bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutational Disruption of
cis
-Acting Replication Element 2C in Coxsackievirus B3 Leads to 5′-Terminal Genomic Deletions
Authors: Smithee S. , Tracy S. , Chapman N. M.
Published: September 2015

Following natural human or experimental murine infections and in cell culture, coxsackievirus B (CVB) RNA can persist for weeks in the absence of a cytopathic effect, yet viral RNA remains detectable. Our earlier studies demonstrated that this persistence produced viral RNA with up to 49 nucleotide deletions at the genomic 5′ terminus which partially degraded the cloverleaf (or domain I), an RNA structure required for efficient viral replication. A
cis
-acting replication element (CRE) in the 2C protein-coding region [CRE(2C)] templates the addition of two uridine residues to the virus genome-encoded RNA replication primer VPg prior to positive-strand synthesis. Because our previous work also demonstrated that the genomes of CVB with a 5′-terminal deletion (CVB-TD) have VPg covalently linked, even though they rarely terminate in the canonical UU donated by CRE(2C)-mediated uridylylation of VPg, we hypothesized that a functional (uridylylating) CRE(2C) would be unnecessary for CVB-TD replication. Using the same 16 mutations in the CVB3 CRE(2C) structure that were considered lethal for this virus by others, we demonstrate here both in infected cell cultures and in mice that wild-type (wt) and CVB3-TD strains carrying these mutations with a nonuridylylating CRE(2C) are viable. While the wt genome with the mutated CRE(2C) displays suppressed replication levels similar to those observed in a CVB3-TD strain, mutation of the CRE(2C) function in a CVB3-TD strain does not further decrease replication. Finally, we show that replication of the parental CVB3 strain containing the mutated CRE(2C) drives the
de novo
generation of genomic deletions at the 5′ terminus.

IMPORTANCE
In this report, we demonstrate that while CVB can replicate without a uridylylating CRE(2C), the replication rate suffers significantly. Further, deletions at the 5′ terminus of the genome are generated in this virus population, with this virus population supplanting the wild-type population. This demonstrates that VPg can prime without being specifically uridylylated and that this priming is error prone, resulting in the loss of sequence information from the 5′ terminus. These findings have significance when considering the replication of human enteroviruses, and we believe that these data are unattainable in a cell-free system due to the poor replication of these CRE-deficient viruses.
Regulation of PACT-Mediated Protein Kinase Activation by the OV20.0 Protein of Orf Virus
Authors: Tseng Yeu-Yang , Liao Guan-Ru , Sen Ganes C. , Lin Fong-Yuan , Hsu Wei-Li
Published: September 2015

Double-stranded RNA (dsRNA)-activated protein kinase (PKR), a major component of the cellular antiviral system, is activated by the binding of either dsRNA or the cellular PKR activator, the PACT protein. The suppression of PKR activation is one of the main strategies that viruses employ to circumvent interferon signaling. Orf virus (ORFV), a parapoxvirus from the
Poxviridae
family, causes contagious pustular dermatitis in small ruminants. Previous studies have demonstrated that various OV20.0 isoforms, encoded by the OV20.0L gene, are able to inhibit PKR activation both by sequestering dsRNA and by physically interacting with PKR
in vitro
. Thus, this gene acts as a virulence factor of ORFV when tested using a mouse infection model. In the present study, the regions within OV20.0 that interact with dsRNA and with PKR have been mapped. Furthermore, this study demonstrates for the first time that OV20.0 is also able to interact with the dsRNA binding domain of PACT and that the presence of dsRNA strengthened the interaction of these two molecules. The presence of OV20.0 diminishes PKR phosphorylation when this is stimulated by PACT. Nevertheless, the association of OV20.0 with PKR, rather than with PACT, was found to be essential for reducing PACT-mediated PKR phosphorylation. These observations elucidate a new strategy whereby innate immunity can be evaded by ORFV.

IMPORTANCE
Our previous study indicated that ORFV's two OV20.0 isoforms act as a PKR antagonist via sequestering the PKR activator, dsRNA, and by interacting with PKR, leading to an inhibition of PKR activation (Y. Y. Tseng, F. Y. Lin, S. F. Cheng, D. Tscharke, S. Chulakasian, C. C. Chou, Y. F. Liu, W. S. Chang, M. L. Wong, and W. L. Hsu, J Virol
89:
4966–4979, 2015, doi:10.1128/JVI.03714-14). In the current study, the possible mechanisms by which OV20.0 protein counteracts PKR activation were studied in depth. OV20.0 is able to bind PKR and its two activators, dsRNA and PACT. In addition, OV20.0 binds directly to the RNA binding domains (RBDs) of PKR, and this interaction does not require dsRNA. Moreover, OV20.0 interacts with or occupies the RBD2 and the kinase domain of PKR, which then prevents PACT binding to PKR. Finally, OV20.0 associates with PACT via the RBDs, which may reduce the ability of PACT to induce PKR activation. The findings in this study provide new concepts in relation to how ORFV modulates PKR activation.
Acupuncture for episodic cluster headache: a trigeminal approach
Authors: Hayhoe Simon
Published: September 2015

Following evidence that acupuncture is clinically feasible and cost-effective in the treatment of headache, the UK National Institute for Health and Care Excellence recommends acupuncture as prophylactic treatment for migraine and tension headache. There has thus been expectation that other forms of headache should benefit also. Unfortunately, acupuncture has not generally been successful for cluster headache. This may be due to acupuncturists approaching the problem as one of severe migraine. In fact, cluster headache is classed as a trigeminal autonomic cephalgia. In this case report, episodic cluster headache is treated in the same way as has been shown effective for trigeminal neuralgia. Acupuncture is applied to the contralateral side at points appropriate for stimulating branches of the trigeminal nerve. Thus, ST2 is used for the infraorbital nerve, BL2 and Yuyao for the supratrochlear and supraorbital nerves, and Taiyang for the temporal branch of the zygomatic nerve.
Clinical deterioration in older adults with delirium during early hospitalisation: a prospective cohort study
Authors: Hsieh S Jean , Madahar Purnema , Hope Aluko A , Zapata Jennifer , Gong Michelle N
Published: September 2015

Objectives

To measure the prevalence and incidence of delirium in older adults as they transition from the emergency department (ED) to the inpatient ward, and to determine the association between delirium during early hospitalisation and subsequent clinical deterioration.

