bluuebunny/crossref_metadata_2025 huggingface dataset:
Alendronate impairs epithelial adhesion, differentiation and proliferation in human oral mucosa
Authors: Donetti E , Gualerzi A , Sardella A , Lodi G , Carrassi A , Sforza C
Published: June 2013

Objective

This study aimed at evaluating from a morphological point of view the effects of alendronate (ALN), a widely used nitrogen‐containing bisphosphonate for the chronic treatment of osteoporosis, on the oral epithelium of healthy keratinized human oral mucosa. Bisphosphonate‐related osteonecrosis of the jaw is a well‐known severe consequence, but the effects during chronic therapy on the oral soft tissues are still matter of debate.

Materials and Methods

Six women over 60 year‐old undergoing treatment of osteoporosis with 70 mg per week of oral ALN (lasting at least 2 years) were recruited and compared with a gender and age‐matched group (n = 6). Proliferation, apoptosis, intercellular adhesion and terminal differentiation (TD) were investigated by immunofluorescence. In parallel, ultrastructural analysis was carried out.

Results

By immunofluorescence, a statistically significant decrease in keratinocyte proliferation was detected in the oral epithelium of the ALN group without any sign of apoptosis, but accompanied by a reduction in desmoglein 1 and keratin 10 expressions. In the uppermost layers of the oral epithelium of the ALN group, thin desmosomes were visible by transmission electron microscopy.

Conclusion

Our results show that epithelial adhesion, TD and proliferation are affected by ALN therapeutic doses in clinically healthy human oral mucosa.
Variability and consistency in lung inflammatory responses to particles with a geogenic origin
Authors: Zosky Graeme R. , Boylen Catherine E. , Wong Russell S. , Smirk Michael N. , Gutiérrez Lucia , Woodward Robert C. , Siah W. Shan , Devine Brian , Maley Fiona , Cook Angus
Published: June 2013

Background and objective

Particulate matter <10 μm (PM10) is well recognized as being an important driver of respiratory health; however, the impact of PM10 of geogenic origin on inflammatory responses in the lung is poorly understood. This study aimed to assess the lung inflammatory response to community sampled geogenic PM10.

Methods

This was achieved by collecting earth material from two regional communities in Western Australia (Kalgoorlie‐Boulder and Newman), extracting the PM10 fraction and exposing mice by intranasal instillation to these particles. The physicochemical characteristics of the particles were assessed and lung inflammatory responses were compared to control particles. The primary outcomes were cellular influx and cytokine production in the lungs of the exposed mice.

Results

The physical and chemical characteristics of the PM10 from Kalgoorlie and Newman differed with the latter having a higher concentration of Fe and a larger median diameter. Control particles (2.5 μm polystyrene) caused a significant influx of inflammatory cells (neutrophils) with little production of proinflammatory cytokines. In contrast, the geogenic particles induced the production of MIP‐2, IL‐6 and a significant influx of neutrophils. Qualitatively, the response following exposure to particles from Kalgoorlie and Newman were consistent; however, the magnitude of the response was substantially higher in the mice exposed to particles from Newman.

Conclusions

The unique physicochemical characteristics of geogenic particles induced a proinflammatory response in the lung. These data suggest that particle composition should be considered when setting community standards for PM exposure, particularly in areas exposed to high geogenic particulate loads.
Comparative study of hair follicle morphology in eight mammalian species and humans
Authors: Mangelsdorf Susanne , Vergou Theognosia , Sterry Wolfram , Lademann Juergen , Patzelt Alexa
Published: June 2013

Background

The objective of the present study was the investigation of hair follicle morphology in eight mammalian species in order to evaluate the species‐specific contribution of hair follicles to skin penetration particularly with regard to the utilization of the different animal species as skin models for human skin.

Methods

Cyanoacrylate skin surface biopsy method (CSSB), light microscopy and also digital photography were used for the measurements of hair follicle morphology.

Results

The results revealed species‐specific differences regarding the pattern of hair follicle distribution and also differences with regard to hair follicle parameters and characteristics. The results also showed that hair follicles generally possess enormous reservoir capacities, regarding the follicular volume. In all examined species, hair follicles reached at least one‐fifth of stratum corneum storage capacity. The results were compared with human data obtained in a previous study.

Conclusion

With regard to hair follicle morphology and skin structure, the porcine skin seems to be the most appropriate skin model for human skin analog to previous investigations, whereas the skin of dog, cat, and rabbit showed the most significant differences.
Regulation of miRNAs in human skeletal muscle following acute endurance exercise and short‐term endurance training
Authors: Russell Aaron P. , Lamon Severine , Boon Hanneke , Wada Shogo , Güller Isabelle , Brown Erin L. , Chibalin Alexander V. , Zierath Juleen R. , Snow Rod J. , Stepto Nigel , Wadley Glenn D. , Akimoto Takayuki
Published: June 2013

Key points

The discovery of microRNAs (miRNAs) has established new mechanisms that control health, but little is known about the regulation of skeletal muscle miRNAs in response to exercise.

This study investigated components of the miRNA biogenesis pathway (Drosha, Dicer and Exportin‐5), muscle enriched miRNAs, (miR‐1, ‐133a, ‐133b and 206), and several miRNAs dysregulated in muscle myopathies, and showed that 3 h following an acute exercise bout, Drosha, Dicer and Exportin‐5, as well as miR‐1, ‐133a, ‐133‐b and miR‐181a were all increased, while miR‐9, ‐23a, ‐23b and ‐31 were decreased.

