bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbohydrate Catabolism in Phaeobacter inhibens DSM 17395, a Member of the Marine Roseobacter Clade
Authors: Wiegmann Katharina , Hensler Michael , Wöhlbrand Lars , Ulbrich Marcus , Schomburg Dietmar , Rabus Ralf
Published: May 2014

Since genome analysis did not allow unambiguous reconstruction of transport, catabolism, and substrate-specific regulation for several important carbohydrates in
Phaeobacter inhibens
DSM 17395, proteomic and metabolomic analyses of
N
-acetylglucosamine-, mannitol-, sucrose-, glucose-, and xylose-grown cells were carried out to close this knowledge gap. These carbohydrates can pass through the outer membrane via porins identified in the outer membrane fraction. For transport across the cytoplasmic membrane, carbohydrate-specific ABC transport systems were identified. Their coding genes mostly colocalize with the respective “catabolic” and “regulatory” genes. The degradation of
N
-acetylglucosamine proceeds via
N
-acetylglucosamine-6-phosphate and glucosamine-6-phosphate directly to fructose-6-phosphate; two of the three enzymes involved were newly predicted and identified. Mannitol is catabolized via fructose, sucrose via fructose and glucose, glucose via glucose-6-phosphate, and xylose via xylulose-5-phosphate. Of the 30 proteins predicted to be involved in uptake, regulation, and degradation, 28 were identified by proteomics and 19 were assigned to their respective functions for the first time. The peripheral degradation pathways feed into the Entner-Doudoroff (ED) pathway, which is connected to the lower branch of the Embden-Meyerhof-Parnas (EMP) pathway. The enzyme constituents of these pathways displayed higher abundances in
P. inhibens
DSM 17395 cells grown with any of the five carbohydrates tested than in succinate-grown cells. Conversely, gluconeogenesis is turned on during succinate utilization. While tricarboxylic acid (TCA) cycle proteins remained mainly unchanged, the abundance profiles of their metabolites reflected the differing growth rates achieved with the different substrates tested. Homologs of the 74 genes involved in the reconstructed catabolic pathways and central metabolism are present in various
Roseobacter
clade members.
Fusion of Self-Assembling Amphipathic Oligopeptides with Cyclodextrin Glycosyltransferase Improves 2-
O
-
d
-Glucopyranosyl-
l
-Ascorbic Acid Synthesis with Soluble Starch as the Glycosyl Donor
Authors: Han Ruizhi , Li Jianghua , Shin Hyun-dong , Chen Rachel R. , Liu Long , Du Guocheng , Chen Jian
Published: May 2014

In this study, we fused six self-assembling amphipathic peptides (SAPs) with cyclodextrin glycosyltransferase (CGTase) from
Paenibacillus macerans
to catalyze 2-
O
-
d
-glucopyranosyl-
l
-ascorbic acid (AA-2G) production with cheap substrates, including maltose, maltodextrin, and soluble starch as glycosyl donors. The results showed that two fusion enzymes, SAP5-CGTase and SAP6-CGTase, increased AA-2G yields to 2.33- and 3.36-fold that of wild-type CGTase when soluble starch was used as a substrate. The cyclization activities of these enzymes decreased, while disproportionation activities increased. Enzymatic characterization of the two fusion enzymes was performed, and kinetics analysis of AA-2G synthesis confirmed the enhanced soluble starch specificity of SAP5-CGTase and SAP6-CGTase compared to that in the wild-type CGTase. As revealed by structure modeling of the fusion and wild-type CGTases, enhanced substrate-binding capacity may result from the increased number of hydrogen bonds present after fusion. This study demonstrates an effective protein fusion approach to improving the substrate specificity of CGTase for AA-2G synthesis. Fusion enzymes, especially SAP6-CGTase, are promising starting points for further development through protein engineering.
Characterization of the Chloroquine Resistance Transporter Homologue in Toxoplasma gondii
Authors: Warring Sally D. , Dou Zhicheng , Carruthers Vern B. , McFadden Geoffrey I. , van Dooren Giel G.
Published: May 2014

Mutations in the
Plasmodium falciparum
chloroquine resistance transporter (
Pf
CRT) protein confer resistance to the antimalarial drug chloroquine.
Pf
CRT localizes to the parasite digestive vacuole, the site of chloroquine action, where it mediates resistance by transporting chloroquine out of the digestive vacuole.
Pf
CRT belongs to a family of transporter proteins called the chloroquine resistance transporter family. CRT family proteins are found throughout the Apicomplexa, in some protists, and in plants. Despite the importance of
Pf
CRT in drug resistance, little is known about the evolution or native function of CRT proteins. The apicomplexan parasite
Toxoplasma gondii
contains one CRT family protein. We demonstrate that
T. gondii
CRT (
Tg
CRT) colocalizes with markers for the vacuolar (VAC) compartment in these parasites. The
Tg
CRT-containing VAC is a highly dynamic organelle, changing its morphology and protein composition between intracellular and extracellular forms of the parasite. Regulated knockdown of
Tg
CRT expression resulted in modest reduction in parasite fitness and swelling of the VAC, indicating that
Tg
CRT contributes to parasite growth and VAC physiology. Together, our findings provide new information on the role of CRT family proteins in apicomplexan parasites.
Influence of the AgrC-AgrA Complex on the Response Time of Staphylococcus aureus Quorum Sensing
Authors: Srivastava Sandeep K. , Rajasree Kalagiri , Fasim Aneesa , Arakere Gayathri , Gopal Balasubramanian
Published: May 2014

