bluuebunny/crossref_metadata_2025 huggingface dataset:
Cluster Ion Implantation System: Claris for Beyond 45nm Device Fabrication (Ii)
Authors: Tanjyo Masayasu , Hamamoto Nariaki , Nagayama Tsutomu , Umisedo Sei , Koga Yuji , Maehara Noriaki , Une Hideyasu , Matsumoto Takao , Nagai Nobuo , Borland John O.
Published: March 2009

Newly developed sweep beam Cluster ion implanter: CLARIS with 0.2-7keV energy range for Boron beam and 1-10keV energy range for Carbon beam is introduced. Novel Cluster ion implantation technology is capable for 45nm beyond device requiring USJ formation (<15nm) with high retain dose (>70%) and low sheet resistivity (<1200Ω/sq). Comparison of retain dose and sheet resistivity of B18, BF2, and B beams with FLA shows the superiority of the B18 implantation for less than 500eV implantation.
New Structure Improves Copper Phthalocyanine (CuPc) Order and Decrease the Device Resistance
Authors: Liu Ge , Liu Ming , Shang Liwei , Ji Zhouyu , Liu Xinghua , Wang Hong , Liu Jiang
Published: March 2009

We fabricated high performance organic field-effect transistors with novel hybrid electrode-semiconductor contact geometry. The HC OFETs contain both the top electrodes and the bottom electrodes in a single transistor simultaneously. The bottom electrodes induce an ordering CuPc film during the active layer depositing. Due to a high order CuPc layers and low total device resistance, as well as little charge effect below the top electrodes, OFETs with the hybrid contact geometry exhibit a higher performance. With convenience of the new structure, the contact resistance between the two traditional contact geometries was studied in one single transistor.
Investigating the Effects of Different Gate Biasing Voltages and Temperatures on RadFETs
Authors: Tang Hao , Liu Yichen , Wang Yi , Wang Jinyan , Jin Yufeng
Published: March 2009

This paper mainly focuses on the effects of different gate biasing voltages and temperatures on several kinds of RadFETs. Four kinds of gate biasing configurations (positive, zero, negative gate voltage and continuous current applied model) have been compared in terms of sensitivity to radiation. Post-irradiation characteristics of annealing or fading under different gate biasing voltages and temperatures are also studied. Samples irradiated by zero and negative voltage biasing have lower sensitivity than that of positive, but don't show significant fading. It is presented that higher temperature can promote the process of annealing.
Hypoxic and hypercapnic ventilatory responses in aging male vs. aging female rats
Authors: Wenninger J. M. , Olson E. B. , Cotter C. J. , Thomas C. F. , Behan M.
Published: March 2009

It is clear that sex hormones impact ventilation. While the effects of the menstrual cycle, pregnancy, testosterone, and progesterone on resting ventilation have been well documented, effects of sex hormones on the hypoxic (HVR) and hypercapnic ventilatory responses (HCVR) are inconclusive. In addition, in no study have systemic sex steroid hormone levels been measured. Age and sex differences in long-term facilitation in response to episodic hypoxia were found in anesthetized rats. The purpose of the present study was to assess the effects of sex and age [young, 3–4 mo; middle age, 12–13 mo; and old, >20 mo] on the HVR and the HCVR of awake rats relative to systemic hormone levels. Based on findings from long-term facilitation studies, we hypothesized that the HVR would be influenced by both sex and age. We found no age-related changes in the HVR or HCVR. However, female rats have a greater HVR than male rats at old age, and at middle age female rats have a greater HCVR than male rats. Additionally, we found no correlation between the minute ventilation/oxygen consumption and the progesterone-to-estrogen ratio during hypoxia or hypercapnia. However, changes in ventilatory responses with age were not similar between the sexes. Thus it is critical to take sex, age, estrous cycle stage, and systemic hormone levels into consideration when conducting and reporting studies on respiratory control.
Application of muscle biopotential measurement for sustained, noninvasive blood glucose survey
Authors: Vol Alexander , Gribova Orna , Berman Sylvia , Siman-Tov Yariv , Efrati Shai
Published: March 2009

Biopotential, the electric potential generated by living tissues, is affected by changes in extracellular electrolyte and glucose concentrations. We aimed to apply correlation between blood glucose concentrations (BGC) and biopotential of peripheral muscles for noninvasive blood glucose measurement. The study included 58 Wistar rats. In part of them, diabetes was induced by streptozotocin injection. Group 1, comprising 19 normal and 5 diabetic rats, received glucose-challenging protocol (intraperitoneal injection of 1 g/ml glucose). Group 2, 24 normal and 6 diabetic rats, received insulin-challenging protocol (three 30 IU insulin injections with 15-min intervals). Four control rats, group 3, were injected with 2-ml saline. BGC were measured by a standard ACCU-CHEK-Sensor Meter and compared with those estimated by biopotential sensor, further designated as GlucoSat, placed around proximal parts of the tails of the anaesthetized animals. GlucoSat results were calculated using the following biopotential equation: BGC( t) = k1 * F1( t) + k2 * F2( t) * k3 * F3( t) + k4, based on an experimental model involving estimation of pH, muscle metabolism, and tissue conductance, where t is time, k1–k4 are coefficients, and F1–F4 are functions. Mean biopotential system measured BGC was 181.7 ± 4.3 mg/dl, not differing statistically from 187.9 ± 4.3 mg/dl estimated by ACCU-CHEK. Pearson's correlation coefficient ( r2) was 0.961 ( P < 0.00001), indicating strong, direct correlation between the results. Within the nondiabetic group, r2 was 0.944 ( P < 0.00001), while, within the diabetic group, r2 was 0.974 ( P < 0.00001). No significant, adverse skin reactions were concomitantly observed in any experimental group. Biopotential measurements may be used for continuous, noninvasive estimation of changes in BGC. Further studies are needed to evaluate the applicability of this method to humans.
Psychomotor Changes in Major Depressive Disorder during Sertraline Treatment
Authors: Schrijvers D. , Maas Y.J. , Pier M.P.B.I. , Madani Y. , Hulstijn W. , Sabbe B.G.C.
Published: March 2009

