bluuebunny/crossref_metadata_2025 huggingface dataset:
TLR9 activation suppresses inflammation in response to Helicobacter pylori infection
Authors: Varga Matthew G. , Piazuelo M. Blanca , Romero-Gallo Judith , Delgado Alberto G. , Suarez Giovanni , Whitaker Morgan E. , Krishna Uma S. , Patel Rachna V. , Skaar Eric P. , Wilson Keith T. , Algood Holly M. S. , Peek Richard M.
Published: October 2016

Helicobacter pylori ( H. pylori) induces chronic gastritis in humans, and infection can persist for decades. One H. pylori strain-specific constituent that augments disease risk is the cag pathogenicity island. The cag island encodes a type IV secretion system (T4SS) that translocates DNA into host cells. Toll-like receptor 9 (TLR9) is an innate immune receptor that detects hypo-methylated CpG DNA motifs. In this study, we sought to define the role of the H. pylori cag T4SS on TLR9-mediated responses in vivo. H. pylori strain PMSS1 or its cagE − mutant, which fails to assemble a T4SS, were used to infect wild-type or Tlr9 −/− C57BL/6 mice. PMSS1-infected Tlr9 −/− mice developed significantly higher levels of inflammation, despite similar levels of colonization density, compared with PMSS1-infected wild-type mice. These changes were cag dependent, as both mouse genotypes infected with the cagE − mutant only developed minimal inflammation. Tlr9 −/− genotypes did not alter the microbial phenotypes of in vivo-adapted H. pylori strains; therefore, we examined host immunological responses. There were no differences in levels of TH1 or TH2 cytokines in infected mice when stratified by host genotype. However, gastric mucosal levels of IL-17 were significantly increased in infected Tlr9 −/− mice compared with infected wild-type mice, and H. pylori infection of IL-17A −/− mice concordantly led to significantly decreased levels of gastritis. Thus loss of Tlr9 selectively augments the intensity of IL-17-driven immune responses to H. pylori in a cag T4SS-dependent manner. These results suggest that H. pylori utilizes the cag T4SS to manipulate the intensity of the host immune response.
Influence of menopause status and age on integrated central and peripheral hemodynamic responses to subsystolic cuffing during submaximal exercise
Authors: Van Iterson Erik H. , Gramm Courtney , Randall Nicholas R. , Olson Thomas P.
Published: October 2016

Although pathophysiological links between postmenopause and healthy aging remain unclear, both factors are associated with increased blood pressure and sympathetic nerve activity (SNA) in women. Activation of polymodal musculoskeletal neural afferents originating within adventia of venules modulates SNA and blood pressure control during exercise in healthy adults. We hypothesized transient subsystolic regional circulatory occlusion (RCO) during exercise sensitizes these afferents leading to augmented systemic vascular resistance (SVR)-mediated increased mean arterial pressure (MAP) in postmenopause vs. premenopause. Normotensive women in premenopause or postmenopause ( n = 14 and 14; ages: 30 ± 9 and 55 ± 7 yr, respectively; P < 0.01) performed: 1) peak exercise testing and 2) fixed-load cycling at 30% peak workload (48 ± 11 and 38 ± 6 W, respectively; P < 0.01), whereby the initial 3 min were control exercise without RCO (CTL), thereafter including 2 min of bilateral-thigh RCO to 20, 40, 60, 80, or 100 mmHg (randomized), with 2 min deflation between RCO. Both MAP (17 ± 4 vs. 4 ± 4%, P = 0.02) and SVR (16 ± 8 vs. −3 ± 8%, P = 0.04) increased at 80 mmHg from CTL in postmenopause vs. premenopause, respectively. However, cardiac index was similar in postmenopause vs. premenopause at 80 mmHg from CTL (1 ± 6 vs. 7 ± 6%, respectively; P = 0.15). There was no continuous effect of aging in MAP ( P = 0.12), SVR ( P = 0.07), or cardiac index ( P = 0.18) models. These data suggest transient locomotor subsystolic RCO sensitizes musculoskeletal afferents, which provoke increased SVR to generate augmented MAP during exercise in postmenopause. These observations provide a novel approach for understanding the age-independent variability in exercise blood pressure control across the normotensive adult pre- to postmenopause spectrum.
Limitations of skeletal muscle oxygen delivery and utilization during moderate-intensity exercise in moderately impaired patients with chronic heart failure
Authors: Niemeijer Victor M. , Spee Ruud F. , Schoots Thijs , Wijn Pieter F. F. , Kemps Hareld M. C.
Published: October 2016

The extent and speed of transient skeletal muscle deoxygenation during exercise onset in patients with chronic heart failure (CHF) are related to impairments of local O2 delivery and utilization. This study examined the physiological background of submaximal exercise performance in 19 moderately impaired patients with CHF (Weber class A, B, and C) compared with 19 matched healthy control (HC) subjects by measuring skeletal muscle oxygenation (SmO2) changes during cycling exercise. All subjects performed two subsequent moderate-intensity 6-min exercise tests (bouts 1 and 2) with measurements of pulmonary oxygen uptake kinetics and SmO2 using near-infrared spatially resolved spectroscopy at the vastus lateralis for determination of absolute oxygenation values, amplitudes, kinetics (mean response time for onset), and deoxygenation overshoot characteristics. In CHF, deoxygenation kinetics were slower compared with HC (21.3 ± 5.3 s vs. 16.7 ± 4.4 s, P < 0.05, respectively). After priming exercise (i.e., during bout 2), deoxygenation kinetics were accelerated in CHF to values no longer different from HC (16.9 ± 4.6 s vs. 15.4 ± 4.2 s, P = 0.35). However, priming did not speed deoxygenation kinetics in CHF subjects with a deoxygenation overshoot, whereas it did reduce the incidence of the overshoot in this specific group ( P < 0.05). These results provide evidence for heterogeneity with respect to limitations of O2 delivery and utilization during moderate-intensity exercise in patients with CHF, with slowed deoxygenation kinetics indicating a predominant O2 utilization impairment and the presence of a deoxygenation overshoot, with a reduction after priming in a subgroup, indicating an initial O2 delivery to utilization mismatch.
Ebselen does not improve oxidative stress and vascular function in patients with diabetes: a randomized, crossover trial
Authors: Beckman Joshua A. , Goldfine Allison B. , Leopold Jane A. , Creager Mark A.
Published: October 2016