The
Staphylococcus aureus
agr
quorum-sensing system plays a major role in the transition from the persistent to the virulent phenotype.
S. aureus
agr
type I to IV strains are characterized by mutations in the sensor domain of the histidine kinase AgrC and differences in the sequences of the secreted autoinducing peptides (AIP). Here we demonstrate that interactions between the cytosolic domain of AgrC (AgrC
Cyto
) and the response regulator domain of AgrA (AgrA
RR
) dictate the spontaneity of the cellular response to AIP stimuli. The crystal structure of AgrC
Cyto
provided a basis for a mechanistic model of AgrC-AgrA interactions. This model enabled an analysis of the biochemical and biophysical parameters of AgrC-AgrA interactions in the context of the conformational features of the AgrC-AgrA complex. This analysis revealed distinct sequence and conformational features that determine the affinity, specificity, and kinetics of the phosphotransfer reaction. This step, which governs the response time for transcriptional reengineering triggered by an AIP stimulus, is independent of the
agr
type and similar for agonist and antagonist stimuli. These experimental data could serve as a basis on which to validate simulations of the quorum-sensing response and for strategies that employ the
agr
quorum-sensing system to combat biofilm formation in
S. aureus
infections.
Genetic Requirements for Sensitivity of Bacteriophage T7 to Dideoxythymidine
Authors: Tran Ngoc Q. , Tabor Stanley , Richardson Charles C.
Published: May 2014

We previously reported that the presence of dideoxythymidine (ddT) in the growth medium selectively inhibits the ability of bacteriophage T7 to infect
Escherichia coli
by inhibiting phage DNA synthese (N. Q. Tran, L. F. Rezende, U. Qimron, C. C. Richardson, and S. Tabor, Proc. Natl. Acad. Sci. U. S. A. 105:9373–9378, 2008, doi:10.1073/pnas.0804164105). In the presence of T7 gene 1.7 protein, ddT is taken up into the
E. coli
cell and converted to ddTTP. ddTTP is incorporated into DNA as ddTMP by the T7 DNA polymerase, resulting in chain termination. We have identified the pathway by which exogenous ddT is converted to ddTTP. The pathway consists of ddT transport by host nucleoside permeases and phosphorylation to ddTMP by the host thymidine kinase. T7 gene 1.7 protein phosphorylates ddTMP and ddTDP, resulting in ddTTP. A 74-residue peptide of the gene 1.7 protein confers ddT sensitivity to the same extent as the 196-residue wild-type gene 1.7 protein. We also show that cleavage of thymidine to thymine and deoxyribose-1-phosphate by the host thymidine phosphorylase greatly increases the sensitivity of phage T7 to ddT. Finally, a mutation in T7 DNA polymerase that leads to discrimination against the incorporation of ddTMP eliminates ddT sensitivity.
Towards tailoring of self-management for patients with chronic heart failure or chronic obstructive pulmonary disease: a protocol for an individual patient data meta-analysis
Authors: Jonkman Nini H , Westland Heleen , Trappenburg Jaap C A , Groenwold Rolf H H , Effing-Tijdhof Tanja W , Troosters Thierry , van der Palen Job , Bourbeau Jean , Jaarsma Tiny , Hoes Arno W , Schuurmans Marieke J
Published: May 2014

Introduction

Self-management interventions in patients with chronic conditions have received increasing attention over the past few years, yet the meta-analyses encountered considerable heterogeneity in results. This suggests that the effectiveness of self-management interventions must be assessed in the context of which components are responsible for eliciting the effect and in which subgroups of patients the intervention works best. The aim of the present study is to identify condition-transcending determinants of success of self-management interventions in two parallel individual patient data meta-analyses of self-management trials in patients with congestive heart failure (CHF) and in patients with chronic obstructive pulmonary disease (COPD).

Methods and analysis

Investigators of 53 randomised trials (32 in CHF and 21 in COPD) will be requested to share their de-identified individual patient data. Data will be analysed using random effects models, taking clustering within studies into account. Effect modification by age, sex, disease severity, symptom status, comorbid conditions and level of education will be assessed. Sensitivity analyses will be conducted to assess the robustness of the findings.

Ethics and dissemination

The de-identified individual patient data are used only for the purpose for which they were originally collected and for which ethical approval has been obtained by the original investigators. Knowledge on the effective ingredients of self-management programmes and identification of subgroups of patients in which those interventions are most effective will guide the development of evidence-based personalised self-management interventions for patients with CHF and COPD as well as with other chronic diseases.

Trial registration number

PROSPERO: CRD42013004698.
The development and exploratory analysis of the Back Pain Attitudes Questionnaire (Back-PAQ)
Authors: Darlow Ben , Perry Meredith , Mathieson Fiona , Stanley James , Melloh Markus , Marsh Reginald , Baxter G David , Dowell Anthony
Published: May 2014

Objectives

To develop an instrument to assess attitudes and underlying beliefs about back pain, and subsequently investigate its internal consistency and underlying structures.

Design

The instrument was developed by a multidisciplinary team of clinicians and researchers based on analysis of qualitative interviews with people experiencing acute and chronic back pain. Exploratory analysis was conducted using data from a population-based cross-sectional survey.

Setting

Qualitative interviews with community-based participants and subsequent postal survey.

Participants

Instrument development informed by interviews with 12 participants with acute back pain and 11 participants with chronic back pain. Data for exploratory analysis collected from New Zealand residents and citizens aged 18 years and above. 1000 participants were randomly selected from the New Zealand Electoral Roll. 602 valid responses were received.

