bluuebunny/crossref_metadata_2025 huggingface dataset:
MIMO Radar Adaptive Waveform Design for Extended Target Recognition
Authors: Wang Lulu , Wong Kai-Kit , Wang Hongqiang , Qin Yuliang
Published: June 2015

The problems of multiple-input multiple-output (MIMO) radar adaptive waveform design in additive white Gaussian noise channels and multitarget recognition based on sequential likelihood ratio test are jointly addressed in this paper. Two information-theoretic waveform design strategies, namely, the optimal waveform for maximizing the mutual information (MI) between the extended target impulse response and the target echoes and the optimal waveform for maximizing the Kullback-Leibler (KL) divergence (or relative entropy), are applied in the multitarget recognition application. For multitarget case, two adaptive waveform design methods for all possible targets based on the current knowledge of each hypothesis are proposed. Method 1 is the probability weighted waveform method. Method 2 is the probability weighted target signature method. The optimal waveform is transmitted and adaptively changed such that a decision is made based on the likelihood ratio after several illuminations. Numerical results demonstrate that the best waveform is the KL divergence-based optimal waveform using Method 1 as it has the lowest average illumination number and the highest correct decision rate for target recognition. By optimally designing and adaptively changing the transmitted waveform, the average number of illuminations required for multitarget recognition can be much reduced.
Dynamic Finite Element Analysis of Bending-Torsion Coupled Beams Subjected to Combined Axial Load and End Moment
Authors: Kashani Mir Tahmaseb , Jayasinghe Supun , Hashemi Seyed M.
Published: June 2015

The dynamic analysis of prestressed, bending-torsion coupled beams is revisited. The axially loaded beam is assumed to be slender, isotropic, homogeneous, and linearly elastic, exhibiting coupled flexural-torsional displacement caused by the end moment. Based on the Euler-Bernoulli bending and St. Venant torsion beam theories, the vibration and stability of such beams are explored. Using the closed-form solutions of the uncoupled portions of the governing equations as the basis functions of approximation space, the dynamic, frequency-dependent, interpolation functions are developed, which are then used in conjunction with the weighted residual method to develop the Dynamic Finite Element (DFE) of the system. Having implemented the DFE in a MATLAB-based code, the resulting nonlinear eigenvalue problem is then solved to determine the coupled natural frequencies of illustrative beam examples, subjected to various boundary and load conditions. The proposed method is validated against limited available experimental and analytical data, those obtained from an in-house conventional Finite Element Method (FEM) code and FEM-based commercial software (ANSYS). In comparison with FEM, the DFE exhibits higher convergence rates and in the absence of end moment it produces exact results. Buckling analysis is also carried out to determine the critical end moment and compressive force for various load combinations.
Advances and Prospects in Tissue-Engineered Meniscal Scaffolds for Meniscus Regeneration
Authors: Guo Weimin , Liu Shuyun , Zhu Yun , Yu Changlong , Lu Shibi , Yuan Mei , Gao Yue , Huang Jingxiang , Yuan Zhiguo , Peng Jiang , Wang Aiyuan , Wang Yu , Chen Jifeng , Zhang Li , Sui Xiang , Xu Wenjing , Guo Quanyi
Published: June 2015

The meniscus plays a crucial role in maintaining knee joint homoeostasis. Meniscal lesions are relatively common in the knee joint and are typically categorized into various types. However, it is difficult for inner avascular meniscal lesions to self-heal. Untreated meniscal lesions lead to meniscal extrusions in the long-term and gradually trigger the development of knee osteoarthritis (OA). The relationship between meniscal lesions and knee OA is complex. Partial meniscectomy, which is the primary method to treat a meniscal injury, only relieves short-term pain; however, it does not prevent the development of knee OA. Similarly, other current therapeutic strategies have intrinsic limitations in clinical practice. Tissue engineering technology will probably address this challenge by reconstructing a meniscus possessing an integrated configuration with competent biomechanical capacity. This review describes normal structure and biomechanical characteristics of the meniscus, discusses the relationship between meniscal lesions and knee OA, and summarizes the classifications and corresponding treatment strategies for meniscal lesions to understand meniscal regeneration from physiological and pathological perspectives. Last, we present current advances in meniscal scaffolds and provide a number of prospects that will potentially benefit the development of meniscal regeneration methods.
Liquiritigenin Protects Rats from Carbon Tetrachloride Induced Hepatic Injury through PGC-1αPathway
Authors: Zhang Yiping , He Yuanqiao , Yu Hongbo , Ma Fuying , Wu Jianguo , Zhang Xiaoyu
Published: June 2015

The lack of effective treatment for liver cirrhosis and hepatocellular carcinomas imposes serious challenges to the healthcare system. Here, we investigated the efficacy and mechanism of liquiritigenin involved in preventing or retarding the progression of liver diseases in a rat model with chronic carbon tetrachloride (CCl4) exposure. Sprague Dawley rats were given CCl4 and lliquiritigenin alone or simultaneously for 8 weeks before liver was harvested to check histological changes by Hematoxylin and Eosin (H&E) staining, apoptosis by TUNEL assay, ROS by dihydroethidium staining, antioxidant enzyme activities and malondialdehyde using specific kits, and gene expression by quantitative real-time PCR and western blot. Chronic CCl4 exposure caused profound changes in liver histology with extensive hepatocyte death (necrosis and apoptosis), fat accumulation, and infiltration of inflammatory cells, accompanied by depressed activities of antioxidant enzymes, increased oxidative stress, elevated expression of inflammation and fibrotic genes, and downregulation of PGC-1α, ND1, and Bcl-x in rat liver. All these changes were abolished or alleviated by lliquiritigenin. The results demonstrated that liquiritigenin is effective in protecting liver from injury or treating chronic liver diseases. The modulation of PGC-1αand its downstream genes might play a critical role in relieving CCl4-induced hepatic pathogenesis by liquiritigenin.
Higher Body Mass Index Is Associated with Subjective Olfactory Dysfunction
Authors: Patel Z. M. , DelGaudio J. M. , Wise S. K.
Published: June 2015

