bluuebunny/crossref_metadata_2025 huggingface dataset:
Deacetylated GM3 Promotes uPAR-Associated Membrane Molecular Complex to Activate p38 MAPK in Metastatic Melanoma
Authors: Yan Qiu , Bach Daniel Q. , Gatla Nandita , Sun Ping , Liu Ji-Wei , Lu Jian-Yun , Paller Amy S. , Wang Xiao-Qi
Published: March 2013

GM3, the simplest ganglioside, regulates cell proliferation, migration, and invasion by influencing cell signaling at the membrane level. Although the classic N-acetylated form of GM3 (NeuAcLacCer) is commonly expressed and has been well studied, deacetylated GM3 (NeuNH2LacCer, d-GM3) has been poorly investigated, despite its presence in metastatic tumors but not in noninvasive melanomas or benign nevi. We have recently found that d-GM3 stimulates cell migration and invasion by activating urokinase plasminogen activator receptor (uPAR) signaling to augment matrix metalloproteinase-2 (MMP-2) function. However, the mechanisms by which d-GM3/uPAR increase MMP-2 expression and activation are not clear. By modifying the expression of d-GM3 genetically and biochemically, we found that decreasing d-GM3 expression inhibits, whereas overexpressing d-GM3 stimulates, p38 mitogen-activated protein kinase (MAPK) activity to influence MMP-2 expression and activation. p38 MAPK (p38) activation requires the formation of a membrane complex that contains uPAR, caveolin-1, and integrin α5β1 in membrane lipid rafts. In addition, knocking down or inhibiting focal adhesion kinase (FAK), phosphoinositide 3-kinase (PI3K), or Src kinase significantly reduces d-GM3–induced p38 phosphorylation and activation. Taken together, these results suggest that d-GM3 enhances the metastatic phenotype by activating p38 signaling through uPAR/integrin signaling with FAK, PI3K, and Src kinase as intermediates. Elucidation of the mechanisms by which d-GM3, a newly discovered, potential biomarker of metastatic melanomas, promotes cell metastasis will help us to understand the function of d-GM3 in metastatic melanomas and may lead to novel GM3-based cancer therapies. Mol Cancer Res; 11(6); 665–75. ©2013 AACR.
Fatty Acid Receptor Gpr40 Mediates Neuromicrovascular Degeneration Induced by Transarachidonic Acids in Rodents
Authors: Honoré Jean-Claude , Kooli Amna , Hamel David , Alquier Thierry , Rivera José-Carlos , Quiniou Christiane , Hou Xin , Kermorvant-Duchemin Elsa , Hardy Pierre , Poitout Vincent , Chemtob Sylvain
Published: March 2013

Objective—

Nitro-oxidative stress exerts a significant role in the genesis of hypoxic-ischemic (HI) brain injury. We previously reported that the ω-6 long chain fatty acids, transarachidonic acids (TAAs), which are nitrative stress-induced nonenzymatically generated arachidonic acid derivatives, trigger selective microvascular endothelial cell death in neonatal neural tissue. The primary molecular target of TAAs remains unidentified. GPR40 is a G protein–coupled receptor activated by long chain fatty acids, including ω-6; it is highly expressed in brain, but its functions in this tissue are largely unknown. We hypothesized that TAAs play a significant role in neonatal HI-induced cerebral microvascular degeneration through GPR40 activation.

Approach and Results—

Within 24 hours of a HI insult to postnatal day 7 rat pups, a cerebral infarct and a 40% decrease in cerebrovascular density was observed. These effects were associated with an increase in nitrative stress markers (3-nitrotyrosine immunoreactivity and TAA levels) and were reduced by treatment with nitric oxide synthase inhibitor. GPR40 was expressed in rat pup brain microvasculature. In vitro, in GPR40-expressing human embryonic kidney (HEK)-293 cells, [
14
C]-14
E
-AA (radiolabeled TAA) bound specifically, and TAA induced calcium transients, extracellular signal–regulated kinase 1/2 phosphorylation, and proapoptotic thrombospondin-1 expression. In vivo, intracerebroventricular injection of TAAs triggered thrombospondin-1 expression and cerebral microvascular degeneration in wild-type mice, but not in GPR40-null congeners. Additionally, HI-induced neurovascular degeneration and cerebral infarct were decreased in GPR40-null mice.

Conclusions—

GPR40 emerges as the first identified G protein–coupled receptor conveying actions of nonenzymatically generated nitro-oxidative products, specifically TAAs, and is involved in (neonatal) HI encephalopathy.
Association of the Thrombomodulin Gene c.1418C>T Polymorphism With Thrombomodulin Levels and With Venous Thrombosis Risk
Authors: Navarro Silvia , Medina Pilar , Bonet Elena , Corral Javier , Martínez-Sales Vicenta , Martos Laura , Rivera Miguel , Roselló-Lletí Esther , Alberca Ignacio , Roldán Vanessa , Mira Yolanda , Ferrando Fernando , Estellés Amparo , Vicente Vicente , Bertina Rogier M. , España Francisco
Published: March 2013

Objective—

To investigate the association of the
THBD
c.1418C>T polymorphism, which encodes for the replacement of Ala455 by Val in thrombomodulin (TM), with venous thromboembolism (VTE), plasma soluble TM, and activated protein C levels. In addition, human umbilical vein endothelial cells (HUVEC) isolated from 100 umbilical cords were used to analyze the relation between this polymorphism and
THBD
mRNA and TM protein expression.

