtle changes in pH fusion threshold identified between H7N9 viruses examined. Our results indicate that despite increased genetic diversity and geographical distribution since their initial detection in 2013, H7N9 viruses have maintained a pathogenic phenotype in mammals and continue to represent an immediate threat to public health.

IMPORTANCE
H7N9 influenza viruses, first isolated in 2013, continue to cause human infection and represent an ongoing public health threat. Now entering the fourth wave of human infection, H7N9 viruses continue to exhibit genetic diversity in avian hosts, necessitating continuous efforts to monitor their pandemic potential. However, viruses isolated post-2013 have not been extensively studied, limiting our understanding of potential changes in virus-host adaptation. In order to ensure that current research with first-wave H7N9 viruses still pertains to more recently isolated strains, we compared the relative virulence and transmissibility of H7N9 viruses isolated during the second and third waves, through 2015, in the mouse and ferret models. Our finding that second- and third-wave viruses generally exhibit disease in mammals comparable to that of first-wave viruses strengthens our ability to extrapolate research from the 2013 viruses to current public health efforts. These data further contribute to our understanding of molecular determinants of pathogenicity, transmissibility, and tropism.
Natural Single-Nucleotide Variations in the HIV-1 Genomic SA1prox Region Can Alter Viral Replication Ability by Regulating Vif Expression Levels
Authors: Nomaguchi Masako , Doi Naoya , Sakai Yosuke , Ode Hirotaka , Iwatani Yasumasa , Ueno Takamasa , Matsumoto Yui , Miyazaki Yasuyuki , Masuda Takao , Adachi Akio
Published: February 2016

We previously found that natural single-nucleotide variations located within a proximal region of splicing acceptor 1 (SA1prox) in the HIV-1 genome could alter the viral replication potential and mRNA expression pattern, especially the
vif
mRNA level. Here, we studied the virological and molecular basis of nucleotide sequence variations in SA1prox for alterations of viral replication ability. Consistent with our previous findings, variant clones indeed expressed Vif at different levels and grew distinctively in cells with various APOBEC3G expression levels. Similar effects were observed for natural variations found in HIV-2 SA1prox, suggesting the importance of the SA1prox sequence. To define nucleotides critical for the regulation of HIV-1 Vif expression, effects of natural SA1prox variations newly found in the HIV Sequence Compendium database on
vif
mRNA/Vif protein levels were examined. Seven out of nine variations were found to produce Vif at lower, higher, or more excessive levels than wild-type NL4-3. Combination experiments of variations giving distinct Vif levels suggested that the variations mutually affected
vif
transcript production. While low and high producers of Vif grew in an APOBEC3G-dependent manner, excessive expressers always showed an impeded growth phenotype due to defects in single-cycle infectivity and/or virion production levels. The phenotype of excessive expressers was not due primarily to inadequate expression of Tat or Rev, although SA1prox variations altered the overall HIV-1 mRNA expression pattern. Collectively, our results demonstrate that HIV SA1prox regulates Vif expression levels and suggest a relationship between SA1prox and viral adaptation/evolution given that variations occurred naturally.

IMPORTANCE
While human cells possess restriction factors to inhibit HIV-1 replication, HIV-1 encodes antagonists to overcome these barriers. Conflicts between host restriction factors and viral counterparts are critical driving forces behind mutual evolution. The interplay of cellular APOBEC3G and viral Vif proteins is a typical example. Here, we demonstrate that naturally occurring single-nucleotide variations in the proximal region of splicing acceptor 1 (SA1prox) of the HIV-1 genome frequently alter Vif expression levels, thereby modulating viral replication potential in cells with various ABOBEC3G levels. The results of the present study reveal a previously unidentified and important way for HIV-1 to compete with APOBEC3G restriction by regulating its Vif expression levels. We propose that SA1prox plays a regulatory role in Vif counteraction against APOBEC3G in order to contribute to HIV-1 replication and evolution, and this may be applicable to other primate lentiviruses.
Nonstructural Protein NP1 of Human Bocavirus 1 Plays a Critical Role in the Expression of Viral Capsid Proteins
Authors: Zou Wei , Cheng Fang , Shen Weiran , Engelhardt John F. , Yan Ziying , Qiu Jianming
Published: February 2016

A novel chimeric parvoviral vector, rAAV2/HBoV1, in which the recombinant adeno-associated virus 2 (rAAV2) genome is pseudopackaged by the human bocavirus 1 (HBoV1) capsid, has been shown to be highly efficient in gene delivery to human airway epithelia (Z. Yan et al., Mol Ther 21:2181–2194, 2013,
http://dx.doi.org/10.1038/mt.2013.92
). In this vector production system, we used an HBoV1 packaging plasmid, pHBoV1NSCap, that harbors HBoV1 nonstructural protein (
NS
) and capsid protein (
Cap
) genes. In order to simplify this packaging plasmid, we investigated the involvement of the HBoV1 NS proteins in capsid protein expression. We found that NP1, a small NS protein encoded by the middle open reading frame, is required for the expression of the viral capsid proteins (VP1, VP2, and VP3). We also found that the other NS proteins (NS1, NS2, NS3, and NS4) are not required for the expression of VP proteins. We performed systematic analyses of the HBoV1 mRNAs transcribed from the pHBoV1NSCap packaging plasmid and its derivatives in HEK 293 cells. Mechanistically, we found that NP1 is required for both the splicing and the read-through of the proximal polyadenylation site of the HBoV1 precursor mRNA, essential functions for the maturation of capsid protein-encoding mRNA. Thus, our study provides a unique example of how a small viral nonstructural protein facilitates the multifaceted regulation of capsid gene expression.