Background. Morbidly obese patients demonstrate altered olfactory acuity. There has been no study directly assessing Body Mass Index (BMI) in patients with olfactory dysfunction. Our purpose was to compare BMI in a group of patients with subjective olfactory dysfunction to those without subjective olfactory complaints.Methods. Retrospective matched case-control study. Sixty patients who presented to a tertiary care otolaryngology center with subjective smell dysfunction over one year were identified. Neoplastic and obstructive etiologies were excluded. Demographics, BMI, and smoking status were reviewed. Sixty age, gender, and race matched control patients were selected for comparison. Chi-square testing was used.Results. 48 out of 60 patients (80%) in the olfactory dysfunction group fell into the overweight or obese categories, compared to 36 out of 60 patients (60%) in the control group. There was a statistically significant difference between the olfactory dysfunction and control groups for this stratified BMI(p= 0.0168).  Conclusion. This study suggests high BMI is associated with olfactory dysfunction. Prospective clinical research should examine this further to determine if increasing BMI may be a risk factor in olfactory loss and to elucidate what role olfactory loss may play in diet and feeding habits of obese patients.
Mental State Inferences Abilities Contribution to Verbal Irony Comprehension in Older Adults with Mild Cognitive Impairment
Authors: Gaudreau G. , Monetta L. , Macoir J. , Poulin S. , Laforce R. Jr. , Hudon C.
Published: June 2015

Objective. The present study examined mentalizing capacities as well as the relative implication of mentalizing in the comprehension of ironic and sincere assertions among 30 older adults with mild cognitive impairment (MCI) and 30 healthy control (HC) subjects.Method. Subjects were administered a task evaluating mentalizing by means of short stories. A verbal irony comprehension task, in which participants had to identify ironic or sincere statements within short stories, was also administered; the design of the task allowed uniform implication of mentalizing across the conditions.Results. Findings indicated that participants with MCI have second-order mentalizing difficulties compared to HC subjects. Moreover, MCI participants were impaired compared to the HC group in identifying ironic or sincere stories, both requiring mental inference capacities.Conclusion. This study suggests that, in individuals with MCI, difficulties in the comprehension of ironic and sincere assertions are closely related to second-order mentalizing deficits. These findings support previous data suggesting a strong relationship between irony comprehension and mentalizing.
Nivolumab and Urelumab Enhance Antitumor Activity of Human T Lymphocytes Engrafted in Rag2−/−IL2Rγnull Immunodeficient Mice
Authors: Sanmamed Miguel F. , Rodriguez Inmaculada , Schalper Kurt A. , Oñate Carmen , Azpilikueta Arantza , Rodriguez-Ruiz Maria E. , Morales-Kastresana Aizea , Labiano Sara , Pérez-Gracia Jose L. , Martín-Algarra Salvador , Alfaro Carlos , Mazzolini Guillermo , Sarno Francesca , Hidalgo Manuel , Korman Alan J. , Jure-Kunkel Maria , Melero Ignacio
Published: June 2015

A current pressing need in cancer immunology is the development of preclinical model systems that are immunocompetent for the study of human tumors. Here, we report the development of a humanized murine model that can be used to analyze the pharmacodynamics and antitumor properties of immunostimulatory monoclonal antibodies (mAb) in settings where the receptors targeted by the mAbs are expressed. Human lymphocytes transferred into immunodeficient mice underwent activation and redistribution to murine organs, where they exhibited cell-surface expression of hCD137 and hPD-1. Systemic lymphocyte infiltrations resulted in a lethal CD4+ T cell–mediated disease (xenograft-versus-host disease), which was aggravated when murine subjects were administered clinical-grade anti-hCD137 (urelumab) and anti-hPD-1 (nivolumab). In mice engrafted with human colorectal HT-29 carcinoma cells and allogeneic human peripheral blood mononuclear cells (PBMC), or with a patient-derived gastric carcinoma and PBMCs from the same patient, we found that coadministration of urelumab and nivolumab was sufficient to significantly slow tumor growth. Correlated with this result were increased numbers of activated human T lymphocytes producing IFNγ and decreased numbers of human regulatory T lymphocytes in the tumor xenografts, possibly explaining the efficacy of the therapeutic regimen. Our results offer a proof of concept for the use of humanized mouse models for surrogate efficacy and histology investigations of immune checkpoint drugs and their combinations. Cancer Res; 75(17); 3466–78. ©2015 AACR.
Therapeutic Targeting of the Warburg Effect in Pancreatic Cancer Relies on an Absence of p53 Function
Authors: Rajeshkumar N.V. , Dutta Prasanta , Yabuuchi Shinichi , de Wilde Roeland F. , Martinez Gary V. , Le Anne , Kamphorst Jurre J. , Rabinowitz Joshua D. , Jain Sanjay K. , Hidalgo Manuel , Dang Chi V. , Gillies Robert J. , Maitra Anirban
Published: June 2015

