bluuebunny/crossref_metadata_2025 huggingface dataset:
In VitroDestruction of Streptococcus pneumoniae Biofilms with Bacterial and Phage Peptidoglycan Hydrolases
Authors: Domenech Mirian , García Ernesto , Moscoso Miriam
Published: July 2011

Host- and phage-coded cell wall hydrolases have been used to fightStreptococcus pneumoniaegrowing as planktonic cellsin vitroas well as in animal models. Until now, however, the usefulness of these enzymes in biofilm-grown pneumococci has gone untested. The antipneumococcal activity of different cell wall hydrolases produced byS. pneumoniaeand a number of its phages was examined in anin vitrobiofilm model. The major pneumococcal autolysin LytA, anN-acetylmuramoyl-l-alanine amidase, showed the greatest efficiency in disintegratingS. pneumoniaebiofilms. The phage-encoded lysozymes Cpl-1 and Cpl-7 were also very efficient. Biofilms formed by the close pneumococcal relativesStreptococcus pseudopneumoniaeandStreptococcus oraliswere also destroyed by the phage endolysins but not by theS. pneumoniaeautolysin LytA. A cooperative effect of LytA and Cpl-1 in the disintegration ofS. pneumoniaebiofilms was recorded.
Pharmacokinetic Modeling of Plasma and Intracellular Concentrations of Raltegravir in Healthy Volunteers
Authors: Wang Lingzhi , Soon Gaik Hong , Seng Kok-Yong , Li Jun , Lee Edmund , Yong Eu-Leong , Goh Boon-Cher , Flexner Charles , Lee Lawrence
Published: July 2011

Raltegravir is a potent inhibitor of HIV integrase. Persistently high intracellular concentrations of raltegravir may explain sustained efficacy despite high pharmacokinetic variability. We performed a pharmacokinetic study of healthy volunteers. Paired blood samples for plasma and peripheral blood mononuclear cells (PBMCs) were collected predose and 4, 8, 12, 24, and 48 h after a single 400-mg dose of raltegravir. Samples of plasma only were collected more frequently. Raltegravir concentrations were determined using liquid chromatography-mass spectrometry. The lower limits of quantitation for plasma and PBMC lysate raltegravir were 2 nmol/liter and 0.225 nmol/liter, respectively. Noncompartmental analyses were performed using WinNonLin. Population pharmacokinetic analysis was performed using NONMEM. Six male subjects were included in the study; their median weight was 67.4 kg, and their median age was 33.5 years. The geometric mean (GM) (95% confidence interval shown in parentheses) maximum concentration of drug (
C
max
), area under the concentration-time curve from 0 to 12 h (AUC
0–12
), and area under the concentration-time curve from 0 h to infinity (AUC
0–∞
) for raltegravir in plasma were 2,246 (1,175 to 4,294) nM, 10,776 (5,770 to 20,126) nM · h, and 13,119 (7,235 to 23,788) nM · h, respectively. The apparent plasma raltegravir half-life was 7.8 (5.5 to 11.3) h. GM intracellular raltegravir
C
max
, AUC
0–12
, and AUC
0–∞
were 383 (114 to 1,281) nM, 2,073 (683 to 6,290) nM · h, and 2,435 (808 to 7,337) nM · h (95% confidence interval shown in parentheses). The apparent intracellular raltegravir half-life was 4.5 (3.3 to 6.0) h. Intracellular/plasma ratios were stable for each patient without significant time-related trends over 48 h. Population pharmacokinetic modeling yielded an intracellular-to-plasma partitioning ratio of 11.2% with a relative standard error of 35%. The results suggest that there is no intracellular accumulation or persistence of raltegravir in PBMCs.
Origin of OXA-181, an Emerging Carbapenem-Hydrolyzing Oxacillinase, as a Chromosomal Gene in Shewanella xiamenensis
Authors: Potron Anaïs , Poirel Laurent , Nordmann Patrice
Published: July 2011

Plasmid-mediated carbapenem-hydrolyzing β-lactamases are becoming emerging threats with
Enterobacteriaceae
. In particular, the carbapenem-hydrolyzing class D β-lactamase OXA-48 and its derivative OXA-181 have been reported increasingly worldwide. Using a PCR-based strategy, environmental samples were screened for
bla
OXA-48
-like genes.
Shewanella xiamenensis
, an environmental species from marine and freshwater, was identified as the progenitor of the
bla
OXA-181
gene. This work identifies the reservoir of an emerging carbapenemase gene that is clinically significant.
Identification of a Novel Virulence Factor in Clostridium Difficile That Modulates Toxin Sensitivity of Cultured Epithelial Cells
Authors: Miura Masashi , Kato Haru , Matsushita Osamu
Published: July 2011

