bluuebunny/crossref_metadata_2025 huggingface dataset:
Failure Performance Analysis of Resistance Spot Welded Advanced High Strength Steel Sheets
Authors: Noh Woo Ram , Koh Young Woo , Hong Jong Hwa , Yang Xin , Chung Kwan Soo
Published: July 2015

A numerical method to predict failure performance was developed for resistance spot welded AHSS (advanced high strength steel) sheets in this work and applied for a TRIP (transformation induced steel sheets) 980 sheet. For the numerical analysis, utilizing the numerical inverse calibration method, hardening data and fracture criteria were characterized for the base and the weld nugget based on the standard simple tension test and a newly designed miniature tension test, respectively. The characterized properties of the base and the weld nugget were then applied to analyze failure performance in the coupon tests of the lap-shear and U-shape tension tests carried out for welded sheets. The analysis was performed under the quasi-static condition in this early effort and showed reasonably good agreement with experiments both in failure modes and strength.
Numerical Simulation of AA2024-T3 Friction Stir Welding (FSW) Process: Sensitivity Analyses and Influence of Decisions during Modelling Stages
Authors: Paulo Rui M.F. , Carlone Pierpaolo , Valente Robertt , Teixeira-Dias Filipe , Palazzo Gaetano S.
Published: July 2015

The main objective of the present work is to assess the influence of several parameters relevant for Finite Element Analysis (FEA) in modelling Friction Stir Welding (FSW) processes on AA2024-T3 plates. Several tests were performed including variations on the type of shell elements, number of integration points across thickness direction and mesh refinement levels, aiming for good accuracy and low computational cost. On the one hand, several setups of the mechanical boundary conditions, modelling the clamping systems, were also tested, leading to the conclusion that the results, in terms of longitudinal residual stresses, are significantly affected by this factor. On the other hand, variations on the heat input distribution showed a reduced effect, or almost null, on the final results.
Rate-Independent Deformation Patterning in Crystal Plasticity
Authors: Lancioni Giovanni , Zitti Gianluca , Yalcinkaya Tuncay
Published: July 2015

Metal forming processes involve continuous strain path changes inducing plastic anisotropywhich could result in the failure of the material. It has been often observed that the formation andevolution of meso-scale dislocation microstructures under monotonic and non-proportional loading have substantial effect on the induced anisotropy. It is therefore quite crucial to study the microstructureevolution to understand the underlying physics of the macroscopic transient plastic behavior. In thiscontext the deformation patterning induced by the non-convex plastic energies is investigated in amulti-slip crystal plasticity framework. An incremental variational approach is followed, which resultsin a rate-independent model exhibiting a number of similarities to the rate-dependent formulationproposed in [Yalcinkaya, Brekelmans, Geers, Int. J. of Solids and Structures, 49, 2625-2636, 2012].However there is a pronounced difference in the dissipative character of the models. The influenceof the plastic potential on the evolution of dislocation microstructures is studied through a Landau-Devonshire double-well plastic potential. Numerical simulations are performed and the results arediscussed with respect to the observed microstructure evolution in metals.
The Bootstrap Analysis of One-Way ANOVA Stability in the Case of the Ceramic Shell Mould of Airfoil Blade Casting
Authors: Szczotok Agnieszka , Nawrocki Jacek , Gądek-Moszczak Aneta , Kołomycki Maciej
Published: July 2015

The analysis of variance (ANOVA) is a classic tool for an identification of discreet factors impact on the measurable output by a specific decomposition on a total variance according to the scheme proposed by R.A Fisher in the 1920s. There are many explicit and implicit assumptions required as a preliminary of ANOVA computations. The ANOVA computations scheme is well known and implemented in many types of software but all estimations are provided with the assumption of a normal and homoscedasticity distribution of the noise disturbing the output. Computation procedures produce a single number output (e.g. F statistics, p-Value) without any analysis of their own dispersion. This paper analyzes the ANOVA output using the bootstrap approach. It seems to be the most convenient as a data-driven procedure. The source raw data are taken from the image analysis conducted during the investigation of the impact of the ceramic layer thickness on the wax pattern assembly of a turbine blade on the (γ+γ’) eutectic in the IN713C superalloy.
An Iterative Shooting Method for the Solution of Higher Order Boundary Value Problems with Additional Boundary Conditions
Authors: Filipowska Renata
Published: July 2015

This paper treats an iterative shooting method based on sensitivity functions for solving non–linear two–point boundary value problems (BVPs), in the form of a fourth–order differential equation and more than four boundary conditions. The solution of this problem is possible only when the equation includes the required number of unknown parameters. In order to use this method, it is necessary to convert the BVP to an appropriate initial value problem (IVP). The presented method has been illustrated with a numerical example.
Ionic Polymer-Metal Composite Actuators: Investigation of Parametric Model Based on Electrical Values
Authors: Dominik Ireneusz , Kaszuba Filip , Dwornicka Renata
Published: July 2015

The aim of this paper is to present the results of laboratory research on Ionic Polymer-Metal Composite (IPMC), with measurements of electrical values (voltage and current) measured simultaneously with the displacement. The obtained values were used to investigate the possibility of parametric model building. The research is focused mainly on constant frequency sine wave voltage signals. Phase offsets between voltage, current and displacement for different frequencies are calculated. Envelope and mean values of the electrical values are also described.
To take a second look at Malachi the book
Authors: Snyman S.D.
Published: July 2015

