bluuebunny/crossref_metadata_2025 huggingface dataset:
Output Regulation Design for a Class of Nonlinear Systems With an Unknown Control Direction
Authors: Xu Dabo , Huang Jie
Published: December 2009

This paper presents the solution of the global robust output regulation problem for a class of nonlinear systems without knowing the control direction. The class of the systems is larger than previously studied strict output feedback systems of relative degree equal to one. The result is also applied to an asymptotic tracking problem associated with the well-known Lorenz system.
Simulation of Droplet Position Control in Digital Microfluidic Systems
Authors: Bhattacharjee Biddut , Najjaran Homayoun
Published: December 2009

Digital microfluidic systems (DMSs) are emerging with high potential to serve as true labs-on-a-chip (LOCs) systems for various chemical and biochemical analyses. Significant research efforts have been devoted toward the design and fabrication of improved LOC systems. Due to design, fabrication, and also runtime uncertainties, feedback control schemes must be incorporated to ensure reliability and accuracy of LOCs for practical use. This paper introduces the basics of the control analysis and design of the DMS, which is a relatively unexplored area in digital microfluidics. Based on the semi-empirical models of the droplet dynamic system, simulation results of the closed-loop position control of a droplet between two adjacent cells of a DMS are presented. The dynamic response is analyzed and discussed in relation to the operational parameters of a DMS.
Laptops and Diesel Generators: Introducing PhET Simulations to Teachers in Uganda
Authors: McKagan Sam
Published: December 2009

This article describes workshops for high school physics teachers in Uganda on inquiry-based teaching and PhET simulations. I hope it increases awareness of the conditions teachers face in developing countries and inspires others to give similar workshops. This work demonstrates what is possible with some concerted, but not extraordinary, effort.
Experimenting with constant current and voltage sources
Authors: Kortemeyer G.
Published: December 2009

While students might be perfectly able to calculate complex electric circuits using Kirchhoff's laws, they frequently fail to solve apparently much simpler conceptual problems involving circuits with just two or three light bulbs and a battery.1 McDermott and Shaffer found that one of the problems is that students conceptualize the battery as a constant current source rather than a constant voltage source.2 To help students confront this common misconception, we present some experiments and concept questions with an actual constant current source.
Inspiring your students
Authors: Riendeau Diane
Published: December 2009

Special thanks this month to Kathy Cloud, Hall High School, West Hartford, CT; Jennifer Groppe, Maret School, Washington, D.C.; and Dean Baird, Rio Americano High School, Carmichael, CA.
Two-dimensional condensation of nucleobases: A comparative study of halogen derivatives of cytosine
Authors: Fojt Lukáš , Vetterl Vladimír , Doneux Thomas
Published: December 2009

The high ability of self-association of nucleic acid components leads to a two-dimensional (2D) condensation at electrode surfaces. The driving force of the process resides in the intermolecular interactions, such as dispersion forces, hydrogen bonding or electrostatic interactions. In this study, the condensation of 5-halogen cytosine derivatives (5-fluorocytosine, 5-bromocytosine and 5-iodocytosine) at the hanging mercury drop electrode was investigated to evaluate the influence of the different types of intermolecular interactions in the phenomenon. All of these derivatives form 2D capacitance pits, but in distinct conditions of pH, concentrations and temperature. Dispersion forces are identified as the main contributor to the 2D condensation of 5-iodocytosine, while for 5-fluorocytosine this is hydrogen bonding in hemiprotonated dimers. The third derivative, 5-bromocytosine, is an intermediate case between the two formers.
Role of insulin-like growth factor 1 receptor and c-Src in endothelin-1- and angiotensin II-induced PKB phosphorylation, and hypertrophic and proliferative responses in vascular smooth muscle cellsThis article is one of a selection of papers published in a special issue on Advances in Cardiovascular Research.
Authors: Bouallegue Ali , Vardatsikos George , Srivastava Ashok K.
Published: December 2009

Endothelin-1 (ET-1) and angiotensin II (Ang II) are vasoactive peptides believed to contribute to the pathogenesis of vascular abnormalities such as hypertension, atherosclerosis, hypertrophy, and restenosis. The concept of transactivation of growth factor receptors, such as epidermal growth factor receptor (EGFR), in triggering vasoactive peptide-induced signaling events has gained much recognition during the past several years. We have demonstrated that insulin-like growth factor type 1 receptor (IGF-1R) plays a role in transducing the effect of H2O2, leading to protein kinase B (PKB) phosphorylation. Since vasoactive peptides elicit their responses through generation of reactive oxygen species, including H2O2, we investigated whether IGF-1R transactivation plays a similar role in ET-1- and Ang II-induced PKB phosphorylation and hypertrophic responses in vascular smooth muscle cells (VSMC). AG1024, a specific inhibitor of IGF-1R protein tyrosine kinase (PTK), attenuated both ET-1- and Ang II-induced PKB phosphorylation in a dose-dependent manner. ET-1 and Ang II treatment also induced the phosphorylation of tyrosine residues in the autophosphorylation sites of IGF-1R, which were blocked by AG1024. In addition, both ET-1 and Ang II evoked tyrosine phosphorylation of c-Src, a nonreceptor PTK, whereas pharmacological inhibition of c-Src PTK activity by PP2, a specific inhibitor of Src-family tyrosine kinase, significantly reduced PKB phosphorylation as well as tyrosine phosphorylation of IGF-1R induced by the 2 vasoactive peptides. Furthermore, protein and DNA synthesis enhanced by ET-1 and Ang II were attenuated by AG1024 and PP2. In conclusion, these data suggest that IGF-1R PTK and c-Src PTK play a critical role in mediating PKB phosphorylation as well as hypertrophic and proliferative responses induced by ET-1 and Ang II in A10 VSMC.
Brain renin–angiotensin–aldosterone system and ventricular remodeling after myocardial infarct: a reviewThis article is one of a selection of papers published in a special issue on Advances in Cardiovascular Research.
Authors: Westcott Katherine V. , Huang Bing S. , Leenen Frans H.H.
Published: December 2009

