bluuebunny/crossref_metadata_2025 huggingface dataset:
Euroview 2010: "Visions of Future Generation Networks"
Authors: Hossfeld Tobias , Tran-Gia Phuoc
Published: July 2011

On August 2nd -- 3rd, 2010, the EuroView 2010 workshop on "Visions of Future Generation Networks" was held at the University of Würzburg. The event was sponsored by the European Network of Excellence Euro-NF, the German Information Technology Society ITG, and the International Teletraffic Congress ITC. EuroView 2010 brought together Internet and network technology researchers, network providers, as well as equipment and device manufacturers. In 2010, the focus was on "Future Internet Design and Experimental Facilities" and on current efforts towards a Future Internet. Special sessions were organized reflecting the latest results of selected testbed expert groups as well as current and future national and international collaborative projects: (1) the German G-Lab project offering a national platform for Future Internet studies, (2) the Future Internet Activities in the European Framework FP7 organized by Max Lemke, and (3) the GENI project in US organized by Aaron Falk. A keynote talk was given by Lawrence Landweber on the challenges and paradigms emerging in the Future (Inter)Network.
Architecting for innovation
Authors: Koponen Teemu , Shenker Scott , Balakrishnan Hari , Feamster Nick , Ganichev Igor , Ghodsi Ali , Godfrey P. Brighten , McKeown Nick , Parulkar Guru , Raghavan Barath , Rexford Jennifer , Arianfar Somaya , Kuptsov Dmitriy
Published: July 2011

We argue that the biggest problem with the current Internet architecture is not a particular functional deficiency, but its inability to accommodate innovation. To address this problem we propose a minimal architectural "framework" in which comprehensive architectures can reside. The proposed Framework for Internet Innovation (FII) --- which is derived from the simple observation that network interfaces should be extensible and abstract --- allows for a diversity of architectures to coexist, communicate, and evolve. We demonstrate FII's ability to accommodate diversity and evolution with a detailed examination of how information flows through the architecture and with a skeleton implementation of the relevant interfaces.
The 3rd workshop on active internet measurements (AIMS-3) report
Authors: claffy kc
Published: July 2011

On February 10-12, 2011, CAIDA hosted the third Workshop on Active Internet Measurements (AIMS-3) as part of our series of Internet Statistics and Metrics Analysis (ISMA) workshops. As with the previous two AIMS workshops, the goals were to further our understanding of the potential and limitations of active measurement research and infrastructure in the wide-area Internet, and to promote cooperative solutions and coordinated strategies to address future data needs of the network and security research communities. For three years, the workshop has fostered interdisciplinary conversation among researchers, operators, and government, focused on analysis of goals, means, and emerging issues in active Internet measurement projects. The first workshop emphasized discussion of existing hardware and software platforms for macroscopic measurement and mapping of Internet properties, in particular those related to cybersecurity. The second workshop included more performance evaluation and data-sharing approaches. This year we expanded the workshop agenda to include active measurement topics of more recent interest: broadband performance; gauging IPv6 deployment; and measurement activities in international research networks.
Tracking IPv6 evolution
Authors: claffy kc
Published: July 2011

Exhaustion of the Internet addressing authority's (IANA) available IPv4 address space, which occurred in February 2011, is finally exerting exogenous pressure on network operators to begin to deploy IPv6. There are two possible outcomes from this transition. IPv6 may be widely adopted and embraced, causing many existing methods to measure and monitor the Internet to be ineffective. A second possibility is that IPv6 languishes, transition mechanisms fail, or performance suffers. Either scenario requires data, measurement, and analysis to inform technical, business, and policy decisions. We survey available data that have allowed limited tracking of IPv6 deployment thus far, describe additional types of data that would support better tracking, and offer a perspective on the challenging future of IPv6 evolution.
Paxillin is a novel cellular target for converging Helicobacter pylori-induced cellular signaling
Authors: Tabassam Fazal H. , Graham David Y. , Yamaoka Yoshio
Published: July 2011

Paxillin is involved in the regulation of Helicobacter pylori -mediated gastric epithelial cell motility. We investigated the signaling pathways regulating H. pylori -induced paxillin phosphorylation and the effect of the H. pylori virulence factors cag pathogenicity island (PAI) and outer inflammatory protein (OipA) on actin stress fiber formation, cell phenotype, and IL-8 production. Gastric cell infection with live H. pylori induced site-specific phosphorylation of paxillin tyrosine (Y) 31 and Y118 in a time- and concentration-dependent manner. Activated paxillin localized in the cytoplasm at the tips of H. pylori -induced actin stress fibers. Isogenic oipA mutants significantly reduced paxillin phosphorylation at Y31 and Y118 and reduced actin stress fiber formation. In contrast, cag PAI mutants only inhibited paxillin Y118 phosphorylation. Silencing of epidermal growth factor receptor (EGFR), focal adhesion kinase (FAK), or protein kinase B (Akt) expression by small-interfering RNAs or inhibiting kinase activity of EGFR, Src, or phosphatidylinositol 3-kinase (PI3K) markedly reduced H. pylori -induced paxillin phosphorylation and morphologic alterations. Reduced FAK expression or lack of Src kinase activity suppressed H. pylori -induced IL-8 production. Compared with infection with the wild type, infection with the cag PAI mutant and oipA mutant reduced IL-8 production by nearly 80 and 50%. OipA-induced IL-8 production was FAK- and Src-dependent, although a FAK/Src-independent pathway for IL-8 production also exists, and the cag PAI may be mainly involved in this pathway. We propose paxillin as a novel cellular target for converging H. pylori -induced EGFR, FAK/Src, and PI3K/Akt signaling to regulate cytoskeletal reorganization and IL-8 production in part, thus contributing to the H. pylori -induced diseases.
Pneumatic pressure bioreactor for cyclic hydrostatic stress application: mechanobiology effects on periodontal ligament cells
Authors: Wenger Karl H. , El-Awady Ahmed R. , Messer Regina L. W. , Sharawy Mohamed M. , White Greg , Lapp Carol A.
Published: July 2011