An investigation into some of the literary features of the book of Malachi reveals that each unit is structured in a twofold way. The macrostructure of the book also shows that the book can be divided into two parts. The results of this investigation strengthens the recent trend in the research of Malachi that it is unlikely that the book underwent an extensive redactional process over a period of time and that it is rather more likely that the book was written in a relatively short period of time.
Corporate Social Responsibility Practices in Banking Industry
Authors: Wong Helen , Wong Raymond
Published: July 2015

Corporate social responsibility is getting more attention from public and business. Besides profit, public and business also concern whether corporations are operating socially responsible nowadays. Although the key objective of a business corporation is to earn maximum profits for shareholders or owners, it is expected to conduct its operations in a manner to fulfill its social obligations. Big corporations are expected to have more corporate social responsibility practices because they have more resources. This study is to examine the current practices of corporate social responsibility in three biggest banking corporations in Hong Kong. The selected banks are ranked top three in terms of total assets and net profit after tax in a banking survey of 2013. Similarities and differences of their practices are discussed in the study. The study provides insights to other banks in taking up the corporate social responsibility, such as resources allocation and action plan towards better community and environment etc. Furthermore, their practices may also act as references to other industries.
A composite double-/single-stranded RNA-binding region in protein Prp3 supports tri-snRNP stability and splicing
Authors: Liu Sunbin , Mozaffari-Jovin Sina , Wollenhaupt Jan , Santos Karine F , Theuser Matthias , Dunin-Horkawicz Stanislaw , Fabrizio Patrizia , Bujnicki Janusz M , Lührmann Reinhard , Wahl Markus C
Published: July 2015

Prp3 is an essential U4/U6 di-snRNP-associated protein whose functions and molecular mechanisms in pre-mRNA splicing are presently poorly understood. We show by structural and biochemical analyses that Prp3 contains a bipartite U4/U6 di-snRNA-binding region comprising an expanded ferredoxin-like fold, which recognizes a 3′-overhang of U6 snRNA, and a preceding peptide, which binds U4/U6 stem II. Phylogenetic analyses revealed that the single-stranded RNA-binding domain is exclusively found in Prp3 orthologs, thus qualifying as a spliceosome-specific RNA interaction module. The composite double-stranded/single-stranded RNA-binding region assembles cooperatively with Snu13 and Prp31 on U4/U6 di-snRNAs and inhibits Brr2-mediated U4/U6 di-snRNA unwinding in vitro. RNP-disrupting mutations in Prp3 lead to U4/U6•U5 tri-snRNP assembly and splicing defects in vivo. Our results reveal how Prp3 acts as an important bridge between U4/U6 and U5 in the tri-snRNP and comparison with a Prp24-U6 snRNA recycling complex suggests how Prp3 may be involved in U4/U6 reassembly after splicing.
Is Oral Contrast Necessary for Multidetector Computed Tomography Imaging of Patients with Acute Abdominal Pain?
Authors: Alabousi Abdullah , Patlas Michael N. , Sne Niv , Katz Douglas S.
Published: July 2015

Purpose

The purpose of our study was to validate the hypothesis that eliminating the use of oral contrast for multidetector computed tomography (MDCT) would not affect the detection of acute abdominal abnormalities in emergency room patients.

Methods

We conducted a retrospective study to assess the effect of discontinuing oral contrast use for MDCT scans of the abdomen and pelvis for patients presenting with acute abdominal pain and body mass index (BMI) >25. Patients with BMI <25 continued to receive oral contrast. The medical records were reviewed to determine the rate of repeat imaging within 7 days from the initial CT scan, as well as delayed or missed diagnoses related to the absence of oral contrast. The study was approved by the research ethics board at our institution.

Results

A total of 1378 patients had an MDCT examination of the abdomen and pelvis between November 1, 2012, and October 31, 2013. 375 patients met the inclusion criteria (174 males and 201 females; mean age 57 years; range 18-97 years). Seven of 375 (1.9%) patients had a repeat CT examination with oral contrast within 7 days. Of these 7 patients, none had a change in the course of their management due to the utilization of oral contrast. No delayed or missed diagnoses related to the absence of oral contrast were identified.

Conclusion

Omitting oral contrast for imaging patients with BMI >25 presenting with acute abdominal pain resulted in no delayed or missed diagnoses, in our retrospective study. The benefits of prompt imaging diagnosis outweigh the unlikely need for repeat imaging.
An HcpR paralog ofDesulfovibrio gigas provides protection against nitrosative stress
Authors: da Silva Sofia M. , Amaral Catarina , Neves Susana S. , Santos Cátia , Pimentel Catarina , Rodrigues-Pousada Claudina
Published: July 2015