After a myocardial infarct (MI), a variety of mechanisms contribute to progressive cardiac remodeling and dysfunction. Progressive activation of central sympathoexcitatory pathways appears to depend on a neuromodulatory pathway, involving local production of aldosterone and release of endogenous ouabain-like compounds (‘ouabain’) possibly from magnocellular neurons in the supraoptic and paraventricular nuclei. ‘Ouabain’ may lower the membrane potential of neurons and thereby enhance activity of angiotensinergic pathways. These central pathways appear to coordinate progressive activation of several peripheral mechanisms such as sympathetic tone and circulating and cardiac renin–angiotensin–aldosterone system (RAAS). Central blockade of aldosterone production, mineralocorticoid receptors, ‘ouabain’ activity, or AT1 receptors similarly prevents activation of these peripheral mechanisms. Cardiac remodeling after MI involves progressive left ventricular dilation, fibrosis, and decrease in contractile performance. Central blockade of this neuromodulatory pathway causes a marked attenuation of the remodeling and dysfunction, presumably by inhibiting increases in (cardiac) sympathetic activity and RAAS. At the cellular level, these systems may contribute to the cardiac remodeling by activating proinflammatory cytokines and cardiac myocyte apoptosis. New therapeutic approaches, specifically preventing activation of this brain neuromodulatory pathway, may lead to more optimal and specific approaches to the prevention of heart failure after MI.
Dual effect of polyphenolic compounds on cardiac Na+/K+-ATPase during development and persistence of hypertension in ratsThis article is one of a selection of papers published in a special issue on Advances in Cardiovascular Research.
Authors: Vlkovičová Jana , Javorková Veronika , Mézešová Lucia , Pecháňová Olga , Andriantsitohaina Ramaroson , Vrbjar Norbert
Published: December 2009

The enzyme kinetics of cardiac Na+/K+-ATPase were used for characterizing the ATP- and Na+-binding sites after administration of red wine polyphenolic compounds (Provinol) during developing and sustained hypertension. Hypertension was induced in rats (LN group) by the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME, 40 mg·kg–1·day–1). Provinol (40 mg·kg–1·day–1) was applied during developing hypertension (LNPF4 group) and sustained hypertension (LNPF7/3 group). Provinol reduced the number of active Na+/K+-ATPase molecules in cardiac tissue, as indicated by decreased Vmaxvalues (by 33% in LNPF4 and 26% in LNPF7/3 compared with LN). Concerning qualitative properties of the enzyme, Provinol induced different effects on the ATP- and Na+-binding sites of Na+/K+-ATPase. The ATP-binding site was impaired by Provinol, as indicated by increased Kmvalue (by 52% in LNPF4 vs. LN), suggesting worsened utilization of substrate by the enzyme. In sustained hypertension, however, Provinol had no effect on the ATP-binding site, as indicated by unchanged Kmvalue (LNPF7/3 vs. LN). On the other hand, the Na+-binding site was protected by Provinol, as suggested by decreased KNavalue (by 72% in LNPF4 and 69% in LNPF7/3 vs. LN), indicating an increased affinity of the enzyme for sodium. Thus, Provinol appeared to stimulate the extrusion of Na+from cardiac cells, especially in the physiologically important range of sodium concentrations (2–10 mmol·L–1), during both developing and sustained hypertension.
TOWARDS A MORE FUNDAMENTAL THEORY BEYOND QUANTUM MECHANICS, AVOIDING THE SCHRÖDINGER PARADOX
Authors: CARAVAGLIOS FRANCESCO
Published: December 2009

The main distinction between classical mechanics and quantum mechanics is the lack in the latter of a full mechanical determinism: different final states can arise from the same physical state, after the measurement. No hidden variable is supposed to exist, nothing can discriminate two apparently identical states even if they give a different result.

In this paper we try to put the basis for a more fundamental theory that (approximately) coincides with quantum mechanics when comparing statistics, but it is more fundamental, since it mathematically describes measurement processes giving an explicit time evolution of the wave function during the collapse. The theory is deterministic even if the Heisenberg uncertainty principle is still valid. The theory distinguishes physical states that collapse and physical states that do not collapse. The theory can be made compatible with all experiments done in the past, but new phenomena such as violations of the Born law or the superposition principle could transpire. However, even if we have probably shown that it is possible to build ad hoc a theory that can describe both the wave function collapse and the Schrödinger linear evolution, a simple and unified construction is still missing.
NEW GAUGE INVARIANT FORMULATION OF THE CHERN–SIMONS GAUGE THEORY: CLASSICAL AND QUANTAL ANALYSIS
Authors: PARK MU-IN , PARK YOUNG-JAI
Published: December 2009

