bluuebunny/crossref_metadata_2025 huggingface dataset:
Superoxide Dismutases Are Involved in Candida albicans Biofilm Persistence against Miconazole
Authors: Bink Anna , Vandenbosch Davy , Coenye Tom , Nelis Hans , Cammue Bruno P. A. , Thevissen Karin
Published: July 2011

We investigated the cellular mechanisms responsible for the occurrence of miconazole-tolerant persisters in
Candida albicans
biofilms. Miconazole induced about 30% killing of sessile
C. albicans
cells at 75 μM. The fraction of miconazole-tolerant persisters, i.e., cells that can survive high doses of miconazole (0.6 to 2.4 mM), in these biofilms was 1 to 2%. Since miconazole induces reactive oxygen species (ROS) in sessile
C. albicans
cells, we focused on a role for superoxide dismutases (Sods) in persistence and found the expression of Sod-encoding genes in sessile
C. albicans
cells induced by miconazole compared to the expression levels in untreated sessile
C. albicans
cells. Moreover, addition of the superoxide dismutase inhibitor
N
,
N
′-diethyldithiocarbamate (DDC) to
C. albicans
biofilms resulted in an 18-fold reduction of the miconazole-tolerant persister fraction and in increased endogenous ROS levels in these cells. Treatment of biofilms of
C. albicans
clinical isolates with DDC resulted in an 18-fold to more than 200-fold reduction of their miconazole-tolerant persister fraction. To further confirm the important role for Sods in
C. albicans
biofilm persistence, we used a Δ
sod4
Δ
sod5
mutant lacking Sods 4 and 5. Biofilms of the Δ
sod4
Δ
sod5
mutant contained at least 3-fold less of the miconazole-tolerant persisters and had increased ROS levels compared to biofilms of the isogenic wild type (WT). In conclusion, the occurrence of miconazole-tolerant persisters in
C. albicans
biofilms is linked to the ROS-detoxifying activity of Sods. Moreover, Sod inhibitors can be used to potentiate the activity of miconazole against
C. albicans
biofilms.
Multicenter Evaluation of a New DNA Microarray for Rapid Detection of Clinically Relevant
bla
Genes from β-Lactam-Resistant Gram-Negative Bacteria
Authors: Bogaerts Pierre , Hujer Andrea M. , Naas Thierry , de Castro Roberta Rezende , Endimiani Andrea , Nordmann Patrice , Glupczynski Youri , Bonomo Robert A.
Published: July 2011

A new commercial low-density microarray which identifies common extended-spectrum β-lactamase plasmid-mediated cephalosporinase genes, as well as carbapenemase (
bla
KPC
and
bla
NDM
) genes, was evaluated. We tested 207 clinical and reference/collection isolates of the
Enterobacteriaceae
possessing different
bla
genes. Overall, the sensitivity and specificity of the microarray were 100% for the detection of the plasmid-mediated
bla
AmpC
,
bla
KPC
, and
bla
NDM
genes using
bla
gene sequencing as the reference method.
In Vitro
Antibacterial Activity of NB-003 against Propionibacterium acnes
Authors: Pannu J. , McCarthy A. , Martin A. , Hamouda T. , Ciotti S. , Ma L. , Sutcliffe J. , Baker J. R.
Published: July 2011

NB-003 and NB-003 gel formulations are oil-in-water nanoemulsions designed for use in bacterial infections.
In vitro
susceptibility of
Propionibacterium acnes
to NB-003 formulations and comparator drugs was evaluated. Both NB-003 formulations were bactericidal against all
P. acnes
isolates, including those that were erythromycin, clindamycin, and/or tetracycline resistant. In the absence of sebum, the MIC
90
s/minimum bactericidal concentrations (MBC
90
s) for NB-003, NB-003 gel, salicylic acid (SA), and benzoyl peroxide (BPO) were 0.5/2.0, 1.0/2.0, 1,000/2,000, and 50/200 μg/ml, respectively. In the presence of 50% sebum, the MIC
90
s/MBC
90
s of NB003 and BPOs increased to 128/1,024 and 400/1,600 μg/ml, respectively. The MIC
90
s/MBC
90
s of SA were not significantly impacted by the presence of sebum. A reduction in the MBC
90
s for NB-003 and BPO was observed when 2% SA or 0.5% BPO was integrated into the formulation, resulting in MIC
90
s/MBC
90
s of 128/256 μg/ml for NB003 and 214/428 μg/ml for BPO. The addition of EDTA enhanced the
in vitro
efficacy of 0.5% NB-003 in the presence or absence of 25% sebum. The addition of 5 mM EDTA to each well of the microtiter plate resulted in a >16- and >256-fold decrease in MIC
90
and MBC
90
, yielding a more potent MIC
90
/MBC
90
of ≤1/<1 μg/ml. The kinetics of bactericidal activity of NB-003 against
P. acnes
were compared to those of a commercially available product of BPO. Electron micrographs of
P. acnes
treated with NB-003 showed complete disruption of bacteria. Assessment of spontaneous resistance of
P. acnes
revealed no stably resistant mutant strains.
A Screening Assay Based on Host-Pathogen Interaction Models Identifies a Set of Novel Antifungal Benzimidazole Derivatives
Authors: Burger-Kentischer Anke , Finkelmeier Doris , Keller Petra , Bauer Jörg , Eickhoff Holger , Kleymann Gerald , Abu Rayyan Walid , Singh Anurag , Schröppel Klaus , Lemuth Karin , Wiesmüller Karl-Heinz , Rupp Steffen
Published: July 2011