Desulfovibrio gigas belongs to the group of sulfate reducing bacteria (SRB). These ubiquitous and metabolically versatile microorganisms are often exposed to reactive nitrogen species (RNS). Nonetheless, the mechanisms and regulatory elements involved in nitrosative stress protection are still poorly understood. The transcription factor HcpR has emerged as a putative regulator of nitrosative stress response among anaerobic bacteria. HcpR is known to orchestrate the expression of the hybrid cluster protein gene,hcp, proposed to be involved in cellular defense against RNS. According to phylogenetic analyses, the occurrence ofhcpR paralog genes is a common feature among severalDesulfovibrio species. Within theD. gigas genome we have identified two HcpR‐related sequences. One of these sequences,hcpR1, was found in the close vicinity of thehcp gene and this finding prompted us to proceed with its functional characterization. We observed that the growth of aD. gigas strain lackinghcpR1 is severely impaired under nitrosative stress. Anin silico search revealed several putative targets of HcpR1 that were experimentally validated. The fact that HcpR1 regulates several genes encoding proteins involved in nitrite and nitrate metabolism, together with the sensitive growth phenotype to NO displayed by anhcpR1 mutant strain, strongly supports a relevant role of this factor under nitrosative stress. Moreover, the finding that severalDesulfovibrio species possess HcpR paralogs, which have been transmitted vertically in the evolution and diversification of the genus, suggests that these sequences may confer adaptive or survival advantage to these organisms, possibly by increasing their tolerance to nitrosative stress.
Development of a flow cytometric method to detect the presence of mutated nucleophosmin 1 in acute myeloid leukemia
Authors: Du Pisani Louis Almero , Shires Karen
Published: July 2015

OBJECTIVE/BACKGROUND:

Nucleophosmin 1 (NPM1) plays multiple roles in cell growth and proliferation. Deletion/insertion mutations in exon 12 of NPM1 (NPM1-DIM), commonly found in patients with acute myeloid leukemia (AML), alter the C-terminal amino acids and disrupt the normal nucleocytoplasmic shuttling function of the protein, which in turn leads to disease pathogenesis. However, this altered function as a result of NPM1-DIM positivity is actually associated with a significantly better response to therapy and overall survival, and thus it is of clinical relevance to investigate the mutation status at diagnosis. Our objective was to design a reliable flow cytometry assay to detect mutated NPM1 in peripheral blood (PB) samples from AML patients, using a polyclonal mutation-specific antibody.

METHODS:

A commercially available NPM1 mutation-specific polyclonal antibody in combination with a secondary goat antirabbit antibody was used to detect the C-terminal-mutated NPM1 by flow cytometry. OCI/AML3 (+) cell line and clinical PB controls were used to optimize the assay and determine sensitivity, reliability, and reproducibility parameters. The assay was then tested on a small cohort of 12 AML patients at diagnosis and compared with NPM1-DIM testing on a standard polymerase chain reaction (PCR) platform.

RESULTS:

Flow cytometry using the polyclonal antibody was able to reliably detect mutated NPM1 populations of at least 10%. Using an objective analysis of the mean fluorescent intensity, clear positive and negative mutated cell populations could be distinguished using the clinical AML samples. From the analysis of 12 patients, 2 were found to be positive using this assay, which corresponded with conventional PCR methodology.

CONCLUSIONS:

Flow cytometry may be used to detect NPM1 C-terminal mutations in AML patients using a polyclonal anti-NPM1 antibody, allowing rapid mutation status determination at diagnosis.
Psychiatric illness, medication and driving: an audit of documentation
Authors: Gallagher A. , Shah S. , Abassi W. , Walsh E.
Published: July 2015

Objectives

Guidelines on advising patients on fitness to drive have been published recently by the Road Safety Authority in collaboration with the Royal College of Physicians of Ireland. The aim of this audit is to assess if the new guidelines are being adhered to.

Method

Examination of the documentation and adherence to the guidelines in the inpatient psychiatric unit, Mayo General Hospital.

Results

Of the 100 patients included in audit cycle one, none had any specific documentation about driving. One patient was admitted with alcohol misuse and was driving. On re-auditing, following presentation at academic meeting and education of team members on the guidelines, there was a minor improvement of 7%.

Conclusion

There was no significant difference in documentation on re-audit. However, an increase of 7% is nonetheless encouraging. Information concerning driving should be a standard part of advice given to all psychiatric patients.
The turbulent wake of a towed grid in a stratified fluid
Authors: Xiang X. , Madison T. J. , Sellappan P. , Spedding G. R.
Published: July 2015

In a stable background density gradient, initially turbulent flows eventually evolve into a state dominated by low-Froude-number dynamics and frequently also contain persistent pattern information. Much empirical evidence has been gathered on these latter stages, but less on how they first got that way, and how information on the turbulence generator may potentially be encoded into the flow in a robust and long-lasting fashion. Here an experiment is described that examines the initial stages of evolution in the vertical plane of a turbulent grid-generated wake in a stratified ambient. Refractive-index-matched fluids allow optically based measurement of early ($Nt<2$) stages of the flow, even when there are strong variations in the local density gradient field. Suitably averaged flow measures show the interplay between internal wave motions and Kelvin–Helmholtz-generated vortical modes. The vertical shear is dominant at the wake edge, and the decay of horizontal vorticity is observed to be independent of $\mathit{Fr}$. Stratified turbulence, originating from Kelvin–Helmholtz instabilities, develops up to non-dimensional time $Nt\approx 10$, and the scale separation between Ozmidov and Kolmogorov scales is independent of $\mathit{Fr}$ at higher $Nt$. The detailed measurements in the near wake, with independent variation of both Reynolds and Froude numbers, while limited to one particular case, are sufficient to show that the initial turbulence in a stratified fluid is neither three-dimensional nor universal. The search for appropriately generalizable initial conditions may be more involved than hoped for.
SURPRISING RESULTS: HIV TESTING AND CHANGES IN CONTRACEPTIVE PRACTICES AMONG YOUNG WOMEN IN MALAWI
Authors: Sennott Christie , Yeatman Sara
Published: July 2015

