bluuebunny/crossref_metadata_2025 huggingface dataset:
Chymase inhibition prevents myocardial fibrosis through the attenuation of NOX4‐associated oxidative stress in diabetic hamsters
Authors: Maeda Yasutaka , Inoguchi Toyoshi , Takei Ryoko , Hendarto Hari , Ide Makoto , Inoue Tomoaki , Kobayashi Kunihisa , Urata Hidenori , Nishiyama Akira , Takayanagi Ryoichi
Published: February 2012

Aims/Introduction:  Diabetic cardiomyopathy entails the cardiac injury induced by diabetes, independent of vascular disease or hypertension. Despite numerous experimental studies and clinical trials, the pathogenesis of diabetic cardiomyopathy remains elusive. Here, we report that chymase, an immediate angiotensin II (AngII)‐forming enzyme in humans and hamsters, and NOX4‐induced oxidative stress have pathogenic roles in myocardial fibrosis in diabetic hamsters.

Materials and Methods:  Expression of chymase was evaluated in the hearts of streptozotocin (STZ)‐induced diabetic hamsters. The impact of chymase‐specific inhibitors, TEI‐E00548 and TEI‐F00806, on myocardial fibrosis, and increased levels of intracardiac AngII, accumulation of 8‐hydroxy‐2′‐deoxyguanosine (an oxidative stress marker in urine and heart tissue) and expression of heart NOX4 in diabetic hamsters were investigated.

Results:  Myocardial chymase expression was markedly upregulated in STZ hamsters in a glucose‐dependent manner. A total of 8 weeks after STZ administration, the diabetic hamsters showed enhanced oxidative stress and NOX4 expression in the heart, in parallel with increased myocardial AngII production. Oral administration of chymase‐specific inhibitors, TEI‐F00806 and TEI‐E00548, normalized heart AngII levels, and completely reversed NOX4‐induced oxidative stress and myocardial fibrosis in STZ‐induced diabetic hamsters, although they did not affect the activity of the systemic renin–angiotensin system or systolic blood pressure.

Conclusions:  Chymase inhibition might prevent oxidative stress and diabetic cardiomyopathy at an early stage by reducing local AngII production. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2012.00202.x, 2012)
Designing a benthic monitoring programme with multiple conflicting objectives
Authors: Bijleveld Allert I. , van Gils Jan A. , van der Meer Jaap , Dekinga Anne , Kraan Casper , van der Veer Henk W. , Piersma Theunis
Published: February 2012

1. Sound conservation and management advice usually requires spatial data on animal and plant abundances. The expense of programmes to determine species distributions and estimates of population sizes often limits sample size. To maximise effectiveness at minimal costs, optimisations of such monitoring efforts are critical. A monitoring programme can have multiple objectives with demands on the optimal sampling design that are often in conflict. Here, we develop an optimal sampling design for monitoring programmes with conflicting objectives, building on an existing intertidal benthic monitoring programme in the Dutch Wadden Sea and simulation models bounded in their parameter spaces by these data.

2. We distinguish three possible objectives: (1) estimation of temporal changes and spatial differences in abundance and (2) mapping, that is, prediction of abundances at unsampled locations. Mapping abundances requires model‐based analyses using autocorrelation models. Such analyses are as good as the model fits the data; therefore, the final objective was (3) accurately estimating model autocorrelation parameters. To compare sampling designs, we used the following criteria: (1) minimum detectable difference in mean between two time periods or two areas, (2) mean prediction error and (3) estimation bias of autocorrelation parameters.

3. Using Monte Carlo simulations, we compared five sampling designs with respect to these criteria (i.e. simple random, grid, two types of transects, and grid with random replacements) at four levels of naturally occurring spatial autocorrelation.

4. The ideal sampling design for objectives (1) and (2) was grid sampling and for objective (3) random sampling. The sampling design that catered best for all three objectives combined was grid sampling with a number of random samples placed on gridlines.

5. Grid sampling with a number of random samples is considered an accurate and powerful tool with the highest effectiveness. This sampling design is widely applicable and allows for accurate estimates of population sizes, monitoring of population trends, comparisons of populations/trends between years or areas, modelling autocorrelation, mapping species distributions and a mechanistic understanding of species distribution processes.
Caspase-mediated pro-apoptotic interaction of panaxadiol and irinotecan in human colorectal cancer cells
Authors: Du Guang-Jian , Wang Chong-Zhi , Zhang Zhi-Yu , Wen Xiao-Dong , Somogyi Jacqueline , Calway Tyler , He Tong-Chuan , Du Wei , Yuan Chun-Su
Published: February 2012

Objectives

Panaxadiol is a purified sapogenin of ginseng saponins that exhibits anticancer activity. Irinotecan is a second-line anticancer drug, but clinical treatment with irinotecan is limited due to its side effects. In this study, we have investigated the possible synergistic anticancer effects of panaxadiol and irinotecan on human colorectal cancer cells and explored the potential role of apoptosis in their synergistic activity.

Key findings

The combination of panaxadiol and irinotecan significantly enhanced antiproliferative effects in HCT-116 cells (P < 0.05). Cell cycle analysis demonstrated that combining irinotecan treatment with panaxadiol significantly increased the G1-phase fractions of cells, compared with irinotecan treatment alone. In apoptotic assays, the combination of panaxadiol and irinotecan significantly increased the percentage of apoptotic cells compared with irinotecan alone (P < 0.01). Increased activity of caspase-3 and caspase-9 was observed after treating with panaxadiol and irinotecan. The synergistic apoptotic effects were supported by docking analysis, which demonstrated that panaxadiol and irinotecan bound two different chains of the caspase-3 protein.