Background: There is a relative scarcity of studies on major depressive disorder that use objective assessment methods to explore the psychomotor effects of antidepressants. Striatal dopaminergic disturbances are known to be involved in the pathogenesis of major depressive disorder that is associated with psychomotor retardation. Because of its additional dopaminergic mechanism, the psychomotor effects of the selective serotonin reuptake inhibitor sertraline merit further exploration. Methods: In 19 patients diagnosed with a current major depressive episode, clinical variables and graphic motor activity were assessed applying digitized figure copying tasks during a 6-week regimen of sertraline. Patients’ baseline and weekly psychomotor performance was compared with the outcomes of 22 healthy, unmedicated controls. Results: Patients’ psychomotor slowing had improved after 6 weeks on sertraline as reflected by reductions in initiation and movement times on the simple line and figure copying tasks and decreased initiation times for the complex figure copying task relative to their baseline outcomes. Conclusions: The current study found evidence pointing to potential beneficial effects of sertraline after a 6-week treatment period in the lower-order cognitive and motor components involved in the graphic motor performance of depressed patients. The present findings are discussed in terms of the mechanism of action of sertraline.
Effect of Genetic Polymorphisms in UDP-Glucuronosyltransferase 1A6 (UGT1A6) on Acetylsalicylic Acid Metabolism in Healthy Female Volunteers
Authors: van Oijen Martijn G.H. , Barthélémy Christine , Janssen Marcel J.R. , Joiris Etienne , Peters Wilbert H.M. , Laheij Robert J.F. , Smits Paul , Odou Pascal , Jansen Jan B.M.J.
Published: March 2009

Objective: To compare plasma concentrations of acetylsalicylic acid (ASA) and its metabolites between genetic polymorphisms in the gene encoding for UDP-glucuronosyltransferase 1A6 (UGT1A6), an enzyme involved in ASA metabolism. Methods: Five UGT1A6*1 and 4 UGT1A6*2 homozygote females were given 320 mg ASA once daily for 8 days. During the first and last day of treatment, several blood samples were taken over a 10-hour time period and analyzed for plasma levels of ASA and its main metabolites salicylic acid (SA) and salicyluric acid (SUA), using a validated HPLC method. The pharmacokinetic data were assessed with the Time Constant Approach and both genotypes were compared using the Mann-Whitney U test. Results: ASA and SUA showed similar pharmacokinetic parameters in the two UGT1A6 genotypes. However, pharmacokinetic parameters for SA differed significantly: the mean area under the pharmacokinetic curve for the UGT1A6*1 and UGT1A6*2 homozygotes was 136 and 94 μg/ml·h (p = 0.04), and median Cmax was 23 and 17 μg/ml (p = 0.01), respectively. Conclusion: In females receiving ASA, the presence of the UGT1A6*2 compared to the UGT1A6*1 homozygote genotype is associated with lower plasma levels of SA, indicating faster pharmacokinetics.
Stunned Myocardium following Ischemic Stroke
Authors: Dias Vasco , Cabral Sofia , Meireles Ana , Gomes Catarina , Antunes Nuno , Vieira Miguel , Caiado Luísa , Torres Severo
Published: March 2009

Neuromediated stunned myocardium is a well-known complication of subarachnoid hemorrhage but has rarely been reported in association with other central nervous system disorders. The pathophysiology of this entity remains unclear, but a catecholamine-induced neurocardiogenic injury has been proposed as a causal factor. Typically, patients have rapid full cardiovascular recovery within a few days. We report a case of ischemic stroke, coexisting with ischemic electrocardiographic changes, increased cardiac-specific necrosis biomarkers, regional wall motion abnormalities and a cardiac SPECT consistent with inferior myocardial infarction despite normal coronary arteries. Interestingly, left-ventricular dysfunction in this case persisted longer than usually described despite full neurologic recovery. This case also illustrates the diagnostic challenges posed by this entity which frequently mimics acute myocardial infarction and emphasizes the investigation needed in this area.
Intraoperative Cholangiography in Modern Surgical Practice
Authors: Akolekar Deepika , Nixon S.J. , Parks R.W.
Published: March 2009

