bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuronal Gamma-Band Synchronization as a Fundamental Process in Cortical Computation
Authors: Fries Pascal
Published: June 2009

Neuronal gamma-band synchronization is found in many cortical areas, is induced by different stimuli or tasks, and is related to several cognitive capacities. Thus, it appears as if many different gamma-band synchronization phenomena subserve many different functions. I argue that gamma-band synchronization is a fundamental process that subserves an elemental operation of cortical computation. Cortical computation unfolds in the interplay between neuronal dynamics and structural neuronal connectivity. A core motif of neuronal connectivity is convergence, which brings about both selectivity and invariance of neuronal responses. However, those core functions can be achieved simultaneously only if converging neuronal inputs are functionally segmented and if only one segment is selected at a time. This segmentation and selection can be elegantly achieved if structural connectivity interacts with neuronal synchronization. I propose that this process is at least one of the fundamental functions of gamma-band synchronization, which then subserves numerous higher cognitive functions.
Cerebellum and Nonmotor Function
Authors: Strick Peter L. , Dum Richard P. , Fiez Julie A.
Published: June 2009

Does the cerebellum influence nonmotor behavior? Recent anatomical studies demonstrate that the output of the cerebellum targets multiple nonmotor areas in the prefrontal and posterior parietal cortex, as well as the cortical motor areas. The projections to different cortical areas originate from distinct output channels within the cerebellar nuclei. The cerebral cortical area that is the main target of each output channel is a major source of input to the channel. Thus, a closed-loop circuit represents the major architectural unit of cerebro-cerebellar interactions. The outputs of these loops provide the cerebellum with the anatomical substrate to influence the control of movement and cognition. Neuroimaging and neuropsychological data supply compelling support for this view. The range of tasks associated with cerebellar activation is remarkable and includes tasks designed to assess attention, executive control, language, working memory, learning, pain, emotion, and addiction. These data, along with the revelations about cerebro-cerebellar circuitry, provide a new framework for exploring the contribution of the cerebellum to diverse aspects of behavior.
Functional analysis of human RhCG: comparison with E. coli ammonium transporter reveals similarities in the pore and differences in the vestibule
Authors: Zidi-Yahiaoui Nedjma , Callebaut Isabelle , Genetet Sandrine , Le Van Kim Caroline , Cartron Jean-Pierre , Colin Yves , Ripoche Pierre , Mouro-Chanteloup Isabelle
Published: June 2009

Rh glycoproteins are members of the ammonium transporter (Amt)/methylamine permease (Mep)/Rh family facilitating movement of NH3 across plasma membranes. Homology models constructed on the basis of the experimental structures of Escherichia coli AmtB and Nitrosomonas europaea Rh50 indicated a channel structure for human RhA (RhAG), RhB (RhBG), and RhC (RhCG) glycoproteins in which external and internal vestibules are linked by a pore containing two strictly conserved histidines. The pore entry is constricted by two highly conserved phenylalanines, “twin-Phe.” In this study, RhCG function was investigated by stopped-flow spectrofluorometry measuring kinetic pH variations in HEK293E cells in the presence of an ammonium gradient. The apparent unitary NH3 permeability of RhCG was determined and was found to be close to that of AmtB. With a site-directed mutagenesis approach, critical residues involved in Rh NH3 channel activity were highlighted. In the external vestibule, the importance of both the charge and the conformation of the conserved aspartic acid was shown. In contrast to AmtB, individual mutations of each phenylalanine of the twin-Phe impaired the function while the removal of both resulted in recovery of the transport activity. The impact of the mutations suggests that, although having a common function and a similar channel structure, bacterial AmtB and human Rh vary in several aspects of the NH3 transport mechanisms.
Temporal changes in vascular reactivity in early diabetes mellitus in rats: role of changes in endothelial factors and in phosphodiesterase activity
Authors: Abboud K. , Bassila J.-C. , Ghali-Ghoul R. , Sabra R.
Published: June 2009

The aims of this study were to study the influence of the duration of diabetes, the role of endothelial-derived vasodilators, and the role of phosphodiesterase (PDE) isoform activity in the early changes in vascular reactivity of aortic rings from diabetic rats. Diabetes mellitus was induced in female rats by intravenous streptozotocin (85 mg/kg). Two or 4 wk later, thoracic aortic rings from control and diabetic rats were isolated, and vascular responses to acetylcholine (ACh), S-nitroso- N-acetylpenicillamine (SNAP) [nitric oxide (NO) donor], DMPPO (PDE5 inhibitor), and phenylephrine (PE) were obtained in the presence and absence of endothelium or other drugs. PDE isoform activity was also measured. At 2 wk, responses to ACh and DMPPO were enhanced, whereas those to PE were attenuated in diabetic rats relative to controls. Indomethacin and SQ-29548 (a thromboxane A2receptor antagonist), but not NG-nitro-l-arginine methyl ester, corrected these differences. The responses to SNAP, and cAMP and cGMP hydrolytic activities, were similar in the two groups. In contrast, at 4 wk, ACh, DMPPO, and PE produced similar responses in the two groups: NG-nitro-l-arginine methyl ester rendered the response to PE lower in the diabetic group, and this was corrected by indomethacin, but not SQ-29548, treatment. The response to SNAP was greater in the diabetic group, and this was corrected by DMPPO. Activity of all PDEs was decreased at 4 wk. We conclude that, at 2 wk, there is modulation of thromboxane A2production, but no change in the NO system or PDE isoform activities. At 4 wk, a reduction in NO activity is superimposed; at this stage, PDE activity is reduced, together with increased production of vasodilating prostaglandins, possibly as a compensatory mechanism to maintain normal vascular reactivity.
Abl knockout differentially affects p130 Crk-associated substrate, vinculin, and paxillin in blood vessels of mice
Authors: Chen Shu , Wang Ruping , Li Qing-Fen , Tang Dale D.
Published: June 2009

