bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase II Clinical Study of BC-3781, a Pleuromutilin Antibiotic, in Treatment of Patients with Acute Bacterial Skin and Skin Structure Infections
Authors: Prince W. T. , Ivezic-Schoenfeld Z. , Lell C. , Tack K. J. , Novak R. , Obermayr F. , Talbot G. H.
Published: February 2013

This study investigated the potential of the novel systemic pleuromutilin antibiotic BC-3781 to treat patients with an acute bacterial skin and skin structure infection (ABSSSI) caused by a Gram-positive pathogen. Patients were randomized to intravenous BC-3781 100 mg, BC-3781 150 mg, or vancomycin 1 g every 12 h. Response to treatment was assessed daily and at test of cure (TOC). The primary endpoint was the clinical success rate at TOC in the modified intent-to-treat (MITT) and clinically evaluable (CE) analysis populations. Baseline characteristics, including the frequency of methicillin-resistant
Staphylococcus aureus
(MRSA), were comparable between the different treatment groups. Of 210 patients randomized, 186 (88.6%) patients completed the study. Clinical success at TOC in the CE population occurred in 54 (90.0%) patients in the BC-3781 100-mg group, 48 (88.9%) in the BC-3781 150-mg group, and 47 (92.2%) in the vancomycin group. At day 3, the clinical response rate was similar across the three treatment groups. Six patients discontinued study medication following an adverse event. The incidence rate for drug-related adverse events was lower for patients receiving BC-3781 (34.3% and 39.4% in the 100-mg and 150-mg groups, respectively) than those receiving vancomycin (53.0%). When BC-3781 was used to treat ABSSSIs caused by a Gram-positive pathogen, including MRSA, clinical success rates were comparable to those of the comparator, vancomycin. BC-3781 was generally well tolerated. These results provide the first proof of concept for the systemic use of a pleuromutilin antibiotic for the treatment of ABSSSIs.
Activities of Vancomycin-Containing Regimens against Colistin-Resistant Acinetobacter baumannii Clinical Strains
Authors: O'Hara Jessica A. , Ambe Lauretta A. , Casella Leila G. , Townsend Bethany M. , Pelletier Mark R. , Ernst Robert K. , Shanks Robert M. Q. , Doi Yohei
Published: February 2013

Treatment of infections due to extensively drug-resistant (XDR)
Acinetobacter baumannii
often involves the use of antimicrobial agents in combination. Various combinations of agents have been proposed, with colistin serving as the backbone in many of them. Recent data suggest that glycopeptides, in particular vancomycin, may have unique activity against laboratory-adapted and clinical strains of
A. baumannii
, alone and in combination with colistin. The aim of the present study was to test this approach against three unique colistin-resistant
A. baumannii
clinical strains using combinations of vancomycin (VAN), colistin (COL), and doripenem (DOR). All three strains possessed the signature phosphoethanolamine modification of the lipid A moiety associated with colistin resistance and unique amino acid changes in the PmrAB two-component signal transduction system not observed in colistin-susceptible strains. In checkerboard assays, synergy (defined as a fractional inhibitory concentration index [FICI] of ≤0.5) was observed between COL and VAN for all three strains tested and between COL and DOR in two strains. In time-kill assays, the combinations of COL-DOR, COL-VAN, and COL-DOR-VAN resulted in complete killing of colistin-resistant
A. baumannii
in 1, 2, and all 3 strains, respectively. In the
Galleria mellonella
moth model of infection, the combinations of DOR-VAN and COL-DOR-VAN led to significantly increased survival of the larvae, compared with other combinations and monotherapy. These findings suggest that regimens containing vancomycin may confer therapeutic benefit for infection due to colistin-resistant
A. baumannii
.
Quantification of the Adenylate Cyclase Toxin of Bordetella pertussisIn Vitroand during Respiratory Infection
Authors: Eby Joshua C. , Gray Mary C. , Warfel Jason M. , Paddock Christopher D. , Jones Tara F. , Day Shandra R. , Bowden James , Poulter Melinda D. , Donato Gina M. , Merkel Tod J. , Hewlett Erik L.
Published: February 2013

Whooping cough results from infection of the respiratory tract withBordetella pertussis, and the secreted adenylate cyclase toxin (ACT) is essential for the bacterium to establish infection. Despite extensive study of the mechanism of ACT cytotoxicity and its effects over a range of concentrationsin vitro, ACT has not been observed or quantifiedin vivo, and thus the concentration of ACT at the site of infection is unknown. The recently developed baboon model of infection mimics the prolonged cough and transmissibility of pertussis, and we hypothesized that measurement of ACT in nasopharyngeal washes (NPW) from baboons, combined with human andin vitrodata, would provide an estimate of the ACT concentration in the airway during infection. NPW contained up to ∼108CFU/mlB. pertussisand 1 to 5 ng/ml ACT at the peak of infection. Nasal aspirate specimens from two human infants with pertussis contained bacterial concentrations similar to those in the baboons, with 12 to 20 ng/ml ACT. When ∼108CFU/ml of a laboratory strain ofB. pertussiswas culturedin vitro, ACT production was detected in 60 min and reached a plateau of ∼60 ng/ml in 6 h. Furthermore, when bacteria were brought into close proximity to target cells by centrifugation, intoxication was increased 4-fold. Collectively, these data suggest that at the bacterium-target cell interface during infection of the respiratory tract, the concentration of ACT can exceed 100 ng/ml, providing a reference point for future studies of ACT and pertussis pathogenesis.
The Cpx Stress Response System Potentiates the Fitness and Virulence of Uropathogenic Escherichia coli
Authors: Debnath Irina , Norton J. Paul , Barber Amelia E. , Ott Elizabeth M. , Dhakal Bijaya K. , Kulesus Richard R. , Mulvey Matthew A.
Published: February 2013