This study uses eight waves of data from the population-based Tsogolo la Thanzi study (2009–2011) in rural Malawi to examine changes in young women’s contraceptive practices, including the use of condoms, non-barrier contraceptive methods and abstinence, following positive and negative HIV tests. The analysis factors in women’s prior perceptions of their HIV status that may already be shaping their behaviour and separates surprise HIV test results from those that merely confirm what was already believed. Fixed-effects logistic regression models show that HIV testing frequently affects the contraceptive practices of young Malawian women, particularly when the test yields an unexpected result. Specifically, women who are surprised to test HIV positive increase their condom use and are more likely to use condoms consistently. Following an HIV-negative test (whether a surprise or expected), women increase their use of condoms and decrease their use of non-barrier contraceptives; the latter may be due to an increase in abstinence following a surprise negative result. Changes in condom use following HIV testing are robust to the inclusion of potential explanatory mechanisms, including fertility preferences, relationship status and the perception that a partner is HIV positive. The results demonstrate that both positive and negative tests can influence women’s sexual and reproductive behaviours, and emphasize the importance of conceptualizing of HIV testing as offering new information only insofar as results deviate from prior perceptions of HIV status.
Investigation of the morphological diversity of the potentially zoonoticTrypanosoma copemaniin quokkas and Gilbert's potoroos
Authors: AUSTEN JILL M. , REID SIMON A. , ROBINSON DERRICK R. , FRIEND JAMES A. , DITCHAM WILLIAM G. F. , IRWIN PETER J. , RYAN UNA
Published: July 2015

Trypanosomes are blood-borne parasites that can cause severe disease in both humans and animals, yet little is known of the pathogenicity and life-cycles of trypanosomes in native Australian mammals.Trypanosoma copemaniis known to be infective to a variety of Australian marsupials and has recently been shown to be potentially zoonotic as it is resistant to normal human serum. In the present study,in vivoandin vitroexamination of blood and cultures from Australian marsupials was conducted using light microscopy, immunofluorescence, scanning electron microscopy and fluorescencein situhybridization. Promastigote, sphaeromastigote and amastigote life-cycle stages were detectedin vivoandin vitro. Novel trypanosome-like stages were also detected bothin vivoandin vitrorepresenting an oval stage, an extremely thin stage, an adherent stage and a tiny round stage. The tiny round and adherent stages appeared to adhere to erythrocytes causing potential haematological damage with clinical effects similar to haemolytic anaemia. The present study shows for the first time that trypomastigotes are not the only life-cycle stages circulating within the blood stream of trypanosome infected Australian native marsupials and provides insights into possible pathogenic mechanisms of this potentially zoonotic trypanosome species.
“People are Getting Lost a Little Bit”: Systemic Factors that Contribute to Falls in Community-Dwelling Octogenarians
Authors: Gotzmeister Dorothy , Zecevic Aleksandra A. , Klinger Lisa , Salmoni Alan
Published: July 2015

Les octogénaires qui habitent aux communautés sont la caractéristique la plus croissante dans la démographie du Canada. Au même temps, ils ont la plus forte prévalence des chutes et neuf fois plus de risques de blessures dues à une chute [par rapport a qui]? Une approche systématique est essentielle pour améliorer la sécurité des octogenaires qui vieillissent en place (chez soi). Comprendre comment les facteurs sociaux interagissent et affectent les aînés peuvent aider à identifier et éliminer les carences en matière de sécurité qui provoquent des chutes. Le but de cette étude était d'identifier les facteurs dans l'ensemble du système qui contribuent aux chutes chez les octogénaires qui habitent aux communautés. Huit chutes ont été étudiées en utilisant une méthode systématique d'examiner les chutes (MSEC). Les participants étaient âgés de 83 à 90 ans. Les analyses à travers des cas ont identifiées 247 facteurs contributifs, regroupés au sein de quatre thèmes distincts: (a) la vie quotidienne est devenu plein de risque; (B) la surveillance est limitée; (C) le système de soins de santé montre la déconnexion; et (d) l'identification et le suivi des chutes est défectueux. Cette étude qualitative permet des apércus systématiques sur comment et pourquoi les chutes se produisent chez les octogénaires dans les communautés.
Diverse Family Structures and the Care of Older Persons
Authors: Roberto Karen A. , Blieszner Rosemary
Published: July 2015

Les tendances démographiques et sociales aboutissent à une variété de contextes structurels internes à un niveau micro qui influent sur la prestation de soins pour les familles avec des membres plus âgés. Les résultats des changements au niveau macro ont attiré peu d'attention sur les études du vieillissement, où une grande partie des recherches sur la prestation de soins a traité de questions dans le contexte de la structure familiale traditionnelle. La plupart des soins aux personnes agées est fournie par des parents, bien qu'avec les modes d'engagement et de responsabilité dans les structures familiales variées. Pourtant, le modèle de la famille nucléaire conventionnelle devient de plus en plus rare, puisque nouveaux modèles pluralistes de la vie familiale apparaîssent dans la société contemporaine. Les familles conventionnelles et pluralistes, tous les deux, font face aux défis en répondant à la nécessité pour les soins de leurs membres les plus anciens, en laissant certaines personnes âgées à risque de ne pas avoir réponse aux besoins. Des recherches supplémentaires seront justifiées au sujet du risque et de la résilience de la famille relative à la prise en charge des parents âgés, particulièrement concernant les modèles pluralistes de la vie familiale.
Challenges of intra-institutional transfer of care from paediatric to adult congenital cardiology: the need for retention as well as transition
Authors: Bohun Claudine M. , Woods Patricia , Winter Christiane , Mitchell Julie , McLarry Joel , Weiss Joseph , Broberg Craig S.
Published: July 2015

Background

Transferring patients with CHD from paediatric to adult care has been challenging, especially across institutions. Within a single institution, some issues such as provider interaction, information exchange, or administrative directives should not play a significant role, and should favour successful transfer.