A bioreactor system was developed to provide high-amplitude cyclic hydrostatic compressive stress (cHSC) using compressed air mixed commercially as needed to create partial pressures of oxygen and carbon dioxide appropriate for the cells under investigation. Operating pressures as high as 300 psi are achievable in this system at cyclic speeds of up to 0.2 Hz. In this study, ligamentous fibroblasts from human periodontal ligaments ( n = 6) were compressed on two consecutive days at 150 psi for 3 h each day, and the mRNA for families of extracellular matrix protein and protease isoforms was evaluated by real-time PCR array. Several integrins were significantly upregulated, most notably alpha-3 (6.4-fold), as was SPG7 (12.1-fold). Among the collagens, Col8a1 was highly upregulated at 53.5-fold, with Col6a1, Col6a2, and Col7a1 also significantly upregulated 4.4- to 8.5-fold. MMP-1 was the most affected at 122.9-fold upregulation. MMP-14 likewise increased 17.8-fold with slight reductions for the gelatinases and a significant increase of TIMP-2 at 5.8-fold. The development of this bioreactor system and its utility in characterizing periodontal ligament fibroblast mechanobiology in intermediate-term testing hold promise for better simulating the conditions of the musculoskeletal system and the large cyclic compressive stresses joints may experience in gait, exertion, and mastication.
Intermittent hypoxia augments pulmonary vascular smooth muscle reactivity to NO: regulation by reactive oxygen species
Authors: Norton Charles E. , Jernigan Nikki L. , Kanagy Nancy L. , Walker Benjimen R. , Resta Thomas C.
Published: July 2011

Intermittent hypoxia (IH) resulting from sleep apnea can lead to pulmonary hypertension. IH causes oxidative stress that may limit bioavailability of the endothelium-derived vasodilator nitric oxide (NO) and thus contribute to this hypertensive response. We therefore hypothesized that increased vascular superoxide anion (O2−) generation reduces NO-dependent pulmonary vasodilation following IH. To test this hypothesis, we examined effects of the O2−scavenger tiron on vasodilatory responses to the endothelium-dependent vasodilator ionomycin and the NO donor S-nitroso- N-acetylpenicillamine in isolated lungs from hypocapnic-IH (H-IH; 3 min cycles of 5% O2/air flush, 7 h/day, 4 wk), eucapnic-IH (E-IH; cycles of 5% O2, 5% CO2/air flush), and sham-treated (air/air cycled) rats. Next, we assessed effects of endogenous O2−on NO- and cGMP-dependent vasoreactivity and measured O2−levels using the fluorescent indicator dihydroethidium (DHE) in isolated, endothelium-disrupted small pulmonary arteries from each group. Both E-IH and H-IH augmented NO-dependent vasodilation; however, enhanced vascular smooth muscle (VSM) reactivity to NO following H-IH was masked by an effect of endogenous O2−. Furthermore, H-IH and E-IH similarly increased VSM sensitivity to cGMP, but this response was independent of either O2−generation or altered arterial protein kinase G expression. Finally, both H-IH and E-IH increased arterial O2−levels, although this response was more pronounced following H-IH, and H-IH exposure resulted in greater protein tyrosine nitration indicative of increased NO scavenging by O2−. We conclude that IH increases pulmonary VSM sensitivity to NO and cGMP. Furthermore, endogenous O2−limits NO-dependent vasodilation following H-IH through an apparent reduction in bioavailable NO.
Cholinergic Hyperresponsiveness of Peripheral Lung Parenchyma in Chronic Obstructive Pulmonary Disease
Authors: Lanças Tatiana , Kasahara David Itiro , Gross Jefferson Luiz , Pires-Neto Ruy Camargo , Deheinzelin Daniel , Mauad Thais , Negri Elnara Márcia , Dolhnikoff Marisa
Published: July 2011

Background: Up to 60% of chronic obstructive pulmonary disease (COPD) patients can present airway hyperresponsiveness. However, it is not known whether the peripheral lung tissue also shows an exaggerated response to agonists in COPD. Objectives: To investigate the in vitro mechanical behavior and the structural and inflammatory changes of peripheral lung tissue in COPD patients and compare to nonsmoking controls. Methods: We measured resistance and elastance at baseline and after acetylcholine (ACh) challenge of lung strips obtained from 10 COPD patients and 10 control subjects. We also assessed the alveolar tissue density of neutrophils, eosinophils, macrophages, mast cells and CD8+ and CD4+ cells, as well as the content of α-smooth muscle actin-positive cells and elastic and collagen fibers. We further investigated whether changes in in vitro parenchymal mechanics correlated to structural and inflammatory parameters and to in vivo pulmonary function. Results: Values of resistance after ACh treatment and the percent increase in tissue resistance (%R) were higher in the COPD group (p ≤ 0.03). There was a higher density of macrophages and CD8+ cells (p < 0.05) and a lower elastic content (p = 0.003) in the COPD group. We observed a positive correlation between %R and eosinophil and CD8+ cell density (r = 0.608, p = 0.002, and r = 0.581, p = 0.001, respectively) and a negative correlation between %R and the ratio of forced expiratory volume in 1 s to forced vital capacity (r = –0.451, p < 0.05). Conclusions: The cholinergic responsiveness of parenchymal lung strips is increased in COPD patients and seems to be related to alveolar tissue eosinophilic and CD8 lymphocytic inflammation and to the degree of airway obstruction on the pulmonary function test.
Truncated Peroxisome Proliferator-Activated Receptor-γ Coactivator 1α Splice Variant Is Severely Altered in Huntington’s Disease
Authors: Johri Ashu , Starkov Anatoly A. , Chandra Abhishek , Hennessey Thomas , Sharma Abhijeet , Orobello Sara , Squitieri Ferdinando , Yang Lichuan , Beal M. Flint
Published: July 2011