Strains of uropathogenic
Escherichia coli
(UPEC) are the primary cause of urinary tract infections, representing one of the most widespread and successful groups of pathogens on the planet. To colonize and persist within the urinary tract, UPEC must be able to sense and respond appropriately to environmental stresses, many of which can compromise the bacterial envelope. The Cpx two-component envelope stress response system is comprised of the inner membrane histidine kinase CpxA, the cytosolic response regulator CpxR, and the periplasmic auxiliary factor CpxP. Here, by using deletion mutants along with mouse and zebrafish infection models, we show that the Cpx system is critical to the fitness and virulence of two reference UPEC strains, the cystitis isolate UTI89 and the urosepsis isolate CFT073. Specifically, deletion of the
cpxRA
operon impaired the ability of UTI89 to colonize the murine bladder and greatly reduced the virulence of CFT073 during both systemic and localized infections within zebrafish embryos. These defects coincided with diminished host cell invasion by UTI89 and increased sensitivity of both strains to complement-mediated killing and the aminoglycoside antibiotic amikacin. Results obtained with the
cpxP
deletion mutants were more complicated, indicating variable strain-dependent and niche-specific requirements for this well-conserved auxiliary factor.
Sensing of Bacterial Type IV Secretion via the Unfolded Protein Response
Authors: de Jong Maarten F. , Starr Tregei , Winter Maria G. , den Hartigh Andreas B. , Child Robert , Knodler Leigh A. , van Dijl Jan Maarten , Celli Jean , Tsolis Renée M.
Published: February 2013

Host cytokine responses to
Brucella abortus
infection are elicited predominantly by the deployment of a type IV secretion system (T4SS). However, the mechanism by which the T4SS elicits inflammation remains unknown. Here we show that translocation of the T4SS substrate VceC into host cells induces proinflammatory responses. Ectopically expressed VceC interacted with the endoplasmic reticulum (ER) chaperone BiP/Grp78 and localized to the ER of HeLa cells. ER localization of VceC required a transmembrane domain in its N terminus. Notably, the expression of VceC resulted in reorganization of ER structures. In macrophages, VceC was required for
B. abortus
-induced inflammation by induction of the unfolded protein response by a process requiring inositol-requiring transmembrane kinase/endonuclease 1. Altogether, these findings suggest that translocation of the T4SS effector VceC induces ER stress, which results in the induction of proinflammatory host cell responses during
B. abortus
infection.

IMPORTANCE
Brucella
species are pathogens that require a type IV secretion system (T4SS) to survive in host cells and to maintain chronic infection. By as-yet-unknown pathways, the T4SS also elicits inflammatory responses in infected cells. Here we show that inflammation caused by the T4SS results in part from the sensing of a T4SS substrate, VceC, that localizes to the endoplasmic reticulum (ER), an intracellular site of
Brucella
replication. Possibly via binding of the ER chaperone BiP, VceC causes ER stress with concomitant expression of proinflammatory cytokines. Thus, induction of the unfolded protein response may represent a novel pathway by which host cells can detect pathogens deploying a T4SS.
Efficient Replication of the Novel Human Betacoronavirus EMC on Primary Human Epithelium Highlights Its Zoonotic Potential
Authors: Kindler Eveline , Jónsdóttir Hulda R. , Muth Doreen , Hamming Ole J. , Hartmann Rune , Rodriguez Regulo , Geffers Robert , Fouchier Ron A. M. , Drosten Christian , Müller Marcel A. , Dijkman Ronald , Thiel Volker
Published: February 2013

The recent emergence of a novel human coronavirus (HCoV-EMC) in the Middle East raised considerable concerns, as it is associated with severe acute pneumonia, renal failure, and fatal outcome and thus resembles the clinical presentation of severe acute respiratory syndrome (SARS) observed in 2002 and 2003. Like SARS-CoV, HCoV-EMC is of zoonotic origin and closely related to bat coronaviruses. The human airway epithelium (HAE) represents the entry point and primary target tissue for respiratory viruses and is highly relevant for assessing the zoonotic potential of emerging respiratory viruses, such as HCoV-EMC. Here, we show that pseudostratified HAE cultures derived from different donors are highly permissive to HCoV-EMC infection, and by using reverse transcription (RT)-PCR and RNAseq data, we experimentally determined the identity of seven HCoV-EMC subgenomic mRNAs. Although the HAE cells were readily responsive to type I and type III interferon (IFN), we observed neither a pronounced inflammatory cytokine nor any detectable IFN responses following HCoV-EMC, SARS-CoV, or HCoV-229E infection, suggesting that innate immune evasion mechanisms and putative IFN antagonists of HCoV-EMC are operational in the new host. Importantly, however, we demonstrate that both type I and type III IFN can efficiently reduce HCoV-EMC replication in HAE cultures, providing a possible treatment option in cases of suspected HCoV-EMC infection.