Actin polymerization has recently emerged as an important cellular process that regulates smooth muscle contraction. Abelson tyrosine kinase (Abl) has been implicated in the regulation of actin dynamics and force development in vascular smooth muscle. In the present study, the systolic blood pressure was lower in Abl−/−knockout mice compared with wild-type mice. The knockout of Abl diminished the tyrosine phosphorylation of p130 Crk-associated substrate (CAS, an adapter protein associated with smooth muscle contraction) in resistance arteries upon stimulation with phenylephrine or angiotensin II. The agonist-elicited enhancement of F-actin-to-G-actin ratios in arteries assessed by fluorescent microscopy was also reduced in Abl−/−mice. It has been known that vinculin is a structural protein that links actin filaments to extracellular matrix via transmembrane integrins, whereas paxillin is a signaling protein associated with focal contacts mediating actin cytoskeleton remodeling. The expression of vinculin and paxillin at protein and messenger levels was lower in arterial vessels from Abl knockout mice. However, the agonist-induced increase in myosin phosphorylation was not attenuated in arteries from Abl knockout mice. These results indicate that Abl differentially regulates Crk-associated substrate, vinculin, and paxillin in arterial vessels. The Abl-regulated cellular process and blood pressure are independent of myosin activation in vascular smooth muscle.
Hypoxia induces B-type natriuretic peptide release in cell lines derived from human cardiomyocytes
Authors: Casals Gregori , Ros Josefa , Sionis Alessandro , Davidson Mercy M. , Morales-Ruiz Manuel , Jiménez Wladimiro
Published: June 2009

B-type natriuretic peptide (BNP) is a peptide hormone of myocardial origin with significant cardioprotective properties. Patients with myocardial ischemia present with high levels of BNP in plasma and elevated expression in the myocardium. However, the molecular mechanisms of BNP induction in the ischemic myocardium are not well understood. The aim of the investigation was to assess whether myocardial hypoxia induces the production of BNP in human ventricular myocytes. To test the hypothesis that reduced oxygen tension can directly stimulate BNP gene expression and release in the absence of hemodynamic or neurohormonal stimuli, we used an in vitro model system of cultured human ventricular myocytes (AC16 cells). Cells were cultured under normoxic (21% O2) or hypoxic (5% O2) conditions for up to 48 h. The accumulation of BNP, atrial natriuretic peptide (ANP), and vascular endothelial growth factor (VEGF) was then measured. Hypoxia stimulated the protein release of BNP and VEGF but not ANP. In concordance, the increased mRNA levels of BNP and VEGF but not ANP were found on culturing AC16 cells under hypoxic conditions. The analysis of the transcriptional activity of the hypoxia-inducible factor 1 (HIF-1) in nuclear extracts showed that HIF-1 activity was induced under hypoxic conditions. Finally, the treatment of AC16 cells with the HIF-1 inhibitor rotenone in hypoxia inhibited BNP and VEGF release. In conclusion, these data indicate that hypoxia induces the synthesis and secretion of BNP in human ventricular myocytes, likely through HIF-1-enhanced transcriptional activity.
Mechanical stress analysis of a rigid inclusion in distensible material: a model of atherosclerotic calcification and plaque vulnerability
Authors: Hoshino Tetsuya , Chow Lori A. , Hsu Jeffrey J. , Perlowski Alice A. , Abedin Moeen , Tobis Jonathan , Tintut Yin , Mal Ajit K. , Klug William S. , Demer Linda L.
Published: June 2009

The role of atherosclerotic calcification in plaque rupture remains controversial. In previous analyses using finite element model analysis, circumferential stress was reduced by the inclusion of a calcium deposit in a representative human anatomical configuration. However, a recent report, also using finite element analysis, suggests that microscopic calcium deposits increase plaque stress. We used mathematical models to predict the effects of rigid and liquid inclusions (modeling a calcium deposit and a lipid necrotic core, respectively) in a distensible material (artery wall) on mechanical failure under uniaxial and biaxial loading in a range of configurations. Without inclusions, stress levels were low and uniform. In the analytical model, peak stresses were elevated at the edges of a rigid inclusion. In the finite element model, peak stresses were elevated at the edges of both inclusions, with minimal sensitivity to the wall distensibility and the size and shape of the inclusion. Presence of both a rigid and a soft inclusion enlarged the region of increased wall stress compared with either alone. In some configurations, the rigid inclusion reduced peak stress at the edge of the soft inclusion but simultaneously increased peak stress at the edge of the rigid inclusion and increased the size of the region affected. These findings suggest that the presence of a calcium deposit creates local increases in failure stress, and, depending on relative position to any neighboring lipid pools, it may increase peak stress and the plaque area at risk of mechanical failure.
Differential structural and functional changes in penile and coronary arteries from obese Zucker rats
Authors: Villalba Nuria , Martínez Pilar , Bríones Ana Maria , Sánchez Ana , Salaíces Mercedes , García-Sacristán Albino , Hernández Medardo , Benedito Sara , Prieto Dolores
Published: June 2009