IMPORTANCE
A novel chimeric parvoviral vector, rAAV2/HBoV1, expressing a full-length cystic fibrosis transmembrane conductance regulator (CFTR) gene, is capable of correcting CFTR-dependent chloride transport in cystic fibrosis human airway epithelium. Previously, an HBoV1 nonstructural and capsid protein-expressing plasmid, pHBoV1NSCap, was used to package the rAAV2/HBoV1 vector, but yields remained low. In this study, we demonstrated that the nonstructural protein NP1 is required for the expression of capsid proteins. However, we found that the other four nonstructural proteins (NS1 to -4) are not required for expression of capsid proteins. By mutating the
cis
elements that function as internal polyadenylation signals in the capsid protein-expressing mRNA, we constructed a simple HBoV1 capsid protein-expressing gene that expresses capsid proteins as efficiently as pHBoV1NSCap does, and at similar ratios, but independently of NP1. Our study provides a foundation to develop a better packaging system for rAAV2/HBoV1 vector production.
Diseases Transmitted by Domestic Livestock: Perils of the Petting Zoo
Authors: Dunn John R. , Behravesh Casey Barton , Angulo Frederick J.
Published: February 2016

Petting zoo venues encourage or permit public contact with animals which provide opportunities for education and entertainment. These venues vary but are common at county or state fairs, zoos, and aquariums. In addition to these common petting zoo settings, animals are present in many other venues where the public is permitted to contact them and their environment. Thus, humans may have contact with animals in a wide range of settings, and transmission of infectious diseases from animals to humans may occur at any of these venues, creating perils associated with petting zoos.

There are many considerations when evaluating perils associated with the wide range of venues where animal contact can occur. First, many venues or events draw large numbers of people; some operate during a short time frame, while others, such as zoos and aquariums, operate year round. Second, petting zoos and other animal contact venues are particularly popular with children, who compared with adults, commonly have less stringent hygienic practices and are more susceptible to severe disease outcomes. Finally, there is remarkable variability in the physical layout of venues that permit animal contact and in the types of animals that may be contacted. Animal contact areas range from well-designed permanent exhibits targeting risk reduction to various temporary or seasonal exhibits established without detailed planning. Many petting zoos house only small ruminant species such as sheep and goats, but other venues house a wide variety of mammalian species, exotic animals, poultry and other avian species, reptiles and amphibians, and aquatic animals.
Canola seed yield and phenological responses to plant density
Authors: Yantai Gan , Harker K. Neil , Kutcher H. Randy , Gulden Robert H. , Irvine Byron , May William E. , O'Donovan John T.
Published: February 2016

Optimal plant density is required to improve plant phenological traits and maximize seed yield in field crops. In this study, we determined the effect of plant density on duration of flowering, post-flowering phase, and seed yield of canola in diverse environments. The field study was conducted at 16 site-years across the major canola growing area of western Canada from 2010 to 2012. The cultivar InVigor® 5440, a glufosinate-resistant hybrid, was grown at five plant densities (20, 40, 60, 80, and 100 plants m−2) in a randomized complete block design with four replicates. Canola seed yield had a linear relationship with plant density at 8 of the 16 site-years, a quadratic relationship at 4 site-years, and there was no correlation between the two variables in the remaining 4 site-years. At site-years with low to medium productivity, canola seed yield increased by 10.2 to 14.7 kg ha−1 for every additional plant per square metre. Averaged across the 16 diverse environments, canola plants spent an average of 22% of their life cycle flowering and another 27% of the time filling seed post-flowering. Canola seed yield had a negative association with duration of flowering and a positive association with the days post-flowering but was not associated with number of days to maturity. The post-flowering period was 12.7, 14.7, and 12.6 d (or 55, 68, and 58%) longer in high-yield experiments than in low-yield experiments in 2010, 2011, and 2012, respectively. We conclude that optimization of plant density for canola seed yield varies with environment and that a longer post-flowering period is critical for increasing canola yield in western Canada.
Simplification Problems for Deterministic Pushdown Automata on Infinite Words
Authors: Löding Christof
Published: February 2016

