bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs
Authors: Chen Tian Sheng , Arslan Fatih , Yin Yijun , Tan Soon Sim , Lai Ruenn Chai , Choo Andre Boon Hwa , Padmanabhan Jayanthi , Lee Chuen Neng , de Kleijn Dominique PV , Lim Sai Kiang 
Published: April 2011

Abstract

Background
Exosomes or secreted bi-lipid vesicles from human ESC-derived mesenchymal stem cells (hESC-MSCs) have been shown to reduce myocardial ischemia/reperfusion injury in animal models. However, as hESC-MSCs are not infinitely expansible, large scale production of these exosomes would require replenishment of hESC-MSC through derivation from hESCs and incur recurring costs for testing and validation of each new batch. Our aim was therefore to investigate if MYC immortalization of hESC-MSC would circumvent this constraint without compromising the production of therapeutically efficacious exosomes.

Methods
The hESC-MSCs were transfected by lentivirus carrying a MYC gene. The transformed cells were analyzed for MYC transgene integration, transcript and protein levels, and surface markers, rate of cell cycling, telomerase activity, karyotype, genome-wide gene expression and differentiation potential. The exosomes were isolated by HPLC fractionation and tested in a mouse model of myocardial ischemia/reperfusion injury, and infarct sizes were further assessed by using Evans' blue dye injection and TTC staining.

Results

MYC-transformed MSCs largely resembled the parental hESC-MSCs with major differences being reduced plastic adherence, faster growth, failure to senesce, increased MYC protein expression, and loss of in vitro adipogenic potential that technically rendered the transformed cells as non-MSCs. Unexpectedly, exosomes from MYC-transformed MSCs were able to reduce relative infarct size in a mouse model of myocardial ischemia/reperfusion injury indicating that the capacity for producing therapeutic exosomes was preserved.

Conclusion
Our results demonstrated that MYC transformation is a practical strategy in ensuring an infinite supply of cells for the production of exosomes in the milligram range as either therapeutic agents or delivery vehicles. In addition, the increased proliferative rate by MYC transformation reduces the time for cell production and thereby reduces production costs.
Conjugate heat transfer of laminar mixed convection of a nanofluid through an inclined tube with circumferentially non-uniform heating
Authors: Allahyari Shahriar , Behzadmehr Amin , Sarvari Seyed Masoud Hosseini 
Published: April 2011

AbstractLaminar mixed convection of a nanofluid consisting of water and Al2O3in an inclined tube with heating at the top half surface of a copper tube has been studied numerically. The bottom half of the tube wall is assumed to be adiabatic (presenting a tube of a solar collector). Heat conduction mechanism through the tube wall is considered. Three-dimensional governing equations with using two-phase mixture model have been solved to investigate hydrodynamic and thermal behaviours of the nanofluid over wide range of nanoparticle volume fractions. For a given nanoparticle mean diameter the effects of nanoparticle volume fractions on the hydrodynamics and thermal parameters are presented and discussed at different Richardson numbers and different tube inclinations. Significant augmentation on the heat transfer coefficient as well as on the wall shear stress is seen.
Design process of the nanofluid injection mechanism in nuclear power plants
Authors: Kang Myoung-suk , Jee Changhyun , Park Sangjun , Bang In Choel , Heo Gyunyoung 
Published: April 2011

Abstract
Nanofluids, which are engineered suspensions of nanoparticles in a solvent such as water, have been found to show enhanced coolant properties such as higher critical heat flux and surface wettability at modest concentrations, which is a useful characteristic in nuclear power plants (NPPs). This study attempted to provide an example of engineering applications in NPPs using nanofluid technology. From these motivations, the conceptual designs of the emergency core cooling systems (ECCSs) assisted by nanofluid injection mechanism were proposed after following a design framework to develop complex engineering systems. We focused on the analysis of functional requirements for integrating the conventional ECCSs and nanofluid injection mechanism without loss of performance and reliability. Three candidates of nanofluid-engineered ECCS proposed in previous researches were investigated by applying axiomatic design (AD) in the manner of reverse engineering and it enabled to identify the compatibility of functional requirements and potential design vulnerabilities. The methods to enhance such vulnerabilities were referred from TRIZ and concretized for the ECCS of the Korean nuclear power plant. The results show a method to decouple the ECCS designs with the installation of a separate nanofluids injection tank adjacent to the safety injection tanks such that a low pH environment for nanofluids can be maintained at atmospheric pressure which is favorable for their injection in passive manner.
Electro-synthesis of novel nanostructured PEDOT films and their application as catalyst support
Authors: Zhou Cuifeng , Liu Zongwen , Yan Yushan , Du Xusheng , Mai Yiu-Wing , Ringer Simon 
Published: April 2011