Background/Aims: The aim of this study was to assess the practice of performing intraoperative cholangiography (IOC) during laparoscopic cholecystectomy in a busy teaching hospital. Methods: Data were obtained from a surgical database for patients who underwent laparoscopic cholecystectomy between January 2000 and December 2003. The findings of IOC and follow-up were analysed. Results: 1,651 patients were included in the study. Of the 745 patients (45.1%) who underwent IOC, this was normal in 586 patients and abnormal in 68 patients. Of these 68 patients, 4 underwent immediate conversion to open common bile duct exploration. 33 patients underwent endoscopic retrograde cholangiopancreatography and 31 patients were observed. During a median follow-up period of 920 days (range 371–1,821), 5 of the 745 patients had retained stones. Two patients re-presented after a failed IOC while 5 of the 906 patients from the non-cholangiogram group returned with stones. Of the 1,651 patients, definite stones were identified in 1.5% patients. Conclusion: When the surgeon deemed that IOC was not required, very few subsequent problems were encountered. An observational policy with monitoring of the liver function tests may be appropriate to avoid unnecessary invasive interventions in patients with an abnormal IOC.
Health and Physiological Effects of an Emotional Disclosure Intervention Adapted for Application at Home: A Randomized Clinical Trial in Rheumatoid Arthritis
Authors: van Middendorp Henriët , Geenen Rinie , Sorbi Marjolijn J. , van Doornen Lorenz J.P. , Bijlsma Johannes W.J.
Published: March 2009

Background: The efficacy of emotional disclosure in alleviating psychological and physical stress has been well documented in controlled laboratory studies. A next step is to evaluate its clinical utility in ‘real world’ settings. We adapted the emotional disclosure intervention for use in home-based settings by stimulating the suggested effective ingredients of cognitive-emotional processing, and evaluated its psychological and clinical effectiveness. Reviews indicated the need to examine the physiological changes brought about by emotional disclosure, which may be particularly relevant in immune-mediated diseases. This study was the first to examine neuroendocrine and immune changes after emotional disclosure in patients with rheumatoid arthritis. Methods: Sixty-eight patients were randomly assigned to four weekly oral emotional disclosure or time management sessions. At baseline and 1 week and 3 months after the sessions, depressed and cheerful mood, joint scores, erythrocyte sedimentation rate, cortisol, noradrenaline, interleukin-6 (IL-6), interferon-γ (IFN-γ), and IL-10 were evaluated. Repeated measures analyses of variance were performed. Results: No effect on psychological well-being and clinical outcome was found (p ≥ 0.10). Cortisol (p = 0.01) and the serum level of the pro-inflammatory cytokine IFN-γ (p = 0.05) were differentially affected by the two conditions. The change of IL-6 nearly reached significance (p = 0.07). Conclusions: The physiological changes are in agreement with theories on the mechanisms underlying emotional disclosure benefits and are suggestive of better disease control after emotional disclosure. General and study-specific reasons for the absence of psychological and clinical effects are discussed. The findings warn against widespread implementation of this home-based emotional disclosure intervention in unselected rheumatoid arthritis samples.
Thalamic Deep Brain Stimulation for Midbrain Tremor Secondary to Cystic Degeneration of the Brainstem
Authors: Sanborn Matthew R. , Danish Shabbar F. , Ranalli Nathan J. , Grady M. Sean , Jaggi Jurg L. , Baltuch Gordon H.
Published: March 2009

Objective: Tremor resulting from damage to midbrain structures is poorly understood and often difficult to treat. The authors report a case of cystic degeneration of the brainstem with resultant Holmes-like tremor which was successfully treated using a stimulating electrode placed in the contralateral ventralis intermedius nucleus (VIM) of the thalamus. Clinical Presentation: A 31-year-old man presented with a multilobulated, multiseptated lesion of the upper brainstem diagnosed after subacute onset of headaches. The patient subsequently developed an incapacitating left-upper-extremity tremor refractory to medical treatment. Intervention: The patient underwent implantation of a deep brain stimulator in the VIM with symptomatic and functional improvement. Conclusions: Deep brain stimulation is an effective and safe intervention for tremor of unusual etiology. Electrode placement should be based on an understanding of the structure-function relationships underlying the various and distinct types of tremor.
Prenatal Detection and Conservative Management of a Partial Fundal Uterine Dehiscence
Authors: Hunter Tamara J. , Maouris Panos , Dickinson Jan E.
Published: March 2009

Uterine defects in pregnancy are rare and may pose difficulties in definition and clinical management. Defects involving the myometrium encompass entities such as uterine rupture, dehiscence, sacculation or diverticulum. There are only a few reported cases of uterine fundal defects where the pregnancy continues into the third trimester. The following case describes the prenatal imaging diagnosis and subsequent clinical management of a large fundal uterine defect in the third trimester of pregnancy.
Elevated CC Chemokine Level in Bronchoalveolar Lavage Fluid Is Predictive of a Poor Outcome of Idiopathic Pulmonary Fibrosis
Authors: Shinoda Hiromi , Tasaka Sadatomo , Fujishima Seitaro , Yamasawa Wakako , Miyamoto Keisuke , Nakano Yasushi , Kamata Hirofumi , Hasegawa Naoki , Ishizaka Akitoshi
Published: March 2009