Objective

We studied patients who were eligible for transfer to the adult congenital heart disease service within our institution in order to identify factors associated with successful transfer to adult care providers versus failure to transfer.

Methods

Patients above18 years of age with CHD who were seen by paediatric cardiologists before January, 2008 were identified through a patient-care database. Records were reviewed to determine follow-up between 2008 and 2011 and to determine whether the patient was seen in the adult congenital cardiology clinic, paediatric cardiology clinic, or had no follow-up, and statistical comparisons were made between groups.

Results

After reviewing 916 records, 229 patients were considered eligible for transition to adult congenital cardiology. Of these, 77 (34%) were transferred successfully to adult congenital cardiology, 47 (21%) continued to be seen by paediatric cardiologists, and 105 (46%) were lost to follow-up. Those who transferred successfully differed with regard to complexity of diagnosis, insurance, and whether a formal referral was made by a paediatric care provider. Only a small fraction of the patients who were lost to follow-up could be contacted.

Conclusion

Within a single institution, with shared information systems, administrations, and care providers, successful transfer from paediatric to adult congenital cardiology was still poor. Efforts for successful retention are just as vital as those for transfer.
Does N-terminal pro-brain natriuretic peptide correlate with measured shunt fraction in children with septal defects?
Authors: Ozyurt Abdullah , Baykan Ali , Argun Mustafa , Pamukcu Ozge , Uzum Kazim , Narin Figen , Narin Nazmi
Published: July 2015

Background

The aim of this study was to investigate the potential role of N-terminal pro-brain natriuretic peptide in the assessment of shunt severity and invasive haemodynamic parameters in children with atrial septal defects and ventricular septal defects.

Methods

This is a prospective, controlled (n:62), observational study. Correlation analysis was performed between N-terminal pro-brain natriuretic peptide levels and various invasive haemodynamic measurements in 127 children (ventricular septal defect: 64; atrial septal defect: 63). A ratio of pulmonary to systemic blood flow (Qp/Qs⩾1.5) was considered to indicate a significant shunt.

Results

Statistically significant relationship was found between the mean N-terminal pro-brain natriuretic peptide values of the patients, with Qp/Qs⩾1.5 in both defect types and control group. For ventricular septal defect, N-terminal pro-brain natriuretic peptide level⩾113.5 pg/ml was associated with high specificity and sensitivity for determining the significant shunt. In addition, the cut-off point for determining the significant shunt for atrial septal defect was 57.9 pg/ml. Significant positive correlation was found between all invasive haemodynamic parameters and N-terminal pro-brain natriuretic peptide levels in patients with ventricular septal defects. Whereas significant positive correlation was found only between mean pulmonary artery pressure, right ventricular end-diastolic pressure, and systemic pressure to pulmonary pressure ratio and N-terminal pro-brain natriuretic peptide levels in patients with atrial septal defects.

Conclusion

Our study demonstrated that the N-terminal pro-brain natriuretic peptide measurements could be used as a supporting parameter in determining significance of the shunt.
Serum digoxin concentrations and clinical signs and symptoms of digoxin toxicity in the paediatric population
Authors: Moffett Brady S. , Garner April , Zapata Troy , Orcutt Jeffrey , Niu Mary , Lopez Keila N.
Published: July 2015

Background

Serum digoxin levels have limited utility for determining digoxin toxicity in adults. Paediatric data assessing the utility of monitoring serum digoxin concentration are scarce. We sought to determine whether serum digoxin concentrations are associated with signs and symptoms of digoxin toxicity in children.

Methods

We carried out a retrospective review of patients <19 years of age who received digoxin and had serum digoxin concentrations assessed between January, 2007 and June, 2013. Data collection included patient demographics, digoxin indication, serum digoxin concentrations, signs and symptoms of digoxin toxicity, electrocardiograms, and co-morbidities. Reviewers performing chart review and electrocardiogram analysis were blinded to digoxin levels. Descriptive statistical methods were used and comparisons were made between patients with and without toxic serum digoxin concentrations (>2 ng/ml).

Results

There were 87 patients who met study criteria (male 46%, mean age 8.4 years). CHD was present in 67.8% and electrocardiograms were performed in 72.4% of the patients. The most common indication for digoxin toxicity was heart failure symptoms (61.5%). Toxic serum digoxin concentrations were present in 6.9% of patients (mean 2.6 ng/ml). Symptoms associated with digoxin toxicity occurred in 48.4%, with nausea/vomiting as the most common symptom (36.4%), followed by tachycardia (29.5%). Compared with those without toxic serum digoxin concentrations, significantly more patients with toxic serum digoxin concentrations were female (p=0.02). The presence of electrocardiogram abnormalities and/or signs and symptoms of digoxin toxicity was not significantly different between patients with and without serum digoxin concentrations (p>0.05).

