bluuebunny/crossref_metadata_2025 huggingface dataset:
Planar Monopoles with Different Radiator Shapes for UWB Body-Centric Wireless Communications
Authors: Sun Y. Y. , Cheung S. W. , Yuk T. I.
Published: July 2013

This paper presents a study on the performances of a group of planar monopoles using radiators of different shapes, such as triangle, rectangle, square, annual ring, circle, horizontal ellipse, vertical ellipse, pentagon, and hexagon, for ultra-wideband (UWB) body-centric wireless communications. The planar monopoles have the radiators with microstrip-fed line printed on one side of the substrate and a ground plane on the other side. Simulation studies show that, among these monopoles, the horizontal elliptical, vertical elliptical, and hexagonal monopoles have better overall performances in terms of bandwidth, gain, efficiency, and radiation pattern in free space. A solid-body phantom mimicking human tissue is used for studies of these three monopoles for body-centric communications. Simulated and measured results of these monopoles on the phantom show that the horizontal elliptical monopole achieves the widest impedance bandwidths, highest average peak gain and efficiency, least path loss, best fidelity, and good radiation pattern, making it a good candidate for UWB body-centric wireless communications.
A VANET-Based A* Route Planning Algorithm for Travelling Time- and Energy-Efficient GPS Navigation App
Authors: Chang Ing-Chau , Tai Hung-Ta , Yeh Feng-Han , Hsieh Dung-Lin , Chang Siao-Hui
Published: July 2013

Most current navigation devices or apps, based on the global positioning system (GPS), only adopt static information for route planning. Although some are equipped with an RDS-TMC receiver to receive real-time traffic events, many of these real-time traffic events are irrelevant to the vehicle. This paper offers three major contributions. First, a vehicular-ad-hoc-network- (VANET-) based [Formula: see text] ([Formula: see text]) route planning algorithm is proposed to calculate the route with the shortest travelling time or the lowest fuel consumption, depending on two real-time traffic information sources, which have not been used in traditional GPS navigation applications. The first traffic information source is the recorded traffic information of the road segment that the vehicle has passed through. It is further exchanged between vehicles through an IEEE 802.11p wireless link. The second traffic information is provided by Google Maps. A GPS navigation app is then implemented on the Android platform to realize [Formula: see text]. Finally, simulations for six route planning algorithms are executed by VANET simulator The ONE, in one congested and one noncongested time period, respectively. In summary, [Formula: see text] achieves significant reductions in both the average travelling time and fuel consumption of the planned route, as compared to traditional route planning algorithms.
Acute and Chronic Toxicity of an Aqueous Fraction of the Stem Bark ofStryphnodendron adstringens(Barbatimão) in Rodents
Authors: Costa Marco Antonio , Palazzo de Mello João Carlos , Kaneshima Edílson Nobuyoshi , Ueda-Nakamura Tânia , Dias Filho Benedito Prado , Audi Elisabeth Aparecida , Nakamura Celso Vataru
Published: July 2013

Stryphnodendron adstringenshas a high tannin content and is used as an antiseptic and antimicrobial and in the treatment of leucorrhea, gonorrhea, wound healing, and gastritis. The present study evaluated the toxic effects of the heptamer prodelphinidin (F2) from the stem bark ofS. adstringensin rodents. In the acute toxicity test, the mice that received oral doses exhibited reversible effects, with an LD50of 3.015 mg·kg−1. In the chronic toxicity test at 90 days, Wistar rats were treated with different doses of F2 (10, 100, and 200 mg·kg−1). In the biochemical, hematological, and histopathological examinations and open-field test, the different dose groups did not exhibit significant differences compared with controls. The present results indicate that F2 from the stem bark ofS. adstringenscaused no toxicity with acute and chronic oral treatment in rodents at the doses administered.
Investigation on the Achievable Flow Length in Injection Moulding of Polymeric Materials with Dynamic Mould Tempering
Authors: Meister Steve , Drummer Dietmar
Published: July 2013

A variety of parts in microsystems technology are manufactured by injection moulding of polymeric materials. In Particular the high cooling velocity affects negatively the process and the resulting part properties. The scope of this paper is to investigate the influence on the reachable flow length in injection moulding of different polymeric materials. The results indicate that the mould temperature has less impact on the achievable flow length of the polymer melt as the injection pressure. A higher mould temperature leads only to a slight increase in flow length. In addition, a transcending of the glass or the crystallization temperature of polymeric materials with the mould temperature shows no effect on the achievable flow length of the material.
Confocal Microscopy in Biopsy Proven Argyrosis
Authors: Palamar Melis , Guven Yilmaz Suzan , Akalin Taner , Egrilmez Sait , Yagci Ayse
Published: July 2013

Purpose. To evaluate the confocal microscopy findings of a 46-year-old male with bilateral biopsy proven argyrosis.Materials and Methods. Besides routine ophthalmologic examination, anterior segment photography and confocal microscopy with cornea Rostoch module attached to HRT II (Heidelberg Engineering GmbH, Heidelberg, Germany) were performed.Findings. Squamous metaplastic changes on conjunctival epithelium and intense highly reflective extracellular punctiform deposits in conjunctival substantia propria were detected. Corneal epithelium was normal. Highly reflective punctiform deposits starting from anterior to mid-stroma and increasing through Descemet’s membrane were evident. Corneal endothelium could not be evaluated due to intense stromal deposits.Conclusion. Confocal microscopy not only supports diagnosis in ocular argyrosis, but also demonstrates the intensity of the deposition in these patients.
Werner Syndrome Helicase Has a Critical Role in DNA Damage Responses in the Absence of a Functional Fanconi Anemia Pathway
Authors: Aggarwal Monika , Banerjee Taraswi , Sommers Joshua A. , Iannascoli Chiara , Pichierri Pietro , Shoemaker Robert H. , Brosh Robert M.
Published: July 2013

