bluuebunny/crossref_metadata_2025 huggingface dataset:
Deactivation of Akt and STAT3 signaling promotes apoptosis, inhibits proliferation, and enhances the sensitivity of hepatocellular carcinoma cells to an anticancer agent, Atiprimod
Authors: Choudhari Sweeta R. , Khan Muhammad A. , Harris Genesis , Picker Donald , Jacob Gary S. , Block Timothy , Shailubhai Kunwar
Published: January 2007

Atiprimod is a novel anticancer and antiangiogenic drug candidate which is currently being evaluated in patients with liver carcinoid and multiple myeloma. In this study, we report that atiprimod selectively inhibited proliferation and induced apoptosis in HCC cells that expressed either hepatitis B virus (HBV) or hepatitis C virus, through deactivation of protein kinase B (Akt) and signal transducers and activators of transcription 3 (STAT3) signaling. In HepG2 AD38 cells, which express HBV genome under the control of a tetracycline-off promoter, both Akt and STAT3 were constitutively activated in response to HBV expression. However, this constitutive activation was not sensitive to lamivudine, a drug that inhibits HBV replication without affecting its gene expression, suggesting that HBV replication per se might not be responsible for the activation. Interestingly, the electrophoretic mobility of p-STAT3 protein bands on immunoblot was slower when AD38 cells were cultured in the absence of tetracycline, suggesting a differential phosphorylation in response to HBV expression. In HCC cells, interleukin 6 stimulates the phosphorylation of STAT3 both at serine 727 and at tyrosine 705 positions. The interleukin 6–stimulated activation of STAT3 and Akt was inhibited not only by atiprimod but also by LY294002, a phosphoinositide-3-kinase–specific inhibitor, and by NS398, a cyclooxygenase-2–selective inhibitor. The combination of these compounds did not produce any additive effect, implying that the mechanisms by which HBV activates Akt and STAT3 might also involve phosphoinositide-3-kinase and cyclooxygenase-2. Collectively, these results suggest that atiprimod could be useful as a multifunctional drug candidate for the treatment of HCC in humans. [Mol Cancer Ther 2007;6(1):112–21]
Developmental Origin of Diencephalic Sensory Relay Nuclei in Teleosts
Authors: Ishikawa Yuji , Yamamoto Naoyuki , Yoshimoto Masami , Yasuda Takako , Maruyama Kouichi , Kage Takahiro , Takeda Hiroyuki , Ito Hironobu
Published: January 2007

We propose here a novel interpretation of the embryonic origin of cells of diencephalic sensory relay nuclei in teleosts based on our recent studies of gene expression patterns in the medaka (Oryzias latipes) embryonic brain and comparative hodological studies. It has been proposed that the diencephalic sensory relay system in teleosts is unique among vertebrates. Teleost relay nuclei, the preglomerular complex (PG), have been assumed to originate from the basal plate (the posterior tuberculum) of the diencephalon, whereas relay nuclei in mammals are derived from the alar plate (dorsal thalamus) of the diencephalon. Our results using in situ hybridization show, however, that many pax6- or dlx2-positive cells migrate laterally and ventrocaudally from the diencephalic alar plate to the basal plate during development. Massive clusters of the migrated alar cells become localized in the mantle layer lateral to the posterior tubercular neuroepithelium, from which main nuclei of the PG appear to differentiate. We therefore consider most if not all neurons in the PG to be of alar, not basal, origin. Thus, the teleost PG, at least in part, can be regarded as migrated alar nuclei. Developmental and hodological data strongly suggest that the teleost PG is homologous to a part of the mammalian dorsal thalamus. The organization and origin of the diencephalic sensory relay system might have been conserved across vertebrates.
Modifications Produced by Indomethacin and L-NAME in the Effect of Ultralow-Dose Aspirin on Platelet Activity in Portal Hypertension
Authors: Eizayaga Francisco X. , Aguejouf Omar , Desplat Vanessa , Belon Philippe , Doutremepuich Christian
Published: January 2007

In our previous study, we demonstrated the effect of ultralow-dose aspirin (ULDA) on platelet activity and bleeding in rats with portal hypertension (PHT) produced by portal vein ligation (PVL). This paper reports modifications in this effect caused by blocking NO production by nitro arginine methyl ester (NAME) and cyclooxygenase (COX) activity with indomethacin. PVL rats and sham-operated controls were treated with placebo, indomethacin or NAME and 30 min thereafter with placebo or ULDA treatment. Platelet activity was studied by a model of in vivo laser-induced thrombus production in the mesenteric circulation, induced hemorrhage time (IHT) and platelet aggregation ex vivo induced by adenosine diphosphate in an aggregometer. The PVL group receiving placebo showed a decreased platelet activity with prolonged IHT, an effect that was reversed by ULDA. Indomethacin induced a decreased platelet activity in the control rats and a prolonged IHT. In PHT with ULDA, in vivo platelet activity was enhanced but the normalization of IHT observed in rats without indomethacin was blunted. The addition of NAME normalized the diminished in vivo platelet aggregation and increased the IHT observed in PVL animals. These changes decreased the effect of ULDA in both sham-operated and PVL animals. The effect of indomethacin was more clearly modified by ULDA than the effect of NAME, thus suggesting that modifications in the COX pathway might alter the effect of ULDA. The simultaneous administration of indomethacin and ULDA could inhibit its beneficial effect on bleeding in rats with PHT.
Functional Analysis of the Factor IX Epidermal Growth Factor-Like Domain Mutation Ile66Thr Associated with Mild Hemophilia B
Authors: Knobe Karin E. , Persson Kristina E.M. , Sjörin Elsy , Villoutreix Bruno O. , Ljung Rolf C.R.
Published: January 2007