Fungal infections are a serious health problem in clinics, especially in the immune-compromised patient. Disease ranges from widespread superficial infections like vulvovaginal infections to life-threatening systemic candidiasis. Especially for systemic mycoses, only a limited arsenal of antifungals is available. The most commonly used classes of antifungal compounds used include azoles, polyenes, and echinocandins. Due to emerging resistance to standard therapy, significant side effects, and high costs for several antifungals, there is a medical need for new antifungals in the clinic and general practice. In order to expand the arsenal of compounds with antifungal activities, we screened a compound library including more than 35,000 individual compounds derived from organic synthesis as well as combinatorial compound collections representing mixtures of compounds for antimycotic activity. In total, more than 100,000 compounds were screened using a new type of activity-selectivity assay, analyzing both the antifungal activity and the compatibility with human cells at the same time. One promising hit, an (
S
)-2-aminoalkyl benzimidazole derivative, was developed among a series of lead compounds showing potent antifungal activity. (
S
)-2-(1-Aminoisobutyl)-1-(3-chlorobenzyl) benzimidazole showed the highest antifungal activity and the best compatibility with human cells in several cell culture models and against a number of clinical isolates of several species of pathogenic
Candida
yeasts. Transcriptional profiling indicates that the newly discovered compound is a potential inhibitor of the ergosterol pathway, in contrast to other benzimidazole derivatives, which target microtubules.
Targeted Disruption of Nonribosomal Peptide Synthetase
pes3
Augments the Virulence of Aspergillus fumigatus
Authors: O'Hanlon Karen A. , Cairns Timothy , Stack Deirdre , Schrettl Markus , Bignell Elaine M. , Kavanagh Kevin , Miggin Sinéad M. , O'Keeffe Grainne , Larsen Thomas O. , Doyle Sean
Published: July 2011

Nonribosomal peptide synthesis (NRPS) is a documented virulence factor for the opportunistic pathogen
Aspergillus fumigatus
and other fungi. Secreted or intracellularly located NRP products include the toxic molecule gliotoxin and the iron-chelating siderophores triacetylfusarinine C and ferricrocin. No structural or immunologically relevant NRP products have been identified in the organism. We investigated the function of the largest gene in
A. fumigatus
, which encodes the NRP synthetase Pes3 (AFUA_5G12730), by targeted gene deletion and extensive phenotypic analysis. It was observed that in contrast to other NRP synthetases, deletion of
pes3
significantly increases the virulence of
A. fumigatus
, whereby the
pes3
deletion strain (
A. fumigatus
Δpes3
) exhibited heightened virulence (increased killing) in invertebrate (
P
< 0.001) and increased fungal burden (
P
= 0.008) in a corticosteroid model of murine pulmonary aspergillosis. Complementation restored the wild-type phenotype in the invertebrate model. Deletion of
pes3
also resulted in increased susceptibility to the antifungal, voriconazole (
P
< 0.01), shorter germlings, and significantly reduced surface β-glucan (
P
= 0.0325). Extensive metabolite profiling revealed that Pes3 does not produce a secreted or intracellularly stored NRP in
A. fumigatus
. Macrophage infections and histological analysis of infected murine tissue indicate that
Δpes3
heightened virulence appears to be mediated by aberrant innate immune recognition of the fungus. Proteome alterations in
A. fumigatus
Δ
pes3
strongly suggest impaired germination capacity. Uniquely, our data strongly indicate a structural role for the Pes3-encoded NRP, a finding that appears to be novel for an NRP synthetase.
The Neogene drainage history of south-central Idaho
Authors: Link Paul K. , Hodges Mary K.V.
Published: July 2011

Study of the distribution of the age-populations of detrital zircons in the Snake River system suggest that specific stream systems can be identified based on the detrital-zircon age-population signature (“barcode”) of ancient and Holocene sand deposits. Detrital zircon studies can be used on regional and local scales to determine changes in drainage patterns using both surface and subsurface data.

Regional study of drainage patterns using detrital zircons found in Neogene strata of Idaho and southwest Montana suggest northeastward late Miocene to Holocene migration of the Continental Divide from the western side of the Pioneer Mountains to the current position in southwest Montana. Specifically, mixed populations of recycled Proterozoic detrital zircons that define the Wood River drainage are not found in the western Snake River Plain until after 7 Ma. Late Miocene eastward drainage from the central Snake River Plain to southwest Montana is suggested by 9–12 Ma detrital zircons found in fluvial strata less than 6 million years old, of the Sixmile Creek Formation

Basalt eruptions of the Eastern Snake River Plain during the Pliocene and Pleistocene also caused drainage diversion. Detrital zircons in Pliocene sands from coreholes at Wendell and Mountain Home Air Force Base contain Big Lost River zircon provenance, suggesting that during the Pliocene, the Big Lost River flowed west along the central Snake River Plain.

Late Pliocene and early Pleistocene basaltic volcanoes and rhyolite dome eruptions resulted in volcanic highlands, the Axial Volcanic Zone of the eastern Snake River Plain and the northwest-trending Arco Volcanic Rift Zone (which includes Craters of the Moon volcanic center). The development of these volcanic highlands disrupted the ancestral drainage of the Pliocene Big Lost River system, confining it to the Big Lost Trough, a volcanically dammed basin of internal drainage on the Idaho National Laboratory.