Werner syndrome is genetically linked to mutations in WRN that encodes a DNA helicase-nuclease believed to operate at stalled replication forks. Using a newly identified small-molecule inhibitor of WRN helicase (NSC 617145), we investigated the role of WRN in the interstrand cross-link (ICL) response in cells derived from patients with Fanconi anemia, a hereditary disorder characterized by bone marrow failure and cancer. In FA-D2−/− cells, NSC 617145 acted synergistically with very low concentrations of mitomycin C to inhibit proliferation in a WRN-dependent manner and induce double-strand breaks (DSB) and chromosomal abnormalities. Under these conditions, ataxia–telangiectasia mutated activation and accumulation of DNA-dependent protein kinase, catalytic subunit pS2056 foci suggested an increased number of DSBs processed by nonhomologous end-joining (NHEJ). Rad51 foci were also elevated in FA-D2−/− cells exposed to NSC 617145 and mitomycin C, suggesting that WRN helicase inhibition interferes with later steps of homologous recombination at ICL-induced DSBs. Thus, when the Fanconi anemia pathway is defective, WRN helicase inhibition perturbs the normal ICL response, leading to NHEJ activation. Potential implication for treatment of Fanconi anemia–deficient tumors by their sensitization to DNA cross-linking agents is discussed. Cancer Res; 73(17); 5497–507. ©2013 AACR.
Molecular Pathways: Inflammation-Associated Nitric-Oxide Production as a Cancer-Supporting Redox Mechanism and a Potential Therapeutic Target
Authors: Grimm Elizabeth A. , Sikora Andrew G. , Ekmekcioglu Suhendan
Published: July 2013

It is widely accepted that many cancers express features of inflammation, driven by both microenvironmental cells and factors, and the intrinsic production of inflammation-associated mediators from malignant cells themselves. Inflammation results in intracellular oxidative stress with the ultimate biochemical oxidants composed of reactive nitrogens and oxygens. Although the role of inflammation in carcinogensis is well accepted, we now present data showing that inflammatory processes are also active in the maintenance phase of many aggressive forms of cancer. The oxidative stress of inflammation is proposed to drive a continuous process of DNA adducts and crosslinks, as well as posttranslational modifications to lipids and proteins that we argue support growth and survival. In this perspective, we introduce data on the emerging science of inflammation-driven posttranslational modifications on proteins responsible for driving growth, angiogenesis, immunosuppression, and inhibition of apoptosis. Examples include data from human melanoma, breast, head and neck, lung, and colon cancers. Fortunately, numerous antioxidant agents are clinically available, and we further propose that the pharmacologic attenuation of these inflammatory processes, particularly the reactive nitrogen species, will restore the cancer cells to an apoptosis-permissive and growth-inhibitory state. Our mouse model data using an arginine antagonist that prevents enzymatic production of nitric oxide directly supports this view. We contend that selected antioxidants be considered as part of the cancer treatment approach, as they are likely to provide a novel and mechanistically justified addition for therapeutic benefit. Clin Cancer Res; 19(20); 5557–63. ©2013 AACR.
Tumor-Infiltrating Lymphocytes in Glioblastoma Are Associated with Specific Genomic Alterations and Related to Transcriptional Class
Authors: Rutledge W. Caleb , Kong Jun , Gao Jingjing , Gutman David A. , Cooper Lee A.D. , Appin Christina , Park Yuna , Scarpace Lisa , Mikkelsen Tom , Cohen Mark L. , Aldape Kenneth D. , McLendon Roger E. , Lehman Norman L. , Miller C. Ryan , Schniederjan Matthew J. , Brennan Cameron W. , Saltz Joel H. , Moreno Carlos S. , Brat Daniel J.
Published: July 2013

Purpose: Tumor-infiltrating lymphocytes (TIL) have prognostic significance in many cancers, yet their roles in glioblastoma have not been fully defined. We hypothesized that TILs in glioblastoma are associated with molecular alterations, histologies, and survival.

Experimental Design: We used data from The Cancer Genome Atlas (TCGA) to investigate molecular, histologic, and clinical correlates of TILs in glioblastomas. Lymphocytes were categorized as absent, present, or abundant in histopathologic images from 171 TCGA glioblastomas. Associations were examined between lymphocytes and histologic features, mutations, copy number alterations, CpG island methylator phenotype, transcriptional class, and survival. We validated histologic findings using CD3G gene expression.

Results: We found a positive correlation between TILs and glioblastomas with gemistocytes, sarcomatous cells, epithelioid cells, and giant cells. Lymphocytes were enriched in the mesenchymal transcriptional class and strongly associated with mutations in NF1 and RB1. These mutations are frequent in the mesenchymal class and characteristic of gemistocytic, sarcomatous, epithelioid, and giant cell histologies. Conversely, TILs were rare in glioblastomas with small cells and oligodendroglioma components. Lymphocytes were depleted in the classical transcriptional class and in EGF receptor (EGFR)-amplified and homozygous PTEN-deleted glioblastomas. These alterations are characteristic of glioblastomas with small cells and glioblastomas of the classical transcriptional class. No association with survival was shown.

