bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of the Essential Kinase PfCDPK1 from Plasmodium falciparum in Toxoplasma gondii Facilitates the Discovery of Novel Antimalarial Drugs
Authors: Gaji Rajshekhar Y. , Checkley Lisa , Reese Michael L. , Ferdig Michael T. , Arrizabalaga Gustavo
Published: February 2014

We have previously shown that genetic disruption of
Toxoplasma gondii
calcium-dependent protein kinase 3 (TgCDPK3) affects calcium ionophore-induced egress. We examined whether
Plasmodium falciparum
CDPK1 (PfCDPK1), the closest homolog of TgCDPK3 in the malaria parasite
P. falciparum
, could complement a TgCDPK3 mutant strain. PfCDPK1 is essential and plays critical roles in merozoite development, motility, and secretion. We show that expression of PfCDPK1 in the TgCDPK3 mutant strain rescues the egress defect. This phenotypic complementation requires the localization of PfCDPK1 to the plasma membrane and kinase activity. Interestingly, PfCDPK1-expressing
Toxoplasma
becomes more sensitive to egress inhibition by purfalcamine, a potent inhibitor of PfCDPK1 with low activity against TgCDPK3. Based on this result, we tested eight small molecules previously determined to inhibit the kinase activity of recombinant PfCDPK1 for their abilities to inhibit ionophore-induced egress in the PfCDPK1-expressing strain. While two of these chemicals did not inhibit egress, we found that six drugs affected this process selectively in PfCDPK1-expressing
Toxoplasma
. Using mutant versions of PfCDPK1 and TgCDPK3, we show that the selectivities of dasatinib and PLX-4720 are regulated by the gatekeeper residue in the ATP binding site. Importantly, we have confirmed that the three most potent inhibitors of egress in the PfCDPK1-expressing strain effectively kill
P. falciparum
. Thus, we have established and validated a recombinant strain of
Toxoplasma
that can be used as a surrogate for the discovery and analysis of PfCDPK1-specific inhibitors that can be developed as antimalarials.
Comparative Microbiological Studies of Transcription Inhibitors Fidaxomicin and the Rifamycins in Clostridium difficile
Authors: Babakhani Farah , Seddon Jaime , Sears Pamela
Published: February 2014

Fidaxomicin (FDX) is a narrow-spectrum antibiotic for the treatment of
Clostridium difficile
-associated diarrhea. While FDX and rifamycins share the same target (RNA polymerase), FDX exhibits a unique mode of action distinct from that of rifamycins. In comparative microbiological studies with
C. difficile
, FDX interacted synergistically with rifamycins, demonstrated a lower propensity for the development of resistance to rifamycins, and exhibited no cross-resistance with rifamycins. These results highlight differences in the mechanisms of action of FDX and rifamycins.
In Vitro
Activity of Plazomicin against 5,015 Gram-Negative and Gram-Positive Clinical Isolates Obtained from Patients in Canadian Hospitals as Part of the CANWARD Study, 2011-2012
Authors: Walkty A. , Adam H. , Baxter M. , Denisuik A. , Lagacé-Wiens P. , Karlowsky J. A. , Hoban D. J. , Zhanel G. G.
Published: February 2014

Plazomicin is a next-generation aminoglycoside that is not affected by most clinically relevant aminoglycoside-modifying enzymes. The
in vitro
activities of plazomicin and comparator antimicrobials were evaluated against a collection of 5,015 bacterial isolates obtained from patients in Canadian hospitals between January 2011 and October 2012. Susceptibility testing was performed using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method, with MICs interpreted according to CLSI breakpoints, when available. Plazomicin demonstrated potent
in vitro
activity against members of the family
Enterobacteriaceae
, with all species except
Proteus mirabilis
having an MIC
90
of ≤1 μg/ml. Plazomicin was active against aminoglycoside-nonsusceptible
Escherichia coli
, with MIC
50
and MIC
90
values identical to those for aminoglycoside-susceptible isolates. Furthermore, plazomicin demonstrated equivalent activities versus extended-spectrum β-lactamase (ESBL)-producing and non-ESBL-producing
E. coli
and
Klebsiella pneumoniae
, with 90% of the isolates inhibited by an MIC of ≤1 μg/ml. The MIC
50
and MIC
90
values for plazomicin against
Pseudomonas aeruginosa
were 4 μg/ml and 16 μg/ml, respectively, compared with 4 μg/ml and 8 μg/ml, respectively, for amikacin. Plazomicin had an MIC
50
of 8 μg/ml and an MIC
90
of 32 μg/ml versus 64 multidrug-resistant
P. aeruginosa
isolates. Plazomicin was active against methicillin-susceptible and methicillin-resistant
Staphylococcus aureus
, with both having MIC
50
and MIC
90
values of 0.5 μg/ml and 1 μg/ml, respectively. In summary, plazomicin demonstrated potent
in vitro
activity against a diverse collection of Gram-negative bacilli and Gram-positive cocci obtained over a large geographic area. These data support further evaluation of plazomicin in the clinical setting.
Pharmacokinetics of Ofloxacin and Levofloxacin for Prevention and Treatment of Multidrug-Resistant Tuberculosis in Children
Authors: Thee S. , Garcia-Prats A. J. , McIlleron H. M. , Wiesner L. , Castel S. , Norman J. , Draper H. R. , van der Merwe P. L. , Hesseling A. C. , Schaaf H. S.
Published: February 2014

