bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deficient brain insulin signalling pathway in Alzheimer's disease and diabetes
Authors: Liu Ying , Liu Fei , Grundke‐Iqbal Inge , Iqbal Khalid , Gong Cheng‐Xin 
Published: April 2011

AbstractBrain glucose metabolism is impaired in Alzheimer's disease (AD), the most common form of dementia. Type 2 diabetes mellitus (T2DM) is reported to increase the risk for dementia, including AD, but the underlying mechanism is not understood. Here, we investigated the brain insulin–PI3K–AKT signalling pathway in the autopsied frontal cortices from nine AD, 10 T2DM, eight T2DM–AD and seven control cases. We found decreases in the levels and activities of several components of the insulin–PI3K–AKT signalling pathway in AD and T2DM cases. The deficiency of insulin–PI3K–AKT signalling was more severe in individuals with both T2DM and AD (T2DM–AD). This decrease in insulin–PI3K–AKT signalling could lead to activation of glycogen synthase kinase‐3β, the major tau kinase. The levels and the activation of the insulin–PI3K–AKT signalling components correlated negatively with the level of tau phosphorylation and positively with protein O‐GlcNAcylation, suggesting that impaired insulin–PI3K–AKT signalling might contribute to neurodegeneration in AD through down‐regulation of O‐GlcNAcylation and the consequent promotion of abnormal tau hyperphosphorylation and neurodegeneration. The decrease in brain insulin–PI3K–AKT signalling also correlated with the activation of calpain I in the brain, suggesting that the decrease might be caused by calpain over‐activation. Our findings provide novel insight into the molecular mechanism by which type 2 diabetes mellitus increases the risk for developing cognitive impairment and dementia in Alzheimer's disease. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Murine rhabdomyosarcoma is immunogenic and responsive to T‐cell‐based immunotherapy
Authors: Meadors Joanna L. , Cui Yonghzi , Chen Qing‐Rong , Song Young K. , Khan Javed , Merlino Glenn , Tsokos Maria , Orentas Rimas J. , Mackall Crystal L. 
Published: April 2011

AbstractBackgroundImmunotherapies targeting cellular immunity are currently approved for treatment of melanoma, renal cell carcinoma, and prostate cancer. Studies on the immunogenicity and immune responsiveness of pediatric tumors are limited, therefore, it remains unclear to what extent T‐cell‐based immunotherapy holds promise for pediatric solid tumors.ProcedureA new rhabdomyosarcoma cell line (M3‐9‐M) was derived from an embryonal rhabdomyosarcoma (ERMS) occurring in a C57BL/6 mouse transgenic for hepatocyte growth factor and heterozygous for mutated p53. Primary tumors and metastases derived from M3‐9‐M were studied for similarities to human ERMS, and for immunogenicity and immune responsiveness.ResultsPrimary and metastatic tumors develop after orthotopic injection of M3‐9‐M into immunocompetent C57BL/6 mice, which mirror human ERMS with regard to histology, gene expression, and metastatic behavior. Whole cell vaccination using irradiated M3‐9‐M cells or M3‐9‐M‐pulsed dendritic cells (DC)‐induced tumor‐specific T‐cell responses that prevent tumor growth following low‐dose tumor injection, and slow tumor growth following higher doses. Administration of anti‐CD25 moAbs to deplete CD4+CD25+FOXP3+ regulatory T cells prior to tumor vaccination enhanced the potency of the ERMS tumor vaccine. Adoptive immunotherapy with M3‐9‐M primed T cells plus DC‐based vaccination resulted in complete eradication of day 10 M3‐9‐M derived tumors.ConclusionsM3‐9‐M derived murine ERMS is immunogenic and immunoresponsive; regulatory T cells contribute to immune evasion by murine rhabdomyosarcoma. Adoptive immunotherapy with DC vaccination can eradicate low tumor burdens. Future work will seek to identify the tumor‐associated antigens that mediate protective and therapeutic immunity in this model. Pediatr Blood Cancer 2011; 57: 921–929. © 2011 Wiley‐Liss, Inc.
A novel lung disease phenotype adjusted for mortality attrition for cystic fibrosis Genetic modifier studies
Authors: Taylor Chelsea , Commander Clayton W. , Collaco Joseph M. , Strug Lisa J. , Li Weili , Wright Fred A. , Webel Aaron D. , Pace Rhonda G. , Stonebraker Jaclyn R. , Naughton Kathleen , Dorfman Ruslan , Sandford Andrew , Blackman Scott M. , Berthiaume Yves , Paré Peter , Drumm Mitchell L. , Zielenski Julian , Durie Peter , Cutting Garry R. , Knowles Michael R. , Corey Mary 
Published: April 2011