The present study focused on the functional role of the mutation Ile66Thr located in the N-terminal epidermal growth factor-like domain of coagulation factor IX (FIX). This mutation causes mild hemophilia B with approximately 25% FIX coagulant activity and FIX antigen levels of around 90% of normal. In the 3-dimensional structure of porcine FIXa and in the subsequent 3-dimensional model of human FIXa that we have previously developed, residue 66 is exposed to the solvent and can be replaced by many amino acids, including Thr, without affecting the major folding/stability of the molecule. This is consistent with the basically normal antigen levels observed. We found that the FIX Ile66Thr mutant was activated to a normal extent by FVIIa/TF and FXIa. However, the ability of FIX Ile66Thr to activate FX was impaired in both the presence and absence of FVIIIa, indicating that Ile66 is not directly involved in the binding of FIX to FVIIIa.
Is There a Continuity between Bipolar and Depressive Disorders?
Authors: Benazzi Franco
Published: January 2007

Background: Recent studies questioned the current categorical split of mood disorders into bipolar disorders (BP) and depressive disorders (MDD). Methods: Medline database search of papers from the last 10 years on the categorical-dimensional classification of mood disorders. Various combinations of the following key words were used: mood disorders, bipolar, unipolar, major depressive disorder, spectrum, category/categorical, classification, continuity. Only English language clinical papers were included, review papers were excluded, similar papers selected by quality. The number of papers found was 1,141. The number of papers selected was 109. Results: The continuity/spectrum between BP (mainly BP-II) and MDD was supported by the following findings:(1) high frequency of mixed states (mixed mania, mixed hypomania, mixed depression, i.e. co-occurring depression and noneuphoric manic/hypomanic symptoms) because opposite polarity symptoms in the same episode do not support a hypomania/mania-depression splitting; (2) MDD was the most common mood disorder in BP probands’ relatives; (3) no bimodal distribution of distinguishing symptoms between BP and MDD; (4) bipolar signs not uncommon in MDD; (5) many MDD shifting to BP; (6) many lifetime manic/hypomanic symptoms in MDD; (7) correlation between lifetime manic/hypomanic symptoms and MDD symptoms; (8) hypomania factors in MDD; (9) MDD often recurrent; (10) similar cognitive style.The categorical distinction between BP (mainly BP-I) and MDD was supported by the following findings: (1) BP more common in BP probands’ relatives; (2) lower age at BP onset; (3) females as common as males in BP-I, more common than males in MDD; (4) BP-I depression more atypical and retarded, MDD depression more sleepless and agitated; (5) BP more recurrent. Conclusions: Focusing on mood spectrum’s extremes (BP-I vs. MDD), a categorical distinction seems supported. Focusing on midway disorders (BP-II and MDD plus bipolar signs), a continuity/spectrum seems supported. Results seem to support both a categorical and a dimensional view of mood disorders.
Bipolar (Spectrum) Disorder and Mood Stabilization: Standing at the Crossroads?
Authors: De Fruyt Jürgen , Demyttenaere Koen
Published: January 2007

Diagnosis and treatment of bipolar disorder has long been a neglected discipline. Recent years have shown an upsurge in bipolar research. When compared to major depressive disorder, bipolar research still remains limited and more expert based than evidence based. In bipolar diagnosis the focus is shifting from classic mania to bipolar depression and hypomania. There is a search for bipolar signatures in symptoms and course of major depressive episodes. The criteria for hypomania are softened, leading to a bipolar prevalence that now equals that of major depressive disorder. Anti-epileptics and atypical antipsychotics have joined lithium in the treatment of bipolar disorder. Fortunately, mood stabilization has become the core issue in bipolar disorder treatment. In contrast with recent trends in the diagnosis of bipolar disorder, treatment research remains more focused on classic mania than depression or hypomania. This leaves the clinician with the difficult task of diagnosing ‘new bipolar patients’ for whom no definite evidence-based treatment is available. An important efficacy-effectiveness gap further compromises the translation of the evidence base on bipolar disorder treatment into clinical practice. The recent upsurge of research on bipolar disorder is to be applauded, but further research is needed: for bipolar disorder in general, and for bipolar depression and the long-term treatment specifically. Given the complexity of the disorder and the many clinical uncertainties, effectiveness studies should be installed.
Anger, Depression and Personality Dimensions in Patients with Migraine without Aura
Authors: Abbate-Daga Giovanni , Fassino Secondo , Lo Giudice Rossana , Rainero Innocenzo , Gramaglia Carla , Marech Lucrezia , Amianto Federico , Gentile Salvatore , Pinessi Lorenzo
Published: January 2007