Limited data on fluoroquinolone pharmacokinetics and cardiac effects in children exist. Among 22 children receiving drug-resistant tuberculosis prophylaxis or treatment, serum concentrations following oral doses of levofloxacin (15 mg/kg of body weight) and ofloxacin (20 mg/kg) were lower than those expected from existing pediatric data, possibly due to differences in the formulations (crushed tablets). Drug exposures were lower than those in adults following standard doses and below the proposed pharmacodynamic targets, likely due to more rapid elimination in children. No QT prolongation was observed.
IcgA Is a Virulence Factor of Rhodococcus equi That Modulates Intracellular Growth
Authors: Wang Xiaoguang , Coulson Garry B. , Miranda-CasoLuengo Aleksandra A. , Miranda-CasoLuengo Raúl , Hondalus Mary K. , Meijer Wim G.
Published: February 2014

Virulence of the intracellular pathogen
Rhodococcus equi
depends on a 21.3-kb pathogenicity island located on a conjugative plasmid. To date, the only nonregulatory pathogenicity island-encoded virulence factor identified is the cell envelope-associated VapA protein. Although the pathogenicity islands from porcine and equine
R. equi
isolates have undergone major rearrangements, the
virR
operon (
virR-icgA-vapH-orf7-virS
) is highly conserved in both, suggesting these genes play an important role in pathogenicity. VirR and VirS are transcriptional regulators controlling expression of pathogenicity island genes, including
vapA
. Here, we show that while
vapH
and
orf7
are dispensable for intracellular growth of
R. equi
, deletion of
icgA
, formerly known as
orf5
, encoding a major facilitator superfamily transport protein, elicited an enhanced growth phenotype in macrophages and a significant reduction in macrophage viability, while extracellular growth in broth remained unaffected. Transcription of
virS
, located downstream of
icgA
, and
vapA
was not affected by the
icgA
deletion during growth in broth or in macrophages, showing that the enhanced growth phenotype caused by deletion of
icgA
was not mediated through abnormal transcription of these genes. Transcription of
icgA
increased 6-fold within 2 h following infection of macrophages and remained significantly higher 48 h postinfection compared to levels at the start of the infection. The major facilitator superfamily transport protein IcgA is the first factor identified in
R. equi
that negatively affects intracellular replication. Aside from VapA, it is only the second pathogenicity island-encoded structural protein shown to play a direct role in intracellular growth of this pathogenic actinomycete.
Live Attenuated Influenza Vaccine Enhances Colonization of Streptococcus pneumoniae and Staphylococcus aureus in Mice
Authors: Mina Michael J. , McCullers Jonathan A. , Klugman Keith P.
Published: February 2014

Community interactions at mucosal surfaces between viruses, like influenza virus, and respiratory bacterial pathogens are important contributors toward pathogenesis of bacterial disease. What has not been considered is the natural extension of these interactions to live attenuated immunizations, and in particular, live attenuated influenza vaccines (LAIVs). Using a mouse-adapted LAIV against influenza A (H3N2) virus carrying the same mutations as the human FluMist vaccine, we find that LAIV vaccination reverses normal bacterial clearance from the nasopharynx and significantly increases bacterial carriage densities of the clinically important bacterial pathogens
Streptococcus pneumoniae
(serotypes 19F and 7F) and
Staphylococcus aureus
(strains Newman and Wright) within the upper respiratory tract of mice. Vaccination with LAIV also resulted in 2- to 5-fold increases in mean durations of bacterial carriage. Furthermore, we show that the increases in carriage density and duration were nearly identical in all aspects to changes in bacterial colonizing dynamics following infection with wild-type (WT) influenza virus. Importantly, LAIV, unlike WT influenza viruses, had no effect on severe bacterial disease or mortality within the lower respiratory tract. Our findings are, to the best of our knowledge, the first to demonstrate that vaccination with a live attenuated viral vaccine can directly modulate colonizing dynamics of important and unrelated human bacterial pathogens, and does so in a manner highly analogous to that seen following wild-type virus infection.

IMPORTANCE
Following infection with an influenza virus, infected or recently recovered individuals become transiently susceptible to excess bacterial infections, particularly
Streptococcus pneumoniae
and
Staphylococcus aureus
. Indeed, in the absence of preexisting comorbidities, bacterial infections are a leading cause of severe disease during influenza epidemics. While this synergy has been known and is well studied, what has not been explored is the natural extension of these interactions to live attenuated influenza vaccines (LAIVs). Here we show, in mice, that vaccination with LAIV primes the upper respiratory tract for increased bacterial growth and persistence of bacterial carriage, in a manner nearly identical to that seen following wild-type influenza virus infections. Importantly, LAIV, unlike wild-type virus, did not increase severe bacterial disease of the lower respiratory tract. These findings may have consequences for individual bacterial disease processes within the upper respiratory tract, as well as bacterial transmission dynamics within LAIV-vaccinated populations
Systems Biology-Based Identification of Mycobacterium tuberculosis Persistence Genes in Mouse Lungs
Authors: Dutta Noton K. , Bandyopadhyay Nirmalya , Veeramani Balaji , Lamichhane Gyanu , Karakousis Petros C. , Bader Joel S.
Published: February 2014

Identifying
Mycobacterium tuberculosis
persistence genes is important for developing novel drugs to shorten the duration of tuberculosis (TB) treatment. We developed computational algorithms that predict
M. tuberculosis
genes required for long-term survival in mouse lungs. As the input, we used high-throughput
M. tuberculosis
mutant library screen data, mycobacterial global transcriptional profiles in mice and macrophages, and functional interaction networks. We selected 57 unique, genetically defined mutants (18 previously tested and 39 untested) to assess the predictive power of this approach in the murine model of TB infection. We observed a 6-fold enrichment in the predicted set of
M. tuberculosis
genes required for persistence in mouse lungs relative to randomly selected mutant pools. Our results also allowed us to reclassify several genes as required for
M. tuberculosis
persistence
in vivo
. Finally, the new results implicated additional high-priority candidate genes for testing. Experimental validation of computational predictions demonstrates the power of this systems biology approach for elucidating
M. tuberculosis
persistence genes.