After the Big Lost Trough was cut off from the main Snake River, basalt eruptions, local subsidence, and climate controlled the courses of the rivers that flowed into it. Detrital-zircon populations in core samples reveal the provenance of specific sand beds from the Big or Little Lost River systems.
Middle Cryogenian (“Sturtian”) Pocatello Formation
Authors: Keeley Joshua A. , Link Paul K.
Published: July 2011

Detailed mapping along the east face of Oxford Ridge in the southern Bannock Range, southeast Idaho determines the stratigraphic placement and lateral extent of strata in the Scout Mountain Member of the Neoproterozoic Pocatello Formation. The lower “transitional unit” overlies the Bannock Volcanic Member and consists of 70 m of massive diamictite with argillitic and vesicular basaltic clasts up to cobble size intercalated with thin metabasalt and hyaloclastite units. Overlying the transitional unit is a 150–190-m-thick, massive, brown-green to purple sandy diamictite with dominantly quartzose cobble clasts. Interbedded with this middle unit is a 60-m-thick epiclastic volcanic interval informally named the Oxford Mountain tuffite. An upper sandstone unit up to 100 m thick lies above the diamictite at the head of Fivemile Creek in the southern portion of the map area.

The volcanic interval contains plagioclase-phyric volcanic lithic sandstone, porphyritic volcanic lithic fragments and rounded cobbles in tuffaceous diamictite and a reworked stratified lapilli-tuff. It is interstratified with quartzose and volcanogenic diamictite and can be traced along 5.5 km of strike. On Oxford Mountain, laser ablation–inductively coupled plasma mass spectrometry U-Pb zircon ages presented here and additional sensitive high-resolution ion microprobe ages constrain the underlying Bannock Volcanic Member to be 717–686 Ma and require that the overlying Scout Mountain Member is younger than 685 Ma.
New descriptions of the cap dolostone and associated strata, Neoproterozoic Pocatello Formation, southeastern Idaho, USA
Authors: Dehler Carol M. , Anderson Kathleen , Nagy Robin
Published: July 2011

An ~90-m-thick interval of mixed siliciclastic-carbonate strata, including a cap dolostone unit, overlies diamictite of the upper Scout Mountain Member of the Pocatello Formation in the Fort Hall Mine area south of Portneuf Narrows, southeastern Idaho, and is ≤ ca. 665 Ma. Six facies comprise this interval: silty sandstone (reworked diamictite matrix), laminated dolomite, dolomite and sandstone, sandstone, dolomite-chip breccia, and argillite and limestone. Sedimentary structures and bedding geometries of facies indicate paleoenvironments ranging from below storm wave base to upper shoreface. The edgewise, mounded, and parallel-bedded dolomite-chip breccia indicates slope failure and reworking of the lower shoreface during large storms.

Facies relationships allow generalized division of these strata into three units. The lowermost unit, Unit A, comprises intimately interbedded laminated dolomite (“cap dolostone”), dolomite-chip breccia, and sandstone facies and is 17 m thick. Unit A apparently grades upward into Unit B, a 45-m-thick interval of the sandstone facies. Unit C, 28 m thick, rests sharply on Unit B, and comprises a basal laminated dolomite facies and the limestone and argillite facies. Units A and B may indicate a regressive wave-dominated coast that was influenced by large storms (highstand systems tract). Unit C indicates near storm wave base deposition and an overall deepening, as shown by dark argillite beds of the overlying upper member of the Pocatello Formation (transgressive systems tract).

δ13C and δ18O values from dolomite and limestone samples of Units A and C are similar to values from local, regional, and transglobal cap carbonate intervals. δ13C values range from −1.9 to −5.6‰ and δ18O values range from −10.2 to −17.4‰, with no systematic correlation between C- and O-isotope values. δ13C values are consistent with previously reported values from the Pocatello Formation and are similar to values from the alleged Marinoan Noonday Formation in Death Valley, California, and the Marinoan Maieberg Formation in Namibia.

Collective data from the cap dolostone and associated strata of the Pocatello Formation suggest protracted mixed siliciclastic-carbonate deposition on a stormdominated shelf at ca. 665 Ma.
Secondary hypertension: a condition not to be missed
Authors: Sukor Norlela
Published: July 2011

Hypertension is a chronic disorder which often entails debilitating cardiovascular and renal complications. Hypertension mostly arises as a complex quantitative trait that is affected by varying combinations of genetic and environmental factors. Secondary hypertension has been encountered with increasing frequency. The common causes of secondary hypertension include renal parenchymal disease, renal artery stenosis, primary aldosteronism, phaeochromocytoma, and Cushing’s syndrome. The detection of a secondary cause is of the utmost importance because it provides an opportunity to convert an incurable disease into a potentially curable one. Early identification and treatment will provide a better opportunity for cure, prevent target organ damage, reduce socioeconomic burden and health expenditure associated with drug costs, and improve patients' quality of life. Hence, it is a condition not to be missed.
AN OPTIMAL LIFTING THEOREM FOR COUPLED CELL NETWORKS
Authors: STEWART IAN
Published: July 2011

The multiarrow formalism for coupled cell networks permits multiple arrows and self-loops. The Lifting Theorem states that any such network is a quotient of a network in which all arrows are single and self-loops do not occur. Previous proofs are inductive, and give no useful estimate of the minimal size of the lift. We give a noninductive proof of the Lifting Theorem, and identify the number of cells in the smallest possible lift. We interpret this construction in terms of the type matrix of the network, which encodes its topology and labeling.
A SIMPLE MEMRISTOR CHAOTIC CIRCUIT WITH COMPLEX DYNAMICS
Authors: BAO BOCHENG , MA ZHENGHUA , XU JIANPING , LIU ZHONG , XU QIANG
Published: July 2011

A simple memristor-based chaotic circuit with an active flux-controlled memristor characterized by a smooth continuous cubic nonlinearity is designed. The proposed chaotic circuit can generate a 2-scroll chaotic attractor on a finite time scale and has an equilibrium set with its stability dependent on the initial state of the memristor. The complex dynamics of the proposed chaotic circuit under different initial state of the memristor are investigated both theoretically and numerically. In particular, some novel transient transition behaviors with different time scales are found in the memristor circuit. Experimental observations based on a universal circuit implementation platform are conducted to partially verify the numerical simulation results.
HOPF BIFURCATIONS AND THEIR DEGENERACIES IN CHUA'S EQUATION
Authors: ALGABA ANTONIO , MERINO MANUEL , FERNÁNDEZ-SÁNCHEZ FERNANDO , RODRÍGUEZ-LUIS ALEJANDRO J.
Published: July 2011