IMPORTANCE
A novel human coronavirus, HCoV-EMC, has recently been described to be associated with severe respiratory tract infection and fatalities, similar to severe acute respiratory syndrome (SARS) observed during the 2002-2003 epidemic. Closely related coronaviruses replicate in bats, suggesting that, like SARS-CoV, HCoV-EMC is of zoonotic origin. Since the animal reservoir and circumstances of zoonotic transmission are yet elusive, it is critically important to assess potential species barriers of HCoV-EMC infection. An important first barrier against invading respiratory pathogens is the epithelium, representing the entry point and primary target tissue of respiratory viruses. We show that human bronchial epithelia are highly susceptible to HCoV-EMC infection. Furthermore, HCoV-EMC, like other coronaviruses, evades innate immune recognition, reflected by the lack of interferon and minimal inflammatory cytokine expression following infection. Importantly, type I and type III interferon treatment can efficiently reduce HCoV-EMC replication in the human airway epithelium, providing a possible avenue for treatment of emerging virus infections.
Recurrent phyllodes sarcoma of breast with complete chest wall invasion; a multidisciplinary approach for radical resection
Authors: Chaudhry Ikram Ulhaq , Asban Ammar , Mahboub Tarek , Arini Ali
Published: February 2013

Phyllodes tumour of the breast is a relatively uncommon condition, and rarely invades the chest wall. We report a case of young women who had recurrent large phyllodes tumour invading the chest wall, following mastectomy, chemotherapy and radiotherapy. A multidisciplinary approach was used for radical resection of the tumour, chest wall and reconstruction.
Physiological states and functional relation between thyrotropin and free thyroxine in thyroid health and disease: in vivo and in silico data suggest a hierarchical model
Authors: Midgley John E M , Hoermann Rudolf , Larisch Rolf , Dietrich Johannes W
Published: February 2013

Aims

Understanding the exact relationship between serum thyrotropin/thyroid stimulating hormone (TSH) and free thyroxine (FT4) is a prerequisite for improving diagnostic reliability and clinical decision making.

Methods

We (1) retrospectively studied the relationship between TSH and FT4in a large unselected clinical sample (n=6641) of primary hypothyroid, euthyroid and hyperthyroid subjects, and (2) applied a mathematical model of thyroid hormone feedback control to assess the relation between structural parameters and TSH levels in the different functional states.

Results

When separately analysing total sample and untreated subjects, the correlation slope for logTSH versus FT4for hypothyroid subjects was significantly different from that of the euthyroid panel and hyperthyroid subjects (the latter being compromised by reaching the TSH assay's lower detection limit). As trends between functional states changed, each functional segment appeared to become differently regulated. Theoretical modelling and sensitivity analysis revealed that the influence of various structural parameters on TSH levels also depends on the overall function of the feedback loop.

Conclusions

Our data suggest that the states of hypothyroidism, euthyroidism and hyperthyroidism can be regarded as differently regulated entities. The apparent complexity could be replicated by mathematical modelling suggesting a hierarchical type of feedback regulation involving patterns of operative mechanisms unique to each condition. For clinical purposes and assay evaluation, neither the standard model relating logTSH with FT4, nor an alternative model based on non-competitive inhibition can be reliably represented by a single correlation comparing all samples for both hormones in one all-inclusive group.
Notch1-Hes1 signalling axis in the tumourigenesis of biliary neuroendocrine tumours
Authors: Harada Kenichi , Sato Yasunori , Ikeda Hiroko , Hsu Maylee , Igarashi Saya , Nakanuma Yasuni
Published: February 2013

Aims

Biliary neuroendocrine tumours (NETs) are rare and mostly exist as a component of mixed adenoneuroendocrine carcinomas (MANECs). Although the NET component in biliary MANECs is generally more malignant and clinically more important to the prognosis than the ordinary adenocarcinomatous component, the histogenesis of biliary NET has not been clarified. In this study, the role of the Notch1-Hes1 signalling axis in the histogenesis of biliary NETs was examined.

Methods

Immunohistochemistry for Notch1, its ligand Jagged1 and Hes1 was performed using surgical specimens from 11 patients with biliary MANEC. Moreover, after the knock-down of Notch1 mRNA expression in a cholangiocarcinoma cell line, the expression of chromogranin A (a neuroendocrine marker) and Ascl1 (a neuroendocrine-inducing molecule inhibited by activated Hes1) was examined by quantitative PCR.

Results

Histological examination revealed that the adenocarcinomatous components were predominately located at the luminal surface of the MANEC and the majority of stromal invasion involved NET components. Ordinary adenocarcinomas and non-neoplastic biliary epithelium constantly expressed Notch1, Jagged1 and Hes1, but the expression of Notch1 and Hes1 was decreased or absent in NET components, suggesting interference with the Notch1-Hes1 signalling axis in biliary NET. Moreover, in the cholangiocarcinoma cell line in which the expression of Notch1 mRNA was knocked down, the mRNA expression of Ascl1 and chromogranin A was increased.

