bluuebunny/crossref_metadata_2025_split huggingface dataset:
Research of Bituminous MortarFatigue Test Method Based on Dynamic Shear Rheometer
Authors: Mo L. T. , Huurman M. , Wu S. P. , Molenaar A. A. A. 
Published: September 2011

Abstract
This paper presents a new test method that allows fatigue characterization on bituminous mortar by means of dynamic shear rheometer (DSR). The studied mortar is composed of bitumen, filler and fine sand at a mass ratio of 0.34:0.30:0.36. Dynamic shear rheometer instruments are widely used for bitumen testing by using parallel plate geometry. However, the parallel plate geometry is not suitable for mortar testing due to the fact that the mortar contains fine sand. To take good advantage of DSR instruments, mortar specimen and clamp system were specially designed so that mortar testing can be performed by using DSR instruments under parallel plate control mode. Due to the complex specimen geometry, finite element simulations were performed to translate the torque and deformation that the specimen was subjected into the real mortar stress and strain. An intensive experimental program indicated that the developed test method was capable to capture the shear fatigue behaviour of mortar at meso-scale by using DSR instruments.
The Immediate Impact of Different Types of Television on Young Children's Executive Function
Authors: Lillard Angeline S. , Peterson Jennifer 
Published: September 2011

OBJECTIVE:
The goal of this research was to study whether a fast-paced television show immediately influences preschool-aged children's executive function (eg, self-regulation, working memory).

METHODS:
Sixty 4-year-olds were randomly assigned to watch a fast-paced television cartoon or an educational cartoon or draw for 9 minutes. They were then given 4 tasks tapping executive function, including the classic delay-of-gratification and Tower of Hanoi tasks. Parents completed surveys regarding television viewing and child's attention.

RESULTS:
Children who watched the fast-paced television cartoon performed significantly worse on the executive function tasks than children in the other 2 groups when controlling for child attention, age, and television exposure.

CONCLUSIONS:
Just 9 minutes of viewing a fast-paced television cartoon had immediate negative effects on 4-year-olds' executive function. Parents should be aware that fast-paced television shows could at least temporarily impair young children's executive function.
Sleep-Wake Transitions in Premature Neonates Predict Early Development
Authors: Weisman Omri , Magori-Cohen Reuma , Louzoun Yoram , Eidelman Arthur I. , Feldman Ruth 
Published: September 2011

OBJECTIVE:To identify patterns of sleep-wake transitions in the neonatal period that might differentiate premature infants who would show better or worse outcomes in multiple developmental domains across the first 5 years of life.METHODS:Participants were 143 low birth weight premature infants (mean birth weight: 1482 g; mean gestational age [GA]: 31.82 weeks). Sleep states were observed at a GA of 37 weeks in 10-second epochs over 4 consecutive evening hours and were analyzed through mathematical clustering. Neurobehavioral maturation was evaluated with the Neonatal Behavior Assessment Scale at discharge, emotional regulation was assessed during infant-mother and infant-father interactions at 3 and 6 months, cognitive development was measured at 6, 12, and 24 months, and verbal IQ, executive functions, and symbolic competence were tested at 5 years.RESULTS:Three types of state-transition patterns were identified, and no differences in birth weight, GA, or medical risk between the 3 groups were found. Infants whose sleep-state transitions were mainly characterized by shifts between quiet sleep and wakefulness exhibited the best development, including greater neonatal neuromaturation, less negative emotionality, better cognitive development, and better verbal, symbolic, and executive competences at 5 years. In comparison, infants who cycled mainly between states of high arousal, such as active sleep and cry, or between short episodes of active and quiet sleep showed poorer outcomes.CONCLUSIONS:Defining sleep organization on the basis of transitions between states proved useful for identifying risk and resilience indicators in neonatal behavior to predict trajectories of neurobehavioral, emotional, and cognitive growth.
Private Practice Rates Among Pediatric Subspecialists
Authors: Freed Gary L. , Dunham Kelly M. , Loveland-Cherry Carol , Martyn Kristy K. , Moote Marc J. ,   the American Board of Pediatrics Research Advisory Committee
Published: September 2011

OBJECTIVE:
Historically, most pediatric subspecialists have conducted their clinical work in academic health centers. However, increases in the absolute numbers of pediatric subspecialists in past decades, combined with greater concentrations of children in urban and suburban settings, might result in more opportunities for pediatric subspecialists to enter private practice. Our goal was to assess the proportions of subspecialists in private practice.

METHODS:
We surveyed a stratified, random, national sample of 1696 subspecialists from 5 subspecialties and assessed the ownership of their current clinical practice settings.

