bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Inducible Tissue-Specific Expression of the Human IL-3/GM-CSF Locus Is Controlled by a Complex Array of Developmentally Regulated Enhancers
Authors: Baxter Euan W. , Mirabella Fabio , Bowers Sarion R. , James Sally R. , Bonavita Aude-Marine , Bertrand Elisabeth , Strogantsev Ruslan , Hawwari Abbas , Bert Andrew G. , Gonzalez de Arce Andrea , West Adam G. , Bonifer Constanze , Cockerill Peter N. 
Published: October 2012

Abstract
The closely linked human IL-3 and GM-CSF genes are tightly regulated and are expressed in activated T cells and mast cells. In this study, we used transgenic mice to study the developmental regulation of this locus and to identify DNA elements required for its correct activity in vivo. Because these two genes are separated by a CTCF-dependent insulator, and the GM-CSF gene is regulated primarily by its own upstream enhancer, the main objective in this study was to identify regions of the locus required for correct IL-3 gene expression. We initially found that the previously identified proximal upstream IL-3 enhancers were insufficient to account for the in vivo activity of the IL-3 gene. However, an extended analysis of DNase I-hypersensitive sites (DHSs) spanning the entire upstream IL-3 intergenic region revealed the existence of a complex cluster of both constitutive and inducible DHSs spanning the −34- to −40-kb region. The tissue specificity of these DHSs mirrored the activity of the IL-3 gene, and included a highly inducible cyclosporin A-sensitive enhancer at −37 kb that increased IL-3 promoter activity 40-fold. Significantly, inclusion of this region enabled correct in vivo regulation of IL-3 gene expression in T cells, mast cells, and myeloid progenitor cells.
Isolation and In Vitro Characterization of Basal and Submucosal Gland Duct Stem/Progenitor Cells from Human Proximal Airways
Authors: Hegab Ahmed E. , Ha Vi Luan , Darmawan Daphne O. , Gilbert Jennifer L. , Ooi Aik T. , Attiga Yasser S. , Bisht Bharti , Nickerson Derek W. , Gomperts Brigitte N. 
Published: October 2012

Abstract
Basal cells and submucosal gland (SMG) duct cells have been isolated and shown to be stem/progenitor cell populations for the murine airway epithelium. However, methods for the isolation of basal and SMG duct cells from human airways have not been defined. We used an optimized two-step enzyme digestion protocol to strip the surface epithelium from tracheal specimens separate from SMG cells, and we then sorted the basal and duct stem/progenitors using fluorescence-activated cell sorting. We used nerve growth factor receptor, as well as a combination of CD166 and CD44, to sort basal cells and also used CD166 to isolate SMG duct cells. Sorted stem/progenitor cells were cultured to characterize their self-renewal and differentiation ability. Both basal and SMG duct cells grew into spheres. Immunostaining of the spheres showed mostly dense spheres with little to no central lumen. The spheres expressed cytokeratins 5 and 14, with some mucus- and serous-secreting cells. The sphere-forming efficiency and the rate of growth of the spheres varied widely between patient samples and correlated with the degree of hyperplasia of the epithelium. We found that only aldehyde dehydrogenase (ALDH)hi basal and duct cells were capable of sphere formation. Global inhibition of ALDH, as well as specific inhibition of the ALDH2 isoform, inhibited self-renewal of both basal and duct cells, thereby producing fewer and smaller spheres. In conclusion, we have developed methods to isolate basal and SMG duct cells from the surface epithelium and SMGs of human tracheas and have developed an in vitro model to characterize their self-renewal and differentiation.
Calculating the Universal Energy‐Level Alignment of Organic Molecules on Metal Oxides
Authors: Ley Lothar , Smets Yaou , Pakes Christopher I. , Ristein Jürgen 
Published: October 2012

