bluuebunny/crossref_metadata_2025 huggingface dataset:
Homocysteine impairs coronary artery endothelial function by inhibiting tetrahydrobiopterin in patients with hyperhomocysteinemia
Authors: He Liyun , Zeng Hui , Li Fuwang , Feng Jieli , Liu Shan , Liu Jinbo , Yu Jie , Mao Jieming , Hong Tianpei , Chen Alex F. , Wang Xian , Wang Guang
Published: September 2010

Hyperhomocysteinemia (HHcy) has been associated with impaired vascular endothelial function. Our previous study demonstrated significantly higher secretion of the chemokine monocyte chemoattractant protein-1 from monocytes in response to lipopolysaccharide in patients with HHcy. In the present study, we investigated whether coronary endothelial function was damaged in patients with chronic HHcy (plasma level of homocysteine >15 μmol/l) and, if so, whether this impaired endothelial function is induced by the uncoupling of endothelial nitric oxide synthase (eNOS). When tetrahydrobiopterin levels are inadequate, eNOS is no longer coupled to l-arginine oxidation, which results in reactive oxygen species rather than nitric oxide production, thereby inducing vascular endothelial dysfunction. The 71 participants were divided into two groups, control ( n = 50) and HHcy ( n = 21). Quantification of coronary flow velocity reserve (CFVR) was after rest and after adenosine administration done by noninvasive Doppler echocardiography. Plasma levels of nitric oxide and tetrahydrobiopterin were significantly lower in patients with HHcy than in controls (99.54 ± 32.23 vs. 119.50 ± 37.68 μmol/l and 1.43 ± 0.46 vs. 1.73 ± 0.56 pmol/ml, all P < 0.05). Furthermore, CFVR was significantly lower in the HHcy than the control group (2.76 ± 0.49 vs. 3.09 ± 0.52, P < 0.05). In addition, plasma level of homocysteine was negatively correlated with CFVR. Chronic HHcy may contribute to coronary artery disease by inducing dysfunction of the coronary artery endothelium. The uncoupling of eNOS induced by HHcy in patients with chronic HHcy may explain this adverse effect in part.
Gastrointestinal Cytoprotection by PPAR Ligands
Authors: Naito Yuji , Takagi Tomohisa , Yoshikawa Toshikazu
Published: September 2010

Peroxisome proliferator-activated receptor (PPAR) is a nuclear receptor that is known to play a central role in lipid metabolism and insulin sensitivity as well as inflammation and cell proliferation. According to the results obtained from studies on several animal models of gastrointestinal inflammation, PPAR has been implicated in the regulation of the immune response, particularly inflammation control, and has gained importance as a potential therapeutic target in the management of gastrointestinal inflammation. In the present paper, we present the current knowledge on the role of PPAR ligands in the gastrointestinal tract.
An Expectation Maximization Algorithm to Model Failure Times by Continuous‐Time Markov Chains
Authors: Duan Qihong , Chen Zhiping , Zhao Dengfu
Published: September 2010

In many applications, the failure rate function may present a bathtub shape curve. In this paper, an expectation maximization algorithm is proposed to construct a suitable continuous‐time Markov chain which models the failure time data by the first time reaching the absorbing state. Assume that a system is described by methods of supplementary variables, the device of stage, and so on. Given a data set, the maximum likelihood estimators of the initial distribution and the infinitesimal transition rates of the Markov chain can be obtained by our novel algorithm. Suppose that there are m transient states in the system and that there are n failure time data. The devised algorithm only needs to compute the exponential of m × m upper triangular matrices for O(nm2) times in each iteration. Finally, the algorithm is applied to two real data sets, which indicates the practicality and efficiency of our algorithm.
Improved Results on Fuzzy H∞ Filter Design for T‐S Fuzzy Systems
Authors: An Jiyao , Wen Guilin , Xu Wei
Published: September 2010

The fuzzy H∞ filter design problem for T‐S fuzzy systems with interval time‐varying delay is investigated. The delay is considered as the time‐varying delay being either differentiable uniformly bounded with delay derivative in bounded interval or fast varying (with no restrictions on the delay derivative). A novel Lyapunov‐Krasovskii functional is employed and a tighter upper bound of its derivative is obtained. The resulting criterion thus has advantages over the existing ones since we estimate the upper bound of the derivative of Lyapunov‐Krasovskii functional without ignoring some useful terms. A fuzzy H∞ filter is designed to ensure that the filter error system is asymptotically stable and has a prescribed H∞ performance level. An improved delay‐derivative‐dependent condition for the existence of such a filter is derived in the form of linear matrix inequalities (LMIs). Finally, numerical examples are given to show the effectiveness of the proposed method.
Optimized Hybrid Resource Allocation in Wireless Cellular Networks with and without Channel Reassignment
Authors: Wu Xin , Jaekel Arunita , Bari Ataul , Ngom Alioune
Published: September 2010

