bluuebunny/crossref_metadata_2025 huggingface dataset:
Intermittency and erraticity of charged particles produced in 28Si-Ag/Br interaction at 14.5 A GeV
Authors: Mali Provash , Mukhopadhyay Amitabha , Singh Gurmukh
Published: September 2011

In this paper, we present the intermittency and the erraticity analyses of the distributions of charged particles produced in 28Si-Ag/Br interaction at incident energy 14.5 A GeV. The experimental results are compared with a Monte Carlo simulation using ultra-relativistic quantum molecular dynamics (UrQMD) model. The experimental data show the presence of a nonstatistical component in the produced charged-particle density. Neither the UrQMD simulation nor the purely statistical simulation was found to match the experimental data. The present set of results are compared to those obtained in similar measurements from earlier high-energy nucleus–nucleus experiments.
Self-compressed inhomogeneous stabilized jellium model and surface relaxation of simple metal thin films
Authors: Payami M. , Mahmoodi T.
Published: September 2011

The interlayer spacing near the surface of a crystal is different from that of the bulk. As a result, the value of the ionic density in the normal direction and near to the surface shows some variation from the bulk value, which is oscillatory in shape. To describe this behavior simply, we have formulated the self-compressed inhomogeneous stabilized jellium model and have applied it to simple metal thin films. In this model, for a ν-layered slab, each ionic layer is replaced by a jellium slice of constant density. The equilibrium densities of the slices are determined by minimizing the total energy per electron of the slab with respect to the slice densities. However, to avoid the complications that arise because of the increasing number of independent slice-density parameters for large-ν slabs, we consider a simplified version of the model that consists of only three jellium slices: one inner bulk slice with density [Formula: see text] and two similar surface slices, each of density [Formula: see text]. In this simplified model, each slice may contain more than one ionic layer. Application of this model to ν-layered slabs (3 ≤ ν ≤ 10) of Al, Na, and Cs shows that, in the equilibrium state, [Formula: see text] differs from [Formula: see text]. The difference is significant in the Al case, and the slab is more stable than that predicted by the homogeneous model with only one density parameter for the whole jellium background. In addition, we have calculated the overall relaxations, the work functions, and the surface energies and compared them with the results of earlier works.
Shock wave solutions of the variants of the Kadomtsev–Petviashvili equation
Authors: Triki Houria , Sturdevant B.J.M. , Hayat T. , Aldossary O.M. , Biswas A.
Published: September 2011

This study obtained the shock wave or kink solutions of the variants of the Kadomtsev–Petviashvili equation with generalized evolution. There are three types of variants of this equation that were considered. The relation between the parameters and the constraint conditions will naturally fall out as a consequence of the derivation of the shock wave solution.
Thujone inhibits lung metastasis induced by B16F-10 melanoma cells in C57BL/6 mice
Authors: Siveen Kodappully S. , Kuttan Girija
Published: September 2011

The antimetastatic potential of thujone, a naturally occurring monoterpene, was evaluated. Metastasis was induced in C57BL/6 mice by injecting highly metastatic B16F-10 melanoma cells through the lateral tail vein. Administration of thujone (1 mg·(kg body weight)–1), prophylactically and simultaneously with tumor induction, inhibited tumor nodule formation in the lungs by 59.45% and 57.54%, respectively, with an increase in the survival rate (33.67% and 32.16%) of the metastatic tumor bearing animals. These results correlated with biochemical parameters such as lung collagen hydroxyproline, hexosamine and uronic acid contents, serum sialic acid and γ-glutamyl transpeptidase levels, and histopathological analysis. Treatment with thujone downregulated the production of proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and granulocyte–monocyte colony-stimulating factor. Thujone administration downregulated the expression of matrix metalloproteinase (MMP)-2, MMP-9, extracellular signal-regulated kinase (ERK)-1, ERK-2, and vascular endothelial growth factor (VEGF) and also upregulated the expression of nm-23, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 in the lung tissue of metastasis-induced animals. Treatment with thujone inhibited the activity of MMP-2 and MMP-9 in gelatin zymographic analysis. Thujone treatment significantly inhibited the invasion of B16F-10 melanoma cells across the collagen matrix in a Boyden chamber. Thujone also inhibited the adhesion of tumor cells to collagen-coated microtire plate wells and the migration of B16F-10 melanoma cells across a polycarbonate filter in vitro. These results indicate that Thujone can inhibit the lung metastasis of B16F-10 cells through inhibition of tumor cell proliferation, adhesion, and invasion, as well as by regulating expression of MMPs, VEGF, ERK-1, ERK-2, TIMPs, nm23, and levels of proinflammatory cytokines and IL-2 in metastatic animals.
INFINITE DIMENSIONAL STATIONARY RANDOM FIELDS OVER A LOCALLY COMPACT ABELIAN GROUP
Authors: HEYER HERBERT , RAO M. M.
Published: September 2011

In this paper we consider spectral representation of infinite dimensional stationary random fields over an abelian locally compact (or LCA) group, and then extend the results of earlier authors who consider wide sense Markov random fields over a Euclidean group ℝn to the general LCA group context and obtain minimality properties. We also indicate possibilities of some extensions of these results to certain nonstationary classes.
ACM's copyright policy
Authors: Boisvert Ronald F. , Davidson Jack W.
Published: September 2011

Addressing the needs of authors, readers, and the Association.
From idea to product
Authors: Reed Daniel , Guzdial Mark
Published: September 2011