AbstractRecently, Greiner et al. [Nat. Mater. 2012, 11, 76] published a survey of the level alignment of about 40 metal oxide/organic molecule interfaces. They observed a striking regularity in the electronic level alignment of the highest occupied molecular orbital (HOMO) and the Fermi level that depends solely on the difference between the substrate work function and the ionization energy of the molecule independent of the details of the electronic structure of the oxide. The authors could reproduce their data under the assumption of thermodynamic equilibrium occupation of the HOMO using four adjustable parameters. A model that quantifies well‐established concepts in heterojunction physics and achieves the same result without any adjustable parameters is presented here. This approach explains why the level alignment is rather independent of the experimental details, such as the electronic structure of the oxide, defects in the oxide, and the thickness of oxide and overlayer. The model can also be extended to organic molecules or polymers on metals without any intermediate oxide as long as certain conditions are met. It also sheds new light on the large polaronic binding energy required to interpret the electronic level alignment of metal‐polymer interfaces.
A Bio‐inspired Platform to Modulate Myogenic Differentiation of Human Mesenchymal Stem Cells Through Focal Adhesion Regulation
Authors: Yu Haiyang , Tay Chor Yong , Pal Mintu , Leong Wen Shing , Li Huaqiong , Li Hai , Wen Feng , Leong David Tai , Tan Lay Poh 
Published: October 2012

AbstractThe use of human mesenchymal stem cells (hMSCs) in cardiac‐tissue engineering has gained widespread attention and many reports have shown that matrix compliance, micro/nano‐patterns could be some of the important biophysical cues that drive hMSCs differentiation. Regardless of the type of biophysical induction cues, cells mainly explore their environment via focal adhesion (FA) and FA plays an important role in many cellular behaviours. Therefore, it is hypothesized that FA modulation through materials manipulation could be an important cue for modulation that would result in the stem cell lineage commitment. In this work, the FA of hMSCs is modulated by a novel microcontact printing method using polyvinyl alcohol as a trans‐print media which can successfully print proteins on soft polydimethylsiloxane (PDMS). The FA is successfully modified into dense FA and elongated FA by micropatterning square and rectangular patterns on 12.6 kPa PDMS respectively. Additionally, the combined effects of stiffness of PDMS substrates (hard (308 kPa), intermediate (12.6 kPa)) and FA patterning on hMSCs differentiation are studied. The results indicate that dense FA does not induce myogenesis while elongated FA can promote cytoskeleton alignment and further myogenesis on PDMS with intermediate stiffness of 12.6 kPa. However, on stiff substrate (308 kPa), with or without patterns, the cytoskeleton alignment and myogenesis are not obvious. This demonstrates for the first time that it is possible to induce the differentiation of hMSCs by regulating the FA using a materials platform even in the absence of any biochemical factors. It also shows that there is a synergistic effect between FA regulation and matrix stiffness that results in a more specific and higher up‐regulated myogenesis. This platform presents a new chemical/biological‐free method to engineer the myogenic differentiation of hMSCs.
Ultra‐High Voltage Multijunction Organic Solar Cells for Low‐Power Electronic Applications
Authors: Sullivan Paul , Schumann Stefan , Da Campo Raffaello , Howells Thomas , Duraud Amelie , Shipman Michael , Hatton Ross A. , Jones Tim S. 
Published: October 2012

AbstractLow power electronics are an ideal application for organic photovoltaics (OPV) where a low‐cost OPV device can be integrated directly with a battery to provide a constant power source. We demonstrate ultra‐high voltage small molecule multijunction devices with open circuit voltage (VOC) values of up to 7V. Optical modelling is employed to aid the optimisation of the complex multi‐layer stacks and ensure current balancing is achieved between sub‐cells, and optimised multijunction devices show power conversion efficiencies of up to 3.4% which is a modest increase over the single junction devices. Sub‐cell donor/acceptor pairs of boron subphthalocyanine chloride (SubPc)/fullerene (C60) and SubPc/Cl6‐SubPc were selected both for their high VOC in order to minimise the required number of junctions, but also for their absorption overlap to reduce the spectral dependence of the device performance. As a result, the devices are shown to directly charge a micro‐energy cell type battery under both low illumination intensity white light and monochromatic illumination.
Matrix metalloproteinase 3 deletion preserves denervated motor endplates after traumatic nerve injury
Authors: Chao Tom , Frump Derek , Lin Michael , Caiozzo Vincent J. , Mozaffar Tahseen , Steward Oswald , Gupta Ranjan 
Published: October 2012