AbstractGenetic studies of lung disease in cystic fibrosis (CF) are hampered by the lack of a severity measure that accounts for chronic disease progression and mortality attrition. Further, combining analyses across studies requires common phenotypes that are robust to study design and patient ascertainment.Using data from the North American Cystic Fibrosis Modifier Consortium (Canadian Consortium for CF Genetic Studies, Johns Hopkins University CF Twin and Sibling Study, and University of North Carolina/Case Western Reserve University Gene Modifier Study), the authors calculated age‐specific CF percentile values of FEV1 which were adjusted for CF age‐specific mortality data.The phenotype was computed for 2,061 patients representing the Canadian CF population, 1,137 extreme phenotype patients in the UNC/Case Western study, and 1,323 patients from multiple CF sib families in the CF Twin and Sibling Study. Despite differences in ascertainment and median age, our phenotype score was distributed in all three samples in a manner consistent with ascertainment differences, reflecting the lung disease severity of each individual in the underlying population. The new phenotype score was highly correlated with the previously recommended complex phenotype, but the new phenotype is more robust for shorter follow‐up and for extreme ages.A disease progression and mortality‐adjusted phenotype reduces the need for stratification or additional covariates, increasing statistical power, and avoiding possible distortions. This approach will facilitate large‐scale genetic and environmental epidemiological studies which will provide targeted therapeutic pathways for the clinical benefit of patients with CF. Pediatr. Pulmonol. 2011; 46:857–869. © 2011 Wiley‐Liss, Inc.
The Facile Synthesis and Energetic Properties of an Energetic Furoxan Lacking Traditional “Explosophore” Moieties: (E,E)‐3,4‐bis(oximomethyl)furoxan (DPX1)
Authors: Klapötke Thomas M. , Piercey Davin G. , Stierstorfer Joerg 
Published: April 2011

AbstractEnergetic furoxan (E,E)‐3,4‐bis(oximomethyl)furoxan (DPX1) was synthesized in 75 % yield, using a literature procedure, from a precursor readily available in one step from nitromethane. DPX1 was characterized for the first time as an energetic material in terms of calculated performance (Vdet = 8245 m s−1;pC‐J = 29.0 GPa) and measured sensitivity (impact: 10 J; friction: 192 N;Tdec: 168 °C). DPX1 exhibits a sensitivity less than that of RDX, and a performance significantly higher than 2,4,6‐trinitrotoluene (TNT).
Superstring cosmology for N4 = 1 → 0 superstring vacua
Authors: Estes J. , Kounnas C. , Partouche H. 
Published: April 2011

AbstractWe study the cosmology of perturbative heterotic superstring theory during the radiation‐like era for semi‐realistic backgrounds with initial 𝒩 = 1 supersymmetry. This analysis is valid for times after the Hagedorn era (or alternatively inflation era) but before the electroweak symmetry breaking transition. We find an attraction to a radiation‐like era with the ratio of the supersymmetry breaking scale to temperature stabilized. This provides a dynamical mechanism for setting the supersymmetry breaking scale and its corresponding hierarchy with the Planck scale. For the internal space, we find that orbifold directions never decompactify, while toroidal directions may decompactify only when they are wrapped by certain geometrical fluxes which break supersymmetry. This suggests a mechanism for generating spatial directions during the radiation‐like era. Moreover, we show that certain moduli may be stabilized during the radiation‐like era with masses near the supersymmetry breaking scale. In addition, the moduli do not dominate at late times, thus avoiding the cosmological moduli problem.
Prioritizing tests for software fault diagnosis
Authors: Gonzalez‐Sanchez Alberto , Piel Éric , Abreu Rui , Gross Hans‐Gerhard , van Gemund Arjan J. C. 
Published: April 2011

