bluuebunny/crossref_metadata_2025 huggingface dataset:
Disruption of the Transcriptional Regulator Cas5 Results in Enhanced Killing of Candida albicans by Fluconazole
Authors: Vasicek Erin M. , Berkow Elizabeth L. , Bruno Vincent M. , Mitchell Aaron P. , Wiederhold Nathan P. , Barker Katherine S. , Rogers P. David
Published: September 2014

Azole antifungal agents such as fluconazole exhibit fungistatic activity against
Candida albicans
. Strategies to enhance azole antifungal activity would be therapeutically appealing. In an effort to identify transcriptional pathways that influence the killing activity of fluconazole, we sought to identify transcription factors (TFs) involved in this process. From a collection of
C. albicans
strains disrupted for genes encoding TFs (O. R. Homann, J. Dea, S. M. Noble, and A. D. Johnson, PLoS Genet. 5:e1000783, 2009,
http://dx.doi.org/10.1371/journal.pgen.1000783
), four strains exhibited marked reductions in minimum fungicidal concentration (MFCs) in both RPMI and yeast extract-peptone-dextrose (YPD) media. One of these genes,
UPC2
, was previously characterized with regard to its role in azole susceptibility. Of mutants representing the three remaining TF genes of interest, one (
CAS5
) was unable to recover from fluconazole exposure at concentrations as low as 2 μg/ml after 72 h in YPD medium. This mutant also showed reduced susceptibility and a clear zone of inhibition by Etest, was unable to grow on solid medium containing 10 μg/ml fluconazole, and exhibited increased susceptibility by time-kill analysis.
CAS5
disruption in highly azole-resistant clinical isolates exhibiting multiple resistance mechanisms did not alter susceptibility. However,
CAS5
disruption in strains with specific resistance mutations resulted in moderate reductions in MICs and MFCs. Genome-wide transcriptional analysis was performed in the presence of fluconazole and was consistent with the suggested role of
CAS5
in cell wall organization while also suggesting a role in iron transport and homeostasis. These findings suggest that Cas5 regulates a transcriptional network that influences the response of
C. albicans
to fluconazole. Further delineation of this transcriptional network may identify targets for potential cotherapeutic strategies to enhance the activity of the azole class of antifungals.
Complete Sequence of a Conjugative IncN Plasmid Harboring
bla
KPC-2
,
bla
SHV-12
, and
qnrS1
from an Escherichia coli Sequence Type 648 Strain
Authors: Li Jun-Jie , Lee Chang-Seop , Sheng Ji-Fang , Doi Yohei
Published: September 2014

We sequenced a novel conjugative
bla
KPC-2
-harboring IncN plasmid, pYD626E, from an
Escherichia coli
sequence type 648 strain previously identified in Pittsburgh, Pennsylvania. pYD626E was 72,800 bp long and carried four β-lactamase genes,
bla
KPC-2
,
bla
SHV-12
,
bla
LAP-1
, and
bla
TEM-1
. In addition, it harbored
qnrS1
(fluoroquinolone resistance) and
dfrA14
(trimethoprim resistance). The plasmid profile and clinical history supported the
in vivo
transfer of this plasmid between
Klebsiella pneumoniae
and
Escherichia coli
.
Antibacterial Synergy of Glycerol Monolaurate and Aminoglycosides in Staphylococcus aureus Biofilms
Authors: Hess Donavon J. , Henry-Stanley Michelle J. , Wells Carol L.
Published: September 2014

Glycerol monolaurate (GML) is a natural surfactant with antimicrobial properties. At ∼0.3 mM, both GML and its component lauric acid were bactericidal for antibiotic-resistant
Staphylococcus aureus
biofilms. With the use of MICs of antibiotics obtained from planktonic cells, GML and lauric acid acted synergistically with gentamicin and streptomycin, but not ampicillin or vancomycin, to eliminate detectable viable biofilm bacteria. Images of GML-treated biofilms suggested that GML may facilitate antibiotic interaction with matrix-embedded bacteria.
Two-Component System VicRK Regulates Functions Associated with Establishment of Streptococcus sanguinis in Biofilms
Authors: Moraes Julianna J. , Stipp Rafael N. , Harth-Chu Erika N. , Camargo Tarsila M. , Höfling José F. , Mattos-Graner Renata O.
Published: September 2014

Streptococcus sanguinis
is a commensal pioneer colonizer of teeth and an opportunistic pathogen of infectious endocarditis. The establishment of
S. sanguinis
in host sites likely requires dynamic fitting of the cell wall in response to local stimuli. In this study, we investigated the two-component system (TCS) VicRK in
S. sanguinis
(VicRK

Ss

), which regulates genes of cell wall biogenesis, biofilm formation, and virulence in opportunistic pathogens. A
vicK
knockout mutant obtained from strain SK36 (SKvic) showed slight reductions in aerobic growth and resistance to oxidative stress but an impaired ability to form biofilms, a phenotype restored in the complemented mutant. The biofilm-defective phenotype was associated with reduced amounts of extracellular DNA during aerobic growth, with reduced production of H
2
O
2
, a metabolic product associated with DNA release, and with inhibitory capacity of
S. sanguinis
competitor species. No changes in autolysis or cell surface hydrophobicity were detected in SKvic. Reverse transcription-quantitative PCR (RT-qPCR), electrophoretic mobility shift assays (EMSA), and promoter sequence analyses revealed that VicR directly regulates genes encoding murein hydrolases (
SSA_0094
,
cwdP
, and
gbpB
) and
spxB
, which encodes pyruvate oxidase for H
2
O
2
production. Genes previously associated with
spxB
expression (
spxR
,
ccpA
,
ackA
, and
tpK
) were not transcriptionally affected in SKvic. RT-qPCR analyses of
S. sanguinis
biofilm cells further showed upregulation of VicRK targets (
spxB
,
gbpB
, and
SSA_0094
) and other genes for biofilm formation (
gtfP
and
comE
) compared to expression in planktonic cells. This study provides evidence that VicRK