Background: Reduced peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α) gene expression has been observed in striatal cell lines, transgenic mouse models of Huntington’s disease (HD), and brain tissue from HD patients. As this protein is a key transcription regulator of the expression of many mitochondrial proteins, these observations strongly support the role of aberrant mitochondrial function in the pathogenesis of HD. The PGC1α protein undergoes posttranslational modifications that affect its transcriptional activity. The N-truncated splice variant of PGC1α (NT-PGC1α) is produced in tissues, but the role of truncated splice variants of PGC1α in HD and in the regulation of mitochondrial gene expression has not been elucidated. Objective: To examine the expression and modulation of expression of NT-PGC1α levels in HD. Methods and Results: We found that the NT-PGC1α protein, a splice variant of ∼38 kDa, but not full-length PGC1α is severely and consistently altered in human HD brain, human HD myoblasts, mouse HD models, and HD striatal cells. NT-PGC1α levels were significantly upregulated in HD cells and mouse brown fat by physiologically relevant stimuli that are known to upregulate PGC1α gene expression. This resulted in an increase in mitochondrial gene expression and cytochrome c content. Conclusion: Our data suggest that NT-PGC1α is an important component of the PGC1α transcriptional network, which plays a significant role in the pathogenesis of HD.
Increased Risk of Coeliac Disease in Patients with Congenital Hypothyroidism
Authors: Stagi Stefano , Manoni Cristina , Cecchi Cecilia , Chiarelli Francesco , de Martino Maurizio
Published: July 2011

Background: In patients with congenital hypothyroidism (CH), the presence of coeliac disease (CD) has been sporadically described. Methods: Seventy-nine consecutive children (58 females and 21 males; age range 3.1–12.1 years) with permanent CH were studied. For all patients, a family history of autoimmune diseases as far as second-degree relatives was collected, and total serum IgA, antigliadin, anti-endomysium and anti-transglutaminase antibodies were evaluated. In the subjects positive for CD antibodies, the CD diagnosis was confirmed by jejunal biopsy. One hundred and eighty-two Italian children from the same geographical area, matched for age and sex, acted as controls. Results: In CH patients, a statistically significant difference was found in the familial occurrence of autoimmune diseases compared to controls (22 vs. 7.9%; p < 0.001). A total of 6 patients (4 girls, 2 boys; 7.6 vs. 1%; p < 0.005) were positive for CD antibodies. In 5 of these patients (6.3%), the diagnosis of CD was confirmed histologically. Conclusion: Our data show a higher prevalence of CD in children with permanent CH and suggest that these patients should be monitored carefully for CD. Other studies are needed to confirm our results and to explain the causes of this possible relationship.
Influence of Repetitive UVA Stimulation on Skin Protection Capacity and Antioxidant Efficacy
Authors: Rohr Mathias , Rieger Ingrid , Jain Anil , Schrader Andreas
Published: July 2011

Background/Aims: Topically applied antioxidants (AOs) are widely used in cosmetic products – especially in day and sun care – to help reduce oxidative stress caused by exogenous influences such as ultraviolet (UV) radiation. Despite several advances in recent years, little is known about the duration of protective effects by application of topical AOs, AO protection capacity (APC) or the activation of an endogenous protection capacity (EPC). Methods: By measuring oxidative-stress-induced photon emission of human skin in vivowith the ICL-S method (induced chemiluminescence of human skin), the protective effect of daily AO treatment for 2 weeks was examined on 4 consecutive days after treatment. UVA-dose-independent effects were investigated by decay curve intersection point analysis. In addition, chemiluminescence signal integration was used to investigate the influence of different UVA doses for stimulation on the determined APC as well as the modulation of the EPC by repetitive UVA stimulation both forming the skin protection capacity (SPC). Results: The SPC showed a strong dependency on the UVA dose used for stimulation. AO pretreatment was more effective against lower UVA doses. Over the course of 4 days, the AO-induced SPC did not change significantly for a given UVA dose. Analyzing the decay curve intersection point for 2 different UVA doses, however, revealed a decrease in SPC with time. In addition, we found that a repetitive UVA irradiation of 1 J/cm2 caused a statistically significant protective effect against UVA irradiation by stimulation of endogenous mechanisms. Conclusion: Topically supplemented AOs provide a protective effect against oxidative stress for at least 3 days, supporting their widespread use in cosmetic products. Especially their interaction with cutaneous protective mechanisms should be investigated in more detail for maximal protection, as endogenous defense mechanisms are already triggered by 2 low-dose UVA irradiations within 24 h. In summary, the in vivo measurement of UVA-induced cutaneous chemiluminescence permits the UVA-dose-independent determination of the AO efficacy for better comparability of the results while also taking endogenous defense mechanisms into account.
Cognitive Profile of Idiopathic Normal Pressure Hydrocephalus
Authors: Saito Makoto , Nishio Yoshiyuki , Kanno Shigenori , Uchiyama Makoto , Hayashi Akiko , Takagi Masahito , Kikuchi Hirokazu , Yamasaki Hiroshi , Shimomura Tatsuo , Iizuka Osamu , Mori Etsuro
Published: July 2011