SUMMARYDuring regression testing, test prioritization techniques select test cases that maximize the confidence on the correctness of the system when the resources for quality assurance (QA) are limited. In the event of a test failing, the fault at the root of the failure has to be localized, adding an extra debugging cost that has to be taken into account as well. However, test suites that are prioritized for failure detection can reduce the amount of useful information for fault localization. This deteriorates the quality of the diagnosis provided, making the subsequent debugging phase more expensive, and defeating the purpose of the test cost minimization. In this paper we introduce a new test case prioritization approach that maximizes the improvement of the diagnostic information per test. Our approach minimizes the loss of diagnostic quality in the prioritized test suite. When considering QA cost as a combination of testing cost and debugging cost, on our benchmark set, the results of our test case prioritization approach show reductions of up to 60% of the overall combined cost of testing and debugging, compared with the next best technique. Copyright © 2011 John Wiley & Sons, Ltd.
Hot Deformation Behaviour of Low Alloy Steel
Authors: Poletti C. , Six J. , Hochegger M. , Degischer H. P. , Ilie S. 
Published: April 2011

AbstractHot deformation of a continuously cast low alloyed steel is studied by means of hot compression and tensile tests by using a Gleeble® 1500 machine after austenitization in a wide range of strain rates and between 720–800 °C. The flow data are evaluated to obtain the strain rate sensitivity and the processing maps. A new calculation method is used, yielding on the instability parameter defined as κJ which correlates well with the microstructural changes. The strain rate sensitivity does not predict any instability but all the others instability parameters do, including the new κJ. Flow instability appears at high temperatures and low strain rates where pores are formed at the austenitic grain boundaries, causing a decay of ductility in the tensile test. During hot deformation more ferrite is formed than corresponding heat treatments without deformation. In these conditions, the deformation is concentrated in the softer ferrite phase. The deformation induced ferrite deforms by dynamic recovery forming new grains as revealed by metallography and is correlated with low coefficients of power dissipation. The sinh type constitutive equation represents the flow data well with a stress exponent n = 4.1 and an apparent activation energy Q = 218 kJ/mol.
Impact of dihydrolipoic acid on mouse embryonic stem cells and related regulatory mechanisms
Authors: Chan Wen‐Hsiung , Houng Wei‐Li , Lin Cheng‐An J. , Lee Chih‐Hsien , Li Po‐Wen , Hsieh Jyun‐Tai , Shen Ji‐Lin , Yeh Hung‐I , Chang Walter H. 
Published: April 2011

Abstractα‐Lipoic acid (LA) is a thiol with antioxidant properties that protects against oxidative stress‐induced apoptosis. LA is absorbed from the diet, taken up by cells and tissues, and subsequently reduced to dihydrolipoic acid (DHLA). Recently, DHLA has been used as the hydrophilic nanomaterial preparations, and therefore, determination of its bio‐safety profile is essential. In this article, we show that DHLA (50–100 μM) induces apoptotic processes in mouse embryonic stem cells (ESC‐B5), but exerts no injury effects at treatment dosages below 50 μM. Higher concentrations of DHLA (50–100 μM) directly increased the reactive oxygen species (ROS) content in ESC‐B5 cells, along with a significant increase in cytoplasmic free calcium and nitric oxide (NO) levels, loss of mitochondrial membrane potential (MMP), activation of caspases‐9 and −3, and cell death. Pretreatment with NO scavengers suppressed the apoptotic biochemical changes induced by 100 μM DHLA and promoted the gene expression levels of p53 and p21 involved in apoptotic signaling. Our results collectively indicate that DHLA at concentrations of 50–100 μM triggers apoptosis of ESC‐B5 cells, which involves both ROS and NO. Importantly, at doses of less than 50 μM (0–25 μM), DHLA does not exert hazardous effects on ESC‐B5 cell properties, including viability, development and differentiation. These results provide important information in terms of dosage safety and biocompatibility of DHLA to facilitate its further use as a precursor for biomaterial preparation. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013.
Heparan sulfate proteoglycans in healthy and diseased systems
Authors: Whitelock John , Melrose James 
Published: April 2011