Oxidative stress is a key driver of vascular dysfunction in diabetes mellitus. Ebselen is a glutathione peroxidase mimetic. A single-site, randomized, double-masked, placebo-controlled, crossover trial was carried out in 26 patients with type 1 or type 2 diabetes to evaluate effects of high-dose ebselen (150 mg po twice daily) administration on oxidative stress and endothelium-dependent vasodilation. Treatment periods were in random order of 4 wk duration, with a 4-wk washout between treatments. Measures of oxidative stress included nitrotyrosine, plasma 8-isoprostanes, and the ratio of reduced to oxidized glutathione. Vascular ultrasound of the brachial artery and plethysmographic measurement of blood flow were used to assess flow-mediated and methacholine-induced endothelium-dependent vasodilation of conduit and resistance vessels, respectively. Ebselen administration did not affect parameters of oxidative stress or conduit artery or forearm arteriolar vascular function compared with placebo treatment. There was no difference in outcome by diabetes type. Ebselen, at the dose and duration evaluated, does not improve the oxidative stress profile, nor does it affect endothelium-dependent vasodilation in patients with diabetes mellitus.
Decoding the vasoregulatory activities of bile acid-activated receptors in systemic and portal circulation: role of gaseous mediators
Authors: Fiorucci Stefano , Zampella Angela , Cirino Giuseppe , Bucci Mariarosaria , Distrutti Eleonora
Published: October 2016

Bile acids are end products of cholesterol metabolism generated in the liver and released in the intestine. Primary and secondary bile acids are the result of the symbiotic relation between the host and intestinal microbiota. In addition to their role in nutrient absorption, bile acids are increasingly recognized as regulatory signals that exert their function beyond the intestine by activating a network of membrane and nuclear receptors. The best characterized of these bile acid-activated receptors, GPBAR1 (also known as TGR5) and the farnesosid-X-receptor (FXR), have also been detected in the vascular system and their activation mediates the vasodilatory effects of bile acids in the systemic and splanchnic circulation. GPBAR1, is a G protein-coupled receptor, that is preferentially activated by lithocholic acid (LCA) a secondary bile acid. GPBAR1 is expressed in endothelial cells and liver sinusoidal cells (LSECs) and responds to LCA by regulating the expression of both endothelial nitric oxide synthase (eNOS) and cystathionine-γ-lyase (CSE), an enzyme involved in generation of hydrogen sulfide (H2S). Activation of CSE by GPBAR1 ligands in LSECs is due to genomic and nongenomic effects, involves protein phosphorylation, and leads to release of H2S. Despite that species-specific effects have been described, vasodilation caused by GPBAR1 ligands in the liver microcirculation and aortic rings is abrogated by inhibition of CSE but not by eNOS inhibitor. Vasodilation caused by GPBAR1 (and FXR) ligands also involves large conductance calcium-activated potassium channels likely acting downstream to H2S. The identification of GPBAR1 as a vasodilatory receptor is of relevance in the treatment of complex disorders including metabolic syndrome-associated diseases, liver steatohepatitis, and portal hypertension.
Whole body heat stress attenuates the pressure response to muscle metaboreceptor stimulation in humans
Authors: Cui Jian , Blaha Cheryl , Sinoway Lawrence I.
Published: October 2016

The effects of whole body heat stress on sympathetic and cardiovascular responses to stimulation of muscle metaboreceptors and mechanoreceptors remains unclear. We examined the muscle sympathetic nerve activity (MSNA), blood pressure, and heart rate in 14 young healthy subjects during fatiguing isometric handgrip exercise, postexercise circulatory occlusion (PECO), and passive muscle stretch during PECO. The protocol was performed under normothermic and whole body heat stress (increase internal temperature ~0.6°C via a heating suit) conditions. Heat stress increased the resting MSNA and heart rate. Heat stress did not alter the mean blood pressure (MAP), heart rate, and MSNA responses (i.e., changes) to fatiguing exercise. During PECO, whole body heat stress accentuated the heart rate response [change (Δ) of 5.8 ± 1.5 to Δ10.0 ± 2.1 beats/min, P = 0.03], did not alter the MSNA response (Δ16.4 ± 2.8 to Δ17.3 ± 3.8 bursts/min, P = 0.74), and lowered the MAP response (Δ20 ± 2 to Δ12 ± 1 mmHg, P < 0.001). Under normothermic conditions, passive stretch during PECO evoked significant increases in MAP and MSNA (both P < 0.001). Of note, heat stress prevented the MAP and MSNA responses to stretch during PECO (both P > 0.05). These data suggest that whole body heat stress attenuates the pressor response due to metaboreceptor stimulation, and the sympathetic nerve response due to mechanoreceptor stimulation.
Strain survey and genetic analysis of vasoreactivity in mouse aorta
Authors: Kim Seung Kyum , Avila Joshua J. , Massett Michael P.
Published: October 2016