Conclusions

Data from this study suggested that caspase-3- and caspase-9-mediated apoptosis may play an important role in the panaxadiol enhanced antiproliferative effects of irinotecan on human colorectal cancer cells.
Preparation and characterisation of novel spray-dried nano-structured para-aminosalicylic acid particulates for pulmonary delivery: impact of ammonium carbonate on morphology, chemical composition and solid state
Authors: Gad Shadeed , Tajber Lidia , Corrigan Owen I , Healy Anne Marie
Published: February 2012

Objectives

The objective of this work was to spray dry p-aminosalicylic acid (PAS) and its ammonium salt and to investigate the impact of the pore-forming agent, ammonium carbonate (AC), on the morphological, aerodynamic and physicochemical properties of the resulting powders.

Methods

Microparticles were prepared by spray drying from ethanol/water solvent systems. Their solid-state properties were evaluated by scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis and in-vitro deposition, using the twin impinger.

Key Findings

The physicochemical properties of PAS were altered on spray drying with AC and a new solid state was produced. The solution composition impacted on the morphology of the resulting powders, which ranged from irregular crystal agglomerates to spherical crystal clusters and porous microparticles. The chemical composition, structure and morphology were dependent on process inlet temperature, low inlet temperatures resulting in a novel solid of stoichiometry; PAS : ammonia : water, 2 : 1 : 0.5. At higher temperatures pure PAS was obtained. In-vitro deposition studies showed an increase in emitted dose from spray dried drug, relative to the micronised PAS.

Conclusions

Under appropriate process conditions AC interacts with the acidic PAS, resulting in the formation of a novel solid-state drug phase. Spray-dried PAS powders have potential for pulmonary delivery.
Dissolution testing of oral modified-release dosage forms
Authors: Garbacz Grzegorz , Klein Sandra
Published: February 2012

Objectives

The in-vivo performance of oral modified-release dosage forms is determined by the interplay of various physiological- and dosage-form-derived parameters. Thus it is often a challenge to predict the in-vivo drug-release behaviour from modified-release dosage forms based solely on in-vitro release rates.

Key findings

For a long time the most common procedure to obtain in-vitro/in-vivo correlations for modified-release formulations was to apply test conditions typically used for quality control on a retrospective basis. Such so-called ‘compendial approaches’ are typically not biorelevant with respect to volumes, composition and physicochemical properties of the test media and also do not take into consideration the mechanical and hydrodynamic forces that may influence dosage-form behaviour during passage through the gastrointestinal tract.

This review provides an overview of physiological conditions relevant to in-vivo drug release and of dissolution models which, based on current scientific findings on human gastrointestinal physiology, have been developed to enable a better prediction of the in-vivo performance of oral MR dosage forms.
School‐related conscientiousness, alcohol drinking, and cigarette smoking in a representative sample of English school pupils
Authors: Hagger‐Johnson Gareth , Bewick Bridgette M. , Conner Mark , O’Connor Daryl , Shickle Darren
Published: February 2012

Objective. Conscientiousness is a strong predictor of health behaviours and better health outcomes. However, longitudinal data from representative samples of the population and from adolescents are rare. Therefore, the objective of this study was to establish whether school‐related conscientiousness was associated with the onset and change in alcohol drinking and cigarette smoking frequency, in a large representative cohort of school pupils in England.

Methods. A school‐related conscientiousness facet in the Longitudinal Study of Young People in England (LSYPE, N= 15,770) was identified, which had concurrent validity with conscientiousness and its facets. Latent growth curve modelling (LGCM) was used to model initial alcohol drinking and cigarette smoking frequency, over 4 years of the study.

Results. For all pupils, higher conscientiousness predicted lower initial alcohol drinking across 4 years (from year 9 to 12). In females, higher conscientiousness was marginally associated with a slower rate of change in the move from non‐drinker to drinker (linear slope), but significantly associated with a faster upturn in this change (quadratic slope). Higher conscientiousness predicted non‐smoker status, greater initial cigarette smoking frequency for pupils (in smokers) but a change towards less frequent smoking (in smokers). Associations were not explained by parental educational, income, or monitoring; regularity of seeing friends; psychiatric morbidity; or birth weight.

Conclusions. School‐related conscientiousness is an important facet, predictive of health behaviour onset and change during adolescence. The study illustrates the value of representative population samples that allow researchers to study associations between personality traits and health behaviours over time.
Let another praise you? The effects of source and attributional content on responses to group‐directed praise
Authors: Rabinovich Anna , Morton Thomas A. , Crook Michael , Travers Claire
Published: February 2012

Not all types of praise may be equally stimulating. Instead, positive feedback carries different meaning depending on the source that delivers it and the attributions for success that it contains. In the present study, source (in‐group vs. out‐group) of praise and its content (attributing success to internal vs. external causes) were experimentally manipulated. The results revealed that there was a significant interaction between source and content of praise on performance in a praise‐related task. As predicted, participants exposed to out‐group praise were motivated by external attributions for success rather than by internal attributions. Conversely, when praise originated from an in‐group source, the attributional content of praise did not affect performance. This effect of source and content of praise on relevant behaviour was mediated by willingness to protect group image. Thus, responses to praise are contingent on what it implies about group success – corresponding to patterns demonstrated in previous work on group‐directed criticism.
Local spectral equidistribution for Siegel modular forms and applications
Authors: Kowalski Emmanuel , Saha Abhishek , Tsimerman Jacob
Published: February 2012