In cellular networks, it is important to determine an optimal channel assignment scheme so that the available channels, which are considered as “limited” resources in cellular networks, are used as efficiently as possible. The objective of the channel assignment scheme is to minimize thecall-blockingand thecall-droppingprobabilities. In this paper, we present two efficient integer linear programming (ILP) formulations, foroptimallyallocating a channel (from a pool of available channels) to an incoming call such that both “hard” and “soft” constraints are satisfied. Our first formulation, ILP1, does not allow channel reassignment of the existing calls, while our second formulation, ILP2, allows such reassignment. Both formulations can handle hard constraints, which includesco-siteandadjacent channelconstraints, in addition to the standardco-channelconstraints. The simplified problem (with only co-channel constraints) can be treated as a special case of our formulation. In addition to the hard constraints, we also consider soft constraints, such as, thepacking condition, resonance condition,andlimiting rearrangements, to further improve the network performance. We present the simulation results on a benchmark 49 cell environment with 70 channels that validate the performance of our approach.
3D Network-on-Chip Architectures Using Homogeneous Meshes and Heterogeneous Floorplans
Authors: de Paulo Vitor , Ababei Cristinel
Published: September 2010

We propose new 3D 2-layer and 3-layer NoC architectures that utilizehomogeneousregular mesh networks on a separate layer and one or twoheterogeneousfloorplanning layers. These architectures combine the benefits of compact heterogeneous floorplans and of regular mesh networks. To demonstrate these benefits, a design methodology that integrates floorplanning, routers assignment, and cycle-accurate NoC simulation is proposed. The implementation of the NoC on a separate layer offers an additional area that may be utilized to improve the network performance by increasing the number of virtual channels, buffers size, or mesh size. Experimental results show that increasing the number of virtual channels rather than the buffers size has a higher impact on network performance. Increasing the mesh size can significantly improve the network performance under the assumption that the clock frequency is given by the length of the physical links. In addition, the 3-layer architecture can offer significantly better network performance compared to the 2-layer architecture.
Towards Inhibition of Vif-APOBEC3G Interaction: Which Protein to Target?
Authors: Cadima-Couto Iris , Goncalves Joao
Published: September 2010

APOBEC proteins appeared in the cellular battle against HIV-1 as part of intrinsic cellular immunity. The antiretroviral activity of some of these proteins is overtaken by the action of HIV-1 Viral Infectivity Factor (Vif) protein. Since the discovery of APOBEC3G (A3G) as an antiviral factor, many advances have been made to understand its mechanism of action in the cell and how Vif acts in order to counteract its activity. The mainstream concept is that Vif overcomes the innate antiviral activity of A3G by direct protein binding and promoting its degradation via the cellular ubiquitin/proteasomal pathway. Vif may also inhibit A3G through mechanisms independent of proteasomal degradation. Binding of Vif to A3G is essential for its degradation since disruption of this interaction is predicted to stimulate intracellular antiviral immunity. In this paper we will discuss the different binding partners between both proteins as one of the major challenges for the development of new antiviral drugs.
Flow‐Induced Vibration Analysis of Supported Pipes Conveying Pulsating Fluid Using Precise Integration Method
Authors: Liu Long , Xuan Fuzhen
Published: September 2010

Dynamic analysis of supported pipes conveying pulsating fluid is investigated in Hamiltonian system using precise integration method (PIM). First, symplectic canonical equations of supported pipes are deduced with state variable vectors composed of displacement and momentum. Then, PIM with linear interpolation formula is proposed to solve these equations. Finally, this approach′s precision is testified by several numerical examples of pinned‐pinned pipes with different fluid velocities and frequencies. The results show that PIM is an efficient and rapid approach for flow‐induced dynamic analysis o f supported pipes.
Anticancer Potentials of Root Extract of Polygala senega and Its PLGA Nanoparticles‐Encapsulated Form
Authors: Paul Saili , Bhattacharyya Soumya Sundar , Boujedaini Naoual , Khuda-Bukhsh Anisur Rahman
Published: September 2010

Ethanolic extract of Polygala senega (EEPS) had little or no cytotoxic effects on normal lung cells, but caused cell death and apoptosis to lung cancer cell line A549. In the present paper, ethanolic root extract of P. senega (EEPS) was nanoencapsulated (size: 147.7 nm) by deploying a biodegradable poly‐(lactic‐co‐glycolic) acid (PLGA). The small size of the NEEPS resulted in an enhanced cellular entry and greater bioavailability. The growth of cancer cells was inhibited better by NEEPS than EEPS. Both EEPS and NEEPS induced apoptosis of A549 cells, which was associated with decreased expression of survivin, PCNA mRNA, and increased expression of caspase‐3, p53 mRNAs of A549 cells. The results show that the anticancer potential of the formulation of EEPS‐loaded PLGA nanoparticles was more effective than EEPS per se, probably due to more aqueous dispersion after nanoencapsulation. Therefore, nanoencapsulated ethanolic root extract of P. senega may serve as a potential chemopreventive agent against lung cancer.
In Vivo Imaging of Particle‐Induced Inflammation and Osteolysis in the Calvariae of NFκB/Luciferase Transgenic Mice
Authors: Takahashi Kunihiko , Onodera Shin , Tohyama Harukazu , Kwon Hyuck Joon , Honma Ken-ichi , Yasuda Kazunori
Published: September 2010