Conclusion

Serum digoxin concentrations in children are not strongly associated with signs and symptoms of digoxin toxicity.
Determining bronchial morphology for the purposes of segregating so-called heterotaxy
Authors: Loomba Rohit S. , Pelech Andrew N. , Shah Parinda H. , Anderson Robert H.
Published: July 2015

Introduction

Heterotaxy is a unique clinical entity in which lateralisation of the thoraco-abdominal organs is abnormal, typically with isomerism of the bronchial tree and atrial appendages. This study was carried out to determine whether routine clinical imaging such as chest radiographs, angiographic images, and CT/MRI can determine bronchial isomerism, and how sidedness of bronchial isomerism correlates with overall features anticipated in hearts with isomeric atrial appendages.

Methods and results

We identified 73 patients with heterotaxy, in whom imaging clearly demonstrated the bronchial tree, seen at our institution since 1998. We calculated bronchial angles and lengths using all the available imaging modalities to determine the presence and sidedness of bronchial isomerism. This was then compared with the anticipated presence of isomeric atrial appendages based on the overall clinical findings, as the appendages themselves had not specifically been imaged.

The ratio of bronchial lengths revealed bronchial isomerism in all patients, with bronchial angles permitting distinction of right as opposed to left isomerism. We noted discordances between the identified bronchial isomerism and the presumed arrangement of the atrial appendages in nearly 20% of the patients in our cohort.

Conclusion

Routine clinical imaging with chest radiographs, angiographic imaging, and CT/MRI can determine the presence of bronchial isomerism in patients with so-called heterotaxy. Right as opposed to left isomerism can be distinguished based on bronchial angles. The finding of bronchial isomerism correlates well, but not totally, with the presumed isomerism of the atrial appendages as predicted from the identified intra-cardiac morphology.
2015 AGU Section and Focus Group Awardees and Named Lecturers
Authors: Davidson Eric
Published: July 2015

AGU section and focus group awards and named lectures recognize some of the most innovative minds in their fields.
Ultrastrong ductile and stable high-entropy alloys at small scales
Authors: Zou Yu , Ma Huan , Spolenak Ralph
Published: July 2015

Refractory high-entropy alloys (HEAs) are a class of emerging multi-component alloys, showing superior mechanical properties at elevated temperatures and being technologically interesting. However, they are generally brittle at room temperature, fail by cracking at low compressive strains and suffer from limited formability. Here we report a strategy for the fabrication of refractory HEA thin films and small-sized pillars that consist of strongly textured, columnar and nanometre-sized grains. Such HEA pillars exhibit extraordinarily high yield strengths of ∼10 GPa—among the highest reported strengths in micro-/nano-pillar compression and one order of magnitude higher than that of its bulk form—and their ductility is considerably improved (compressive plastic strains over 30%). Additionally, we demonstrate that such HEA films show substantially enhanced stability for high-temperature, long-duration conditions (at 1,100 °C for 3 days). Small-scale HEAs combining these properties represent a new class of materials in small-dimension devices potentially for high-stress and high-temperature applications.
Dynamic structural evolution of supported palladium–ceria core–shell catalysts revealed by in situ electron microscopy
Authors: Zhang Shuyi , Chen Chen , Cargnello Matteo , Fornasiero Paolo , Gorte Raymond J. , Graham George W. , Pan Xiaoqing
Published: July 2015

The exceptional activity for methane combustion of modular palladium–ceria core–shell subunits on silicon-functionalized alumina that was recently reported has created renewed interest in the potential of core–shell structures as catalysts. Here we report on our use of advanced ex situ and in situ electron microscopy with atomic resolution to show that the modular palladium–ceria core–shell subunits undergo structural evolution over a wide temperature range. In situ observations performed in an atmospheric gas cell within this temperature range provide real-time evidence that the palladium and ceria nanoparticle constituents of the palladium–ceria core–shell participate in a dynamical process that leads to the formation of an unanticipated structure comprised of an intimate mixture of palladium, cerium, silicon and oxygen, with very high dispersion. This finding may open new perspectives about the origin of the activity of this catalyst.
Understanding Dengue Virus Capsid Protein Interaction with Key Biological Targets
Authors: Faustino André F. , Martins Ivo C. , Carvalho Filomena A. , Castanho Miguel A. R. B. , Maurer-Stroh Sebastian , Santos Nuno C.
Published: July 2015