Short‐term training increased miR‐1 and miR‐29b, while miR‐31 remained decreased.

Negative correlations were observed between miR‐9 and HDAC4 protein, miR‐31 and HDAC4 protein and between miR‐31 and NRF1 protein, 3 h after exercise.

miR‐31 binding to the HDAC4 and NRF1 3′ untranslated region (UTR) reduced luciferase reporter activity.

Exercise rapidly and transiently regulates several miRNA species potentially involved in the regulation of skeletal muscle regeneration, gene transcription and mitochondrial biogenesis.

Abstract  The identification of microRNAs (miRNAs) has established new mechanisms that control skeletal muscle adaptation to exercise. The present study investigated the mRNA regulation of components of the miRNA biogenesis pathway (Drosha, Dicer and Exportin‐5), muscle enriched miRNAs, (miR‐1, ‐133a, ‐133b and ‐206), and several miRNAs dysregulated in muscle myopathies (miR‐9, ‐23, ‐29, ‐31 and ‐181). Measurements were made in muscle biopsies from nine healthy untrained males at rest, 3 h following an acute bout of moderate‐intensity endurance cycling and following 10 days of endurance training. Bioinformatics analysis was used to predict potential miRNA targets. In the 3 h period following the acute exercise bout, Drosha, Dicer and Exportin‐5, as well as miR‐1, ‐133a, ‐133‐b and ‐181a were all increased. In contrast miR‐9, ‐23a, ‐23b and ‐31 were decreased. Short‐term training increased miR‐1 and ‐29b, while miR‐31 remained decreased. Negative correlations were observed between miR‐9 and HDAC4 protein (r=−0.71; P= 0.04), miR‐31 and HDAC4 protein (r =−0.87; P= 0.026) and miR‐31 and NRF1 protein (r =−0.77; P= 0.01) 3 h following exercise. miR‐31 binding to the HDAC4 and NRF1 3′ untranslated region (UTR) reduced luciferase reporter activity. Exercise rapidly and transiently regulates several miRNA species in muscle. Several of these miRNAs may be involved in the regulation of skeletal muscle regeneration, gene transcription and mitochondrial biogenesis. Identifying endurance exercise‐mediated stress signals regulating skeletal muscle miRNAs, as well as validating their targets and regulatory pathways post exercise, will advance our understanding of their potential role/s in human health.
Transient Temperature Measurements in the Contact Zone Between Brush Seals of Kevlar and Metallic Type for Bearing Chamber Sealing Using a Pyrometric Technique
Authors: Flouros Michael , Stadlbauer Martin , Cottier Francois , Proestler Stephan , Beichl Stefan
Published: June 2013

For the past 25 years brush seal technologies have evolved into the aero engine designs and, more generally, into the gas turbine world, not only for sealing gas areas at different pressure levels but also for sealing gas/liquid environments. This is the case in an aero engine where the bearing chambers are sealed. Aero engine bearing chambers enclose oil lubricated components such bearings and gears. In order to avoid contamination of the turbo machinery through oil loss, air blown seals are used to retain the oil into the bearing chamber. Oil loss may cause coking or ignition with the probability of an uncontained destruction of rotating parts such as disks or blades. It may also cause contamination of the air conditioning system with oil fumes thus causing health problems to the passengers and crew from such exposure. The most widely known seals for bearing chamber sealing are the labyrinth seals, however, in recent years brush seals and carbon seals have also been used. The latter are contact seals; that is, they may be installed having zero clearance to the rotating part and lift during operation when their air side is pressurized. During this survey an actual aero engine bearing chamber was modified to run with brush seals in a simulating rig. Two types of brush seals were used: (a) with bristles made of Kevlar, and (b) bristles made of a metallic material. Both types were installed with an overlap to the rotor. The targets set were twofold: (a) to measure the transient temperatures in the rotor and particularly in the contact zone between the bristles and the rotor, and (b) to measure the air leakage through the seals at different operating conditions. In order to obtain the transient temperature measurements with high fidelity, a new pyrometric technique was developed and was applied for the first time in brush seals. This technique has enabled placement of the pyrometer into the bristle's pack of the seal adjacent to the rotating surface and it could record the frictional temperature evolution in the bristles/rotor contact zone during acceleration or deceleration of the rotor. Additionally, the air consumption of the seals was measured and was compared to the air consumption through the labyrinth seals. For the metallic brush seal, up to 80% of the required sealing air can be saved, which can result, in turn, into a reduction in fuel burned by up to 1%. Furthermore, a design simplification of the bearing chamber architecture can be achieved by taking into account the reduced air flow. Even though the rotor was accelerated to high speeds up to 19,500 rpm, the produced temperature overshoots in the seal/rotor contact zone have caused no deterioration in either the materials or the oil.
Dosimetric accuracy of proton therapy for chordoma patients with titanium implants
Authors: Verburg Joost M. , Seco Joao
Published: June 2013

Purpose:

To investigate dosimetric errors in proton therapy treatment planning due to titanium implants, and to determine how these affect postoperative passively scattered proton therapy for chordoma patients with orthopedic hardware.