Wear debris causes biological response which can result in periprosthetic osteolysis after total joint replacement surgery. Nuclear factor‐kappa B (NFκB), a representative transcription factor involved in inflammation, is believed to play an important role in this event by regulating the production of proinflammatory mediators and osteoclastogenesis. In this study, we sought to determine whether activation of NFκB in response to stimulation by particles could be visualized by in vivo imaging. We loaded polyethylene (PE) particles onto the calvaria of NFκB/luciferase transgenic mouse, and detected luminescence generated by activation of NFκB. On day 7 after loading, the level of luminescence was maximal. Levels of luminescence were significantly correlated with the levels of luciferase activity, proinflammatory mediator mRNAs, and bone resorption parameters. This system, which enabled us to evaluate particle‐induced inflammation and osteolysis without sacrificing mice, constitutes a useful tool for evaluating the efficacy of prophylaxis or treatments for particle‐induced osteolysis.
Farletuzumab, a Humanized Monoclonal Antibody against Folate Receptor α, in Epithelial Ovarian Cancer: a Phase I Study
Authors: Konner Jason A. , Bell-McGuinn Katherine M. , Sabbatini Paul , Hensley Martee L. , Tew William P. , Pandit-Taskar Neeta , Els Nicholas Vander , Phillips Martin D. , Schweizer Charles , Weil Susan C. , Larson Steven M. , Old Lloyd J.
Published: September 2010

Purpose: Folate receptor α expression is highly restricted in normal adult tissues but upregulated in a wide range of human cancer types, including epithelial ovarian cancer. Farletuzumab, a humanized monoclonal antibody against folate receptor α, has shown antitumor activity and favorable toxicity in preclinical evaluation. This phase I, dose-escalation study was conducted to determine the safety of weekly i.v. farletuzumab and establish the maximum tolerated dose (MTD).

Experimental Design: Patients with platinum-refractory or platinum-resistant epithelial ovarian cancer received farletuzumab (12.5-400 mg/m2) on days 1, 8, 15, and 22 of a 5-week cycle. Intrapatient dose escalation was not permitted. Dose-limiting toxicity (DLT) was defined by treatment-related adverse event of grade 3 or higher, and the MTD was the highest dose at which one or none of six patients experienced a DLT. Disease progression was recorded using Response Evaluation Criteria in Solid Tumors criteria and serum CA-125.

Results: Twenty-five heavily pretreated patients were included in the safety, efficacy, and pharmacokinetic analyses. No DLTs or MTDs were encountered, and dose escalation was continued to farletuzumab 400 mg/m2. Cmax and AUC0-24 (area under the serum concentration-time curve) increased in an approximately dose-proportional manner, and a nuclear imaging substudy confirmed tumor targeting. There were no objective responses. Stable disease by Response Evaluation Criteria in Solid Tumors was observed in nine (36%) patients and CA-125 reduction in four. Three patients received continued therapy and completed a total of up to three cycles.

Conclusions: In this phase I study, farletuzumab administered as an i.v. infusion at doses of 12.5 to 400 mg/m2 was generally safe and well tolerated in the management of heavily pretreated patients with epithelial ovarian cancer. Clin Cancer Res; 16(21); 5288–95. ©2010 AACR.
Orally Administered Particulate β-Glucan Modulates Tumor-Capturing Dendritic Cells and Improves Antitumor T-Cell Responses in Cancer
Authors: Li Bing , Cai Yihua , Qi Chunjian , Hansen Richard , Ding Chuanlin , Mitchell Thomas C. , Yan Jun
Published: September 2010

Purpose: The beneficial properties of β-glucans have been recognized for centuries. Their proposed mechanisms of action in cancer therapy occur via stimulation of macrophages and priming of innate neutrophil complement receptor 3 for eliciting complement receptor 3–dependent cellular cytotoxicity of iC3b-opsonized tumor cells. The current study is to investigate whether β-glucan therapy has any effect on antitumor adaptive T-cell responses.

Experimental Design: We first examined the trafficking of orally administered particulate yeast-derived β-glucan and its interaction with dendritic cells (DC) that captured tumor materials. Antigen-specific T cells were adoptively transferred into recipient mice to determine whether oral β-glucan therapy induces augmented T-cell responses. Lewis lung carcinoma and RAM-S lymphoma models were used to test oral β-glucan therapeutic effect. Further mechanistic studies including tumor-infiltrating T cells and cytokine profiles within the tumor milieu were determined.

Results: Orally administered particulate β-glucan trafficked into spleen and lymph nodes and activated DCs that captured dying tumor cells in vivo, leading to the expansion and activation of antigen-specific CD4 and CD8 T cells. In addition, IFN-γ production of tumor-infiltrating T cells and CTL responses were significantly enhanced on β-glucan treatment, which ultimately resulted in significantly reduced tumor burden. Moreover, β-glucan–treated tumors had significantly more DC infiltration with the activated phenotype and significant levels of Th1-biased cytokines within the tumor microenvironment.

Conclusions: These data highlight the ability of yeast-derived β-glucan to bridge innate and adaptive antitumor immunity and suggest that it can be used as an adjuvant for tumor immunotherapy. Clin Cancer Res; 16(21); 5153–64. ©2010 AACR.
Quantification of Diffuse Myocardial Fibrosis and Its Association With Myocardial Dysfunction in Congenital Heart Disease
Authors: Broberg Craig S. , Chugh Sumeet S. , Conklin Catherine , Sahn David J. , Jerosch-Herold Michael
Published: September 2010

Background—

The etiology of ventricular dysfunction in adult congenital heart disease (ACHD) is not well understood. Diffuse fibrosis is a likely common final pathway and is quantifiable using MRI.