Conclusions: TILs were enriched in glioblastomas of the mesenchymal class, strongly associated with mutations in NF1 and RB1 and typical of histologies characterized by these mutations. Conversely, TILs were depleted in the classical class, EGFR-amplified, and homozygous PTEN-deleted tumors and rare in histologies characterized by these alterations. Clin Cancer Res; 19(18); 4951–60. ©2013 AACR.
A Randomized Pilot Trial of Dietary Modification for the Chemoprevention of Noninvasive Bladder Cancer: The Dietary Intervention in Bladder Cancer Study
Authors: Parsons J. Kellogg , Pierce John P. , Natarajan Loki , Newman Vicky A. , Barbier Leslie , Mohler James , Rock Cheryl L. , Heath Dennis D. , Guru Khurshid , Jameson Michael B. , Li Hongying , Mirheydar Hossein , Holmes Michael A. , Marshall James
Published: July 2013

Epidemiological data suggest robust associations of high vegetable intake with decreased risks of bladder cancer incidence and mortality, but translational prevention studies have yet to be conducted. We designed and tested a novel intervention to increase vegetable intake in patients with noninvasive bladder cancer. We randomized 48 patients aged 50 to 80 years with biopsy-proven noninvasive (Ta, T1, or carcinoma in situ) urothelial cell carcinoma to telephone- and Skype-based dietary counseling or a control condition that provided print materials only. The intervention behavioral goals promoted seven daily vegetable servings, with at least two of these as cruciferous vegetables. Outcome variables were self-reported diet and plasma carotenoid and 24-hour urinary isothiocyanate (ITC) concentrations. We used two-sample t tests to assess between-group differences at 6-month follow-up. After 6 months, intervention patients had higher daily intakes of vegetable juice (P = 0.02), total vegetables (P = 0.02), and cruciferous vegetables (P = 0.07); lower daily intakes of energy (P = 0.007), fat (P = 0.002) and energy from fat (P = 0.06); and higher plasma α-carotene concentrations (P = 0.03). Self-reported cruciferous vegetable intake correlated with urinary ITC concentrations at baseline (P < 0.001) and at 6 months (P = 0.03). Although urinary ITC concentrations increased in the intervention group and decreased in the control group, these changes did not attain between-group significance (P = 0.32). In patients with noninvasive bladder cancer, our novel intervention induced diet changes associated with protective effects against bladder cancer. These data show the feasibility of implementing therapeutic dietary modifications to prevent recurrent and progressive bladder cancer. Cancer Prev Res; 6(9); 971–8. ©2013 AACR.
Classification of Schizophrenia Patients and Healthy Controls Using P100 Event-Related Potentials for Visual Processing
Authors: Tanaka Shoji , Maezawa Yosuke , Kirino Eiji
Published: July 2013

The study of event-related potentials (ERPs) is capable of elucidating the abnormalities in brain network dynamics relevant to the information-processing deficits in schizophrenia patients. In contrast to P50 and P300 ERPs, however, the results of P100 ERP studies in schizophrenia patients are less consistent. We have previously reported that P100 amplitudes did not differ significantly between patients with schizophrenia and healthy subjects. This result raised a question as to whether P100 ERPs carry information on brain network dynamics in schizophrenia patients that is distinct from normal controls. To answer this question, in this study we performed discrimination analysis on the P100 data. The rate of correct classification of patients and controls was high (80-90% depending on stimulus categories), indicating that patients have spatial patterns of P100 amplitudes that are distinguishable from those in healthy subjects. To further explore this possibility, we performed principal component analysis on the P100 data. For the patients, the first principal component represented global activity, the second component represented the reciprocal anterior-posterior activation, and the third component represented the hemispheric reciprocity in activity. The first and second components were similar to those of the control group; however, the third component in control subjects showed activation of the center versus anterior and posterior regions. This result is consistent with the notion of abnormalities in hemispheric asymmetries during the processing of sensory information in schizophrenia. In conclusion, this ERP study demonstrated that P100 amplitudes have information that can successfully classify patients and controls.
Occurrence of Slipped Capital Femoral Epiphysis in Children Undergoing Gonadotropin-Releasing Hormone Agonist Therapy for the Treatment of Central Precocious Puberty
Authors: Inman Mark , Hursh Brenden E. , Mokashi Arati , Pinto Teresa , Metzger Daniel L. , Cummings Elizabeth A.
Published: July 2013

Background: Obesity, age and hormone imbalances including hypothyroidism and growth hormone deficiency and therapy, but not gonadotropin-releasing hormone agonist (GnRHa) therapy, have been identified as risk factors for slipped capital femoral epiphysis (SCFE). Five of 7 reported cases describe SCFE in children shortly after GnRHa therapy cessation. Methods: We report 3 cases of SCFE that occurred in children on GnRHa therapy for the treatment of central precocious puberty (CPP) and discuss possible promoting factors. Results: An otherwise healthy 8.75-year-old girl [body mass index (BMI) Z score +1.75] developed SCFE 6.75 years into GnRHa therapy for idiopathic CPP. A second girl (with a history of acute lymphoblastic leukemia requiring total body irradiation) was 10.6 years old (BMI Z score +1.06) when she developed SCFE 3.3 years into GnRHa therapy. The third case was an 8.75-year-old female with CPP secondary to a hypothalamic hamartoma (BMI Z score +1.65) who developed bilateral SCFE 5.6 years into therapy. Conclusion: Increasing evidence suggests an association between GnRHa therapy for CPP and the occurrence of SCFE. We suggest that a lack of adequate sex hormone exposure at a ‘critical period' of bone formation may result in a weakened epiphysis that becomes susceptible to slipping.
Diffuse Alveolar Hemorrhage due to Ketorolac Tromethamine
Authors: Marak Creticus P. , Alappan Narendrakumar , Shim Chang , Guddati Achuta K.
Published: July 2013