Two glucosylating toxins named toxins A and B play a role in the pathogenesis of
Clostridium Difficile
infection. The interaction of the toxins with host cell factors proceeds to downstream stages of cytotoxic effects in cells, in which involvement of other
C. difficile
factors remains unknown. We utilized culture filtrate of
C. difficile
with a low dilution to characterize the influence of putative minor proteins on the organization of the actin cytoskeleton in cultured epithelial cells and found a previously uncharacterized F-actin aggregated structure, termed “actin aggregate,” at the juxtanuclear region. We reasoned that formation of actin aggregate was due to an additional factor(s) in the culture filtrate rather than the glucosylating toxins, because treatment of purified toxins rarely caused actin aggregate in cells. We focused on a previously uncharacterized hypothetical protein harboring a KDEL-like sequence as a candidate. The product of the candidate gene was detected in culture filtrate of
C. difficile
ATCC 9689 and was renamed Srl. Purified glutathione
S
-transferase-tagged Srl triggered formation of actin aggregate in the cells in the presence of either toxin A or B and enhanced cytotoxicity of each of the two toxins, including decreases in both cell viability and transepithelial resistance of cultured epithelial monolayer, although the recombinant Srl alone did not show detectable cytotoxicity. Srl-neutralized culture filtrate partially inhibited morphological changes of the cells in parallel with decreased actin aggregate formation in the cells. Thus, Srl might contribute to the modulation of toxin sensitivity of intestinal epithelial cells by enhancing cytotoxicity of
C. difficile
toxins.
Role of Interleukin-23-Dependent Antifungal Immune Responses in Dendritic Cell-Vaccinated Mice
Authors: Zheng Mingquan , Rapaka Rekha R. , Yu Amy C. , Shellito Judd E. , Kolls Jay K.
Published: July 2011

CD40 ligand (CD40L) transduction of antigen-pulsed dendritic cells (DCs) can result in antigen-specific humoral immune responses even in CD4
+
T-cell-depleted settings. Here, we show that CD40L transduction of DCs results in the induction of interleukin-12p40 (IL-12p40), IL-12p70, and IL-23. Using DCs that were deficient in IL-12p40, IL-12p35, or IL-23p19, we show that these molecules are dispensable for primary IgG1 responses to
Pneumocystis
, but IgG2c was dependent on IL-12p40 and IL-23p19 but not IL-12p35. Antigen-specific recall responses in CD4-deficient mice were critically dependent on IL-12p40 and IL-23p19 expression in DCs and were not affected by the lack of IL-12p35. To confirm that this defect in recall was due to IL-23, transduction of IL-12p40
−/−
DCs with a recombinant adenovirus expressing functional IL-23 restored recall responses in DC-vaccinated CD4-deficient mice. These data show that DC-produced IL-23 is critical for vaccine-induced antigen-specific IgG2c and recall antibody responses in the setting of CD4
+
T-cell depletion.
Geology of the Chenier Plain of Cameron Parish, southwestern Louisiana
Authors: Owen Donald E.
Published: July 2011

The Chenier Plain of southwestern coastal Louisiana is a Holocene strand plain composed of wooded beach ridges (cheniers) and intervening mudflat grassy wetlands. The mudflats form as prograding tidal flats along the open, but low-energy Gulf of Mexico coast; cheniers form from winnowing of sand and shells from the mudflats by waves during transgression. Mudflats are deposited when a Mississippi River delta lobe is nearby to the east, and cheniers are formed when distributaries switch to a more distant location farther east. All of the cheniers have formed within approximately the past 3000 yr or less and are progressively younger toward the present coastline. Spits are attached to the cheniers at estuaries; they grow westward in response to the dominant longshore currents. Currently, mudflats are prograding in Vermillion Parish to the east, while cheniers form in eastern Cameron Parish along with some regressive beach ridge development in western Cameron Parish.

This coast is microtidal with low wave energy. A high rate of subsidence as well as sea-level rise characterizes the Chenier Plain, which is subject to increased wave energy and mud transport every year during many cold-front passages and periodic storm surges associated with tropical cyclones of much lower frequency. Major storm surges can inundate the entire Chenier Plain, wreaking havoc on human settlements.
Neogene drainage development of Marsh and Portneuf valleys, eastern Idaho
Authors: Thackray Glenn D. , Rodgers David W. , Drabick Andrew
Published: July 2011

Neogene drainage development in southeastern Idaho has been influenced by drainage capture, Basin and Range faulting, volcanism, and the Late Pleistocene Lake Bonneville overflow and Bonneville Flood. In Marsh Valley, the Middle to Late Pleistocene sedimentary sequence is dominated by alternating lacustrine/paludal and alluvial sediments, which have yielded new 40Ar/39Ar, amino acid racemization, and luminescence age estimates. The pattern of sedimentation through time indicates poor drainage integration of southern Marsh Valley through most of the last ca. 640 ka and suggests slow basin subsidence along Quaternary faults mapped on the basin edges. Marsh Valley initially incised into that valley fill sequence ca. 19 ka, shortly before the Bonneville Flood. Marsh Creek is a markedly underfit stream occupying a meandering, broad valley carved into the valley fill sequence. These geomorphic and sedimentologic patterns suggest non-catastrophic Lake Bonneville overflow before and after the Bonneville Flood.

In Portneuf Valley, ca. 8.5–7.4 Ma basin fill and a bedrock pediment are perched 800 m above the modern valley floor. Major incision of basin fill and bedrock by the ancestral Portneuf drainage system occurred prior to the Middle to Late Pleistocene, when two cut-fill events resulted in accumulation of alluvial fan deposits extending ~10–60 m above the modern valley floor and basalt extending ~10 m below to 20 m above the modern valley floor. Final incision by Lake Bonneville overflow is evident but relatively minor in comparison to the cumulative downcutting. Overall, incision is attributed to isostatic subsidence of the eastern Snake River Plain, which served as base level for the Portneuf drainage system after passage of the Yellowstone hot spot in late Miocene time.
Impact of learning HIV status on contraceptive use in the MIRA trial
Authors: Blanchard Kelly , Holt Kelsey , Bostrom Alan , van der Straten Ariane , Ramjee Gita , de Bruyn Guy , Chipato Tsungai , Montgomery Elizabeth T , Padian Nancy S
Published: July 2011

Background and methodology

We examined the effect of becoming HIV-positive on contraceptive practices in a Phase III randomised controlled trial of the diaphragm for HIV prevention. We coded self-reported contraceptive use into seven categories of methods in order of effectiveness. We compared the proportion using each category of contraception at baseline and last visit between women who did and did not become HIV-positive. We compared changes in the proportion using each category of contraception from baseline to last visit and calculated the percentage of women that moved to a more or less effective method category or stayed the same. We examined immediate and long-term changes in contraceptive use category after learning HIV-positive status.