We perform an analytical study of the Hopf bifurcations and their degeneracies in Chua's equation. In the case of the equilibrium at the origin only codimension-two Hopf bifurcations appear. However, for the nontrivial equilibria we prove the existence of codimension-three Hopf bifurcations. Numerical results are in strong agreement with the analytical ones.
HOMOGENIZATION OF FIRST-ORDER EQUATIONS WITH u/∊-PERIODIC HAMILTONIAN: RATE OF CONVERGENCE AS ∊ → 0 AND NUMERICAL METHODS
Authors: ACHDOU YVES , PATRIZI STEFANIA
Published: July 2011

We consider homogenization problems for first-order Hamilton–Jacobi equations with u∊/∊ periodic dependence, recently introduced by Imbert and Monneau, and also studied by Barles: this unusual dependence leads to nonstandard cell problems. We study the rate of convergence of the solution to the solution of the homogenized problem when the parameter ∊ tends to 0. We obtain the same rates as those obtained by Capuzzo Dolcetta and Ishii for the more usual homogenization problems without the dependence in u∊/∊. In the second part, we study Eulerian schemes for the approximation of the cell problems. We prove that when the grid steps tend to zero, the approximation of the effective Hamiltonian converges to the effective Hamiltonian.
Resonance Raman spectroscopic examination of ferrochelatase-induced porphyrin distortion
Authors: Franco Ricardo , Al-Karadaghi Salam , Ferreira Gloria C.
Published: July 2011

Ferrochelatase, the terminal enzyme of the heme biosynthetic pathway, catalyzes the insertion of ferrous iron into protoporphyrin IX to give heme. Resonance Raman spectroscopy has been instrumental in defining the distortion (mode and extent) of the porphyrin substrate, which is a critical step in the catalytic mechanism of ferrochelatase. Saddling is the predominant porphyrin out-of-plane deformation induced upon binding to ferrochelatase. Our analysis demonstrated that the intensity of the γ15 line, which is assigned to an out-of-plane porphyrin vibration, in resonance Raman spectra obtained for wild-type- and variant ferrochelatase-bound porphyrin, correlates with the saddling deformation undergone by the porphyrin substrate. Further analysis of the three dimensional X-ray structures of bacterial, human and yeast ferrochelatases and the type and extent of distortion of the protein-bound porphyrin substrate and inhibitors using normal structure decomposition, support the view that ferrochelatase catalysis involves binding of a distorted porphyrin substrate and releasing of a flatter, metalated porphyrin.
Evolution of dendritic nanosheets into durable holey sheets: a lattice gas simulation study
Authors: Challa Sivakumar R. , Song Yujiang , Shelnutt John A. , Miller James E. , Swol Frank van
Published: July 2011

Monte Carlo lattice gas simulations are performed to study sintering in a realistic dendritic platinum nanosheet. The morphological and topological transformations observed in the simulations are in good agreement with sintering experiments. Employing an intuitive method of quantifying surface area, the stability of the surface area of the dendritic nanosheets is analyzed. The surface area is found to have a double exponential decay, one decay corresponding to rapid coarsening of dendritic features into pores and the other decay corresponding to a slow disappearance of unstable pores. Long duration simulations indicate that the thickness of the dendritic nanosheet remains fairly stable. Stability simulations of a single model pore in a sheet establish that there exists a narrow range of sheet thickness and pore size combinations that produces stable holey sheets. Outside this parameter range pores either rapidly close or expand without bound. The thickness of the engineered dendritic platinum nanosheet and the size of the crevices between dendritic arms put the Pt sheet into this stable range, further corroborating the detailed simulations and explaining the persistence of pores observed in actual dendritic platinum nanosheets.
PRODUCT OFFERING AS PART OF THE NPD PROCESS IN TECHNOLOGY COMPANIES
Authors: HAVERILA MATTI J.
Published: July 2011

We present an exploratory investigation of how managers conceptualize and perceive the product offering effort variables in successful and unsuccessful New Product Development (NPD) projects, and explore the role that product offering effort variables play in differentiating between successful and unsuccessful NPD outcomes. Our findings indicate that managers rely on two broad types of product offering factors, "product effort" and "price/cost effort", during the NPD process so that there are differences in metric equivalence across successful and unsuccessful NPD projects. Also, although all product effort variables, but none of the price/cost efficiency variables, are positively related to NPD success, managers in Finnish technology companies attach somewhat lower relative importance to product offering variables in comparison to studies of NPD intelligence in other countries. Limitation and practical implications are discussed.
Transcriptional regulator RBP-J regulates the number and plasticity of renin cells
Authors: Castellanos Rivera Ruth M. , Monteagudo Maria C. , Pentz Ellen S. , Glenn Sean T. , Gross Kenneth W. , Carretero Oscar , Sequeira-Lopez Maria Luisa S. , Gomez R. Ariel
Published: July 2011