Approach and Results—

The
THBD
c.1418C>T polymorphism was genotyped in 1173 patients with VTE and 1262 control subjects. Levels of soluble TM and activated protein C were measured in 414 patients with VTE (not on oral anticoagulants) and 451 controls. HUVECs were genotyped for the polymorphism and analyzed for
THBD
mRNA and TM protein expression and for the ability to enhance protein C activation by thrombin. The 1418T allele frequency was lower in patients than in controls (
P
<0.001), and its presence was associated with a reduced VTE risk, reduced soluble TM levels, and increased circulating activated protein C levels (
P
<0.001). In cultured HUVEC, the 1418T allele did not influence
THBD
expression but was associated with increased TM in cell lysates, increased rate of protein C activation, and reduced soluble TM levels in conditioned medium.

Conclusions—

The
THBD
1418T allele is associated with lower soluble TM, both in plasma and in HUVEC-conditioned medium, and with an increase in functional membrane–bound TM in HUVEC, which could explain the increased activated protein C levels and the reduced VTE risk observed in individuals carrying this allele.
Leptin-Dependent and Leptin-Independent Paracrine Effects of Perivascular Adipose Tissue on Neointima Formation
Authors: Schroeter Marco R. , Eschholz Norman , Herzberg Sebastian , Jerchel Isabel , Leifheit-Nestler Maren , Czepluch Frauke S. , Chalikias Georgios , Konstantinides Stavros , Schäfer Katrin
Published: March 2013

Objective—

Clinical and experimental evidence suggests that periadventitial adipose tissue may modulate vascular lesion formation. The aim of this study was to determine the role of perivascular leptin expression on neointima formation and to differentiate it from local inflammation and systemically elevated leptin levels.

Approach and Results—

Increased neointima formation after carotid artery injury was observed in hyperleptinemic, diet–induced obese wild-type mice, but not in leptin-deficient
ob/ob
mice. High-fat diet was associated with increased leptin expression in visceral adipose tissue (VAT) as well as in perivascular adipose tissue. Perivascular leptin overexpression achieved by adenoviral vectors enhanced intimal cell proliferation and neointima formation in wild-type mice, but not in leptin receptor–deficient mice. Perivascular transplantation of VAT from high-fat diet–induced obese wild-type mice around the carotid artery of immunodeficient mice also promoted neointima formation, without affecting body weight or systemic leptin levels, and this effect was absent, if VAT from
ob/ob
mice was used. On the contrary, perivascular transplantation of VAT from
ob/ob
mice fed high-fat diet, characterized by marked immune cell accumulation, promoted neointimal hyperplasia also in the absence of leptin. In vitro, recombinant leptin and VAT-conditioned medium increased human arterial smooth muscle cell proliferation in a (partly) leptin-dependent manner.

Conclusions—

Our findings suggest that locally elevated leptin levels may promote neointima formation, independent of obesity and systemic hyperleptinemia, but also underline the importance of perivascular inflammation in mediating the increased cardiovascular risk in obesity.
β-Arrestin-2 Deficiency Attenuates Abdominal Aortic Aneurysm Formation in Mice
Authors: Trivedi Darshini B. , Loftin Charles D. , Clark James , Myers Page , DeGraff Laura M. , Cheng Jennifer , Zeldin Darryl C. , Langenbach Robert
Published: March 2013

Rationale:

Abdominal aortic aneurysms (AAAs) are a chronic inflammatory vascular disease for which pharmacological treatments are not available. A mouse model of AAA formation involves chronic infusion of angiotensin II (AngII), and previous studies indicated a primary role for the AngII type 1a receptor in AAA formation. β-arrestin (βarr)-2 is a multifunctional scaffolding protein that binds G-protein–coupled receptors such as AngII type 1a and regulates numerous signaling pathways and pathophysiological processes. However, a role for βarr2 in AngII-induced AAA formation is currently unknown.

Objective:

To determine whether βarr2 played a role in AngII-induced AAA formation in mice.

Methods and Results:

Treatment of βarr2
+/+
and βarr2
−/−
mice on the hyperlipidemic apolipoprotein E–deficient (apoE
−/−
) background or on normolipidemic C57BL/6 background with AngII for 28 days indicated that βarr2 deficiency significantly attenuated AAA formation. βarr2 deficiency attenuated AngII-induced expression of cyclooxygenase-2, monocyte chemoattractant protein-1, macrophage inflammatory protein 1α, and macrophage infiltration. AngII also increased the levels of phosphorylated extracellular signal-regulated kinase 1/2 in apoE
−/−
/βarr2
+/+
aortas, whereas βarr2 deficiency diminished this increase. Furthermore, inhibition of extracellular signal-regulated kinase 1/2 activation with CI1040 (100 mg/kg per day) reduced the level of AngII-induced cyclooxygenase-2 expression in apoE
−/−
/βarr2
+/+
mice to the level observed in apoE
−/−
/βarr2
−/−
mice. AngII treatment also increased matrix metalloproteinase expression and disruption of the elastic layer in apoE
−/−
/βarr2
+/+
aortas, and βarr2 deficiency reduced these effects.