The “Warburg effect” describes a peculiar metabolic feature of many solid tumors, namely their increased glucose uptake and high glycolytic rates, which allow cancer cells to accumulate building blocks for the biosynthesis of macromolecules. During aerobic glycolysis, pyruvate is preferentially metabolized to lactate by the enzyme lactate dehydrogenase-A (LDH-A), suggesting a possible vulnerability at this target for small-molecule inhibition in cancer cells. In this study, we used FX11, a small-molecule inhibitor of LDH-A, to investigate this possible vulnerability in a panel of 15 patient-derived mouse xenograft (PDX) models of pancreatic cancer. Unexpectedly, the p53 status of the PDX tumor determined the response to FX11. Tumors harboring wild-type (WT) TP53 were resistant to FX11. In contrast, tumors harboring mutant TP53 exhibited increased apoptosis, reduced proliferation indices, and attenuated tumor growth when exposed to FX11. [18F]-FDG PET-CT scans revealed a relative increase in glucose uptake in mutant TP53 versus WT TP53 tumors, with FX11 administration downregulating metabolic activity only in mutant TP53 tumors. Through a noninvasive quantitative assessment of lactate production, as determined by 13C magnetic resonance spectroscopy (MRS) of hyperpolarized pyruvate, we confirmed that FX11 administration inhibited pyruvate-to-lactate conversion only in mutant TP53 tumors, a feature associated with reduced expression of the TP53 target gene TIGAR, which is known to regulate glycolysis. Taken together, our findings highlight p53 status in pancreatic cancer as a biomarker to predict sensitivity to LDH-A inhibition, with regard to both real-time noninvasive imaging by 13C MRS as well as therapeutic response. Cancer Res; 75(16); 3355–64. ©2015 AACR.
Neutrophils Increase Oral Squamous Cell Carcinoma Invasion through an Invadopodia-Dependent Pathway
Authors: Glogauer Judah E. , Sun Chun X. , Bradley Grace , Magalhaes Marco A.O.
Published: June 2015

Neutrophils have recently been shown to promote invasion and correlate with a poor prognosis in different cancers, including head and neck squamous cell carcinomas. In this study, we analyze the effects of neutrophils in the invasion of oral squamous cell carcinoma (OSCC) using a combination of conditioned media, direct and indirect coculture of human peripheral blood neutrophils, and UMSCC47 cells (OSCC cell line). Invasion and matrix degradation were determined using a modified in vitro invasion assay and an invadopodia assay, respectively. UMSCC47 and neutrophil cocultures or conditioned media from cocultures increased UMSCC47 invasion, invadopodia formation, and matrix degradation. Further analysis revealed an increase in TNFα and IL8 in supernatants of cocultures compared with neutrophil or UMSCC47 cultures alone and that inhibition of TNFα and IL8 significantly decreased OSCC invasion. Our results show that neutrophils increase the invasiveness of OSCC through the activation of invadopodia and matrix degradation, suggesting a paracrine activation loop between the two cells. Importantly, the presence of neutrophils in the oral environment may modulate the clinical behavior of OSCC. Cancer Immunol Res; 3(11); 1218–26. ©2015 AACR.
Follicle-Stimulating Hormone Receptor as a Target in the Redirected T-cell Therapy for Cancer
Authors: Urbanska Katarzyna , Stashwick Caitlin , Poussin Mathilde , Powell Daniel J.
Published: June 2015

Adoptive transfer of T cells engineered to express chimeric immunoreceptors is an effective strategy to treat hematologic cancers; however, the use of this type of therapy for solid cancers, such as ovarian cancer, remains challenging because a safe and effective immunotherapeutic target has not yet been identified. Here, we constructed and evaluated a novel redirected T-cell–based immunotherapy targeting human follicle-stimulating hormone receptor (FSHR), a highly conserved molecule in vertebrate animals with expression limited to gonadal tissues, ovarian cancer, and cancer-associated vasculature. Receptor ligand–based anti-FSHR immunoreceptors were constructed that contained small binding fragments from the ligand for FSHR, FSH, fused to T-cell transmembrane and T-cell signaling domains. Human T cells transduced to express anti-FSHR immunoreceptors were specifically immunoreactive against FSHR-expressing human and mouse ovarian cancer cell lines in an MHC-nonrestricted manner and mediated effective lysis of FHSR-expressing tumor cells, but not FSHR-deficient targets, in vitro. Similarly, the outgrowth of human ovarian cancer xenografts in immunodeficient mice was significantly inhibited by the adoptive transfer of FSHR-redirected T cells. Our experimental observations show that FSHR is a promising immunotherapeutic target for ovarian cancer and support further exploration of FSHR-targeted immune therapy approaches for patients with cancer. Cancer Immunol Res; 3(10); 1130–7. ©2015 AACR.
Histaminergic H3-Heteroreceptors as a Potential Mediator of Betahistine-Induced Increase in Cochlear Blood Flow
Authors: Bertlich Mattis , Ihler Friedrich , Freytag Saskia , Weiss Bernhard G. , Strupp Michael , Canis Martin
Published: June 2015

Objective: Betahistine is a histamine-like drug that is considered beneficial in Ménière's disease by increasing cochlear blood flow. Acting as an agonist at the histamine H1-receptor and as an inverse agonist at the H3-receptor, these receptors as well as the adrenergic α2-receptor were investigated for betahistine effects on cochlear blood flow. Materials and Methods: A total of 54 Dunkin-Hartley guinea pigs were randomly assigned to one of nine groups treated with a selection of H1-, H3- or α2-selective agonists and antagonists together with betahistine. Cochlear blood flow and mean arterial pressure were recorded for 3 min before and 15 min after infusion. Results: Blockage of the H3- or α2-receptors caused a suppression of betahistine-mediated typical changes in cochlear blood flow or blood pressure. Activation of H3-receptors caused a drop in cochlear blood flow and blood pressure. H1-receptors showed no involvement in betahistine-mediated changes of cochlear blood flow. Conclusion: Betahistine most likely affects cochlear blood flow through histaminergic H3-heteroreceptors.
Evaluation of Salt Intake, Urinary Sodium Excretion and Their Relationship to Overhydration in Chronic Kidney Disease Patients
Authors: Hallvass Andrea E.C. , Claro Lígia Maria , Gonçalves Simone , Olandoski Márcia , Nerbass Fabiana Baggio , Aita Carlos Alberto Mayora , de Moraes Thyago Proença , Pecoits-Filho Roberto
Published: June 2015