Methods:

The presence of titanium hardware near the tumor may affect the dosimetric accuracy of proton therapy. Artifacts in the computed tomography (CT) scan can cause errors in the proton stopping powers used for dose calculation, which are derived from CT numbers. Also, clinical dose calculation algorithms may not accurately simulate proton beam transport through the implants, which have very different properties as compared to human tissue. The authors first evaluated the impact of these two main issues. Dose errors introduced by metal artifacts were studied using phantoms with and without titanium inserts, and patient scans on which a metal artifact reduction method was applied. Pencil‐beam dose calculations were compared to models of nuclear interactions in titanium and Monte Carlo simulations. Then, to assess the overall impact on treatment plans for chordoma, the authors compared the original clinical treatment plans to recalculated dose distributions employing both metal artifact reduction and Monte Carlo methods.

Results:

Dose recalculations of clinical proton fields showed that metal artifacts cause range errors up to 6 mm distal to regions affected by CT artifacts. Monte Carlo simulations revealed dose differences >10% in the high‐dose area, and range differences up to 10 mm. Since these errors are mostly local in nature, the large number of fields limits the impact on target coverage in the chordoma treatment plans to a small decrease of dose homogeneity.

Conclusions:

In the presence of titanium implants, CT metal artifacts and the approximations of pencil‐beam dose calculations cause considerable errors in proton dose calculation. The spatial distribution of the errors however limits the overall impact on passively scattered proton therapy for chordoma.
Rapgef2 Connects GPCR-Mediated cAMP Signals to ERK Activation in Neuronal and Endocrine Cells
Authors: Emery Andrew C. , Eiden Maribeth V. , Mustafa Tomris , Eiden Lee E.
Published: June 2013

The guanine nucleotide exchange factor Rapgef2 links cAMP and ERK signaling to mediate neuritogenesis.
Radiologic Responses in Cynomolgus Macaques for Assessing Tuberculosis Chemotherapy Regimens
Authors: Lin Philana Ling , Coleman Teresa , Carney Jonathan P. J. , Lopresti Brian J. , Tomko Jaime , Fillmore Dan , Dartois Veronique , Scanga Charles , Frye L. James , Janssen Christopher , Klein Edwin , Barry Clifton E. , Flynn JoAnne L.
Published: June 2013

Trials to test new drugs currently in development against tuberculosis in humans are impractical. All animal models to prioritize new regimens are imperfect, but nonhuman primates (NHPs) infected with
Mycobacterium tuberculosis
develop active tuberculosis (TB) disease with a full spectrum of lesion types seen in humans. Serial 2-deoxy-2-[
18
F]-fluoro-
d
-glucose (FDG) positron emission tomography (PET) with computed tomography (CT) imaging was performed on cynomolgus macaques during infection and chemotherapy with individual agents or the four-drug combination therapy most widely used globally. The size and metabolic activity of lung granulomas varied among animals and even within a single animal during development of disease. Individual granulomas within untreated animals had highly local and independent outcomes, some progressing in size and FDG uptake, while others waned, illustrating the highly dynamic nature of active TB. At necropsy, even untreated animals were found to have a proportion of sterile lesions consistent with the dynamics of this infection. A more marked reduction in overall metabolic activity in the lungs (decreased FDG uptake) was associated with effective treatment. A reduction in the size of individual lesions correlated with a lower bacterial burden at necropsy. Isoniazid treatment was associated with a transient increase in metabolic activity in individual lesions, whereas a net reduction occurred in most lesions from rifampin-treated animals. Quadruple-drug therapy resulted in the highest decrease in FDG uptake. The findings of PET-CT imaging may provide an important early correlate of the efficacy of novel combinations of new drugs that can be directly translated to human clinical trials.
Determination of
In Vitro
Activities of Solithromycin at Different pHs and Its Intracellular Activity against Clinical Isolates of Neisseria gonorrhoeae from a Laboratory Collection
Authors: Mallegol Julia , Fernandes Prabhavathi , Seah Christine , Guyard Cyril , Melano Roberto G.
Published: June 2013

We evaluated the activity of solithromycin against 196 clinical gonococcal isolates collected at the Public Health Ontario Laboratories, Toronto, Canada, including isolates with different levels of azithromycin resistance, as well as the role of pH in MIC determinations using pH-adjusted agar plates (pH range, 5.6 to 7.6).
In vitro
invasion assays were performed using monolayers of HeLa epithelial cells and clinical gonococci displaying different azithromycin MICs; infected cultures were treated with solithromycin, and its intracellular activity was determined by CFU assays after 3 and 20 h of exposure. Solithromycin displayed a MIC
50
and MIC
90
of 0.0625 and 0.125 μg/ml, respectively, making its activity at least 4-fold higher than that of azithromycin. Clinical isolates with elevated MICs for azithromycin (MICs of ≥2,048 μg/ml and 4 to 8 μg/ml) showed solithromycin MIC values of 8 and 0.5 μg/ml, respectively. In contrast to azithromycin, solithromycin MICs were not significantly affected by acidic pHs, suggesting more stability at lower pH. Moreover, when intracellular
Neisseria gonorrhoeae
isolates were incubated with solithromycin at 4 times, 1 times, and one-fourth of the MIC, the exposure to solithromycin resulted in the progressive loss of viability of most isolates over time. The intracellular activity of solithromycin, combined with the low MICs to this agent, indicates that it may be an attractive option for gonorrhea treatment if clinical trials in development reveal that this drug can be used safely in adult indications, especially when multidrug-resistant clinical isolates are now emerging.
Prototypical Recombinant Multi-Protease-Inhibitor-Resistant Infectious Molecular Clones of Human Immunodeficiency Virus Type 1
Authors: Varghese Vici , Mitsuya Yumi , Fessel W. Jeffrey , Liu Tommy F. , Melikian George L. , Katzenstein David A. , Schiffer Celia A. , Holmes Susan P. , Shafer Robert W.
Published: June 2013