IMPORTANCE
Mycobacterium tuberculosis
, the causative agent of tuberculosis (TB), has a genetic repertoire that permits it to persist in the face of host immune responses. Identification of such persistence genes could reveal novel drug targets and elucidate mechanisms by which the organism eludes the immune system and resists drugs. Genetic screens have identified a total of 31 persistence genes, but to date only 15% of the ~4,000
M. tuberculosis
genes have been tested experimentally. In this paper, as an alternative to brute force experimental screens, we describe computational methods that predict new persistence genes by combining known examples with growing databases of biological networks. Experimental testing demonstrated that these predictions are highly accurate, validating the computational approach and providing new information about
M. tuberculosis
persistence in host tissues. Using the new experimental results as additional input highlights additional genes for testing. Our approach can be extended to other data types and target organisms to characterize host-pathogen interactions relevant to this and other infectious diseases.
Dual Role for Inflammasome Sensors NLRP1 and NLRP3 in Murine Resistance to Toxoplasma gondii
Authors: Gorfu Gezahegn , Cirelli Kimberly M. , Melo Mariane B. , Mayer-Barber Katrin , Crown Devorah , Koller Beverly H. , Masters Seth , Sher Alan , Leppla Stephen H. , Moayeri Mahtab , Saeij Jeroen P. J. , Grigg Michael E.
Published: February 2014

Induction of immunity that limitsToxoplasma gondiiinfection in mice is critically dependent on the activation of the innate immune response. In this study, we investigated the role of cytoplasmic nucleotide-binding domain and leucine-rich repeat containing a pyrin domain (NLRP) inflammasome sensors during acute toxoplasmosis in mice. We show thatin vitro Toxoplasmainfection of murine bone marrow-derived macrophages activates the NLRP3 inflammasome, resulting in the rapid production and cleavage of interleukin-1β (IL-1β), with no measurable cleavage of IL-18 and no pyroptosis. Paradoxically,Toxoplasma-infected mice produced large quantities of IL-18 but had no measurable IL-1β in their serum. Infection of mice deficient in NLRP3, caspase-1/11, IL-1R, or the inflammasome adaptor protein ASC led to decreased levels of circulating IL-18, increased parasite replication, and death. Interestingly, mice deficient in NLRP1 also displayed increased parasite loads and acute mortality. Using mice deficient in IL-18 and IL-18R, we show that this cytokine plays an important role in limiting parasite replication to promote murine survival. Our findings revealT. gondiias a novel activator of the NLRP1 and NLRP3 inflammasomesin vivoand establish a role for these sensors in host resistance to toxoplasmosis.

IMPORTANCEInflammasomes are multiprotein complexes that are a major component of the innate immune system. They contain “sensor” proteins that are responsible for detecting various microbial and environmental danger signals and function by activating caspase-1, an enzyme that mediates cleavage and release of the proinflammatory cytokines interleukin-1β (IL-1β) and IL-18.Toxoplasma gondiiis a highly successful protozoan parasite capable of infecting a wide range of host species that have variable levels of resistance. We report here thatT. gondiiis a novel activator of the NLRP1 and NLRP3 inflammasomesin vivoand establish a role for these sensors in host resistance to toxoplasmosis. Using mice deficient in IL-18 and IL-18R, we show that the IL-18 cytokine plays a pivotal role by limiting parasite replication to promote murine survival.
Bilateral hip arthritis in a case of renal osteodystrophy
Authors: Vaishya Raju , Nyokabi David Ndegwa , Vaish Abhishek
Published: February 2014

Chronic renal disease is often associated with secondary hyperparathyroidism (HPP) and rarely with tertiary HPP. Hip arthritis with protrusio acetabuli, secondary to tertiary HPP, is a rare case scenario and has not been described well in the literature. We present a rare case of bilateral hip arthritis with protrusio acetabuli secondary to renal osteodystrophy due to tertiary HPP. The diagnosis and aetiology of hip arthritis and its treatment have been discussed along with a detailed review of literature of skeletal lesions due to HPP.
Fetal ascites and hydrometrocolpos due to persistent urogenital sinus and cloaca: a rare congenital anomaly and review of literature
Authors: Nigam Aruna , Kumar Manisha , Gulati Shilpa
Published: February 2014