Results

A total of 4645 women remained HIV-negative and 309 became HIV-positive. The proportion using each category of contraception was similar between groups at baseline and last visit. In both groups approximately one-fifth changed to a less effective method category between baseline and last visit. Few women reported using long-acting methods. Among HIV-positive women, shorter-term changes in the proportion using each category of contraception were similar to longer-term changes, though somewhat more women were using a method in the same category 3 months after seroconversion.

Discussion and conclusions

Learning about HIV-positive status did not appear to significantly change patterns of use of effective contraceptives or the probability of switching to a more or less effective method. Information about, and access to, long-acting methods should receive more attention and be a routine part of family planning programmes and prevention trials.
Increased gonorrhoea and chlamydia testing did not increase case detection in an HIV clinical cohort 1999–2007
Authors: Berry Stephen A , Ghanem Khalil G , Page Kathleen R , Gange Stephen J , Thio Chloe L , Moore Richard D , Gebo Kelly A
Published: July 2011

Objectives

Since 2003, US organisations have recommended universal screening, rather than targeted screening, of HIV-infected persons for gonorrhoea and chlamydia. The objective of this study was to determine whether wider testing resulting from these guidelines would produce an increase in gonorrhoea/chlamydia diagnoses.

Methods

3283 patients receiving HIV care in 1999–2007 in the Johns Hopkins Hospital HIV clinic were studied. The two primary outcomes were the occurrence of any gonorrhoea/chlamydia testing in each year of care and the occurrence of any positive result(s) in years of testing. The proportion of all patients in care who were diagnosed with gonorrhoea/chlamydia was defined as the number of patients with positive results divided by the number of patients in care. Trends were analysed with repeated measures logistic regression.

Results

The proportion of patients tested for gonorrhoea/chlamydia increased steadily from 0.12 in 1999 to 0.33 in 2007 (OR per year for being tested 1.17, 95% CI 1.15 to 1.19). The proportion positive among those tested decreased significantly after 2003 (OR per year 0.67, 95% CI 0.55 to 0.81). The proportion of all patients in care diagnosed with gonorrhoea/chlamydia therefore remained generally stable in 1999–2007 (OR per year 0.97, 95% CI 0.91 to 1.04).

Conclusions

Universal annual screening, as implemented, did not increase the proportion of all patients in care who were diagnosed with gonorrhoea/chlamydia. Similarly low implementation rates have been reported in cross-sectional studies. If future efforts to enhance implementation do not yield increases in diagnoses, then guidelines focusing on targeted screening of high-risk groups rather than universal screening may be warranted.
CONDITIONS FOR APPEARANCE AND DISAPPEARANCE OF LIMIT CYCLES IN THE SHIMIZU–MORIOKA SYSTEM
Authors: LIU LINGLING , GAO BO
Published: July 2011

This paper deals with the Shimizu–Morioka system, a special generalized Lorenz canonical form. Using techniques of elimination in the computation of algebraic varieties we obtain parameter-dependent normal forms on a center manifold. Our computation shows that the maximal number of limit cycles produced from Hopf bifurcations is four and only even number of limit cycles can be bifurcated near the two equilibria because of [Formula: see text]-symmetry. Our parameter-dependent normal forms enable us to give parameter conditions for the cases of none, two and four limit cycles separately. Furthermore, considering exterior perturbations, we give conditions under which one or three limit cycles can be produced from Hopf bifurcations. Moreover, we also give conditions for fold bifurcations, under which limit cycles coincide or disappear. Finally, our results are illustrated by numerical simulations.
A SYNCHRONIZATION CONDITION FOR COUPLED NONLINEAR SYSTEMS WITH TIME-DELAY: A FREQUENCY DOMAIN APPROACH
Authors: OGUCHI TOSHIKI , NIJMEIJER HENK
Published: July 2011

This paper considers the synchronization problem for nonlinear systems with time-delay couplings. We assume that the error dynamics can be rewritten as a feedback connection of a linear delay system with multiple inputs and outputs and nonlinear elements which are decentralized and satisfy a sector condition. Then, we derive a synchronization condition for time-delay coupled systems by applying the multivariable circle criterion. Unlike the conventional synchronization criteria, the derived criterion is based on a frequency-domain stability condition and avoids the use of the Lyapunov–Krasovskii approach. As a result, the condition based on the circle criterion does not contain the conservativeness caused by the Lyapunov–Krasovskii approach. The effectiveness of the proposed criterion is shown by examples of coupled Chua systems with delay coupling.
SELECTING THE LORENZ PARAMETERS FOR WIDEBAND RADAR WAVEFORM GENERATION
Authors: WILLSEY MATT S. , CUOMO KEVIN M. , OPPENHEIM ALAN V.
Published: July 2011

