bluuebunny/crossref_metadata_2025 huggingface dataset:
Ontogeny of bivalve immunity: assessing the potential of next‐generation sequencing techniques
Authors: Bassim Sleiman , Genard Bertrand , Gauthier‐Clerc Sophie , Moraga Dario , Tremblay Réjean
Published: June 2014

Living organisms are constantly evolving to secure their survival via adaptations at the molecular and cellular level. Most marine bivalves have microscopic planktonic larval stages until settlement to the benthic environment. These pelagic stages are generally more sensitive than their adult counterparts to environmental and pathogen threats. Adaptive capacities could improve survival of these early stages. Recent advancements in data mining and pipeline analysis should shed light on the currently unknown processes that occur during these first stages. Existing data on early stages are fragmented compared with the abundance of information available for adult. Exploring diversity through aquaculture and lessening the impact of common issues, for example, massive mortalities of larvae, especially within the current conditions of a changing climate, ultimately rests on our knowledge of the molecular processes responsible for phenotypic plasticity. Although it is somewhat difficult to assess immune mechanisms by tracking circulating immunocytes in larvae, studies on the development of immune processes are now feasible at the transcript level. Next‐generation techniques offer outstanding solutions for wide‐range transcriptome analysis. We present a short review of the early ontogeny of the immune system in marine bivalves, with particular focus on next‐generation sequencing applications. Like all reviews of this nature, there is a trade‐off between the depth of the coverage and the number of subjects discussed. We will thus restrict the scope to bivalve immunity and focus on the central concepts across a wide range of topics, that is, the ontogeny of immunity and advancements in molecular studies.
A combined study of radar facies, lithofacies and three‐dimensional architecture of an alpine alluvial fan (Illgraben fan, Switzerland)
Authors: Franke Daniel , Hornung Jens , Hinderer Matthias
Published: June 2014

Alluvial fans serve as useful archives that record the history of depositional and erosional processes in mountainous regions and thus can reveal the environmental controls that influenced their development. Economically, they play an important role as groundwater reservoirs as well as host rocks for hydrocarbons in deeply buried systems. The interpretation of these archives and the evaluation of their reservoir architecture, however, are problematic because marked heterogeneity in the distribution of sedimentary facies makes correlation difficult. This problem is compounded because the accumulated sedimentary deposits of modern unconsolidated fan systems tend to be poorly exposed and few such systems have been the focus of investigation using high‐resolution subsurface analytical techniques. To overcome this limitation of standard outcrop–analogue studies, a geophysical survey of an alpine alluvial fan was performed using ground‐penetrating radar to devise a scaled three‐dimensional subsurface model. Radar facies were classified and calibrated to lithofacies within a fan system that provided outcropping walls and these were used to derive a three‐dimensional model of the sedimentary architecture and identify evolutionary fan stages. The Illgraben fan in the Swiss Alps was selected as a case study and a network of ca 60 km sections of ground‐penetrating radar was surveyed. Seven radar facies types could be distinguished, which were grouped into debris‐flow deposits and stream‐flow deposits. Assemblages of these radar facies types show three depositional units, which are separated by continuous, fan‐wide reflectors; they were interpreted as palaeo‐surfaces corresponding to episodes of sediment starvation that affected the entire fan. An overall upward decline in the proportion of debris‐flow deposits from ca 50% to 15% and a corresponding increase in stream‐flow deposits were identified. The uppermost depositional unit is bounded at its base by a significant incision surface up to 700 m wide, which was subsequently filled up mostly by stream‐flow deposits. The pronounced palaeo‐surfaces and depositional trends suggest that allocyclic controls governed the evolution of the Illgraben fan, making this fan a valuable archive from which to reconstruct past sediment fluxes and environmental change in the Alps. The results of the integrated outcrop–geophysical approach encourage similar future studies on fans to retrieve their depositional history as well as their potential reservoir properties.
Experimental design and parameter estimation for threshold models in seed germination
Authors: Onofri A , Mesgaran M B , Neve P , Cousens R D
Published: June 2014

Hydrotime threshold models are used to describe the dynamics of seed germination in response to reduced water availability. Although these models provide several biologically relevant parameters, it is unclear which statistical technique is best suited to their estimation. Most commonly, these models are fitted to the observed cumulative proportions of germinated seeds, using nonlinear regression. However, this approach has been questioned, due to its inability to account for some characteristics of data sets obtained from germination assays, such as interval censoring and correlated observations. We used Monte Carlo simulations to determine the bias and precision of nonlinear regression estimators for a wide range of experimental designs and hypothetical plant species. Results showed that point estimates of model parameters were almost unbiased, while standard errors obtained from nonlinear regression were on average 3–4 times smaller than the Monte Carlo precision. Standard errors obtained by nonparametric resampling methods were comparable to Monte Carlo precision and provided good coverage (very close to the nominal 95% value), with at least 4–8 treatments by four replicates and 50 seeds per Petri dish. With 10 seeds per Petri dish, a higher number of replicates were necessary to achieve good coverage. In particular, good results were obtained with the grouped jackknife (delete‐a‐Petri‐dish), which accounts for repeated observations on the same Petri dish. It is suggested that nonlinear regression may be used to fit the hydrotime model, in association with resampling methods, particularly when the purpose is to compare ‘hydrotime’ parameters across treatments or plant species.
A Complex Variable Solution Based Analysis of Electric Displacement Saturation for a Cracked Piezoelectric Material
Authors: Linder Christian
Published: June 2014