The article surveys some decidability results concerning simplification problems for DPDAs on infinite words (ω-DPDAs). We summarize some recent results on the regularity problem, which asks for a given ω-DPDA, whether its language can also be accepted by a finite automaton. The results also give some insights on the equivalence problem for a subclass of ω-DPDA. Furthermore, we present some new results on the parity index problem for ω-DPDAs. For the specification of a parity condition, the states of the ω-DPDA are assigned priorities (natural numbers), and a run is accepting if the highest priority that appears infinitely often during a run is even. The basic simplification question asks whether one can determine the minimal number of priorities that are needed to accept the language of a given ω-DPDA. We provide some decidability results on variations of this question for some classes of ω-DPDAs.
No Gap Second-order Optimality Conditions for a Matrix Cone Programming Induced by the Nuclear Norm
Authors: Zhang Ning , Zhang Liwei
Published: February 2016

The first-order and the second-order directional derivatives of singular values are used to characterize the tangent cone, the normal cone and the second-order tangent set of the epigraph of the nuclear norm of matrices. Based on the variational geometry of the epigraph, the no gap second-order optimality conditions for the optimization problem, whose constraint is defined by the matrix cone induced by the nuclear norm, are established.
Cobalt(III) and gallium(III) complexes of meso-free corroles with distinct position-dependent substituent effects
Authors: Ooi Shota , Tanaka Takayuki , Osuka Atsuhiro
Published: February 2016

Co(III) and Ga(III) complexes of 5,10-bis(pentafluorophenyl)corrole and 5,15-bis(pentafluorophenyl)corrole were synthesized by metalations with Co(OAc)2 •4H2O and GaCl3, respectively. The structures of these complexes have been all unambiguously revealed by X-ray diffraction analysis. Their optical and electrochemical properties have been studied, which reveals small but distinctly different substituent effects depending upon the substitution positions.
Changing calcium: CRAC channel (STIM and Orai) expression, splicing, and posttranslational modifiers
Authors: Niemeyer Barbara A.
Published: February 2016

A wide variety of cellular function depends on the dynamics of intracellular Ca2+ signals. Especially for relatively slow and lasting processes such as gene expression, cell proliferation, and often migration, cells rely on the store-operated Ca2+ entry (SOCE) pathway, which is particularly prominent in immune cells. SOCE is initiated by the sensor proteins (STIM1, STIM2) located within the endoplasmic reticulum (ER) registering the Ca2+ concentration within the ER, and upon its depletion, cluster and trap Orai (Orai1-3) proteins located in the plasma membrane (PM) into ER-PM junctions. These regions become sites of highly selective Ca2+ entry predominantly through Orai1-assembled channels, which, among other effector functions, is necessary for triggering NFAT translocation into the nucleus. What is less clear is how the spatial and temporal spread of intracellular Ca2+ is shaped and regulated by differential expression of the individual SOCE genes and their splice variants, their heteromeric combinations and pre- and posttranslational modifications. This review focuses on principle mechanisms regulating expression, splicing, and targeting of Ca2+ release-activated Ca2+ (CRAC) channels.
Optogenetic activation of mechanically insensitive afferents in mouse colorectum reveals chemosensitivity
Authors: Feng Bin , Joyce Sonali C. , Gebhart G. F.
Published: February 2016

The sensory innervation of the distal colorectum includes mechanically insensitive afferents (MIAs; ∼25%), which acquire mechanosensitivity in persistent visceral hypersensitivity and thus generate de novo input to the central nervous system. We utilized an optogenetic approach to bypass the process of transduction (generator potential) and focus on transformation (spike initiation) at colorectal MIA sensory terminals, which is otherwise not possible in typical functional studies. From channelrhodopsin2-expressing mice (driven by Advillin-Cre), the distal colorectum with attached pelvic nerve was harvested for ex vivo single-fiber recordings. Afferent receptive fields (RFs) were identified by electrical stimulation and tested for response to mechanical stimuli (probing, stroking, and stretch), and afferents were classified as either MIAs or mechanosensitive afferents (MSAs). All MIA and MSA RFs were subsequently stimulated optically and MIAs were also tested for activation/sensitization with inflammatory soup (IS), acidic hypertonic solution (AHS), and/or bile salts (BS). Responses to pulsed optical stimuli (1–10 Hz) were comparable between MSAs and MIAs whereas 43% of MIAs compared with 86% of MSAs responded tonically to stepped optical stimuli. Tonic-spiking MIAs responded preferentially to AHS (an osmotic stimulus) whereas non-tonic-spiking MIAs responded to IS (an inflammatory stimulus). A significant proportion of MIAs were also sensitized by BS. These results reveal transformation as a critical factor underlying the differences between MIAs (osmosensors vs. inflammatory sensors), revealing a previously unappreciated heterogeneity of MIA endings. The current study draws attention to the sensory encoding of MIA nerve endings that likely contribute to afferent sensitization and thus have important roles in visceral pain.
Intact urothelial barrier function in a mouse model of ketamine-induced voiding dysfunction
Authors: Rajandram Retnagowri , Ong Teng Aik , Razack Azad H. A. , MacIver Bryce , Zeidel Mark , Yu Weiqun
Published: February 2016