AbstractHeparin and heparan sulfate (HS) are glycosaminoglycans (GAGs) that are synthesized in the tissues and organs of mammals. They are synthesized and attached to a core protein as proteoglycans through serine–glycine concensus motifs along the core protein. These GAGs are linear polysaccharides composed of repeating disaccharide saccharide units that are variously modified along their length. As a consequence of these modifications naturally occurring heparin and HS are extremely heterogeneous in their structures. A diverse range of proteins bind heparin and HS. The types of proteins that bind are dictated by the structure of the HS or heparin chains with which they are interacting. Heparan sulfates play major roles in tissue development and in maintaining homeostasis within healthy individuals. Recent genetic studies illustrate that alterations in their structural organization can have important consequences often giving rise to, or directly causing, a disease situation. A greater understanding of the repertoire of proteins with which heparin and HS interact and the diseases that can be caused by perturbations in the structures of heparin and HS proteoglycan may provide insights into possible therapeutic interventions. These issues are discussed with a focus on musculoskeletal phenotypes and diseases. WIREs Syst Biol Med 2011 3 739–751 DOI: 10.1002/wsbm.149This article is categorized under:

Physiology > Mammalian Physiology in Health and Disease
ON NONNILPOTENT SUBSETS IN GENERAL LINEAR GROUPS
Authors: AZAD AZIZOLLAH 
Published: April 2011

AbstractLetGbe a group. A subsetXofGis said to be nonnilpotent if for any two distinct elementsxandyinX, 〈x,y〉 is a nonnilpotent subgroup ofG. If, for any other nonnilpotent subsetX′inG, ∣X∣≥∣X′∣, thenXis said to be a maximal nonnilpotent subset and the cardinality of this subset is denoted byω(𝒩G) . Using nilpotent nilpotentizers we find a lower bound for the cardinality of a maximal nonnilpotent subset of a finite group and apply this to the general linear group GL (n,q) . For all prime powersqwe determine the cardinality of a maximal nonnilpotent subset of the projective special linear group PSL (2,q) , and we characterize all nonabelian finite simple groupsGwithω(𝒩G)≤57 .
Patriotism, Nationalism and China's US Policy: Structures and Consequences of Chinese National Identity
Authors: Gries Peter Hays , Zhang Qingmin , Crowson H. Michael , Cai Huajian 
Published: April 2011

AbstractWhat is the nature of Chinese patriotism and nationalism, how does it differ from American patriotism and nationalism, and what impact do they have on Chinese foreign policy attitudes? To explore the structure and consequences of Chinese national identity, three surveys were conducted in China and the US in the spring and summer of 2009. While patriotism and nationalism were empirically similar in the US, they were highly distinct in China, with patriotism aligning with a benign internationalism and nationalism with a more malign blind patriotism. Chinese patriotism/internationalism, furthermore, had no impact on perceived US threats or US policy preferences, while nationalism did. The role of nationalist historical beliefs in structures of Chinese national identity was also explored, as well as the consequences of historical beliefs for the perception of US military and humiliation threats.
EFFICIENTLY GENERATED SPACES OF CLASSICAL SIEGEL MODULAR FORMS AND THE BÖCHERER CONJECTURE
Authors: RAUM MARTIN 
Published: April 2011

AbstractWe state and verify up to weight 172 a conjecture on the existence of a certain generating set for spaces of classical Siegel modular forms. This conjecture is particularly useful for calculations involving Fourier expansions. Using this generating set, we verify the Böcherer conjecture for nonrational eigenforms and discriminants with class number greater than one. As a further application we verify another conjecture for weights up to 150 and investigate an analog of the Victor–Miller basis. Additionally, we describe some arithmetic properties of the basis we found.
Evidence-Based Practice for Children With Speech Sound Disorders: Part 1 Narrative Review
Authors: Baker Elise , McLeod Sharynne 
Published: April 2011