This paper presents an analysis of the effect of electric displacement saturation for a failing piezoelectric ceramic material based on a complex variable solution of a Mode III and a Mode I crack. This particular electric nonlinearity is caused by a reduction of the ionic movement in the material in the presence of high electric fields. Total and strain energy release rates are computed for varying far field stresses, electric displacements, and electric fields and compared for cases without and with full electric displacement saturation to further advance the understanding of failure initiation in piezoelectric ceramics.
Experimental Validation of a Computational Fluid Dynamics Methodology for Transitional Flow Heat Transfer Characteristics of a Steady Impinging Jet
Authors: Alimohammadi Sajad , Murray Darina B. , Persoons Tim
Published: June 2014

This paper presents a computational fluid dynamics (CFD) methodology to accurately predict the heat transfer characteristics of an unconfined steady impinging air jet in the transitional flow regime, impinging on a planar constant-temperature surface. The CFD methodology is validated using detailed experimental measurements of the local surface heat transfer coefficient. The numerical model employs a transitional turbulence model which captures the laminar–turbulent transition in the wall jet which precisely predicts the intensity and extent of the secondary peak in the radial Nusselt number distribution. The paper proposes a computationally low-cost turbulence model which yields the most accurate results for a wide range of operating and geometrical conditions. A detailed analysis of the effect of mesh grid size and properties, inflow conditions, turbulence model, and turbulent Prandtl number Prt is presented. The numerical uncertainty is quantified by the grid convergence index (GCI) method. In the range of Reynolds number 6000 ≤ Re ≤ 14,000 and nozzle-to-surface distance 1 ≤ H/D ≤ 6, the model is in excellent agreement with the experimental data. For the case of H/D = 1 and Re = 14,000, the maximum deviations are 5%, 3%, and 2% in terms of local, area-averaged and stagnation point Nusselt numbers, respectively. Experimental and numerical correlations are presented for the stagnation point Nusselt number.
Analysis of Coupled Bending-Torsional Vibration of Beams in the Presence of Uncertainties
Authors: Rao Singiresu S. , Jin Hongling
Published: June 2014

Several methods are presented for the modeling and analysis of uncertain beams and other structural elements/systems. By representing each uncertain parameter as an interval number, the vibration problem associated with any uncertain system can be expressed in the form of a system of nonlinear interval equations. The resulting equations can be solved using the exact or a truncation-based interval analysis method. An universal grey number-based approach and an interval-discretization method are proposed to obtain more efficient and/or more accurate solutions. Specifically, the problem of the coupled bending-torsional vibration of a beam involving uncertainties is considered. It is found that the range of the solution (response) increases with increasing levels of uncertainty in all the methods. Numerical examples are presented to illustrate the computational aspects of the methods presented and also to indicate the high accuracy of the interval-discretization approach in finding the solution of practical uncertain systems. The results given by the different interval analysis methods (including the universal grey number-based analysis) are compared with those given by the Monte Carlo method (probabilistic approach) and the results are found to be in good agreement with those given by the interval analysis-based methods for similar data.
Three-Dimensional Natural Vibration Analysis With Meshfree Solution Structure Method
Authors: Kosta Tomislav , Tsukanov Igor
Published: June 2014

This paper describes the pioneering application of the meshfree solution structure method (SSM) to computer simulation of natural vibrations of 3D mechanical parts and structures. Using several carefully chosen examples, we investigate the accuracy and convergence of the computed natural frequencies. The salient feature of our approach is exact treatment of the prescribed boundary conditions that are enforced using approximate distance functions that vanish on the boundaries of a geometric model. Ability to use spatial meshes that do not necessarily conform to the shape of the geometric model makes it possible to eliminate or substantially simplify the finite element meshing. This defines unprecedented geometric flexibility of the SSM as well as the complete automation of the solution procedure.
Large amplitude oscillatory shear and Fourier transform rheology analysis of branched polymer melts
Authors: Hoyle D. M. , Auhl D. , Harlen O. G. , Barroso V. C. , Wilhelm M. , McLeish T. C. B.
Published: June 2014

In this paper, the predictions of the Pompom constitutive model in medium and large amplitude oscillatory shear (LAOS) are examined using Fourier transform rheology (FTR). FTR is commonly used in combination with small amplitude oscillatory shear to fit linear Maxwell parameters to dynamic moduli, and in this paper, this process is expanded to larger strain amplitudes and to further terms in the Fourier series. For both small and large amplitudes, these higher harmonics are dependent on the nonlinear Pompom parameters and the Pompom parameter space is explored to see how experimental oscillatory shear data can infer molecular detail. In the regime of small and medium strain amplitude, there exists an asymptotic solution to the Pompom equations which depends only on the ratio of the orientation and stretch relaxation times, τb and τs. This asymptotic solution is found to be accurate up to strains of order unity and the branching priority, q, only affects the stress response at larger strains. The Pompom parameters fitted to extensional data are compared to LAOS data for three materials; two lightly branched metallocene catalyzed high density polyethylenes and a densely branched low density polyethylenes. In general, the Pompom model performs well in LAOS but tends to over predict experimental results at high strain amplitudes.
Memo Is a Copper-Dependent Redox Protein with an Essential Role in Migration and Metastasis
Authors: MacDonald Gwen , Nalvarte Ivan , Smirnova Tatiana , Vecchi Manuela , Aceto Nicola , Doelemeyer Arno , Frei Anna , Lienhard Susanne , Wyckoff Jeffrey , Hess Daniel , Seebacher Jan , Keusch Jeremy J. , Gut Heinz , Salaun Daniele , Mazzarol Giovanni , Disalvatore Davide , Bentires-Alj Mohamed , Di Fiore Pier Paolo , Badache Ali , Hynes Nancy E.
Published: June 2014