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Daniel Reed discusses how researchers communicate their project ideas to companies and product groups and get them successfully adopted. Mark Guzdial considers whether schools of education could create more high school CS teachers.
Seeing is not enough
Authors: Geller Tom
Published: September 2011

A new DARPA program is teaching cameras visual intelligence---how to spot and understand human behavior.
The world according to LINQ
Authors: Meijer Erik
Published: September 2011

Big data is about more than size, and LINQ is more than up to the task.
Verification of safety-critical software
Authors: Andersen B. Scott , Romanski George
Published: September 2011

Avionics software safety certification is achieved through objective-based standards.
Computational journalism
Authors: Cohen Sarah , Hamilton James T. , Turner Fred
Published: September 2011

How computer scientists can empower journalists, democracy's watchdogs, in the production of news in the public interest.
Understanding sources of ineffciency in general-purpose chips
Authors: Hameed Rehan , Qadeer Wajahat , Wachs Megan , Azizi Omid , Solomatnikov Alex , Lee Benjamin C. , Richardson Stephen , Kozyrakis Christos , Horowitz Mark
Published: September 2011

Scaling the performance of a power limited processor requires decreasing the energy expended per instruction executed, since energy/op * op/second is power. To better understand what improvement in processor efficiency is possible, and what must be done to capture it, we quantify the sources of the performance and energy overheads of a 720p HD H.264 encoder running on a general-purpose four-processor CMP system. The initial overheads are large: the CMP was 500 x less energy efficient than an Application Specific Integrated Circuit (ASIC) doing the same job. We explore methods to eliminate these overheads by transforming the CPU into a specialized system for H.264 encoding. Broadly applicable optimizations like single instruction, multiple data (SIMD) units improve CMP performance by 14 x and energy by 10x, which is still 50x worse than an ASIC. The problem is that the basic operation costs in H.264 are so small that even with a SIMD unit doing over 10 ops per cycle, 90% of the energy is still overhead. Achieving ASIC-like performance and effciency requires algorithm-specifc optimizations. For each subalgorithm of H.264, we create a large, specialized functional/storage unit capable of executing hundreds of operations per instruction. This improves energy effciency by 160x (instead of 10x), and the final customized CMP reaches the same performance and within 3x of an ASIC solution's energy in comparable area.
Building Rome in a day
Authors: Agarwal Sameer , Furukawa Yasutaka , Snavely Noah , Simon Ian , Curless Brian , Seitz Steven M. , Szeliski Richard
Published: September 2011

We present a system that can reconstruct 3D geometry from large, unorganized collections of photographs such as those found by searching for a given city (e.g., Rome) on Internet photo-sharing sites. Our system is built on a set of new, distributed computer vision algorithms for image matching and 3D reconstruction, designed to maximize parallelism at each stage of the pipeline and to scale gracefully with both the size of the problem and the amount of available computation. Our experimental results demonstrate that it is now possible to reconstruct city-scale image collections with more than a hundred thousand images in less than a day.
Computing for the masses
Authors: Xu Zhiwei , Li Guojie
Published: September 2011

A new paradigm is needed to cope with the application, technology, and discipline challenges to our computing profession in the coming decades.
Extracellular chloride regulation of Kv2.1, contributor to the major outward Kv current in mammalian outer hair cells
Authors: Li Xiantao , Surguchev Alexei , Bian Shumin , Navaratnam Dhasakumar , Santos-Sacchi Joseph
Published: September 2011

Outer hair cells (OHC) function as both receptors and effectors in providing a boost to auditory reception. Amplification is driven by the motor protein prestin, which is under anionic control. Interestingly, we now find that the major, 4-AP-sensitive, outward K+ current of the OHC ( IK) is also sensitive to Cl−, although, in contrast to prestin, extracellularly. IK is inhibited by reducing extracellular Cl− levels, with a linear dependence of 0.4%/mM. Other voltage-dependent K+ (Kv) channel conductances in supporting cells, such as Hensen and Deiters' cells, are not affected by reduced extracellular Cl−. To elucidate the molecular basis of this Cl−-sensitive IK, we looked at potential molecular candidates based on Cl− sensitivity and/or similarities in kinetics. For IK, we identified three different Ca2+-independent components of IK based on the time constant of inactivation: a fast, transient outward current, a rapidly activating, slowly inactivating current ( Ik1), and a slowly inactivating current ( Ik2). Extracellular Cl− differentially affects these components. Because the inactivation time constants of Ik1 and Ik2 are similar to those of Kv1.5 and Kv2.1, we transiently transfected these constructs into CHO cells and found that low extracellular Cl− inhibited both channels with linear current reductions of 0.38%/mM and 0.49%/mM, respectively. We also tested heterologously expressed Slick and Slack conductances, two intracellularly Cl−-sensitive K+ channels, but found no extracellular Cl− sensitivity. The Cl− sensitivity of Kv2.1 and its robust expression within OHCs verified by single-cell RT-PCR indicate that these channels underlie the OHC's extracellular Cl− sensitivity.
Chronic AMPK stimulation attenuates adaptive signaling in dystrophic skeletal muscle
Authors: Ljubicic Vladimir , Khogali Shiemaa , Renaud Jean-Marc , Jasmin Bernard J.
Published: September 2011