A recently proposed new gauge invariant formulation of the Chern–Simons gauge theory is considered in detail. This formulation is consistent with the gauge fixed formulation. Furthermore, it is found that the canonical (Noether) Poincaré generators are not gauge invariant even on the constraints surface and do not satisfy the Poincaré algebra contrast to usual case. It is the improved generators, constructed from the symmetric energy–momentum tensor, which are (manifestly) gauge invariant and obey the quantum as well as classical Poincaré algebra. The physical states are constructed and it is found in the Schrödinger picture that unusual gauge invariant longitudinal mode of the gauge field is crucial for constructing the physical wave-functional which is genuine to (pure) Chern–Simons theory. In matching to the gauge fixed formulation, we consider three typical gauges, Coulomb, axial and Weyl gauges as explicit examples. Furthermore, recent several confusions about the effect of Dirac's dressing function and the gauge fixings are clarified. The analysis according to old gauge independent formulation á la Dirac is summarized in an appendix.
ETV6-RUNX1Rearrangement in Tunisian Pediatric B-Lineage Acute Lymphoblastic Leukemia
Authors: Gmidène Abir , Elghezal Hatem , Sennana Hlima , Ben Youssef Yosra , Meddeb Balkiss , Elloumi Moez , Khlif Abderrahim , Saad Ali
Published: December 2009

In this study, Forty-one out of fifty-seven Tunisian children with B-lineage acute lymphoblastic leukemia (B-ALL), and without cytogenetically detectable recurrent abnormalities at the time of the diagnosis, were evaluated by fluorescence in situ hybridization (FISH) for the t(12;21). This translocation leadsETV6-RUNX1(previouslyTEL-AML1) fusion gene. 16 patients (28%) hadETV6-RUNX1rearrangement. In addition to this rearrangement, two cases showed a loss of the normalETV6allele, and three others showed an extra signal of theRUNX1gene. Seven patients withoutETV6-RUNX1rearrangement showed extra signals of theRUNX1gene. One out of the 7 patients was also associated with a t(3;12) identified by FISH. This is the first Tunisian study in which we report the incidence of t(12;21) among childhood B-lineage ALL and in which we have found multiple copies ofRUNX1. Finally, our findings confirm that additional or secondary genetic changes are commonly encountered in pediatric B-lineage ALL withETV6-RUNX1gene fusion which is envisaged to play a pivotal role in disease progression.
On Two Iterative Methods for Mixed Monotone Variational Inequalities
Authors: Lu Xiwen , Xu Hong-Kun , Yin Ximing
Published: December 2009

A mixed monotone variational inequality (MMVI) problem in a Hilbert space "Equation missing" is formulated to find a point "Equation missing" such that "Equation missing" for all "Equation missing", where "Equation missing" is a monotone operator and "Equation missing" is a proper, convex, and lower semicontinuous function on "Equation missing". Iterative algorithms are usually applied to find a solution of an MMVI problem. We show that the iterative algorithm introduced in the work of Wang et al., (2001) has in general weak convergence in an infinite-dimensional space, and the algorithm introduced in the paper of Noor (2001) fails in general to converge to a solution.
Approximating Fixed Points of Nonexpansive Nonself Mappings in CAT(0) Spaces
Authors: Laowang W , Panyanak B
Published: December 2009

Suppose that "Equation missing" is a nonempty closed convex subset of a complete CAT(0) space "Equation missing" with the nearest point projection "Equation missing" from "Equation missing" onto "Equation missing". Let "Equation missing" be a nonexpansive nonself mapping with "Equation missing". Suppose that "Equation missing" is generated iteratively by "Equation missing", "Equation missing", "Equation missing", where "Equation missing" and "Equation missing" are real sequences in "Equation missing" for some "Equation missing". Then "Equation missing""Equation missing"-converges to some point "Equation missing" in "Equation missing". This is an analog of a result in Banach spaces of Shahzad (2005) and extends a result of Dhompongsa and Panyanak (2008) to the case of nonself mappings.
The Vocal Repertoire of the Ringtailed Lemur (Lemur catta)
Authors: Macedonia Joseph M.
Published: December 2009

The vocal repertoire of the ringtailed lemur (Lemur cαttα) is described quantitatively and spectrographically. Structure, usage and inferred function of the vocalizations of adults and immatures are examined and discussed. The size, acoustic variability and development of the ringtailed lemur’s vocal repertoire are compared to prior assessments for this species as well as for other primates. With up to 22 different adult call types, the ringtailed lemur has a moderately large vocal repertoire for a primate.
Malignant Diseases in Noonan Syndrome and Related Disorders
Authors: Hasle Henrik
Published: December 2009

The overall risk of cancer in children with Noonan (NS), cardio-facial-cutaneous, Costello or LEOPARD syndrome is high, although no precise estimates are available. There are few data on cancer in adults with NS, but the reported numbers of malignancies in adults do not seem excessive. Juvenile myelomonocytic leukemia (JMML) is a rare aggressive leukemia in young children. A JMML-like myeloproliferative disorder has been described in about 30 neonates with NS and the PTPN11 mutation. The disorder often regresses spontaneously, but fatal complications may occur. A review of the literature indicates an increased risk of acute lymphoblastic leukemia and acute myeloid leukemia in NS. Young children with Costello syndrome have an extremely high risk of rhabdomyosarcoma, and also an increased risk of neuroblastoma and bladder carcinoma. Registry-based studies of patients with NS and related disorders diagnosed with molecular genetics and a high-quality long-term follow-up are necessary to further estimate the incidence of malignancy.
Growth in Noonan Syndrome
Authors: Otten B.J. , Noordam C.
Published: December 2009