Conclusions

The Notch1-Hes1 signalling axis suppresses neuroendocrine differentiation and maintains tubular/acinar features in adenocarcinoma and non-neoplastic epithelium in the biliary tree. Moreover, a disruption of this signalling axis may be associated with the tumourigenesis of NETs in biliary MANEC.
RATIONAL TIME-FREQUENCY VECTOR-VALUED SUBSPACE GABOR FRAMES AND BALIAN-LOW THEOREM
Authors: LI YUN-ZHANG , ZHANG YAN
Published: February 2013

This paper addresses vector-valued subspace Gabor frames with rational time-frequency product. By introduction of a suitable Zak transform matrix, we characterize vector-valued subspace Gabor frames, Riesz bases and orthonormal bases. We characterize the uniqueness of Gabor duals of type I and type II. Using the uniqueness results, we extend the classical Balian-Low theorem to vector-valued subspace Gabor frames. We also point out Ron-Shen duality principe does not hold for a general vector-valued subspace Gabor frame.
A FAMILY OF NONSEPARABLE SMOOTH COMPACTLY SUPPORTED WAVELETS
Authors: ANTOLÍN A. SAN , ZALIK R. A.
Published: February 2013

We construct smooth nonseparable compactly supported refinable functions that generate multiresolution analyses on L2(ℝd), d > 1. Using these refinable functions we construct smooth nonseparable compactly supported orthonormal wavelet systems. These systems are nonseparable, in the sense that none of its constituent functions can be expressed as the product of two functions defined on lower dimensions. Both the refinable functions and the wavelets can be made as smooth as desired. Estimates for the supports of these scaling functions and wavelets, are given.
PREVIEW CONTROL FOR A CLASS OF LINEAR CONTINUOUS TIME-VARYING SYSTEMS
Authors: XU YUJIE , LIAO FUCHENG , CUI LIMIN , WU JIANG
Published: February 2013

A design method of an optimal preview controller for a class of linear continuous time-varying systems is presented in this paper. By differentiating both the output error signal and the two sides of the state equation, an augmented error system is constructed, which contains the error signal, the state vector and the derivative of the state vector. Then the performance index function is introduced and the control problem is solved by optimal control theory. Thus the optimal preview control input for the original time-varying system is found. The proposed controller includes the previewable future signal, so the response speed is accelerated. Meanwhile, the integrators in the controller make the output vector track the target signal better. The numerical simulations illustrate the validity of the proposed method.
APPROXIMATE SOLUTION OF MODIFIED CAMASSA–HOLM AND DEGASPERIS–PROCESI EQUATIONS USING WAVELET OPTIMIZED FINITE DIFFERENCE METHOD
Authors: BEHERA RATIKANTA , MEHRA MANI
Published: February 2013

In this paper, we apply wavelet optimized finite difference method to solve modified Camassa–Holm and modified Degasperis–Procesi equations. The method is based on Daubechies wavelet with finite difference method on an arbitrary grid. The wavelet is used at regular intervals to adaptively select the grid points according to the local behaviour of the solution. The purpose of wavelet-based numerical methods for solving linear or nonlinear partial differential equations is to develop adaptive schemes, in order to achieve accuracy and computational efficiency. Since most of physical and scientific phenomena are modeled by nonlinear partial differential equations, but it is difficult to handle nonlinear partial differential equations analytically. So we need approximate solution to solve these type of partial differential equation. Numerical results are presented for approximating modified Camassa–Holm and modified Degasperis–Procesi equations, which demonstrate the advantages of this method.
A FAST METHOD OF FUNDAMENTAL SOLUTIONS FOR SOLVING HELMHOLTZ-TYPE EQUATIONS
Authors: JIANG XINRONG , CHEN WEN , CHEN C. S.
Published: February 2013

The method of fundamental solution (MFS) has been known as a simple and effective boundary meshless method. However, the MFS generates dense square coefficient matrix and thus requires a large amount of computational time and memory storage for solving large-scale problems. The fast multipole method (FMM) is a technique that reduces computational operations and storage requirements for solving such dense matrix equations. This study makes the first attempt to apply the FMM to the MFS calculation of acoustic problems, where the operations are reduced to O(N log N) while O(N2) operations are required for the traditional MFS using the standard iterative methods. Numerical examples with up to 100,000 points are successfully tested on a desktop personal computer. Our results clearly demonstrate efficiency and accuracy of the fast multipole MFS for solving large-scale Helmholtz-type problems.
Metallothionein prevents diabetes-induced cardiac pathological changes, likely via the inhibition of succinyl-CoA:3-ketoacid coenzyme A transferase-1 nitration at Trp374
Authors: Cong Weitao , Ma Weide , Zhao Ting , Zhu Zhongxin , Wang Yuehui , Tan Yi , Li Xiaokun , Jin Litai , Cai Lu
Published: February 2013

We previously demonstrated that metallothionein (MT)-mediated protection from diabetes-induced pathological changes in cardiac tissues is related to suppression of superoxide generation and protein nitration. The present study investigated which diabetes-nitrated protein(s) mediate the development of these pathological changes by identifying the panel of nitrated proteins present in diabetic hearts of wild-type (WT) mice and not in those of cardiac-specific MT-overexpressing transgenic (MT-TG) mice. At 2, 4, 8, and 16 wk after streptozotocin induction of diabetes, histopathological examination of the WT and MT-TG diabetic hearts revealed cardiac structure derangement and remodeling, significantly increased superoxide generation, and 3-nitrotyrosine accumulation. A nitrated protein of 58 kDa, succinyl-CoA:3-ketoacid CoA transferase-1 (SCOT), was identified by mass spectrometry. Although total SCOT expression was not significantly different between the two types of mice, the diabetic WT hearts showed significantly increased nitration content and dramatically decreased catalyzing activity of SCOT. Although SCOT nitration sites were identified at Tyr76, Tyr117, Tyr135, Tyr226, Tyr368, and Trp374, only Tyr76and Trp374were found to be located in the active site by three-dimensional structure modeling. However, only Trp374showed a significantly different nitration level between the WT and MT-TG diabetic hearts. These results suggest that MT prevention of diabetes-induced pathological changes in cardiac tissues is most likely mediated by suppression of SCOT nitration at Trp374.
Determination of steady-state protein breakdown rate in vivo by the disappearance of protein-bound tracer-labeled amino acids: a method applicable in humans
Authors: Holm Lars , O'Rourke Bruce , Ebenstein David , Toth Michael J. , Bechshoeft Rasmus , Holstein-Rathlou Niels-Henrik , Kjaer Michael , Matthews Dwight E.
Published: February 2013