Background: CC chemokines play important roles in the pathogenesis of interstitial lung diseases. Elevated CC chemokine levels have been observed in bronchoalveolar lavage (BAL) fluid of patients with idiopathic pulmonary fibrosis (IPF). Objectives:We aimed to examine whether the levels of four CC chemokines, i.e. monocyte chemoattractant protein-1 (MCP-1/CCL2), macrophage inflammatory protein-1α (MIP-1α/CCL3), thymus- and activation-regulated chemokine (TARC/CCL17), and macrophage-derived chemokine (MDC/CCL22), in BAL fluid are predictive of the prognosis of IPF patients. Methods: We compared the chemokine levels of patients alive 5 years after diagnosis and those who had died. Lung function data, CT scores, and serum markers were also compared. Results: Among 39 patients (29 males, median age, 60 years), 19 patients (48%) died within 5 years after the diagnosis. Whereas percent vital capacity was not different, percent lung diffusion capacity for carbon monoxide was significantly higher in the surviving patients than in the nonsurviving patients (p < 0.01). Median CCL2 levels of surviving and nonsurviving patients were 154.3 (interquartile range, IQR: 67.3–381.8) and 427.2 (IQR: 329.2–1184.1) pg/ml, respectively (p < 0.02). CCL3 levels in BAL fluid did not differ between the surviving and nonsurviving patients. CCL17 was detected in BAL fluid of 7 patients, 6 of whom died within 5 years. CCL22 was detectable in BAL fluid of 10 patients, only 1 of whom survived. Serum levels of KL-6 and lactate dehydrogenase did not differ between the surviving and nonsurviving patients. Conclusion: Elevated levels of CCL2, CCL17 and CCL22 in BAL fluid might be predictive of a poor outcome in patients with IPF.
Static Stretch Induces Active Morphological Remodeling and Functional Impairment of Alveolar Epithelial Cells
Authors: Ren Yanhong , Zhan Qingyuan , Hu Qinghua , Sun Bing , Yang Chun , Wang Chen
Published: March 2009

Background: Static stretch is frequently observed in the lung. Both static stretch and cyclic stretch can induce cell death and Na+/K+-ATPase trafficking, but stretch-induced alveolar epithelial cell (AEC) functions are much less responsive to static than to cyclic stretch. AEC remodeling under static stretch may be partly explained. Objective: The aim of this study was to explore the AEC remodeling and functional changes under static stretch conditions. Method: We used A549 cells as a model of AEC type II cells. We assessed F-actin content and cell viability by fluorescence staining at various static-stretch magnitudes and time points. Specifically, we used scanning electron microscopy to explore the possible biological mechanisms used by A549 cells to ‘escape’ static-stretch-induced injury. Finally, we measured choline cytidylyltransferase-α (CCTα) mRNA and protein by real-time PCR and Western blot to evaluate cellular secretory function. Results: The results showed that the magnitude of static stretch was the primary determinant of static-stretch-induced cell death and cytoskeleton organization, but an extended duration of high static deformation/stretch (37% change in surface area) had no cumulative effects on cell death and cytoskeleton organization. AEC remodeling (expansion-contraction-reexpansion) under static stretch conditions may explain this interesting phenomenon partly. After cell remodeling, CCTα expression in A549 cells was influenced not only by stretch magnitude but also by stretch time. Conclusion: Under static stretch conditions, A549 cells undergo morphological and functional changes. They can survive stress failure from overstretching by remodeling their body to ‘escape’ the injury. During this complex course of remodeling, cellular function was partly damaged.
Overexpression, Purification and Characterization of Organic Solvent Stable Lipase from Bacillus licheniformis RSP-09
Authors: Madan Bhawna , Mishra Prashant
Published: March 2009

The lipase gene (543 bp) from Bacillus licheniformis RSP-09, a thermophilic isolate, was overexpressed in Escherichia coli BL21 (DE3). It encodes a polypeptide of 181 residues and has 96% identity with Bacillus pumilus B26 lipase gene. The recombinant lipase was purified 19-fold to electrophoretic homogeneity by His-tag chromatography. The molecular mass of the purified recombinant B. licheniformis RSP-09 lipase was found to be 24 kDa. The purified recombinant B. licheniformis RSP-09 lipase exhibited optimal activity at pH 10.0 and 40°C. The apparent Km and Vmax values for pNPP were found to be 453 ± 118 μM and 288.5 ± 33.67 μmol min–1 mg protein–1, respectively. The purified recombinant lipase had a wide range of substrate specificity and exhibited tolerance to both detergents and organic solvents. Thus, enzyme has potential to be employed in detergents and biocatalysis in nonaqueous solvents.
Mechanisms of Vessel Branching
Authors: De Smet Frederik , Segura Inmaculada , De Bock Katrien , Hohensinner Philipp J. , Carmeliet Peter
Published: March 2009

Filopodia, “the fingers that do the walking,” have been identified on endothelial cells at the tip of sprouting vessels for half a century, but the key role of the tip cell in vessel branching has been recognized only in the past few years. A model is emerging, whereby tip cells lead the way in a branching vessel, stalk cells elongate the sprout, and a very recently discovered phalanx cell ensures quiescence and perfusion of the newly formed branch. Recent genetic studies have shed light on the molecular signature of these distinct endothelial phenotypes; this provides a novel conceptual framework of how vessel morphogenesis occurs. Here, we will discuss the molecular candidates that participate in the decision of endothelial cells to adapt these distinct fates and highlight the emerging insights on how these cells send out filopodia while navigating.
Paclitaxel Versus Sirolimus Stents in Diabetic and Nondiabetic Patients
Authors: Chiu Maria , Ko Dennis T. , Austin Peter C. , Cohen Eric A. , Velianou James L. , Goeree Ron , Blackhouse Gord , Tu Jack V.
Published: March 2009

Background—

Drug-eluting stents are more effective in reducing restenosis than bare-metal stents. Less certain is the relative performance of 2 widely used drug-eluting stents—sirolimus- and paclitaxel-eluting stents—in diabetic and nondiabetic patients undergoing percutaneous coronary intervention in routine clinical practice. We therefore studied the long-term effectiveness and safety of sirolimus versus paclitaxel stents overall and stratified by the absence or presence of diabetes.