RESULTS:
The response rate was 77%. Two-thirds of respondents (65% [n = 705]) reported that they work in academic hospitals or outpatient clinics. Compared with other subspecialists, greater proportions of neonatologists (38% [n = 92]) and critical care physicians (19% [n = 44]) reported that they work in community hospitals. Larger proportions of cardiologists (27% [n = 58]) and gastroenterologists (24% [n = 47]) reported that they work in private outpatient practices.

CONCLUSIONS:
There were significant proportions of pediatric subspecialists in private practice in most of the 5 subspecialties studied. Ensuring children's access to pediatric subspecialists likely will require a robust workforce in both academic and private clinical settings. Ongoing studies of the career trajectories of pediatric subspecialists with respect to their venues of practice will be essential for future workforce planning.
Advanced Glycation End Products Are Direct Modulators of β-Cell Function
Authors: Coughlan Melinda T. , Yap Felicia Y.T. , Tong David C.K. , Andrikopoulos Sofianos , Gasser Anna , Thallas-Bonke Vicki , Webster Diane E. , Miyazaki Jun-ichi , Kay Thomas W. , Slattery Robyn M. , Kaye David M. , Drew Brian G. , Kingwell Bronwyn A. , Fourlanos Spiros , Groop Per-Henrik , Harrison Leonard C. , Knip Mikael , Forbes Josephine M. 
Published: September 2011

OBJECTIVE
Excess accumulation of advanced glycation end products (AGEs) contributes to aging and chronic diseases. We aimed to obtain evidence that exposure to AGEs plays a role in the development of type 1 diabetes (T1D).

RESEARCH DESIGN AND METHODS
The effect of AGEs was examined on insulin secretion by MIN6N8 cells and mouse islets and in vivo in three separate rodent models: AGE-injected or high AGE–fed Sprague-Dawley rats and nonobese diabetic (NODLt) mice. Rodents were also treated with the AGE-lowering agent alagebrium.

RESULTS
β-Cells exposed to AGEs displayed acute glucose-stimulated insulin secretory defects, mitochondrial abnormalities including excess superoxide generation, a decline in ATP content, loss of MnSOD activity, reduced calcium flux, and increased glucose uptake, all of which were improved with alagebrium treatment or with MnSOD adenoviral overexpression. Isolated mouse islets exposed to AGEs had decreased glucose-stimulated insulin secretion, increased mitochondrial superoxide production, and depletion of ATP content, which were improved with alagebrium or with MnTBAP, an SOD mimetic. In rats, transient or chronic exposure to AGEs caused progressive insulin secretory defects, superoxide generation, and β-cell death, ameliorated with alagebrium. NODLt mice had increased circulating AGEs in association with an increase in islet mitochondrial superoxide generation, which was prevented by alagebrium, which also reduced the incidence of autoimmune diabetes. Finally, at-risk children who progressed to T1D had higher AGE concentrations than matched nonprogressors.

CONCLUSIONS
These findings demonstrate that AGEs directly cause insulin secretory defects, most likely by impairing mitochondrial function, which may contribute to the development of T1D.
Intervention With an Erythropoietin-Derived Peptide Protects Against Neuroglial and Vascular Degeneration During Diabetic Retinopathy
Authors: McVicar Carmel M. , Hamilton Ross , Colhoun Liza M. , Gardiner Tom A. , Brines Michael , Cerami Anthony , Stitt Alan W. 
Published: September 2011

OBJECTIVE
Erythropoietin (EPO) may be protective for early stage diabetic retinopathy, although there are concerns that it could exacerbate retinal angiogenesis and thrombosis. A peptide based on the EPO helix-B domain (helix B-surface peptide [pHBSP]) is nonerythrogenic but retains tissue-protective properties, and this study evaluates its therapeutic potential in diabetic retinopathy.

RESEARCH DESIGN AND METHODS
After 6 months of streptozotocin-induced diabetes, rats (n = 12) and age-matched nondiabetic controls (n = 12) were evenly split into pHBSP and scrambled peptide groups and injected daily (10 μg/kg per day) for 1 month. The retina was investigated for glial dysfunction, microglial activation, and neuronal DNA damage. The vasculature was dual stained with isolectin and collagen IV. Retinal cytokine expression was quantified using real-time RT-PCR. In parallel, oxygen-induced retinopathy (OIR) was used to evaluate the effects of pHBSP on retinal ischemia and neovascularization (1–30 μg/kg pHBSP or control peptide).