Growth failure in Noonan syndrome is mainly postnatal of character and is dominated by slow maturation and late puberty. The postnatal early decline seems to be an intrinsic part of the syndrome. Reported adult heights are about –2 SD and are indicative of a secular trend.
Noonan Syndrome: Growth to Growth Hormone – The Experience of Observational Studies
Authors: Ranke Michael B.
Published: December 2009

Short stature is one of the key features of Noonan syndrome (NS). Attempts have therefore been made to improve height by means of recombinant human growth hormone (rhGH) treatment. Most of these endeavors were carried out either as case studies or observational studies. The overall experience in treating NS is still rather limited, and, in general, it can be said that the NS patients who received GH treatment represent a very narrow segment. The dosages applied in both the case studies and observational studies tended to be higher than those used in the replacement therapy of GH-deficient patients, but lower than in Turner syndrome patients. The NS studies have shown that the overall height gain of patients is small (5–10 cm), and that treatment usually begins at the age of about 10 years, at a height of approximately –3.0 SDS. This small response to treatment reflects the external treatment conditions (i.e. late age at GH start, low GH dose), but may also be associated with the fact that impaired sensitivity to GH is common in NS. Both case studies and observational studies are necessary in order to obtain further evidence about the efficacy and safety of GH treatment in NS.
Growth Hormone and the Heart in Noonan Syndrome
Authors: Noordam C.
Published: December 2009

Background: The clinical hallmarks of Noonan syndrome (NS) are facial dysmorphism, short stature and cardiac defects. As one of the common cardiac defects in NS is hypertrophic cardiomyopathy, there have been concerns regarding cardiac safety since the start of human growth hormone (hGH) therapy for NS. Methods: Review of currently available data on the prevalence of cardiac defects, the theoretical effects of hGH on the heart and the results of studies on the effects of hGH on the heart. Results: The prevalence of cardiac defects in NS is high, and the spectrum is very broad. Progression of ventricular wall thickness during hGH therapy has never been reported. There are barely any data available on children with NS and hypertrophic cardiomyopathy collected during hGH therapy. In post-marketing surveillance studies, there are no reports of adverse cardiac events related to hGH therapy. Conclusion: The reported absence of negative effects of hGH therapy on the heart in NS and especially on ventricular wall thickness is reassuring. Still, keeping in mind the current limited experience, any effects on the heart resulting from hGH therapy should be monitored carefully in NS.
Genetic and Pathogenetic Aspects of Noonan Syndrome and Related Disorders
Authors: Zenker Martin
Published: December 2009

Noonan syndrome (NS) and the clinically overlapping disorders cardio-facio-cutaneous syndrome, LEOPARD syndrome, Costello syndrome and Neurofibromatosis-Noonan syndrome share the clinical features of short stature, the same spectrum of congenital heart defects, and a similar pattern of craniofacial anomalies. It is now known that all these disorders are caused by mutations in components of the RAS-MAPK signaling pathway. This pathway was previously known for its involvement in tumorigenesis. This article reviews the current knowledge on underlying genetic alterations and possible pathogenetic mechanisms responsible for NS and related disorders. It discusses the relationship between a group of developmental disorders and oncogenes. Potential future treatment prospects are based on the possibility of inhibiting RAS-MAPK signaling by pharmaceuticals.
Brain Volume and Metabolism in Fetuses With Congenital Heart Disease
Authors: Limperopoulos Catherine , Tworetzky Wayne , McElhinney Doff B. , Newburger Jane W. , Brown David W. , Robertson Richard L. , Guizard Nicolas , McGrath Ellen , Geva Judith , Annese David , Dunbar-Masterson Carolyn , Trainor Bethany , Laussen Peter C. , du Plessis Adré J.
Published: December 2009

Background—

Adverse neurodevelopmental outcome is an important source of morbidity in children with congenital heart disease (CHD). A significant proportion of newborns with complex CHD have abnormalities of brain size, structure, or function, which suggests that antenatal factors may contribute to childhood neurodevelopmental morbidity.

Methods and Results—

Brain volume and metabolism were compared prospectively between 55 fetuses with CHD and 50 normal fetuses with the use of 3-dimensinal volumetric magnetic resonance imaging and proton magnetic resonance spectroscopy. Fetal intracranial cavity volume, cerebrospinal fluid volume, and total brain volume were measured by manual segmentation. Proton magnetic resonance spectroscopy was used to measure the cerebral
N
-acetyl aspartate: choline ratio (NAA:choline) and identify cerebral lactate. Complete fetal echocardiograms were performed. Gestational age at magnetic resonance imaging ranged from 25

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to 37

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weeks (median, 30 weeks). During the third trimester, there were progressive and significant declines in gestational age–adjusted total brain volume and intracranial cavity volume in CHD fetuses relative to controls. NAA:choline increased progressively over the third trimester in normal fetuses, but the rate of rise was significantly slower (
P
<0.001) in CHD fetuses. On multivariable analysis adjusted for gestational age and weight percentile, cardiac diagnosis and percentage of combined ventricular output through the aortic valve were independently associated with total brain volume. Independent predictors of lower NAA:choline included diagnosis, absence of antegrade aortic arch flow, and evidence of cerebral lactate (
P
<0.001).