Measures

The 34-item Back Pain Attitudes Questionnaire (Back-PAQ) was developed. Internal consistency was evaluated by the Cronbach α coefficient. Exploratory analysis investigated the structure of the data using Principal Component Analysis.

Results

The 34-item long form of the scale had acceptable internal consistency (α=0.70; 95% CI 0.66 to 0.73). Exploratory analysis identified five two-item principal components which accounted for 74% of the variance in the reduced data set: ‘vulnerability of the back’; ‘relationship between back pain and injury’; ‘activity participation while experiencing back pain’; ‘prognosis of back pain’ and ‘psychological influences on recovery’. Internal consistency was acceptable for the reduced 10-item scale (α=0.61; 95% CI 0.56 to 0.66) and the identified components (α between 0.50 and 0.78).

Conclusions

The 34-item long form of the scale may be appropriate for use in future cross-sectional studies. The 10-item short form may be appropriate for use as a screening tool, or an outcome assessment instrument. Further testing of the 10-item Back-PAQ's construct validity, reliability, responsiveness to change and predictive ability needs to be conducted.
Preterm nutritional intake and MRI phenotype at term age: a prospective observational study
Authors: Vasu Vimal , Durighel Giuliana , Thomas Louise , Malamateniou Christina , Bell Jimmy D , Rutherford Mary A , Modi Neena
Published: May 2014

Objective

To describe (1) the relationship between nutrition and the preterm-at-term infant phenotype, (2) phenotypic differences between preterm-at-term infants and healthy term born infants and (3) relationships between somatic and brain MRI outcomes.

Design

Prospective observational study.

Setting

UK tertiary neonatal unit.

Participants

Preterm infants (<32 weeks gestation) (n=22) and healthy term infants (n=39)

Main outcome measures

Preterm nutrient intake; total and regional adipose tissue (AT) depot volumes; brain volume and proximal cerebral arterial vessel tortuosity (CAVT) in preterm infants and in term infants.

Results

Preterm nutrition was deficient in protein and high in carbohydrate and fat. Preterm nutrition was not related to AT volumes, brain volume or proximal CAVT score; a positive association was noted between human milk intake and proximal CAVT score (r=0.44, p=0.05). In comparison to term infants, preterm infants had increased total adiposity, comparable brain volumes and reduced proximal CAVT scores. There was a significant negative correlation between deep subcutaneous abdominal AT volume and brain volume in preterm infants (r=−0.58, p=0.01).

Conclusions

Though there are significant phenotypic differences between preterm infants at term and term infants, preterm macronutrient intake does not appear to be a determinant. Our preliminary data suggest that (1) human milk may exert a beneficial effect on cerebral arterial vessel tortuosity and (2) there is a negative correlation between adiposity and brain volume in preterm infants at term. Further work is warranted to see if our findings can be replicated and to understand the causal mechanisms.
Trends in family planning and counselling for women with sickle cell disease in the UK over two decades
Authors: Eissa Asma A , Tuck Susan M , Rantell Khadija , Stott Daniel
Published: May 2014

Background

Pregnancies in women with sickle cell disease (SCD) are known to have high rates of maternal and fetal mortality and morbidity. Given these pregnancy-associated problems for women with SCD, advice both about pregnancy planning and about effective contraception are of paramount importance. This study sought to discover the contraception methods used by women with SCD, what complications women with SCD encounter with contraception, and their experiences of pre-pregnancy counselling and pregnancy planning, and how such issues may have changed over the past two decades.

Method

The study was a multicentre, interview-based, cross-sectional study. Interviews were carried out with 102 women with SCD, in north and central London during 2010, concerning their current and previous contraceptive use, their pregnancy history, their menstrual history, and the advice they received concerning pregnancy planning and contraception. Patient information was anonymised and ethical approval was obtained. These data were compared with data from a similar study undertaken in 1993.

Results

There were significant differences in a number of key areas: the number of unplanned pregnancies decreased from 64% in 1993 to 53% in 2010. The number of women with SCD who were advised not to become pregnant also fell, from 36% to 15%. The use of combined oral contraceptive pills declined, from 45% of the women in 1993 to 31% in 2010. Conversely the use of depot medroxyprogesterone acetate contraception (DMPA) and the levonorgestrel intrauterine system (LNG-IUS) both increased.

Conclusions

Significant changes in the contraceptive methods used by women with SCD are demonstrated in the London population. LNG-IUS use in SCD has not been investigated before. There has been an encouraging decrease in the number of women with SCD who are advised not to become pregnant, perhaps reflecting an improvement in their overall health. Although the number of unplanned pregnancies has fallen, it remains high – emphasising the continuing need for women with SCD to have access to informed advice about pregnancy-associated issues and contraception.
Mavacoxib and meloxicam for canine osteoarthritis: a randomised clinical comparator trial
Authors: Walton M. B. , Cowderoy E. C. , Wustefeld‐Janssens B. , Lascelles B. D. X. , Innes J. F.
Published: May 2014