Dengue virus (DENV) causes over 500,000 hospitalizations and 20,000 deaths worldwide every year. Dengue epidemics now reach temperate regions due to globalization of trade and travel and climate changes. Currently, there are no successful therapeutic or preventive approaches. We previously developed a peptide drug lead, pep14-23, that inhibits the biologically relevant interaction of DENV capsid (C) protein with lipid droplets (LDs). Surprisingly, pep14-23 also inhibits DENV C interaction with very low-density lipoproteins (VLDL). We thus investigated the similarity between the proposed DENV C molecular targets in LDs and VLDL, respectively, the proteins perilipin 3 (PLIN3) and apolipoprotein E (APOE). APOE N-terminal and PLIN3 C-terminal regions are remarkably similar, namely APOE α-helix 4 (APOEα4) and PLIN3 α-helix 5 (PLIN3α5) sequences, which are also highly superimposable structurally. Interestingly, APOE α-helical N-terminal sequence and structure superimposes with DENV C α-helices α1 and α2. Moreover, the DENV C hydrophobic cleft can accommodate the structurally analogous APOEα4 and PLIN3α5 helical regions. Mirroring DENV C-LDs interaction (previously shown experimentally to require PLIN3), we experimentally demonstrated that DENV C-VLDL interaction requires APOE. Thus, the results fit well with previous data and suggest future drug development strategies targeting the above mentioned α-helical structures.
Understanding the Control of Singlet-Triplet Splitting for Organic Exciton Manipulating: A Combined Theoretical and Experimental Approach
Authors: Chen Ting , Zheng Lei , Yuan Jie , An Zhongfu , Chen Runfeng , Tao Ye , Li Huanhuan , Xie Xiaoji , Huang Wei
Published: July 2015

Developing organic optoelectronic materials with desired photophysical properties has always been at the forefront of organic electronics. The variation of singlet-triplet splitting (ΔEST) can provide useful means in modulating organic excitons for diversified photophysical phenomena, but controlling ΔESTin a desired manner within a large tuning scope remains a daunting challenge. Here, we demonstrate a convenient and quantitative approach to relate ΔESTto the frontier orbital overlap and separation distanceviaa set of newly developed parameters using natural transition orbital analysis to consider whole pictures of electron transitions for both the lowest singlet (S1) and triplet (T1) excited states. These critical parameters revealed that both separated S1and T1states leads to ultralow ΔEST; separated S1and overlapped T1states results in small ΔEST; and both overlapped S1and T1states induces large ΔEST. Importantly, we realized a widely-tuned ΔESTin a range from ultralow (0.0003 eV) to extra-large (1.47 eV)viaa subtle symmetric control of triazine molecules, based on time-dependent density functional theory calculations combined with experimental explorations. These findings provide keen insights into ΔESTcontrol for feasible excited state tuning, offering valuable guidelines for the construction of molecules with desired optoelectronic properties.
Integrative proteomics to understand the transmission mechanism of Barley yellow dwarf virus-GPV by its insect vector Rhopalosiphum padi
Authors: Wang Hui , Wu Keke , Liu Yan , Wu Yunfeng , Wang Xifeng
Published: July 2015

Barley yellow dwarf virus-GPV (BYDV-GPV) is transmitted by Rhopalosiphum padi and Schizaphis graminum in a persistent nonpropagative manner. To improve our understanding of its transmission mechanism by aphid vectors, we used two approaches, isobaric tags for relative and absolute quantitation (iTRAQ) and yeast two-hybrid (YTH) system, to identify proteins in R. padi that may interact with or direct the spread of BYDV-GPV along the circulative transmission pathway. Thirty-three differential aphid proteins in viruliferous and nonviruliferous insects were identified using iTRAQ coupled to 2DLC-MS/MS. With the yeast two-hybrid system, 25 prey proteins were identified as interacting with the readthrough protein (RTP) and eight with the coat protein (CP), which are encoded by BYDV-GPV. Among the aphid proteins identified, most were involved in primary energy metabolism, synaptic vesicle cycle, the proteasome pathway and the cell cytoskeleton organization pathway. In a systematic comparison of the two methods, we found that the information generated by the two methods was complementary. Taken together, our findings provide useful information on the interactions between BYDV-GPV and its vector R. padi to further our understanding of the mechanisms regulating circulative transmission in aphid vectors.
Oxytocin evokes a pulsatile PGE2 release from ileum mucosa and is required for repair of intestinal epithelium after injury
Authors: Chen Dawei , Zhao Junhan , Wang Haoyi , An Ning , Zhou Yuping , Fan Jiahui , Luo Junwen , Su Wenlong , Liu Chuanyong , Li Jingxin
Published: July 2015

We measured the short-circuit current (Isc) in rat ileum mucosa to identify the effect of oxytocin (OT) on mucosal secretion in small intestine. We identified a COX-2-derived pulsatile PGE2 release triggered by OT in rat ileum mucosa. OT receptors (OTR) are expressed in intestine crypt epithelial cells. Notably, OT evoked a dynamic change of [Ca2+]i in ileum crypts, which was responsible for this pulsatile release of PGE2. OT ameliorated 5-FU-, radiation- or DSS- induced injury in vivo, including the improvement of weight loss, reduced villus height and impaired survival of crypt transit-amplifying cells as well as crypt. Moreover, these protective effects of OT against intestinal injury were eliminated by coadministration of a selective inhibitor of PGE2, AH6809. Our findings strongly suggest that OT, a novel and important regulator of intestine mucosa barrier, is required for repair of intestinal epithelium after injury. Considering that OT is an FDA-approved drug, this work reveals a potential novel and safe way to combat or prevent chemo-radiotherapy induced intestine injury or to treat IBD.
Exogenous and endogenous determinants of vitamin K status in cystic fibrosis
Authors: Krzyżanowska Patrycja , Pogorzelski Andrzej , Skorupa Wojciech , Moczko Jerzy , Grebowiec Philip , Walkowiak Jarosław
Published: July 2015