In the present study, we evaluated how a pharmacologically induced phenotype shift in dystrophic skeletal muscle would affect subsequent intracellular signaling in response to a complementary, adaptive physiological stimulus. mdx mice were treated with the AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR; 500 mg·kg−1·day−1) for 30 days, and then one-half of the animals were subjected to a bout of treadmill running to induce acute AMPK and p38 MAPK signaling. The mRNA levels of phenotypic modifiers, including peroxisome proliferator-activated receptor-δ (PPARδ), PPARγ coactivator-1α (PGC-1α), receptor interacting protein 140 (RIP 140), and silent information regulator two ortholog 1 (SIRT1) were assessed in skeletal muscle, as well as the expression of the protein arginine methyltransferase genes PRMT1 and CARM1. We found unique AMPK and p38 phosphorylation and expression signatures between dystrophic and healthy muscle. In dystrophic skeletal muscle, treadmill running induced PPARδ, PGC-1α, and SIRT1 mRNAs, three molecules that promote the slow, oxidative myogenic program. In the mdx animals that received the chronic AICAR treatment, running-elicited AMPK and p38 phosphorylation was attenuated compared with vehicle-treated mice. Similarly, acute stress-evoked expression of PPARδ, PGC-1α, and SIRT1 was also blunted by chronic pharmacological AMPK stimulation. Skeletal muscle PRMT1 and CARM1 protein contents were higher in mdx mice compared with wild-type littermates. The acute running-evoked induction of PRMT1 and CARM1 mRNAs was also attenuated by the AICAR treatment. Our data demonstrate that prior pharmacological conditioning is a salient determinant in how dystrophic muscle adapts to subsequent complementary, acute physiological stress stimuli. These results provide insight into possible therapeutic applications of synthetic agonists in neuromuscular diseases, such as during chronic administration to Duchenne muscular dystrophy patients.
Large-scale phosphotyrosine proteomic profiling of rat renal collecting duct epithelium reveals predominance of proteins involved in cell polarity determination
Authors: Zhao Boyang , Knepper Mark A. , Chou Chung-Lin , Pisitkun Trairak
Published: September 2011

Although extensive phosphoproteomic information is available for renal epithelial cells, previous emphasis has been on phosphorylation of serines and threonines with little focus on tyrosine phosphorylation. Here we have carried out large-scale identification of phosphotyrosine sites in pervanadate-treated native inner medullary collecting ducts of rat, with a view towards identification of physiological processes in epithelial cells that are potentially regulated by tyrosine phosphorylation. The method combined antibody-based affinity purification of tyrosine phosphorylated peptides coupled with immobilized metal ion chromatography to enrich tyrosine phosphopeptides, which were identified by LC-MS/MS. A total of 418 unique tyrosine phosphorylation sites in 273 proteins were identified. A large fraction of these sites have not been previously reported on standard phosphoproteomic databases. All results are accessible via an online database: http://helixweb.nih.gov/ESBL/Database/iPY/ . Analysis of surrounding sequences revealed four overrepresented motifs: [D/E]xxY*, Y*xxP, DY*, and Y*E, where the asterisk symbol indicates the site of phosphorylation. These motifs plus contextual information, integrated using the NetworKIN tool, suggest that the protein tyrosine kinases involved include members of the insulin- and ephrin-receptor kinase families. Analysis of the gene ontology (GO) terms and KEGG pathways whose protein elements are overrepresented in our data set point to structures involved in epithelial cell-cell and cell-matrix interactions (“adherens junction,” “tight junction,” and “focal adhesion”) and to components of the actin cytoskeleton as major sites of tyrosine phosphorylation in these cells. In general, these findings mesh well with evidence that tyrosine phosphorylation plays a key role in epithelial polarity determination.
Linkage of gut microbiome with cognition in hepatic encephalopathy
Authors: Bajaj Jasmohan S. , Ridlon Jason M. , Hylemon Phillip B. , Thacker Leroy R. , Heuman Douglas M. , Smith Sean , Sikaroodi Masoumeh , Gillevet Patrick M.
Published: September 2011

Hepatic encephalopathy (HE) has been related to gut bacteria and inflammation in the setting of intestinal barrier dysfunction. We aimed to link the gut microbiome with cognition and inflammation in HE using a systems biology approach. Multitag pyrosequencing (MTPS) was performed on stool of cirrhotics and age-matched controls. Cirrhotics with/without HE underwent cognitive testing, inflammatory cytokines, and endotoxin analysis. Patients with HE were compared with those without HE using a correlation-network analysis. A select group of patients with HE ( n = 7) on lactulose underwent stool MTPS before and after lactulose withdrawal over 14 days. Twenty-five patients [17 HE (all on lactulose, 6 also on rifaximin) and 8 without HE, age 56 ± 6 yr, model for end-stage liver disease score 16 ± 6] and ten controls were included. Fecal microbiota in cirrhotics were significantly different (higher Enterobacteriaceae , Alcaligeneceae , and Fusobacteriaceae and lower Ruminococcaceae and Lachnospiraceae ) compared with controls. We found altered flora (higher Veillonellaceae ), poor cognition, endotoxemia, and inflammation (IL-6, TNF-α, IL-2, and IL-13) in HE compared with cirrhotics without HE. In the cirrhosis group, Alcaligeneceae and Porphyromonadaceae were positively correlated with cognitive impairment. Fusobacteriaceae , Veillonellaceae , and Enterobacteriaceae were positively and Ruminococcaceae negatively related to inflammation. Network-analysis comparison showed robust correlations (all P < 1E-5) only in the HE group between the microbiome, cognition, and IL-23, IL-2, and IL-13. Lactulose withdrawal did not change the microbiome significantly beyond Fecalibacterium reduction. We concluded that cirrhosis, especially when complicated with HE, is associated with significant alterations in the stool microbiome compared with healthy individuals. Specific bacterial families ( Alcaligeneceae , Porphyromonadaceae , Enterobacteriaceae ) are strongly associated with cognition and inflammation in HE.
Short-term exercise preserves myocardial glutathione and decreases arrhythmias after thiol oxidation and ischemia in isolated rat hearts
Authors: Frasier Chad R. , Sloan Ruben C. , Bostian Phillip A. , Gonzon Michael D. , Kurowicki Jennifer , LoPresto Steven J. , Anderson Ethan J. , Brown David A.
Published: September 2011