Radar waveforms based on chaotic systems have occasionally been suggested for a variety of radar applications. In this paper, radar waveforms are constructed with solutions from a particular chaotic system, the Lorenz system, and are called Lorenz waveforms. Waveform properties, which include the peak autocorrelation function side-lobe and the transmit power level, are related to the system parameters of the Lorenz system. Additionally, scaling the system parameters is shown to correspond to an approximate time and amplitude scaling of Lorenz waveforms and also corresponds to scaling the waveform bandwidth. The Lorenz waveforms can be generated with arbitrary time lengths and bandwidths and each waveform can be represented with only a few system parameters. Furthermore, these waveforms can then be systematically improved to yield constant-envelope output waveforms with low autocorrelation function sidelobes and limited spectral leakage.
A NEW FAMILY OF FIRST-ORDER TIME-DELAYED CHAOTIC SYSTEMS
Authors: ZHANG XIAOMING , CHEN JUFANG , PENG JIANHUA
Published: July 2011

A general method for formulating first-order time-delayed chaotic systems with simple linear time-delayed term is proposed. The formulated systems are realized with electronic circuit experiments. In order to determine the unknown coefficients in a general delayed differential equations for having chaotic solutions, we follow the route of period-doubling bifurcation to chaos. Firstly, the conditions for a time-delayed system having a stable periodic solution, generating from a destablized steady state, is analyzed with Hopf bifurcation theory. Then the delay time parameter is changed according to the bifurcation direction to search the chaotic state, which is identified by the Lyapunov exponents spectra. The theoretical analysis is well confirmed by numerical simulations and circuit experiments.
DYNAMICS OF THE LÜ SYSTEM ON THE INVARIANT ALGEBRAIC SURFACE AND AT INFINITY
Authors: LIU YONGJIAN , YANG QIGUI
Published: July 2011

Firstly, the dynamics of the Lü system having an invariant algebraic surface are analyzed. Secondly, by using the Poincaré compactification in ℝ3, a global analysis of the system is presented, including the complete description of its dynamic behavior on the sphere at infinity. Lastly, combining analytical and numerical techniques, it is shown that for the parameter value b = 0, the system presents an infinite set of singularly degenerate heteroclinic cycles. The chaotic attractors for the Lü system in the case of small b > 0 are found numerically, hence the singularly degenerate heteroclinic cycles.
DISTURBANCE CHAOTIC ANT SWARM
Authors: GE FANGZHEN , WEI ZHEN , LU YANG , LI LIXIANG , YANG YIXIAN
Published: July 2011

Chaotic Ant Swarm (CAS) is an optimization algorithm based on swarm intelligence theory, which has been applied to find the global optimum solution in search space. However, it often loses its effectiveness and advantages when applied to large and complex problems, e.g. those with high dimensions. To resolve the problems of high computational complexity and low solution accuracy existing in CAS, we propose a Disturbance Chaotic Ant Swarm (DCAS) algorithm to significantly improve the performance of the original algorithm. The aim of this paper is achieved by three strategies which include modifying the method of updating ant's best position, neighbor selection method and establishing a self-adaptive disturbance strategy. The global convergence of the DCAS algorithm is proved in this paper. Extensive computational simulations and comparisons are carried out to validate the performance of the DCAS on two sets of benchmark functions with up to 1000 dimensions. The results show clearly that DCAS substantially enhances the performance of the CAS paradigm in terms of computational complexity, global optimality, solution accuracy and algorithm reliability for complex high-dimensional optimization problems.
CONTROLLABLE HOPF BIFURCATIONS OF CODIMENSIONS ONE AND TWO IN LINEAR CONTROL SYSTEMS
Authors: DE CARVALHO BRAGA DENIS , MELLO LUIS FERNANDO , ROCŞOREANU CARMEN , STERPU MIHAELA
Published: July 2011

Given a linear time-invariant control system, the purpose of this work is to define a four-parameter family of static state feedback such that the corresponding closed-loop control system exhibits controllable Hopf bifurcation of codimensions one and two.
HOMOCLINIC AND HETEROCLINIC ORBITS AND BIFURCATIONS OF A NEW LORENZ-TYPE SYSTEM
Authors: LI XIANYI , WANG HAIJUN
Published: July 2011

In this paper, a new Lorenz-type system with chaotic attractor is formulated. The structure of the chaotic attractor in this new system is found to be completely different from that in the Lorenz system or the Chen system or the Lü system, etc., which motivates us to further study in detail its complicated dynamical behaviors, such as the number of its equilibrium, the stability of the hyperbolic and nonhyperbolic equilibrium, the degenerate pitchfork bifurcation, the Hopf bifurcation and the local manifold character, etc., when its parameters vary in their space. The existence or nonexistence of homoclinic and heteroclinic orbits of this system is also rigorously proved. Numerical simulation evidences are also presented to examine the corresponding theoretical analytical results.
A MODIFIED CHUA CIRCUIT SIMULATES A V-SHAPED TROUGH IN AUTONOMIC ACTIVITY AS A PRECURSOR OF SUDDEN CARDIAC DEATH
Authors: OSAKA MOTOHISA
Published: July 2011

Recently we have reported that a previously unidentified V-trough of sympathetic nerve activity (SNA) is a potential precursor of lethal cardiac events by examining 24-hour ambulatory electrocardiograms in which such an event was recorded by chance. The V-trough was marked by three consecutive compartments: a small variation lasting two hours, an abrupt descent lasting 30 min and a sharp ascent for 40 min. We reported that the hemodynamics consisting of heart rate, SNA and blood pressure (BP) is modeled excellently by the modification of a known chaotic electrical circuit, Chua circuit. A V-trough of SNA appears by increasing the resistive element between SNA and BP in the circuit, which corresponds to the impaired regulation of BP by SNA. This finding is consistent with an acknowledged finding that the depressed baroreflex (reflex of BP by SNA) may trigger a lethal arrhythmia.
ABELIAN INTEGRALS FOR THE ONE-PARAMETER BOGDANOV–TAKENS SYSTEM
Authors: ZHANG YONGKANG , LI BAOYI , LI CUIPING
Published: July 2011