RESULTS
pHBSP or scrambled peptide treatment did not alter hematocrit. In the diabetic retina, Müller glial expression of glial fibrillary acidic protein was increased when compared with nondiabetic controls, but pHBSP significantly reduced this stress-related response (P &lt; 0.001). CD11b+ microglia and proinflammatory cytokines were elevated in diabetic retina responses, and some of these responses were attenuated by pHBSP (P &lt; 0.01–0.001). pHBSP significantly reduced diabetes-linked DNA damage as determined by 8-hydroxydeoxyguanosine and transferase-mediated dUTP nick-end labeling positivity and also prevented acellular capillary formation (P &lt; 0.05). In OIR, pHBSP had no effect on preretinal neovascularization at any dose.

CONCLUSIONS
Treatment with an EPO-derived peptide after diabetes is fully established can significantly protect against neuroglial and vascular degenerative pathology without altering hematocrit or exacerbating neovascularization. These findings have therapeutic implications for disorders such as diabetic retinopathy.
Prospective Associations of Vitamin D With β-Cell Function and Glycemia
Authors: Kayaniyil Sheena , Retnakaran Ravi , Harris Stewart B. , Vieth Reinhold , Knight Julia A. , Gerstein Hertzel C. , Perkins Bruce A. , Zinman Bernard , Hanley Anthony J. 
Published: September 2011

OBJECTIVETo examine the prospective associations of baseline vitamin D [25-hydroxyvitamin D; 25(OH)D] with insulin resistance (IR), β-cell function, and glucose homeostasis in subjects at risk for type 2 diabetes.RESEARCH DESIGN AND METHODSWe followed 489 subjects, aged 50 ± 10 years, for 3 years. At baseline and follow-up, 75-g oral glucose tolerance tests (OGTTs) were administered. IR was measured using the Matsuda index (ISOGTT) and the homeostasis model assessment of IR (HOMA-IR), β-cell function was determined using both the insulinogenic index divided by HOMA-IR (IGI/IR) and the insulin secretion sensitivity index-2 (ISSI-2), and glycemia was assessed using the area under the glucose curve (AUCglucose). Regression models were adjusted for age, sex, ethnicity, season, and baseline value of the outcome variable, as well as baseline and change in physical activity, vitamin D supplement use, and BMI.RESULTSMultivariate linear regression analyses indicated no significant association of baseline 25(OH)D with follow-up ISOGTT or HOMA-IR. There were, however, significant positive associations of baseline 25(OH)D with follow-up IGI/IR (β = 0.005, P = 0.015) and ISSI-2 (β = 0.002, P = 0.023) and a significant inverse association of baseline 25(OH)D with follow-up AUCglucose (β = −0.001, P = 0.007). Progression to dysglycemia (impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes) occurred in 116 subjects. Logistic regression analyses indicated a significant reduced risk of progression with higher baseline 25(OH)D (adjusted odds ratio 0.69 [95% CI 0.53–0.89]), but this association was not significant after additional adjustment for baseline and change in BMI (0.78 [0.59–1.02]).CONCLUSIONSHigher baseline 25(OH)D independently predicted better β-cell function and lower AUCglucose at follow-up, supporting a potential role for vitamin D in type 2 diabetes etiology.
Increased Phagocyte-Like NADPH Oxidase and ROS Generation in Type 2 Diabetic ZDF Rat and Human Islets
Authors: Syed Ismail , Kyathanahalli Chandrashekara N. , Jayaram Bhavaani , Govind Sudha , Rhodes Christopher J. , Kowluru Renu A. , Kowluru Anjaneyulu 
Published: September 2011

OBJECTIVE
To determine the subunit expression and functional activation of phagocyte-like NADPH oxidase (Nox), reactive oxygen species (ROS) generation and caspase-3 activation in the Zucker diabetic fatty (ZDF) rat and diabetic human islets.

RESEARCH DESIGN AND METHODS
Expression of core components of Nox was quantitated by Western blotting and densitometry. ROS levels were quantitated by the 2′,7′-dichlorofluorescein diacetate method. Rac1 activation was quantitated using the gold-labeled immunosorbent assay kit.

RESULTS
Levels of phosphorylated p47phox, active Rac1, Nox activity, ROS generation, Jun NH2-terminal kinase (JNK) 1/2 phosphorylation, and caspase-3 activity were significantly higher in the ZDF islets than the lean control rat islets. Chronic exposure of INS 832/13 cells to glucolipotoxic conditions resulted in increased JNK1/2 phosphorylation and caspase-3 activity; such effects were largely reversed by SP600125, a selective inhibitor of JNK. Incubation of normal human islets with high glucose also increased the activation of Rac1 and Nox. Lastly, in a manner akin to the ZDF diabetic rat islets, Rac1 expression, JNK1/2, and caspase-3 activation were also significantly increased in diabetic human islets.