Erectile dysfunction frequently coexists with coronary artery disease and has been proposed as a potential marker for silent coronary artery disease in type 2 diabetes. In the present study, we comparatively assessed the structural and functional changes of both penile arteries (PAs) and coronary arteries (CAs) from a prediabetic animal model. PAs and CAs from 17- to 18-wk-old obese Zucker rats (OZRs) and from their control counterparts [lean Zucker rats (LZRs)] were mounted in microvascular myographs to evaluate vascular function, and stained arteries were subjected to morphometric analysis. Endothelial nitric oxide (NO) synthase (eNOS) protein expression was also assessed. The internal diameter was reduced and the wall-to-lumen ratio was increased in PAs from OZRs, but structure was preserved in CAs. ACh-elicited relaxations were severely impaired in PAs but not in CAs from OZRs, although eNOS expression was unaltered. Contractions to norepinephrine and 5-HT were significantly enhanced in both PAs and CAs, respectively, from OZRs. Blockade of NOS abolished endothelium-dependent relaxations in PAs and CAs and potentiated norepinephrine and 5-HT contractions in arteries from LZRs but not from OZRs. The vasodilator response to the phosphodiesterase 5 inhibitor sildenafil was reduced in both PAs and CAs from OZRs. Pretreatment with SOD reduced the enhanced vasoconstriction in both PAs and CAs from OZRs but did not restore ACh-induced relaxations in PAs. In conclusion, the present results demonstrate vascular inward remodeling in PAs and a differential impairment of endothelial relaxant responses in PAs and CAs from insulin-resistant OZRs. Enhanced superoxide production and reduced basal NO activity seem to underlie the augmented vasoconstriction in both PAs and CAs. The severity of the structural and functional abnormalities in PAs might anticipate the vascular dysfunction of the more preserved coronary vascular bed.
Olive oil-supplemented diet alleviates acute heat stress-induced mitochondrial ROS production in chicken skeletal muscle
Authors: Mujahid Ahmad , Akiba Yukio , Toyomizu Masaaki
Published: June 2009

We have previously shown that avian uncoupling protein (avUCP) is downregulated on exposure to acute heat stress, stimulating mitochondrial reactive oxygen species (ROS) production and oxidative damage. In this study, we investigated whether upregulation of avUCP could attenuate oxidative damage caused by acute heat stress. Broiler chickens ( Gallus gallus) were fed either a control diet or an olive oil-supplemented diet (6.7%), which has been shown to increase the expression of UCP3 in mammals, for 8 days and then exposed either to heat stress (34°C, 12 h) or kept at a thermoneutral temperature (25°C). Skeletal muscle mitochondrial ROS (measured as H2O2) production, avUCP expression, oxidative damage, mitochondrial membrane potential, and oxygen consumption were studied. We confirmed that heat stress increased mitochondrial ROS production and malondialdehyde levels and decreased the amount of avUCP. As expected, feeding birds an olive oil-supplemented diet increased the expression of avUCP in skeletal muscle mitochondria and decreased ROS production and oxidative damage. Studies on mitochondrial function showed that heat stress increased membrane potential in state 4, which was reversed by feeding birds an olive oil-supplemented diet, although no differences in basal proton leak were observed between control and heat-stressed groups. These results show that under heat stress, mitochondrial ROS production and olive oil-induced reduction of ROS production may occur due to changes in respiratory chain activity as well as avUCP expression in skeletal muscle mitochondria.
Histone deacetylase-2 is a key regulator of diabetes- and transforming growth factor-β1-induced renal injury
Authors: Noh Hyunjin , Oh Eun Young , Seo Ji Yeon , Yu Mi Ra , Kim Young Ok , Ha Hunjoo , Lee Hi Bahl
Published: June 2009

Excessive accumulation of extracellular matrix (ECM) in the kidneys and epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells contributes to the renal fibrosis that is associated with diabetic nephropathy. Histone deacetylase (HDAC) determines the acetylation status of histones and thereby controls the regulation of gene expression. This study examined the effect of HDAC inhibition on renal fibrosis induced by diabetes or transforming growth factor (TGF)-β1 and determined the role of reactive oxygen species (ROS) as mediators of HDAC activation. In streptozotocin (STZ)-induced diabetic kidneys and TGF-β1-treated normal rat kidney tubular epithelial cells (NRK52-E), we found that trichostatin A, a nonselective HDAC inhibitor, decreased mRNA and protein expressions of ECM components and prevented EMT. Valproic acid and class I-selective HDAC inhibitor SK-7041 also showed similar effects in NRK52-E cells. Among the six HDACs tested (HDAC-1 through -5 and HDAC-8), HDAC-2 activity significantly increased in the kidneys of STZ-induced diabetic rats and db/db mice and TGF-β1-treated NRK52-E cells. Levels of mRNA expression of fibronectin and α-smooth muscle actin were decreased, whereas E-cadherin mRNA was increased when HDAC-2 was knocked down using RNA interference in NRK52-E cells. Interestingly, hydrogen peroxide increased HDAC-2 activity, and the treatment with an antioxidant, N-acetylcystein, almost completely reduced TGF-β1-induced activation of HDAC-2. These findings suggest that HDAC-2 plays an important role in the development of ECM accumulation and EMT in diabetic kidney and that ROS mediate TGF-β1-induced activation of HDAC-2.
Soluble epoxide hydrolase gene deletion attenuates renal injury and inflammation with DOCA-salt hypertension
Authors: Manhiani Marlina , Quigley Jeffrey E. , Knight Sarah F. , Tasoobshirazi Shiva , Moore TarRhonda , Brands Michael W. , Hammock Bruce D. , Imig John D.
Published: June 2009