Abstract
Poly(3,4-ethylenedioxythiophene) (PEDOT) films doped with nitric and chlorine ions have been electrochemically deposited simply by a one-step electrochemical method in an aqueous media in the absence of any surfactant. The fabricated PEDOT films were characterized by scanning electron microscopy, transmission electron microscopy, and Raman spectroscopy. The results indicate that the hierarchical structured PEDOT film doped with nitric ions displays a 'lunar craters' porous morphology consisting of PEDOT nano-sheets with a thickness of less than 2 nm. The effect of counter ions on the electro-polymerization, the electrochemistry, and the morphology of the polymer film was studied. Compared with PEDOT film doped with nitric acid, PEDOT film deposited in the presence of chlorine ions shows irregular morphology and less electrochemical activity. The specific nanostructure of the polymer was further studied as catalyst support for platinum nanoparticles to methanol electro-oxidation.
A situational analysis of HIV and AIDS in Pakistan
Authors: Ilyas Muhammad , Asad Sultan , Ali Liaqat , Shah Masaud , Badar Sadaf , Sarwar Muhammad Tahir , Sumrin Aleena 
Published: April 2011

Abstract
HIV (Human immunodeficiency virus) transmission has been reduced by protected sex and screening of blood products and other body fluids in the developed countries. It has been reported that Pakistan is at high risk of HIV/AIDS infection but presently the prevalence rate is considerably low. The number of reported cases of HIV/AIDS in Pakistan has been continuously increasing since 1987. By 2010 the total number of registered cases has reached to 6000 and this figure is on the rise with the passage of time. Some serious strategies must be implemented to control this deadly disease.
Impact of sphingomyelin levels on coronary heart disease and left ventricular systolic function in humans
Authors: Chen Xueying , Sun Aijun , Zou Yunzeng , Ge Junbo , Lazar Jason M , Jiang Xian-Cheng 
Published: April 2011

Abstract
Sphingomyelin (SM) is an abundant phospholipid in cell membranes and in lipoproteins. In human plasma, SM is mainly found in atherogenic lipoproteins; therefore, higher levels of SM may promote atherogenesis. We investigated the relations between plasma SM levels and the presence of angiographic coronary heart disease (CHD) and left ventricular systolic dysfunction. We studied 732 patients referred for coronary angiography. Median SM levels were higher among patients with CHD and in those with LV systolic dysfunction (LVEF<50%) than in patients without CHD or LV dysfunction. SM levels were significantly correlated with fibrinogen levels, diabetes, apoB, and triglyceride levels. On multivariate analyses, higher median SM levels were associated with a higher risk of CHD and lower LV ejection fraction. The pro-atherogenic property of plasma SM might be related to 1) CHD; 2) LV systolic dysfunction; and 3) metabolism of apoB-containing or triglyceride-rich lipoproteins.
Thoracic aorta pseudoaneurysm with hemopericardium: unusual presentation of warfarin overdose
Authors: Tien Ya-Chih , Chen Ying-Cheng , Liao Chiung-Ying , Chang Chia-Chu 
Published: April 2011