Methods and Results—

Patients with ACHD (n=50) were studied with cardiac MRI to quantify systemic ventricular volume and function and diffuse fibrosis. The fibrosis index for a single midventricular plane of the systemic ventricle was quantified by measuring T1 values for blood pool and myocardium before and after administration of gadolinium (0.15 mmol/kg) and then adjusted for hematocrit. Results were compared to healthy volunteers (normal controls, n=14) and patients with acquired heart failure (positive controls, n=4). Patients studied (age, 37±12 years; female sex, 40%) included 11 with a systemic right ventricle (RV), 17 with tetralogy of Fallot, 10 with cyanosis, and 12 with other lesions. The fibrosis index was significantly elevated in patients with ACHD compared to normal controls (31.9±4.9% versus 24.8±2.0%;
P
=0.001). Values were highest in patients with a systemic RV (35.0±5.8%;
P
<0.001) and those who were cyanotic (33.7±5.6%;
P
<0.001). The fibrosis index correlated with end-diastolic volume index (
r
=0.60;
P
<0.001) and ventricular ejection fraction (
r
=−0.53;
P
<0.001) but not with age or oxygen saturation in patients who were cyanotic. Late gadolinium enhancement did not account for the differences seen.

Conclusions—

Patients with ACHD have evidence of diffuse, extracellular matrix remodeling similar to patients with acquired heart failure. The fibrosis index may facilitate studies on the mechanisms and treatment of myocardial fibrosis and heart failure in these patients.
Serial Measurement of Growth-Differentiation Factor-15 in Heart Failure
Authors: Anand Inder S. , Kempf Tibor , Rector Thomas S. , Tapken Heike , Allhoff Tim , Jantzen Franziska , Kuskowski Michael , Cohn Jay N. , Drexler Helmut , Wollert Kai C.
Published: September 2010

Background—

Growth-differentiation factor-15 (GDF-15) is emerging as a prognostic biomarker in patients with coronary artery disease. Little is known about GDF-15 as a biomarker in patients with heart failure.

Methods and Results—

The circulating concentration of GDF-15 was measured at baseline (n=1734) and at 12 months (n=1517) in patients randomized in the Valsartan Heart Failure Trial (Val-HeFT). GDF-15 levels at baseline ranged from 259 to 25 637 ng/L and were abnormally high (>1200 ng/L) in 85% of patients. Higher levels were associated with features of worse heart failure and biomarkers of neurohormonal activation, inflammation, myocyte injury, and renal dysfunction. Baseline GDF-15 levels (per 100 ng/L) were associated with the risks of mortality (hazard ratio, 1.017; 95% confidence interval, 1.014 to 1.019;
P
<0.001) and first morbid event (hazard ratio, 1.020; 95% confidence interval, 1.017 to 1.023;
P
<0.001). In a comprehensive multiple-variable Cox regression model that included clinical prognostic variables, B-type natriuretic peptide, high-sensitivity C-reactive protein, and high-sensitivity troponin T, GDF-15 remained independently associated with mortality (hazard ratio, 1.007; 95% confidence interval, 1.001 to 1.014;
P
=0.02) but not first morbid event. At 12 months, the GDF-15 levels had increased by a similar amount in the placebo and valsartan groups (
P
=0.94). Increases in GDF-15 over 12 months were independently associated with the risks of future mortality and first morbid event also after adjustment for clinical prognostic variables, B-type natriuretic peptide, high-sensitivity C-reactive protein, and high-sensitivity troponin T and their changes.

Conclusions—

GDF-15 reflects information from several pathological pathways and provides independent prognostic information in heart failure. GDF-15 levels increase over time, suggesting that GDF-15 reflects a pathophysiological axis that is not completely addressed by the therapies prescribed in Val-HeFT.
Podoplanin-Expressing Cells Derived From Bone Marrow Play a Crucial Role in Postnatal Lymphatic Neovascularization
Authors: Lee Ji Yoon , Park Changwon , Cho Yong Pil , Lee Eugine , Kim Hyongbum , Kim Pilhan , Yun Seok H. , Yoon Young-sup
Published: September 2010

Background—

Emerging evidence has suggested a contribution of bone marrow (BM) cells to lymphatic vessel formation; however, the exact phenotype of the cells with lymphatic endothelial progenitor cell function has yet to be identified. Here, we investigate the identity of BM-derived lymphatic endothelial progenitor cells and their role in lymphatic neovascularization.

Methods and Results—

Culture of BM-mononuclear cells in the presence of vascular endothelial growth factors A and C and endothelial growth factor resulted in expression of lymphatic endothelial cell markers. Among these cells, podoplanin
+
cells were isolated by magnetic-activated cell sorting and characterized by fluorescence-activated cell sorter analysis and immunocytochemistry. These podoplanin
+
cells highly express markers for lymphatic endothelial cells, hematopoietic lineages, and stem/progenitor cells; on further cultivation, they generate lymphatic endothelial cells. We further confirmed that podoplanin
+
cells exist in small numbers in BM and peripheral blood of normal mice but are significantly (15-fold) augmented on lymphangiogenic stimuli such as tumor implantation. Next, to evaluate the potential of podoplanin
+
cells for the formation of new lymphatic vessels in vivo, we injected culture-isolated or freshly isolated BM-derived podoplanin
+
cells into wound and tumor models. Immunohistochemistry demonstrated that the injected cells were incorporated into the lymphatic vasculature, displayed lymphatic endothelial cell phenotypes, and increased lymphatic vascular density in tissues, suggesting lymphvasculogenesis. Podoplanin
+
cells also expressed high levels of lymphangiogenic cytokines and increased proliferation of lymphatic endothelial cells during coculture, suggesting a lymphangiogenic or paracrine role.