Understanding the genetic influence on vascular reactivity is important for identifying genes underlying impaired vascular function. The purpose of this study was to characterize the genetic contribution to intrinsic vascular function and to identify loci associated with phenotypic variation in vascular reactivity in mice. Concentration response curves to phenylephrine (PE), potassium chloride (KCl), acetylcholine (ACh), and sodium nitroprusside (SNP) were generated in aortic rings from male mice (12 wk old) from 27 inbred mouse strains. Significant strain-dependent differences were found for both maximal responses and sensitivity for each agent, except for SNP Max (%). Strain differences for maximal responses to ACh, PE, and KCl varied by two- to fivefold. On the basis of these large strain differences, we performed genome-wide association mapping (GWAS) to identify loci associated with variation in responses to these agents. GWAS for responses to ACh identified four significant and 19 suggestive loci. Several suggestive loci for responses to SNP, PE, and KCl (including one significant locus for KCl EC50) were also identified. These results demonstrate that intrinsic endothelial function, and more generally vascular function, is genetically determined and associated with multiple genomic loci. Furthermore, these results are supported by the finding that several genes residing in significant and suggestive loci for responses to ACh were previously identified in rat and/or human quantitative trait loci/GWAS for cardiovascular disease. This study represents the first step toward the unbiased comprehensive discovery of genetic determinants that regulate intrinsic vascular function, particularly endothelial function.
mTORC2 Signaling Drives the Development and Progression of Pancreatic Cancer
Authors: Driscoll David R. , Karim Saadia A , Sano Makoto , Gay David M. , Jacob Wright , Yu Jun , Mizukami Yusuke , Gopinathan Aarthi , Jodrell Duncan I. , Evans T.R. Jeffry , Bardeesy Nabeel , Hall Michael N. , Quattrochi Brian J. , Klimstra David S. , Barry Simon T. , Sansom Owen J. , Lewis Brian C. , Morton Jennifer P.
Published: October 2016

mTOR signaling controls several critical cellular functions and is deregulated in many cancers, including pancreatic cancer. To date, most efforts have focused on inhibiting the mTORC1 complex. However, clinical trials of mTORC1 inhibitors in pancreatic cancer have failed, raising questions about this therapeutic approach. We employed a genetic approach to delete the obligate mTORC2 subunit Rictor and identified the critical times during which tumorigenesis requires mTORC2 signaling. Rictor deletion resulted in profoundly delayed tumorigenesis. Whereas previous studies showed most pancreatic tumors were insensitive to rapamycin, treatment with a dual mTORC1/2 inhibitor strongly suppressed tumorigenesis. In late-stage tumor-bearing mice, combined mTORC1/2 and PI3K inhibition significantly increased survival. Thus, targeting mTOR may be a potential therapeutic strategy in pancreatic cancer. Cancer Res; 76(23); 6911–23. ©2016 AACR.
Gamma Knife Radiosurgery in Recurrent Glioblastoma
Authors: Frischer Josa M. , Marosi Christine , Woehrer Adelheid , Hainfellner Johannes A. , Dieckmann Karin Ute , Eiter Helmut , Wang Wei-Te , Mallouhi Ammar , Ertl Adolf , Knosp Engelbert , Filipits Martin , Kitz Klaus , Gatterbauer Brigitte
Published: October 2016

Background: We evaluated Gamma Knife radiosurgery (GKRS) as a treatment option for patients with recurrent glioblastoma. Patients and Methods: 42 patients with histopathologically diagnosed recurrent grade IV tumor were treated with GKRS. All patients had undergone standard multimodal first-line treatment. The average time from diagnosis to GKRS was 17.0 months. The median target volume was 5.1 cm3. The median margin dose was 10 Gy and the median central dose 20 Gy. In a subset of patients, O6-methylguanine methyltransferase (MGMT) promoter methylation analysis by pyrosequencing was performed. Results: Most patients did not develop complications after GKRS. Time to radiological progression after initial GKRS was 4.4 months (95% CI: 3.1-5.7 months). Radiological progression mainly occurred beyond the GKRS-irradiated area. The median survival time after initial GKRS was 9.6 months (95% CI: 7.7-11.5 months). The median overall survival time from diagnosis was 25.6 months (95% CI: 21.8-29.3 months). Patients with MGMT promoter methylation survived significantly longer (33.4 months; 95% CI: 21.2-45.5 months) compared to patients without MGMT promoter methylation (16.0 months; 95% CI: 8.0-23.9 months). Conclusion: GKRS seems to be a relatively safe salvage treatment option for recurrent glioblastoma for highly selected patients but must be seen as part of a multimodal treatment algorithm.
Fzd7 (Frizzled-7) Expressed by Endothelial Cells Controls Blood Vessel Formation Through Wnt/β-Catenin Canonical Signaling
Authors: Peghaire Claire , Bats Marie Lise , Sewduth Raj , Jeanningros Sylvie , Jaspard Beatrice , Couffinhal Thierry , Duplàa Cécile , Dufourcq Pascale
Published: October 2016

Objective—

Vessel formation requires precise orchestration of a series of morphometric and molecular events controlled by a multitude of angiogenic factors and morphogens. Wnt/frizzled signaling is required for proper vascular formation. In this study, we investigated the role of the Fzd7 (frizzled-7) receptor in retinal vascular development and its relationship with the Wnt/β-catenin canonical pathway and Notch signaling.