Design

Prospective cohort study.

Setting

Urban tertiary care hospital in Bronx, New York.

Participants

Adults aged 65 years or older admitted to the inpatient ward from the ED (n=260).

Measurements

Beginning in the ED, delirium was assessed daily for 3 days, using the Confusion Assessment Method for the Intensive Care Unit.

Outcomes

(1) Clinical deterioration, defined as unanticipated intensive care unit (ICU) admission or in-hospital death (primary outcome); (2) decline in discharge status, defined as discharge to higher level of care, hospice or in-hospital death.

Results

38 of 260 participants (15%) were delirious at least once during the first 3 days of hospitalisation. Of the 29 (11%) patients with delirium in the ED (ie, hospital day 1), delirium persisted into hospital day 2 in 72% (n=21), and persisted for all 3 days in 52% (n=15). In multivariate analyses, as little as 1 episode of delirium during the first 3 days was associated with increased odds of unanticipated ICU admission or in-hospital death (adjusted OR 8.07 (95% CI 1.91 to 34.14); p=0.005). Delirium that persisted for all 3 days was associated with a decline in discharge status, even after adjusting for factors such as severity of illness and baseline cognitive impairment (adjusted OR 4.70 (95% CI 1.41 to 15.63); p=0.012).

Conclusions

Delirium during the first few days of hospitalisation was associated with poor outcomes in older adults admitted from the ED to the inpatient ward. These findings suggest the need for serial delirium monitoring that begins in the ED to identify a high-risk population that may benefit from closer follow-up and intervention.
Corneal infections in the 21st century
Authors: Ong Hon Shing , Corbett Melanie C
Published: September 2015

Ninety years ago, the first issue of the Postgraduate Medical Journal published a review of an article written by Mr Robert Lindsay-Rea, a consultant ophthalmic surgeon in the Western Ophthalmic Hospital and an oculist in the West End Hospital for Nervous Diseases, entitled “A preliminary report on the treatment of keratitis”. Today, microbial keratitis remains an important cause of avoidable visual impairment in the world. The aetiology of microbial keratitis has changed greatly over the past century due to the discovery of antibiotics, improvement in sanitation and education, the rising trend of contact lens wear and increased air travel. Significant advances have also been made in our understanding and management of this important disorder. This article highlights some of these changes and discusses the current management and research.
Protection conferred by live infectious bronchitis vaccine viruses against variant Middle East IS/885/00‐like and IS/1494/06‐like isolates in commercial broiler chicks
Authors: Awad Faez , Forrester Anne , Baylis Matthew , Lemiere Stephane , Ganapathy Kannan , Hussien Hussein Aly , Capua Ilaria
Published: September 2015

The ability of the infectious bronchitis H120 (a Massachusetts strain) and CR88 (a 793B strain) live attenuated vaccine viruses to protect from two Middle East infectious bronchitis virus isolates, IS/885/00‐like (IS/885) and IS/1494/06‐like (IS/1494) in broiler chicks was investigated. Day‐old chicks were separated into three groups, (I) vaccinated with H120 at day‐old followed by CR88 at 14 days‐old, (II) vaccinated with H120 and CR88 simultaneously at day‐old and again with CR88 at 14 days‐old, (III) control unvaccinated. At 30 days‐old, each of the groups was challenged with virulent IS/885 or IS/1494. Protection was evaluated based on the clinical signs, tracheal and kidney gross lesions and tracheal ciliostasis. Results showed that administering combined live H120 and CR88 vaccines simultaneously at day‐old followed by CR88 vaccine at 14 days‐old gave more than 80 per cent tracheal ciliary protection from both of the Middle East isolates. In addition, this programme conferred 100 per cent protection from clinical signs and tracheal or kidney lesions. The other vaccination programme, H120 at day‐old followed by CR88 at 14 days‐old, the tracheal ciliary protection conferred were 60 per cent and 80 per cent from IS/885/00‐like and IS/1494/06‐like, respectively.
Vets and aquaculture: an evolving relationship
Authors: Soutar Ronnie
Published: September 2015

Aquaculture is one of the largest farming sectors in the UK, particularly in Scotland. Although veterinary involvement remains small, vets have proved their worth in the industry. As part of Veterinary Record 's continuing series of articles discussing the state of different sectors of the veterinary profession, Ronnie Soutar describes the growth of aquaculture and the evolving relationship between the industry and profession
Self-starting cumulative sum harvest control rule (SS-CUSUM-HCR) for status-quo management of data-limited fisheries
Authors: Pazhayamadom Deepak George , Kelly Ciarán J. , Rogan Emer , Codling Edward A.
Published: September 2015