Drug-induced lung disease (DILD) is a common but frequently missed diagnosis. Therefore, a high index of clinical suspicion and familiarity with the clinical syndromes associated with DILD are important in making the diagnosis. Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the mostly commonly used classes of medications. NSAIDs are safe when used at prescribed doses. Side effects from use of NSAIDs are not uncommon and can affect almost every organ system in the body. NSAIDs are notorious for causing pulmonary toxicity, the common ones being bronchospasm and hypersensitivity reactions. Diffuse alveolar hemorrhage (DAH) secondary to NSAIDs is uncommon. Here, we report a case of DAH secondary to the use of ketorolac tromethamine.
High Circulatory Titer of Platelet-Associated Autoantibodies in Childhood Onset Schizophrenia and Its Diagnostic Implications
Authors: Ebert Tanya , Schechtman Mila , Ram Anka , Kosov Ira , Weizman Abraham , Shinitzky Meir , Spivak Baruch
Published: July 2013

Background: It has been suggested that the etiology of schizophrenia, in a distinct group of patients, originates from an autoimmune reaction against platelets. Previous studies have demonstrated significantly higher blood titers of platelet-associated autoantibodies (PAA) in adult schizophrenia patients as compared to normal healthy subjects. In addition, young adult schizophrenia patients at their early stages of the disorder displayed higher PAA titers than older patients with longer duration of the disorder. Aim: To assess the blood titers of PAA in children with schizophrenia as compared to matched control subjects without psychotic disorders, as a possible diagnostic parameter. Methods: Twenty-nine children with DSM-IV schizophrenia in the active psychotic state, with an age range of 6-12 years (mean ± SD: 9.6 ± 1.5 years), with average Positive and Negative Syndrome Scale scores of 108 ± 19.2, were assessed. The control group consisted of 25 children with DSM-IV conduct disorder in a similar age range of 5-12 years (mean ± SD: 9.5 ± 1.6 years). The blood titers of PAA were evaluated using an optimized ELISA test, expressed by a linear optical density (OD) scale. The blood samples of all participants were tested anonymously and were scored under a code number. A test recording above 1.4 OD units was predefined as positive. Results: The titers of PAA of children with schizophrenia (1.9 ± 0.5 OD units, range: 0.7-2.44 units) were significantly (p < 0.00001) higher than those of the control group (1.0 ± 0.4 OD units, range: 0.45-2.28 units). In 83% of the children with schizophrenia (24 out of the 29 patients) a positive test, i.e. OD >1.4, was detected. In contrast, in the control group, only 12% (3 of the 25 subjects) displayed a positive test, p < 0.00001. Conclusions: High titers of PAA in children with schizophrenia as compared with nonpsychotic controls may indicate an active autoimmune process in the early onset of schizophrenia. The PAA level may therefore provide a supportive diagnostic biomarker for childhood schizophrenia.
Fertility-Sparing Surgery in Ovarian Cancer: A Systematic Review
Authors: du Bois Andreas , Heitz Florian , Harter Philipp
Published: July 2013

Background: Ovarian cancer is rarely diagnosed in women of reproductive age; however, this coincidence seems to increase due to changes in lifestyle. Available evidence on the prognostic impact of fertility-sparing surgery (FSS) is sparse, and there is an emerging need to consolidate such evidence. Materials and Methods: Systematic review of the literature, including testing for heterogeneity and meta-analytical odds ratio (OR) calculations. Results: 15 studies comprising 913 patients met the inclusion criteria for this review. Out of the 913 patients undergoing FSS, 11.4% developed recurrence during observation. Stage IB/C tumors were nearly twice as likely to recur as stage IA tumors (OR 1.72, 95% confidence interval (CI) 1.12-2.64, p < 0.05), and the risk of recurrence was 4 times higher in G2/3 compared to G1 tumors (4.26, 95% CI 2.31-7.86, p < 0.0001; and stage IC/G2/3 vs. stage IC/G1: OR 2.04, 95% CI 0.86-4.85, p > 0.05). A non-significant risk elevation was attributed to stage IC/G1 compared to stage IA/G1 (OR 1.48, 95% CI 0.66-3.16, p > 0.05). Conclusions: FSS with unilateral salpingo-oophorectomy is only advisable for unilateral grade 1 tumors. Further studies employing contemporary classification criteria, such as low- versus highgrade malignancies, a strictly standardized regimen of surgical staging, and meticulous reporting of recurrence localization, may help develop more differentiated recommendations.
Rictor in Perivascular Adipose Tissue Controls Vascular Function by Regulating Inflammatory Molecule Expression
Authors: Bhattacharya Indranil , Drägert Katja , Albert Verena , Contassot Emmanuel , Damjanović Marlen , Hagiwara Asami , Zimmerli Lukas , Humar Rok , Hall Michael N. , Battegay Edouard J. , Haas Elvira
Published: July 2013

Objective—

Perivascular adipose tissue (PVAT) wraps blood vessels and modulates vasoreactivity by secretion of vasoactive molecules. Mammalian target of rapamycin complex 2 (mTORC2) has been shown to control inflammation and is expressed in adipose tissue. In this study, we investigated whether adipose-specific deletion of rictor and thereby inactivation of mTORC2 in PVAT may modulate vascular function by increasing inflammation in PVAT.