Conclusions:

βarr2 contributes to AngII-induced AAA formation in mice by phosphorylated extracellular signal-regulated kinase 1/2–mediated cyclooxygenase-2 induction and increased inflammation. These studies suggest that for the AngII type 1a receptor, G-protein–independent, βarr2-dependent signaling plays a major role in AngII-induced AAA formation.
Control of Cholesterol Metabolism and Plasma High-Density Lipoprotein Levels by microRNA-144
Authors: Ramírez Cristina M. , Rotllan Noemi , Vlassov Alexander V. , Dávalos Alberto , Li Mu , Goedeke Leigh , Aranda Juan F. , Cirera-Salinas Daniel , Araldi Elisa , Salerno Alessandro , Wanschel Amarylis , Zavadil Jiri , Castrillo Antonio , Kim Jungsu , Suárez Yajaira , Fernández-Hernando Carlos
Published: March 2013

Rationale:

Foam cell formation because of excessive accumulation of cholesterol by macrophages is a pathological hallmark of atherosclerosis, the major cause of morbidity and mortality in Western societies. Liver X nuclear receptors (LXRs) regulate the expression of the adenosine triphosphate–binding cassette (ABC) transporters, including adenosine triphosphate–binding cassette transporter A1 (ABCA1) and adenosine triphosphate–binding cassette transporter G1 (ABCG1). ABCA1 and ABCG1 facilitate the efflux of cholesterol from macrophages and regulate high-density lipoprotein (HDL) biogenesis. Increasing evidence supports the role of microRNA (miRNAs) in regulating cholesterol metabolism through ABC transporters.

Objective:

We aimed to identify novel miRNAs that regulate cholesterol metabolism in macrophages stimulated with LXR agonists.

Methods and Results:

To map the miRNA expression signature of macrophages stimulated with LXR agonists, we performed an miRNA profiling microarray analysis in primary mouse peritoneal macrophages stimulated with LXR ligands. We report that LXR ligands increase miR-144 expression in macrophages and mouse livers. Overexpression of miR-144 reduces ABCA1 expression and attenuates cholesterol efflux to apolipoproteinA1 in macrophages. Delivery of miR-144 oligonucleotides to mice attenuates ABCA1 expression in the liver, reducing HDL levels. Conversely, silencing of miR-144 in mice increases the expression of ABCA1 and plasma HDL levels. Thus, miR-144 seems to regulate both macrophage cholesterol efflux and HDL biogenesis in the liver.

Conclusions:

miR-144 regulates cholesterol metabolism via suppressing ABCA1 expression and modulation of miRNAs may represent a potential therapeutical intervention for treating dyslipidemia and atherosclerotic vascular disease.
MicroRNA-22 Regulates Cardiac Hypertrophy and Remodeling in Response to Stress
Authors: Huang Zhan-Peng , Chen Jinghai , Seok Hee Young , Zhang Zheng , Kataoka Masaharu , Hu Xiaoyun , Wang Da-Zhi
Published: March 2013

Rationale:

The adult heart is composed primarily of terminally differentiated, mature cardiomyocytes that express signature genes related to contraction. In response to mechanical or pathological stress, the heart undergoes hypertrophic growth, a process defined as an increase in cardiomyocyte cell size without an increase in cell number. However, the molecular mechanism of cardiac hypertrophy is not fully understood.

Objective:

To identify and characterize microRNAs that regulate cardiac hypertrophy and remodeling.

Methods and Results:

Screening for muscle-expressed microRNAs that are dynamically regulated during muscle differentiation and hypertrophy identified microRNA-22 (miR-22) as a cardiac- and skeletal muscle–enriched microRNA that is upregulated during myocyte differentiation and cardiomyocyte hypertrophy. Overexpression of miR-22 was sufficient to induce cardiomyocyte hypertrophy. We generated mouse models with global and cardiac-specific miR-22 deletion, and we found that cardiac miR-22 was essential for hypertrophic cardiac growth in response to stress. miR-22–null hearts blunted cardiac hypertrophy and cardiac remodeling in response to 2 independent stressors: isoproterenol infusion and an activated calcineurin transgene. Loss of miR-22 sensitized mice to the development of dilated cardiomyopathy under stress conditions. We identified Sirt1 and Hdac4 as miR-22 targets in the heart.

Conclusions:

Our studies uncover miR-22 as a critical regulator of cardiomyocyte hypertrophy and cardiac remodeling.
Drug Screening Using a Library of Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes Reveals Disease-Specific Patterns of Cardiotoxicity
Authors: Liang Ping , Lan Feng , Lee Andrew S. , Gong Tingyu , Sanchez-Freire Veronica , Wang Yongming , Diecke Sebastian , Sallam Karim , Knowles Joshua W. , Wang Paul J. , Nguyen Patricia K. , Bers Donald M. , Robbins Robert C. , Wu Joseph C.
Published: March 2013

Background—

Cardiotoxicity is a leading cause for drug attrition during pharmaceutical development and has resulted in numerous preventable patient deaths. Incidents of adverse cardiac drug reactions are more common in patients with preexisting heart disease than the general population. Here we generated a library of human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) from patients with various hereditary cardiac disorders to model differences in cardiac drug toxicity susceptibility for patients of different genetic backgrounds.