A method to determine the rate of protein breakdown in individual proteins was developed and tested in rats and confirmed in humans, using administration of deuterium oxide and incorporation of the deuterium into alanine that was subsequently incorporated into body proteins. Measurement of the fractional breakdown rate of proteins was determined from the rate of disappearance of deuterated alanine from the proteins. The rate of disappearance of deuterated alanine from the proteins was calculated using an exponential decay, giving the fractional breakdown rate (FBR) of the proteins. The applicability of this protein-specific FBR approach is suitable for human in vivo experimentation. The labeling period of deuterium oxide administration is dependent on the turnover rate of the protein of interest.
Direction-of-Arrival Estimation of Closely Spaced Emitters Using Compact Arrays
Authors: Lui Hoi-Shun , Hui Hon Tat
Published: February 2013

Performance evaluation of direction-of-arrival (DOA) estimation algorithms has continuously drawn significant attention in the past years. Most previous studies were conducted under the situation that antenna element separation is about half wavelength in order to avoid the appearance of grating lobes. On the other hand, recent developments in wireless communications have favoured the use of portable devices that utilize compact arrays with antenna element separations of less than half wavelength. Performance evaluation of DOA estimation algorithms employing compact arrays is an important and fundamental issue, but it has not been fully studied. In this paper, the performance of the matrix pencil method (MPM) that applies to DOA estimations is investigated through Monte Carlo simulations. The results show that closely spaced emitters can be accurately resolved using linear compact array with an array aperture as small as around half wavelength.
Using Protein Clusters from Whole Proteomes to Construct and Augment a Dendrogram
Authors: Zhou Yunyun , Call Douglas R. , Broschat Shira L.
Published: February 2013

In this paper we present a new ab initio approach for constructing an unrooted dendrogram using protein clusters, an approach that has the potential for estimating relationships among several thousands of species based on their putative proteomes. We employ an open-source software program calledpClustthat was developed for use in metagenomic studies. Sequence alignment is performed bypClustusing the Smith-Waterman algorithm, which is known to give optimal alignment and, hence, greater accuracy than BLAST-based methods. Protein clusters generated bypClustare used to create protein profiles for each species in the dendrogram, these profiles forming a correlation filter library for use with a new taxon. To augment the dendrogram with a new taxon, a protein profile for the taxon is created using BLASTp, and this new taxon is placed into a position within the dendrogram corresponding to the highest correlation with profiles in the correlation filter library. This work was initiated because of our interest in plasmids, and each step is illustrated using proteomes from Gram-negative bacterial plasmids. Proteomes for 527 plasmids were used to generate the dendrogram, and to demonstrate the utility of the insertion algorithm twelve recently sequenced pAKD plasmids were used to augment the dendrogram.
A Case-Based Study of Students' Visuohaptic Experiences of Electric Fields around Molecules: Shaping the Development of Virtual Nanoscience Learning Environments
Authors: Höst Gunnar E. , Schönborn Konrad J. , Lundin Palmerius Karljohan E.
Published: February 2013

Recent educational research has suggested that immersive multisensory virtual environments offer learners unique and exciting knowledge-building opportunities for the construction of scientific knowledge. This paper delivers a case-based study of students’ immersive interaction with electric fields around molecules in a multisensory visuohaptic virtual environment. The virtual architecture presented here also has conceptual connections to the flourishing quest in contemporary literature for the pressing need to communicate nanoscientific ideas to learners. Five upper secondary school students’ prior conceptual understanding of electric fields and their application of this knowledge to molecular contexts, were probed prior to exposure to the virtual model. Subsequently, four students interacted with the visuohaptic model while performing think-aloud tasks. An inductive and heuristic treatment of videotaped verbal and behavioural data revealed distinct interrelationships between students’ interactive strategies implemented when executing tasks in the virtual system and the nature of their conceptual knowledge deployed. The obtained qualitative case study evidence could serve as an empirical basis for informing the rendering and communication of overarching nanoscale ideas. At the time of composing this paper for publication in the current journal, the research findings of this study have been put into motion in informing a broader project goal of developing educational virtual environments for depicting nanophenomena.
Study of Dynamic Flow and Mixing Performances of Tri-Screw Extruders with Finite Element Method
Authors: Zhu X. Z. , Wang G. , He Y. D. , Cheng Z. F.
Published: February 2013