We demonstrate a harvest control rule based on the self-starting cumulative sum (SS-CUSUM) control chart that can maintain a fish stock at its starting (status-quo) level. The SS-CUSUM is an indicator monitoring tool commonly used in quality control engineering and does not require a long time series or predefined reference point for detecting temporal trends. The reference points in SS-CUSUM are calibrated in the form of running means that are updated on an ongoing basis when new observations become available. The SS-CUSUM can be initiated with as few as two observations in the time series and can be applied long before many other methods, soon after initial data become available. A wide range of stock indicators can be monitored, but in this study, we demonstrate the method using an equally weighted sum of two indicators: a recruitment indicator and a large fish indicator from a simulated fishery. We assume that no life history data are available other than 2 years of both indicator data and current harvest levels when the SS-CUSUM initiates. The signals generated from SS-CUSUM trigger a harvest control rule (SS-CUSUM-HCR), where the shift that occurs in the indicator time series is computed and is used as an adjustment factor for updating the total allowable catch. Our study shows that the SS-CUSUM-HCR can maintain the fish stock at its starting status-quo level (even for overfished initial states) but has limited scope if the fishery is already in an undesirable state such as a stock collapse. We discuss how the SS-CUSUM approach could be adapted to move beyond a status-quo management strategy, if additional information on the desirable state of the fishery is available.
Could the DiversiLab® semi-automated repetitive-sequence-based PCR be an acceptable technique for typing isolates ofPseudomonas aeruginosa? An answer from our experience and a review of the literature
Authors: Brossier Florence , Micaelo Maïté , Luyt Charles-Edouard , Lu Qin , Chastre Jean , Arbelot Charlotte , Trouillet Jean-Louis , Combes Alain , Rouby Jean-Jacques , Jarlier Vincent , Aubry Alexandra
Published: September 2015

Recently the DiversiLab® (DL) system (bioMérieux) was developed as an automated platform that uses repetitive element polymerase chain reaction (rep-PCR) technology for standardized, reproducible DNA fingerprinting of bacteria. The purpose of this study was to evaluate the usefulness of DL rep-PCR for typing Pseudomonas aeruginosa isolates. The performance of DL rep-PCR was compared with that of pulsed-field gel electrophoresis (PFGE) in a prospective multicenter study of patients with ventilator-associated pneumonia due to P. aeruginosa, conducted in 3 intensive care units over a 31-month period. In total, 203 P. aeruginosa isolates from 66 patients, from whom at least 2 consecutive respiratory samples each were collected more than 48 h apart, were typed using DL rep-PCR. Forty isolates (corresponding to 20 patients) were also typed using PFGE of SpeI-digested DNA. The typeability was 100% with DL rep-PCR and 95% with PFGE. The discriminatory power was close for DL rep-PCR and for PFGE (Simpson’s diversity indices of 0.901 and 0.947, respectively). Insufficient agreement between DL rep-PCR and PFGE typing results was observed for the 40 selected isolates (adjusted Rand coefficient of 0.419), mostly due to isolates of the same DL rep-PCR type but of different PFGE types (adjusted Wallace coefficients of 0.306 for DL rep-PCR with PFGE, and of 0.667 for PFGE with DL rep-PCR). Considered together with published data, DL rep-PCR results should be interpreted with caution for the investigation of outbreaks caused by P. aeruginosa and evaluated in conjunction with epidemiological data.
The Alexander polynomial as an intersection of two cycles in a symmetric power
Authors: Kalinin Nikita
Published: September 2015

We consider a braid β which acts on a punctured plane. Then we construct a local system on this plane and find a homology cycle D in its symmetric power, such that D ⋅ β(D) coincides with the Alexander polynomial of the plait closure of β.
Neutrino quantum kinetic equations
Authors: Volpe Cristina
Published: September 2015

Neutrinos propagate in astrophysical and cosmological environments modifying their flavor in intriguing ways. The study of neutrino propagation in media is based on the mean-field, extended mean-field and Boltzmann equations. We summarize salient features of these evolution equations and the methods employed so far to derive them. We emphasize applications to situations of observational interest.
VOLATILITY IN COPPER PRICES IN INDIA
Authors: CHOUDHARY NIDHI , NAIR GIRISH K. , PUROHIT HARSH
Published: September 2015

Copper is more popularly known as “Dr. Copper” especially in developed nations, for it is considered as the pulse of the economy. The metal is considered as most erudite to forecast the level of economic activities. But how much is it relevant for Indian Economy? The proposed study explores this face of the situation and considers if in India copper is capable of influencing the economic activities or if the vice versa situation exists. The study uses the nonlinear cointegration and causality tests to understand the direction of causality in volatility of copper prices in India. The volatility in copper prices are studied with respect to movement in Sensex which is considered as the barometer of capital market in India, movement in INR/USD exchange rate which is a major factor behind volatility in copper prices as per MCX and movement in International Copper prices.
IMPROVED DETECTION OF RARE-EVENT RISK OF A PORTFOLIO WITH U.S. REITs
Authors: SO LEH-CHYAN , YU JUN-YANG
Published: September 2015

In measuring the market risks of a portfolio, value-at-risk (VaR) is one of the most commonly used tools. In this paper, the copula-generalized autoregressive conditional heteroskedasticity (GARCH) method is used to determine whether it is a better alternative for estimating the VaR of portfolios containing U.S. real estate investment trusts (REITs). The FTSE NAREIT US Real Estate Index, all REITs and the S&P 500 index are used to construct a portfolio. In total, 2800 daily data covering the period of the subprime mortgage crisis of 2007–2009 are used in this paper. We used six constant and two time-varying copula models combined with two GARCH models to form sixteen copula-GARCH models to depict the joint distribution of the two assets in the portfolio. We then computed corresponding one-day VaRs. Compared with the traditional VaR models, our results showed that the time-varying symmetrized Joe–Clayton (SJC) copula model combined with the GARCH Student-t innovation (tvSJC-copula–GARCHt) performed the best, regardless of the market situation. Hence, it could be served as a better way of detecting rare-event risk.
Plasticity in breathing and arterial blood pressure following acute intermittent hypercapnic hypoxia in infant rat pups with a partial loss of 5-HT neurons
Authors: Magnusson Jennifer , Cummings Kevin J.
Published: September 2015