The many genetic manifestations of HIV-1 protease inhibitor (PI) resistance present challenges to research into the mechanisms of PI resistance and the assessment of new PIs. To address these challenges, we created a panel of recombinant multi-PI-resistant infectious molecular clones designed to represent the spectrum of clinically relevant multi-PI-resistant viruses. To assess the representativeness of this panel, we examined the sequences of the panel's viruses in the context of a correlation network of PI resistance amino acid substitutions in sequences from more than 10,000 patients. The panel of recombinant infectious molecular clones comprised 29 of 41 study-defined PI resistance amino acid substitutions and 23 of the 27 tightest amino acid substitution clusters. Based on their phenotypic properties, the clones were classified into four groups with increasing cross-resistance to the PIs most commonly used for salvage therapy: lopinavir (LPV), tipranavir (TPV), and darunavir (DRV). The panel of recombinant infectious molecular clones has been made available without restriction through the NIH AIDS Research and Reference Reagent Program. The public availability of the panel makes it possible to compare the inhibitory activities of different PIs with one another. The diversity of the panel and the high-level PI resistance of its clones suggest that investigational PIs active against the clones in this panel will retain antiviral activity against most if not all clinically relevant PI-resistant viruses.
Polymyxin B Induces Apoptosis in Kidney Proximal Tubular Cells
Authors: Azad Mohammad A. K. , Finnin Ben A. , Poudyal Anima , Davis Kathryn , Li Jinhua , Hill Prue A. , Nation Roger L. , Velkov Tony , Li Jian
Published: June 2013

The nephrotoxicity of polymyxins is a major dose-limiting factor for treatment of infections caused by multidrug-resistant Gram-negative pathogens. The mechanism(s) of polymyxin-induced nephrotoxicity is not clear. This study aimed to investigate polymyxin B-induced apoptosis in kidney proximal tubular cells. Polymyxin B-induced apoptosis in NRK-52E cells was examined by caspase activation, DNA breakage, and translocation of membrane phosphatidylserine using Red-VAD-FMK [Val-Ala-Asp(O-Me) fluoromethyl ketone] staining, a terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, and double staining with annexin V-propidium iodide (PI). The concentration dependence (50% effective concentration [EC
50
]) and time course for polymyxin B-induced apoptosis were measured in NRK-52E and HK-2 cells by fluorescence-activated cell sorting (FACS) with annexin V and PI. Polymyxin B-induced apoptosis in NRK-52E cells was confirmed by positive labeling from Red-VAD-FMK staining, TUNEL assay, and annexin V-PI double staining. The EC
50
(95% confidence interval [CI]) of polymyxin B for the NRK-52E cells was 1.05 (0.91 to 1.22) mM and was 0.35 (0.29 to 0.42) mM for HK-2 cells. At lower concentrations of polymyxin B, minimal apoptosis was observed, followed by a sharp rise in the apoptotic index at higher concentrations in both cell lines. After treatment of NRK-52E cells with 2.0 mM polymyxin B, the percentage of apoptotic cells (mean ± standard deviation [SD]) was 10.9% ± 4.69% at 6 h and reached plateau (>80%) at 24 h, whereas treatment with 0.5 mM polymyxin B for 24 h led to 93.6% ± 5.57% of HK-2 cells in apoptosis. Understanding the mechanism of polymyxin B-induced apoptosis will provide important information for discovering less nephrotoxic polymyxin-like lipopeptides.
The Trypanosoma brucei gambiense Secretome Impairs Lipopolysaccharide-Induced Maturation, Cytokine Production, and Allostimulatory Capacity of Dendritic Cells
Authors: Garzón Edwin , Holzmuller Philippe , Bras-Gonçalves Rachel , Vincendeau Philippe , Cuny Gérard , Lemesre Jean Loup , Geiger Anne
Published: June 2013

Trypanosoma brucei gambiense, a parasitic protozoan belonging to kinetoplastids, is the main etiological agent of human African trypanosomiasis (HAT), or sleeping sickness. One major characteristic of this disease is the dysregulation of the host immune system. The present study demonstrates that the secretome (excreted-secreted proteins) ofT. b. gambienseimpairs the lipopolysaccharide (LPS)-induced maturation of murine dendritic cells (DCs). The upregulation of major histocompatibility complex class II, CD40, CD80, and CD86 molecules, as well as the secretion of cytokines such as tumor necrosis factor alpha, interleukin-10 (IL-10), and IL-6, which are normally released at high levels by LPS-stimulated DCs, is significantly reduced when these cells are cultured in the presence of theT. b. gambiensesecretome. Moreover, the inhibition of DC maturation results in the loss of their allostimulatory capacity, leading to a dramatic decrease in Th1/Th2 cytokine production by cocultured lymphocytes. These results provide new insights into a novel efficient immunosuppressive mechanism directly involving the alteration of DC function which might be used byT. b. gambienseto interfere with the host immune responses in HAT and promote the infectious process.
Poison Domains Block Transit of Translocated Substrates via the Legionella pneumophila Icm/Dot System
Authors: Amyot Whitney M. , deJesus Dennise , Isberg Ralph R.
Published: June 2013