Ketamine is a popular choice for young drug abusers. Ketamine abuse causes lower urinary tract symptoms, with the underlying pathophysiology poorly understood. Disruption of urothelial barrier function has been hypothesized to be a major mechanism for ketamine cystitis, yet the direct evidence of impaired urothelial barrier function is still lacking. To address this question, 8-wk-old female C57BL/6J mice were injected intraperitoneally with 30 mg·kg−1·day−1ketamine for 12 wk to induce ketamine cystitis. A spontaneous voiding spot assay showed that ketamine-treated mice had increased primary voiding spot numbers and smaller primary voiding spot sizes than control mice ( P < 0.05), indicating a contracted bladder and bladder overactivity. Consistently, significantly increased voiding frequency was observed in ketamine-treated mice on cystometrograms. These functional experiments indicate that ketamine induces voiding dysfunction in mice. Surprisingly, urothelial permeability in ketamine-treated mice was not changed when measured using an Ussing chamber system with isotopic urea and water. Mouse urothelial structure was also not altered, and intact umbrella cell structure was observed by both transmission and scanning electron microscopy. Furthermore, immunostaining and confocal microscopy confirmed the presence of a well-defined distribution of zonula occuldens-1 in tight junctions and uroplakin in umbrella cells. In conclusion, these data indicate that ketamine injection induces voiding dysfunction in mice but does not necessarily disrupt mouse bladder barrier function. Disruption of urothelial barrier function may not be the major mechanism in ketamine cystitis.
Effects of GABAA kinetics on cortical population activity: computational studies and physiological confirmations
Authors: Chemla Sandrine , Chavane Frédéric
Published: February 2016

Voltage-sensitive dye (VSD) imaging produces an unprecedented real-time and high-resolution mesoscopic signal to measure the cortical population activity. We have previously shown that the neuronal compartments contributions to the signal are dynamic and stimulus-dependent (Chemla S, Chavane F. Neuroimage 53: 420–438, 2010). Moreover, the VSD signal can also be strongly affected by the network state, such as in anesthetized vs. awake preparations. Here, we investigated the impact of the network state, through GABAA receptors modulation, on the VSD signal using a computational approach. We therefore systematically measured the effect of the GABAA-mediated inhibitory postsynaptic potentials (IPSPs) decay time constant (τG) on our modeled VSD response to an input stimulus of increasing strength. Our simulations suggest that τG strongly modulates the dynamics of the VSD signal, affecting the amplitude, input response function, and the transient balance of excitation and inhibition. We confirmed these predictions experimentally on awake and anesthetized monkeys, comparing VSD responses to drifting gratings stimuli of various contrasts. Lastly, one in vitro study has suggested that GABAA receptors may also be directly affected by the VSDs themselves (Mennerick S, Chisari M, Shu H, Taylor A, Vasek M, Eisenman L, Zorumski C. J Neurosci 30: 2871–2879, 2010). Our modeling approach suggests that the type of modulation described in this study would actually have a negligible influence on the population response. This study highlights that functional results acquired with different techniques and network states must be compared with caution. Biophysical models are proposed here as an adequate tool to delineate the domain of VSD data interpretation.
Neural Network of Predictive Motor Timing in the Context of Gender Differences
Authors: Filip Pavel , Lošák Jan , Kašpárek Tomáš , Vaníček Jiří , Bareš Martin
Published: February 2016

Time perception is an essential part of our everyday lives, in both the prospective and the retrospective domains. However, our knowledge of temporal processing is mainly limited to the networks responsible for comparing or maintaining specific intervals or frequencies. In the presented fMRI study, we sought to characterize the neural nodes engaged specifically in predictive temporal analysis, the estimation of the future position of an object with varying movement parameters, and the contingent neuroanatomical signature of differences in behavioral performance between genders. The established dominant cerebellar engagement offers novel evidence in favor of a pivotal role of this structure in predictive short-term timing, overshadowing the basal ganglia reported together with the frontal cortex as dominant in retrospective temporal processing in the subsecond spectrum. Furthermore, we discovered lower performance in this task and massively increased cerebellar activity in women compared to men, indicative of strategy differences between the genders. This promotes the view that predictive temporal computing utilizes comparable structures in the retrospective timing processes, but with a definite dominance of the cerebellum.
The Difference between the Two Representative Kampo Formulas for Treating Dysmenorrhea: An Observational Study
Authors: Yoshino Tetsuhiro , Katayama Kotoe , Horiba Yuko , Munakata Kaori , Yamaguchi Rui , Imoto Seiya , Miyano Satoru , Mima Hideki , Watanabe Kenji , Mimura Masaru
Published: February 2016