Background: Migraine without aura causes acute and chronic pain and partially compromises patients’ social functioning and work performance. Over the past years, psychiatric comorbidities were frequently observed in these patients, together with coping difficulties and typical personality traits. The aim of this study was to identify whether migraine patients and controls share distinctive personality traits. Methods: 105 consecutive patients suffering from migraine without aura referred to the Headache Center of Turin University were enrolled in the study and compared to a control group of 79 healthy subjects. Patients and controls completed several psychometric questionnaires, including the Temperament and Character Inventory, the Beck Depression Inventory and the State-Trait Anger Expression Inventory. Results: Patients suffering from migraine show more depressive symptoms, difficult anger management with a tendency to hypercontrol, and a distinctive personality profile with high harm avoidance, high persistence and low self-directedness. When a logistic regression was performed, the only significant predictors of migraine were temperament variables. Conclusions: The results suggest that the personality traits and psychosomatic mechanisms of migraine patients may make them vulnerable to stress and less skilled in coping with pain. These traits correlate with dysregulated neurotransmitter systems which may also be part of the psychobiological components of personality, depressive disorders and migraine itself.
Reduced Force Generating Capacity in Myocytes From Chronically Ischemic, Hibernating Myocardium
Authors: Bito Virginie , van der Velden Jolanda , Claus Piet , Dommke Christoph , Van Lommel Alfons , Mortelmans Luc , Verbeken Erik , Bijnens Bart , Stienen Ger , Sipido Karin R.
Published: January 2007

The contractile dysfunction of the hibernating myocardium in situ results from local environmental factors, but also from intrinsic cellular remodelling that may determine reversibility. Previous studies have suggested defects in myofilament Ca
2+
responsiveness. We prepared single myocytes from control (CTRL, n
pigs
=7) and from hibernating myocardium (HIB, n
pigs
=8), removed the membranes and measured isometric force development during direct activation of the myofilaments. One- and 2-dimensional polyacrylamide gel electrophoresis and specific phosphoprotein immunoblotting were performed on tissue homogenates from matched samples. Cellular ultrastructure was evaluated using electron microscopy. Normalized for cross-sectional area, passive force was not different but maximal isometric force was significantly reduced in myocytes from HIB (11.6±1.5 kN/m
2
versus 18.7±1.6 kN/m
2
in CTRL,
P
<0.05). Ca
2+
sensitivity and steepness of the normalized force-pCa relationship were not different, and neither was the rate of force redevelopment (K
tr
). No alterations were observed in isoform expression, phosphorylation or degradation of specific myofibrillar proteins. However, in HIB samples the total protein volume density was decreased by 23% (
P
<0.05). Histology showed glycogen accumulation and electron microscopy confirmed a reduction in myofilament density from 69.9±1.9% in CTRL to 57.1±0.9% of cell volume in HIB (
P
<0.05). In conclusion, decreased potential for force development in the hibernating myocardium is related to a reduction of myofibrillar protein per cell volume unit with replacement by glycogen and mitochondria. These changes may contribute to slow functional recovery on revascularization.
Forkhead Transcription Factor FOXO3a Is a Negative Regulator of Angiogenic Immediate Early Gene CYR61, Leading to Inhibition of Vascular Smooth Muscle Cell Proliferation and Neointimal Hyperplasia
Authors: Lee Hae-Young , Chung Jae-Woong , Youn Seock-Won , Kim Ju-Young , Park Kyung-Woo , Koo Bon-Kwon , Oh Byung-Hee , Park Young-Bae , Chaqour Brahim , Walsh Kenneth , Kim Hyo-Soo
Published: January 2007

Cysteine-rich angiogenic protein 61 (CYR61, CCN1) is an immediate early gene expressed in vascular smooth muscle cells (VSMCs) on growth factor stimulation, and its expression has been suggested to be associated with postangioplasty restenosis. The forkhead transcription factors are reported to play various roles in cellular proliferation, apoptosis, and even adaptation to cellular stress. We hypothesized that the forkhead transcription factor FOXO3a may regulate CYR61 expression in VSMCs and investigated the CYR61-modulating effect of FOXO3a in the process of vascular response to vasoactive signals and vascular injury. To evaluate the effect of FOXO3a on CYR61 expression, rat VSMCs were infected with adenoviral vectors expressing constitutively active FOXO3a (Ad-TM-FOXO3a). Constitutively active FOXO3a gene transduction suppressed CYR61 expression. Luciferase assay with the deletion constructs of the forkhead factor binding motif in CYR61 promoter region, which resulted in a significant decrease in luciferase expression compared with the intact construct, and chromatin immunoprecipitation analysis confirmed transcriptional regulation of CYR61 by FOXO3a. Serum and angiotensin II rapidly induced CYR61 expression, which was significantly reduced by Ad-TM-FOXO3a. Reduction of VSMC proliferation and migration associated with FOXO3a activation was significantly reversed by cotransfection of adenoviral vector expressing CYR61, whereas apoptosis induction by FOXO3a was not influenced. In a rat balloon carotid arterial injury model, CYR61 was rapidly induced in VSMCs in the early stage of injury and remained elevated until 14 days, which was suppressed by Ad-TM-FOXO3a transfection. After 14 days, there was a significant reduction in neointima by FOXO3a transduction compared with the control group (0.06±0.02 versus 0.20±0.07 mm
2
,
P
<0.01). Such reduction of neointimal hyperplasia by Ad-TM-FOXO3a was reversed by CYR61 replenishment. These data suggest that FOXO3a is a negative transcription factor of CYR61 and that suppression of CYR61 is among several mechanisms by which FOXO3a inhibits VSMC proliferation and neointimal hyperplasia.
Molecular Pathway for the Localized Formation of the Sinoatrial Node
Authors: Mommersteeg Mathilda T.M. , Hoogaars Willem M.H. , Prall Owen W.J. , de Gier-de Vries Corrie , Wiese Cornelia , Clout Danielle E.W. , Papaioannou Virginia E. , Brown Nigel A. , Harvey Richard P. , Moorman Antoon F.M. , Christoffels Vincent M.
Published: January 2007