Approach and Results—

Rictor, an essential mTORC2 component, was deleted specifically in mouse adipose tissue (rictor
ad−/−
). Phosphorylation of mTORC2 downstream target Akt at Serine 473 was reduced in PVAT from rictor
ad−/−
mice but unaffected in aortic tissue. Ex vivo functional analysis of thoracic aortae revealed increased contractions and impaired dilation in rings with PVAT from rictor
ad−/−
mice. Adipose rictor knockout increased gene expression and protein release of interleukin-6, macrophage inflammatory protein-1α, and tumor necrosis factor-α in PVAT as shown by quantitative real-time polymerase chain reaction and Bioplex analysis for the cytokines in the conditioned media, respectively. Moreover, gene and protein expression of inducible nitric oxide synthase was upregulated without affecting macrophage infiltration in PVAT from rictor
ad−/−
mice. Inhibition of inducible nitric oxide synthase normalized vascular reactivity in aortic rings from rictor
ad−/−
mice with no effect in rictor
fl/fl
mice. Interestingly, in perivascular and epididymal adipose depots, high-fat diet feeding induced downregulation of rictor gene expression.

Conclusions—

Here, we identify mTORC2 as a critical regulator of PVAT-directed protection of normal vascular tone. Modulation of mTORC2 activity in adipose tissue may be a potential therapeutic approach for inflammation-related vascular damage.
Compartmentalized Protective and Detrimental Effects of Endogenous Macrophage Migration-Inhibitory Factor Mediated by CXCR2 in a Mouse Model of Myocardial Ischemia/Reperfusion
Authors: Liehn Elisa A. , Kanzler Isabella , Konschalla Simone , Kroh Andreas , Simsekyilmaz Sakine , Sönmez Tolga Taha , Bucala Richard , Bernhagen Jürgen , Weber Christian
Published: July 2013

Objective—

Here, we aimed to clarify the role of CXC chemokine receptor (CXCR) 2 in macrophage migration-inhibitory factor (MIF)–mediated effects after myocardial ischemia and reperfusion. As a pleiotropic chemokine-like cytokine, MIF has been identified to activate multiple receptors, including CD74 and CXCR2. In models of myocardial infarction, MIF exerts both proinflammatory effects and protective effects in cardiomyocytes. Similarly, CXCR2 displays opposing effects in resident versus circulating cells.

Approach and Results—

Using bone marrow transplantation, we generated chimeric mice with Cxcr2
−/−
bone marrow–derived inflammatory cells and wild-type (wt) resident cells (wt/Cxcr2
−/−
), Cxcr2
−/−
cardiomyocytes and wt bone marrow–derived cells (Cxcr2
−/−
/wt), and wt controls reconstituted with wt bone marrow (wt/wt). All groups were treated with anti-MIF or isotype control antibody before they underwent myocardial ischemia and reperfusion. Blocking MIF increased infarction size and impaired cardiac function in wt/wt and wt/CXCR2
−/−
mice but ameliorated functional parameters in Cxcr2
−/−
/wt mice, as analyzed by echocardiography and Langendorff perfusion. Neutrophil infiltration and angiogenesis were unaltered by MIF blockade or Cxcr2 deficiency. Monocyte infiltration was blunted in wt/Cxcr2
−/−
mice and reduced by MIF blockade in wt/wt and Cxcr2
−/−
/wt mice. Furthermore, MIF blockade attenuated collagen content in all groups in a CXCR2-independent manner.

Conclusions—

The compartmentalized and opposing effects of MIF after myocardial ischemia and reperfusion are largely mediated by CXCR2. Although MIF confers protective effects by improving myocardial healing and function through CXCR2 in resident cells, thereby complementing paracrine effects through CD74/AMP-activated protein kinase, it exerts detrimental effects on CXCR2-bearing inflammatory cells by increasing monocyte infiltration and impairing heart function. These dichotomous findings should be considered when developing novel therapeutic strategies to treat myocardial infarction.
NOD2-Mediated Innate Immune Signaling Regulates the Eicosanoids in Atherosclerosis
Authors: Liu Hui-Qing , Zhang Xiao-Ying , Edfeldt Kristina , Nijhuis Manon Oude , Idborg Helena , Bäck Magnus , Roy Joy , Hedin Ulf , Jakobsson Per-Johan , Laman Jon D. , de Kleijn Dominique P. , Pasterkamp Gerard , Hansson Göran K. , Yan Zhong-Qun
Published: July 2013

Objective—

The activity of eicosanoid pathways is critical to the inflammatory and immune responses that are associated with the progression of atherosclerosis. Yet, the signals that regulate these pathways are poorly understood. Here, we address whether the innate immune signals of nucleotide-binding oligomerization domain–containing protein (NOD) 2 affect eicosanoids metabolism in atherosclerosis.

Approach and Results—

Analysis of human carotid plaques revealed that NOD2 was abundantly expressed at both mRNA and protein levels by endothelial cells and macrophages. Stimulation of NOD2 in ex vivo–cultured carotid plaques by muramyl dipeptide, an extrinsic ligand of NOD2, led to release of prostaglandin E
2
, upregulation of cyclooxygenase-2 and microsomal prostaglandin E synthase-1, and to downregulation of cyclooxygenase-1. NOD2 was coexpressed with cyclooxygenase-2 in lesional macrophages. NOD2-induced cyclooxygenase-2 expression in macrophages was dependent on p38 mitogen-activated protein kinase activation and was mediated by interleukin-1β and tumor necrosis factor-α. Selective lipidomic analysis of the eicosanoids released by the carotid plaques characterized the metabolites of 12-, 5-, and 15-lipoxygenase as the predominant eicosanoids that were produced by the atherosclerotic lesion in the absence of additional stimuli. Unlike the prostaglandin E
2
pathway, metabolic activity of the lipoxygenase pathways was not altered on the short-term activation of NOD2 in carotid plaques.