Methods and Results—

We compared sirolimus and paclitaxel stents in a propensity-score matched cohort of 2054 pairs of patients (835 matched pairs of diabetic patients and 1219 matched pairs of nondiabetic patients) undergoing percutaneous coronary intervention in Ontario between December 1, 2003 and March 31, 2006. The cohort was derived from the Cardiac Care Network of Ontario percutaneous coronary intervention registry and linked to population-based administrative health databases. In the overall cohort, there was no difference in rates of target-vessel revascularization (
P
=0.47), myocardial infarction (
P
=0.71), or death (
P
=0.49). As compared with paclitaxel stents, the use of sirolimus stents was associated with a significantly lower 3-year rate of target-vessel revascularization in nondiabetic patients (8.3% versus 10.0%,
P
=0.01), but not in diabetic patients (12.7% versus 10.3%,
P
=0.07). Rates of all-cause mortality were similar in patients receiving sirolimus stents versus paclitaxel stents in both the diabetic (8.4% versus 9.2%,
P
=0.91) and nondiabetic (4.6% versus 3.0%,
P
=0.22) groups.

Conclusions—

In this large observational study, patients receiving paclitaxel and sirolimus stents had similar mortality rates, but nondiabetic patients receiving sirolimus stents were significantly less likely to require repeat revascularization.
Nitroxyl Activates SERCA in Cardiac Myocytes via Glutathiolation of Cysteine 674
Authors: Lancel Steve , Zhang Jingmei , Evangelista Alicia , Trucillo Mario P. , Tong XiaoYong , Siwik Deborah A. , Cohen Richard A. , Colucci Wilson S.
Published: March 2009

Nitroxyl (HNO) exerts inotropic and lusitropic effects in myocardium, in part via activation of SERCA (sarcoplasmic reticulum calcium ATPase). To elucidate the molecular mechanism, adult rat ventricular myocytes were exposed to HNO derived from Angeli’s salt. HNO increased the maximal rate of thapsigargin-sensitive Ca
2+
uptake mediated by SERCA in sarcoplasmic vesicles and caused reversible oxidative modification of SERCA thiols. HNO increased the
S
-glutathiolation of SERCA, and adenoviral overexpression of glutaredoxin-1 prevented both the HNO-stimulated oxidative modification of SERCA and its activation, as did overexpression of a mutated SERCA in which cysteine 674 was replaced with serine. Thus, HNO increases the maximal activation of SERCA via
S
-glutathiolation at cysteine 674.
Age-Accelerated Atherosclerosis Correlates With Failure to Upregulate Antioxidant Genes
Authors: Collins Alan R. , Lyon Christopher J. , Xia Xuefeng , Liu Joey Z. , Tangirala Rajendra K. , Yin Fen , Boyadjian Rima , Bikineyeva Alfiya , Praticò Domenico , Harrison David G. , Hsueh Willa A.
Published: March 2009

Excess food intake leads to obesity and diabetes, both of which are well-known independent risk factors for atherosclerosis, and both of which are growing epidemics in an aging population. We hypothesized that aging enhances the metabolic and vascular effects of high fat diet (HFD) and therefore examined the effect of age on atherosclerosis and insulin resistance in lipoprotein receptor knockout (LDLR
−/−
) mice. We found that 12-month-old (middle-aged) LDLR
−/−
mice developed substantially worse metabolic syndrome, diabetes, and atherosclerosis than 3-month-old (young) LDLR
−/−
mice when both were fed HFD for 3 months, despite similar elevations in total cholesterol levels. Microarray analyses were performed to analyze the mechanism responsible for the marked acceleration of atherosclerosis in middle-aged mice. Chow-fed middle-aged mice had greater aortic expression of multiple antioxidant genes than chow-fed young mice, including glutathione peroxidase-1 and -4, catalase, superoxide dismutase-2, and uncoupling protein-2. Aortic expression of these enzymes markedly increased in young mice fed HFD but decreased or only modestly increased in middle-aged mice fed HFD, despite the fact that systemic oxidative stress and vascular reactive oxygen species generation, measured by plasma F2α isoprostane concentration (systemic) and dihydroethidium conversion and p47phox expression (vascular), were greater in middle-aged mice fed HFD. Thus, the mechanism for the accelerated vascular injury in older LDLR
−/−
mice was likely the profound inability to mount an antioxidant response. This effect was related to a decrease in vascular expression of 2 key transcriptional pathways regulating the antioxidant response, DJ-1 and forkhead box, subgroup O family (FOXOs). Treatment of middle-aged mice fed HFD with the antioxidant apocynin attenuated atherosclerosis, whereas treatment with the insulin sensitizer rosiglitazone attenuated both metabolic syndrome and atherosclerosis. Both treatments decreased oxidative stress. A novel effect of rosiglitazone was to increase expression of Nrf2 (nuclear factor [erythroid-derived 2]-like 2), a downstream target of DJ-1 contributing to enhanced expression of vascular antioxidant enzymes. This investigation underscores the role of oxidative stress when multiple atherosclerotic risk factors, particularly aging, converge on the vessel wall and emphasizes the need to develop effective strategies to inhibit oxidative stress to protect aging vasculature.
Vascular Lipid Accumulation, Lipoprotein Oxidation, and Macrophage Lipid Uptake in Hypercholesterolemic Zebrafish
Authors: Stoletov Konstantin , Fang Longhou , Choi Soo-Ho , Hartvigsen Karsten , Hansen Lotte F. , Hall Chris , Pattison Jennifer , Juliano Joseph , Miller Elizabeth R. , Almazan Felicidad , Crosier Phil , Witztum Joseph L. , Klemke Richard L. , Miller Yury I.
Published: March 2009