NSAIDs are the cornerstone of medical management of canine osteoarthritis (OA). Meloxicam is a daily‐administered NSAID widely available in a liquid formulation and manufacturer's summary of product characteristics (SPC) advise that it is given at the lowest effective dose. Mavacoxib is a long‐acting NSAID given as a monthly tablet. This study compares these drugs in the management of canine OA. In all, 111 dogs with OA of the elbow, hip or stifle were randomly assigned to receive one of these NSAIDs for a 12‐week period, and to administer them as per the manufacturer's SPC. Outcomes, including ground reaction forces and three validated clinical metrology instruments, were measured at baseline, 6 and 12 weeks. Improvements were seen in all outcome measures for both groups to a similar degree, and adverse events occurred at a similar rate. There were significant improvements in outcome measures from week 6 to week 12, as well as from baseline. Long‐term meloxicam dose was more important than recent dose. Clinical efficacy and adverse event rates are similar for meloxicam and mavacoxib when administered as per their UK SPC. This is relevant information for veterinary surgeons when prescribing NSAID treatment for canine OA.
Topological phase transition in asymmetric nuclear matter
Authors: Phat Tran Huu , Thu Nguyen Van
Published: May 2014

Starting from an effective model of asymmetric nuclear matter we show that at finite temperature T and baryon chemical potential μB there exists a topological phase transition from state of non-Fermi liquid to that of Fermi liquid which is protected by winding numbers. At low μB the transition is first-order, then extends to a second-order phase transition at larger μB through a tri-critical point. The isospin dependences of the tri-critical point and the phase diagram in the (T, μB)-plane are established. The distinction between this type of phase transition and the similar phenomenon caused by the Silver Blaze property (SBP) at T = 0 is confirmed for isospin varying from 0 to 1. We reveal that the topological phase transition could emerge in a large class of nuclear theories.
HDAC6 contributes to pathological responses of heart and skeletal muscle to chronic angiotensin-II signaling
Authors: Demos-Davies Kimberly M. , Ferguson Bradley S. , Cavasin Maria A. , Mahaffey Jennifer H. , Williams Sarah M. , Spiltoir Jessica I. , Schuetze Katherine B. , Horn Todd R. , Chen Bo , Ferrara Claudia , Scellini Beatrice , Piroddi Nicoletta , Tesi Chiara , Poggesi Corrado , Jeong Mark Y. , McKinsey Timothy A.
Published: May 2014

Little is known about the function of the cytoplasmic histone deacetylase HDAC6 in striated muscle. Here, we addressed the role of HDAC6 in cardiac and skeletal muscle remodeling induced by the peptide hormone angiotensin II (ANG II), which plays a central role in blood pressure control, heart failure, and associated skeletal muscle wasting. Comparable with wild-type (WT) mice, HDAC6 null mice developed cardiac hypertrophy and fibrosis in response to ANG II. However, whereas WT mice developed systolic dysfunction upon treatment with ANG II, cardiac function was maintained in HDAC6 null mice treated with ANG II for up to 8 wk. The cardioprotective effect of HDAC6 deletion was mimicked in WT mice treated with the small molecule HDAC6 inhibitor tubastatin A. HDAC6 null mice also exhibited improved left ventricular function in the setting of pressure overload mediated by transverse aortic constriction. HDAC6 inhibition appeared to preserve systolic function, in part, by enhancing cooperativity of myofibrillar force generation. Finally, we show that HDAC6 null mice are resistant to skeletal muscle wasting mediated by chronic ANG-II signaling. These findings define novel roles for HDAC6 in striated muscle and suggest potential for HDAC6-selective inhibitors for the treatment of cardiac dysfunction and muscle wasting in patients with heart failure.
Heparan sulfate side chains have a critical role in the inhibitory effects of perlecan on vascular smooth muscle cell response to arterial injury
Authors: Gotha Lara , Lim Sang Yup , Osherov Azriel B. , Wolff Rafael , Qiang Beiping , Erlich Ilana , Nili Nafiseh , Pillarisetti Sivaram , Chang Ya-Ting , Tran Phan-Kiet , Tryggvason Karl , Hedin Ulf , Tran-Lundmark Karin , Advani Suzanne L. , Gilbert Richard E. , Strauss Bradley H.
Published: May 2014

Perlecan is a proteoglycan composed of a 470-kDa core protein linked to three heparan sulfate (HS) glycosaminoglycan chains. The intact proteoglycan inhibits the smooth muscle cell (SMC) response to vascular injury. Hspg2Δ3/Δ3 (MΔ3/Δ3) mice produce a mutant perlecan lacking the HS side chains. The objective of this study was to determine differences between these two types of perlecan in modifying SMC activities to the arterial injury response, in order to define the specific role of the HS side chains. In vitro proliferative and migratory activities were compared in SMC isolated from MΔ3/Δ3 and wild-type mice. Proliferation of MΔ3/Δ3 SMC was 1.5× greater than in wild type ( P < 0.001), increased by addition of growth factors, and showed a 42% greater migratory response than wild-type cells to PDGF-BB ( P < 0.001). In MΔ3/Δ3 SMC adhesion to fibronectin, and collagen types I and IV was significantly greater than wild type. Addition of DRL-12582, an inducer of perlecan expression, decreased proliferation and migratory response to PDGF-BB stimulation in wild-type SMC compared with MΔ3/Δ3. In an in vivo carotid artery wire injury model, the medial thickness, medial area/lumen ratio, and macrophage infiltration were significantly increased in the MΔ3/Δ3 mice, indicating a prominent role of the HS side chain in limiting vascular injury response. Mutant perlecan that lacks HS side chains had a marked reduction in the inhibition of in vitro SMC function and the in vivo arterial response to injury, indicating the critical role of HS side chains in perlecan function in the vessel wall.
MicroRNAs associated with ischemia-reperfusion injury and cardioprotection by ischemic pre- and postconditioning: protectomiRs
Authors: Varga Zoltán V. , Zvara Ágnes , Faragó Nóra , Kocsis Gabriella F. , Pipicz Márton , Gáspár Renáta , Bencsik Péter , Görbe Anikó , Csonka Csaba , Puskás László G. , Thum Thomas , Csont Tamás , Ferdinandy Péter
Published: May 2014