We study the distribution, in the space of Satake parameters, of local components of Siegel cusp forms of genus 2 and growing weight k, subject to a specific weighting which allows us to apply results concerning Bessel models and a variant of Petersson’s formula. We obtain for this family a quantitative local equidistribution result, and derive a number of consequences. In particular, we show that the computation of the density of low-lying zeros of the spinor L-functions (for restricted test functions) gives global evidence for a well-known conjecture of Böcherer concerning the arithmetic nature of Fourier coefficients of Siegel cusp forms.
A non-Archimedean Montel’s theorem
Authors: Favre Charles , Kiwi Jan , Trucco Eugenio
Published: February 2012

We prove a version of Montel’s theorem for analytic functions over a non-Archimedean complete valued field. We propose a definition of normal family in this context, and give applications of our results to the dynamics of non-Archimedean entire functions.
Sex, ageing and resting blood pressure: gaining insights from the integrated balance of neural and haemodynamic factors
Authors: Hart Emma C. , Joyner Michael J. , Wallin B. Gunnar , Charkoudian Nisha
Published: February 2012

Young women tend to have lower blood pressure, and less risk of hypertension, compared to young men. As people age, both blood pressure and the risk of hypertension increase in both sexes; this occurs most strikingly in women after menopause. However, the mechanisms for these influences of sex and age remain incompletely understood. In this review we are specifically interested in the interaction between neural (sympathetic nerve activity; SNA) and haemodynamic factors (cardiac output, blood pressure and vascular resistance) and how these change with sex and age. While peripheral vascular SNA can vary 7‐ to 10–fold among normotensive young men and women, it is reproducible in a given individual. Surprisingly, higher levels of SNA are not associated with higher blood pressures in these groups. In young men, high SNA is associated with higher total peripheral vascular resistance (TPR), and appears to be balanced by lower cardiac output and less peripheral vascular responsiveness to adrenergic stimulation. Young women do not exhibit the SNA–TPR relationship. Recent evidence suggests that β–adrenergic vasodilatation offsets the vasoconstrictor effects of α–adrenergic vasoconstriction in young women, which may contribute to the generally lower blood pressures in this group. Sympathetic nerve activity increases with age, and in groups over 40, levels of SNA are more tightly linked to levels of blood pressure. The potentially protective β–adrenergic effect seen in young women appears to be lost after menopause and probably contributes to the increased blood pressure and increased risk of hypertension seen in older women.
Peripheral vasodilatation determines cardiac output in exercising humans: insight from atrial pacing
Authors: Bada A. A. , Svendsen J. H. , Secher N. H. , Saltin B. , Mortensen S. P.
Published: February 2012

Key points 

During exercise, cardiac output is regulated to match oxygen delivery to the metabolic demand.

This study evaluated the role of heart rate and peripheral vasodilation in the regulation of cardiac output during exercise.

We increased heart rate by atrial pacing in 10 healthy male individuals during three different conditions: at rest, during exercise and during femoral arterial ATP infusion at rest.

Increasing the heart rate by atrial pacing by up to 54 beats min−1 did not increase cardiac output in any of the three given conditions as there was a proportional decrease in stroke volume.

These results indicate that cardiac output is regulated by changes in peripheral vasodilatation, whereas an increase in heart rate is less important.
Epidermal growth factor chronically upregulates Ca2+‐dependent Cl− conductance and TMEM16A expression in intestinal epithelial cells
Authors: Mroz Magdalena S. , Keely Stephen J.
Published: February 2012

Key points 

Cl− secretion, the predominant driving force for fluid secretion in the intestine, can be dysregulated in conditions of disease, such as cystic fibrosis.

We have previously shown that acute exposure to epidermal growth factor (EGF) chronically upregulates the capacity of colonic epithelial cells to secrete Cl−.

Here, we show that the effects of EGF are mediated by upregulation of the Ca2+‐dependent Cl− channel, transmembrane protein 16A (TMEM16A), in the apical membrane of colonic epithelial cells.

EGF‐induced TMEM16A expression is mediated by sequential activation of phosphatidylinositol 3‐kinase and PKCδ.

These findings are among the first to elucidate molecular mechanisms that regulate TMEM16A expression in epithelial cells and suggest the channel represents a good target for development of new therapeutics for intestinal transport disorders.
NHE1 knockout reduces blood pressure and arterial media/lumen ratio with no effect on resting pHi in the vascular wall
Authors: Boedtkjer Ebbe , Damkier Helle H. , Aalkjaer Christian
Published: February 2012

Key points 

Small arteries are important for regulation of blood pressure and local blood flow.

Changes in intracellular pH alter artery tone although the mechanistic background has been unclear.

Using knockout mice for Na+/H+ exchanger NHE1 with reduced acid extrusion from cells in the arterial wall and low intracellular pH in the absence of CO2/HCO3‐, we show that intracellular acidification alters enzymatic activity and consequently artery dilatation and contraction.

Although lack of NHE1 does not affect intracellular pH in the arterial wall when CO2/HCO3− is present, arteries from NHE1 knockout mice have thinner walls and produce less active force due to reduced volume and cross‐sectional area of individual smooth muscle cells.