Ss

regulates functions crucial for
S. sanguinis
establishment in biofilms and identifies novel VicRK targets potentially involved in hydrolytic activities of the cell wall required for these functions.
Vaccine Protection of Leukopenic Mice against Staphylococcus aureus Bloodstream Infection
Authors: Rauch Sabine , Gough Portia , Kim Hwan Keun , Schneewind Olaf , Missiakas Dominique
Published: September 2014

The risk for
Staphylococcus aureus
bloodstream infection (BSI) is increased in immunocompromised individuals, including patients with hematologic malignancy and/or chemotherapy. Due to the emergence of antibiotic-resistant strains, designated methicillin-resistant
S. aureus
(MRSA), staphylococcal BSI in cancer patients is associated with high mortality; however, neither a protective vaccine nor pathogen-specific immunotherapy is currently available. Here, we modeled staphylococcal BSI in leukopenic CD-1 mice that had been treated with cyclophosphamide, a drug for leukemia and lymphoma patients. Cyclophosphamide-treated mice were highly sensitive to
S. aureus
BSI and developed infectious lesions lacking immune cell infiltrates. Virulence factors of
S. aureus
that are key for disease establishment in immunocompetent hosts—α-hemolysin (Hla), iron-regulated surface determinants (IsdA and IsdB), coagulase (Coa), and von Willebrand factor binding protein (vWbp)—are dispensable for the pathogenesis of BSI in leukopenic mice. In contrast, sortase A mutants, which cannot assemble surface proteins, display delayed time to death and increased survival in this model. A vaccine with four surface antigens (ClfA, FnBPB, SdrD, and SpA
KKAA
), which was identified by genetic vaccinology using sortase A mutants, raised antigen-specific immune responses that protected leukopenic mice against staphylococcal BSI.
Molecular Characterization of Protease Activity in Serratia sp. Strain SCBI and Its Importance in Cytotoxicity and Virulence
Authors: Petersen Lauren M. , Tisa Louis S.
Published: September 2014

A newly recognized
Serratia
species, termed South African
Caenorhabditis briggsae
isolate (SCBI), is both a mutualist of the nematode
Caenorhabditis briggsae
KT0001 and a pathogen of lepidopteran insects.
Serratia
sp. strain SCBI displays high proteolytic activity, and because secreted proteases are known virulence factors for many pathogens, the purpose of this study was to identify genes essential for extracellular protease activity in
Serratia
sp. strain SCBI and to determine what role proteases play in insect pathogenesis and cytotoxicity. A bank of 2,100 transposon mutants was generated, and six SCBI mutants with defective proteolytic activity were identified. These mutants were also defective in cytotoxicity. The mutants were found defective in genes encoding the following proteins: alkaline metalloprotease secretion protein AprE, a BglB family transcriptional antiterminator, an inosine/xanthosine triphosphatase, GidA, a methyl-accepting chemotaxis protein, and a PIN domain protein. Gene expression analysis on these six mutants showed significant downregulation in mRNA levels of several different types of predicted protease genes. In addition, transcriptome sequencing (RNA-seq) analysis provided insight into how inactivation of AprE, GidA, and a PIN domain protein influences motility and virulence, as well as protease activity. Using quantitative reverse transcription-PCR (qRT-PCR) to further characterize expression of predicted protease genes in wild-type
Serratia
sp. SCBI, the highest mRNA levels for the alkaline metalloprotease genes (termed
prtA1
to
prtA4
) occurred following the death of an insect host, while two serine protease and two metalloprotease genes had their highest mRNA levels during active infection. Overall, these results indicate that proteolytic activity is essential for cytotoxicity in
Serratia
sp. SCBI and that its regulation appears to be highly complex.
The TetR-Type MfsR Protein of the Integrative and Conjugative Element (ICE) ICE
clc
Controls both a Putative Efflux System and Initiation of ICE Transfer
Authors: Pradervand Nicolas , Delavat François , Sulser Sandra , Miyazaki Ryo , van der Meer Jan Roelof
Published: September 2014

Integrative and conjugating elements (ICE) are self-transferable DNAs widely present in bacterial genomes, which often carry a variety of auxiliary genes of potential adaptive benefit. One of the model ICE is ICE
clc
, an element originally found in
Pseudomonas knackmussii
B13 and known for its propensity to provide its host with the capacity to metabolize chlorocatechols and 2-aminophenol. In this work, we studied the mechanism and target of regulation of MfsR, a TetR-type repressor previously found to exert global control on ICE
clc
horizontal transfer. By using a combination of ICE
clc
mutant and transcriptome analysis, gene reporter fusions, and DNA binding assays, we found that MfsR is a repressor of both its own expression and that of a gene cluster putatively coding for a major facilitator superfamily efflux system on ICE
clc
(named
mfsABC
). Phylogenetic analysis suggests that
mfsR
was originally located immediately adjacent to the efflux pump genes but became displaced from its original
cis
target DNA by a gene insertion. This resulted in divergence of the original bidirectional promoters into two separated individual regulatory units. Deletion of
mfsABC
did not result in a strong phenotype, and despite screening a large number of compounds and conditions, we were unable to define the precise current function or target of the putative efflux pump. Our data reconstruct how the separation of an ancestor
mfsR-mfsABC
system led to global control of ICE
clc
transfer by MfsR.
Transcriptional Analysis of the Global Regulatory Networks Active in Pseudomonas syringae during Leaf Colonization
Authors: Yu Xilan , Lund Steven P. , Greenwald Jessica W. , Records Angela H. , Scott Russell A. , Nettleton Dan , Lindow Steven E. , Gross Dennis C. , Beattie Gwyn A.
Published: September 2014