An explicit upper bound Z(2, n) ≤ n + m - 1 is derived for the number of zeros of Abelian integrals M1(h) = ∮γ(h) P(x, y) dy - Q(x, y) dx on the open interval (0, 1/6), where γ(h) is an oval lying on the algebraic curve Hλ = (1/2)x2 + (1/2)y2 - (1/3)x3 - λy3 = h, P(x, y), Q(x, y) are polynomials of x and y, and max { deg P(x, y), deg Q(x, y)} = n. The proof exploits the expansion of the first order Melnikov function M1(h, λ) near λ = 0 and assume (∂m/∂λm)M1(h, λ)|λ = 0 not vanish identically.
CHARACTERISTICS OF STOCHASTIC RESONANCE IN ASYMMETRIC DUFFING OSCILLATOR
Authors: ARATHI S. , RAJASEKAR S. , KURTHS J.
Published: July 2011

We study the characteristics of stochastic resonance (SR) in the Duffing oscillator with three types of asymmetries in its double-well potential. The asymmetries controlled by a parameter α are introduced in the potential by varying (i) the depth of the left-well alone, (ii) the location of the minimum of the left-well alone and (iii) both depth and location of the minimum of the left-well alone. The characteristics of SR in the asymmetric cases are different from the symmetric case (α = 1). We find that asymmetry has a strong influence on the optimum noise intensity at which signal-to-noise ratio (SNR) is maximum, mean residence time at resonance and the probability distribution of residence time in the left- and right-wells. For a range of values of α, α ≠ 1, SNR is found to be relatively higher than for α = 1.
ELLIPTICITY OF STRUCTURES IN CMB SKY MAPS
Authors: AURICH RALF , JANZER HOLGER S. , LUSTIG SVEN , STEINER FRANK
Published: July 2011

We study the ellipticity of contour lines in the sky maps of the cosmic microwave background (CMB) as well as other measures of elongation. The sensitivity of the elongation on the resolution of the CMB maps, which depends on the pixelization and the beam profile of the detector, is investigated. It is shown that the current experimental accuracy does not allow one to discriminate between cosmological models which differ in curvature by ΔΩ tot = 0.05. Analytical expressions are given for the case that the statistical properties of the CMB are those of two-dimensional Gaussian random fields.
EXPANSIONFREE FLUID EVOLUTION AND SKRIPKIN MODEL IN f(R) THEORY
Authors: SHARIF M. , KAUSAR H. RIZWANA
Published: July 2011

We consider the modified f(R) theory of gravity whose higher-order curvature terms are interpreted as a gravitational fluid or dark source. The gravitational collapse of a spherically symmetric star, made up of locally anisotropic viscous fluid, is studied under the general influence of the curvature fluid. Dynamical equations and junction conditions are modified in the context of f(R) dark energy and by taking into account the expansionfree evolution of the self-gravitating fluid. As a particular example, the Skripkin model is investigated which corresponds to isotropic pressure with constant energy density. The results are compared with corresponding results in General Relativity.
Using spectroscopic tools to probe porphyrin deformation and porphyrin-protein interactions
Authors: Schweitzer-Stenner Reinhard
Published: July 2011

The reactivity and functionality of heme proteins are to a significant extent determined by the conformation of their functional heme groups and by the interaction of axial ligands with their protein environment. This review focuses on experimental methods and theoretical concepts for elucidating symmetry lowering perturbations of the heme induced by the protein environment of the heme pocket. First, we discuss a variety of methods which can be used to probe the electric field at the heme, including spectral hole burning as well as low temperature absorption and room temperature circular dichroism spectroscopy. Second, we show how heme deformations can be described as superposition of deformations along normal coordinates, thereby using the irreducible representations of the D4h point group as a classification tool. Finally, resonance Raman spectroscopy is introduced as a tool to probe the deformations of metalloprophyrins in solution and in protein matrices by measuring and comparing intensities and depolarization properties rather than wavenumber positions.
Responsive porphyrinoid nanoparticles: development and applications
Authors: Aggarwal Amit , Qureshy Meroz , Johnson Jason , Batteas James D. , Drain Charles Michael , Samaroo Diana
Published: July 2011

The economy of space and materials and the continuously increasing demand for advanced functionalities for diverse technologies requires the development of new synthetic methods. Many nanomaterials have enhanced photophysical and photochemical properties in solutions and/or on surfaces, while others have enhanced chemical properties, compared to the atomic, molecular, or bulk phases. Nanomaterials have a wide range of applications in catalysis, sensors, photonic devices, drug delivery, and as therapeutics for treatment of a variety of diseases. Inorganic nanoparticles are widely studied, but the formation of organic nanomaterials via supramolecular chemistry is more recent, and porphyrinoids are at the forefront of this research because of their optical, chemical, and structural properties. The formation of nanoscaled materials via self-assembly and/or self-organization of molecular subunits is an attractive approach because of reduced energy requirements, simpler molecular subunits, and the material can be adaptive to environmental changes. The presence of biocompatible groups such as peptides, carbohydrates, polyglycols and mixtures of these on the periphery of the porphyrin macrocycle may make nanoparticles suitable for therapeutics. This perspective focuses on responsive, non-crystalline porphyrinoid nanomaterials that are less than about 100 nm in all dimensions and used for catalytic or therapeutic applications.
Impact of aging vs. estrogen loss on cardiac gene expression: estrogen replacement and inflammation
Authors: Pechenino Angela S. , Lin Li , Mbai Fiona N. , Lee Alison R. , He Xian-Min , Stallone John N. , Knowlton A. A.
Published: July 2011