ObjectiveTraumatic peripheral nerve injuries often produce permanent functional deficits despite optimal surgical and medical management. One reason for the impaired target organ reinnervation is degradation of motor endplates during prolonged denervation. Here we investigate the effect of preserving agrin on the stability of denervated endplates. Because matrix metalloproteinase 3 (MMP3) is known to degrade agrin, we examined the changes in endplate structure following traumatic nerve injury in MMP3 knockout mice.MethodsAfter creation of a critical size nerve defect to preclude reinnervation, we characterized receptor area, receptor density, and endplate morphology in denervated plantaris muscles in wild‐type and MMP3 null mice. The level of agrin and muscle‐specific kinase (MuSK) was assessed at denervated endplates. In addition, denervated muscles were subjected to ex vivo stimulation with acetylcholine. Finally, reinnervation potential was compared after long‐term denervation.ResultsIn wild‐type mice, the endplates demonstrated time‐dependent decreases in area and receptor density and conversion to an immature receptor phenotype. In striking contrast, all denervation‐induced changes were attenuated in MMP3 null mice, with endplates retaining their differentiated form. Agrin and MuSK were preserved in endplates from denervated MMP3 null animals. Furthermore, denervated muscles from MMP3 null mice demonstrated greater endplate efficacy and reinnervation.InterpretationThese results demonstrate a critical role for MMP3 in motor endplate remodeling, and reveal a potential target for therapeutic intervention to prevent motor endplate degradation following nerve injury. ANN NEUROL 2013;73:210–223
Clay modeling versus written modules as effective interventions in understanding human anatomy
Authors: Bareither Mary Lou , Arbel Vered , Growe Meghan , Muszczynski Emily , Rudd Adam , Marone Jane R. 
Published: October 2012

AbstractThe effectiveness of clay modeling to written modules is examined to determine the degree of improvement in learning and retention of anatomical 3D relationships among students with different learning preferences. Thirty‐nine undergraduate students enrolled in a cadaver dissection course completed a pre‐assessment examination and the VARK questionnaire, classifying learning preference as visual, auditory, read/write, or kinesthetic. Students were divided into clay, module, and control groups with preference for learning style distributed among groups. The clay and module groups participated in weekly one‐hour classes using either clay models or answering written questions (modules) about anatomical relationships, respectively. The control group received no intervention. Post‐assessment and retention examinations were administered at the end of the semester, and three months later, respectively. Two variables (Δ1, Δ2) represented examination score differences between pre‐ and post‐assessment and between post‐assessment and retention examinations, respectively. The Δ1 for clay and module groups were each significantly higher than controls (21.46 ± 8.2 vs. 15.70 ± 7.5, P ≤ 0.05; and 21.31 ± 6.9 vs. 15.70 ± 7.5, P ≤0.05, respectively). The Δ2 for clay and module groups approached but did not achieve significance over controls (−6.09 ± 5.07 vs. −8.80 ± 4.60, P = 0.16 and −5.73 ± 4.47 vs. −8.80 ± 4.60, P = 0.12, respectively). No significant differences were seen between interventions or learning preferences in any group. However, students of some learning styles tended to perform better when engaging in certain modalities. Multiple teaching modalities may accommodate learning preferences and improve understanding of anatomy. Anat Sci Educ. © 2013 American Association of Anatomists.
An integrated model for evacuation routing and traffic signal optimization with background demand uncertainty
Authors: Ren Gang , Huang Zhengfeng , Cheng Yang , Zhao Xing , Zhang Yong 
Published: October 2012

SUMMARYEmergency evacuation in congested urban networks can be influenced by uncertain background travel demands, but this issue has not been fully investigated. In this study, evacuation links are prepared for exclusive use by evacuees. Under this assumption, an integrated model is proposed for determining flows on emergency evacuation routes and traffic signals at intersections in the presence of uncertain background travel demands. The problem is formulated as a bi‐objective bi‐level programming model based on the concept of robust optimization. It is assumed that background travel demands belong to an ellipsoidal likelihood region whose parameters are determined by a singly constrained gravity model. With the aim of maximizing the background traffic impact degree in the lower‐level model with a logit‐based stochastic assignment constraint and background demands constraint (the aforementioned ellipsoidal likelihood region), background traffic corresponding to worst‐case demands is determined by the Lagrange multiplier method. In the upper‐level model, two objectives, minimizing both the total travel time of evacuation flows and performance index of the whole network flows, are constructed to determine optimal evacuation flows and traffic signals. The Non‐dominated Sorting Genetic Algorithm II is employed to determine the Pareto solutions of this optimization problem. An example using Sioux Falls networks illustrates the validity of the algorithm. A field case involving the Jianye network around the Nanjing Olympics Sports Center shows the applicability of this algorithm. Copyright © 2012 John Wiley & Sons, Ltd.
The Impact of Stressor Patterns on Clinical Features in Patients With Tako‐tsubo Cardiomyopathy: Experiences of Two Tertiary Cardiovascular Centers
Authors: Song Bong Gun , Yang Hyun Suk , Hwang Hweung Kon , Kang Gu Hyun , Park Yong Hwan , Chun Woo Jung , Oh Ju Hyeon 
Published: October 2012