There is a special circumfluence in the center region of cross-section for a tri-screw extruder. To study the effect of the dynamic center region on the flow and mixing mechanism of the tri-screw extruder, 2D finite element modeling was used to reduce the axial effects. Based on the particle tracking technology, the nonlinear dynamics of a typical particle motions in the center region was carried out and the mixing process in the tri-screw extruder was analyzed with Poincaré maps. Moreover, mixing evaluations of the tri-screw and twin-screw extruders were analyzed and compared. The results show that there are many multiple and fractional excitation frequencies in the Fast Fourier Transform (FFT) spectrums, and it shows a chaotic motion in the center region. Poincaré section maps in the tri-screw show the better particles diffusive ability than those in the twin-screw extrude due to the excellent diffluent ability. Furthermore, the tri-screw extruder has the better dispersive, distributive mixing abilities and stretching mixing efficiency than the twin-screw extruder in the cross-section.
Mathematical and Metaheuristic Applications in Design Optimization of Steel Frame Structures: An Extensive Review
Authors: Saka Mehmet Polat , Geem Zong Woo
Published: February 2013

The type of mathematical modeling selected for the optimum design problems of steel skeletal frames affects the size and mathematical complexity of the programming problem obtained. Survey on the structural optimization literature reveals that there are basically two types of design optimization formulation. In the first type only cross sectional properties of frame members are taken as design variables. In such formulation when the values of design variables change during design cycles, it becomes necessary to analyze the structure and update the response of steel frame to the external loading. Structural analysis in this type is a complementary part of the design process. In the second type joint coordinates are also treated as design variables in addition to the cross sectional properties of members. Such formulation eliminates the necessity of carrying out structural analysis in every design cycle. The values of the joint displacements are determined by the optimization techniques in addition to cross sectional properties. The structural optimization literature contains structural design algorithms that make use of both type of formulation. In this study a review is carried out on mathematical and metaheuristic algorithms where the effect of the mathematical modeling on the efficiency of these algorithms is discussed.
Eugenia unifloraL. Essential Oil as a Potential Anti-LeishmaniaAgent: Effects onLeishmania amazonensisand Possible Mechanisms of Action
Authors: Rodrigues Klinger Antonio da Franca , Amorim Layane Valéria , Oliveira Jamylla Mirck Guerra de , Dias Clarice Noleto , Moraes Denise Fernandes Coutinho , Andrade Eloisa Helena de Aguiar , Maia Jose Guilherme Soares , Carneiro Sabrina Maria Portela , Carvalho Fernando Aécio de Amorim
Published: February 2013

Eugenia unifloraL. is a member of the Myrtaceae family and is commonly known as Brazilian cherry tree. In this study, we evaluated the chemical composition ofEugenia unifloraL. essential oil (EuEO) by using gas chromatography-mass spectrometry (GC-MS) and assessed its anti-Leishmaniaactivity. We also explored the potential mechanisms of action and cytotoxicity of EuEO. Thirty-two compounds were identified, which constituted 92.65% of the total oil composition. The most abundant components were sesquiterpenes (91.92%), with curzerene (47.3%),γ-elemene (14.25%), andtrans-β-elemenone (10.4%) being the major constituents. The bioactivity shown by EuEO against promastigotes (IC50, 3.04 μg·mL−1) and amastigotes (IC50, 1.92 μg·mL−1) suggested significant anti-Leishmaniaactivity. In the cytotoxicity determination, EuEO was 20 times more toxic to amastigotes than to macrophages. Hemolytic activity was 63.22% at the highest concentration tested (400 μg·mL−1); however, there appeared to be no toxicity at 50 μg·mL−1. While the data show that EuEO activity is not mediated by nitric oxide production, they do suggest that macrophage activation may be involved in EuEO anti-Leishmaniaactivity, as evidenced by increases in both the phagocytic capacity and the lysosomal activity. More studies are needed to determinein vivoactivity as well as additional mechanisms of the anti-Leishmaniaactivity.
Existence and Multiplicity of Homoclinic Orbits for Second-Order Hamiltonian Systems with Superquadratic Potential
Authors: Lv Ying , Tang Chun-Lei
Published: February 2013

We investigate the existence and multiplicity of homoclinic orbits for second-order Hamiltonian systems with local superquadratic potential by using the Mountain Pass Theorem and the Fountain Theorem, respectively.
Design, Synthesis, and Pharmacological Screening of Novel Porphyrin Derivatives
Authors: Fadda Ahmed A. , El-Mekawy Rasha E. , El-Shafei Ahmed , Freeman Harold S. , Hinks David , El-Fedawy Manal
Published: February 2013

A series of porphyrin derivatives 2a–f was synthesized, namely, 5,10,15,20‐mesotetrakis[p‐methoxyphenyl]‐21H,23H‐porphyrin (2a), 5,10,15,20‐mesotetrakis[2,6‐dichloro‐phenyl]‐21H,23H‐porphyrin (2b), 5,10,15,20‐mesotetrakis[4‐hydroxy‐3,5‐dimethoxyphenyl]‐21H,23H‐porphyrin (2c), 5,10,15,20‐mesotetrakis[3,4‐dimethoxyphenyl]‐21H,23H‐porphyrin (2d), 5,10,15,20‐mesotetrakis[2,4‐dichlorophenyl]‐21H,23H‐porphyrin (2e), and 5,10,15,20‐mesotetrakis[3,4,5‐trimethoxyphenyl]‐21H,23H‐porphyrin (2f), in high yields using a new method via a capping mechanism. These dyes were used as a model to study the free radical‐induced damage of biological membranes and the protective effects of these porphyrins. It was demonstrated that these dyes were effective in the inhibition of the free radical‐induced oxidative haemolysis of rat blood cells. Dyes 2d and 2f which bear methoxy functionality exhibited markedly higher antihaemolysis activity than the other analogs. Molecular modeling methods using ZINDO/INDO‐1, with a configuration interaction of 26, and TD‐DFT using the energy functional B3LYP and the basis set DGTZVP were used to study the vertical electronic excitations of porphyrins 2a–f and it was shown that the λmax
calculated using TD‐DFT method was in excellent agreement with the experimental results, while the ZINDO method was inferior. Moreover, excellent correlation between the LUMO energy and cytotoxicity of dyes 2a–f was found.
Adaptive Fuzzy Tracking Control for Uncertain Nonlinear Time-Delay Systems with Unknown Dead-Zone Input
Authors: Chiang Chiang-Cheng
Published: February 2013