In Kampo medicine, two different formulas are effective for treating dysmenorrhea—tokishakuyakusan and keishibukuryogan; however, the criteria by which specialists select the appropriate formula for each patient are not clear. We compared patients treated with tokishakuyakusan and those with keishibukuryogan and proposed a predictive model. The study included 168 primary and secondary dysmenorrhea patients who visited the Kampo Clinic at Keio University Hospital. We collected clinical data from 128 dysmenorrhea patients, compared the two patient groups and selected significantly different factors as potential predictors, and used logistic regression to establish a model. An external validation was performed using 40 dysmenorrhea patients. Lightheadedness, BMI < 18.5, and a weak abdomen were significantly more frequent in the tokishakuyakusan group; tendency to sweat, heat intolerance, leg numbness, a cold sensation in the lower back, a strong abdomen, and paraumbilical tenderness and resistance were more frequent in the keishibukuryogan group. The final model fitted the data well. Internally estimated accuracy was 81.2%, and a leave‐one‐out cross‐validation estimate of accuracy was 80.5%. External validation accuracy was 85.0%. We proposed a model for predicting the use of two Kampo formulas for dysmenorrhea, which should be validated in prospective trials.
RLT Code Based Handshake-Free Reliable MAC Protocol for Underwater Sensor Networks
Authors: Du Xiujuan , Li Keqin , Liu Xiuxiu , Su Yishan
Published: February 2016

The characteristics of underwater acoustic channels such as long propagation delay and low bit rate cause the medium access control (MAC) protocols designed for radio channels to either be inapplicable or have low efficiency for underwater sensor networks (UWSNs). Meanwhile, due to high bit error, conventional end-to-end reliable transfer solutions bring about too many retransmissions and are inefficient in UWSN. In this paper, we present a recursive LT (RLT) code. With small degree distribution and recursive encoding, RLT achieves reliable transmission hop-by-hop while reducing the complexity of encoding and decoding in UWSN. We further propose an RLT code based handshake-free (RCHF) reliable MAC protocol. In RCHF protocol, each node maintains a neighbor table including the field of state, and packages are forwarded according to the state of a receiver, which can avoid collisions of sending-receiving and overhearing. The transmission-avoidance time in RCHF decreases data-ACK collision dramatically. Without RTS/CTS handshaking, the RCHF protocol improves channel utilization while achieving reliable transmission. Simulation results show that, compared with the existing reliable data transport approaches for underwater networks, RCHF can improve network throughput while decreasing end-to-end overhead.
Automated Residential Demand Response Based on Advanced Metering Infrastructure Network
Authors: Seo Jongkwan , Jin Ju , Kim Jin Young , Lee Jae-Jo
Published: February 2016

Demand response (DR) is a major contributor to grid stabilization during peak times. As the scope and functions of DR increase, DR participation of residential customers has attracted great attention. The main issue of DR design for the residential sector is to build an integrated network for exchange of DR signals between the utility operator and home users who want to participate in DR services at various locations. In this paper, we introduce an automated residential DR model based on advanced metering infrastructure (AMI) network. The internationally recognized standard protocol, known as the open automated demand response version 2.0 (OpenADR 2.0), is applied to realize a fully automated DR (ADR). In order to utilize existing AMI devices as ADR resources, the smart meter is modified while retaining current structure and functions, and various ADR devices are developed based on OpenADR 2.0 protocol. Simulation and demonstration tests are conducted to confirm conformance of the protocol and to verify load variations of home appliances under our ADR model. The developed software programs have obtained an international certification from the OpenADR Alliance.
Serum Amyloid a Promotes Visfatin Expression in Macrophages
Authors: Wang Shixun , Zhang Xincai , Tan Lei
Published: February 2016

Visfatin has been reported to exert an important role in the development of atherosclerosis. However, the mechanism that regulated the expression of Visfatin has not been elucidated yet. This study aimed to investigate the effect of SAA on the regulation of Visfatin, as well as the potential pathway. After RAW264.7 macrophages and primary monocytes were stimulated with SAA, the mRNA and protein expression of Visfatin was detected with real-time PCR and western blot, respectively. The concentration of Visfatin in the supernatant was measured with ELISA. Formyl peptide receptor 2 (FPR2) agonist (WKYMVm) and inhibitor (WRW4), extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor (PD98059), and peroxisome proliferator-activated receptor-γ(PPAR-γ) agonist (Rosiglitazone) and inhibitor (GW9662) were used to investigate the mechanism of regulation of Visfatin. The results demonstrated that SAA upregulated Visfatin expression in cultured RAW264.7 macrophages and in the primary monocytes. WRW4decreased SAA-induced Visfatin production, while WKYMVm could induce Visfatin expression. PD98059 reduced SAA-induced Visfatin production. What is more, GW9662 inhibited SAA-induced Visfatin production, while Rosiglitazone promoted Visfatin expression. These results demonstrate that SAA upregulates Visfatin expression via a FPR2/ERK1/2/PPAR-γsignaling pathway.
Biochemical Markers of Bone Turnover in Patients withβ-Thalassemia Major: A Single Center Study from Southern Pakistan
Authors: Sultan Sadia , Irfan Syed Mohammed , Ahmed Syed Ijlal
Published: February 2016