Inhibition of soluble epoxide hydrolase (sEH) has been shown to be renal protective in rat models of salt-sensitive hypertension. Here, we hypothesize that targeted disruption of the sEH gene (Ephx2) prevents both renal inflammation and injury in deoxycorticosterone acetate plus high salt (DOCA-salt) hypertensive mice. Mean arterial blood pressure (MAP) increased significantly in the DOCA-salt groups, and MAP was lower in Ephx2−/− DOCA-salt (129 ± 3 mmHg) compared with wild-type (WT) DOCA-salt (145 ± 2 mmHg) mice. Following 21 days of treatment, WT DOCA-salt urinary MCP-1 excretion increased from control and was attenuated in the Ephx2−/− DOCA-salt group. Macrophage infiltration was reduced in Ephx2−/− DOCA-salt compared with WT DOCA-salt mice. Albuminuria increased in WT DOCA-salt (278 ± 55 μg/day) compared with control (17 ± 1 μg/day) and was blunted in the Ephx2−/− DOCA-salt mice (97 ± 23 μg/day). Glomerular nephrin expression demonstrated an inverse relationship with albuminuria. Nephrin immunofluorescence was greater in the Ephx2−/− DOCA-salt group (3.4 ± 0.3 RFU) compared with WT DOCA-salt group (1.1 ± 0.07 RFU). Reduction in renal inflammation and injury was also seen in WT DOCA-salt mice treated with a sEH inhibitor { trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid; tAUCB}, demonstrating that the C-terminal hydrolase domain of the sEH enzyme is responsible for renal protection with DOCA-salt hypertension. These data demonstrate that Ephx2 gene deletion decreases blood pressure, attenuates renal inflammation, and ameliorates glomerular injury in DOCA-salt hypertension.
Dendritic Calcium Channels and Their Activation by Synaptic Signals in Auditory Coincidence Detector Neurons
Authors: Blackmer Trillium , Kuo Sidney P. , Bender Kevin J. , Apostolides Pierre F. , Trussell Laurence O.
Published: June 2009

The avian nucleus laminaris (NL) encodes the azimuthal location of low-frequency sound sources by detecting the coincidence of binaural signals. Accurate coincidence detection requires precise developmental regulation of the lengths of the fine, bitufted dendrites that characterize neurons in NL. Such regulation has been suggested to be driven by local, synaptically mediated, dendritic signals such as Ca2+. We examined Ca2+ signaling through patch clamp and ion imaging experiments in slices containing nucleus laminaris from embryonic chicks. Voltage-clamp recordings of neurons located in the NL showed the presence of large Ca2+ currents of two types, a low voltage–activated, fast inactivating Ni2+ sensitive channel resembling mammalian T-type channels, and a high voltage–activated, slowly inactivating Cd2+ sensitive channel. Two-photon Ca2+ imaging showed that both channel types were concentrated on dendrites, even at their distal tips. Single action potentials triggered synaptically or by somatic current injection immediately elevated Ca2+ throughout the entire cell. Ca2+ signals triggered by subthreshold synaptic activity were highly localized. Thus when electrical activity is suprathreshold, Ca2+ channels ensure that Ca2+ rises in all dendrites, even those that are synaptically inactive.
Slow Oscillation State Facilitates Epileptiform Events in the Hippocampus
Authors: Nazer Farhang , Dickson Clayton T.
Published: June 2009

In mesial temporal lobe (MTL) epilepsy, which typically involves the hippocampus (HPC), epileptiform events are enhanced during slow wave sleep (SWS). It remains unclear how and why the electroencephalographic (EEG) states that constitute SWS might predispose the HPC to this type of pathological activity. Recently our laboratory has described a novel state of deactivated hippocampal EEG activity that occurs during both SWS and urethan anesthesia: the slow oscillation (SO). This activity is characterized by a high-amplitude ∼1-Hz signal, high synchrony within the hippocampus, and a dynamic coordination with neocortical SO. To assess how this activity state might influence epileptiform discharges, we studied the properties of stimulation-evoked and spontaneous epileptiform events elicited in the HPC of urethan-anesthetized rats. We compared those elicited during the SO to those occurring during the theta rhythm. The average duration but not the amplitude of evoked afterdischarges (ADs) was consistently larger during the SO. In addition, spontaneous epileptiform events were more frequent and of higher amplitude during the SO. Last, the bilateral propagation of both ADs and spontaneous events in the hippocampus was enhanced during the SO. These results imply that the threshold for the generation and propagation of epileptiform activity in the hippocampus is lowered during the SO and that this state may be a seed for the initiation, maintenance, and generalization of MTL epilepsy. Further examination of the pathophysiology of sleep-epilepsy interactions in the HPC will be of benefit for an understanding of the mechanisms, prognosis, and therapy for this form of epilepsy.
Brain Stem Feedback in a Computational Model of Birdsong Sequencing
Authors: Gibb Leif , Gentner Timothy Q. , Abarbanel Henry D. I.
Published: June 2009