The sinoatrial node, which resides at the junction of the right atrium and the superior caval vein, contains specialized myocardial cells that initiate the heart beat. Despite this fundamental role in heart function, the embryonic origin and mechanisms of localized formation of the sinoatrial node have not been defined. Here we show that subsequent to the formation of the
Nkx2-5
–positive heart tube, cells bordering the inflow tract of the heart tube give rise to the
Nkx2-5
–negative myocardial cells of the sinoatrial node and the sinus horns. Using genetic models, we show that as the myocardium of the heart tube matures, Nkx2-5 suppresses pacemaker channel gene
Hcn4
and T-box transcription factor gene
Tbx3
, thereby enforcing a progressive confinement of their expression to the forming
Nkx2-5
–negative sinoatrial node and sinus horns. Thus, Nkx2-5 is essential for establishing a gene expression border between the atrium and sinoatrial node. Tbx3 was found to suppress chamber differentiation, providing an additional mechanism by which the
Tbx3
-positive sinoatrial node is shielded from differentiating into atrial myocardium.
Pitx2c
-deficient fetuses form sinoatrial nodes with indistinguishable molecular signatures at both the right and left sinuatrial junction, indicating that Pitx2c functions within the left/right pathway to suppress a default program for sinuatrial node formation on the left. Our molecular pathway provides a mechanism for how pacemaker activity becomes progressively relegated to the most recently added components of the venous pole of the heart and, ultimately, to the junction of the right atrium and superior caval vein.
β-Adrenergic Enhancement of Sarcoplasmic Reticulum Calcium Leak in Cardiac Myocytes Is Mediated by Calcium/Calmodulin-Dependent Protein Kinase
Authors: Curran Jerald , Hinton Mark J. , Ríos Eduardo , Bers Donald M. , Shannon Thomas R.
Published: January 2007

Enhanced cardiac diastolic Ca leak from the sarcoplasmic reticulum (SR) ryanodine receptor may reduce SR Ca content and contribute to arrhythmogenesis. We tested whether β-adrenergic receptor (β-AR) agonists increased SR Ca leak in intact rabbit ventricular myocytes and whether this depends on protein kinase A or Ca/calmodulin-dependent protein kinase II (CaMKII) activity. SR Ca leak was assessed by acute block of the ryanodine receptor by tetracaine and assessment of the consequent shift of Ca from cytosol to SR (measured at various SR Ca loads induced by varying frequency). Cytosolic [Ca] ([Ca]
i
) and SR Ca load ([Ca]
SRT
) were assessed using fluo-4. β-AR activation by isoproterenol dramatically increased SR Ca leak. However, this effect was not inhibited by blocking protein kinase A by H-89, despite the expected reversal of the isoproterenol-induced enhancement of Ca transient amplitude and [Ca]
i
decline rate. In contrast, inhibitors of CaMKII, KN-93, or autocamtide-2–related inhibitory peptide II or β-AR blockade reversed the isoproterenol-induced enhancement of SR Ca leak, and CaMKII inhibition could even reduce leak below control levels. Forskolin, which bypasses the β-AR in activating adenylate cyclase and protein kinase A, did not increase SR Ca leak, despite robust enhancement of Ca transient amplitude and [Ca]
i
decline rate. The results suggest that β-AR stimulation enhances diastolic SR Ca leak in a manner that is (1) CaMKII dependent, (2) not protein kinase A dependent, and 3) not dependent on bulk [Ca]
i
.
Dynamics of Eddy-Driven Low-Frequency Dipole Modes. Part I: A Simple Model of North Atlantic Oscillations
Authors: Luo Dehai , Lupo Anthony R. , Wan Han
Published: January 2007

A simple theoretical model is proposed to clarify how synoptic-scale waves drive the life cycle of the North Atlantic Oscillation (NAO) with a period of nearly two weeks. This model is able to elucidate what determines the phase of the NAO and an analytical solution is presented to indicate a high similarity between the dynamical processes of the NAO and zonal index, which is not derived analytically in previous theoretical studies. It is suggested theoretically that the NAO is indeed a nonlinear initial-value problem, which is forced by both preexisting planetary-scale and synoptic-scale waves. The eddy forcing arising from the preexisting synoptic-scale waves is shown to be crucial for the growth and decay of the NAO, but the preexisting low-over-high (high-over-low) dipole planetary-scale wave must be required to match the preexisting positive-over-negative (negative-over-positive) dipole eddy forcing so as to excite a positive (negative) phase NAO event. The positive and negative feedbacks of the preexisting dipole eddy forcing depending upon the background westerly wind seem to dominate the life cycle of the NAO and its life period.