Conclusions—

Third-trimester fetuses with some forms of CHD have smaller gestational age– and weight-adjusted total brain volumes than normal fetuses and evidence of impaired neuroaxonal development and metabolism. Hemodynamic factors may play an important role in this abnormal development.
Histone Deacetylase 3 Is Critical in Endothelial Survival and Atherosclerosis Development in Response to Disturbed Flow
Authors: Zampetaki Anna , Zeng Lingfang , Margariti Andriana , Xiao Qingzhong , Li Hongling , Zhang Zhongyi , Pepe Anna Elena , Wang Gang , Habi Ouassila , deFalco Elena , Cockerill Gillian , Mason Justin C. , Hu Yanhua , Xu Qingbo
Published: December 2009

Background—

Histone deacetylase 3 (HDAC3) is known to play a crucial role in the differentiation of endothelial progenitors. The role of HDAC3 in mature endothelial cells, however, is not well understood. Here, we investigated the function of HDAC3 in preserving endothelial integrity in areas of disturbed blood flow, ie, bifurcation areas prone to atherosclerosis development.

Methods and Results—

En face staining of aortas from apolipoprotein E-knockout mice revealed increased expression of HDAC3, specifically in these branching areas in vivo, whereas rapid upregulation of HDAC3 protein was observed in endothelial cells exposed to disturbed flow in vitro. Interestingly, phosphorylation of HDAC3 at serine/threonine was observed in these cells, suggesting that disturbed flow leads to posttranscriptional modification and stabilization of the HDAC3 protein. Coimmunoprecipitation experiments showed that HDAC3 and Akt form a complex. Using a series of constructs harboring deletions, we found residues 136 to 206 of HDAC3 to be crucial in this interaction. Enforced expression of HDAC3 resulted in increased phosphorylation of Akt and upregulation of its kinase activity. In line with these findings, knockdown of HDAC3 with lentiviral vectors (shHDAC3) led to a dramatic decrease in cell survival accompanied by apoptosis in endothelial cells. In aortic isografts of apolipoprotein E-knockout mice treated with shHDAC3, a robust atherosclerotic lesion was formed. Surprisingly, 3 of the 8 mice that received shHDAC3-infected grafts died within 2 days after the operation. Miller staining of the isografts revealed disruption of the basement membrane and rupture of the vessel.

Conclusions—

Our findings demonstrated that HDAC3 serves as an essential prosurvival molecule with a critical role in maintaining the endothelial integrity via Akt activation and that severe atherosclerosis and vessel rupture in isografted vessels of apolipoprotein E-knockout mice occur when HDAC3 is knocked down.
LIM and Cysteine-Rich Domains 1 Regulates Cardiac Hypertrophy by Targeting Calcineurin/Nuclear Factor of Activated T Cells Signaling
Authors: Bian Zhou-Yan , Huang He , Jiang Hong , Shen Di-Fei , Yan Ling , Zhu Li-Hua , Wang Lang , Cao Feng , Liu Chen , Tang Qi-Zhu , Li Hongliang
Published: December 2009

LIM domain proteins are important regulators in cell growth, cell fate determination, cell differentiation, and remodeling of the cell cytoskeleton. LIM and cysteine-rich domains 1 (Lmcd1) is a novel protein that contain 2 LIM domains with regular spacing in the carboxy-terminal region. However, its roles in cardiac growth remain unknown. Here, we investigated whether Lmcd1 regulates cardiac hypertrophy in vitro and in vivo and elucidated the underlying molecular mechanisms. We used primary cultured cardiac myocytes and cardiac-specific Lmcd1 transgenic mice. In wild-type mice subjected to the aortic banding, cardiac hypertrophy was evident at 8 weeks. In transgenic mice, however, cardiac hypertrophy was significantly greater than that in wild-type mice, as estimated by heart weight:body weight ratio, cardiomyocyte area, and echocardiographic measurements, as well as cardiac atrial natriuretic peptide and B-type natriuretic peptide mRNA and protein levels. Our results further showed that cardiac fibrosis observed in wild-type aortic banding mice was augmented in transgenic aortic banding mice. Importantly, calcineurin activity and nuclear factor of activated T cells activation level were increased more in transgenic mice than those in wild-type mice after 8-week aortic banding. In vitro experiments in cardiac myocytes further revealed that angiotensin II-induced calcineurin activity and nuclear factor of activated T cells activation were enhanced by overexpression but blunted by downregulation of Lmcd1. In conclusion, our results suggest that Lmcd1 plays a critical role in the development of cardiac hypertrophy via activation of calcineurin/nuclear factor of activated T cells signaling pathway.
Decoding Poisson Spike Trains by Gaussian Filtering
Authors: Lehky Sidney R.
Published: December 2009