Uncovering the roles of neural feedback in the brain is an active area of experimental research. In songbirds, the telencephalic premotor nucleus HVC receives neural feedback from both forebrain and brain stem areas. Here we present a computational model of birdsong sequencing that incorporates HVC and associated nuclei and builds on the model of sparse bursting presented in our preceding companion paper. Our model embodies the hypotheses that 1) different networks in HVC control different syllables or notes of birdsong, 2) interneurons in HVC not only participate in sparse bursting but also provide mutual inhibition between networks controlling syllables or notes, and 3) these syllable networks are sequentially excited by neural feedback via the brain stem and the afferent thalamic nucleus Uva, or a similar feedback pathway. We discuss the model's ability to unify physiological, behavioral, and lesion results and we use it to make novel predictions that can be tested experimentally. The model suggests a neural basis for sequence variations, shows that stimulation in the feedback pathway may have different effects depending on the balance of excitation and inhibition at the input to HVC from Uva, and predicts deviations from uniform expansion of syllables and gaps during HVC cooling.
Measurement of Brain Function of Car Driver Using Functional Near‐Infrared Spectroscopy (fNIRS)
Authors: Tsunashima Hitoshi , Yanagisawa Kazuki
Published: June 2009

The aim of this study is to propose a method for analyzing measured signal obtained
from functional Near‐Infrared Spectroscopy (fNIRS), which is applicable for
neuroimaging studies for car drivers. We developed a signal processing method by
multiresolution analysis (MRA) based on discrete wavelet transform. Statistical group
analysis using Z‐score is conducted after the extraction of task‐related signal using
MRA. Brain activities of subjects with different level of mental calculation are
measured by fNIRS and fMRI. Results of mental calculation with nine subjects by using
fNIRS and fMRI showed that the proposed methods were effective for the evaluation of
brain activities due to the task. Finally, the proposed method is applied for evaluating
brain function of car driver with and without adaptive cruise control (ACC) system for
demonstrating the effectiveness of the proposed method. The results showed that frontal
lobe was less active when the subject drove with ACC.
Tea Polyphenols Decrease Serum Levels of Prostate-Specific Antigen, Hepatocyte Growth Factor, and Vascular Endothelial Growth Factor in Prostate Cancer Patients and Inhibit Production of Hepatocyte Growth Factor and Vascular Endothelial Growth Factor In vitro
Authors: McLarty Jerry , Bigelow Rebecca L.H. , Smith Mylinh , Elmajian Don , Ankem Murali , Cardelli James A.
Published: June 2009

The purpose of this study was to determine the effects of short-term supplementation with the active compounds in green tea on serum biomarkers in patients with prostate cancer.

Twenty-six men with positive prostate biopsies and scheduled for radical prostatectomy were given daily doses of Polyphenon E, which contained 800 mg of (−)-epigallocatechin-3-gallate (EGCG) and lesser amounts of (−)-epicatechin, (−)-epigallocatechin, and (−)-epicatechin-3-gallate (a total of 1.3 g of tea polyphenols), until time of radical prostatectomy. Serum was collected before initiation of the drug study and on the day of prostatectomy. Serum biomarkers hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF)-I, IGF binding protein-3 (IGFBP-3), and prostate-specific antigen (PSA) were analyzed by ELISA. Toxicity was monitored primarily through liver function enzymes. Changes in serum components were analyzed statistically using the Wilcoxon signed rank test. Cancer-associated fibroblasts were treated with EGCG, and HGF and VEGF protein and mRNA levels were measured.

HGF, VEGF, PSA, IGF-I, IGFBP-3, and the IGF-I/IGFBP-3 ratio decreased significantly during the study. All of the liver function tests also decreased, five of them significantly: total protein, albumin, aspartate aminotransferase, alkaline phosphatase, and amylase. The decrease in HGF and VEGF was confirmed in prostate cancer–associated fibroblasts in vitro.

Our results show a significant reduction in serum levels of PSA, HGF, and VEGF in men with prostate cancer after brief treatment with EGCG (Polyphenon E), with no elevation of liver enzymes. These findings support a potential role for Polyphenon E in the treatment or prevention of prostate cancer.
Lower Risk of Cervical Intraepithelial Neoplasia in Women with High Plasma Folate and Sufficient Vitamin B12 in the Post-Folic Acid Fortification Era
Authors: Piyathilake Chandrika J. , Macaluso Maurizio , Alvarez Ronald D. , Bell Walter C. , Heimburger Douglas C. , Partridge Edward E.
Published: June 2009

The purpose of this study was to determine the influence of plasma folate and vitamin B12 concentrations on cervical cancer risk in the U.S. after the folic acid fortification era. The study included 376 premenopausal women of childbearing age who tested positive for infections with high-risk (HR) human papillomaviruses (HPVs) and were diagnosed with cervical intraepithelial neoplasia (CIN) grade 2 or higher (CIN 2+, cases) or ≤CIN 1 (noncases). CIN 2+ (yes/no) was the dependent variable in logistic regression models that specified plasma folate concentrations combined with plasma B12 concentrations as the independent predictors of primary interest, adjusting for age, race, education, smoking, parity, number of life-time male sexual partners, use of contraceptives, waist circumference, physical activity, healthy eating index, and circulating concentrations of vitamins A, C, tocopherol, and total carotene. Women with supraphysiologic concentrations of plasma folate (>19.8 ng/mL) who also had sufficient plasma vitamin B12 (≥200.6 pg/mL) had 70% lower odds of being diagnosed with CIN 2+ (P = 0.04) when compared with women with plasma folate of ≤19.8 ng/mL and plasma vitamin B12 of <200.6 pg/mL. Our results do not corroborate the concern that supraphysiologic plasma folate concentrations seen in the post-U.S. folic acid fortification era increase the risk of CIN in premenopausal women of childbearing age. In fact, higher folate is associated with significantly lower risk of CIN, especially when vitamin B12 is sufficient, demonstrating the importance of vitamin B12 in the high-folate environment created by the folic acid fortification program.
Comparison of Three Motion Cueing Algorithms for Curve Driving in an Urban Environment
Authors: Valente Pais A. R , Wentink M , van Paassen M. M , Mulder M
Published: June 2009