Methods and Results—

Action potential duration and drug-induced arrhythmia were measured at the single cell level in hiPSC-CMs derived from healthy subjects and patients with hereditary long QT syndrome, familial hypertrophic cardiomyopathy, and familial dilated cardiomyopathy. Disease phenotypes were verified in long QT syndrome, hypertrophic cardiomyopathy, and dilated cardiomyopathy hiPSC-CMs by immunostaining and single cell patch clamp. Human embryonic stem cell–derived cardiomyocytes (hESC-CMs) and the human
ether-a-go-go
–related gene expressing human embryonic kidney cells were used as controls. Single cell PCR confirmed expression of all cardiac ion channels in patient-specific hiPSC-CMs as well as hESC-CMs, but not in human embryonic kidney cells. Disease-specific hiPSC-CMs demonstrated increased susceptibility to known cardiotoxic drugs as measured by action potential duration and quantification of drug-induced arrhythmias such as early afterdepolarizations and delayed afterdepolarizations.

Conclusions—

We have recapitulated drug-induced cardiotoxicity profiles for healthy subjects, long QT syndrome, hypertrophic cardiomyopathy, and dilated cardiomyopathy patients at the single cell level for the first time. Our data indicate that healthy and diseased individuals exhibit different susceptibilities to cardiotoxic drugs and that use of disease-specific hiPSC-CMs may predict adverse drug responses more accurately than the standard human
ether-a-go-go
–related gene test or healthy control hiPSC-CM/hESC-CM screening assays.
Using Mentally Incompetent Adults as Living Organ Donors: Widely Diverging Regulations in Europe
Authors: Van Assche Kristof , Genicot Gilles , Sterckx Sigrid
Published: March 2013

Abstract

With the current situation in Belgium as its initial focus, this article will examine the regulatory framework that governs the use of mentally incompetent adults as living organ donors in Europe. Our survey of the national regulation of 22 countries will reveal widely diverging viewpoints, ranging from an absolute prohibition on organ procurement to a barely restricted authorisation to retrieve even non-regenerable organs. We also have a look at the way in which American and English court decisions have applied the best interests standard in an attempt to define the contours of acceptable organ removal from mentally incompetent donors. Taking the best interests of the mentally incompetent person as a yardstick, we suggest that legally prohibiting organ removal from mentally incompetents may be problematic, even if it concerns only non-regenerable organs, and that regulations should be refined accordingly.
California Winter Precipitation Change under Global Warming in the Coupled Model Intercomparison Project Phase 5 Ensemble
Authors: Neelin J. David , Langenbrunner Baird , Meyerson Joyce E. , Hall Alex , Berg Neil
Published: March 2013

Projections of possible precipitation change in California under global warming have been subject to considerable uncertainty because California lies between the region anticipated to undergo increases in precipitation at mid-to-high latitudes and regions of anticipated decrease in the subtropics. Evaluation of the large-scale model experiments for phase 5 of the Coupled Model Intercomparison Project (CMIP5) suggests a greater degree of agreement on the sign of the winter (December–February) precipitation change than in the previous such intercomparison, indicating a greater portion of California falling within the increased precipitation zone. While the resolution of global models should not be relied on for accurate depiction of topographic rainfall distribution within California, the precipitation changes depend substantially on large-scale shifts in the storm tracks arriving at the coast. Significant precipitation increases in the region arriving at the California coast are associated with an eastward extension of the region of strong Pacific jet stream, which appears to be a robust feature of the large-scale simulated changes. This suggests that effects of this jet extension in steering storm tracks toward the California coast constitute an important factor that should be assessed for impacts on incoming storm properties for high-resolution regional model assessments.
Greenland Ice Sheet Mass Balance Reconstruction. Part II: Surface Mass Balance (1840–2010)*
Authors: Box Jason E.
Published: March 2013

Meteorological station records, ice cores, and regional climate model output are combined to develop a continuous 171-yr (1840–2010) reconstruction of Greenland ice sheet climatic surface mass balance (Bclim) and its subcomponents including near-surface air temperature (SAT) since the end of the Little Ice Age. Independent observations are used to assess and compensate errors. Melt water production is computed using separate degree-day factors for snow and bare ice surfaces. A simple meltwater retention scheme yields the time variation of internal accumulation, runoff, and bare ice area.

At decadal time scales over the 1840–2010 time span, summer (June–August) SAT increased by 1.6°C, driving a 59% surface meltwater production increase. Winter warming was +2.0°C. Substantial interdecadal variability linked with episodic volcanism and atmospheric circulation anomalies is also evident. Increasing accumulation and melt rates, bare ice area, and meltwater retention are driven by increasing SAT. As a consequence of increasing accumulation and melt rates, calculated meltwater retention by firn increased 51% over the period, nearly compensating a 63% runoff increase. Calculated ice sheet end of melt season bare ice area increased more than 5%.

Multiple regression of interannual SAT and precipitation anomalies suggests a dominance of melting on Bclim and a positive SAT precipitation sensitivity (+32 Gt yr−1 K−1 or 6.8% K−1).