Approach and Results—

Using transgenic mice, we demonstrated that Fzd7 is required for postnatal vascular formation. Endothelial cell (EC) deletion of
fzd7
(
fzd7
ECKO
) delayed retinal plexus formation because of an impairment in tip cell phenotype and a decrease in stalk cell proliferation. Dvl (dishevelled) proteins are a main component of Wnt signaling and play a functionally redundant role. We found that
Dvl3
depletion in
dvl1
−/−
mice mimicked the
fzd7
ECKO
vascular phenotype and demonstrated that Fzd7 acted via β-catenin activation by showing that LiCl treatment rescued impairment in tip and stalk cell phenotypes induced in
fzd7
mutants. Deletion of
fzd7
or
Dvl1/3
induced a strong decrease in Wnt canonical genes and Notch partners’ expression. Genetic and pharmacological rescue strategies demonstrated that Fzd7 acted via β-catenin activation, upstream of Notch signaling to control Dll4 and Jagged1 EC expression.

Conclusions—

Fzd7 expressed by EC drives postnatal angiogenesis via activation of Dvl/β-catenin signaling and can control the integrative interaction of Wnt and Notch signaling during postnatal angiogenesis.
Small GTPase ARF6 Regulates Endocytic Pathway Leading to Degradation of ATP-Binding Cassette Transporter A1
Authors: Mukhamedova Nigora , Hoang Anh , Cui Huanhuan L. , Carmichael Irena , Fu Ying , Bukrinsky Michael , Sviridov Dmitri
Published: October 2016

Objective—

ABCA1 (ATP-binding cassette transporter A1) is the principal protein responsible for cellular cholesterol efflux. Abundance and functionality of ABCA1 is regulated both transcriptionally and post-translationally, with endocytosis of ABCA1 being an important element of post-translational regulation. Functional ABCA1 resides on the plasma membrane but can be internalized and either degraded or recycled back to the plasma membrane. The interaction between the degradative and recycling pathways determines the abundance of ABCA1 and may contribute to the efflux of intracellular cholesterol.

Approach and Results—

Here, we show that the principal pathway responsible for the internalization of ABCA1 leading to its degradation in macrophages is ARF6-dependent endocytic pathway. This pathway was predominant in the regulation of ABCA1 abundance and efflux of plasma membrane cholesterol. Conversely, the efflux of intracellular cholesterol was predominantly controlled by ARF6-independent pathways, and inhibition of ARF6 shifted ABCA1 into recycling endosomes enhancing efflux of intracellular cholesterol.

Conclusions—

We conclude that ARF6-dependent pathway is the predominant route responsible for the ABCA1 internalization and degradation, whereas ARF6-independent endocytic pathways may contribute to ABCA1 recycling and efflux of intracellular cholesterol.
Temporal Trends in Care and Outcomes of Patients Receiving Fibrinolytic Therapy Compared to Primary Percutaneous Coronary Intervention: Insights From the Get With The Guidelines Coronary Artery Disease (GWTG‐CAD) Registry
Authors: Hira Ravi S. , Bhatt Deepak L. , Fonarow Gregg C. , Heidenreich Paul A. , Ju Christine , Virani Salim S. , Bozkurt Biykem , Petersen Laura A. , Hernandez Adrian F. , Schwamm Lee H. , Eapen Zubin J. , Albert Michelle A. , Liang Li , Matsouaka Roland A. , Peterson Eric D. , Jneid Hani
Published: October 2016

Background

Timely reperfusion after ST‐elevation myocardial infarction (
STEMI
) improves survival. Guidelines recommend primary percutaneous coronary intervention (
PPCI
) within 90 minutes of arrival at a
PCI
‐capable hospital. The alternative is fibrinolysis within 30 minutes for those in those for whom timely transfer to a
PCI
‐capable hospital is not feasible.

Methods and Results

We identified
STEMI
patients receiving reperfusion therapy at 229 hospitals participating in the
Get With the Guidelines—Coronary Artery Disease
(
GWTG
‐
CAD
) database (January 1, 2003 through December 31, 2008). Temporal trends in the use of fibrinolysis and
PPCI
, its timeliness, and in‐hospital mortality outcomes were assessed. We also assessed predictors of fibrinolysis versus
PPCI
and compliance with performance measures. Defect‐free care was defined as 100% compliance with all performance measures. We identified 29 190
STEMI
patients, of whom 2441 (8.4%) received fibrinolysis; 38.2% of these patients achieved door‐to‐needle times ≤30 minutes. Median door‐to‐needle times increased from 36 to 60 minutes (
P
=0.005) over the study period. Among
PPCI
patients, median door‐to‐balloon times decreased from 94 to 64 minutes (
P
<0.0001) over the same period. In‐hospital mortality was higher with fibrinolysis than with
PPCI
(4.6% vs 3.3%,
P
=0.001) and did not change significantly over time. Patients receiving fibrinolysis were less likely to receive defect‐free care compared with their
PPCI
counterparts.

Conclusions

Use of fibrinolysis for
STEMI
has decreased over time with concomitant worsening of door‐to‐needle times. Over the same time period, use of
PPCI
increased with improvement in door‐to‐balloon times. In‐hospital mortality was higher with fibrinolysis than with
PPCI
. As reperfusion for
STEMI
continues to shift from fibrinolysis to
PPCI
, it will be critical to ensure that door‐to‐needle times and outcomes do not worsen.
Cardiac Vulnerability to Cerebrogenic Stress as a Possible Cause of Troponin Elevation in Stroke
Authors: Ahn Sung‐Ho , Kim Young‐Hak , Shin Chol‐Ho , Lee Ji‐Sung , Kim Bum‐Joon , Kim Yeon‐Jung , Noh Sang‐Mi , Kim Seung‐Min , Kang Hyun‐Goo , Kang Dong‐Wha , Kim Jong S. , Kwon Sun U.
Published: October 2016

Background

Troponin elevation with electrocardiography changes is not uncommon in patients with acute ischemic stroke; however, it is still unclear whether the mechanism of these changes is due to cardiac problems or neurally mediated myocytic damage. Thus, we investigated cardiac and neurological predictors of troponin elevation in those patients.