The role of serotonin (5-HT) neurons in cardiovascular responses to acute intermittent hypoxia (AIH) has not been studied in the neonatal period. We hypothesized that a partial loss of 5-HT neurons would reduce arterial blood pressure (BP) at rest, increase the fall in BP during hypoxia, and reduce the long-term facilitation of breathing (vLTF) and BP following AIH. We exposed 2-wk-old, 5,7-dihydroxytryptamine-treated and controls to AIH (10% O2; n = 13 control, 14 treated), acute intermittent hypercapnia (5% CO2; n = 12 and 11), or acute intermittent hypercapnic hypoxia (AIHH; 10% O2, 5% CO2; n = 15 and 17). We gave five 5-min challenges of AIH and acute intermittent hypercapnia, and twenty ∼20-s challenges of AIHH to mimic sleep apnea. Systolic BP (sBP), diastolic BP, mean arterial pressure, heart rate (HR), ventilation (V̇e), and metabolic rate (V̇o2) were continuously monitored. 5,7-Dihydroxytryptamine induced an ∼35% loss of 5-HT neurons from the medullary raphe. Compared with controls, pups deficient in 5-HT neurons had reduced resting sBP (∼6 mmHg), mean arterial pressure (∼5 mmHg), and HR (56 beats/min), and experienced a reduced drop in BP during hypoxia. AIHH induced vLTF in both groups, reflected in increased V̇e and V̇e/V̇o2, and decreased arterial Pco2. The sBP of pups deficient in 5-HT neurons, but not controls, was increased 1 h following AIHH. Our data suggest that a relatively small loss of 5-HT neurons compromises resting BP and HR, but has no influence on ventilatory plasticity induced by AIHH. AIHH may be useful for reversing cardiorespiratory defects related to partial 5-HT system dysfunction.
Spatial variability in cortex-muscle coherence investigated with magnetoencephalography and high-density surface electromyography
Authors: Piitulainen Harri , Botter Alberto , Bourguignon Mathieu , Jousmäki Veikko , Hari Riitta
Published: September 2015

Cortex-muscle coherence (CMC) reflects coupling between magnetoencephalography (MEG) and surface electromyography (sEMG), being strongest during isometric contraction but absent, for unknown reasons, in some individuals. We used a novel nonmagnetic high-density sEMG (HD-sEMG) electrode grid (36 mm × 12 mm; 60 electrodes separated by 3 mm) to study effects of sEMG recording site, electrode derivation, and rectification on the strength of CMC. Monopolar sEMG from right thenar and 306-channel whole-scalp MEG were recorded from 14 subjects during 4-min isometric thumb abduction. CMC was computed for 60 monopolar, 55 bipolar, and 32 Laplacian HD-sEMG derivations, and two derivations were computed to mimic “macroscopic” monopolar and bipolar sEMG (electrode diameter 9 mm; interelectrode distance 21 mm). With unrectified sEMG, 12 subjects showed statistically significant CMC in 91–95% of the HD-sEMG channels, with maximum coherence at ∼25 Hz. CMC was about a fifth stronger for monopolar than bipolar and Laplacian derivations. Monopolar derivations resulted in most uniform CMC distributions across the thenar and in tightest cortical source clusters in the left rolandic hand area. CMC was 19–27% stronger for HD-sEMG than for “macroscopic” monopolar or bipolar derivations. EMG rectification reduced the CMC peak by a quarter, resulted in a more uniformly distributed CMC across the thenar, and provided more tightly clustered cortical sources than unrectifed sEMGs. Moreover, it revealed CMC at ∼12 Hz. We conclude that HD-sEMG, especially with monopolar derivation, can facilitate detection of CMC and that individual muscle anatomy cannot explain the high interindividual CMC variability.
GnRH suppresses excitability of visual processing neurons in the optic tectum
Authors: Umatani Chie , Misu Ryosuke , Oishi Shinya , Yamaguchi Kazuhiko , Abe Hideki , Oka Yoshitaka
Published: September 2015

Animals change their behavior in response to sensory cues in the environment as well as their physiological status. For example, it is generally accepted that their sexual behavior is modulated according to seasonal environmental changes or the individual's maturational/reproductive status, and neuropeptides have been suggested to play important roles in this process. Some behavioral modulation arises from neuropeptide modulation of sensory information processing in the central nervous system, but the neural mechanisms still remain unknown. Here we focused on the neural basis of neuropeptide modulation of visual processing in vertebrates. The terminal nerve neurons that contain gonadotropin-releasing hormone 3 (TN-GnRH3 neurons) are suggested to modulate reproductive behavior and have massive projections to the optic tectum (OT), which plays an important role in visual processing. In the present study, to examine whether GnRH3 modulates retino-tectal neurotransmission in the OT, we analyzed the effect of GnRH3 electrophysiologically and morphologically. We found that field potentials evoked by optic tract fiber stimulation, which represent retino-tectal neurotransmission, were modulated postsynaptically by GnRH3. Whole cell recording from postsynaptic neurons in the retino-tectal pathway suggested that GnRH3 activates large-conductance Ca2+-activated K+ (BK) channels and thereby suppresses membrane excitability. Furthermore, our improved morphological analysis using fluorescently labeled GnRH peptides showed that GnRH receptors are localized mainly around the cell bodies of postsynaptic neurons. Our results indicate that TN-GnRH3 neurons modulate retino-tectal neurotransmission by suppressing the excitability of projection neurons in the OT, which underlies the neuromodulation of behaviorally relevant visual information processing by the neuropeptide GnRH3.
Gender Differences in the Appetite Response to a Satiating Diet
Authors: Bédard Alexandra , Hudon Anne-Marie , Drapeau Vicky , Corneau Louise , Dodin Sylvie , Lemieux Simone
Published: September 2015