The plant pathogen
Pseudomonas syringae
pv. syringae B728a grows and survives on leaf surfaces and in the leaf apoplast of its host, bean (
Phaseolus vulgaris
). To understand the contribution of distinct regulators to B728a fitness and pathogenicity, we performed a transcriptome analysis of strain B728a and nine regulatory mutants recovered from the surfaces and interior of leaves and exposed to environmental stresses in culture. The quorum-sensing regulators AhlR and AefR influenced few genes
in planta
or
in vitro
. In contrast, GacS and a downstream regulator, SalA, formed a large regulatory network that included a branch that regulated diverse traits and was independent of plant-specific environmental signals and a plant signal-dependent branch that positively regulated secondary metabolite genes and negatively regulated the type III secretion system. SalA functioned as a central regulator of iron status based on its reciprocal regulation of pyoverdine and achromobactin genes and also sulfur uptake, suggesting a role in the iron-sulfur balance. RetS functioned almost exclusively to repress secondary metabolite genes when the cells were not on leaves. Among the sigma factors examined, AlgU influenced many more genes than RpoS, and most AlgU-regulated genes depended on RpoN. RpoN differentially impacted many AlgU- and GacS-activated genes in cells recovered from apoplastic versus epiphytic sites, suggesting differences in environmental signals or bacterial stress status in these two habitats. Collectively, our findings illustrate a central role for GacS, SalA, RpoN, and AlgU in global regulation in B728a
in planta
and a high level of plasticity in these regulators’ responses to distinct environmental signals.

IMPORTANCE
Leaves harbor abundant microorganisms, all of which must withstand challenges such as active plant defenses and a highly dynamic environment. Some of these microbes can influence plant health. Despite knowledge of individual regulators that affect the fitness or pathogenicity of foliar pathogens, our understanding of the relative importance of various global regulators to leaf colonization is limited.
Pseudomonas syringae
strain B728a is a plant pathogen and a good colonist of both the surfaces and interior of leaves. This study used global transcript profiles of strain B728a to investigate the complex regulatory network of putative quorum-sensing regulators, two-component regulators, and sigma factors in cells colonizing the leaf surface and leaf interior under stressful
in vitro
conditions. The results highlighted the value of evaluating these networks
in planta
due to the impact of leaf-specific environmental signals and suggested signal differences that may enable cells to differentiate surface versus interior leaf habitats.
An audit of anticoagulant management to assess anticoagulant control using decision support software
Authors: Harper Paul , Harper Joe , Hill Claire
Published: September 2014

Objective

To evaluate the effectiveness of a computerised self-adjusting anticoagulant algorithm to predict appropriate warfarin dosing and to assess its use in clinical practice.

Design

A 3-year audit of anticoagulant control in patients managed by doctors and pharmacists using computer decision support and an evaluation of the impact of dose adjustments made by the users.

Participants

3660 patients on oral anticoagulants; one-third of patients managed by doctors and two-thirds by pharmacists.

Setting

Anticoagulant supervision in primary care and pharmacies at 60 sites in New Zealand.

Main outcome measures

The time in the therapeutic range (TTR), the outcome of adherence to the computer dosing algorithm, the percentage of time the clinicians over-ride the algorithm and the impact of their intervention on anticoagulant control.

Results

A TTR of 72.9% was achieved for all patients. The TTR was significantly better in patients managed by pharmacists than doctors (75.1% versus 67.4%, p<0.0001). The computer algorithm provides appropriate dose recommendations for INR results from 1.5 to 4. Users administered a dose that differed from the computer recommendation 23.3% of the time. The doctors adjusted the dose more frequently (28.2% versus 21.1% of tests) and made larger dose changes than the pharmacists.

Conclusions

The clinicians predominantly change the dose when the INR is below the therapeutic range. The changes are not necessary to correct for inaccuracies in the algorithm. The most likely explanation is the clinician's belief that their own dose adjustment would achieve better control; however, in practice, their changes tend to underdose patients. The doctors achieved poorer control than the pharmacists; this is in part due to the action of the doctors over-riding the algorithm. Our results imply that clinicians could achieve better anticoagulant control if they more closely followed the computer algorithm.
Compassionate Conversations
Authors: Gardner Sharryn , Bray Dominic
Published: September 2014

Staff engagement is much more than just a bonus in any organisation. CQC data shows that it is very clearly linked to positive results in both patient and staff outcomes (fewer complaints, improved safety, reduced sickness, fewer accidents, and more as per Michael West). Staff engagement may seem nebulous but is in fact measured routinely annually in the National Staff Survey. The problem is that often Trust Boards with poor Staff Survey results may struggle to increase staff engagement as staff see management initiatives as 'management fads' or 'tick-box exercises' purely for targets, not their own benefit.