We aimed to characterize early changes in microRNA expression in acute cardioprotection by ischemic pre- and postconditioning in rat hearts. Hearts isolated from male Wistar rats were subjected to 1) time-matched nonischemic perfusion, 2) ischemia-reperfusion (30 min of coronary occlusion and 120 min of reperfusion), 3) preconditioning (3 × 5 min of coronary occlusion) followed by ischemia-reperfusion, or 4) ischemia-reperfusion with postconditioning (6 × 10 s of global ischemia-reperfusion at the onset of reperfusion). Infarct size was significantly reduced by both interventions. Of 350 different microRNAs assessed by microarray analysis, 147–160 microRNAs showed detectable expression levels. Compared with microRNA alterations induced by ischemia-reperfusion versus time-matched nonischemic controls, five microRNAs were significantly affected by both pre- and postconditioning (microRNA-125b*, microRNA-139-3p, microRNA-320, microRNA-532-3p, and microRNA-188), four microRNAs were significantly affected by preconditioning (microRNA-487b, microRNA-139-5p, microRNA-192, and microRNA-212), and nine microRNAs were significantly affected by postconditioning (microRNA-1, microRNA let-7i, microRNA let-7e, microRNA let-7b, microRNA-181a, microRNA-208, microRNA-328, microRNA-335, and microRNA-503). Expression of randomly selected microRNAs was validated by quantitative real-time PCR. By a systematic comparison of the direction of microRNA expression changes in all groups, we identified microRNAs, specific mimics, or antagomiRs that may have pre- and postconditioning-like cardioprotective effects (protectomiRs). Transfection of selected protectomiRs (mimics of microRNA-139-5p, microRNA-125b*, microRNA let-7b, and inhibitor of microRNA-487b) into cardiac myocytes subjected to simulated ischemia-reperfusion showed a significant cytoprotective effect. This is the first demonstration that the ischemia-reperfusion-induced microRNA expression profile is significantly influenced by both pre- and postconditioning, which shows the involvement of microRNAs in cardioprotective signaling. Moreover, by analysis of microRNA expression patterns in cardioprotection by pre- and postconditioning, specific protectomiRs can be revealed as potential therapeutic tools for the treatment of ischemia-reperfusion injury.
Static frequency tuning accounts for changes in neural synchrony evoked by transient communication signals
Authors: Walz Henriette , Grewe Jan , Benda Jan
Published: May 2014

Although communication signals often vary continuously on the underlying signal parameter, they are perceived as distinct categories. We here report the opposite case where an electrocommunication signal is encoded in four distinct regimes, although the behavior described to date does not show distinct categories. In particular, we studied the encoding of chirps by P-unit afferents in the weakly electric fish Apteronotus leptorhynchus. These fish generate an electric organ discharge that oscillates at a certain individual-specific frequency. The interaction of two fish in communication contexts leads to the emergence of a beating amplitude modulation (AM) at the frequency difference between the two individual signals. This frequency difference represents the social context of the encounter. Chirps are transient increases of the fish's frequency leading to transient changes in the frequency of the AM. We stimulated the cells with the same chirp on different, naturally occurring backgrounds beats. The P-units responded either by synchronization or desynchronization depending on the background. Although the duration of a chirp is often shorter than a full cycle of the AM it elicits, the distinct responses of the P-units to the chirp can be predicted solely from the frequency of the AM based on the static frequency tuning of the cells.
Adaptive Control of Nonlinear Discrete-Time Systems by Using OS-ELM Neural Networks
Authors: Li Xiao-Li , Jia Chao , Liu De-xin , Ding Da-wei
Published: May 2014

As a kind of novel feedforward neural network with single hidden layer, ELM (extreme learning machine) neural networks are studied for the identification and control of nonlinear dynamic systems. The property of simple structure and fast convergence of ELM can be shown clearly. In this paper, we are interested in adaptive control of nonlinear dynamic plants by using OS-ELM (online sequential extreme learning machine) neural networks. Based on data scope division, the problem that training process of ELM neural network is sensitive to the initial training data is also solved. According to the output range of the controlled plant, the data corresponding to this range will be used to initialize ELM. Furthermore, due to the drawback of conventional adaptive control, when the OS-ELM neural network is used for adaptive control of the system with jumping parameters, the topological structure of the neural network can be adjusted dynamically by using multiple model switching strategy, and an MMAC (multiple model adaptive control) will be used to improve the control performance. Simulation results are included to complement the theoretical results.
A Weighted Voting Classifier Based on Differential Evolution
Authors: Zhang Yong , Zhang Hongrui , Cai Jing , Yang Binbin
Published: May 2014

Ensemble learning is to employ multiple individual classifiers and combine their predictions, which could achieve better performance than a single classifier. Considering that different base classifier gives different contribution to the final classification result, this paper assigns greater weights to the classifiers with better performance and proposes a weighted voting approach based on differential evolution. After optimizing the weights of the base classifiers by differential evolution, the proposed method combines the results of each classifier according to the weighted voting combination rule. Experimental results show that the proposed method not only improves the classification accuracy, but also has a strong generalization ability and universality.
Long-Term Maintenance Scheduling of Smart Distribution System through a PSO-TS Algorithm
Authors: Wang Jianxue , Lu Jianming , Bie Zhaohong , You Shutang , Cao Xiaoyu
Published: May 2014