We examined gender differences in appetite sensations when exposed to Mediterranean diet (MedDiet) meals and determined whether there are gender differences in the change in the satiating properties of the MedDiet over time. Thirty-eight men and 32 premenopausal women consumed a 4-week isoenergetic MedDiet under controlled conditions. Visual analogue scales were used to measure perceived appetite sensations before and immediately after each meal consumed over the course of one day (Wednesday) of the first and the fourth week of intervention. Women reported greater decreases for desire to eat, hunger, and appetite score than men in response to the consumption of the MedDiet meals (gender-by-meal interactions, resp.,P=0.04,P=0.048, andP=0.03). Fullness and prospective food consumption responses did not significantly differ between men and women. Between the first and the fourth week of intervention, premeal prospective food consumption increased with time in men (P=0.0007) but not in women (P=0.84;Pfor gender-by-time interaction = 0.04). These results indicate gender differences in appetite sensations when exposed to the MedDiet. These results may be useful in order to have a better understanding of gender issues for body weight management.
Backward Surface Wave Propagation and Radiation along a One-Dimensional Folded Cylindrical Helix Array
Authors: Xu Bin , Li Yang
Published: September 2015

Wave propagation along a closely spaced folded cylindrical helix (FCH) array is investigated for the purpose of designing compact array for energy transport and antenna radiation. It is found that the height of this surface wave guiding structure can be decreased from 0.24λ0to 0.06λ0by replacing the monopole element with the FCH. Both the propagation constant and the mode distribution of the dominant wave mechanism are extracted by ESPRIT algorithm, which indicates that a backward propagating surface wave is supported by the array structure. A compact backfire FCH antenna array is designed and measured based on the identified dominant wave mechanism.
Anatomical Study of Chiari Network and the Remnant of Left Venous Valve in the Interior of Right Atrium
Authors: Jansirani D. Devi , Deep S. Shiva , Anandaraja S.
Published: September 2015

Chiari network occurs due to incomplete resorption of right valve of sinus venosus. It is often noticed as fenestrated membranous structure or reticular network like structure in the valve of inferior vena cava and coronary sinus. The remnant of left venous valve is observed as trabeculae over the fossa ovalis. The incidence of Chiari network and the remnant of left venous valve were studied in 80 cadaveric hearts utilized for teaching the undergraduates. The right atrium was opened anterior to sulcus terminalis and the interior was examined for the presence of these embryological remnants. The incidence of Chiari network and left venous valve in the present study is 3.75% and 7.5%, respectively. Chiari network was observed as a fenestrated membranous structure in 2 specimens and a reticular network in 1 specimen, with variable extension to coronary sinus opening and right atrial wall. The remnant of left venous valve was observed as multiple fine strands in 3 specimens and trabecular structure in 3 specimens. These structures may create diagnostic confusion, difficulty in interventional procedures, and complications like thromboembolic events. Hence, the knowledge about the incidence, morphology, and clinical manifestations of these rare embryological remnants is mandatory.
Prediction of Crack for Drilling Process on Alumina Using Neural Network and Taguchi Method
Authors: Lee Kingsun
Published: September 2015

This study analyzes a variety of significant drilling conditions on aluminum oxide (withL18orthogonal array) using a diamond drill. The drilling parameters evaluated are spindle speed, feed rate, depth of cut, and diamond abrasive size. An orthogonal array, signal-to-noise (S/N) ratio, and analysis of variance (ANOVA) are employed to analyze the effects of these drilling parameters. The results were confirmed by experiments, which indicated that the selected drilling parameters effectively reduce the crack. The neural network is applied to establish a model based on the relationship between input parameters (spindle speed, feed rate, depth of cut, and diamond abrasive size) and output parameter (cracking area percentage). The neural network can predict individual crack in terms of input parameters, which provides faster and more automated model synthesis. Accurate prediction of crack ensures that poor drilling parameters are not suitable for machining products, avoiding the fabrication of poor-quality products. Confirmation experiments showed that neural network precisely predicted the cracking area percentage in drilling of alumina.
Social Support and Self-Reported Stress Levels in a Predominantly African American Sample of Women with Systemic Lupus Erythematosus
Authors: Williams Edith Marie , Zhang Jiajia , Anderson Judith , Bruner Larisa , Tumiel-Berhalter Laurene
Published: September 2015

Lupus patients should avoid stress because physical or emotional stress can affect overall physical health. It has been suggested that social support has a positive influence on health status, but there is a lack of information in the literature on the association between the two among lupus patients. The current study investigated the association between social support and self-reported stress and coping status among African American women with lupus using data collected from two linked cross-sectional surveys. No social support differences in groups of high and low stress/coping were revealed; a duplicate study with a larger sample size is required.
A Nondominated Genetic Algorithm Procedure for Multiobjective Discrete Network Design under Demand Uncertainty
Authors: Changzhi Bian
Published: September 2015