Background/Aims: Frontal lobe dysfunction is believed to be a primary cognitive symptom in idiopathic normal pressure hydrocephalus (iNPH); however, the neuropsychology of this disorder remains to be fully investigated. The objective of this study was to delineate a comprehensive profile of cognitive dysfunction in iNPH and evaluate the effects of cerebrospinal fluid (CSF) shunt surgery on cognitive dysfunction. Methods: A total of 32 iNPH patients underwent neuropsychological testing of memory, attention, language, executive function, and visuoperceptual and visuospatial abilities. Of these 32 patients, 26 were reevaluated approximately 1 year following CSF shunt surgery. The same battery of tests was performed on 32 patients with Alzheimer’s disease (AD) and 30 healthy elderly controls. Results: The iNPH patients displayed baseline deficits in attention, executive function, memory, and visuoperceptual and visuospatial functions. Impairments of attention, executive function, and visuoperceptual and visuospatial abilities in iNPH patients were more severe than in those with AD, whereas the degree of memory impairment was comparable to that in AD patients. A significant improvement in executive function was observed following shunt surgery. Conclusion: Patients with iNPH are impaired in various aspects of cognition involving both ‘frontal’ executive functions and ‘posterior cortical’ functions. Shunt treatment can ameliorate executive dysfunction.
The Yin and Yang of Microglia
Authors: Czeh Melinda , Gressens Pierre , Kaindl Angela M.
Published: July 2011

Microglia, the resident immune cells of the mammalian central nervous system (CNS), play a pivotal role in both physiological and pathological conditions such as the restoration of CNS integrity and the progression of neurodegenerative disorders. Extensive data have been published that describe neuroinflammation by microglial activation to have detrimental consequences on the developing and mature brain. On the other hand, a properly directed and limited inflammatory response is known to be a natural healing process after an insult in several other tissues. Thus, it is not surprising that research results illustrating benefits of neuroinflammation have been emerging over the past decade. Inflammation-mediated benefits for CNS outcomes include mechanisms such as neuroprotection, mobilization of neural precursors for repair, remyelination and axonal regeneration. Here, we review data that highlight the dual aspects of microglia with a focus on the developing brain, i.e. as aggressors potentiating damage and as helpers in the recovery process following CNS damage.
Circulating Interleukin-10 and Risk of Cardiovascular Events
Authors: Welsh Paul , Murray Heather M. , Ford Ian , Trompet Stella , de Craen Anton J.M. , Jukema J. Wouter , Stott David J. , McInnes Iain B. , Packard Chris J. , Westendorp Rudi G.J. , Sattar Naveed
Published: July 2011

Objective—

The goal of this study was to examine the association of the antiinflammatory interleukin-10 (IL-10) with risk of cardiovascular disease (CVD).

Methods and Results—

In the PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) cohort, we related baseline concentrations of circulating IL-10 to risk of CVD events in a nested case (n=819)-control (n=1618) study of 3.2 years of follow-up. Circulating IL-10 showed few strong associations with classical risk factors but was positively correlated with IL-6 and C-reactive protein. IL-10 was positively associated with risk of CVD events (odds ratio [OR] 1.17, 95% CI 1.05 to 1.31 per unit increase in log IL-10) after adjusting for classical risk factors and C-reactive protein. Furthermore, IL-10 was associated more strongly with CVD risk among those with no previous history of CVD (OR 1.42, 95% CI 1.18 to 1.70), compared with those with previous CVD (OR 1.04, 95% CI 0.90 to 1.19;
P
=0.018). Overall, IL-10 showed a modest ability to add discrimination to classical risk factors (C-statistic +0.005,
P
=0.002).

Conclusion—

Baseline circulating levels of the antiinflammatory IL-10 are
positively
associated with risk of CVD among the elderly without prior CVD events, although the association is less evident in those with a history of CVD. Additional epidemiological and mechanistic studies investigating the role of IL-10 in CVD are warranted.
Assessment of Genetic Determinants of the Association of γ′ Fibrinogen in Relation to Cardiovascular Disease
Authors: Lovely Rehana S. , Yang Qiong , Massaro Joseph M. , Wang Jing , D'Agostino Ralph B. , O'Donnell Christopher J. , Shannon Jackilen , Farrell David H.
Published: July 2011

Objective—

γ′ fibrinogen is a newly emerging biomarker that is associated with cardiovascular disease (CVD). However, the genetic determinants of γ′ fibrinogen levels are unknown. We therefore conducted a genome-wide association study on 3042 participants from the Framingham Heart Study Offspring Cohort.

Methods and Results—

A genome-wide association study with 2.5 million single-nucleotide polymorphisms (SNPs) was carried out for γ′ fibrinogen levels from the cycle 7 examination. Fifty-four SNPs in or near the fibrinogen gene locus demonstrated genome-wide significance (
P
<5.0×10
−8
) for association with γ′ fibrinogen levels. The top-signal SNP was rs7681423 (
P
=9.97×10
−110
) in the fibrinogen gene locus near
FGG
, which encodes the γ chain. Conditional on the top SNP, the only other SNP that remained genome-wide significant was rs1049636. Associations between SNPs, γ′ fibrinogen levels, and prevalent CVD events were examined using multiple logistic regression. γ′ fibrinogen levels were associated with prevalent CVD (
P
=0.02), although the top 2 SNPs associated with γ′ fibrinogen levels were not associated with CVD. These findings contrast those for total fibrinogen levels, which are associated with different genetic loci, particularly
FGB
, which encodes the Bβ chain.