An important finding in the theoretical model is that negative-phase NAO events could be excited repeatedly after the first event has decayed, but for the positive phase downstream isolated dipole blocks could be produced after the first event has decayed. This is supported by observed cases of the NAO events presented in this paper. In addition, a statistical study of the relationship between the phase of the NAO and blocking activity over Europe in terms of the seasonal mean NAO index shows that blocking events over Europe are more frequent and long-lived for strong positive-phase NAO years, indicating that the positive-phase NAO favors the occurrence of European blocking events.
Linear and Nonlinear Signatures in the Planetary Wave Dynamics of an AGCM: Probability Density Functions
Authors: Berner Judith , Branstator Grant
Published: January 2007

To identify and quantify indications of linear and nonlinear planetary wave behavior and their impact on the distribution of atmospheric states, characteristics of a very long integration of an atmospheric general circulation model (GCM) in a four-dimensional phase space are examined. The phase space is defined by the leading four empirical orthogonal functions of 500-hPa geopotential heights.

First it is established that nonlinear tendencies similar to those reported in an earlier study of the phase space behavior in this GCM have the potential to lead to non-Gaussian features in the probability density function (PDF) of planetary waves. Then using objective measures it is demonstrated that the model’s distribution of states has distinctive non-Gaussian features. These features are characterized in various subspaces of dimension as high as four. A key feature is the presence of three radial ridges of enhanced probability emanating from the mode, which is shifted away from the climatological mean. There is no evidence of multiple maxima in the full PDF, but the radial ridges lead to three distinct modes in the distribution of circulation patterns.

It is demonstrated that these key aspects of non-Gaussianity are captured by a two-Gaussian mixture model fitted in four dimensions. The two circulation states at the centroids of the component Gaussians are very similar to those associated with two nonlinear features identified by Branstator and Berner in their analysis of the trajectories of the GCM. These two dynamical features are locally linear, so it is concluded that the behavior of planetary waves can be conceptualized as being approximately piecewise-linear, leading to a two-Gaussian mixture with three preferred patterns.
Impact of Atmosphere–Ocean Coupling on the Predictability of Monsoon Intraseasonal Oscillations*
Authors: Fu Xiouhua , Wang Bin , Waliser Duane E. , Tao Li
Published: January 2007

The impact of air–sea coupling on the predictability of monsoon intraseasonal oscillations (MISO) has been investigated with an atmosphere–ocean coupled model and its atmospheric component. From a 15-yr coupled control run, 20 MISO events are selected. A series of twin perturbation experiments have been conducted for all the selected events using both the coupled model and the atmosphere-only model. Two complementary measures are used to quantify the MISO predictability: (i) the ratio of signal-to-forecast error and (ii) the spatial anomaly correlation coefficient (ACC).

In the coupled model, the MISO predictability is generally higher over the Indian sector than that over the western Pacific with a maximum of 35 days in the eastern equatorial Indian Ocean. Air–sea coupling significantly improves the predictability in almost the entire Asian–western Pacific region. The mean predictability of the MISO-related rainfall over its active area (10°S–30°N, 60°–160°E) reaches about 24 days in the coupled model and is about 17 days in the atmosphere-only model. This result suggests that including an interactive ocean allows the MISO predictability of an atmosphere-only model to be extended by about a week. The extended predictability is primarily due to the coupled model capturing the two-way interactions between the MISO and underlying sea surface. The MISO forces a coherent intraseasonal SST response in underlying ocean that in return exerts an external control on the future evolutions of the MISO.

The break phase of the MISO is more predictable than the active phase in both the atmosphere-only model and the coupled model as revealed in the observations. Air–sea coupling appears to extend the MISO predictability uniformly regardless of the active or break phases.
Numerical and Experimental Investigation of the Neutral Atmospheric Surface Layer
Authors: Drobinski Philippe , Carlotti Pierre , Redelsperger Jean-Luc , Masson Valery , Banta Robert M. , Newsom Rob K.
Published: January 2007

This study combines the experimental measurements with large-eddy simulation (LES) data of a neutral planetary boundary layer (PBL) documented by a 60-m tower instrumented with eight sonic anemometers, and a high-resolution Doppler lidar during the 1999 Cooperative Atmospheric and Surface Exchange Study (CASES-99) experiment. The target of the paper is (i) to investigate the multiscale nature of the turbulent eddies in the surface layer (SL), (ii) to explain the existence of a −1 power law in the velocity fluctuation spectra, and (iii) to investigate the different nature of turbulence in the two sublayers within the SL, which are the eddy surface layer (ESL; lower sublayer of the SL lying between the surface and about 20-m height) and the shear surface layer (SSL; lying between the ESL top and the SL top). The sonic anemometers and Doppler lidar prove to be proper instruments for LES validation, and in particular, the Doppler lidar because of its ability to map near-surface eddies.