The temporal waveform of neural activity is commonly estimated by low-pass filtering spike train data through convolution with a gaussian kernel. However, the criteria for selecting the gaussian width σ are not well understood. Given an ensemble of Poisson spike trains generated by an instantaneous firing rate function λ(t), the problem was to recover an optimal estimate of λ(t) by gaussian filtering. We provide equations describing the optimal value of σ using an error minimization criterion and examine how the optimal σ varies within a parameter space defining the statistics of inhomogeneous Poisson spike trains. The process was studied both analytically and through simulations. The rate functions λ(t) were randomly generated, with the three parameters defining spike statistics being the mean of λ(t), the variance of λ(t), and the exponent α of the Fourier amplitude spectrum 1/fαof λ(t). The value of σoptfollowed a power law as a function of the pooled mean interspike interval I, σopt= aIb, where a was inversely related to the coefficient of variation CVof λ(t), and b was inversely related to the Fourier spectrum exponent α. Besides applications for data analysis, optimal recovery of an analog signal waveform λ(t) from spike trains may also be useful in understanding neural signal processing in vivo.
Emission Scenario Dependency of Precipitation on Global Warming in the MIROC3.2 Model
Authors: Shiogama Hideo , Emori Seita , Takahashi Kiyoshi , Nagashima Tatsuya , Ogura Tomoo , Nozawa Toru , Takemura Toshihiko
Published: December 2009

The precipitation sensitivity per 1 K of global warming in twenty-first-century climate projections is smaller in an emission scenario with larger greenhouse gas concentrations and aerosol emissions, according to the Model for Interdisciplinary Research on Climate 3.2 (MIROC3.2) coupled atmosphere–ocean general circulation model. The authors examined the reasons for the precipitation sensitivity to emission scenarios by performing separated individual forcing runs under high and low emission scenarios. It was found that the dependency on emission scenario is mainly caused by differences in black and organic carbon aerosol forcing (the sum of which is cooling forcing) between the emission scenarios and that the precipitation is more sensitive to carbon aerosols than well-mixed greenhouse gases. They also investigated the reason for the larger precipitation sensitivity (larger magnitude of precipitation decrease per 1 K cooling of temperature) in the carbon aerosol runs. Surface dimming due to the direct and indirect effects of carbon aerosols effectively decreases evaporation and precipitation, which enhances the precipitation sensitivity in the carbon aerosol runs. In terms of the atmospheric moisture cycle, although changes of vertical circulation offset the effects of changes in the atmospheric moisture in both the carbon aerosol and greenhouse gas runs, the amplitude of vertical circulation change per 1 K temperature change is less in the carbon aerosol runs. Furthermore, the second indirect effect of organic carbon aerosol counteracts the influence of the vertical circulation change. These factors lead to suppression of changes in the moisture’s atmospheric residence time and increase of the precipitation sensitivity in the carbon aerosol runs.
PreDisorder: ab initio sequence-based prediction of protein disordered regions
Authors: Deng Xin , Eickholt Jesse , Cheng Jianlin
Published: December 2009

Background

Disordered regions are segments of the protein chain which do not adopt stable structures. Such segments are often of interest because they have a close relationship with protein expression and functionality. As such, protein disorder prediction is important for protein structure prediction, structure determination and function annotation.

Results

This paper presents our protein disorder prediction server, PreDisorder. It is based on our ab initio prediction method (MULTICOM-CMFR) which, along with our meta (or consensus) prediction method (MULTICOM), was recently ranked among the top disorder predictors in the eighth edition of the Critical Assessment of Techniques for Protein Structure Prediction (CASP8). We systematically benchmarked PreDisorder along with 26 other protein disorder predictors on the CASP8 data set and assessed its accuracy using a number of measures. The results show that it compared favourably with other ab initio methods and its performance is comparable to that of the best meta and clustering methods.

Conclusion

PreDisorder is a fast and reliable server which can be used to predict protein disordered regions on genomic scale. It is available at http://casp.rnet.missouri.edu/predisorder.html.
The role of virulence factors in the outcome of staphylococcal peritonitis in CAPD patients
Authors: Barretti Pasqual , Montelli Augusto C , Batalha Jackson EN , Caramori Jacqueline CT , Cunha Maria de Lourdes RS
Published: December 2009

Background

Peritonitis continues to be the most frequent cause of peritoneal dialysis (PD) failure, with an important impact on patient mortality. Gram-positive cocci such as Staphylococcus epidermidis, other coagulase-negative staphylococci (CoNS), and Staphylococcus aureus are the most frequent etiological agents of PD-associated peritonitis worldwide. The objective of the present study was to compare peritonitis caused by S. aureus and CoNS and to evaluate the factors influencing outcome.

Methods

Records of 86 new episodes of staphylococcal peritonitis that occurred between 1996 and 2000 in the Dialysis unit of a single university hospital were studied (35 due to S. aureus, 24 to S. epidermidis and 27 to other CoNS). The production of slime, lipase, lecithinase, nuclease (DNAse), thermonuclease (TNAse), α- and β-hemolysin, enterotoxins (SEA, SEB, SEC, SED) and toxic shock syndrome toxin-1 (TSST-1) was studied in S. aureus and CoNS. Antimicrobial susceptibility was evaluated based on the minimal inhibitory concentration determined by the E-test. Outcome predictors were evaluated by two logistic regression models.

Results

The oxacillin susceptibility rate was 85.7% for S. aureus, 41.6% for S. epidermidis, and 51.8% for other CoNS (p = 0.001). Production of toxins and enzymes, except for enterotoxin A and α-hemolysin, was associated with S. aureus episodes (p < 0.001), whereas slime production was positive in 23.5% of CoNS and 8.6% of S. aureus strains (p = 0.0047). The first model did not include enzymes and toxins due to their association with S. aureus. The odds of resolution were 9.5 times higher for S. epidermidis than for S. aureus (p = 0.02) episodes, and were similar for S. epidermidis and other CoNS (p = 0.8). The resolution odds were 68 times higher for non-slime producers (p = 0.001) and were not influenced by oxacillin resistance among vancomycin-treated cases (p = 0.89). In the second model, the resolution rate was similar for S. aureus and S. epidermidis (p = 0.70), and slime (p = 0.001) and α-hemolysin (p = 0.04) production were independent predictors of non-resolution.