Lipid accumulation in arteries induces vascular inflammation and atherosclerosis, the major cause of heart attack and stroke in humans. Extreme hyperlipidemia induced in mice and rabbits enables modeling many aspects of human atherosclerosis, but microscopic examination of plaques is possible only postmortem. Here we report that feeding adult zebrafish (
Danio rerio
) a high-cholesterol diet (HCD) resulted in hypercholesterolemia, remarkable lipoprotein oxidation, and fatty streak formation in the arteries. Feeding an HCD supplemented with a fluorescent cholesteryl ester to optically transparent
fli1:EGFP
zebrafish larvae in which endothelial cells express green fluorescent protein (GFP), and using confocal microscopy enabled monitoring vascular lipid accumulation and the endothelial cell layer disorganization and thickening in a live animal. The HCD feeding also increased leakage of a fluorescent dextran from the blood vessels. Administering ezetimibe significantly diminished the HCD-induced endothelial cell layer thickening and improved its barrier function. Feeding HCD to
lyz:DsRed2
larvae in which macrophages and granulocytes express DsRed resulted in the accumulation of fluorescent myeloid cells in the vascular wall. Using a fluorogenic substrate for phospholipase A
2
(PLA
2
), we observed an increased vascular PLA
2
activity in live HCD-fed larvae compared to control larvae. Furthermore, by transplanting genetically modified murine cells into HCD-fed larvae, we demonstrated that toll-like receptor-4 was required for efficient in vivo lipid uptake by macrophages. These results suggest that the novel zebrafish model is suitable for studying temporal characteristics of certain inflammatory processes of early atherogenesis and the in vivo function of vascular cells.
Causes of Death by Level of Dependency at 6 Months After Ischemic Stroke in 3 Large Cohorts
Authors: Slot Karsten Bruins , Berge Eivind , Sandercock Peter , Lewis Steff C. , Dorman Paul , Dennis Martin
Published: March 2009

Background and Purpose—

We assessed the influence of functional status at 6 months after ischemic stroke on cause of death during long-term follow-up in 3 prospective cohorts.

Methods—

The cohorts were 7710 patients from the Oxfordshire Community Stroke Project, Lothian Stroke Register, and International Stroke Trial. Functional status was assessed at 6 months after stroke onset. Causes of death were identified from death certificates, and were also classified into “stroke-related” or “other” causes. We calculated the relative risk with 95% CI to assess the association between dependency level and cause of death. We also performed a multivariable regression analysis to adjust for other relevant factors.

Results—

Six months after stroke onset 5961 (78%) patients were still alive. At the end of follow-up period, 1620 (47%) patients who were functionally dependent at 6 months after stroke onset had died vs 711 (28%) independent patients. Dependent patients had a relative risk of dying from stroke of 1.70 (95% CI, 1.44–2.00) compared to independent patients. Overall, dependent patients had a relative risk of 1.68 (95% CI, 1.49–1.91) of dying from stroke-related causes. Dependency remained significantly (
P
<0.01) associated with stroke-related causes of death in a multivariable regression analysis.

Conclusion—

Stroke-related deaths continue to be a problem during the years after an ischemic stroke, especially in patients who are functionally dependent at 6 months after onset. Better acute treatments to reduce dependency and adequate secondary prevention remain high priorities.
Atherosclerotic Plaque Surface Morphology in the Carotid Bifurcation Assessed With Multidetector Computed Tomography Angiography
Authors: de Weert Thomas T. , Cretier Sander , Groen Harald C. , Homburg Philip , Cakir Hamit , Wentzel Jolanda J. , Dippel Diederik W.J. , van der Lugt Aad
Published: March 2009

Background and Purpose—

Complicated (irregular or ulcerated) carotid plaques have proven to be independent predictors of stroke. We analyzed the frequency and location of plaque irregularities in a large cohort of patients with ischemic cerebrovascular disease and the relation with severity of stenosis, cardiovascular risk factors, and symptomatology.

Methods—

Multidetector CT angiography images from 406 patients were evaluated. Plaque surface morphology was classified as smooth, irregular, or ulcerated. The location of the ulceration was defined as proximal or distal to the point of maximum stenosis.

Results—

Atherosclerotic plaques with an open lumen were present in 448 carotid arteries; these plaques were classified as: smooth, 276 (62%); irregular, 99 (22%); and ulcerated, 73 (16%). Sixty-two (69%) of the ulcerations were located proximal to the point of maximum luminal stenosis. Complicated plaques were significantly (
P
<0.001) more common in carotid arteries with stenosis >30% than in those with stenosis <30%. There is an association between complicated plaques and hypercholesterolemia (OR, 3.0) and a trend toward an association with smoking (OR, 1.9). Complicated plaques are more often present in the symptomatic carotid artery than in the contralateral asymptomatic carotid artery; however, this is fully attributed to a significantly higher degree of stenosis in the symptomatic arteries.