Conclusion—

γ′ fibrinogen is associated with prevalent CVD and with SNPs exclusively in and near the fibrinogen gene locus.
JAGGED1 Signaling Regulates Hemangioma Stem Cell–to–Pericyte/Vascular Smooth Muscle Cell Differentiation
Authors: Boscolo Elisa , Stewart Camille L. , Greenberger Shoshana , Wu June K. , Durham Jennifer T. , Herman Ira M. , Mulliken John B. , Kitajewski Jan , Bischoff Joyce
Published: July 2011

Objective—

The aim of our study is to determine the cellular and molecular origin for the pericytes in infantile hemangioma (IH) and their functional role in the formation of pathological blood vessels.

Methods and Results—

Here we show that IH-derived stem cells (HemSCs) form pericyte-like cells. With in vitro studies, we demonstrate that HemSC-to-pericyte differentiation depends on direct contact with endothelial cells. JAGGED1 expressed ectopically in fibroblasts was sufficient to induce HemSCs to acquire a pericyte-like phenotype, indicating a critical role for JAGGED1. In vivo, we blocked pericyte differentiation with recombinant JAGGED1, and we observed reduced formation of blood vessels, with an evident lack of pericytes. Silencing
JAGGED1
in the endothelial cells reduced blood vessel formation and resulted in a paucity of pericytes.

Conclusion—

Our data show that endothelial JAGGED1 controls HemSC-to-pericyte differentiation in a murine model of IH and suggests that pericytes have a fundamental role in formation of blood vessels in IH.
Haploinsufficiency of Target of Rapamycin Attenuates Cardiomyopathies in Adult Zebrafish
Authors: Ding Yonghe , Sun Xiaojing , Huang Wei , Hoage Tiffany , Redfield Margaret , Kushwaha Sudhir , Sivasubbu Sridhar , Lin Xueying , Ekker Stephen , Xu Xiaolei
Published: July 2011

Rationale:

Although a cardioprotective function of target of rapamycin (TOR) signaling inhibition has been suggested by pharmacological studies using rapamycin, genetic evidences are still lacking. We explored adult zebrafish as a novel vertebrate model for dissecting signaling pathways in cardiomyopathy.

Objective:

We generated the second adult zebrafish cardiomyopathy model induced by doxorubicin. By genetically analyzing both the doxorubicin and our previous established anemia-induced cardiomyopathy models, we decipher the functions of TOR signaling in cardiomyopathies of different etiology.

Methods and Results:

Along the progression of both cardiomyopathy models, we detected dynamic TOR activity at different stages of pathogenesis as well as distinct effects of TOR signaling inhibition. Nevertheless, cardiac enlargement in both models can be effectively attenuated by inhibition of TOR signaling through short-term rapamycin treatment. To assess the long-term effects of TOR reduction, we used a zebrafish target of rapamycin (
ztor
) mutant identified from an insertional mutagenesis screen. We show that TOR haploinsufficiency in the
ztor
heterozygous fish improved cardiac function, prevented pathological remodeling events, and ultimately reduced mortality in both adult fish models of cardiomyopathy. Mechanistically, these cardioprotective effects are conveyed by the antihypertrophy, antiapoptosis, and proautophagy function of TOR signaling inhibition.

Conclusions:

Our results prove adult zebrafish as a conserved novel vertebrate model for human cardiomyopathies. Moreover, we provide the first genetic evidence to demonstrate a long-term cardioprotective effect of TOR signaling inhibition on at least 2 cardiomyopathies of distinct etiology, despite dynamic TOR activities during their pathogenesis.
An Economic Analysis of Robot-Assisted Therapy for Long-Term Upper-Limb Impairment After Stroke
Authors: Wagner Todd H. , Lo Albert C. , Peduzzi Peter , Bravata Dawn M. , Huang Grant D. , Krebs Hermano I. , Ringer Robert J. , Federman Daniel G. , Richards Lorie G. , Haselkorn Jodie K. , Wittenberg George F. , Volpe Bruce T. , Bever Christopher T. , Duncan Pamela W. , Siroka Andrew , Guarino Peter D.
Published: July 2011

Background and Purpose—

Stroke is a leading cause of disability. Rehabilitation robotics have been developed to aid in recovery after a stroke. This study determined the additional cost of robot-assisted therapy and tested its cost-effectiveness.

Methods—

We estimated the intervention costs and tracked participants' healthcare costs. We collected quality of life using the Stroke Impact Scale and the Health Utilities Index. We analyzed the cost data at 36 weeks postrandomization using multivariate regression models controlling for site, presence of a prior stroke, and Veterans Affairs costs in the year before randomization.

Results—

A total of 127 participants were randomized to usual care plus robot therapy (n=49), usual care plus intensive comparison therapy (n=50), or usual care alone (n=28). The average cost of delivering robot therapy and intensive comparison therapy was $5152 and $7382, respectively (
P
<0.001), and both were significantly more expensive than usual care alone (no additional intervention costs). At 36 weeks postrandomization, the total costs were comparable for the 3 groups ($17 831 for robot therapy, $19 746 for intensive comparison therapy, and $19 098 for usual care). Changes in quality of life were modest and not statistically different.