Legionella pneumophila
uses the Icm/Dot type 4B secretion system (T4BSS) to deliver translocated protein substrates to the host cell, promoting replication vacuole formation. The conformational state of the translocated substrates within the bacterial cell is unknown, so we sought to determine if folded substrates could be translocated via this system. Fusions of
L. pneumophila
Icm/Dot-translocated substrates (IDTS) to dihydrofolate reductase (DHFR) or ubiquitin (Ub), small proteins known to fold rapidly, resulted in proteins with low translocation efficiencies. The folded moieties did not cause increased aggregation of the IDTS and did not impede interaction with the adaptor protein complex IcmS/IcmW, which is thought to form a soluble complex that promotes translocation. The translocation defect was alleviated with a Ub moiety harboring mutations known to destabilize its structure, indicating that unfolded proteins are preferred substrates. Real-time analysis of translocation, following movement during the first 30 min after bacterial contact with host cells, revealed that the folded moiety caused a kinetic defect in IDTS translocation. Expression of an IDTS fused to a folded moiety interfered with the translocation of other IDTS, consistent with it causing a blockage of the translocation channel. Furthermore, the folded protein fusions also interfered with intracellular growth, consistent with inefficient or impaired translocation of proteins critical for
L. pneumophila
intracellular growth. These studies indicate that substrates of the Icm/Dot T4SS are translocated to the host cytosol in an unfolded conformation and that folded proteins are stalled within the translocation channel, impairing the function of the secretion system.
Human and Mouse Macrophages Collaborate with Neutrophils To Kill Larval Strongyloides stercoralis
Authors: Bonne-Année Sandra , Kerepesi Laura A. , Hess Jessica A. , O'Connell Amy E. , Lok James B. , Nolan Thomas J. , Abraham David
Published: June 2013

Macrophages are multifunctional cells that are active in TH1- and TH2-mediated responses. In this study, we demonstrate that human and mouse macrophages collaborate with neutrophils and complement to kill the parasiteStrongyloides stercoralis in vitro. Infection of mice with worms resulted in the induction of alternatively activated macrophages (AAMϕ) within the peritoneal cavity. These cells killed the wormsin vivoand collaborated with neutrophils and complement during thein vitrokilling process. AAMϕ generatedin vitrokilled larvae more rapidly than naive macrophages, which killed larvae after a longer time period. In contrast, classically activated macrophages were unable to kill larvae eitherin vitroorin vivo. This study adds macrophages to the armamentarium of immune components that function in elimination of parasitic helminths and demonstrate a novel function by which AAMϕ control large extracellular parasites.
LacR Mutations Are Frequently Observed in Streptococcus intermedius and Are Responsible for Increased Intermedilysin Production and Virulence
Authors: Tomoyasu Toshifumi , Imaki Hidenori , Masuda Sachiko , Okamoto Ayumi , Kim Hyejin , Waite Richard D. , Whiley Robert A. , Kikuchi Ken , Hiramatsu Keiichi , Tabata Atsushi , Nagamune Hideaki
Published: June 2013

Streptococcus intermedius
secretes a human-specific cytolysin, intermedilysin (ILY), which is considered to be the major virulence factor of this pathogen. We screened for a repressor of
ily
expression by using random gene disruption in a low-ILY-producing strain (PC574). Three independent high-ILY-producing colonies that had plasmid insertions within a gene that has high homology to
lacR
were isolated. Validation of these observations was achieved through disruption of
lacR
in strain PC574 with an erythromycin cassette, which also led to higher hemolytic activity, increased transcription of
ily
, and higher cytotoxicity against HepG2 cells, compared to the parental strain. The direct binding of LacR within the
ily
promoter region was shown by a biotinylated DNA probe pulldown assay, and the amount of ILY secreted into the culture supernatant by PC574 cells was increased by adding lactose or galactose to the medium as a carbon source. Furthermore, we examined
lacR
nucleotide sequences and the hemolytic activity of 50 strains isolated from clinical infections and 7 strains isolated from dental plaque. Of the 50 strains isolated from infections, 13 showed high ILY production, 11 of these 13 strains had one or more point mutations and/or an insertion mutation in LacR, and almost all mutations were associated with a marked decline in LacR function. These results strongly suggest that mutation in
lacR
is required for the overproduction of ILY, which is associated with an increase in pathogenicity of
S. intermedius
.
THE CURRENT–VOLTAGE CHARACTERISTICS OF THE Au/MBEn-GaAs SCHOTTKY DIODES IN A WIDE TEMPERATURE RANGE
Authors: EFEOǦLU HASAN , TURUT ABDULMECIT
Published: June 2013

The Au/MBE n- GaAs Schottky diodes have been fabricated by us. The slope of the conventional ln (I0/T2) versus (kT)-1 plotted in the temperature range of 120–350 K has given a Richardson constant (RC) of 7.69 A (cmK)-2 which is in close agreement with the value of 8.16 A/cm2 K 2 known for n-type GaAs . The barrier height (BH) value in 40–160 K range has decreased obeying to Gaussian distribution (GD) model of the BH based on thermionic emission current theory. The modified RC plot according to the GD model has given a RC value of 2.45 A (cmK)-2 or a value of 2.38 A (cmK)-2 by taking into account the temperature dependence of the standard deviation. Therefore, we have modified the Richardson's plot using the temperature dependent values of the effective area of the patches introduced by lateral inhomogeneity of the BHs and we have obtained a RC value of 8.10 A (cmK)-2.
3D STRUCTURE FROM MOTION WITH FOURIER DESCRIPTOR TRANSFORMATION
Authors: ELHADY GAMAL F.
Published: June 2013