Copper chelators could help to reduce metastasis from breast tumors.
Evaluation of a Fluorescence-Based Method for Antibabesial Drug Screening
Authors: Guswanto Azirwan , Sivakumar Thillaiampalam , Rizk Mohamed Abdo , Elsayed Shimaa Abd Elsalam , Youssef Mohamed Ahmed , ElSaid ElSaid El Shirbini , Yokoyama Naoaki , Igarashi Ikuo
Published: June 2014

In vitro
evaluation of chemotherapeutic agents against
Babesia
and
Theileria
parasites has become routine, and the effectiveness of these chemicals is usually determined by comparing the parasitemia dynamics of untreated and treated parasites. Although microscopy is widely used to calculate parasitemia, several disadvantages are associated with this technique. The present study evaluated a fluorescence-based method using SYBR green I stain (SG I) to screen antibabesial agents in
in vitro
cultures of
Babesia bovis
. The linearity between relative fluorescence units (RFU) and parasitemia was found to be well correlated with a 0.9944 goodness-of-fit (
r
2
) value. Subsequently, 50% inhibitory concentration (IC
50
) values were calculated for 3 antiprotozoan agents, diminazene aceturate, nimbolide, and gedunin, by this method. For diminazene aceturate and nimbolide, the IC
50
s determined by the fluorescence-based method (408 nM and 8.13 μM, respectively) and microscopy (400.3 nM and 9.4 μM, respectively) were in agreement. Furthermore, the IC
50
of gedunin determined by the fluorescence-based method (19 μM) was similar to the recently described microscopy-based value (21.7 μM) for
B. bovis
. Additionally, the Z′ factor (0.80 to 0.90), signal-to-noise (S/N) ratio (44.15 to 87.64), coefficient of variation at the maximum signal (%CVmax) (0.50 to 2.85), and coefficient of variation at the minimum signal (%CVmin) (1.23 to 2.21) calculated for the fluorescence method using diminazene aceturate were comparable to those previously determined in malaria research for this assay. These findings suggest that the fluorescence-based method might be useful for antibabesial drug screening and may have potential to be developed into a high-throughput screening (HTS) assay.
Population Structure of KPC-Producing Klebsiella pneumoniae Isolates from Midwestern U.S. Hospitals
Authors: Wright Meredith S. , Perez Federico , Brinkac Lauren , Jacobs Michael R. , Kaye Keith , Cober Eric , van Duin David , Marshall Steven H. , Hujer Andrea M. , Rudin Susan D. , Hujer Kristine M. , Bonomo Robert A. , Adams Mark D.
Published: June 2014

Genome sequencing of carbapenem-resistant
Klebsiella pneumoniae
isolates from regional U.S. hospitals was used to characterize strain diversity and the
bla
KPC
genetic context. A phylogeny based on core single-nucleotide variants (SNVs) supports a division of sequence type 258 (ST258) into two distinct groups. The primary differences between the groups are in the capsular polysaccharide locus (
cps
) and their plasmid contents. A strict association between clade and KPC variant was found. The
bla
KPC
gene was found on variants of two plasmid backbones. This study indicates that highly similar
K. pneumoniae
subpopulations coexist within the same hospitals over time.
Efficacy of Repeated Intravenous Administration of Peramivir against Highly Pathogenic Avian Influenza A (H5N1) Virus in Cynomolgus Macaques
Authors: Kitano Mitsutaka , Itoh Yasushi , Ishigaki Hirohito , Nakayama Misako , Ishida Hideaki , Pham Van Loi , Arikata Masahiko , Shichinohe Shintaro , Tsuchiya Hideaki , Kitagawa Naoko , Kobayashi Masanori , Yoshida Ryu , Sato Akihiko , Le Quynh Mai , Kawaoka Yoshihiro , Ogasawara Kazumasa
Published: June 2014

Highly pathogenic avian influenza A (H5N1) viruses cause severe and often fatal disease in humans. We evaluated the efficacy of repeated intravenous dosing of the neuraminidase inhibitor peramivir against highly pathogenic avian influenza virus A/Vietnam/UT3040/2004 (H5N1) infection in cynomolgus macaques. Repeated dosing of peramivir (30 mg/kg/day once a day for 5 days) starting immediately after infection significantly reduced viral titers in the upper respiratory tract, body weight loss, and cytokine production and resulted in a significant body temperature reduction in infected macaques compared with that of macaques administered a vehicle (
P
< 0.05). Repeated administration of peramivir starting at 24 h after infection also resulted in a reduction in viral titers and a reduction in the period of virus detection in the upper respiratory tract, although the body temperature change was not statistically significant. The macaque model used in the present study demonstrated that inhibition of viral replication at an early time point after infection by repeated intravenous treatment with peramivir is critical for reduction of the production of cytokines, i.e., interleukin-6 (IL-6), tumor necrosis factor α, gamma interferon, monocyte chemotactic protein 1, and IL-12p40, resulting in amelioration of symptoms caused by highly pathogenic avian influenza virus infection.
Glucose-6-Phosphate Dehydrogenase Status and Risk of Hemolysis in Plasmodium falciparum-Infected African Children Receiving Single-Dose Primaquine
Authors: Eziefula Alice C. , Pett Helmi , Grignard Lynn , Opus Salome , Kiggundu Moses , Kamya Moses R. , Yeung Shunmay , Staedke Sarah G. , Bousema Teun , Drakeley Chris
Published: June 2014