Despite an abundance of evidence to the contrary from animal studies, large clinical trials on humans have shown that estrogen administered to postmenopausal women increases the risk of cardiovascular disease. However, timing may be everything, as estrogen is often administered immediately after ovariectomy (Ovx) in animal studies, while estrogen administration in human studies occurred many years postmenopause. This study investigates the discrepancy by administering 17β-estradiol (E2) in a slow-release capsule to Norway Brown rats both immediately following Ovx and 9 wk post-Ovx (Late), and studying differences in gene expression between these two groups compared with age-matched Ovx and sham-operated animals. Two different types of microarray were used to analyze the left ventricles from these groups: an Affymetrix array ( n = 3/group) and an inflammatory cytokines and receptors PCR array ( n = 4/group). Key genes were analyzed by Western blotting. Ovx without replacement led to an increase in caspase 3, caspase 9, calpain 2, matrix metalloproteinase (MMP)9, and TNF-α. Caspase 6, STAT3, and CD11b increased in the Late group, while tissue inhibitor of metalloproteinase 2, MMP14, and collagen I α1 were decreased. MADD and fibronectin were increased in both Ovx and Late. TNF-α and inducible nitric oxide synthase (iNOS) protein levels increased with Late replacement. Many of these changes were prevented by early E2 replacement. These findings suggest that increased expression of inflammatory genes, such as TNF-α and iNOS, may be involved in some of the deleterious effects of delayed E2 administration seen in human studies.
Perioperative Nerve Blockade: Clues from the Bench
Authors: Suter M. R. , Siegenthaler A. , Decosterd I. , Ji R. R.
Published: July 2011

Peripheral and neuraxial nerve blockades are widely used in the perioperative period. Their values to diminish acute postoperative pain are established but other important outcomes such as chronic postoperative pain, or newly, cancer recurrence, or infections could also be influenced. The long-term effects of perioperative nerve blockade are still controversial. We will review current knowledge of the effects of blocking peripheral electrical activity in different animal models of pain. We will first go over the mechanisms of pain development and evaluate which types of fibers are activated after an injury. In the light of experimental results, we will propose some hypotheses explaining the mitigated results obtained in clinical studies on chronic postoperative pain. Finally, we will discuss three major disadvantages of the current blockade: the absence of blockade of myelinated fibers, the inappropriate duration of blockade, and the existence of activity-independent mechanisms.
Vascular Complications following Isolated Limb Perfusion for Local Recurrence of Extremity Melanoma: A Case Report and Literature Review
Authors: Trezzi M. , Parolari A. , Loardi C. , Alamanni F.
Published: July 2011

Introduction. To evaluate the role of hyperthermic isolated limb perfusion (HILP) in arterial thrombosis following melanoma-soft tissue sarcoma chemotherapy.Report. Here is presented one case of iliac-common femoral artery subacute thrombosis and a review of the appropriate literature performed using a MEDLINE search. Acute/subacute arterial occlusion is one of the most feared vascular complications of HILP, located nearly always in the external iliac-femoral artery axis, being those vessels cannulated for perfusion.Conclusions. The small number of reported cases indicates either the rarity of this complication or unawareness of its existence. The true incidence of this complication is probably underreported.
Hybrid Processing Combining Electrostatic Levitation and Laser Heating: Application to Terrestrial Analogues of Asteroid Materials
Authors: Paradis Paul-François , Ishikawa Takehiko , Watanabe Yuki , Okada Junpei
Published: July 2011

Electrostatic levitation combined with laser heating is becoming a mature technique that has been used for several fundamental and applied studies in fluid and materials sciences (synthesis, property determination, solidification studies, atomic dynamic studies, etc.). This is attributable to the numerous processing conditions (containerless, wide heating temperature range, cooling rates, atmospheric compositions, etc.) that levitation and radiative heating offer, as well as to the variety of diagnostics tools that can be used. In this paper, we describe the facility, highlighting the combined advantages of electrostatic levitation and laser processing. The various capabilities of the facility are discussed and are exemplified with the measurements of the density of selected iron-nickel alloys taken over the liquid phase.
Acute Immobilization Stress Modulate GABA Release from Rat Olfactory Bulb: Involvement of Endocannabinoids—Cannabinoids and Acute Stress Modulate GABA Release
Authors: Delgado Alejandra , Jaffé Erica H.
Published: July 2011

We studied the effects of cannabinoids and acute immobilization stress on the regulation of GABA release in the olfactory bulb. Glutamate-stimulated 3H-GABA release was measured in superfused slices. We report that cannabinoids as WIN55, 212-2, methanandamide, and 2-arachidonoylglycerol were able to inhibit glutamate- and KCl-stimulated 3H-GABA release. This effect was blocked by the CB1 antagonist AM281. On the other hand, acute stress was ableper seto increase endocannabinoid activity. This effect was evident since the inhibition of stimulated GABA release by acute stress was reversed with AM281 and tetrahydrolipstatin. Inhibition of the endocannabinoid transport or its catabolism showed reduction of GABA release, antagonized by AM281 in control and stressed animals. These results point to endocannabinoids as inhibitory modulators of GABA release in the olfactory bulb acting through an autocrine mechanism. Apparently, stress increases the endocannabinoid system, modulating GABAergic synaptic function in a primary sensory organ.
Analysis of the Indentation Size Effect in the Microhardness Measurements inB6O
Authors: Machaka Ronald , Derry Trevor E. , Sigalas Iakovos , Herrmann Mathias
Published: July 2011