Fetal ascites can occur due to many heterogeneous disorders. Its association with hydrometrocolpos because of persistent urogenital sinus and cloaca is extremely rare. A 29-year-old primigravida presented at 32 weeks of gestation with ultrasonographic evidence of fetal ascites, a cystic pelvic mass, hydronephrosis and oligohydramnios. Fetal ascites in this case was due to fetal urine draining through fallopian tubes into the abdomen as a result of vesicovaginal fistula and distal vaginal atresia. The antenatal ultrasound results along with autopsy findings are discussed. Though rare, a persistent urogenital sinus is to be suspected in isolated fetal ascites cases where the viral tests are negative and there is no evidence of cardiac anomalies as this is a treatable anomaly if diagnosed at early gestational age.
Iatrogenic takotsubo cardiomyopathy induced by locally applied epinephrine and cocaine
Authors: Sundbøll Jens , Pareek Manan , Høgsbro Morten , Madsen Esben Hjorth
Published: February 2014

A 67-year-old man underwent surgery under general anaesthesia to obtain a biopsy from a tumour in the left maxillary sinus. Before the procedure a mucosal detumescence containing epinephrine and cocaine was applied onto the nasal mucosa. Shortly after termination of anaesthesia the patient developed tachycardia and an abrupt rise in blood pressure followed by a drop to critical levels. The patient turned pale and clammy but denied chest pain at any time. An ECG showed inferolateral ST-segment elevation, and troponin T was elevated at 0.773 ng/mL. An acute coronary angiography demonstrated normal coronary arteries; however, left ventriculography showed apical ballooning of the left ventricle, and the diagnosis of takotsubo cardiomyopathy was made. This was confirmed by a subsequent transthoracic echocardiography. Four days later the patient had complete resolution of the symptoms, and a new echocardiography showed normalisation of the left ventricular systolic function with no signs of apical ballooning.
Fracture and aspiration of a tracheostomy tube
Authors: Loh Tze Ling , Chin Ronald , Flynn Peter , Jayachandra Shruti
Published: February 2014

A 70-year-old woman presented with a fracture and aspiration of her polyvinyl chloride tracheostomy tube. Her chest X-ray showed that a foreign body was lodged in the right main bronchus. She was otherwise asymptomatic. The foreign body was removed under general anaesthesia using a flexible bronchoscope. The patient developed pneumonia after the procedure and was admitted to the intensive care unit. She was discharged home 5 days after the event with no permanent complications.
A randomised double-blind control study of early intracoronary autologous bone marrow cell infusion in acute myocardial infarction (REGENERATE-AMI)
Authors: Hamshere Stephen , Choudhury Tawfiq , Jones Daniel A , Locca Didier , Mills Peter , Rothman Martin , Knight Charles , Parmar Mahesh , Agrawal Samir , Martin John , Mathur Anthony
Published: February 2014

Introduction

Acute myocardial infarction (AMI) remains a major cause of mortality and morbidity worldwide despite the latest therapeutic advances designed to decrease myocardial injury. Preclinical and emerging clinical evidence show that the intracoronary injection of autologous bone marrow mononuclear cells (BMCs) following AMI leads to improvement in left ventricular ejection function (LVEF). In this clinical trial we will for the first time assess the effect of early (<24 h) infusion of autologous BMCs following AMI on cardiac function.

Methods and analysis

REGENERATE-AMI is a double-blind, randomised, multicentre, placebo-controlled trial to determine whether early (<24 h) intracoronary infusion of BMCs improves LVEF after AMI. The study will enrol 100 patients presenting with an anterior AMI demonstrating anterior regional wall motion abnormality. Patients will be randomised to receive intracoronary infusion of BMCs or placebo (0.9% saline). Primary endpoint will be change in LVEF at 1 year compared to baseline, measured by cardiac MRI. Secondary endpoints at 6 months include the change in global LVEF relative to baseline measured by quantitative left ventriculography and echocardiography, as well as major adverse cardiac events which is also measured at 1 year.

Ethics and dissemination

The study will be performed in agreement with the Declaration of Helsinki and is approved by local ethics committee (NRES Committee London West London: 07/Q0603/76).

Trial registration

http://clincialtrials.gov(NCT00765453). The results of the trial will be published according to the CONSORT statement and will be presented at conferences and reported in peer-reviewed journals.
Protocol for an HTA report: Does therapeutic writing help people with long-term conditions? Systematic review, realist synthesis and economic modelling
Authors: Meads C , Nyssen O P , Wong G , Steed L , Bourke L , Ross C A , Hayman S , Field V , Lord J , Greenhalgh T , Taylor S J C
Published: February 2014

Introduction

Long-term medical conditions (LTCs) cause reduced health-related quality of life and considerable health service expenditure. Writing therapy has potential to improve physical and mental health in people with LTCs, but its effectiveness is not established. This project aims to establish the clinical and cost-effectiveness of therapeutic writing in LTCs by systematic review and economic evaluation, and to evaluate context and mechanisms by which it might work, through realist synthesis.

Methods

Included are any comparative study of therapeutic writing compared with no writing, waiting list, attention control or placebo writing in patients with any diagnosed LTCs that report at least one of the following: relevant clinical outcomes; quality of life; health service use; psychological, behavioural or social functioning; adherence or adverse events. Searches will be conducted in the main medical databases including MEDLINE, EMBASE, PsycINFO, The Cochrane Library and Science Citation Index. For the realist review, further purposive and iterative searches through snowballing techniques will be undertaken. Inclusions, data extraction and quality assessment will be in duplicate with disagreements resolved through discussion. Quality assessment will include using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Data synthesis will be narrative and tabular with meta-analysis where appropriate. De novo economic modelling will be attempted in one clinical area if sufficient evidence is available and performed according to the National Institute for Health and Care Excellence (NICE) reference case.
Exploring the relationship between earthquake intensity and building damage using single and multi-degree of freedom models
Authors: Nazri Fadzli Mohamed , Alexander Nicholas A.
Published: February 2014