The purpose of this study was to estimate sodium intake in a group of patients with chronic kidney disease (CKD) and to correlate the results with the urinary excretion values of sodium and signs of fluid overload. We included patients with CKD in different stages. Urinary sodium was measured in 24 h urine samples. Body composition monitor (BCM) was used to estimate the hydration status. Sixty patients (38 ± 15 ml/min of GFR) presented 4.14 ± 1.71 g/24 h of urinary sodium excretion. Overhydration was detected in 50% of the patients by the BCM. There was a positive correlation between the measured sodium excretion values and BCM, ICW, ECW and TBW. In conclusion, markers of overhydration evaluated by BCM were positively correlated with urinary sodium excretion.
Tedizolid Adsorption and Transmembrane Clearance during in vitro Continuous Renal Replacement Therapy
Authors: Lewis Susan J. , Switaj Lynn A. , Mueller Bruce A.
Published: June 2015

Background/Aims: To study transmembrane clearance (CLTM) and adsorption of tedizolid, a novel oxazolidinone antibiotic, in continuous hemofiltration (CVVH) and continuous hemodialysis (CVVHD). Methods: In vitro CVVH/CVVHD models with polysulfone and AN69 hemodiafilters were used. Tedizolid CLTM during CVVH/CVVHD was assessed at various ultrafiltrate (Quf) and dialysate rates (Qd). Tedizolid adsorption was tested in a recirculating CVVH model over 4 h. Results: In CVVH, CLTM did not differ between filter types. In CVVHD, tedizolid CLTM was significantly higher with the polysulfone hemodiafilter at Qd 6 l/h (p < 0.02). Tedizolid exhibited irreversible adsorption to the CRRT apparatus and bound significantly higher to the polysulfone hemodiafilter. Conclusion: Tedizolid's CLTM is dependent on Qd, Quf, and hemodiafilter type. At conventional CRRT rates, tedizolid CLTM appears modest relative to total body clearance and is unlikely to require dose adjustments. CRRT adsorption in the clinical setting is likely less than what we observed in this in vitro, continuously recirculating blood model.
Mesenteric-Based Surgery Exploits Gastrointestinal, Peritoneal, Mesenteric and Fascial Continuity from Duodenojejunal Flexure to the Anorectal Junction - A Review
Authors: Coffey J. Calvin , Dillon Mary , Sehgal Rishabh , Dockery Peter , Quondamatteo Fabio , Walsh Dara , Walsh Leon
Published: June 2015

Introduction: It is now well established that mesenteric-based colorectal surgery is associated with superior outcomes. Recent anatomic observations have demonstrated that the mesenteric organ is contiguous from the duodenojejunal to the anorectal junction. This led to similar observations in relation to associated peritoneum and fascia. The aim of this review was to demonstrate the relevance of the contiguity principle to resectional colorectal surgery. Methods: All literature in relation to mesenteric anatomy was reviewed from 1873 to the present, without language restriction. Results: Mesenteric-based surgery (i.e. complete mesocolic excision, total mesocolic and mesorectal excision) requires division of the peritoneal reflection (i.e. peritonotomy), and mesenteric mobilisation in the mesofascial plane. These are the fundamental technical elements of mesenterectomy. Mesenteric, peritoneal and fascial contiguity mean that in resectional surgery, these technical elements can be reproducibly applied at all levels from the origin at the superior mesenteric root, to the anorectal junction. Conclusions: The goals of complete mesocolic, total mesocolic and mesorectal excision can be universally achieved at any level from duodenojejunal flexure to anorectal junction, by adopting technical elements based on mesenteric, peritoneal and fascial contiguity.
Influence of Chronic Kidney Disease on Physical Function and Quality of Life in Patients after Coronary Artery Bypass Grafting
Authors: Kuo Yueh-Ting , Chiu Kuan-Ming , Tsang Yuk-Ming , Chiu Cheng-Ming , Chien Meng-Yueh
Published: June 2015

Aims: The purposes of this study were (1) to compare body composition, physical function, and quality of life (QOL) between patients after coronary artery bypass grafting (CABG) with and without chronic kidney disease (CKD) and (2) to analyze the factors associated with physical function and QOL domains in these patients. Methods: Thirty male post-CABG patients with CKD and 30 matched controls were recruited. All subjects underwent dual-energy X-ray absorptiometry for body composition evaluation. Physical function tests included the grip strength test, 30-second chair stand test (30CST), and 6-min walk test (6MWT). Physical activity and QOL were assessed using the long form of the International Physical Activity Questionnaire and the World Health Organization Quality of Life Instrument (WHOQOL)-BREF, respectively. Results: Post-CABG patients with CKD exhibited a lower arm lean mass and higher percent leg fat mass than those without CKD (p < 0.05). The patients with CKD also had lower 30CST scores, 6MWT distances, and QOL domain of social relationships scores than those without CKD after adjusting for covariates (p < 0.05). If NYHA class was considered in the model, NYHA class became the most important factor associated with 6MWT distances (β = -0.647, p < 0.001) and the QOL domains of psychological health (β = -0.285, p = 0.027) and environment (β = -0.406, p = 0.001). Conclusion: Post-CABG patients with CKD had worse body composition, physical function, and QOL than those without CKD, and this might be associated with a worse NYHA class.
Both MC
1
and MC
3
Receptors Provide Protection From Cerebral Ischemia-Reperfusion–Induced Neutrophil Recruitment
Authors: Holloway Paul M. , Durrenberger Pascal F. , Trutschl Marjan , Cvek Urska , Cooper Dianne , Orr A. Wayne , Perretti Mauro , Getting Stephen J. , Gavins Felicity N.E.
Published: June 2015