Asset management of distribution systems is an important issue for smart grid. Maintenance scheduling, as an important part of asset management, affects the reliability of distribution equipment and power supply. This research focuses on long-term distribution system maintenance scheduling aided by available operation information, which is a prominent advantage of smart grid over conventional distribution systems. In this paper, the historical and future operation information in smart grid is taken into account through a decoupled time-varying reliability model of equipment. Based on distribution system reliability assessment, a maintenance scheduling model is proposed to determine the optimal implementation time of maintenance activities to minimize distribution systems’ total cost, while satisfying reliability requirements. A combined algorithm that consists of particle swarm optimization and tabu search is designed and applied to the optimization problem. Numerical result verifies that the proposed method can schedule long-term maintenance of distribution systems in smart grid economically and effectively.
Zeolite Y: Synthesis, Modification, and Properties—A Case Revisited
Authors: Lutz Wolfgang
Published: May 2014

Y zeolites dealuminated by steaming were introduced as fluid-cracking catalysts in the year 1970. Extensive research has been done to develop suitable dealumination techniques, to investigate crystal structure, and to characterize catalytic behaviour. However, the origin of the secondary pore system formed in the zeolite structure during dealumination process remained completely obscure over a period of four decades. Open questions concerned also the existence of extraframework siliceous admixture in addition to extraframework aluminium species which can dramatically change the catalytic properties of these zeolites. This paper gives a review on the synthesis of DAY materials and provides some answers to several open questions.
Salivary Auto-Antibodies as Noninvasive Diagnostic Markers of Oral Cavity Squamous Cell Carcinoma
Authors: Wu Chih-Ching , Chang Ya-Ting , Chang Kai-Ping , Liu Yu-Ling , Liu Hao-Ping , Lee I-Ling , Yu Jau-Song , Chiang Wei-Fan
Published: May 2014

Background: Oral cavity squamous cell carcinoma (OSCC) is one of the most common cancers worldwide, and its incidence is still increasing. Approximately 50% of patients with OSCC die within 5 years after diagnosis, mostly ascribed to the fact that the majority of patients present advanced stages of OSCC at the time of diagnosis.

Methods: To discover salivary biomarkers for ameliorating the detection of OSCC, herein, we developed a multiplexed bead-based platform to simultaneously detect auto-antibodies (auto-Abs) in salivary samples.

Results: Compared with healthy individuals, the salivary levels of anti-p53, anti-survivin, anti-Hsp60, and anti-RPLP0 were significantly elevated in patients with OSCC. Noteworthily, the elevated levels of anti-p53, anti-survivin, and anti-Hsp60 were already observed in individuals with oral potentially malignant disorder. Moreover, the salivary levels of anti-p53, anti-survivin, anti-Hsp60, anti-RPLP0, and anti-CK8 were significantly elevated in patients with early-stage OSCC compared with those in healthy individuals. Most importantly, the use of a combined panel of salivary anti-p53, anti-survivin, anti-Hsp60, and anti-RPLP0 largely improves the detection of OSCC.

Conclusion: Collectively, our results reveal that the salivary auto-Abs are effective OSCC biomarkers and the four-auto-Ab panel provides a novel and practicable approach for OSCC screening.

Impact: This study provides the first evidence for the potential clinical application of salivary auto-Abs in OSCC diagnosis. Cancer Epidemiol Biomarkers Prev; 23(8); 1569–78. ©2014 AACR.
Effects of Physical Activity on Melatonin Levels in Previously Sedentary Men and Women
Authors: Thrift Aaron P. , Xiao Liren , Patel Sanjay R. , Tworoger Shelley S. , McTiernan Anne , Duggan Catherine
Published: May 2014

Background: The inverse association between physical activity and cancer risk may be mediated by higher melatonin levels. However, few studies have examined the effect of increased physical activity on melatonin levels.

Methods: The parent study was a randomized controlled trial that randomized 51 men and 49 women to a 12-month moderate-to-vigorous aerobic exercise intervention (“exercisers”) and 51 men and 51 women to a stretching control (“controls”). Participants were of ages 40 to 75 years, and previously sedentary. Levels of the principal urinary metabolite of melatonin, 6-sulfatoxymelatonin (aMT6s), corrected for creatinine levels, were measured in spot morning urine samples by immunoassay at baseline and 12 months. Changes in levels between exercisers and controls were compared using generalized estimating equations for linear regression.

Results: We observed no statistically significant difference in the change in aMT6s levels from baseline to 12 months in exercisers compared with controls (change in aMT6s levels: exercisers, +6.5%; controls, +13%; P = 0.66). There was no evidence of effect modification by age, sex, or body mass index.

Conclusions: A 12-month moderate-intensity exercise intervention did not affect levels of aMT6s.

Impact: Further research needs to focus on other potential mechanisms through which physical activity may reduce the risk of cancer. Cancer Epidemiol Biomarkers Prev; 23(8); 1696–9. ©2014 AACR.
FGFR1/3 Tyrosine Kinase Fusions Define a Unique Molecular Subtype of Non–Small Cell Lung Cancer
Authors: Wang Rui , Wang Lei , Li Yuan , Hu Haichuan , Shen Lei , Shen Xuxia , Pan Yunjian , Ye Ting , Zhang Yang , Luo Xiaoyang , Zhang Yiliang , Pan Bin , Li Bin , Li Hang , Zhang Jie , Pao William , Ji Hongbin , Sun Yihua , Chen Haiquan
Published: May 2014

Purpose: The fibroblast growth factor receptor (FGFR)-3 fusion genes have been recently demonstrated in a subset of non–small cell lung cancer (NSCLC). To aid in identification and treatment of these patients, we examined the frequency, clinicopathologic characteristics, and treatment outcomes of patients who had NSCLC with or without FGFR fusions.