The correlation between intensity and damage measure for generic moment-resisting steel frames (MRSF) that are subjected to earthquake shaking was analysed using optimised nonlinear single degree of freedom (SDOF) models. The parameters for these SDOF models are based on nonlinear quasi-static pushover analyses of the multi-degree of freedom (MDOF) building systems. This intensity–damage relationship was then compared with those obtained from incremental dynamic analysis (IDA), that is a MDOF approach. Results show that the general trend line of intensity–damage measures for nonlinear SDOF model was qualitatively similar to the MDOF model that in this case represents a full nonlinear finite element analysis of the MRSF. While the SDOF model is not a precise match to the MDOF model, results suggests that it can be used in the vital role of ground motion record selection because of its computational efficiency. Furthermore, it is shown that the accuracy of intensity–damage estimates from the SDOF models can be improved if optimal damping, pseudo-yield, and ultimate loads are chosen. The efficacy of various intensity measures on damage are compared and contrasted.
A study of thin film flow of an Oldroyd 8-constant fluid on a moving belt using variational iteration approach
Authors: Siddiqui A.M. , Farooq A.A. , Haroon T. , Rana M.A.
Published: February 2014

In this paper, we model a steady thin film flow of an Oldroyd 8-constant fluid on a vertically moving belt. The governing nonlinear differential equation is first integrated exactly and then solved by applying the variational iteration method and the Adomian decomposition method. The numerical results obtained by these methods are then compared through graphs and tables and no visible difference is observed. This study highlights the significant features of the proposed methods and their ability for solving nonlinear problems arising in non-Newtonian fluid mechanics. Moreover, a reasonable estimation for the belt speed to lift the non-Newtonian fluid is also recorded. This estimation can be used for experimental verification.
Study of equilibrium isotherms of biosorption of lead ions onto Posidonica oceanica biomass: estimation of steric and energetic parameters using a statistical mechanics approach
Authors: Khalfaoui Mohamed , Nakhli Asma , Aguir Chadlia , Omri Aref , M’henni Mohamed Farouk , Lamine Abdelmottaleb Ben
Published: February 2014

Experimental adsorption isotherms of metal ions, such as Pb2+, from an aqueous solution onto raw and modified Posidonia materials with various contents of succinyl groups (from 29.8% to 39.2%) have been analyzed using a multilayer adsorption model. For such a purpose, a double layer model was selected to describe the adsorption process. The establishment of the model expression is based on a statistical physics treatment, and especially on the grand canonical formalism. We mainly introduce four parameters affecting the adsorption process, namely, the fraction or the number of adsorbed ions per site, the receptor site density, and the energetic parameters related to each adsorbed layer. The study of the anchorage number allows us to follow the evolution of the lead adsorption when varying the experimental conditions. The evolution of the effectively occupied receptor site density shows that the van der Waals and hydrogen bonds are involved during the adsorption process. The magnitudes of the adsorption energies indicate that lead ions are physisorbed onto Posidonia. Furthermore, the disorder during the adsorption process was followed via the investigation of the entropy. The adsorption process was spontaneous as it is indicated by the free adsorption enthalpy.
Structural dynamics of viral nanomachines
Authors: Kam Joanna , Demmert Andrew C. , Tanner Justin R. , McDonald Sarah M. , Kelly Deborah F.
Published: February 2014

Rotavirus double-layered particles (DLPs) are formed immediately following entry of virions into a host cell. To study the structural dynamics of actively transcribing rotavirus DLPs, we implemented high resolution imaging procedures along with automated computing routines to visualize mRNA synthesis at the nanoscale. Our combined technologies demonstrate a new approach to monitor dynamic structural processes, such as capsid rearrangements, that may be applied to the study of other viruses.
A combined magnetophoresis/dielectrophoresis based microbead array as high-throughput biomolecular tweezers
Authors: Cao Lizhi , Peng Zhengchun , Lam Wilbur , Barker Thomas H.
Published: February 2014

In this paper we describe a combined magnetophoresis (MAP) and dielectrophoresis (DEP) based platform for high throughput characterization of specific biomolecular interactions. The magnetic manipulation enables parallel loading of individual magnetic beads onto a magnetic pad array, while the combination of tightly controlled opposing magnetic and dielectrophoretic (DEP) forces is employed to produce characteristic out-of-plane (z-axial) bead displacement. We optimized design parameters to evenly load 2.8 μm biomolecule functionalized paramagnetic beads onto magnetic pads, and demonstrate the ability of our tweezers to discriminate between specific antibody-antigen bond from non-specific bond formed between bead and pad surface.
Molecular and metabolic profiles suggest that increased lipid catabolism in adipose tissue contributes to leanness in domestic chickens
Authors: Ji Bo , Middleton Jesse L. , Ernest Ben , Saxton Arnold M. , Lamont Susan J. , Campagna Shawn R. , Voy Brynn H.
Published: February 2014