These results highlight the interplay between intracellular pH and artery function, provide new targets to consider for modulating artery structure, and underscore the need to evaluate acid–base transport in conditions of vascular disease and blood pressure disturbances.
Are all spinal segments equal: intrinsic membrane properties of superficial dorsal horn neurons in the developing and mature mouse spinal cord
Authors: Tadros M. A. , Harris B. M. , Anderson W. B. , Brichta A. M. , Graham B. A. , Callister R. J.
Published: February 2012

Key points 

Much of what we know about pain signalling in the spinal cord comes from studies undertaken in lumbosacral spinal segments that innervate the hindlimb.

Clinical evidence suggests sensory information from viscera and head and neck tissues is processed differently from sensations arising in the hindlimb.

Here we show that intrinsic membrane properties, a major determinate of neuronal output, change dramatically during development in superficial dorsal horn (SDH) neurons from lumbar, thoracic and upper cervical segments in the mouse. In contrast, intrinsic membrane properties are generally conserved in SDH neurons along the length of the spinal cord in both neonates and adults.

Our data suggest the intrinsic membrane properties of SDH neurons involved in pain signalling do not contribute to the marked differences in pain experienced in the limbs, viscera and head and neck.
Computational Fluid Dynamics Simulations of Flow and Heat Transfer in a Preswirl System: Influence of Rotating-Stationary Domain Interface
Authors: Karnahl Joachim , von Wolfersdorf Jens , Tham Kok-Mun , Wilson Mike , Lock Gary
Published: February 2012

This paper presents computational fluid dynamics (CFD) predictions of flow and heat transfer for an over-swirled low-radius preswirl system and comparison with experimental data. The rotor-stator CFD model comprises a stationary domain with the preswirl nozzles and a rotating domain with the receiver holes. The fluid-dynamic conditions feature an over-swirled system with a swirl ratio at the nozzle radius βp = 1.4−1.5 and rotational Reynolds number ReΦ = 0.8 × 106 and 1.2 × 106. Three different treatments for the rotating and stationary domain interface are used to evaluate the influence on the flow and heat transfer behavior: a stationary approach (including Coriolis forces in the rotating domain) with “direct connection” and fixed angle between preswirl nozzle and receiver holes; a stationary approach with circumferential averaging of the velocity at radial bands; and a full transient simulation with the rotating domain capturing the unsteady flow due to the rotating receiver holes. Results at different circumferential angles show high variability in pressure and velocity distributions at the preswirl inlet nozzle radius. Circumferential averaging of these flow parameters lead to an alignment of the pressures and velocities between the three different interface approaches. Comparison with experimental pressure and swirl-ratio data show a quantitative agreement but the CFD results feature a systematic overestimation outward of the preswirl nozzle radius. Heat transfer coefficient distributions at the rotor surface show the effect of the different interface approaches and dependence on the flow structure (for example the impinging jet and vortex structures). The three different interface approaches result in significant differences in the computed heat transfer coefficients between pairs of receiver holes. Circumferentially averaged heat transfer coefficients inward of the receiver holes radius show good agreement between the transient and stationary direct connection interfaces, whereas those for the circumferential averaging interface differ, contrary to the flow parameters, due to smoothing of local effects from the preswirl jets.
Flagellin Takes Its Toll
Authors: Mueller Kristen L.
Published: February 2012

Bacterially derived flagellin binds to an innate immune receptor to form a tail-to-tail heterodimeric signaling complex.
From NO to Complement
Authors: Ash Caroline
Published: February 2012

Expression of nitric oxide synthase followed by peroxidase activity makes
Plasmodium
visible to the insect’s complement system.
Molecular Epidemiological Analysis of Escherichia coli Sequence Type ST131 (O25:H4) and
bla
CTX-M-15
among Extended-Spectrum-β-Lactamase-Producing E. coli from the United States, 2000 to 2009
Authors: Johnson James R. , Urban Carl , Weissman Scott J. , Jorgensen James H. , Lewis James S. , Hansen Glen , Edelstein Paul H. , Robicsek Ari , Cleary Timothy , Adachi Javier , Paterson David , Quinn John , Hanson Nancy D. , Johnston Brian D. , Clabots Connie , Kuskowski Michael A. ,   the AMERECUS Investigators
Published: February 2012