The Bclim component magnitudes from this study are compared with results from Hanna et al. Periods of shared interannual variability are evident. However, the long-term trend in accumulation differs in sign.
A novel non-crimped thermoplastic fabric prepreg from waste carbon and polyester fibres
Authors: Akonda MH , EL-Dessouky HM , Lawrence CA , Weager BM
Published: March 2013

A biaxial non-crimped fabric, 400 ± 10 g/m2, +45°/−45° lay-up protocol, was made from a unidirectional tape comprised of a 60/40 wt% carded blend of virgin waste carbon fibres, 60 mm chopped length, and polyester resin fibres, 60 mm staple length. The non-crimped fabric was used as a thermoplastic prepreg to produce laminated composite panels. The prepreg exhibited a high degree of drapeability. The physical and mechanical properties of composite samples were determined; the density, void contents, tensile and flexural strengths and moduli were found to be 1.5 g/cm3, 10%, 180.7 MPa, 260.5 MPa, 34.2 GPa and 30.4 GPa, respectively. Modification of the consolidation process and the use of finer polyester fibres should decrease the void content. It was concluded that waste carbon fibres can be converted into flexible/drapeable dry prepreg materials, potentially useful for the manufacturing of thermoplastic composite products by hot press compaction.
Controlling Access to Territory
Authors: Avdan Nazli
Published: March 2013

Previous scholarship has largely failed to address the effect of economic interdependence on issue areas other than interstate conflict. This study seeks to redress this lacuna by focusing on states’ visa policies and examining the impact of trade and capital interdependence in the context of transnational terrorism. The article argues that economic ties affect visa policies through a reconfiguration of preferences and the opportunity costs of economic loss and by tempering the impact of terrorism. To support this claim, the study conducts statistical analysis using directed dyad data on the visa policies of 207 states and independent political units. The article shows that the impact of economic interdependence is contingent on whether states are directly targeted in attacks of terrorism or face indirect threats from global terror. The study finds that economic incentives overwhelm security concerns when threats are indirect but have relatively limited influence, given threats against a state’s own citizens or territory.
Interaction of IL-1β and P2X3 Receptor in Pathologic Masseter Muscle Pain
Authors: Noma N. , Shinoda M. , Honda K. , Kiyomoto M. , Dezawa K. , Nakaya Y. , Komiyama O. , Imamura Y. , Iwata K.
Published: March 2013

The exact mechanism underlying chronic masseter muscle pain, a conspicuous symptom in temporomandibular disorder, remains unclear. We investigated whether expression of P2X3 receptor (P2X3R) is involved in mechanical hyperalgesia after contraction of masseter muscle (CMM). As compared with sham rats, the head-withdrawal threshold (HWT) to mechanical pressure stimulation of masseter muscle (MM) (but not after similar stimulation of facial skin) was significantly lower, and IL-1β level was significantly higher, in CMM rats on day 7 after CMM. The mean percentage of FG-labeled P2X3R-positive neurons was significantly increased in TG following successive IL-1β injections into the MM for 7 days. Successive administration of an IL-1β receptor-antagonist into the MM attenuated the increase of P2X3-IR cells in the TG. ATP release from MM after 300-g pressure stimulation of MM was also significantly enhanced after CMM. Administration into MM of the selective P2X3,2/3 receptor antagonist A-317491 attenuated the decrement of HWT in CMM rats. A significant increase in HWT was also observed at 30 min after A-317491 (60 µg) injection in IL-1β-injected rats. These findings suggest that P2X3R expression associated with enhanced IL-1β expression and ATP release in MM has a possible important role in MM mechanical hyperalgesia after excessive muscular contraction.
Lexical retrieval for nouns and verbs in typically developing bilectal children
Authors: Kambanaros Maria , Grohmann Kleanthes K. , Michaelides Michalis
Published: March 2013

Previous evidence shows that nouns are easier for many language users to retrieve than verbs, but scant research has been conducted with children in bilectal environments (where both standard and non-standard forms of a language are spoken). This study investigates object and action naming in children who are native speakers of a non-standard variety, Cypriot Greek (CG), but instructed scholastically in the official variety, Standard Modern Greek (SMG). Participants were typically developing Greek Cypriot preschoolers and early school-aged children who completed the Cypriot Object and Action Test (COAT). Results revealed a significant grammatical word class effect favoring nouns over verbs in Modern Greek, with a developmental change in the size of the noun–verb gap. Both age groups showed similar error patterns for both object and action targets. For action names, children produced more semantic descriptions or circumlocutions (e.g., hitting the nail for hammering), whereas omissions were the prominent error type for object names. The findings are discussed in relation to cross-linguistic evidence of grammatical word class differences using the picture naming paradigm for monolingual (pre)school-aged children.
Developmental Sentence Scoring for Japanese
Authors: Miyata Susanne , MacWhinney Brian , Otomo Kiyoshi , Sirai Hidetosi , Oshima-Takane Yuriko , Hirakawa Makiko , Shirai Yasuhiro , Sugiura Masatoshi , Itoh Keiko
Published: March 2013

This article reports on the development and use of the Developmental Sentence Scoring for Japanese (DSSJ), a new morpho-syntactical measure for Japanese constructed after the model of Lee’s English Developmental Sentence Scoring model. Using this measure, the authors calculated DSSJ scores for 84 children divided into six age groups between 2;8 and 5;2 on the basis of 100-sentence samples collected from free-play child–adult conversations. The analysis showed a high correlation of the DSSJ overall score with the Mean Length of Utterance. The analysis of the DSSJ sub-area scores revealed large variations between these sub-area scores for children with similar overall DSSJ scores. When investigating the high-scoring children (over 1 SD over group average), most children scored high in three to five sub-areas, but the combination of scores for these sub-areas varied from child to child. It is concluded that DSSJ is a valuable tool especially for language acquisition research. The overall DSSJ score reliably reflects the overall morpho-syntactic development of Japanese children, and the sub-area scores provide specific information on individual acquisition patterns.
Performance Evaluation of the Next‐Generation Sequencing Approach for Molecular Diagnosis of Hereditary Hearing Loss
Authors: Sivakumaran Theru A. , Husami Ammar , Kissell Diane , Zhang Wenying , Keddache Mehdi , Black Angela P. , Tinkle Brad T. , Greinwald John H. , Zhang Kejian
Published: March 2013

Objective

To evaluate the performance of a next‐generation sequencing (NGS)–based targeted resequencing genetic test, OtoSeq, to identify the sequence variants in the genes causing sensorineural hearing loss (SNHL).