Glucose-6-phosphate dehydrogenase (G6PD) enzyme function and genotype were determined in Ugandan children with uncomplicated falciparum malaria enrolled in a primaquine trial after exclusion of severe G6PD deficiency by fluorescent spot test. G6PD A− heterozygotes and hemizygotes/homozygotes experienced dose-dependent lower hemoglobin concentrations after treatment. No severe anemia was observed.
Bile Acids Repress Hypoxia-Inducible Factor 1 Signaling and Modulate the Airway Immune Response
Authors: Legendre Claire , Reen F. Jerry , Woods David F. , Mooij Marlies J. , Adams Claire , O'Gara Fergal
Published: June 2014

Gastroesophageal reflux (GER) frequently occurs in patients with respiratory disease and is particularly prevalent in patients with cystic fibrosis. GER is a condition in which the duodenogastric contents of the stomach leak into the esophagus, in many cases resulting in aspiration into the respiratory tract. As such, the presence of GER-derived bile acids (BAs) has been confirmed in the bronchoalveolar lavage fluid and sputum of affected patients. We have recently shown that bile causes cystic fibrosis-associated bacterial pathogens to adopt a chronic lifestyle and may constitute a major host trigger underlying respiratory infection. The current study shows that BAs elicit a specific response in humans in which they repress hypoxia-inducible factor 1α (HIF-1α) protein, an emerging master regulator in response to infection and inflammation. HIF-1α repression was shown to occur through the 26S proteasome machinery via the prolyl hydroxylase domain (PHD) pathway. Further analysis of the downstream inflammatory response showed that HIF-1α repression by BAs can significantly modulate the immune response of airway epithelial cells, correlating with a decrease in interleukin-8 (IL-8) production, while IL-6 production was strongly increased. Importantly, the effects of BAs on cytokine production can also be more dominant than the bacterium-mediated effects. However, the effect of BAs on cytokine levels cannot be fully explained by their ability to repress HIF-1α, which is not surprising, given the complexity of the immune regulatory network. The suppression of HIF-1 signaling by bile acids may have a significant influence on the progression and outcome of respiratory disease, and the molecular mechanism underpinning this response warrants further investigation.
Host Response to Nontuberculous Mycobacterial Infections of Current Clinical Importance
Authors: Orme Ian M. , Ordway Diane J.
Published: June 2014

The nontuberculous mycobacteria are a large group of acid-fast bacteria that are very widely distributed in the environment. WhileMycobacterium aviumwas once regarded as innocuous, its high frequency as a cause of disseminated disease in HIV-positive individuals illustrated its potential as a pathogen. Much more recently, there is growing evidence that the incidence ofM. aviumand related nontuberculous species is increasing in immunocompetent individuals. The same has been observed forM. abscessusinfections, which are very difficult to treat; accordingly, this review focuses primarily on these two important pathogens. Like the host response toM. tuberculosisinfections, the host response to these infections is of the TH1 type but there are some subtle and as-yet-unexplained differences.
A (p)ppGpp-Null Mutant of Haemophilus ducreyi Is Partially Attenuated in Humans Due to Multiple Conflicting Phenotypes
Authors: Holley Concerta , Gangaiah Dharanesh , Li Wei , Fortney Kate R. , Janowicz Diane M. , Ellinger Sheila , Zwickl Beth , Katz Barry P. , Spinola Stanley M.
Published: June 2014

(p)ppGpp responds to nutrient limitation through a global change in gene regulation patterns to increase survival. The stringent response has been implicated in the virulence of several pathogenic bacterial species.
Haemophilus ducreyi
, the causative agent of chancroid, has homologs of both
relA
and
spoT
, which primarily synthesize and hydrolyze (p)ppGpp in
Escherichia coli
. We constructed
relA
and
relA spoT
deletion mutants to assess the contribution of (p)ppGpp to
H. ducreyi
pathogenesis. Both the
relA
single mutant and the
relA spoT
double mutant failed to synthesize (p)ppGpp, suggesting that
relA
is the primary synthetase of (p)ppGpp in
H. ducreyi
. Compared to the parent strain, the double mutant was partially attenuated for pustule formation in human volunteers. The double mutant had several phenotypes that favored attenuation, including increased sensitivity to oxidative stress. The increased sensitivity to oxidative stress could be complemented in
trans
. However, the double mutant also exhibited phenotypes that favored virulence. When grown to the mid-log phase, the double mutant was significantly more resistant than its parent to being taken up by human macrophages and exhibited increased transcription of
lspB
, which is involved in resistance to phagocytosis. Additionally, compared to the parent, the double mutant also exhibited prolonged survival in the stationary phase. In
E. coli
, overexpression of DksA compensates for the loss of (p)ppGpp; the
H. ducreyi
double mutant expressed higher transcript levels of
dksA
than the parent strain. These data suggest that the partial attenuation of the double mutant is likely the net result of multiple conflicting phenotypes.
Superantigens Subvert the Neutrophil Response To Promote Abscess Formation and Enhance Staphylococcus aureus SurvivalIn Vivo
Authors: Xu Stacey X. , Gilmore Kevin J. , Szabo Peter A. , Zeppa Joseph J. , Baroja Miren L. , Haeryfar S. M. Mansour , McCormick John K.
Published: June 2014