Experimental Design: Fourteen known FGFR fusion variants, including FGFR1, FGFR2, and FGFR3, were detected by RT-PCR and verified by direct sequencing in 1,328 patients with NSCLC. All patients were also analyzed for mutations in EGFR, KRAS, HER2, BRAF, ALK, RET, and ROS1. Clinical characteristics, including age, sex, smoking status, stage, subtypes of lung adenocarcinoma, relapse-free survival, and overall survival, were collected.

Results: Of 1,328 tumors screened, two (0.2%) were BAG4-FGFR1 fusion and 15 (1.1%) were FGFR3-TACC3 fusion. Six of 1,016 patients with lung adenocarcinoma were FGFR3-TACC3 fusions and 11 of 312 lung squamous cell carcinoma harbored BAG4-FGFR1 or FGFR3-TACC3 fusions. Compared with the FGFR fusion-negative group, patients with FGFR fusions were more likely to be smokers (94.1%, 16 of 17 patients, P < 0.001), significantly associated with larger tumor (>3 cm; 88.2%, 15 of 17 patients, P < 0.001) and with a tendency to be more poorly differentiated (53.9%, nine of 17 patients, P = 0.095).

Conclusions: FGFR fusions define a molecular subset of NSCLC with distinct clinical characteristics. FGFR is a druggable target and patients with FGFR fusions may benefit from FGFR-targeted therapy, which needs further clinical investigation. Clin Cancer Res; 20(15); 4107–14. ©2014 AACR.
Prestroke Physical Activity Is Associated with Good Functional Outcome and Arterial Recanalization after Stroke due to a Large Vessel Occlusion
Authors: Ricciardi Ana Clara , López-Cancio Elena , Pérez de la Ossa Natalia , Sobrino Tomás , Hernández-Pérez María , Gomis Meritxell , Munuera Josep , Muñoz Lucía , Dorado Laura , Millán Mónica , Dávalos Antonio , Arenillas Juan F.
Published: May 2014

Background: Although multiple studies and meta-analyses have consistently suggested that regular physical activity (PhA) is associated with a decreased stroke risk and recurrence, there is limited data on the possible preconditioning effect of prestroke PhA on stroke severity and prognosis. We aimed to study the association of prestroke PhA with different outcome variables in patients with acute ischemic stroke due to an anterior large vessel occlusion. Methods: The Prestroke Physical Activity and Functional Recovery in Patients with Ischemic Stroke and Arterial Occlusion trial is an observational and longitudinal study that included consecutive patients with acute ischemic stroke admitted to a single tertiary stroke center. Main inclusion criteria were: anterior circulation ischemic stroke within 12 h from symptom onset; presence of a confirmed anterior large vessel occlusion, and functional independence previous to stroke. Prestroke PhA was evaluated with the International Physical Activity Questionnaire and categorized into mild, moderate and high levels by means of metabolic equivalent (MET) minutes per week thresholds. The primary outcome measure was good functional outcome at 3 months (modified Rankin scale ≤2). Secondary outcomes were severity of stroke at admission, complete early recanalization, early dramatic neurological improvement and final infarct volume. Results: During the study period, 159 patients fulfilled the above criteria. The mean age was 68 years, 62% were men and the baseline NIHSS score was 17. Patients with high levels of prestroke PhA were younger, had more frequently distal occlusions and had lower levels of blood glucose and fibrinogen at admission. After multivariate analysis, a high level of prestroke PhA was associated with a good functional outcome at 3 months. Regarding secondary outcome variables and after adjustment for relevant factors, a high level of prestroke PhA was independently associated with milder stroke severity at admission, early dramatic improvement, early arterial recanalization after intravenous thrombolysis and lower final infarct volume. The beneficial association of prestroke PhA with stroke outcomes was already present with a cutoff point of 1,000 MET min/week, a level of PhA easily achieved by walking 1 h/day during 5 days or by doing a vigorous aerobic activity 1 h/day twice a week. Conclusions: Prestroke PhA is independently associated with favorable stroke outcomes after a large vessel occlusion. Future research on the underlying mechanisms is needed to understand this neuroprotective effect of PhA.
Adeno-Associated Virus Vectors as Therapeutic and Investigational Tools in the Cardiovascular System
Authors: Zacchigna Serena , Zentilin Lorena , Giacca Mauro
Published: May 2014

The use of vectors based on the small parvovirus adeno-associated virus has gained significant momentum during the past decade. Their high efficiency of transduction of postmitotic tissues in vivo, such as heart, brain, and retina, renders these vectors extremely attractive for several gene therapy applications affecting these organs. Besides functional correction of different monogenic diseases, the possibility to drive efficient and persistent transgene expression in the heart offers the possibility to develop innovative therapies for prevalent conditions, such as ischemic cardiomyopathy and heart failure. Therapeutic genes are not only restricted to protein-coding complementary DNAs but also include short hairpin RNAs and microRNA genes, thus broadening the spectrum of possible applications. In addition, several spontaneous or engineered variants in the virus capsid have recently improved vector efficiency and expanded their tropism. Apart from their therapeutic potential, adeno-associated virus vectors also represent outstanding investigational tools to explore the function of individual genes or gene combinations in vivo, thus providing information that is conceptually similar to that obtained from genetically modified animals. Finally, their single-stranded DNA genome can drive homology-directed gene repair at high efficiency. Here, we review the main molecular characteristics of adeno-associated virus vectors, with a particular view to their applications in the cardiovascular field.
Proprotein Convertase Subtilisin Kexin Type 9 Promotes Intestinal Overproduction of Triglyceride-Rich Apolipoprotein B Lipoproteins Through Both Low-Density Lipoprotein Receptor–Dependent and –Independent Mechanisms
Authors: Rashid Shirya , Tavori Hagai , Brown Patrick E. , Linton MacRae F. , He Jane , Giunzioni Ilaria , Fazio Sergio
Published: May 2014