Objectives. Skeletal complications inβ-homozygous thalassemic patients are uncommon but often debilitating, even amongst children and adolescent patients with well maintained transfusion and chelation therapy. The aim is to evaluate the biochemical markers of bone turnover in regularly transfused thalassemic patients and its possible correlations with demographic data and hematological and biochemical markers.Methods. In this prospective cross-sectional study, 36β-thalassemia major patients were enrolled from March 2012 to March 2014. All patients underwent complete blood counts, LFTs, serum ferritin, serum calcium, phosphorus, serum albumin, alkaline phosphatase, 25-OH vitamin D, and parathormone (PTH) levels.Results. There were 17 males and 19 females with mean age of 12.56 ± 5.9 years. Hypocalcemia and hypophosphatemia were seen in 66.6% and 19.4%, respectively, while 25-OH vitamin D deficiency was present in 72.2% of thalassemic children and adolescents. Hypoparathyroidism was seen in 13.8% while hyperparathyroidism was detected in 8.3% of patients. There was direct correlation between serum phosphorus and ferritin levels (P<0.05). No correlation was found between indirect bilirubin and skeletal parameters, calcium and parathyroid hormone (P>0.05).Conclusions. Biochemical profile is significantly altered in patients withβ-thalassemia major and bone associated biochemical abnormalities like hypocalcaemia, 25-OH vitamin D deficiency, and hypophosphatemia are not uncommon in Pakistani patients with thalassemia major.
Mismatch Negativity and P50 Sensory Gating in Abstinent Former Cannabis Users
Authors: Broyd Samantha J. , Greenwood Lisa-marie , van Hell Hendrika H. , Croft Rodney J. , Coyle Hannah , Lee-Bates Ben , Todd Juanita , Johnstone Stuart J. , Michie Patricia T. , Solowij Nadia
Published: February 2016

Prolonged heavy exposure to cannabis is associated with impaired cognition and brain functional and structural alterations. We recently reported attenuated mismatch negativity (MMN) and altered P50 sensory gating in chronic cannabis users. This study investigated the extent of brain functional recovery (indexed by MMN and P50) in chronic users after cessation of use. Eighteen ex-users (median 13.5 years prior regular use; median 3.5 years abstinence) and 18 nonusers completed(1)a multifeature oddball task with duration, frequency, and intensity deviants and(2)a P50 paired-click paradigm. Trend level smaller duration MMN amplitude and larger P50 ratios (indicative of poorer sensory gating) were observed in ex-users compared to controls. Poorer P50 gating correlated with prior duration of cannabis use. Duration of abstinence was positively correlated with duration MMN amplitude, even after controlling for age and duration of cannabis use. Impaired sensory gating and attenuated MMN amplitude tended to persist in ex-users after prolonged cessation of use, suggesting a lack of full recovery. An association with prolonged duration of prior cannabis use may indicate persistent cannabis-related alterations to P50 sensory gating. Greater reductions in MMN amplitude with increasing abstinence (positive correlation) may be related to either self-medication or an accelerated aging process.
An Efficient Siphon-Based Deadlock Prevention Policy for a Class of Generalized Petri Nets
Authors: Hou YiFan , Zhao Mi , Liu Ding , Hong Liang
Published: February 2016

We propose a new deadlock prevention policy for an important class of resource allocation systems (RASs) that appear in the modeling of flexible manufacturing systems (FMSs). The model of this class in terms of generalized Petri nets is, namely, S4PR. On the basis of recent structural analysis results related to the elementary siphons in generalized Petri nets on one hand and an efficient deadlock avoidance policy proposed for the class of conjunctive/disjunctive (C/D) RASs on the other hand, we show how one can generate monitors to be added to a net system such that all its strict minimal siphons aremax′-controlled and no insufficiently marked siphon is generated. Thereby, a new, simple, and more permissive liveness-enforcing supervisor synthesis method for S4PR is established.
Dynamic Analysis of the High Speed Train and Slab Track Nonlinear Coupling System with the Cross Iteration Algorithm
Authors: Lei Xiaoyan , Wu Shenhua , Zhang Bin
Published: February 2016

A model for dynamic analysis of the vehicle-track nonlinear coupling system is established by the finite element method. The whole system is divided into two subsystems: the vehicle subsystem and the track subsystem. Coupling of the two subsystems is achieved by equilibrium conditions for wheel-to-rail nonlinear contact forces and geometrical compatibility conditions. To solve the nonlinear dynamics equations for the vehicle-track coupling system, a cross iteration algorithm and a relaxation technique are presented. Examples of vibration analysis of the vehicle and slab track coupling system induced by China’s high speed train CRH3 are given. In the computation, the influences of linear and nonlinear wheel-to-rail contact models and different train speeds are considered. It is found that the cross iteration algorithm and the relaxation technique have the following advantages: simple programming; fast convergence; shorter computation time; and greater accuracy. The analyzed dynamic responses for the vehicle and the track with the wheel-to-rail linear contact model are greater than those with the wheel-to-rail nonlinear contact model, where the increasing range of the displacement and the acceleration is about 10%, and the increasing range of the wheel-to-rail contact force is less than 5%.
Comparison of Three Tests to Distinguish Platelet Reactivity in Patients with Renal Impairment during Dual Antiplatelet Therapy
Authors: Guo Long Zhe , Kim Moo Hyun , Kim Tae Hyung , Park Jong Seong , Jin Enze , Shim Chang Heon , Choi Sun Young , Serebruany Victor L.
Published: February 2016