This paper addresses the multiobjective discrete network design problem under demand uncertainty. The OD travel demands are supposed to be random variables with the given probability distribution. The problem is formulated as a bilevel stochastic optimization model where the decision maker’s objective is to minimize the construction cost, the expectation, and the standard deviation of total travel time simultaneously and the user’s route choice is described using user equilibrium model on the improved network under all scenarios of uncertain demand. The proposed model generates globally near-optimal Pareto solutions for network configurations based on the Monte Carlo simulation and nondominated sorting genetic algorithms II. Numerical experiments implemented on Nguyen-Dupuis test network show trade-offs among construction cost, the expectation, and standard deviation of total travel time under uncertainty are obvious. Investment on transportation facilities is an efficient method to improve the network performance and reduce risk under demand uncertainty, but it has an obvious marginal decreasing effect.
Unidirectional Cordenka Fibre-Reinforced Furan Resin Full Biocomposite: Properties and Influence of High Fibre Mass Fraction
Authors: Malaba Talent , Wang Jiajun
Published: September 2015

A full biocomposite was fabricated from Cordenka CR fibre and furan resin. High fibre mass fractions (FMF) were achieved by pressing the CR fibres into unidirectional sheets prior to incorporation into the resin. Results of testing indicated that the tensile properties of the biocomposite were improved by the initial increase of FMF from 51 to 64%, with a subsequent increase of FMF to 75% resulting in a deterioration of those properties. Examination of the tensile fracture surfaces with a scanning electron microscope (SEM) revealed moderate deterioration in fibre-matrix adhesion after the initial increase of FMF. Further increase of the FMF to 75% was shown by SEM to result in worse fibre-matrix adhesion. On the other hand, the flexural, interlaminar-shear, and dynamic mechanical properties were adversely affected by the increase in fibre-mass fraction from 51 through 75%. These effects were mainly attributed to reduced fibre wetting that resulted in weakened fibre-matrix interfacial bonding and subsequent poor stress exchange at the fibre-matrix interface. Observations made with a digital microscope revealed normal crack behaviour in the laminated composite, and the shear fracture modes were I and II. This biocomposite has mechanical properties comparable to those of flax and glass fibre-reinforced furan resin biocomposites.
Realization of SVM Algorithm for Indirect Matrix Converter and Its Application in Power Factor Control
Authors: Li Gang
Published: September 2015

Compared with AC‐DC‐AC converter, matrix converter (MC) has several advantages for its bidirectional power flow, controllable power factor, and the absence of large energy storage in dc‐link. The topology of MC includes direct matrix converter (DMC) and indirect matrix converter (IMC). IMC has received great attention worldwide because of its easy implementation and safe commutation. Space vector PWM (SVM) algorithm for indirect matrix converter is realized on DSP and CPLD platform in this paper. The control of the rectifier and inverter in IMC can be decoupled because of the intermediate dc‐link. The space vector modulation scheme for IMC is discussed and the PWM sequences for the rectifier and inverter are generated. And a two‐step commutation of zero current switching (ZCS) in the rectifier is achieved. Input power factor of IMC can be changed by adjusting the angle of the reference current vector. Experimental tests have been conducted on a RB‐IGBT based indirect matrix converter prototype. The results verify the performance of the SVM algorithm and the ability of power factor correction.
Identification of Structural Damage in Bridges Using High-Frequency Vibrational Responses
Authors: Mekjavić Ivana
Published: September 2015

The present research aims to develop an effective and applicable structural damage detection method. A damage identification approach using only the changes of measured natural frequencies is presented. The structural damage model is assumed to be associated with a reduction of a contribution to the element stiffness matrix equivalent to a scalar reduction of the material modulus. The computational technique used to identify the damage from the measured data is described. The performance of the proposed technique on numerically simulated real concrete girder bridge is evaluated using imposed damage scenarios. To demonstrate the applicability of the proposed method by employing experimental measured natural frequencies this technique is applied for the first time to a simply supported reinforced concrete beam statically loaded incrementally to failure. The results of the damage identification procedure show that the proposed method can accurately locate the damage and predict the extent of the damage using high-frequency (here beyond the 4th order) vibrational responses.
Mechanisms of Cancer Cell Dormancy—Another Hallmark of Cancer?
Authors: Yeh Albert C. , Ramaswamy Sridhar
Published: September 2015

Disease relapse in cancer patients many years after clinical remission, often referred to as cancer dormancy, is well documented but remains an incompletely understood phenomenon on the biologic level. Recent reviews have summarized potential models that can explain this phenomenon, including angiogenic, immunologic, and cellular dormancy. We focus on mechanisms of cellular dormancy as newer biologic insights have enabled better understanding of this process. We provide a historical context, synthesize current advances in the field, and propose a mechanistic framework that treats cancer cell dormancy as a dynamic cell state conferring a fitness advantage to an evolving malignancy under stress. Cellular dormancy appears to be an active process that can be toggled through a variety of signaling mechanisms that ultimately downregulate the RAS/MAPK and PI(3)K/AKT pathways, an ability that is preserved even in cancers that constitutively depend on these pathways for their growth and survival. Just as unbridled proliferation is a key hallmark of cancer, the ability of cancer cells to become quiescent may be critical to evolving malignancies, with implications for understanding cancer initiation, progression, and treatment resistance. Cancer Res; 75(23); 5014–22. ©2015 AACR.
Hypoxia Promotes Synergy between Mitomycin C and Bortezomib through a Coordinated Process of Bcl-xL Phosphorylation and Mitochondrial Translocation of p53
Authors: Song Xinxin , Dilly Ashok-Kumar , Choudry Haroon Asif , Bartlett David L. , Kwon Yong Tae , Lee Yong J.
Published: September 2015