Abstract
There have been few case reports which discuss a relationship between warfarin overdose and aortic pseudoaneurysm leakage. We report the case of a female receiving warfarin who presented with dsypnea. Her international normalized ratio was > 10. Chest radiograph revealed cardiomegaly, and chest computed tomography (CT) showed a bulging pouch-like lesion below the aortic arch greater than 6x6 cm in size and a fluid collection suggesting blood in the pericardium. Thoracic endovascular aneurysm repair (TEVAR) was successfully performed by a cardiovascular surgeon. Aortic pseudoaneurysm formation and leakage may be considered as a rare complication in patients receiving warfarin therapy. Further study regarding warfarin use and the incidence of pseudoaneurysm leakage is needed.
Molecular analysis of mucopolysaccharidosis type I in Tunisia: identification of novel mutation and eight Novel polymorphisms
Authors: Chkioua Latifa , Khedhiri Souhir , Kassab Asma , Bibi Amina , Ferchichi Salima , Froissart Roseline , Vianey-Saban Christine , Laradi Sandrine , Miled Abdelhedi 
Published: April 2011

Abstract
Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder caused by a genetic defect in alpha-L-iduronidase (IDUA) which is involved in the degradation of dermatan and heparan sulfates. The disease has severe and milder phenotypic subtypes. The aim of this study was the detection of mutations in the IDUA gene from 12 additional MPS I patients with various clinical phenotypes (severe, 8 cases; intermediate, 3 cases; mild, 1 case).

Patients and methods

In this study, the IDUA mutations in eight unrelated Tunisian families were performed by amplifying and sequencing the IDUA exons and intron-exon jonctions.

Results

Five IDUA mutations were detected: one is the L578Q, a novel mutation found, in milder patient. The others were the previously described: P533R, Y581X, F602X and R628X that produce a severe and intermediate phenotype. In addition, eighteen variants, including eight previously unreported polymorphisms (IVS6+21c > a, IVS7+79c > t, IVS7-45 g > c, IVS9+36t > c, IVS10+140c > a, IVS11+33c > t, IVS12+13c > t and IVS12-31c > g), were detected.

Conclusion

This paper, showed a heterogeneous pattern of mutations and polymorphisms among Tunisian patients.
Gene expression profiling of human dermal fibroblasts exposed to bleomycin sulphate does not differentiate between radiation sensitive and control patients
Authors: Westbury Charlotte B , Sahlberg Kristine Kleivi , Borresen-Dale Anne-Lise , Isacke Clare M , Yarnold John R 
Published: April 2011

Abstract

Background
Gene expression profiling of the transcriptional response of human dermal fibroblasts to in vitro radiation has shown promise as a predictive test of radiosensitivity. This study tested if treatment with the radiomimetic drug bleomycin sulphate could be used to differentiate radiation sensitive patients and controls in patients who had previously received radiotherapy for early breast cancer.

Findings
Eight patients who developed marked late radiation change assessed by photographic breast appearance and 8 matched patients without any change were selected from women entered in a prospective randomised trial of breast radiotherapy fractionation. Gene expression profiling of primary skin fibroblasts exposed in vitro to bleomycin sulphate and mock treated fibroblast controls was performed. 973 genes were up-regulated and 923 down-reguated in bleomycin sulphate treated compared to mock treated control fibroblasts. Gene ontology analysis revealed enriched groups were cellular localisation, apoptosis, cell cycle and DNA damage response for the deregulated genes. No transcriptional differences were identified between fibroblasts from radiation sensitive cases and control patients; subgroup analysis using cases exhibiting severe radiation sensitivity or with high risk alleles present in TGF β1 also showed no difference.

Conclusions
The transcriptional response of human dermal fibroblasts to bleomycin sulphate has been characterised. No differences between clinically radiation sensitive and control patients were detected using this approach.
Steroid-triggered, cell-autonomous death of a Drosophila motoneuron during metamorphosis
Authors: Winbush Ari , Weeks Janis C 
Published: April 2011

Abstract

Background
The metamorphosis of Drosophila melanogaster is accompanied by elimination of obsolete neurons via programmed cell death (PCD). Metamorphosis is regulated by ecdysteroids, including 20-hydroxyecdysone (20E), but the roles and modes of action of hormones in regulating neuronal PCD are incompletely understood.