Compassionate Conversations are a ground-level initiative focused primarily on supporting and motivating individual staff as the primary focus. This allows the benefits to patients and in Human Resources to be an unspoken anticipated benefit. They are led by a Psychologist and Consultant in a coaching supportive atmosphere in an open or selected group.

The Conversations have been rated 9/10 or higher by 64% of participants, while 75% of all participants voluntarily provided feedback. Feedback initially was that Conversations were too clinically-focused and further Conversations were more wide-ranging in topic and included departmental roadshows.
In vitro activity of tylvalosin against Spanish field strains of Mycoplasma hyopneumoniae
Authors: Tavío M. M. , Poveda C. , Assunção P. , Ramírez A. S. , Poveda J. B.
Published: September 2014

Mycoplasma hyopneumoniae is involved in the porcine enzootic pneumonia and respiratory disease complex; therefore, the search for new treatment options that contribute to the control of this organism is relevant. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations of tylvalosin and 19 other antimicrobial agents against 20 Spanish field isolates of M. hyopneumoniae were determined using the broth microdilution method, with the type strain (J) as a control strain. Tylvalosin had MIC50 and MIC90 values of 0.016 and 0.06 µg/ml, respectively, and was the second‐most effective of the assayed antibiotics, after valnemulin. Tiamulin, tylosin and lincomycin were also among the antibiotics with the lowest MIC50 and MIC90 values against the 20 field isolates (0.06–0.25 µg/ml). However, resistance to tylosin and spiramycin, which like tylvalosin, are 16‐membered macrolides, was observed. The MIC50 and MIC90 values for ciprofloxacin and enrofloxacin ranged from 0.125 to 1 µg/ml; the corresponding values ranged from 2 to 4 µg/ml for oxytetracyline, which was the most active tetracycline. Furthermore, tylvalosin and valnemulin exhibited the highest bactericidal activities. In conclusion, the macrolide tylvalosin and the pleuromutilin valnemulin exhibited the highest in vitro antimicrobial activities against M. hyopneumoniae field isolates in comparison with the other tested antibiotics.
Spatiotemporal occurrence of loggerhead turtles (Caretta caretta) on the West Florida Shelf and apparent overlap with a commercial fishery
Authors: Hardy Robert F. , Tucker Anton D. , Foley Allen M. , Schroeder Barbara A. , Giove Robin J. , Meylan Anne B.
Published: September 2014

Information on the spatial and temporal distribution of protected marine species is critical for the development of conservation strategies. We examined a 12-year dataset describing the postnesting residence areas of 81 adult female loggerhead turtles (Caretta caretta) on the West Florida Shelf (WFS) in the northeastern Gulf of Mexico. The aggregation of loggerheads on the WFS represents at least four US recovery units for this protected species. We identified several seasonally persistent residence areas that were shared by multiple loggerheads on the WFS. The majority (69%) of individuals remained within a discrete residence area throughout the tracking period. We placed our results within the context of a related fishery management concern — loggerhead bycatch within the bottom longline component of the Gulf commercial reef-fish fishery. We characterized loggerhead residence areas and compared that information with fishing activity. Our results provide information on the distribution of WFS loggerhead residence areas and the extent to which residence areas overlap with areas of high fishing effort. Loggerheads were present year-round on portions of the WFS, within or near to areas with high fishing effort. Interactions among loggerheads and fishing activities could be reduced by conservation management strategies that consider these spatial and seasonal patterns of occurrence.
Spatial segregation and the influence of habitat on the foraging behavior of northern fur seals (Callorhinus ursinus)
Authors: Kuhn C.E. , Ream R.R. , Sterling J.T. , Thomason J.R. , Towell R.G.
Published: September 2014

Central place foraging by colonial breeders can lead to depleted prey resources around breeding areas. Segregation of foraging areas both within and between large colonies may act as a mechanism to reduce competition for prey resulting in increased foraging success. We reassessed horizontal (spatial) foraging habitat segregation for northern fur seals (Callorhinus ursinus (L., 1758)) within and between colonies on the Pribilof Islands, Alaska (St. Paul and St. George islands), after the population declined by approximately 40%. Additionally, we examined vertical habitat segregation, where foraging ranges overlapped, and describe the influence of different foraging habitats on northern fur seal dive behavior. Spatial habitat segregation in northern fur seal foraging areas occurred between islands but was variable within islands, which is similar to the pattern previously described. There was no evidence for vertical habitat segregation when fur seals from different rookeries on St. George Island used the same foraging area. Additionally, fur seals from St. Paul Island rookeries that foraged in similar habitats showed fewer differences in dive behavior, indicating that foraging habitat plays a significant role in shaping dive behavior. The use of multiple foraging strategies within the Pribilof Island fur seal population could indicate that a complex management and conservation strategy may be necessary to stop the continuing decline of this population.
Effects of Berberine in the Gastrointestinal Tract — A Review of Actions and Therapeutic Implications
Authors: Chen Chunqiu , Yu Zhen , Li Yongyu , Fichna Jakub , Storr Martin
Published: September 2014