The purpose of this study was to determine if exercise (Ex) protects hearts from arrhythmias induced by glutathione oxidation or ischemia-reperfusion (I/R). Female Sprague-Dawley rats were divided into two experimental groups: sedentary controls (Sed) or short-term Ex (10 days of treadmill running). Twenty-four hours after the last session, hearts were excised and exposed to either perfusion with the thiol oxidant diamide (200 μM) or global I/R. Ex significantly delayed the time to the onset of ventricular arrhythmia after irreversible diamide perfusion. During a shorter diamide perfusion protocol with washout, Ex significantly decreased the incidence of arrhythmia, as evidenced by a delayed time to the first observed arrhythmia, lower arrhythmia scores, and lower incidence of ventricular fibrillation. Ex hearts exposed to I/R (30-min ischemia/30-min reperfusion) also showed lower arrhythmia scores and incidence of ventricular fibrillation compared with Sed counterparts. Our finding that Ex protected intact hearts from thiol oxidation was corroborated in isolated ventricular myocytes. In myocytes from Ex animals, both the increase in H2O2fluorescence and incidence of cell death were delayed after diamide. Although there were no baseline differences in reduced-to-oxidized glutathione ratios (GSH/GSSG) between the Sed and Ex groups, GSH/GSSG was better preserved in Ex groups after diamide perfusion and I/R. Myocardial glutathione reductase activity was significantly enhanced after Ex, and this was preserved in the Ex group after diamide perfusion. Our results show that Ex protects the heart from arrhythmias after two different oxidative stressors and support the hypothesis that sustaining the GSH/GSSG pool stabilizes cardiac electrical function during conditions of oxidative stress.
Gene Regulation by Cohesin in Cancer: Is the Ring an Unexpected Party to Proliferation?
Authors: Rhodes Jenny M. , McEwan Miranda , Horsfield Julia A.
Published: September 2011

Cohesin is a multisubunit protein complex that plays an integral role in sister chromatid cohesion, DNA repair, and meiosis. Of significance, both over- and underexpression of cohesin are associated with cancer. It is generally believed that cohesin dysregulation contributes to cancer by leading to aneuploidy or chromosome instability. For cancers with loss of cohesin function, this idea seems plausible. However, overexpression of cohesin in cancer appears to be more significant for prognosis than its loss. Increased levels of cohesin subunits correlate with poor prognosis and resistance to drug, hormone, and radiation therapies. However, if there is sufficient cohesin for sister chromatid cohesion, overexpression of cohesin subunits should not obligatorily lead to aneuploidy. This raises the possibility that excess cohesin promotes cancer by alternative mechanisms. Over the last decade, it has emerged that cohesin regulates gene transcription. Recent studies have shown that gene regulation by cohesin contributes to stem cell pluripotency and cell differentiation. Of importance, cohesin positively regulates the transcription of genes known to be dysregulated in cancer, such as Runx1, Runx3, and Myc. Furthermore, cohesin binds with estrogen receptor α throughout the genome in breast cancer cells, suggesting that it may be involved in the transcription of estrogen-responsive genes. Here, we will review evidence supporting the idea that the gene regulation function of cohesin represents a previously unrecognized mechanism for the development of cancer. Mol Cancer Res; 9(12); 1587–607. ©2011 AACR.
High Levels of Comorbidity and Disability Cancel Out the Dementia Effect in Predictions of Long-Term Mortality after Discharge in the Very Old
Authors: Zekry Dina , Herrmann François R. , Graf Christophe E. , Giannelli Sandra , Michel Jean-Pierre , Gold Gabriel , Krause Karl-Heinz
Published: September 2011

Background/Aims: The relative weight of various etiologies of dementia as predictors of long-term mortality after other risk factors have been taken into account remains unclear. We investigated the 5-year mortality risk associated with dementia in elderly people after discharge from acute care, taking into account comorbid conditions and functionality. Methods: A prospective cohort study of 444 patients (mean age: 85 years; 74% female) discharged from the acute geriatric unit of Geneva University Hospitals. On admission, each subject underwent a standardized diagnostic evaluation: demographic variables, cognitive, comorbid medical conditions and functional assessment. Patients were followed yearly by the same team. Predictors of survival at 5 years were evaluated by Cox proportional hazards models. Results: The univariate model showed that being older and male, and having vascular and severe dementia, comorbidity and functional disability, were predictive of shorter survival. However, in the full multivariate model adjusted for age and sex, the effect of dementia type or severity completely disappeared when all the variables were added. In multivariate analysis, the best predictor was higher comorbidity score, followed by functional status (R2 = 23%). Conclusions: The identification of comorbidity and functional impairment effects as predictive factors for long-term mortality independent of cognitive status may increase the accuracy of long-term discharge planning.
Role of Arginase in Impairing Relaxation of Lung Parenchyma of Hyperoxia-Exposed Neonatal Rats
Authors: Ali Nuzhat K.M. , Jafri Anjum , Sopi Ramadan B. , Prakash Y.S. , Martin Richard J. , Zaidi Syed I.A.
Published: September 2011