Results
We used targeted expression of GFP to track the fate of a larval motoneuron, RP2, in ventral ganglia. RP2s in abdominal neuromeres two through seven (A2 to A7) exhibited fragmented DNA by 15 hours after puparium formation (h-APF) and were missing by 20 h-APF. RP2 death began shortly after the 'prepupal pulse' of ecdysteroids, during which time RP2s expressed ecdysteroid receptors (EcRs). Genetic manipulations showed that RP2 death required the function of EcR-B isoforms, the death-activating gene, reaper (but not hid), and the apoptosome component, Dark. PCD was blocked by expression of the caspase inhibitor p35 but unaffected by manipulating Diap1. In contrast, aCC motoneurons in neuromeres A2 to A7, and RP2s in neuromere A1, expressed EcRs during the prepupal pulse but survived into the pupal stage under all conditions tested. To test the hypothesis that ecdysteroids trigger RP2's death directly, we placed abdominal GFP-expressing neurons in cell culture immediately prior to the prepupal pulse, with or without 20E. 20E induced significant PCD in putative RP2s, but not in control neurons, as assessed by morphological criteria and propidium iodide staining.

Conclusions
These findings suggest that the rise of ecdysteroids during the prepupal pulse acts directly, via EcR-B isoforms, to activate PCD in RP2 motoneurons in abdominal neuromeres A2 to A7, while sparing RP2s in A1. Genetic manipulations suggest that RP2's death requires Reaper function, apoptosome assembly and Diap1-independent caspase activation. RP2s offer a valuable 'single cell' approach to the molecular understanding of neuronal death during insect metamorphosis and, potentially, of neurodegeneration in other contexts.
Systems biology approach to identify transcriptome reprogramming and candidate microRNA targets during the progression of polycystic kidney disease
Authors: Pandey Priyanka , Qin Shan , Ho Jacqueline , Zhou Jing , Kreidberg Jordan A 
Published: April 2011

Abstract

Background
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by cyst formation throughout the kidney parenchyma. It is caused by mutations in either of two genes, PKD1 and PKD2. Mice that lack functional Pkd1 (Pkd1

-/-
), develop rapidly progressive cystic disease during embryogenesis, and serve as a model to study human ADPKD. Genome wide transcriptome reprogramming and the possible roles of micro-RNAs (miRNAs) that affect the initiation and progression of cyst formation in the Pkd1

-/-
have yet to be studied. miRNAs are small, regulatory non-coding RNAs, implicated in a wide spectrum of biological processes. Their expression levels are altered in several diseases including kidney cancer, diabetic nephropathy and PKD.

Results
We examined the molecular pathways that modulate renal cyst formation and growth in the Pkd1

-/-
model by performing global gene-expression profiling in embryonic kidneys at days 14.5 and 17.5. Gene Ontology and gene set enrichment analysis were used to identify overrepresented signaling pathways in Pkd1

-/-
kidneys. We found dysregulation of developmental, metabolic, and signaling pathways (e.g. Wnt, calcium, TGF-β and MAPK) in Pkd1

-/-
kidneys. Using a comparative transcriptomics approach, we determined similarities and differences with human ADPKD: ~50% overlap at the pathway level among the mis-regulated pathways was observed. By using computational approaches (TargetScan, miRanda, microT and miRDB), we then predicted miRNAs that were suggested to target the differentially expressed mRNAs. Differential expressions of 9 candidate miRNAs, miRs-10a, -30a-5p, -96, -126-5p, -182, -200a, -204, -429 and -488, and 16 genes were confirmed by qPCR. In addition, 14 candidate miRNA:mRNA reciprocal interactions were predicted. Several of the highly regulated genes and pathways were predicted as targets of miRNAs.