Conclusion

Bacterial species and virulence factors rather than antibiotic resistance influence the outcome of staphylococcal peritonitis.
Quality assessment of DNA derived from up to 30 years old formalin fixed paraffin embedded (FFPE) tissue for PCR-based methylation analysis using SMART-MSP and MS-HRM
Authors: Kristensen Lasse S , Wojdacz Tomasz K , Thestrup Britta B , Wiuf Carsten , Hager Henrik , Hansen Lise Lotte
Published: December 2009

Background

The High Resolution Melting (HRM) technology has recently been introduced as a rapid and robust analysis tool for the detection of DNA methylation. The methylation status of multiple tumor suppressor genes may serve as biomarkers for early cancer diagnostics, for prediction of prognosis and for prediction of response to treatment. Therefore, it is important that methodologies for detection of DNA methylation continue to evolve. Sensitive Melting Analysis after Real Time - Methylation Specific PCR (SMART-MSP) and Methylation Sensitive - High Resolution Melting (MS-HRM) are two methods for single locus DNA methylation detection based on HRM.

Methods

Here, we have assessed the quality of DNA extracted from up to 30 years old Formalin Fixed Paraffin Embedded (FFPE) tissue for DNA methylation analysis using SMART-MSP and MS-HRM. The quality assessment was performed on DNA extracted from 54 Non-Small Cell Lung Cancer (NSCLC) samples derived from FFPE tissue, collected over 30 years and grouped into five years intervals. For each sample, the methylation levels of the CDKN2A (p16) and RARB promoters were estimated using SMART-MSP and MS-HRM assays designed to assess the methylation status of the same CpG positions. This allowed for a direct comparison of the methylation levels estimated by the two methods for each sample.

Results

CDKN2A promoter methylation levels were successfully determined by SMART-MSP and MS-HRM in all 54 samples. Identical methylation estimates were obtained by the two methods in 46 of the samples. The methylation levels of the RARB promoter were successfully determined by SMART-MSP in all samples. When using MS-HRM to assess RARB methylation five samples failed to amplify and 15 samples showed a melting profile characteristic for heterogeneous methylation. Twenty-seven of the remaining 34 samples, for which the methylation level could be estimated, gave the same result as observed when using SMART-MSP.

Conclusion

MS-HRM and SMART-MSP can be successfully used for single locus methylation studies using DNA derived from up to 30 years old FFPE tissue. Furthermore, it can be expected that MS-HRM and SMART-MSP will provide similar methylation estimates when assays are designed to analyze the same CpG positions.
Mutation analysis of the AATF gene in breast cancer families
Authors: Haanpää Maria , Reiman Mervi , Nikkilä Jenni , Erkko Hannele , Pylkäs Katri , Winqvist Robert
Published: December 2009

Background

About 5-10% of breast cancer is due to inherited disease predisposition. Many previously identified susceptibility factors are involved in the maintenance of genomic integrity. AATF plays an important role in the regulation of gene transcription and cell proliferation. It induces apoptosis by associating with p53. The checkpoint kinases ATM/ATR and CHEK2 interact with and phosphorylate AATF, enhancing its accumulation and stability. Based on its biological function, and direct interaction with several known breast cancer risk factors, AATF is a good candidate gene for being involved in heritable cancer susceptibility.

Methods

Here we have screened the entire coding region of AATF in affected index cases from 121 Finnish cancer families for germline defects, using conformation sensitive gel electrophoresis and direct sequencing.

Results

Altogether seven different sequence changes were observed, one missense variant and six intronic ones. Based on the in silico analyses of these sequence alterations, as well as their occurrence in cases and controls, none of them, however, were predicted to be pathogenic.

Conclusions

To our knowledge, this is the first study reporting the mutation screening of the AATF gene in familial breast cancer cases. No evidence for the association with breast cancer was observed.
Prognostic impact of H3K27me3 expression on locoregional progression after chemoradiotherapy in esophageal squamous cell carcinoma
Authors: He Li-Ru , Liu Meng-Zhong , Li Bin-Kui , Rao Hui-Lan , Liao Yi-Ji , Guan Xin-Yuan , Zeng Yi-Xin , Xie Dan
Published: December 2009

Background

Trimethylation of lysine 27 on histone H3 (H3K27me3) by enhancer of zeste homolog 2 (EZH2) is an epigenetic mark that mediates gene silencing. EZH2 is overexpressed and correlates with poor prognosis in many cancers. However, the clinical implication of H3K27me3 in human malignancies has not been well established. We wished to ascertain whether a correlation exists between the expression of H3K27me3 and clinical outcome in a group of patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (CRT).

Methods

The method of immunohistochemistry (IHC) was utilized to examine the protein expression of H3K27me3 in 98 pretreatment biopsy specimens of ESCC and in 30 samples of normal esophageal mucosa. The clinical/prognostic significance of H3K27me3 expression was statistically analyzed.