Renin-expressing cells are crucial in the control of blood pressure and fluid-electrolyte homeostasis. Notch receptors convey cell-cell signals that may regulate the renin cell phenotype. Because the common downstream effector for all Notch receptors is the transcription factor RBP-J, we used a conditional knockout approach to delete RBP-J in cells of the renin lineage. The resultant RBP-J conditional knockout (cKO) mice displayed a severe reduction in the number of renin-positive juxtaglomerular apparatuses (JGA) and a reduction in the total number of renin positive cells per JGA and along the afferent arterioles. This reduction in renin protein was accompanied by a decrease in renin mRNA expression, decreased circulating renin, and low blood pressure. To investigate whether deletion of RBP-J altered the ability of mice to increase the number of renin cells normally elicited by a physiological threat, we treated RBP-J cKO mice with captopril and sodium depletion for 10 days. The resultant treated RBP-J cKO mice had a 65% reduction in renin mRNA levels (compared with treated controls) and were unable to increase circulating renin. Although these mice attempted to increase the number of renin cells, the cells were unusually thin and had few granules and barely detectable amounts of immunoreactive renin. As a consequence, the cells were incapable of fully adopting the endocrine phenotype of a renin cell. We conclude that RBP-J is required to maintain basal renin expression and the ability of smooth muscle cells along the kidney vasculature to regain the renin phenotype, a fundamental mechanism to preserve homeostasis.
An Efficient Feature Extraction Method, Global Between Maximum and Local Within Minimum, and Its Applications
Authors: Wang Lei , Zhang Jiangshe , Zang Fei
Published: July 2011

Feature extraction plays an important role in preprocessing procedure in
dealing with small sample size problems. Considering the fact that LDA, LPP, and many other existing methods are confined to one case of the data set. To solve
this problem, we propose an efficient method in this paper, named global
between maximum and local within minimum. It not only considers the
global structure of the data set, but also makes the best of the local geometry of
the data set through dividing the data set into four domains. This method
preserves relations of the nearest neighborhood, as well as demonstrates an
excellent performance in classification. Superiority of the proposed method
in this paper is manifested in many experiments on data visualization, face
representative, and face recognition.
Efficient Silicon Light-Emitting-Diodes with a p-Si/Ultrathin SiO2/n-Si Structure
Authors: Chu Shucheng , Kan Hirofumi
Published: July 2011

We report the efficient enhancement of light emission from silicon crystal by covering the silicon surface with an ultrathin (several nm) SiO2layer. The photoluminescence of Si band edge emission (1.14 μm band) at room temperature is enhanced by two orders of magnitude. Compared with a p-Si/n-Si diode, light emission from a p-Si/SiO2/n-Si diode by current injection via direct tunneling is enhanced by more than 3 orders of magnitude. The light-emission enhancement is attributed to the diminishment of nonradiation recombination at the surface/interface and to the space confinement of the carrier recombination. The simple structure and low operating bias (approximately 1 volt) of our light emitting diodes supply a new choice for realizing efficient current injection light source in silicon compatible with conventional ULSI technology.
Joint Estimation Using Quadratic Estimating Function
Authors: Liang Y. , Thavaneswaran A. , Abraham B.
Published: July 2011

A class of martingale estimating functions is convenient and plays an important role for inference for nonlinear time series models. However, when the information about the first four conditional moments
of the observed process becomes available, the quadratic estimating functions are more informative. In this paper, a general framework for joint estimation of conditional mean and variance parameters in time series models using quadratic estimating functions is developed. Superiority of the approach is demonstrated by comparing the information associated with the optimal quadratic estimating function with the information associated with other estimating functions. The method is used to study the optimal quadratic estimating functions of the parameters of autoregressive conditional duration (ACD) models, random coefficient autoregressive (RCA) models, doubly stochastic models and regression models with ARCH errors. Closed‐form expressions for the information gain are also discussed in some detail.
Field Studies on the Relationship betweenFusarium verticillioidesand Maize (Zea maysL.): Effect of Biocontrol Agents on Fungal Infection and Toxin Content of Grains at Harvest
Authors: Pereira Paola , Nesci Andrea , Castillo Carlos , Etcheverry Miriam
Published: July 2011

Maize (Zea maysL.) is a staple food for the majority of the world's population.Fusarium verticillioides(Sacc.) Nirenberg (Teleomorph:Gibberella moniliformisWineland; synonym:F. moniliformis) is both a saprophyte and a parasite of maize and can also be found as an endophyte. The presence of this fungus in maize constitutes an imminent risk due to its ability to produce fumonisins, mycotoxins with proven carcinogenic effects. The present work investigated biocontrol activity ofBacillus amyloliquefaciensandMicrobacterium oleovoransagainstF. verticillioidesinfection and fumonisin B1production in field-grown maize during four consecutive growing seasons. Treatment withB. amyloliquefaciensconsistently reducedF. verticillioidesinoculum and fumonisin content of harvested grains.F. verticillioidescount and fumonisin levels correlated negatively with rainfall regimes; however, none of these parameters showed significant correlation with yields. Treatment with these biocontrol agents may improve phytosanitary quality of the grains and reduce toxicological risk in the maize agroecosystem.
Pancreatic Cancer Cell Lines Can Induce Prostaglandin E2 Production from Human Blood Mononuclear Cells
Authors: Grekova Svitlana P. , Angelova Assia , Daeffler Laurent , Raykov Zahari
Published: July 2011

Accumulating evidence suggests an important role for cyclooxygenase-2 (COX-2) in the pathogenesis of a wide range of malignancies. The protumorigenic properties of COX-2 are generally thought to be mediated by its product, PGE2, which is shown to promote tumor spread and growth by multiple mechanisms but most importantly through modulation of the local immune response in the tumor. Pancreatic tumor cells produce various amounts of PGE2, some of them being even deficient in COX enzymes or other PGE2synthases. Here we describe that, beside pancreatic tumor cells or stromal fibroblasts, human peripheral blood mononuclear cells can also produce PGE2upon coculture with pancreatic cancer cells. Stimulating of cellular cPLA2 within PBMCs by secreted factors, presumably sPLA2, from tumor cells appeared crucial, while the direct contact between PBMCs and PDACs seemed to be dispensable for this effect. Our data is emphasizing the complex interactions participating in the formation of the tolerogenic immune milieu within pancreatic tumors.
A Survey of Linear Network Coding and Network Error Correction Code Constructions and Algorithms
Authors: Sanna Michele , Izquierdo Ebroul
Published: July 2011