Background: Prolonged exposure of immature lungs to hyperoxia contributes to neonatal lung injury and airway hyperreactivity. We have previously demonstrated that neonatal exposure of rat pups to ≧95% O2 impairs airway relaxation due to disruption of nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling. Objective: We now hypothesize that these impaired relaxation responses are secondary to hyperoxia-induced upregulation of arginase, which competes with NO synthase for L-arginine. Methods: Rat pups were exposed to moderate neonatal hyperoxia (50% O2) or room air for 7 days from birth. In additional hyperoxic and room air groups, exogenous L-arginine (300 mg/kg/day i.p.) or arginase inhibitor (Nω-hydroxy-nor-arginine, 30 mg/kg/day i.p.) were administered daily. After 7 days, animals were anesthetized and sacrificed either for preparation of lung parenchymal strips or lung perfusion. Results: In response to electrical field stimulation (EFS), bethanechol-preconstricted lung parenchymal strips from hyperoxic pups exhibited significantly reduced relaxation compared to room air controls. Supplementation of L-arginine or arginase blockade restored hyperoxia-induced impairment of relaxation. Expression of arginase I in airway epithelium was increased in response to hyperoxia but reduced by arginase blockade. Arginase activity was also significantly increased in hyperoxic lungs as compared to room air controls and reduced following arginase blockade. EFS-induced production of NO was decreased in hyperoxia-exposed airway smooth muscle and restored by arginase blockade. Conclusion: These data suggest that NO-cGMP signaling is disrupted in neonatal rat pups exposed to even moderate hyperoxia due to increased arginase activity and consequent decreased bioavailability of the substrate L-arginine. We speculate that supplementation of arginine and/or inhibition of arginase may be a useful therapeutic tool to prevent or treat neonatal lung injury.
Early Postnatal Surge of Serum Clara Cell Secretory Protein in Newborn Infants
Authors: Loughran-Fowlds A.S. , Lin J.W. , Oei J. , Michalowski J. , Henry R. , Lui K.
Published: September 2011

Background: Clara cell secretory protein (CCSP) is an anti-inflammatory mediator, but its role in neonatal lung adaptation and diseases is uncertain. Objective: To characterize postnatal changes in serum CCSP in relation to gestation, respiratory disease (RDS) and bronchopulmonary dysplasia (BPD) in comparison with other anti-inflammatory cytokines (IL-4, -10 and -13). Methods: Blood was collected from 76 infants (26 of 23–29 weeks’ gestation, 33 of 30–36 weeks’ gestation and 17 term infants) at birth (preterm cord blood); on admission; at 12, 24 and 48 h; and on days 3–4 and 7 of life. CCSP was assayed by ELISA and cytokines by Bio-Plex. Results: Median serum CCSP in extremely and moderately preterm infants rose from a baseline of 13.6 and 15.9 to 33.4 ng/ml (p = 0.04) and 59.8 ng/ml (p = 0.03) at 12 h of age, respectively. CCSP levels were highest in term infants (80.7 ng/ml at 12 h). CCSP then decreased to 22.5 ng/ml on days 3–4 (p = 0.001). CCSP of 37 RDS infants fell to a lower baseline on days 4 and 7 than that of the 22 non-RDS preterms. The 8 infants who developed BPD had persistently low serum CCSP (12.7 ng/ml at 12 h). In contrast, early postnatal changes were not seen in IL-4, -10 and -13 levels, but low IL-10 and -13 levels were found on day 7 in BPD infants. Conclusions: Serum CCSP levels were characterized by an early postnatal surge. This apparent gestation-influenced surge may represent an initiation of a protective cascade against postnatal lung injury during extrauterine adaptation.
Toll-Like Receptor 1/2 Stimulation Induces Elevated Interleukin-8 Secretion in Polymorphonuclear Leukocytes Isolated from Preterm and Term Newborn Infants
Authors: Thornton Nathan L. , Cody Mark J. , Yost Christian C.
Published: September 2011

Background: Neonatal neutrophil dysfunction contributes to inflammatory tissue damage in newborn infants. Toll-like receptors (TLRs) activate the innate immune response through recognition of pathogen-associated molecular patterns. Expression and function of TLRs by neonatal neutrophils has not well been characterized. Objective: We hypothesized that, compared to polymorphonuclear leukocytes (PMNs) isolated from adults, neonatal PMNs isolated from either term or preterm infants express and release different levels of inflammatory cytokines and chemokines in response to stimulation with TLR1–9 agonists. Methods: We stimulated PMNs isolated from preterm (n = 12) and term (n = 10) infants as well as adults (n = 10) with agonists recognized by TLRs1–9 and quantified chemokine and cytokine expression and secretion by ELISA and Luminex® multiplex quantification assay. Results: Neonatal and adult PMNs stimulated with agonists recognized by TLRs1–9 differentially secrete inflammatory products. Signaling via TLR2 heterodimers is a potent mechanism for release of interleukin-8, a critical proinflammatory chemokine, by neonatal PMNs – a previously unrecognized facet of neonatal inflammation. Following TLR1/2 (PAM3CSK4) stimulation, interleukin-8 secretion by neonatal PMNs, whether term or preterm, substantially exceeds that of adult PMNs assayed in parallel. Conclusions: These studies provide new insights relevant to the inflammatory biology of neonates, both term and preterm, and implicate exaggerated PMN recruitment in neonatal syndromes of dysregulated inflammation such as necrotizing enterocolitis or neonatal chronic lung disease.
Thin Bronchoscope for Evaluating Stenotic Airways during Stenting Procedures
Authors: Oki Masahide , Saka Hideo
Published: September 2011