Objective—

Neutrophil recruitment is a key process in the pathogenesis of stroke, and may provide a valuable therapeutic target. Targeting the melanocortin (MC) receptors has previously shown to inhibit leukocyte recruitment in peripheral inflammation, however, it is not known whether treatments are effective in the unique cerebral microvascular environment. Here, we provide novel research highlighting the effects of the MC peptides on cerebral neutrophil recruitment, demonstrating important yet discrete roles for both MC
1
and MC
3
.

Approach and Results—

Using intravital microscopy, in 2 distinct murine models of cerebral ischemia-reperfusion (I/R) injury, we have investigated MC control for neutrophil recruitment. After global I/R, pharmacological treatments suppressed pathological neutrophil recruitment. MC
1
selective treatment rapidly inhibited neutrophil recruitment while a nonselective MC agonist provided protection even when coadministered with an MC
3/4
antagonist, suggesting the importance of early MC
1
signaling. However, by 2-hour reperfusion, MC
1
-mediated effects were reduced, and MC
3
anti-inflammatory circuits predominated. Mice bearing a nonfunctional MC
1
displayed a transient exacerbation of neutrophil recruitment after global I/R, which diminished by 2 hours. However importantly, enhanced inflammatory responses in both MC
1
mutant and MC
3
−/−
mice resulted in increased infarct size and poor functional outcome after focal I/R. Furthermore, we used an in vitro model of leukocyte recruitment to demonstrate these anti-inflammatory actions are also effective in human cells.

Conclusions—

These studies reveal for the first time MC control for neutrophil recruitment in the unique pathophysiological context of cerebral I/R, while also demonstrating the potential therapeutic value of targeting multiple MCs in developing effective therapeutics.
Increased High-Density Lipoprotein Cholesterol Levels in Mice With XX Versus XY Sex Chromosomes
Authors: Link Jenny C. , Chen Xuqi , Prien Christopher , Borja Mark S. , Hammerson Bradley , Oda Michael N. , Arnold Arthur P. , Reue Karen
Published: June 2015

Objective—

The molecular mechanisms underlying sex differences in dyslipidemia are poorly understood. We aimed to distinguish genetic and hormonal regulators of sex differences in plasma lipid levels.

Approach and Results—

We assessed the role of gonadal hormones and sex chromosome complement on lipid levels using the four core genotypes mouse model (XX females, XX males, XY females, and XY males). In gonadally intact mice fed a chow diet, lipid levels were influenced by both male–female gonadal sex and XX–XY chromosome complement. Gonadectomy of adult mice revealed that the male–female differences are dependent on acute effects of gonadal hormones. In both intact and gonadectomized animals, XX mice had higher HDL cholesterol (HDL-C) levels than XY mice, regardless of male–female sex. Feeding a cholesterol-enriched diet produced distinct patterns of sex differences in lipid levels compared with a chow diet, revealing the interaction of gonadal and chromosomal sex with diet. Notably, under all dietary and gonadal conditions, HDL-C levels were higher in mice with 2 X chromosomes compared with mice with an X and Y chromosome. By generating mice with XX, XY, and XXY chromosome complements, we determined that the presence of 2 X chromosomes, and not the absence of the Y chromosome, influences HDL-C concentration.

Conclusions—

We demonstrate that having 2 X chromosomes versus an X and Y chromosome complement drives sex differences in HDL-C. It is conceivable that increased expression of genes escaping X-inactivation in XX mice regulates downstream processes to establish sexual dimorphism in plasma lipid levels.
Acute Hyperglycemia Impairs Vascular Function in Healthy and Cardiometabolic Diseased Subjects
Authors: Loader Jordan , Montero David , Lorenzen Christian , Watts Rani , Méziat Cindy , Reboul Cyril , Stewart Simon , Walther Guillaume
Published: June 2015

Objectives—

Controversy exists over the effect of acute hyperglycemia on vascular function. In this systematic review, we compared the effect of acute hyperglycemia on endothelial and vascular smooth muscle functions across healthy and cardiometabolic diseased subjects.

Approach and Results—

A systematic search of MEDLINE, EMBASE, and Web of Science from inception until July 2014 identified articles evaluating endothelial or vascular smooth muscle function during acute hyperglycemia and normoglycemia. Meta-analyses compared the standardized mean difference (SMD) in endothelial and vascular smooth muscle functions between acute hyperglycemia and normoglycemia. Subgroup analyses and metaregression identified sources of heterogeneity. Thirty-nine articles (525 healthy and 540 cardiometabolic subjects) were analyzed. Endothelial function was decreased (39 studies; n=1065; SMD, −1.25; 95% confidence interval, −1.52 to −0.98;
P
<0.01), whereas vascular smooth muscle function was preserved (6 studies; n=144; SMD, −0.07; 95% confidence interval, −0.30 to 0.16;
P
=0.55) during acute hyperglycemia compared with normoglycemia. Significant heterogeneity was detected among endothelial function studies (
P
<0.01). A subgroup analysis revealed that endothelial function was decreased in the macrocirculation (30 studies; n=884; SMD, −1.40; 95% confidence interval, −1.68 to −1.12;
P
<0.01) but not in the microcirculation (9 studies; n=181; SMD, −0.63; 95% confidence interval, −1.36 to 0.11;
P
=0.09). Similar results were observed according to health status. Macrovascular endothelial function was inversely associated with age, blood pressure, and low-density lipoprotein cholesterol and was positively associated with the postocclusion interval of vascular assessment.