Network coding was introduced by Ahlswede et al. in a pioneering work in 2000. This paradigm encompasses coding and retransmission of messages at the intermediate nodes of the network. In contrast with traditional store-and-forward networking, network coding increases the throughput and the robustness of the transmission. Linear network coding is a practical implementation of this new paradigm covered by several research works that include rate characterization, error-protection coding, and construction of codes. Especially determining the coding characteristics has its importance in providing the premise for an efficient transmission. In this paper, we review the recent breakthroughs in linear network coding for acyclic networks with a survey of code constructions literature. Deterministic construction algorithms and randomized procedures are presented for traditional network coding and for network-control network coding.
Secondary Leukemia in a non-Hodgkin's Lymphoma Patient Presenting as Myeloid Sarcoma of the Breast
Authors: Pitini Vincenzo , Arrigo Carmela , Sauta Maria Grazia , Altavilla Giuseppe
Published: July 2011

As defined by the World Health Organization classification of tumors of hematopoietic and lymphoid tissue, myeloid sarcoma (MS) is a tumor mass of myeloblasts or immature myeloid cells that can arise before, concurrent with, or following acute myeloid leukaemia. We describe a case of secondary leukemia presenting itself as MS of the breast in a patient previously treated for a non-Hodgkin's Lymphoma.
A 26-Year-Old Male with Mesothelioma Due to Asbestos Exposure
Authors: Zarogoulidis P. , Orfanidis M. , Constadinidis T. C. , Eleutheriadou E. , Kontakiotis T. , Kerenidi T. , Sakkas L. , Courcoutsakis N. , Zarogoulidis K.
Published: July 2011

Mesothelioma is a malignancy with poor prognosis, with an average 5-year survival rate being less than 9%. This type of cancer is almost exclusively caused by exposure to asbestos. A long exposure can cause mesothelioma and so can short ones, as each exposure is cumulative. We report a case of a 26-year-old male who was exposed to asbestos during his primary school years from the age of 6 to 12. Although the tumor mainly affects older men who in their youth were occupationally exposed to asbestos, malignant mesothelioma can also occur in young adults. A medical history was carefully taken and asbestos exposure was immediately mentioned by the patient. We conducted biopsy on the right supraclavicular lymph node. The patient was not a candidate for surgery, and chemotherapy treatment was initiated. While patient's chemotherapy is still ongoing, no other similar cases of students or teachers have been traced up to date from his school. The school building was demolished in January 2009.
Endometrial Carcinoma Presenting as Vasculitic Sensorimotor Polyneuropathy
Authors: Vasku Marketa , Papathemelis Thomas , Maass Nicolai , Meinhold-Heerlein Ivo , Bauerschlag Dirk
Published: July 2011

Paraneoplastic syndromes (PNS) are a heterogeneous group of symptoms which are indirectly caused by primary or metastatic tumor. Paraneoplastic polyneuropathy (PNP) is mostly related to small cell lung cancer (5%), prostate, gastric, and breast cancer. Only sporadic cases have been reported to be associated with endometrial cancer. We present a case of a premenopausal woman with severe vasculitic, asymmetric sensorimotor polyneuropathy that developed in conjunction with an endometrial carcinoma responding to surgical therapy of primary tumor combined to steroid therapy. Neurological symptoms such as asymmetrical sensorimotor deficits and painful paresthesias are suspicious when they occur in otherwise healthy women with no medical history. The phenomenon of a paraneoplastic syndrome can point to an underlying malignancy and can be used as marker of progression or regression of the tumor. Due to the rarity of PNP, there is no standard treatment. Recommended therapy is stage-adjusted treatment of the primary tumor.
Synthetic Triterpenoid Cyano Enone of Methyl Boswellate Activates Intrinsic, Extrinsic, and Endoplasmic Reticulum Stress Cell Death Pathways in Tumor Cell Lines
Authors: Ravanan Palaniyandi , Sano Renata , Talwar Priti , Ogasawara Satoshi , Matsuzawa Shu-ichi , Cuddy Michael , Singh Sanjay K. , Rao G.S.R. Subba , Kondaiah Paturu , Reed John C.
Published: July 2011

We explored the effect of a novel synthetic triterpenoid compound cyano enone of methyl boswellates (CEMB) on various prostate cancer and glioma cancer cell lines. CEMB displayed concentration-dependent cytotoxic activity with submicromolar lethal dose 50% (LD50) values in 10 of 10 tumor cell lines tested. CEMB-induced cytotoxicity is accompanied by activation of downstream effector caspases (caspases 3 and 7) and by upstream initiator caspases involved in both the extrinsic (caspase 8) and intrinsic (caspase 9) apoptotic pathways. By using short interfering RNAs (siRNA), we show evidence that knockdown of caspase 8, DR4, Apaf-1, and Bid impairs CEMB-induced cell death. Similar to other proapoptotic synthetic triterpenoid compounds, CEMB-induced apoptosis involved endoplasmic reticulum stress, as shown by partial rescue of tumor cells by siRNA-mediated knockdown of expression of genes involved in the unfolded protein response such as IRE1α, PERK, and ATF6. Altogether, our results suggest that CEMB stimulates several apoptotic pathways in cancer cells, suggesting that this compound should be evaluated further as a potential agent for cancer therapy. Mol Cancer Ther; 10(9); 1635–43. ©2011 AACR.
Survivin Downregulation Is Associated with Vasectomy-Induced Spermatogenic Damage and Apoptosis
Authors: Al-Maghrebi May , Kehinde Elijah O. , Anim Jehoram T.
Published: July 2011