Background: Flexible bronchoscopy can play an important role in the evaluation of an airway lumen during therapeutic bronchoscopic procedures. Despite its potential usefulness, however, evaluation with a standard-sized bronchoscope, which cannot pass completely through a severely stenosed airway, is often unsatisfactory. Objectives: This study aimed to evaluate the usefulness of prototype thin bronchoscopes for assessing stenotic airways during stenting procedures. Methods: Forty-six patients with central airway stenosis requiring stent implantation were enrolled in this prospective study. After inserting a rigid bronchoscope under general anesthesia, a flexible bronchoscopic evaluation using a 5.9- or 6.0-mm standard bronchoscope was performed, followed by evaluation using a prototype 3.4- or 3.5-mm thin bronchoscope for airways beyond the site of stenosis, which could not be visualized by the standard bronchoscope. Results: A standard bronchoscope could not pass through the stenotic airway in 15 of 46 patients (33%). On univariate analysis, the grade of stenosis (p < 0.001), the presence or absence of atelectasis (p = 0.04) and the presence or absence of viscous secretions (p = 0.02) were related to the rate of successful passage by a standard bronchoscope. On multivariate analysis, only the grade of stenosis remained independently associated with the success rate. In 12 of the 15 patients (80%), the airway lumen beyond the stenotic lesion, which could not be reached by a standard bronchoscope, was successfully visualized and evaluated with a thin bronchoscope. No significant complications were associated with the procedures. Conclusion: The thin bronchoscope can be a useful tool for evaluating a severely stenosed airway during the stenting procedure.
Left Ventricular Noncompaction in a Patient with Fabry Disease: Overdiagnosis, Morphological Manifestation of Fabry Disease or Two Unrelated Rare Conditions in the Same Patient?
Authors: Azevedo Olga , Gaspar Paulo , Sá Miranda Clara , Cunha Damião , Medeiros Rosa , Lourenço António
Published: September 2011

We report a clinical case of a young female with Fabry disease but without left ventricular hypertrophy, which fulfills the diagnostic criteria of left ventricular noncompaction (LVNC). To our knowledge, this is the first report of LVNC in a patient with Fabry disease. The possibility of an overdiagnosis of LVNC is discussed based on the limitations of the current diagnostic criteria. This case was further investigated by genetic analysis, which came to demonstrate the limited usefulness of genetic testing in the diagnosis of LVNC. Assuming a true trabecular pattern of LVNC, the hypothesis that the same patient has two unrelated and rare conditions, although possible, is unlikely. The genetic and clinical heterogeneity of LVNC is discussed and supports, along with this clinical case, the hypothesis that LVNC is a morphological expression of different diseases rather than a distinct cardiomyopathy. Accordingly, LVNC could be a rare cardiac manifestation of Fabry disease.
Thalidomide in 42 Patients with Prurigo Nodularis Hyde
Authors: Andersen Tina P. , Fogh Karsten
Published: September 2011

The aim of this study was to describe the use of thalidomide in the treatment of prurigo nodularis Hyde (PNH) refractory to other treatments or in cases where other treatments cannot be used due to side effects. 77 medical records were retrospectively reviewed for the following data: sex, age, age at the beginning of thalidomide treatment, dermatological diagnosis, duration of the skin disease, previous treatments, indications for treatment with thalidomide, effect of treatment, duration of treatment with thalidomide, reasons for cessation of thalidomide treatment, and side effects. 54 patients had PNH. All patients were refractory to standard therapy or had side effects to treatment. 42 patients were treated with thalidomide and the majority of patients experienced clinical improvement. The most common reason for discontinuation of therapy was side effects, the most frequent being peripheral neuropathy and sedation. Thalidomide effectively treats PNH refractory to standard medications. However, physicians must be aware of possible side effects, especially peripheral neuropathy.
Serum Response Factor Regulates Expression of Phosphatase and Tensin Homolog Through a MicroRNA Network in Vascular Smooth Muscle Cells
Authors: Horita Henrick N. , Simpson Peter A. , Ostriker Allison , Furgeson Seth , Van Putten Vicki , Weiser-Evans Mary C.M. , Nemenoff Raphael A.
Published: September 2011

Objective—

Serum response factor (SRF) is a critical transcription factor in smooth muscle cells (SMCs) controlling differentiation and proliferation. Our previous work demonstrated that depleting SRF in cultured SMCs decreased expression of SMC markers but increased proliferation and inflammatory mediators. A similar phenotype has been observed in SMCs silenced for phosphatase and tensin homolog (PTEN), suggesting that SRF and PTEN may lie on a common pathway. Our goal was to determine the effect of SRF depletion on PTEN levels and define mechanisms mediating this effect.

Methods and Results—

In SRF-silenced SMCs, PTEN protein levels but not mRNA levels were decreased, suggesting posttranscriptional regulation. Reintroduction of PTEN into SRF-depleted SMCs reversed increases in proliferation and cytokine/chemokine production but had no effect on SMC marker expression. SRF-depleted cells showed decreased levels of microRNA (miR)-143 and increased miR-21, which was sufficient to suppress PTEN. Increased miR-21 expression was dependent on induction of Fos related antigen (FRA)-1, which is a direct target of miR-143. Introducing miR-143 into SRF-depleted SMCs reduced FRA-1 expression and miR-21 levels and restored PTEN expression.