Research on new automotive systems currently relies on car driving simulators, as they are a cheaper, faster, and safer alternative to tests on real tracks. However, there is increasing concern about the motion cues provided in the simulator and their influence on the validity of these studies. Especially for curve driving, providing large sustained acceleration is difficult in the limited motion space of simulators. Recently built simulators, such as Desdemona, offer a large motion space showing great potential as automotive simulators. The goal of this research is: first, to develop a motion drive algorithm for urban curve driving in the Desdemona simulator; and second, to evaluate the solution through a simulator driving experiment. The developed algorithm, the one-to-one yaw algorithm, is compared to a classical washout algorithm (adapted to the Desdemona motion space) and a control condition where only road rumble is provided. Results show that regarding lateral motion, the absence of cues in the rumble condition is preferred over the presence of false cues in the classical algorithm. “No motion” seems to be favored over “bad motion.” In terms of longitudinal motion, the one-to-one yaw and the classical algorithm are voted better than the rumble condition, showing that the addition of motion cues is beneficial to the simulation of braking. In a general way, the one-to-one yaw algorithm is classified better than the other two algorithms.
Beyond the Happy Consensus about Democratic Elitism
Authors: Körösényi András
Published: June 2009

A growing number of studies assign elites and leaders a larger role than democratic elitism assumes. Democratic elitism is not a coherent theory because it papers over three quite distinct models of political representation and democratic control: Robert Dahl's mandate model; the accountability model associated chiefly with John Plamenatz; and the authorization model set forth by Adam Przeworski and colleagues. This last model, wherein elites and leaders conceptualize and present voters' choices, best captures elite-voter relations in today's democracies. This authorization model is decidedly pessimistic about controlling elites and leaders in a democracy, but it is nonetheless compatible with a skeptical reading of Schumpeter.
Identity, Unity and Historiography: The Piketberg Ecclesial Narrative Revisted
Authors: Julius Elize
Published: June 2009

The aim of this essay is to develop a critical assessment of the history of the family of Dutch Reformed churches in Piketberg. The purpose of this is to determine a more adequate theological framework for the deconstruction of the traditional ecclesiological and socio-cultural anthropologies as a first step in the process of establishing sound ecclesiological and socio-cultural relations in the ongoing process of being church. Within this ecclesiological exploration, the focus will be on the schism within the once one Reformed congregation of Piketberg into three separate congregations and specifically on the unique understandings of the reasons for the divide along racial lines. The emphasis for this study is on the theological accountability of the church and all her members, with a specific emphasis on theological identity within the Reformed church in South Africa. The case study will thus focus on the stories of one particular place in the hope of raising more general ecclesiological questions of identity, culture and race.
Die Rhetorik der Degeneration in der antisemitischen Literatur Das Bild des ,,entarteten“ jüdischen Künstlers
Authors: Pelloni Gabriella
Published: June 2009

This essay analyses the specific rhetoric of degeneration which was observable in the antisemitic polemic discourse of the last decades of 19th century. It provides an overview of the representation of Jewish art und artists as it took shape in the antisemitic literature of the Wilhelminian epoch. The growing emphasis placed by psychiatrists and racial theorists on the pathologies of the ,,Jewish race“, such as hysteria or degeneration, resulted in the tendency to pathologize Jewish art and artists, which were deemed responsible for the alleged decline of German culture. Mere aesthetic categories underwent a process of reduction and ideologization and were finally used for defamatory purposes, as shown in the case of the antisemitic denigration of Heinrich Heine. In order to demonstrate this, the analysis outlines the strict dichotomic logic of these argumentations, as the definition and consolidation of an ideal German essence was usually based on the construction of a degenerated Jewish identity.
Ethnic Identity and the Gospel of Reconciliation
Authors: Pachuau Lalsangkima
Published: June 2009

Closer proximity through powerful communication systems seems to have made people more assertive of their identities, especially their cultural or ethnic identities. The consciousness of the cultural self and the cultural other has become one of the most important political tools in the societal life. Ethnic identity assertions have been blamed as the cause of much dissensions and violence. In dealing with ethnic relations, scholars have found that the proximate other is the most difficult other to deal with. Is identity assertion then the enemy of reconciliation? This article argues that it need not be. By arguing that identity is a relational entity formed in the consciousness of the self in relation to the other (non-self), a healthy and respectful way of perceiving the other can be cultivated. A truthful recognition of the otherness of the other leads to what theologian Miroslav Volf calls "double vision" (the ability to view not only "from here" but also "from there") which is the essential step to "embrace" the other. Christian mission is about crossing the boundary between the self and the other, and the challenge is to love the neighbor (proximate other) as oneself. Self-privileging through self-consciousness of being the elect of God withheld the Christian sense of its missionary nature for a long time. The Church's missionary calling of being other-centered rather than being self-centered is the theological foundation for a conciliatory existence.
Missiological Reflections on Difference: Foundations in the Gospel of Luke
Authors: Glanville Elizabeth
Published: June 2009