The simultaneous recovery of three-dimensional (3D) structure from motion (SfM) for the sequences of images, is one of the more difficult problems in computer vision. Classical approaches to the problem rely on using algebraic techniques to solve for these unknowns given two or more image. Motion analysis and 3D shape estimation based on the estimated motion is an important problem in computer vision. The correspondence problem is an important tool in SfM where in this paper a general 3D motion based on a simple rotation, tilt, roll and translation is proposed, and then is used for 3D shape estimation. The current work expands the 2D motion estimation (shift, rotation) to accommodate general 3D motion (shift, rotation, tilt and roll). The proposed work in this paper of motion estimation of moving object is based on Fourier Descriptor Transformation (FDT) analysis before and after motion. The FDT is also used to resolve the correspondence problem in a sequence of images. We test our method on several large-scale photo collections, show the efficacy of the introduced approach to improve reconstruction accuracy.
MARGINALLY TRAPPED MERIDIAN SURFACES OF PARABOLIC TYPE IN THE FOUR-DIMENSIONAL MINKOWSKI SPACE
Authors: GANCHEV GEORGI , MILOUSHEVA VELICHKA
Published: June 2013

A marginally trapped surface in the four-dimensional Minkowski space is a spacelike surface whose mean curvature vector is lightlike at each point. We introduce meridian surfaces of parabolic type as one-parameter systems of meridians of a rotational hypersurface with lightlike axis in Minkowski 4-space and find their basic invariants. We find all marginally trapped meridian surfaces of parabolic type and give a geometric construction of these surfaces.
LOWER BOUND OF THE LIFESPAN OF SOLUTIONS TO SEMILINEAR WAVE EQUATIONS IN AN EXTERIOR DOMAIN
Authors: KATAYAMA SOICHIRO , KUBO HIDEO
Published: June 2013

We consider the Cauchy–Dirichlet problem for semilinear wave equations in a three space-dimensional domain exterior to a bounded and non-trapping obstacle. We obtain a detailed estimate for the lower bound of the lifespan of classical solutions when the size of initial data tends to zero, in a similar spirit to that of the works of John and Hörmander where the Cauchy problem was treated. We show that our estimate is sharp at least for radially symmetric case.
LAGRANGIAN FLOWS FOR VECTOR FIELDS WITH GRADIENT GIVEN BY A SINGULAR INTEGRAL
Authors: BOUCHUT FRANÇOIS , CRIPPA GIANLUCA
Published: June 2013

We prove quantitative estimates on flows of ordinary differential equations with vector field with gradient given by a singular integral of an L1 function. Such estimates allow to prove existence, uniqueness, quantitative stability and compactness for the flow, going beyond the BV theory. We illustrate the related well-posedness theory of Lagrangian solutions to the continuity and transport equations.
RIEMANN SOLUTIONS FOR VERTICAL FLOW OF THREE PHASES IN POROUS MEDIA: SIMPLE CASES
Authors: RODRÍGUEZ-BERMÚDEZ PANTERS , MARCHESIN DAN
Published: June 2013

We study Riemann solutions for a system of two nonlinear conservation laws that models buoyancy-driven flow of three immiscible fluids in a porous medium, which do not exchange mass. We also assume that the fluids are incompressible and the flow occurs in the vertical spatial dimension. We consider the simplified case in which two of the three fluids have equal densities, obtaining the Riemann solutions by the wave curve method. As expected, the solutions contain waves traveling both upwards and downwards. The sequences of waves contain rarefactions, shocks (sometimes traveling with characteristic speed), and constant states. The shocks found in this work are proper or generalized Lax shock waves. The solutions we found are L1-continuous with respect to the initial data. Waves involving only two fluids often take part in three-phase flow Riemann solutions; this is the basis of a useful tool (the wedge construction) to obtain shocks separating states in distinct two-phase regimes having a common fluid. This tool is similar to fractional flow theory, or Oleinik's convex construction. In this investigation, the wave curve method from the theory of conservation laws is combined with numerical calculations.
Oxazolochlorins 11: Tuning the dynamic high pH sensing range of [meso-tetraarylporpholactonato]M(II) complexes by variation of the central metal ion, the aryl substituents, and introduction of a β-nitro group
Authors: Worlinsky Jill L. , Zarate Gloria , Zeller Matthias , Ghandehari Masoud , Khalil Gamal , Brückner Christian
Published: June 2013

Based on the high pH-sensing ability of [meso-tetrakis(pentafluorophenyl) porpholactonato]-platinum(II), we investigated the influence of the metal ( M = Zn ( II ), Ni ( II ), Cu ( II ), Pd ( II ), Ag ( II ), Pt ( II )), the aryl group ( Ar = C 6 H 5, C 6 F 5), and the presence of a β- NO 2 group on the pH sensing range. The syntheses of the novel β-nitroporpholactone derivatives are described, and their regiochemistry deduced by spectroscopic and single crystal X-ray diffraction methods. The UV-vis base titration midpoints for all derivatives were determined in an aqueous solution containing a surfactant, showing that the metal has the least influence, thus identifying a cheaper and easier method to prepare porpholactone M complex-based high pH-sensors. The influence of the pentafluorophenyl groups and the β-nitration were comparable with respect to their ability to increase the nucleophilicity of the porpholactone toward hydroxide, but the optical response for the pentafluorophenyl-substituted derivative were stronger. β-Nitration and pentafluorophenyl-substitution had additive effects.
b-VALUE ANOMALIES ALONG THE NORTHERN SEGMENT OF THE SUMATRA–ANDAMAN SUBDUCTION ZONE: IMPLICATIONS FOR UPCOMING EARTHQUAKES
Authors: PAILOPLEE SANTI , SURAKIATCHAI PEERASIT , CHARUSIRI PUNYA
Published: June 2013