Study Design

Retrospective study.

Setting

Tertiary children's hospital.

Subjects and Methods

A total of 8 individuals presenting with prelingual hearing loss were used in this study. The coding and flanking intronic regions of 24 well‐studied SNHL genes were enriched using microdroplet polymerase chain reaction and sequenced on an Illumina HiSeq 2000 sequencer. The filtered high‐quality sequence reads were mapped to reference sequence, and variants were detected using NextGENe software.

Results

A total of 1148 sequence variants were detected in 8 samples in 24 genes. Using in‐house developed NGS data analysis criteria, we classified 810 (~71%) of these variants as potential true variants that include previously detected pathogenic mutations in 5 patients. To validate our strategy, we Sanger sequenced the target regions of 5 of the 24 genes, accounting for about 29.2% of all target sequence. Our results showed >99.99% concordance between NGS and Sanger sequencing in these 5 genes, resulting in an analytical sensitivity and specificity of 100% and 99.997%, respectively. We were able to successfully detect single base substitutions, small deletions, and insertions of up to 22 nucleotides.

Conclusion

This study demonstrated that our NGS‐based mutation screening strategy is highly sensitive and specific in detecting sequence variants in the SNHL genes. Therefore, we propose that this NGS‐based targeted sequencing method would be an alternative to current technologies for identifying the multiple genetic causes of SNHL.
Pharyngeal Dysphagia in Children with Down Syndrome
Authors: O'Neill Ashley C. , Richter Gresham T.
Published: March 2013

Objective

Pharyngeal dysphagia (PD) in children with Down syndrome (DS) has not been examined. This study aims to describe the incidence, duration, and precipitating factors of PD in a large cohort of children with DS.

Study Design

Case series with chart review.

Setting

Tertiary care children's hospital.

Methods

The International Classification of Diseases, Ninth Revision (ICD‐9) code for DS was used to identify all children treated at a single institution from 1992 to 2012. Patient charts were reviewed for signs, symptoms, and documentation of PD. Videofluoroscopic swallow studies (VFSS) established the final diagnosis of PD in affected patients. Otolaryngologic interventions and their impact on PD were also explored.

Results

A total of 228 patients with the ICD‐9 code for DS were found. Twenty‐seven patients (11.8%) were excluded due to record deficiencies. Thus, of the 201 children with DS who were available for complete review, 116 (57.7%) had and established diagnosis of PD by VFSS. The mean age at first diagnosis of PD was 1.69 years. At the time of the study, the cohort mean age was 7.45 years, with only 20 patients demonstrating resolution of PD. Patients with a tracheotomy or significant neurologic delays were more likely to have worsening or prolonged PD. Laryngeal clefts were identified in 3 patients, whereas 78 (67%) underwent surgery for upper airway obstruction that did not consistently improve PD.

Conclusion

This study suggests that PD is common, persistent, and should be routinely explored in children with DS. Intervention for upper airway obstruction had a limited role for PD in this study cohort.
Beyond the polemics of Christian–Muslim Relations: Exploring a Dialogical Approach
Authors: Griggs Jennifer
Published: March 2013

Against the historical backdrop of early Christian–Muslim apologetics in the Middle East, an apologetics that was overwhelmingly polemical in its scope, I consider the contribution of the mystics, in providing a dialogical model that would overcome the state of impasse that inter-religious debate had reached. Dialogue moves beyond the established polemical binaries of two rival belief systems, towards the clarification of defensible difference, in which the other is allowed to speak in all its polyvocality and even to impinge on the truth claims of one’s own tradition.
Comparing EQ-5D Valuation Studies
Authors: Xie Feng , Gaebel Kathryn , Perampaladas Kuhan , Doble Brett , Pullenayegum Eleanor
Published: March 2013

Background. There has been a growing interest around the world in developing country-specific scoring algorithms for the EQ-5D. This study systematically reviews all existing EQ-5D valuation studies to highlight their strengths and limitations, explores heterogeneity in observed utilities using meta-regression, and proposes a methodological checklist for reporting EQ-5D valuation studies. Methods. We searched Medline, EMBASE, the National Health Service Economic Evaluation Database (NHS EED) via Wiley’s Cochrane Library, and Wiley’s Health Economic Evaluation Database from inception through November 2012, as well as bibliographies of key papers and the EuroQol Plenary Meeting Proceedings from 1991 to 2012 for English-language reports of EQ-5D valuation studies. Two reviewers independently screened the titles and abstracts for relevance. Three reviewers performed data extraction and compared the characteristics and scoring algorithms developed in the included valuation studies. Results. Of the 31 studies included in the review, 19 used the time trade-off (TTO) technique, 10 used the visual analogue scale (VAS) technique, and 2 used both TTO and VAS. Most studies included respondents from the general population selected by random or quota sampling and used face-to-face interviews or postal surveys. Studies valued between 7 and 198 total states, with 1–23 states valued per respondent. Different model specifications have been proposed for scoring. Some sample or demographic factors, including gender, education, percentage urban population, and national health care expenditure, were associated with differences in observed utilities for moderate or severe health states. Conclusions. EQ-5D valuation studies conducted to date have varied widely in their design and in the resulting scoring algorithms. Therefore, we propose the Checklist for Reporting Valuation Studies of the EQ-5D (CREATE) for those conducting valuation studies.
The Therapeutic Encounter Within the Event of Forensic Psychotherapy
Authors: Polizzi David , Draper Matthew
Published: March 2013