AbstractBackground:Tako‐tsubo cardiomyopathy (TTC) is typically triggered by an acute emotional or physical stress event. The aim of this study was to investigate the impact of stressor patterns on clinical features, laboratory parameters, and electrocardiographic and echocardiographic findings in patients with TTC.Hypothesis:Clinical features are different according to stressor patterns.Methods:Of 137 patients enrolled from the TTC registry database, 14 patients had emotional triggers (E group), 96 had physical triggers (P group), and 27 had no triggers (N group).Results:Most clinical presentations and in‐hospital courses were similar among the groups. However, the E group had a higher prevalence of chest pain (P = 0.006) and palpitation (P = 0.006), whereas the P group had a higher prevalence of cardiogenic shock (P = 0.040), than other groups. The P group had a significantly higher heart rate (P = 0.001); higher high‐sensitivity C‐reactive protein (P = 0.006), creatine kinase MB fraction (P = 0.045), and N terminal‐probrain natriuretic peptide (P = 0.036) levels; higher left ventricular end‐diastolic pressure (P = 0.019) and left ventricular end‐systolic diameter (P = 0.002); but lower left ventricular ejection fraction (P = 0.018). The E group had lesser prevalence of apical ballooning pattern (P = 0.038) than other groups. The P group required more frequent use of inotropics (P = 0.041) and diuretics (P = 0.047) and had significantly longer intensive care unit (P = 0.014) and in‐hospital stays (P = 0.001).Conclusions:The clinical features of TTC are different according to preceding stressor patterns. The TTC group with preceding physical stressors was less likely to have preserved cardiovascular reserve and more likely to require hemodynamic support than other groups. The overall prognosis of TTC is excellent, regardless of triggering stressors. Clin. Cardiol. 2011 DOI: 10.1002/clc.22053The authors have no funding, financial relationships, or conflicts of interest to disclose.
Prediction of Contrast‐Induced Nephropathy With Persistent Renal Dysfunction and Adverse Long‐term Outcomes in Patients With Acute Myocardial Infarction Using the Mehran Risk Score
Authors: Wi Jin , Ko Young‐Guk , Shin Dong‐Ho , Kim Jung‐Sun , Kim Byeong‐Keuk , Choi Donghoon , Ha Jong‐Won , Hong Myeong‐Ki , Jang Yangsoo 
Published: October 2012