The tracking control problem of uncertain nonlinear time-delay systems with unknown dead-zone input is tackled by a robust adaptive fuzzy control scheme. Because the nonlinear gain function and the uncertainties of the controlled system including matched and unmatched uncertainties are supposed to be unknown, fuzzy logic systems are employed to approximate the nonlinear gain function and the upper bounded functions of these uncertainties. Moreover, the upper bound of the uncertainty caused by the fuzzy modeling error is also estimated. According to these learning fuzzy models and some feasible adaptive laws, a robust adaptive fuzzy tracking controller is developed in this paper without constructing the dead-zone inverse. Based on the Lyapunov stability theorem, the proposed controller not only guarantees that the robust stability of the whole closed-loop system in the presence of uncertainties and unknown dead-zone input can be achieved, but it also obtains that the output tracking error can converge to a neighborhood of zero exponentially. Some simulation results are provided to demonstrate the effectiveness and performance of the proposed approach.
Effects of Vitrectomy on Recurrent Macular Edema due to Branch Retinal Vein Occlusion after Intravitreal Injection of Bevacizumab
Authors: Yunoki Tatsuya , Mitarai Keiichi , Yanagisawa Shuichiro , Kato Tsuyoshi , Ishida Nobuo , Hayashi Atsushi
Published: February 2013

Purpose. To evaluate the effects of pars plana vitrectomy (PPV) on recurrent macular edema due to branch retinal vein occlusion (BRVO) after intravitreal injections of bevacizumab (IVB).Methods. This retrospective study included 22 eyes of 22 patients who underwent single or multiple IVB injections for macular edema due to BRVO and showed a recurrence of macular edema. All patients then underwent PPV and were followed up for more than 6 months after the surgery with examinations of best corrected visual acuity (BCVA) and optical coherence tomography (OCT). OCT parameters were central macular thickness (CMT) and average retinal thickness in a 1-mm-diameter circular region at the fovea (MRT).Results. Mean BCVA, CRT, and MRT were significantly improved from the baseline after PPV. Greater improvement of BCVA, CRT, and MRT was obtained after 1 month of IVB than after 6 months of PPV. No eyes showed worsening of macular edema after the surgery.Conclusion. PPV improved BCVA and recurrent macular edema due to BRVO, but PPV that was less effective than IVB had been in the same patients. PPV may be one of the treatment options for recurrent macular edema due to BRVO after IVB.
Eosinophil-Derived Neurotoxin Is Elevated in Patients with Amyotrophic Lateral Sclerosis
Authors: Liu Guan-Ting , Hwang Chi-Shin , Hsieh Chia-Hung , Lu Chih-Hao , Chang Sunny Li-Yun , Lee Jin-Ching , Huang Chien-Fu , Chang Hao-Teng
Published: February 2013

Background and Objectives. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by loss of motor neurons in the brainstem, motor cortex, and spinal cord. Oxidative stress and neuroinflammation have been implicated in the pathophysiology of ALS. Members of the family of damage-associated molecular patterns, including reactive oxygen species, high-mobility group box 1, and eosinophil-derived neurotoxin (EDN), may participate in pathological conditions. In this study, we aim to discover new biomarker for detecting ALS.Materials and Methods. We examined 44 patients with ALS, 41 patients with Alzheimer’s disease, 41 patients with Parkinson’s disease, and 44 healthy controls. The concentration of serum EDN was measured using an enzyme-linked immunosorbent assay.Results. EDN levels were significantly increased 2.17-fold in the serum of patients with ALS as compared with healthy controls (P<0.05). No correlation between the levels of serum EDN and various clinical parameters of ALS was found. Moreover, the levels of serum EDN in patients with Parkinson’s disease and Alzheimer’s disease and healthy controls were similar.Conclusion. A higher level of serum EDN was found specifically in patients with ALS, indicating that EDN may participate in the pathophysiology of ALS.
Integrating Traditional Chinese Medicine Services in Community Health Centers: Insights into Utilization Patterns in the Pearl River Region of China
Authors: Chung Vincent C. H. , Ma Polly H. X. , Wang Harry H. X. , Wang Jia Ji , Hong Lau Chun , Wei Xiaolin , Wong Samuel Y. S. , Tang Jin Ling , Griffiths Sian M.
Published: February 2013