Escherichia coli
sequence type ST131 (from phylogenetic group B2), often carrying the extended-spectrum-β-lactamase (ESBL) gene
bla
CTX-M-15
, is an emerging globally disseminated pathogen that has received comparatively little attention in the United States. Accordingly, a convenience sample of 351 ESBL-producing
E. coli
isolates from 15 U.S. centers (collected in 2000 to 2009) underwent PCR-based phylotyping and detection of ST131 and
bla
CTX-M-15
. A total of 200 isolates, comprising 4 groups of 50 isolates each that were (i)
bla
CTX-M-15
negative non-ST131, (ii)
bla
CTX-M-15
positive non-ST131, (iii)
bla
CTX-M-15
negative ST131, or (iv)
bla
CTX-M-15
positive ST131, also underwent virulence genotyping, antimicrobial susceptibility testing, and pulsed-field gel electrophoresis (PFGE). Overall, 201 (57%) isolates exhibited
bla
CTX-M-15
, whereas 165 (47%) were ST131. ST131 accounted for 56% of
bla
CTX-M-15
-positive- versus 35% of
bla
CTX-M-15
-negative isolates (
P
< 0.001). Whereas ST131 accounted for 94% of the 175 total group B2 isolates, non-ST131 isolates were phylogenetically distributed by
bla
CTX-M-15
status, with groups A (
bla
CTX-M-15
-positive isolates) and D (
bla
CTX-M-15
-negative isolates) predominating. Both
bla
CTX-M-15
and ST131 occurred at all participating centers, were recovered from children and adults, increased significantly in prevalence post-2003, and were associated with molecularly inferred virulence. Compared with non-ST131 isolates, ST131 isolates had higher virulence scores, distinctive virulence profiles, and more-homogeneous PFGE profiles.
bla
CTX-M-15
was associated with extensive antimicrobial resistance and ST131 with fluoroquinolone resistance. Thus,
E. coli
ST131 and
bla
CTX-M-15
are emergent, widely distributed, and predominant among ESBL-positive
E. coli
strains in the United States, among children and adults alike. Enhanced virulence and antimicrobial resistance have likely promoted the epidemiological success of these emerging public health threats.
Complete Genome Sequence of Salmonella enterica Serovar Typhimurium Bacteriophage SPN3UB
Authors: Lee Ju-Hoon , Shin Hakdong , Ryu Sangryeol
Published: February 2012

Salmonella
is one of the major pathogenic bacteria that cause food poisoning. To elucidate the host infection mechanism of
Salmonella enterica
serovar Typhimurium-targeting phages, the bacteriophage SPN3UB was isolated from a chicken fecal sample. This phage belongs morphologically to the
Siphoviridae
family and infects the host via the O antigen of lipopolysaccharide (LPS). To further understand its infection mechanism, we completely sequenced and analyzed the genome. Here, we announce its complete genome sequence and report major findings from the genomic analysis results.
How they won Rugby World Cup through height, mass and collective experience
Authors: Sedeaud Adrien , Marc Andy , Schipman Julien , Tafflet Muriel , Hager Jean-Philippe , Toussaint Jean-François
Published: February 2012

Objectives

To investigate the evolution of anthropometric characteristics in World Cup rugby players and identify elements associated with performance.

Design

Age, weight and height were collected for 2692 World Cup rugby players as well as rankings in each World Cup, and collective experience of winners, finalists, semifinalists and quarter finalists in comparison to the rest of the competitors. Anthropometric parameters were compared according to age and position (back and forwards).

Results

From 1987 to 2007, forwards and backs have become heavier by 6.63 and 6.68 kg and taller by 0.61 and 1.09 cm, respectively. The collective experience of the forwards' pack is a value increasing with the final ranking attained, as well as the weight of forwards and the height of backs.

Conclusions

For all Rugby World Cups, the highest performing teams have the tallest backs and heaviest forwards with the highest percentage of collective experience.
THREE QUASI-LOCAL MASSES
Authors: KATZ NEIL N. , KHURI MARCUS A.
Published: February 2012

We propose a definition of quasi-local mass based on the Penrose Inequality. Two further definitions are given by measuring distortions of the exponential map.
BIFURCATION IN A PIECEWISE LINEAR CIRCUIT WITH SWITCHING BOUNDARIES
Authors: ZHANG ZHENGDI , BI QINSHENG
Published: February 2012

By introducing time-dependent power source, a periodically excited piecewise linear circuit with double-scroll is established. In the absence of the excitation, all possible equilibrium points as well as the stability conditions are presented. Analyzing the corresponding characteristic equations with perturbation method, Hopf bifurcation conditions associated with the equilibria are derived, which can be demonstrated by the numerical simulations. The Hopf bifurcations of the two symmetric equilibrium points may cause two symmetric periodic orbits, which lead to single-scroll chaotic attractors via sequences of period-doubling bifurcations with the variation of the parameters. The two chaotic attractors expand to interact with each other to form an enlarged chaotic attractor with double-scroll. The behaviors on the switching boundaries are investigated by the generalized Jacobian matrix. When periodic excitation is applied to work on the circuit, three periodic orbits with the frequency of the excitation may exist, which can be called generalized equilibrium points (GEPs) with the same characteristic polynomials as those of the corresponding equilibrium points for the autonomous case. It is shown that when the trajectories do not pass across the switching boundaries, the solutions are the same as the GEPs. However, when the trajectories pass across the switching boundaries, complicated behaviors will take place. Three forms of chaotic attractors via different bifurcations can be observed and the influence of the switching boundaries on the phase portraits is discussed to explore the mechanism of the dynamical evolution.
A NOVEL RESULT IN THE FIELD OF NONLINEAR STABILITY ANALYSIS OF BOILING WATER REACTORS
Authors: LANGE CARSTEN , HENNIG DIETER , HURTADO ANTONIO
Published: February 2012

The nonlinear stability analysis of boiling water nuclear reactors (BWRs) is conducted with the aid of so-called advanced, well validated, system codes and an advanced reduced order model to build a detailed mathematical understanding of the BWR behavior in the practical relevant parameter space. In the last years, the existence of Hopf-bifurcation points was confirmed by some researchers. In the framework of this paper, a parameter region was analyzed in which the coexistence of different stability states is realized. As a novel result, we found a parameter region in which stable fixed points, unstable limit cycles and stable limit cycles coexist. This system behavior can be explained by a saddle-node bifurcation of cycles (turning point). The existence of this solution type in a BWR system indicates the possibility of large amplitude limit cycle oscillations in the linear stable region.
ANALYSIS OF NEW FOUR-DIMENSIONAL CHAOTIC CIRCUITS WITH EXPERIMENTAL AND NUMERICAL METHODS
Authors: HUANG GUO-QING , WU XIN
Published: February 2012