Objective: To evaluate the expression of the apoptotic genes survivin, Bax and Bcl-2 in vasectomized rabbits and to determine their relation with vasectomy-induced spermatogenic impairment and germ cell apoptosis. Materials and Methods: Twelve adult rabbits (6–12 months old) were divided into three groups: sham control, unilateral vasectomy or bilateral vasectomy. Six months after vasectomy, testicular tissue was analyzed for germ cell apoptosis and DNA fragmentation by the TUNEL assay and gel electrophoresis, respectively. Spermatogenesis was assessed using the Johnsen score. The relative gene expression of survivin, Bax and Bcl-2 was measured using reverse transcription followed by real-time PCR. Results: Compared to sham animals, a significant decrease in testicular survivin mRNA levels was measured in the two vasectomy animal groups (p < 0.05). This was accompanied by a significant increase in the Bax:Bcl-2 ratio in the vasectomized animals (p < 0.05). In addition, these data showed positive correlation with enhanced apoptotic index, damage to spermatogenesis and DNA fragmentation after vasectomy. Conclusion: These findings demonstrate that vasectomy-induced damage to spermatogenesis due to testicular apoptosis may be associated with survivin downregulation and Bax overexpression.
Optical Imaging in Cancer Research: Basic Principles, Tumor Detection, and Therapeutic Monitoring
Authors: Solomon Metasebya , Liu Yang , Berezin Mikhail Y. , Achilefu Samuel
Published: July 2011

Accurate and rapid detection of diseases is of great importance for assessing the molecular basis of pathogenesis, preventing the onset of complications, and implementing a tailored therapeutic regimen. The ability of optical imaging to transcend wide spatial imaging scales ranging from cells to organ systems has rejuvenated interest in using this technology for medical imaging. Moreover, optical imaging has at its disposal diverse contrast mechanisms for distinguishing normal from pathologic processes and tissues. To accommodate these signaling strategies, an array of imaging techniques has been developed. Importantly, light absorption, and emission methods, as well as hybrid optical imaging approaches are amenable to both small animal and human studies. Typically, complex methods are needed to extract quantitative data from deep tissues. This review focuses on the development of optical imaging platforms, image processing techniques, and molecular probes, as well as their applications in cancer diagnosis, staging, and monitoring therapeutic response.
Postoperative Analgesia in Impacted Third Molar Surgery: The Role of Preoperative Diclofenac Sodium, Paracetamol and Lornoxicam
Authors: Tuzuner Oncul Aysegul Mine , Yazicioglu Duygu , Alanoglu Zekeriyya , Demiralp Samimi , Ozturk Adnan , Ucok Cahit
Published: July 2011

Objective: The aim of this study was to compare the postoperative analgesic effects of preoperative intravenous (i.v.) paracetamol, diclofenac sodium and lornoxicam (nonsteroidal anti-inflammatory drugs). Subjects and Methods: Sixty patients with impacted third molar who underwent surgical removal were randomly allocated into three groups: group P (n = 20), group D (n = 20) and group L (n = 20). Group P received preoperatively 1 g paracetamol i.v., group D 75 mg diclofenac sodium i.m. and group L 8 mg lornoxicam i.v. Postoperative pain intensity, additional consumption of analgesics postoperatively and postoperative complications were compared among groups. Results: The groups were comparable for pain scores (p > 0.05). Maximum pain scores were recorded in postoperative 4th h in all groups (group L 22, 14–44 mm; group P 24, 13–43 mm; group D 14, 10–24 mm, p = 0.117). Patients experienced high satisfaction scores which were comparable among groups (group L 85, 75–100 mm; group P 87, 70–95 mm; group D 84, 77–98 mm, p = 0.457). Conclusion: Preoperative intramuscular diclofenac, intravenous paracetamol and lornoxicam effectively decreased the pain scores. The patients were satisfied with the three postoperative pain management regimens.
Role of Endorectal Magnetic Resonance Spectroscopic Imaging in Two Different Gleason Scores in Prostate Cancer
Authors: Nagarajan Rajakumar , Margolis Daniel , McClure Tim , Raman Steve , Thomas M. Albert
Published: July 2011

Objective: The major goal of the work was to record three-dimensional magnetic resonance spectroscopic imaging (MRSI) and to compare metabolite ratios between different Gleason scores (GS). Materials and Methods: MRSI localized by endorectal coil-acquired point-resolved spectroscopy was performed in 14 men with prostate cancer of GS 6 (n = 7) and 7 (n = 7) using a 1.5-tesla MRI scanner. Results: The ratio of (choline + creatine)/citrate was increased with an increase of GS, i.e. 0.590 ± 0.171 in the target lesion and 0.321 ± 0.157 in the contralateral region of patients with a GS of 6 as opposed to 1.082 ± 0.432 in the target lesion and 0.360 ± 0.243 in the contralateral region of patients with a GS of 7. Conclusion: Our pilot results demonstrated that MRSI was an additional biochemical tool which is complementary to the current imaging modalities for early diagnosis and therapeutic management of prostate cancer.
Quality of Care in Chronic Leg Ulcer in the Community: Introduction of Quality Indicators and a Scoring System
Authors: Augustin Matthias , Rustenbach Stephan Jeff , Debus Sebastian , Grams Lena , Münter Karl-Christian , Tigges Wolfgang , Schäfer Elmar , Herberger Katharina
Published: July 2011