Methods and Results

We retrospectively analyzed medical data of the prospectively registered ischemic stroke patients on stroke registry who were admitted and underwent a serum cardiac troponin I and 12‐lead electrocardiography within 24 hours of symptom onset. However, patients with well‐known troponin‐elevating comorbidities were excluded from the analysis. Among 1404 ischemic stroke patients, 121 (8.7%) had elevated troponin, which was defined as more than 0.04 mg/mL. Multivariable analysis identified electrocardiography abnormalities such as
QT
c‐prolongation (odds ratio [
OR
]: 1.52, 95%
CI
: 1.02–2.28), left ventricular hypertrophy (
OR
: 2.14, 95%
CI
1.43–3.19), Q‐wave (
OR
: 2.53, 95%
CI
: 1.48–4.32), and
ST
elevation (
OR
: 2.74, 95%
CI
: 1.12–6.72) as cardiac variables associated with troponin elevation, and higher National Institutes of Health Stroke Scale score (
OR
: 1.04, 95%
CI
: 1.01–1.07) and insular cortical lesions (
OR
: 2.78, 95%
CI
: 1.85–4.19) as neurological variables associated with troponin elevation. Incidence of troponin elevation as well as
QT
c‐prolongation was increased further in combination with cardiac and neurological factors.

Conclusions

Certain cardiac and neurological conditions in acute ischemic stroke may contribute to troponin elevation. The proposed concept of cardiac vulnerability to cerebrogenic stress can be a practical interpretation of troponin elevation and electrocardiography abnormalities in stroke patients.
Uric Acid Therapy Prevents Early Ischemic Stroke Progression
Authors: Amaro Sergio , Laredo Carlos , Renú Arturo , Llull Laura , Rudilosso Salvatore , Obach Víctor , Urra Xabier , Planas Anna M. , Chamorro Ángel
Published: October 2016

Background and Purpose—

Identification of neuroprotective therapies in acute ischemic stroke is imperative. We report a predefined analysis of the URICO-ICTUS trial (Efficacy Study of Combined Treatment With Uric Acid and r-tPA in Acute Ischemic Stroke) assessing the efficacy of uric acid (UA) compared with placebo to prevent early ischemic worsening (EIW) and the relevance of collateral circulation.

Methods—

URICO-ICTUS was a double-blind, placebo-controlled, phase 2b trial where a total of 411 patients treated with alteplase within 4.5 hours of stroke onset were randomized (1:1) to receive UA 1000 mg (n=211) or placebo (n=200) before the end of alteplase infusion. EIW defined an increment ≥4 points in the National Institutes of Health Stroke Scale score within 72 hours of treatment in the absence of hemorrhage or recurrent stroke. Logistic regression models assessed the interaction between therapy and the collateral circulation in 112 patients who had a pretreatment computed tomographic angiography.

Results—

EIW occurred in 2 of 149 (1%) patients with good outcome and 23 of 262 (9%) patients with poor outcome (χ
2
;
P
=0.002). EIW occurred in 7 of 204 (3%) patients treated with UA and in 18 of 200 (9%) patients treated with placebo (χ
2
;
P
=0.01). There was a significant interaction between the efficacy of UA to prevent EIW and collaterals (
P
=0.029), with lower incidence in patients with good collaterals treated with UA compared with placebo (2% versus 15%, respectively;
P
=0.048).

Conclusions—

UA therapy may prevent EIW after acute stroke in thrombolysed patients. Optimal access of UA to its molecular targets through appropriate collaterals may modify the magnitude of the neuroprotective effect.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00860366.
Textual Deixis and the ‘Anchoring’ Use of the Latin Pronoun hic
Authors: Kroon Caroline
Published: October 2016

This article evaluates the results of prior research on anaphoric reference in Latin, and tries to account for the various observations within a single explanatory framework. This framework combines insights from cognitive linguistic theory and from ongoing empirical research on the linguistic marking of discourse organization in Latin. After a brief discussion of recent cognitive linguistic views on the relation between deixis and anaphora, I concentrate on the various uses of the Latin demonstrativehicin Virgil’sAeneid. The examples discussed show thathic’s deictic aspect of proximity can be discerned in all its uses, the variety of which can best be described in terms of a ‘cline’, running from canonical deixis to canonical anaphora. It is argued that in its anaphoric use, Latinhicbehaves as a linguistic ‘anchoring’ device, and is used as part of a communicative strategy referred to as‘reculer pour mieux sauter’.
Ominous Swans in Philostratus’ Life of Apollonius (1.5)
Authors: Miles Graeme
Published: October 2016

The opening chapters of Philostratus’Life of Apollonius of Tyanapresent readers with a series of signs foreshadowing the future character of the text’s protagonist. This article addresses a little discussed omen at Apollonius’ birth: the appearance of swans who set up a chorus around the future philosopher’s mother, startling her and bringing on his birth, before departing, apparently on their annual migration. This curious avian episode is, on closer inspection, laden with evocations, which have so far been only partially explored: of the god Apollo, and of the philosophers Pythagoras, Plato and Socrates, specifically as Apollonian philosophers.
Temple Dedication Assessment: Redaction and Transmission; Toward the Resolution of an Enigmatic Talmud Yerushalmi Sugya
Authors: Pinchuk Moshe
Published: October 2016