Background: Clopidogrel and aspirin combination remains a cornerstone for modern dual antiplatelet therapy (DAPT) following coronary stenting. Although monitoring is not currently recommended, certain high-risk cohorts may benefit from tailoring antiplatelet options to reduce thrombotic or/and hemorrhagic risks. Patients with diminished estimated glomerular filtration rate (eGFR) are prone to both vascular occlusions and bleeding events in whom monitoring may be especially advantageous. We compared the residual platelet reactivity assessed by 3 conventional tests during the maintenance antiplatelet therapy dependent on eGFR. Methods: Post-stenting patients (n = 701) receiving aspirin 100 mg/daily and clopidogrel 75 mg/daily were prospectively enrolled in the cross-sectional single-center study. Patients were dichotomized into 5 groups: eGFR >90, 60-89, 30-59, <30 ml/min/1.73 m2, and dialysis. Platelet reactivity by VerifyNow™, light transmittance aggregometry (LTA), and Multiplate analyzer by multiple electrode platelet aggregometry (MEA) assays together with eGFR calculations were done simultaneously at 1 month after coronary stenting. Results: VerifyNow assay distinguished residual platelet reactivity dependent on eGFR deterioration (191 ± 72 vs. 216 ± 78 vs. 248 ± 80 vs. 264 ± 70 vs. 317 ± 96 PRU; p < 0.001). In contrast, LTA (34.3 ± 18.1 vs. 34.7 ± 18.1 vs. 38.0 ± 16.6 vs. 33.0 ± 17.3 vs. 34.1 ± 29.3%; p = 0.242), or MEA (37.2 ± 19.6 vs. 33.8 ± 18.4 vs. 38.6 ± 21.4 vs. 36.5 ± 20.5 vs. 38.3 ± 28.3 AU/min; p = 0.086) failed to triage platelet reactivity in renal patients. Agreement among assays to identify patients with impaired platelet reactivity and eGFR during antiplatelet therapy was low. The multivariable regression analyses confirmed the VerifyNow advantage, since the differences in the platelet reactivity were highly significant for all renal impairment (RI) groups. In contrast, LTA did not distinguish RI patients, and for the MEA, only RI5 (dialysis) cohort exhibit borderline significant decline of residual platelet reactivity. Conclusion: Among 3 assays, VerifyNow was capable to reliably triage residual platelet reactivity in post-stenting DAPT patients dependent on the gradual decline of eGFR during therapy with clopidogrel and aspirin. These data should be confirmed in a large validation longitudinal trial, and may justify future platelet activity monitoring for potential regimen/dose adjustment in high-risk patients. The clinical implications of these data are still unclear, but may give an indication as to whether or when DAPT dose adjustment will become a reality.
Potassium Channel Subfamily K Member 3 (KCNK3) Contributes to the Development of Pulmonary Arterial Hypertension
Authors: Antigny Fabrice , Hautefort Aurélie , Meloche Jolyane , Belacel-Ouari Milia , Manoury Boris , Rucker-Martin Catherine , Péchoux Christine , Potus François , Nadeau Valérie , Tremblay Eve , Ruffenach Grégoire , Bourgeois Alice , Dorfmüller Peter , Breuils-Bonnet Sandra , Fadel Elie , Ranchoux Benoît , Jourdon Philippe , Girerd Barbara , Montani David , Provencher Steeve , Bonnet Sébastien , Simonneau Gérald , Humbert Marc , Perros Frédéric
Published: February 2016

Background—

Mutations in the
KCNK3
gene have been identified in some patients suffering from heritable pulmonary arterial hypertension (PAH).
KCNK3
encodes an outward rectifier K
+
channel, and each identified mutation leads to a loss of function. However, the pathophysiological role of potassium channel subfamily K member 3 (KCNK3) in PAH is unclear. We hypothesized that loss of function of KCNK3 is a hallmark of idiopathic and heritable PAH and contributes to dysfunction of pulmonary artery smooth muscle cells and pulmonary artery endothelial cells, leading to pulmonary artery remodeling: consequently, restoring KCNK3 function could alleviate experimental pulmonary hypertension (PH).

Methods and Results—

We demonstrated that KCNK3 expression and function were reduced in human PAH and in monocrotaline-induced PH in rats. Using a patch-clamp technique in freshly isolated (not cultured) pulmonary artery smooth muscle cells and pulmonary artery endothelial cells, we found that KCNK3 current decreased progressively during the development of monocrotaline-induced PH and correlated with plasma-membrane depolarization. We demonstrated that KCNK3 modulated pulmonary arterial tone. Long-term inhibition of KCNK3 in rats induced distal neomuscularization and early hemodynamic signs of PH, which were related to exaggerated proliferation of pulmonary artery endothelial cells, pulmonary artery smooth muscle cell, adventitial fibroblasts, and pulmonary and systemic inflammation. Lastly, in vivo pharmacological activation of KCNK3 significantly reversed monocrotaline-induced PH in rats.