Conclusions—

The added cost of delivering robot or intensive comparison therapy was recuperated by lower healthcare use costs compared with those in the usual care group. However, uncertainty remains about the cost-effectiveness of robotic-assisted rehabilitation compared with traditional rehabilitation.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique identifier: NCT00372411.
Dual-Enhanced Cardiac CT for Detection of Left Atrial Appendage Thrombus in Patients With Stroke
Authors: Hur Jin , Kim Young Jin , Lee Hye-Jeong , Nam Ji Eun , Ha Jong-Won , Heo Ji Hoe , Chang Hyuk-Jae , Kim Hua Sun , Hong Yoo Jin , Kim Hee Yeong , Choe Kyu Ok , Choi Byoung Wook
Published: July 2011

Background and Purpose—

A noninvasive method with high reliability and accuracy comparable to transesophageal echocardiography for identification of left atrial appendage thrombus would be of significant clinical value. The aim of this study was to assess the diagnostic performance of a dual-enhanced cardiac CT protocol for detection of left atrial appendage thrombi and for differentiation between thrombus and circulatory stasis in patients with stroke.

Methods—

We studied 83 consecutive patients with stroke (56 men and 27 women; mean age, 62.6 years) who had high risk factors for thrombus formation and had undergone both dual-source CT and transesophageal echocardiography within a 3-day period. CT was performed with prospective electrocardiographic gating, and scanning began 180 seconds after the test bolus.

Results—

Among the 83 patients, a total of 13 thrombi combined with spontaneous echo contrast and 14 spontaneous echo contrasts were detected by transesophageal echocardiography. All 13 thrombi combined with spontaneous echo contrast were correctly diagnosed on CT. Using transesophageal echocardiography as the reference standard, the overall sensitivity and specificity of CT for the detection of thrombi and circulatory stasis in the left atrial appendage were 96% (95% CI, 78% to 99%), and 100% (95% CI, 92% to 100%), respectively. On CT, the mean left atrial appendage/ascending aorta Hounsfield unit ratios were significantly different between thrombus and circulatory stasis (0.15 Hounsfield unit versus 0.27 Hounsfield unit,
P
=0.001). The mean effective radiation dose was 3.11 mSv.

Conclusions—

Dual-enhanced cardiac CT with prospective electrocardiographic gating is a noninvasive and sensitive modality for detecting left atrial appendage thrombus with an acceptable radiation dose.
Differential Association of Docosahexaenoic and Eicosapentaenoic Acids With Carotid Intima-Media Thickness
Authors: Sekikawa Akira , Kadowaki Takashi , El-Saed Aiman , Okamura Tomonori , Sutton-Tyrrell Kim , Nakamura Yasuyuki , Evans Rhobert W. , Mitsunami Ken-ichi , Edmundowicz Daniel , Nishio Yoshihiko , Nakata Katsumi , Kadota Aya , Otake Teruo , Miura Katsuyuki , Choo Jina , Abbott Robert D. , Kuller Lewis H. , Curb J. David , Ueshima Hirotsugu ,   for the ERA JUMP Study group
Published: July 2011

Background and Purpose—

Recent studies reported the differential effect of docosahexaenoic (DHA) and eicosapentaenoic acids (EPA). We examined the differential association of DHA and EPA with carotid intima-media thickness (IMT) in Japanese individuals in Japan and in U.S. white individuals and explored whether DHA or EPA contributes to the difference in IMT between the two groups.

Methods—

A population-based cross-sectional study in 608 Japanese and U.S. white men aged 40 to 49 was conducted to assess IMT, serum DHA, EPA, and other cardiovascular risk factors.

Results—

Japanese compared to U.S. whites had significantly lower IMT (mean±SD, 618±81 and 672±94 μm for Japanese and whites, respectively;
P
<0.001) and had >2-fold higher levels of DHA and EPA. DHA, but not EPA, had an inverse association with IMT in both Japanese and U.S. whites. The inverse association remained only in Japanese men after adjusting for risk and other factors. The significant difference in multivariable-adjusted IMT became nonsignificant after further adjusting for DHA (mean difference, 17 μm; 95% CI, −8 to 43;
P
=0.177) but not EPA. In this multivariable-adjusted model, DHA but not EPA was a significant predictor of IMT (
P
=−0.032 versus 0.863, respectively).

Conclusions—

These data suggest that DHA may have a more potent antiatherogenic effect than EPA, especially in levels observed in the Japanese, independent of risk factors.
Relationship Between C-Reactive Protein, Systemic Oxygen Consumption, and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage
Authors: Badjatia Neeraj , Carpenter Amanda , Fernandez Luis , Schmidt J. Michael , Mayer Stephan A. , Claassen Jan , Lee Kiwon , Connolly E. Sander , Seres David , Elkind Mitchell S.V.
Published: July 2011

Background and Purpose—

Subarachnoid hemorrhage (SAH) is known to result in elevated systemic oxygen consumption (V
o
2
) and increases in high-sensitivity C-reactive protein (hsCRP), although the relationship among hsCRP, V
o
2
, and delayed cerebral ischemia (DCI) after SAH remains unknown. We hypothesized that hsCRP is directly associated with V
o
2
and that elevated V
o
2
is a predictor of DCI after SAH.

Methods—

Prospective serial assessments of V
o
2
and hsCRP over 4 prespecified time periods during the first 14 days after bleed in consecutive SAH patients admitted to a single academic medical center for a 2-year period.

Results—

One hundred ten SAH patients met study criteria (mean age, 55±16 years; 62% women), with a median admission Hunt Hess grade of 3 (interquartile range, 2–4). In multivariate generalized estimating equation model of the first 14 days after bleed, V
o
2
was associated with younger age (
P
=0.01), male gender (
P
=0.01), and hsCRP levels (
P
=0.03). Twenty-four (22%) patients had DCI develop, with a median onset on day 7 after bleed (interquartile range, 5–11). The mean V
o
2
(291±65 mL/min versus 226±55 mL/min;
P
=0.003) was higher in DCI patients. In a multivariable Cox proportional hazards model, younger age (hazard ratio, 1.2 per 5 years; 95% CI, 1.1–1.3), a higher modified Fisher scale score (hazard ratio, 3.4 per 1-point increase; 95% CI, 1.7–6.9), and higher V
o
2
(HR, 1.2 per 50-mL/min increase; 95% CI, 1.1–1.3) were predictive of DCI.