CONCLUSIONS
We provide the first in vitro and in vivo evidence in support of an accelerated Rac1–Nox–ROS–JNK1/2 signaling pathway in the islet β-cell leading to the onset of mitochondrial dysregulation in diabetes.
Elevated Depressive Symptoms, Antidepressant Use, and Diabetes in a Large Multiethnic National Sample of Postmenopausal Women
Authors: Ma Yunsheng , Balasubramanian Raji , Pagoto Sherry L. , Schneider Kristin L. , Culver Annie L. , Olendzki Barbara , Tinker Lesley , Liu Simin , Safford Monika , Sepavich Deidre M. , Rosal Milagros C. , Ockene Judith K. , Carnethon Mercedes , Zorn Martha , Hébert James R. 
Published: September 2011

OBJECTIVE
To examine elevated depressive symptoms and antidepressant use in relation to diabetes incidence in the Women’s Health Initiative.

RESEARCH DESIGN AND METHODS
A total of 161,808 postmenopausal women were followed for over an average of 7.6 years. Hazard ratios (HRs) estimating the effects of elevated depressive symptoms and antidepressant use on newly diagnosed incident diabetes were obtained using Cox proportional hazards models adjusted for known diabetes risk factors.

RESULTS
Multivariable-adjusted HRs indicated an increased risk of incident diabetes with elevated baseline depressive symptoms (HR 1.13 [95% CI 1.07–1.20]) and antidepressant use (1.18 [1.10–1.28]). These associations persisted through year 3 data, in which respective adjusted HRs were 1.23 (1.09–1.39) and 1.31 (1.14–1.50).

CONCLUSIONS
Postmenopausal women with elevated depressive symptoms who also use antidepressants have a greater risk of developing incident diabetes. In addition, longstanding elevated depressive symptoms and recent antidepressant medication use increase the risk of incident diabetes.
Talin-1 and Kindlin-3 Regulate α4β1 Integrin-Mediated Adhesion Stabilization, but Not G Protein-Coupled Receptor-Induced Affinity Upregulation
Authors: Hyduk Sharon J. , Rullo Jacob , Cano Adrianet Puig , Xiao Haiyan , Chen Mian , Moser Markus , Cybulsky Myron I. 
Published: September 2011

Abstract
Chemokine/chemoattractant G protein-coupled receptors trigger an inside–out signaling network that rapidly activates integrins, a key step in inflammatory leukocyte recruitment. Integrins mediate leukocyte arrest and adhesion to endothelium through multivalent binding, and they transmit outside–in signals to stabilize adhesion and coordinate cell spreading and migration. In the present study, we used RNA interference in the U937 monocytic cell line to investigate the role of talin-1, kindlin-3, and α-actinin-1 in the fMLF- and SDF-1α–induced upregulation of α4β1 integrin affinity and consequent adhesive events. Affinity upregulation of α4β1 integrin was not impaired by small interfering RNA knockdown of talin-1, kindlin-3, or α-actinin-1. Only kindlin-3 knockdown increased flow-induced detachment from VCAM-1–coated surfaces in response to fluid flow, whereas knockdown of either talin-1 or kindlin-3 increased detachment from ICAM-1–coated surfaces. Biochemical analyses revealed that α4β1 expression was highly enriched in U937 cell microridges and murine lymphocyte microvilli. Kindlin-3 was present throughout the cell, whereas talin-1 was largely excluded from microridges/microvilli. The subcellular colocalization of α4β1 and kindlin-3 in microridges may explain why kindlin-3 rapidly associates with α4β1 after G protein-coupled receptor signaling and contributes to adhesion strengthening. Talin-1 contributed to α4β1-dependent chemotaxis, suggesting that it participates in a later stage of the leukocyte adhesion cascade when the leukocyte cytoskeleton undergoes dramatic rearrangement.
Increased Susceptibility of ST2-Deficient Mice to Polymicrobial Sepsis Is Associated with an Impaired Bactericidal Function
Authors: Buckley Julliette M. , Liu Jing Hua , Li Chong Hui , Blankson Siobhan , Wu Qiong Di , Jiang Yong , Redmond H. Paul , Wang Jiang Huai 
Published: September 2011