Background: Treatment of chronic wounds is complex, particularly as a standard for the assessment and evaluation of quality of care is missing. Objectives: To develop indicators for quality of care in chronic wounds in general, and to evaluate the quality of care in leg ulcers in Hamburg, Germany, in particular. Methods: Twenty indicators were derived from a national Delphi expert consensus to compute a single index of quality of care. This index was applied in a cross-sectional study involving a large spectrum of care providers and leg ulcer patients in the community. Trained wound experts interviewed and examined the patients, who had to complete standardized questionnaires. Results: On average, 64% of the quality criteria were met in the consecutive sample of 502 patients with chronic leg ulcers of any origin; 75% of the patients were satisfied with their wound care. Predictors of quality of care are presented. Conclusions: This instrument is feasible, valid and ready for comparisons of patient groups, regions and care systems, and for optimization processes in wound care.
Single-Photon Emission Computed Tomography Enhanced Tc-99m-Pertechnetate Disodium-Labelled Red Blood Cell Scintigraphy in the Localization of Small Intestine Bleeding: A Single-Centre Twelve-Year Study
Authors: Dolezal Jiri , Vizda Jaroslav , Kopacova Marcela
Published: July 2011

Aim: To present our experience with the detection of bleeding in the small intestine by means of scintigraphy with in vivo-labelled red blood cells (RBCs) in the period of 1998–2009. Materials and Methods: A 12-year prospective study was accomplished with 40 patients (23 men, 17 women, aged 12–91, mean 56 years) who had lower gastrointestinal bleeding (obscure-overt bleeding) and underwent scintigraphy with in vivo-labelled RBCs by means of technetium 99m. The scintigraphy was usually performed after other diagnostic tests had failed to locate the bleeding. Results: A total of 26 patients had a positive scintigraphy with in vivo-labelled RBCs and 14 patients had negative scintigraphy. The final diagnosis was confirmed in 20 of 26 patients with a positive scintigraphy by push enteroscopy (6/20), intraoperative enteroscopy (7/20), surgery (4/20), duodenoscopy (1/20), double-balloon enteroscopy (1/20) and X-ray angiography (1/20). The correct location of the bleeding site was identified by RBC scintigraphy in 15 of 20 (75%) patients with the confirmed source. The locations of the bleeding site identified by scintigraphy and enteroscopy (push, intraoperative) and surgical investigations were highly correlated in patients with a positive scintigraphy within the first 3 h. Eleven of the 20 correctly localized studies and none of the incorrectly localized studies were positive in the dynamic phase of imaging. In 5 patients (all erroneously localized), scintigraphy was positive only at a period longer than 18 h. Conclusion: RBC scintigraphy is an effective imaging modality in localizing lower gastrointestinal bleeding in patients for whom other diagnostic tests have failed to locate the bleeding. RBC scintigraphy can be successful in the detection of bleeding sites in the small intestine.
Change in Myasthenia Gravis Epidemiology in Trento, Italy, after Twenty Years
Authors: Pallaver Fabrizio , Riviera Anna Pia , Piffer Silvano , Ricciardi Roberta , Roni Riccardo , Orrico Daniele , Bonifati Domenico Marco
Published: July 2011

Background: The recent literature suggests that the incidence and prevalence of myasthenia gravis (MG) are changing. We performed a population-based study of MG in the province of Trentino (524,826 inhabitants) and compared the results with those collected 20 years ago. Methods: Multiple sources of information (discharge diagnosis, antibody tests and anticholinesterase drugs) were analyzed. Incidence was calculated from 2005 to 2009. Prevalence was calculated on December 31, 2009. Comparison was made with descriptive statistics for 1981–1990 for the identical region. Results: Incidence and prevalence greatly increased in comparison with 1981–1990 data. The prevalence rate increased from 82.9 (95% confidence interval, CI, 58.4–114.3) in 1990 to 129.6 (95% CI 100.6–164.3) per million population, whereas the average annual incidence increased from 7.4 (95% CI 5–10.4) per million person-years in 1981–1990 to 14.8 (95% CI 10.5–20.3) in 2005–2009. This increase was mainly due to male patients with late-onset MG. Conclusions: The study confirms the increase in incidence and prevalence of late-onset MG in the same region 20 years apart. So we should consider MG also as a disease of the elderly.
Dapsone Therapy for Hidradenitis Suppurativa: A Series of 24 Patients
Authors: Yazdanyar Shiva , Boer Jurr , Ingvarsson Gisli , Szepietowski Jacek C. , Jemec Gregor B.E.
Published: July 2011

Background: Hidradenitis suppurativa (HS) is an inflammatory skin disease with a chronic intermittent course. HS is difficult to treat, and the evidence for the effect of most treatments consists of smaller open studies. The use of dapsone in the treatment of HS is based on a few published cases successfully treated. Objective: To evaluate the potential of dapsone treatment for HS in an open case series. Methods: An exploratory and retrospective review of case notes from HS patients treated with dapsone was performed. Patients were included irrespective of treatment outcome. Prior to the treatment the level of glucose-6-phosphate dehydrogenase in the blood was tested for all patients. Results: A total of 24 HS patients were included and treated with dapsone. Improvement was seen in 9 out of 24 (38%) treated patients, whereas 15 out of 24 (62%) did not experience any improvement. None of the 4 cases with severe disease experienced improvement. Side effects leading to discontinuation of the treatment occurred in 2 of 24 patients (8%). Recurrence of disease at the cessation of treatment was described as rapid. Limitations: The study is limited by lacking a control group. Conclusion: Therapy with dapsone for patients with HS is possible, particularly in milder cases. The effect may be due to either antibacterial or anti-inflammatory effects of the drug, or both. Rapid recurrence after stopping treatment however suggests that anti-inflammatory effects may predominate. The effect appears to be smaller than that reported with combination therapy using clindamycin and rifampicin. To clarify the true effect of dapsone future randomized controlled trials are necessary.