Domestic broiler chickens rapidly accumulate fat and are naturally hyperglycemic and insulin resistant, making them an attractive model for studies of human obesity. We previously demonstrated that short-term (5 h) fasting rapidly upregulates pathways of fatty acid oxidation in broiler chickens and proposed that activation of these pathways may promote leanness. The objective of the current study was to characterize adipose tissue from relatively lean and fatty lines of chickens and determine if heritable leanness in chickens is associated with activation of some of the same pathways induced by fasting. We compared adipose gene expression and metabolite profiles in white adipose tissue of lean Leghorn and Fayoumi breeds to those of fattier commercial broiler chickens. Both lipolysis and expression of genes involved in fatty acid oxidation were upregulated in lean chickens compared with broilers. Although there were strong similarities between the lean lines compared with broilers, distinct expression signatures were also found between Fayoumi and Leghorn, including differences in adipogenic genes. Similarities between genetically lean and fasted chickens suggest that fatty acid oxidation in white adipose tissue is adaptively coupled to lipolysis and plays a role in heritable differences in fatness. Unique signatures of leanness in Fayoumi and Leghorn lines highlight distinct pathways that may provide insight into the basis for leanness in humans. Collectively, our results provide a number of future directions through which to fully exploit chickens as unique models for the study of human obesity and adipose metabolism.
Numerical Investigation of the Influence of Injection Scheme on the Ethylene Supersonic Combustion
Authors: Ouyang Hao , Liu Weidong , Sun Mingbo
Published: February 2014

Ethylene supersonic combustion flow field in different injection schemes was studied numerically in the flight Mach 4. The results show that injection pressure has significant influence on the location of the separation zone and the heat release region, but the starting point of the separation region was mostly influenced by the heat release rather than by the injection pressure; the combustion efficiency of the injection schemes including two injection points is higher than that of three injection points, while the total pressure recovery coefficient of the former injection schemes is lower than the latter; excessive ethylene injected in upstream will lead to the change of free-stream flow conditions, which behaves as the inlet unstart in practical application; more ethylene could be injected in downstream to avoid the problem; on the condition of avoiding thermal choke in isolator, it is more advantageous that injection points were arranged more closely to the starting point of separation zone in upside and to the front of the cavity in downside.
Influence of Turbulence, Orientation, and Site Configuration on the Response of Buildings to Extreme Wind
Authors: Aly Aly Mousaad
Published: February 2014

Atmospheric turbulence results from the vertical movement of air, together with flow disturbances around surface obstacles which make low- and moderate-level winds extremely irregular. Recent advancements in wind engineering have led to the construction of new facilities for testing residential homes at relatively high Reynolds numbers. However, the generation of a fully developed turbulence in these facilities is challenging. The author proposed techniques for the testing of residential buildings and architectural features in flows that lack fully developed turbulence. While these methods are effective for small structures, the extension of the approach for large and flexible structures is not possible yet. The purpose of this study is to investigate the role of turbulence in the response of tall buildings to extreme winds. In addition, the paper presents a detailed analysis to investigate the influence of upstream terrain conditions, wind direction angle (orientation), and the interference effect from the surrounding on the response of high-rise buildings. The methodology presented can be followed to help decision makers to choose among innovative solutions like aerodynamic mitigation, structural member size adjustment, and/or damping enhancement, with an objective to improve the resiliency and the serviceability of buildings.
Tuning of Transport and Magnetic Properties in Epitaxial LaMnO3+δThin Films
Authors: Chen J. , Hu L. , Lu W. J. , Yuan B. , Zhang K. J. , Dai J. M. , Sun Y. P.
Published: February 2014

The effect of compressive strain on the transport and magnetic properties of epitaxial LaMnO3+δthin films has been investigated. It is found that the transport and magnetic properties of the LaMnO3+δthin films grown on the LaAlO3substrates can be tuned by the compressive strain through varying film thickness. And the insulator-metal transition, charge/orbital ordering transition, and paramagnetic-ferromagnetic transition are suppressed by the compressive strain. Consequently, the related electronic and magnetic transition temperatures decrease with an increase in the compressive strain. The present results can be explained by the strain-controlled lattice deformation and the consequent orbital occupation. It indicates that the lattice degree of freedom is crucial for understanding the transport and magnetic properties of the strongly correlated LaMnO3+δ.
Expansion/Facemask Treatment of an Adult Class III Malocclusion
Authors: Jackson Gregory W. , Kravitz Neal D.
Published: February 2014

The orthodontic treatment of class III malocclusion with a maxillary deficiency is often treated with maxillary protraction with or without expansion. Skeletal and dental changes have been documented which have combined for the protraction of the maxilla and the correction of the class III malocclusion. Concerning the ideal time to treat a developing class III malocclusion, studies have reported that, although early treatment may be the most effective, face mask therapy can provide a viable option for older children as well. But what about young adults? Can the skeletal and dental changes seen in expansion/facemask therapy in children and adolescents be demonstrated in this age group as well, possibly eliminating the need for orthodontic dental camouflage treatment or orthognathic surgery? A case report is presented of an adult class III malocclusion with a Class III skeletal pattern and maxillary retrusion. Treatment was with nonextraction, comprehensive edgewise mechanics with slow maxillary expansion with a bonded expander and protraction facemask.
Hybrid Machine Learning Technique for Forecasting Dhaka Stock Market Timing Decisions
Authors: Banik Shipra , Khodadad Khan A. F. M. , Anwer Mohammad
Published: February 2014