PurposeThis article provides a comprehensive narrative review of intervention studies for children with speech sound disorders (SSD). Its companion paper (Baker & McLeod, 2011) provides a tutorial and clinical example of how speech-language pathologists (SLPs) can engage in evidence-based practice (EBP) for this clinical population.MethodStudies reporting speech sound intervention for children with SSDs published from 1979 to 2009 were identified and coded.ResultsOne hundred thirty-four intervention studies were identified. Intervention typically was conducted by an SLP in a one-to-one individual format for 30- to 60-min sessions 2 to 3 times per week. Total duration of intervention (from assessment to discharge) was reported for 10 studies and ranged from 3 to 46 months. Most studies were either Level IIb (quasi-experimental studies, 41.5%) or Level III (nonexperimental case studies, 32.6%). Single-case experimental design (29.6%) was the most frequently used experimental research design. There were 7 distinct approaches to target selection and 46 distinct intervention approaches, with 23 described in more than 1 publication. Each approach was associated with varying quantities and levels of evidence, according to research design.ConclusionCollaborative research reflecting higher levels of evidence using rigorous experimental designs is needed to compare the relative benefits of different intervention approaches.
Assessment and Treatment of Working Memory Deficits in School-Age Children: The Role of the Speech-Language Pathologist
Authors: Boudreau Donna , Costanza-Smith Amy 
Published: April 2011

PurposeTo review research addressing the relationship of working memory (WM) to language development and academic functioning and to consider the role of the speech-language pathologist (SLP) in assessment and intervention of WM difficulties in school-age children.MethodAspects of WM critical to language acquisition and academic success are defined, and the importance of WM to language development and learning is discussed. Subsequently, strategies for assessing WM skills in children are presented. Following a discussion regarding the assessment of WM demands in the classroom, intervention strategies are provided.ResultsChildren with poor WM skills are likely to experience significant difficulty in academic settings. Evidence-based strategies for both reducing WM demands and improving functional WM skills are reviewed.ConclusionResearch to date has documented that children with language impairments frequently have poor WM skills. SLPs can support poor WM skills by considering both modifications to the environment and child-enacted knowledge and skills, which may serve to reduce the impact of poor WM skills on learning and academic success.
Functional Seating for School-Age Children With Cerebral Palsy: An Evidence-Based Tutorial
Authors: Costigan F. Aileen , Light Janice 
Published: April 2011

PurposeThis tutorial is designed to teach speech-language pathologists (SLPs) best practices to support functional seating of children with cerebral palsy (CP) in the classroom and in school-based therapy sessions. This tutorial teaches SLPs to (a) recognize the positive effects of seating intervention, (b) identify the characteristics of functional seating that may produce these positive effects, and (c) realize their role in supporting functional seating for school-age children with CP.MethodThe research reporting positive effects of seating intervention for school-age children with CP is presented according to theInternational Classification of Functioning, Disability and Health(World Health Organization, 2001). Recommended guidelines for functional seating for school-age children with CP are gleaned from the research evidence. The specific role of the SLP in providing functional seating for children with CP is then discussed.ConclusionSeating intervention may produce positive body structure and function, activities, and participation effects for school-age children with CP when appropriate equipment is provided for weight bearing, the pelvis is positioned for stability and mobility, and the body is properly aligned. SLPs can support functional seating for school-age children with CP by communicating with professionals with seating expertise and by invoking and monitoring recommended guidelines for children with basic and complex seating needs, respectively.
Expository Language Skills of Young School-Age Children
Authors: Westerveld Marleen F. , Moran Catherine A. 
Published: April 2011

Purpose
This research investigated the expository language skills of young school-age children with the ultimate aim of obtaining normative data for clinical practice. Specifically, this study examined (a) the level of expository language performance of 6- and 7-year-old children with typical development and (b) age-related differences between young and older school-age children.

Method

Expository discourse was elicited from two groups of children using the favorite game or sport (FGS) task. Performance of the younger age group (
n
= 61), age 6;0 (years;months) to 7;11, was compared to that of a group of twenty 11-year-old children from an earlier study. Samples were analyzed on measures of verbal productivity, syntactic complexity, grammatical accuracy, and verbal fluency.

Results
The FGS task was effective in eliciting text-level discourse from young school-age children. These children produced discourse that resulted in a fairly normal distribution across some of the language production measures. Age-related differences were observed on measures of verbal productivity, grammatical accuracy, and verbal fluency, but not on syntactic complexity.

Conclusion
The findings suggest that expository discourse sampling may be a useful addition to a language assessment protocol, even for very young school-age children.