Berberine is an isoquinoline alkaloid present in several plant species, including Coptis sp. and Berberis sp. In traditional medicine, extracts of berberine are used in the treatment of diarrhea of different origins. Recent studies have shown that berberine and its derivatives have significant biological effects on gastrointestinal (GI) and other functions and may become therapeutics for the treatment of diarrhea, gastroenteritis, diabetes, hyperlipidemia, cardiovascular diseases and inflammatory conditions. This paper summarizes the current knowledge on the actions of berberine in the GI tract. Binding and target sites, activated intracellular pathways, as well as the absorption and metabolism of berberine are discussed. Effects that may be useful in future clinical treatment, like antidiarrheal, anti-inflammatory and antitumor effects are critically reviewed and potential clinical applications are presented in detail.
Glue-mesons: Their conception needs all of QCD in the infrared: The trace anomaly and modification of canonical structure
Authors: Minkowski Peter
Published: September 2014

The regularities implied at large distances by complete gauge invariance in QCD are shown to bear nontrivial consequences for the selection among inequivalent representations of canonical (anti-)commutation rules for gauge boson — and quark fields. The trace anomaly forces a modification of the gauge boson Lagrangian and by this of the entire associated canonical structure.
Pure gauge QCD and holography
Authors: Trinchero R. C.
Published: September 2014

Holographic models for the pure gauge quantum chromodynamics (QCD) vacuum are explored. The holographic renormalization of these models is considered as required by a phenomenological approach that takes the β-functions of the models as the only input. This approach is done taking the dilaton as the coordinate orthogonal to the border. This choice greatly simplifies the analysis and gives a geometrical interpretation for the fixed points of the renormalization group flow. Examples are constructed that present asymptotic freedom, confinement of static quarks, either with vanishing or nonvanishing gluon condensate G2. The latter models require an extension of the dilaton-gravity models already considered in the literature. This extension is also determined by the only input, i.e. the β-function. In addition, the restrictions imposed by the trace anomaly equation (TAE) are studied. In doing so, a holographic derivation of this equation is presented.
Discrete Möbius energy
Authors: Scholtes Sebastian
Published: September 2014

We investigate a discrete version of the Möbius energy, that is of geometric interest in its own right and is defined on equilateral polygons with n segments. We show that the Γ-limit regarding Lq or W1,q convergence, q ∈ [1, ∞] of these energies as n → ∞ is the smooth Möbius energy. This result directly implies the convergence of almost minimizers of the discrete energies to minimizers of the smooth energy if we can guarantee that the limit of the discrete curves belongs to the same knot class. Additionally, we show that the unique minimizer amongst all polygons is the regular n-gon. Moreover, discrete overall minimizers converge to the round circle.
Modular classes revisited
Authors: Grabowski Janusz
Published: August 2014

We present a graded-geometric approach to modular classes of Lie algebroids and their generalizations, introducing in this setting an idea of relative modular class of a Dirac structure for certain type of Courant algebroids, called projectable. This novel approach puts several concepts related to Poisson geometry and its generalizations in a new light and simplifies proofs. It gives, in particular, a nice geometric interpretation of modular classes of twisted Poisson structures on Lie algebroids.
Enhanced re-endothelialization of acellular kidney scaffolds for whole organ engineering via antibody conjugation of vasculatures
Authors: Ko In Kap , Abolbashari Mehran , Huling Jennifer , Kim Cheil , Mirmalek-Sani Sayed-Hadi , Moradi Mahmoudreza , Orlando Giuseppe , Jackson John D. , Aboushwareb Tamer , Soker Shay , Yoo James J. , Atala Anthony
Published: September 2014

Decellularization of whole organs, such as the kidney hold great promise in addressing donor shortage for transplantation. However, successful implantation of engineered whole kidney constructs has been challenged by the inability to maintain endothelial cell coverage of the vasculature matrix, resulting in excessive blood clots, loss of vascular patency, and cell death within the construct. In this study, we describe an endothelial cell seeding approach that permits effective coating of the vascular matrix of the decellularized porcine kidney scaffold using a combination of static and ramping perfusion cell seeding. Furthermore, conjugation of CD31 antibodies to the vascular matrix improved endothelial cell retention on the vasculatures, which enhanced vascular patency of the implanted scaffold. These results demonstrate that our endothelial cell seeding method combined with antibody conjugation improves endothelial cell attachment and retention leading to vascular patency of tissue-engineered whole kidney in vivo.
An Opportune Life: 50 Years in Human Cytogenetics
Authors: Jacobs Patricia A.
Published: September 2014

This article is one person's view of human cytogenetics over the past 50 years. The flowering of human cytogenetics led the way to the establishment of clinical genetics as one of the most important developments in medicine in the twentieth century. The article is written from the viewpoint of a scientist who never tired of analyzing the images of dividing cells on the light microscope and interpreting the wealth of information contained in them.
Determining pancreatic β-cell compensation for changing insulin sensitivity using an oral glucose tolerance test
Authors: Solomon Thomas P. J. , Malin Steven K. , Karstoft Kristian , Knudsen Sine H. , Haus Jacob M. , Laye Matthew J. , Pedersen Maria , Pedersen Bente K. , Kirwan John P.
Published: September 2014