Dynamically qualitative properties of individual orbits in a new four-dimensional nonlinear circuit are observed on an oscilloscope. Meanwhile, they are also traced numerically with the help of some methods for finding chaos. Comparisons show that the observed results are consistent with the computed ones to a great extent. In addition, the bifurcation, Lyapunvon spectra, fast Lyapunov indicators and small alignment indexes represent almost the same rules of transitivity to chaos on a control parameter. It is found when the parameter has a threshold value from order to chaos, and the chaos gets stronger and stronger, the parameter is smoothly varied from small to large. In particular, the entire set of Lyapunov exponents can lead to another threshold value of the parameter from chaotic to hyperchaotic behaviors.
Neuroinflammation in the Aging Down Syndrome Brain; Lessons from Alzheimer's Disease
Authors: Wilcock Donna M.
Published: February 2012

Down syndrome (DS) is the most genetic cause of mental retardation and is caused by the triplication of chromosome 21. In addition to the disabilities caused early in life, DS is also noted as causing Alzheimer's-disease-like pathological changes in the brain, leading to 50–70% of DS patients showing dementia by 60–70 years of age. Inflammation is a complex process that has a key role to play in the pathogenesis of Alzheimer's disease. There is relatively little understood about inflammation in the DS brain and how the genetics of DS may alter this inflammatory response and change the course of disease in the DS brain. The goal of this review is to highlight our current understanding of inflammation in Alzheimer's disease and predict how inflammation may affect the pathology of the DS brain based on this information and the known genetic changes that occur due to triplication of chromosome 21.
Chinese Herb and Formulas for Promoting Blood Circulation and Removing Blood Stasis and Antiplatelet Therapies
Authors: Liu Yue , Yin Hui-Jun , Shi Da-zhuo , Chen Ke-ji
Published: February 2012

Atherothrombosis, which directly threatens people's health and lives, is the main cause of morbidity and mortality all over the world. Platelets play a key role in the development of acute coronary syndromes (ACSs) and contribute to cardiovascular events. Oral antiplatelet drugs are a milestone in the therapy of cardiovascular atherothrombotic diseases. In recent years, many reports have shown the possibility that “resistance” to oral anti-platelet drugs and many adverse reactions, such as serious bleeding risk, which provides an impetus for developing new anti-platelet drugs possesses highly efficiency and fewer adverse effects. Study on the blood stasis syndrome and promoting blood circulation and removing blood stasis is the most active field of research of integration of traditional and western medicine in China. Blood-stasis syndrome and platelet activation have close relationship, many Chinese herb and formulas for promoting blood circulation and removing blood stasis possess definite anti-platelet effect. This paper covers the progress of anti-platelet mechanism of Chinese herb and formulas for promoting blood circulation and removing blood stasis and is to be deeply discussed in further research.
Studies on the Transport of Aromatic Solvents through Filled Natural Rubber
Authors: Igwe Isaac O. , Ezeani Obumneme E.
Published: February 2012

The transport of three aromatic solvents (benzene, toluene and xylene) through snail shell powder filled natural rubber was studied at 313, 333, and 353 K by conventional weight-gain experiments. The effects of snail shell powder content, particle size, nature of solvent, and temperature on the transport characteristics of natural rubber were determined. The estimated Arrhenius activation energies for the processes of sorption, diffusion, and permeation showed that the activation energies were highest in xylene at all the filler contents investigated. The calculated enthalpies, and entropies of sorption were all positive for the solvents investigated. Similarly, the change in the estimated free energies of sorption were all positive; an indication of the non-spontaneity of the solubility of snail shell powder filled natural rubber in the aromatic solvents at 313 k.
The Treatment of Breast Cancer Using Liposome Technology
Authors: Brown Sarah , Khan David R.
Published: February 2012

Liposome-based chemotherapeutics used in the treatment of breast cancer can in principle enhance the therapeutic index of otherwise unencapsulated anticancer drugs. This is partially attributed to the fact that encapsulation of cytotoxic agents within liposomes allows for increased concentrations of the drug to be delivered to the tumor site. In addition, the presence of the phospholipid bilayer prevents the encapsulated active form of the drug from being broken down in the body prior to reaching tumor tissue and also serves to minimize exposure of the drug to healthy sensitive tissue. While clinically approved liposome-based chemotherapeutics such as Doxil have proven to be quite effective in the treatment of breast cancer, significant challenges remain involving poor drug transfer between the liposome and cancerous cells. In this review, we discuss the recent advancements made in the development of liposome-based chemotherapeutics with respect to improved drug transfer for use in breast cancer therapy.
Softening the “Crystal Scaffold” for Life’s Emergence
Authors: Mitra-Delmotte Gargi , Mitra Asoke Nath
Published: February 2012