Conclusions—

These results suggest that atherosclerosis may involve enhanced NOD2-mediated innate immunity. Activation of NOD2 preferentially upregulates the prostaglandin E
2
pathway. Nevertheless, lipoxygenase pathways, such as 12-lipoxygenase, predominate the basal synthesis and metabolism of eicosanoids in atherosclerotic plaques. These findings provide new insights into the regulation of eicosanoids in atherosclerosis.
LRP1 Protects the Vasculature by Regulating Levels of Connective Tissue Growth Factor and HtrA1
Authors: Muratoglu Selen C. , Belgrave Shani , Hampton Brian , Migliorini Mary , Coksaygan Turhan , Chen Ling , Mikhailenko Irina , Strickland Dudley K.
Published: July 2013

Objective—

Low-density lipoprotein receptor–related protein 1 (LRP1) is a large endocytic and signaling receptor that is abundant in vascular smooth muscle cells. Mice in which the
lrp1
gene is deleted in smooth muscle cells (smLRP1
−/−
) on a low-density lipoprotein receptor–deficient background display excessive platelet derived growth factor-signaling, smooth muscle cell proliferation, aneurysm formation, and increased susceptibility to atherosclerosis. The objectives of the current study were to examine the potential of LRP1 to modulate vascular physiology under nonatherogenic conditions.

Approach and Results—

We found smLRP1
−/−
mice to have extensive in vivo aortic dilatation accompanied by disorganized and degraded elastic lamina along with medial thickening of the arterial vessels resulting from excess matrix deposition. Surprisingly, this was not attributable to excessive platelet derived growth factor-signaling. Rather, quantitative differential proteomic analysis revealed that smLRP1
−/−
vessels contain a 4-fold increase in protein levels of high-temperature requirement factor A1 (HtrA1), which is a secreted serine protease that is known to degrade matrix components and to impair elastogenesis, resulting in fragmentation of elastic fibers. Importantly, our study discovered that HtrA1 is a novel LRP1 ligand. Proteomics analysis also identified excessive accumulation of connective tissue growth factor, an LRP1 ligand and a key mediator of fibrosis.

Conclusions—

Our findings suggest a critical role for LRP1 in maintaining the integrity of vessels by regulating protease activity as well as matrix deposition by modulating HtrA1 and connective tissue growth factor protein levels. This study highlights 2 new molecules, connective tissue growth factor and HtrA1, which contribute to detrimental changes in the vasculature and, therefore, represent new target molecules for potential therapeutic intervention to maintain vessel wall homeostasis.
Novel Formulation of a Reconstituted High-Density Lipoprotein (CSL112) Dramatically Enhances ABCA1-Dependent Cholesterol Efflux
Authors: Diditchenko Svetlana , Gille Andreas , Pragst Ingo , Stadler Dominik , Waelchli Marcel , Hamilton Ross , Leis Andrew , Wright Samuel D.
Published: July 2013

Objective—

The ability of high-density lipoprotein (HDL) to remove cholesterol from atherosclerotic plaque is thought to underlie its inverse correlation with cardiovascular risk. Our objective was to produce and characterize a human apolipoprotein AI (apoA-I) product optimized to treat clinical atherosclerotic disease.

Approach and Results—

A new formulation of full length, plasma-derived human apoA-I termed CSL112 was designed to maximize the cholesterol efflux from cells and exhibit favorable pharmacological properties. CSL112 is a disc-shaped particle that strongly elevates cholesterol esterification and shows good pharmacokinetics in rabbits. Infusion of CSL112 into rabbits caused a strong and immediate increase in the ATP binding cassette transporter A1 (ABCA1)-dependent efflux capacity of plasma, an increase in plasma unesterified cholesterol and rapid subsequent cholesterol esterification. In the presence of human plasma, CSL112 was significantly more potent than native HDL at enhancing cholesterol efflux from macrophages, and the efflux elevation was predominantly via the ABCA1 transporter. Consistent with this observation, addition of CSL112 to plasma led to generation of high levels of HDL-VS, a favorable substrate for ABCA1. The lipid profile of plasma did not affect these behaviors. In studies with whole human blood, CSL112 reduced expression of intercellular adhesion molecule 1 and cytokine secretion, and as with cholesterol efflux, these activities were substantially greater than those of native HDL assayed in parallel.

Conclusions—

CSL112 has favorable pharmacological properties and strongly elevates the ability of plasma to withdraw cholesterol from cells. Preferential elevation of ABCA1-dependent efflux may target atherosclerotic plaque for cholesterol removal and this property makes CSL112 a promising candidate therapy for acute coronary syndrome.
Noninvasive Assessment of Pulmonary Hemodynamics in Patients With Chronic Thromboembolic Pulmonary Hypertension by High Temporal Resolution Phase-Contrast MRI
Authors: Kreitner Karl-Friedrich , Wirth Gesine Maria , Krummenauer Frank , Weber Stefan , Pitton Michael Bernhard , Schneider Jens , Mayer Eckhard , Dueber Christoph
Published: July 2013

Background—

Right heart catheterization is the gold standard for assessment of pulmonary hemodynamics in patients with chronic thromboembolic pulmonary hypertension. To date, MRI has not been able to produce precise measurements of mean pulmonary arterial pressure (mPAP). The purpose of the study was to create a model for estimating mPAP and pulmonary vascular resistance in patients with chronic thromboembolic pulmonary hypertension by high temporal resolution phase-contrast MRI (PC-MRI) and to correlate the results with simultaneously acquired, invasive catheter-based measurements (simultaneously measured mPAP) and with right heart catheterization measurements.