Conclusions—

Multidetector CT angiography allows the classification of atherosclerotic carotid plaque surface. Complicated plaques are frequent in atherosclerotic carotid disease, especially with higher stenosis degree. Ulcerations are mostly located in the proximal part of the atherosclerotic plaque. Hypercholesterolemia and smoking are related with the presence of complicated plaques.
How Do We Empathize with Someone Who Is Not Like Us? A Functional Magnetic Resonance Imaging Study
Authors: Lamm Claus , Meltzoff Andrew N. , Decety Jean
Published: March 2009

Previous research on the neural underpinnings of empathy has been limited to affective situations experienced in a similar way by an observer and a target individual. In daily life we also interact with people whose responses to affective stimuli can be very different from our own. How do we understand the affective states of these individuals? We used functional magnetic resonance imaging to assess how participants empathize with the feelings of patients who reacted with no pain to surgical procedures but with pain to a soft touch. Empathy for pain of these patients activated the same areas (insula, medial/anterior cingulate cortex) as empathy for persons who responded to painful stimuli in the same way as the observer. Empathy in a situation that was aversive only for the observer but neutral for the patient recruited areas involved in self–other distinction (dorsomedial prefrontal cortex) and cognitive control (right inferior frontal cortex). In addition, effective connectivity between the latter and areas implicated in affective processing was enhanced. This suggests that inferring the affective state of someone who is not like us can rely upon the same neural structures as empathy for someone who is similar to us. When strong emotional response tendencies exist though, these tendencies have to be overcome by executive functions. Our results demonstrate that the fronto-cortical attention network is crucially involved in this process, corroborating that empathy is a flexible phenomenon which involves both automatic and controlled cognitive mechanisms. Our findings have important implications for the understanding and promotion of empathy, demonstrating that regulation of one's egocentric perspective is crucial for understanding others.
Dynamic Cultural Influences on Neural Representations of the Self
Authors: Chiao Joan Y. , Harada Tokiko , Komeda Hidetsugu , Li Zhang , Mano Yoko , Saito Daisuke , Parrish Todd B. , Sadato Norihiro , Iidaka Tetsuya
Published: March 2009

People living in multicultural environments often encounter situations which require them to acquire different cultural schemas and to switch between these cultural schemas depending on their immediate sociocultural context. Prior behavioral studies show that priming cultural schemas reliably impacts mental processes and behavior underlying self-concept. However, less well understood is whether or not cultural priming affects neurobiological mechanisms underlying the self. Here we examined whether priming cultural values of individualism and collectivism in bicultural individuals affects neural activity in cortical midline structures underlying self-relevant processes using functional magnetic resonance imaging. Biculturals primed with individualistic values showed increased activation within medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC) during general relative to contextual self-judgments, whereas biculturals primed with collectivistic values showed increased response within MPFC and PCC during contextual relative to general self-judgments. Moreover, degree of cultural priming was positively correlated with degree of MPFC and PCC activity during culturally congruent self-judgments. These findings illustrate the dynamic influence of culture on neural representations underlying the self and, more broadly, suggest a neurobiological basis by which people acculturate to novel environments.
Numerical Values Leave a Semantic Imprint on Associated Signs in Monkeys
Authors: Diester Ilka , Nieder Andreas
Published: March 2009

Animals and humans share an evolutionary ancient quantity representation which is characterized by analog magnitude features: Discriminating magnitudes becomes more difficult with increasing set sizes (size effect) and with decreasing distance between two numerosities (distance effect). Humans show these effects even with number symbols. We wondered whether monkeys would show the same psychophysical effects with numerical signs and addressed this issue by training three monkeys to associate visual shapes with numerosities. We then confronted the monkeys with trials in which they had to match these visual signs with each other. The monkeys' performance in this shape versus shape protocol was positively correlated with the numerical distance and the magnitudes associated with the signs. Additionally, the monkeys responded significantly slower for signs with higher assigned numerical values. These findings suggest that the numerical values imprint their analog magnitudes characteristics onto the associated visual sign in monkeys, an effect that we also found reflected in the discharges of prefrontal neurons. This provides evidence for a precursor of the human number symbol knowledge.
Kosovo Negotiations: Re-visiting the Role of Mediation
Authors: Fridl Daniella D.
Published: March 2009

Why do negotiations fail, how do we explain this failure through negotiations theory and what lessons can we draw for the future? What is the role of the mediator and to what extent do a mediator’s values and interests affect the outcome of the negotiations? These questions are analyzed and answered through a discussion of the Kosovo negotiations and theoretical concepts of power imbalance, mediator’s formula, trust, interests and perceptions. The analysis evaluates why the mediation eff orts failed to produce a mutually acceptable agreement.
Inter-Species Embryos and Human Clones:
Authors: Laing Jacqueline A.
Published: March 2009

The United Kingdom’s Human Fertilisation and Embryology Bill, introduced into Parliament on the 8th of November 2007 contains a number of controversial proposals inter alia expressly permitting the creation of inter-species embryos for research and destruction and increasing the scope for human cloning also for destructive research. It is supposed that there ought not to be a blanket ban on the creation of human clones, hybrids, cybrids and chimeras because these embryos are valuable for research purposes. The prohibition on the gestation of non-permitted embryos and interspecies embryos is used to generate confidence that embryos with compromised origins would not be gestated and reared. The argument outlined here demonstrates how uncertain are any legal prohibitions on gestation. Accordingly, the practical import of the distinction between compromised embryos for research and the same for live birth is equally dubious. The legislation would not, on this analysis, supply effective controls over this reproductive technology.
The Defense of Superior Orders in International Law: Some Implications for the Codification of International Criminal Law
Authors: Sato Hiromi
Published: March 2009