Conclusions—

Systemic oxygen consumption is associated with hsCRP levels in the first 14 days after SAH and is an independent predictor of DCI.
Short-Term Outcomes After Symptomatic Internal Carotid Artery Occlusion
Authors: Burke Matthew J. , Vergouwen Mervyn D.I. , Fang Jiming , Swartz Rick H. , Kapral Moira K. , Silver Frank L. , Casaubon Leanne K.
Published: July 2011

Background and Purpose—

Previous studies concerning internal carotid artery (ICA) occlusion have focused on long-term prognosis. The purpose of the present study was to evaluate short-term outcomes of patients with symptomatic ICA occlusion.

Methods—

We used data from the Registry of the Canadian Stroke Network on consecutive patients presenting to 11 stroke centers in Ontario. We included patients with noncardioembolic ischemic stroke or transient ischemic attack within the anterior circulation. The resulting cohort was divided into 4 groups based on vascular imaging of the ipsilateral extracranial ICA: occlusion, severe stenosis, moderate stenosis, and mild/no stenosis. Logistic regression modeling was used to evaluate the association between the degree of stenosis/occlusion of the symptomatic ICA and a series of short-term outcome measures.

Results—

Of the 4144 patients who met study criteria, 283 patients had a symptomatic ICA occlusion. Compared with patients with ICA occlusion, patients with all other degrees of stenosis had a lower risk of in-hospital death, neurological worsening, and poor functional outcome. Particularly, severe stenosis was associated with a lower risk of in-hospital death (adjusted OR, 0.40; 95% CI, 0.20 to 0.79), neurological worsening (adjusted OR, 0.52; 95% CI, 0.34 to 0.78), and poor functional outcome (adjusted OR, 0.62; 95% CI, 0.41 to 0.94) compared with the ICA occlusion group.

Conclusions—

The results of our study showed that patients with symptomatic ICA occlusion are at a high risk of adverse outcomes that is as severe, if not worse, than any other degree of ICA stenosis in the short term. Thus, more aggressive management may be warranted for patients with acute, symptomatic ICA occlusion.
Intracranial Vessel Wall Imaging at 7.0-T MRI
Authors: van der Kolk Anja G. , Zwanenburg Jaco J.M. , Brundel Manon , Biessels Geert-Jan , Visser Fredy , Luijten Peter R. , Hendrikse Jeroen
Published: July 2011

Background and Purpose—

Conventional imaging methods cannot depict the vessel wall of intracranial arteries at sufficient resolutions. This hampers the evaluation of intracranial arterial disease. The aim of the present study was to develop a high-resolution MRI method to image intracranial vessel wall.

Methods—

We developed a volumetric (3-dimensional) turbo spin-echo (TSE) sequence for intracranial vessel wall imaging at 7.0-T MRI. Inversion recovery was used to null cerebrospinal fluid to increase contrast with the vessel wall. Magnetization preparation was applied before inversion to improve signal-to-noise ratio. Seven healthy volunteers and 35 patients with ischemic stroke or transient ischemic attack underwent imaging to test the magnetization preparation inversion recovery TSE sequence. Gadolinium-based contrast agent (Gadobutrol, 0.1 mL/kg) was administered to assess possible lesion enhancement in the patients.

Results—

The walls of intracranial arterial vessels could be visualized in all volunteers and patients with good contrast between wall, blood, and cerebrospinal fluid. The quality of the vessel wall depiction was independent of the vessel orientation relative to the plane of acquisition. In 21 of the 35 patients, a total number of 52 intracranial vessel wall lesions were identified. Eleven of the 52 lesions showed enhancement after contrast administration. Only 14 of the 52 lesions resulted in stenosis of the arterial lumen.

Conclusions—

Intracranial vessel wall and its pathology can be depicted with the magnetization preparation inversion recovery TSE sequence at 7.0 T. The magnetization preparation inversion recovery TSE sequence will make it possible to study the role of intracranial arterial wall pathology in ischemic stroke.

Clinical Trial Registration Information—

URL:
http://www.trialregister.nl/trialreg/index.asp
. Unique identifier: NTR2119.
Local-Global Interaction and the Emergence of Scale-Free Networks with Community Structures
Authors: Liu Jing , Abbass Hussein A. , Zhong Weicai , Green David G.
Published: July 2011

Understanding complex networks in the real world is a nontrivial task. In the study of community structures we normally encounter several examples of these networks, which makes any statistical inferencing a challenging endeavor. Researchers resort to computer-generated networks that resemble networks encountered in the real world as a means to generate many networks with different sizes, while maintaining the real-world characteristics of interest. The generation of networks that resemble the real world turns out in itself to be a complex search problem. We present a new rewiring algorithm for the generation of networks with unique characteristics that combine the scale-free effects and community structures encountered in the real world. The algorithm is inspired by social interactions in the real world, whereby people tend to connect locally while occasionally they connect globally. This local-global coupling turns out to be a powerful characteristics that is required for our proposed rewiring algorithm to generate networks with community structures, power law distributions both in degree and in community size, positive assortative mixing by degree, and the rich-club phenomenon.
Information Content of Colored Motifs in Complex Networks
Authors: Adami Christoph , Qian Jifeng , Rupp Matthew , Hintze Arend
Published: July 2011