Scholars have devoted relatively little attention to the development and redaction of the Talmud Yerushalmi. This is understandable, as scholars are generally more concerned with solving the Yerushalmi’s severe textual and exegetical problems than with questions of redaction. Moreover, almost everything we know about the Yerushalmi’s development and redaction is based on literary analysis of its sugyot. Thus questions of redaction are aggravated by exegetical difficulties and vice versa. Here I propose a solution to two problematic parallel pericopae. This solution may also afford us a rare glimpse into the activity of the redactor, in his attempt to merge two conflicting sugyot revolving about the same subject matter.
Contingent Efficacies in Buryat Tibetan Medicine
Authors: Chudakova Tatiana
Published: October 2016

Focusing on sites of encounter between post-socialist biomedicine and Tibetan medicine in Eastern Siberia, this article explores overlapping ideologies of efficacy at work. In the absence of a single framework for determining its potencies, Tibetan medicine is caught between multiple regimes of legitimacy necessitated by scientific research, clinical protocols, and state regulatory frameworks. Through an exploration of three ethnographic case studies, this article tracks how those working with Tibetan medicine highlight instead the conditional nature of its therapeutic action. By adopting the frame ofcontingent efficacies, the article explores how practitioners of Tibetan medicine in Russia conceive of the medicines and techniques they deploy as always already situated extensions of specific social relations, political formations, forms of practice, and epistemological commitments. By pointing to the failures at commensuration with different regimes of abstraction these accounts offer a lens into the cultural politics of medical pluralism in Inner Asia.
Sinophone, Chinese, and prc Internet
Authors: Leong Susan
Published: October 2016

Recently, while there have been some who advocate the notion of a Sinophone internet, approximately coterminous with a Chinese-literate user base (Sullivan & Chen 2015), others have argued the internet in China should be known as the Chinese internet (Yang 2015: 1). This paper extends from the call to specificity to ask how the suggestion of the Chinese internet might manifest itself and what it might mean for the Chinese overseas. This is specifically in light of the multiplicity and heterogeneity of the Chinese diaspora in Australia, where many individuals of Chinese ancestry may or may not speak, read, or understandPutonghua(i.e. Mandarin). Rather than the Chinese internet, this paper proposes that we think of the People’s Republic of China (prc) internet as one component of the multiple internets.
Internet Use and Political Efficacy among Chinese University Students
Authors: Xuelian Jin , Deshan Yang
Published: October 2016

This article adopts a multi-case study approach to understand how users of internet technologies actually use the technology, and to explore the extent to which users perceive the technologies’ purported democratic and deliberative capacities. In-depth interviews, a focus group, a search and analysis of web content, and digital auto-ethnography were used to produce qualitative data. Those participants who engaged in online political expression with strangers or on public platforms reported a belief in their competence to make a difference through the internet, while those who did so only with acquaintances, and those who engaged in no political expression online, did not. Most of the participants articulated a strong belief that ‘we’, internet users as a whole, are influential, because they believed online public opinion contributed to better solutions to some social problems. This study casts new light on the relationship between internet use, political attitudes, and online political expression.
Mapping the Trafficking of Women across Colonial Southeast Asia, 1600s–1930s
Authors: Martínez Julia
Published: October 2016

While slavery in the seventeenth century included a substantial traffic in Asian women, it was only in the late nineteenth century that the rise in trafficking in women in Asia came to the attention of international humanitarians who sought to combat this new form of post-abolition slavery. The increasing emphasis on women as slaves, held for the purposes of sexual exploitation, was to a large extent brought to public attention as the result of the enactment of the British Contagious Diseases Ordinance of 1870, which required that women working in prostitution be registered and counted. It was European colonialism in Southeast Asia and its reliance on the labor of Asian male migrant workers that had encouraged the increase in trafficking of women into Southeast Asia. Despite this, however, most European colonial officials sought to portray themselves as abolitionists and regarded trafficking as an Asian problem. This rhetoric of Asian slavery and European abolition was mobilized to provide moral justification for colonial expansion. By the early twentieth century international observers, under the auspices of the League of Nations, again sought to raise public awareness of the traffic in women, highlighting the cases of Chinese and Japanese women travelling into Southeast Asia. Once again, however, colonial governments sought to underplay any suggestions that they might be complicit in encouraging such traffic.
Three new species of Graphidaceae (Ostropales, Ascomycota) from Atlantic Forest in Northeast Brazil
Authors: LIMA EDVANEIDE LEANDRO DE , LÜCKING ROBERT , CÁCERES MARCELA EUGENIA DA SILVA
Published: October 2016

Three species of Graphidaceae are here described as new to science, based on material found in the Reserva Biológica Guaribas and Área de Proteção Ambiental da Barra do Rio Mamanguape, in Paraíba State, Northeastern Brazil. Astrochapsa submuralis E.L. Lima, Lücking & M. Cáceres, with thickly pruinose ascomata and small submuriform ascospores, Chapsa angustispora E.L. Lima, Lücking & M. Cáceres, with a combination of inspersed hymenium and comparatively narrow muriform ascospores, and Graphis cilindrospora E.L. Lima, Lücking & M. Cáceres, with very large and narrow muriform, brownish ascospores. These findings underline the importance of the northern Atlantic rain forest, including the poorly studied Restinga vegetation, for the continuous discovery of new lichen taxa.
Hedotettix angulatus sp. nov. (Orthoptera: Tetrigoidea:Tetrigidae, Tetriginae) a new pygmy grasshopper species from India
Authors: GUPTA SUNIL KUMAR , SHI JIAN-PING , CHANDRA KAILASH
Published: October 2016