This paper explores missiological reflections on the Gospel of Luke for valuing differences in order to develop an understanding of human identity. Our identity in Jesus Christ supersedes racial, ethnic, and social identity and is based on an understanding of difference that affirms the uniqueness of each individual.A perspective that values human dignity and the dignity of difference, as per Rabbi Jonathan Sacks, stands in sharp contrast to the biblical images of Pharisees who separated themselves from the sinners, tax-collectors, and others. Likewise, Jesus, himself, in the Gospel of Luke, sets his message of the Kingdom of God over against the perspective of differences that established divisions as taught and practiced by the Pharisees. Andrew Walls and Paul Hiebert expound the need to value the contributions of other cultures to the understanding of God which will enrich the entire Body of Christ. Together these perspectives provide a foundation for exploring biblical passages for missiological reflections on difference.Missiological implications of difference that value human dignity are drawn and applied to relationships within the body, crossing cultural barriers with the message of Jesus Christ, and interfaith dialogue.
Mission and Human Identity in the Light of Edinburgh 1910
Authors: Stanley Brian
Published: June 2009

Christian theology makes two bold claims relevant to the theme of reconciliation and human identity: first, that the propagation of the gospel of Christ offers the best prospect for reconciliation between human persons; and second, that human beings find their identity most completely by being "in Christ". These two claims are, however, hotly disputed. Both non-Christian writers (such as Jonathan Sacks) and Christian ones (such as S.J. Samartha) regard the Christian missionary project of conversion as a denial of the "dignity of difference", and hence as a serious obstacle to human reconciliation. The second claim is also subject to challenge, not least because of historical evidence from European encounters with the successive New Worlds of the Americas and the South Pacific that Christians have used it to deny that indigenous peoples beyond Christendom deserve to be treated as fully human. Nevertheless, both claims may still be defended by Christians. The Christian idea of reconciliation is distinctive, based on the idea of exchange and the prior initiative of unmerited forgiveness which is at the heart of the doctrine of the atonement. As with the atonement itself, it does not ignore the demands of justice. The experience of the Truth and Reconciliation Commission in South Africa offers one example of how a distinctively Christian approach to reconciliation can work politically. Equally, the second claim that humanity finds its true identity in Christ is rightly understood as an affirmation that the several (and developing) identities of different cultures all have a crucial contribution to make to the catholicity of the Christian faith: this perception was expounded at the World Missionary Conference at Edinburgh in 1910 by Bishop Charles Gore.
Human Identity and the Gospel of Reconciliation: Agenda For Mission Studies and Praxis in the 21st Century: An African Reflection
Authors: Mwaura Philomena Njeri
Published: June 2009

In her Presidential address, Philomena Mwaura explores the challenges posed to Christian identity in Africa by ethnocenticism which questions its authenticity despite a century of evangelization and the Church's tremendous growth. Tracing the markers of Christian identity to the New Testament which are characterized by transformation in Christ, love, unity and embrace of the other, she argues that only a people who are secure in their Christian identity can witness authentically to the Gospel and its appealing power. The ministry of reconciliation, as articulated by Paul, is an imperative in diverse contexts characterized by conflicting and competing identities that are ethnic, national and religious among others. The Church requires to equip itself for this ministry by being prophetic, vigilant, intrusive and in solidarity with the marginalized.
Response of ENSO and the Mean State of the Tropical Pacific to Extratropical Cooling and Warming: A Study Using the IAP Coupled Model
Authors: Yu Y. , Sun D-Z.
Published: June 2009

The coupled model of the Institute of Atmospheric Physics (IAP) is used to investigate the effects of extratropical cooling and warming on the tropical Pacific climate. The IAP coupled model is a fully coupled GCM without any flux correction. The model has been used in many aspects of climate modeling, including the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4) climate change and paleoclimate simulations. In this study, the IAP coupled model is subjected to cooling or heating over the extratropical Pacific. As in an earlier study, the cooling and heating is imposed over the extratropical region poleward of 10°N–10°S.

Consistent with earlier findings, an elevated (reduced) level of ENSO activity in response to an increase (decrease) in the cooling over the extratropical region is found. The changes in the time-mean structure of the equatorial upper ocean are also found to be very different between the case in which ocean–atmosphere is coupled over the equatorial region and the case in which the ocean–atmosphere over the equatorial region is decoupled. For example, in the uncoupled run, the thermocline water across the entire equatorial Pacific is cooled in response to an increase in the extratropical cooling. In the corresponding coupled run, the changes in the equatorial upper-ocean temperature in the extratropical cooling resemble a La Niña situation—a deeper thermocline in the western and central Pacific accompanied by a shallower thermocline in the eastern Pacific. Conversely, with coupling, the response of the equatorial upper ocean to extratropical cooling resembles an El Niño situation. These results ascertain the role of extratropical ocean in determining the amplitude of ENSO. The results also underscore the importance of ocean–atmosphere coupling in the interaction between the tropical Pacific and the extratropical Pacific.
Diagnosing the Southern Ocean Overturning from Tracer Fields
Authors: Zika Jan D. , Sloyan Bernadette M. , McDougall Trevor J.
Published: June 2009