Conclusions—

To our knowledge, this is the first systematic review and meta-analysis of its kind. In healthy and diseased subjects, we found evidence for macrovascular but not microvascular endothelial dysfunction during acute hyperglycemia.
Foamy Monocytes Form Early and Contribute to Nascent Atherosclerosis in Mice With Hypercholesterolemia
Authors: Xu Lu , Dai Perrard Xiaoyuan , Perrard Jerry L. , Yang Donglin , Xiao Xinhua , Teng Ba-Bie , Simon Scott I. , Ballantyne Christie M. , Wu Huaizhu
Published: June 2015

Objective—

To examine infiltration of blood foamy monocytes, containing intracellular lipid droplets, into early atherosclerotic lesions and its contribution to development of nascent atherosclerosis.

Approach and Results—

In apoE
–/–
mice fed Western high-fat diet (WD), >10% of circulating monocytes became foamy monocytes at 3 days on WD and >20% of monocytes at 1 week. Foamy monocytes also formed early in blood of Ldlr
–/–
Apobec1
–/–
(LDb) mice on WD. Based on CD11c and CD36, mouse monocytes were categorized as CD11c
–
CD36
–
, CD11c
–
CD36
+
, and CD11c
+
CD36
+
. The majority of foamy monocytes were CD11c
+
CD36
+
, whereas most nonfoamy monocytes were CD11c
–
CD36
–
or CD11c
–
CD36
+
in apoE
–/–
mice on WD. In wild-type mice, CD11c
+
CD36
+
and CD11c
–
CD36
+
, but few CD11c
–
CD36
–
, monocytes took up cholesteryl ester–rich very low-density lipoproteins (CE-VLDLs) isolated from apoE
–/–
mice on WD, and CE-VLDL uptake accelerated CD11c
–
CD36
+
to CD11c
+
CD36
+
monocyte differentiation. Ablation of CD36 decreased monocyte uptake of CE-VLDLs. Intravenous injection of DiI-CE-VLDLs in apoE
–/–
mice on WD specifically labeled CD11c
+
CD36
+
foamy monocytes, which infiltrated into nascent atherosclerotic lesions and became CD11c
+
cells that were selectively localized in atherosclerotic lesions. CD11c deficiency reduced foamy monocyte infiltration into atherosclerotic lesions. Specific and consistent depletion of foamy monocytes (for 3 weeks) by daily intravenous injections of low-dose clodrosome reduced development of nascent atherosclerosis.

Conclusions—

Foamy monocytes, which form early in blood of mice with hypercholesterolemia, infiltrate into early atherosclerotic lesions in a CD11c-dependent manner and play crucial roles in nascent atherosclerosis development.
Fibroblast Growth Factor 23 Is Associated With Carotid Plaque Presence and Area
Authors: Shah Nirav H. , Dong Chuanhui , Elkind Mitchell S.V. , Sacco Ralph L. , Mendez Armando J. , Hudson Barry I. , Silverberg Shonni , Wolf Myles , Rundek Tatjana , Wright Clinton B.
Published: June 2015

Objective—

Elevated fibroblast growth factor 23 (FGF23), a hormone that regulates phosphate homeostasis, has been associated with mortality, cardiovascular events, and stroke, and to arterial calcification in chronic kidney disease, but its role in atherosclerosis is unclear and population-based studies are lacking. We hypothesized that elevated FGF23 would associate with carotid plaque presence, area, and echogenicity in the race/ethnically diverse community-based Northern Manhattan Study (NOMAS) sample.

Approach and Results—

There were 1512 stroke-free NOMAS participants with FGF23 and 2-dimensional carotid ultrasound data (mean age, 68±9 years; 61% women; 62% Hispanic, 18% black, and 18% white). We used multivariable linear and logistic regression to evaluate FGF23, continuously and by quintiles, as a correlate of carotid plaque, plaque area (cubic root transformed), and echogenicity adjusting for sociodemographic and vascular risk factors. Participants with FGF23 levels in the top quintile were more likely to have carotid plaque (odds ratio, 1.49; 95% confidence interval, 1.02–2.19;
P
=0.04) and larger plaque area (β=0.32 mm
2
, 95% confidence interval, 0.10–0.53 mm
2
;
P
=0.004) than those in the lowest quintile, adjusting for estimated glomerular filtration rate, demographics, and vascular risk factors. Linear regression models also showed that log transformed FGF23 (LnFGF23) associated with greater odds of plaque presence (odds ratio, 1.26 per LnFGF23; 95% confidence interval, 1.01–1.58;
P
=0.04), and plaque area (β=0.19 mm
2
per LnFGF23; 95% confidence interval, 0.07–0.31 mm
2
;
P
=0.002).

Conclusions—

Higher FGF23 associated with greater likelihood and burden of carotid atherosclerosis independent of CKD. Atherosclerosis may be a mechanism through which FGF23 increases cardiovascular events and stroke.
Loss-of-Function
SCN5A
Mutations Associated With Sinus Node Dysfunction, Atrial Arrhythmias, and Poor Pacemaker Capture
Authors: Chiang David Y. , Kim Jeffrey J. , Valdes Santiago O. , de la Uz Caridad , Fan Yuxin , Orcutt Jeffrey , Domino Melissa , Smith Melissa , Wehrens Xander H.T. , Miyake Christina Y.
Published: June 2015

Background—

Cardiac device implantation can be complicated by inability to adequately place leads because of significant lead capture issues. This study sought to determine whether there are genetic bases that underlie poor lead capture.