Conclusions—

Our results provide compelling evidence that BM-derived podoplanin
+
cells, a previously unrecognized cell type, function as lymphatic endothelial progenitor cells and participate in postnatal lymphatic neovascularization through both lymphvasculogenesis and lymphangiogenesis.
Transmural Differences in Myocardial Contraction in Long-QT Syndrome
Authors: Haugaa Kristina Hermann , Amlie Jan P. , Berge Knut Erik , Leren Trond P. , Smiseth Otto A. , Edvardsen Thor
Published: September 2010

Background—

Long-QT syndrome (LQTS) is characterized by prolonged myocardial action potential duration. The longest action potential duration is reported in the endomyocardium and midmyocardium. Prolonged action potential duration in LQTS may cause prolonged cardiac contraction, which can be assessed by strain echocardiography. We hypothesized that myocardial contraction is most prolonged in subendocardial myofibers in LQTS patients and that inhomogeneous transmural contraction is related to the risk of spontaneous arrhythmia.

Methods and Results—

We included 101 genotyped LQTS mutation carriers and 35 healthy individuals. A history of cardiac arrhythmias was present in 48 mutations carriers, and 53 were asymptomatic. Myocardial contraction duration was assessed by strain echocardiography as time from the ECG Q wave to peak strain in 16 LV segments. Strain was assessed along the longitudinal axis, predominantly representing subendocardial fibers, and along the circumferential axis, representing midmyocardial fibers. Mean contraction duration was longer in LQTS mutation carriers compared with healthy individuals (445±45 versus 390±40 milliseconds;
P
<0.001) and longer in symptomatic compared with asymptomatic LQTS mutation carriers (460±40 versus 425±45 milliseconds;
P
<0.001). Contraction duration by longitudinal strain was longer than by circumferential strain in symptomatic LQTS patients (460±45 versus 445±45 milliseconds;
P
=0.008) but not in asymptomatic patients and healthy individuals, indicating transmural mechanical dispersion. This time difference was present in a majority of LV segments and was most evident in patients with LQT2 and the Jervell and Lange-Nielsen syndrome.

Conclusion—

Contraction duration in symptomatic LQTS mutation carriers was longer in the subendocardium than in the midmyocardium, indicating transmural mechanical dispersion, which was not present in asymptomatic and healthy individuals.
The Functional c.-2G>C Variant of the Mineralocorticoid Receptor Modulates Blood Pressure, Renin, and Aldosterone Levels
Authors: van Leeuwen Nienke , Caprio Massimiliano , Blaya Carolina , Fumeron Frédéric , Sartorato Paola , Ronconi Vanessa , Giacchetti Gilberta , Mantero Franco , Fernandes-Rosa Fabio L. , Simian Christophe , Peyrard Sévrine , Zitman Frans G. , Penninx Brenda W.J.H. , de Kloet E. Ron , Azizi Michel , Jeunemaitre Xavier , DeRijk Roel H. , Zennaro Maria-Christina
Published: September 2010

The mineralocorticoid receptor (MR) is essential in the regulation of volemia and blood pressure. Rare mutations in the MR gene cause type 1 pseudohypoaldosteronism and hypertension. In this study we characterized the common MR polymorphism c.-2G>C (rs2070951) in vitro and tested its influence on parameters related to blood pressure regulation and the renin-angiotensin system. In vitro studies showed that the G allele was associated with decreased MR protein levels and reduced transcriptional activation compared with the C allele. Association studies were performed with several outcome variables in 3 independent cohorts: a mild hypertensive group subjected to a salt-sensitivity test, a healthy normotensive group included in a crossover study to receive both a high and low Na/K diet, and a large cohort (The Netherlands Study of Depression and Anxiety), in which blood pressure was measured. Subjects with the GG genotype had significantly higher plasma renin levels both in the mild hypertensive group and in normal volunteers compared with homozygous C carriers. The GG genotype was also correlated with higher plasma aldosterone levels in healthy subjects. In both the mild hypertensive group and The Netherlands Study of Depression and Anxiety cohort the genotype GG was associated with higher systolic blood pressure in males. In conclusion, the G allele of the common functional genetic polymorphism c.-2G>C in the MR gene associates with increased activation of the renin-angiotensin-aldosterone axis and with increased blood pressure, probably related to decreased MR expression.
Plasma From Preeclamptic Women Increases Blood-Brain Barrier Permeability
Authors: Amburgey Ödül A. , Chapman Abbie C. , May Victor , Bernstein Ira M. , Cipolla Marilyn J.
Published: September 2010