Conclusions
We have described global transcriptional reprogramming during the progression of PKD in the Pkd1

-/-
model. We propose a model for the cascade of signaling events involved in cyst formation and growth. Our results suggest that several miRNAs may be involved in regulating signaling pathways in ADPKD. We further describe novel putative miRNA:mRNA signatures in ADPKD, which will provide additional insights into the pathogenesis of this common genetic disease in humans.
Statistical Inference Methods for Sparse Biological Time Series Data
Authors: Ndukum Juliet , Fonseca Luís L , Santos Helena , Voit Eberhard O , Datta Susmita 
Published: April 2011

Abstract

Background
Comparing metabolic profiles under different biological perturbations has become a powerful approach to investigating the functioning of cells. The profiles can be taken as single snapshots of a system, but more information is gained if they are measured longitudinally over time. The results are short time series consisting of relatively sparse data that cannot be analyzed effectively with standard time series techniques, such as autocorrelation and frequency domain methods. In this work, we study longitudinal time series profiles of glucose consumption in the yeast Saccharomyces cerevisiae under different temperatures and preconditioning regimens, which we obtained with methods of in vivo nuclear magnetic resonance (NMR) spectroscopy. For the statistical analysis we first fit several nonlinear mixed effect regression models to the longitudinal profiles and then used an ANOVA likelihood ratio method in order to test for significant differences between the profiles.

Results
The proposed methods are capable of distinguishing metabolic time trends resulting from different treatments and associate significance levels to these differences. Among several nonlinear mixed-effects regression models tested, a three-parameter logistic function represents the data with highest accuracy. ANOVA and likelihood ratio tests suggest that there are significant differences between the glucose consumption rate profiles for cells that had been--or had not been--preconditioned by heat during growth. Furthermore, pair-wise t-tests reveal significant differences in the longitudinal profiles for glucose consumption rates between optimal conditions and heat stress, optimal and recovery conditions, and heat stress and recovery conditions (p-values <0.0001).

Conclusion
We have developed a nonlinear mixed effects model that is appropriate for the analysis of sparse metabolic and physiological time profiles. The model permits sound statistical inference procedures, based on ANOVA likelihood ratio tests, for testing the significance of differences between short time course data under different biological perturbations.
“It is her responsibility”: partner involvement in prevention of mother to child transmission of HIV programmes, northern Tanzania
Authors: Falnes Eli Fjeld , Moland Karen Marie , Tylleskär Thorkild , de Paoli Marina Manuela , Msuya Sia E , Engebretsen Ingunn MS 
Published: April 2011

BackgroundPartner involvement has been deemed fundamental in prevention of mother to child transmission (PMTCT) programmes, but is difficult to achieve. This study aimed to explore acceptability of the PMTCT programme components and to identify structural and cultural challenges to male involvement.MethodsThe study was conducted during 2007‐2008 in rural and urban areas of Moshi in the Kilimanjaro region of Tanzania. Mixed methods were used, and included focus group discussions with fathers and mothers, in‐depth interviews with fathers, mothers and health personnel, and a survey of 426 mothers bringing their four‐week‐old infants for immunization at five reproductive and child health clinics.ResultsRoutine testing for HIV of women at the antenatal clinic was highly acceptable and appreciated by men, while other programme components, notably partner testing, condom use and the infant feeding recommendations, were met with continued resistance. Very few men joined their wives for testing and thus missed out on PMTCT counselling. The main barriers reported were that women did not have the authority to request their husbands to test for HIV and that the arena for testing, the antenatal clinic, was defined as a typical female domain where men were out of place.ConclusionsDeep‐seated ideas about gender roles and hierarchy are major obstacles to male participation in the PMTCT programme. Empowering women remains a huge challenge. Empowering men to participate by creating a space within the PMTCT programme that is male friendly should be feasible and should be highly prioritized for the PMTCT programme to achieve its potential.
Mammalian target of rapamycin and head and neck squamous cell carcinoma
Authors: Liao Yu-Min , Kim Charles , Yen Yun 
Published: April 2011

Abstract
Head and neck squamous cell carcinoma (HNSCC), a significant cause of cancer deaths worldwide, has multiple stepwise malignant evolutions. Mammalian target of rapamycin (mTOR) plays a critical role in tumor development, invasion, metastasis and angiogenesis that impact local recurrence and survival. mTOR can also act as a biomarker for personalized adjuvant therapy. In in vivo and in vitro studies, mTOR inhibitor suppresses tumor growth and sensitizes HNSCC to radiation, cytotoxic agents and epidermoid growth factor receptor inhibitors. We have reviewed the pathogenesis of HNSCC, mTOR pathway, mTOR inhibitor and the role of mTOR in HNSCC.