Staphylococcus aureusis a versatile bacterial pathogen that produces T cell-activating toxins known as superantigens (SAgs). Although excessive immune activation by SAgs can induce a dysregulated cytokine storm as a component of what is known as toxic shock syndrome (TSS), the contribution of SAgs to the staphylococcal infection process is not well defined. Here, we evaluated the role of the bacterial superantigen staphylococcal enterotoxin A (SEA) in a bacteremia model using humanized transgenic mice expressing SAg-responsive HLA-DR4 molecules. Infection withS. aureusNewman induced SEA-dependent Vβ skewing of T cells and enhanced bacterial survival in the liver compared with infection byseaknockout strain. SEA-induced gamma interferon, interleukin-12, and chemokine responses resulted in increased infiltration of CD11b+Ly6G+neutrophils into the liver, promoting the formation of abscesses that contained large numbers of viable staphylococci. Hepatic abscesses occurred significantly more frequently inS. aureusNewman-infected livers than in livers infected with the Newmanseaknockout strain, promoting the survival ofS. aureusin vivo. This represents a novel mechanism during infection wherebyS. aureusutilizes SAgs to form a specialized niche and manipulate the immune system.
Differential Effects of Escherichia coli Subtilase Cytotoxin and Shiga Toxin 2 on Chemokine and Proinflammatory Cytokine Expression in Human Macrophage, Colonic Epithelial, and Brain Microvascular Endothelial Cell Lines
Authors: Wang Hui , Rogers Trisha J. , Paton James C. , Paton Adrienne W.
Published: June 2014

Subtilase cytotoxin (SubAB) is the prototype of a recently emerged family of AB5 cytotoxins produced by Shiga-toxigenic
Escherichia coli
(STEC). Its mechanism of action involves highly specific A-subunit-mediated proteolytic cleavage of the essential endoplasmic reticulum (ER) chaperone BiP. Our previous
in vivo
studies showed that intraperitoneal injection of purified SubAB causes a major redistribution of leukocytes and elevated leukocyte apoptosis in mice, as well as profound splenic atrophy. In the current study, we investigated selected chemokine and proinflammatory cytokine responses to treatment with SubAB, a nontoxic derivative (SubA
A272
B), or Shiga toxin 2 (Stx2) in human macrophage (U937), brain microvascular endothelial (HBMEC), and colonic epithelial (HCT-8) cell lines, at the levels of secreted protein, cell-associated protein, and gene expression. Stx2 treatment upregulated expression of chemokines and cytokines at both the protein and mRNA levels. In contrast, SubAB induced significant decreases in secreted interleukin-8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) in all three tested cell lines and a significant decrease in secreted IL-6 in HBMECs. The downregulation of secreted chemokines or cytokines was not observed in SubA
A272
B-treated cells, indicating a requirement for BiP cleavage. The downregulation of secreted chemokines and cytokines by SubAB was not reflected at the mRNA and cell-associated protein levels, suggesting a SubAB-induced export defect.
The Ctp Type IVb Pilus Locus of Agrobacterium tumefaciens Directs Formation of the Common Pili and Contributes to Reversible Surface Attachment
Authors: Wang Yi , Haitjema Charles H. , Fuqua Clay
Published: June 2014

Agrobacterium tumefaciens
can adhere to plant tissues and abiotic surfaces and forms biofilms. Cell surface appendages called pili play an important role in adhesion and biofilm formation in diverse bacterial systems. The
A. tumefaciens
C58 genome sequence revealed the presence of the
ctpABCDEFGHI
genes (
c
luster of
t
ype IV
p
ili; Atu0216 to Atu0224), homologous to
tad
-type pilus systems from several bacteria, including
Aggregatibacter actinomycetemcomitans
and
Caulobacter crescentus
. These systems fall into the type IVb pilus group, which can function in bacterial adhesion. Transmission electron microscopy of
A. tumefaciens
revealed the presence of filaments, significantly thinner than flagella and often bundled, associated with cell surfaces and shed into the external milieu. In-frame deletion mutations of all of the
ctp
genes, with the exception of
ctpF
, resulted in nonpiliated derivatives. Mutations in
ctpA
(a pilin homologue),
ctpB
, and
ctpG
decreased early attachment and biofilm formation. The adherence of the
ctpA
mutant could be restored by ectopic expression of the paralogous
pilA
gene. The Δ
ctpA
Δ
pilA
double pilin mutant displayed a diminished biovolume and lower biofilm height than the wild type under flowing conditions. Surprisingly, however, the
ctpCD
,
ctpE
,
ctpF
,
ctpH
, and
ctpI
mutants formed normal biofilms and showed enhanced reversible attachment. In-frame deletion of the
ctpA
pilin gene in the
ctpCD
,
ctpE
,
ctpF
,
ctpH
, and
ctpI
mutants caused the same attachment-deficient phenotype as the
ctpA
single mutant. Collectively, these findings indicate that the
ctp
locus is involved in pilus assembly and that nonpiliated mutants, which retain the CtpA pilin, are proficient in attachment and adherence.
Transcription of the Lysine-2,3-Aminomutase Gene in the
kam
Locus of Bacillus thuringiensis subsp. kurstaki HD73 Is Controlled by Both σ
54
and σ
K
Factors
Authors: Zhang Zhe , Yang Min , Peng Qi , Wang Guannan , Zheng Qingyun , Zhang Jie , Song Fuping
Published: June 2014