The Vickers microhardness measurements of boron suboxide (B6O) ceramics prepared by uniaxial hot-pressing was investigated at indentation test loads in the range from 0.10 to 2.0 kgf. Results from the investigation indicate that the measured microhardness exhibits an indentation load dependence. Based on the results, we present a comprehensive model intercomparison study of indentation size effects (ISEs) in the microhardness measurements of hot-pressed B6O discussed using existing models, that is, the classical Meyer's law, Li and Bradt's proportional specimen resistance model (PSR), the modified proportional specimen resistance model (MPSR), and Carpinteri's multifractal scaling law (MFSL). The best correlation between literature-cited load-independent Vickers microhardness values, the measured values, and applied models was achieved in the case of the MPSR and the MFSL models.
Balanced Propofol Sedation in Patients Undergoing EUS-FNA: A Pilot Study to Assess Feasibility and Safety
Authors: Pagano N. , Arosio M. , Romeo F. , Rando G. , Del Conte G. , Carlino A. , Strangio G. , Vitetta E. , Malesci A. , Repici A.
Published: July 2011

Introduction and aims. Balanced propofol sedation (BPS) administered by gastroenterologists has gained popularity in endoscopic procedures. Few studies exist about the safety of this approach during endosonography with fine needle aspiration (EUS-FNA). We assessed the safety of BPS in EUS-FNA. Materials and methods. 112 consecutive patients, referred to our unit to perform EUS-FNA, from February 2008 to December 2009, were sedated with BPS. A second gastroenterologist administered the drugs and monitorized the patient. Results. All the 112 patients (62 males, mean age 58.35) completed the examination. The mean dose of midazolam and propofol was, respectively, of 2.1 mg (range 1–4 mg) and 350 mg (range 180–400). All patients received oxygen with a mean flux of 4 liter/minute (range 2–6 liters/minute). The mean recovery time after procedure was 25 minutes (range 18–45 minutes). No major complications related to sedation were registered during all procedures. The oxygen saturation of all patients never reduced to less than 85%. Blood systolic pressure during and after the procedure never reduced to less than 100 mmHg. Conclusions. In our experience BPS administered by non-anaesthesiologists provided safe and successful sedation in patients undergoing EUS-FNA.
Stents in Renal Artery Bifurcation Stenosis: A Case Report
Authors: Leonardou Polytimi , Pappas Paris
Published: July 2011

A 39-year-old patient presented with poorly controlled hypertension, and she was referred to renal angiogram and potential renal angioplasty. Renal angiogram showed a bifurcation lesion of the right renal artery. A guide wire was used to cross the upper branch, while the lower branch was protected by another same-type guide wire through the same introducer. Two thin monorail balloons were used to dilate the two branches; however, despite balloon dilatation, the stenosis of the vessels persisted. The “kissing balloon” technique was then attempted by simultaneously inflating both branches using the same balloons, but more than a 70% residual stenosis persisted in each branch. Two stents were finally placed in a “kissing” way through the main renal artery. The imaging and clinical results were good, without any procedure-related complications. Three years clinical followup was also good, without any reason for further interventional approach.
Sharpe (Ratio) Thinking about the Investment Opportunity Set and CAPM Relationship
Authors: Zakamulin Valeriy
Published: July 2011

In the presence of a risk‐free asset the investment opportunity set obtained via the Markowitz portfolio optimization procedure is usually characterized in terms of the vector of excess returns on individual risky assets and the variance‐covariance matrix. We show that the investment opportunity set can alternatively be characterized in terms of the vector of Sharpe ratios of individual risky assets and the correlation matrix. This implies that the changes in the characteristics of individual risky assets that preserve the Sharpe ratios and the correlation matrix do not change the investment opportunity set. The alternative characterization makes it simple to perform a comparative static analysis that provides an answer to the question of what happens with the investment opportunity set when we change the risk‐return characteristics of individual risky assets. We demonstrate the advantages of using the alternative characterization of the investment opportunity set in the investment practice. The Sharpe ratio thinking also motivates reconsidering the CAPM relationship and adjusting Jensen′s alpha in order to properly measure abnormal portfolio performance.
Solution of Higher‐Order ODEs Using Backward Difference Method
Authors: Bin Suleiman Mohamed , Binti Ibrahim Zarina Bibi , Bin Rasedee Ahmad Fadly Nurullah
Published: July 2011

The current numerical technique for solving a system of higher‐order ordinary differential equations (ODEs) is to reduce it to a system of first‐order equations then solving it using first‐order ODE methods. Here, we propose a method to solve higher‐order ODEs directly. The formulae will be derived in terms of backward difference in a constant stepsize formulation. The method developed will be validated by solving some higher‐order ODEs directly with constant stepsize. To simplify the evaluations of the integration coefficients, we find the relationship between various orders. The result presented confirmed our hypothesis.
Higher-Resolution Determination of Zero-Offset Common-Reflection-Surface Stack Parameters
Authors: Asgedom Endrias G. , Gelius Leiv J. , Tygel Martin
Published: July 2011