Plasma glucose, insulin, and C-peptide responses during an OGTT are informative for both research and clinical practice in type 2 diabetes. The aim of this study was to use such information to determine insulin sensitivity and insulin secretion so as to calculate an oral glucose disposition index (DIOGTT) that is a measure of pancreatic β-cell insulin secretory compensation for changing insulin sensitivity. We conducted an observational study of n = 187 subjects, representing the entire glucose tolerance continuum from normal glucose tolerance to type 2 diabetes. OGTT-derived insulin sensitivity (SI OGTT) was calculated using a novel multiple-regression model derived from insulin sensitivity measured by hyperinsulinemic euglycemic clamp as the independent variable. We also validated the novel SI OGTT in n = 40 subjects from an independent data set. Plasma C-peptide responses during OGTT were used to determine oral glucose-stimulated insulin secretion (GSISOGTT), and DIOGTT was calculated as the product of SI OGTT and GSISOGTT. Our novel SI OGTT showed high agreement with clamp-derived insulin sensitivity (typical error = +3.6%; r = 0.69, P < 0.0001) and that insulin sensitivity was lowest in subjects with impaired glucose tolerance and type 2 diabetes. GSISOGTT demonstrated a significant inverse relationship with SI OGTT. GSISOGTT was lowest in normal glucose-tolerant subjects and greatest in those with impaired glucose tolerance. DIOGTT was sequentially lower with advancing glucose intolerance. We hereby derive and validate a novel OGTT-derived measurement of insulin sensitivity across the entire glucose tolerance continuum and demonstrate that β-cell compensation for changing insulin sensitivity can be readily calculated from clinical variables collected during OGTT.
Kisspeptin induction of somatolactin-α release in goldfish pituitary cells: functional role of cAMP/PKA-, PLC/PKC-, and Ca2+/calmodulin-dependent cascades
Authors: Jiang Quan , He Mulan , Ko Wendy K. W. , Wong Anderson O. L.
Published: September 2014

Although the importance of kisspeptin in the pituitary is firmly established, the signaling mechanisms for the pituitary actions of kisspeptin are still largely unknown. Somatolactin (SL), a member of the growth hormone (GH)/prolactin (PRL) family, is a pituitary hormone with pleiotropic functions in fish, but its regulation by kisspeptin has not been examined. To investigate the functional role of kisspeptin in SL regulation, expression of two paralogues of goldfish Kiss1 receptors (Kiss1ra and Kiss1rb) were confirmed in immunoidentified SLα but not SLβ cells isolated by RT-PCR coupled with laser capture microdissection. In goldfish pituitary cells prepared from neurointermediate lobe (NIL), synthetic goldfish Kiss decapeptides (gKiss1-10 and gKiss2-10) could increase SLα release. Consistent with the lack of Kiss1r expression in SLβ cells, SLβ release was not altered by kisspeptin stimulation. In parallel experiments, goldfish gKiss1-10 could elevate cyclic adenosine monophosphate (cAMP) production, upregulate protein kinase A (PKA) and protein kinase C (PKC) activities, and trigger a rapid rise in intracellular Ca2+levels in goldfish NIL cells. Using a pharmacological approach, cAMP/PKA and phospholipase C (PLC)/PKC pathways and subsequent activation of Ca2+/calmodulin (CaM)-dependent cascades were shown to be involved in SLα release induced by gKiss1-10. Apparently, the Ca2+-dependent cascades were triggered by extracellular Ca2+entry via voltage-sensitive Ca2+channels and mobilization of inositol trisphosphate-sensitive intracellular Ca2+stores. Our results demonstrate that gKiss1-10 can act directly at the pituitary level to trigger SLα release via a complex network of post-receptor signaling mechanisms.
Gonadal transcriptomic analysis of yellow catfish (Pelteobagrus fulvidraco): identification of sex-related genes and genetic markers
Authors: Lu Jianguo , Luan Peixian , Zhang Xiaofeng , Xue Shuqun , Peng Lina , Mahbooband Shahid , Sun Xiaowen
Published: September 2014

Yellow catfish ( Pelteobagrus fulvidraco) has been recognized as a vital freshwater aquaculture species in East and Southeast Asia. In addition to its commercial interest, it is also attracted much attention because of its value in studying sex-determination mechanisms. A comprehensive gonadal transcriptome analysis is believed to provide a resource for genome annotation, candidate gene identification, and molecular marker development. Herein, we performed a de novo assembly of yellow catfish gonad transcriptome by high-throughput Illumina sequencing. A total of 82,123 contigs were obtained, ranging from 351 to 21,268 bp, and N50 of 2,329 bp. Unigenes of 21,869 in total were identified. Of these, 229 and 1,188 genes were found to be specifically expressed in XY gonad tissue for 1 yr and 2 yr old yellow catfish, respectively; correspondingly, 51 and 40 genes were identified in XX gonad tissue at those two stages. Gene ontology and KEGG analysis were conducted and classified all contigs into different categories. A large number of unigenes involved in sex determination were identified, as well as microsatellites and SNP variants. The expression patterns of sex-related genes were then validated by quantitative real-time PCR (qRT-PCR) suggesting the high reliability of RNA-Seq results. In this study, the transcriptome of yellow catfish gonad was first sequenced, assembled, and characterized; it provides a valuable genomic resource for better understanding of yellow catfish sex determination as well as development of molecular markers, thereby assisting in the production of monosex yellow catfish for aquaculture.
RobustH∞Control for a Class of Discrete Time-Delay Stochastic Systems with Randomly Occurring Nonlinearities
Authors: Wang Yamin , Alsaadi Fuad E. , Lauria Stanislao , Liu Yurong
Published: August 2014