Lysine 2,3-aminomutase (KAM; EC 5.4.3.2) catalyzes the interconversion of
l
-lysine and
l
-β-lysine. The transcription and regulation of the
kam
locus, including lysine-2,3-aminomutase-encoding genes, in
Bacillus thuringiensis
were analyzed in this study. Reverse transcription-PCR (RT-PCR) analysis revealed that this locus forms two operons:
yodT
(
yodT-yodS-yodR-yodQ-yodP-kamR
) and
kamA
(
kamA-yokU-yozE
). The transcriptional start sites (TSSs) of the
kamA
gene were determined using 5′ rapid amplification of cDNA ends (RACE). A typical −12/−24 σ
54
binding site was identified in the promoter P

kamA

, which is located upstream of the
kamA
gene TSS. A β-galactosidase assay showed that P

kamA

, which directs the transcription of the
kamA
operon, is controlled by the σ
54
factor and is activated through the σ
54
-dependent transcriptional regulator KamR. The
kamA
operon is also controlled by σ
K
and regulated by the GerE protein in the late stage of sporulation.
kamR
and
kamA
mutants were prepared by homologous recombination to examine the role of the
kam
locus. The results showed that the sporulation rate in
B. thuringiensis
HD(Δ
kamR
) was slightly decreased compared to that in HD73, whereas that in HD(Δ
kamA
) was similar to that in HD73. This means that other genes regulated by KamR are important for sporulation.
Atypical cutaneous leishmaniasis in the immunosuppressed
Authors: Micallef Clayton , Mallia Azzopardi Charles
Published: June 2014

A 45-year-old woman, known case of seronegative arthritis and on immunosuppressive therapy, presented with a 2-week history of a macular lesion on the left calf that became papular and eventually ulcerated. The rest of the history was otherwise unremarkable and systemic examination did not reveal any abnormalities. The lesion was repeatedly biopsied but failed to revealLeishmania donovanibodies. ConcurrentLeishmaniaIgG was positive but IgM was negative.LeishmaniaIgG confirmatory testing by ELISA was negative. A biopsy from the lesion eventually tested positive forL. donovanithrough PCR. The patient was treated with sodium stibogluconate together with intravenous ciprofloxacin and amoxicillin to cover the secondary cutaneous bacterial infection. This led to complete resolution of the lesion.
Prevalence of prediabetes in England from 2003 to 2011: population-based, cross-sectional study
Authors: Mainous Arch G , Tanner Rebecca J , Baker Richard , Zayas Cilia E , Harle Christopher A
Published: June 2014

Objective

Prediabetes is a high-risk state for developing diabetes and associated complications. The purpose of this paper was to report trends in prevalence of prediabetes for individuals aged 16 and older in England without previously diagnosed diabetes.

Setting

Data collected by the Health Survey for England (HSE) in England in the years 2003, 2006, 2009 and 2011.

Participants

Individuals aged 16 and older who participated in the HSE and provided a blood sample.

Primary outcome variable

Individuals were classified as having prediabetes if glycated haemoglobin was between 5.7% and 6.4% and were not previously diagnosed with diabetes.

Results

The prevalence rate of prediabetes increased from 11.6% to 35.3% from 2003 to 2011. By 2011, 50.6% of the population who were overweight (body mass index (BMI)>25) and ≥40 years of age had prediabetes. In bivariate relationships, individuals with greater socioeconomic deprivation were more likely to have prediabetes in 2003 (p=0.0008) and 2006 (p=0.0246), but the relationship was not significant in 2009 (p=0.213) and 2011 (p=0.3153). In logistic regressions controlling for age, sex, race/ethnicity, BMI and high blood pressure, the second most socioeconomically deprived had a significantly elevated risk of having prediabetes (2011, OR=1.45; 95% CI 1.26 to 1.88).

Conclusions

There has been a marked increase in the proportion of adults in England with prediabetes. The socioeconomically deprived are at substantial risk. In the absence of concerted and effective efforts to reduce risk, the number of people with diabetes is likely to increase steeply in coming years.
Determinants of treatment plan implementation in multidisciplinary team meetings for patients with chronic diseases: a mixed-methods study
Authors: Raine Rosalind , Xanthopoulou Penny , Wallace Isla , Nic a’ Bháird Caoimhe , Lanceley Anne , Clarke Alex , Livingston Gill , Prentice Archie , Ardron Dave , Harris Miriam , King Michael , Michie Susan , Blazeby Jane M , Austin-Parsons Natalie , Gibbs Simon , Barber Julie
Published: June 2014

Objective

Multidisciplinary team (MDT) meetings are assumed to produce better decisions and are extensively used to manage chronic disease in the National Health Service (NHS). However, evidence for their effectiveness is mixed. Our objective was to investigate determinants of MDT effectiveness by examining factors influencing the implementation of MDT treatment plans. This is a proxy measure of effectiveness, because it lies on the pathway to improvements in health, and reflects team decision making which has taken account of clinical and non-clinical information. Additionally, this measure can be compared across MDTs for different conditions.