Hedotettix angulatus sp. nov. is described from Chhattisgarh, India. The new species is similar to Hedotettix grossus Hancock, 1915, it differs from the latter by (i) anterior margin of vertex angulate, (ii) ovipositor robust, length of upper valves 2.2 times its width, (iii) antennal grooves situated above the lower margin of the compound eyes, (iv) median carina of vertex strong and extended up to the posterior end of depression, (v) facial carinae are all most parallel, (vi) frontal costa bifurcation starts in about ¼ of the compound eye height, (vii) anterior margin of middle carina of pronotum depressed. A key to known species of the genus Hedotettix from the Indian subcontinent is provided. Type specimens are deposited in the Central Entomological Laboratory (CEL) of the Zoological Survey of India, Kolkata.
A remarkable new species of the sharpshooter genus Erythrogonia Melichar (Hemiptera: Cicadellidae: Cicadellini) from southern Brazil with taxonomic notes on the genus
Authors: MEJDALANI GABRIEL , CAVICHIOLI RODNEY R.
Published: October 2016

A new species of Erythrogonia Melichar, 1926, E. brunnea, is described and illustrated based on specimens from the state of Paraná, southern Brazil (Atlantic Forest). The new species can be distinguished from the other ones of the genus by the male genitalia and color pattern, especially by the presence of a conspicuous pale yellow arc behind the ocelli that continues posteriorly as a pair of lateral longitudinal stripes over the pronotum and forewings to the base of the third apical cell. Although E. brunnea does not show the typical color pattern of Erythrogonia species, features of both the male and female genitalia justify its assignment to this genus (including a dorsal sclerite located at the base of the rami of the ovipositor valvulae II). Two taxonomic changes are proposed: (1) the monotypic genus Spinagonalia Cavichioli, 2008 is synonymized with Erythrogonia (E. separata Melichar, 1926 = S. rubrovittata Cavichioli, 2008 syn. nov.); (2) Erythrogonia jucunda (Walker, 1851) is transferred to Pawiloma Young, 1977 (P. jucunda (Walker, 1851) comb. nov. = P. rubra Cavichioli, 1998 syn. nov.).
Redescription of Garra elegans (Günther, 1868), a poorly known species from the Tigris River drainage (Teleostei: Cyprinidae)
Authors: FREYHOF JÖRG
Published: October 2016

Tylognathus elegans, from the lower Tigris River drainage in Iraq, was previously placed in Pseudogarra and Hemigrammocapoeta. Studies based on mitochondrial (COI) and nuclear molecular markers (Rhodopsin) place T. elegans in Garra. As the species is poorly known, it is redescribed here.
Suppression of Baroclinic Instabilities in Buoyancy-Driven Flow over Sloping Bathymetry
Authors: Hetland Robert D.
Published: October 2016

Baroclinic instabilities are ubiquitous in many types of geostrophic flow; however, they are seldom observed in river plumes despite strong lateral density gradients within the plume front. Supported by results from a realistic numerical simulation of the Mississippi–Atchafalaya River plume, idealized numerical simulations of buoyancy-driven flow are used to investigate baroclinic instabilities in buoyancy-driven flow over a sloping bottom. The parameter space is defined by the slope Burger number S = Nf−1α, where N is the buoyancy frequency, f is the Coriolis parameter, and α is the bottom slope, and the Richardson number Ri = N2f2M−4, where M2 = |∇Hb| is the magnitude of the lateral buoyancy gradients. Instabilities only form in a subset of the simulations, with the criterion that SH ≡ SRi−1/2 = Uf−1W−1 = M2f−2α 0.2, where U is a horizontal velocity scale and SH is a new parameter named the horizontal slope Burger number. Suppression of instability formation for certain flow conditions contrasts linear stability theory, which predicts that all flow configurations will be subject to instabilities. The instability growth rate estimated in the nonlinear 3D model is proportional to ωImaxS−1/2, where ωImax is the dimensional growth rate predicted by linear instability theory, indicating that bottom slope inhibits instability growth beyond that predicted by linear theory. The constraint SH 0.2 implies a relationship between the inertial radius Li = Uf−1 and the plume width W. Instabilities may not form when 5Li > W; that is, the plume is too narrow for the eddies to fit.
An Efficient Way to Account for Observation Error Correlations in the Assimilation of Data from the Future SWOT High-Resolution Altimeter Mission
Authors: Ruggiero Giovanni Abdelnur , Cosme Emmanuel , Brankart Jean-Michel , Le Sommer Julien , Ubelmann Clement
Published: October 2016

Most data assimilation algorithms require the inverse of the covariance matrix of the observation errors. In practical applications, the cost of computing this inverse matrix with spatially correlated observation errors is prohibitive. Common practices are therefore to subsample or combine the observations so that the errors of the assimilated observations can be considered uncorrelated. As a consequence, a large fraction of the available observational information is not used in practical applications. In this study, a method is developed to account for the correlations of the errors that will be present in the wide-swath sea surface height measurements, for example, the Surface Water and Ocean Topography (SWOT) mission. It basically consists of the transformation of the observation vector so that the inverse of the corresponding covariance matrix can be replaced by a diagonal matrix, thus allowing to genuinely take into account errors that are spatially correlated in physical space. Numerical experiments of ensemble Kalman filter analysis of SWOT-like observations are conducted with three different observation error covariance matrices. Results suggest that the proposed method provides an effective way to account for error correlations in the assimilation of the future SWOT data. The transformation of the observation vector proposed herein yields both a significant reduction of the root-mean-square errors and a good consistency between the filter analysis error statistics and the true error statistics.
Viability of Cloud Computing for Real-Time Numerical Weather Prediction
Authors: Siuta David , West Gregory , Modzelewski Henryk , Schigas Roland , Stull Roland
Published: October 2016