The defense of obedience to superior orders has been one of the most controversial issues in international criminal law. Although the Nuremberg Trials put forth the “Nuremberg Principle” on the superior orders defense, the principle has remained unclear on the so-called moral choice test. Basically, the situation has not been changed throughout the subsequent international rule-making process. International society has apparently rejected automatic immunity by the superior orders defense; however, a consensus has not been achieved on the question of conditional immunity, particularly on the grounds of coercion. In tackling these remaining problems, it would be advisable to examine the legal and theoretical characteristics of each component of the relevant discussion. It would also be desirable to consider some essential difficulties incidental to international rule-making. This article, in conclusion, draws attention to the possibility of certain self-constraint with regard to international law, leaving the issue of the coercion defense to the respective national legal system.
The Developmental Consequences for Asylum-seeking Children Living With the Prospect for Five Years or More of Enforced Return to Their Home Country
Authors: Kalverboer M.E. , Zijlstra A.E. , Knorth E.J.
Published: March 2009

This study examines the European legal framework and policy on children’s rights and on the development and developmental risks of children from asylum-seeking families who have lived in asylum centres for over five years with the prospect of being forced to return to their home country. The legal procedures and practices of Member States in the Western European countries seem to be far too lengthy, and the standards for reception far too low to protect the children’s positive development.
Rate of Work Done by Atmospheric Pressure on the Ocean General Circulation and Tides
Authors: Ponte Rui M.
Published: March 2009

Quantitative analysis of the energetics of the ocean is crucial for understanding its circulation and mixing. The power input by fluctuations in atmospheric pressure pa resulting from the S1 and S2 air tides and the stochastic continuum is analyzed here, with a focus on globally integrated, time-mean values. Results are based on available 1° × 1° near-global pa and sea level fields and are intended as mainly order-of-magnitude estimates. The rate of work done on the radiational and gravitational components of the S2 ocean tide is estimated at 14 and −60 GW, respectively, mostly occurring at low latitudes. The net extraction of energy at a rate of −46 GW is about 10% of available estimates of the work rates by gravity on the S2 tide. For the mainly radiational S1 tide, the power input by pa is much weaker (0.25 GW). Based on daily mean quantities, the stochastic pa continuum contributes ∼3 GW to the nontidal circulation, with substantial power input being associated with the pa-driven dynamic response in the Southern Ocean at submonthly time scales. Missing contributions from nontidal variability at the shortest periods (≤ 2 days) may be substantial, but the rate of work done by pa on the general circulation is likely to remain < 1% of the available wind input estimates. The importance of pa effects when considering local, time-variable energetics remains a possibility, however.
School Violence Beyond Columbine
Authors: Henry Stuart
Published: March 2009

Before Columbine, people tended to look at school violence in fragmented ways, which reflected a disciplinary analysis of social problems. Explanations about the causes of school violence tended toward psychological and developmental explanations about why school-age children become violent and social control theory about the lack of attachment and involvement by youth in conventional culture. Corresponding policies to deal with the problem focused on better detection, preemptive intervention, closer supervision, zero tolerance, and peer mediation. This narrow microanalytical framing of the issue failed to consider the multiple causal components of this complex problem, which includes the interrelated role of teachers, school administrators, educational practices and effective pedagogy, school district policy, cultural framing, gendered educational expectations, and the changing state of family and community relations in a postmodern “heartless” society. Taking an interdisciplinary approach suggests simultaneous considerations of the interrelated components constituting the problem from micro to macro and the multiple levels in which the problem is manifest.
“In the Same Way a Poem Contains the Alphabet”: the Significance of Translation in William I. Grossman's fReud
Authors: Reed Gail S.
Published: March 2009

William I. Grossman's contributions to psychoanalysis have been insufficiently appreciated, perhaps because his writing is concentrated and his meaning consequently difficult to unpack. One of his most important contributions is a remarkable description of the systematic way Freud imagined, thought, and theorized, beginning long before he created psychoanalysis. This way of thinking exemplifies Freud's theories even as it organizes his thinking. It is flexible, expandable, hierarchical, and recursive. Grossman's reading provides a window into Freud's texts that yields exciting new insights, including the idea that a transformative version of translation, a perception of the way Freud thinks creatively, may help psychoanalysts of different cultures and systems of thought communicate across boundaries. André Green's concept of the pathological negative is used as an example of how Grossman's Freud can facilitate a crossing of cultural and theoretical boundaries.
Making Reconstruction Work: Civil Society and Information after War’s End
Authors: Kage Rieko
Published: March 2009

This article develops and tests a general framework for explaining variations in the extent of postwar reconstruction. Existing studies point to the importance of economic resources and a coherent state apparatus in promoting effective reconstruction. This study argues that because reconstruction inherently requires coordination between numerous societal actors as well as between state and society, a full explanation for the extent of reconstruction must examine the linkages among those actors, especially civil society. By generating greater amounts of information, a more vibrant civil society leads to (a) better identification of needs, (b) more efficient implementation, and (c) more effective monitoring. Statistical analyses of newly assembled data from 46 Japanese prefectures lend support to the propositions advanced in the article.