Methods

We undertook a prospective mixed-methods study of 12 MDTs in London and North Thames. Data were collected by observation of 370 MDT meetings, interviews with 53 MDT members, and from 2654 patient medical records. We examined the influence of patient-related factors (disease, age, sex, deprivation, whether their preferences and other clinical/health behaviours were mentioned) and MDT features (as measured using the ‘Team Climate Inventory’ and skill mix) on the implementation of MDT treatment plans.

Results

The adjusted odds (or likelihood) of implementation was reduced by 25% for each additional professional group represented at the MDT meeting. Implementation was more likely in MDTs with clear goals and processes and a good ‘Team Climate’ (adjusted OR 1.96; 95% CI 1.15 to 3.31 for a unit increase in Team Climate Inventory (TCI) score). Implementation varied by disease category, with the lowest adjusted odds of implementation in mental health teams. Implementation was also lower for patients living in more deprived areas (adjusted odds of implementation for patients in the most compared with least deprived areas was 0.60, 95% CI 0.39 to 0.91).

Conclusions

Greater multidisciplinarity is not necessarily associated with more effective decision making. Explicit goals and procedures are also crucial. Decision implementation should be routinely monitored to ensure the equitable provision of care.
MicroRNA as potential biomarker in HCV-associated diffuse large B-cell lymphoma
Authors: Augello Claudia , Gianelli Umberto , Savi Federica , Moro Alessia , Bonoldi Emanuela , Gambacorta Marcello , Vaira Valentina , Baldini Luca , Bosari Silvano
Published: June 2014

Aims

To identify molecular characteristics to hepatitis C virus (HCV)-associated diffuse large B-cell lymphoma (DLBCL) through a comprehensive miRNAs expression profiling.

Methods

In this study, miRNA profiles were obtained from 37 patients with DLBCLs and 60 patients with reactive lymph nodes, equally distributed according to HCV presence. Germinal centres, from reactive lymph nodes were used as controls. Clinical features at presentation were available for all patients.

Results

A set of 52 miRNAs define a signature for HCV-associated DLBCL. Importantly, decreased expression of miR-138-5p and increased expression of miR-147a, miR-147b and miR-511-5p in HCV DLBCL was found to be a poor prognostic factor for HCV-positive DLBCL patients.

Conclusions

These data reveal molecular differences in diffuse DLBCL patients according to HCV presence, potentially useful as novel prognostic or therapeutic biomarkers.
Pathogenic autoantibodies from patients with lupus nephritis cause reduced tyrosine phosphorylation of podocyte proteins, including tubulin
Authors: Manson Jessica J , Mills Kevin , Jury Elizabeth , Mason Lesley , D'Cruz David P , Ni Lan , Saleem Moin , Mathieson Peter , Isenberg David , Rahman Anisur
Published: June 2014

Introduction

The tertiary structure of normal podocytes prevents protein from leaking into urine. Patients with lupus nephritis (LN) develop proteinuria, and kidney biopsies from these patients display a number of podocyte abnormalities including retraction of podocyte processes. Autoantibodies have been shown to deposit in the kidneys of patients and mice with LN and are believed to play a key role in causing renal inflammation and dysfunction. The objective of this research was to study the effects of IgG antibodies from patients with LN on cultured human podocytes.

Methods

We exposed a human podocyte cell line to heat-inactivated (HI) plasma and purified polyclonal IgG from the following groups of subjects; patients with LN, patients with lupus without nephritis, patients with rheumatoid arthritis and healthy controls. We measured expression and intracellular distribution of podocyte-specific proteins and global phosphorylation of tyrosine. We then used mass spectrometry to identify the major protein targets of this phosphorylation.

Results

HI LN plasma did not alter expression or cellular distribution of podocyte-specific proteins but caused a significant reduction in podocyte protein tyrosine phosphorylation compared with plasma from healthy controls (p=0.0008). This result was replicated using purified IgG but was not seen with plasma from rheumatoid arthritis or non-renal lupus patients. The dominant tyrosine phosphorylated protein in podocytes was 55 kDa in size and was identified as tubulin.

Conclusions

Since tubulin is an important component of podocyte major processes, these results suggest that autoantibodies from LN patients may exert an important pathogenic effect by dephosphorylation of this protein in podocytes.
Adverse pregnancy outcomes and subsequent risk of cardiovascular disease in women with systemic lupus erythematosus
Authors: Lin Pin , Rhew Elisa , Ness Roberta B , Peaceman Alan , Dyer Alan , McPherson David , Kondos George T , Edmundowicz Daniel , Sutton-Tyrrell Kim , Thompson Trina , Ramsey-Goldman Rosalind
Published: June 2014

Background/objective

Patients with systemic lupus erythematosus (SLE) are at increased risk for adverse pregnancy outcomes and cardiovascular disease (CVD). The objective of this exploratory study was to investigate the association between a history of adverse pregnancy outcomes and subsequent risk of subclinical CVD assessed by imaging studies and verified clinical CVD events in 129 women with SLE.