In this article, we draw upon the works of Jean-Luc Marion and Claude Romano to offer a phenomenological hermeneutic of clinical forensics. We introduce Marion’s description of givenness and the event, and apply these ideas to clinical forensics. First, we describe Romano’s conceptualization of the transformative effect of the event, relative to the “openness” of the participants to this encounter. Second, we contextualize different possibilities of therapy relative to the openness and closedness of the therapist and patient.
Recognizing and Transforming Madness, Citizenship, and Social Justice
Authors: Arrigo Bruce A.
Published: March 2013

Psychological Jurisprudence (PJ) is a philosophy about the self in society and it is a cultural critique of captivity and risk management. This article further clarifies or amplifies several of PJ’s central arguments relative to its rediagnosis of madness, deconstruction of citizenship, and reconstitution of social justice. These concerns draw attention to the theory, method, and praxis of PJ, including their relevancies for institutional and community-based reform within the mental health and criminal justice systems. These matters are provisionally addressed, mindful of the respective comments developed by Professors Brown and Ward.
Leaving Home
Authors: Cheek Cheryl , Piercy Kathleen W. , Grainger Sarah
Published: March 2013

Using the concepts in the Fogg Behavioral Model, 37 volunteers aged 50 and older described their preparation for intensive volunteering with faith-based organizations. Their multistage preparation process included decision points where respondents needed to choose whether to drop out or continue preparation. Ability was a stronger determinant of serving than motivation, particularly in terms of health and finances. This model can facilitate understanding of the barriers to volunteering and aid organizations in tailoring support at crucial points for potential older volunteers in intensive service.
WAIS-IV and Clinical Validation of the Four- and Five-Factor Interpretative Approaches
Authors: Weiss Lawrence G. , Keith Timothy Z. , Zhu Jianjun , Chen Hsinyi
Published: March 2013

The fourth edition of the Wechsler Adult Intelligence Scale (WAIS-IV) is a revised and substantially updated version of its predecessor. The purposes of this research were to determine the constructs measured by the test and the consistency of measurement across large normative and clinical samples. Competing higher order WAIS-IV four- and five-factor models were analyzed using the WAIS-IV’s sample of 1,800 normative adults and 411 clinical adults. When all 15 WAIS-IV subtests were considered, both four- and five-factor models were suitable, but the five-factor model provided a better fit. The WAIS-IV PRI differentiated into two composites as follows: POI(Gv) consisting of Block Design, Visual Puzzles and Picture Completion; and FRI(Gf) consisting Matrix Reasoning, Arithmetic and Figure Weights. The five-factor solution included Quantitative Reasoning (RQ), consisting of Arithmetic and Figure Weights, as a narrow ability subsumed under FRI(Gf). Arithmetic, Vocabulary, and Figure Weights subtests had the highest g loadings. Cancellation had the lowest g loading. The WAIS-IV generally demonstrated full factor invariance between clinical and nonclinical samples.
The Science of Intelligence Testing
Authors: Goldstein Sam
Published: March 2013

Intelligence has been defined in multiple ways throughout history. In the last 100 years a psychometric approach to define the concept of intelligence has come to dominate the concept. This Commentary provides a brief overview of the history and concepts of intelligence with an emphasis on intellectual assessment. Particular focus is placed on the last 20 years reflecting substantial improvements in the quality of intellectual measures. An argument is made that although confirmatory factor analysis is one way to interpret and understand the Wechsler Scales, another way is to begin with a clearly articulated theory of intellect and to create an instrument designed and validated to fit that theory. Although application of a confirmatory factor analysis to the Wechsler Scales can generate alternate or additional factors that may be interpreted in light of other theories of intelligence such as Cattell-Horn-Carroll (CHC), the opinion is offered that the articles in this issue of JPA offer compelling data that Wechsler’s vision was and is still vibrant and valuable.
The activation of satellite cells by nanofibrous poly ɛ-caprolacton constructs
Authors: Hosseinzadeh Simzar , Soleimani Masoud , Rezayat Sayed Mahdi , Ai Jafar , Vasei Mohammad
Published: March 2013

Nanoscale patterning of scaffolds provides broad surface for adhesion and differentiation of stem cells. As we know, the combination of tissue engineering with stem cells technology hold the key for regeneration of damaged tissues for example skeletal muscle tissues. On the other hand, the mechanical assessments of poly ɛ-caprolacton nanofibers determined the required features of biomedical scaffold for skeletal muscle tissue. In this study, skeletal muscle satellite cells as the main group of stem cells were cultivated on the electrospun poly ɛ-caprolacton nanofibers. Our results indicated that in comparison with tissue culture polystyrene, the nanoscale of scaffolds provided more induction to matured cells of skeletal muscle. Moreover, the immobilization of cells by collagen on poly ɛ-caprolacton nanofibers significantly improved the differential potency of satellite cells.
Seeking Accountability Through State-Appointed Emergency District Management
Authors: Arsen David , Mason Mary L.
Published: March 2013