We study complex networks in which the nodes are tagged with different colors depending on their function (colored graphs), using information theory applied to the distribution of motifs in such networks. We find that colored motifs can be viewed as the building blocks of the networks (much more than the uncolored structural motifs can be) and that the relative frequency with which these motifs appear in the network can be used to define its information content. This information is defined in such a way that a network with random coloration (but keeping the relative number of nodes with different colors the same) has zero color information content. Thus, colored motif information captures the exceptionality of coloring in the motifs that is maintained via selection. We study the motif information content of the C. elegans brain as well as the evolution of colored motif information in networks that reflect the interaction between instructions in genomes of digital life organisms. While we find that colored motif information appears to capture essential functionality in the C. elegans brain (where the color assignment of nodes is straightforward), it is not obvious whether the colored motif information content always increases during evolution, as would be expected from a measure that captures network complexity. For a single choice of color assignment of instructions in the digital life form Avida, we find rather that colored motif information content increases or decreases during evolution, depending on how the genomes are organized, and therefore could be an interesting tool to dissect genomic rearrangements.
Combating Ineffectiveness: Climate Change Bandwagoning and the UN Convention to Combat Desertification
Authors: Conliffe Alexandra
Published: July 2011

This article examines the role of linkage politics in revitalizing the largely ineffective UN Convention to Combat Desertification (UNCCD). I argue that the UNCCD Secretariat has taken a leadership role in driving a regime linkage agenda that has focused disproportionately on linkages to the UN Framework Convention on Climate Change (UNFCCC). By comparing the UNCCD Secretariat's attempts to build desertification-mitigation and desertification-adaptation linkages, I propose three criteria for predicting whether regime linkages are likely to benefit source regimes (here the UNCCD): the linkage's contribution to source governance goals; the credibility of knowledge presented by the source regime; and the linkage's political feasibility for the target regime. This analysis shows secretariats to be important actors in linkage politics whose actions can lead to both beneficial and harmful outcomes for the regimes they are intended to serve. Finally, by asking whether desertification issues that overlap with climate change might be better addressed under the UNFCCC, I question when regime overlap indicates regime redundancy and warrants regime death.
Building the Forest-Climate Bandwagon: REDD+ and the Logic of Problem Amelioration
Authors: McDermott Constance L. , Levin Kelly , Cashore Benjamin
Published: July 2011

For those championing an international institutional solution to climate change, the forest-climate linkage through reduced emissions from deforestation and forest degradation and forest enhancement (REDD+) may be one of the most promising strategic linkages to date. Following a series of forest-focused interventions that did not live up to their promise, global forest politics have now, through REDD+ deliberations, been institutionally subsumed into the climate regime. We argue that to realize its potential, REDD+ policy mechanisms must be careful to move away from the commodification of forest stewardship that reinforces short-term strategic positions of powerful producing and consuming interests whose current activities are the culprits of global forest decline. To achieve such an outcome, we argue that institutions must develop on the basis of a “logic of problem amelioration” in which the rationale for achieving clearly defined environmental and social goals is rendered transparent. This could be achieved through the formalization of a “dual effectiveness test” in which interventions are evaluated for their potential to simultaneously ameliorate both global climate change and forest degradation.
Threats or Vulnerabilities? Assessing the Link between Climate Change and Security
Authors: Detraz Nicole
Published: July 2011

This article analyzes how climate change has been strategically linked to security issues in recent decades by a variety of actors. I begin by elaborating on two general discourses on the relationship between environment and security, which I call environmental conflict and environmental security. Using discourse analysis, I examine the particular ways that security and climate change have been linked by scholars, policymakers and the media. I then explore some of the potential implications that discussing climate change through each of these security discourses have for policy outcomes within the climate regime. I conclude that the environmental security discourse is the most useful for stressing vulnerabilities and the human security concerns linked to climate change.
Finite-Amplitude Wave Activity and Mean Flow Adjustments in the Atmospheric General Circulation. Part II: Analysis in the Isentropic Coordinate
Authors: Nakamura Noboru , Solomon Abraham
Published: July 2011

The finite-amplitude wave activity diagnostic developed for quasigeostrophic (QG) flows in Part I is extended to the global primitive equation system in the isentropic coordinate. The Rossby wave activity density A is proportional to Kelvin’s circulation around the wavy potential vorticity (PV) contour minus that around the zonal circle that encloses the same isentropic mass. A quasi-conservative, eddy-free reference state flow uREF is constructed from the observed Kelvin’s circulation by zonalizing the PV contours conservatively while enforcing gradient balance. The departure of the observed zonal-mean flow of the atmosphere from the reference state is defined as the net adjustment by the eddies. Then Δu is further partitioned into the direct eddy drag −A and the residual impulse ΔuR consistent with the time-integrated transformed Eulerian mean (TEM) zonal-wind equation.

The analyzed climatological-mean wave activity in the 40-yr European Centre for Medium-Range Weather Forecasts Re-Analysis (ERA-40) is similar to that in Part I. The net adjustment Δu is mainly due to the direct eddy drag (Δu ≈ −A) in the winter polar stratosphere and can reach approximately −60 m s−1 in the Northern Hemisphere. In the extratropical troposphere Δu is a small residual (ΔuR ≈ A), yet it clearly reveals a 5–6 m s−1 eddy driving of the Southern Hemisphere jet as well as a 7–8 m s−1 eddy drag in the subtropical upper troposphere of both hemispheres. The local maxima in wave activity in the equatorial upper troposphere and the extratropical lower stratosphere found in Part I are undetected, while negative wave activity is found where the isentropes intersect the ground. As in the QG case, uREF exhibits significantly less transient and interannual variability than , implying a better signal-to-noise ratio as a climate variable.