Methods

The occurrence of adverse pregnancy outcomes, specifically pre-eclampsia, preterm birth and low birth weight was ascertained by questionnaire. Subclinical CVD was assessed by coronary artery calcium (CAC) as measured by electron beam CT and carotid plaque measured by B mode ultrasound. Clinical CVD events were verified by medical record review. Logistic regression was used to estimate the association of pregnancy complications with occurrence of subclinical CVD and clinical CVD with a priori adjustment for age, which is associated with CVD and SLE disease duration as a measure of SLE disease burden.

Results

Fifty-six women reported at least one pregnancy complication while 73 had none. Twenty-six women had at least one pregnancy complicated by pre-eclampsia and were more likely to have a CAC score greater than or equal to 10 (adjusted OR=3.7; 95% CI 1.2 to 11.9), but the presence of plaque was not associated with this pregnancy complication, OR=1.1, (95% CI 0.4 to 2.8). Low birth weight and preterm birth were not associated with CAC or plaque.

Conclusions

Patients with SLE with a history of pre-eclampsia had a higher rate of subclinical CVD as measured by CAC score. Future studies are needed to confirm the relationship between adverse pregnancy outcomes and subsequent subclinical CVD and clinical CVD events.
Selection Procedures for Simulations with Multiple Constraints under Independent and Correlated Sampling
Authors: Healey Christopher , Andradóttir Sigrún , Kim Seong-Hee
Published: June 2014

We consider the problem of selecting the best feasible system with constraints on multiple secondary performance measures. We develop fully sequential indifference-zone procedures to solve this problem that guarantee a nominal probability of correct selection. In addition, we address two issues critical to the efficiency of these procedures: namely, the allocation of error between feasibility determination and selection of the best system, and the use of Common Random Numbers. We provide a recommended error allocation as a function of the number of constraints, supported by an experimental study and an approximate asymptotic analysis. The validity and efficiency of the new procedures with independent and CRN are demonstrated through both analytical and experimental results.
Animation of Deformable Bodies with Quadratic Bézier Finite Elements
Authors: Bargteil Adam W. , Cohen Elaine
Published: June 2014

In this article, we investigate the use of quadratic finite elements for graphical animation of deformable bodies. We consider both integrating quadratic elements with conventional linear elements to achieve a computationally efficient adaptive-degree simulation framework as well as wholly quadratic elements for the simulation of nonlinear rest shapes. In both cases, we adopt the Bézier basis functions and employ a co-rotational linear strain formulation. As with linear elements, the co-rotational formulation allows us to precompute per-element stiffness matrices, resulting in substantial computational savings. We present several examples that demonstrate the advantages of quadratic elements in general and our adaptive-degree system in particular. Furthermore, we demonstrate, for the first time in computer graphics, animations of volumetric deformable bodies with nonlinear rest shapes.
Poisson-Based Continuous Surface Generation for Goal-Based Caustics
Authors: Yue Yonghao , Iwasaki Kei , Chen Bing-Yu , Dobashi Yoshinori , Nishita Tomoyuki
Published: June 2014

We present a technique for computing the shape of a transparent object that can generate user-defined caustic patterns. The surface of the object generated using our method is smooth. Thanks to this property, the resulting caustic pattern is smooth, natural, and highly detailed compared to the results btained using previous methods. Our method consists of two processes. First, we use a differential geometry approach to compute a smooth mapping between the distributions of the incident light and the light reaching the screen. Second, we utilize this mapping to compute the surface of the object. We solve Poisson's equation to compute both the mapping and the surface of the object.
Architecture and Performance of the Hardware Accelerators in IBM’s PowerEN Processor
Authors: Heil Timothy , Krishna Anil , Lindberg Nicholas , Toussi Farnaz , Vanderwiel Steven
Published: June 2014

Computation at the edge of a datacenter has unique characteristics. It deals with streaming data from multiple sources, going to multiple destinations, often requiring repeated application of one or more of several standard algorithmic kernels. These kernels, related to encryption, compression, XML Parsing and regular expression searching on the data, demand a high data processing rate and power efficiency. This suggests the use of hardware acceleration for key functions. However, robust general purpose processing support is necessary to orchestrate the flow of data between accelerators, as well as perform tasks that are not suited to acceleration. Further, these accelerators must be tightly integrated with the general purpose computation in order to keep invocation overhead and latency low. The accelerators must be easy for software to use, and the system must be flexible enough to support evolving networking standards.In this article, we describe and evaluate the architecture of IBM’s PowerEN processor, with a focus on PowerEN’s architectural enhancements and its on-chip hardware accelerators.PowerEN unites the throughput of application-specific accelerators with the programmability of general purpose cores on a single coherent memory architecture. Hardware acceleration improves throughput by orders of magnitude in some cases compared to equivalent computation on the general purpose cores. By offloading work to the accelerators, general purpose cores are freed to simultaneously work on computation less suited to acceleration.
Offering Verified Credentials in Massive Open Online Courses
Authors: Maas Andrew , Heather Chris , Do Chuong (Tom) , Brandman Relly , Koller Daphne , Ng Andrew
Published: June 2014

Massive open online courses (MOOCs) enable the delivery of high-quality educational experiences to large groups of students. Coursera, one of the largest MOOC providers, developed a program to provide students with verified credentials as a record of their MOOC performance. Such credentials help students convey achievements in MOOCs to future employers and academic programs. This article outlines the process and biometrics Coursera uses to establish and verify student identity during a course. We additionally present data that suggest verified certificate programs help increase student success rates in courses.