Cystic fibrosis (CF) patients are at high risk for vitamin K deficiency. The effects of vitamin K supplementation are very ambiguous. Therefore, we aimed to define the determinants of vitamin K deficiency in a large cohort of supplemented - 146 (86.9%) and non-supplemented - 22 (13.1%) CF patients. Vitamin K status was assessed using prothrombin inducted by vitamin K absence (PIVKA-II) and undercarboxylated osteocalcin (u-OC). The pathological PIVKA-II concentration (≥2 ng/ml) and abnormal percentage of osteocalcin (≥20%) were found in 72 (42.8%) and 60 (35.7%) subjects, respectively. We found that liver involvement, diabetes and glucocorticoid therapy were potential risk factors for vitamin K deficiency. Pathological concentrations of PIVKA-II occurred more frequently in patients with pancreatic insufficiency and those who have two severe mutations in both alleles of the CFTR gene. Pathological percentage of u-OC was found more frequently in adult CF patients and those not receiving vitamin K. However, it seems that there are no good predictive factors of vitamin K deficiency in CF patients in everyday clinical care. Early vitamin K supplementation in CF patients seems to be warranted. It is impossible to clearly determine the supplementation dose. Therefore, constant monitoring of vitamin K status seems to be justified.
Rapid fusion between mesenchymal stem cells and cardiomyocytes yields electrically active, non-contractile hybrid cells
Authors: Shadrin Ilya Y. , Yoon Woohyun , Li Liqing , Shepherd Neal , Bursac Nenad
Published: July 2015

Cardiac cell therapies involving bone marrow-derived human mesenchymal stem cells (hMSCs) have shown promising results, although their mechanisms of action are still poorly understood. Here, we investigated direct interactions between hMSCs and cardiomyocytes in vitro. Using a genetic Ca2+ indicator gCaMP3 to efficiently label hMSCs in co-cultures with neonatal rat ventricular myocytes (NRVMs), we determined that 25–40% of hMSCs (from 4 independent donors) acquired periodic Ca2+ transients and cardiac markers through spontaneous fusion with NRVMs. Sharp electrode and voltage-clamp recordings in fused cells showed action potential properties and Ca2+ current amplitudes in between those of non-fused hMSCs and NRVMs. Time-lapse video-microscopy revealed the first direct evidence of active fusion between hMSCs and NRVMs within several hours of co-culture. Application of blebbistatin, nifedipine or verapamil caused complete and reversible inhibition of fusion, suggesting potential roles for actomyosin bridging and Ca2+ channels in the fusion process. Immunostaining for Cx43, Ki67 and sarcomeric α-actinin showed that fused cells remain strongly coupled to surrounding NRVMs, but downregulate sarcomeric structures over time, acquiring a non-proliferative and non-contractile phenotype. Overall, these results describe the phenotype and mechanisms of hybrid cell formation via fusion of hMSCs and cardiomyocytes with potential implications for cardiac cell therapy.
A Nanotechnology-Based Platform for Extending the Pharmacokinetic and Binding Properties of Anti-methamphetamine Antibody Fragments
Authors: Nanaware-Kharade Nisha , Thakkar Shraddha , Gonzalez III Guillermo A. , Peterson Eric C.
Published: July 2015

To address the need for effective medications to aid in the treatment of methamphetamine (METH) abuse, we used a nanotechnology approach to customize the in vivo behavior of an anti-METH single chain antibody (scFv7F9Cys). Anti-METH scFv7F9Cys was conjugated to dendrimer nanoparticles via a polyethylene glycol (PEG) linker to generate high-order conjugates termed dendribodies. We found that the high affinity (KD = 6.2 nM) and specificity for METH was unchanged after nanoparticle conjugation. The dendribodies were administered in an i.v. bolus to male Sprague Dawley rats after starting a s.c. infusion of METH. The PCKN values for clearance and volume of distribution of scFv7F9Cys after conjugation to dendrimers decreased 45 and 1.6-fold respectively and the terminal elimination half-life increased 20-fold. Organ distribution of scFv7F9Cys and dendribody in blood and urine agreed well with the PCKN data. Renal clearance appeared to be the major route of elimination for both experimental medications. We have thus successfully developed a novel multivalent METH-binding nanomedicine by conjugating multiple anti-METH scFvs to dendrimer nanoparticles, extending the scFv half-life from 1.3 (±0.3) to 26 (±2.6) hr. These data suggest that the dendribody design could be a feasible platform for generating multivalent antibodies with customizable PCKN profiles.
Small-angle X-ray scattering method to characterize molecular interactions: Proof of concept
Authors: Allec Nicholas , Choi Mina , Yesupriya Nikhil , Szychowski Brian , White Michael R. , Kann Maricel G. , Garcin Elsa D. , Daniel Marie-Christine , Badano Aldo
Published: July 2015

Characterizing biomolecular interactions is crucial to the understanding of biological processes. Existing characterization methods have low spatial resolution, poor specificity and some lack the capability for deep tissue imaging. We describe a novel technique that relies on small-angle X-ray scattering signatures from high-contrast molecular probes that correlate with the presence of biomolecular interactions. We describe a proof-of-concept study that uses a model system consisting of mixtures of monomer solutions of gold nanoparticles (GNPs) as the non-interacting species and solutions of GNP dimers linked with an organic molecule (dimethyl suberimidate) as the interacting species. We report estimates of the interaction fraction obtained with the proposed small-angle X-ray scattering characterization method exhibiting strong correlation with the known relative concentration of interacting and non-interacting species.