Del Giudice’s group studies how water can organize on hydrophilic surfaces forming coherent domains (loaning energy from the quantum vacuum), plus quasifree electrons, whose excitations produce cold vortices, aligning to ambient fields. Their electric and magnetic dipolar modes can couple to oscillatory (electric-organic dipoles) and/or rotary (magnetic-mineral dipoles), besides responding to magnetic potentials. Thus, imprinted electromagnetic patterns of catalytic colloids—compared with Cairns-Smith’s “crystal scaffold”—on their structured water partners could have equipped the latter with a selection basis for “choosing” their context-based “soft-matter” (de Gennes) replacements. We consider the potential of the scenario of an external control on magnetic colloids forming in the Hadean hydrothermal setting (of Russell and coworkers)—via a magnetic rock field—conceptually enabling self-assembly, induction of asymmetries, response effects towards close-to-equilibrium dynamics, and associative networks, besides providing a coherent environment for stabilizing associated symmetry-broken quanta and their feedback interactions with those of coherent water domains, to address the emergence of metabolism and replication.
Characterisation of Flavonoid Aglycones by Negative Ion Chip-Based Nanospray Tandem Mass Spectrometry
Authors: Gates Paul J. , Lopes Norberto P.
Published: February 2012

Flavonoids are one of the most important classes of natural products having a wide variety of biological activities. There is wide interest in a range of medical and dietary applications, and having a rapid, reliable method for structural elucidation is essential. In this study a range of flavonoid standards are investigated by chip-based negative ion nanospray mass spectrometry. It was found that the different classes of flavonoid studied have a combination of distinct neutral losses from the precursor ion [M-H]−along with characteristic low-mass ions. By looking only for this distinct pattern of product ions, it is possible to determine the class of flavonoid directly. This methodology is tested here by the analysis of a green tea extract, where the expected flavonoids were readily identified, along with quercetin, which is shown to be present at only about 2% of the most intense ion in the spectrum.
Evaluation the Effects of Some Relevant Parameters on Elastic Modulus of Pumpkin Seed and Its Kernel
Authors: Abbaspour-Fard Mohammad Hossein , Khodabakhshian Rasool , Emadi Bagher , Sadrnia Hasan
Published: February 2012

The elastic modulus of two varieties of Iranian pumpkin seed and its kernel (namely, Zaria and Gaboor) were evaluated as a function of size (large, medium, and small), loading rate (2, 5, 8, and 10 mm/min), and moisture content (4, 7.8, 14, and 20% d.b) under quasistatic compression loading. The results showed that elastic modulus of pumpkin seed and its kernel decreased with increasing moisture content and also increasing loading rate, for the varieties under study. The average modulus of elasticity of pumpkin seed from 68.86 to 46.65 Mpa and from 97.14 to 74.93 Mpa was obtained for moisture levels ranging from 4 to 20%, for Zaria and Gaboor varieties, respectively. The elastic modulus of pumpkin seed decreased from 73.55 to 43.04 Mpa and from 101.83 to 71.32 Mpa with increasing loading rate from 2 to 10 mm/min for Zaria and Gaboor varieties, respectively.
Effects of Saponins against ClinicalE. coliStrains and Eukaryotic Cell Line
Authors: Arabski Michał , Węgierek-Ciuk Aneta , Czerwonka Grzegorz , Lankoff Anna , Kaca Wiesław
Published: February 2012

Saponins are detergent-like substances showing antibacterial as well as anticancer potential. In this study, the effects of saponins fromQuillaja saponariawere analyzed against prokaryotic and eukaryotic cells. Multidrug-resistant clinicalE. colistrains were isolated from human urine. As eukaryotic cells, the CHO-K1 cell lines were applied. Antibacterial effect of ampicillin, streptomycin, and ciprofloxacin in the presence of saponins was measured by cultivation methods. Properties of saponins against CHO-K1 cells were measured by the MTT test, hemolysis assay and flow cytometry. Saponin fromQuillaja saponariahas a cytotoxic effect at concentrations higher than 25 μg/mL and in the range of 12–50 μg/mL significantly increases the level of early apoptotic cells. Saponin at dose of 12 μg/mL enhances the sixE. colistrains growth. We postulate that saponins increase the influx of nutrients from the medium intoE. colicells. Saponins do not have synergetic effects on antibacterial action of tested antibiotics. In contrary, in the presence of saponins and antibiotics, more CFU/mLE. colicells were observed. This effect was similar to saponins action alone towardsE. colicells. In conclusion, saponins was cytotoxic against CHO-K1 cells, whereas againstE. colicells this effect was not observed.
Calcitriol Inhibits Hedgehog Signaling and Induces Vitamin D Receptor Signaling and Differentiation in thePatchedMouse Model of Embryonal Rhabdomyosarcoma
Authors: Uhmann Anja , Niemann Hannah , Lammering Bérénice , Henkel Cornelia , Heß Ina , Rosenberger Albert , Dullin Christian , Schraepler Anke , Schulz-Schaeffer Walter , Hahn Heidi
Published: February 2012

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Aberrant Hedgehog (Hh) signaling is characteristic of the embryonal subtype (ERMS) and of fusion-negative alveolar RMS. In the mouse, ERMS-like tumors can be induced by mutations in the Hh receptor Patched1 (Ptch). As in humans these tumors show increased Hh pathway activity. Here we demonstrate that the treatment with the active form of vitamin D3, calcitriol, inhibits Hh signaling and proliferation of murine ERMSin vivoandin vitro. Concomitantly, calcitriol activates vitamin D receptor (Vdr) signaling and induces tumor differentiation. In addition, calcitriol inhibits ERMS growth inPtch-mutant mice, which is, however, a rather late response. Taken together, our results suggest that exogenous supply of calcitriol could be beneficial in the treatment of RMS, especially in those which are associated with aberrant Hh signaling activity.
The Clinical and Prognostic Significance of Activated AKT-mTOR Pathway in Human Astrocytomas
Authors: El Habr Elias A. , Adamopoulos Christos , Levidou Georgia , Saetta Aggeliki A. , Korkolopoulou Penelope , Piperi Christina
Published: February 2012