Methods and Results—

A total of 19 patients with chronic thromboembolic pulmonary hypertension underwent right heart catheterization and—after digital subtraction angiography of the pulmonary arteries—subsequent PC-MRI at 1.5 T with simultaneous recording of mPAP. Velocity– and flow–time curves of PC-MRI were used to calculate absolute acceleration time (Ata), maximum of mean velocities (MV), volume of acceleration (AV), and maximum flow acceleration (dQ/dt). On the basis of these parameters, multiple linear regression analysis revealed maximum achievable model fit (B=0.902) for the following linear combination equation to calculate mPAP (mPAP_cal): mPAP_cal=69.446−(0.521×Ata)−(0.570×MV)+(1.507×AV)+(0.002×dQ/dt). There was a statistically significant equivalence of mPAP_cal and simultaneously measured mPAP with a goodness of fit of 0.892. Pulmonary vascular resistance was overestimated by calculated pulmonary vascular resistance on the basis of PC-MRI in comparison with right heart catheterization–based measurements by a median of −112 dyn·s·cm
−5
, the pairwise regression formula revealed a goodness of fit of 0.792.

Conclusions—

PC-MRI–derived parameters enable noninvasive assessment of pulmonary hemodynamics in patients with chronic thromboembolic pulmonary hypertension.
Pericytes in Development and Pathology of Skeletal Muscle
Authors: Cappellari Ornella , Cossu Giulio
Published: July 2013

Increasing attention is currently devoted to the multiple roles that pericytes (also defined as mural, Rouget, or perivascular cells) may play during angiogenesis, vascular homeostasis, and pathology. Many recent excellent reviews thoroughly address these topics (see below); hence, we will not discuss them in detail here. However, not much is known about origin, heterogeneity, gene expression, and developmental potential of pericytes during fetal and postnatal development. This is likely because of the paucity of markers expressed by pericytes and the absence of truly unique ones. Thus, in vivo identification and ex perspective isolation are challenging and explain the relative little data available in comparison with neighbor but far more characterized cells such as the endothelium. Despite this preliminary knowledge, we will propose that contribution to growing mesoderm tissues may be an important role for pericytes. Thus, their ability to contribute to tissue regeneration may be a consequence of their role in tissue growth. However, in a severely damaged or diseased tissue, acute or chronic inflammation likely results in the production of signaling molecules that are different from those present in developing tissues, thus explaining why pericytes are easily diverted from a regenerative to a fibrotic fate.
Provider Specialty and Atrial Fibrillation Treatment Strategies in United States Community Practice: Findings From the ORBIT‐AF Registry
Authors: Fosbol Emil L. , Holmes DaJuanicia N. , Piccini Jonathan P. , Thomas Laine , Reiffel James A. , Mills Roger M. , Kowey Peter , Mahaffey Kenneth , Gersh Bernard J. , Peterson Eric D. ,   the ORBIT‐AF Investigators and Patients
Published: July 2013

Background

The prevalence of atrial fibrillation (
AF
) continues to increase; however, there are limited data describing the division of care among practitioners in the community and whether care differs depending on provider specialty.

Methods and Results

Using the Outcomes Registry for Better Informed Treatment of
AF
(
ORBIT
‐
AF
) Registry, we described patient characteristics and
AF
management strategies in ambulatory clinic practice settings, including electrophysiology (
EP
), general cardiology, and primary care. A total of 10 097 patients were included; of these, 1544 (15.3%) were cared for by an
EP
provider, 6584 (65.2%) by a cardiology provider, and 1969 (19.5%) by an internal medicine/primary care provider. Compared with those patients who were cared for by cardiologists or internal medicine/primary care providers, patients cared for by
EP
providers were younger (median age, 73 years [interquartile range,
IQR
, 64, 80 years, Q1, Q3] versus 75 years [
IQR
, 67, 82 years] for cardiology and versus 76 years [
IQR
, 68, 82 years] for primary care). Compared with cardiology and internal medicine/primary care providers,
EP
providers used rhythm control (versus rate control) management more often (44.2% versus 29.7% and 28.8%, respectively,
P
<0.0001; adjusted odds ratio [
OR
]
EP
versus cardiology, 1.66 [95% confidence interval,
CI
, 1.05 to 2.61]; adjusted
OR
for internal medicine/primary care versus cardiology, 0.91 [95%
CI
, 0.65 to 1.26]). Use of oral anticoagulant therapy was high across all providers, although it was higher for cardiology and
EP
providers (overall, 76.1%;
P
=0.02 for difference between groups).

Conclusions

Our data demonstrate important differences between provider specialties, the demographics of the
AF
patient population treated, and treatment strategies—particularly for rhythm control and anticoagulation therapy.
Spatiotemporal Variability of Summer Precipitation in Southeastern Arizona
Authors: Stillman Susan , Zeng Xubin , Shuttleworth William J. , Goodrich David C. , Unkrich Carl L. , Zreda Marek
Published: July 2013

The Walnut Gulch Experimental Watershed (WGEW) in southeastern Arizona covers ~150 km2 and receives the majority of its annual precipitation from highly variable and intermittent summer storms during the North American monsoon. In this study, the patterns of precipitation in the U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) 88-rain-gauge network are analyzed for July through September from 1956 to 2011. Because small-scale convective systems generate most of this summer rainfall, the total (T), intensity (I), and frequency (F) exhibit high spatial and temporal variability. Although subsidiary periods may have apparent trends, no significant trends in T, I, and F were found for the study period as a whole. Observed trends in the spatial coverage of storms change sign in the late 1970s, and the multidecadal variation in I and spatial coverage of storms have statistically significant correlation with the Pacific decadal oscillation and the Atlantic multidecadal oscillation indices. Precipitation has a pronounced diurnal cycle with the highest T and F occurring between 1500 and 2200 LT, and its average fractional coverage over 2- and 12-h periods is less than 40% and 60% of the gauges, respectively. Although more gauges are needed to estimate area-averaged daily precipitation, 5–11 gauges can provide a reasonable estimate of the area-averaged monthly total precipitation during the period from July through September.
Resolution and Accuracy of an Airborne Scanning Laser System for Beach Surveys
Authors: Middleton J. H. , Cooke C. G. , Kearney E. T. , Mumford P. J. , Mole M. A. , Nippard G. J. , Rizos C. , Splinter K. D. , Turner I. L.
Published: July 2013