Michigan’s Local Government and School District Accountability Act of 2011 empowers the governor to appoint emergency managers (EMs) in financially troubled school districts. EMs assume all powers of the superintendent and school board. They can reshape academic programs, nullify labor contracts, and open and close schools. This article analyzes the law’s political origins and early implementation. Relative to prevailing accountability mechanisms applicable to all school districts, in what respects are EM districts more accountable, and in what respects are they less accountable? Our analysis reveals that although the law concentrates control over school operations, it weakens most standard dimensions of district accountability.
Nonprofit Virtual Accountability
Authors: Dumont Georgette E.
Published: March 2013

This article introduces the Nonprofit Virtual Accountability Index (NPVAI) as a tool for nonprofits to strategically plan their online accountability, as well as for researchers to empirically analyze nonprofit Web sites. The index is developed first from the theoretical literature on nonprofit accountability, on government virtual accountability, and on best practice in website design. An exploratory factor analysis is then carried out on the index adapted from these sources. The nonprofit virtual accountability components identified were accessibility, engagement, performance, governance, and mission. The index is applied to nonprofits in Illinois to test its validity. The findings confirm the validity of the index as a tool to measure nonprofit virtual accountability.
Reducing the influence of partial admission on unstable synchronous vibration of turbines by bearing elevation optimization
Authors: Zhang WanFu , Yang JianGang , Gao QingShui , Li Jie
Published: March 2013

To investigate the rotor-bearing dynamics and solve the unstable synchronous vibration problem under partial admission conditions in axial steam turbines, a three-dimensional computational fluid dynamics model of the governing stage for a 350 MW turbogenerator unit was established. Steam force under different partial admission cases was calculated. Results show that the uneven steam force in the horizontal direction was fairly as strong as that in the vertical direction. The maximal horizontal steam force was about 40% of the high intermediate pressure cylinder rotor weight. Synchronous vibration faults caused by partial admission may occur in practice. The finite element model was further built to analyze the rotor-bearing dynamics under partial admission conditions. Large fluctuation of the synchronous vibration was observed during the variation of control valve sequence. Finally, the effect of bearing elevation on the rotor-bearing dynamics was studied. The sensitivity of bearing load varies for different bearing elevations. An effective solution to the unstable synchronous vibration faults caused by partial admission was achieved by optimizing the distribution of bearing elevation. A relevant case was presented through practical test.
Finite-element simulation of mixed convection flow of micropolar fluid over a shrinking sheet with thermal radiation
Authors: Gupta Diksha , Kumar Lokendra , Bég O Anwar , Singh Bani
Published: March 2013

An analysis is carried out to investigate the effect of thermal radiation on mixed convection flow of a msicropolar fluid over a shrinking sheet with prescribed surface heat flux. The velocity of the shrinking sheet and the surface heat flux are assumed to vary as a linear function of the distance from the origin. Using the boundary layer approximation and similarity transformations, the governing partial differential equations are transformed into a system of nonlinear coupled ordinary differential equations which are solved numerically by using a variational finite element method. The effects of suction, radiation, and buoyancy parameters on velocity, microrotation, and temperature functions are examined in detail. The skin-friction coefficient, local couple stress, and the local Nusselt number have also been computed. Under special conditions, an analytical solution is obtained only for the flow velocity, which is compared with the numerical results obtained by finite element method. An excellent agreement of the two sets of solutions is observed, which confirms the validity of the finite element method employed herein. Also, in order to check the convergence of numerical solutions, the calculations are executed by reducing the mesh size. The sensitivity of the solution as a function of suction through the permeable sheet has also been examined. The current study has important applications in industrial polymeric materials processing.
Dynamic characteristics of suction valves for reciprocating compressor with stepless capacity control system
Authors: Tang Bin , Zhao Yuanyang , Li Liansheng , Wang Le , Liu Guangbin , Yang Qichao , Xu Haiping , Zhu Feng , Meng Wenhui
Published: March 2013

The dynamic characteristics of suction valves for reciprocating compressor with a stepless capacity control system are studied in this article. The self-acting valve model that is applicable for stepless capacity control condition is derived. For the suction valve movement controlled by actuator, a simulation of the hydraulic and mechanical system is conducted. An experimental platform is setup, which is used to test the valve dynamic when it is controlled by actuator. The results from the mathematical model show that the valve impact speeds are influenced by the valve lift, Mach number of the flow in the valve clearance and the initial crank rotation angle of the valve closing process. The simulation results agree well with experimental results. The simulated maximum speed is about 0.53 m/s, and the maximum speed tested by experiment is about 0.58 m/s, both of which are much lower than the speed of the automatic valve (3 m/s). In addition, simulation results show that the maximum speed is at constant when the hydraulic piston stroke increases, which is much different from the automatic valve. It becomes apparent from the aforementioned results that with stepless capacity control system the dynamic characteristics of the suction valve are changed. The valve can be limited at a low speed, and the valve impact speeds to seat and stopper decrease significantly, which would be helpful for extending the life of the valve plate.