Methods and Results—

Retrospective review of all patients with structurally normal hearts who underwent new device implantation at Texas Children’s Hospital between 2009 and 2014 was performed. Patients with inability to capture at 10 V or a final capture threshold ≥3 V at 0.4 ms during implant were analyzed. Among a total of 136 patients (median age, 13 years; range, 3 days to 46 years), 11 patients (8.1%) who underwent dual chamber device implantation had elevated thresholds in the atria (4), ventricle (3), or both chambers (4; atrial-lead threshold, 4.7±4.3 versus 0.7±0.3 V; ventricular-lead, 3.0±3.3 versus 0.7±0.3 V). All 11 patients presented with sinus node dysfunction and 10 had atrial arrhythmias. At implant, inability to find atrial capture was seen in 4 patients. Three demonstrated intermittent complete loss of ventricular capture after implantation: 1 has recurrent syncope, 2 eventually died. Genetic testing performed in 10 demonstrated 7 patients with 6 distinct
SCN5A
mutations, all predicted to be severe loss-of-function mutations by bioinformatic analyses. In the remaining patients, although putative pathogenic mutations were not found, multiple
SCN5A
polymorphisms were identified in 2 and a desmin mutation in 1.

Conclusions—

This study suggests that significant capture issues at implant may be because of loss-of-function
SCN5A
mutations, providing new insights into
SCN5A
function. Recognition of this association may be critical for planning device implantation strategies and patient follow-up.
Association of Interstage Home Monitoring With Mortality, Readmissions, and Weight Gain
Authors: Oster Matthew E. , Ehrlich Alexandra , King Eileen , Petit Christopher J. , Clabby Martha , Smith Sherry , Glanville Michelle , Anderson Jeffrey , Darbie Lynn , Beekman Robert H.
Published: June 2015

Background—

Daily home monitoring of oxygen saturation and weight has been reported to improve outcomes for patients with single-ventricle heart disease during the period between stage I palliation and stage II palliation. However, these studies have been limited to single institutions and used historical control subjects. Our objective was to determine the association of various interstage home monitoring strategies with outcomes using a multicenter cohort with contemporary control subjects.

Methods and Results—

We performed a retrospective cohort study using prospectively collected data from the National Pediatric Cardiology Quality Improvement Collaborative from 2008 to 2012. We compared interstage mortality, unscheduled readmissions, and change in weight-for-age
Z
score for various home monitoring strategies of oxygen saturation (n=494) or weight (n=472), adjusting for sex, syndrome, tricuspid regurgitation, arch obstruction, and shunt type. Overall interstage mortality was 8.1%, and 47% had ≥1 unscheduled readmission. We did not find any associations of home oxygen saturation or weight monitoring with mortality or readmission. Although there was no difference in weight-for-age
Z
score for daily (0.33±0.12) versus weekly (0.34±0.18,
P
=0.98) weight monitoring, daily home weight monitoring was superior to no home weight monitoring (−0.15±0.18;
P
<0.01).

Conclusions—

Home weight monitoring is associated with improved weight gain during the interstage period, but we did not find any benefits in other clinical outcomes for either home oxygen saturation monitoring or home weight monitoring.
Columnea longipedicellata, a new species of Gesneriaceae from Colombia
Authors: AMAYA–MÁRQUEZ MARISOL , CLAVIJO LAURA , MARÍN–GÓMEZ OSCAR HUMBERTO
Published: June 2015

Columnea longipedicellata, a new species from Antioquia and Chocó Departments in Colombia (Cordillera Occidental) is described and illustrated. The new species is distinguished by the presence of elongate pedicels and leaves uniformly green abaxially.
Taxonomic reexamination of Portulaca boninensis (Portulacaceae) in the Bonin (Ogasawara) Islands of Japan using molecular and morphological data
Authors: KOKUBUGATA Goro , Kato Hidetoshi , IAMONICO DUILIO , Umemoto Hana , Ito Takuro , Nakamura Koh , Murakami Noriaki , Yokota Masatsugu
Published: June 2015

Molecular phylogenetic analyses, morphological observations, and nomenclatural studies were carried out to investigate the taxonomic status of Portulaca boninensis, endemic species from the Bonin (Ogasawara) Islands (Japan). The results addressed controversy between the widely naturalized P. boninensis and P. pilosa, indicating that they are phylogenetically and morphologically distinct. Furthermore, P. boninensis was showed to be conspecific to P. psammotropha which is until now recorded in southern China, Taiwan, and the northern Philippines, but not in the Ryukyus. The name of P. psammotropha was lectotypified on a specimen preserved at K. Based on phylogeography, P. psammotropha likely migrated to the Oceanic Bonin Islands oversea by sea-current dispersal or by exo- and/or end ozoochory through migratory birds without passing through Ryukyus.
New Ocean Winds Satellite Mission to Probe Hurricanes and Tropical Convection
Authors: Ruf Christopher S. , Atlas Robert , Chang Paul S. , Clarizia Maria Paola , Garrison James L. , Gleason Scott , Katzberg Stephen J. , Jelenak Zorana , Johnson Joel T. , Majumdar Sharanya J. , O’brien Andrew , Posselt Derek J. , Ridley Aaron J. , Rose Randall J. , Zavorotny Valery U.
Published: June 2015