In China's healthcare reform, community health centers (CHCs) are designed to take a pivotal role in providing primary care. Whilst about 20% of all outpatient care in China is delivered by the traditional Chinese medicine (TCM) sector, hospitals, instead of CHCs, are major providers. Using current patterns of patient utilization this study aims to inform CHCs on how they may strengthen access to TCM services. Three thousand three hundred and sixty CHC patients from six cities within the urban Pearl Delta Region were enumerated using multistage cluster sampling. Fifty-two percent had visited herbalists within three months with a mean visit frequency of 1.50 times. Herbal treatments, which are cheaper than western medicines, were more popular amongst those who needed to pay out of pocket including the uninsured. Herbal medicines appeared to be an alternative for those who are underinsured. Acupuncturists and massage therapists were visited by smaller proportions, 6.58% and 5.98%, respectively, with a mean three-month visit of 0.27 and 0.26 times. Access was restricted by lack of social insurance coverage. Whilst increasing provision of TCM in CHCs might respond to patient demand, increasing insurance coverage for TCM needs to be evaluated using current evidence on safety and effectiveness.
Individual and Neighborhood Socioeconomic Status and Healthcare Resources in Relation to Black-White Breast Cancer Survival Disparities
Authors: Akinyemiju Tomi F. , Soliman Amr S. , Johnson Norman J. , Altekruse Sean F. , Welch Kathy , Banerjee Mousumi , Schwartz Kendra , Merajver Sofia
Published: February 2013

Background.Breast cancer survival has improved significantly in the US in the past 10–15 years. However, disparities exist in breast cancer survival between black and white women.Purpose.To investigate the effect of county healthcare resources and SES as well as individual SES status on breast cancer survival disparities between black and white women.Methods.Data from 1,796 breast cancer cases were obtained from the Surveillance Epidemiology and End Results and the National Longitudinal Mortality Study dataset. Cox Proportional Hazards models were constructed accounting for clustering within counties. Three sequential Cox models were fit for each outcome including demographic variables; demographic and clinical variables; and finally demographic, clinical, and county-level variables.Results.In unadjusted analysis, black women had a 53% higher likelihood of dying of breast cancer and 32% higher likelihood of dying of any cause (P<0.05) compared with white women. Adjusting for demographic variables explained away the effect of race on breast cancer survival (HR, 1.40; 95% CI, 0.99–1.97), but not on all-cause mortality. The racial difference in all-cause survival disappeared only after adjusting for county-level variables (HR, 1.27; CI, 0.95–1.71).Conclusions.Improving equitable access to healthcare for all women in the US may help eliminate survival disparities between racial and socioeconomic groups.
Scattering Analysis of Electromagnetic Materials Using Fast Dipole Method Based on Volume Integral Equation
Authors: Deng Xiaoqiao , Gu Changqing , Xu Bingzheng , Li Zhuo , Chen Xinlei
Published: February 2013

The fast dipole method (FDM) is extended to analyze the scattering of dielectric and magnetic materials by solving the volume integral equation (VIE). The FDM is based on the equivalent dipole method (EDM) and can achieve the separation of the field dipole and source dipole, which reduces the complexity of interactions between two far groups (such as groupiand groupj) fromO(NiNj)toO(Ni+Nj), whereNiandNjare the numbers of dipoles in groupiand groupj, respectively. Targets including left-handed materials (LHMs), which are a kind of dielectric and magnetic materials, are calculated to demonstrate the merits of the FDM. Furthermore, in this study we find that the convergence may become much slower when the targets include LHMs compared with conventional electromagnetic materials. Numerical results about convergence characteristics are presented to show this property.
Swimming and Asthma: Differences between Women and Men
Authors: Päivinen Marja Kristiina , Keskinen Kari Lasse , Tikkanen Heikki Olavi
Published: February 2013

Background and Aim. Asthma is common in endurance athletes including swimmers. Our aim was to study gender differences in asthma, allergy, and asthmatic symptoms in swimmers and investigate the effects of varying intensities of physical exercise on competitive swimmers with asthma.Methods. Three hundred highly trained swimmers (156 females and 144 males) were studied by a questionnaire. Their mean (±SD) ages were17±3and19±3years, and they had training history of7±2and7±3years in females and males, respectively. Gender differences in asthma, allergy, and respiratory symptoms were examined. Special attention was focused on asthmatic swimmers, their allergies and respiratory symptoms during swimming at different intensities.Results. The prevalence of physician-diagnosed asthma was 19% for females and males. No gender differences in asthma or respiratory symptoms were found. Males reported allergies significantly more often than females (P=0.007). Gender difference was found in respiratory symptoms among swimmers with physician-diagnosed asthma because females reported symptoms significantly more often (P=0.017) than males. Asthmatic females also reported symptoms significantly more often at moderate intensity swimming (P=0.003) than males especially for coughing.Discussion. Gender difference in prevalence of asthma was not found in swimmers. However, allergy was reported significantly more by male swimmers. Male swimmers with asthma reported significantly more cases having family history of asthma, which may be a sign of selection of asthma-friendly sport. Moderate intensity swimming seemed to induce significantly more symptoms especially coughing in asthmatic females.
Exact Group Sequential Methods for Estimating a Binomial Proportion
Authors: Chen Zhengjia , Chen Xinjia
Published: February 2013

We first review existing sequential methods for estimating a binomial proportion. Afterward, we propose a new family of group sequential sampling schemes for estimating a binomial proportion with prescribed margin of error and confidence level. In particular, we establish the uniform controllability of coverage probability and the asymptotic optimality for such a family of sampling schemes. Our theoretical results establish the possibility that the parameters of this family of sampling schemes can be determined so that the prescribed level of confidence is guaranteed with little waste of samples. Analytic bounds for the cumulative distribution functions and expectations of sample numbers are derived. Moreover, we discuss the inherent connection of various sampling schemes. Numerical issues are addressed for improving the accuracy and efficiency of computation. Computational experiments are conducted for comparing sampling schemes. Illustrative examples are given for applications in clinical trials.