Conclusion—

SRF regulates PTEN expression in SMCs through a miR network involving miR-143, targeting FRA-1, which regulates miR-21. Cross-talk between SRF and PTEN likely represents a critical axis in phenotypic remodeling of SMCs.
Positive Cross-Talk Between Hypoxia Inducible Factor-1α and Liver X Receptor α Induces Formation of Triglyceride-Loaded Foam Cells
Authors: Na Tae-Young , Lee Hyo-Jeong , Oh Hyeon-Jeong , Huh Seung , Lee In-Kyu , Lee Mi-Ock
Published: September 2011

Objective—

Atherosclerosis is a chronic and progressive inflammatory disease of the arteries that is characterized by subendothelial accumulation of lipid-rich macrophages, called foam cells. We sought to identify the molecular details of cross-talk between liver X receptor α (LXRα) and hypoxia-inducible factor 1α (HIF-1α) for the formation of triglyceride-rich foam cells under hypoxic conditions.

Methods and Results—

We first observed that expression of LXRα and its target lipogenic genes was time-dependently induced in human primary macrophages and RAW 264.7 cells under hypoxia. Similarly, TO901317, an activator of LXRα, enhanced the expression level and the transcriptional activity of HIF-1α. Second, we demonstrated that LXRα increased HIF-1α protein stability through a physical interaction between the ligand binding domain of LXRα and the oxygen-dependent degradation domain of HIF-1α. Third, we found that the activation of HIF-1α or LXRα synergistically induced triglyceride accumulation in macrophages. Finally, we showed that LXRα and HIF-1α were codistributed in the macrophages of atherosclerotic lesions of patients.

Conclusion—

These results suggest that the positive feed-forward regulation of transcriptional activity and protein stability of LXRα and HIF-1α has an important impact in foam cell formation.
Novel In Vivo Method for Measuring Cholesterol Mass Flux in Peripheral Macrophages
Authors: Weibel Ginny L. , Hayes Sara , Wilson Aisha , Phillips Michael C. , Billheimer Jeffrey , Rader Daniel J. , Rothblat George H.
Published: September 2011

Objective—

Reverse cholesterol transport is the process by which excess cholesterol is removed from peripheral tissue by HDL and delivered to the liver for excretion. Presently, methods of measuring in vivo reverse cholesterol transport do so by monitoring the appearance in the feces of labeled cholesterol that originated from peripheral macrophage foam cells. These methods do not account for changes in macrophage cholesterol mass. We have developed an in vivo assay to measure cholesterol mass changes in atherosclerotic foam cells.

Methods and Results—

Macrophages are entrapped in semipermeable (pore size 0.2 μm) hollow fibers and surgically implanted into the peritoneum of recipient mice. The fibers are removed from the peritoneum 24 hours after implantation. This method allows the complete recovery of the macrophages for quantification of changes in cholesterol mass and cellular protein. In wild-type mice we measured a significant reduction in total cell cholesterol (TC) when hollow fibers containing cholesterol-enriched macrophage cells were implanted (TC before implantation=105±18 μg/mg cell protein, TC 24 hours after implantation=60±16 μg/mg protein). Additionally, there was an increase in cholesterol content when hollow fibers containing cholesterol-normal macrophages were implanted in an atherogenic mouse model (LDLr/apobec dko) compared to a wild-type mouse (initial TC content=57±24 μg/mg protein, TC 24 hours after implantation: wild-type mice=52±10 μg/mg protein; LDLr/apobec dko mice=118±27 μg/mg protein).

Conclusion—

This assay can quantify in vivo both cholesterol mass accumulation, and reduction, in macrophages. This method permits quantitative analysis of the progression and regression of foam cells.
AMP-Activated Protein Kinase Suppresses Endothelial Cell Inflammation Through Phosphorylation of Transcriptional Coactivator p300
Authors: Zhang Yuan , Qiu Jian , Wang Xiaoming , Zhang Yuhua , Xia Min
Published: September 2011

Objective—

Considerable evidence supports the early involvement of monocyte/macrophage recruitment to activated endothelial cells by leukocyte adhesion molecules during atherogenesis. AMP-activated protein kinase (AMPK) is highly expressed in vascular endothelial cells, but its impact on monocyte adhesion and the related mechanisms are not fully understood. The present study was designed to evaluate the impact of and gain mechanistic insight into the signaling coupling AMPK function to the antiinflammatory response.

Methods and Results—

5-Aminoimidazole-4-carboxamide-1-β-
d
-ribonucleotide (AICAR) treatment or overexpression of constitutively active AMPK markedly reduced human monocytic human acute monocytic leukemia cell line-1 cell adhesion and the expression of vascular cell adhesion molecule-1 in tumor necrosis factor-α–activated human aortic endothelial cells. Furthermore, AICAR or constitutively active AMPK overexpression strongly inhibited the histone acetyltransferase activity of the transcriptional coactivator p300 by phosphorylation of Ser89, which in turn decreased tumor necrosis factor-α-activated p300-mediated acetylation of nuclear factor-κB p65 on Lys221 and reduced the DNA binding activity of nuclear factor-κB by inhibiting its recruitment to its target gene promoters. AMPK phosphorylates the transcriptional coactivator p300 via the atypical protein kinase Cι/λ.