Forecasting stock market has been a difficult job for applied researchers owing to nature of facts which is very noisy and time varying. However, this hypothesis has been featured by several empirical experiential studies and a number of researchers have efficiently applied machine learning techniques to forecast stock market. This paper studied stock prediction for the use of investors. It is always true that investors typically obtain loss because of uncertain investment purposes and unsighted assets. This paper proposes a rough set model, a neural network model, and a hybrid neural network and rough set model to find optimal buy and sell of a share on Dhaka stock exchange. Investigational findings demonstrate that our proposed hybrid model has higher precision than the single rough set model and the neural network model. We believe this paper findings will help stock investors to decide about optimal buy and/or sell time on Dhaka stock exchange.
Explaining Attitudes and Adherence to Antipsychotic Medication: The Development of a Process Model
Authors: Wiesjahn Martin , Jung Esther , Lamster Fabian , Rief Winfried , Lincoln Tania M.
Published: February 2014

Although nonadherence to antipsychotic medication poses a threat to outcome of medical treatment, the processes preceding the intake behavior have not been investigated sufficiently. This study tests a process model of medication adherence derived from the Health Belief Model which is based on cost-benefit considerations. The model includes an extensive set of potential predictors for medication attitudes and uses these attitudes as a predictor for medication adherence. We conducted an online study of 84 participants with a self-reported psychotic disorder and performed a path analysis. More insight into the need for treatment, a higher attribution of the symptoms to a mental disorder, experience of less negative side effects, presence of biological causal beliefs, and less endorsement of psychological causal beliefs were significant predictors of more positive attitudes towards medication. The results largely supported the postulated process model. Mental health professionals should consider attitudes towards medication and the identified predictors when they address adherence problems with the patient in a shared and informed decision process.
Calibration and Motion Control of a Cable-Driven Parallel Manipulator Based Triple-Level Spatial Positioner
Authors: Duan Xuechao , Qiu Yuanying , Duan Qingjuan , Du Jingli
Published: February 2014

This paper deals with the kinematic calibration and motion control of a triple-level spatial positioner consisting of the cable-driven parallel manipulator (CDPM), active gyro stabilizer (AGS), and the Stewart platform. A six-degree-of-freedom laser tracker is employed when calibrating the benchmark positions and measuring the real-time position and orientation in motion control, which makes it a straightforward solution to tackle with hierarchical mechatronic system actuated by servomotors with incremental encoders. Then the trajectory planning and motion control of the triple-level robotic spatial positioner are explored to verify the correctness and to what extent the calibration improves the system. This CDPM based spatial positioner has an accuracy of several millimeters though it has a ten-meter workspace.
Cancer Stem Cells Accountability in Progression of Head and Neck Squamous Cell Carcinoma: The Most Recent Trends!
Authors: Routray Samapika , Mohanty Neeta
Published: February 2014

Cancer stem cells (CSCs) play a major role in local recurrence and metastatic spread in head and neck squamous cell carcinomas (HNSCC). Evidence suggests that cancer stem cells are resistant to conventional therapy. So the emerging concepts of the role of cancer stem cells in the pathobiology of HNSCC should be understood carefully to be able to create new paradigms in treatment plans.
Comparison of the Effects of Glucose and Fructose on Exercise Metabolism, Perceived Exertion, and Recovery in Untrained Females
Authors: Folarin Babatunde O. , Macdonald Ian A. , Khaled Latif , Jill Patterson , Hannah Capocci , Phil Thirkell , Joy Macdermid C.
Published: February 2014

This double-blinded, crossover randomized controlled trial study was designed to establish if combined ingestion of glucose and fructose (GLU + FRU) at the moderate rate 0.5 g·min−1 would result in higher rates of carbohydrate (CHO) oxidation compared with glucose (GLU) alone. Eight untrained females (VO2max: 25.8 ± 3.2 mL·kg−1·min−1) cycled on two different occasions for 60 min at 50% of maximal power output (60% ± 1 % VO2max) and consumed 12% CHO solution of either providing 0.33 g·min−1 glucose + 0.17 g·min−1 fructose (GLU + FRUC) or 0.5 g·min−1 of glucose (GLU) alone. Heart rate (HR) and rate of perceived exertion (RPE) were assessed during exercise and subjective exercise experience assessed two days after each trial. CHO oxidation was not significantly different (P>0.05) between GLU + FRU and GLU (0.8 ± 0.06 g·min−1 and 0.78 ± 0.05 g·min−1, resp.). CHO oxidation rates during the final 30 min of the recovery period were not significantly different between GLU + FRU and GLU (0.17 ± 0.04 g·min−1 and 0.14 ± 0.05 g·min−1, resp.). Experience of distress was significantly higher (P<0.05) for GLU compared to GLU + FRU. The results reveal that consuming modest amounts of glucose plus fructose does not boost CHO oxidation above that of glucose alone during submaximal exercise.
Toughness Calculation of Postfire Normal Concrete
Authors: Chen Qingyang , Tang Anjing , Lu Zhoudao
Published: February 2014

Fracture tests of postfire normal concrete with ten temperatures up to 600°C are implemented. Residual fracture toughness using analytical method is determined. Two situations are divided at critical load when calculating the cohesive fracture toughness. The initial and critical fracture toughness could be calculated from the complete load-crack opening displacement curves. Finally, the validation of double-Kfracture model to the postfire concrete specimens is proved.
A Generalization of the Havrda-Charvat and Tsallis Entropy and Its Axiomatic Characterization
Authors: Kumar Satish , Ram Gurdas
Published: February 2014