This study shows the different nature of turbulence in the ESL and the SSL in terms of organized eddies, velocity fluctuation spectra, and second-order moment statistics. If quantitative agreement is found in the SSL between the LES and the measurements, only qualitative similarity is found in the ESL due to the subgrid-scale model, indicating that the LES captures part of the physics of the ESL. The LES helps explain the origin of the −1 power-law spectral subrange evidence in the velocity fluctuation spectra computed in the SL using the CASES-99 dataset: strong interaction between the mean flow and the fluctuating vorticities is found in the SL, and turbulent production is found to be larger than turbulent energy transfer for k1z > 1 (k1 being the longitudinal wavenumber and z the height), which is the condition of the −1 power-law existence.
Sensor and control technology for cardiac pacing
Authors: Werner Jürgen , Meine Mathias , Hoeland Karsten , Hexamer Martin , Kloppe Axel
Published: January 2007

Pacemakers are implanted on account of deficiencies in rhythm generation and excitation conduction in the heart. The aim of sensor-controlled pacemaker systems is, apart from the preservation of life, the greatest possible restoration of physiological adaptation to circulatory stress. If the intrinsic rhythm generator breaks down, this cannot be achieved ideally by a technical shunt, but approximately by sensing physical and/or physiological variables suited to heart rate control. The latter leads both to feedforward control systems and to feedback (closed) control loops. After an overview on existing sensors the authors offer two new sensor technologies for closed-loop systems which are optimally suited to restore the original physiological control loop to the utmost extent. One uses sensors measuring the atrio-ventricular delay in the heart (dromotropic pacemaker), and the other uses a fibre optic sensor measuring the contraction of the heart (inotropic pacemaker).
Implementation of a robust PID autotuner in a control design environment
Authors: Leva Alberto , Colombo Antonio M.
Published: January 2007

This paper describes a robust PID autotuner embedded in a block library for constructing both simulated and real control systems. The library has been implemented in a visual programming tool and contains all the functions for building complete systems, similar to those provided by a typical CACSD (computer-aided control system design) environment. After a brief overview of the library, the paper concentrates on describing the PID autotuning tool, its implementation and operation. The underlying theoretical background is simply sketched out to permit the necessary degree of comprehension, and for its complete illustration the interested reader is referred to more specific works. Some examples of the autotuner’s operation, one of which refers to a laboratory plant, are also reported.
D-Type learning control for nonlinear time-varying systems with unknown initial states and inputs
Authors: Yan X. G. , Chen I. M. , Lam J.
Published: January 2007

In this paper, D-type iterative learning control schemes, which guarantee that the desired output is tracked precisely through iteration, are presented. Both off-line and on-line schemes are considered for a class of nonlinear systems. In both schemes, the learning gain may be time-varying and thus possesses larger scope for adjustment. Specifically, not only the input but also the initial state is iterated in the algorithms, and the output channel is fully nonlinear. Then, sufficient conditions are presented which guarantee the convergence of the proposed algorithms. The desired input and desired state are not assumed to be known a priori. Finally, the results are applied to a robotic system through simulation, which demonstrates the effectiveness of the method.
Comparative study of sliding mode speed and position control of a vector-controlled induction machine
Authors: Yu X. , Dunnigan M. W. , Williams B. W.
Published: January 2007

This paper demonstrates that high performance speed and position control can be obtained by using sliding mode control methods for a vector-controlled induction machine. Four sliding mode control laws are studied and compared for speed and position control. An extended Kalman filter scheme for rotor resistance estimation is used. Simulation results show that the proposed scheme can achieve accurate speed/position tracking in the presence of load disturbances and rotor resistance variation. Important conclusions are reached regarding the merits and drawbacks of each of the sliding mode techniques.
Predictive maintenance of pumps based on signal analysis of pressure and differential pressure (flow) measurements
Authors: Higham E. H. , Perovic S.
Published: January 2007

Maintenance of process equipment is one of the inescapable tasks associated with the operation of process plants and, until relatively recently, it was implemented either on a routine basis or after the failure of equipment. Attitudes are changing and now many organizations are adopting methods for identifying incipient faults, so that maintenance can be scheduled before there has been a failure which would lead to loss of production and spoilage of raw material. These methods include schemes in which all the measurement signals in a plant are gathered and, in addition to providing the input to the various control systems, they are compared with model-based values for individual sections throughout the entire process, so that a warning or an alarm can be raised, according to the seriousness of the observed discrepancy. Although these methods represent a considerable advance on ‘routine maintenance’ and ‘repair after failure’, their effectiveness is limited by the quality and detail of the information that is gathered. Each process measurement should be regarded as a ‘window’ through which the operation of the process can be observed. However, the majority of existing process measurement systems have been designed to provide the input signal to a process control system, for which the primary requirement is a good average value. Typically, this is obtained by filtering out all the components of the sensor signal having frequencies greater than about 5 Hz, with the result that the ‘window’ is only translucent, rather than transparent, and much of the detailed information which is available at the interface between the process and the sensor is lost. If, on the other hand, the measurement system has a wide frequency response, then much of the information that is available at the interface between the process and the sensor can be gathered and analysed to provide a clear view of the operation and status of both the process and the measurement system. This concept involves two significant departures from the conventional approach to process measurements and to the utilization of measurement information. In the first place, the measurement systems should be designed to have the widest possible frequency response, so that the maximum information regarding the measured process parameter that is present at the interface between the process and the sensor is gathered. Secondly, instead of conditioning the primary sensor signal to provide a good average value for process control, it is analysed using well established techniques to provide not only the signal for process control but also information on which predictive maintenance procedures can be based.
Effects of centrifugal and roller pumps on survival of autologous red cells in cardiopulmonary bypass surgery
Authors: Valeri C R , Macgregor H , Ragno G , Healey N , Fonger J , Khuri S F
Published: January 2007