Airborne scanning laser technology provides an effective method to systematically survey surface topography and changes in that topography with time. In this paper, the authors describe the capability of a rapid-response lidar system in which airborne observations are utilized to describe results from a set of surveys of Narrabeen–Collaroy Beach, Sydney, New South Wales, Australia, over a short period of time during which significant erosion and deposition of the subaerial beach occurred. The airborne lidar data were obtained using a Riegl Q240i lidar coupled with a NovAtel SPAN-CPT integrated Global Navigation Satellite System (GNSS) and inertial unit and flown at various altitudes. A set of the airborne lidar data is compared with ground-truth data acquired from the beach using a GNSS/real-time kinematic (RTK) system mounted on an all-terrain vehicle. The comparison shows consistency between systems, with the airborne lidar data being less than 0.02 m different from the ground-truth data when four surveys are undertaken, provided a method of removing outliers—developed here and designated as “weaving”—is used. The combination of airborne lidar data with ground-truth data provides an excellent method of obtaining high-quality topographic data. Using the results from this analysis, it is shown that airborne lidar data alone produce results that can be used for ongoing large-scale surveys of beaches with reliable accuracy, and that the enhanced accuracy resulting from multiple airborne surveys can be assessed quantitatively.
An Observational Study of Tropical Cyclone Spinup in Supertyphoon Jangmi (2008) from 24 to 27 September
Authors: Sanger Neil T. , Montgomery Michael T. , Smith Roger K. , Bell Michael M.
Published: July 2013

An observational study of tropical cyclone intensification is performed using dropsondes, in situ flight-level data, satellite imagery, and Electra Doppler Radar (ELDORA) during the spinup of Tropical Storm Jangmi (2008) in the western North Pacific. This event was observed with research aircraft during the Tropical Cyclone Structure 2008 (TCS08) field experiment over the course of 3 days as Jangmi intensified rapidly from a tropical storm to a supertyphoon. The dropsonde analysis indicates that the peak azimuthally averaged storm-relative tangential wind speed occurs persistently within the boundary layer throughout the spinup period and suggests that significant supergradient winds are present near and just within the radius of maximum tangential winds. An examination of the ELDORA data in Tropical Storm Jangmi reveals multiple rotating updrafts near the developing eye beneath cold cloud top temperatures ≤−65°C. In particular, there is a 12-km-wide, upright updraft with a peak velocity of 9 m s−1 with collocated strong low-level (z < 2 km) convergence of 2 × 10−3 s−1 and intense relative vorticity of 4 × 10−3 s−1. The analysis of the corresponding infrared satellite imagery suggests that vortical updrafts are common before and during rapid intensification. The findings of this study support a recent paradigm of tropical cyclone intensification in which rotating convective clouds are important elements in the spinup process. In a system-scale view of this process, the maximum tangential wind is found within the boundary layer, where the tangential wind becomes supergradient before the air ascends into the eyewall updraft.
Airborne Measurements of Terrain-Induced Pressure Perturbations
Authors: Parish Thomas R. , Geerts Bart
Published: July 2013

Airborne measurement of the horizontal pressure field using differential GPS technology has been established during the last few years. Accurate aircraft measurement of the horizontal pressure gradient force requires an independent determination of the height of the airborne platform above some reference level. Here the authors demonstrate a differential GPS technique that uses data from a fixed reference station to refine the vertical position of the aircraft. A series of research flight legs by the University of Wyoming King Air research aircraft (UWKA) were conducted during the winter seasons of 2008 and 2009 over the Medicine Bow Mountains in southern Wyoming. Flight patterns consisted of a series of geographically fixed, parallel legs along a quasi-isobaric surface above the mountainous terrain, allowing the finescale mapping of the horizontal pressure (or geopotential height) field. The removal of the large-scale gradient and tendency isolates the terrain-induced pressure perturbation field. Results obtained using differential GPS measurements of aircraft height show that the Medicine Bow Range induces pronounced horizontal pressure perturbations, with a leeside region of low pressure downwind of the crest, in two cases: on 11 February 2008 and 20 February 2009. A wind maximum is found downwind of the elevated terrain consistent with this pressure gradient. Simulations of these two cases were performed using the Weather Research and Forecasting Model (WRF). The WRF height patterns for the time of the UWKA flight matched the general isobaric height patterns observed. Simulations and observations consistently show that the cross-mountain acceleration is stronger when the perturbation pressure gradient is larger.
Concepts of Self-Repairing Systems
Authors: Bell Colin , McWilliam Richard , Purvis Alan , Tiwari Ashutosh
Published: July 2013

Systems fail. Period. No matter how much planning and fault analysis is performed, it is impossible to create a perfectly reliable machine. The existing approach to improving reliability invariably involves advances in fault prediction and detection to include specific mechanisms to overcome a particular failure or mitigate its effect. While this has gone a long way in increasing the operational life of a machine, the overall complexity of systems has improved sharply, and it is becoming more and more difficult to predict and account for all possible failure modes. What is discussed here is a possible shift in approach from specific repair strategies to autonomous self-repair. Rather than focusing on mitigating or reducing the probability of failure, the focus is instead on what can be done to correct a failure that will invariably occur at some point during operation. By taking this approach, it is not just expected failure that can be designed for, unexpected failure modes are also inherently compensated for, extending the potential life of a system and reducing the need for through-life servicing.