The potential areas of upcoming earthquakes were investigated along the Northern segment of the Sumatra–Andaman Subduction Zone according to the b-value of the frequency-magnitude distribution. After enhancing the completeness of the earthquake catalogue, two datasets, those recorded during (i) 1980–1994 and (ii) 1980–2003, were tested in order to verify the effective correlation between precursory b-values and the location of subsequent earthquakes. The results confirmed that areas with low b-values agreed well with the locations of the subsequent earthquakes in that region. Accordingly, the present-day dataset from 1980–2010 was carefully evaluated to determine the b-values across the region. Within this spatial investigation, three areas of low b-values and so potential hazards were found. These consisted of the (i) West coast of Myanmar, and (ii) North and (iii) South of the Nicobar Islands. From 2010–2012, a major earthquake with magnitude 7.5 mbwas recorded as being generated in the region South of the Nicobar Islands. Thus, attention should be paid to the remaining two until now quiescent areas, and mitigation plans should be raised for both seismic and tsunami hazards.
ANALYTIC-APPROXIMATE SOLUTION FOR A CLASS OF NONLINEAR OPTIMAL CONTROL PROBLEMS BY HOMOTOPY ANALYSIS METHOD
Authors: Effati Sohrab , Saberi Nik Hassan , Shirazian Mohammad
Published: June 2013

In this paper, we apply the homotopy analysis method (HAM) for nonlinear quadratic optimal control problems (OCP's). This method is employed to solve extreme conditions obtained from the Pontryagin's maximum principle (PMP). Applying the HAM, we in essence transfer a nonlinear two-point boundary value problem (TPBVP), into an infinite number of linear sub-problems, and then use the sum of the solutions of its first several sub-problems to approximate the exact solution. Note that such a kind of transformation does not need the existence of any small or large parameters in governing equation and initial/boundary conditions. The comparison of the HAM results with the Measure theory method, Modal series and collocation method solutions are made. Some illustrative examples are given to demonstrate the simplicity and efficiency of the proposed method.
On the Complexity of Approximating a Nash Equilibrium
Authors: Daskalakis Constantinos
Published: June 2013

We show that computing a relatively (i.e., multiplicatively as opposed to additively) approximate Nash equilibrium in two-player games is PPAD-complete, even for constant values of the approximation. Our result is the first constant inapproximability result for Nash equilibrium, since the original results on the computational complexity of the problem [Daskalakis et al. 2006a; Chen and Deng 2006]. Moreover, it provides an apparent---assuming that PPAD is not contained in TIME(n
O(log n)
)---dichotomy between the complexities of additive and relative approximations, as for constant values of additive approximation a quasi-polynomial-time algorithm is known [Lipton et al. 2003]. Such a dichotomy does not exist for values of the approximation that scale inverse-polynomially with the size of the game, where both relative and additive approximations are PPAD-complete [Chen et al. 2006]. As a byproduct, our proof shows that (unconditionally) the sparse-support lemma [Lipton et al. 2003] cannot be extended to relative notions of constant approximation.
Discriminant malware distance learning on structuralinformation for automated malware classification
Authors: Kong Deguang , Yan Guanhua
Published: June 2013

In this work, we explore techniques that can automatically classify malware variants into their corresponding families. Our framework extracts structural information from malware programs as attributed function call graphs, further learns discriminant malware distance metrics, finally adopts an ensemble of classifiers for automated malware classification. Experimental results show that our method is able to achieve high classification accuracy.
Detecting user dissatisfaction and understanding the underlying reasons
Authors: Arvidsson Ake , Zhang Ying
Published: June 2013

Quantifying quality of experience for network applications is challenging as it is a subjective metric with multiple dimensions such as user expectation, satisfaction, and overall experience. Today, despite various techniques to support differentiated Quality of Service (QoS), the operators still lack of automated methods to translate QoS to QoE, especially for general web applications.

In this work, we take the approach of identifying unsatisfactory performance by searching for user initiated early terminations of web transactions from passive monitoring. However, user early abortions can be caused by other factors such as loss of interests. Therefore, naively using them to represent user dissatisfaction will result in large false positives. In this paper, we propose a systematic method for inferring user dissatisfaction from the set of early abortion behaviors observed from identifying the traffic traces. We conduct a comprehensive analysis on the user acceptance of throughput and response time, and compare them with the traditional MOS metric. Then we present the characteristics of early cancelation from dimensions like the types of URLs and objects. We evaluate our approach on four data sets collected in both wireline network and a wireless cellular network.
Accelerating GPGPU architecture simulation
Authors: Yu Zhibin , Eeckhout Lieven , Goswami Nilanjan , Li Tao , John Lizy , Jin Hai , Xu Chengzhong
Published: June 2013