Background: Either a roller pump or a centrifugal pump can be used in the extracorporeal circuit during surgery with cardiopulmonary bypass. In this study, we assessed the effect of these two pumps on the 24-h post–transfusion survival values of autologous red blood cells (RBC). Study design and methods: Fourteen male patients subjected to extracorporeal bypass procedures were studied. In seven patients, the autologous red cells were collected following the cardiopulmonary bypass procedure using the roller pump, and in seven patients, autologous red cells were collected following the cardiopulmonary procedure using the centrifugal pump. The 24-h post–transfusion survival values of the autologous RBC were measured using the 51 disodium chromate/99m technetium double isotope procedure. The effects of the extracorporeal bypass procedures using the roller pump and the centrifugal pump were also assessed by the measurements of hematocrit, platelet count, plasma hemoglobin, and serum lactate dehydrogenase levels. Results: The 51 disodium chromate 24-h post–transfusion survival values of the autologous RBC were similar whether the roller pump or the centrifugal pump was used in the extracorporeal circulation, as were the hematocrit, platelet count, plasma hemoglobin and serum lactate dehydrogenase levels. Conclusion: The 24-h post–transfusion survival values of autologous RBC, measured by the 51 disodium chromate/99m technetium double isotope procedure, were not significantly different, whether the roller pump or the centrifugal pump was used in the extracorporeal circuit using membrane oxygenators during cardiopulmonary surgical procedures.
The application of a modified technique of SCP under DHCA during total aortic arch replacement combined with stented elephant trunk implantation
Authors: Ji Bingyang , Sun Lizhong , Liu Jinping , Liu Mingzheng , Sun Guimin , Wang Guyan , Liu Zhigang , Feng Zhengyi , Long Cun
Published: January 2007

We reviewed the perfusion experiences of 60 cases with a modified technique of selected cerebral perfusion (SCP) under deep hypothermic circulatory arrest (DHCA) during ascending aorta and total aortic arch replacement combined with transaortic stented graft implantation into the descending aorta for acute and chronic type A aortic dissection. Right auxiliary artery cannulation was routinely used for cardiopulmonary bypass (CPB) and SCP in this procedure. Generally, this technique requires two main pumps for two arterial lines before we applied the modified technique; one for CPB and the other for SCP. In order to simplify the circuit of the extracorporeal circuit (ECC) to operate easily, the arterial line was separated into two branches with a Y–connector on the operating table, one for axillary artery perfusion and the other for graft perfusion connected to the ECC set–up. This method is easy for the perfusionist to install and convenient for the surgeon. This is a safe and simple to use modified technique for SCP under DHCA during ascending aorta and total aortic arch replacement combined with transaortic stented graft implantation into the descending aorta.
Delayed thrombin generation is not associated with fibrinopeptide formation during prolonged cardiopulmonary bypass with hirudin anticoagulation
Authors: Belway D , Rubens F D , Henley B , Babaev A , Mesana T
Published: January 2007

Patients with heparin-induced thrombocytopenia urgently requiring surgery with cardiopulmonary bypass (CPB) present a unique management challenge that must be addressed by the use of alternative anticoagulants. Although clinical success with the direct thrombin inhibitor hirudin has been reported, there is sparse information in the literature supporting the efficacy of this drug as an anti-thrombotic to prevent fibrin formation during CPB. In this report, we describe the efficacy of this drug to prevent thrombin-mediated fibrin formation during CPB.
A new oxygenator change-out system and procedure
Authors: Da Broi U , Adami V , Falasca E , Malangone W , Crini S , Degrassi A
Published: January 2007

Official reports relate that, in the US, one patient/month dies as a result of the emergency oxygenator change-out procedure, and the permanent injury of some patients is the result of current oxygenator change-out procedures or oxygenator failures, both in extracorporeal circulation (ECC) and extracorporeal membrane oxygenation (ECMO).

The aim of this article is to evaluate a new system and procedure, dedicated to oxygenator change-out, represented by two three-way stopcocks inserted in the ECC line in use. A dedicated back-up oxygenator and circuit can be easily primed and connected to the dedicated connector on the stopcocks, then blood flow is diverted to the new oxygenator without interruption of the ECC.