Astrocytomas, the most common type of gliomas, and especially grade IV glioblastomas are “endowed” with strong proliferation and invasion potentials, high recurrence rate, and poor patients' prognosis. Aberrant signaling of AKT-mTOR (mammalian target of rapamycin) has been implicated in carcinogenesis. This paper is focused on the impact of deregulated AKT-mTOR signaling components in the clinical outcome and prognosis of human astrocytomas. Current therapeutic targeting of astrocytomas with AKT-mTOR inhibitors in preclinical and clinical stage is also discussed, including future perspectives regarding the management of these devastating tumors.
Fabrication of Aligned Side‐by‐Side TiO2/SnO2 Nanofibers via Dual‐Opposite‐Spinneret Electrospinning
Authors: Xu Fu , Li Luming , Cui Xiaojie
Published: February 2012

Well‐aligned and uniform side‐by‐side bicomponent fibers have been produced via dual‐opposite‐spinneret electrospinning. Side‐by‐side TiO2/SnO2 nanofibers were obtained after calcining as‐spun fibers. The thermal degradation of the electrospun fibers was evaluated using combined thermogravimetry and differential thermal analysis (TG‐DTA), and the crystal structure of calcined nanofibers was investigated by X‐ray diffraction (XRD). The fabricated TiO2/SnO2 nanofibers expose both TiO2 mainly consisting of anatase phase and rutile‐type SnO2 to the surface, which is appropriate for photocatalytic materials.
Calreticulin Is a Negative Regulator of Bronchial Smooth Muscle Cell Proliferation
Authors: Miglino Nicola , Roth Michael , Lardinois Didier , Tamm Michael , Borger Peter
Published: February 2012

Background. Calreticulin controls the C/EBPαp42/p30 at the translational level trough a cis-regulatory CNG rich loop in the CEBPA mRNA. We determined the effects of steroids and long-acting beta-agonists on the p42/p30 ratio and on calreticulin expression in primary human bronchial smooth muscle (BSM) cells.Methods. The effects of budesonide (10−8 M) and formoterol (10−8 M) were studied in BSM cells pre-treated with siRNA targeting calreticulin. The expression of C/EBPαand calreticulin was determined by immuno-blotting. Automated cell counts were performed to measure proliferation.Results. All tested BSM cell lines (n=5) expressed C/EBPαand calreticulin. In the presence of 5% FBS, the p42/p30 ratio significantly decreased (n=3,P<0.05) and coincided with BSM cell proliferation. High levels of calreticulin were associated with a decreased p42/p30 isoform ratio. FBS induced the expression of calreticulin (n=3,P<0.05), which was further increased by formoterol. siRNA targeting calreticulin increased the p42/p30 ratio in non-stimulated BSM cells and significantly inhibited the proliferation of PDGF-BB-stimulated BSM cells (n=5,P<0.05). Neither budesonide nor formoterol restored the p42 isoform expression.Conclusions. Our data show calreticulin is a negative regulator of C/EBPαprotein expression in BSM cells. Modulation of calreticulin levels may provide a novel target to reduce BSM remodeling.
Genetic Testing for Minors: Comparison between Italian and British Guidelines
Authors: Tozzo Pamela , Caenazzo Luciana , Rodriguez Daniele
Published: February 2012

Genetic testing in children raises many important ethical, legal, and social issues. One of the main concerns is the ethically inappropriate genetic testing of minors. Various European countries established professional guidelines which reflect the different countries perspectives regarding the main ethical issues involved. In this paper, we analyze the Italian and the British guidelines by highlighting differences and similarities. We discuss presymptomatic, predictive, and carrier testing because we consider them to be the more ethically problematic types of genetic testing in minors. In our opinion, national guidelines should take into account the different needs in clinical practice. At the same time, in the case of genetic testing the national and supranational protection of minors could be strengthened by approving guidelines based on a common framework of principles and values. We suggest that the Oviedo Convention could represent an example of such a common framework or, at least, it could lead to articulate it.
Electrodeposition and Characterization of Nanocrystalline Ni‐Mo Catalysts for Hydrogen Production
Authors: Halim J. , Abdel-Karim R. , El-Raghy S. , Nabil M. , Waheed A.
Published: February 2012

Ni‐Mo nanocrystalline deposits (7–43 nm) with a nodular morphology were prepared by electrodeposition using direct current from citrate‐ammonia solutions. They exhibited a single Ni‐Mo solid solution phase. The size of the nodules increased as electroplating current density increased. The molybdenum content—estimated using EDX analysis—in the deposits decreased from about 31 to 11 wt% as the current density increased from 5 to 80 mA·cm−2. The highest microhardness value (285 Hv) corresponded to nanodeposits with 23% Mo. The highest corrosion resistance accompanied by relatively high hardness was detected for electrodeposits containing 15% Mo. Mo content values between 11 and 15% are recommended for obtaining better electrocatalytic activity for HER.