The strength and structure of the Southern Hemisphere meridional overturning circulation (SMOC) is related to the along-isopycnal and vertical mixing coefficients by analyzing tracer and density fields from a hydrographic climatology. The meridional transport of Upper Circumpolar Deep Water (UCDW) across the Antarctic Circumpolar Current (ACC) is expressed in terms of the along-isopycnal (K) and diapycnal (D) tracer diffusivities and in terms of the along-isopycnal potential vorticity mixing coefficient (KPV). Uniform along-isopycnal (<600 m2 s−1) and low vertical mixing (10−5 m2 s−1) can maintain a southward transport of less than 60 Sv (Sv = 106 m2 s−1) of UCDW across the ACC, which is distributed largely across the South Pacific and east Indian Ocean basins. For vertical mixing rates of O(10−4 m2 s−1) or greater, the inferred transport is significantly enhanced. The transports inferred from both tracer and density distributions suggest a ratio K to D of O(2 × 106) particularly on deeper layers of UCDW. Given the range of observed southward transports of UCDW, it is found that K = 300 ± 150 m2 s−1 and D = 10−4 ± 0.5 × 10−4 m2 s−1 in the Southern Ocean interior. A view of the SMOC is revealed where dense waters are converted to lighter waters not only at the ocean surface, but also on depths below that of the mixed layer with vertical mixing playing an important role.
Toward Improved Convection-Allowing Ensembles: Model Physics Sensitivities and Optimizing Probabilistic Guidance with Small Ensemble Membership
Authors: Schwartz Craig S. , Kain John S. , Weiss Steven J. , Xue Ming , Bright David R. , Kong Fanyou , Thomas Kevin W. , Levit Jason J. , Coniglio Michael C. , Wandishin Matthew S.
Published: June 2009

During the 2007 NOAA Hazardous Weather Testbed Spring Experiment, the Center for Analysis and Prediction of Storms (CAPS) at the University of Oklahoma produced a daily 10-member 4-km horizontal resolution ensemble forecast covering approximately three-fourths of the continental United States. Each member used the Advanced Research version of the Weather Research and Forecasting (WRF-ARW) model core, which was initialized at 2100 UTC, ran for 33 h, and resolved convection explicitly. Different initial condition (IC), lateral boundary condition (LBC), and physics perturbations were introduced in 4 of the 10 ensemble members, while the remaining 6 members used identical ICs and LBCs, differing only in terms of microphysics (MP) and planetary boundary layer (PBL) parameterizations. This study focuses on precipitation forecasts from the ensemble.

The ensemble forecasts reveal WRF-ARW sensitivity to MP and PBL schemes. For example, over the 7-week experiment, the Mellor–Yamada–Janjić PBL and Ferrier MP parameterizations were associated with relatively high precipitation totals, while members configured with the Thompson MP or Yonsei University PBL scheme produced comparatively less precipitation. Additionally, different approaches for generating probabilistic ensemble guidance are explored. Specifically, a “neighborhood” approach is described and shown to considerably enhance the skill of probabilistic forecasts for precipitation when combined with a traditional technique of producing ensemble probability fields.
Addressing Concerns and Taking on the Third Rail
Authors: Bieschke Kathleen J. , Mintz Laurie B.
Published: June 2009

In this rejoinder, the authors begin by addressing some of the questions raised about the Values Statement. They then focus on next steps, first briefly summarizing a few excellent suggestions made by the authors of the reaction papers and then zeroing in on the tension-wrought issue of when values regarding sexual orientation and religion collide. Reasons for the polarization in the field regarding this issue are discussed, and the contribution of the Values Statement to addressing this polarization is reviewed. A next step to decrease this polarization, developing Implementing Regulations for Footnote 4, is also suggested. The authors conclude with the hope that this Major Contribution has helped to move the field toward an approach to training that provides guidance when resolving highly charged values conflicts.
Commemoration and Propaganda in Salazar's Portugal: The Mundo Português Exposition of 1940
Authors: Corkill David , Pina Almeida José Carlos
Published: June 2009

Salazar's Portugal is often represented as a colourless, pale imitation of the fascist dictatorships in other parts of Europe during the 1930s and 1940s. Yet, in its consolidation phase, the regime embraced the concept of the `festival state', and commemorative events and expositions became key ingredients in the attempt to forge a new, highly selective cultural identity for the Portuguese people. The centerpiece of these efforts was the Mundo Português Exposition of 1940, when the symbols of a new hybrid identity grafted the discourse of Empire onto the traditional conservatism of the New State ( Estado Novo). This major cultural event served a triple function for the regime's propagandists: in their quest for regime legitimacy, for propagating Salazar's nationalist version of the nation's history, and in shaping the national consciousness of the Portuguese people in order to eliminate the `anti-national'.
Seventy Years On: Historians and Repression During and After the Spanish Civil War
Authors: Ruiz Julius
Published: June 2009

The issue of repression remains one of the most controversial issues arising from the Spanish Civil War and General Franco's unconditional victory in 1939. This article discusses the (mainly Spanish) historiography of both Francoist and Republican political violence, and questions the widely held belief that a `pact of forgetfulness' characterized Spanish historians' treatment of the subject following the death of Franco in November 1975. It argues that the dominant characteristic of repression historiography has been the persistence of contemporary Republican explanations, in particular the alleged contrast between Francoist `plans of extermination' and Republican `uncontrollable' violence. The article rejects such interpretations, and points to new trends in research.