Tests performed showed that oxygenator change-out can be completed by perfusionists in 62.139+11.12 sec. Results obtained show that the new system and procedure allows fast, safe and reproducible oxygenator change-out without interruption of the ECC.
Leucocyte depletion in a drowning victim during rewarming with extracorporeal circulation may limit pulmonary oedema
Authors: Vermeijden Wytze J , de Vries Hans , Kieboom Joke , Waterbolk Tjalling
Published: January 2007

Introduction: We report two drowning victims with hypothermic circulatory arrest who were resuscitated with the use of extracorporeal circulation (ECC). The first patient developed severe post–bypass pulmonary oedema and inspired us to use a leucocyte–depletion filter in the second patient to attenuate leucocyte–mediated pulmonary reperfusion injury. Methods: In the first patient, a standard extracorporeal circuit was used. In the second patient, systemic leucocyte depletion was applied using leucocyte–depletion filters (Pall RS 1, Pall, Portsmouth, UK), in the venous side of the extracorporeal circuit. Circulating leucocyte counts were measured and arterial blood gas analysis and chest X–rays were performed. Results: Both patients showed a decrease of the circulating leucocyte counts during rewarming and had nearly similar leucocyte counts on arrival at the intensive care unit (ICU). The first patient developed severe pulmonary oedema, with poor arterial blood gases, whereas the second patient, who had leucocyte–depletion by filtration, did not develop severe pulmonary oedema, and had good arterial blood gases. Conclusion: Profound leucocyte–depletion by means of filtration may have contributed to limit leucocyte–mediated pulmonary reperfusion injury.
Satellite remote sensing of natural Mediterranean vegetation: a review within an ecological context
Authors: Shoshany Maxim
Published: January 2007

Mediterrranean regions are characterized by high spatiotemporal heterogeneity of vegetation patterns. Understanding the dynamic nature of these environments requires detailed data for wide regions regarding changes in their phyto-ecology, biomass and productivity. This article assesses the current status of satellite remote sensing in this field of application. Mapping the five main life-forms (physiognomic classes) in Mediterranean regions (forests, woodlands, scrub, dwarf shrubs and herbaceous growth) has attracted major attention in recent years. Methodologies developed for this purpose are based on the spectral, temporal and spatial (textural) information domains provided by satellite data. Wide regional vegetation mapping was achieved using phenological classification of vegetation indices derived mainly from NOAA AVHRR images. More detailed mapping was conducted with multispectral techniques in local areas using mainly Landsat TM images. Assessments of multispectral and multi-temporal categories have shown limitations in their applicability over wide regions due mainly to the heterogeneity of Mediterranean regions. This heterogeneity cannot be regarded as a simple mixing of life-forms over large areas but, rather, the formation of transitional zones of varying mixtures resulting from disturbance and recovery cycles. Productivity and biomass monitoring has been found to be an active methodological development due to the introduction of new off-nadir viewing sensors in the visible and infrared spectral bands, and because of the development of methodologies for the retrieval of biophysical information from Synthetic Aperature Radar (SAR) data. Studies of ecosystem evolution using satellite data were conducted mainly in the fields of fire disturbance and desertification. Further progress in the remote sensing of Mediterranean vegetation ecology requires a better synergy of sensors, methods and ancillary data.
Combustion in tropical biomass fires: a critical review
Authors: Stott Philip
Published: January 2007

Despite the publication of a number of recent books, mainly edited compilations, on both fire ecology in general and, more specifically, fire ecology in the tropics, it remains difficult to obtain accessible overviews of many aspects of the subject. This is particularly so with regard to tropical biomass fires. The review presented here attempts to fill this gap with regard to the subjects of ignition and combustion in such fires, focusing on natural and anthropogenic ignition sources, the processes of ignition, the stages of combustion, combustion efficiency, fuel type, fuel flammability, fuel preparation, fuel loading and oxygenation of the environment.
Satellite remote sensing of biomass burning with optical and thermal sensors
Authors: Fuller Douglas O.
Published: January 2007

A major goal in satellite remote sensing of fire is to derive globally accurate measurements of the spatial and temporal distribution of burning. To date, the main sensor employed in fire and fire-scar detection has been the Advanced Very High Resolution Radiometer (AVHRR) on board NOAA polar-orbiting platforms. Other sources supporting fire observation over large areas include the Defense Meteorological Satellite Program -Optical Linescan (DMSP-OLS), the Geostationary Operational Environmental Satellite - 8 (GOES-8) and the Along Track Scanning Radiometer (ATSR). These sources have often been used in conjunction with high spatial-resolution imagery provided by the Landsat Thematic Mapper and SPOT to assess the accuracy of proposed fire and fire-scar retrieval algorithms.

Although a range of fire detection algorithms have been proposed based on more than a decade of research on the AVHRR data, it remains to be seen whether variations in land-cover type, surface temperature and fire regimes will permit application of global thresholds of temperature and reflectance. Moreover, the emerging set of satellite sensors with demonstrated utility in fire monitoring indicates substantial possibilities for greater synergy of current and future remote-sensing systems leading to improved monitoring of fire extent and frequency. As a more complete global picture of biomass burning emerges with the launch of new sensors for fire monitoring (e.g., MODIS), this information, combined with detailed data from field experiments, can help provide reliable budgets of trace gases and particulate species that affect global energy balance and climate.
Why are tropical rain forests so species rich? Classifying, reviewing and evaluating theories
Authors: Hill J. L. , Hill R. A.
Published: January 2007

Two classifications are presented that organize the major processes and theories addressing the high species diversity of tropical rain forests. The first typology organizes environmental and biological processes within a spatio-temporal hierarchy, whilst the second classifies 12 theories according to over-arching driving forces: genetic differentiation, environmental change, niche/habitat diversification and biotic interaction. The theories are reviewed and evaluated by delineating the development and current state of academic knowledge pertaining to each. General issues that arise from examining species diversity within the tropical realm are discussed and this indicates where the academic debate stands today. Some thoughts concerning future research avenues are included.