In this paper, we consider the robustH∞control problem for a class of discrete time-delay stochastic systems with randomly occurring nonlinearities. The parameter uncertainties enter all the system matrices; the stochastic disturbances are both state and control dependent, and the randomly occurring nonlinearities obey the sector boundedness conditions. The purpose of the problem addressed is to design a state feedback controller such that, for all admissible uncertainties, nonlinearities, and time delays, the closed-loop system is robustly asymptotically stable in the mean square, and a prescribedH∞disturbance rejection attenuation level is also guaranteed. By using the Lyapunov stability theory and stochastic analysis tools, a linear matrix inequality (LMI) approach is developed to derive sufficient conditions ensuring the existence of the desired controllers, where the conditions are dependent on the lower and upper bounds of the time-varying delays. The explicit parameterization of the desired controller gains is also given. Finally, a numerical example is exploited to show the usefulness of the results obtained.
The Framework for Simulation of Bioinspired Security Mechanisms against Network Infrastructure Attacks
Authors: Shorov Andrey , Kotenko Igor
Published: August 2014

The paper outlines a bioinspired approach named “network nervous system" and methods of simulation of infrastructure attacks and protection mechanisms based on this approach. The protection mechanisms based on this approach consist of distributed prosedures of information collection and processing, which coordinate the activities of the main devices of a computer network, identify attacks, and determine nessesary countermeasures. Attacks and protection mechanisms are specified as structural models using a set-theoretic approach. An environment for simulation of protection mechanisms based on the biological metaphor is considered; the experiments demonstrating the effectiveness of the protection mechanisms are described.
Ultrasubwavelength Ferroelectric Leaky Wave Antenna in a Planar Substrate-Superstrate Configuration
Authors: Lovat G. , Burghignoli P. , Araneo R. , Celozzi S.
Published: August 2014

The possibility of achieving directive fan-beam radiation with planar Fabry-Pérot cavity antennas constituted by an upper ferroelectric thin film and a lower ground plane having ultrasubwavelength thickness is studied by means of a simple transverse-equivalent-network approach and a cylindrical leakywave analysis, deriving simple design formulas. The performance of the proposed antenna is investigated in terms of power density radiated at broadside and directivity in the principal planes, pointing out the main limitations and tradeoffs associated with the reduced thickness.
Stable Hovering Flight for a Small Unmanned Helicopter Using Fuzzy Control
Authors: Khizer Arbab Nighat , Yaping Dai , Amjad Ali Syed , Xiangyang Xu
Published: August 2014

Stable hover flight control for small unmanned helicopter under light air turbulent environment is presented. Intelligent fuzzy logic is chosen because it is a nonlinear control technique based on expert knowledge and is capable of handling sensor created noise and contradictory inputs commonly encountered in flight control. The fuzzy nonlinear control utilizes these distinct qualities for attitude, height, and position control. These multiple controls are developed using two‐loop control structure by first designing an inner‐loop controller for attitude angles and height and then by establishing outer‐loop controller for helicopter position. The nonlinear small unmanned helicopter model used comes from X‐Plane simulator. A simulation platform consisting of MATLAB/Simulink and X‐Plane© flight simulator was introduced to implement the proposed controls. The main objective of this research is to design computationally intelligent control laws for hovering and to test and analyze this autopilot for small unmanned helicopter model on X‐Plane under ideal and mild turbulent condition. Proposed fuzzy flight controls are validated using an X‐Plane helicopter model before being embedded on actual helicopter. To show the effectiveness of the proposed fuzzy control method and its ability to cope with the external uncertainties, results are compared with a classical PD controller. Simulated results show that two‐loop fuzzy controllers have a good ability to establish stable hovering for a class of unmanned rotorcraft in the presence of light turbulent environment.
Impact Strength and Flexural Properties Enhancement of Methacrylate Silane Treated Oil Palm Mesocarp Fiber Reinforced Biodegradable Hybrid Composites
Authors: Eng Chern Chiet , Ibrahim Nor Azowa , Zainuddin Norhazlin , Ariffin Hidayah , Yunus Wan Md. Zin Wan
Published: August 2014

Natural fiber as reinforcement filler in polymer composites is an attractive approach due to being fully biodegradable and cheap. However, incompatibility between hydrophilic natural fiber and hydrophobic polymer matrix restricts the application. The current studies focus on the effects of incorporation of silane treated OPMF into polylactic acid (PLA)/polycaprolactone (PCL)/nanoclay/OPMF hybrid composites. The composites were prepared by melt blending technique and characterize the composites with Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). FTIR spectra indicated that peak shifting occurs when silane treated OPMF was incorporated into hybrid composites. Based on mechanical properties results, incorporation of silane treated OPMF enhances the mechanical properties of unmodified OPMF hybrid composites with the enhancement of flexural and impact strength being 17.60% and 48.43%, respectively, at 10% fiber loading. TGA thermogram shows that incorporation of silane treated OPMF did not show increment in thermal properties of hybrid composites. SEM micrographs revealed that silane treated OPMF hybrid composites show good fiber/matrix adhesion as fiber is still embedded in the matrix and no cavity is present on the surface. Water absorption test shows that addition of less hydrophilic silane treated OPMF successfully reduces the water uptake of hybrid composites.
Developing “the Wings to Really Fly”: The Experiences of Four Postdoctoral Research Fellows within an Australian University Faculty of Education
Authors: Turunen Tuija A. , Wong Sandie , Bristol Laurette , Ho Siew Yin
Published: August 2014