Circulating factors in preeclamptic women are thought to cause endothelial dysfunction and thereby contribute to the progression of this hypertensive condition. Despite the involvement of neurological complications in preeclampsia, there is a paucity of data regarding the effect of circulating factors on cerebrovascular function. Using a rat model of pregnancy, we investigated blood-brain barrier permeability, myogenic activity, and the influence of endothelial vasodilator mechanisms in cerebral vessels exposed intraluminally to plasma from normal pregnant or preeclamptic women. In addition, the role of vascular endothelial growth factor signaling in mediating changes in permeability in response to plasma was investigated. A 3-hour exposure to 20% normal pregnant or preeclamptic plasma increased blood-brain barrier permeability by ≈6.5- and 18.0-fold, respectively, compared with no plasma exposure (
P
<0.01). Inhibition of vascular endothelial growth factor receptor kinase activity prevented the increase in permeability in response to preeclamptic plasma but had no effect on changes in permeability of vessels exposed to normal pregnant plasma. Circulating factors in preeclamptic plasma did not affect myogenic activity or the influence of endothelium on vascular tone. These findings demonstrate that acute exposure to preeclamptic plasma has little effect on reactivity of cerebral arteries but significantly increases blood-brain barrier permeability. Prevention of increased permeability by inhibition of vascular endothelial growth factor signaling suggests that activation of this pathway may be responsible for increased blood-brain barrier permeability after exposure to preeclamptic plasma.
Pregnancy Downregulates Actin Polymerization and Pressure-Dependent Myogenic Tone in Ovine Uterine Arteries
Authors: Xiao Daliao , Huang Xiaohui , Yang Shumei , Longo Lawrence D. , Zhang Lubo
Published: September 2010

Pregnancy is associated with significantly decreased uterine vascular tone and increased uterine blood flow. The present study tested the hypothesis that the downregulation of actin polymerization plays a key role in reduced vascular tone of uterine arteries in the pregnant state. Uterine arteries were isolated from nonpregnant and near-term pregnant sheep. Activation of protein kinase C significantly increased the filamentous:globular actin ratio and contractions in the uterine arteries, which were inhibited by an actin polymerization inhibitor cytochalasin B. The basal levels of filamentous:globular actin were significantly higher in nonpregnant uterine arteries than those in near-term pregnant sheep. Prolonged treatment (48 hours) of nonpregnant sheep with 17β-estradiol (0.3 nmol/L) and progesterone (100.0 nmol/L) caused a significant decrease in the filamentous:globular actin. In accordance, the treatment of near-term pregnant sheep for 48 hours with an estrogen antagonist ICI 182 780 (10.0 μmol/L) and progesterone antagonist RU 486 (1.0 μmol/L) significantly increased the levels of filamentous:globular actin. Increased intraluminal pressure from 20 to 100 mm Hg resulted in an initial increase in uterine arterial diameter and vascular wall Ca
2+
concentrations, followed by a decrease in the diameter at a constant steady-state level of Ca
2+
. Cytochalasin B blocked pressure-induced myogenic constrictions without effect on vascular wall Ca
2+
levels and eliminated the differences in pressure-dependent myogenic tone between nonpregnant sheep and near-term pregnant sheep. The results indicate a key role of actin polymerization in protein kinase C–induced myogenic contractions and suggest a novel mechanism of sex steroid hormone–mediated downregulation of actin polymerization underlying the decreased myogenic tone of uterine arteries in pregnancy.
Psychophysically Tuned Divisive Normalization Approximately Factorizes the PDF of Natural Images
Authors: Malo Jesús , Laparra Valero
Published: September 2010

The conventional approach in computational neuroscience in favor of the efficient coding hypothesis goes from image statistics to perception. It has been argued that the behavior of the early stages of biological visual processing (e.g., spatial frequency analyzers and their nonlinearities) may be obtained from image samples and the efficient coding hypothesis using no psychophysical or physiological information. In this work we address the same issue in the opposite direction: from perception to image statistics. We show that psychophysically fitted image representation in V1 has appealing statistical properties, for example, approximate PDF factorization and substantial mutual information reduction, even though no statistical information is used to fit the V1 model. These results are complementary evidence in favor of the efficient coding hypothesis.
A Theoretical Basis for Emergent Pattern Discrimination in Neural Systems Through Slow Feature Extraction
Authors: Klampfl Stefan , Maass Wolfgang
Published: September 2010

Neurons in the brain are able to detect and discriminate salient spatiotemporal patterns in the firing activity of presynaptic neurons. It is open how they can learn to achieve this, especially without the help of a supervisor. We show that a well-known unsupervised learning algorithm for linear neurons, slow feature analysis (SFA), is able to acquire the discrimination capability of one of the best algorithms for supervised linear discrimination learning, the Fisher linear discriminant (FLD), given suitable input statistics. We demonstrate the power of this principle by showing that it enables readout neurons from simulated cortical microcircuits to learn without any supervision to discriminate between spoken digits and to detect repeated firing patterns that are embedded into a stream of noise spike trains with the same firing statistics. Both these computer simulations and our theoretical analysis show that slow feature extraction enables neurons to extract and collect information that is spread out over a trajectory of firing states that lasts several hundred ms. In addition, it enables neurons to learn without supervision to keep track of time (relative to a stimulus onset, or the initiation of a motor response). Hence, these results elucidate how the brain could compute with trajectories of firing states rather than only with fixed point attractors. It also provides a theoretical basis for understanding recent experimental results on the emergence of view- and position-invariant classification of visual objects in inferior temporal cortex.
Change-Based Inference in Attractor Nets: Linear Analysis
Authors: Moazzezi Reza , Dayan Peter
Published: September 2010