Abstract
ST2, a member of the Toll/IL-1R superfamily, negatively regulates both TLR2 and TLR4 signaling. In this study, we report that ST2-deficient mice were more susceptible to polymicrobial sepsis than their wild-type littermates, with increased production of proinflammatory cytokines. Bacterial clearance from the circulation and visceral organs following polymicrobial infection was markedly impaired in ST2-deficient mice. This was associated with substantially reduced uptake, phagocytosis, and intracellular killing of both Gram-positive and Gram-negative bacteria by ST2-deficient phagocytes. Consistent with a reduced antimicrobial response, phagocytes lacking ST2 displayed a defect in bactericidal activity in response to bacterial challenges with severely impaired phagosome maturation and NOX2 function. Thus, ST2-deficient mice exhibit an increased susceptibility to polymicrobial infection with impaired bacterial clearance, which is associated with defects in phagosome maturation and NOX2-derived production of reactive oxygen species characterized in ST2-deficient phagocytes.
Autophagy-Mediated Dendritic Cell Activation Is Essential for Innate Cytokine Production and APC Function with Respiratory Syncytial Virus Responses
Authors: Morris Susan , Swanson Michele S. , Lieberman Andrew , Reed Michelle , Yue Zhenyu , Lindell Dennis M. , Lukacs Nicholas W. 
Published: September 2011

Abstract
The regulation of innate immune responses during viral infection is a crucial step to promote antiviral reactions. Recent studies have drawn attention to a strong relationship of pathogen-associated molecular pattern recognition with autophagy for activation of APC function. Our initial observations indicated that autophagosomes formed in response to respiratory syncytial virus (RSV) infection of dendritic cells (DC). To further investigate whether RSV-induced DC activation and innate cytokine production were associated with autophagy, we used several methods to block autophagosome formation. Using 3-MA, small interfering RNA inhibition of LC3, or Beclin+/− mouse-derived DC, studies established a relationship between RSV-induced autophagy and enhanced type I IFN, TNF, IL-6, and IL-12p40 expression. Moreover, autophagosome formation induced by starvation also promoted innate cytokine expression in DC. The induction of starvation-induced autophagy in combination with RSV infection synergistically enhanced DC cytokine expression that was blocked by an autophagy inhibitor. The latter synergistic responses were differentially altered in DC from MyD88−/− and TRIF−/− mice, supporting the concept of autophagy-mediated TLR signaling. In addition, blockade of autophagy in RSV-infected DC inhibited the maturation of DC as assessed by MHC class II and costimulatory molecule expression. Subsequently, we demonstrated that inhibition of autophagy in DC used to stimulate primary OVA-induced and secondary RSV-infected responses significantly attenuated cytokine production by CD4+ T cells. Thus, these studies have outlined that autophagy in DC after RSV infection is a crucial mechanism for driving innate cytokine production, leading to altered acquired immune responses.
B Cell-Derived IL-15 Enhances CD8 T Cell Cytotoxicity and Is Increased in Multiple Sclerosis Patients
Authors: Schneider Raphael , Mohebiany Alma Nazlie , Ifergan Igal , Beauseigle Diane , Duquette Pierre , Prat Alexandre , Arbour Nathalie 
Published: September 2011

AbstractMultiple lines of evidence suggest that CD8 T cells contribute to the pathogenesis of multiple sclerosis (MS). However, the sources and involvement of cytokines such as IL-15 in activating these cells is still unresolved. To investigate the role of IL-15 in enhancing the activation of CD8 T cells in the context of MS, we determined cell types expressing the bioactive surface IL-15 in the peripheral blood of patients and evaluated the impact of this cytokine on CD8 T cell cytotoxicity and migration. Flow cytometric analysis showed a significantly greater proportion of B cells and monocytes from MS patients expressing IL-15 relative to controls. We established that CD40L activation of B cells from healthy donors increased their IL-15 levels, reaching those of MS patients. We also demonstrated an enhanced cytotoxic profile in CD8 T cells from MS patients upon stimulation with IL-15. Furthermore, we showed that IL-15 expressed by B cells and monocytes is sufficient and functional, enhancing granzyme B production by CD8 T cells upon coculture. Exposure of CD8 T cells to this cytokine enhanced their ability to kill glial cells as well as to migrate across an in vitro inflamed human blood–brain barrier. The elevated levels of IL-15 in patients relative to controls, the greater susceptibility of CD8 T cells from patients to IL-15, in addition to the enhanced cytotoxic responses by IL-15–exposed CD8 T cells, stresses the potential of therapeutic strategies to reduce peripheral sources of IL-15 in MS.