We developed a higher resolution method for the estimation of the three travel-time parameters that are used in the 2D zero-offset, Common-Reflection-Surface stack method. The underlying principle in this method is to replace the coherency measure performed using semblance with that of MUSIC (multiple signal classification) pseudospectrum that utilizes theeigenstructureof the data covariance matrix. The performance of the two parameter estimation techniques (i.e., semblance and MUSIC) was investigated using both synthetic seismic diffraction and reflection data corrupted with white Gaussian noise, as well as a multioffset ground penetrating radar (GPR) field data set. The estimated parameters employing MUSIC were shown to be superior of those from semblance.
Normal Criteria of Function Families Related to a Result of Drasin
Authors: Bing Zhu , Jianming Lin , Wenjun Yuan
Published: July 2011

We study the normality of families of meromorphic functions related to a result of Drasin. We consider whether a
family meromorphic functions ℱ whose each function does not take
zero is normal in D, if for every pair of functions f and g in ℱ, f(z) and g(z) share ∞ or H(f) − 1 and H(g) − 1 share 0, where H(f) : = f(k)(z) + ak−1f(k−1)(z) + ⋯, a0f(z). Some examples show that the conditions in our results are best possible.
Nest Digging by Leaf-Cutting Ants: Effect of Group Size and Functional Structures
Authors: Camargo Roberto da Silva , Fujihara Ricardo Toshio , Forti Luiz Carlos
Published: July 2011

Leaf-cutting ant workers dig underground chambers, for housing their symbiotic fungus, interconnected by a vast quantity of tunnels whose function is to permit the entrance of food (leaves), gaseous exchanges, and movement of workers, offspring, and the queen. Digging is a task executed by a group of workers, but little is known about the group effect and group-constructed functional structures. Thus, we analyzed the structures formed by worker groups (5, 10, 20, and 40 individuals) of the leaf-cutting ant,Atta sexdens rubropilosa, for 2 days of excavation. The digging arena was the same for the 4 groups, with each group corresponding to a different density. Our results verified a pattern of tunneling by the workers, but no chamber was constructed. The group effect is well known, since the 40-worker group dug significantly more than the groups of 5, 10, and 20. These groups did not differ statistically from each other. Analysis of load/worker verified that workers of the smallest group carried the greatest load. Our paper demonstrates the group effect on the digging of nests, namely, that excavation is proportional to group size, but without emergence of a functional structure such as a chamber.
Insulin Increases De Novo Steroidogenesis in Prostate Cancer Cells
Authors: Lubik Amy A. , Gunter Jennifer H. , Hendy Stephen C. , Locke Jennifer A. , Adomat Hans H. , Thompson Vanessa , Herington Adrian , Gleave Martin E. , Pollak Michael , Nelson Colleen C.
Published: July 2011

Androgen-dependent pathways regulate maintenance and growth of normal and malignant prostate tissues. Androgen deprivation therapy (ADT) exploits this dependence and is used to treat metastatic prostate cancer; however, regression initially seen with ADT gives way to development of incurable castration-resistant prostate cancer (CRPC). Although ADT generates a therapeutic response, it is also associated with a pattern of metabolic alterations consistent with metabolic syndrome including elevated circulating insulin. Because CRPC cells are capable of synthesizing androgens de novo, we hypothesized that insulin may also influence steroidogenesis in CRPC. In this study, we examined this hypothesis by evaluating the effect of insulin on steroid synthesis in prostate cancer cell lines. Treatment with 10 nmol/L insulin increased mRNA and protein expression of steroidogenesis enzymes and upregulated the insulin receptor substrate insulin receptor substrate 2 (IRS-2). Similarly, insulin treatment upregulated intracellular testosterone levels and secreted androgens, with the concentrations of steroids observed similar to the levels reported in prostate cancer patients. With similar potency to dihydrotestosterone, insulin treatment resulted in increased mRNA expression of prostate-specific antigen. CRPC progression also correlated with increased expression of IRS-2 and insulin receptor in vivo. Taken together, our findings support the hypothesis that the elevated insulin levels associated with therapeutic castration may exacerbate progression of prostate cancer to incurable CRPC in part by enhancing steroidogenesis. Cancer Res; 71(17); 5754–64. ©2011 AACR.
Definition of the Landscape of Promoter DNA Hypomethylation in Liver Cancer
Authors: Stefanska Barbara , Huang Jian , Bhattacharyya Bishnu , Suderman Matthew , Hallett Michael , Han Ze-Guang , Szyf Moshe
Published: July 2011

We use hepatic cellular carcinoma (HCC), one of the most common human cancers, as a model to delineate the landscape of promoter hypomethylation in cancer. Using a combination of methylated DNA immunoprecipitation and hybridization with comprehensive promoter arrays, we have identified approximately 3,700 promoters that are hypomethylated in tumor samples. The hypomethylated promoters appeared in clusters across the genome suggesting that a high-level organization underlies the epigenomic changes in cancer. In normal liver, most hypomethylated promoters showed an intermediate level of methylation and expression, however, high-CpG dense promoters showed the most profound increase in gene expression. The demethylated genes are mainly involved in cell growth, cell adhesion and communication, signal transduction, mobility, and invasion; functions that are essential for cancer progression and metastasis. The DNA methylation inhibitor, 5-aza-2′-deoxycytidine, activated several of the genes that are demethylated and induced in tumors, supporting a causal role for demethylation in activation of these genes. Previous studies suggested that MBD2 was involved in demethylation of specific human breast and prostate cancer genes. Whereas MBD2 depletion in normal liver cells had little or no effect, we found that its depletion in human HCC and adenocarcinoma cells resulted in suppression of cell growth, anchorage-independent growth and invasiveness as well as an increase in promoter methylation and silencing of several of the genes that are hypomethylated in tumors. Taken together, the findings define the potential functional role of hypomethylation in cancer. Cancer Res; 71(17); 5891–903. ©2011 AACR.