Background—

Proprotein convertase subtilisin kexin type 9 (PCSK9) promotes the degradation of the low-density lipoprotein (LDL) receptor (LDLR), and its deficiency in humans results in low plasma LDL cholesterol and protection against coronary heart disease. Recent evidence indicates that PCSK9 also modulates the metabolism of triglyceride-rich apolipoprotein B (apoB) lipoproteins, another important coronary heart disease risk factor. Here, we studied the effects of physiological levels of PCSK9 on intestinal triglyceride-rich apoB lipoprotein production and elucidated for the first time the cellular and molecular mechanisms involved.

Methods and Results—

Treatment of human enterocytes (CaCo-2 cells) with recombinant human PCSK9 (10 μg/mL for 24 hours) increased cellular and secreted apoB48 and apoB100 by 40% to 55% each (
P
<0.01 versus untreated cells), whereas short-term deletion of
PCSK9
expression reversed this effect. PCSK9 stimulation of apoB was due to a 1.5-fold increase in apoB mRNA (
P
<0.01) and to enhanced apoB protein stability through both LDLR-dependent and LDLR-independent mechanisms. PCSK9 decreased LDLR protein (
P
<0.01) and increased cellular apoB stability via activation of microsomal triglyceride transfer protein. PCSK9 also increased levels of the lipid-generating enzymes
FAS, SCD
, and
DGAT2
(
P
<0.05). In mice, human PCSK9 at physiological levels increased intestinal microsomal triglyceride transfer protein levels and activity regardless of LDLR expression.

Conclusions—

PCSK9 markedly increases intestinal triglyceride-rich apoB production through mechanisms mediated in part by transcriptional effects on apoB, microsomal triglyceride transfer protein, and lipogenic genes and in part by posttranscriptional effects on the LDLR and microsomal triglyceride transfer protein. These findings indicate that targeted PCSK9-based therapies may also be effective in the management of postprandial hypertriglyceridemia.
Making Sense of Timing and Attention: Modality Effect in Timing with a Break
Authors: Viau-Quesnel Charles , Gaudreault Rémi , Ouellet Andrée-Anne , Fortin Claudette
Published: May 2014

Tones are perceived longer than visual stimuli of same durations. One interpretation of this modality effect is that auditory stimuli capture attention more easily than visual stimuli, resulting in more efficient temporal processing. During a time interval production, expecting a break signal lengthens the produced interval, an effect explained by attention sharing between timing and monitoring for the signal occurrence. In the present study, participants produced a brief time interval defined by a visual or an auditory stimulus and in most trials, there was a break in stimulus presentation. The effect of break expectancy was significantly stronger when the timing stimulus was presented in the visual than in the auditory modality, an interaction supporting attentional interpretations of the modality and expectancy effects. We conclude that auditory stimuli orient attention to time more readily than visual stimuli in a context of attention sharing, which reduces the distracting effect of break expectancy.
Retrospective Analysis of Beta-Blocker Instituted for Treatment of Hemangiomas (RABBIT Study)
Authors: Chu Derek H. , Castelo-Soccio Leslie , Wan Joy , Gelfand Joel M. , Shaddy Robert E. , Shah Kara N. , Perman Marissa J. , Treat James R. , Yan Albert C.
Published: May 2014

Objective. To evaluate the safety and efficacy of our institutional beta-blocker protocol for treatment of complicated infantile hemangiomas (IH). Study Design. A retrospective descriptive study of 76 infants/children with IH treated with oral propranolol at the Children’s Hospital of Philadelphia between June 2008 and August 2010 was performed, assessing both the safety and efficacy of propranolol. Based on preliminary data showing hemangioma recrudescence off-treatment, we reviewed 9 additional patients with recrudescence between August 2010 and December 2011. Results. Mild adverse events included asymptomatic bradycardia, gastrointestinal symptoms, asymptomatic hypotension, cool hands/feet, asymptomatic hypoglycemia, and sleep disturbance. Sixteen patients had recrudescence of IH off-treatment, with propranolol discontinued at a median age of 14 months (interquartile range 10-15 months). Conclusions. Propranolol appears to be associated with minor, not severe symptomatic adverse events. Propranolol appears to be effective in treating complicated IH. Recrudescence can occur off-treatment, even with discontinuing propranolol as late as 15 months of age.
On auto-ethnography
Authors: Denshire Sally
Published: May 2014

Auto-ethnography, an alternative method and form of writing, can make for uncomfortable reading. A transgressive account in the context of professional practice opens out a professional’s life, remaking power relations in the process. Relational ethics is an emerging growth area for auto-ethnographers, given the ethical implications for everyone represented in a transgressive telling. Future directions include fresh juxtapositions of layered auto-ethnographic texts and collaborative accounts that break with the self–other dichotomy.