Colorectal peritoneal carcinomatosis (CPC) exhibits severe tumor hypoxia, leading to drug resistance and disease aggressiveness. This study demonstrates that the combination of the chemotherapeutic agent mitomycin C with the proteasome inhibitor bortezomib induced synergistic cytotoxicity and apoptosis, which was even more effective under hypoxia in colorectal cancer cells. The combination of mitomycin C and bortezomib at sublethal doses induced activation of c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase and resulted in Bcl-xL phosphorylation at Serine 62, leading to dissociation of Bcl-xL from proapoptotic Bak. Interestingly, the intracellular level of p53 became elevated and p53 translocated to the mitochondria during the combinatorial treatment, in particular under hypoxia. The coordinated action of Bcl-xL phosphorylation and p53 translocation to the mitochondria resulted in conformational activation of Bak oligomerization, facilitating cytochrome c release and apoptosis induction. In addition, the combinatorial treatment with mitomycin C and bortezomib significantly inhibited intraperitoneal tumor growth in LS174T cells and increased apoptosis, especially under hypoxic conditions in vivo. This study provides a preclinical rationale for the use of combination therapies for CPC patients.

Implications: The combination of a chemotherapy agent and proteasome inhibitor at sublethal doses induced synergistic apoptosis, in particular under hypoxia, in vitro and in vivo through coordinated action of Bcl-xL and p53 on Bak activation. Mol Cancer Res; 13(12); 1533–43. ©2015 AACR.
Metformin Use and Risk of Prostate Cancer: Results from the REDUCE Study
Authors: Feng Tom , Sun Xizi , Howard Lauren E. , Vidal Adriana C. , Gaines Alexis R. , Moreira Daniel M. , Castro-Santamaria Ramiro , Andriole Gerald L. , Freedland Stephen J.
Published: September 2015

The role of metformin in prostate cancer chemoprevention remains unclear. REDUCE, which followed biopsy-negative men with protocol-dictated PSA-independent biopsies at 2- and 4-years, provides an opportunity to evaluate the link between metformin use and prostate cancer diagnosis with minimal confounding from screening biases. In diabetic men from REDUCE, we tested the association between metformin use, use of other antidiabetic medications, versus no antidiabetic medication use, and prostate cancer diagnosis as well as prostate cancer grade (low-grade Gleason 4–6 and high-grade Gleason 7–10) using logistic regression. Of the 540 diabetic men with complete data, 205 (38%) did not report use of any antidiabetic medications, 141 (26%) reported use of at least one antidiabetic medication other than metformin, and 194 (36%) reported use of metformin. During the 4-year study, 122 men (23%) were diagnosed with prostate cancer. After adjusting for various clinical and demographic characteristics, we found that metformin use was not significantly associated with total (OR, 1.19; P = 0.50), low- (OR, 1.01; P = 0.96), or high-grade (OR, 1.83; P = 0.19) prostate cancer diagnosis. Likewise, there was no significant association between the use of non-metformin antidiabetic medications and prostate cancer risk in both crude (OR, 1.02; P = 0.95) and multivariable analysis (OR, 0.85; P = 0.56). Furthermore, the interactions between antidiabetic medication use and BMI, geographic location, coronary artery disease, smoking, and treatment group were not significant (all P > 0.05). Among diabetic men with a negative prestudy biopsy who all underwent biopsies largely independent of PSA, metformin use was not associated with reduced risk of prostate cancer diagnosis. Cancer Prev Res; 8(11); 1055–60. ©2015 AACR.
The FDA Guidance on Therapeutic Cancer Vaccines: The Need for Revision to Include Preventive Cancer Vaccines or for a New Guidance Dedicated to Them
Authors: Finn Olivera J. , Khleif Samir N. , Herberman Ronald B.
Published: September 2015

Cancer vaccines based on antigens derived from self molecules rather than pathogens have been under basic and clinical investigations for many years. Up until very recently, they had been tested primarily in the setting of metastatic disease with the goal to engage the immune system in slowing down disease progression. Many therapeutic vaccine trials, either investigator initiated or led by pharmaceutical companies, have been completed and many are currently ongoing, following the FDA Guidance on therapeutic cancer vaccines published in 2011. In recent years, the target of cancer vaccines is being shifted to early cancer and even premalignant disease with the goal of preventing cancer. Although some issues addressed in the FDA Guidance on therapeutic vaccines apply to preventive vaccines, many do not. Here, we discuss a set of recommendations for revising the current Guidance to also cover preventive vaccines, or to include in a new Guidance dedicated specifically to vaccines for cancer prevention. Cancer Prev Res; 8(11); 1011–6. ©2015 AACR.
Plasma Proendothelin-1 as an Early Marker of Bronchopulmonary Dysplasia
Authors: Baumann Philipp , Fouzas Sotirios , Pramana Isabelle , Grass Beate , Niesse Oliver , Bührer Christoph , Spanaus Katharina , Wellmann Sven
Published: September 2015