In this communication, we characterize a measure of information of typesα,β, andγby taking certain axioms parallel to those considered earlier by Havrda and Charvat along with the recursive relationHn(p1,…,pn;α,β,γ)-Hn-1(p1+p2,p3,…,pn;α,β,γ)=(A(α,γ)/(A(α,γ)-A(β,γ)))p1+p2α/γH2(p1/(p1+p2),p2/(p1+p2);α,γ)+(A(β,γ)/(A(β,γ)-A(α,γ)))(p1+p2)(β/γ)H2(p1/(p1+p2),p2/(p1+p2);γ,β),α≠γ≠β,α,β,γ>0. Some properties of this measure are also studied. This measure includes Shannon’s information measure as a special case.
Fast Model Predictive Control Method for Large-Scale Structural Dynamic Systems: Computational Aspects
Authors: Peng Haijun , Gao Qiang , Wu Zhigang , Zhong Wanxie
Published: February 2014

A fast and accurate model predictive control method is presented for dynamic systems representing large-scale structures. The fast model predictive control formulation is based on highly efficient computations of the state transition matrix, that is, the matrix exponential, using an improved precise integration method. The enhanced efficiency for model predictive control is achieved by exploiting the sparse structure of the matrix exponential at each discrete time step. Accuracy is maintained using the precise integration method. Compared with the general model predictive control method, the reduced central processing unit (CPU) time required by the fast model predictive control scheme can result in a shorter control update interval and a lower online computational burden. Therefore, the proposed method is more efficient for large-scale structural dynamic systems.
Interactions between Neutrophils, Th17 Cells, and Chemokines during the Initiation of Experimental Model of Multiple Sclerosis
Authors: Wojkowska Dagmara Weronika , Szpakowski Piotr , Ksiazek-Winiarek Dominika , Leszczynski Marcin , Glabinski Andrzej
Published: February 2014

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS) in which activated T cell and neutrophil interactions lead to neuroinflammation. In this study the expression of CCR6, CXCR2, and CXCR6 in Th17 cells and neutrophils migrating to the brain during EAE was measured, alongside an evaluation of the production of IL-17, IL-23, CCL-20, and CXCL16 in the brain. Next, inflammatory cell subpopulations accumulating in the brain after intracerebral injections of IL-17 or CXCL1, as well as during modulation of EAE with anti-IL-23R or anti-CXCR2 antibodies, were analyzed. Th17 cells upregulate CXCR2 during the preclinical phase of EAE and a significant migration of these cells to the brain was observed. Neutrophils upregulated CCR6, CXCR2, and CXCR6 during EAE, accumulating in the brain both prior to and during acute EAE attacks. Production of IL-17, IL-23, CCL20, and CXCL16 in the CNS was increased during both preclinical and acute EAE. Intracerebral delivery of CXCL1 stimulated the early accumulation of neutrophils in normal and preclinical EAE brains but reduced the migration of Th17 cells to the brain during the preclinical stage of EAE. Modulation of EAE by anti-IL-23R antibodies ameliorated EAE by decreasing the intracerebral accumulation of Th17 cells.
Investigation of Coronal Leakage of Root Fillings after Smear Layer Removal with EDTA or Er,Cr:YSGG Laser through Capillary Flow Porometry
Authors: Vergauwen Tom Edgard Maria , Michiels Rafaël , Torbeyns Dries , Meire Maarten , De Bruyne Mieke , De Moor Roeland Jozef Gentil
Published: February 2014

No studies have been performed evaluating the marginal seal of root fillings after direct exposure of root canal (RC) walls to Er,Cr:YSGG laser irradiation. Therefore, 75 root filled teeth (5 × 15–cold lateral condensation) were analyzed for through-and-through leakage (TTL) using capillary flow porometry (CFP). The cleaning protocol determined the experimental groups: (1) irrigation with NaOCl 2.5% and EDTA 17% or standard protocol (SP), (2) SP + Er,Cr:YSGG lasing (dried RC), (3) NaOCl 2.5% + Er,Cr:YSGG lasing (dried RC), (4) SP + Er,Cr:YSGG lasing (wet RC), and (5) NaOCl 2.5% + Er,Cr:YSGG lasing (wet RC). Groups 6 to 10 consisted of the same filled teeth with resected apices. Resection was performed after the first CFP measurement. CFP was used to assess minimum, mean flow, and maximum pore diameters after 48 h. Statistics were performed using nonparametric tests (P>0.05). Additional three roots per group were submitted to SEM of the RC walls. TTL was observed in all groups without statistically significant differences between the different groups for minimum, mean, and maximum pore diameter (P>0.05). In this study, the use of EDTA and/or Er,Cr:YSGG laser did not reduce through-and-through leakage in nonresected and resected roots.
Exploring the Best Classification from Average Feature Combination
Authors: Hou Jian , Liu Wei-Xue , Karimi Hamid Reza
Published: February 2014

Feature combination is a powerful approach to improve object classification performance. While various combination algorithms have been proposed, average combination is almost always selected as the baseline algorithm to be compared with. In previous work we have found that it is better to use only a sample of the most powerful features in average combination than using all. In this paper, we continue this work and further show that the behaviors of features in average combination can be integrated into thek-Nearest-Neighbor (kNN) framework. Based on the kNN framework, we then propose to use a selection based average combination algorithm to obtain the best classification performance from average combination. Our experiments on four diverse datasets indicate that this selection based average combination performs evidently better than the ordinary average combination, and thus serves as a better baseline. Comparing with this new and better baseline makes the claimed superiority of newly proposed combination algorithms more convincing. Furthermore, the kNN framework is helpful in understanding the underlying mechanism of feature combination and motivating novel feature combination algorithms.