AbstractBackground:Contrast‐induced nephropathy (CIN) has been generally considered to be transient and associated with unfavorable clinical outcomes.Hypothesis:The aim of this study was to investigate whether Mehran risk score could predict CIN with persistent renal dysfunction and long‐term clinical outcomes in acute myocardial infarction (AMI) patients undergoing percutaneous coronary intervention (PCI).Methods:We analyzed the clinical data of 1041 AMI patients. The primary end point was defined as major adverse cardiovascular and cerebrovascular event (MACCE) including death, reinfarction, target vessel revascularization, heart failure requiring hospital admission, and stroke. Patients were categorized into 4 groups according to risk scores: low (≤ 5, n = 596), moderate (6–10, n = 265), high (11–15, n = 111), and very high (≥16, n = 69).Results:Among the 148 patients (14.2%) who developed CIN, persistent renal dysfunction was observed in 68 patients. Presence in high‐ or very high‐risk groups was the most important independent risk factor of CIN with persistent renal dysfunction (odds ratio: 3.35, 95 confidence interval [CI]: 1.89–5.92, P < 0.001). Furthermore, patients in higher‐risk groups experienced significantly more MACCE and mortality 2 years after PCI. Using multivariate analysis, significant increase in the hazard ratio (HR) for MACCE was noted in moderate‐ (HR: 1.40, 95% CI: 0.97–2.03, P = 0.075), high‐ (HR 1.96, 95% CI: 1.22–3.15, P = 0.006), and very high‐risk (HR 2.40, 95% CI: 1.36–4.21, p = 0.002) groups, compared with the low‐risk group. The very high‐risk group had approximately 6‐fold increase in mortality over the low‐risk group (HR: 6.22, 95% CI: 2.77–13.95, P < 0.001).Conclusions:Mehran risk score predicted CIN with persistent renal dysfunction and long‐term clinical outcomes in patients with AMI.Drs. Jin Wi and Young‐Guk Ko contributed equally to the preparation of the article.This study was supported partly by grants from the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea (No. A085012, A102064, and A110879); the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (No.A08 5136); Yonsei University (6‐2009‐0008); Korea Institute of Medicine; and the Cardiovascular Research Center, Seoul, Korea.The authors have no other funding, financial relationships, or conflicts of interest to disclose.
Regulation of organization and function of microtubules by the mitogen‐activated protein kinase cascade during plant cytokinesis
Authors: Sasabe Michiko , Machida Yasunori 
Published: October 2012

AbstractCytokinesis in eukaryotes involves specific arrays of microtubules (MTs), which are known as the central spindle in animals, the anaphase spindle in yeasts, and the phragmoplast in plants. In plants, a mitogen‐activated protein kinase (MAPK) cascade stimulates the turnover of phragmoplast MTs, which allows the expansion of the phragmoplast that is essential for cytokinesis including the formation of cell plates. A prerequisite for activation of this cascade is the interaction between mitotic kinesin NACK1 in tobacco (HINKEL in Arabidopsis) and MAPK kinase kinase NPK1 (ANP1, 2, 3 in Arabidopsis). Other members of this cascade are NQK1 MAPK kinase and NRK1/NTF6 MAPK in tobacco and the respective orthologs in Arabidopsis. All the components in the pathway (designated the NACK‐PQR pathway) concentrate at the midzone of the phragmoplast in plant cells during cytokinesis. Downstream MAPKs in both plant species phosphorylate microtubule‐associated protein 65 (MAP65). Interestingly, activities of components in the NACK‐PQR pathway are downregulated by depolymerization of MTs. In the present review, we summarize current views on the mechanisms involved in activating the kinase cascade, a role of MAP65 phosphorylation by MAPK during cytokinesis, and the feedback mechanism for regulating inactivation of the kinase cascade. © 2012 Wiley Periodicals, Inc
Treatment planning for a TCPC test case: A numerical investigation under rigid and moving wall assumptions
Authors: Mirabella Lucia , Haggerty Christopher M. , Passerini Tiziano , Piccinelli Marina , Powell Andrew J. , Del Nido Pedro J. , Veneziani Alessandro , Yoganathan Ajit P. 
Published: October 2012

SUMMARYThe hemodynamics in patients with total cavopulmonary connections (TCPC) is generally very complex and characterized by patient‐to‐patient variability. To better understand its effect on patients’ outcome, CFD models are widely used, also to test and optimize surgical options before their implementation. These models often assume rigid geometries, despite the motion experienced by thoracic vessels that could influence the hemodynamics predictions. By improving their accuracy and expanding the range of simulated interventions, the benefit of treatment planning for patients is expected to increase. We simulate three types of intervention on a patient‐specific 3D model, and compare their predicted outcome with baseline condition: a decrease in pulmonary vascular resistance obtainable with medications; a surgical revision of the connection design; the introduction of a fenestration in the TCPC wall. The simulations are performed both with rigid wall assumption and including patient‐specific TCPC wall motion, reconstructed from a 4DMRI dataset. The results show the effect of each option on clinically important metrics and highlight the impact of patient‐specific wall motion. The largest differences between rigid and moving wall models are observed in measures of energetic efficiency of TCPC as well as in hepatic flow distribution and transit time of seeded particles through the connection.Copyright © 2012 John Wiley & Sons, Ltd.