Background: Bronchopulmonary dysplasia (BPD) is a common complication in preterm infants. Clinical prediction of BPD at an early stage in life is difficult. Plasma proendothelin-1 (CT-proET-1) is a lung injury biomarker in pulmonary hypertension and respiratory distress. Objective: To assess the prognostic ability of CT-proET-1 in BPD. Methods: In 227 prospectively enrolled preterm infants born at <32 weeks gestational age (GA), plasma CT-proET-1 was measured at birth, day of life (DOL) 2, 3, 6 and 28, and at 36 weeks postmenstrual age (PMA). BPD was defined as mild in infants requiring supplemental oxygen at DOL 28 and moderate/severe in those requiring it at 36 weeks PMA. Results: The predictive ability of CT-proET-1 for any BPD was poor at birth [area under the ROC curve (AUC) 0.654, 95% CI 0.494-0.814], moderate at DOL 2 and 3 (AUC 0.769, 95% CI 0.666-0.872) and excellent at DOL 6 (AUC 0.918, 95% CI 0.840-0.995). Multivariable regression analysis revealed that CT-proET-1 levels at DOL 2, 3, 6 and 28 were strongly related to the duration of oxygen supplementation, independently of GA and the duration of respiratory support. Conclusions: CT-proET-1 is a novel promising biomarker for predicting the development of BPD in preterm infants when measured at the end of the first week of life.
Radiosurgery for Large Arteriovenous Malformations as a Single-Session or Staged Treatment
Authors: Chytka Tomas , Liscak Roman , Kozubiková Petra , Vymazal Josef
Published: September 2015

Background/Objectives: The treatment of large arteriovenous malformations (AVMs) presents a challenge and the effectiveness of radiosurgery decreases with increasing treatment volume. Here, we analyzed and compared single-session treatment for AVMs >15 cm3 with staged treatment, when the volume of a large AVM was divided into 2 or more compartments, which were subsequently treated at intervals of a few months. In the event that complete obliteration was not achieved within 3 years, repeat radiosurgery was considered. Methods/Results: Between 1993 and 2011, gamma-knife radiosurgery was performed on 50 patients with large AVMs. A total of 27 of them, with volumes ranging from 15.1 to 27 cm3 (median = 17.8), were treated in a single session, with a marginal dose ranging from 10 to 17 Gy (median = 15). Complete obliteration was achieved in 7 (26%) of these; in 14 patients the treatment was repeated after a median of 38 months. The volume of AVMs subjected to repeat treatment regressed and ranged from 6.76 to 16.4 cm3 (median = 7.7), with the marginal dose ranging from 13 to 18 Gy (median = 17); 10 patients later achieved complete obliteration at a median of 79 months after the initial treatment. Overall, 63% of patients achieved complete obliteration of AVM after treatment. Rebleeding in a latent period was recorded in 3 patients (11%) and symptomatic collateral edema in 2 (7%); 23 patients were treated using the staged method, with the interval between staged treatments usually being 6 months. Their overall AVM volume ranged from 13.2 to 46.6 cm3 (median = 23.3), the volume for a single stage ranged from 4.5 to 31.3 cm3 (median 11.7), and the marginal dose ranged from 10 to 18 Gy (median = 17). Complete obliteration was achieved in 4 (17%) of them, in 8 patients the treatment was repeated at a median of 53 months after the first treatment, and a third retreatment was performed on 2 patients 98 and 102 months, respectively, after the first treatment. The volume for repeated treatment of AVMs ranged from 0.81 to 7.7 cm3 (median = 3.3), with the marginal dose ranging from 14 to 20 Gy (median 17.5). Of all the retreated patients, 5 AVMs subsequently achieved complete obliteration. Overall, 9 patients (39%) were totally cured. Rebleeding in a latent period was observed in 1 of these patients (4.3%) and symptomatic edema in another 1 (4.3%). Conclusions: Radiosurgery of large AVMs is a valuable treatment either as a single-session or staged treatment, with a reasonable chance of cure and a low risk of complications.
Human Chorionic Gonadotropin Stimulation Test in Prepubertal Children with Micropenis Can Accurately Predict Leydig Cell Function in Pubertal or Postpubertal Adolescents
Authors: Ishii Tomohiro , Matsuo Nobutake , Sato Seiji , Ogata Tsutomu , Tamai Shinya , Anzo Makoto , Kamimaki Tsutomu , Sasaki Goro , Inokuchi Mikako , Hori Naoaki , Amano Naoko , Narumi Satoshi , Shibata Hironori , Hasegawa Tomonobu
Published: September 2015

Background/Aim: To evaluate the accuracy of the human chorionic gonadotropin (hCG) stimulation test in children with micropenis in predicting later Leydig cell function. Methods: We conducted a retrospective investigation of testosterone response to a 3-day hCG test (3,000 IU/m2/day) in prepuberty to indicate the need for hormone replacement therapy (HRT) in adolescence. Results: Fifty Japanese boys (range, 0.8-15.4 years of age; median, 8.9) with micropenis were enrolled. Thirty-four spontaneously developed puberty and preserved the ability of testosterone production (group 1), while 16 did not develop any pubertal signs without HRT (group 2). Serum testosterone levels after the hCG test (post-hCG T) in group 2 (range, <0.05-1.1 ng/ml; median, 0.24) were significantly lower than in group 1 (range, 0.5-8.7 ng/ml; median, 2.4; p < 0.0001). Based on true positives who required continuous HRT, the area under the receiver-operating characteristics curve for post-hCG T was 0.983 [95% confidence interval (CI), 0.90-1.00]. The post-hCG T cut-off level corresponding to the Youden index was 1.1 ng/ml (95% CI, 1.0-1.1), with a sensitivity of 100.0% (95% CI, 79.4-100.0) and a specificity of 94.1% (95% CI, 80.3-99.3). Conclusions: The hCG test in prepubertal children with micropenis can be useful for predicting Leydig cell function in pubertal or postpubertal adolescents. The post-hCG T cut-off level of 1.1 ng/ml is recommended to screen for those who will likely require HRT for pubertal development.