One standard interpretation of networks of cortical neurons is that they form dynamical attractors. Computations such as stimulus estimation are performed by mapping inputs to points on the networks' attractive manifolds. These points represent population codes for the stimulus values. However, this standard interpretation is hard to reconcile with the observation that the firing rates of such neurons constantly change following presentation of stimuli. We have recently suggested an alternative interpretation according to which computations are realized by systematic changes in the states of such networks over time. This way of performing computations is fast, accurate, readily learnable, and robust to various forms of noise. Here we analyze the computation of stimulus discrimination in this change-based setting, relating it directly to the computation of stimulus estimation in the conventional attractor-based view. We use a common linear approximation to compare the two methods and show that perfect performance at estimation implies chance performance at discrimination.
Robust Observer-Based Tracking Control of Hodgkin-Huxley Neuron Systems Under Environmental Disturbances
Authors: Chen Bor-Sen , Li Cheng-Wei
Published: September 2010

A nervous system consists of a large number of highly interconnected nerve cells. Nerve cells communicate by generation and transmission of short electrical pulses (action potential). In addition, membrane voltage is the only measurable state in nervous systems. A robust observer-based model reference tracking control is proposed for Hodgkin-Huxley (HH) neuron systems to generate a desired reference response in spite of environmental noises, uncertain initial values, and diffusion currents from other interconnected nerve cells. In order to simplify the robust tracking control design of nonlinear stochastic HH neuron systems, a fuzzy interpolation method is employed to interpolate several linear stochastic systems to approximate a nonlinear stochastic HH neuron system so that the nonlinear robust tracking control problem can be solved by the linear matrix inequality (LMI) technique with the help of Robust Control Toolbox in Matlab. The proposed robust observer-based tracking control scheme can provide new methods for desired action potential generation, suppression of oscillations, and blockage of action potential transmission under environmental noise and diffusion currents. These new methods are useful for patients with different neuron system dysfunctions. Finally, three simulation examples of tracking control of nervous systems are given to illustrate the design procedure and confirm the tracking performance of the proposed method.
Chinese Ghosts in Mongolia
Authors: Delaplace Gregory
Published: September 2010

This paper explores a rumour that has been circulating lately in Mongolia's capital city, Ulaanbaatar. People report encounters with Chinese ghosts, who appear in the form of long-bearded old men dressed in silken clothes. These curious apparitions are recognised by the population as the souls of Chinese merchants, who remained attached to the place where they buried the wealth they accumulated during their life. At a time when Chinese economic expansion raises concerns among the Mongolian population, these ghosts of the colonial era sound like a warning against present-day Chinese migrants. Introducing several of these stories, this paper shows that Chinese people are imagined as essentially parasitic beings, who not only come to Mongolia to trade but stick to the place, even beyond their own death, to suck out its vital resources.
Power, Social Life, and Public Memory in Uzbekistan and Kyrgyzstan
Authors: Dadabaev Timur
Published: September 2010

This article attempts to analyse the memory of people through recollections of the everyday life of people in Soviet times in the Central Asian republics of Kyrgyzstan and Uzbekistan. By using extensive interviews with seventy-five elderly people in Uzbekistan and Kyrgyzstan regarding their Soviet-time experiences, this article argues that the public view of history in post-Soviet Central Asia often falls in between Soviet historiography advocating advances of Soviet past and post-Soviet historical discourses rejecting the Soviet past. Public perceptions of history in Central Asia are mostly shaped by and related to the everyday needs, experiences, identifications and mentality of people as opposed to the ideologies and political doctrines of the time. They often reflect not only the perceptions of people regarding their past but also their perceptions regarding their present.
Understated Legacies: Uses of Oral History and Tibetan Studies
Authors: Barnett Robert
Published: September 2010

This paper aims to stimulate discussion about the complexity of oral history as a practice by recalling its origins and early associations, such as criminal confessions, war-reporting, the novel, exotic art and other early forms of first-person narratives, and by tracing some of their recurrent echoes in contemporary work. It looks at some of the uses to which oral history or related practices have been put in the field of Tibetan studies, ranging from rigorously academic studies through nostalgic political testimonies to wholly invented pseudo-histories. It discusses the importance of silent oral histories, the ones that cannot be recorded, as well as of failed ones, which are recorded but rejected by certain types of researchers because they do not meet their desires for a certain kind of narrative. Commoditisation of the archive is described, not just in the obvious cases where large amounts of money are exchanged, but also an instance in Tibetan studies in which an important archive was stolen, apparently just for the prestige of secretly possessing it. These forms of prototypical oral history and its near relatives still hover on the sidelines of the practice, despite the efforts of scholars to insulate academic practice from them. The widespread circulation of fabricated narratives produced within the contemporary Tibetan exile economy to gain access to western countries underlines the pervasive and under-acknowledged role of the state throughout all these practices, banning, allowing, celebrating, regulating and exploiting all forms of oral history.
Voices of Hunters on Socialist Modernisation: From a Case Study of the Udehe in the Russian Far East
Authors: Sasaki Shiro
Published: September 2010

In this paper I discuss how different the socialist modernisation of the equipment and techniques of indigenous hunters in Siberia and the Russian Far East was from the 'snowmobile revolution' in Finland and Alaska, and what the results of this modernisation were. In this discussion I analyse hunters' performance and narratives observed and collected in my field research on the hunting culture of the Udehe, one of the indigenous minorities in the Primor'e region in Russia. As a result, I conclude that socialist modernisation had delocalised the fundamental materials for hunting activities such as fuel, equipment for transportation and weapons. However, the serious techno-economic differentiation that had been observed in the case of the Saami in Finland seldom occurred among the indigenous hunters, because socialist egalitarian policies and standardisation of products often provided equal access to the modernised equipment. Especially in the case of the Bikin River basin, where I did my field research, differentiation between the Russian and indigenous hunters was not observed. However, the delocalisation of the fundamental equipment and materials thoroughly deprived them of the alternatives that consisted of the more traditional and pre-modern equipment and techniques. This factor seriously influenced their social and economic conditions after the collapse of the Soviet Union.
Honour, Head-coverings and Headship: 1 Corinthians 11.2-16 in its Social Context
Authors: Finney Mark
Published: September 2010