As cloud-service providers like Google, Amazon, and Microsoft decrease costs and increase performance, numerical weather prediction (NWP) in the cloud will become a reality not only for research use but for real-time use as well. The performance of the Weather Research and Forecasting (WRF) Model on the Google Cloud Platform is tested and configurations and optimizations of virtual machines that meet two main requirements of real-time NWP are found: 1) fast forecast completion (timeliness) and 2) economic cost effectiveness when compared with traditional on-premise high-performance computing hardware. Optimum performance was found by using the Intel compiler collection with no more than eight virtual CPUs per virtual machine. Using these configurations, real-time NWP on the Google Cloud Platform is found to be economically competitive when compared with the purchase of local high-performance computing hardware for NWP needs. Cloud-computing services are becoming viable alternatives to on-premise compute clusters for some applications.
What Are the Odds? Modern Relevance and Bayes Factor Solutions for MacAlister’s Problem From the 1881 Educational Times
Authors: Jamil Tahira , Marsman Maarten , Ly Alexander , Morey Richard D. , Wagenmakers Eric-Jan
Published: October 2016

In 1881, Donald MacAlister posed a problem in the Educational Times that remains relevant today. The problem centers on the statistical evidence for the effectiveness of a treatment based on a comparison between two proportions. A brief historical sketch is followed by a discussion of two default Bayesian solutions, one based on a one-sided test between independent rates, and one on a one-sided test between dependent rates. We demonstrate the current-day relevance of MacAlister’s original question with a modern-day example about the effectiveness of an educational program.
Observation-Oriented Modeling: Going Beyond “Is It All a Matter of Chance”?
Authors: Grice James W. , Yepez Maria , Wilson Nicole L. , Shoda Yuichi
Published: October 2016

An alternative to null hypothesis significance testing is presented and discussed. This approach, referred to as observation-oriented modeling, is centered on model building in an effort to explicate the structures and processes believed to generate a set of observations. In terms of analysis, this novel approach complements traditional methods based on means, variances, and covariances with methods of pattern detection and analysis. Using data from a previously published study by Shoda et al., the basic tenets and methods of observation-oriented modeling are demonstrated and compared with traditional methods, particularly with regard to null hypothesis significance testing.
Atlantic reflections on Giuseppe Ungaretti: The man, the journeys, the poet
Authors: Ciamparella Anna
Published: October 2016

In this article I offer an Atlantic-world reading of Giuseppe Ungaretti’s life and poetry. Focusing on several important events in his biography and on how they contributed to the shaping of his poetics, I argue that Ungaretti can be fruitfully appreciated as an Atlantic poet, beyond the national confines of the Italian literary tradition. While Ungaretti’s oeuvre fits readily into a cosmopolitan ambience, the application of a specifically Atlantic-world paradigm to his works and days allows us to fully understand his famous claim of being a “docile fibra dell’universo.” This allusive subjective claim suggests that from the onset of his career he saw himself as a citizen of the world, a self-conscious status that nicely captures the way he approached his writing and the way he understood human experience in general. Furthermore, it is on this basis that I would also like to suggest a cultural dialogue between his work and the spirit of the blues, inasmuch as his poems are often the extemporaneous product of a particular biographical experience that tends to trespass geographical continents to become universal.
Experimental and numerical study of multi-scale tensile behaviors of Kevlar® 49 fabric
Authors: Zhu Deju , Zhang Xiaotong , Ou Yunfu , Huang Mengying
Published: October 2016

Kevlar® 49 fabrics have excellent performances such as high elastic modulus and high impact resistance, which are widely used in ballistic systems, aerospace, fabric reinforced composite materials and other fields. The present work studied the multi-scale mechanical behaviors of Kevlar® 49 in the forms of fiber, yarn and fabric subjected to uniaxial tension. The experimental results showed that the material mechanical properties are dependent on structural size scale and gage length of samples. The tensile strengths decrease with increasing gage length and structural size scale from fiber to yarn, and to fabric, and follow Weibull distribution by conducting statistical analysis, which is used to quantify the degree of variability in the tensile strengths of fiber and yarn with different gage lengths. At last, user-defined subroutines (UMAT) in ANSYS were implemented to simulate the tensile behaviors of single yarn and fabric by using the constitutive models of fiber and yarn, respectively, which considered their Weibull distribution in tensile strength. This probabilistic approach can simulate the multi-scale tensile behaviors of Kevlar® 49 accurately and reveal the mechanisms of deformation and failure process based on the various size scales. This approach is also applicable to study the multi-scale behaviors of other fabrics once their properties and Weibull parameters are determined.
3D geometric modelling of discontinuous fibre composites using a force-directed algorithm
Authors: Harper LT , Qian CC , Luchoo R , Warrior NA
Published: October 2016

A geometrical modelling scheme is presented to produce representative architectures for discontinuous fibre composites, enabling downstream modelling of mechanical properties. The model generates realistic random fibre architectures containing high filament count bundles (>3k) and high (∼50%) fibre volume fractions. Fibre bundles are modelled as thin shells using a multidimensional modelling strategy, in which fibre bundles are distributed and compacted to simulate pressure being applied from a matched mould tool. Finite element simulations are performed to benchmark the in-plane mechanical properties obtained from the numerical model against experimental data, with a detailed study presented to evaluate the tensile properties at various fibre volume fractions and specimen thicknesses. Tensile modulus predictions are in close agreement (less than 5% error) with experimental data at volume fractions below 45%. Ultimate tensile strength predictions are within 4.2% of the experimental data at volume fractions between 40 and 55%. This is a significant improvement over existing 2D modelling approaches, as the current model offers increased levels of fidelity, capturing dominant failure mechanisms and the influence of out-of-plane fibres.