The Cyclone Global Navigation Satellite System (CYGNSS) is a new NASA earth science mission scheduled to be launched in 2016 that focuses on tropical cyclones (TCs) and tropical convection. The mission’s two primary objectives are the measurement of ocean surface wind speed with sufficient temporal resolution to resolve short-time-scale processes such as the rapid intensification phase of TC development and the ability of the surface measurements to penetrate through the extremely high precipitation rates typically encountered in the TC inner core. The mission’s goal is to support significant improvements in our ability to forecast TC track, intensity, and storm surge through better observations and, ultimately, better understanding of inner-core processes. CYGNSS meets its temporal sampling objective by deploying a constellation of eight satellites. Its ability to see through heavy precipitation is enabled by its operation as a bistatic radar using low-frequency GPS signals. The mission will deploy an eight-spacecraft constellation in a low-inclination (35°) circular orbit to maximize coverage and sampling in the tropics. Each CYGNSS spacecraft carries a four-channel radar receiver that measures GPS navigation signals scattered by the ocean surface. The mission will measure inner-core surface winds with high temporal resolution and spatial coverage, under all precipitating conditions, and over the full dynamic range of TC wind speeds.
An Experiment on Risk-Based Decision-Making in Water Management Using Monthly Probabilistic Forecasts
Authors: Crochemore Louise , Ramos Maria-Helena , Pappenberger Florian , Andel Schalk Jan van , Wood Andrew W.
Published: June 2015

The use of probabilistic forecasts is necessary to take into account uncertainties and allow for optimal risk-based decisions in streamflow forecasting at monthly to seasonal lead times. Such probabilistic forecasts have long been used by practitioners in the operation of water reservoirs, in water allocation and management, and more recently in drought preparedness activities. Various studies assert the potential value of hydrometeorological forecasting efforts, but few investigate how these forecasts are used in the decision-making process. Role-playing games can help scientists, managers, and decision-makers understand the extremely complex process behind risk-based decisions. In this paper, we present an experiment focusing on the use of probabilistic forecasts to make decisions on reservoir outflows. The setup was a risk-based decision-making game, during which participants acted as water managers. Participants determined monthly reservoir releases based on a sequence of probabilistic inflow forecasts, reservoir volume objectives, and release constraints. After each decision, consequences were evaluated based on the actual inflow. The analysis of 162 game sheets collected after eight applications of the game illustrates the importance of leveraging not only the probabilistic information in the forecasts but also predictions for a range of lead times. Winning strategies tended to gradually empty the reservoir in the months before the peak inflow period to accommodate its volume and avoid overtopping. Twenty percent of the participants managed to do so and finished the management period without having exceeded the maximum reservoir capacity or violating downstream release constraints. The role-playing approach successfully created an open atmosphere to discuss the challenges of using probabilistic forecasts in sequential decision-making.
Assessment of the Sources of Variation in Changes of Precipitation Characteristics over the Rhine Basin Using a Linear Mixed-Effects Model
Authors: Hanel Martin , Buishand T. Adri
Published: June 2015

A linear mixed-effects (LME) model is developed to discriminate the sources of variation in the changes of several precipitation characteristics over the Rhine basin as projected by an ensemble of 191 global climate model (GCM) simulations from phase 5 of the Coupled Model Intercomparison Project (CMIP5). The uncertainty in climate change projections originates from natural internal variability, imperfect climate models, and the unpredictability of future greenhouse gas forcing. The LME model allows for the quantification of the contribution of these sources of uncertainty as well as the interaction between greenhouse gas forcing and climate model. In addition, dependence between climate models can be accounted for by using a two-level LME model in which the GCMs are grouped according to their atmospheric circulation model. Statistical models of varied complexity are assessed by the Akaike information criterion. More than 60% of the variance of the changes in mean summer precipitation and various quantiles of 5-day summer precipitation at the end of the twenty-first century can be explained by the climate model. Differences between climate models are also the main source of uncertainty for the changes in three drought characteristics in the summer half-year. In winter, the differences between GCMs are smaller, and natural variability explains a large proportion of the variance of the changes. Natural variability is also the main source of uncertainty for the changes in two indices of extreme precipitation. The contribution of the forcing scenario to the variance of the changes is generally less than 25%.
Characteristics, Energetics, and Origins of Agulhas Current Meanders and Their Limited Influence on Ring Shedding
Authors: Elipot Shane , Beal Lisa M.
Published: June 2015

The Agulhas Current intermittently undergoes dramatic offshore excursions from its mean path because of the downstream passage of mesoscale solitary meanders or Natal pulses. New observations and analyses are presented of the variability of the current and its meanders using mooring observations from the Agulhas Current Time-Series Experiment (ACT) near 34°S. Using a new rotary EOF method, mesoscale meanders and smaller-scale meanders are differentiated and each captured in a single mode of variance. During mesoscale meanders, an onshore cyclonic circulation and an offshore anticyclonic circulation act together to displace the jet offshore, leading to sudden and strong positive conversion of kinetic energy from the mean flow to the meander via nonlinear interactions. Smaller meanders are principally represented by a single cyclonic circulation spanning the entire jet that acts to displace the jet without extracting kinetic energy from the mean flow. Synthesizing in situ observations with altimeter data leads to an account of the number of mesoscale meanders at 34°S: 1.6 yr−1 on average, in agreement with a recent analysis by Rouault and Penven (2011) and significantly less than previously understood. The links between meanders and the arrival of Mozambique Channel eddies or Madagascar dipoles at the western boundary upstream are found to be robust in the 20-yr altimeter record. Yet, only a small fraction of anomalies arriving at the western boundary result in meanders, and of those, two-thirds can be related to ring shedding. Most Agulhas rings are shed independently of meanders.