Postdoctoral research fellowships are a recent phenomenon in teacher education and little has been documented about them. This paper presents findings from a study in which the experiences of research fellows in a rural university were investigated. The data were gathered as audio recordings from peer mentoring meetings, notes from these meetings, individual reflective journals, and interviews conducted with six key informants. The analysis highlights that the experience of research fellowships was marked by a need to negotiate four competing, though not necessarily exclusive, demands related to the institute’s research productivity, its research culture and teaching, and personal professional goals. A range of institutional practices and individual characteristics mediated these negotiations.
Experimental Study of the Composition and Structure of Granular Media in the Shear Bands Based on the HHC-Granular Model
Authors: Wang Guang-jin , Kong Xiang-yun , Yang Chun-he
Published: August 2014

The researchers cannot control the composition and structure of coarse grained soil in the indoor experiment because the granular particles of different size have the characteristics of random distribution and no sorting. Therefore, on the basis of the laboratory tests with the coarse grained soil, the HHC-Granular model, which could simulate the no sorting and random distribution of different size particles in the coarse-grained soil, was developed by use of cellular automata method. Meanwhile, the triaxial numerical simulation experiments of coarse grained soil were finished with the different composition and structure soil, and the variation of shear strength was discussed. The results showed that the internal friction angle was likely to reduce with the increasing of gravel contents in the coarse-grained soil, but the mean internal friction angle significantly increased with the increment of gravel contents. It indicated that the gravel contents of shear bands were the major factor affecting the shear strength.
Trends in Demand for Acute Medical Care at Two Football Clubs over an Eighteen-Year Period
Authors: Heinink Thomas P. , Fogarty Andrew W. , Wiles Matthew D.
Published: September 2014

Introduction. Following the Hillsborough disaster, there is a requirement for crowd doctors to be present during football matches. However, there are little data on long-term trends in utilisation of crowd doctor services at sporting events. Methods. A retrospective service evaluation of presentations to the crowd doctor for 18 consecutive English Football League seasons: 13 seasons at Northampton Town Football Club (NTFC) followed by five seasons at Leicester City Football Club (LCFC). Data were analysed to determine the reason for, and severity of, presentation and the magnitude of the intervention required. Results. There were 429 recorded presentations to the crowd doctor over the 18 seasons. Patients’ age ranged from 3 to 93 years. 76% of presentations were due to an injury or illness arising at the match. The majority of presentations were with minor ailments (76%) requiring only minor intervention (88%); there were a small number of life-threatening presentations (1%) including three cardiac arrests. Conclusion. Crowd doctors may see patients in all age groups, presenting in a variety of ways. Most patients will have minor symptoms, but occasionally patients present with life-threatening problems. The crowd doctor must be competent assessing and treating all of these potential patient groups and pathologies.
A New Approach to the Fuzzification of Convex Structures
Authors: Shi Fu-Gui , Xiu Zhen-Yu
Published: August 2014

A new approach to the fuzzification of convex structures is introduced. It is also called anM-fuzzifying convex structure. In the definition ofM-fuzzifying convex structure, each subset can be regarded as a convex set to some degree. AnM-fuzzifying convex structure can be characterized by means of itsM-fuzzifying closure operator. AnM-fuzzifying convex structure and itsM-fuzzifying closure operator are one-to-one corresponding. The concepts ofM-fuzzifying convexity preserving functions, substructures, disjoint sums, bases, subbases, joins, product, and quotient structures are presented and their fundamental properties are obtained inM-fuzzifying convex structure.
Photocatalytic Degradation of Trifluralin, Clodinafop-Propargyl, and 1,2-Dichloro-4-Nitrobenzene As Determined by Gas Chromatography Coupled with Mass Spectrometry
Authors: Mir Niyaz A. , Khan A. , Muneer M. , Vijayalakhsmi S.
Published: August 2014

Phototransformation is considered one of the most key factors affecting the fate of pesticides. Therefore, our study focused on photocatalytic degradation of three selected pesticide derivatives: trifluralin (1), clodinafop-propargyl (2), and 1,2-dichloro-4-nitrobenzene (3). The degradation was carried out in acetonitrile/water medium in the presence of titanium dioxide (TiO2) under continuous purging of atmospheric air. The course of degradation was followed by thin-layer chromatography and gas chromatography-mass spectrometry techniques. Electron ionization mass spectrometry was used to identify the degradation species. GC-MS analysis indicates the formation of several intermediate products which have been characterized on the basis of molecular ion, mass fragmentation pattern, and comparison with NIST library. The photocatalytic degradation of pesticides of different chemical structures manifested distinctly different degradation mechanism. The major routes for the degradation of pesticides were found to be (a) dealkylation, dehalogenation, and decarboxylation, (b) hydroxylation, (c) oxidation of side chain, if present, (d) isomerization and cyclization, (e) cleavage of alkoxy bond, and (f) reduction of triple bond to double bond and nitro group to amino.
Steepest-Descent Approach to Triple Hierarchical Constrained Optimization Problems
Authors: Ceng Lu-Chuan , Liao Cheng-Wen , Pang Chin-Tzong , Wen Ching-Feng
Published: August 2014

We introduce and analyze a hybrid steepest-descent algorithm by combining Korpelevich’s extragradient method, the steepest-descent method, and the averaged mapping approach to the gradient-projection algorithm. It is proven that under appropriate assumptions, the proposed algorithm converges strongly to the unique solution of a triple hierarchical constrained optimization problem (THCOP) over the common fixed point set of finitely many nonexpansive mappings, with constraints of finitely many generalized mixed equilibrium problems (GMEPs), finitely many variational inclusions, and a convex minimization problem (CMP) in a real Hilbert space.