Results

The expression frequency and expression levels of H3K27me3 were significantly higher in ESCCs than in normal tissues. There was a positive correlation between H3K27me3 expression and WHO grade (P = 0.016), tumor size (P = 0.019), T status (P = 0.024), locoregional progression (P = 0.009) and EZH2 expression (P = 0.036). High H3K27me3 expression was associated with poor locoregional progression-free survival (LPFS) (P = 0.010) in ESCC. Further analysis demonstrated that H3K27me3 could stratify patient outcome in T2-3 (P = 0.048), N0 (P = 0.005) and M0 (P = 0.018) stages as well as in CRT effective group (P = 0.022).

Conclusions

Our data suggests that H3K27me3 expression examined by IHC might be useful for stratifying LPFS for different subsets of ESCC patients treated with definitive CRT.
Chronic kidney-disease screening service quality: questionnaire survey research evidence from Taichung city
Authors: Lin Deng-Juin , Li Ya-Hsin , Pai Jar-Yuan , Sheu Ing-Cheau , Glen Robert , Chou Ming-Jen , Lee Ching-Yi
Published: December 2009

Background

Chronic kidney disease (CKD) is a serious public health problem in Taiwan and the world. The most effective, affordable treatments involve early prevention/detection/intervention, requiring screening. Successfully implementing CKD programs requires good patient participation, affected by patient perceptions of screening service quality. Service quality improvements can help make such programs more successful. Thus, good tools for assessing service quality perceptions are important. Aim: to investigate using a modified SERVQUAL questionnaire in assessing patient expectations, perceptions, and loyalty towards kidney disease screening service quality.

Method

1595 kidney disease screening program patients in Taichung City were requested to complete and return a modified kidney disease screening SERVQUAL questionnaire. 1187 returned them. Incomplete ones (102) were culled and 1085 were chosen as effective for use. Paired t-tests, correlation tests, ANOVA, LSD test, and factor analysis identified the characteristics and factors of service quality. The paired t-test tested expectation score and perception score gaps. A structural equation modeling system examined satisfaction-based components' relationships.

Results

The effective response rate was 91.4%. Several methods verified validity. Cronbach's alpha on internal reliability was above 0.902. On patient satisfaction, expectation scores are high: 6.50 (0.82), but perception scores are significantly lower 6.14 (1.02). Older patients' perception scores are lower than younger patients'. Expectation and perception scores for patients with different types of jobs are significantly different. Patients higher on education have lower scores for expectation (r = -0.09) and perception (r = -0.26). Factor analysis identified three factors in the 22 item SERVQUAL form, which account for 80.8% of the total variance for the expectation scores and 86.9% of the total variance for the satisfaction scores. Expectation and perception score gaps in all 22 items are significant. The goodness-of-fit summary of the SEM results indicates that expectations and perceptions are positively correlated, perceptions and loyalty are positively correlated, but expectations and loyalty are not positively correlated.

Conclusions

The results of this research suggest that the SERVQUAL instrument is a useful measurement tool in assessing and monitoring service quality in kidney disease screening services, enabling the staff to identify where service improvements are needed from the patients' perspectives.
Gene cloning and characterization of a novel esterase from activated sludge metagenome
Authors: Zhang Tao , Han Wen-Jun , Liu Zhi-Pei
Published: December 2009

A metagenomic library was prepared using pCC2FOS vector containing about 3.0 Gbp of community DNA from the microbial assemblage of activated sludge. Screening of a part of the un-amplified library resulted in the finding of 1 unique lipolytic clone capable of hydrolyzing tributyrin, in which an esterase gene was identified. This esterase/lipase gene consists of 834 bp and encodes a polypeptide (designated EstAS) of 277 amino acid residuals with a molecular mass of 31 kDa. Sequence analysis indicated that it showed 33% and 31% amino acid identity to esterase/lipase from Gemmata obscuriglobus UQM 2246 (ZP_02733109) and Yarrowia lipolytica CLIB122 (XP_504639), respectively; and several conserved regions were identified, including the putative active site, HSMGG, a catalytic triad (Ser92, His125 and Asp216) and a LHYFRG conserved motif. The EstAS was overexpressed, purified and shown to hydrolyse p-nitrophenyl (NP) esters of fatty acids with short chain lengths (≤ C8). This EstAS had optimal temperature and pH at 35°C and 9.0, respectively, by hydrolysis of p-NP hexanoate. It also exhibited the same level of stability over wide temperature and pH ranges and in the presence of metal ions or detergents. The high level of stability of esterase EstAS with its unique substrate specificities make itself highly useful for biotechnological applications.
Characterisation of carbon nanotubes in the context of toxicity studies
Authors: Berhanu Deborah , Dybowska Agnieszka , Misra Superb K , Stanley Chris J , Ruenraroengsak Pakatip , Boccaccini Aldo R , Tetley Teresa D , Luoma Samuel N , Plant Jane A , Valsami-Jones Eugenia
Published: December 2009

Nanotechnology has the potential to revolutionise our futures, but has also prompted concerns about the possibility that nanomaterials may harm humans or the biosphere. The unique properties of nanoparticles, that give them novel size dependent functionalities, may also have the potential to cause harm. Discrepancies in existing human health and environmental studies have shown the importance of good quality, well-characterized reference nanomaterials for toxicological studies.

Here we make a case for the importance of the detailed characterization of nanoparticles, using several methods, particularly to allow the recognition of impurities and the presence of chemically identical but structurally distinct phases. Methods to characterise fully, commercially available multi-wall carbon nanotubes at different scales, are presented.