A significant yet missing dimension of scholarly engagement with 1 Cor. 11.2-16 is the consideration of honour-shame and its critical importance in ancient cultures. As this section of Paul’s letter abounds in honour-shame terminology, analysis of the text within such a framework will allow a profitable exploration of the reasons why the Corinthians are changing their attire (for purposes of this paper, their head-coverings), in a way that appears to be contrary to what may be considered the Pauline norm. The argument offered here is that notions of honour come to the fore and higher-status male Corinthians are employing modes of head attire to maintain distinctions of status. At the same time, Paul insists upon female head-coverings to safeguard the honour of the community within a context of the potential presence of non-believers in a communal service of worship.
Why Does the Deliverer Come έκ Σιών (Romans 11.26)?
Authors: Kirk J.R. Daniel
Published: September 2010

A viable interpretation of Rom. 11.25-27 must be able to explain four interrelated problems: (1) Paul’s use of καì οűтως to connect vv. 25 and 26, (2) the phrase Πȃς Ἰσραήλ in v. 26, (3) how Paul intends for his citation of Isa. 59.20, 27.9 to support his argument, and (4) why Paul’s citation of Isa. 59.20 says the deliverer comes έκ (rather than ένεκεν) Σiών. Beginning with the change to Isa. 59.20, this article argues that Paul is intentionally altering Isaiah’s salvation-historical scheme, in keeping with his earlier arguments in chs. 10—11, such that the glorification of the Gentiles draws Israel into the realm of salvation rather than vice versa. Paul cites and redacts Isa. 59.20 to support his claim for an in-time instrumentality at work through the ingathering of the Gentiles for the sake of Israel’s salvation, analogous to the jealousy arguments found earlier in Rom. 11.
Acute and subchronic effects of bilastine (20 and 40 mg) and hydroxyzine (50 mg) on actual driving performance in healthy volunteers
Authors: Conen Silke , Theunissen Eef L , Van Oers Anita CM , Valiente Román , Ramaekers Johannes G
Published: September 2010

Bilastine is a new second-generation H1 antagonist. Although bilastine has been demonstrated to produce little or no performance impairment in laboratory tests, it cannot be excluded that it produces impairments in real-life performance such as driving. This study aims to assess the effects of two doses of bilastine (20 and 40 mg) on actual driving after single and repeated administration. Hydroxyzine 50 mg was included as an active control. Twenty-two particpants (11 females, 11 males) were tested in a placebo-controlled, randomized, double-blind, four-way cross-over design. Participants were treated with once-daily doses for eight consecutive days. On day 1 and 8 of each treatment period participants performed an actual highway driving test. The primary variable was standard deviation of lateral position (SDLP), a measure of weaving. Results demonstrated that hydroxyzine significantly increased SDLP on days 1 and 8 of treatment. Bilastine did not affect SDLP. It is concluded that hydroxyzine produces severe driving impairment after single doses and that this impairment only partly mitigates over time due to a lack of complete tolerance. Bilastine did not produce any driving impairment after single and repeated doses and can be safely used in traffic in doses up to 40 mg.
Babel, Suspense, and the Introduction to the Terah-Abram Narrative
Authors: Awabdy Mark A.
Published: September 2010

Many Genesis interpreters view Gen. 11.27—12.9 as the foundation of the Abraham narrative (Gen. 11.27—25.11) and the opening response to the Primeval History (Gen. 1— 11). Employing a narrative critical approach that is sensitive to diachronic issues, this article proposes that 11.27—12.9 also functions as a response to the preceding Tower of Babel episode (11.1-9). The Tower of Babel scene leaves readers with substantive gaps in their knowledge about the fate of the divine—human relationship. The suspense generated by such knowledge gaps is initially resolved in the introduction to the Terah—Abram narrative (11.27—12.9). This article first offers a literary rationale for reading Gen. 11.27— 12.9 in light of 11.1-9, and then considers how suspense and partial resolution are expressed through verbal repetition of ‘reputation’, plot equivalencies, and contrasts related to migration and settlement, and a variation on the theme of capability.
Polite Israel and Impolite Edom: Israel’s Request to Travel through Edom in Numbers 20.14-21
Authors: Bridge Edward
Published: September 2010

In Num. 20.14-21, Israel requests passage to pass through Edom but is denied. Of interest are the elements that add to Israel’s request (e.g. historical preamble, and self-imposed conditions to encourage Edom to accept their request). Using politeness theory, this article finds these elements to be strategies of politeness, and also show that Israel has a strategy of increasing politeness during the communication with Edom. In contrast, Edom is impolite, which indicates it wishes to be superior to Israel. This is consistent with the Bible’s portrayal of Edom as a ‘bad brother’ to Israel. The ability of politeness theory to bring out subtleties in communication in the Bible shows that it is a useful heuristic device to assist with the interpretation of biblical texts.