Conclusion—

Our findings demonstrate that transcriptional coactivator p300 phosphorylation at Ser89 by AMPK is critical for the therapeutic effect of AMPK and may be a potential target for pharmaceutical intervention in inflammatory diseases such as atherosclerosis.
Blood–Brain Barrier Breakdown in Acute and Chronic Cerebrovascular Disease
Authors: Yang Yi , Rosenberg Gary A.
Published: September 2011

Disruptions of the blood–brain barrier (BBB) and edema formation both play key roles in the development of neurological dysfunction in acute and chronic cerebral ischemia. Animal studies have revealed the molecular cascades that are initiated with hypoxia/ischemia in the cells forming the neurovascular unit and that contribute to cell death. Matrix metalloproteinases cause reversible degradation of tight junction proteins early after the onset of ischemia, and a delayed secondary opening during a neuroinflammatory response occurring from 24 to 72 hours after. Cyclooxygenases are important in the delayed opening as the neuroinflammatory response progresses. An early opening of the BBB within the 3-hour therapeutic window for tissue-type plasminogen activator can allow it to enter the brain and increase the risk of hemorrhage. Chronic hypoxic hypoperfusion opens the BBB, which contributes to the cognitive changes seen with lacunar strokes and white matter injury in subcortical ischemic vascular disease. This review will describe the molecular and cellular events associated with BBB disruption and potential therapies directed toward restoring the integrity of the neurovascular unit.
Meta-analysis of Dysphagia and Aspiration Pneumonia in Frail Elders
Authors: van der Maarel-Wierink C.D. , Vanobbergen J.N.O. , Bronkhorst E.M. , Schols J.M.G.A. , de Baat C.
Published: September 2011

As part of a systematic literature review, a comprehensive literature search was carried out to identify risk factors for aspiration pneumonia in frail older people. A prominent risk factor found was dysphagia with evidence level 2a, according to the Oxford Centre for Evidence-based Medicine Levels of Evidence. Subsequently, a meta-analysis of 4 cohort, 1 case-cohort, and 1 case-control study on dysphagia as a risk factor of aspiration pneumonia in frail older people was performed. Using a random effects model, we found a positive correlation between dysphagia and aspiration pneumonia: OR = 9.84; 95%CI = 4.15 - 23.33 (test for statistical homogeneity: p < 0.001). Then, a subgroup meta-analysis was performed with 4 cohort studies, all including patients with a cerebrovascular disease. Once again, a positive correlation was found between dysphagia and aspiration pneumonia: OR = 12.93; 95%CI = 8.61 - 19.44. The test for statistical homogeneity revealed no statistically significant result (p = 0.15). It was concluded that dysphagia is a serious risk factor for aspiration pneumonia in frail older people, particularly in those suffering from a cerebrovascular disease.
Periodontitis Predicts Elevated C-reactive Protein Levels in Chronic Kidney Disease
Authors: Ioannidou E. , Swede H. , Dongari-Bagtzoglou A.
Published: September 2011

Based on the existing evidence supporting a state of chronic inflammation in chronic kidney disease (CKD), we hypothesized that periodontal infection may affect the systemic inflammatory status of a nationally representative CKD population as measured by serum C-reactive protein (CRP). We examined this hypothesis using the National Health and Nutrition Examination Survey 1988-1994 (NHANES III) dataset including 2303 individuals. We followed the American Academy of Periodontology (AAP)/Centers for Disease Control and Prevention (CDC) case definition for periodontitis. We used a cutoff point of 30% sites with (PD) ≥ 5 mm and (CAL) ≥ 4 mm to define generalized periodontitis cases. We estimated glomerular filtration rate based on cystatin C levels using the relevant equation. Urinary albumin-to-creatinine ratio was calculated in milligrams per gram with a cutoff point of 30 mg/g. CKD was defined based on eGFR < 60 mL/min/1.73m2 and albuminuria ≥ 30 mg/g. Periodontitis was found in 427 (12.3%) individuals. Of individuals with periodontitis, 41.8% had serum CRP higher than 0.3 mg/dL compared with 27.1% of non-periodontitis and 53.1% of edentulous individuals (p = 0.001 for all comparisons). When the extent of periodontitis was used as one of the independent variables, the parsimonious model showed a strong independent association between extent of periodontitis and serum CRP levels (OR = 2.0, CI95% = 1.2-3.6).
Effect of UVA-activated Riboflavin on Dentin Bonding
Authors: Cova A. , Breschi L. , Nato F. , Ruggeri A. , Carrilho M. , Tjäderhane L. , Prati C. , Di Lenarda R. , Tay F.R. , Pashley D.H. , Mazzoni A.
Published: September 2011

Recent studies have reported collagen cross-linking after exposure to riboflavin followed by ultraviolet-A (UVA) exposure. This study is the first to investigate the effect of a riboflavin-containing primer on adhesive interface stability and dentinal matrix metalloproteinase activity. Human dentin was etched with 35% phosphoric acid, treated with 0.1% riboflavin, exposed to UVA for 2 min, and bonded with a two-step etch-and-rinse adhesive. Adhesive was applied to control specimens without riboflavin/UVA. Specimens were subjected to microtensile bond strength tests and pulled to failure after storage for 24 hrs, 6 mos, or 1 yr. Interfacial nanoleakage was evaluated by light and transmission electron microscopy. To investigate dentinal matrix metalloproteinase activity, we performed correlative zymographic assays on protein extracts obtained from phosphoric-acid-etched dentin powder with or without riboflavin/UVA treatment and XP Bond. Ultraviolet-activated riboflavin treatment increased the immediate bond strength to dentin at all aging intervals (p < 0.05 vs. control) and decreased interfacial nanoleakage in aged specimens (1 yr; p < 0.05). Zymograms revealed that riboflavin/UVA pre-treatment inhibited dentinal matrix metalloproteinase activity (especially MMP-9). In conclusion, dentinal collagen cross-linking induced by riboflavin/UVA increased immediate bond strength, stabilized the adhesive interface, and inhibited dentin matrix metalloproteinases, thereby increasing the durability of resin-dentin bonds.