Recently, graphics processing units (GPUs) have opened up new opportunities for speeding up general-purpose parallel applications due to their massive computational power and up to hundreds of thousands of threads enabled by programming models such as CUDA. However, due to the serial nature of existing micro-architecture simulators, these massively parallel architectures and workloads need to be simulated sequentially. As a result, simulating GPGPU architectures with typical benchmarks and input data sets is extremely time-consuming. This paper addresses the GPGPU architecture simulation challenge by generating miniature, yet representative GPGPU kernels. We first summarize the static characteristics of an existing GPGPU kernel in a profile, and analyze its dynamic behavior using the novel concept of the divergence flow statistics graph (DFSG). We subsequently use a GPGPU kernel synthesizing framework to generate a miniature proxy of the original kernel, which can reduce simulation time significantly. The key idea is to reduce the number of simulated instructions by decreasing per-thread iteration counts of loops. Our experimental results show that our approach can accelerate GPGPU architecture simulation by a factor of 88X on average and up to 589X with an average IPC relative error of 5.6%.
Exploiting the past to reduce delay in CSMA scheduling
Authors: Kwak Jaewook , Lee Chul-Ho , Eun Do Young
Published: June 2013

Recently several CSMA algorithms based on the Glauber dynamics model have been proposed for multihop wireless scheduling, as viable solutions to achieve the throughput optimality, yet are simple to implement. However, their delay performances still remain unsatisfactory, mainly due to the nature of the underlying Markov chains that imposes a fundamental constraint on how the link state can evolve over time. In this paper, we propose a new approach toward better queueing and delay performance, based on our observation that the algorithm needs not be Markovian, as long as it can be implemented in a distributed manner, achieving the same throughput optimality and better delay performance. Our approach hinges upon utilizing past state information observed by local link and then constructing a high-order Markov chain for the evolution of the feasible link schedules. Our proposed algorithm, named delayed CSMA, adds virtually no additional overhead onto the existing CSMA-based algorithms, achieves the throughput optimality under the usual choice of link weight as a function of queue length, and also provides much better delay performance by effectively resolving temporal link starvation problem. From our extensive simulations we observe that the delay under our algorithm can be often reduced by a factor of 20 over a wide range of scenarios, compared to the standard Glauber-dynamics-based CSMA algorithm.
A large-scale service system with packing constraints
Authors: Stolyar Alexander L. , Zhong Yuan
Published: June 2013

We consider a large-scale service system model proposed in [14], which is motivated by the problem of efficient placement of virtual machines to physical host machines in a network cloud, so that the total number of occupied hosts is minimized. Customers of different types arrive to a system with an infinite number of servers. A server packing configuration is the vector k = {k
i
}, where k
i
is the number of type-i customers that the server "contains". Packing constraints are described by a fixed finite set of allowed configurations. Upon arrival, each customer is placed into a server immediately, subject to the packing constraints; the server can be idle or already serving other customers. After service completion, each customer leaves its server and the system. It was shown in [14] that a simple real-time algorithm, called Greedy, is asymptotically optimal in the sense of minimizing ∑
k
X
k
1+α
in the stationary regime, as the customer arrival rates grow to infinity. (Here α > 0, and X
k
denotes the number of servers with configuration k.) In particular, when parameter α is small, and in the asymptotic regime where customer arrival rates grow to infinity, Greedy solves a problem approximating one of minimizing ∑
k
X
k
, the number of occupied hosts. In this paper we introduce the algorithm called Greedy with sublinear Safety Stocks (GSS), and show that it asymptotically solves the exact problem of minimizing ∑
k
X
k
. An important feature of the algorithm is that sublinear safety stocks of X
k
are created automatically - when and where necessary - without having to determine
a priori
where they are required. Moreover, we also provide a tight characterization of the rate of convergence to optimality under GSS. The GSS algorithm is as simple as Greedy, and uses no more system state information than Greedy does.
Online load balancing under graph constraints
Authors: Moharir Sharayu , Sanghavi Sujay , Shakkottai Sanjay
Published: June 2013

In several data center settings, each arriving job may only be served by one of a subset of servers. Such a graph constraint can arise due to several reasons. One is locality of the data needed by a job; for example, in content farms (e.g. in Netflix or YouTube) a video request can only be served by a machine that possesses a copy. Motivated by this, we consider a setting where each job, on arrival, reveals a deadline and a subset of servers that can serve it. The job needs to be immediately allocated to one of these servers, and cannot be moved thereafter. Our objective is to maximize the fraction of jobs that are served before their deadlines. For this online load balancing problem, we prove an upper bound of 1-1/e on the competitive ratio of non-preemptive online algorithms for systems with a large number of servers. We propose an algorithm - INSERT RANKING - which achieves this upper bound. The algorithm makes decisions in a correlated random way and it is inspired by the work of Karp, Vazirani and Vazirani on online matching for bipartite graphs. We also show that two more natural algorithm, based on independent randomness, are strictly suboptimal, with a competitive ratio of 1/2.
Lingering issues in distributed scheduling
Authors: Simatos Florian , Bouman Niek , Borst Sem
Published: June 2013

Recent advances have resulted in queue-based algorithms for medium access control which operate in a distributed fashion, and yet achieve the optimal throughput performance of centralized scheduling algorithms. However, fundamental performance bounds reveal that the "cautious" activation rules involved in establishing throughput optimality tend to produce extremely large delays, typically growing exponentially in 1/(1-r), with r the load of the system, in contrast to the usual linear growth. Motivated by that issue, we explore to what extent more "aggressive" schemes can improve the delay performance. Our main finding is that aggressive activation rules induce a lingering effect, where individual nodes retain possession of a shared resource for excessive lengths of time even while a majority of other nodes idle. Using central limit theorem type arguments, we prove that the idleness induced by the lingering effect may cause the delays to grow with 1/(1-r) at a quadratic rate. To the best of our knowledge, these are the first mathematical results illuminating the lingering effect and quantifying the performance impact.

In addition extensive simulation experiments are conducted to illustrate and validate the various analytical results.