Conclusions—

In PAH and experimental PH, KCNK3 expression and activity are strongly reduced in pulmonary artery smooth muscle cells and endothelial cells. KCNK3 inhibition promoted increased proliferation, vasoconstriction, and inflammation. In vivo pharmacological activation of KCNK3 alleviated monocrotaline-induced PH, thus demonstrating that loss of KCNK3 is a key event in PAH pathogenesis and thus could be therapeutically targeted.
‘We Intend to Move Together in Moving the World’
Authors: Vogelaar Huub
Published: February 2016

The words ‘we intend to move together’ were expressed in the Message of the Assembly of the World Council of Churches (wcc) held in Busan, the second largest city of South Korea. It was a nuanced version of the original phrase of the first Assembly which took place in Amsterdam in 1948 expressing the strong commitment ‘we intend to stay together’. How the 345 member churches of the wcc plan to move together in the upcoming seven years till the next assembly is done in a so-called pilgrimage of justice and peace also communicated in the Message of the Assembly. Below we describe the main characteristics of the vivid 10th assembly, its appealing contexts, as well some of its outcomes. This article will however not comprise the missionary aspects of the assembly. Besides the study of assembly papers my review is also partly a personal account as I took part in the Busan Assembly with a media accreditation.
China as the Guardian of the International Seabed Area in the Central Arctic Ocean
Authors: Magnússon Bjarni Már
Published: February 2016

China has been engaging more actively in the Arctic, as echoed by the Arctic Council’s admittance of China as a permanent observer in May 2013. China’s interest in the Arctic can to a large extent be explained by climate change shrinking the ice cover of the Arctic Ocean, which has sparked interest with respect to possible exploitation of natural resources and new shipping routes. One aspect of the possible exploitation of natural resources concerns the International Seabed Area. The Stockholm International Peace Research Institute’s policy paper on China’s Arctic aspirations stated that “many Chinese scholars believe that UNCLOS does not entirely safeguard China’s perceived Arctic interests” concerning the continental shelf beyond 200 nautical miles. One scholar noted that “[i]f the Arctic states succeed in their claims to extend their outer continental shelves, the international community’s and China’s right to fairly benefit from Arctic resources will be weakened”.

This article asks whether China can act as a watchdog against excessive continental shelf claims beyond 200 nautical miles by the littoral states and shield the idea of the common heritage of mankind, as enshrined in the Area. More precisely, the article will ask whether China can bring a case before an international court or tribunal against one of the littoral states if it establishes the outer limits of the extended continental shelf beyond what they are entitled to according to UNCLOS.
Arctic Mining: The Case of Greenland
Authors: Mortensen Bent Ole Gram
Published: February 2016

Contrary to the Antarctic, the Arctic is populated with people who have needs that must be fulfilled. Modern welfare demands income and, in the Arctic, mining is a potential source. This paper will focus on Greenland, an autonomous region where the indigenous people are still the majority. Greenland is part of the Kingdom of Denmark (the Realm) but in recent years has taken an increasing number of steps towards independence. The Self-Government Act (2009) is the last major step. Hard minerals and oil extraction are hoped to form an economic basis for independence.
Nationalism in Today’s Antarctic
Authors: Hemmings Alan D. , Chaturvedi Sanjay , Leane Elizabeth , Liggett Daniela , Salazar Juan Francisco
Published: February 2016

Whilst nationalism is a recognised force globally, its framing is predicated on experience in conventionally occupied parts of the world. The familiar image of angry young men waving Kalashnikovs means that the idea that nationalism might be at play in Antarctica has to overcome much instinctive resistance, as well as the tactical opposition of the keepers of the present Antarctic political arrangements. The limited consideration of nationalism in Antarctica has generally been confined to the past, particularly “Heroic-Era” and 1930s–1940s expeditions. This article addresses the formations of nationalism in the Antarctic present. Antarctic nationalism need not present in the same shape as nationalisms elsewhere to justify being called nationalism. Here it occurs in a virtual or mediated form, remote from the conventional metropolitan territories of the states and interests concerned. The key aspect of Antarctic nationalism is its contemporary form and intensity. We argue that given the historic difficulties of Antarctic activities, and the geopolitical constraints of the Cold War, it has only been since the end of that Cold War that a more muscular nationalism has been able to flourish in Antarctica. Our assessment is that there at least 11 bases upon which Antarctic nationalism might arise: (i) formally declared claims to territorial sovereignty in Antarctica; (ii) relative proximity of Antarctica to one’s metropolitan territory; (iii) historic and institutional associations with Antarctica; (iv) social and cultural associations; (v) regional or global hegemonic inclinations; (vi) alleged need in relation to resources; (vii) contested uses or practices in Antarctica; (viii) carry-over from intense antipathies outside Antarctica; (ix) national pride in, and mobilisation through, national Antarctic programmes; (x) infrastructure and logistics arrangements; or (xi) denial or constraint of access by one’s strategic competitors or opponents. In practice of course, these are likely to be manifested in combination. The risks inherent in Antarctic nationalism are the risks inherent in unrestrained nationalism anywhere, compounded by its already weak juridical situation. In Antarctica, the intersection of nationalism with resources poses a particular challenge to the regional order and its commitments to shareable public goods such as scientific research and environmental protection.